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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. Recurrent and sporadic Forbush-effects in deep solar minimum

    Kryakunova, O.; Belov, A.; Abunin, A.; Abunina, M.; Eroshenko, E.; Malimbayev, A.; Tsepakina, I.; Yanke, V.

    2015-08-01

    The effects of high-speed solar wind streams from low-latitude coronal holes and coronal mass ejections (CMEs) on cosmic ray intensity in 2007 are studied. The database on Forbush effects created at IZMIRAN, with cosmic ray density and anisotropy calculated by the Global Survey Method (GSM) on the basis of Neutron Monitor network data has been used. The behaviour of the mean characteristics by all the Forbush-effects in 2007 caused by coronal holes (interplanetary magnetic field intensity and solar wind velocity, 10 GV cosmic ray density and equatorial component of the cosmic ray anisotropy) is calculated by the epoch method. Features of the Forbush-effects caused by high-speed solar wind streams from low- latitude coronal holes and coronal mass ejections are described.

  3. Searching for possible effects on midlatitude sporadic E layer, caused by tropospheric lightning.

    Barta, Veronika; Haldoupis, Christos; Sátori, Gabriella; Buresova, Dalia

    2016-07-01

    Thunderstorms in the troposphere may affect the overlying ionosphere through electrodynamic and/or neutral atmosphere wave coupling processes. For example, it is well known that lightning discharges may impact upper atmosphere through quasi-electrostatic fields and strong electromagnetic pulses, leading to transient luminous phenomena, such as sprites and elves, along with electron heating and ionization changes in the upper D and lower E-region ionosphere that have been detected in VLF transmissions propagating in the earth-ionosphere waveguide. On the other hand, mechanical coupling between the troposphere and the ionosphere may be caused by neutral atmosphere gravity waves which are known to have their origin in massive thunderstorms. The effects of troposphere-ionosphere coupling during thunderstorms, are not yet fully established and understood, therefore there is need for more correlative studies, for example by using concurrent ionospheric and lightning observations. In the present work an effort is made to investigate a possible relationship between tropospheric lighting and sporadic E layer, which are known to dominate at bottomside ionosphere and at middle latitudes during summer. For this, a correlative analysis was undertaken using lightning data obtained with the LINET lightning detection network in Central Europe, and E region ionospheric parameters (fmin, foE, foEs, fbEs) measured with the Pruhonice (50° N, 14.5° E) DPS-4D digisonde in the summer of 2009. For direct correlation with the digisonde data, the lightning activity was quantified every 15 minutes in coincidence with the measured ionogram parameters. In the search for relation between lightning and sporadic E, the digisonde observations during lightning were also compared with those taken during a number of tropospheric storm-free days in Pruhonice. The results of this correlative study did not provide evidence of significance that favors a relationship between tropospheric lightning and

  4. 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

  5. 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.

  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. [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

  8. Evaporation of high speed sporadic meteors

    E. Murad

    2004-01-01

    Full Text Available Recent measurements conducted at the Arecibo Observatory report high-speed sporadic meteors having velocities near 50 km/s. The results seem to indicate a bimodal velocity distribution in the sporadic meteors (maxima at ~20 km/s and ~50 km/s. The particles have a maximum mass of ~1µg. This paper will present an analysis of the ablation of 1µg meteoroids having velocities of 20, 30, 50, and 70 km/s. The calculations show that there is fractionation even for the fast meteoroids, the effect being particularly noticeable for the 1µg sporadic particles, and less so for the heavier particles. The relevance of the calculations to the radar observations of the sporadic meteors will be discussed.

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

    Khalili, Mohsen; Hamzeh, Faezeh

    2010-01-01

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

  10. Genetics Home Reference: sporadic hemiplegic migraine

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

  11. Effect of Royal Jelly on spatial learning and memory in rat model of streptozotocin-induced sporadic Alzheimer's disease

    Zohre Zamani; Parham Reisi; Hojjatallah Alaei; Ali Asghar Pilehvarian

    2012-01-01

    Background: It has been recently demonstrated that Royal jelly (RJ) has a beneficial role on neural functions. Alzheimer′s disease (AD) is associated with impairments of learning and memory. Therefore, the present study was designed to examine the effect of RJ on spatial learning and memory in rats after intracerebroventricular injection of streptozotocin (icv-STZ). Materials and Methods: Rats were infused bilaterally with an icv injection of STZ, while sham rats received vehicle only. Th...

  12. Aberrant Gene Promoter Methylation Associated with Sporadic Multiple Colorectal Cancer

    Victoria Gonzalo; Juan José Lozano; Jenifer Muñoz; Francesc Balaguer; Maria Pellisé; Cristina Rodríguez de Miguel; Montserrat Andreu; Rodrigo Jover; Xavier Llor; M Dolores Giráldez; Teresa Ocaña; Anna Serradesanferm; Virginia Alonso-Espinaco; Mireya Jimeno; Miriam Cuatrecasas

    2010-01-01

    BACKGROUND: Colorectal cancer (CRC) multiplicity has been mainly related to polyposis and non-polyposis hereditary syndromes. In sporadic CRC, aberrant gene promoter methylation has been shown to play a key role in carcinogenesis, although little is known about its involvement in multiplicity. To assess the effect of methylation in tumor multiplicity in sporadic CRC, hypermethylation of key tumor suppressor genes was evaluated in patients with both multiple and solitary tumors, as a proof-of-...

  13. Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: The Netherlands cohort study on diet and cancer

    Engeland, M. van; Weijenberg, M.P.; Roemen, G.M.J.M.; Brink, M.; Bruïne, A.P. de; Goldbohm, R.A.; Brandt, P.A. van den; Baylin, S.B.; Goeij, A.F.P.M. de; Herman, J.G.

    2003-01-01

    Sporadic colorectal cancer (CRC) is characterized by genetic and epigenetic changes such as regional DNA hypermethylation and global DNA hypomethylation. Epidemiological and animal studies suggest that aherrant DNA methylation is associated with low dietary folate intake, which is aggravated by high

  14. Does sporadic Leber's disease exist?

    Nikoskelainen, E; Nummelin, K; Savontaus, M L

    1988-12-01

    This study gives some illustrative case reports of the difficulties in the diagnosis of Leber's hereditary optic neuroretinopathy. It underlies the importance of careful family history and search for peripapillary microangiopathy in the maternal relatives of patients suspected to suffer from Leber's disease. The article casts doubt on the existence of so-called sporadic Leber's disease. PMID:2977137

  15. Sporadic ampullary hamartoma simulating cancer

    Moyana, Terence N.; Miller, Grant G.; Keith, Roger G.

    1997-01-01

    Ampullary tumours are uncommon. They may occur with familial polyposis syndromes or neurofibromatosis. It can be difficult to distinguish them from their periampullary counterparts on clinical, radiologic or histologic grounds. Because most ampullary and periampullary tumours are malignant, they tend to be treated by radical surgery. A 67-year-old man was seen with a sporadic ampullary hamartoma that simulated cancer. It was succesfully treated by local excision through a transverse duodenotomy.

  16. 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

  17. Sporadic Layer es and Siesmic Activity

    Alimov, Obid; Blokhin, Alexandr; Kalashnikova, Tatyana

    2016-07-01

    To determine the influence of seismogenic disturbances on the calm state of the iono-sphere and assess the impact of turbulence development in sporadic-E during earthquake prepa-ration period we calculated the variation in the range of semitransparency ∆fES = f0ES - fbES. The study was based primarily on the ionograms obtained by vertical sounding of the ionosphere at Dushanbe at nighttime station from 15 to 29 August 1986. In this time period four successive earthquakes took place, which serves the purpose of this study of the impact of seis-mogenic processes on the intensity of the continuous generation of ionospheric turbulence. Analysis of the results obtained for seismic-ionospheric effects of 1986 earthquakes at station Dushanbe has shown that disturbance of ionospheric parameters during earthquake prepa-ration period displays a pronounced maximum with a duration of t = 1-6 hours. Ionospheric effects associated with the processes of earthquake preparation emerge quite predictably, which verifies seismogenic disturbances in the ionosphere. During the preparation of strong earthquakes, ionograms of vertical sounding produced at station Dushanbe - near the epicenter area - often shown the phenomenon of spreading traces of sporadic Es. It is assumed that the duration of manifestation of seismic ionospheric precursors in Du-shanbe τ = 1 - 6 hours may be associated with deformation processes in the Earth's crust and var-ious faults, as well as dissimilar properties of the environment of the epicentral area. It has been shown that for earthquakes with 4.5 ≤ M ≤ 5.5 1-2 days prior to the event iono-spheric perturbations in the parameters of the sporadic layer Es and an increase in the value of the range of semitransparency Es - ΔfEs were observed, which could lead to turbulence at altitudes of 100-130 km.

  18. 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.

  19. 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.

  20. 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.

  1. Sporadic wind wave horse-shoe patterns

    S. Yu. Annenkov

    1999-01-01

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

  2. 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.)

  3. Sporadic Ataxia and Multiple System Atrophy (MSA)

    ... It is unclear why some people with sporadic ataxia progress to develop MSA whereas others do not. Many people with adult onset cerebellar degeneration may have the dominantly inherited form, which ...

  4. Effects of sporadic E-layer characteristics on spread-F generation in the nighttime ionosphere near a northern equatorial anomaly crest during solar minimum

    Lee, C. C.; Chen, W. S.

    2015-06-01

    This study is to know how the characteristics of sporadic E-layer (Es-layer) affect the generation of spread-F in the nighttime ionosphere near the crest of equatorial ionization anomaly during solar minimum. The data of Es-layer parameters and spread-F are obtained from the Chungli ionograms of 1996. The Es-layer parameters include foEs (critical frequency of Es-layer), fbEs (blanketing frequency of Es-layer), and Δf (≡foEs-fbEs). Results show that the nighttime variations of foEs and fbEs medians (Δf medians) are different from (similar to) that of the occurrence probabilities of spread-F. Because the total number of Es-layer events is greater than that of spread-F events, the comparison between the medians of Es-layer parameters and the occurrence probabilities of spread-F might have a shortfall. Further, we categorize the Es-layer and spread-F events into each frequency interval of Es-layer parameters. For the occurrence probabilities of spread-F versus foEs, an increasing trend is found in post-midnight of all three seasons. The increasing trend also exists in pre-midnight of the J-months and in post-midnight of all seasons, for the occurrence probabilities of spread-F versus Δf. These demonstrate that the spread-F occurrence increases with increasing foEs and/or Δf. Moreover, the increasing trends indicate that polarization electric fields generated in Es-layer assist to produce spread-F, through the electrodynamical coupling of Es-layer and F-region. Regarding the occurrence probabilities of spread-F versus fbEs, the significant trend only appears in post-midnight of the E-months. This implies that fbEs might not be a major factor for the spread-F formation.

  5. 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.

  6. 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.

  7. Sporadically Torqued Accretion Disks Around Black Holes

    Garofalo, D; Garofalo, David; Reynolds, Christopher S.

    2005-01-01

    The assumption that black hole accretion disks possess an untorqued inner boundary, the so-called zero torque boundary condition, has been employed by models of black hole disks for many years. However, recent theoretical and observational work suggests that magnetic forces may appreciably torque the inner disk. This raises the question of the effect that a time-changing magnetic torque may have on the evolution of such a disk. In particular, we explore the suggestion that the ``Deep Minimum State'' of the Seyfert galaxy MCG--6-30-15 can be identified as a sporadic inner disk torquing event. This suggestion is motivated by detailed analyses of changes in the profile of the broad fluorescence iron line in XMM-Newton spectra. We find that the response of such a disk to a torquing event has two phases; an initial damming of the accretion flow together with a partial draining of the disk interior to the torque location, followed by a replenishment of the inner disk as the system achieves a new (torqued) steady-st...

  8. Segregation and sporadic cases in families with Hunter's syndrome.

    Machill, G; Barbujani, G; Danieli, G A; Herrmann, F H

    1991-01-01

    Segregation analysis on five samples of families with Hunter's syndrome (158 cases overall) shows that the mutant allele segregates in agreement with Mendelian expectations for an X linked recessive disease, but the proportion of sporadic cases is significantly lower than expected under mutation-selection equilibrium. Heterogeneity among the samples is apparent, but it is caused entirely by a sample of Ashkenazi families, whose segregation pattern has previously been interpreted as supporting the hypothesis of prenatal selection in favour of the pathological allele. Conversely, our joint analysis of the five samples by a maximum likelihood approach does not suggest segregation distortion. Possible reasons for the apparent lack of sporadic cases include the effect of ascertainment bias. PMID:1908009

  9. 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).

  10. Neurofibromatosis Type 1 and Sporadic Optic Gliomas

    J Gordon Millichap

    2002-01-01

    The natural history of sporadic optic gliomas was compared with that of optic gliomas associated with neurofibromatosis type 1 (NF1) in a study using a Children’s Tumor Registry (CTR) and an NF1 Database (NF1DB) at St Mary’s Hospital, Manchester, UK.

  11. Neurofibromatosis Type 1 and Sporadic Optic Gliomas

    J Gordon Millichap

    2002-10-01

    Full Text Available The natural history of sporadic optic gliomas was compared with that of optic gliomas associated with neurofibromatosis type 1 (NF1 in a study using a Children’s Tumor Registry (CTR and an NF1 Database (NF1DB at St Mary’s Hospital, Manchester, UK.

  12. Unique case of sporadic multiple gastro intestinal stromal tumour

    Luigina Graziosi

    2015-01-01

    Conclusion: We are presenting a sporadic and exemplary case of 42 multiple GISTs in a young female patient localized trough out all the gastrointestinal tract. This is the only case of sporadic multiple GISTs reported in literature.

  13. 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

  14. Molecular pathogenesis of sporadic colorectal cancers.

    Yamagishi, Hidetsugu; Kuroda, Hajime; Imai, Yasuo; Hiraishi, Hideyuki

    2016-01-01

    Colorectal cancer (CRC) results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma. Approximately 75% of CRCs are sporadic and occur in people without genetic predisposition or family history of CRC. During the past two decades, sporadic CRCs were classified into three major groups according to frequently altered/mutated genes. These genes have been identified by linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on the basis of functional data. In the first half of this review, we describe the genetic pathways of sporadic CRCs and their clinicopathologic features. Recently, large-scale genome analyses have detected many infrequently mutated genes as well as a small number of frequently mutated genes. These infrequently mutated genes are likely described in a limited number of pathways. Gene-oriented models of CRC progression are being replaced by pathway-oriented models. In the second half of this review, we summarize the present knowledge of this research field and discuss its prospects. PMID:26738600

  15. 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.

  16. Human Immunodeficiency Virus Associated Sporadic Nonfamilial Porphyria Cutanea Tarda.

    Guha, Sibashish Kamal; Bandyopadhyay, Debabrata; Saha, Abanti; Lal, Niharika Ranjan

    2016-01-01

    Porphyria cutanea tarda (PCT), a relatively uncommon metabolic disease, is the most common cutaneous porphyria. Here, we present the case of a patient diagnosed with sporadic, nonfamilial PCT that presented with classical cutaneous findings and multiple risk factors, including alcohol abuse, human immunodeficiency virus/AIDS, that have been strongly associated with the sporadic form of PCT. PMID:27293254

  17. Tumour suppressor genes in sporadic epithelial ovarian cancer

    Liu, Ying; Ganesan, Trivadi S

    2002-01-01

    Ovarian cancer is the most frequent cause of death from gynaecological malignancies in the western world, and sporadic epithelial ovarian cancer is its most predominant form. The aetiology of sporadic ovarian cancer remains unknown. Genetic studies have enabled a better understanding of the evolu...

  18. Reflection of radio waves by sporadic-E layers

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

    1977-01-01

    A full-wave analysis of the reflection coefficient is developed and applied to electron-density profiles of midlatitude sporadic-E layers observed by rocket-borne probes. It is shown that partial reflection from the large electron-density gradients at the upper and lower boundaries of sporadic-E layers does not account for the partial transparency observed by ionosondes.

  19. Human immunodeficiency virus associated sporadic nonfamilial porphyria cutanea tarda

    Sibashish Kamal Guha; Debabrata Bandyopadhyay; Abanti Saha; Niharika Ranjan Lal

    2016-01-01

    Porphyria cutanea tarda (PCT), a relatively uncommon metabolic disease, is the most common cutaneous porphyria. Here, we present the case of a patient diagnosed with sporadic, nonfamilial PCT that presented with classical cutaneous findings and multiple risk factors, including alcohol abuse, human immunodeficiency virus/AIDS, that have been strongly associated with the sporadic form of PCT.

  20. Human Immunodeficiency Virus Associated Sporadic Nonfamilial Porphyria Cutanea Tarda

    Guha, Sibashish Kamal; Bandyopadhyay, Debabrata; Saha, Abanti; Lal, Niharika Ranjan

    2016-01-01

    Porphyria cutanea tarda (PCT), a relatively uncommon metabolic disease, is the most common cutaneous porphyria. Here, we present the case of a patient diagnosed with sporadic, nonfamilial PCT that presented with classical cutaneous findings and multiple risk factors, including alcohol abuse, human immunodeficiency virus/AIDS, that have been strongly associated with the sporadic form of PCT.

  1. [Sporadic Late-Onset Nemaline Myopathy Associated with MGUS].

    Nagai, Taiji; Sunada, Yoshihide

    2015-12-01

    Sporadic late-onset nemaline myopathy is an uncommon disease. Clinically, it is characterized by progressive muscle weakness that can develop in limbs or axial muscles. Asymmetrical distal weakness, facial weakness, dropped head, and dysphagia can also occur. Since the serum creatine kinase level usually remains within the normal range, patients can be misdiagnosed with motor neuron disease. Recognition of nemaline rods on muscle biopsy is crucial for accurate diagnosis. If it is associated with monoclonal gammopathy of undetermined significance, the outcome is known to be unfavorable. In spite of various immunotherapies such as corticosteroids, immunosuppressants, and plasmapheresis, most patients die of respiratory failure within 5 years. Since the efficacy of autologous stem cell transplantation following high-dose melphalan was first reported in 2008, there have been accumulating reports that showed the positive effect of this therapy for the disease. PMID:26618766

  2. Aberrant gene promoter methylation associated with sporadic multiple colorectal cancer.

    Victoria Gonzalo

    Full Text Available BACKGROUND: Colorectal cancer (CRC multiplicity has been mainly related to polyposis and non-polyposis hereditary syndromes. In sporadic CRC, aberrant gene promoter methylation has been shown to play a key role in carcinogenesis, although little is known about its involvement in multiplicity. To assess the effect of methylation in tumor multiplicity in sporadic CRC, hypermethylation of key tumor suppressor genes was evaluated in patients with both multiple and solitary tumors, as a proof-of-concept of an underlying epigenetic defect. METHODOLOGY/PRINCIPAL FINDINGS: We examined a total of 47 synchronous/metachronous primary CRC from 41 patients, and 41 gender, age (5-year intervals and tumor location-paired patients with solitary tumors. Exclusion criteria were polyposis syndromes, Lynch syndrome and inflammatory bowel disease. DNA methylation at the promoter region of the MGMT, CDKN2A, SFRP1, TMEFF2, HS3ST2 (3OST2, RASSF1A and GATA4 genes was evaluated by quantitative methylation specific PCR in both tumor and corresponding normal appearing colorectal mucosa samples. Overall, patients with multiple lesions exhibited a higher degree of methylation in tumor samples than those with solitary tumors regarding all evaluated genes. After adjusting for age and gender, binomial logistic regression analysis identified methylation of MGMT2 (OR, 1.48; 95% CI, 1.10 to 1.97; p = 0.008 and RASSF1A (OR, 2.04; 95% CI, 1.01 to 4.13; p = 0.047 as variables independently associated with tumor multiplicity, being the risk related to methylation of any of these two genes 4.57 (95% CI, 1.53 to 13.61; p = 0.006. Moreover, in six patients in whom both tumors were available, we found a correlation in the methylation levels of MGMT2 (r = 0.64, p = 0.17, SFRP1 (r = 0.83, 0.06, HPP1 (r = 0.64, p = 0.17, 3OST2 (r = 0.83, p = 0.06 and GATA4 (r = 0.6, p = 0.24. Methylation in normal appearing colorectal mucosa from patients with multiple and solitary CRC showed no relevant

  3. 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

  4. 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

  5. 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

  6. 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; Miller, Bruce L.; 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 (...

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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...

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

    Lisa Placanica; Lei Zhu; Yue-Ming Li

    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 gamma-secretase result in rare forms of early onset AD due to the aberrant production of Abeta42 peptides, which are the major constituents of senile plaques. However, the effect of age and gender on gamma-secret...

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

    Khan, Amil H.; Deepa Rasaily

    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 evaluat...

  14. 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.

  15. Genetic alterations and expression of inhibitor of growth 1 in human sporadic colorectal cancer

    Li-Sheng Chen; Jian-Bao Wei; Yong-Chun Zhou; Sen Zhang; Jun-Lin Liang; Yun-Fei Cao; Zong-Jiang Tang; Xiao-Long Zhang; Feng Gao

    2005-01-01

    AIM: To explore the effect and significance of inhibitor of growth 1 (ING1) gene in carcinogenesis and progression of human sporadic colorectal cancer.METHODS: mRNA expression, mutation, and loss of heterozygosity (LOH) of ING1 gene in 35 specimens of sporadic colorectal cancer tissues and the matched normal mucous membrane tissues were detected by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR),PCR-single strain conformation polymorphism (PCR-SSCP)and PCR-simple sequence length polymorphism (PCR-SSLP)using microsatellite markers, respectively.RESULTS: The average ratios of light intensities of p33ING1b and p47ING1a mRNA expression in the cancerous tissues were significantly lower than those in normal tissues.The difference between the two mRNA splices was not significant in the matched tissues. In addition, the ratios of light intensities of p33INB1b and p47ING1a mRNA expression in the cancerous tissues of Dukes' stages C and D were significantly lower than those in cancerous tissues of Dukes'stages A and B. However, no mutation of ING1 gene was detected in all 35 cases; only 4 cases of LOH (11.4%)were found.CONCLUSION: p33ING1b and p47ING1a mRNA expressions are closely related with the carcinogenesis and progression of human sporadic colorectal cancer. No mutation of ING1gene is found, and there are only few LOH in sporadic colorectal cancers. These might not be the main reasons for the down regulation of ING1 expression. Its low expression may happen in transcription or post-transcription.

  16. 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.

  17. 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

  18. Interpretation of electrodiagnostic findings in sporadic progressive muscular atrophy

    Visser, J.; de Visser, M.; Van den Berg-Vos, R. M.; Van den Berg, L. H.; Wokke, J. H. J.; De Jong, J. M. B. V.; Franssen, H.

    2008-01-01

    Objective We present the electrophysiologic data at baseline of 37 patients who were included in our prospective study on sporadic adult-onset progressive muscular atrophy (PMA). The aim was to correlate electrophysiological. signs of lower motor neuron (LMN) loss with clinical signs of LMN loss, an

  19. 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...... and excluded 61.5% of the tumors from MMR testing. This clinicopathologic index thus successfully selects MMR-defective colon cancers. Udgivelsesdato: 2008-Feb...

  20. Risk factors for sporadic colorectal cancer in southern Chinese

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

    2009-01-01

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

  1. 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

  2. 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.

  3. 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.

  4. Segregation and sporadic cases in families with Hunter's syndrome.

    Machill, G; Barbujani, G.; Danieli, G A; Herrmann, F H

    1991-01-01

    Segregation analysis on five samples of families with Hunter's syndrome (158 cases overall) shows that the mutant allele segregates in agreement with Mendelian expectations for an X linked recessive disease, but the proportion of sporadic cases is significantly lower than expected under mutation-selection equilibrium. Heterogeneity among the samples is apparent, but it is caused entirely by a sample of Ashkenazi families, whose segregation pattern has previously been interpreted as supporting...

  5. Fusion systems with some sporadic J-components

    Lynd, Justin; Rainbolt, Julianne

    2016-01-01

    Aschbacher's program for the classification of simple fusion systems of "odd" type at the prime 2 has two main stages: the classification of 2-fusion systems of subintrinsic component type and the classification of 2-fusion systems of J-component type. We make a contribution to the latter stage by classifying 2-fusion systems with a J-component isomorphic to the 2-fusion systems of several sporadic groups under the assumption that the centralizer of such a component is cyclic.

  6. Sporadic cases are the norm for complex disease

    Yang, Jian; Visscher, Peter M; Wray, Naomi R.

    2009-01-01

    The results of genome-wide association studies have revealed that most human complex diseases (for example, cancer, diabetes and psychiatric disorders) are affected by a large number of variants, each of which explains a small increase in disease risk, suggesting a pattern of polygenic inheritance. At the same time, it has been argued that most complex diseases are genetically heterogeneous because many sporadic cases are observed, as well as cases with a family history. In this study, under ...

  7. Brain sonography in African infants with complicated sporadic bacterial meningitis

    Kenneth C Eze; Sam U Enukegwu; Odike, Angela I.

    2013-01-01

    Background: To determine the structural findings in brain sonography of African infants with complicated sporadic bacterial meningitis. Materials and Methods: Retrospective assessment of medical records of patients who underwent brain sonography on account of complicated bacterial meningitis. The brain sonography was carried out over a 4-year period (between September 15, 2004 and September 14, 2008). Result : A total of 86 infants were studied (40 boys and 46 girls in a ratio of 1:1.1); more...

