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Sample records for sporadic error-increasing effects

  1. Selective antagonism of the error-increasing effect of morphine by naloxone in a repeated-acquisition task.

    D. M. Thompson; Moerschbaecher, J M

    1981-01-01

    Pigeons acquired a different four-response chain each session by responding sequentially on three keys in the presence of four colors. The response chain was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. When either morphine or naloxone was administered alone, the overall response rate decreased with increasing doses. The rate-decreasing effect was accompanied by an increase in percent errors with morphine but not wi...

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

    Chen, G.; Zhao, Z.(Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China; Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui, China; Department of Physics, Nanjing University, Nanjing, Jiangsu, China; School of Physics, Shandong University, Jinan, Shandong, China; Physics Department, Shanghai Jiao Tong University, Shanghai, China); Zhou, C.; Yang, G.; Y. Zhang

    2010-01-01

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

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

    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

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

    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.

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

    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.

  6. Introduction to Sporadic Groups

    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.

  7. Introduction to Sporadic Groups

    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.

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

    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

  9. Sporadic Ataxia and Multiple System Atrophy (MSA)

    FAQ NATIONAL ATAXIA FOUNDATION FREQUENTLY ASKED QUESTIONS ABOUT... Sporadic Ataxia and Multiple System Atrophy (MSA) What is sporadic ataxia? What is Multiple System Atrophy (MSA)? Sporadic ataxia ...

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

    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.

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

    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...... 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...

  12. Genetics Home Reference: sporadic hemiplegic migraine

    ... Home Health Conditions sporadic hemiplegic migraine sporadic hemiplegic migraine Enable Javascript to view the expand/collapse boxes. ... All Open All Close All Description Sporadic hemiplegic migraine is a rare form of migraine headache. Migraines ...

  13. BRCAness Profile of Sporadic Ovarian Cancer Predicts Disease Recurrence

    Wysham, Weiya Z.; Mhawech-Fauceglia, Paulette; Li, Hong; Hays, Laura; Syriac, Suzanna; Skrepnik, Tijana; Wright, Jay; Pande, Nupur; Hoatlin, Maureen; Pejovic, Tanja

    2012-01-01

    Background The consequences of defective homologous recombination (HR) are not understood in sporadic ovarian cancer, nor have the potential role of HR proteins other than BRCA1 and BRCA2 been clearly defined. However, it is clear that defects in HR and other DNA repair pathways are important to the effectiveness of current therapies. We hypothesize that a subset of sporadic ovarian carcinomas may harbor anomalies in HR pathways, and that a BRCAness profile (defects in HR or other DNA repair ...

  14. 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

    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.

  15. 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

    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.

  16. Dynamical model for the toroidal sporadic meteors

    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.

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

    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.

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

    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

  19. Adult onset sporadic ataxias: a diagnostic challenge

    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.

  20. Vascular changes in sporadic ergotism

    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.)

  1. 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)

    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.

  2. 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

    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.

  3. Antigliadin antibody in sporadic adult ataxia

    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.

  4. Synchrony in Metapopulations with Sporadic Dispersal

    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.

  5. Sungrazing dust particles against the sporadic meteor background

    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 approaching the Sun, terminates. The number of sporadic sungrazing meteoroids detected after their passage in the vicinity of the Sun is approximately 20 times smaller than the number of similar particles in the preperihelion part of the trajectory. This result is of special importance for studying the thermodesorption effect of meteoroids (i.e., the change in the content of chemical elements in meteoroids as a function of the perihelion distance).

  6. Predicting sporadic Grid data transfers

    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

  7. Predicting sporadic Grid data transfers.

    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.

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

    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.)

  9. Molecular pathogenesis of sporadic prion diseases in man

    Safar, Jiri G.

    2012-01-01

    The yeast, fungal and mammalian prions determine heritable and infectious traits that are encoded in alternative conformations of proteins. They cause lethal sporadic, familial and infectious neurodegenerative conditions in man, including Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), kuru, sporadic fatal insomnia (SFI) and likely variable protease-sensitive prionopathy (VPSPr). The most prevalent of human prion diseases is sporadic (s)CJD. Recent advances in ...

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

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

    2015-01-01

    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) aft...

  11. Allele doses of apolipoprotein E type {epsilon}4 in sporadic late-onset Alzheimer`s disease

    Lucotte, G.; Aouizerate, A.; Gerard, N. [Regional Center of Neurogenetics, Paris (France)] [and others

    1995-12-18

    Apoliprotein E, type {epsilon}4 allele (ApoE-{epsilon}4) is associated with late-onset sporadic Alzheimer`s disease (AD). We have found that the cumulative probability of remaining unaffected over time decreases for each dose of ApoE-{epsilon}4 in sporadic, late-onset French AD. The effect of genotypes on age at onset of AD was analyzed using the product limit method, to compare unaffected groups during aging. 26 refs., 2 figs., 1 tab.

  12. Sporadic aurorae observed in East Asia

    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".

  13. Sporadic aurorae observed in East Asia

    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".

  14. Aneurysm in a Large Sporadic Renal Angiomyolipoma.

    Al Omran, Bedoor; Ansari, Naseem

    2016-05-01

    Angiomyolipomas (AMLs) are the most common mesenchymal renal neoplasms and are classified as neoplasms of perivascular epithelioid cells (PEComa). AML is usually a benign neoplasm arising most often in the kidney although it has been described in a wide variety of sites. Most patients are adults, and one-third suffer from tuberous sclerosis. We describe a case of renal AML in a 54-year-old Bahraini woman who presented to the Bahrain Defence Force Hospital with right flank pain and hematuria, and who was known to have rheumatoid arthritis but had no cutaneous or other stigmata of tuberous sclerosis. It is the largest AML reported in Bahrain and is also striking for the fact that it contained an intratumoral aneurysm that ruptured causing symptoms leading to the radiological diagnosis of renal mass. Furthermore, the occurrence of an aneurysm in sporadic AML, as in our case, is rare since the large majority tend to be seen in association with tuberous sclerosis. PMID:27162594

  15. Anterior cervical hypertrichosis: a sporadic case.

    Bostan, Sezen; Yaşar, Şirin; Serdar, Zehra Aşiran; Gizlenti, Sevda

    2016-03-01

    Anterior cervical hypertrichosis is a very rare form of primary localized hypertrichosis. It consists of a tuft of terminal hair on the anterior neck just above the laryngeal prominence. The etiology is still unknown. In this article, we reported a 15-year-old female patient who presented to our clinic with a complaint of hypertrichosis on the anterior aspect of the neck for the last five years. Her past medical history revealed no pathology except for vesicoureteral reflux. On the basis of clinical presentation, our patient was diagnosed with anterior cervical hypertrichosis and she was considered to be a sporadic case due to lack of other similar cases in familial history. To date, 33 patients with anterior cervical hypertrichosis have been reported. Anterior cervical hypertrichosis can be associated with other abnormalities, but it frequently presents as an isolated defect (70%). The association of vesicoureteral reflux and anterior cervical hypertrichosis which was observed in our patient might be coincidental. So far, no case of anterior cervical hypertrichosis associated with vesicoureteral reflux has been reported in the literature. PMID:27103865

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

    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.

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

    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 ...

  18. Sporadic ataxia with adult onset: classification and diagnostic criteria.

    Klockgether, Thomas

    2010-01-01

    In most patients with adult-onset progressive ataxia, the condition manifests without an obvious familial background. The classification and correct diagnosis of such patients remain a challenge, because almost the entire spectrum of non-genetic and genetic causes of ataxia has to be considered. A wide range of potential causes of acquired ataxia exist, including chronic alcohol use, various other toxic agents, immune-mediated inflammation, vitamin deficiency, chronic leptomeningeal deposition of iron leading to superficial siderosis, and chronic CNS infection. Mutations in single genes can also underlie sporadic ataxia in adults. Finally, patients might have a sporadic degenerative disease, such as multiple system atrophy of cerebellar type or sporadic adult-onset ataxia of unknown aetiology. The definition of clinical criteria and delineation of characteristic MRI features have greatly facilitated the early and correct recognition of sporadic ataxias. In addition, specific serological and genetic markers are available that allow a definite diagnosis in many cases. PMID:20083040

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

    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

  20. Sporadic Corticobasal Syndrome due to FTLD-TDP

    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 (...

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

    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.

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

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

    1994-09-01

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

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

    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

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

    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.

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

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

    2015-01-01

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

  6. Stream and sporadic meteoroids associated with Near Earth Objects

    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.

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

    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...

  8. Gender- and Age-Dependent γ-Secretase Activity in Mouse Brain and Its Implication in Sporadic Alzheimer Disease

    Placanica, Lisa; Zhu, Lei; Li, Yue-Ming

    2009-01-01

    Alzheimer disease (AD) is an age-related disorder. Aging and female gender are two important risk factors associated with sporadic AD. However, the mechanism by which aging and gender contribute to the pathogenesis of sporadic AD is unclear. It is well known that genetic mutations in γ-secretase result in rare forms of early onset AD due to the aberrant production of Aβ42 peptides, which are the major constituents of senile plaques. However, the effect of age and gender on γ-secretase has not...

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

    Li Ling-Hui

    2011-06-01

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

  10. Tumour suppressor genes in sporadic epithelial ovarian cancer

    Liu, Ying; Ganesan, Trivadi S

    2002-01-01

    evolution of tumour progression. A major focus of research has been to identify tumour suppressor genes implicated in sporadic ovarian cancer over the past decade. Several tumour suppressor genes have been identified by strategies such as positional cloning and differential expression display. Further...

  11. Impaired proteasome function in sporadic amyotrophic lateral sclerosis.

    Kabashi, Edor; Agar, Jeffrey N; Strong, Michael J; Durham, Heather D

    2012-06-01

    Abstract The ubiquitin-proteasome system, important for maintaining protein quality control, is compromised in experimental models of familial ALS. The objective of this study was to determine if proteasome function is impaired in sporadic ALS. Proteasomal activities and subunit composition were evaluated in homogenates of spinal cord samples obtained at autopsy from sporadic ALS and non-neurological control cases, compared to cerebellum as a clinically spared tissue. The level of 20S α structural proteasome subunits was assessed in motor neurons by immunohistochemistry. Catalysis of peptide substrates of the three major proteasomal activities was substantially reduced in ALS thoracic spinal cord, but not in cerebellum, accompanied by alterations in the constitutive proteasome machinery. Chymotrypsin-like activity was decreased to 60% and 65% of control in ventral and dorsal spinal cord, respectively, concomitant with reduction in the β5 subunit with this catalytic activity. Caspase- and trypsin-like activities were reduced to a similar extent (46% - 68% of control). Proteasome levels, although generally maintained, appeared reduced specifically in motor neurons by immunolabelling. In conclusion, there are commonalities of findings in sporadic ALS patients and presymptomatic SOD1-G93A transgenic mice and these implicate inadequate proteasome function in the pathogenesis of both familial and sporadic ALS. PMID:22632443

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

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

    2014-12-01

    Sporadic Creutzfeldt-Jakob disease is considered primarily a disease of grey matter, although the extent of white matter involvement has not been well described. We used diffusion tensor imaging to study the white matter in sporadic Creutzfeldt-Jakob disease compared to healthy control subjects and to correlated magnetic resonance imaging findings with histopathology. Twenty-six patients with sporadic Creutzfeldt-Jakob disease and nine age- and gender-matched healthy control subjects underwent volumetric T1-weighted and diffusion tensor imaging. Six patients had post-mortem brain analysis available for assessment of neuropathological findings associated with prion disease. Parcellation of the subcortical white matter was performed on 3D T1-weighted volumes using Freesurfer. Diffusion tensor imaging maps were calculated and transformed to the 3D-T1 space; the average value for each diffusion metric was calculated in the total white matter and in regional volumes of interest. Tract-based spatial statistics analysis was also performed to investigate the deeper white matter tracts. There was a significant reduction of mean (P=0.002), axial (P=0.0003) and radial (P=0.0134) diffusivities in the total white matter in sporadic Creutzfeldt-Jakob disease. Mean diffusivity was significantly lower in most white matter volumes of interest (Pstatistics analysis showed significant reductions of mean diffusivity within the white matter of patients with sporadic Creutzfeldt-Jakob disease, mainly in the left hemisphere, with a strong trend (P=0.06) towards reduced mean diffusivity in most of the white matter bilaterally. In contrast, by visual assessment there was no white matter abnormality either on T2-weighted or diffusion-weighted images. Widespread reduction in white matter mean diffusivity, however, was apparent visibly on the quantitative attenuation coefficient maps compared to healthy control subjects. Neuropathological analysis showed diffuse astrocytic gliosis and activated microglia in the white matter, rare prion deposition and subtle subcortical microvacuolization, and patchy foci of demyelination with no evident white matter axonal degeneration. Decreased mean diffusivity on attenuation coefficient maps might be associated with astrocytic gliosis. We show for the first time significant global reduced mean diffusivity within the white matter in sporadic Creutzfeldt-Jakob disease, suggesting possible primary involvement of the white matter, rather than changes secondary to neuronal degeneration/loss. PMID:25367029

  13. A Study Of Sporadic Adult Onset Degenerative Cerebellar Ataxias

    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.

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

    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, and proximal tumor location were combined with the morphologic features with the highest relative...... risks (RRs), eg, mucinous differentiation (RR, 9.0), tumor-infiltrating lymphocytes (RR, 7.5), absence of necrosis (RR, 7.5), and expanding growth pattern (RR, 5.0) into a 7-factor index, the presence of at least 4 features identified the MMR-defective tumors with 92.3% sensitivity and 75.3% specificity...

  15. On permanent and sporadic pulsations of the magnetosphere

    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.

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

    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...

  17. Application of dopplionograms to an understanding of sporadic E

    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

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

    Carlos Henrique F. Camargo; Sarah Teixeira Camargos; Nilson Becker; Renato Puppi Munhoz; Salmo Raskin; Cardoso, Francisco Eduardo C.; Teive, Hélio Afonso G.

    2014-01-01

    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 lat...

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

    Fritzsche Markus

    2002-01-01

    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 excesse...

  20. Genetics and Genetic Biomarkers in Sporadic Colorectal Cancer.

    Carethers, John M; Jung, Barbara H

    2015-10-01

    Sporadic colorectal cancer (CRC) is a somatic genetic disease in which pathogenesis is influenced by the local colonic environment and the patient's genetic background. Consolidating the knowledge of genetic and epigenetic events that occur with initiation, progression, and metastasis of sporadic CRC has identified some biomarkers that might be utilized to predict behavior and prognosis beyond staging, and inform treatment approaches. Modern next-generation sequencing of sporadic CRCs has confirmed prior identified genetic alterations and has classified new alterations. Each patient's CRC is genetically unique, propelled by 2-8 driver gene alterations that have accumulated within the CRC since initiation. Commonly observed alterations across sporadic CRCs have allowed classification into a (1) hypermutated group that includes defective DNA mismatch repair with microsatellite instability and POLE mutations in ∼15%, containing multiple frameshifted genes and BRAF(V600E); (2) nonhypermutated group with multiple somatic copy number alterations and aneuploidy in ∼85%, containing oncogenic activation of KRAS and PIK3CA and mutation and loss of heterozygosity of tumor suppressor genes, such as APC and TP53; (3) CpG island methylator phenotype CRCs in ∼20% that overlap greatly with microsatellite instability CRCs and some nonhypermutated CRCs; and (4) elevated microsatellite alterations at selected tetranucleotide repeats in ∼60% that associates with metastatic behavior in both hypermutated and nonhypermutated groups. Components from these classifications are now used as diagnostic, prognostic, and treatment biomarkers. Additional common biomarkers may come from genome-wide association studies and microRNAs among other sources, as well as from the unique alteration profile of an individual CRC to apply a precision medicine approach to care. PMID:26216840

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

    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.

  2. Sporadic hemangioblastomas are characterized by cryptic VHL inactivation.

    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

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

    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. Molecular pathogenesis of sporadic prion diseases in man.

    Safar, Jiri G

    2012-01-01

    The yeast, fungal and mammalian prions determine heritable and infectious traits that are encoded in alternative conformations of proteins. They cause lethal sporadic, familial and infectious neurodegenerative conditions in man, including Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), kuru, sporadic fatal insomnia (SFI) and likely variable protease-sensitive prionopathy (VPSPr). The most prevalent of human prion diseases is sporadic (s)CJD. Recent advances in amplification and detection of prions led to considerable optimism that early and possibly preclinical diagnosis and therapy might become a reality. Although several drugs have already been tested in small numbers of sCJD patients, there is no clear evidence of any agent's efficacy. Therefore, it remains crucial to determine the full spectrum of sCJD prion strains and the conformational features in the pathogenic human prion protein governing replication of sCJD prions. Research in this direction is essential for the rational development of diagnostic as well as therapeutic strategies. Moreover, there is growing recognition that fundamental processes involved in human prion propagation - intercellular induction of protein misfolding and seeded aggregation of misfolded host proteins - are of far wider significance. This insight leads to new avenues of research in the ever-widening spectrum of age-related human neurodegenerative diseases that are caused by protein misfolding and that pose a major challenge for healthcare. PMID:22421210

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

    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.

  6. Seed Set and Natural Regeneration of Dendrocalamus membranaceus Munro after Mass and Sporadic Flowering in Yunnan, China.

    Xie, Ning; Chen, Ling-Na; Wong, Khoon-Meng; Cui, Yong-Zhong; Yang, Han-Qi

    2016-01-01

    The flowering periods of woody bamboos, seed set, natural regeneration and death after flowering have been rarely observed and evaluated in the field. Dendrocalamus membranaceus Munro, a tropical woody bamboo mainly distributed in the Yunnan, displayed both sporadic as well as gregarious (mass) flowering and fruited from 2006 to 2013 following severe droughts. The aim of this study is to examine potential differences in seed set and natural regeneration between the two flowering patterns in natural D. membranaceus forests. We investigated and analyzed seed set, seed germination, seedling growth and mortality in both mass and sporadic flowering populations. Observations were made over a period of three years to record changes in bamboo seedling density, height and culm diameter. We observed a low natural seed set ranging from 1.76% to 7.49%, and a relatively high seed germination rate in the nursery from 59.6% to 71.0% for both types of flowering populations. Seeds germinated in 5-7 days after sowing and the germination period lasted 10-15 days. Seed set and germination rates in mass-flowering populations were significantly higher than those of sporadically flowering stands. The seedlings within sporadically flowering populations died within two years. In comparison, seedling mortality in the mass flowering population increased over two periods of observation from 64.92% to 98.89%, yet there was good seedling establishment left over, which showed mean height and mean culm diameter increasing by 1053.25% and 410.71%, respectively, in the second year of observations, and 137.10%, and 217.48%, respectively, in the third year. There are significant differences in seed set, natural regeneration ability and sustainability of bamboo populations between the mass flowering and sporadically flowering populations of D. membranaceus. Sporadic flowering populations failed to produce effective regeneration, while mass flowering populations were able to regenerate successfully. This study provides useful insights for conservation and natural forest management of D. membranaceus. We consider the merits of introducing other genetic provenances towards long-term maintenance of the stand features at sporadically flowering sites; meanwhile, the most economic option for mass flowering stands is to allow natural regeneration to take place through protecting such sites from further disturbance. PMID:27077651

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

    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

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

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

    2005-01-01

    Electric field and plasma density data gathered on a sounding rocket launched from Uchinoura Space Center, Japan, reveal a complex electrodynamics associated with sporadic-E layers and simultaneous observations of quasiperiodic radar echoes. The electrodynamics are characterized by spatial and temporal variations that differed considerably between the rocket's up-leg and down-leg traversals of the lower ionosphere. Within the main sporadic-E layer (95- 110 km) on the up-leg, the electric fields were variable, with amplitudes of 2 4 mV1m 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 down-leg, 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 9mV/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.

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

    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 μl 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.

  10. Application of quantitative DTI metrics in sporadic CJD

    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.

  11. INTUSSUSCEPTION IN A CHILD WITH SPORADIC BURKITT LYMPHOMA

    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.

  12. Application of quantitative DTI metrics in sporadic CJD.

    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

  13. Application of quantitative DTI metrics in sporadic CJD?

    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

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

    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.

  15. Feasibility Analysis of Sporadic Real-Time Multiprocessor Task Systems

    Bonifaci, Vincenzo

    2010-01-01

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

  16. Sporadic diffuse gastric polyposis: Report of a case.

    Spaziani, Erasmo; Picchio, Marcello; Di Filippo, Annalisa; Narilli, Piero; Di Cristofano, Claudio; Petrozza, Vincenzo; De Angelis, Francesco; Ragona, Giuseppe

    2011-10-01

    A 50-year-old woman was admitted because of severe sideropenic anemia. The gastrin levels were within normal ranges. Esophagogastroduodenoscopy showed diffuse gastric polyposis with signs of diffuse oozing. Colonoscopy showed the presence of a 3-cm wide pedunculated polyp of the ascending colon, which was removed by diathermy. The patient was treated by total gastrectomy with Roux-Y esophagojejunostomy. Histological examination showed the presence of diffuse gastric polyposis with the contemporary occurrence of hyperplastic polyps and mixed hyperplastic and adenomatous polyps, with a tubular pattern and the focal aspect of serrate adenoma. This is the first case report of sporadic diffuse hyperplastic and adenomatous polyposis of the stomach. PMID:21922371

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

    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

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

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

    1995-05-01

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

  19. Diffusion MR imaging in sporadic Creutzfeldt-Jakob disease

    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

  20. A role for genetic susceptibility in sporadic focal segmental glomerulosclerosis.

    Yu, Haiyang; Artomov, Mykyta; Brähler, Sebastian; Stander, M Christine; Shamsan, Ghaidan; Sampson, Matthew G; White, J Michael; Kretzler, Matthias; Miner, Jeffrey H; Jain, Sanjay; Winkler, Cheryl A; Mitra, Robi D; Kopp, Jeffrey B; Daly, Mark J; Shaw, Andrey S

    2016-03-01

    Focal segmental glomerulosclerosis (FSGS) is a syndrome that involves kidney podocyte dysfunction and causes chronic kidney disease. Multiple factors including chemical toxicity, inflammation, and infection underlie FSGS; however, highly penetrant disease genes have been identified in a small fraction of patients with a family history of FSGS. Variants of apolipoprotein L1 (APOL1) have been linked to FSGS in African Americans with HIV or hypertension, supporting the proposal that genetic factors enhance FSGS susceptibility. Here, we used sequencing to investigate whether genetics plays a role in the majority of FSGS cases that are identified as primary or sporadic FSGS and have no known cause. Given the limited number of biopsy-proven cases with ethnically matched controls, we devised an analytic strategy to identify and rank potential candidate genes and used an animal model for validation. Nine candidate FSGS susceptibility genes were identified in our patient cohort, and three were validated using a high-throughput mouse method that we developed. Specifically, we introduced a podocyte-specific, doxycycline-inducible transactivator into a murine embryonic stem cell line with an FSGS-susceptible genetic background that allows shRNA-mediated targeting of candidate genes in the adult kidney. Our analysis supports a broader role for genetic susceptibility of both sporadic and familial cases of FSGS and provides a tool to rapidly evaluate candidate FSGS-associated genes. PMID:26901816

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

    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...