  8. Field Cancerization in Sporadic Colon Cancer

    Park, Soo-Kyung; Song, Chang Seok; Yang, Hyo-Joon; Jung, Yoon Suk; Choi, Kyu Yong; Koo, Dong Hoe; Kim, Kyung Eun; Jeong, Kyung Uk; Kim, Hyung Ook; Kim, Hungdai; Chun, Ho-Kyung; Park, Dong Il

    2016-01-01

    Background/Aims Aberrant DNA methylation has a specific role in field cancerization. Certain molecular markers, including secreted frizzled-related protein 2 (SFRP2), tissue factor pathway inhibitor 2 (TFPI2), N-Myc downstream-regulated gene 4 (NDRG4) and bone morphogenic protein 3 (BMP3), have previously been shown to be hypermethylated in colorectal cancer (CRC). We aim to examine field cancerization in CRC based on the presence of aberrant DNA methylation in normal-appearing tissue from CRC patients. Methods We investigated promoter methylation in 34 CRC patients and five individuals with normal colonoscopy results. CRC patients were divided into three tissue groups: tumor tissue, adjacent and nonadjacent normal-appearing tissue. The methylation status (positive: methylation level >20%) of SFRP2, TFPI2, NDRG4, and BMP3 promoters was investigated using methylation-specific PCR. Results The methylation frequencies of the SFRP2, TFPI2, NDRG4 and BMP3 promoters in tumor/adjacent/nonadjacent normal-appearing tissue were 79.4%/63.0%/70.4%, 82.4%/53.6%/60.7%, 76.5%/61.5%/69.2%, 41.2%/35.7%/50.0%, respectively. The methylation levels of the SFRP,TFPI2, NDRG4 and BMP3 promoters in tumor tissues were significantly higher than those in normal-appearing tissue (SFRP2, p=0.013; TFPI2, p<0.001; NDRG4, p=0.003; BMP3, p=0.001). No significant correlation was observed between the methylation levels of the promoters and the clinicopathological variables. Conclusions The field effect is present in CRC and affects both the adjacent and nonadjacent normal-appearing mucosa. PMID:27114416

  9. Stable and sporadic symbiotic communities of coral and algal holobionts.

    Hester, Eric R; Barott, Katie L; Nulton, Jim; Vermeij, Mark Ja; Rohwer, Forest L

    2016-05-01

    Coral and algal holobionts are assemblages of macroorganisms and microorganisms, including viruses, Bacteria, Archaea, protists and fungi. Despite a decade of research, it remains unclear whether these associations are spatial-temporally stable or species-specific. We hypothesized that conflicting interpretations of the data arise from high noise associated with sporadic microbial symbionts overwhelming signatures of stable holobiont members. To test this hypothesis, the bacterial communities associated with three coral species (Acropora rosaria, Acropora hyacinthus and Porites lutea) and two algal guilds (crustose coralline algae and turf algae) from 131 samples were analyzed using a novel statistical approach termed the Abundance-Ubiquity (AU) test. The AU test determines whether a given bacterial species would be present given additional sampling effort (that is, stable) versus those species that are sporadically associated with a sample. Using the AU test, we show that coral and algal holobionts have a high-diversity group of stable symbionts. Stable symbionts are not exclusive to one species of coral or algae. No single bacterial species was ubiquitously associated with one host, showing that there is not strict heredity of the microbiome. In addition to the stable symbionts, there was a low-diversity community of sporadic symbionts whose abundance varied widely across individual holobionts of the same species. Identification of these two symbiont communities supports the holobiont model and calls into question the hologenome theory of evolution. PMID:26555246

  10. 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.

  11. 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

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

    Takebayashi, Shigeo [Department of Radiology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama 232-0024 (Japan)], E-mail: take2922@urahp.yokohama-cu.ac.jp; Horikawa, Ayumi; Arai, Mito; Iso, Shinichiroh [Department of Radiology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama 232-0024 (Japan); Noguchi, Kazumi [Department of Urology, Yokohama City University Medical Center, Yokohama (Japan)

    2009-10-15

    Purpose: We evaluated the efficacy and side effects of transarterial ethanol ablation in sporadic and non-hemorrhaging angiomyolipomas (AMLs) in the kidney. Material and Methods: A total of 10 patients with solitary and sporadic AMLs underwent selective transarterial absolute ethanol ablation for prophylaxis against hemorrhage. We confirmed the ratio areas of tumor vessel on angiogram, those of infraction on post-ablation computed tomography (CT) and those of tumor reduction in a 3-, 6- and 12-month follow-up CT. Results: Once or twice a single infusion of 1 or 2 ml absolute ethanol achieved in a total occlusion of 22 feeding arteries which consisted of 7 proximal interlobar arteries, 12 distal interlobar arteries and 3 renal capsular arteries. Nontarget occlusion did not occur by ethanol reflux in any cases but occurred causing spasms provoked by repeated inflation and deflation of the balloon in one case. Total occlusion of tumor vessels was observed in 7 patients and 92-95% occlusion in 3. Ethanol ablation produced 1.8-22.5% (mean 8.4 {+-} 6.8%) areas of infarctions but the outcome was not serious in all cases. Mean percentage areas of tumor reduction were 29.4 {+-} 10.6% in a 3-month follow-up, 45.7 {+-} 11.9% in a 6-month and 59.3 {+-} 11.5% in a 12-month follow-up. Conclusions: Absolute ethanol ablation for sporadic and non-hemorrhaging AML is safe and effective in reducing majority of tumor area in a 1-year follow-up.

  13. 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.

  14. EphB2 SNPs and sporadic prostate cancer risk in African American men.

    Christiane M Robbins

    Full Text Available The EphB2 gene has been implicated as a tumor suppressor gene somatically altered in both prostate cancer (PC and colorectal cancer. We have previously shown an association between an EphB2 germline nonsense variant and risk of familial prostate cancer among African American Men (AAM. Here we set out to test the hypothesis that common variation within the EphB2 locus is associated with increased risk of sporadic PC in AAM. We genotyped a set of 341 single nucleotide polymorphisms (SNPs encompassing the EphB2 locus, including known and novel coding and noncoding variants, in 490 AA sporadic PC cases and 567 matched controls. Single marker-based logistical regression analyses revealed seven EphB2 SNPs showing statistically significant association with prostate cancer risk in our population. The most significant association was achieved for a novel synonymous coding SNP, TGen-624, (Odds Ratio (OR  = 0.22; 95% Confidence Interval (CI 0.08-0.66, p = 1×10(-5. Two other SNPs also show significant associations toward a protective effect rs10465543 and rs12090415 (p = 1×10(-4, OR = 0.49 and 0.7, respectively. Two additional SNPs revealed trends towards an increase in risk of prostate cancer, rs4612601 and rs4263970 (p = 0.001, OR = 1.35 and 1.31, respectively. Furthermore, haplotype analysis revealed low levels of linkage disequilibrium within the region, with two blocks being associated with prostate cancer risk among our population. These data suggest that genetic variation at the EphB2 locus may increase risk of sporadic PC among AAM.

  15. 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.

  16. 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.

  17. 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.

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

    HAN Shun-chang

    2013-04-01

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

  19. Sporadic Cerebral Amyloid Angiopathy: Pathophysiology, Neuroimaging Features, and Clinical Implications.

    Boulouis, Gregoire; Charidimou, Andreas; Greenberg, Steven M

    2016-06-01

    Sporadic cerebral amyloid angiopathy is a small vessel disorder defined pathologically by progressive amyloid deposition in the walls of cortical and leptomeningeal vessels resulting from disruption of a complex balance between production, circulation, and clearance of amyloid-β peptide (Aβ) in the brain. Cerebral amyloid angiopathy is a major cause of lobar symptomatic intracerebral hemorrhage, transient focal neurologic episodes, and a key contributor to vascular cognitive impairment. The mechanisms and consequences of amyloid-β deposition at the pathological level and its neuroimaging manifestations, clinical consequences, and implications for patient care are addressed in this review. PMID:27214698

  20. 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

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

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina;

    2008-01-01

    were linked to MMR status based on immunostaining and BRAF mutation status.MMR defects were identified in 22.7% of the tumors, with 46 classified as sporadic. When the clinical parameters of age, sex, and proximal tumor location were combined with the morphologic features with the highest relative...... 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...

  2. 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

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

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

    2015-01-01

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

  4. 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

  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. 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...

  7. Study of sporadic-E clouds by backscatter radar

    Z. Houminer

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

  8. 白芍总苷联合吡美莫司治疗散发型白癜风的临床疗效及相关实验研究%Clinical Effect and Relevant Experimental Study in Patients with Sporadic Vitiligo by the Combination of Total Glucosides of Paeony and Pimecrolimus

    叶蓉; 聂李平; 胡小平; 黄星涛; 江晓君

    2013-01-01

    Objective To investigate treatment effect in patients with sporadic vitiligo by the combination of total glucosides of paeony (TGP) and pimecrolimus.Methods According to the course of disease,45 patients were divided into three groups:less than six months,between six months and two years,more than two years.All groups were treated with the combination ofTGP and pimeerolimus.The CD47CD8+ T lymphocyte ratio and the CD4+CD25+ Treg level in patients of the three groups,before and after treatment,were detected by flow cytometrv.Meanwhile,the skin lesion recovery was evaluated.Results In the same group,the lesions in patients had different degree of recovery after treatment,the CD4+/CD8+ T lymphocyte ratio and the CD4+CD25+ Treg level increased after treatment (P<0.05).The group which course of disease was less than six months,increased significantly (P<0.05).Conclusion TGP combined with pimecrolimus could promote the recovery of skin lesions in patients with sporadic vitiligo,improve the CD4+/CD8+ T lymphocyte ratio and the CD4+CD25+ Treg level in peripheral blood.%目的 评价白芍总苷联合吡美莫司对散发型自癜风患者的治疗效果.方法 45例患者根据病程分3组:<6个月组、6个月~2年组及≥2年组,均给予白芍总苷联合吡美莫司软膏治疗,用流式细胞仪对3组患者治疗前后外周血CD4+/CD8+T细胞比值及CD4+CD25+调节性T细胞水平进行检测,同时评价皮损恢复情况 结果 与治疗前相比,治疗后3组散发型白癜风患者皮损均有不同程度的恢复,外周血中CD4+/CD8+T细胞比值和CD4+CD25+调节性T细胞水平均升高(P<0.05),且<6个月组明显高于另2组,差异有统计学意义(P<0.05) 结论 白芍总苷联合吡美莫司能促进散发型白癜风患者皮损恢复,改善外周血CD47CD8+T细胞比值,提高CD4+CD25+调节性T细胞水平.

  9. Estrogen and progesterone receptor gene polymorphisms and sporadic breast cancer risk: a Spanish case-control study.

    Fernández, L P; Milne, R L; Barroso, E; Cuadros, M; Arias, J I; Ruibal, A; Benítez, J; Ribas, G

    2006-07-15

    Estrogens, and to a lesser extent progesterones, influence the proliferation, differentiation and physiology of breast tissue as well as the development and progression of breast cancer. Genetic variants in the steroid hormone receptor genes ESR1 and PGR (belonging to the nuclear receptor superfamily) could therefore modify sporadic breast cancer susceptibility. Two studies have shown a protective effect associated with variants in ESR1 in 2 distinct populations. We studied 4 single nucleotide polymorphisms (SNPs) in ESR1 and 4 in PGR in 550 consecutive and unrelated sporadic Spanish breast cancer patients and 564 healthy Spanish controls. We observed a dominant protective effect for the S10S variant in ESR1, with an estimated odds ratio (OR) of 0.75 (95% CI = 0.58-0.97; p = 0.03) although functional studies did not show changes in the RNA stability. A small subset of individuals carried a haplotype combination that corroborates this protection. No other SNP considered in either gene was found to be associated with sporadic breast cancer. Our results obtained in a European population confirm the protective role of the S10S variant in ESR1, previously reported in an Asian and a European-American population. PMID:16477637

  10. Sporadic impact flashes on the Moon and their implications

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

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

  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. Aging and renewal events in sporadically modulated systems

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

  13. 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

  14. Paraplegin mutations in sporadic adult-onset upper motor neuron syndromes.

    Brugman, F.; Scheffer, H.; Wokke, J.H.; Nillesen, W.M.; Visser, M. de; Aronica, E.; Veldink, J.H.; Berg, LH van den

    2008-01-01

    OBJECTIVE: To investigate the frequency of autosomal recessive paraplegin mutations in patients with sporadic adult-onset upper motor neuron (UMN) syndromes. METHODS: We analyzed the paraplegin gene in 98 Dutch patients with a sporadic adult-onset UMN syndrome. Inclusion criteria were a progressive

  15. 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....

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

    J. Höffner

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

  17. Artificial periodic irregularities in the lower ionosphere, atmospheric waves and sporadic E-layer

    Bakhmetieva, Nataliya V.; Egerev, M. N.; Tolmacheva, A. V.; Vyakhirev, V. D.

    2010-05-01

    the ?(h) dependence makes it possible to determine electron density profile N(h). The profile is used for determination of the neutral temperature and density, the turbulent velocity and also the sporadic E-layer parameters (Belikovich V.V. Radiophys. Quantum Electron., 2006, Vol. 49, No. 9). Vertical velocity was determined by measuring the phase of the probe radio waves scattered from API after switching off the power heating facility, i.e., at the API relaxation stage. The velocity and N(h) data have been used for estimation the total density metallic ions and the effective recombination rate at the sporadic E-layer maximum. The measured vertical velocity shift was about 5×10-3-10-4 c-1. The shift can be caused by acoustic gravity waves and is sufficient for collecting of metal ions in sporadic E-layer.

  18. 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

  19. 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.

  20. Neurosecretases provide strategies to treat sporadic and familial Alzheimer disorders.

    Marks, Neville; Berg, Martin J

    2008-01-01

    Recent discoveries on neurosecretases and their trafficking to release fibril-forming neuropeptides or other products, are of interest to pathology, cell signaling and drug discovery. Nomenclature arose from the use of amyloid precursor protein (APP) as a prototypic type-1 substrate leading to the isolation of beta-secretase (BACE), multimeric complexes (gamma-secretase, gamma-SC) for intramembranal cleavage, and attributing a new function to well-characterized metalloproteases of the ADAM family (alpha-secretase) for normal APP turnover. While purified alpha/beta-secretases facilitate drug discovery, gamma-SC presents greater challenges for characterization and mechanisms of catalysis. The review comments on links between mutation or polymorphisms in relation to enzyme mechanisms and disease. The association between lipoprotein receptor LRP11 variants and sporadic Alzheimer's disease (SAD) offers scope to integrate components of pre- and post-Golgi membranes, or brain clathrin-coated vesicles within pathways for trafficking as targets for intervention. The presence of APP and metabolites in brain clathrin-coated vesicles as significant cargo with lipoproteins and adaptors focuses attention as targets for therapeutic intervention. This overview emphasizes the importance to develop new therapies targeting neurosecretases to treat a major neurological disorder that has vast economic and social implications. PMID:17719698

  1. 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

  2. Radiosurgical treatment of sporadic vestibular schwannomas: A prospective cohort study

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

  3. 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

  4. Clinicopathological Study of Sporadic Burkitt Lymphoma in Children

    Hui Huang; Zhi-Liang Liu; Hua Zeng; Shou-Hua Zhang; Chuan-Sheng Huang; Hong-Yan Xu; Yan Wu

    2015-01-01

    Background:Non-Hodgkin lymphoma is the fourth most common malignant tumors in children,Burkitt lymphoma (BL) accounts for 30-50% of all pediatric lymphomas.The aim of this study was to investigate the clinicopathologic features,immunophenotype,Epstein-Barr virus (EBV) infection and c-myc gene rearrangement of sporadic BL in children.Methods:Ninety-two cases of pediatric BL were retrospectively analyzed for clinical features,immunohistochemistry,EBV-encoded RNA (EBER) status by in situ hybridization and c-myc gene rearrangement by fluorescence in situ hybridization.Results:In the 92 cases,male is predominant in sex distribution (M:F =3.38:1).The average age at diagnosis was 4.97 years.Polypoid BL showed a lower clinical stage (P =0.002),and advanced clinical stage and low serum albumin level at diagnosis were associated with poor outcome (P =0.024 and 0.053,respectively).The positive expression of CD10,B-cell lymphoma-6,MUM1 and EBER were 95.7% (88 cases),92.4% (85 cases),22.8% (21 cases),41.3% (38 cases),respectively.The expression of MUM1 were not associated with EBV infection status (P =1.000).c-myc gene rearrangement was detected in 94.6% (87/92).Clinical treatment information for 54 cases was collected,21 patients died of tumor after surgery alone,33 patients received surgery and chemotherapy,and of which six patients died shortly afterwords (MUM 1 positive expression in 3 cases,P =0.076).Conclusions:The anatomical location,growth pattern and serum albumin level of BL were associated with biological behavior.MUM1 may be a potential adverse prognostic marker,and not associated with EBV infection status.

  5. 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

  6. 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.

  7. Clinicopathological Study of Sporadic Burkitt Lymphoma in Children

    Hui Huang

    2015-01-01

    Full Text Available Background: Non-Hodgkin lymphoma is the fourth most common malignant tumors in children, Burkitt lymphoma (BL accounts for 30-50% of all pediatric lymphomas. The aim of this study was to investigate the clinicopathologic features, immunophenotype, Epstein-Barr virus (EBV infection and c-myc gene rearrangement of sporadic BL in children. Methods: Ninety-two cases of pediatric BL were retrospectively analyzed for clinical features, immunohistochemistry, EBV-encoded RNA (EBER status by in situ hybridization and c-myc gene rearrangement by fluorescence in situ hybridization. Results: In the 92 cases, male is predominant in sex distribution (M: F = 3.38:1. The average age at diagnosis was 4.97 years. Polypoid BL showed a lower clinical stage (P = 0.002, and advanced clinical stage and low serum albumin level at diagnosis were associated with poor outcome (P = 0.024 and 0.053, respectively. The positive expression of CDl0, B-cell lymphoma-6, MUMl and EBER were 95.7% (88 cases, 92.4% (85 cases, 22.8% (21 cases, 41.3% (38 cases, respectively. The expression of MUM1 were not associated with EBV infection status (P = 1.000. c-myc gene rearrangement was detected in 94.6% (87/92. Clinical treatment information for 54 cases was collected, 21 patients died of tumor after surgery alone, 33 patients received surgery and chemotherapy, and of which six patients died shortly afterwords (MUM1 positive expression in 3 cases, P = 0.076. Conclusions: The anatomical location, growth pattern and serum albumin level of BL were associated with biological behavior. MUM1 may be a potential adverse prognostic marker, and not associated with EBV infection status.

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

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

    2013-12-15

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

  9. 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.

  10. Brain sonography in African infants with complicated sporadic bacterial meningitis

    Kenneth C Eze

    2013-01-01

    Full Text Available Background: To determine the structural findings in brain sonography of African infants with complicated sporadic bacterial meningitis. Materials and Methods: Retrospective assessment of medical records of patients who underwent brain sonography on account of complicated bacterial meningitis. The brain sonography was carried out over a 4-year period (between September 15, 2004 and September 14, 2008. Result : A total of 86 infants were studied (40 boys and 46 girls in a ratio of 1:1.1; more than 70% of the patients were aged below 6 months. Presenting complaint included convulsion with fever in 34 (39.53%, persistent fever 20 (23.26%, bulging fontanelles 8 (9.30%, coma 7 (8.14% and sepsis with convulsion 6 (6.98%, among others. Patients′ place of previous treatment included specialist hospitals 33 (38.37%, private hospitals 21 (24.42%, herbal home centres 12 (13.95%, nursing homes 8 (9.30%, patent medicine stores 7 (8.14% and other non-doctor attended clinics 5 (5.81% infants. The sonographic findings included hydrocephalus 36 (41.86%, cerebral infarction 12 (13.95%, encephalocoele 9 (10.49% and intracerebral abscess 7 (8.14% infants. Cerebritis 5 (5.81%, intracerebral hemorrhage 3 (3.49%, porocephalic cysts 2 (2.33%, cerebral oedema 2 (2.33%, intraventricular haemorrhage 1 (1.16% and subdural collection 1 (1.16% infants; 8 patients (9.30% had normal findings. Conclusion: Hydrocephalus, cerebral infarction and intracerebral abscess were the most common complications elicited by sonography in this study. Early and adequate treatment with antibiotics in patients with persistent fever and convulsion with fever will reduce the complications of meningitis and its long-term neurological sequelae.

  11. 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.

  12. 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

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

    Sotiris; Lakis; Theodora; Papamitsou; Constantina; Pana

    2010-01-01

    AIM: To analyze α-methylacyl CoA racemase (AMACR) expression in relation to various dysplasia phenotypes and clinicopathological parameters of sporadic colorectal adenomas.METHODS: Fifty-f ive cases of sporadic colorectal adenomas were categorized according to the Vienna classif ication for Gastrointestinal Neoplasia.These corresponded to a total of 98 different intra-lesion microscopic f ields that were further independently assigned a histological grade based on the old nomenclature (mild,moderate,severe ...

  14. Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps.

    Wu, T. T.; Rezai, B.; Rashid, A.; Luce, M.C.; Cayouette, M. C.; Kim, C.; Sani, N.; Mishra, L; Moskaluk, C A; Yardley, J. H.; Hamilton, S R

    1997-01-01

    Juvenile polyps are regarded as hamartomatous polyps and occur in sporadic and familial syndromic settings. There is increased risk of gastrointestinal neoplasia in patients with juvenile polyposis syndrome, but the molecular mechanisms are not known. We therefore studied 78 colorectal juvenile polyposis from 12 patients with juvenile polyps syndrome and 34 sporadic juvenile polyps for epithelial dysplasia and genetic changes associated with colorectal neoplasia. Dysplasia occurred in 31% of ...

  15. 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

  16. Somatic PIK3CA mutations as a driver of sporadic venous malformations

    Castel, Pau; Carmona, F. Javier; Grego-Bessa, Joaquim; Berger, Michael F.; Viale, Agnès; Anderson, Kathryn V.; Bague, Silvia; Scaltriti, Maurizio; Antonescu, Cristina R.; Baselga, Eulàlia; Baselga, José

    2016-01-01

    Venous malformations (VM) are vascular malformations characterized by enlarged and distorted blood vessel channels. VM grow over time and cause substantial morbidity because of disfigurement, bleeding, and pain, representing a clinical challenge in the absence of effective treatments (Nguyen et al., 2014; Uebelhoer et al., 2012). Somatic mutations may act as drivers of these lesions, as suggested by the identification of TEK mutations in a proportion of VM (Limaye et al., 2009). We report that activating PIK3CA mutations gives rise to sporadic VM in mice, which closely resemble the histology of the human disease. Furthermore, we identified mutations in PIK3CA and related genes of the PI3K (phosphatidylinositol 3-kinase)/AKT pathway in about 30% of human VM that lack TEK alterations. PIK3CA mutations promote downstream signaling and proliferation in endothelial cells and impair normal vasculogenesis in embryonic development. We successfully treated VM in mouse models using pharmacological inhibitors of PI3Kα administered either systemically or topically. This study elucidates the etiology of a proportion of VM and proposes a therapeutic approach for this disease. PMID:27030594

  17. 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.

  18. Distribution of gene mutations in sporadic congenital cataract in a Han Chinese population

    Li, Dan; Wang, Siying; Ye, Hongfei; Tang, Yating; Qiu, Xiaodi; Fan, Qi; Rong, Xianfang; Liu, Xin; Chen, Yuhong; Yang, Jin

    2016-01-01

    Purpose This study aimed to investigate the genetic effects underlying non-familial sporadic congenital cataract (SCC). Methods We collected DNA samples from 74 patients with SCC and 20 patients with traumatic cataract (TC) in an age-matched group and performed genomic sequencing of 61 lens-related genes with target region capture and next-generation sequencing (NGS). The suspected SCC variants were validated with MassARRAY and Sanger sequencing. DNA samples from 103 healthy subjects were used as additional controls in the confirmation examination. Results By filtering against common variants in public databases and those associated with TC cases, we identified 23 SCC-specific variants in 17 genes from 19 patients, which were predicted to be functional. These mutations were further confirmed by examination of the 103 healthy controls. Among the mutated genes, CRYBB3 had the highest mutation frequency with mutations detected four times in four patients, followed by EPHA2, NHS, and WDR36, the mutation of which were detected two times in two patients. We observed that the four patients with CRYBB3 mutations had three different cataract phenotypes. Conclusions From this study, we concluded the clinical and genetic heterogeneity of SCC. This is the first study to report broad spectrum genotyping for patients with SCC. PMID:27307692

  19. 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.)

  20. 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.

  1. Linking β-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

  2. 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.

  3. 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.

  4. Electron temperature in nighttime sporadic E layer at mid-latitude

    Oyama, K.-I.; Abe, T.; Mori, H; Liu, J. Y.

    2008-01-01

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

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

    Mukhtar Azeem

    2014-01-01

    by the IEEE 802.15.4 standard. The proposed control protocol ensures that a given offline sporadic schedule can be adapted online in a timely manner such that the static periodic schedule has not been disturbed and the IEEE 802.15.4 standard compliance remains intact. The proposed protocol is simulated in OPNET. The simulation results are analyzed and presented in this paper to prove the correctness of the proposed protocol regarding the efficient real-time sporadic event delivery along with the periodic event propagation.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. Animal model for identifying therapetucually useful compounds for the treatment of sporadic amyotrophic lateral sclerosis

    Gil Ayuso-Gontán, Carmen; Martínez, Ana

    2012-01-01

    [EN] The invention relates to a method for identifying compounds that are potentially useful for the treatment of sporadic amyotrophic lateral sclerosis (ALS), comprising the use of an animal model of rats, developed by means of the administration of β-Ν-methylamino-L-alanine (L-BMAA)

  11. 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

  12. APC mutations in sporadic coloretal carcinomas from The Netherlands Cohort Study

    Lüchtenborg, M.; Weijenberg, M.P.; Roemen, G.M.J.M.; Bruïne, A.P. de; Brandt, P.A. van den; Lentjes, M.H.F.M.; Brink, M.; Engeland, M. van; Goldbohm, R.A.; Goeij, A.F.P.M. de

    2004-01-01

    The adenomatous polyposis coli (APC) gene is considered to be a gatekeeper in colorectal tumourigenesis. Inactivating mutations in APC have been reported in 34-70% of sporadic colorectal cancer patients, the majority of which occur in the mutation cluster region (MCR). In this study, tumour tissue f

  13. Single nucleotide polymorphisms and haplotypes analysis of DFNB1 locus in Chinese sporadic hearing impairment population

    CHENG Hong-bo; CHEN Zhi-bin; WEI Qing-jun; LU Ya-jie; XING Guang-qian; CAO Xin

    2009-01-01

    Background The DFNB1 locus, which contains the gap junction beta-2 (GJB2) and gap junction beta-6 (GJB6) genes, plays a key role in the nonsyndromic and sporadic hearing impairment. Mutations of DFNB1 result in autosomal recessive nonsyndromic hearing impairment (ARNSHI). Previous researches have identified mutations in GJB2 and GJB6, but single nucleotide polymorphisms (SNPs) of DFNB1 locus have not been studied. So we chose five SNPs to evaluate whether there is difference between deafness people and normal-hearing people in Han Chinese. Methods Five SNPs in the DFNB1 region were examined using a case-control association study between cases with sporadic hearing impairment and controls with normal hearing. The HWEsoft and SHEsis softwares were used to analyze the results.Results Single-locus association analysis showed a positive association for three SNPs: rs9315400, rs2274084 and 235delC. When we compared the distributions of the haplotypes, we also found significant differences between cases and controls in the haplotype combination of rs2274084 and rs2274083 (X2=12.978, df=3, global P=0.004719).Conclusions The haplotypes composed of rs2274084 and rs2274083 suggested that C-C may be a risk haplotype for the sporadic hearing impairment while T-T may be protective against hearing impairment. From that point of view, we can conclude that the SNPs of DFNB1 locus also plays an important role in sporadic hearing impairment cases.

  14. CSF Neurofilament Proteins Levels are Elevated in Sporadic Creutzfeldt-Jakob Disease

    van Eijk, Jeroen J. J.; van Everbroeck, Bart; Abdo, W. Farid; Kremer, Berry P. H.; Verbeek, Marcel M.