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

    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

  3. On Permanent and Sporadic Oscillations of the Magnetosphere

    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...

  4. A Case Of Sporadic Mesenteric Fibromatosis Mimicking Pancreatic Mass

    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

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

    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.

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

    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

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

    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

  8. Sporadic observation of the Fleischmann-Pons heat effect

    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).

  9. Reactive GTS Allocation Protocol for Sporadic Events Using the IEEE 802.15.4

    Mukhtar Azeem; Majid I. Khan; Yasir Faheem; Manzoor Illahi Tamimy; Najmus Saqib Malik; Abid Khan; Mansoor Ahmed

    2014-01-01

    Wireless sensor networks (WSNs) find applications in the industrial automation where periodic and sporadic events occur. The combined propagation of information generated by periodic and sporadic events from a sensor node to an actuator node is challenging due to random nature of sporadic events, particularly, if the deadlines are hard. The IEEE 802.15.4 standard provides the basis for a real-time communication mechanism between neighboring nodes of the WSN at the media access control layer. ...

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

    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

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

    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

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

    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

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

    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.

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

    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

  15. 29 CFR 553.30 - Occasional or sporadic employment-section 7(p)(2).

    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...

  16. Sporadic norovirus infections among hospitalized and non-hospitalized 0-3-year-old infants.

    Kele, Beatrix; Abrok, Marianna Papp; Deak, Judith

    2009-01-01

    Little is known of the frequency of norovirus infections in sporadic gastroenteritis cases. In a 4-y study, we examined 1152 rota-, adeno- and astrovirus negative stool samples for human noroviruses; 187 (16.2%) proved to be positive. Stool samples were from paediatric patients with acute gastroenteritis. All isolates were verified as sporadic cases: there was no accumulation. PMID:18985543

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

    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....

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

    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

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

    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......-related hospitalization, biological treatment, and surgery in familial versus sporadic cases of IBD. RESULTS: A total of 27,886 IBD cases, including 1006 IBD-relative pairs, were followed-up for up to 16 years, totaling 164,979 person-years. We observed no difference in risk of hospital admissions between familial and...... functional effects, which is consoling for newly diagnosed CD or UC patients with a family history of IBD....

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

    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.

  1. Thyroid Sporadic Goiter with Adult Heterotopic Bone Formation

    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

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

    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

  3. De novo variants in sporadic cases of childhood onset schizophrenia.

    Ambalavanan, Amirthagowri; Girard, Simon L; Ahn, Kwangmi; Zhou, Sirui; Dionne-Laporte, Alexandre; Spiegelman, Dan; Bourassa, Cynthia V; Gauthier, Julie; Hamdan, Fadi F; Xiong, Lan; Dion, Patrick A; Joober, Ridha; Rapoport, Judith; Rouleau, Guy A

    2016-06-01

    Childhood-onset schizophrenia (COS), defined by the onset of illness before age 13 years, is a rare severe neurodevelopmental disorder of unknown etiology. Recently, sequencing studies have identified rare, potentially causative de novo variants in sporadic cases of adult-onset schizophrenia and autism. In this study, we performed exome sequencing of 17 COS trios in order to test whether de novo variants could contribute to this disease. We identified 20 de novo variants in 17 COS probands, which is consistent with the de novo mutation rate reported in the adult form of the disease. Interestingly, the missense de novo variants in COS have a high likelihood for pathogenicity and were enriched for genes that are less tolerant to variants. Among the genes found disrupted in our study, SEZ6, RYR2, GPR153, GTF2IRD1, TTBK1 and ITGA6 have been previously linked to neuronal function or to psychiatric disorders, and thus may be considered as COS candidate genes. PMID:26508570

  4. Analysis of GLRA 1 in familial and sporadic hyperekplexia

    Elmslie, F.V.; Rees, M. [UCL Medical School, London (United Kingdom); Covanis, A. [Aghia Sofia Hospital, Athens (Greece)] [and others

    1994-09-01

    Hyperekplexia or familial startle syndrome is an autosomal dominant condition, causing an exaggerated startle response to unexpected stimuli. Infants have variable hypertonia in the neonatal period, with a startle response causing sustained muscular contraction. The gene was localized to chromosome 5q in 1992 and subsequently mutations were detected in the alpha{sub 1} subunit of the glycine receptor in four large pedigrees with hyperekplexia. Eight probands with hyperekplexia have been ascertained, including three sporadic and four familial cases. In one pedigree, hyperekplexia appears to be associated with spastic paraparesis, and the hyperekplexia/spastic paraparesis is linked to marker loci on chromosome 5q. Genomic DNA was extracted from white cells. GLRA1 exons were amplified from genomic DNA by PCR using specific oligonucleotide primers. Amplified exon 6 fragments are being screened for the previously described mutations by restriction enzyme analysis using Bfa1 and Xho1. In addition, all exons have been screened by single-stranded conformational polymorphism (SSCP) and are currently being screened by heteroduplex analysis. No sequence changes have been detected to date. Products displaying aberrant bands on screening will be analyzed further by di-deoxy sequencing.

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

    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.

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

    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.

  7. Evaluation of sporadic cases of odontogenic keratocysts in multicentric study.

    Valter, K; Pavelić, B; Katanec, D; Sokler, K; Galić, N; Segović, S; Donath, K; Herman, R

    2002-12-01

    The aim of this retrospective study was to report frequency of sporadic odontogenic keratocysts (sOKC) according to the age and gender, as well as location (mandible, maxilla, soft tissues, and maxillary sinus). Four hundred and twenty nine sOKC confirmed pathohistologically in a period from 1965-1998 were included in this study. The average age of patients with sOKC was 43.11 (age range 10-91), in males 42.06 and in females 44.72 years. More frequently sOKC were found in males (60.61%) in comparison to the females (39.39%). Therefore, ratio between males and females was 1.5:1. Diagnosis of sOKC is usually established in patients aged 21-30 (18.88%), in males usually aged between 21-30 (23.46%), and in females aged between 11-20 (18.93%). sOKC are more frequent in males according to the age groups, except between age 61-70 where sOKC were more frequent in females. Most frequently, sOKC occurred in the mandible 70.16%, 12.35% of sOKC were found in the maxilla, 12.82% in soft tissues and 4.66% in the maxillary sinuses. PMID:12674852

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

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

    2010-01-01

    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...... response in some patients with Parkin-associated PD may not be related to differences in cortical recruitment. In conclusion, our findings corroborate a substantial pathophysiologic overlap between Parkin-associated and sporadic PD and lend further support to the notion that Parkin-associated PD is a...

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

    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.

  10. CAMS newly detected meteor showers and the sporadic background

    Jenniskens, P.; Nénon, Q.; Gural, P. S.; Albers, J.; Haberman, B.; Johnson, B.; Morales, R.; Grigsby, B. J.; Samuels, D.; Johannink, C.

    2016-03-01

    The Cameras for Allsky Meteor Surveillance (CAMS) video-based meteoroid orbit survey adds 60 newly identified showers to the IAU Working List of Meteor Showers (numbers 427, 445-446, 506-507, and part of 643-750). 28 of these are also detected in the independent SonotaCo survey. In total, 230 meteor showers and shower components are identified in CAMS data, 177 of which are detected in at least two independent surveys. From the power-law size frequency distribution of detected showers, we extrapolate that 36% of all CAMS-observed meteors originated from ∼700 showers above the N = 1 per 110,000 shower limit. 71% of mass falling to Earth from streams arrives on Jupiter-family type orbits. The transient Geminids account for another 15%. All meteoroids not assigned to streams form a sporadic background with highest detected numbers from the apex source, but with 98% of mass falling in from the antihelion source. Even at large ∼7-mm sizes, a Poynting-Robertson drag evolved population is detected, which implies that the Grün et al. collisional lifetimes at these sizes are underestimated by about a factor of 10. While these large grains survive collisions, many fade on a 104-y timescale, possibly because they disintegrate into smaller particles by processes other than collisions, leaving a more resilient population to evolve. The meteors assigned to the various showers are identified in the CAMS Meteoroid Orbit Database 2.0 submitted to the IAU Meteor Data Center, and can be accessed also at

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

    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

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

    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

  13. Upregulated Genes In Sporadic, Idiopathic Pulmonary Arterial Hypertension

    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.

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

    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

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

    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.

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

    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

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

    Ainur R. Akilzhanova; Bagdat Nyshanbekkyzy; Zhannur M. Nurkina; Ivan I. Shtephanov; Abay K. Makishev; Tasbolat A. Adylkhanov; Tolebay K. Rakhypbekov; Erlan M. Ramanculov; Kuvat T. Momynaliev

    2013-01-01

    Background: A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Kazakhstan women. Aim: To evaluate the role of BRCA1/2 mutations in Kazakhstan women presenting with sporadic breast cancer. Methods: We investigated the distribution and nature of polymorphisms in BRCA1 and BRCA2 entire coding regions in 156 Kazakhstan sporadic breast cancer cases...

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

    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...

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

    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...

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

    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

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

    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

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

    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

  3. Sporadic E Morphology from GPS-CHAMP Radio Occultation

    Wu, Dong L.; Ao, Chi O.; Hajj, George A.; de la Torre Juarez, Manuel; Mannucci, Anthony J.

    2005-01-01

    The scintillations of phase and amplitude in terms of signal-to-noise ratio (SNR) of the GPS radio occultation signal are caused by thin ionization layers. These thin irregular electron density layers in the E region ionosphere are often called sporadic E (Es). For a monthly retrieval of Es morphology we use the variances of the phase and SNR fluctuations of worldwide 6000 GPS/CHAMP occultations in the E region. The Es climatology is studied globally with the SNR and phase variances in terms of monthly zonal means, seasonal maps, and diurnal and long-term variations. The zonal mean variances reveal strong, extended Es activities at summertime midlatitudes but weak, confined activities in wintertime high latitudes, peaking at 105 km. Global maps at 105-km altitude show clear dependence of Es activities on the geomagnetic dip angle, where the summertime midlatitude Es occurs mostly at dip angles of 30 deg. - 60 deg. and the wintertime high-latitude enhancement occurs mostly at dip angles greater than 80 deg. The midlatitude Es variances exhibit a strong semidiurnal variation with peak hours near 0800 1000 and 2000 local solar time, respectively. The peak hours are delayed slightly with decreasing height, suggesting influences from the semidiurnal tide. To provide more insights on the observed SNR and phase variances, we model radio wave propagation for the CHAMP observing geometry under several perturbed cases in the E region ionosphere. The model simulations indicate that the SNR variance has the maximum response to Es perturbations at vertical wavelengths of 1.2 km, whereas the phase response maximizes at 2 km (for the 1-s variance analysis). The characteristic scale depends little on the truncation time used in the SNR variance analysis, but it increases with the truncation time for the phase variances. Initial studies show that reasonable global Es morphology can be produced on a monthly and seasonal basis with the CHAMP one-antenna occultations. Better results from other existing and upcoming GPS occultation missions are anticipated in future studies, and they will significantly improve our understanding of this important phenomenon.

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

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

    2012-06-15

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

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

    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.

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

    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.

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

    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

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

    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.)

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

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

    MelissaA.Burgess

    2014-02-01

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

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

    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.

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

    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

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

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

  14. Midlatitude sporadic-E layers and vertical metallic ion drift profiles

    Royrvik, O.

    1983-02-01

    An investigation of the relationship between the occurrence of midlatitude sporadic-E-layers and convergent points in the ion drift profiles has been made using the 430 MHz incoherent scatter radar at the Arecibo Observatory. Electron concentration profiles were obtained using a 13 baud Barker coded pulse yielding 600 m range resolution, while a 5-pulse sequence with 2.4 km range resolution was used to obtain line-of-sight ion drift velocities. With some exceptions, observed sporadic-E layers occur near convergent points in the vertical metallic ion drift profile, and vertical motions of these layers follow the vertical motions of the convergent point. A sudden increase in the altitude of a sporadic-E layer has been observed. This is attributed to the disappearance of the convergent point, releasing the layer, followed by an ascent of the layer to the closest overlying convergent point.

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

    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.

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

    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.

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

    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

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

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

    2011-04-15

    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

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

    Zhang, Shujun; WANG, JINGJING; Yuan, Quan; Ge, Shengxiang; Zhang, Jun; Xia, Ningshao; Tian, Deying

    2011-01-01

    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...

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

    Xia Ningshao; Zhang Jun; Ge Shengxiang; Yuan Quan; Wang Jingjing; Zhang Shujun; Tian Deying

    2011-01-01

    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%), fati...

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

    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...

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

    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

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

    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

  4. Sporadic Retinoblastoma and Parental Smoking and Alcohol Consumption before and after Conception: A Report from the Children’s Oncology Group

    Azary, Saeedeh; Ganguly, Arupa; Bunin, Greta R.; Lombardi, Christina; Park, Andrew S.; Ritz, Beate; Heck, Julia E.

    2016-01-01

    Background Retinoblastoma is the most frequent tumor of the eye in children and very little is known about the etiology of non-familial (sporadic) retinoblastoma. In this study we examined whether parental tobacco smoking or alcohol consumption (pre- or post-conception) contribute to the two phenotypes (bilateral or unilateral) of sporadic retinoblastoma. Methods Two large multicenter case-control studies identified 488 cases through eye referral centers in the United States and Canada or through the Children’s Oncology Group. Controls (n = 424) were selected from among friends and relatives of cases and matched by age. Risk factor information was obtained via telephone interview. We employed multivariable logistic regression to estimate the effects of parental tobacco smoking and alcohol consumption on retinoblastoma. Findings Maternal smoking before and during pregnancy contributed to unilateral retinoblastoma risk in the child: year before pregnancy conditional Odds Ratio (OR), 8.9; 95% confidence interval (CI) 1.5–51, and unconditional OR, 2.4; 95% CI, 1.3–4.7; month before or during pregnancy, conditional OR, 3.3; 95% CI, 0.5–20.8, and unconditional OR, 2.8; 95% CI, 1.1–7.0. No association was found for maternal or paternal alcohol consumption. Conclusion The results of this study indicate that maternal active smoking during pregnancy may be a risk factor for sporadic retinoblastoma. Our study supports a role for tobacco exposures in embryonal tumors. PMID:26991078

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

    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.

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

    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.

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

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

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

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

    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. Sporadic Cerebral Cavernous Malformations: Report of Further Mutations of CCM Genes in 40 Italian Patients

    D'Angelo, Rosalia; Alafaci, Concetta; Scimone, Concetta; Ruggeri, Alessia; Salpietro, Francesco Maria; Bramanti, Placido; Tomasello, Francesco; Sidoti, Antonina

    2013-01-01

    Cerebral cavernous malformations (CCMs) are vascular lesions characterized by abnormally enlarged capillary cavities, affecting the central nervous system. CCMs can occur sporadically or as a familial autosomal dominant condition with incomplete penetrance and variable clinical expression attributable to mutations in three different genes: CCM1 (K-Rev interaction trapped 1 (KRIT1)), CCM2 (MGC4607), and CCM3 (PDCD10). CCMs occur as a single or multiple malformations that can lead to seizures, focal neurological deficits, hemorrhagic stroke, and headache. However, patients are frequently asymptomatic. In our previous mutation screening, performed in a cohort of 95 Italian patients, both sporadic and familial, we have identified several mutations in CCM genes, three of which in three distinct sporadic patients. In this study, representing further molecular screening of the three CCM genes, in a south Italian cohort of CCM patients enrolled by us in the last three years, we report the identification of other four new mutations in 40 sporadic patients with either single or multiple CCM. PMID:24058906

  11. Atypical sporadic lymphosarcoma in a 7-month-old Holstein heifer.

    Dubreuil, P.; Lanevschi, A; Perrone, M A; Desnoyers, M

    1998-01-01

    A 7-month-old calf with a firm, diffuse infiltration of the left hind limb with sciatic nerve motor deficit was presented. The cytology indicated a malignant, round cell tumor and at necropsy, tissues were positive to a Kappa-lambda immunohistochemistry test. The final diagnosis was sporadic bovine leukosis, juvenile form.

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

    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...

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

    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...

  14. Prevalence of BRCA-1 associated protein 1 germline mutation in sporadic malignant pleural mesothelioma cases

    Rusch, Andreas; Ziltener, Gabriela; Nackaerts, Kristiaan; Weder, Walter; Rolf A. Stahel; Felley-Bosco, Emanuela

    2015-01-01

    23% of mesothelioma tumor specimens have a mutation in the BRCA1-associated protein 1 (BAP1) gene and germline BAP1 mutations predispose to malignant pleural mesothelioma (MPM). Our aim was to investigate germline BAP1 mutations in sporadic MPM patients.

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

    Saad M. Al Suwayri

    2016-01-01

    Full Text Available 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 consistent with current diagnostic criteria for sporadic KLS. Results: Six reviews and 11 case reports describing cases of familial KLS were identified. In 17 of the 29 familial cases identified, sufficient clinical details were described to be confident that these cases were familial and consistent with the description of KLS in the International Classification of Sleep Disorders 3rd edition (ICSD-3, and recent detailed reviews of sporadic KLS. Conclusion: A significant number of familial cases of KLS have been described that are consistent with the ICSD-3 description of KLS, and indistinguishable from sporadic KLS. This suggests that study of familial KLS using modern genetic techniques may be useful in elucidating the pathogenesis of this rare condition.

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

    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)

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

    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.

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

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

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

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

    2011-05-01

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

  20. Observations and Modeling of Sporadic Metal Layers over the Arecibo Observatory

    Delgado Gilewski, Ruben

    Nighttime observations of the atmospheric potassium and iron layers were performed using lidar, between September 2001 and December 2005, to determine the frequency and characteristics of potassium (Ks) and iron (Fes) sporadic metal layers over the Arecibo Observatory. Ks and Fes were observed to occur once every six hours of measurements, lasting about 90 minutes. Occurrence probability, peak height and full width half maxima (FWHM), strength factor and duration were determined from 1312 and 299 hours of observations for potassium and iron, respectively. Ab initio and density functional calculations were carried out to calculate the geometry and vibrational frequencies of the neutral and ionic form of KN2 and KCO2 to study the binding energy, the adiabatic ionization energy (AIE), and the vertical ionization energy (VIE). KCO 2+ and KN2+ have a significant role in Ks, acting as sinks and reservoirs in the ligand-switching recombination reactions used to describe the mesospheric potassium ion-chemistry. Finally, we present an analysis of two separate and distinct sporadic layer events in the mesosphere and lower thermosphere region above the Arecibo Observatory. One sporadic event was a high altitude layer, in which both atomic and ion sporadic layers were positioned above 100 km altitude. This represents a rather typical sporadic layer visible in both ions and neutrals at Arecibo. The other observation was less typical, with a lower altitude and more diffuse sporadic E layer, extending from below 90 km to above 95 km, which dissipated coincident with growth of a sporadic neutral K layer. We analyze these separate events using a temperature-dependent chemical model. First, we find that the high altitude layer of 12--13 June 2002 has a distinct and important temperature dependence, and that the neutral layer would not have formed had the temperature profile matched the MSIS-90 model. Second, the temperature dependent chemistry model reproduced K+ in close agreement with electron densities on 14--15 June 2002, but the neutrals do not agree well with model above 90 km and it likely requires inclusion of dynamical forcing and advection. The model, using commonly accepted chemical processes, successfully reproduces results on 12--13 June 2002. We speculate that the deficiency of the model is primarily due to the lack of realistic gravity wave parameterization.

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

    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.

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

    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

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

    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 α = 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 α = 0.05 level. A GO category was determined to replicate if that category was significant at the α = 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.

  4. Precipitation increases the occurrence of sporadic legionnaires' disease in Taiwan.

    Chen, Nai-Tzu; Chen, Mu-Jean; Guo, Chao-Yu; Chen, Kow-Tong; Su, Huey-Jen

    2014-01-01

    Legionnaires' disease (LD) is an acute form of pneumonia, and changing weather is considered a plausible risk factor. Yet, the relationship between weather and LD has rarely been investigated, especially using long-term daily data. In this study, daily data was used to evaluate the impacts of precipitation, temperature, and relative humidity on LD occurrence in Taiwan from 1995-2011. A time-stratified 2:1 matched-period case-crossover design was used to compare each case with self-controlled data using a conditional logistic regression analysis, and odds ratios (ORs) for LD occurrence was estimated. The city, gender and age were defined as a stratum for each matched set to modify the effects. For lag day- 0 to 15, the precipitation at lag day-11 significantly affected LD occurrence (pprecipitation. In addition, stratified analyses further showed that positive associations of precipitation with LD incidence were only significant in male and elderly groups and during the warm season ORs = 1.023-1.029). However, such an effect was not completely linear. Only precipitations at 21-40 (OR = 1.643 (95% CIs = 1.074-2.513)) and 61-80 mm (OR = 2.572 (1.106-5.978)) significantly increased the risk of LD occurrence. Moreover, a negative correlation between mean temperature at an 11-day lag and LD occurrence was also found (OR = 0.975 (0.953-0.996)). No significant association between relative humidity and LD occurrence was identified (p>0.05). In conclusion, in warm, humid regions, an increase of daily precipitation is likely to be a critical weather factor triggering LD occurrence where the risk is found particularly significant at an 11-day lag. Additionally, precipitation at 21-40 and 61-80 mm might make LD occurrence more likely. PMID:25474539

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

    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.)

  6. Molecular epidemiology of noroviruses associated with sporadic gastroenteritis in Guangzhou, China, 2013-2015.

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

    2016-05-01

    Norovirus diarrhea is a great threat to public health worldwide. To characterize the prevalence of circulating noroviruses associated with sporadic gastroenteritis cases in Guangzhou, 215 stool specimens were collected during two consecutive cold seasons in 2013-2015. Noroviruses were detected in 25 (11.63 %) samples, and GII.4 (6/9) and GII.17 (10/16) were identified as the most predominant variants of each of those seasons. The remaining strains belonged to the genotypes GII.P12/GII.3, GII.2, and GI.Pb/GI.6. The phylogenetic relationships of the GII.17 strains were analyzed based on their capsid protein sequences. This study suggests a significant shift of predominant variants associated with sporadic gastroenteritis in Guangzhou. PMID:26906693

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

    Williams, B. P.; Croskey, C. L.; She, C. Y.; Mitchell, J. D.; Goldberg, R. A.

    2006-07-01

    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.

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

    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.

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

    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

  10. Somatic GATA5 mutations in sporadic tetralogy of Fallot.

    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

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

    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...

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

    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...

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

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

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

    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...

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

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

    1994-09-15

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

  16. Association Studies of Sporadic Parkinson’s Disease in the Genomic Era

    Labbé, Catherine; Ross, Owen A.

    2014-01-01

    Parkinson’s disease is a common age-related progressive neurodegenerative disorder. Over the last 10 years, advances have been made in our understanding of the etiology of the disease with the greatest insights perhaps coming from genetic studies, including genome-wide association approaches. These large scale studies allow the identification of genomic regions harboring common variants associated to disease risk. Since the first genome-wide association study on sporadic Parkinson’s disease p...

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

    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 ...

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

    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...

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

    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...

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

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

    1994-09-01

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

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

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

    1999-01-01

    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 ...

  2. Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer

    Birgisdottir, Valgerdur; Stefansson, Olafur A.; Bodvarsdottir, Sigridur K; Hilmarsdottir, Holmfridur; Jonasson, Jon G.; Eyfjord, Jorunn E.

    2006-01-01

    Introduction BRCA1 or BRCA2 germline mutations increase the risk of developing breast cancer. Tumour cells from germline mutation carriers have frequently lost the wild-type allele. This is predicted to result in genomic instability where cell survival depends upon dysfunctional checkpoint mechanisms. Tumorigenic potential could then be acquired through further genomic alterations. Surprisingly, somatic BRCA mutations are not found in sporadic breast tumours. BRCA1 methylation has been shown ...

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

    Ainur R. Akilzhanova

    2013-05-01

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

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

    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...

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

    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

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

    Abdul Wahid Khan, Zia Ud Din, Abdul Salam

    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...

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

    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...

  8. Clinical endpoints for developing pharmaceuticals to manage patients with sporadic or genetic risk of colorectal cancer

    Rial, Nathaniel S; Zell, Jason A.; Cohen, Alfred M.; GERNER, EUGENE W.

    2012-01-01

    To reduce the morbidity and mortality from colorectal cancer, current clinical practice focuses on screening for early detection and polypectomy as a form of secondary prevention, complemented with surgical interventions when appropriate. No pharmaceutical agent is currently approved for use in clinical practice for the management of patients with risk of colorectal cancer. This article will review earlier attempts to develop pharmaceuticals for use in managing patients with sporadic or genet...

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

    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...

  10. Predictors of survival in sporadic Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies.

    Pocchiari, Maurizio; M. Puopolo; Croes, Esther; Budka, Herbert; Gelpi, E.; Collins, Steven; Lewis, Victoria; Sutcliffe, T; Guilivi, A; Delasnerie-Laupretre, N; Brandel, J-P.; Alperovitch, A; Zerr, Inga; Poser, S.; Kretzschmar, Hans

    2004-01-01

    A collaborative study of human transmissible spongiform encephalopathies has been carried out from 1993 to 2000 and includes data from 10 national registries, the majority in Western Europe. In this study, we present analyses of predictors of survival in sporadic (n = 2304), iatrogenic (n = 106) and variant Creutzfeldt-Jakob disease (n = 86) and in cases associated with mutations of the prion protein gene (n = 278), including Gerstmann-Straussler-Scheinker syndrome (n = 24) and fatal familial...

  11. Predictors of survival in sporadic Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies.

    Pocchiari, M; M. Puopolo; Croes, E.A.; Budka, H.; Gelpi, E.; COLLINS S.; Lewis, V; Sutcliffe, T; Guilivi, A; Delasnerie-Laupretre, N; Brandel, J-P.; Alperovitch, A; Zerr, I; Poser, S.; Kretzschmar, H. A.

    2004-01-01

    A collaborative study of human transmissible spongiform encephalopathies has been carried out from 1993 to 2000 and includes data from 10 national registries, the majority in Western Europe. In this study, we present analyses of predictors of survival in sporadic (n = 2304), iatrogenic (n = 106) and variant Creutzfeldt-Jakob disease (n = 86) and in cases associated with mutations of the prion protein gene (n = 278), including Gerstmann-Sträussler-Scheinker syndrome (n = 24) and fatal familial...

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

    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

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

    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...

  14. Height and critical frequency variations of the sporadic-E layer at midlatitudes

    Å auli, Petra; Bourdillon, A.

    2008-01-01

    Roč. 70, č. 15 (2008), s. 1904-1910. ISSN 1364-6826 R&D Projects: GA AV ČR IAA300420704 Grant ostatní: European Union(XE) COST 296 Institutional research plan: CEZ:AV0Z30420517 Keywords : Sporadic E * Planetary waves * Tidal waves * Mid-latitude ionosphere * Wavelet transform Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 1.667, year: 2008

  15. Mutations in WT1 in boys with sporadic isolated steroid-resistant nephrotic syndrome.

    Yang, Y; Zhao, F; Tu, X; Yu, Z

    2016-01-01

    Mutations in the Wilms' tumor gene, WT1, can lead to syndromic steroid-resistant nephrotic syndrome and isolated steroid-resistant nephrotic syndrome. WT1 mutations have been identified in the majority of children with Denys-Drash or Frasier syndrome. WT1 mutations have not previously been identified in boys with sporadic isolated steroid-resistant nephrotic syndrome, but, recently, four boys with isolated nephrotic syndrome were identified to have WT1 mutations. However, whether boys with sporadic isolated steroid-resistant nephrotic syndrome should be routinely subjected to mutation analysis of WT1 has not been established. We examined 35 boys with sporadic isolated steroid-resistant nephrotic syndrome for mutations in WT1. Mutation analysis of all 10 exons of WT1 was performed by polymerase chain reaction and direct sequencing. Karyotype analysis or Y chromosome identification was performed for all patients. A Y chromosome or a 46, XY karyotype was demonstrated for all 35 patients. No causative WT1 mutation was identified in any of the patients. The WT1 mutation, IVS4+14T>C, which is not predicted to affect splicing, was identified in one patient who achieved complete remission after 8 weeks of oral prednisone treatment, indicating that IVS4+14T>C is not a causative mutation. Five WT1 polymorphisms were also identified in some patients and controls. Our results suggest that mutation analysis of WT1 should not be routinely performed for genetically defined boys with sporadic isolated steroid-resistant nephrotic syndrome. PMID:26985958

  16. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis.

    Kabashi, Edor; Valdmanis, Paul N; Dion, Patrick; Spiegelman, Dan; McConkey, Brendan J; Vande Velde, Christine; Bouchard, Jean-Pierre; Lacomblez, Lucette; Pochigaeva, Ksenia; Salachas, Francois; Pradat, Pierre-Francois; Camu, William; Meininger, Vincent; Dupre, Nicolas; Rouleau, Guy A

    2008-05-01

    Recently, TDP-43 was identified as a key component of ubiquitinated aggregates in amyotrophic lateral sclerosis (ALS), an adult-onset neurological disorder that leads to the degeneration of motor neurons. Here we report eight missense mutations in nine individuals--six from individuals with sporadic ALS (SALS) and three from those with familial ALS (FALS)--and a concurring increase of a smaller TDP-43 product. These findings further corroborate that TDP-43 is involved in ALS pathogenesis. PMID:18372902

  17. Paleolithic and Mediterranean Diet Pattern Scores and Risk of Incident, Sporadic Colorectal Adenomas

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

    2014-01-01

    The Western dietary pattern is associated with higher risk of colorectal neoplasms. Evolutionary discordance could explain this association. We investigated associations of scores for 2 proposed diet patterns, the “Paleolithic” and the Mediterranean, with incident, sporadic colorectal adenomas in a case-control study of colorectal polyps conducted in Minnesota (1991–1994). Persons with no prior history of colorectal neoplasms completed comprehensive questionnaires prior to elective, outpatien...

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

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

    . Identifying the most important sources of human disease is essential for prioritizing food safety interventions and setting public health goals. Numerous case-control studies of sporadic infections of salmonellosis and campylobacteriosis have been published. These studies investigate a variety of potential...... 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...

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

    Santama Niovi

    2007-01-01

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

  20. Microsatellite D21D210 (GT-12) allele frequencies in sporadic Alzheimer`s disease

    Lannfelt, L.; Lilius, L.; Viitanen, M.; Winblad, B.; Basun, H. [Huddinge Hospital, Karolinska Institute, Dept. of Geriatric Medicine, (Sweden); Houlden, H.; Rossor, M. [St. Mary`s Hospital, Dept. of Neurology, Medical School, London (United Kingdom); Hardy, J. [University of South Florida, Suncoast Alzheimer`s Disease Research Labs, Department of Psychiatry, Tampa (United States)

    1995-02-01

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

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

    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

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

    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

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

    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

  4. Distinct disruptions of resting-state functional brain networks in familial and sporadic schizophrenia

    Zhu, Jiajia; Zhuo, Chuanjun; Liu, Feng; Qin, Wen; Xu, Lixue; Yu, Chunshui

    2016-01-01

    Clinical and brain structural differences have been reported between patients with familial and sporadic schizophrenia; however, little is known about the brain functional differences between the two subtypes of schizophrenia. Twenty-six patients with familial schizophrenia (PFS), 26 patients with sporadic schizophrenia (PSS) and 26 healthy controls (HC) underwent a resting-state functional magnetic resonance imaging. The whole-brain functional network was constructed and analyzed using graph theoretical approaches. Topological properties (including global, nodal and edge measures) were compared among the three groups. We found that PFS, PSS and HC exhibited common small-world architecture of the functional brain networks. However, at a global level, only PFS showed significantly lower normalized clustering coefficient, small-worldness, and local efficiency, indicating a randomization shift of their brain networks. At a regional level, PFS and PSS disrupted different neural circuits, consisting of abnormal nodes (increased or decreased nodal centrality) and edges (decreased functional connectivity strength), which were widely distributed throughout the entire brain. Furthermore, some of these altered network measures were significantly correlated with severity of psychotic symptoms. These results suggest that familial and sporadic schizophrenia had segregated disruptions in the topological organization of the intrinsic functional brain network, which may be due to different etiological contributions. PMID:27032817

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

    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

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

    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.

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

    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.

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

    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...

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

    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-...

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

    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 ...

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

    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

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

    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

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

    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.

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

    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.

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

    Manjit Singh

    2014-12-01

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

  16. Numbers and masses of different populations of sporadic meteoroids from photographic and television records

    Double and multistation data on meteors from photographic and television records are used, to derive relative and absolute numbers of sporadic meteoroids coming to the Earth's vicinity and their mass accession. Seven different meteoroid populations are dealt with separately inside a mass interval of 2x107 g to 2x10-5 g and their cumulative numbers with decreasing mass determined. The paper is an abstract of a more extensive paper, which will be published in Bull. Astron. Inst. Czechosl. in 1988. (author). 2 figs., 3 tabs., 20 refs

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

    Bahl, J.M.; Heegaard, N.H.; Falkenhorst, G.; Laursen, H.; Hogenhaven, H.; Molbak, K.; Jespersgaard, C.; Hougs, L.; Waldemar, G.; Johannsen, P.; Christiansen, M.

    2009-01-01

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

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

    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...

  19. Epidemiological evaluation of sporadic cases of Norovirus infection in comunitary and hospitalized patients

    Sara Giordana Rimoldi

    2009-03-01

    Full Text Available Surveillace of viral gastoenteritis infections is very poor in Italy, even if starting from 2004 Norovirus became one of the most causative agent of infections in all the seasons. The aim of our study was to evaluate the isolation of Norovirus both in hospitalizes patients and communitary patients. From October 2006 to March 2008 we examined 400 samples. Our results showed only 15 sporadic cases in pediatric, HIV comunitary patients. These cases were analyzed by using an ELISA screening (Biopharm and the results were confirmed with real time PCT (Argene.

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

    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...

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

    Cracco Laura; Zou Wen-Quan; Maddox Ryan A; Schonberger Lawrence B; Moody Karen M; Cali Ignazio

    2011-01-01

    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 identifie...

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

    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...

  3. A4V superoxide dismutase mutation in apparently sporadic ALS resembling neuralgic amyotrophy.

    Weiss, M D; Ravits, J M; Schuman, N; Carter, G T

    2006-03-01

    We report a case of apparently sporadic amyotrophic lateral sclerosis (ALS) in a young pregnant woman presenting subacutely with severe left shoulder pain followed by progressive weakness and wasting of the left arm, mimicking neuralgic amyotrophy. She was later found electrophysiologically to have widespread denervation involving more than just the arm and an alanine for valine substitution in codon 4 (A4V) in the gene for Cu/Zn superoxide dismutase 1 (SOD1). Her case illustrates that pain on initial presentation, though uncommon, does not exclude a diagnosis of ALS. PMID:16546761

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

    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.

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

    Brożek Izabela

    2006-11-01

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

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

    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.

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

    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.

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

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

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

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

    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

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

    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.

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

    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

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

    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

  14. Possible relations between meteors, enhanced electron density layers, and sporadic sodium layers

    Dou, X.-K.; Xue, X.-H.; Li, T.; Chen, T.-D.; Chen, C.; Qiu, S.-C.

    2010-06-01

    In this paper, we studied the possible relations between incoming meteors, sporadic E (Es) layers, and sporadic (or sudden) sodium atom layers (SSLs) using the data from the FORMOSAT-3/COSMIC constellation, a meteor radar (Wuhan, 31°N, 114°E), and a sodium fluorescent lidar (Hefei, 31.8°N, 117.3°E). From a statistical point of view, a seasonal dependence of SSL correlates well with the annual variation of Es and is also consistent with seasonal meteor deposition except for February and March. It suggests that a “meteor-Es-SSL” chain could be reasonable if the recombination process were taken into consideration. Detailed study on the relationship between electron density profiles provided by the COSMIC radio occultation and the observations of SSLs by the University of Science and Technology of China via lidar illustrates that the appearance of Es accompanying SSL (i.e., 56.3%) is three times greater than that in the “normal” sodium layer. It also indicates that tides play an important role in causing the lower SSLs, which might be able to carry the upper dense electrons and ions in the Es layer formed by wind shear to the lower altitudes through downward phase propagations.

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

    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

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

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

    2011-03-01

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

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

    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

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

    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.

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

    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.

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

    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...

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

    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.

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

    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

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

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

    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 ...

  5. Association of the I1307K APC mutation with hereditary and sporadic breast/ovarian cancer: more questions than answers

    Gershoni-Baruch, R; Patael, Y; Dagan,; Figer, A.; Kasinetz, L; Kadouri, E; Sade, R Bruchim Bar; Friedman, E.

    2000-01-01

    The frequency of the APC I1307K mutation and its association with disease pattern was examined in 996 Ashkenazi women consisting of individuals with either sporadic (n = 382) or hereditary (n = 143) breast and/or ovarian cancer; asymptomatic BRCA1/2 mutation carriers (185delAG, 5382insC and 6174delT) (n = 53) and healthy controls (n = 418). The I1307K allele was equally distributed among women with sporadic (17/382; 4.6%) and inherited (10/143; 7%) breast and/or ovarian cancer irrespective of...

  6. Determination of sporadic E radio wave propagation parameters based on vertical and oblique sounding

    Sherstyukov, O. N.; Akchurin, A. D.; Sherstyukov, R. O.

    2015-09-01

    Sporadic E layer is often determined for HF radio communication. We have to deal with oblique radiowave propagation in the radio practice. The limiting frequencies at oblique propagation depend heavily on the transmitter power and the receiver sensitivity. The reason for this, as in the case of vertical propagation, is the dependence of Es reflection coefficient, ρEs (reflection loss R(dB)), on Es operation frequencies. This paper describes the characteristics of HF Es propagation in relation to foEs obtained from ionospheric vertical observations. It was found that characteristics of Es propagation depend on the type and height of the Es layer. Also the foEs diurnal variation at definite R(dB) was detected. This investigation allows improving the prediction of limiting frequencies for HF radio propagation.

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

    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

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

    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)

  9. Height comparison of midlatitude E region field-aligned irregularities and sporadic E Layer

    Ogawa, Tadahiko; Sekito, Norihide; Nozaki, Kenrou; Yamamoto, Mamoru

    We present for the first time detailed comparison of heights of MU radar field-aligned echoes and sporadic E (Es) layer by applying an FM-CW sounding technique for observing Es virtual height with high spatial (750 m) and time (one minute) resolutions. The production of typical, discrete quasi-periodic (QP) radar echoes appearing after sunset is closely related to the oscillation of Es height, supporting a theory of the QP echo generation. No Es height oscillations, however, were observed for the QP echoes appearing around midnight. Continuous radar echoes appearing after sunrise are located at 90-100 km heights that are lower than the Es heights (≥100 km), suggesting that a new mechanism other than the gradient-drift plasma instability is necessary for producing these morning continuous echoes.

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

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

    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.

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

    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

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

    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

  14. Morphology of the Sporadic E layers over Arecibo derived from Incoherent Scatter Radar (ISR) measurements

    Franco, E.; Brum, C. G. M.; Raizada, S.

    2014-12-01

    One of the interesting phenomena of the ionosphere is the occurrence of Sporadic E layers (Es), which is characterized by strong electron concentrations, and is related to the vertical tidal wind shear in the lower thermosphere. We will use the incoherent Scatter Radar (ISR) data from Arecibo to investigate the characteristics of the Es below 110km during nighttime. The goal of this project is to study the variability of the nighttime ionization using electron density profiles obtained at the Arecibo Observatory. We will focus on determining the strength of Es, their peak altitude and other parameters between the 90 - 110 km altitude ranges. Previous work has showed that the descending layers are dominated by the tidal influence that displays seasonal variability. To understand the reasons of this variability, we will fit Gaussian profiles to electron density concentrations to extract the layer parameters. Such analysis will allow us to study the role of solar activity, and geomagnetic indices on the layer distributions.

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

    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

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

    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.

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

    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

    as non-secreting pituitary adenomas have been reported, most mutation-positive patients have had growth hormone-producing adenomas diagnosed at relatively young age. Pituitary adenomas are also component tumors of some familial endocrine neoplasia syndromes such as multiple endocrine neoplasia type 1...... (MEN1) and Carney complex (CNC). Genes underlying MEN1 and CNC are rarely mutated in sporadic pituitary adenomas, but more often in other lesions contributing to these two syndromes. Thus far, the occurrence of somatic AIP mutations has not been studied in endocrine tumors other than pituitary adenomas....... Here, we have analyzed 32 pituitary adenomas and 79 other tumors of the endocrine system for somatic AIP mutations by direct sequencing. No somatic mutations were identified. However, two out of nine patients with prolactin-producing adenoma were shown to harbor a Finnish founder mutation (Q14X) with a...

  18. MC1R variants in Chinese Han patients with sporadic Parkinson's disease.

    Shi, Chang-He; Wang, Hui; Mao, Cheng-Yuan; Yang, Jing; Song, Bo; Liu, Yu-Tao; Yang, Zhi-Hua; Luo, Hai-Yang; Zhang, Shu-Yu; Wu, Jun; Xu, Yu-Ming

    2016-06-01

    Recently, a variant p.R160W in the MC1R gene was identified that increased the risk of Parkinson's disease (PD) in Spanish population. To explore whether the MC1R gene variants are associated with sporadic PD in Chinese population, we performed a case-control comparison study for comprehensive MC1R variant screening in 510 Chinese Han patients and 495 healthy controls as ethnically matched controls. We identify 5 nonsynonymous variants, including rs34090186 (p.R67Q), rs2228479 (p.V92M), rs33932559 (p.I120T), rs885479 (p.R163Q), and rs372152373 (p.R223W). However, variants mentioned previously did not show association with PD. Our results suggest that variants in MC1R do not play a major role in PD in the Chinese population. PMID:27084066

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

    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

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

    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.

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

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

    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

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

    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.

  4. Comparative proteomic analysis of bronchoalveolar lavage of familial and sporadic cases of idiopathic pulmonary fibrosis.

    Carleo, A; Bargagli, E; Landi, C; Bennett, D; Bianchi, L; Gagliardi, A; Carnemolla, C; Perari, M G; Cillis, G; Armini, A; Bini, L; Rottoli, P

    2016-01-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive deterioration of the alveolar integrity. Among IPF identified phenotypes, that of familial (f-)IPF is usually associated with several gene mutations which are seldom observed in sporadic (s-)IPF. This study aimed at investigating the molecular patterns and variability in f-IPF and s-IPF patients through a differential proteomic analysis. Protein patterns of bronchoalveolar lavage fluid (BALF) samples from 10 familial and 17 sporadic IPF patients were compared using 2D electrophoresis and mass spectrometry. Principal component analysis (PCA) was applied to proteomic data and an enrichment analysis was also performed to characterize specific pathogenic mechanisms and to identify potential biomarkers. BALF samples from f-IPF showed 87 protein spots differentially expressed than those from s-IPF samples; once identified, these spots revealed 22 unique proteins. The functional analysis showed that the endothelial reticulum stress probably plays a central pathogenetic role in f-IPF with an up-regulation of proteins involved in wounding and immune responses, coagulation system, and ion homeostasis. Up-regulated proteins in the s-IPF group were those involved in the oxidative stress response. PCA analysis of differentially expressed proteins clearly distinguished f-IPF from s-IPF patients, and in agreement with radiological and histological patterns, pointed out a higher heterogeneity in f-IPF than s-IPF samples. The 'Slit/Robo signaling', 'clathrin-coated vesicle' and 'cytoskeleton remodelling', were extrapolated by 'pathways analysis' and the results of 'diseases (by biomarkers)' highlighted a 'connective tissue and autoimmune disease', two aspects of increasing interest in IPF. PMID:27082636

  5. Somatic mosaicism underlies X-linked acrogigantism syndrome in sporadic male subjects.

    Daly, Adrian F; Yuan, Bo; Fina, Frederic; Caberg, Jean-Hubert; Trivellin, Giampaolo; Rostomyan, Liliya; de Herder, Wouter W; Naves, Luciana A; Metzger, Daniel; Cuny, Thomas; Rabl, Wolfgang; Shah, Nalini; Jaffrain-Rea, Marie-Lise; Zatelli, Maria Chiara; Faucz, Fabio R; Castermans, Emilie; Nanni-Metellus, Isabelle; Lodish, Maya; Muhammad, Ammar; Palmeira, Leonor; Potorac, Iulia; Mantovani, Giovanna; Neggers, Sebastian J; Klein, Marc; Barlier, Anne; Liu, Pengfei; Ouafik, L'Houcine; Bours, Vincent; Lupski, James R; Stratakis, Constantine A; Beckers, Albert

    2016-04-01

    Somatic mosaicism has been implicated as a causative mechanism in a number of genetic and genomic disorders. X-linked acrogigantism (XLAG) syndrome is a recently characterized genomic form of pediatric gigantism due to aggressive pituitary tumors that is caused by submicroscopic chromosome Xq26.3 duplications that includeGPR101 We studied XLAG syndrome patients (n= 18) to determine if somatic mosaicism contributed to the genomic pathophysiology. Eighteen subjects with XLAG syndrome caused by Xq26.3 duplications were identified using high-definition array comparative genomic hybridization (HD-aCGH). We noted that males with XLAG had a decreased log2ratio (LR) compared with expected values, suggesting potential mosaicism, whereas females showed no such decrease. Compared with familial male XLAG cases, sporadic males had more marked evidence for mosaicism, with levels of Xq26.3 duplication between 16.1 and 53.8%. These characteristics were replicated using a novel, personalized breakpoint junction-specific quantification droplet digital polymerase chain reaction (ddPCR) technique. Using a separate ddPCR technique, we studied the feasibility of identifying XLAG syndrome cases in a distinct patient population of 64 unrelated subjects with acromegaly/gigantism, and identified one female gigantism patient who had had increased copy number variation (CNV) threshold forGPR101that was subsequently diagnosed as having XLAG syndrome on HD-aCGH. Employing a combination of HD-aCGH and novel ddPCR approaches, we have demonstrated, for the first time, that XLAG syndrome can be caused by variable degrees of somatic mosaicism for duplications at chromosome Xq26.3. Somatic mosaicism was shown to occur in sporadic males but not in females with XLAG syndrome, although the clinical characteristics of the disease were similarly severe in both sexes. PMID:26935837

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

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

    2014-12-01

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

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

    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

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

    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

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

    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

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

    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

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

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

    2004-01-01

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

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

    Naccarati, Alessio; Pardini, B.; Hemminki, K.; Vodička, Pavel

    2007-01-01

    Roč. 635, 2-3(2007), s.118-145. ISSN 1383-5742 R&D Projects: GA MZd NR8563; GA ČR 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

  13. Large-scale screening in sporadic amyotrophic lateral sclerosis identifies genetic modifiers in C9orf72 repeat carriers.