    2010-01-01

    In this study we investigated the cerebrospinal fluid (CSF) levels of neurofilament light (NFL) and heavy chain (NFHp35), total tau (t-tau), and glial fibrillary acidic protein (GFAP) to detect disease specific profiles in sporadic Creutzfeldt Jakob disease (sCJD) patients and Alzheimer's disease (A

  15. 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

  16. Screening of PEO1 and mitochondrial genes in sporadic cases of ophthalmoplegia

    Ashok Singh

    2013-01-01

    Full Text Available Aim: To screen the gene PEO1 and mitochondrial genes in sporadic cases of rare progressive external ophthalmoplegia (PEO patients from North India. Materials and Methods: The nuclear and mitochondrial DNA was isolated from the sporadic PEO patients, and bi-directional sequencing was done in gene PEO1 and mitochondrial genes to capture the mutations relevant to the PEO disease. Results: In the present study, none of the mutations were reported in the coding region of PEO1 gene, while four mutations were observed in mtDNA genes, namely NADH dehydrogenase subunit 2 (ND2, tRNA-Trp, non-coding nucleotides (MT-NC3, and NADH dehydrogenase subunit 5 (MT-ND5. Our study revealed two novel mutations, one in tRNA-Trp and the other in ND2 gene, which may have role in sporadic cases of PEO patients. The absence of novel conserved mutation in tRNA-Trp gene was also confirmed in 110 ethnically matched controls. Conclusion: The sporadic case of PEO disease is not associated with mutations in nuclear gene PEO1. The novel mutation in tRNA-Trp gene and ND2 mutations may have role in the disease.

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

    Hartvigsen, A; Myrhøj, T; Bülow, Steffen;

    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...

  18. 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.

  19. ATM down-regulation is associated with poor prognosis in sporadic breast carcinomas

    Bueno, R C; Canevari, R A; Villacis, R A R;

    2014-01-01

    BACKGROUND: Ataxia telangiectasia-mutated (ATM) gene downexpression has been reported in sporadic breast carcinomas (BC); however, the prognostic value and mechanisms of ATM deregulation remain unclear. PATIENTS AND METHODS: ATM and miRNAs (miR-26a, miR-26b, miR-203, miR-421, miR-664, miR-576-5p...

  20. 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.

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

    van Eimeren, Thilo; Binkofski, Ferdinand; Buhmann, Carsten;

    2010-01-01

    Treatment-related motor complications such as dyskinesias are a major problem in the long-term management of Parkinson's disease (PD). In sporadic PD, a relatively early onset of the disease is known to be associated with an early development of dyskinesias. Although linked with early onset...

  2. 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.

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

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

    2009-01-01

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

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

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

    1994-09-01

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

  5. Frequent NF2 gene transcript mutations in sporadic meningiomas and vestibular schwannomas

    Deprez, R.H.L.; Groen, N.A.; Zwarthoff, E.C.; Hagemeijer, A.; Van Drunen, E.; Bootsma, D.; Koper, J.W.; Avezaat, C.J.J. (Erasmus Univ., Rotterdam (Netherlands)); Bianchi, A.B.; Seizinger, B.R. (Bristol Myers-Squibb Pharmaceutical Research Institute, Princeton, NY (United States))

    1994-06-01

    The gene for the hereditary disorder neurofibromatosis type 2 (NF2), which predisposes for benign CNS tumors such as vestibular schwannomas and meningiomas, has been assigned to chromosome 22 and recently has been isolated. Mutations in the NF2 gene were found in both sporadic meningiomas and vestibular schwannomas. However, so far only 6 of the 16 exons of the gene have been analyzed. In order to extend the analysis of an involvement of the NF2 gene in the sporadic counterparts of these NF2-related tumors, the authors have used reverse transcriptase-PCR amplification followed by SSCP and DNA sequence analysis to screen for mutations in the coding region of the NF2 gene. Analysis of the NF2 gene transcript in 53 unrelated patients with meningiomas and vestibular schwannomas revealed mutations in 32% of the sporadic meningiomas (n = 44), in 50% of the sporadic vestibular schwannomas (n = 4), in 100% of the tumors found in NF2 patients (n = 2), and in one of three tumors from multiple-meningioma patients. Of the 18 tumors in which a mutation in the NF2 gene transcript was observed and the copy number of chromosome 22 could be established, 14 also showed loss of (parts of) chromosome 22. This suggests that in sporadic meningiomas and NF2-associated tumors the NF2 gene functions as a recessive tumor-suppressor gene. The mutations detected resulted mostly in frameshifts, predicting truncations starting within the N-terminal half of the putative protein. 23 refs., 2 figs. 3 tabs.

  6. A genome-wide investigation of copy number variation in patients with sporadic brain arteriovenous malformation.

    Nasrine Bendjilali

    Full Text Available BACKGROUND: Brain arteriovenous malformations (BAVM are clusters of abnormal blood vessels, with shunting of blood from the arterial to venous circulation and a high risk of rupture and intracranial hemorrhage. Most BAVMs are sporadic, but also occur in patients with Hereditary Hemorrhagic Telangiectasia, a Mendelian disorder caused by mutations in genes in the transforming growth factor beta (TGFβ signaling pathway. METHODS: To investigate whether copy number variations (CNVs contribute to risk of sporadic BAVM, we performed a genome-wide association study in 371 sporadic BAVM cases and 563 healthy controls, all Caucasian. Cases and controls were genotyped using the Affymetrix 6.0 array. CNVs were called using the PennCNV and Birdsuite algorithms and analyzed via segment-based and gene-based approaches. Common and rare CNVs were evaluated for association with BAVM. RESULTS: A CNV region on 1p36.13, containing the neuroblastoma breakpoint family, member 1 gene (NBPF1, was significantly enriched with duplications in BAVM cases compared to controls (P = 2.2×10(-9; NBPF1 was also significantly associated with BAVM in gene-based analysis using both PennCNV and Birdsuite. We experimentally validated the 1p36.13 duplication; however, the association did not replicate in an independent cohort of 184 sporadic BAVM cases and 182 controls (OR = 0.81, P = 0.8. Rare CNV analysis did not identify genes significantly associated with BAVM. CONCLUSION: We did not identify common CNVs associated with sporadic BAVM that replicated in an independent cohort. Replication in larger cohorts is required to elucidate the possible role of common or rare CNVs in BAVM pathogenesis.

  7. 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.

  8. Blood Plasma TGF- β1 Concentration in Sporadic Dilatative Pathology of Ascending Aorta: More Questions than Answers.

    Ramune Sepetiene

    Full Text Available Transforming growth factor β1 (TGF- β1 is a cytokine that participates in a broad range of cellular regulatory processes and is associated with various diseases including aortic aneurysm. Increased TGF- β1 levels are associated with Marfan syndrome (MFS caused by FBN1 mutations and subsequent defects in signaling system. We studied TGF- β1 levels in 62 patients with sporadic, non syndromic, dilatative pathology of ascending aorta (DPAA and in reference group subjects (n = 212. An initial screening of 212 reference individuals identified TGF- β1 gender discrepancies and age-dependent cytokine increase in women. Patients with DPAA had increased levels of TGF- β1 in comparison to reference group subjects (median 7.7 ng/ml, range 2.1-25.3, and median 6.2 ng/ml, range 1.0-33.1, respectively. There is a significant association between TGF-β1 concentration and DPAA (OR 1.084, CI 1.027-1.144, p = 0.004 but the mechanisms of cause and effect have not been established yet. Slightly increased TGF-β1 concentrations in patients with sporadic DPAA in comparison to the reference subjects show a potential use of TGF-β1 as a biomarker for the disease. However, cytokine dependence on age, gender, and other unknown factors among individuals with no cardiovascular complains reduces its specificity for DPAA. We would also like to raise awareness regarding the choice of methods when measuring TGF-β1 levels with an emphasis on preanalytical phase and the choice of sample.

  9. 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

  10. 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

  11. 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.

  12. 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.

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

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

    2015-01-01

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

  14. 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

    or statistical analysis of data, and conclusions. With the objective of identifying the most important risk factors for human sporadic salmonellosis and campylobacteriosis, we performed a SR of case-control studies and meta-analysis of the obtained results. From 1,295 identified references, 132...... passed the relevance screening, 73 passed the quality assessment stage, and data was extracted from 72. Of these studies, 34 investigated risk factors for human salmonellosis and 37 focused on campylobacteriosis. Heterogeneity between the studies and possible sources of bias were assessed. Information on....... 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...

  15. 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...

  16. 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. 

  17. Lack of association of PON polymorphisms with sporadic ALS in an Italian population.

    Ricci, Claudia; Battistini, Stefania; Cozzi, Lorena; Benigni, Michele; Origone, Paola; Verriello, Lorenzo; Lunetta, Christian; Cereda, Cristina; Milani, Pamela; Greco, Giuseppe; Patrosso, Maria Cristina; Causarano, Renzo; Caponnetto, Claudia; Giannini, Fabio; Corbo, Massimo; Penco, Silvana

    2011-03-01

    Paraoxonase (PON) gene polymorphisms have been associated with susceptibility to sporadic amyotrophic lateral sclerosis (ALS). We have investigated the role of the previously associated single nucleotide polymorphisms rs854560, rs662, and rs6954345 in 350 ALS patients and 376 matched controls from Italy. No significant association was observed at genotype and haplotype level. Our data suggest that PON polymorphisms are not involved in ALS pathogenesis in an Italian population. PMID:20381198

  18. 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

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

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

    2009-01-01

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

  20. 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...

  1. 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

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

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

    2014-01-01

    Aims This study’s primary purpose was to determine whether earlier findings suggesting an association between sporadic Creutzfeldt-Jakob disease (sCJD), a transmissible spongiform encephalopathy of humans and specific dietary components could be replicated. The a priori hypotheses were that consumption of (i) foods likely to contain organ tissue and (ii) raw/rare meat are associated with increased sCJD risk. Study Design Population-based case-control study. Place and Duration of Study Departm...

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

    Emmanuel Uttah & Dominic C. Ibeh

    2011-01-01

    Background & objectives: The study was aimed at determining the pattern of co-occurrence of species ofmicrofilaraemia between onchocerciasis endemic and sporadic populations.Methods: From every consenting person of one year and above, 50 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 sing...

  4. Irrelevance of microsatellite instability in the epidemiology of sporadic pancreatic ductal adenocarcinoma

    Laghi, L; Beghelli, S; Spinelli, A.; Bianchi, P; Basso, G; Di Caro, G; Brecht, A.; Celesti, G; Turri, G.; Bersani, S.; Schumacher, G.; C. Rocken; I. Grantzdorffer; Roncalli, M; Zerbi, A

    2012-01-01

    Background and Aims Pancreatic cancer risk is increased in Lynch syndrome (LS) patients with mismatch repair gene defects predisposing to colonic and extracolonic cancers with microsatellite instability (MSI). However, the frequency of MSI pancreatic cancers has never been ascertained in consecutive, unselected clinical series, and their contribution to the sporadic and inherited burden of pancreatic cancer remains to be established. Aims of the study were to determine the prevalence of MSI i...

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

    Bourdon Violaine; Noguchi Tetsuro; Rousseau Guillaume; Sobol Hagay; Olschwang Sylviane

    2011-01-01

    Abstract Background Schwannomatosis is a disease characterized by multiple non-vestibular schwannomas. Although biallelic NF2 mutations are found in schwannomas, no germ line event is detected in schwannomatosis patients. In contrast, germline mutations of the SMARCB1 (INI1) tumor suppressor gene were described in familial and sporadic schwannomatosis patients. Methods To delineate the SMARCB1 gene contribution, the nine coding exons were sequenced in a series of 56 patients affected with a v...

  6. 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.

  7. Alterations in axonal transport motor proteins in sporadic and experimental Parkinson’s disease

    Chu, Yaping; Morfini, Gerardo A.; Langhamer, Lori B.; He, Yinzhen; Brady, Scott T.; KORDOWER, JEFFREY H.

    2012-01-01

    The progressive loss of the nigrostriatal pathway is a distinguishing feature of Parkinson’s disease. As terminal field loss seems to precede cell body loss, we tested whether alterations of axonal transport motor proteins would be early features in Parkinson’s disease. There was a decline in axonal transport motor proteins in sporadic Parkinson’s disease that preceded other well-known nigral cell-related pathology such as phenotypic downregulation of dopamine. Reductions in conventional kine...

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

    Šauli, 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

  9. Investigating novel therapeutic approaches for sporadic inclusion body myositis (sIBM)

    Ahmed, M.

    2012-01-01

    Sporadic inclusion body myositis (sIBM) is the most common acquired muscle disease affecting adults over the age of 50. Although the aetiology of this disease remains unclear, there is evidence for both inflammatory and myodegenerative processes in sIBM muscle pathology. In particular, abnormal protein aggregation is characteristic of affected muscle, with inclusion bodies incorporating amyloid-beta precursor protein (β-APP) among many others. Therapeutic interventions tested to date for s...

  10. Diagnostic value of markers of muscle degeneration in sporadic inclusion body myositis

    Dubourg, O.; Wanschitz, J; Maisonobe, T.; Béhin, A.; Allenbach, Y.; Herson, S; Benveniste, O

    2011-01-01

    Sporadic inclusion body myositis (s-IBM) is characterized histologically by the association of concomitant inflammatory and degenerative processes. We evaluated the sensitivity and specificity of different markers of the degenerative process in order to refine the histological diagnosis. We performed an immunohistochemical study with antibodies directed against ubiquitin, amyloid-β precursor protein (AβPP), amyloid-β (Aβ), SMI-31, SMI-310, Tar-DNA binding protein-43 (TDP-43) and p62 on s-IBM ...

  11. Familial and sporadic porphyria cutanea tarda: clinical and biochemical features and risk factors in 152 patients.

    Muñoz-Santos, Carlos; Guilabert, Antonio; Moreno, Nemesio; To-Figueras, Jordi; Badenas, Celia; Darwich, Esteve; Herrero, Carmen

    2010-03-01

    Porphyria cutanea tarda is the most frequent porphyria and occurs in both sporadic and familial forms. We conducted the current study in a series of 152 consecutive patients with porphyria cutanea tarda attending the Porphyria Unit of the Hospital Clinic of Barcelona, Spain, to update the clinical manifestations of the disease and to study the sex differences, the proportion of familial forms, and the role of different risk factors in this population. Patients were classified as familial and sporadic cases according to erythrocyte uroporphyrinogen-decarboxylase activity and uroporphyrinogen-decarboxylase genotyping. In our cohort, skin fragility and blisters on the hands were the most frequent clinical manifestations. Women more frequently had facial hypertrichosis (84.8%; p = 0.004), affected areas other than the hands and face (33.3%; p = 0.008), and pruritus (27.3%; p = 0.041) compared with men. Of our patients, 11.8% did not present the typical clinical onset of the disease, with facial hypertrichosis and hyperpigmentation the more frequent complaints in these cases. Analysis of risk factors showed a high prevalence of hepatitis C virus infection (65.8%) and alcohol abuse (59.9%), both being more frequent in men (p < 0.001). Hepatitis C virus infection was the only risk factor that showed differences between the sporadic and familial forms in the logistic regression model (odds ratio, 0.05; 95% confidence interval, 0.006-0.46). In conclusion, atypical forms of presentation of porphyria cutanea tarda should be considered in order to prevent delayed diagnosis. We note the sustained role of hepatitis C virus infection in the precipitation of sporadic porphyria cutanea tarda. Therefore, in countries with a high prevalence of hepatitis C virus infection, the absence of such infection in a patient with porphyria cutanea tarda may suggest a possible familial case. PMID:20517178

  12. Mitochondrial DNA Haplogroups and the Risk of Sporadic Parkinson's Disease in Han Chinese

    Ya-Fang Chen,; Wan-Jin Chen; Xiao-Zhen Lin; Qi-Jie Zhang; Jiang-Ping Cai; Chia-Wei Liou; Ning Wang

    2015-01-01

    Background: Mitochondrial dysfunction is linked to the pathogenesis of Parkinson′s disease (PD). However, the precise role of mitochondrial DNA (mtDNA) variations is obscure. On the other hand, mtDNA haplogroups have been inconsistently reported to modify the risk of PD among different population. Here, we try to explore the relationship between mtDNA haplogroups and sporadic PD in a Han Chinese population. Methods: Nine single-nucleotide polymorphisms, which define the major Asian mtDNA ...

  13. Novel multiple endocrine neoplasia type 1 variations in patients with sporadic primary hyperparathyroidism

    S Birla

    2016-01-01

    Full Text Available Background and Objectives: Primary hyperparathyroidism (PHPT can occur either as a sporadic case or in association with syndromes such as multiple endocrine neoplasia. Multiple endocrine neoplasia type 1 (MEN1 is a rare autosomal-dominant disease resulting from mutations in MEN1 gene encoding a 621 amino acid long tumor suppressor protein “menin.” We report here the results of MEN1 screening in 31 patients diagnosed with sporadic PHPT. Materials and Methods: Diagnosis of sporadic PHPT was made when blood urea and serum creatinine were normal, serum parathyroid hormone was high, and parathyroid enlargement could be localized on ultrasound and/or parathyroid scan. A total of 31 patients and 50 healthy volunteers were recruited for molecular analysis after taking informed consent. Results: Major symptoms at presentation were bone pain, fatigue, muscle weakness, and renal stones. Molecular genetic analysis revealed the presence of two novel intronic variations, c. 913-79T>A and c. 784-129T>A which by human splicing finder are predicted to cause potential alteration of splicing by either activating an intronic cryptic acceptor site or converting a conserved exonic splicing silencer sequence to an exonic splicing enhancer site. Apart from these, two reported polymorphisms rs144677807 and rs669976 were seen only in patients and none of the controls. Other reported polymorphisms rs2071313 and rs654440 were identified both in controls and patients. Conclusions: This is the first study of MEN1 gene screening in sporadic PHPT in India reporting on the clinical and genetic findings, wherein two novel intronic variations c. 913-79T>A and c. 784-129T>A were identified showing their possible role in disease causation.

  14. Notch1 hallmarks fibrillary depositions in sporadic Alzheimer’s disease

    Brai, Emanuele; Raio, Noemi Alina; Alberi, Lavinia

    2016-01-01

    Background Notch1 signaling is a cellular cascade with a fundamental role from brain development to adult brain function. Reduction in Notch1 affects synaptic plasticity, memory and olfaction. On the other hand, Notch1 overactivation after brain injury is detrimental for neuronal survival. Some familial Alzheimer’s disease (FAD) mutations in Presenilins can affect Notch1 processing/activation. Others report that Notch1 is overexpressed in sporadic Alzheimer’s disease (AD). These works indicat...

  15. 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

  16. Induction of HSF1 expression is associated with sporadic colorectal cancer

    Hui Cen; Shu Zheng; Yong-Ming Fang; Xiao-Ping Tang; Qi Dong

    2004-01-01

    AIM: To explore the activation of signal transduction pathways related with the carcinogenesis of sporadic colon cancers.METHODS: A gene array monitoring the activation of 8 signal transduction pathways (PathwayFinder GEArray) was used to screen the differentially expressed genes between colorectal cancer and normal colon tissues. The differentially expressed genes were further analyzed by RT-PCR, using RNA derived from colorectal cancer and normal colon tissue of 35 patients.RESULTS: The expression of HSF1, HSF27, HSP90 and iNOS was increased in colon cancer tissues compared to normal colon tissue using PathwayFinder GEArray. The RT-PCR results showed that the expression of HSF1 was increased in 86% (30/35) patients and the expression of iNOS was increased in 63% (22/35) patients.CONCLUSION: The induction of HSF1 gene expression is associated with sporadic colon cancer. HSF1 induces heat shock stress signaling pathway, which might play a role in the carcinogenesis of sporadic colorectal cancer.

  17. 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

  18. Mutational analysis of the thyrotropin receptor gene in sporadic and familial feline thyrotoxicosis.

    Pearce, S H; Foster, D J; Imrie, H; Myerscough, N; Beckett, G J; Thoday, K L; Kendall-Taylor, P

    1997-12-01

    The characterization of a spontaneous animal model equivalent to a human form of thyrotoxicosis would provide a useful resource for the investigation of the human disorder. Feline thyrotoxicosis is the only common form of hyperthyroidism found in domestic or laboratory animals, but its etiopathogenesis remains poorly defined. We have used the polymerase chain reaction (PCR) to amplify codons 480-640 of the previously uncharacterized feline thyrotropin receptor (TSHR) gene, and have determined the DNA sequence in this transmembrane domain region. We have analyzed single stranded conformational polymorphisms in thyroid DNA from 11 sporadic cases of feline thyrotoxicosis and leukocyte DNA from two cases of familial feline thyrotoxicosis. We have also determined the DNA sequence of this region of the TSHR in five of the cases of sporadic feline thyrotoxicosis and the two familial thyrotoxic cats. The normal feline TSHR sequence between codons 480-640 is highly homologous to that of other mammalian TSHRs, with 95%, 92%, and 90% amino acid identity between the feline receptor and canine, human, and bovine TSHRs, respectively. Thyroid gland DNA from 11 cats with sporadic thyrotoxicosis did not have mutations in this region of the TSHR gene. Leukocyte DNA from two littermates with familial feline thyrotoxicosis did not harbor mutations of this region of the TSHR gene. These studies suggest that TSHR gene mutations are not a common cause of feline thyrotoxicosis. PMID:9459639

  19. Occurrence of the blanketing sporadic E layer during the recovery phase of the October 2003 superstorm

    Denardini, Clezio Marcos; Resende, Laysa Cristina Araújo; Moro, Juliano; Chen, Sony Su

    2016-05-01

    We have routinely monitored the total frequency ( ftEs) and the blanketing frequency ( fbEs) of sporadic E layers with the digital sounder under the magnetic equator in the Brazilian sector. Sporadic layers appear in the equatorial region (Esq) at heights between 90 and 130 km, mainly due to irregularities in the equatorial electrojet current. However, during the recovery phase of the October 2003 superstorm, an anomalous intensification of the ionospheric density that exceeded the normal ambient background values for local time and location was observed. The parameter fbEs rose to almost 7.5 MHz during this event, due to a type "c" blanketing sporadic layer (Esc), which is driven by wind shear. This result is discussed in terms of the atmosphere dynamics based on magnetic signature of the equatorial electrojet current using magnetometer data. Also, using data measured by sensors onboard the Geostationary Operational Environmental Satellite (GOES) 10 we analyze the possible influence of the solar flare-associated X-ray flux as an additional source of ionization.

  20. TDP-43 is not a common cause of sporadic amyotrophic lateral sclerosis.

    Rita J Guerreiro

    Full Text Available BACKGROUND: TAR DNA binding protein, encoded by TARDBP, was shown to be a central component of ubiquitin-positive, tau-negative inclusions in frontotemporal lobar degeneration (FTLD-U and amyotrophic lateral sclerosis (ALS. Recently, mutations in TARDBP have been linked to familial and sporadic ALS. METHODOLOGY/PRINCIPAL FINDINGS: To further examine the frequency of mutations in TARDBP in sporadic ALS, 279 ALS cases and 806 neurologically normal control individuals of European descent were screened for sequence variants, copy number variants, genetic and haplotype association with disease. An additional 173 African samples from the Human Gene Diversity Panel were sequenced as this population had the highest likelihood of finding changes. No mutations were found in the ALS cases. Several genetic variants were identified in controls, which were considered as non-pathogenic changes. Furthermore, pathogenic structural variants were not observed in the cases and there was no genetic or haplotype association with disease status across the TARDBP locus. CONCLUSIONS: Our data indicate that genetic variation in TARDBP is not a common cause of sporadic ALS in North American.

  1. 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.).

  2. Comparison of genomic abnormalities between BRCAX and sporadic breast cancers studied by comparative genomic hybridization.

    Gronwald, Jacek; Jauch, Anna; Cybulski, Cezary; Schoell, Brigitte; Böhm-Steuer, Barbara; Lener, Marcin; Grabowska, Ewa; Górski, Bohdan; Jakubowska, Anna; Domagała, Wenancjusz; Chosia, Maria; Scott, Rodney J; Lubiński, Jan

    2005-03-20

    Very little is known about the chromosomal regions harbouring genes involved in initiation and progression of BRCAX-associated breast cancers. We applied comparative genomic hybridization (CGH) to identify the most frequent genomic imbalances in 18 BRCAX hereditary breast cancers and compared them to chromosomal aberrations detected in a group of 27 sporadic breast cancers. The aberrations observed most frequently in BRCAX tumours were gains of 8q (83%), 19q (67%), 19p (61%), 20q (61%), 1q (56%), 17q (56%) and losses of 8p (56%), 11q (44%) and 13q (33%). The sporadic cases most frequently showed gains of 1q (67%), 8q (48%), 17q (37%), 16p (33%), 19q (33%) and losses of 11q (26%), 8p (22%) and 16q (19%). Losses of 8p and gains 8q, 19 as well as gains of 20q (with respect to ductal tumours only) were detected significantly more often in BRCAX than in sporadic breast cancers. Analysis of 8p-losses and 8q-gains showed that these aberrations are early events in the tumorigenesis of BRCAX tumors. The findings of this report indicate similarities between BRCAX and BRCA2 tumours, possibly suggesting a common pathway of disease. These findings need confirmation by more extensive studies because only a limited number of cases were analysed and there are relatively few reports published. PMID:15540206

  3. Exon dosage analysis of parkin gene in Chinese sporadic Parkinson's disease.

    Guo, Ji-Feng; Dong, Xiao-Li; Xu, Qian; Li, Nan; Yan, Xin-Xiang; Xia, Kun; Tang, Bei-Sha

    2015-09-14

    Parkin gene mutations are by far the most common mutations in both familial Parkinson's disease (PD) and sporadic PD. Approximately, 50% of parkin mutations is exon dosage mutations (i.e., deletions and duplications of entire exons). Here, we first established a MLPA assay for quick detection of parkin exon rearrangements. Then, we studied parkin exon dosage mutations in 755 Chinese sporadic PDdisease patients using the established MLPA assay. We found that there were 25 (3.3%) patients with exon dosage alterations including deletions and duplications, 20 (11.4%) patients with exon rearrangements in 178 early-onset patients, and 5 (0.86%) patients with exon rearrangement mutations in 579 later-onset patients. The percentage of individuals with parkin dosage mutations is more than 33% when the age at onset is less than 30 years old, but less than 7% when the age at onset is more than 30. In these mutations, deletion is the main mutational style, especially in exon 2-5. Our results indicated that exon dosage mutations in parkin gene might be the main cause for sporadic PD, especially in EOP. PMID:26240990

  4. Expression and clinical significance of the genes of Hedgehog signaling pathway in sporadic keratocystic odontogenic tumor of the jaw bones

    Kong Li; Yuan Rong-tao; Jia Mu-yun; Wang Ke; Wang Bingchao; Yang Yinhui

    2015-01-01

    PURPOSE It was to study the role of genes of Hedgehog signaling pathway in sporadic keratocystic odontogenic tumor (KCOT)of the jaw bones.METHODS Fresh specimens of sporadic KCOT and the same patient 's normal oral mucosa were obtained.Then RNA was extracted.Gene chip was used to detect the genes of Hedgehog signaling pathway.RESULTS Com-pared to normal oral mucosa,there were five genes of Hedgehog signaling pathway in KCOT changed,including PRKX ,WNT5a,PTCH1 up -regulated.CONCLUSION There were abnormal ex-pressions of genes of Hedgehog pathway in sporadicKCOT.Genes of Hedgehog pathway played roles in sporadic KCOT.