    Dekker, Annelot M; Seelen, Meinie; van Doormaal, Perry T C; van Rheenen, Wouter; Bothof, Reinoud J P; van Riessen, Tim; Brands, William J; van der Kooi, Anneke J; de Visser, Marianne; Voermans, Nicol C; Pasterkamp, R Jeroen; Veldink, Jan H; van den Berg, Leonard H; van Es, Michael A

    2016-03-01

    Sporadic amyotrophic lateral sclerosis (ALS) is considered to be a complex disease with multiple genetic risk factors contributing to the pathogenesis. Identification of genetic risk factors that co-occur frequently could provide relevant insight into underlying mechanisms of motor neuron degeneration. To dissect the genetic architecture of sporadic ALS, we undertook a large sequencing study in 755 apparently sporadic ALS cases and 959 controls, analyzing 10 ALS genes: SOD1, C9orf72, TARDBP, FUS, ANG, CHMP2B, ATXN2, NIPA1, SMN1, and UNC13A. We observed sporadic cases with multiple genetic risk variants in 4.1% compared with 1.3% in controls. The overall difference was not in excess of what is to be expected by chance (binomial test, p = 0.59). We did, however, observe a higher frequency than expected of C9orf72 repeat carriers with co-occurring susceptibility variants (ATXN2, NIPA1, and SMN1; p = 0.001), which is mainly because of the co-occurrence of NIPA1 repeats in 15% of C9orf72 repeat carriers (p = 0.006). PMID:26777436

  14. Population Structure of Listeria monocytogenes Serotype 4b Isolates from Sporadic Human Listeriosis in the United States, 2003-2008

    Listeria monocytogenes can cause severe foodborne disease (listeriosis). Serotype 4b strains have resulted in numerous outbreaks, repeatedly involving three epidemic clones (ECI, ECII, and ECIa). Little is known about population structure of L. monocytogenes serotype 4b from sporadic listeriosis, ev...

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

    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...

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

    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.

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

    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

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

    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

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

    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, β2-microglobulin (β2m), 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 β2m 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 β2m 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

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

    Maria Salete Costa Gurgel

    2011-12-01

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

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

    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.

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

    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.

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

    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

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

    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.

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

    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.

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

    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

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

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

    2014-10-01

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

  8. Cerebrospinal Fluid from Sporadic Amyotrophic Lateral Sclerosis Patients Induces Mitochondrial and Lysosomal Dysfunction.

    Sharma, Aparna; Varghese, Anu Mary; Vijaylakshmi, Kalyan; Sumitha, Rajendrarao; Prasanna, V K; Shruthi, S; Chandrasekhar Sagar, B K; Datta, Keshava K; Gowda, Harsha; Nalini, Atchayaram; Alladi, Phalguni Anand; Christopher, Rita; Sathyaprabha, Talakad N; Raju, Trichur R; Srinivas Bharath, M M

    2016-05-01

    In our laboratory, we have developed (1) an in vitro model of sporadic Amyotrophic Lateral Sclerosis (sALS) involving exposure of motor neurons to cerebrospinal fluid (CSF) from sALS patients and (2) an in vivo model involving intrathecal injection of sALS-CSF into rat pups. In the current study, we observed that spinal cord extract from the in vivo sALS model displayed elevated reactive oxygen species (ROS) and mitochondrial dysfunction. Quantitative proteomic analysis of sub-cellular fractions from spinal cord of the in vivo sALS model revealed down-regulation of 35 mitochondrial proteins and 4 lysosomal proteins. Many of the down-regulated mitochondrial proteins contribute to alterations in respiratory chain complexes and organellar morphology. Down-regulated lysosomal proteins Hexosaminidase, Sialidase and Aryl sulfatase also displayed lowered enzyme activity, thus validating the mass spectrometry data. Proteomic analysis and validation by western blot indicated that sALS-CSF induced the over-expression of the pro-apoptotic mitochondrial protein BNIP3L. In the in vitro model, sALS-CSF induced neurotoxicity and elevated ROS, while it lowered the mitochondrial membrane potential in rat spinal cord mitochondria in the in vivo model. Ultra structural alterations were evident in mitochondria of cultured motor neurons exposed to ALS-CSF. These observations indicate the first line evidence that sALS-CSF mediated mitochondrial and lysosomal defects collectively contribute to the pathogenesis underlying sALS. PMID:26646005

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

    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

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

    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.

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

    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...

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

    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.

  13. Fumarate hydratase gene mutation in two young patients with sporadic uterine fibroids.

    Kubinova, Kristyna; Tesarova, Marketa; Hansikova, Hana; Vesela, Kamila; Kuzel, David; Mara, Michal

    2013-01-01

    Fumarate hydratase (FH) is a key enzyme of the Krebs cycle. Germline mutations in the FH gene encoding fumarate hydratase cause autosomal dominant syndromes multiple cutaneous and uterine leiomyomata and hereditary leiomyomatosis and renal cell cancer (HLRCC). Few data have been published on the role of FH gene mutation in development of uterine fibroids outside the context of multiple cutaneous and uterine leiomyomata /HLRCC. We report two FH gene mutations, one novel and one previously described, in two young patients with sporadic uterine fibroids and decreased fumarate hydratase activity in lymphocytes. In patient 1, a novel heterozygous mutation c.892G>C was found. In patient 2 we detected heterozygous mutation c.584T>C. Both the patients had a negative family history for renal cancer and cutaneous leiomyomatosis. None of the relatives, however, underwent renal imaging at the time of writing. FH mutation carriers may be easily identified by analysis of fumarate hydratase activity in blood lymphocytes. We suggest performing fumarate hydratase activity or FH mutation screening in women with onset of uterine fibroids in their 20s and family history of uterine fibroids or other HLRCC-associated malignancies. PMID:22764886

  14. A novel TUBB3 mutation in a sporadic patient with asymmetric cortical dysplasia.

    Shimojima, Keiko; Okamoto, Nobuhiko; Yamamoto, Toshiyuki

    2016-04-01

    Recent advances in molecular technology have led to the discovery of several genes related to human malformations of cortical development (MCDs). The beta-tubulin class III gene (TUBB3) was identified as a gene responsible for MCDs. Although mouse-model experiments have not revealed any findings of neuronal migration disorders, human TUBB3 mutations have been identified in patients with congenital fibrosis of the extraocular muscles. Since the discovery of a TUBB3 mutation, only 15 mutations have been identified. In this study, comprehensive mutation screening through next-generation sequencing identified a novel TUBB3 mutation (p.Ser230Leu) in a sporadic patient with moderate developmental delay associated with mild MCD. Compared to patients with the alpha-tubulin class 1a gene (TUBA1A) mutations, patients with TUBB3 mutations show milder phenotypic manifestations and milder MCD. Therefore, patients with milder MCD manifestations may be under-diagnosed, and TUBB3 mutations may be rarely identified. Additional genotype-phenotype information should be accumulated for further understanding of the TUBB3 functional relevance. © 2016 Wiley Periodicals, Inc. PMID:26739025

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

    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.

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

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

    1994-09-01

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

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

    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

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

    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

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

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

    2014-04-01

    Burkitt's lymphoma (BL) is the fastest growing malignancy of the lymphoreticular system to affect humans and has a potential ability to double in size every day. A case of maxillary sporadic BL (sBL) associated with neuro-orbital involvement in an Indian male is presented. sBL initially presented as maxillary swelling with no obvious dental and periodontal changes. Histological specimen from incisional biopsy revealed a round cell malignant tumor and immunohistochemistry reactions favored nonHodgkin's lymphoma consistent with BL. Four weeks later, patient presented with orbital involvement as diplopia, sixth cranial nerve palsy, and medial rectus palsy. Chemotherapy regimen according to LMB 89 protocol was started. During chemotherapy regimen patient showed bradycardia and Babinski response, suggestive of central nervous system involvement. sBL associated with orbital involvement is extremely rare and only seven cases have been reported. Our case showed unusual presentation; despite the aggressive tumor did not show any common clinical, radiological, and hematological findings. We also discussed the role of oral medicine specialist, importance of early diagnosis, and prompt referral in management of maxillary sBL. PMID:24963253

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

    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

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

    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

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

    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.

  3. Sodium lidar observed gravity wave breaking event and its associated significant sodium sporadic layer

    Ban, C.; Li, T.; Fang, X.; Dou, X.; Xiong, J.; Russell, J. M., III; Wu, Q.

    2014-12-01

    On the night of July 29th, 2013 (UT day 13210), the University of Science and Technology of China (USTC) sodium temperature/wind lidar, located at Hefei, China (31N, 117E), observed a significant zonal wind shear of -60 m/s/km near ~100 km between 13:15 and 13:30UT, accompanied with a significant cooling near 96-100 km lasting for 1 hr (13:30-14:30 UT). This suggested a significant gravity wave breaking possibly induced by the dynamic instability. The lidar zonal wind is compared with the wind observed by a meteor radar located at Wuhan, ~200 km west of lidar site, and the lidar temperature is compared with SABER temperature, the results further confirmed this possible significant gravity wave breaking event. After the wave breaking, the sodium density was suddenly enhanced by 10-12 times near 94km. Unlike most sporadic sodium layer (SSL) reported in the literatures, this SSL propagated upward, and passed the west lidar beam around 2min earlier than the east lidar beam (~ 50 km separated in the MLT region). The propagate direction of SSL is agreed with enhanced meridional wind observed by Wuhan meteor radar, indicating that this enhanced sodium layer is likely transported from the north of Hefei.

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

    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.

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

    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.

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

    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.

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

    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.

  8. Sporadic Burkitt's lymphoma/acute B-cell leukaemia presenting with progressive proptosis and orbital mass in a child.

    Grasso, Daniela; Borreggine, Carmela; Ladogana, Saverio; De Santis, Raffaela; Delle Noci, Nicola; Grilli, Gianpaolo; Macarini, Luca

    2016-06-01

    Burkitt's lymphoma (BL) is an aggressive B-cell non-Hodgkin lymphoma that is found predominantly in children, with the highest incidence occurring in Africa. The sporadic form occurs in non-endemic areas and typically involves the ileo-caecum and the bowel, whereas orbital and paranasal sinus involvement is rare. Here, we present an unusual case of sporadic BL in a Caucasian male child with rapidly progressive painful proptosis of the right eye. Magnetic resonance imaging showed an oval-shaped, extraconal mass in the supero-lateral part of the right orbit that deformed and dislocated the eyeball antero-inferiorly. The patient underwent anterior orbitotomy, and a biopsy of the excised tissue revealed a starry-sky appearance characteristic of BL. Postoperative aggressive chemotherapy was initiated with a good response after one week. PMID:27006106

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

    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

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

    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...

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

    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.

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

    Walsh Tom; Garcia Rochelle L; Taniguchi Toshiyasu; Gonzalez Rachel M; Swisher Elizabeth M; Goff Barbara A; Welcsh Piri

    2009-01-01

    Abstract Background DNA repair genes critically regulate the cellular response to chemotherapy and epigenetic regulation of these genes may be influenced by chemotherapy exposure. Restoration of BRCA1 and BRCA2 mediates resistance to platinum chemotherapy in recurrent BRCA1 and BRCA2 mutated hereditary ovarian carcinomas. We evaluated BRCA1, BRCA2, and MLH1 protein expression in 115 sporadic primary ovarian carcinomas, of which 31 had paired recurrent neoplasms collected after chemotherapy. A...

  13. Brain microglia were activated in sporadic CJD but almost unchanged in fatal familial insomnia and G114V genetic CJD

    Shi, Qi; Xie, Wu-Ling; Zhang, Baoyun; Chen, Li-Na; Xu, Yin; Wang, Ke; REN, KE; Zhang, Xiao-Mei; Chen, Cao; Zhang, Jin; Dong, Xiao-Ping

    2013-01-01

    Background Microglial activations have been described in different subtypes of human prion diseases such as sporadic Creutzfeldt-Jakob disease (CJD), variant CJD, Kuru and Gerstmann-Sträussler-Scheinker disease (GSS). However, the situation of microglia in other genetic prion diseases such as fatal familial insomnia (FFI) and familial CJD remains less understood. The brain microglia was evaluated comparatively between the FFI, G114V and sCJD cases in the study. Methods Specific Western blots,...

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

    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

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

    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...

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

    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 ...

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

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

    2012-01-01

    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...

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

    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 ...

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

    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

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

    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.

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

    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.

  2. Temperature controlled icy dust reservoir of sodium: A possible mechanism for the formation of sporadic sodium layers

    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 (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.

  3. [Sporadic cutaneous lymphosarcoma of T-cell origin with involvement of lymph nodes and internal organs in a Holstein cow].

    Freick, M; Lapko, L; Neubert, M; Hardt, M; Behn, H; Passarge, O; Schöniger, S

    2016-02-16

    Sporadic lymphosarcomas in adult cattle are rare entities with an unknown etiology. This case report describes the course of the disease in a 3.5-year-old cow of the breed German Holstein, which was presented to the veterinarian due to multifocal nodular skin lesions. Several superficial lymph nodes (Lymphonodi mandibulares, parotidei and mammariae) were enlarged, had a tight-elastic consistency and were freely movable. The histopathological and immunohistochemical examination of skin biopsies showed the presence of multifocal cutaneous T-cell lymphosarcomas consistent with a skin leukosis. Bovine leukemia virus infection was excluded by serological investigation of a milk sample and virological examination of a tissue sample, respectively. Seven weeks after the first clinical examination, the cow deteriorated rapidly and was euthanized. A post mortem examination revealed the presence of neoplastic cells within lymph nodes (all superficial lymph nodes of the carcass and Lymphonodi pulmonales), kidney and lungs as well as a liver rupture. Additionally, an overview of the case reports of sporadic bovine cutaneous lymphosarcomas published during the previous 15 years will be provided. The legal background for a further utilization of affected animals for milk and meat production will be discussed. This case report illustrates that sporadic bovine leukosis represents an important differential diagnosis for viral-, bacterial- and parasitic-induced skin lesions and enlargement of lymph nodes in adult cattle. PMID:26763070

  4. An atypical presentation of small bowel obstruction and perforation secondary to sporadic synchronous intra-abdominal desmoid tumours

    Abdalla, Sala; Wilkinson, Michelle; Wilsher, Mark; Uzkalnis, Aleksandras

    2016-01-01

    Introduction Desmoid tumours (DTs) are rare, soft tissue tumours which account for 0.03% of all neoplasms. They are characteristically locally invasive but do not metastasize. There is frequent association with females of reproductive age, a history of abdominal surgery or trauma and a family history of fibromatoses. Intra-abdominal DTs are infrequently sporadic and more commonly associated with inherited disorders such as familial adenomatous polyposis (FAP), attenuated FAP and Gardener’s syndrome. Presentation of case The authors report a rare case of small bowel obstruction and perforation secondary to sporadic, synchronous intra-abdominal DTs in a 54-year old man with atypical symptoms and no risk factors or family history. Discussion Intra-abdominal DTs have a worse prognosis as they can cause intestinal bleeding, obstruction and perforation. Due to the rarity of these tumours there are no clear guidelines on their management and this is instead based on small case series from specialist centres. In the non-acute setting patients with sporadic intra-abdominal DTs should be managed in a specialist sarcoma unit by a multidisciplinary team. In the presence of FAP or other polyposis syndromes patients with DTs should be managed at a specialist colorectal unit. Emergent presentations require emergency surgery in suitable candidates. Conclusion In non-emergency presentations of DTs, it is essential to exclude FAP, AFAP and other hereditary polyposis syndromes since this affects treatment and subsequent follow-up. PMID:26866881

  5. Mitochondrial dysfunction: the missing link between aging and sporadic Alzheimer's disease.

    Grimm, Amandine; Friedland, Kristina; Eckert, Anne

    2016-04-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease that represents the most common form of dementia among the elderly. Despite the fact that AD was studied for decades, the underlying mechanisms that trigger this neuropathology remain unresolved. Since the onset of cognitive deficits occurs generally within the 6th decade of life, except in rare familial case, advancing age is the greatest known risk factor for AD. To unravel the pathogenesis of the disease, numerous studies use cellular and animal models based on genetic mutations found in rare early onset familial AD (FAD) cases that represent less than 1 % of AD patients. However, the underlying process that leads to FAD appears to be distinct from that which results in late-onset AD. As a genetic disorder, FAD clearly is a consequence of malfunctioning/mutated genes, while late-onset AD is more likely due to a gradual accumulation of age-related malfunction. Normal aging and AD are both marked by defects in brain metabolism and increased oxidative stress, albeit to varying degrees. Mitochondria are involved in these two phenomena by controlling cellular bioenergetics and redox homeostasis. In the present review, we compare the common features observed in both brain aging and AD, placing mitochondrial in the center of pathological events that separate normal and pathological aging. We emphasize a bioenergetic model for AD including the inverse Warburg hypothesis which postulates that AD is a consequence of mitochondrial deregulation leading to metabolic reprogramming as an initial attempt to maintain neuronal integrity. After the failure of this compensatory mechanism, bioenergetic deficits may lead to neuronal death and dementia. Thus, mitochondrial dysfunction may represent the missing link between aging and sporadic AD, and represent attractive targets against neurodegeneration. PMID:26468143

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

    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

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

    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

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

    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

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

    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

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

    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

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

    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.

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

    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

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

    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.)

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

    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.)

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

    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.

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

    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

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

    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

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

    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

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

    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

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

    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.

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

    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

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

    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

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

    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

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

    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.

  5. Lack of sequence variation in sporadic bovine leucosis in regions of tumour suppressor genes p53 and p16.

    Mayr, B; Grüneis, C; Brem, G; Reifinger, M; Schaffner, G; Hochsteiner, W

    2001-08-01

    Regions of the promoter and exons 5-8 of the tumour suppressor gene p53 were analysed in 25 cases of sporadic bovine leucosis. The study included 17 cases of juvenile leucosis, five cases of adult leucosis and three cases of skin leucosis. Exon 2 of tumour suppressor gene p16 was also investigated in the same samples. No sequence variations were present in the analysed areas of the genes. In p53, this fact represents a clear difference in comparison with enzootic bovine leucosis. In p16, no comparative data are available. PMID:11554494

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

    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 β (Aβ) in the brain, which is reflected by low concentration of the Aβ1-42 peptide in the cerebrospinal fluid (CSF). There are at least 15 additional Aβ peptides in human CSF and their relative abundance pattern is thought to reflect the production and degradation of Aβ. Here, we test the hypothesis that AD is characterized by a specific CSF Aβ isoform pattern that is distinct when comparing sporadic AD (SAD...

  7. A retrospective study of sporadic bovine abortions, stillbirths, and neonatal abnormalities in Atlantic Canada, from 1990 to 2001

    Khodakaram-Tafti, Azizollah; Ikede, Basil O.

    2005-01-01

    In a retrospective study on 265 cases of sporadic bovine abortions, stillbirths, and neonatal deaths in Atlantic Canada (1990 to 2001), an etiological diagnosis was made in 117 cases (44.2%). The cases were divided into 2 groups: 234 abortions, and 31 stillbirths and neonatal deaths. Identified causes of abortion were bacteria (24.4%), fungi (6.8%), viruses (6.0%), protozoa (Neospora spp.) (2.1%), congenital anomalies (0.4%), and miscellaneous conditions (1.3%). In addition, placentitis witho...

  8. Highly increased CSF tau protein and decreased ?-amyloid (1-42) in sporadic CJD: a discrimination from Alzheimer's disease?

    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

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

    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 identifying the most important risk factors for salmonellosis, we performed a systematic review of case...

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

    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.

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

    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.

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

    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.

  13. [Sporadic upper urinary tract urothelial cell carcinomas: identification of interaction between toxic carcinogens and individuals genetic susceptibility].

    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

  14. Polymorphisms in protein disulfide isomerase are associated with sporadic amyotrophic lateral sclerosis in the Chinese Han population.

    Yang, Qin; Guo, Zhi-Bao

    2016-07-01

    Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease that targets the motor system; it is caused by the loss of motor neurons in the spinal cord, brain stem, and cerebral cortex. However, the etiology of ALS remains unknown, although genetic factors may play an important role in its development. The purpose of this study was to investigate the association between common polymorphisms in protein disulfide isomerase (PDI) with sporadic amyotrophic lateral sclerosis (SALS) in a Chinese Han population. Two single nucleotide polymorphisms (SNPs) in P4HB (rs876016 and rs2070872) were genotyped in 322 patients with SALS and 265 control subjects using polymerase chain reaction-restriction fragment length polymorphism. Our results showed that SNPs rs876016 and rs2070872 were significantly associated with ALS. The minor allele frequencies of rs876016 (C) and rs2070872 (G) were significantly higher in patients with sporadic ALS than in control subjects (P = 0.035 and 0.003, respectively). The genotype frequencies of rs876016 and rs2070872 were significantly different between SALS patients and control subjects (genotypic P < 0.001). Individuals carrying rs876016/ rs2070872 C/G genotypes were associated with a significantly increased risk of SALS. These results suggest that common variants in PDI might contribute to the development of SALS in the Chinese Han population. PMID:26000911

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

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

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

    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

  17. On the role of electric field direction in the formation of sporadic E-layers in the southern polar cap ionosphere

    Parkinson, M. L.; Dyson, P. L.; Monselesan, D. P.; Morris, R. J.

    1998-03-01

    Measurements of the occurrence of sporadic E (Es)-layers and F-region electric fields were obtained with a modern, HF digital ionosonde located at Casey, Antarctica (66.3°S, 110.5°E, 81°S CGM latitude) during the late austral summer of 1995/96. The occurrence of Es-layers was inferred from the presence of appropriate traces in normal swept-frequency ionograms, and the electric fields were inferred from F-region ``drift-mode'' velocities assuming that the plasma convection velocities given by E × B/B2 were measured, on average, by the interferometer. The theory of formation of high-latitude Es-layers predicts that electric fields directed toward the south west (SW) should be particularly effective at producing thin layers in the southern hemisphere. Our measurements made at a true polar cap station are consistent with this expectation, and are contrasted with observations made by incoherent scatter radars in the northern hemisphere, which also show the importance of SW electric fields, whereas the same theory predicts that NW electric fields should be important at northern latitudes. We reconcile the interhemispheric differences with simple calculations of ion convergence driven by the electric fields specified by the IZMIRAN electrodynamic model (IZMEM) in both hemispheres. The importance of the interplanetary magnetic field in the control of high-latitude Es formation is emphasised as an important adjunct to space weather modelling and forecasting.

  18. Frequency and spectrum of c-Ki-ras mutations in human sporadic colon carcinoma, carcinomas arising in ulcerative colitis, and pancreatic adenocarcinoma

    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.

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

    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.

  20. A Founding Locus within the RET Proto-Oncogene May Account for a Large Proportion of Apparently Sporadic Hirschsprung Disease and a Subset of Cases of Sporadic Medullary Thyroid Carcinoma

    Borrego, Salud; Wright, Fred A.; Fernández, Raquel M.; Williams, Nita; López-Alonso, Manuel; Davuluri, Ramana; Antiñolo, Guillermo; Eng, Charis

    2003-01-01

    Hirschsprung disease (HSCR) is a common congenital disorder characterized by aganglionosis of the gut. The seemingly unrelated multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism. Yet, germline mutations in the RET proto-oncogene are associated with both MEN 2 and HSCR. In the former, gain-of-function mutations in a limited set of codons is found, whereas, in the latter, loss-of-function mutations are found. However, germline RET mutation is associated with only 3% of a population-based series of isolated HSCR, and little is known about susceptibility to sporadic MTC. We have found previously that specific haplotypes comprising RET coding single-nucleotide polymorphisms (SNPs) comprising exon 2 SNP A45A were strongly associated with HSCR, whereas haplotypes associated with exon 14 SNP S836S were associated with MTC. In this study, we describe three novel intron 1 SNPs, and, together with the coding SNP haplotypes, the data suggest the presence of distinct ancestral haplotypes for HSCR and sporadic MTC in linkage disequilibrium with a putative founding susceptibility locus/loci. The data are consistent with the presence of a very ancient, low-penetrance founder locus ∼20–30 kb upstream of SNP A45A, but the failure of the SNPs to span the locus presents challenges in modeling mode of transmission or ancestry. We postulate that this founding locus is germane to both isolated HSCR and MTC but also that different mutations in this locus would predispose to one or the other. PMID:12474140

  1. [Clinical typing and diagnosis of sporadic human prion diseases (classic sproadic CJD, MM2-cortical form CJD, MM2-thalamic form CJD)].

    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

  2. Legionelosis esporádica: un problema sin resolver Sporadic legionellosis: an unsolved problem egionelose esporádica: um problema não resolvido

    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.

  3. On the solar cycle dependence of the amplitude modulation characterizing the mid-latitude sporadic E layer diurnal periodicity

    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.

  4. Neuropsychological and quantitative oculometric study of a case of sporadic Creutzfeldt-Jakob disease at predementia stage.

    Zarei, M; Nouraei, S A R; Caine, D; Hodges, J R; Carpenter, R H S

    2002-07-01

    A quantitative assessment of eye movements and a detailed neuropsychological profile were conducted at predementia stage in a patient who later had histological confirmation of sporadic Creutzfeldt-Jakob disease (CJD). The patient was a middle aged man who presented with abnormal eye movements and poor balance. Neuropsychological deficits suggested orbito-mesial dysfunction, resembling progressive supranuclear palsy. Oculometry showed accurate but dramatically slowed saccades, with normal pursuit movements. Neuropsychology and quantitative oculometry may be of value in the differential diagnosis and earlier detection of dementia-akinetic-rigid syndromes; in particular, because of the highly stereotyped nature of saccades, routine quantitative oculometry can reveal significant impairment at a very early stage in some cases and could thus facilitate earlier diagnosis. PMID:12082046

  5. Lidar Probing of the Mesosphere: Simultaneous Observations of Sporadic Sodium and Iron Formations, Calcium Ion Layers, Neutral Temperature and Winds

    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.

  6. Synchronous sporadic medullary carcinoma of the thyroid and small-cell carcinoma of lung: A rare entity

    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.

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

    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.

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

    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.

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

    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

  10. ?-N-methylamino-l-alanine causes neurological and pathological phenotypes mimicking Amyotrophic Lateral Sclerosis (ALS): the first step towards an experimental model for sporadic ALS.

    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

  11. Mutational Analysis of p27 (CDKN1 B and p18 (CDKN2C in Sporadic Pancreatic Endocrine Tumors Argues against Tumor-Suppressor Function

    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.

  12. 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.

    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

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

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

    2015-04-01

    Low intracerebroventricular (icv) doses of streptozotocin (STZ) produce regionally specific brain neurochemical changes in rats that are similar to those found in the brain of patients with sporadic Alzheimer's disease (sAD). Since oxidative stress is thought to be one of the major pathologic processes in sAD, catalase (CAT) activity was estimated in the regional brain tissue of animals treated intracerebroventricularly with STZ and the multitarget iron chelator, antioxidant and MAO-inhibitor M30 [5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline]. Five-day oral pre-treatment of adult male Wistar rats with 10 mg/kg/day M30 dose was followed by a single injection of STZ (1 mg/kg, icv). CAT activity was measured colorimetrically in the hippocampus (HPC), brain stem (BS) and cerebellum (CB) of the control, STZ-, M30- and STZ + M30-treated rats, respectively, 4 weeks after the STZ treatment. STZ-treated rats demonstrated significantly lower CAT activity in all three brain regions in comparison to the controls (p < 0.05 for BS and CB, p < 0.01 for HPC). M30 pre-treatment of the control rats did not influence the CAT activity in HPC and CB, but significantly increased it in BS (p < 0.05). M30 pre-treatment of STZ-treated rats significantly increased CAT activity in the HPC in comparison to the STZ treatment alone (p < 0.05) and normalized to the control values. These findings are in line with the assumption that reactive oxygen species contribute to the pathogenesis of STZ in a rat model of sAD and indicate that multifunctional iron chelators such as M30 might also have beneficial effects in this non-transgenic sAD model. PMID:25252744

  14. A polymorphism in the YWHAH gene encoding 14-3-3 eta that is not associated with sporadic Creutzfeldt-Jakob disease (CJD).

    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

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

    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.

  16. Integral analysis of p53 and its value as prognostic factor in sporadic colon cancer

    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

  17. Fast magnetic reconnection supported by sporadic small-scale Petschek-type shocks

    Shibayama, Takuya; Kusano, Kanya; Miyoshi, Takahiro; Nakabou, Takashi; Vekstein, Grigory

    2015-10-01

    Standard magnetohydrodynamic (MHD) theory predicts reconnection rate that is far too slow to account for a wide variety of reconnection events observed in space and laboratory plasmas. Therefore, it was commonly accepted that some non-MHD (kinetic) effects play a crucial role in fast reconnection. A recently renewed interest in simple MHD models is associated with the so-called plasmoid instability of reconnecting current sheets. Although it is now evident that this effect can significantly enhance the rate of reconnection, many details of the underlying multiple-plasmoid process still remain controversial. Here, we report results of a high-resolution computer simulation which demonstrate that fast albeit intermittent magnetic reconnection is sustained by numerous small-scale Petschek-type shocks spontaneously formed in the current sheet due to its plasmoid instability.

  18. Assessment of risk factors for earlier onset of sporadic Alzheimer?s disease dementia

    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 ...

  19. TP53 mutations in ovarian carcinomas from sporadic cases and carriers of two distinct BRCA1 founder mutations; relation to age at diagnosis and survival

    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

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

    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.

  1. Evidence for lightning-associated enhancement of the ionospheric sporadic E layer dependent on lightning stroke energy

    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.

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

    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.

  3. No evidence of association between polymorphisms in four genes and sporadic amyotrophic lateral sclerosis in Han Chinese.

    An, Ran; Xi, Jing; Yang, Xinglong; Yao, Xiaoli; Xu, Yanming

    2015-06-01

    The four single nucleotide polymorphisms (SNPs) rs34517613, rs3849943, rs8141797 and rs6703183, each located in a different gene, have recently been associated with risk of developing sporadic amyotrophic lateral sclerosis (SALS) in European and northern Chinese populations, but no data are yet available for other ethnic groups. Here we explored the possible association between these four SNPs and SALS in Han Chinese primarily from southern and south-western China. A total of 298 individuals with SALS from three centres in mainland China and 486 unrelated healthy controls were recruited. All subjects were successfully genotyped using the ligase detection reaction (LDR). We found no evidence that any of these SNPs are associated with risk of disease in either heterozygous or homozygous individuals (p > 0.05). Subgroup analysis based on gender showed a similar lack of association. However, subgroup analysis based on spinal- or bulbar-onset SALS revealed significant differences in the genotype distributions (p = 0.009) and minor allele frequencies of rs6703183 (p = 0.004). In conclusion, it may be premature to conclude associations between these four SNPs and SALS, which should be examined in additional ethnic groups. PMID:25677198

  4. An investigation of the potential for epigenetic inactivation by transcription read-through in a sporadic colorectal cancer.

    Srivastava, Sameer; Ludwig, Anne K; Wong, Jason W H; Hesson, Luke B

    2016-07-01

    Aberrant transcription read-through of a gene promoter as a result of genetic structural rearrangements can cause the epigenetic inactivation of a neighbouring gene. All reported cases have involved copy number alterations that remove the 3' poly(A) transcription terminator sequence of a gene leading to transcription read-through (TRT) and methylation of the gene promoter of a downstream gene. We aimed to determine whether deletion of poly (A) transcription terminator sequences was associated with the methylation of neighbouring genes in a CRC with extensive copy number alterations. We performed a high resolution CGH array and methylation analysis on a CRC specimen to identify such alterations. Analysis of the CRC using high-resolution CGH identified 6 genes with deletions in the 3' part of the gene that encompassed the poly(A) transcription terminator sequence. Bisulphite sequencing of the promoter region of neighbouring (affected) genes at these six regions showed all candidate genes were unmethylated. Considering the fact that six TRT affected genes in a CRC with multiple deletions show no signs of hypermethylated promoters, it would be fairly appropriate to suggest that epigenetic inactivation by TRT might be a rare phenomenon in sporadic CRCs. PMID:27016300

  5. Sodium lidar-observed gravity wave breaking followed by an upward propagation of sporadic sodium layer over Hefei, China

    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.

  6. Application of genetic testing to define the surgical approach in a sporadic case of multiple endocrine neoplasia type 1

    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.

  7. A molecular analysis by gene expression profiling reveals Bik/NBK overexpression in sporadic breast tumor samples of Mexican females

    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

  8. Atypical sporadic CJD-MM phenotype with white matter kuru plaques associated with intranuclear inclusion body and argyrophilic grain disease.

    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

  9. Sporadic Creutzfeldt-Jakob disease diagnostic accuracy is improved by a new CSF ELISA 14-3-3γ assay.

    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 (panalysis 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

  10. Thalamic form of Creutzfeldt-Jakob disease or fatal insomnia? Report of a sporadic case with normal prion protein genotype.

    Kawasaki, K; Wakabayashi, K; Kawakami, A; Higuchi, M; Kitamoto, T; Tsuji, S; Takahashi, H

    1997-03-01

    We describe a 68-year-old man with a 53-month history of progressive dementia and clinical features of a progressive supranuclear palsy-like syndrome and dysautonomia. In the late stage of his illness, the patient also developed generalized myoclonic seizures. There was no family history of similar disorders. Histological examination revealed neuronal loss and gliosis with spongiosis in the cerebral cortex. In addition, more severe neuronal loss and gliosis without spongiosis were observed in the thalamus, especially in the anterior ventral and mediodorsal nuclei, and the inferior olivary nucleus. There was also obvious loss of Purkinje cells. Immunohistochemically, no protease-resistant prion protein (PrPres)-positive structures were demonstrated. However, Western blotting revealed the presence of PrPres in the cerebral cortex. This patient had a wild type of PrP genotype. We initially considered this to be a case of the thalamic form of Creutzfeldt-Jakob disease (CJD) with a long duration. However, it is noteworthy that essentially similar pathology, albeit with less severe cerebral cortical changes, has also been reported in fatal familial insomnia, a newly identified phenotypically different prion disease with a mutation in the PrP gene. On the basis of clinicopathological features, we eventually felt that this patient was more likely to have been a sporadic case of fatal insomnia (FI) of long duration. The present case appears to draw further attention to the possible relationship between CJD and FI. PMID:9083566

  11. PEMT G523A (V175M) is associated with sporadic Alzheimer's disease in a Chinese population.

    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

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

    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.

  13. Superoxide dismutase gene mutations in Italian patients with familial and sporadic amyotrophic lateral sclerosis: identification of three novel missense mutations.

    Gellera, C; Castellotti, B; Riggio, M C; Silani, V; Morandi, L; Testa, D; Casali, C; Taroni, F; Di Donato, S; Zeviani, M; Mariotti, C

    2001-05-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons. The majority of the patients are sporadic cases (SALS), while 5-10% of the patients have a family history of ALS (familial ALS or FALS). Mutations in the gene coding for cytoplasmic Cu/Zn superoxide dismutase (SOD1) have been identified in about 20% of FALS cases. We found SOD1-gene mutations in five of 34 unrelated FALS, and in two of 44 SALS patients. Three FALS patients carried the previously described A4V (two cases) and L84F mutations (one case), while two FALS patients carried new missense mutations: a G12R substitution in exon 1, and a F45C substitution in exon 2, respectively. The newly identified mutations were both associated with a slowly progressive disease course. Two SALS patients carried the homozygous D90A and the heterozygous I113T mutation, respectively. In addition, in one SALS patient we identified an A95T amino acid substitution, that is apparently a non-pathogenic SOD1 variant. Our study increases the number of ALS-associated SOD1 gene mutations. PMID:11369193

  14. Regular effects of random inhomogeneities of the ionosphere in the case of inclined radiowave reflection from the sporadic E layer

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

    Figueiredo-Pereira Maria E

    2009-07-01

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

  16. BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein

    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

  17. Interaction between lifestyle factors and the XRCC1, XPD, and XRCC3 genetic variations modulates the risk for sporadic colorectal cancer

    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. Assessment of risk factors for earlier onset of sporadic Alzheimer′s disease dementia

    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.

  19. Intermittent thermal plasma acceleration linked to sporadic motions of the magnetopause, first Cluster results

    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?

    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. DNA methylation changes in genes frequently mutated in sporadic colorectal cancer and in the DNA repair and Wnt/β-catenin signaling pathway genes

    Farkas, S. A.; Vymetálková, Veronika; Vodičková, Ludmila; Vodička, Pavel; Torbjörn, K. N.

    2014-01-01

    Roč. 6, č. 2 (2014), s. 179-191. ISSN 1750-1911 R&D Projects: GA ČR GPP304/11/P715; GA ČR(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

  2. Nine-month follow-up of the insulin receptor signalling cascade in the brain of streptozotocin rat model of sporadic Alzheimer's disease

    Osmanović Barilar, Jelena; Knezović, Ana; Grünblatt, Edna; Riederer, Peter; Šalković-Petrišić, Melita

    2015-01-01

    Sporadic Alzheimer disease (sAD) is associated with impairment of insulin receptor (IR) signalling in the brain. Rats used to model sAD develop insulin-resistant brain state following intracerebroventricular treatment with a betacytotoxic drug streptozotocin (STZ-icv). Brain IR signalling has been explored usually at only one time point in periods ≤3 months after the STZ-icv administration. We have investigated insulin signalling in the rat hippocampus at five time points in periods ≤9 months...

  3. Mutational Analysis of p27 (CDKN1B) and p18 (CDKN2C) in Sporadic Pancreatic Endocrine Tumors Argues against Tumor-Suppressor Function1

    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...

  4. Tissue classification for the epidemiological assessment of surgical transmission of sporadic Creutzfeldt-Jakob disease. A proposal on hypothetical risk levels

    Calero Miguel; Siden Åke; Mølbak Kåre; de Pedro-Cuesta Jesús; Rábano Alberto; Laursen Henning

    2005-01-01

    Abstract Background Epidemiological studies on the potential role of surgery in Creutzfeldt-Jakob Disease transmission have disclosed associations with history of specific surgical interventions or reported negative results. Methods Within the context of a case-control study designed to address surgical risk of sporadic Creutzfeldt-Jakob Disease in Nordic European countries (EUROSURGYCJD Project), a strategy was adopted to categorise reported surgical procedures in terms of potential risk of ...

  5. Molecular Characterization of Clostridium perfringens Isolates from Humans with Sporadic Diarrhea: Evidence for Transcriptional Regulation of the Beta2-Toxin-Encoding Gene

    Harrison, Ben; Raju, Deepa; Garmory, Helen S.; Brett, Moira M.; Titball, Richard W.; Sarker, Mahfuzur R.

    2005-01-01

    Clostridium perfringens type A food poisoning is caused by C. perfringens isolates carrying a chromosomal enterotoxin gene (cpe), while non-food-borne gastrointestinal (GI) diseases, such as antibiotic-associated diarrhea (AAD) and sporadic diarrhea (SD), are caused by C. perfringens plasmid cpe isolates. A recent study reported the association of beta2 toxin (CPB2) with human GI diseases, and particularly AAD/SD, by demonstrating that a large percentage of AAD/SD isolates, in contrast to a s...

  6. Wide mutation spectrum and frequent variant Ala27Thr of FBN1 identified in a large cohort of Chinese patients with sporadic TAAD

    Jun Guo; Lun Cai; Lixin Jia; Xiaoyan Li; Xin Xi; Shuai Zheng; Xuxia Liu; Chunmei Piao; Tingting Liu; Zhongsheng Sun; Tao Cai; Jie Du

    2015-01-01

    Genetic etiology in majority of patients with sporadic thoracic aortic aneurysm and dissections (STAAD) remains unknown. Recent GWAS study suggested common variant(s) in FBN1 is associated with STAAD. The present study aims to test this hypothesis and to identify mutation spectrum by targeted exome sequencing of the FBN1 gene in 146 unrelated patients with STAAD. Totally, 15.75% of FBN1 variants in STAAD were identified, including 5 disruptive and 18 missense mutations. Most of the variants w...

  7. Assessing Heavy Metal and PCB Exposure from Tap Water by Measuring Levels in Plasma from Sporadic Breast Cancer Patients, a Pilot Study

    Anne Marie Zimeri; Sara Wagner Robb; Hassan, Sayed M.; Rupali R. Hire; Davis, Melissa B.

    2015-01-01

    Breast cancer (BrCA) is the most common cancer affecting women around the world. However, it does not arise from the same causative agent among all women. Genetic markers have been associated with heritable or familial breast cancers, which may or may not be confounded by environmental factors, whereas sporadic breast cancer cases are more likely attributable to environmental exposures. Approximately 85% of women diagnosed with BrCA have no family history of the disease. Given this overwhelmi...

  8. The Epidemiological, Clinical, and Laboratory Features of Sporadic Creutzfeldt-Jakob Disease Patients in China: Surveillance Data from 2006 to 2010

    Gao, Chen; Shi, Qi; Tian, Chan; Chen, Cao; Han, Jun; Zhou, Wei; Zhang, Bao-Yun; Jiang, Hui-Ying; Zhang, Jin; Dong, Xiao-Ping

    2011-01-01

    Background Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive fatal central nervous system disorder, which consists of three main catalogues: sporadic, familial, and iatrogenic CJD. Methodology/Principal Findings In China, the surveillance for CJD started in 2006, covering 12 provincial Centers for Disease Control and Prevention (CDCs) and 15 hospitals. From 2006 to 2010, 624 suspected patients were referred to China CJD surveillance. The epidemiological, clinical and laboratory f...

  9. BRCA1 promoter hypermethylation in sporadic epithelial ovarian carcinoma: Association with low expression of BRCA1, improved survival and co-expression of DNA methyltransferases

    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...

  10. Somatic deletion of the 5' ends of both the COL4A5 and COL4A6 genes in a sporadic leiomyoma of the esophagus.

    Heidet, L; BOYE, E.; Cai, Y.; Sado, Y.; Zhang, X.; Fléjou, J. F.; Fékété, F.; Ninomiya, Y.; Gubler, M. C.; Antignac, C

    1998-01-01

    Leiomyomata of the esophagus are sporadic benign tumors of unknown etiology. We studied a collection of nine tumors for the expression of extracellular matrix components and found the same aberrant expression pattern as previously observed in inherited diffuse leiomyomatosis. We demonstrate here the occurrence of a somatic deletion at the COL4A5/COL4A6 locus at Xq22 in a frozen leiomyoma sample. These data confirm the hypothesis that the same underlying etiology is responsible for circumscrib...

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

    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.

  12. Genomic instability at 13q31 locus and somatic mtDNA mutation in D-loop site correlate with tumor aggressiveness in sporadic Brazilian breast cancer cases

    Gilson Costa dos Santos, Jr; de Souza Góes, AC; de Vitto, H; Moreira, CC; Avvad, E; Rumjanek, FD; de Moura GalloI, CV

    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 ...

  13. Diagnostic microRNA markers to screen for sporadic human colon cancer in blood.

    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

  14. LAMINAR DISTRIBUTION OF THE PATHOLOGICAL CHANGES IN SPORADIC FRONTOTEMPORAL LOBAR DEGENERATION WITH TDP-43 PROTEINOPATHY: A QUANTITATIVE STUDY USING POLYNOMIAL CURVE FITTING

    Armstrong, Richard A.; Hamilton, Ronald L.; Mackenzie, Ian R. A.; Hedreen, John; Cairns, Nigel J.