  5. 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.

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

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

    2001-01-01

    In addition to the mutations that underlie most cases of the multiple endocrine neoplasia type 1 (MEN1) syndrome, somatic mutations of the MEN1 gene have also been described in sporadic tumors like gastrinomas, insulinomas and bronchial carcinoid neoplasm. We examined exon 2 of this gene, where most of the mutations have been described, in 148 endocrine and nonendocrine sporadic tumors. DNA was obtained by phenol/chloroform extraction and ethanol precipitation from 92 formalin-fixed, paraffin...

  7. 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-...

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

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

    1998-01-01

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

  9. Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation: indicators of tumor staging and metastasis in adenocarcinomatous sporadic colorectal cancer in Indian population.

    Rupal Sinha

    Full Text Available OBJECTIVE: Colorectal cancer (CRC development involves underlying modifications at genetic/epigenetic level. This study evaluated the role of Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation together/independently in sporadic CRC in Indian population and correlation with clinicopathological variables of the disease. METHODS: One hundred and twenty four consecutive surgically resected tissues (62 tumor and equal number of normal adjacent controls of primary sporadic CRC were included and patient details including demographic characteristics, lifestyle/food or drinking habits, clinical and histopathological profiles were recorded. Polymerase chain reaction - Restriction fragment length polymorphism and direct sequencing for Kras gene mutation and Methylation Specific-PCR for RASSF1A, FHIT and MGMT genes was performed. RESULTS: Kras gene mutation at codon 12 & 13 and methylated RASSF1A, FHIT and MGMT gene was observed in 47%, 19%, 47%, 37% and 47% cases, respectively. Alcohol intake and smoking were significantly associated with presence of Kras mutation (codon 12 and MGMT methylation (p-value <0.049. Tumor stage and metastasis correlated with presence of mutant Kras codon 12 (p-values 0.018, 0.044 and methylated RASSF1A (p-values 0.034, 0.044, FHIT (p-values 0.001, 0.047 and MGMT (p-values 0.018, 0.044 genes. Combinatorial effect of gene mutation/methylation was also observed (p-value <0.025. Overall, tumor stage 3, moderately differentiated tumors, presence of lymphatic invasion and absence of metastasis was more frequently observed in tumors with mutated Kras and/or methylated RASSF1A, FHIT and MGMT genes. CONCLUSION: Synergistic interrelationship between these genes in sporadic CRC may be used as diagnostic/prognostic markers in assessing the overall pathological status of CRC.

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

    N. Christakis

    2009-03-01

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

  11. 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.

  12. Low penetrance alleles as risk modifiers in familial and sporadic breast cancer.

    Esteban Cardeñosa, Eva; de Juan Jiménez, Inmaculada; Palanca Suela, Sarai; Chirivella González, Isabel; Segura Huerta, Angel; Santaballa Beltran, Ana; Casals El Busto, María; Barragán González, Eva; Fuster Lluch, Oscar; Bermúdez Edo, José; Bolufer Gilabert, Pascual

    2012-12-01

    The aim of the study is to investigate the relevance of rs1056663 and rs2708861 HUS1 polymorphisms, and rs104548, rs2981582 and rs2910164 polymorphisms of CASP8, FGFR2 and micro RNA 146A genes, respectively, as risk modifiers in hereditary breast or ovarian cancer (BC/OC) and risk factors in sporadic BC. We performed a case-control study in 189 healthy controls (CG) and 538 BC/OC cases, 340 with familial history of BC/OC (130 carriers of BRCA1/2 mutations and 210 non-carriers) and 198 sporadic BC/OC. The polymorphisms were assessed by real-time PCR using primers and fluorescent-labelled hybridization probes. We found statistically significant differences between familial BC/OC and CG for rs1056663 and rs2708861 HSU1 polymorphisms and rs2981582 FGFR2 polymorphism, particularly in non-carriers of BRCA1/2 mutations. In this group we found statistical differences for rs1056663 HSU1 and rs2981582 FGFR2 polymorphisms (p-trend risk of cancer (OR = 1.87; 95 % CI 1.19, 2.92). Furthermore, we found that the presence of rs1056663 and rs2708861 HUS1 polymorphisms is associated with early age of presentation of BC (p = 0.015) in the group of non-carriers of BRCA1/2 mutations. In addition, no association of the polymorphisms studied in sporadic BC was observed. In conclusion, the HUS1 and FGFR2 polymorphisms act as risk BC modifiers in familial BC/OC, particularly in the group of non-carriers of BRCA1/2 mutations. PMID:22926736

  13. Tidal wind as a possible link of coupling between atmospheric waves activity and sporadic E formation

    Dalakishvili, Giorgi; Didebulidze, Goderdzi G.; Matiashvili, Giorgi

    2016-04-01

    The horizontal tidal wind in the mesosphere lower thermosphere region (MLT) is considered as a source of atmospheric gravity waves (AGWs) and vortical type perturbations generation. It is shown that at mid-latitude these atmospheric waves, evolving in the tidal wind, can lead to vertical convergence of heavy metallic ions of this region and Formation of sporadic E (Es) layer. The process of sporadic E formation by short-period AGWs (close to Bunt-Vaisala period) and by the stationary type vortical perturbations with the same spatial scale, excited in the horizontal shear flow is demonstrated using numerical simulations. The possibility of oscillation of Es layers electron/ions density by period less than BV period under influence of short-period AGWs is shown and the possible coupling of these processes with quasi-periodic echoes is also noted. In our numerical experiment the mid-latitude nighttime Es layers formed under influence of these atmospheric waves, which are possibly generated by horizontal tidal wind, mostly move downward, this is an observed phenomena. It is noted that investigation of sporadic E formation by atmospheric waves evolving in the tidal wind is important for study of the in situ developing processes in the lower thermosphere determining atmosphere-ionosphere dynamical coupling as well as for revealing their possible dynamical coupling with lower atmosphere. Acknowledgements: This work has been supported by Shota Rustaveli National Science Foundation grant No 31/81 and the Shota Rustaveli National Science Foundation grant No FR/51/6-300/14.

  14. The incidence of sporadic viral hepatitis in North India:a preliminary study

    Subrat Kumar; Radha Kanta Ratho; Yogesh Kumar Chawla; India

    2007-01-01

    BACKGROUND:Viral hepatitis is one of the major causes of mortality and morbidity in developing countries. Hepatitis E virus (HEV) among the major etiological agents is responsible for both sporadic and epidemic outbreaks. The epidemic outbreak is water-borne whereas the sporadic outbreak is possibly through contact. Various diagnostic tools at times fail to pinpoint the cause of viral hepatitis. This study was carried out to evaluate the utility of ELISA and nRT-PCR (nested reverse transcriptase polymerase chain reaction) for the diagnosis of sporadic and acute viral hepatitis (AVH) caused by HEV in an endemic situation in North India. METHODS:Serum samples were collected from all the affected and suspected persons and subjected to serological detection of HAV IgM, HBsAg, HCV antibody and HEV IgM. The samples that were positive for HEV IgM were further processed for the detection of HEV RNA by nRT-PCR. RESULTS:A total of 843 samples were collected from 685 patients with AVH, 70 patients with fulminant hepatic failure (FHF), 53 patients with chronic liver disease (CLD), 11 patients with antituberculosis therapy (ATT)-induced jaundice, and 24 pregnant women. The percentage of positivity for anti-HEV IgM was 58.3% in the pregnant women, 41.4% in the paients with FHF, 38.6% in the patients with AVH, 9.4% in the patients with CLD and 18.2% in the patients with ATT induced jaundice. 9.4%of HBsAg carriers were positive for anti-HEV IgM. Males outnumbered females (62.8% vs. 37.1%). Furthermore, the rates of fulminant and acute outbreaks of hepatitis with HEV RNA positivity were 41.4% and 9.4%, respectively. CONCLUSION:Serological and molecular analysis should be combined for the diagnosis of viral infections, especially in endemic areas.

  15. 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.

  16. 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.

  17. Radio wave diffraction during the passage of an acoustic shock through a sporadic E layer

    Bistatic HF Doppler measurements of the ionospheric disturbance arising from a large ground-level chemical explosion have revealed a peculiar HF return which begins at large positive Doppler (greater than +5 Hz) and linearly evolves to large negative Doppler (less than -5 Hz). Various pieces of evidence in the data suggest that an HF wave which is diffracted from the intersection of the acoustic shock and an extensive plane of sporadic E ionization at 110 km was observed. From these measurements the horizontal trace velocity of the locus of intersection is estimated. 16 references

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

    M. S. S. R. K. N Sarma; C. Raghava Reddy; Niranjan, K.

    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...

  19. EphB2 SNPs and Sporadic Prostate Cancer Risk in African American Men

    Christiane M Robbins; Stanley Hooker; Kittles, Rick A.; John D. Carpten

    2011-01-01

    The EphB2 gene has been implicated as a tumor suppressor gene somatically altered in both prostate cancer (PC) and colorectal cancer. We have previously shown an association between an EphB2 germline nonsense variant and risk of familial prostate cancer among African American Men (AAM). Here we set out to test the hypothesis that common variation within the EphB2 locus is associated with increased risk of sporadic PC in AAM. We genotyped a set of 341 single nucleotide polymorphisms (SNPs) enc...

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

    Boudjadar, Jalil; David, Alexandre; Kim, Jin Hyun;

    2014-01-01

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

  1. Post-transcriptional regulation of mRNA associated with DJ-1 in Sporadic Parkinson disease

    Blackinton, Jeff; Kumaran, Ravindran; van der Brug, Marcel P.; Ahmad, Rili; Olson, Lars; Galter, Dagmar; Lees, Andrew; Bandopadhyay, Rina; Cookson, Mark R

    2009-01-01

    Mutations in DJ-1 lead to a monogenic form of early onset recessive parkinsonism. DJ-1 can respond to oxidative stress, which has been proposed to be involved in the pathogenesis of sporadic Parkinson disease (PD). We have recently reported that DJ-1 interacts with mRNA in an oxidation dependent manner. Here, we confirm interaction of DJ-1 and RNA in human brain using immunoprecipitation followed by quantitative real time PCR. We confirmed previous reports that DJ-1 is more oxidized in cortex...

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

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

  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

    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 ...

  4. A genome wide association study links glutamate receptor pathway to sporadic Creutzfeldt-Jakob disease risk

    Sanchez-Juan, Pascual; Bishop, Matthew; Kovacs, Gabor; Calero, Miguel; Aulchenko, Yurii; Ladogana, Anna; Boyd, Alison; Lewis, Victoria; Ponto, C. (Claudia); Calero, O. (Olga); Poleggi, Anna; Carracedo, Angel; van der Lee, S. J.; Ströbel, Thomas; Rivadeneira Ramirez, Fernando

    2015-01-01

    textabstractWe 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...

  5. 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

    2014-01-01

    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 ...

  6. A genome wide association study links glutamate receptor pathway to Sporadic Creutzfeldt-Jakob disease risk.

    Sanchez-Juan, Pascual; Bishop, Matthew; Kovacs, Gabor; Calero, Miguel; Aulchenko, Yuri; Ladogana, Anna; Boyd, Alison; Lewis, Victoria; Ponto, Claudia; Calero, Olga; Poleggi, Anna; Carracedo, Angel; van der Lee, Sven; Strobel, Thomas; Rivadeneira, Fernando

    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 1109sCJD 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 f...

  7. 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...

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

    Bahl, Justyna Maria Czarna; Heegaard, Niels Henrik Helweg; Falkenhorst, Gerhard;

    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...

  9. Muscle fiber conduction velocity in the diagnosis of sporadic hypokalemic periodic paralysis.

    Brouwer, O F; Zwarts, M J; Links, T P; Wintzen, A R

    1992-01-01

    A 6-year-old girl presented with episodes of profound muscle weakness since the age of 2 years. On the basis of decreased ictal serum potassium level and lack of metabolic disorder, primary hypokalemic periodic paralysis (HPP) was diagnosed. Both parents and 3 sibs were unaffected clinically. In all of them asymptomatic heterozygosity was very unlikely by the finding of normal muscle fiber conduction velocities, whereas in the patient interictal muscle fiber conduction velocity was lowered. Determination of muscle fiber conduction velocity can be helpful in documenting sporadic occurrence of HPP. PMID:1324813

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

    Kun-Rodrigues, C.; Ganos, C.; Guerreiro, R.; Schneider, S A; Schulte, C.; Lesage, S.; Darwent, L; Holmans, P.; Singleton, A.; International Parkinson's Disease Genomics Consortium (IPDGC); Bhatia, K; Bras, J

    2015-01-01

    Despite the many advances in our understanding of the genetic basis of Mendelian forms of Parkinson's disease (PD), a large number of early-onset cases still remain to be explained. Many of these cases, present with a form of disease that is identical to that underlined by genetic causes, but do not have mutations in any of the currently known disease-causing genes. Here, we hypothesized that de novo mutations may account for a proportion of these early-onset, sporadic cases. We performed exo...

  11. Reduction of the Hall-Paige conjecture to sporadic simple groups

    Wilcox, Stewart

    2010-01-01

    A complete mapping of a group $G$ is a permutation $\\phi:G\\rightarrow G$ such that $g\\mapsto g\\phi(g)$ is also a permutation. Complete mappings of $G$ are equivalent to tranversals of the Cayley table of $G$, considered as a latin square. In 1953, Hall and Paige proved that a finite group admits a complete mapping only if its Sylow-2 subgroup is trivial or non-cyclic. They conjectured that this condition is also sufficient. We prove that it is sufficient to check the conjecture for the 26 sporadic simple groups and the Tits group.

  12. 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.

  13. Sporadic inclusion body myositis: variability in prevalence and phenotype and influence of the MHC

    Mastaglia, Fl

    2009-01-01

    Sporadic inclusion body myositis (sIBM) is the most common myopathy presenting over the age of 40 years but its prevalence varies considerably in different populations. Genetic factors play a part in the pathogenesis of sIBM and in Caucasians susceptibility has been linked to the HLA-DR3 allele and the 8.1 MHC ancestral haplotype (AH) which is also associated with other autoimmune diseases. The variable prevalence of sIBM in different populations may be related to differences in the populatio...

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

    Akchurin, Adel; Yusupov, Kamil

    Investigation of the inhomogeneities structure produced in the ionospheric E layer, and their relationship with the rest of the ionosphere have a long history. The main long source of information about irregularities in the E layer is vertical sounding (VS), where the main inhomogeneities seen as sporadic E layer or Es. The main feature of the Es-layer is the semitransparent at VS. To explain the transparence use three main models that are closely related to the inhomogeneities structural characteristics. This is cloud (large-scale inhomogeneities), blob or scattering (array of small-scale inhomogeneities) models and model of a thin layer with significant gradients of the electron density at the boundaries. If the semitransparency of the first two models based on the "gap" between the inhomogeneities, the third based on the effects of tunneling through a thin layer and appearance of transparent windows (with half the electron gyrofrequency size) in the presence of the characteristic modes intermode coupling of propagation in ionospheric magnetized plasma. Based on these models and frequent sounding with the high height resolution will be analyzed the contribution of each model in the reflected signal for about a two-year series. Focus will be on the model of a thin layer in the presence of the intermode coupling. According to the theory, intermode coupling is possible with longitudinal propagation in the polar regions, with high frequency of electron collisions, and the electron density steep gradient. Attempts to detect this coupling in conditions close to the longitudinal propagation were not very successful. Namely, it has not yet succeeded in the polar regions (as in [Jalonen, 1981]) to find beatings by type of coupling between two ordinary modes (o-z-o and o) as an interference pattern with a decreasing step between minima with increasing frequency, except individual cases. At middle latitudes this effect is weaker and may have a slightly different form, e

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

    Martín Sívori; Gabriel E. Rodríguez; Daniel Pascansky; César Séenz; Roberto E.P. Sica

    2007-01-01

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

  16. Equatorial sporadic E-layer abnormal density enhancement during the recovery phase of the December 2006 magnetic storm: A case study

    Resende, L. C. A.; Denardini, C. M.

    2012-04-01

    Sporadic layers appear in the equatorial region ( E sq) between 90 and 130 km mainly due to irregularities in the electrojet equatorial (EEJ) current. In the present work, we have analyzed the behavior of the frequency parameters associated with these sporadic layers, covering the days before, during, and subsequent to, the intense magnetic storm that occurred on December 14, 2006. The parameters used in our analyses are the top frequency ( f t E s) and blanketing frequency ( f b E s) of the E s layer as measured over São Luís, Brazil (2.33°S, 44.2°W, dip: -4.5°) by digital ionosonde. A tentative association between these parameters and X-ray data measured by sensors on board the GOES satellite was carried out. Also, we investigated the effects on the dynamics of the equatorial electrojet using magnetometer data related to the presence of these E s layers. Our analyses show that there are notable changes in the f b E s, which are characterized by the occurrence of peaks that exceed the ambient background values.

  17. Sporadic inclusion body myositis in Japanese is associated with the MHC ancestral haplotype 52.1.

    Scott, Adrian Phillip; Allcock, Richard James Nigel; Mastaglia, Frank; Nishino, Ichizo; Nonaka, Ikuya; Laing, Nigel

    2006-05-01

    In Caucasians, sporadic inclusion body myositis has been associated with the MHC ancestral haplotypes; HLA-A1, B8, DR3 (8.1AH) and HLA-B35, DR1 (35.2AH). It is not known whether these haplotypes carry susceptibility for the disease in other ethnic groups. We report here the results of HLA-B and -DRB1 typing using a high-resolution sequence-based technique in a cohort of 31 Japanese patients with definite sIBM. Patient allele frequencies were 40.3% for HLA-B*5201 (10.7% in controls: pHLA-DRB1*1502 (10% in controls: p<0.001). Both alleles were found together as part of a conserved haplotype (52.1AH) at a frequency of 37.1% in patients (8.4% in controls: p<0.001). This is the first description of a haplotypic MHC association with sporadic inclusion body myositis in Japanese patients. These findings indicate that different MHC ancestral haplotypes are associated with sIBM in different ethnic groups and further emphasize the importance of genetic factors in this condition. PMID:16564169

  18. 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

  19. LADEE NMS Observations of Sporadic Water and Carbon Dioxide Signatures in the Lunar Exosphere

    Benna, M.; Mahaffy, P. R.; Hurley, D.; Stubbs, T. J.; Hodges, R. R., Jr.; Elphic, R. C.

    2014-12-01

    During its six months in orbit, the Lunar Atmosphere and Dust Environment Explorer (LADEE) has detected signatures of water and carbon dioxide in the exosphere of the Moon. The signature of these two volatile gases has been measured by the Neutral Mass Spectrometer (NMS) as sporadic short-lived signal increases above instrument background. Following the detection of these two species in the exosphere, a systematic measurement campaign with a cadence of few hours over four main lunar local time sectors (sunrise, midnight, sunset, and noon) was put in place and continued to the end of the mission. While this measurement campaign did not reveal any local time dependence for these sporadic signal events, it showed that they are globally correlated with predicted micrometeoroid streams. Moreover, a subset of these NMS observations were acquired at low altitudes when water and carbon dioxide signals were below instrumental background, and used to establish new upper limits of the background abundances of these two gases in the exosphere.

  20. 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

  1. A novel RET gene mutation in a patient with apparently sporadic pheochromocytoma.

    Scollo, Claudia; Russo, Marco; De Gregorio, Laura; Terranova, Rosa; Mangione, Erika; Castoro, Carlotta; Squatrito, Sebastiano; Pellegriti, Gabriella

    2016-01-01

    Pheochromocytoma (Pheo) is a chromaffin tumor arising from the adrenal medulla. The recent discovery of new germline mutations in RET, SDHA, SDHB, SDHC, SDHD, VHL, NF1, TMEM127, MAX genes, increased the rate of genetic disease from 10% to 28% in patients with apparently sporadic tumor. RET germline mutations cause multiple endocrine neoplasia type 2 syndrome (MEN 2A) characterized by complete penetrance of medullary thyroid cancer (MTC), and lower prevalence of Pheo and hyperparathyroidism. We describe the genetic etiology of an apparently sporadic case of monolateral Pheo in a 42-year-old male patient. A new (not previously reported) MEN 2A-associated germline RET mutation located in exon 11 (Glu632Gly, caused by an A>G point mutation at position 1895 of the RET cDNA) was found in the patient but not in his living first-degree relatives. This observation increases the number of possible germline RET mutations. Genotype-phenotype correlation of this new genetic alteration is unknown, but this rare mutation is probably associated with a low risk for MTC (usually the first tumor diagnosed in MEN 2A syndrome) and with the development of Pheo before the onset of MTC. Since we expect MTC to occur in our patient, strict follow-up is mandatory. Our findings emphasize the relevance of genetic testing in patients with Pheo, especially when the clinical presentation (family history, young age at diagnosis, multiple locations, malignant lesions, and bilateralism) is suggestive. PMID:26497911

  2. Hereditary and Sporadic Forms of Aβ-Cerebrovascular Amyloidosis and Relevant Transgenic Mouse Models

    Samir Kumar-Singh

    2009-04-01

    Full Text Available Cerebral amyloid angiopathy (CAA refers to the specific deposition of amyloid fibrils in the leptomeningeal and cerebral blood vessel walls, often causing secondary vascular degenerative changes. Although many kinds of peptides are known to be deposited as vascular amyloid, amyloid-β (Aβ-CAA is the most common type associated with normal aging, sporadic CAA, Alzheimer’s disease (AD and Down’s syndrome. Moreover, Aβ-CAA is also associated with rare hereditary cerebrovascular amyloidosis due to mutations within the Aβ domain of the amyloid precursor protein (APP such as Dutch and Flemish APP mutations. Genetics and clinicopathological studies on these familial diseases as well as sporadic conditions have already shown that CAA not only causes haemorrhagic and ischemic strokes, but also leads to progressive dementia. Transgenic mouse models based on familial AD mutations have also successfully reproduced many of the features found in human disease, providing us with important insights into the pathogenesis of CAA. Importantly, such studies have pointed out that specific vastopic Aβ variants or an unaltered Aβ42/Aβ40 ratio favor vascular Aβ deposition over parenchymal plaques, but higher than critical levels of Aβ40 are also observed to be anti-amyloidogenic. These data would be important in the development of therapies targeting amyloid in vessels.

  3. Lentivirus-mediated somatic recombination and development of a novel mouse model for sporadic colorectal cancer.

    Vaish, Vivek; Kim, Joohwee; Shim, Minsub

    2016-07-01

    In this study, we have developed a novel mouse model for sporadic colorectal cancer (CRC) by utilizing APC conditional knockout (Apc(CKO) ) mouse and lentivirus encoding Cre recombinase and a reporter gene (EGFP or LacZ). Lentiviral transduction of colonic crypt stem cells allowed for the long-term expression of reporter gene as well as excision of floxed Apc alleles, which resulted in tumor development. Tumors represented adenoma stages along with the nuclear accumulation of β-catenin. Loss of E-cadherin at the cellular junctions and strong expression of Vimentin suggested the sign of active epithelial-mesenchymal transition. Moreover, nuclear staining of Ki67 inside epithelial cells of aberrant crypts demonstrated their higher proliferative nature. Erratic downstream signaling of activated Wnt/β-catenin, AKT/mTOR, and Notch pathways provided strong evidence towards the higher proliferative index of epithelial cells inside the aberrant crypts. These results do recapitulate the findings of previous APC mutant mouse models. Our model represents sporadic CRC more precisely as (i) tumors result from somatic mutations but not from germline; (ii) tumors develop in colon not in small intestine; (iii) few tumors develop at the distal end of colons. Additionally, our model allows for the long-term expression of the gene(s), which get integrated into the host cell genome and provides an ability to track the tumor growth. © 2016 Wiley Periodicals, Inc. PMID:27037682

  4. 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...

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

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

    2010-09-01

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

  6. 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.

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

    T. Ono

    2005-10-01

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

  8. Hereditary/familial versus sporadic prostate cancer: few indisputable genetic differences and many similar clinicopathological features.