    2012-01-01

    Aims Previous data suggest heterogeneity in laminar distribution of the pathology in the molecular disorder frontotemporal lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43kDa (TDP-43) proteinopathy (FTLD-TDP). To study this heterogeneity, we quantified the changes in density across the cortical laminae of neuronal cytoplasmic inclusions (NCI), glial inclusions (GI), neuronal intranuclear inclusions (NII), dystrophic neurites (DN), surviving neurons, abnormally enlarged neurons (EN), and vacuoles in regions of the frontal and temporal lobe. Methods Changes in density of histological features across cortical gyri were studied in ten sporadic cases of FTLD-TDP using quantitative methods and polynomial curve-fitting. Results Our data suggest that laminar neuropathology in sporadic FTLD-TDP is highly variable. Most commonly, NCI, DN, and vacuolation were abundant in the upper laminae and GI, NII, EN, and glial cell nuclei in the lower laminae. TDP-43-immunoreactive inclusions affected more of the cortical profile in longer duration cases, their distribution varied with disease subtype, but was unrelated to Braak tangle score. Different TDP-43-immunoreactive inclusions were not spatially correlated. Conclusions Laminar distribution of pathological features in ten sporadic cases of FTLD-TDL is heterogeneous and may be accounted for, in part, by disease subtype and disease duration. In addition, the feed-forward and feed-back cortico-cortical connections may be compromised in FTLD-TDP. PMID:22804696

  15. The correlation of mammographic-and histologic patterns of breast cancers in BRCA1 gene mutation carriers, compared to age-matched sporadic controls

    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.)

  16. The correlation of mammographic-and histologic patterns of breast cancers in BRCA1 gene mutation carriers, compared to age-matched sporadic controls

    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.)

  17. MicroRNA (miRNA) Signaling in the Human CNS in Sporadic Alzheimer’s Disease (AD)-Novel and Unique Pathological Features

    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

  18. Large C9orf72 repeat expansions are seen in Chinese patients with sporadic amyotrophic lateral sclerosis.

    Chen, Yongping; Lin, Ziqiang; Chen, Xueping; Cao, Bei; Wei, Qianqian; Ou, Ruwei; Zhao, Bi; Song, Wei; Wu, Ying; Shang, Hui-Fang

    2016-02-01

    An intronic GGGGCC hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 (C9orf72) gene was considered as the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in Caucasian populations. Using repeat-primed polymerase chain reaction analysis and Southern blotting methods, we assessed the frequency and size of hexanucleotide repeat expansion in a cohort of 918 sporadic ALS (SALS) patients and 632 control individuals of Han Chinese origin. We identified 8 (0.87%) of the SALS patients and none of control individuals as carriers of C9orf72 expansions with 700-3500 repeats. A comprehensive neuropsychological battery was conducted on 4 expansion-positive ALS patients, where 3 patients were found to have cognitive impairment. All expansion-positive patients were genotyped for the previously reported 20 single-nucleotide polymorphism (SNP) risk haplotypes on chromosome 9p21. Among them, 13 SNP risk haplotypes were shared in all expansion carriers, suggesting a common founder from European ancestry. Further meta-analysis demonstrated that the intermediate expansion size with 24-30 repeats, rare in both patients and controls, were significantly associated with the risk for ALS. To our knowledge, this is the first study to identify a proportion of Chinese SALS patients carrying this pathologic expansion of up to ∼3500 repeats and to completely elaborate the 20-SNP risk haplotypes in Chinese expansion-positive patients, providing indispensable evidence for the origin, geographical range, and population prevalence of the C9orf72-associated ALS. PMID:26725464

  19. Electron density and plasma waves in mid-latitude sporadic-E layer observed during the SEEK-2 campaign

    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

  20. Characterization of N-acetyltransferase 1 and 2 polymorphisms and haplotype analysis for inflammatory bowel disease and sporadic colorectal carcinoma

    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.

  1. Mimivirus reveals Mre11/Rad50 fusion proteins with a sporadic distribution in eukaryotes, bacteria, viruses and plasmids

    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.

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

    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.)

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

    Galasko Douglas

    2010-01-01

    Full Text Available Abstract Background Alzheimer's disease (AD is associated with deposition of amyloid β (Aβ in the brain, which is reflected by low concentration of the Aβ1-42 peptide in the cerebrospinal fluid (CSF. There are at least 15 additional Aβ peptides in human CSF and their relative abundance pattern is thought to reflect the production and degradation of Aβ. Here, we test the hypothesis that AD is characterized by a specific CSF Aβ 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 Aβ 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 Aβ1-42 and high levels of Aβ1-16 distinguished SAD patients and FAD mutation carriers from healthy controls and depressed patients. SAD and FAD were characterized by similar changes in Aβ1-42 and Aβ1-16, but FAD mutation carriers exhibited very low levels of Aβ1-37, Aβ1-38 and Aβ1-39. Conclusion SAD patients and PSEN1 A431E mutation carriers are characterized by aberrant CSF Aβ isoform patterns that hold clinically relevant diagnostic information. PSEN1 A431E mutation carriers exhibit low levels of Aβ1-37, Aβ1-38 and Aβ1-39; fragments that are normally produced by γ-secretase, suggesting that the PSEN1 A431E mutation modulates γ-secretase cleavage site preference in a disease-promoting manner.

  4. Sporadic meningioangiomatosis-associated atypical meningioma mimicking parenchymal invasion of brain: a case report and review of the literature

    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.

  5. Simultaneous middle and upper atmosphere radar and ionospheric sounder observations of midlatitude E region irregularities and sporadic E layer

    Ogawa, T.; Takahashi, O.; Otsuka, Y.; Nozaki, K.; Yamamoto, M.; Kita, K.

    2002-10-01

    We made middle and upper atmosphere (MU) radar observations of midlatitude E region field-aligned irregularities (FAIs) in the summer of 1999 and 2000. Sporadic E (Es) layer was monitored with a routine ionosonde, and its altitude was measured with an FM-CW sounder (FCS). In this paper we draw attention to two findings. First, we show that quasiperiodic (QP) radar echoes appearing before 0200 LT are more enhanced with increasing foEs - fbEs, which means that the FAI generation is closely related to localized density gradients within Es, and extend from 100 to 130 km in altitude, while Es altitudes determined from the FCS soundings are between 100 and 110 km. The latter fact suggests that existing models for the QP echo generation, which require a deep modulation of Es altitude, are not applicable to our observational results. We propose a new working model for generating QP echoes in which polarization electric fields originated from high-density plasma clouds within Es are mapped upward along the geomagnetic field to produce relatively weak irregularities above the Es layer. Second, we show new findings obtained from the current observations, namely, two types of QP echoes that occur below 100 km in the morning: one is the morning QP (MQP) echoes with periods of 4-8 min, and the other is the QP echoes with periods of ˜1 min. The latter type can be categorized as low-altitude QP echoes that were found from previous nighttime MU radar observations. Until now the MU radar QP echoes have been believed to occur above 100 km for the period from sunset to midnight. Although we do not know the generation mechanisms of the low-altitude MQP echoes, we suppose that these echoes might be caused by a weak Es that exists below 100 km.

  6. Detection of low-prevalence somatic TSC2 mutations in sporadic pulmonary lymphangioleiomyomatosis tissues by deep sequencing.

    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 (digital PCR. As LAM tissues are likely to be composed of heterogeneous cell populations, mutant allele frequencies can be low. Our results confirm the consistent finding of TSC2 mutations in LAM samples, and highlight the benefit of laser capture microdissection and in-depth allele analyses for detection, such as NGS. PMID:26563443

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

    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.

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

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

    2016-05-01

    At present, the testing of 14-3-3 protein in cerebrospinal fluid (CSF) is a standard biomarker test in suspected sporadic Creutzfeldt-Jakob disease (sCJD) diagnosis. Increasing 14-3-3 test referrals in CJD reference laboratories in the last years have led to an urgent need to improve established 14-3-3 test methods. The main result of our study was the validation of a commercially available 14-3-3 ELISA next to the commonly used Western blot method as a high-throughput screening test. Hereby, 14-3-3 protein expression was quantitatively analyzed in CSF of 231 sCJD and 2035 control patients. We obtained excellent sensitivity/specificity values of 88 and 96 % that are comparable to the established Western blot method. Since standard protocols and preanalytical sample handling have become more important in routine diagnostic, we investigated in a further step the reproducibility and stability of 14-3-3 as a biomarker for human prion diseases. Ring trial data from 2009 to 2013 revealed an increase of Fleiss' kappa from 0.51 to 0.68 indicating an improving reliability of 14-3-3 protein detection. The stability of 14-3-3 protein under short-term and long-term storage conditions at various temperatures and after repeated freezing/thawing cycles was confirmed. Contamination of CSF samples with blood appears likely to be an important factor at a concentration of more than 2500 erythrocytes/μL. Hemolysis of erythrocytes with significant release of 14-3-3 protein started after 2 days at room temperature. We first define clear standards for the sample handling, short- and long-term storage of CSF samples as well as the handling of blood- contaminated samples which may result in artificially elevated CSF levels of 14-3-3. PMID:25947081

  9. Phosphorylated Smad2/3 immunoreactivity in sporadic and familial amyotrophic lateral sclerosis and its mouse model.

    Nakamura, Masataka; Ito, Hidefumi; Wate, Reika; Nakano, Satoshi; Hirano, Asao; Kusaka, Hirofumi

    2008-03-01

    Phosphorylated Smad2/3 (pSmad2/3), the central mediators of transforming growth factor (TGF)-beta signaling, were recently identified in tau-positive inclusions in certain neurodegenerative disorders. To clarify whether the localization of pSmad2/3 is altered in amyotrophic lateral sclerosis (ALS), we immunohistochemically examined spinal cords from sporadic ALS (SALS), from familial ALS (FALS) patients with the A4V mutation in their Cu/Zn superoxide dismutase (SOD1) gene, and from G93A mutant SOD1 transgenic (mSOD1 Tg) mice. In control spinal cords, pSmad2/3 immunoreactivity was observed exclusively in neuronal and glial nuclei. In SALS and FALS patients the nuclei showed increased immunoreactivity for pSmad2/3. Noticeably, round hyaline inclusions (RHIs) and skein-like inclusions of SALS patients were immunoreactive for pSmad2/3. Double immunofluorescence staining for pSmad2/3 and transactive response-DNA-binding protein (TDP)-43 revealed co-localization of these proteins within RHIs. In contrast, Bunina bodies in SALS and Lewy body-like hyaline inclusions (LBHIs) in FALS were devoid of labeling for pSmad2/3. Similarly, in the mSOD1 Tg mice pSmad2/3 immunoreactivity was increased in the nuclei, while LBHIs were not labeled. These findings suggest increased TGF-beta-Smad signaling in SALS, FALS, and mSOD1 Tg mice, as well as impaired TGF-beta signal transduction in RHI-bearing neurons of SALS patients, presumably at the step of pSmad2/3 translocation into the nucleus. The pathomechanisms, including the process of inclusion development, appears to be different between SALS and mSOD1-related FALS or Tg mice. PMID:18210139

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

    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.

  11. Characterization of Recurrent and Sporadic Listeria monocytogenes Isolates from Raw Milk and Nondairy Foods by Pulsed-Field Gel Electrophoresis, Monocin Typing, Plasmid Profiling, and Cadmium and Antibiotic Resistance Determination

    Harvey, J; Gilmour, A.

    2001-01-01

    Following previous surveys to assess the incidence of Listeria monocytogenes in raw milk and nondairy foods processed in Northern Ireland, isolates were characterized as recurrent or sporadic on the basis of multilocus enzyme electrophoresis (MEE) analysis and restriction fragment length polymorphism typing. In the present study, 45 representative recurrent and sporadic electrophoretic types (ETs) previously identified by MEE were subjected to pulsed-field gel electrophoresis (PFGE) of genomi...

  12. Serological profile of sporadic acute viral hepatitis in an area of hyper-endemic hepatitis B virus infection

    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.

  13. Relationship of immunohistochemistry, copy number aberrations and epigenetic disorders with BRCAness pattern in hereditary and sporadic breast cancer.

    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

  14. Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations.

    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

  15. I-123 -FP-CIT and Tc-99m -HMPAO single photon emission computed tomography in a new sporadic case of rapid-onset dystonia-parkinsonism

    Rapid-onset dystonia-parkinsonism (RDP) is a rare, autosomal-dominantly inherited syndrome characterized by abrupt onset, over hours to days, of dystonic and parkinsonian symptoms. To date, RDP has been described in a small number of families, and in only four sporadic cases. Methods: We here report a new sporadic case of RDP who has a novel de novo mutation in the ATP1A3 gene. Striatal dopamine transporters have been assessed quantitatively using [123I]-FP-CIT SPECT. A volume of interest (VOI) was drawn within the occipital cortex to obtain non-specific activity and specific to nonspecific binding ratios (BR) were calculated. A single template of predefined VOI 3D-drawn on right and left caudate nucleus and putamen was applied to the spatially normalized BR images. BR values were compared to those obtained from an age-matched control group and from a group of patients suffering from Parkinson's disease (Hoehn and Yahr score 2 or 3). A [99mTc]-HMPAO cerebral blood flow study was also performed. Results: In the control group, BR values (mean Standard Deviation) were 3.5 ± 0.4 for the left striatum and 3.3 ± 0.3 for the right one. RDP patient's values were 3 and 2.7, respectively. In the Parkinson group, values were 1.6 ± 0.3 and 1.7 ± 0.4, respectively. [99mTc]-HMPAO scan showed homogeneous cortical and sub-cortical perfusion. Conclusion: Quantification of striatal [123I]-FP-CIT uptake in a new Sporadic case of RDP with a novel mutation in the ATP1A3 gene showed values just within the range of normality. [99mTc]-HMPAO scan was normal. (authors)

  16. I-123 -FP-CIT and Tc-99m -HMPAO single photon emission computed tomography in a new sporadic case of rapid-onset dystonia-parkinsonism

    Zanotti-Fregonara, P.; Ravasi, L. [CEA, DSV, I2BM, SHF, LMNRB, F-91401 Orsay (France); Vidailhet, M.; Roze, E. [Hop La Pitie Salpetriere, Serv Neurol, Paris (France); Vidailhet, M. [Univ Paris 06, INSERM, U679, Paris (France); Kas, A. [URA CNRS CEA 2210, Orsay (France); Kas, A. [Hop La Pitie Salpetriere, Nucl Med Serv, Paris (France); Ozelius, L.J. [Mt Sinai Sch Med, Dept Genet and Genome Sci, New York, NY (United States); Clot, F. [INSERM, UMR Neurol et Therapeut Expt S679, Paris (France); Clot, F. [Univ Paris 06, UPMC, UMR S679, Paris (France); Clot, F. [Hop La Pitie Salpetriere, Inst Federat Neurosci IFR70, Paris (France); Clot, F. [Hop La Pitie Salpetriere, AP-HP, Dept Genet et Cytogenet, Paris (France); Hindie, E. [Hop St Louis, Nucl Med Serv, Paris (France); Hindie, E. [Univ Paris 07, Imagerie Mol Diagnost et Ciblage Therapeut, Ecole Doctorale B2T, IUH, Paris (France); Devaux, J.Y. [Hop St Antoine, Nucl Med Serv, F-75571 Paris (France); Roze, E. [Univ Paris 06, CNRS, UMR 7102, Paris (France)

    2008-07-01

    Rapid-onset dystonia-parkinsonism (RDP) is a rare, autosomal-dominantly inherited syndrome characterized by abrupt onset, over hours to days, of dystonic and parkinsonian symptoms. To date, RDP has been described in a small number of families, and in only four sporadic cases. Methods: We here report a new sporadic case of RDP who has a novel de novo mutation in the ATP1A3 gene. Striatal dopamine transporters have been assessed quantitatively using [{sup 123}I]-FP-CIT SPECT. A volume of interest (VOI) was drawn within the occipital cortex to obtain non-specific activity and specific to nonspecific binding ratios (BR) were calculated. A single template of predefined VOI 3D-drawn on right and left caudate nucleus and putamen was applied to the spatially normalized BR images. BR values were compared to those obtained from an age-matched control group and from a group of patients suffering from Parkinson's disease (Hoehn and Yahr score 2 or 3). A [{sup 99m}Tc]-HMPAO cerebral blood flow study was also performed. Results: In the control group, BR values (mean Standard Deviation) were 3.5 {+-} 0.4 for the left striatum and 3.3 {+-} 0.3 for the right one. RDP patient's values were 3 and 2.7, respectively. In the Parkinson group, values were 1.6 {+-} 0.3 and 1.7 {+-} 0.4, respectively. [{sup 99m}Tc]-HMPAO scan showed homogeneous cortical and sub-cortical perfusion. Conclusion: Quantification of striatal [{sup 123}I]-FP-CIT uptake in a new Sporadic case of RDP with a novel mutation in the ATP1A3 gene showed values just within the range of normality. [{sup 99m}Tc]-HMPAO scan was normal. (authors)

  17. Fibrodysplasia ossificans progressiva with minor unilateral hallux anomaly in a sporadic case from Northern Tanzania with the common ACVR1c.617G>A mutation

    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. Laparoscopic cryoablation of angiomyolipomas in adolescents and young adults: a report of 4 cases associated with tuberous sclerosis and 1 case of sporadic origin

    Trelborg, Karina; Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Olsen, L. Henning

    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....... 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...

  19. Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma

    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.

  20. Negative Regulation of BRCA1 Gene Expression by HMGA1 Proteins Accounts for the Reduced BRCA1 Protein Levels in Sporadic Breast Carcinoma

    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. ...

  1. A statistical study of sporadic sodium layer observed by Sodium lidar at Hefei (31.8° N, 117.3° E)

    Dou, X.-K.; Xue, X.-H.; Chen, T.-D.; Wan, W.-X.; Cheng, X.-W.; Li, T; Chen, C.; Qiu, S.; Chen, Z.-Y.

    2009-01-01

    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 ...

  2. A statistical study of sporadic sodium layer observed by Sodium lidar at Hefei (31.8° N, 117.3° E)

    Qiu, S.; Li, T; Chen, C.; X.-W. Cheng; W.-X. Wan; T.-D. Chen; X.-H. Xue; X.-K. Dou; Z.-Y. Chen

    2009-01-01

    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...

  3. Analysis of germline CDKN1C (p57KIP2) mutations in familial and sporadic Beckwith-Wiedemann syndrome (BWS) provides a novel genotype-phenotype correlation.

    Lam, W W; Hatada, I; Ohishi, S; Mukai, T; Joyce, J A; Cole, T R; Donnai, D; Reik, W; Schofield, P N; Maher, E R

    1999-07-01

    Beckwith-Wiedemann syndrome (BWS) is a human imprinting disorder with a variable phenotype. The major features are anterior abdominal wall defects including exomphalos (omphalocele), pre- and postnatal overgrowth, and macroglossia. Additional less frequent complications include specific developmental defects and a predisposition to embryonal tumours. BWS is genetically heterogeneous and epigenetic changes in the IGF2/H19 genes resulting in overexpression of IGF2 have been implicated in many cases. Recently germline mutations in the cyclin dependent kinase inhibitor gene CDKN1C (p57KIP2) have been reported in a variable minority of BWS patients. We have investigated a large series of familial and sporadic BWS patients for evidence of CDKN1C mutations by direct gene sequencing. A total of 70 patients with classical BWS were investigated; 54 were sporadic with no evidence of UPD and 16 were familial from seven kindreds. Novel germline CDKN1C mutations were identified in five probands, 3/7 (43%) familial cases and 2/54 (4%) sporadic cases. There was no association between germline CDKN1C mutations and IGF2 or H19 epigenotype abnormalities. The clinical phenotype of 13 BWS patients with germline CDKN1C mutations was compared to that of BWS patients with other defined types of molecular pathology. This showed a significantly higher frequency of exomphalos in the CDKN1C mutation cases (11/13) than in patients with an imprinting centre defect (associated with biallelic IGF2 expression and H19 silencing) (0/5, p<0.005) or patients with uniparental disomy (0/9, p<0.005). However, there was no association between germline CDKN1C mutations and risk of embryonal tumours. No CDKN1C mutations were identified in six non-BWS patients with overgrowth and Wilms tumour. These findings (1) show that germline CDKN1C mutations are a frequent cause of familial but not sporadic BWS, (2) suggest that CDKN1C mutations probably cause BWS independently of changes in IGF2/H19 imprinting, (3) provide evidence that aspects of the BWS phenotype may be correlated with the involvement of specific imprinted genes, and (4) link genotype-phenotype relationships in BWS and the results of murine experimental models of BWS. PMID:10424811

  4. Clinical and epidemiological evaluation of patients with sporadic colorectal cancer / Avaliação clínica e epidemiológica de pacientes com câncer colorretal esporádico

    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.

  5. Homozygous T172T and Heterozygous G135C Variants of Homologous Recombination Repairing Protein RAD51 are Related to Sporadic Breast Cancer Susceptibility.

    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

  6. Factores de riesgo de casos esporádicos de gastroenteritis por Campylobacter en niños Risk factors for sporadic cases of Campylobacter infection in children

    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.

  7. The rare intracellular RET mutation p.Ser891Ala in an apparently sporadic medullary thyroid carcinoma: a case report and review of the literature

    Carla Brauner Blom

    2012-11-01

    Full Text Available Medullary thyroid carcinoma (MTC is a malignant tumor originating from parafollicular C-cells and accounts for 4-10% of all thyroid carcinomas. MTC develops in either sporadic (75% or hereditary form (25%. Mutations in the RET proto-oncogene are responsible for hereditary MTC and the rate of heritable disease among apparently sporadic MTC (sMTC cases varies from 6 to 15%. RET genetic testing is now considered fundamental in MTC management but the extent of the molecular analysis required to exclude inherited disease is still controversial. While the screening of all known mutation loci is recommended by some authors, the high costs associated with a full analysis should be also taken into consideration. Here, we illustrate and discuss this controversial issue by reporting a patient who present all characteristic features of sMTC, and in whom a standard genetic analysis by restriction enzyme restriction excluded hereditary disease. Nevertheless, an extensive molecular analysis that included all codons was prompted by the diagnosis of thyroid neoplasm in a patient's sister, and identified the rare intracellular RET p.Ser891Ala mutation. Arq Bras Endocrinol Metab. 2012;56(8:586-91

  8. Interaction between lifestyle factors and the XRCC1, XPD, and XRCC3 genetic variations modulates the risk for sporadic colorectal cancer

    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.

  9. An assessment of the frequency of mutations in the GBA and VPS35 genes in Hungarian patients with sporadic Parkinson's disease.

    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

  10. A statistical study of sporadic sodium layer observed by Sodium lidar at Hefei (31.8° N, 117.3° E

    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.

  11. Assessing Heavy Metal and PCB Exposure from Tap Water by Measuring Levels in Plasma from Sporadic Breast Cancer Patients, a Pilot Study.

    Zimeri, Anne Marie; Robb, Sara Wagner; Hassan, Sayed M; Hire, Rupali R; Davis, Melissa B

    2015-12-01

    Breast cancer (BrCA) is the most common cancer affecting women around the world. However, it does not arise from the same causative agent among all women. Genetic markers have been associated with heritable or familial breast cancers, which may or may not be confounded by environmental factors, whereas sporadic breast cancer cases are more likely attributable to environmental exposures. Approximately 85% of women diagnosed with BrCA have no family history of the disease. Given this overwhelming bias, more plausible etiologic mechanisms should be investigated to accurately assess a woman's risk of acquiring breast cancer. It is known that breast cancer risk is highly influenced by exogenous environmental cues altering cancer genes either by genotoxic mechanisms (DNA mutations) or otherwise. Risk assessment should comprehensively incorporate exposures to exogenous factors that are linked to a woman's individual susceptibility. However, the exact role that some environmental agents (EA) play in tumor formation and/or cancer gene regulation is unclear. In this pilot project, we begin a multi-disciplinary approach to investigate the intersection of environmental exposures, cancer gene response, and BrCA risk. Here, we present data that show environmental exposure to heavy metals and PCBs in drinking water, heavy metal presence in plasma of nine patients with sporadic BrCA, and Toxic Release Inventory and geological data for a metal of concern, uranium, in Northeast Georgia. PMID:26690196

  12. Assessing Heavy Metal and PCB Exposure from Tap Water by Measuring Levels in Plasma from Sporadic Breast Cancer Patients, a Pilot Study

    Anne Marie Zimeri

    2015-12-01

    Full Text Available Breast cancer (BrCA is the most common cancer affecting women around the world. However, it does not arise from the same causative agent among all women. Genetic markers have been associated with heritable or familial breast cancers, which may or may not be confounded by environmental factors, whereas sporadic breast cancer cases are more likely attributable to environmental exposures. Approximately 85% of women diagnosed with BrCA have no family history of the disease. Given this overwhelming bias, more plausible etiologic mechanisms should be investigated to accurately assess a woman’s risk of acquiring breast cancer. It is known that breast cancer risk is highly influenced by exogenous environmental cues altering cancer genes either by genotoxic mechanisms (DNA mutations or otherwise. Risk assessment should comprehensively incorporate exposures to exogenous factors that are linked to a woman’s individual susceptibility. However, the exact role that some environmental agents (EA play in tumor formation and/or cancer gene regulation is unclear. In this pilot project, we begin a multi-disciplinary approach to investigate the intersection of environmental exposures, cancer gene response, and BrCA risk. Here, we present data that show environmental exposure to heavy metals and PCBs in drinking water, heavy metal presence in plasma of nine patients with sporadic BrCA, and Toxic Release Inventory and geological data for a metal of concern, uranium, in Northeast Georgia.

  13. Patients with familial non-medullary thyroid cancer have an outcome similar to that of patients with sporadic papillary thyroid tumors

    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.

  14. A statistical study of sporadic sodium layer observed by Sodium lidar at Hefei (31.8° N, 117.3° E)

    Dou, X.-K.; Xue, X.-H.; Chen, T.-D.; Wan, W.-X.; Cheng, X.-W.; Li, T.; Chen, C.; Qiu, S.; Chen, Z.-Y.

    2009-06-01

    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.

  15. Allele loss and mutation screen at the Peutz-Jeghers (LKB1) locus (19p13.3) in sporadic ovarian tumours.

    Wang, Z J; Churchman, M; Campbell, I G; Xu, W H; Yan, Z Y; McCluggage, W G; Foulkes, W D; Tomlinson, I P

    1999-04-01

    Germline mutations in the LKB1 (STK11) gene (chromosome sub-band 19p13.3) cause characteristic hamartomas and pigmentation to develop in patients with Peutz-Jeghers syndrome. Peutz-Jeghers syndrome carries an overall risk of cancer that may be up to 20 times that of the general population and Peutz-Jeghers patients are at increased risk of benign and malignant ovarian tumours, particularly granulosa cell tumours. Loss of heterozygosity (allele loss, LOH) has been reported in about 50% of ovarian cancers on 19p13.3. LKB1 is therefore a candidate tumour suppressor gene for sporadic ovarian tumours. We found allele loss at the marker D19S886 (19p13.3) in 12 of 49 (24%) sporadic ovarian adenocarcinomas. Using SSCP analysis, we screened ten ovarian cancers with LOH, 35 other ovarian cancers and 12 granulosa cell tumours of the ovary for somatic mutations in LKB1. No variants were detected in any of the adenocarcinomas. Two mutations were detected in one of the granulosa cell tumours: a mis-sense mutation affecting the putative 'start' codon (ATG --> ACG, M1T); and a silent change in exon 7 (CTT --> CTA, leucine). Like BRCA1 and BRCA2, therefore, it appears that LKB1 mutations can cause ovarian tumours when present in the germline, but occur rarely in the soma. The allele loss on 19p13.3 in ovarian cancers almost certainly targets a different gene from LKB1. PMID:10389980

  16. The Southern Argentina Agile MEteor Radar Orbital System (SAAMER-OS): An Initial Sporadic Meteoroid Orbital Survey in the Southern Sky

    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.

  17. Over-representation of the APOE*4 allele in autopsy confirmed early- and late-onset sporadic Alzheimer`s disease

    Kamboh, M.I.; DeKosky, S.T.; Ferrell, R.E. [Univ. of Pittsburgh, PA (United States)

    1994-09-01

    Apolipoprotein E binds to {beta}-amyloid peptide in senile plaques and neurofibrillary tangles in Alzheimer`s disease (AD). Recent studies have identified the APOE*4 allele as a major predisposing genetic factor for late-onset familial AD as well as in sporadic AD. Most of these association studies are based on clinically diagnosed AD cases with little data available on autopsy confirmed, definite AD. To characterize the distribution of APOE polymorphism in autopsy confirmed sporadic AD cases, we determined APOE genotypes in 111 DNA samples (aged 51-101 years) extracted from brain tissues which were available from the University of Pittsburgh Alzheimer`s Disease Research Center. The APOE data was compared between the AD group and 3 samples of population controls from Western Pennsylvania consisting of a young cohort (N=473, aged 18-48 years), middle cohort (N=473, aged 42-50 years) and an old cohort (N=870, aged 65-90 years). The frequency of the APOE*4 allele was similar in the young and middle cohorts (0.12) and slightly lower in the old cohort (0.10). However, the frequency of the APOE*4 allele was three times higher in both early-onset (<65 years; 0.36) and late-onset ({ge}65 years; 0.38) sporadic AD cases compared to the control groups (p<0.0001). In the AD cohort the frequency of the APOE*4 allele was similar across all age groups (<65, 65-75, 76-85, 86+) and so was in men and women (0.40 vs. 0.37). The E*4 homozygosity was observed in 18% of AD cases compared to 1% in each of the three control groups. The E*4 heterozygosity was present in 50% of AD cases compared to 17% in the control old cohort and 22% in both the young and middle control cohorts. These data confirm that the APOE*4 allele is a major risk factor for AD regardless of age-at-diagnosis or family history.

  18. Rydberg Matter clusters of alkali metal atoms: the link between meteoritic matter, polar mesosphere summer echoes (PMSE), sporadic sodium layers, polar mesospheric clouds (PMCs, NLCs), and ion chemistry

    Olofson, Frans; Holmlid, Leif

    2010-01-01

    A material exists which links together the influx of meteoritic matter from interplanetary space, the polar mesosphere summer echoes (PMSE), the sporadic sodium layers, the polar mesospheric clouds (PMCs, NLCs), and the observed ion chemistry in the mesosphere. The evidence in these research fields is here analyzed and found to agree well with the properties of Rydberg Matter (RM). This material has been studied with numerous methods in the laboratory. Alkali atoms, mainly Na, reach the mesosphere in the form of interplanetary (meteoritic, cometary) dust. The planar RM clusters NaN usually contain N = 19, 37 or 61 atoms, and have the density of air at 90 km altitude where they float. The diameters of the clusters are 10-100 nm from laboratory high precision radio frequency spectroscopic studies. Such experiments show that RM clusters interact strongly with radar frequencies: this explains the radio frequency heating and reflection studies of PMSE layers. The clusters give the low temperature in the mesosphere...

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

    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.

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

    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

  1. Common NOD2/CARD15 variants are not associated with susceptibility or the clinicopathologic characteristics of sporadic colorectal cancer in Hungarian patients

    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.

  2. Molecular Characterization of Sporadic Pediatric Thyroid Carcinoma with the DNA/RNA ThyroSeq v2 Next-Generation Sequencing Assay.

    Picarsic, Jennifer L; Buryk, Melissa A; Ozolek, John; Ranganathan, Sarangarajan; Monaco, Sara E; Simons, Jeffrey P; Witchel, Selma F; Gurtunca, Nursen; Joyce, Judith; Zhong, Shan; Nikiforova, Marina N; Nikiforov, Yuri E

    2016-01-01

    The aim of this study was to test the hypothesis that our 60-gene DNA/RNA ThyroSeq v2 next-generation sequence (NGS) assay would identify additional genetic markers, including gene fusions in sporadic pediatric differentiated thyroid carcinomas (DTC) that had no known molecular alterations. Sporadic pediatric DTCs with informative molecular testing (n  =  18) were studied. We previously tested 15 cases by our standard 7-gene (BRAF, NRAS, HRAS, KRAS, RET/PTC1, RET/PTC3, PAX8/PPARg) mutation panel. Three cases were not tested previously. The standard 7-gene panel identified molecular alterations in 9 of 15 tumors (60%). Cases analyzed by ThyroSeq v2 NGS included the six previously negative cases by the standard 7-gene panel and three cases not previously tested. The NGS assay revealed new gene fusions in four of six previously negative cases (67%). These gene fusions included ETV6/NTRK3 (n  =  3) and TPR/NTRK1 (n  =  1). A point mutation (BRAF-V600E) was detected in one of three untested cases. While standard testing could identify only molecular alterations in 60% of cases, with the addition of the ThyroSeq v2 NGS, this increased to 87% (n  =  13/15). Some cases with chromosomal rearrangements, including ETV6/NTRK3, appear to be associated with an aggressive histopathologic phenotype, but had no documented history of radiation exposure. Additional work is needed to investigate if pediatric DTCs could benefit from a reclassification based on molecular subtypes, which may better reflect their underlying biologic potential. Our data support the use of broad gene panels for the molecular diagnostics of pediatric thyroid nodules to aid future classification, treatment, and clinical management recommendations. PMID:26367451

  3. 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.

    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

  4. Comparative genomic analysis of two novel sporadic Shiga toxin-producing Escherichia coli O104:H4 strains isolated 2011 in Germany.

    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. Style-by-style analysis of two sporadic self-compatible Solanum chacoense lines supports a primary role for S-RNases in determining pollen rejection thresholds.

    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

  6. Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study

    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.

  7. Enfermedad de Creutzfeldt-Jakob esporádica: dos casos en medicina intensiva Sporadic Creutzfeldt-Jakob disease: two cases in intensive care

    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.

  8. Rearrangements at the 11p15 locus and overexpression of insulin-like growth factor-II gene in sporadic adrenocortical tumors

    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.

  9. Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study

    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

  10. Xenotropic Murine Leukemia Virus-Related Virus and RNase L R462Q Variants in Iranian Patients With Sporadic Prostate Cancer

    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.

  11. Uptake of 4-borono-2-[{sup 18}F]fluoro-L-phenylalanine in sporadic and neurofibromatosis 2-related schwannoma and meningioma studied with PET

    Havu-Auren, Katja; Kiiski, Johanna; Lehtioe, Kaisa; Eskola, Olli; Oikonen, Vesa [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); Kulvik, Martti; Vaehaetalo, Jyrki [Helsinki University Central Hospital, Department of Neurology, Helsinki (Finland); Vuorinen, Ville [Turku University Central Hospital, Department of Neurosurgery, Turku (Finland); Jaeaeskelaeinen, Juha [Kuopio University Central Hospital, Department of Neurosurgery, Kuopio (Finland); Minn, Heikki [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); Turku University Central Hospital, Department of Oncology and Radiotherapy, Turku (Finland)

    2007-01-15

    Meningiomas and schwannomas associated with neurofibromatosis 2 (NF2) are difficult to control by microsurgery and stereotactic radiotherapy alone. Boron neutron capture therapy (BNCT) is a chemically targeted form of radiotherapy requiring increased concentration of boron-10 in tumour tissue. PET with the boron carrier 4-borono-2-[{sup 18}F]fluoro-L-phenylalanine ([{sup 18}F]FBPA) allows investigation of whether 4-borono-L-phenylalanine (BPA) concentrates in NF2 tumours, which would make BNCT feasible. We studied dynamic uptake of [{sup 18}F]FBPA in intracranial meningiomas (n=4) and schwannomas (n=6) of five sporadic and five NF2 patients. Tracer input function and cerebral blood volume were measured. [{sup 18}F]FBPA uptake in tumour and brain was assessed with a three-compartmental model and graphical analysis. These, together with standardised uptake values (SUVs), were used to define tumour-to-brain [{sup 18}F]FBPA tissue activity gradients. Model fits with three parameters K{sub 1} (transport), k{sub 2} (reverse transport) and k{sub 3} (intracellular metabolism) were found to best illustrate [{sup 18}F]FBPA uptake kinetics. Maximum SUV was two- to fourfold higher in tumour as compared with normal brain and independent of NF2 status. The increased uptake was due to higher transport of [{sup 18}F]FBPA in tumour. In multiple-time graphical analysis (MTGA, Gjedde-Patlak plot) the tumour-to-brain [{sup 18}F]FBPA influx constant (K{sub i} -MTGA) ratios varied between 1.8 and 5.4 in NF2-associated tumours while in sporadic tumours the ratio was 1-1.4. [{sup 18}F]FBPA PET offers a viable means to evaluate BPA uptake in meningiomas and schwannomas in NF2. Based on our results on tumour uptake of [{sup 18}F]FBPA, some of these benign neoplasms may be amenable to BNCT. (orig.)

  12. Nearby Supernova Factory Observations of SN 2006D: On SporadicCarbon Signatures in Early Type Ia Supernova Spectra

    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.

  13. Novel FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins imply a role for its DNA binding domain.

    Sen, Partha; Yang, Yaping; Navarro, Colby; Silva, Iris; Szafranski, Przemyslaw; Kolodziejska, Katarzyna E; Dharmadhikari, Avinash V; Mostafa, Hasnaa; Kozakewich, Harry; Kearney, Debra; Cahill, John B; Whitt, Merrissa; Bilic, Masha; Margraf, Linda; Charles, Adrian; Goldblatt, Jack; Gibson, Kathleen; Lantz, Patrick E; Garvin, A Julian; Petty, John; Kiblawi, Zeina; Zuppan, Craig; McConkie-Rosell, Allyn; McDonald, Marie T; Peterson-Carmichael, Stacey L; Gaede, Jane T; Shivanna, Binoy; Schady, Deborah; Friedlich, Philippe S; Hays, Stephen R; Palafoll, Irene Valenzuela; Siebers-Renelt, Ulrike; Bohring, Axel; Finn, Laura S; Siebert, Joseph R; Galambos, Csaba; Nguyen, Lananh; Riley, Melissa; Chassaing, Nicolas; Vigouroux, Adeline; Rocha, Gustavo; Fernandes, Susana; Brumbaugh, Jane; Roberts, Kari; Ho-Ming, Luk; Lo, Ivan F M; Lam, Stephen; Gerychova, Romana; Jezova, Marta; Valaskova, Iveta; Fellmann, Florence; Afshar, Katayoun; Giannoni, Eric; Muhlethaler, Vincent; Liang, Jinlong; Beckmann, Jacques S; Lioy, Janet; Deshmukh, Hitesh; Srinivasan, Lakshmi; Swarr, Daniel T; Sloman, Melissa; Shaw-Smith, Charles; van Loon, Rosa Laura; Hagman, Cecilia; Sznajer, Yves; Barrea, Catherine; Galant, Christine; Detaille, Thierry; Wambach, Jennifer A; Cole, F Sessions; Hamvas, Aaron; Prince, Lawrence S; Diderich, Karin E M; Brooks, Alice S; Verdijk, Robert M; Ravindranathan, Hari; Sugo, Ella; Mowat, David; Baker, Michael L; Langston, Claire; Welty, Stephen; Stankiewicz, Pawel

    2013-06-01

    Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA-binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis. PMID:23505205

  14. Intrachromosomal genomic instability in human sporadic colorectal cancer measured by genome-wide allelotyping and inter-(simple sequence repeat) PCR.

    Anderson, G R; Brenner, B M; Swede, H; Chen, N; Henry, W M; Conroy, J M; Karpenko, M J; Issa, J P; Bartos, J D; Brunelle, J K; Jahreis, G P; Kahlenberg, M S; Basik, M; Sait, S; Rodriguez-Bigas, M A; Nowak, N J; Petrelli, N J; Shows, T B; Stoler, D L

    2001-11-15

    We have used genome-wide allelotyping with 348 polymorphic autosomal markers spaced, on average, 10 cM apart to quantitate the extent of intrachromosomal instability in 59 human sporadic colorectal carcinomas. We have compared instability measured by this method with that measured by inter-(simple sequence repeat) PCR and microsatellite instability assays. Instability quantitated by fractional allelic loss rates was found to be independent of that detected by microsatellite instability analyses but was weakly associated with that measured by inter-(simple sequence repeat) PCR. A set of seven loci were identified that were most strongly associated with elevated rates of fractional allelic loss and/or inter-(simple sequence repeat) PCR instability; these seven loci were on chromosomes 3, 8, 11, 13, 14, 18, and 20. A lesser association was seen with two loci flanking p53 on chromosome 17. Coordinate loss patterns for these loci suggest that at least two separate sets of cooperating loci exist for intrachromosomal genomic instability in human colorectal cancer. PMID:11719460

  15. Association of prion protein genotype and scrapie prion protein type with cellular prion protein charge isoform profiles in cerebrospinal fluid of humans with sporadic or familial prion diseases.

    Schmitz, Matthias; Lüllmann, Katharina; Zafar, Saima; Ebert, Elisabeth; Wohlhage, Marie; Oikonomou, Panteleimon; Schlomm, Markus; Mitrova, Eva; Beekes, Michael; Zerr, Inga

    2014-05-01

    The present study investigates whether posttranslational modifications of cellular prion protein (PrP(C)) in the cerebrospinal fluid (CSF) of humans with prion diseases are associated with methionine (M) and/or valine (V) polymorphism at codon 129 of the prion protein gene (PRNP), scrapie prion protein (PrP(Sc)) type in sporadic Creutzfeldt-Jakob disease (sCJD), or PRNP mutations in familial Creutzfeldt-Jakob disease (fCJD/E200K), and fatal familial insomnia (FFI). We performed comparative 2-dimensional immunoblotting of PrP(C) charge isoforms in CSF samples from cohorts of diseased and control donors. Mean levels of total PrP(C) were significantly lower in the CSF from fCJD patients than from those with sCJD or FFI. Of the 12 most abundant PrP(C) isoforms in the examined CSF, one (IF12) was relatively decreased in (1) sCJD with VV (vs. MM or MV) at PRNP codon 129; (2) in sCJD with PrP(Sc) type 2 (vs. PrP(Sc) type 1); and (3) in FFI versus sCJD or fCJD. Furthermore, truncated PrP(C) species were detected in sCJD and control samples without discernible differences. Finally, serine 43 of PrP(C) in the CSF and brain tissue from CJD patients showed more pronounced phosphorylation than in control donors. PMID:24360565

  16. 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.

    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

  17. 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

    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

  18. Characterisation of human outbreaks of brucellosis and sporadic cases by the use of hyper-variable octameric oligonucleotide fingerprint (HOOF) variable number tandem repeats.

    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

  19. A common functional allele of the Nogo receptor gene, reticulon 4 receptor (RTN4R), is associated with sporadic amyotrophic lateral sclerosis in a French population.

    Amy, Maïté; Staehlin, Oliver; René, Frédérique; Blasco, Hélène; Marouillat, Sylviane; Daoud, Hussein; Vourc'h, Patrick; Gordon, Paul H; Camu, William; Corcia, Philippe; Loeffler, Jean-Philippe; Palkovits, Miklós; Sommer, Wolfgang H; Andres, Christian R

    2015-01-01

    Amyotrophic lateral sclerosis is sporadic (SALS) in 90% of cases and has complex environmental and genetic influences. Nogo protein inhibits neurite outgrowth and is overexpressed in muscle in ALS. Our aims were to study the reticulon 4 receptor gene RTN4R which encodes Nogo 1 receptor (NgR1) in SALS, to test if the variants were associated with variable expression of the gene and whether NgR1 protein expression was modified in a transgenic mouse model of ALS. We genotyped three single nucleotide polymorphisms (SNPs; rs701421, rs701427, and rs1567871) of the RTN4R gene in 364 SALS French patients and 430 controls. We examined expression of RTN4R mRNA by quantitative PCR in control post mortem human brain tissue. We determined the expression of NgR1 protein in spinal motor neurons from a SOD1 G86R ALS mouse model. We observed significant associations between SALS and RTN4R alleles. Messenger RNA expression from RTN4R in human cortical brain tissue correlated significantly with the genotypes of rs701427. NgR1 protein expression was reduced in Nogo A positive motor neurons from diseased transgenic animals. In conclusion, these observations suggest that a functional RTN4R gene variant is associated with SALS. This variant may act in concert with other genetic variants or environmental influences. PMID:26083872

  20. 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)

    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...

  1. Multilocus Variable-Number Tandem-Repeat Analysis, Pulsed-Field Gel Electrophoresis, and Antimicrobial Susceptibility Patterns in Discrimination of Sporadic and Outbreak-Related Strains of Yersinia enterocolitica

    Skurnik Mikael

    2011-02-01

    Full Text Available Abstract Background We assessed the potential of multilocus variable-number tandem-repeat analysis (MLVA, pulsed-field gel electrophoresis (PFGE, and antimicrobial susceptibility testing for discriminating 104 sporadic and outbreak-related Yersinia enterocolitica (YE bio/serotype 3-4/O:3 and 2/O:9 isolates. MLVA using six VNTR markers was performed in two separate multiplex PCRs, and the fluorescently labeled PCR products were accurately sized on an automated DNA sequencer. Results MLVA discriminated 82 sporadic YE 3-4/O:3 and 2/O:9 strains into 77 types, whereas PFGE with the restriction enzyme NotI discriminated the strains into 23 different PFGE pulsotypes. The discriminatory index for a sporadic strain was 0.862 for PFGE and 0.999 for MLVA. MLVA confirmed that a foodborne outbreak in the city of Kotka, Finland in 2003 had been caused by a multiresistant YE 4/O:3 strain that was distinctly different from those of epidemiologically unrelated strains with an identical PFGE pulsotype. The multiresistance of Y. enterocolitica strains (19% of the sporadic strains correlated significantly (p = 0.002 with travel abroad. All of the multiresistant Y. enterocolitica strains belonged to four PFGE pulsotypes that did not contain any susceptible strains. Resistance to nalidixic acid was related to changes in codons 83 or 87 that stemmed from mutations in the gyrA gene. The conjugation experiments demonstrated that resistance to CHL, STR, and SUL was carried by a conjugative plasmid. Conclusions MLVA using six loci had better discriminatory power than PFGE with the NotI enzyme. MLVA was also a less labor-intensive method than PFGE and the results were easier to analyze. The conjugation experiments demonstrated that a resistance plasmid can easily be transferred between Y. enterocolitica strains. Antimicrobial multiresistance of Y. enterocolitica strains was significantly associated with travel abroad.