    Alberti, C

    2010-01-01

    Genetic factors and their interactions with environmental conditions and internal microenvironment influence the prostate cancer (PC) development, so that gene expression couldn't strictly occur on the basis of reductionist determinisms of DNA causality but should also conform to multifactorial and stochastic events, moreover, considering the pre-RNA alternative splicing-mediated multi-protein assemblying mechanisms. Nevertheless, after age and ethnic background, the strongest epidemiological risk factor for PC is a positive family history. However, apart from RNaseL-, ElaC2-, MSR1-genes, there are not other identified high-risk genetic variants which might be considered responsible for hereditary PC, moreover suggesting that familial PC is a genetically heterogeneous disease, many gene loci rather than a specific major susceptibility gene predisposing to it. Gene-environment interactions play a crucial role in cancer development especially when low penetrance genes, such as in case of genetic polymorphisms, are the major players. Several epidemiological studies show, in some families, a possible, either syncronous or metachronous, association of other tumors (breast, brain, gastrointestinal tumors, lymphomas) with PC, thus suggesting a common genetic background. As far as the role of androgen metabolism and androgen receptor (AR)-related genes in the development of familial PC is concerned, a small number of either guanine-guanine-cytosine (risk. Regarding the expression of both androgen and estrogen receptor-related genes in sporadic and hereditary PC, the immunohistochemistry findings show that the percentage of AR-positive cancer cells is higher in hereditary PC than in sporadic forms, whereas the mean number of estrogen-alpha-receptor-positive stromal cells is higher in sporadic PC rather than in that hereditary. As for 5-alpha-steroid-reductase-2 gene, the dinucleotide thymine-adenine repeated 18 times on the last exon, confers an increased PC predisposition

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

    Full text: Introduction. BRCA1 protein is a tumor suppressor subjected to a nuclear-cytoplasmic shuttle, involved in the tumorigenesis of breast cancer. Controversy exists regarding the meaning of the expression and subcellular localization in sporadic breast cancer, particularly the one with triple-negative phenotype. The purpose of this study was to evaluate the pattern of expression and subcellular localization of BRCA1 in a well- characterized breast tumors sporadic, and compared with adjacent normal breast. Methods. We analyzed, by immunofluorescence, the expression / localization of BRCA1 in cuts of tumor and adjacent normal tissue fixed in formaldehyde and embedded in paraffin, of 22 cases, majority being triple negative phenotype. 3 sections were studied tumor and normal tissue per patient (03.05 fields / section) using con focal microscopy and evaluated the percentage of cells with BRCA1 nuclear foci. For statistical analysis of differences in expression / BRCA1 localization between tumor and normal tissue was used Mann Whitney U test, and to determine the associations with the content and status of estrogen receptor (E R) and progesterone (P R), fraction of activated A kt and clinico pathologic characteristics test was used of Spea rman rank correlation was considered significant when p < 0.05. Results. We observed cytoplasmic and nuclear expression of BRCA1 in all sections of normal and tumor tissue analyzed, although the latter showed a significantly larger cell with BRCA1 nuclear foci (53%)compared with the corresponding adjacent normal tissue (33 %, p = 0.004, n = 12). Furthermore, a positive correlation was obtained between the percentage of cells with nuclear foci and content (p = 0.003)and status (p = 0.002)of R E in the total cases studied. No correlation was found between the percentage of cells with nuclear foci and the contents of R P (p = 0.996), activated Ak t fraction (p = 0.753), age (p = 0.695)and lymph node involvement (p = 0

  10. Early-Life Toxic Insults and Onset of Sporadic Neurodegenerative Diseases-an Overview of Experimental Studies.

    Tartaglione, Anna Maria; Venerosi, Aldina; Calamandrei, Gemma

    2016-01-01

    The developmental origin of health and disease hypothesis states that adverse fetal and early childhood exposures can predispose to obesity, cardiovascular, and neurodegenerative diseases (NDDs) in adult life. Early exposure to environmental chemicals interferes with developmental programming and induces subclinical alterations that may hesitate in pathophysiology and behavioral deficits at a later life stage. The mechanisms by which perinatal insults lead to altered programming and to disease later in life are still undefined. The long latency between exposure and onset of disease, the difficulty of reconstructing early exposures, and the wealth of factors which the individual is exposed to during the life course make extremely difficult to prove the developmental origin of NDDs in clinical and epidemiological studies. An overview of animal studies assessing the long-term effects of perinatal exposure to different chemicals (heavy metals and pesticides) supports the link between exposure and hallmarks of neurodegeneration at the adult stage. Furthermore, models of maternal immune activation show that brain inflammation in early life may enhance adult vulnerability to environmental toxins, thus supporting the multiple hit hypothesis for NDDs' etiology. The study of prospective animal cohorts may help to unraveling the complex pathophysiology of sporadic NDDs. In vivo models could be a powerful tool to clarify the mechanisms through which different kinds of insults predispose to cell loss in the adult age, to establish a cause-effect relationship between "omic" signatures and disease/dysfunction later in life, and to identify peripheral biomarkers of exposure, effects, and susceptibility, for translation to prospective epidemiological studies. PMID:26695168

  11. Association study between XRCC1 gene polymorphisms and sporadic amyotrophic lateral sclerosis.

    Coppedè, Fabio; Migheli, Francesca; Lo Gerfo, Annalisa; Fabbrizi, Maria Rita; Carlesi, Cecilia; Mancuso, Michelangelo; Corti, Stefania; Mezzina, Nicoletta; del Bo, Roberto; Comi, Giacomo P; Siciliano, Gabriele; Migliore, Lucia

    2010-01-01

    The aim of the present study was to investigate the possible contribution of three common functional polymorphisms in the DNA repair protein X-ray repair cross-complementing group 1 (XRCC1), namely Arg194Trp (rs1799782), Arg280His (rs25489) and Arg399Gln (rs25487), to sporadic amyotrophic lateral sclerosis (SALS). We genotyped 206 Italian SALS patients and 203 matched controls for XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms by means of PCR/RFLP technique, searching for association between any of the studied polymorphisms and disease risk, age and site of onset. We observed a statistically significant difference in XRCC1 Gln399 allele frequencies between SALS cases and controls (0.39/0.28; p=0.001). The present study suggests that the XRCC1 Arg399Gln polymorphism might contribute to SALS risk. PMID:19707910

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

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

    1977-01-01

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

  13. Contribution of the Atmospheric Dynamics to the Sporadic Sodium Layer Formation

    杨国韬; 王嘉珉; 刘炳模; 程学武; 万卫星; 龚顺生

    2002-01-01

    We report on a sporadic sodium layer (SSL) event observed by our Na fluorescence lidar at Wuhan, China (31°N, 114°E) on 16 March 1999, and we reveal some special behaviour. From careful analysis of various sodium content variations of the layer during the development of this SSL event, it is found that besides the sodium injection mechanism as expected, another mechanism which we call atmospheric dynamics also made a noticeable contribution to this SSL formation. Computer simulations confirmed that under the combined action ora suitable sodium injection and a bi-direction vertical wind field, an SSL profile can be reproduced with a pronounced SSL peak on a normal sodium layer, as we observed in this event. From these results, it is emphasized that atmospheric dynamics is important for SSL formation.

  14. LOSS OF HETEROZYGOSITY FOR MARKERS ON 22CHROMOSOME IN SPORADIC SCHWANNOMA

    2000-01-01

    Objective To analyze the loss of heterozygosity ( LOH) for markers on chromosome 22 ( CHR 22 ) and its significance with their clinical behaviors. Methods The frequency of CHR22 LOH in 36 schwannomas was observed by dena tured polyacrylamide gels and silver staining, and the proliferative index of schwannoma was calculated by Ki-67 and PCNA im munohistochemistry. Results 15 schwannomas (41.6%) showed allele loss. The proliferative index of schwannomas with LOH were significantly higher than those without LOH (P<0.05). In acoustic neuromas, patients with LOH were younger at the age of diagnosis, larger size of tumor, shorter history and higher growth rate than those without LOH, but with no signifi cance. Conclusion CHR22 LOH was the frequent event in the tumorigenesis of sporadic schwannoma. There were some links between CHR22 LOH and clinical behavior.

  15. Sporadic Gastric Well-Differentiated Neuroendocrine Tumors Have a Higher Ki-67 Proliferative Index.

    Lee, Hee Eun; Mounajjed, Taofic; Erickson, Lori A; Wu, Tsung-Teh

    2016-09-01

    Well-differentiated neuroendocrine tumor (WDNET) of the stomach can arise in three distinct clinical settings: (1) in association with autoimmune atrophic gastritis, (2) in association with multiple neuroendocrine neoplasia type I (MEN I) or Zollinger-Ellison syndrome (ZES), or (3) sporadic. The Ki-67 proliferative index (PI) in gastric WDNETs in these three distinct clinical settings has not been evaluated in detail. Forty-five gastric WNETs underwent polypectomy (n = 4), endoscopic mucosal resection (n = 12), and surgical resection (n = 29) between 1994 and 2015 were included. H&E slides from each case were reviewed, and Ki-67 immunostain was performed on one representative tumor block. Ki-67 PI was determined by quantitative Aperio image analysis software in areas of strongest nuclear labeling ("hot spots"), and correlated with underlying clinical and pathological features. Twenty-one patients were male and 24 female with a median age of 57 years (range, 30-80 years). Tumors were classified as type I (n = 17), type II (n = 6), and type III (n = 22) WDNETs. Types II and III showed more advanced TNM stage compared to type I (p = 0.02, overall). WHO grade based on Ki-67 PI was higher in type III WDNETs [grade 1 (G1), n = 3; grade 2 (G2), n = 15; and grade 3 (G3), n = 4] than in type I WDNETs [G1, n = 5; G2, n = 12] and in type II WDNETs [G1, n = 2; G2, n = 4] (p = 0.050, overall). Ki-67 PI was significantly higher in type III WDNETs (mean ± SD = 13.0 ± 13.3 %) than in non-sporadic (type I and II) WDNETs (mean ± SD = 5.3 ± 3.3 %; p = 0.015). There was no difference in Ki-67 PI between type I WDNETs (mean ± SD = 5.2 ± 3.5 %) and type II WDNETs (mean ± SD = 5.6 ± 3.1%; p = 0.817). Higher Ki-67 PI was associated with higher tumor T stage (p = 0.003) and also tended to be associated with lymph node metastasis (p = 0.071). In the Kaplan-Meier survival analysis, type I was associated with a

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

    Fernandez Bridget A

    2012-08-01

    Full Text Available Abstract Background Idiopathic pulmonary fibrosis (IPF is an adult-onset Idiopathic Interstitial Pneumonia (IIP usually diagnosed between age 50 to 70 years. Individuals with Familial Pulmonary Fibrosis (FPF have at least one affected first or second-degree relative and account for 0.5-20% of cases. Methods We ascertained and collected DNA samples from a large population-based cohort of IPF patients from Newfoundland, Canada. For each proband, a family history was documented and medical records were reviewed. Each proband was classified as familial (28 patients or sporadic (50 patients and all 78 probands were screened for variants in four highly penetrant, adult-onset PF genes (SFTPC, SFTPA2, TERT,TERC. Results Seventy-eight IPF probands were enrolled of whom 28 (35.9% had a positive family history. These 28 familial patients led to the recruitment of an additional 49 affected relatives (total of 77 FPF patients. By age 60 years, 42% of the familial cohort had been diagnosed with PF compared with only 16% of the sporadic patient collection (χ2 = 8.77, p = 0.003. Mean age of diagnosis in the familial group was significantly younger than the sporadic group (61.4 years vs. 66.6 yrs, p = 0.012 with a wider age range of diagnosis (19–92 years compared with 47–82 years. Thirty-three of 77 (42.8% FPF patients had a tissue diagnosis and all but five had usual interstitial pneumonia histology. Compared with other published case series, the familial IIP histologies were more homogeneous. Three of 28 familial probands (10.7% and none of the 50 sporadic probands had pathogenic variants in the four genes tested. All three familial probands had mutations in TERT. Other phenotypes associated with telomerase deficiency were present in these families including cirrhosis, bone marrow hypoplasia and premature graying. Telomere length assays were performed on mutation carriers from two families and confirmed telomere-related deficiency

  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. 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.

  19. 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

  20. A Sporadic Case of Ichthyosis Curth Macklin: Rare Presentation of a Rare Disease.

    Mehta, Sharad; Agarwal, Uma Shankar; Agarwal, Nidheesh

    2015-01-01

    Ichthyosis hystrix is a rare autosomal dominant genodermatosis, characterized by persistent spiny hyperkeratotic scales which cover a significant part of the skin surface. Based on the pattern of distribution, five clinical variants namely Brocq type, Lambert type, Curth-Macklin type, Rheydt type and Bδfverstedt type have been described. We report the case of an 11-year-old male child with spiny, hyperkeratotic scales all over the body since birth with sparing of scalp and central part of the face. Palmoplantar keratoderma was also present. These clinical features are suggestive of Ichthyosis Curth Macklin, which has been typically described in families. However, family history was negative in our patient. The case is being reported on account of rarity of the disease, that too with a very rare sporadic presentation. PMID:26538731

  1. 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.

  2. Autoimmune encephalitis mimicking sporadic Creutzfeldt-Jakob disease: A retrospective study.

    Chen, Yu; Xing, Xiao-Wei; Zhang, Jia-Tang; Wang, Ruo-Xi; Zhao, Wei; Tan, Qing-Che; Liu, Ruo-Zhuo; Wang, Xiang-Qing; Huang, Xu-Sheng; Yu, Sheng-Yuan

    2016-06-15

    Autoimmune encephalitis associated with anti-voltage-gated potassium channel antibodies are most likely to be misdiagnosed as sporadic Creutzfeldt-Jakob disease (sCJD). Our goal was to delineate patients who were initially suspected to have CJD but were later found to have AE. We performed a retrospective clinical review of cases of individuals and made a comparison between groups of patients diagnosed with sCJD and AE. Patients who had rapidly progressing dementia and focal neurological impairment, such as aphasia, gait disturbance, visual disturbance, and depression, at onset were diagnosed with sCJD, whereas epilepsy, hyponatremia and dysautonomia were strong hints for AE. Fluoroscope-positron emission tomography (PET) of patients with AE revealed variable metabolism and normative and long-term immunosuppression were less likely to relapse. PMID:27235341

  3. 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

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

    Chiò, Adriano; Schymick, Jennifer C; Restagno, Gabriella; Scholz, Sonja W; Lombardo, Federica; Lai, Shiao-Lin; Mora, Gabriele; Fung, Hon-Chung; Britton, Angela; Arepalli, Sampath; Gibbs, J Raphael; Nalls, Michael; Berger, Stephen; Kwee, Lydia Coulter; Oddone, Eugene Z; Ding, Jinhui; Crews, Cynthia; Rafferty, Ian; Washecka, Nicole; Hernandez, Dena; Ferrucci, Luigi; Bandinelli, Stefania; Guralnik, Jack; Macciardi, Fabio; Torri, Federica; Lupoli, Sara; Chanock, Stephen J; Thomas, Gilles; Hunter, David J; Gieger, Christian; Wichmann, H Erich; Calvo, Andrea; Mutani, Roberto; Battistini, Stefania; Giannini, Fabio; Caponnetto, Claudia; Mancardi, Giovanni Luigi; La Bella, Vincenzo; Valentino, Francesca; Monsurrò, Maria Rosaria; Tedeschi, Gioacchino; Marinou, Kalliopi; Sabatelli, Mario; Conte, Amelia; Mandrioli, Jessica; Sola, Patrizia; Salvi, Fabrizio; Bartolomei, Ilaria; Siciliano, Gabriele; Carlesi, Cecilia; Orrell, Richard W; Talbot, Kevin; Simmons, Zachary; Connor, James; Pioro, Erik P; Dunkley, Travis; Stephan, Dietrich A; Kasperaviciute, Dalia; Fisher, Elizabeth M; Jabonka, Sibylle; Sendtner, Michael; Beck, Marcus; Bruijn, Lucie; Rothstein, Jeffrey; Schmidt, Silke; Singleton, Andrew; Hardy, John; Traynor, Bryan J

    2009-04-15

    The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 [odds ratio (OR) = 1.17 and 1.18, and P-values = 6.98 x 10(-7) and 1.16 x 10(-6)], were located on chromosome 7p13.3 within a 175 kb linkage disequilibrium block containing the SUNC1, HUS1 and C7orf57 genes. These associations did not achieve genome-wide significance in the original cohort and failed to replicate in an additional independent cohort of 989 US cases and 327 controls (OR = 1.18 and 1.19, P-values = 0.08 and 0.06, respectively). Thus, we chose to cautiously interpret our data as hypothesis-generating requiring additional confirmation, especially as all previously reported loci for ALS have failed to replicate successfully. Indeed, the three loci (FGGY, ITPR2 and DPP6) identified in previous GWAS of sporadic ALS were not significantly associated with disease in our study. Our findings suggest that ALS is more genetically and clinically heterogeneous than previously recognized. Genotype data from our study have been made available online to facilitate such future endeavors. PMID:19193627

  5. 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

  6. 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 (Aβ) 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 Aβ 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 Aβ. 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

  7. Irrelevance of microsatellite instability in the epidemiology of sporadic pancreatic ductal adenocarcinoma.

    Luigi Laghi

    Full Text Available BACKGROUND AND AIMS: Pancreatic cancer risk is increased in Lynch syndrome (LS patients with mismatch repair gene defects predisposing to colonic and extracolonic cancers with microsatellite instability (MSI. However, the frequency of MSI pancreatic cancers has never been ascertained in consecutive, unselected clinical series, and their contribution to the sporadic and inherited burden of pancreatic cancer remains to be established. Aims of the study were to determine the prevalence of MSI in surgically resected pancreatic cancers in a multicentric, retrospective study, and to assess the occurrence of pancreatic cancer in LS. METHODS: MS-status was screened by a panel of 5 mononucleotide repeats (Bat26, Bat25, NR-21, NR-24 and NR-27 in 338 consecutive pancreatic ductal adenocarcinoma (PDAC, resected at two Italian and one German referral centres. The personal history of pancreatic cancer was assessed in an independent set of 58 probands with LS and in 138 first degree relatives who had cancers. RESULTS: Only one PDAC (0.3% showed MSI. This was a medullary type cancer, with hMLH1-deficiency, and no identified germ-line mutation but methylation of hMLH1. Pancreatic cancer occurred in 5 (2.5% LS patients. Histological sampling was available for 2 cases, revealing PDAC in one case and an ampullary cancer in the other one. CONCLUSIONS: MSI prevalence is negligible in sporadic, resected PDAC. Differently, the prevalence of pancreatic cancer is 2.5% in LS patients, and cancers other than PDAC may be encountered in this setting. Surveillance for pancreatic cancer should be advised in LS mutation carriers at referral centers.

  8. 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

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

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

    2015-12-01

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

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

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

    2008-01-01

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

  11. Rainfall is a risk factor for sporadic cases of Legionella pneumophila pneumonia.

    Carolina Garcia-Vidal

    Full Text Available It is not known whether rainfall increases the risk of sporadic cases of Legionella pneumonia. We sought to test this hypothesis in a prospective observational cohort study of non-immunosuppressed adults hospitalized for community-acquired pneumonia (1995-2011. Cases with Legionella pneumonia were compared with those with non-Legionella pneumonia. Using daily rainfall data obtained from the regional meteorological service we examined patterns of rainfall over the days prior to admission in each study group. Of 4168 patients, 231 (5.5% had Legionella pneumonia. The diagnosis was based on one or more of the following: sputum (41 cases, antigenuria (206 and serology (98. Daily rainfall average was 0.556 liters/m(2 in the Legionella pneumonia group vs. 0.328 liters/m(2 for non-Legionella pneumonia cases (p = 0.04. A ROC curve was plotted to compare the incidence of Legionella pneumonia and the weighted median rainfall. The cut-off point was 0.42 (AUC 0.54. Patients who were admitted to hospital with a prior weighted median rainfall higher than 0.42 were more likely to have Legionella pneumonia (OR 1.35; 95% CI 1.02-1.78; p = .03. Spearman Rho correlations revealed a relationship between Legionella pneumonia and rainfall average during each two-week reporting period (0.14; p = 0.003. No relationship was found between rainfall average and non-Legionella pneumonia cases (-0.06; p = 0.24. As a conclusion, rainfall is a significant risk factor for sporadic Legionella pneumonia. Physicians should carefully consider Legionella pneumonia when selecting diagnostic tests and antimicrobial therapy for patients presenting with CAP after periods of rainfall.

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

    de Pedro-Cuesta, Jesús; Mahillo-Fernández, Ignacio; Rábano, Alberto;

    2011-01-01

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

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

    Borad, Mitesh J.; Champion, Mia D.; Egan, Jan B.; Liang, Winnie S.; Rafael Fonseca; Bryce, Alan H.; Ann E McCullough; Barrett, Michael T.; Katherine Hunt; Maitray D Patel; Young, Scott W.; Collins, Joseph M.; Silva, Alvin C; Condjella, Rachel M.; Matthew Block

    2014-01-01

    Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited. During the course of a clinical trial of whole genomic sequencing seeking druggable targets, we examined six patients with advanced cholangiocarcinoma. Integrated genome-wide and whole transcriptome sequence analyses were performed on tumors from six patients with advanced, sporadic intrahepatic cholangiocarcinoma (SIC) to identify potential therapeutically actionable events. Among...

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

    Xuelian Ji; Longfei Jia; Jianping Jia; Li Qi

    2012-01-01

    A missense C/T polymorphism in exon 6 (the NCBI rsID is rs2227564) of the urokinase-type plasminogen activator gene has been identified as a possible hot spot for Alzheimer's disease risk.The present study analyzed urokinase-type plasminogen gene polymorphisms of rs2227564 with sporadic Alzheimer's disease by PCR-restriction fragment length polymorphism.Results showed that CC,CT and TT genotype distribution frequencies had significant differences between sporadic Alzheimer's disease patients and healthy controls.In-depth analysis of the association between urokinase-type plasminogen gene rs2227564 polymorphisms and sporadic Alzheimer's disease indicated that people with the C-positive genotype CC + CT were at a higher risk for developing sporadic Alzheimer's disease.These results support the contribution of the polymorphisms of rs2227564 in the urokinase-type plasminogen gene to the pathogenesis of sporadic Alzheimer's disease in the Han Chinese population.

  18. Loss of WIF-1 and Wnt5a expression is related to aggressiveness of sporadic breast cancer in Tunisian patients.

    Trifa, Fatma; Karray-Chouayekh, Sondes; Jmal, Emna; Jmaa, Zeineb Ben; Khabir, Abdelmajid; Sellami-Boudawara, Tahia; Frikha, Mounir; Daoud, Jamel; Mokdad-Gargouri, Raja

    2013-06-01

    Activation of the Wnt/β-catenin signaling pathway is common in various human cancers. The aim of this study was to investigate the expression of 2 members of the Wnt family (WIF-1 and Wnt5a) in sporadic and hereditary breast cancer tissues. WIF-1, is a secreted antagonist that binds Wnt ligands, and therefore inhibits the canonical Wnt/β-catenin pathway. Wnt5a is one of the members of the noncanonical Wnt family that mainly acts through calcium signaling pathway. The expression of WIF-1 was analyzed by methylation-specific PCR and RT-PCR, and the level of Wnt5a ligand was quantified by RT-QPCR in breast cancer tissues. Methylation of WIF-1 was detected in 71.3 % and 81.8 % of sporadic and hereditary cases, respectively. Aberrant methylation of WIF-1 was associated with advanced TNM stage and triple negative cases in sporadic breast carcinoma (p=0.001 and p=0.037, respectively). In hereditary cases, methylation of WIF-1 correlated with age at diagnosis (p=0.027) and p53 status (p=0.035). Regarding patients' survival, WIF-1 methylated promoter conferred a reduced overall survival rate, and particularly in a group of patients with advanced TNM stage (p log rank=0.006). Furthermore, aberrant CpG methylation of the WIF-1 promoter was significantly associated with transcriptional silencing of this tumor suppressor gene in sporadic breast cancer tissues (p=0.036). On the other hand, in sporadic tumor tissues, the level of Wnt5a mRNA was significantly lower compared to normal tissues (p=0.031) and lower still in those showing more aggressive behavior, suggesting that Wnt5a, a ligand involved in the noncanonical Wnt/β-catenin pathway, could act as a tumor suppressor gene in breast cancer. PMID:23417837

  19. Results of Experimental and Theoretical Studies of the Atmospheric Turbulence, Internal Gravity Waves and Sporadic-E Layers by Resonant Scattering of Radio Waves on Artificial Periodic Irregularities

    Bakhmetieva, Nataliya V.; Grigoriev; Tolmacheva, Ariadna V.

    Artificial periodic irregularities (API) formed by the powerful standing radio waves in the ionospheric plasma give the good chance for the lower ionosphere comprehensive studies. In this paper we present some applications of the API technique for experimental studies of sporadic E-layers (E _{s}), internal gravity waves and turbulent events in the lower ionosphere. API are formed in the field of the standing radio wave produced by interference of the incident wave and reflected one from the ionosphere (in more details about the API technique one can see in the book Belikovich et al., Ionospheric Research by Means of Artificial Periodic Irregularities - Katlenburg-Lindau, Germany. 2002. Copernicus GmbH. ISBN 3-936586-03-9). The spatial period of the irregular structure is equal to the standing wavelength Lambda or one-half the powerful wavelength lambda/2. API diagnostics are carried out at the API relaxation or decay stage by their sounding of probing radio pulses. Based on the measurement of an amplitude and a phase of the API scattered signal their relaxation time and regular vertical plasma velocity are measured. In the E-region of the ionosphere API are formed as a result of the diffusion redistribution of the non-uniformly heated plasma. The relaxation of the periodic structure is specified by the ambipolar diffusion process. The diffusion time is tau=(K (2) D _{a}) (-1) where K=2pi/Lambda and D _{a} is the ambipolar diffusion rate. The atmospheric turbulence causes reduction of the API relaxation time in comparison the diffusion time. Determination of the turbulent velocity is based on this fact. The vertical plasma velocity is determined by measuring the phase of the scattered signal. Atmospheric waves having the periods from 5-10 minutes to 5-6 hours give the contribution to temporal variations of the velocity. Parameters and effects of atmospheric waves and the turbulence on the API relaxation process are presented. Determination of the masses of the

  20. Mitochondrial DNA Haplogroups and the Risk of Sporadic Parkinson's Disease in Han Chinese

    Ya-Fang Chen; Wan-Jin Chen; Xiao-Zhen Lin; Qi-Jie Zhang; Jiang-Ping Cai; Chia-Wei Liou; Ning Wang

    2015-01-01

    Background:Mitochondrial dysfunction is linked to the pathogenesis of Parkinson's disease (PD).However,the precise role of mitochondrial DNA (mtDNA) variations is obscure.On the other hand,mtDNA haplogroups have been inconsistently reported to modify the risk of PD among different population.Here,we try to explore the relationship between mtDNA haplogroups and sporadic PD in a Han Chinese population.Methods:Nine single-nucleotide polymorphisms,which define the major Asian mtDNA haplogroups (A,B,C,D,F,G),were detected via polymerase chain reaction-restriction fragment length polymorphism or denaturing polyacrylamide gel electrophoresis in 279 sporadic PD patients and 510 matched controls of Han population.Results:Overall,the distribution ofmtDNA haplogroups did not show any significant differences between patients and controls.However,after stratification by age at onset,the frequency of haplogroup B was significantly lower in patients with early-onset PD (EOPD) compared to the controls (odds ratio [OR] =0.225,95% confidence interval [CI]:0.082-0.619,P =0.004),while other haplogroups did not show significant differences.After stratification by age at examination,among subjects younger than 50 years of age:Haplogroup B also showed a lower frequency in PD cases (OR =0.146,95% CI:0.030-0.715,P =0.018) while haplogroup D presented a higher risk of PD (OR =3.579,95% CI:1.112-11.523,P =0.033),other haplogroups also did not show significant differences in the group.Conclusions:Our study indicates that haplogroup B might confer a lower risk for EOPD and people younger than 50 years in Han Chinese,while haplogroup D probably lead a higher risk of PD in people younger than 50 years of age.In brief,particular Asian mtDNA haplogroups likely play a role in the pathogenesis of PD among Han Chinese.

  1. 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

  2. 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

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

    Ślaska Brygida

    2014-12-01

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

  4. 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.

  5. Lack of association between the APEX1 Asp148Glu polymorphism and sporadic amyotrophic lateral sclerosis.

    Coppedè, Fabio; Lo Gerfo, Annalisa; Carlesi, Cecilia; Piazza, Selina; Mancuso, Michelangelo; Pasquali, Livia; Murri, Luigi; Migliore, Lucia; Siciliano, Gabriele

    2010-02-01

    Impairments in DNA repair enzymes have been observed in amyotrophic lateral sclerosis (ALS) tissues, particularly in the activity of the apurinic/apyrimidinic endonuclease 1 (APEX1). Moreover, it was suggested that the common APEX1 Asp148Glu polymorphism might be associated with ALS risk. To further address this question we performed the present study aimed at evaluating the contribution of the APEX1 Asp148Glu polymorphism in sporadic ALS (sALS) risk and clinical presentation, including age and site of onset and disease progression. We screened 134 sALS Italian patients and 129 matched controls for the presence of the APEX1 Asp148Glu polymorphism. No difference in APEX1 Asp148Glu allele and genotype frequencies was found between the groups, nor was the polymorphism associated with age and site of onset or disease progression. Present results do not support a role for the APEX1 Asp148Glu polymorphism in sALS pathogenesis in the Italian population. PMID:18482781

  6. Health-related quality of life in sporadic adult-onset ataxia.

    Abele, Michael; Klockgether, Thomas

    2007-02-15

    Despite progressive disability in sporadic adult-onset ataxia (SAOA), little is known about patients' assessment of their ataxic disorder and its impact on health-related quality of life (Hr-QoL). This study investigated Hr-QoL by means of the following self-administered scales: Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Beck Depression Inventory (BDI), and the Medical Outcome Study Short Form (SF-36). Twenty-two unselected ataxia patients were included. Sleep-related complaints were found in 9 (41%) of 22 and symptoms of depression in 6 (38%) of 16 patients. Compared to a large german control group, SAOA patients had lower scores in all SF-36 dimensions except for bodily pain. The greatest impairment was found in the domain physical functioning, followed by the domains social functioning and role limitations (emotional problems). There was a significant negative correlation of all nonmotor SF-36 dimensions with the BDI score. Walking aid dependency was significantly correlated with poorer health status perception in several motor and nonmotor domains. In addition, impaired sleep quality was correlated with an impaired general health perception and with bodily pain. The study demonstrates a great impact of SAOA on Hr-QoL. Adequate treatment of depression, motor disability, and impaired sleep quality is essential to improve Hr-QoL in ataxic patients. PMID:17149704

  7. 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.

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

    Sarma, M. S. S. R. K. N.; Raghava Reddy, C.; Niranjan, K.

    2009-02-01

    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 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.

  9. Complex mitochondrial DNA rearrangements in individual cells from patients with sporadic inclusion body myositis

    Rygiel, Karolina A.; Tuppen, Helen A.; Grady, John P.; Vincent, Amy; Blakely, Emma L.; Reeve, Amy K.; Taylor, Robert W.; Picard, Martin; Miller, James; Turnbull, Doug M.

    2016-01-01

    Mitochondrial DNA (mtDNA) rearrangements are an important cause of mitochondrial disease and age related mitochondrial dysfunction in tissues including brain and skeletal muscle. It is known that different mtDNA deletions accumulate in single cells, but the detailed nature of these rearrangements is still unknown. To evaluate this we used a complementary set of sensitive assays to explore the mtDNA rearrangements in individual cells from patients with sporadic inclusion body myositis, a late-onset inflammatory myopathy with prominent mitochondrial changes. We identified large-scale mtDNA deletions in individual muscle fibres with 20% of cytochrome c oxidase-deficient myofibres accumulating two or more mtDNA deletions. The majority of deletions removed only the major arc but ∼10% of all deletions extended into the minor arc removing the origin of light strand replication (OL) and a variable number of genes. Some mtDNA molecules contained two deletion sites. Additionally, we found evidence of mitochondrial genome duplications allowing replication and clonal expansion of these complex rearranged molecules. The extended spectrum of mtDNA rearrangements in single cells provides insight into the process of clonal expansion which is fundamental to our understanding of the role of mtDNA mutations in ageing and disease. PMID:27131788

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

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

  11. 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.

  12. 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, PPARγ. 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, 3р26. 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.

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

    Rakesh Kumar Manne

    2014-01-01

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

  14. Differential expression of molecular motors in the motor cortex of sporadic ALS.

    Pantelidou, Maria; Zographos, Spyros E; Lederer, Carsten W; Kyriakides, Theodore; Pfaffl, Michael W; Santama, Niovi

    2007-06-01

    The molecular mechanisms underlying the selective neurodegeneration of motor neurons in amyotrophic lateral sclerosis (ALS) are inadequately understood. Recent breakthroughs have implicated impaired axonal transport, mediated by molecular motors, as a key element for disease onset and progression. The current work identifies the expression of 15 kinesin-like motors in healthy human motor cortex, including three novel isoforms. Our comprehensive quantitative mRNA analysis in control and sporadic ALS (SALS) motor cortex specimens detects SALS-specific down-regulation of KIF1Bbeta and novel KIF3Abeta, two isoforms we show to be enriched in the brain, and also of SOD1, a key enzyme linked to familial ALS. This is accompanied by a marked reduction of KIF3Abeta protein levels. In the motor cortex KIF3Abeta localizes in cholinergic neurons, including upper motor neurons. No mutations causing splicing defects or altering protein-coding sequences were identified in the genes of the three proteins. The present study implicates two motor proteins as possible candidates in SALS pathology. PMID:17418584

  15. Lidar observations of Ca and K metallic layers from Arecibo and comparison with micrometeor sporadic activity

    Raizada, S.; Tepley, C. A.; Janches, D.; Friedman, J. S.; Zhou, Q.; Mathews, J. D.

    2004-04-01

    We report on the first simultaneous observations of Ca and K metallic layers using the low-latitude lidar systems located at the Arecibo Observatory in Puerto Rico (18.35°N, 66.75°W). We often observe sudden increases in both Ca and K densities during early morning hours on nights where meteor showers take place. During these periods, the Ca/K abundance ratio varied between 2 and 3. On occasion, differences were observed in Ca and K layers, which relate to differences in the chemistry of the two metals. It is known that metallic layers display distinct seasonal variations, but chemistry alone cannot explain the measured differences. Thus, we examined whether or not the seasonal distribution of micrometeoroids, derived from meteor observations using the Arecibo 430MHz radar, can account for the dissimilar metallic observations. We found that the deposition flux of micrometeoroids, with particle sizes ranging between 0.5 and 100μm, increased by a factor of two during the summer as compared with the winter, suggesting a seasonal variation of their sporadic activity. In addition, our data support the idea that differential ablation leads to a depletion of Ca atoms in the mesosphere.

  16. 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.

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

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

    2009-01-01

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

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

    Bourdon Violaine

    2011-01-01

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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. [Increased incidence of multiple melanoma in sporadic and familial dysplastic nevus cell syndrome].

    Sigg, C; Pelloni, F; Schnyder, U W

    1989-09-01

    In 280 melanoma patients all data concerning familial and personal history, histology, and therapy were verified. All patients underwent total-body skin examination to check for the presence of dysplastic nevus syndrome (DNS). In 257/280 patients (91.8%) solitary melanomas were found, while in 23/280 patients (8.2%) multiple melanomas occurring simultaneously or consecutively were ascertained. Surprisingly, among the 12/280 patients (4.2%) with familial variants of melanoma, multiple melanomas were not found in a increased frequency. In patients with DNS (regardless of whether sporadic or familial) the frequency of multiple melanomas is higher: in patients with solitary melanomas DNS was found in 27/257 (10.5%), while in patients with multiple melanomas DNS was diagnosed in 11/23 (47.8%) (P less than 0.0005). In both groups (solitary and multiple melanomas) the mean age of patients with DNS was around 10 years lower. The frequency of additional primary malignancies in patients with cutaneous melanomas was 8.6%, and did not vary according as whether patients had solitary or multiple melanomas with or without DNS. PMID:2807914

  4. Migraine-Induced Epistaxis and Sporadic Hemiplegic Migraine: Unusual Features in the Same Patient

    José Barros

    2012-06-01

    Full Text Available Background: Since the mid-19th century, epistaxis and migraine have been occasionally associated with each other. Nevertheless, we found only two cases in the contemporary medical literature. Sporadic hemiplegic migraine is a subtype of migraine with reversible motor deficits, without similar episodes in relatives. Case: We describe a 47-year-old male with a history of migraine with a scintillating scotoma starting at the age of 20. In some of the episodes, he developed epistaxis in the resolution phase of migraine. At the age of 35, he experienced a visual aura followed by transient aphasia, left crural weakness and headache. Contralateral similar episodes occurred in the subsequent months. Neurological examination and MRI were normal. Mutations in CACNA1A, ATP1A2, SCN1A and NOTCH3 were excluded. Discussion: Three distinct aspects deserve our consideration. This is the first report of migraine-induced epistaxis involving aura; the scarcity of similar reports may be due to the lack of a guided anamnesis. The complex aura presented had a peculiar topography, inconsistent with the classical analytical neurological semiology. This may suggest that the spreading depression affects the brain bilaterally but in an uneven and elective manner. Lastly, the present report conveys that the late appearance of complex auras requires improbable interactions between environmental and endogenous conditions in individuals with a genetic predisposition.

  5. Spatio-temporal genetic heterogeneity of CTNNB1 mutations in sporadic desmoid type fibromatosis lesions.

    Doyen, Jérôme; Duranton-Tanneur, Valérie; Hostein, Isabelle; Karanian-Philippe, Marie; Chevreau, Christine; Breibach, Florence; Coutts, Michael; Dadone, Bérengère; Saint-Paul, Marie-Christine; Gugenheim, Jean; Duffaud, Florence; Pedeutour, Florence

    2016-03-01

    Desmoid type fibromatosis (DT) is a rare lesion of unclear pathogenesis that most often presents a mutation of the (β-catenin) gene. The natural history and clinical evolution are highly variable between patients and to date there is no consensus on optimal therapy. We report two cases of a patient with multiple DT lesions. Molecular investigations performed in both patients on multiple tumors at different anatomical sites revealed non-identical CTNNB1 mutations. The first patient was a 39-year-old man with a history of recurrent DT. In two of the DT lesions, three different mutations were found in codons 41 and 45, respectively. The lesions showed marked inflammatory features, characterized by IgG4 positive lymphoplasmacytic infiltrates and a foreign body reaction, which increased in intensity over time. The patient was eventually treated with a COX-2 inhibitor and the remaining mass was stabilized. In the two DT lesions of the second patient, CTNNB1 mutations S45P and T41A were found. The presence of different mutations in multiple focally recurrent sporadic DT lesions indicates that they do not have a clonal relationship. Our data suggest that a CTNNB1 mutation is a necessary event probably by providing a selective growth advantage. An IgG4 host antigen response is discussed as a potential predisposing factor for one of the patients. PMID:26666421

  6. 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.

  7. 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.

  8. 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.

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

    Schlehofer, B; Schlaefer, K; Blettner, M;

    2007-01-01

    The only known risk factor for sporadic acoustic neuroma is high-dose ionising radiation. Environmental exposures, such as radiofrequency electromagnetic fields and noise are under discussion, as well as an association with allergic diseases. We performed a population-based case-control study...... in Germany investigating these risk factors in 97 cases with acoustic neuroma, aged 30 to 69 years, and in 194 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in multiple logistic regression models. Increased risks were found for exposure to persistent noise (OR=2.......31; 95% CI 1.15-4.66), and for hay fever (OR=2.20; 95% CI 1.09-4.45), but not for ionising radiation (OR=0.91; 95 % CI 0.51-1.61) or regular mobile phone use (OR=0.67; 95% CI 0.38-1.19). The study confirms results of recently published studies, although the pathogenetic mechanisms are still unknown....

  10. 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

  11. Frequency of the LRRK2 G2019S mutation in late-onset sporadic patients with Parkinson’s disease

    Hsin Fen Chien

    2014-05-01

    Full Text Available Mutations in the LRRK2 gene, predominantly G2019S, have been reported in individuals with autosomal dominant inheritance and sporadic Parkinson’s disease (PD. The G2019S mutation has an age-dependent penetrance and evidence shows common ancestry. The clinical manifestations are indistinguishable from idiopathic PD. Its prevalence varies according to the population studied ranging from less than 0.1% in Asians to 41% in North African Arabs. This study aimed to identify G2019S mutation in Brazilian idiopathic PD patients. Method: We sampled 100 PD patients and 100 age- and gender-matched controls. Genetical analysis was accomplished by polymerase chain reaction (PCR. Results: No G2019S mutations were found in both patients with sporadic PD and controls. Conclusions: Our results may be explained by the relatively small sample size.

  12. The Correlation between Microsatellite Instability and the Features of Sporadic Colorectal Cancer in the North Part of Iran

    Masoumeh Faghani

    2012-01-01

    Full Text Available Background. The aim of this study was to determine the correlation between MSI and sporadic colorectal cancer in Guilan province, North part of Iran. Materials and Methods. A total of 96 patients who underwent resection for sporadic colorectal cancer in Guilan province were studied. No patients had positive family history of cancers. The frequencies of MSI were analyzed by testing the BAT-26 and BAT-25 markers. Results. MSI analysis revealed that 22.9% of the tumors (22 patients were microsatellite instability positive and 77.1% (74 patients were microsatellite instability negative. The highest rate of MSI (40.9% was found in the rectal region. MSI-H status was seen more frequently in distal tumors (P=0.04, odds ratio = 3.13, 0.96–10.14. Conclusions. Distal tumor location and MSI may associate with special clinicopathological features. It seems that there may be correlation with underlying genetic and immunologic mechanisms.

  13. 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

  14. Kuru prions and sporadic Creutzfeldt-Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice

    Wadsworth, J D F; Joiner, S; Linehan, J M; Desbruslais, M.; Fox, K; Cooper, S.; Cronier, S.; Asante, E. A.; Mead, S.; Brandner, S; Hill, A. F.; Collinge, J.

    2008-01-01

    Kuru provides our principal experience of an epidemic human prion disease and primarily affected the Fore linguistic group of the Eastern Highlands of Papua New Guinea. Kuru was transmitted by the practice of consuming dead relatives as a mark of respect and mourning (transumption). To date, detailed information of the prion strain type propagated in kuru has been lacking. Here, we directly compare the transmission properties of kuru prions with sporadic, iatrogenic, and variant Creutzfeldt–J...

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

    Costa S.C.

    2001-01-01

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

  16. Motor Neurone Disease (MND/ALS) among Maltese in Malta and Australia : many sporadic cases were related

    Wyatt, H V

    2014-01-01

    Objective: to look for genetic links between cases of MND. Method: to search for ancestors of Maltese cases dying in Malta and Australia and to record dispensations for consanguineous marriages. Results: the median age of death was similar in both countries and in Malta was similar for men and women. Almost 45 % of the cases were related to one or more other cases: however, more than half were sporadic and widely dispersed. Conclusions: MND is not affected by emigration to the southern hemisp...

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

    Liu, Ying; Dodds, Phillippa; Emilion, Gracy;

    2002-01-01

    In sporadic ovarian cancer, we have previously reported allele loss at D6S193 (62%) on chromosome 6q27, which suggested the presence of a putative tumour suppressor gene. Based on our data and that from another group, the minimal region of allele loss was between D6S264 and D6S149 (7.4 cM). To id...

  18. 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

  19. GTP cyclohydrolase I and tyrosine hydroxylase gene mutations in familial and sporadic dopa-responsive dystonia patients.

    Cai, Chunyou; Shi, Wentao; Zeng, Zheng; Zhang, Meiyun; Ling, Chao; Chen, Lei; Cai, Chunquan; Zhang, Benshu; Li, Wei-Dong

    2013-01-01

    Dopa-responsive dystonia (DRD) is a rare inherited dystonia that responds very well to levodopa treatment. Genetic mutations of GTP cyclohydrolase I (GCH1) or tyrosine hydroxylase (TH) are disease-causing mutations in DRD. To evaluate the genotype-phenotype correlations and diagnostic values of GCH1 and TH mutation screening in DRD patients, we carried out a combined study of familial and sporadic cases in Chinese Han subjects. We collected 23 subjects, 8 patients with DRD, 5 unaffected family members, and 10 sporadic cases. We used PCR to sequence all exons and splicing sites of the GCH1 and TH genes. Three novel heterozygous GCH1 mutations (Tyr75Cys, Ala98Val, and Ile135Thr) were identified in three DRD pedigrees. We failed to identify any GCH1 or TH mutation in two affected sisters. Three symptom-free male GCH1 mutation carriers were found in two DRD pedigrees. For those DRD siblings that shared the same GCH1 mutation, symptoms and age of onset varied. In 10 sporadic cases, only two heterozygous TH mutations (Ser19Cys and Gly397Arg) were found in two subjects with unknown pathogenicity. No GCH1 and TH mutation was found in 40 unrelated normal Han Chinese controls. GCH1 mutation is the main etiology of familial DRD. Three novel GCH1 mutations were identified in this study. Genetic heterogeneity and incomplete penetrance were quite common in DRD patients, especially in sporadic cases. Genetic screening may help establish the diagnosis of DRD; however, a negative GCH1 and TH mutation test would not exclude the diagnosis. PMID:23762320

  20. GTP cyclohydrolase I and tyrosine hydroxylase gene mutations in familial and sporadic dopa-responsive dystonia patients.

    Chunyou Cai

    Full Text Available Dopa-responsive dystonia (DRD is a rare inherited dystonia that responds very well to levodopa treatment. Genetic mutations of GTP cyclohydrolase I (GCH1 or tyrosine hydroxylase (TH are disease-causing mutations in DRD. To evaluate the genotype-phenotype correlations and diagnostic values of GCH1 and TH mutation screening in DRD patients, we carried out a combined study of familial and sporadic cases in Chinese Han subjects. We collected 23 subjects, 8 patients with DRD, 5 unaffected family members, and 10 sporadic cases. We used PCR to sequence all exons and splicing sites of the GCH1 and TH genes. Three novel heterozygous GCH1 mutations (Tyr75Cys, Ala98Val, and Ile135Thr were identified in three DRD pedigrees. We failed to identify any GCH1 or TH mutation in two affected sisters. Three symptom-free male GCH1 mutation carriers were found in two DRD pedigrees. For those DRD siblings that shared the same GCH1 mutation, symptoms and age of onset varied. In 10 sporadic cases, only two heterozygous TH mutations (Ser19Cys and Gly397Arg were found in two subjects with unknown pathogenicity. No GCH1 and TH mutation was found in 40 unrelated normal Han Chinese controls. GCH1 mutation is the main etiology of familial DRD. Three novel GCH1 mutations were identified in this study. Genetic heterogeneity and incomplete penetrance were quite common in DRD patients, especially in sporadic cases. Genetic screening may help establish the diagnosis of DRD; however, a negative GCH1 and TH mutation test would not exclude the diagnosis.

  1. 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.

  2. Successful outcome after laparoscopic surgery for sporadic colonic desmoid tumor with β-catenin mutation: a case report

    Gunji, Shutaro; Kawada, Kenji; Kawada, Mayumi; Hasegawa, Suguru; Sakai, Yoshiharu

    2013-01-01

    Introduction Desmoid tumors (also called aggressive fibromatosis) are histologically benign, but have a strong tendency to recur locally after resection. They are rare neoplastic tumors that may occur sporadically or in association with familial adenomatous polyposis caused by a germline mutation in the adenomatous polyposis coli gene. The etiology of desmoid tumors is unknown, but their association with a history of abdominal surgery, trauma, and estrogen therapy is well known. Case presenta...

  3. 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

  4. 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

  5. [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

  6. 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

  7. 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.

  8. 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.

  9. Clinical-epidemiological features of meningococcal infection in children during sporadic morbidity

    G. P. Martynova

    2015-07-01

    Full Text Available Purpose: to evaluate epidemiologic situation as to meningococcal infection and reveal clinical-epidemiological features of the disease on the territory of Krasnoyarsk сity and Krasnoyarsk Krai at the present stage. Data and methods: The research gives the analysis of MI morbidity and mortality rates in children of the region according to official information from the Federal Service for Supervision of Consumer Rights Protection and Human Welfare in Krasnoyarsk Krai for the period 2000–2014. The work studies clinical and epidemiological features of the disease in 53 patients with the generalized form of meningococcal infection (GFMI who were treated in the infectious disease department of the Regional Interdistrict Children’s Clinical Hospital of Krasnoyarsk for the period 2010–2014. Results: The epidemiological situation as to MI in Krasnoyarsk for the period 2000-2013 years is characterized by the signs of interepidemic period with morbidity rises in the winter-spring period. Children from 1 year to 3 years (54,7% prevail over all MI diseased. The number of children in the first year of life decreased almost two times (from 40% to 20,7%. At the same time the proportion of children older than 4 years increased. The leading serotype among laboratory-confirmed cases of MI in Krasnoyarsk Krai is still the B group meningitis (64,7%. Conclusion: On the territory of Krasnoyarsk Krai the MI morbidity is sporadic. The generalized forms of meningococcal infection are characterized by early overt symptoms which make it possible to set a diagnosis. The clinical picture of the generalized forms of the disease almost did not change significantly. 

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

    Lina Marcela Barrera

    2010-12-01

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

  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. Association of the hOGG1 Ser326Cys polymorphism with sporadic amyotrophic lateral sclerosis.

    Coppedè, Fabio; Mancuso, Michelangelo; Lo Gerfo, Annalisa; Carlesi, Cecilia; Piazza, Selina; Rocchi, Anna; Petrozzi, Lucia; Nesti, Claudia; Micheli, Dario; Bacci, Andrea; Migliore, Lucia; Murri, Luigi; Siciliano, Gabriele

    2007-06-13

    Amyotropic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disease causing the loss of motoneurons of the brain and the spinal cord. The etiology of ALS is still uncertain, but males are at increased risk for the disease than females. Several studies have suggested that motoneurons in ALS might be subjected to the double insult of increased DNA oxidative damage and deficiencies in DNA repair systems. Particularly, increased levels of 8-oxoguanine and impairments of the DNA base excision repair system have been observed in neurons of ALS patients. There is evidence that the Ser326Cys polymorphism of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene is associated with a reduced DNA repair activity. To evaluate the role of the hOGG1 Ser326Cys polymorphism in sporadic ALS (sALS), we screened 136 patients and 129 matched controls. In the total population, we observed association between both the Cys326 allele (p=0.02) and the combined Ser326Cys+Cys326Cys genotype (OR=1.65, 95% CI=1.06-2.88) and increased risk of disease. After stratification by gender, the Cys326 allele (p=0.01), both the Ser326Cys genotype (OR=2.14, 95% CI=1.09-4.19) and the combined Ser326Cys+Cys326Cys genotype (OR=2.15, 95% CI=1.16-4.01) were associated with sALS risk only in males. No significant association between the Ser326Cys polymorphism and disease phenotype, including age and site of onset and disease progression, was observed. Present results suggest a possible involvement of the hOGG1 Ser326Cys polymorphism in sALS pathogenesis. PMID:17531381

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

    Edward C. Mader

    2013-02-01

    Full Text Available The clinical diagnosis of Creutzfeldt-Jakob disease (CJD is largely based on the 1998 World Health Organization diagnostic criteria. Unfortunately, rigid compliance with these criteria may result in failure to recognize sporadic CJD (sCJD, especially early in its course when focal findings predominate and traditional red flags are not yet present. A 61-year-old man presented with a 3-week history of epilepsia partialis continua (jerking of the left upper extremity and a 2-week history of forgetfulness and left hemiparesis; left hemisensory neglect was also detected on admission. Repeated brain magnetic resonance imaging (MRI showed areas of restricted diffusion in the cerebral cortex, initially on the right but later spreading to the left. Electroencephalography (EEG on hospital days 7, 10, and 14 showed right-sided periodic lateralized epileptiform discharges. On day 20, the EEG showed periodic sharp wave complexes leading to a diagnosis of probable sCJD and subsequently to definite sCJD with brain biopsy. Neurological decline was relatively fast with generalized myoclonus and akinetic mutism developing within 7 weeks from the onset of illness. CJD was not immediately recognized because of the patient’s focal/lateralized manifestations. Focal/lateralized clinical, EEG, and MRI findings are not uncommon in sCJD and EEG/MRI results may not be diagnostic in the early stages of sCJD. Familiarity with these caveats and with the most current criteria for diagnosing probable sCJD (University of California San Francisco 2007, MRI-CJD Consortium 2009 will enhance the ability to recognize sCJD and implement early safety measures.

  14. 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.

  15. 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.)

  16. Distinct Patterns of Structural and Numerical Chromosomal Instability Characterize Sporadic Ovarian Cancer

    Jane Bayani

    2008-10-01

    Full Text Available Sporadic ovarian cancer is a particularly aggressive tumor characterized by highly abnormal karyotypes exhibiting many features of genomic instability. More complex genomic changes in tumors arise as a consequence of chromosomal instability (CIN, which can generate both numerical [(N-CIN] and structural chromosomal instability [(S-CIN]. In this study, molecular cytogenetic analysis was used to evaluate the relative levels of both (N-CIN and (S-CIN. Six tumors had a near-diploid chromosome number, two were near-tetraploid, and two were near-triploid. (N-CIN levels increased as a function of overall tumor genomic content, with near-diploid tumors exhibiting numerical instability indices ranging from 7.0 to 21.0 and near-tetraploid and triploid tumors exhibiting instability indices ranging from 24.9 to 54.9. In contrast, the extent of (S-CIN was generally more evident in the diploid tumors compared with the near-tetraploid tumors. To determine whether the associated chromosomal constitution and/or ploidy changes were influenced by mitotic segregation errors, centrosome analyses were performed on all 10 tumors. The near-diploid tumors, with the lowest numerical change, were observed to possess fewer cells with centrosome abnormalities (5.5% to 14.0%, whereas the near-tetraploid tumors possessed much higher levels of (N-CIN and were characterized by a trend of elevating percentages of cells with abnormal centrosomes (16.0% to 20.5%. These observations suggest that two distinct processes governing genome stability may be disrupted in ovarian cancer: those that impact on numerical segregation and ploidy of chromosomes and those that affect the fidelity of DNA repair and lead to structural aberrations.

  17. 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

  18. 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

  19. The field of a radio signal in the case of the simultaneous existence of two sporadic-E layers in the ionosphere

    Kerblai, T. S.; Nosova, G. N.; Palacio, L.; Melendez, B.

    1988-02-01

    The paper presents an analysis of signal amplitude recorded at two frequencies (12 and 20 MHz) on a Santiago de Cuba-Havana radio channel during the simultaneous appearance of several sporadic-E layers on oblique-sounding ionograms obtained at the median point of the channel. It is shown that the dependence of the amplitude of the 12-MHz signal on the altitude of the reflecting sporadic-E layer is mainly determined by absorption variations. For the 20-MHz signal, the presence of a lower sporadic-E layer with high screening frequencies can lead to a decrease in signal amplitude in the case of reflection from the upper sporadic-E layer.