  2. 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

    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 ...

  3. Multiple γ-secretase product peptides are coordinately increased in concentration in the cerebrospinal fluid of a subpopulation of sporadic Alzheimer’s disease subjects

    Hata Saori

    2012-04-01

    Full Text Available Abstract Background Alcadeinα (Alcα is a neuronal membrane protein that colocalizes with the Alzheimer's amyloid-β precursor protein (APP. Successive cleavage of APP by β- and γ-secretases generates the aggregatable amyloid-β peptide (Aβ, while cleavage of APP or Alcα by α- and γ-secretases generates non-aggregatable p3 or p3-Alcα peptides. Aβ and p3-Alcα can be recovered from human cerebrospinal fluid (CSF. We have previously reported alternative processing of APP and Alcα in the CSF of some patients with sporadic mild cognitive impairment (MCI and AD (SAD. Results Using the sandwich enzyme-linked immunosorbent assay (ELISA system that detects total p3-Alcα, we determined levels of total p3-Alcα in CSF from subjects in one of four diagnostic categories (elderly controls, MCI, SAD, or other neurological disease derived from three independent cohorts. Levels of Aβ40 correlated with levels of total p3-Alcα in all cohorts. Conclusions We confirm that Aβ40 is the most abundant Aβ species, and we propose a model in which CSF p3-Alcα can serve as a either (1 a nonaggregatable surrogate marker for γ-secretase activity; (2 as a marker for clearance of transmembrane domain peptides derived from integral protein catabolism; or (3 both. We propose the specification of an MCI/SAD endophenotype characterized by co-elevation of levels of both CSF p3-Alcα and Aβ40, and we propose that subjects in this category might be especially responsive to therapeutics aimed at modulation of γ-secretase function and/or transmembrane domain peptide clearance. These peptides may also be used to monitor the efficacy of therapeutics that target these steps in Aβ metabolism

  4. Low Latitude Field-aligned Irregularities Observed In The E Region With The Piura Vhf Radar: Morphology, Long-term Periodicities and Their Relationship With Sporadic E Layers

    Chau, J. L.; Haldoupis, C.

    Between 1991 and 1999, the Piura VHF radar (5.2S, 80.6W, 7.0N dip latitude) in northern Peru has been operated intermittently to observe coherent backscatter from 3-m E-region field-aligned irregularities. These echoes are detected by pointing the antenna beam to the north at 14 zenith angle, i.e., perpendicular to the magnetic field lines, in an area just outside the equatorial electrojet zone and far from mid latitudes. Studies of these observations have shown that the spectral and diurnal characteris- tics of backscatter are reminiscent of midlatitude E region irregularities rather than those at the equatorial electrojet. Since January 2000, "continuous" (2 minutes every 12 minutes) observations have been started in order to study in more detail the diur- nal and seasonal morphology of backscatter. In this paper, we analyze these data to study the morphology of the echoes (diurnal and seasonal) and compare it to the mor- phology of sporadic E (Es) layers observed in low latitude ionosonde stations. The results show the occurrence of the Piura E region irregularities to be in close relation with the characteristics of Es layers and their morphology. This indicates that E re- gion coherent backscatter even at very low latitudes is basically of the same nature as that observed at midlatitude, therefore it relates to plasma instabilities operating inside Es layers. In addition, we investigate the long-term (periods of days) variability seen in echo occurrence and intensity of the Piura backscatter and examine how these variations compare with similar ones measured at midlatitude, and also their possible relationship with planetary waves which are known to exist in the mesosphere and lower thermosphere.

  5. Enfermedad de Creutzfeldt-Jakob esporádica: dos casos en medicina intensiva / Sporadic Creutzfeldt-Jakob disease: two cases in intensive care

    P., Cardinal; I., Pedemonte; J., Castelli; E., Zitto; A., Cacciatore; N., Zefferino.

    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 heredi [...] taria o genética. Realizar el diagnóstico de «enfermedad de Creutzfeldt-Jakob» es un verdadero desafío para el médico intensivista dada la variabilidad en la presentación clínica y su baja incidencia. Se presentan 2 pacientes admitidos en la UCI en los que, tras descartar varias patologías, se diagnosticó con un nivel de «probabilidad», de acuerdo a la clasificación de la OMS, enfermedad de Creutzfeldt-Jakob esporádica. Se analizan aspectos diagnósticos clínicos y analíticos de la enfermedad resaltando la utilidad de la identificación de la proteína 14-3-3 en el líquido cefalorraquídeo. Abstract in english Prion diseases or spongiform encephalopathies are a family of rare neurodegenerative diseases characterized by long incubation periods associated with slow, irreversible and invariably fatal evolution. In humans, they are classified as sporadic, acquired and hereditary or genetic. Diagnosing sporadi [...] c "Creutzfeldt-Jakob Disease" (sCJD) is a real challenge for the intensive care physician, given the variability in its clinical presentation and its low incidence. The cases of two patients admitted to the Intensive Care Unit are presented. After ruling out other diseases, they were diagnosed with sCJD with a likelihood level according to the World Health Organization Classification. Clinical and laboratory diagnostic aspects of the disease were analyzed, highlighting the utility of 14-3-3 protein identification in the cerebrospinal fluid.

  6. Refinements in the use of equivalent latitude for assimilating sporadic inhomogeneous stratospheric tracer observations, 1: Detecting transport of Pinatubo aerosol across a strong vortex edge

    P. Good

    2004-01-01

    Full Text Available The use of PV equivalent latitude for assimilating stratospheric tracer observations is discussed - with particular regard to the errors in the equivalent latitude coordinate, and to the assimilation of sparse data. Some example measurements are assimilated: they sample the stratosphere sporadically and inhomogeneously. The aim was to obtain precise information about the isentropic tracer distribution and evolution as a function of equivalent latitude. Precision is important, if transport across barriers like the vortex edge are to be detected directly. The main challenges addressed are the errors in modelled equivalent latitude, and the non-ideal observational sampling. The methods presented allow first some assessment of equivalent latitude errors and a picture of how good or poor the observational coverage is. This information determines choices in the approach for estimating as precisely as possible the true equivalent latitude distribution of the tracer, in periods of good and poor observational coverage. This is in practice an optimisation process, since better understanding of the equivalent latitude distribution of the tracer feeds back into a clearer picture of the errors in the modelled equivalent latitude coordinate. Error estimates constrain the reliability of using equivalent latitude to make statements like 'this observation samples air poleward of the vortex edge' or that of more general model-measurement comparisons. The approach is demonstrated for ground-based lidar soundings of the Mount Pinatubo aerosol cloud, focusing on the 1991-92 arctic vortex edge between 475-520K. Equivalent latitude is estimated at the observation times and locations from Eulerian model tracers initialised with PV and forced by UK Meteorological Office analyses. With the model formulation chosen, it is shown that tracer transport of a few days resulted in an error distribution that was much closer to Gaussian form, although the mean error was not significantly affected. The analysis of the observations revealed a small amount of irreversible transport of aerosol across the vortex edge during late January 1992, coincident with a strongly disturbed vortex.

  7. Human Noroviruses and Sporadic Gastroenteritis

    2008-08-05

    In this podcast, Dan Rutz speaks with Dr. Manish Patel, a medical officer with the Division of Viral Diseases at CDC, about an article in August 2008 issue of Emerging Infectious Diseases reporting on nororviruses. Dr. Patel reviewed 235 studies and identified 31 original studies about noroviruses. Norovirus is the leading cause of epidemic gastroenteritis.  Created: 8/5/2008 by Emerging Infectious Diseases.   Date Released: 7/30/2008.

  8. Nine-month follow-up of the insulin receptor signalling cascade in the brain of streptozotocin rat model of sporadic Alzheimer's disease.

    Barilar, J Osmanovic; Knezovic, A; Grünblatt, E; Riederer, P; Salkovic-Petrisic, M

    2015-04-01

    Sporadic Alzheimer disease (sAD) is associated with impairment of insulin receptor (IR) signalling in the brain. Rats used to model sAD develop insulin-resistant brain state following intracerebroventricular treatment with a betacytotoxic drug streptozotocin (STZ-icv). Brain IR signalling has been explored usually at only one time point in periods ≤3 months after the STZ-icv administration. We have investigated insulin signalling in the rat hippocampus at five time points in periods ≤9 months after STZ-icv treatment. Male Wistar rats were given vehicle (control)- or STZ (3 mg/kg)-icv injection and killed 0.5, 1, 3, 6 and 9 months afterwards. Insulin-1 (Ins-1), IR, phospho- and total (p/t)-glycogen synthase kinase 3-β (GSK-3β), p/t-tau and insulin degrading enzyme (IDE) mRNA and/or protein were measured. Acute upregulation of tau and IR mRNA (p < 0.05) was followed by a pronounced downregulation of Ins-1, IR and IDE mRNA (p < 0.05) in the course of time. Acute decrement in p/t-tau and p/t-GSK-3β ratios (p < 0.05) was followed by increment in both ratios (3-6 months, p < 0.05) after which p/t-tau ratio demonstrated a steep rise and p/t-GSK-3β ratio a steep fall up to 9 months (p < 0.05). Acute decline in IDE and IR expression (p < 0.05) was followed by a slow progression of the former and a slow recovery of the latter in 3-9 months. Results indicate a biphasic pattern in time dependency of onset and progression of changes in brain insulin signalling of STZ-icv model (partly reversible acute toxicity and chronic AD-like changes) which should be considered when using this model as a tool in translational sAD research. PMID:25503661

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

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

    1996-04-01

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

  10. Características mamográficas do câncer de mama associadas aos polimorfismos GSTM1 e GSTT1 Polymorphisms GSTM1 and GSTT1 and sporadic breast cancer mammographic features

    Lívia Martins Tavares Scianni Morais

    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 mama. 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.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. OBJECTIVE: 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.

  11. Tables, bounds and graphics of the smallest known sizes of complete arcs in the plane $\\mathrm{PG}(2,q)$ for all $q\\le160001$ and sporadic $q$ in the interval $[160801\\ldots 430007]$

    Bartoli, Daniele; Davydov, Alexander A.; Faina, Giorgio; Kreshchuk, Alexey A.; Marcugini, Stefano; Pambianco, Fernanda

    2013-01-01

    In the projective planes $\\mathrm{PG}(2,q)$, we collect the smallest known sizes of complete arcs for the regions \\begin{align*} &\\mbox{all } q\\le160001,~~ q \\mbox{ prime power};\\\\ &Q_{4}=\\{34 \\mbox{ sporadic }q'\\mbox{s in the interval }[160801\\ldots430007], \\mbox{ see Table 3}\\}. \\end{align*} For $q\\le160001$, the collection of arc sizes is complete in the sense that arcs for all prime powers are considered. This proves new upper bounds on the smallest size $t_{2}(2,q)$ of a complete arc in ...

  12. Tratamiento de schwanomas vestibulares esporádicos mediante radiocirugía: Estudio prospectivo de cohorte Radiosurgical treatment of sporadic vestibular schwannomas: A prospective cohort study

    Freddy Martel V

    2008-12-01

    Full Text Available Objetivo: Analizar los resultados iniciales de un estudio prospectivo en pacientes con schwanomas vestibulares tratados con radiocirugía en la Pontificia Universidad Católica de Chile. Material y método: Se presentan 17 pacientes portadores de schwanomas vestibulares esporádicos tratados con radiocirugía y seguidos entre 6 y 26 meses. El tratamiento fue realizado con acelerador lineal Varían clinac21 EX, con equipamiento Varían-Zmed. La dosis marginal administrada al tumor fue de 12 a 12,5 Gray El seguimiento a 6, 12 y 24 meses consta de resonancia magnética, audiometríay evaluación clínica. Resultados: La dosis marginal de irradiación usada fue entre 12y 12,5 Gray normalizada a la isodosis 70% u 80%. En todos los pacientes se documentó disminución de la captación de contraste del tumor y en 16 (94% se observaron áreas de necrosis centro tumoral. No hubo mortalidad, la preservación de audición útil fue 62,5% actuaría! a 2 años. No ha existido deterioro de la función de los nervios facial ni trigémino. Todos los pacientes que previamente estaban trabajando retornaron a sus labores en promedio 11,5 días luego del tratamiento. Conclusiones: Los resultados iniciales de esta serieison comparables a los resultados publicados en la literatura y refuerzan el demostrado rol de la radiocirugía en el tratamiento de los schwanomas vestibulares.Objective: To analyze the preliminary experience of radiosurgery for Vestibular Schwannomas at the Pontificia Universidad Católica de Chile. Material and methods: Thefirst 17 patients with sporadic Vestibular Schwannomas treated by radiosurgery at our institution are reponed. The marginal dose used was 12 to 12.5 Gy. prescribed at the 70 or 80 isodose Une. Patients were controlled at 6, 12 and 24 months with magnetic resonance, audiometric study and clinical examination. Results: In all of the 17 patients treated a decrease tumor enhancement on MR was demonstrated. In 16 patients (94% a pattern of central tumor necrosis was observed during the firsyear Actuaría! useful hearing was maintained in 62.5% at 2 year after treatment. Facial nerve function was maintained in all of the 15 patients with normal function at treatment (100%. Trigémina! function was maintained in all of the 14 patients (100% with previous normal trigeminal function. The mean time to return to work or normal activities was 11.5 days after treatment Conclusions: These preliminary results are comparable with results published in the literature and reinforce the demónstrate role oí radiosurgery in the management oí vestibular schwannomas.

  13. Monoclonal B-cell lymphocytosis in individuals from sporadic (non-familial chronic lymphocytic leukemia families persists over time, but does not progress to chronic B-cell lymphoproliferative diseases

    Daniel Mazza Matos

    2015-10-01

    Full Text Available BACKGROUND: Monoclonal B-cell lymphocytosis is classified as 'high-count or clinical' monoclonal B-cell lymphocytosis and 'low-count or population' monoclonal B-cell lymphocytosis. Previously, 167 first-degree relatives pertaining to sporadic (non-familial chronic lymphocytic leukemia families were studied and the presence of seven monoclonal B-cell lymphocytosis individuals was reported.OBJECTIVE: The aim of this report is to describe the outcomes of five of the original monoclonal B-cell lymphocytosis individuals.METHODS: Flow cytometry analysis was performed on mononuclear cells previously isolated from peripheral blood samples. A strategy of sequential gating designed to identify the population of CD19+/CD5+ B-lymphocytes was used and, subsequently, the monoclonal B-cell lymphocytosis cells were characterized by the CD20weak/CD79bweak/negative phenotype.RESULTS: The monoclonal B-cell lymphocytosis clone showed consistent stability over time with little variations in size. After a median follow-up of 7.6 years, none of the five monoclonal B-cell lymphocytosis individuals progressed to chronic lymphocytic leukemia or other B-cell lymphoproliferative disease.CONCLUSIONS: The data of this study suggest that chronic lymphocytic leukemia-like monoclonal B-cell lymphocytosis detected in the context of sporadic chronic lymphocytic leukemia families is not prone to clinical evolution and could be just a sign of immune senescence.

  14. FISH studies in a girl with sporadic aniridia and an apparently balanced de novo t(11;13(p13;q33 translocation detect a microdeletion involving the WAGR region

    Llerena Jr. J.C.

    2000-01-01

    Full Text Available Conventional cytogenetic studies on a female infant with sporadic aniridia revealed what appeared to be a balanced de novo t(11;13 (p13;q33 translocation. Fluorescence in situ hybridization (FISH investigations, however, detected the presence of a cryptic 11p13p14 deletion which included the WAGR region and involved approximately 7.5 Mb of DNA, including the PAX6 and WT1 genes. These results account for the patient's aniridia, and place her at high risk for developing Wilms' tumour. The absence of mental retardation in the patient suggests that the position of the distal breakpoint may also help to refine the mental retardation locus in the WAGR contiguous gene syndrome (Wilms', aniridia, genital anomalies and mental retardation.

  15. Towards Alzheimer's root cause: ECSIT as an integrating hub between oxidative stress, inflammation and mitochondrial dysfunction. Hypothetical role of the adapter protein ECSIT in familial and sporadic Alzheimer's disease pathogenesis.

    Soler-López, Montserrat; Badiola, Nahuai; Zanzoni, Andreas; Aloy, Patrick

    2012-07-01

    Here we postulate that the adapter protein evolutionarily conserved signalling intermediate in Toll pathway (ECSIT) might act as a molecular sensor in the pathogenesis of Alzheimer's disease (AD). Based on the analysis of our AD-associated protein interaction network, ECSIT emerges as an integrating signalling hub that ascertains cell homeostasis by the specific activation of protective molecular mechanisms in response to signals of amyloid-beta or oxidative damage. This converges into a complex cascade of patho-physiological processes. A failure to repair would generate severe mitochondrial damage and ultimately activate pro-apoptotic mechanisms, promoting synaptic dysfunction and neuronal death. Further support for our hypothesis is provided by increasing evidence of mitochondrial dysfunction in the disease etiology. Our model integrates seemingly controversial hypotheses for familial and sporadic forms of AD and envisions ECSIT as a biomarker to guide future therapies to halt or prevent AD. PMID:22513506

  16. Positive selection at codon 38 of the human KCNE1 (= minK gene and sporadic absence of 38Ser-coding mRNAs in Gly38Ser heterozygotes

    Pfeufer Arne

    2009-08-01

    Full Text Available Abstract Background KCNE1 represents the regulatory beta-subunit of the slowly activating delayed rectifier potassium channel (IKs. Variants of KCNE1 have repeatedly been linked to the long-QT syndrome (LQTS, a disorder which predisposes to deafness, ventricular tachyarrhythmia, syncope, and sudden cardiac death. Results We here analyze the evolution of the common Gly38Ser variant (rs1805127, using genomic DNAs, complementary DNAs, and HEK293-expressed variants of altogether 19 mammalian species. The between species comparison reveals that the human-specific Gly38Ser polymorphism evolved under strong positive Darwinian selection, probably in adaptation to specific challenges in the fine-tuning of IKs channels. The involved amino acid exchanges (Asp > Gly, Gly > Ser are moderately radical and do not induce apparent changes in posttranslational modification. According to population genetic analyses (HapMap phase II a heterozygote advantage accounts for the maintenance of the Gly38Ser polymorphism in humans. On the other hand, the expression of the 38Ser allele seems to be disadvantageous under certain conditions, as suggested by the sporadic deficiency of 38Ser-coding mRNAs in heterozygote Central Europeans and the depletion of homozygotes 38Ser in the Yoruban sample. Conclusion We speculate that individual differences in genomic imprinting or genomic recoding might have contributed to conflicting results of recent association studies between Gly38Ser polymorphism and QT phenotype. The findings thus highlight the relevance of mRNA data in future association studies of genotypes and clinical disorders. To the best of our knowledge, they moreover provide first time evidence for a unique pattern; i.e. coincidence of positive Darwinian selection and polymorphism with a sporadically suppressed expression of one allele.

  17. Investigation of the seasonal and local time variations of the high-altitude sporadic Na layer (Nas) formation and the associated midlatitude descending E layer (Es) in lower E region

    Yuan, T.; Wang, Jihong; Cai, Xuguang; Sojka, J.; Rice, D.; Oberheide, J.; Criddle, N.

    2014-07-01

    Recent studies have suggested that the major reservoir for the sporadic sodium layer (Nas) above 95 km in altitude is likely the sodium ion (Na+) within the sporadic E layer (Es) in the lower E region. However, theoretical and laboratory works have demonstrated that the metal ion's neutralization process is quite difficult above 100 km, while intensive neutral metal layers are consistently observed in the lower E region between 100 km and 125 km. In this paper, the multiyear observations of a Na lidar and an ionosonde at Utah State University (41.7°N, 111.8°W) and the nearby Bear Lake Observatory (41.9°N, 111.4°W) are utilized to understand their seasonal and local time variations. The comparison study between this set of the Nas and the nocturnal Nas observations in Beijing China (40.2°N, 116.1°E) reveals similar variations, but major differences are also noticed. To investigate the mechanism of these variations, the Hamburg Model of the Neutral and Ionized Atmosphere and the Climatological Tidal Model of the Thermosphere are utilized to simulate the ion vertical drift in the lower E region. The simulation shows that the lower E region is dominated by convergence of metal ions in summer, and ion diffusion prevails during winter. The tidal wind modulates the ion vertical drift speed and increases the likelihood of Es evolution at certain local times during the summer, while the tidal components of atmospheric density facilitate Nas formation by neutralizing the Na+ within the Es.

  18. Nanocoatings size effect in nanostructured films

    Aliofkhazraei, Mahmood

    2014-01-01

    Size effect in structures has been taken into consideration over the last years. In comparison with coatings with micrometer-ranged thickness, nanostructured coatings usually enjoy better and appropriate properties, such as strength and resistance. These coatings enjoy unique magnetic properties and are used with the aim of producing surfaces resistant against erosion, lubricant system, cutting tools, manufacturing hardened sporadic alloys, being resistant against oxidation and corrosion. This book reviews researches on fabrication and classification of nanostructured coatings with focus on size effect in nanometric scale. Size effect on electrochemical, mechanical and physical properties of nanocoatings are presented.

  19. Variability of sporadic E-layer semi transparency (foEs-fbEswith magnitude and distance from earthquake epicenters to vertical sounding stations

    E. V. Liperovskaya

    2003-01-01

    Full Text Available Variations of the Es-layer semi transparency co-efficient were analyzed for more than 100 earthquakes with magnitudes M > 4 and depths h Es-layer X = (foEs – fbEs/fbEs can characterize, for thin layers, the presence of small scale plasma turbulence. It is shown that the turbulence level decreases by ~ 10% during three days before earthquakes probably due to the heating of the atmosphere. On the contrary, the turbulence level increases by the same value from one to three days after the shocks. For earthquakes with magnitudes M > 5 the effect exists at distances up to 300 km from the epicenters. The effect could also exist for weak (M ~ 4 and shallow (depth < 50 km earthquakes at a distance smaller than 200 km from the epicenters.

  20. Effectively managing wound exudate.

    Chamanga, Edwin

    2015-09-01

    The management of wound exudate remains a clinical challenge despite technological advances in products with better exudate-handling capacities. This clinical challenge is occasionally encountered when thick exudate (viscous exudate) is present, and when most modern dressings do not possess the capabilities to manage the viscosity while enabling exudate absorption. Maceration to the peri-wound area poses another challenge, irrespective of the number of topical barrier application products on the market and the innovation of dressing products that lock exudate away or those that encourage vertical wicking. In addition to all the above, in clinical practice, the assessment and documentation of wound exudate remains sporadic, leading to the challenges of effective wound exudate dressing selection and cost-effective dressings. PMID:26322408