  20. 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

  1. 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

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

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

  3. Lymphangiogenic and angiogenic microvessel density in human primary sporadic colorectal carcinoma

    Ge Yan; Xiao-Yan Zhou; San-Jun Cai; Gui-Hong Zhang; lun-Jie Peng; Xiang Du

    2008-01-01

    AIM:To investigate the distribution pattern of lymphatic vessels and microvessels in sporadic colorectal carcinoma (SCRC) and their relationship to metastasis and prognosis.METHODS: The lymphatic vessel density (LVD) and microvessel density (MVD) in tumor tissue obtained from 132 patients with primary SCRC, including 74 with metastases and 58 without metastases, were evaluated by immunohistochemistry using antibodies directed against D2-40 and von Willebrand factor (vWF). RESULTS: (1) The lymphatic vessels and microvessels at central portions of SCRC often had a reticular architecture with numerous tiny and ill-defined lumina, while those at tumor borders had large and open lumina. The LVD and MVD were both obviously higher in colorectal cancer patients with metastases than in those without (P < 0.001). (2) For each one lymphatic vessel increased, there was a 1.45-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of LVD in predicting metastasis or non-metastasis in SCRC were 71.62% and 56.90%, respectively, and the corresponding LVD was 5. For each one microvessel increased, there was a 1.11-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of MVD were 66.22% and 51.72%, respectively. (3) Double labeling immunohistochemistry showed D2-40 immunoreactivity to be specific for lymphatic vessels. (4) Univariate analysis indicated that high LVD, high MVD, as well as co-accounting of high LVD and high MVD were associated with patient's poor disease-free survival (Puni< 0.05); multivariate analysis indicated that co-accounting of LVD and MVD was an independent prognostic factor of colorectal cancer. CONCLUSION: D2-40 is a new specific antibody for lymphatic endothelial cells. Lymphogenesis and angiogenesis are commonly seen in SCRC, especially at tumor borders. The detection of LVD and MVD at tumor borders may be useful in predicting metastasis and prognosis in patients with SCRC, and, in particular, co

  4. 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

    2014-01-01

    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

  5. Chinese specific characteristics of sporadic Creutzfeldt-Jakob disease: a retrospective analysis of 57 cases.

    Wei Zhao

    Full Text Available OBJECTIVE: Sporadic Creutzfeldt-Jakob disease (sCJD is a fatal and transmissible neurodegenerative disorder. However, no studies have reported Chinese specific characteristics of sCJD. We aimed to identify differences in sCJD between Chinese patients and patients from other countries. METHODS: The data from 57 Chinese sCJD patients were retrospectively analyzed, including demographic data, clinical manifestations, laboratory examinations, electroencephalograms (EEGs, diffusion-weighted imaging (DWI scans, positron emission tomography (PET scans, and pathological results. RESULT: The disease was pathologically confirmed in 11 patients. 39 cases were diagnosed as probable sCJD, and 7 were possible. Of the total cases, 33 were male, and 24 were female. The onset age ranged from 36 to 75 years (mean: 55.5, median: 57. Disease onset before the age of 60 occurred in 57.9% of patients. The disease duration from onset to death ranged 5-22 months (mean: 11.6, median: 11, and 51.9% of patients died 7 to 12 months after disease onset. The majority of patients presented with sub-acute onset with progressive dementia. 3 of the 9 patients who took 14-3-3 protein analysis had positive results (33.3%. The sensitivity of EEG was 79.6% (43/54. For DWI and PET examinations, the sensitivities were 94% (47/50 and 94.1% (16/17, respectively. In seven patients who did not show typical hyper-intensities on the first DWI examination, abnormalities of hypo-metabolism in the cerebral cortex were clearly detected by PET. In 13 out of the 17 patients, PET detected extra abnormal regions in addition to the hyper-intense areas observed in DWI. CONCLUSION: This is the first study to indicate that Chinese sCJD patients have a much earlier onset age and a longer disease duration than other populations, which is most likely related to racial differences. The longer disease duration may also be a probable characteristic of Asian populations. PET had high sensitivity for the

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

    Lintell Nicholas A

    2009-09-01

    Full Text Available Abstract Background The novel breast cancer metastasis modulator gene signal-induced proliferation-associated 1 (Sipa1 underlies the breast cancer metastasis efficiency modifier locus Mtes 1 and has been shown to influence mammary tumour metastatic efficiency in the mouse, with an ectopically expressing Sipa1 cell line developing 1.5 to 2 fold more surface pulmonary metastases. Sipa1 encodes a mitogen-inducible GTPase activating (GAP protein for members of the Ras-related proteins; participates in cell adhesion and modulates mitogen-induced cell cycle progression. Germline SIPA1 SNPs showed association with positive lymph node metastasis and hormonal receptor status in a Caucasian cohort. We hypothesized that SIPA1 may also be correlated to breast carcinoma incidence as well as prognosis. Therefore, this study investigated the potential relationship of SIPA1 and human breast cancer incidence by a germline SNP genotype frequency association study in a case-control Caucasian cohort in Queensland, Australia. Methods The SNPs genotyped in this study were identified in a previous study and the genotyping assays were carried out using TaqMan SNP Genotyping Assays. The data were analysed with chi-square method and the Monte Carlo style CLUMP analysis program. Results Results indicated significance with SIPA1 SNP rs3741378; the CC genotype was more frequently observed in the breast cancer group compared to the disease-free control group, indicating the variant C allele was associated with increased breast cancer incidence. Conclusion This observation indicates SNP rs3741378 as a novel potential sporadic breast cancer predisposition SNP. While it showed association with hormonal receptor status in breast cancer group in a previous pilot study, this exonic missense SNP (Ser (S to Phe (F changes a hydrophilic residue (S to a hydrophobic residue (F and may significantly alter the protein functions of SIPA1 in breast tumourgenesis. SIPA1 SNPs rs931127 (5

  7. 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

  8. Different patterns of allelic imbalance in sporadic tumors and tumors associated with long-term exposure to gamma-radiation.

    Litviakov, Nikolai V; Freidin, Maxim B; Sazonov, Aleksey E; Khalyuzova, Maria V; Buldakov, Mikhail A; Karbyshev, Mikhail S; Albakh, Еlena N; Isubakova, Daria S; Gagarin, Аleksey A; Nekrasov, Gennadiy B; Mironova, Elena B; Izosimov, Аndrey S; Takhauov, Ravil M; Karpov, Аndrei B

    2015-12-01

    The study aimed to reveal cancer related mutations in DNA repair and cell cycle genes associated with chronic occupational exposure to gamma-radiation in personnel of the Siberian Group of Chemical Enterprises (SGCE). Mutations were analyzed by comparing genotypes of malignant tumors and matched normal tissues of 255 cancer patients including 98 exposed to external gamma-radiation (mean dose 128.1±150.5mSv). Also a genetic association analysis was carried out in a sample of 149 cancer patients and 908 healthy controls occupationally exposed to gamma-radiation (153.2±204.6mSv and 150.5±211.2mSv, respectively). Eight SNPs of genes of DNA excision repair were genotyped (rs13181, rs1052133, rs1042522, rs2305427, rs4244285, rs1045642, rs1805419 and rs1801133). The mutation profiles in heterozygous loci for selected SNP were different between sporadic tumors and tumors in patients exposed to radiation. In sporadic tumors, heterozygous genotype Arg/Pro of the rs1042522 SNP mutated into Arg/0 in 15 cases (9.6%) and 0/Pro in 14 cases (8.9%). The genotype Lys/Gln of the rs13181 SNP mutated into Lys/0 and 0/Gln in 9 and 4 cases, respectively. In tumors of patients exposed to low-level radiation, the rs1042522 Arg/0 mutated genotype was found in 12 cases (12.1%), while in 2 cases (2%) 0/Pro mutation was observed. Finally, the rs13181 0/Gln mutated genotype was observed in 15 cases (16,5%) . Thus, our study showed the difference in patterns of allelic imbalance in tumors appeared under low-level radiation exposure and spontaneous tumors for selected SNPs. This suggests different mechanisms of inactivation of heterozygous genotypes in sporadic and radiation-induced tumors. PMID:26653978

  9. Analysis of mutations in the p16/CDKN2A gene in sporadic and familial melanoma in the Polish population.

    Lamperska, Katarzyna; Karezewska, Aldona; Kwiatkowska, Eliza; Mackiewicz, Andrzej

    2002-01-01

    Mutations in CDKN2A have been found in sporadic cutaneous malignant (CMM), in familial CMM and in other syndromes associated with melanoma. In this study DNA was obtained from 207 individuals and five cell lines. There were 157 CMM patients and 50 healthy members of melanoma patients families. The CMM group included patients with one or two melanoma cases in the family, families with dysplastic nevus syndrom (DNS) and patients with a spectrum of other types of cancers in the family. PCR-SSCP analysis and sequencing identified: six substitutions in codon 58 CGA/TGA (Arg/Stop), 16 substitutions GAC/GAT in codon 84 (Asp/Asp), six substitutions CGA/TGA in codon 148 (Arg/Thr), 14 substitutions G/C in 3'UTR and 4 double changes (two in codon 84 and 3'UTR; two in codon 148 and 3'UTR). The mutation identified in codon 58 was found in tissue only. Other substitutions were polymorphisms found in DNA from tissue and blood samples. Most of them were identified in sporadic CMM (six in codon 148 Ala/Thr, 12 in codon 84 Asp/Asp and six in 3'UTR). The frequency of the polymorphisms was also high in DNS and CMM/DNS families (four in codon 84 Asp/Asp and six in 3'UTR). No mutations or polymorphisms were found in CMM patients with one or two melanoma cases and CMM patients, with other cancers in family history. The analysis of the CDKN2A gene mutations in the Polish population demonstrated: (i) no germline mutations; (ii) a relatively high number of genetic changes in sporadic melanoma; (iii) a high number of polymorphisms in DNS and CMM/DNS families. PMID:12362978

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

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

    1986-01-01

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

  11. 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...

  12. 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

  13. Toga-like virus as a cause of fulminant hepatitis attributed to sporadic non-A, non-B.

    Fagan, E A; Ellis, D S; Tovey, G M; Lloyd, G; Portmann, B; Williams, R; Zuckerman, A J

    1989-07-01

    Virus-like particles (60-70 nm) with spiked surfaces budding into cell vacuoles and rod-shaped inclusions were detected in nuclei of hepatocytes from a British patient transplanted for sporadic non-A, non-B fulminant hepatitis (NANB-FHF), probably contracted in Kenya. Identical particles were seen in two successive grafts (days 2 and 10) at regrafting for recurrent FHF. Ultrastructural features resembled those of the RNA-containing arbovirus, Rift Valley fever virus, but serological markers against a representative panel for arboviruses (Togaviruses) and transmission in mice proved negative. The particles shared features with the different arboviruses seen in the hepatectomy specimen of a second patient with NANB-FHF, and in both patients an insect vector was implicated in the clinical history. The particles were identical in size to those of a third patient with NANB-FHF, who had remained in the United Kingdom. These findings, together with the recent report of isolation of an RNA-containing virus resembling the Togaviridae, in parenteral NANB, suggest that several exotic virus-like agents resembling the arboviruses may be involved in the aetiology of NANB, including in the sporadic forms of FHF in the United Kingdom. PMID:2502604

  14. 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

  15. Performance of Verbal Fluency as an Endophenotype in Patients with Familial versus Sporadic Schizophrenia and Their Parents.

    Liang, Sugai; Deng, Wei; Wang, Qiang; Ma, Xiaohong; Li, Mingli; Brown, Matthew R G; Hu, Xun; Li, Xinmin; Greenshaw, Andrew J; Li, Tao

    2016-01-01

    What's the neurocognitive deficit as an endophenotype to familial schizophrenia? Here, we investigate the neurocognitive endophenotype in first-episode patients with familial schizophrenia (FS) and sporadic schizophrenia (SS), and their parents. 98 FS patients and their 105 parents; 190 SS patients and their 207 parents; 195 controls matched with patients, and 190 controls matched with the patients' parents, were assessed with the short version of the Wechsler Adult Intelligence Scale-Revised in China (WAIS-RC), the immediate and delayed logical memory tests from the Wechsler Memory Scale-Revised in China (WMS-RC), the Verbal Fluency Test (VFT), the Trail Making Test Parts A and B-Modified (TMA, TMB-M), and the Modified Wisconsin Card Sorting Test (WCST-M). The results showed that with age, gender, and education as covariates, after controlling for false discovery rates, the FS group and their parent group performed worse than the SS group and their parent group on VFT. No significant differences were found for other neurocognitive tests between the FS and SS patient groups, and their respective parent groups. Our findings suggest the patients with familial and sporadic schizophrenia and their respective parent groups may have a different genetic predisposition in relation to a cognitive endophenotype. PMID:27581658

  16. 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

  17. Prognostic and Predictive Value of CpG Island Methylator Phenotype in Patients with Locally Advanced Nonmetastatic Sporadic Colorectal Cancer

    Yuwei Wang

    2014-01-01

    Full Text Available Purpose. In the present study, the prognostic significance of CpG island methylator phenotype (CIMP in stage II/III sporadic colorectal cancer was evaluated using a five-gene panel. Methods. Fifty stage II/III colorectal cancer patients who received radical resection were included in this study. Promoter methylation of p14ARF, hMLH1, p16INK4a, MGMT, and MINT1 was determined by methylation specific polymerase chain reaction (MSP. CIMP positive was defined as hypermethylation of three or more of the five genes. Impact factors on disease-free survival (DFS and overall survival (OS were analyzed using Kaplan-Meier method (log-rank test and adjusted Cox proportional hazards model. Results. Twenty-four percent (12/50 of patients were characterized as CIMP positive. Univariate analysis showed stage III (P=0.049 and CIMP positive (P=0.014 patients who had significantly inferior DFS. In Cox regression analysis, CIMP positive epigenotype was independently related with poor DFS with HR = 2.935 and 95% CI: 1.193–7.220 (P=0.019. In patients with CIMP positive tumor, those receiving adjuvant chemotherapy had a poor DFS than those without adjuvant chemotherapy (P=0.023. Conclusions. CIMP positive was significantly correlated with decreased DFS in stage II/III colorectal cancer. Patients with CIMP positive locally advanced sporadic colorectal cancers may not benefit from 5-fluorouracil based adjuvant chemotherapy.

  18. The reliability of serogroup determination in the detection of Escherichia coli as a causative agent of sporadic and epidemic occurrence of enterocolitis

    Stojanović Valentina

    2002-01-01

    Full Text Available The purpose of this study was to determine the presence of virulence factors (heat-labile, heat-stable enterotoxin, verotoxin, invasiveness, localized, aggregative and diffuse adherence among E. coli strains isolated from sporadic cases and outbreaks of enterocolitis, which belonged to serogroups characteristic for enteropathogenic E. coli. Serogroup was determined in 57.2% of 622 strains isolated from sporadic cases, and among them virulence factors were detected in 23.6%. Serogroup was also determined in 73.3% of 90 outbreaks isolates tested and virulence factors were detected in 97% of them. The detection rate of virulence factors rarely exceeded 50% among strains belonging to any of serogroup that was determined. The obtained data suggested that the identification of E. coli as a causative agent of enterocolitis by serogroup determination was a reliable method in outbreaks, but not in sporadic cases of this disease.

  19. Distinct cerebral lesions in sporadic and 'D90A' SOD1 ALS: studies with [11C]flumazenil PET.

    Turner, M R; Hammers, A; Al-Chalabi, A; Shaw, C E; Andersen, P M; Brooks, D J; Leigh, P N

    2005-06-01

    Five to ten percent of amyotrophic lateral sclerosis (ALS) cases are associated with mutations of the superoxide dismutase-1 (SOD1) gene, and the 'D90A' mutation is associated with a unique phenotype and markedly slower disease progression (mean survival time 14 years). Relative sparing of inhibitory cortical neuronal circuits might be one mechanism contributing to the slower progression in patients homozygous for the D90A mutation (homD90A). The GABA(A) receptor PET ligand [11C]flumazenil has demonstrated motor and extra-motor cortical changes in sporadic ALS. In this study, we used [11C]flumazenil PET to explore differences in the pattern of cortical involvement between sporadic and genetically homogeneous ALS groups. Twenty-four sporadic ALS (sALS) and 10 homD90A patients underwent [11C]flumazenil PET of the brain. In addition, two subjects homozygous for the D90A mutation, but without symptoms or signs ('pre-symptomatic', psD90A), also underwent imaging. Results for each group were compared with those for 24 healthy controls of similar age. Decreases in the binding of [11C]flumazenil in the sALS group were found within premotor regions, motor cortex and posterior motor association areas. In the homD90A group of ALS patients, however, decreases were concentrated in the left fronto-temporal junction and anterior cingulate gyrus. In the two psD90A subjects, a small focus of reduced [11C]flumazenil binding at the left fronto-temporal junction was seen, similar to the pattern seen in the clinically affected patients. Within the sALS group, there was no statistically significant association between decreases in cortical [11C]flumazenil binding and revised ALS functional rating scale (ALSFRS-R score), whereas the upper motor neuron (UMN) score correlated with widespread and marked cortical decreases over the dominant hemisphere. In the homD90A group, there was a stronger statistical association between reduced cortical [11C]flumazenil binding and the ALSFRS-R, rather

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

    Mikel Etxeberria Agirresarobe

    2013-06-01

    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 frequ

  1. 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.

  2. 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;

    2012-01-01

    for investigated risk factors were collected and analysed. In the meta-analysis, heterogeneity between the studies and possible sources of bias were investigated, and pooled odds ratios for identified risk factors were estimated. Results suggest that travelling abroad, eating undercooked chicken...... 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...

  3. 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;

    2012-01-01

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

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

    Fujiwara Yoshinori

    2008-02-01

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

  5. Germline Heterozygous Variants in SEC23B Are Associated with Cowden Syndrome and Enriched in Apparently Sporadic Thyroid Cancer

    Yehia, Lamis; Niazi, Farshad; Ni, Ying; Ngeow, Joanne; Sankunny, Madhav; Liu, Zhigang; Wei, Wei; Mester, Jessica L.; Keri, Ruth A.; Zhang, Bin; Eng, Charis

    2015-01-01

    Cancer-predisposing genes associated with inherited cancer syndromes help explain mechanisms of sporadic carcinogenesis and often inform normal development. Cowden syndrome (CS) is an autosomal-dominant disorder characterized by high lifetime risks of epithelial cancers, such that ∼50% of affected individuals are wild-type for known cancer-predisposing genes. Using whole-exome and Sanger sequencing of a multi-generation CS family affected by thyroid and other cancers, we identified a pathogenic missense heterozygous SEC23B variant (c.1781T>G [p.Val594Gly]) that segregates with the phenotype. We also found germline heterozygous SEC23B variants in 3/96 (3%) unrelated mutation-negative CS probands with thyroid cancer and in The Cancer Genome Atlas (TCGA), representing apparently sporadic cancers. We note that the TCGA thyroid cancer dataset is enriched with unique germline deleterious SEC23B variants associated with a significantly younger age of onset. SEC23B encodes Sec23 homolog B (S. cerevisiae), a component of coat protein complex II (COPII), which transports proteins from the endoplasmic reticulum (ER) to the Golgi apparatus. Interestingly, germline homozygous or compound-heterozygous SEC23B mutations cause an unrelated disorder, congenital dyserythropoietic anemia type II, and SEC23B-deficient mice suffer from secretory organ degeneration due to ER-stress-associated apoptosis. By characterizing the p.Val594Gly variant in a normal thyroid cell line, we show that it is a functional alteration that results in ER-stress-mediated cell-colony formation and survival, growth, and invasion, which reflect aspects of a cancer phenotype. Our findings suggest a different role for SEC23B, whereby germline heterozygous variants associate with cancer predisposition potentially mediated by ER stress “addiction.” PMID:26522472

  6. 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

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

    Mitesh J Borad

    2014-02-01

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

  8. Investigation of CD28 gene polymorphisms in patients with sporadic breast cancer in a Chinese Han population in Northeast China.

    Shuang Chen

    Full Text Available BACKGROUND: CD28 is one of a number of costimulatory molecules that play crucial roles in immune regulation and homeostasis. Accumulating evidence indicates that immune factors influence breast carcinogenesis. To clarify the relationships between polymorphisms in the CD28 gene and breast carcinogenesis, a case-control study was conducted in women from Heilongjiang Province in northeast of China. METHODOLOGY/PRINCIPAL FINDINGS: Our research subjects consisted of 565 female patients with sporadic breast cancer and 605 age- and sex-matched healthy controls. In total, 12 single nucleotide polymorphisms (SNPs in the CD28 gene were successfully determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP method. The relationship between the CD28 variants and clinical features, including histological grade, tumor size, lymph node metastasis, human epidermal growth factor receptor 2 (C-erbB2, estrogen receptor (ER, progesterone receptor (PR, and tumor protein 53 (P53 status were analyzed. A statistically significant association was observed between rs3116496 and breast cancer risk under different genetic models (additive P = 0.0164, dominant P = 0.0042. Different distributions of the rs3116496 'T' allele were found in patients and controls, which remained significant after correcting the P value for multiple testing using Haploview with 10,000 permutations (corrected P = 0.0384. In addition, significant associations were observed between rs3116487/rs3116494 (D' = 1, r(2 = 0.99 and clinicopathological features such as C-erbB2 and ER status, in breast cancer patients. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that CD28 gene polymorphisms contribute to sporadic breast cancer risk and have a significant association with clinicopathological features in a northeast Chinese Han population.

  9. 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

  10. β-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

    β-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 GSK3β could play a role in some neuropathological processes, we analyzed the alterations occurring in GSK3β levels in L-BMAA treated rats, we have observed an increase in the active form of GSK3β 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. Localizing a putative mutation as the major contributor to the development of sporadic Hirschsprung disease to the RET genomic sequence between the promoter region and exon 2

    Burzynski, GM; Nolte, IM; Osinga, J; Ceccherini, [No Value; Twigt, B; Maas, S; Brooks, A; Verheij, J; Menacho, IP; Buys, CHCM; Hofstra, RMW

    2004-01-01

    Hirschsprung disease (HSCR), a congenital disorder characterized by intestinal obstruction due to absence of enteric ganglia along variable lengths of the intestinal tract, occurs both in familial and sporadic cases. RET mutations have been found in approximately 50% of the families, but explains on

  12. Inference on germline BAP1 mutations and asbestos exposure from the analysis of familial and sporadic mesothelioma in a high-risk area.

    Betti, Marta; Casalone, Elisabetta; Ferrante, Daniela; Romanelli, Antonio; Grosso, Federica; Guarrera, Simonetta; Righi, Luisella; Vatrano, Simona; Pelosi, Giuseppe; Libener, Roberta; Mirabelli, Dario; Boldorini, Renzo; Casadio, Caterina; Papotti, Mauro; Matullo, Giuseppe; Magnani, Corrado; Dianzani, Irma

    2015-01-01

    Inherited loss-of-function mutations in the BAP1 oncosuppressor gene are responsible for an inherited syndrome with predisposition to malignant mesothelioma (MM), uveal and keratinocytic melanoma, and other malignancies. Germline mutations that were inherited in an autosomal dominant fashion were identified in nine families with multiplex MM cases and 25 families with multiple melanoma, renal cell carcinoma, and other tumors. Germline mutations were also identified in sporadic MM cases, suggesting that germline mutations in BAP1 occur frequently. In this article, we report the analysis of BAP1 in five multiplex MM families and in 103 sporadic cases of MM. One family carried a new truncating germline mutation. Using immunohistochemistry, we show that BAP1 is not expressed in tumor tissue, which is in accordance with Knudson's two hits hypothesis. Interestingly, whereas the three individuals who were possibly exposed to asbestos developed MM, the individual who was not exposed developed a different tumor type, that is, mucoepidermoid carcinoma. This finding suggests that the type of carcinogen exposure may be important for the cancer type that is developed by mutation carriers. On the contrary, the other families or the 103 sporadic patients did not show germline mutations in BAP1. Our data show that BAP1 mutations are very rare in patients with sporadic MM, and we report a new BAP1 mutation, extend the cancer types associated with these mutations, and suggest the existence of other yet unknown genes in the pathogenesis of familial MM. PMID:25231345

  13. 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;

    tuberous sclerosis (TS) and one had AML of sporadic origin, all five patients underwent laparoscopic cryoablation. Perioperative data was prospectively registered in a nation-wide laparoscopy database with follow-up data collected from the patients’ chart. Independent radiologists reassessed all imaging...

  14. 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.

  15. 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

  16. Turkeys Development Assistance to Fragile States: From Sporadic Actions to System Building Practices

    Gole, Deniz

    2014-01-01

    This article aims at presenting policy recommendations for Turkish decision makers with a view to address Turkey's needs to ensure effective and timely development assistance to fragile states. The analysis begins with a quick look at the controversial relation between aid, growth and poverty in order to provide a basis for understanding aid effectiveness as well as some of the ongoing debates and limitations in the development assistance field. It then gives an insight on the current state o...

  17. 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

  18. 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

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

    Shibayama, Takuya, E-mail: shibayama@stelab.nagoya-u.ac.jp; Nakabou, Takashi [Institute for Space-Earth Environmental Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601 (Japan); Kusano, Kanya [Institute for Space-Earth Environmental Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601 (Japan); Japan Agency for Marine-Earth Science and Technology (JAMSTEC), Kanazawa-ku, Yokohama, Kanagawa 236-0001 (Japan); Miyoshi, Takahiro [Department of Physical Science, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8526 (Japan); Vekstein, Grigory [Jodrell Bank Centre for Astrophysics, University of Manchester, Manchester M13 9PL (United Kingdom)

    2015-10-15

    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.

  20. Sporadic inclusion body myositis: HLA-DRB1 allele interactions influence disease risk and clinical phenotype.

    Mastaglia, Frank L; Needham, Merrilee; Scott, Adrian; James, Ian; Zilko, Paul; Day, Timothy; Kiers, Lynette; Corbett, Alastair; Witt, Campbell S; Allcock, Richard; Laing, Nigel; Garlepp, Michael; Christiansen, Frank T

    2009-11-01

    Susceptibility to sIBM is strongly associated with the HLA-DRB1*03 allele and the 8.1 MHC ancestral haplotype (HLA-A1, B8, DRB1*03) but little is known about the effects of allelic interactions at the DRB1 locus or disease-modifying effects of HLA alleles. HLA-A, B and DRB1 genotyping was performed in 80 Australian sIBM cases and the frequencies of different alleles and allele combinations were compared with those in a group of 190 healthy controls. Genotype-phenotype correlations were also investigated. Amongst carriers of the HLA-DRB1*03 allele, DRB1*03/*01 heterozygotes were over-represented in the sIBM group (pHLA-DRB1*03 allele and other alleles at the DRB1 locus can influence disease susceptibility and the clinical phenotype in sIBM. PMID:19720533

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

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

    2008-01-01

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

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

    Ratner Marcia H.; Farb David H.; Ozer Josef; Feldman Robert G.; Durso Raymon

    2014-01-01

    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 mi...

  3. 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

  4. 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

  5. Stereotypic Movements in Case of Sporadic Creutzfeldt-Jakob Disease: Possible Role of Anti-NMDA Receptor Antibodies

    Michelle Molina

    2012-12-01

    Full Text Available Sporadic Creutzfeldt-Jakob disease (sCJD and anti-NMDA receptor antibody encephalitis (NMDAE can both produce a rapidly progressive dementia with resulting state of catatonia or akinetic mutism. Both are associated with movement disorders. In published case series, myoclonus appears to be the most frequent movement disorder in sCJD, while stereotypic, synchronized, one-cycle-per-second movements such as arm or leg elevation, jaw opening, grimacing, head turning, and eye deviation are seen in NMDAE. We report a case of a 59-year-old woman with rapidly worsening cognitive disturbance leading to a nearly catatonic state interrupted by stereotypic movements. sCJD was diagnosed via periodic sharp wave complexes on EEG as well as cerebrospinal fluid (CSF 14-3-3 and tau protein elevation. Characteristic movement disorder of NMDAE was present in absence of ovarian mass or CSF pleiocytosis. Given prior case reports of presence of anti-NMDA receptor antibodies in sCJD, we propose that the movement disorder in this case was caused by anti-NMDA receptor antibodies whose formation was secondary to neuronal damage from prion disease. It is important to consider sCJD even in cases that have some clinical features suggestive of NMDAE.

  6. 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

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

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

    2014-05-15

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

  8. 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

  9. 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

  10. FRAGILE HISTIDINE TRIAD GENE EXPRESSION AND ITS CORRALATION WITH MISMATCH REPAIR PROTEIN IN HUMAN SPORADIC COLORECTAL CARCINOMA

    姚成才; 林从尧

    2004-01-01

    Objective: To investigate the expression of fragile histidine triad (FHIT) gene and its correlation with clinicopathological features and correlation with mismatch repair protein (mainly MLH1 and MSH2) in human sporadic colorectal carcinoma (SCC). Methods:Immunohistochemistry SP method was used to determine the expression of FHIT, MLH1 and MSH2 protein in surgically resected specimens of 84 human SCC. Results:The positive rates of FHIT, MLH1 and MSH2 protein expression were 48.81%, 92.86% and 100% respectively.Loss or reduced expression of FHIT protein was not related with tumors clinicopathological features such as age, gender,tumors site and histological type (P>0.05), but was correlated with tumors invade depth, degree of the differentiation, Ducks' stage and metastasis (P<0.05). There was no relationship between FHIT gene expression and MLH1 protein (r=0.0991, P>0.05) and MSH2 protein (r=0.0000, P=l.00) expression in human SCC. Conclusion:Absent or reduction of FHIT gene expression consists of high proportion and is a frequent event in SCC. FHIT gene is involved in the development and progression of human SCC and may be a candidate tumors suppressor gene. The relationship between alteration of FHIT gene expression and mismatch repair protein (mainly MLH1 and MSH2)deserved further study in human SCC.

  11. 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.

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

    Carmody J

    2011-04-01

    Full Text Available John Carmody1, Raghunath P Misra1,2, Marlyn P Langford1, William A Byrd1, Lauren Ditta1, Bryan Vekovius1, Donald E Texada11Department of Ophthalmology, 2Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA, USAAbstract: A case of sporadic Burkitt lymphoma (sBL presenting with jaw and lid involvement in a diabetic adult African American female and a review of adult orbital Burkitt lymphoma cases are presented. Lid edema, visual loss, ophthalmoparesis, proptosis, and sinusitis progressed over 4 weeks despite antibiotic and steroid treatment. Upper lid biopsy histopathological evaluation and immunophenotyping revealed a homogenous mass of atypical CD10 and CD20-negative B-cells and tingible body macrophages yielding a "starry sky" appearance. Cytogenetic analysis detected a minor variant c-MYC translocation, but no Epstein–Barr virus RNA. Detection of multiple lesions prompted a diagnosis of stage IV disease that totally regressed following radiation and chemotherapy. Review results of the six adult orbital sBL cases support a poor prognosis and a heightened suspicion of variant CD10, CD20 and BCL6 positive sBL in adults presenting with jaw pain and rapidly progressive orbital symptoms, particularly in female, African American, and diabetic patients.Keywords: B-cells, Burkitt lymphoma, cancer, diabetes, eye, Epstein–Barr virus, orbit, tumor

  14. Racial and ethnic differences in individuals with sporadic Creutzfeldt-jakob disease in the United States of America.

    Brian S Appleby

    Full Text Available BACKGROUND: Little is known about racial and ethnic differences in individuals with sporadic Creutzfeldt-Jakob disease (sCJD. The authors sought to examine potential clinical, diagnostic, genetic, and neuropathological differences in sCJD patients of different races/ethnicities. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective study of 116 definite and probable sCJD cases from Johns Hopkins and the Department of Veterans Affairs Healthcare Systems was conducted that examined differences in demographic, clinical, diagnostic, genetic, and neuropathological characteristics among racial/ethnic groups. Age at disease onset differed among racial/ethnic groups. Non-Hispanic Whites had a significantly older age at disease onset compared to the other groups (65 vs. 60, p = 0.036. Non-Whites were accurately diagnosed more rapidly than Whites (p = 0.008 and non-Hispanic Whites were more likely to have normal appearing basal ganglia on brain magnetic resonance imaging (MRI compared to minorities (p = 0.02. Whites were also more likely to undergo post-mortem evaluation compared to non-Whites (p = 0.02. CONCLUSIONS/SIGNIFICANCE: Racial/ethnic groups affected by sCJD demonstrated differences in age at disease onset, time to correct diagnosis, clinical presentation, and diagnostic test results. Whites were more likely to undergo autopsy compared to non-Whites. These results have implications in regards to case ascertainment, diagnosis, and surveillance of sCJD and possibly other human prion diseases.

  15. 家族性及散发性伴镶边空泡远端肌病患者临床、病理、辅助检查及随访对比研究%Familial and sporadic distal myopathy with rimmed vacuoles: comparison of the clinical, pathological, laboratory test and follow-up data

    鲁向辉; 蒲传强; 黄旭升; 毛燕玲; 刘洁晓; 罗萍

    2011-01-01

    correlation was found between the disease duration and the level of muscle enzymes. The pathological findings were similar between the cases, and Gomori staining showed rimmed vacuoles and inclusion bodies without inflammatory cell infiltration. Follow-up results of 29 cases showed no significant difference between the two groups. The disease was slowly progressive and severely affected the quality of life of the patients, but did not produce obvious effect on the life expectancy. Conclusion The clinical, pathological and laboratory data of Chinese DMRV patients are basically similar to those of Japanese cases. Sporadic cases tend to show more dysmorphic features than the familial ones, and occasional sporadic cases have early disease onset in early childhood.

  16. 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 PGJ

  17. Contralateral risk reducing mastectomy in patients with sporadic breast cancer. Benefits and hazards.

    Boccardo, C; Gentilini, O

    2016-07-01

    During the last years an improving outcome of breast conserving surgery was observed along with the availability of diagnostic procedures allowing early diagnosis. Nevertheless, women with breast cancer are more frequently requesting a radical approach comprising contralateral mastectomy even if they do not have a demonstrated increased genetic risk. In this paper we reviewed the main reasons patients ask for aggressive preventive surgery, the perceived and the real risks of developing contralateral breast cancer, and the potential, if any, survival benefits along with the hazards associated to contralateral risk reducing mastectomy. A respectful management should be given to these women within a multi-disciplinary team. Psychological support is highly encouraged cope fears and uncertainties but treating physicians should provide patients with comprehensive and unbiased data to take the best decision for the single person. Physicians should also give clear information on the benefits of adjuvant therapies which are reducing the incidence of contralateral breast cancer and also of the possible influences of healthy lifestyle (weight control, physical activity, diet) as effective preventive methods. PMID:27189832

  18. 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 ...

  19. 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...

  20. WNT-pathway components as predictive markers useful for diagnosis, prevention and therapy in inflammatory bowel disease and sporadic colorectal cancer

    Serafino, Annalucia; Moroni, Noemi; Zonfrillo, Manuela; Andreola, Federica; Mercuri, Luana; Nicotera, Giuseppe; Nunziata, Joseph; Ricci, Riccardo; Antinori, Armando; Rasi, Guido; Pierimarchi, Pasquale

    2014-01-01

    The key role of the Wnt/β-catenin signaling in colorectal cancer (CRC) insurgence and progression is now recognized and several therapeutic strategies targeting this pathway are currently in developing. Wnt/β-catenin signaling not only dominates the early stages of sporadic colorectal cancer (SCC), but could also represent the connection between inflammatory bowel diseases (IBD) and increased risk of developing SCC. The knowledge on the sequential molecular events of Wnt-signaling cascade in ...

  1. Abnormal accumulation of prion protein mRNA in muscle fibers of patients with sporadic inclusion-body myositis and hereditary inclusion-body myopathy.

    Sarkozi, E; Askanas, V.; Engel, W K

    1994-01-01

    Sporadic inclusion-body myositis is the most common progressive muscle disease of older patients. The muscle biopsy demonstrates mononuclear cell inflammation and vacuolated muscle fibers containing paired helical filaments and 6 to 10-nm fibrils, both resembling those of Alzheimer brain, and Congo-red positivity. Hereditary inclusion-body myopathy designates patients cytopathologically similar but without inflammation. In both muscle diseases, prion, and several proteins characteristic of Al...

  2. 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 ...

  3. 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...

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. The sporadic radiant and distribution of meteors in the atmosphere as observed by VHF radar at Arctic, Antarctic and equatorial latitudes

    P. T. Younger

    2009-07-01

    Full Text Available Results are presented of a study of the temporal and spatial variability in meteor count rate observations from three VHF meteor radars. These radar are located in the Arctic (at Esrange, 68° N, in the Antarctic (at Rothera, 68° S and near the Equator (on Ascension Island, 8° S. It is found that for all three locations there is a strong diurnal cycle in observed hourly meteor counts and the time of maxima and minima in these counts depends on the month of the year. In addition, at high latitude there is a strong annual cycle in observed monthly-mean meteor counts, whereas for the radar at low latitude there is a semi-annual cycle. At high latitude there is also an annual cycle in the mean height at which meteors are observed. However, no such annual cycle is found in observed meteor count rates from the low latitude radar. The meteor count data from all the radars are combined to investigate the sporadic radiant distribution (i.e. the distribution of direction of arrival on the celestial sphere of sporadic meteors. This combined radiant distribution shows that there are six main source regions for meteors. The latitudinal and temporal dependence in observed meteor count rates appears to result from a combination of the sporadic radiant distribution, annual fluctuations in atmospheric density, the sensitivity of the radar to meteors from different source directions and the temporal and spatial variability in meteor fluxes.

  9. 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.)

  10. 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.)

  11. 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.

  12. Genetic Characterization of Cronobacter sakazakii Recovered from the Environmental Surveillance Samples During a Sporadic Case Investigation of Foodborne Illness.

    Sulaiman, Irshad M; Jacobs, Emily; Segars, Katharine; Simpson, Steven; Kerdahi, Khalil

    2016-08-01

    Cronobacter sakazakii is an opportunistic human-pathogenic bacterium known to cause acute meningitis and necrotizing enterocolitis in neonates and immunocompromised individuals. This human-pathogenic microorganism has been isolated from a variety of food and environmental samples, and has been also linked to foodborne outbreaks associated with powdered infant formula (PIF). The U.S. Food and Drug Administration have a policy of zero tolerance of these organisms in PIF. Thus, this agency utilizes the presence of these microorganisms as one of the criteria in implementing regulatory actions and assessing adulteration of food products of public health importance. In this study, we recovered two isolates of Cronobacter from the 91 environmental swab samples during an investigation of sporadic case of foodborne illness following conventional microbiological protocols. The isolated typical colonies were identified using VITEK2 and real-time PCR protocols. The recovered Cronobacter isolates were then characterized for species identification by sequencing the 16S rRNA locus. Further, multilocus sequence typing (MLST) was accomplished characterizing seven known C. sakazakii-specific MLST loci (atpD, fusA, glnS, gltB, gyrB, infB, and pps). Results of this study confirmed all of the recovered Cronobacter isolates from the environmental swab samples to be C. sakazakii. The MLST profile matched with the published profile of the complex 31 of C. sakazakii. Thus, rRNA and 7-loci MLST-based sequencing protocols are robust techniques for rapid detection and differentiation of Cronobacter species, and these molecular diagnostic tools can be used in implementing successful surveillance program and in the control and prevention of foodborne illness. PMID:27155844

  13. 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.)

  14. 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

  15. 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 (pratio - 88%). From WB inconclusive results (n=44), ELISA 14-3-3γ correctly classified 41 patients. Additionally, logistic regression analysis selected ELISA 14-3-3γ as the best single predictive marker for sCJD (overall accuracy=93%). ApoE and PRNP genotypes did not influence ELISA 14-3-3γ levels. Despite specificity for 14-3-3γ isoform, ELISA results not only match WB evaluation but also help discrimination of inconclusive results. Our results therefore reinforce this assay as a single screening test, allowing higher sample throughput and unequivocal results. PMID:26940479

  16. Functional analysis of human Na~+/K~+-ATPase familial or sporadic hemiplegic migraine mutations expressed in Xenopus oocytes

    Susan; Spiller; Thomas; Friedrich

    2014-01-01

    AIM: Functional characterization of ATP1A2 mutations that are related to familial or sporadic hemiplegic migraine(FHM2, SHM). METHODS: cRNA of human Na+/K+-ATPase α2- and β1-subunits were injected in Xenopus laevis oocytes. FHM2 or SHM mutations of residues located in putative α/β interaction sites or in the α2-subunit’s C-terminal region were investigated. Mutants were analyzed by the twoelectrode voltage-clamp(TEVC) technique on Xenopus oocytes. Stationary K+-induced Na+/K+ pump currents were measured, and the voltage dependence of apparent K+ affinity was investigated. Transient currents were recorded as ouabain-sensitive currents in Na+ buffers to analyze kinetics and voltage-dependent presteady state charge translocations. The expression of constructs was verified by preparation of plasma membrane and total membrane fractions of cRNA-injected oocytes. RESULTS: Compared to the wild-type enzyme, the mutants G900R and E902K showed no significant dif-ferences in the voltage dependence of K+-induced currents, and analysis of the transient currents indicated that the extracellular Na+ affinity was not affected. Mutant G855R showed no pump activity detectable by TEVC. Also for L994del and Y1009X, pump currents could not be recorded. Analysis of the plasma and total membrane fractions showed that the expressed proteins were not or only minimally targeted to the plasma membrane. Whereas the mutation K1003E had no impact on K+ interaction, D999H affected the voltage dependence of K+-induced currents. Furthermore, kinetics of the transient currents was altered compared to the wild-type enzyme, and the apparent affinity for extracellular Na+ was reduced. CONCLUSION: The investigated FHM2/SHM mutations influence protein function differently depending on the structural impact of the mutated residue.

  17. Occurrence of Sporadic -E layer during the Low Solar Activity over the Anomaly Crest Region Bhopal, India

    Bhawre, Purushottam

    2016-07-01

    Ionospheric anomaly crest regions are most challenging for scientific community to understand its mechanism and investigation, for this purpose we are investigating some inospheric result for this region. The study is based on the ionogram data recorded by IPS-71 Digital Ionosonde installed over anomaly crust region Bhopal (Geo.Lat.23.2° N, Geo. Long77.4° E, Dip latitude18.4°) over a four year period from January 2007 to December 2010, covering the ending phase of 23rd Solar Cycle and starting phase of 24th solar cycle. This particular period is felt to be very suitable for examining the sunspot number and it encompasses periods of low solar activities. Quarterly ionograms are analyzed for 24 hours during these study years and have been carefully examined to note down the presence of sporadic- E. We also note down the space weather activities along with the study. The studies are divided in mainly four parts with space and geomagnetic activities during these periods. The occurrence probability of this layer is highest in summer solstice, moderate during equinox and low during winter solstice. Remarkable occurrence peaks appear from June to July in summer and from December to January in winter. The layer occurrence showed a double peak variation with distinct layer groups, in the morning (0200 LT) and the other during evening (1800 LT).The morning layer descent was associated with layer density increase indicating the strengthening of the layer while it decreased during the evening layer descent. The result indicates the presence of semi-diurnal tide over the location while the higher descent velocities could be due to the modulation of the ionization by gravity waves along with the tides. The irregularities associated with the gradient-drift instability disappear during the counter electrojet and the current flow is reversed in westward.

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

    Dorival Martins

    2014-01-01

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

  19. 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.

  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. Heterogeneity of cerebral TDP-43 pathology in sporadic amyotrophic lateral sclerosis: Evidence for clinico-pathologic subtypes.

    Takeuchi, Ryoko; Tada, Mari; Shiga, Atsushi; Toyoshima, Yasuko; Konno, Takuya; Sato, Tomoe; Nozaki, Hiroaki; Kato, Taisuke; Horie, Masao; Shimizu, Hiroshi; Takebayashi, Hirohide; Onodera, Osamu; Nishizawa, Masatoyo; Kakita, Akiyoshi; Takahashi, Hitoshi

    2016-01-01

    Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are types of major TDP-43 (43-kDa TAR DNA-binding protein) proteinopathy. Cortical TDP-43 pathology has been analyzed in detail in cases of FTLD-TDP, but is still unclear in cases of ALS. We attempted to clarify the cortical and subcortical TDP-43 pathology in Japanese cases of sporadic ALS (n = 96) using an antibody specific to phosphorylated TDP-43 (pTDP-43). The cases were divided into two groups: those without pTDP-43-positive neuronal cytoplasmic inclusions in the hippocampal dentate granule cells (Type 1, n = 63), and those with such inclusions (Type 2, n = 33). Furthermore, the Type 2 cases were divided into two subgroups based on semi-quantitative estimation of pTDP-43-positive dystrophic neurites (DNs) in the temporal neocortex: Type 2a (accompanied by no or few DNs, n = 22) and Type 2b (accompanied by abundant DNs, n = 11). Clinico-pathologic analysis revealed that cognitive impairment was a feature in patients with Type 2a and Type 2b, but not in those with Type 1, and that importantly, Type 2b is a distinct subtype characterized by a poor prognosis despite the less severe loss of lower motor neurons, the unusual subcortical dendrospinal pTDP-43 pathology, and more prominent glial involvement in cortical pTDP-43 pathology than other two groups. Considering the patient survival time and severity of motor neuron loss in each group, transition from Type 1 to Type 2, or from Type 2a to Type 2b during the disease course appeared unlikely. Therefore, each of these three groups was regarded as an independent subtype. PMID:27338935

  2. 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.

  3. 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.

  4. Risk Factors for Sporadic Domestically Acquired Campylobacter Infections in Norway 2010-2011: A National Prospective Case-Control Study.

    Emily MacDonald

    Full Text Available Campylobacteriosis is the most frequently reported food- and waterborne infection in Norway. We investigated the risk factors for sporadic Campylobacter infections in Norway in order to identify areas where control and prevention measures could be improved.A national prospective case-control study of factors associated with Campylobacter infection was conducted from July 2010 to September 2011. Cases were recruited from the Norwegian Surveillance System of Communicable Diseases (MSIS. Controls were randomly selected from the Norwegian Population Registry. Cases and controls were mailed a paper questionnaire with a prepaid return envelope. Univariable analyses using logistic regression were conducted for all exposures. A final parsimonious multivariable model was developed using regularized/penalized logistic regression, and adjusted odds ratios were calculated.A total of 995 cases and 1501 controls were included in the study (response proportion 55% and 30%, respectively. Exposures that had significant increases in odds of Campylobacter infection in multivariable analysis were drinking water directly from river, stream, or lake (OR: 2.96, drinking purchased bottled water (OR: 1.78, eating chicken (1.69, eating meat that was undercooked (OR: 1.77, eating food made on a barbecue (OR: 1.55, living on a farm with livestock (OR: 1.74, having a dog in the household (OR: 1.39, and having household water supply serving fewer than 20 houses (OR: 1.92.Consumption of poultry and untreated water remain important sources of Campylobacter infection in Norway, despite ongoing control efforts. The results justify the need for strengthening education for consumers and food handlers about the risks of cross-contamination when preparing poultry and with consuming raw or undercooked chicken. The public should also be reminded to take precautions when drinking untreated water in nature and ensure continued vigilance in order to protect and maintain the quality of

  5. 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

  6. Association between polymorphisms in transforming growth factor-β1 and sporadic Alzheimer's disease in a Chinese population.

    Yang, Qin; Wang, En-Yin; Jia, Hui-Wen; Wang, Yan-Ping

    2016-11-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder of the brain. It causes the slow progressive loss of cognitive functions that ultimately leads to dementia and death in the elderly. The etiology and mechanism of late-onset AD (LOAD) are poorly understood, and genetic factors might play an important role in the development of AD. The aim of this study was to investigate the association between common polymorphisms in TGF-β1 with LOAD in a Chinese Han population. Two single nucleotide polymorphisms in TGF-β1 (rs1800469 and rs1982073) were genotyped in 202 patients with sporadic LOAD and 225 control subjects using polymerase chain reaction restriction fragment length polymorphism. Our results showed that rs1800469 in TGF-β1 were significantly associated with LOAD. The frequencies of the AC genotypes of rs1800469 were significantly higher in the LOAD patients than in the control subjects (42.5% vs 28.6%; P = 0.001). The minor allele (C) frequency was significantly higher in patients with LOAD than in control subjects (30.7% vs. 21.0%; P = 0.001). The genotypes and allele of rs1982073 in TGF-β1 were also significantly associated with LOAD. The frequency of the TG genotype of rs1982073 was significantly higher in the LOAD patients than in the control subjects (38.1% vs. 27.1%; P = 0.013). The minor allele (G) frequency was significantly higher in patients with LOAD than in control subjects (22.2% vs. 16.7%; P = 0.032). These results suggest that common variants in TGF-β1 might contribute to the development of LOAD in the Chinese population. PMID:26327336

  7. Sporadic urban leptospirosis

    Forouhar, Elena; Mitsani, Dimitra

    2011-01-01

    Severe leptospirosis (Weil Syndrome) was diagnosed in an otherwise healthy environmental worker in Baltimore alleys in late November 2010. He developed multiple organ failure but responded to antibiotic therapy and experienced a full recovery within 4 weeks. His diagnosis was confirmed by a rise in indirect hemagglutinin titer (acute 0, convalescent 400). The subject had close contact with Baltimore alley rats; a similar epidemiologic exposure and location reported in an outbreak 15 years ago.

  8. Sporadic urban leptospirosis

    Forouhar, Elena; Mitsani, Dimitra

    2011-01-01

    Severe leptospirosis (Weil Syndrome) was diagnosed in an otherwise healthy environmental worker in Baltimore alleys in late November 2010. He developed multiple organ failure but responded to antibiotic therapy and experienced a full recovery within 4 weeks. His diagnosis was confirmed by a rise in indirect hemagglutinin titer (acute 0, convalescent 400). The subject had close contact with Baltimore alley rats; a similar epidemiologic exposure and location reported in an outbreak 15 years ago...

  9. 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.

  10. 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

  11. Limited family structure and triple-negative breast cancer (TNBC) subtype as predictors of BRCA mutations in a genetic counseling cohort of early-onset sporadic breast cancers.

    Zugazagoitia, Jon; Pérez-Segura, Pedro; Manzano, Arancha; Blanco, Ignacio; Vega, Ana; Custodio, Ana; Teulé, Alex; Fachal, Laura; Martínez, Beatriz; González-Sarmiento, Rogelio; Cruz-Hernández, Juan Jesús; Chirivella, Isabel; Garcés, Vicente; Garre, Pilar; Romero, Atocha; Caldés, Trinidad; Díaz-Rubio, Eduardo; de la Hoya, Miguel

    2014-11-01

    Early-onset diagnosis is an eligibility criterion for BRCA1 and BRCA2 (BRCA) testing in sporadic breast cancer patients. Limited family structure has been proposed as a predictor of BRCA mutation status in this group of patients. An overwhelming amount of data supports a strong association between BRCA1 mutations and triple-negative breast cancer (TNBC). Here, we analyze the feasibility of using limited family structure and TNBC as predictors of BRCA mutation status in early-onset breast cancer patients attending genetic counseling units. We have conducted the study in a cohort of sporadic early-onset (≤35 years) breast cancer patients (N = 341) previously selected for BRCA genetic testing in Academic Hereditary Cancer Clinics from Spain. A retrospective review of medical records available at the time of risk assessment allowed us classifying patients according to family structure and TNBC. In addition, BRCAPRO score was calculated for all patients. Association between categorical variables was investigated using the Fisher's exact test. Binary Logistic Regression Analysis was used for multivariate analysis. Limited family structure (OR 3.61, p = 0.013) and TNBC (OR 3.14, p = 0.013) were independent predictors of BRCA mutation status. Mutation prevalence in the subgroup of patients with at least one positive predictor was 14%, whereas it dropped to 3% in non-TNBCs with adequate family history (OR 5.31, 95% CI 1.38-23.89, p = 0.006). BRCAPRO correctly discerned between limited and adequate family structures. Limited family structure and TNBC are feasible predictors of BRCA mutation status in sporadic early-onset (≤35 years) breast cancer patients attending genetic counseling units. The low prevalence of mutations observed in non-TNBCs with adequate family structure suggests that this subgroup of patients might be excluded from genetic testing. PMID:25342642

  12. DNA-methyltransferase 3B 39179 G > T polymorphism and risk of sporadic colorectal cancer in a subset of Iranian population

    Abdolreza Daraei

    2011-01-01

    Full Text Available Background: Epigenetic event is a biological regulation that influences the expression of various genes involved in cancer. DNA methylation is established by DNA methyltransferases, particularly DNAmethyltransferase 3B (DNMT3B. It seems to play an oncogenic role in the creation of abnormal methylation during tumorigenesis. The polymorphisms of the DNMT3B gene may influence DNMT3B activity in DNA methylation and increase the susceptibility to several cancers. These genetic polymorphisms have been studied in several cancers in different populations. Methods: In this study, we performed a case-control study with 125 colorectal cancer patients and 135 cancer-free controls to evaluate the association between DNMT3B G39179T polymorphism (rs1569686 in the promoter region and the risk of sporadic colorectal cancer. Up to now, few studies have investigated the role of this gene variant in sporadic colorectal cancer with no familial history. The genotypes of DNMT3B G39179T polymorphism was analyzed by PCR-RFLP. Results: We found that compared with G allele carriers, statistically the DNMT3B TT genotype (%34 was significantly associated with increased risk of colorectal cancer (adjusted OR, 3.993, 95% CI, 1.726-9.238, P = 0.001. Compared with DNMT3B TT genotype, the GT and GG genotypes had lower risk of developing sporadic colorectal cancer (OR = 0.848, 95% CI = 0.436-1.650. Conclusions: Our findings were consistent with that of previously reported case-control studies with colorectal cancer. These results suggest that the DNMT3B G39179T polymorphism influences DNMT3B expression, thus contributing to the genetic susceptibility to colorectal cancer. Further mechanistic studies are needed to unravel the causal molecular mechanisms.

  13. The epidemiological, clinical, and laboratory features of sporadic Creutzfeldt-Jakob disease patients in China: surveillance data from 2006 to 2010.

    Chen Gao

    Full Text Available 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 features of sporadic CJD (sCJD were analysed. Both groups of probable and possible sCJD showed highest incidences in the population of 60 to 69 year-olds. The most common presenting symptoms were progressive dementia and mental-related symptoms (neurological symptoms including sleeping turbulence, depression, anxiety and stress. Among the four main clinical manifestations, myoclonus was more frequently observed in the probable sCJD patients. About 2/3 of probable sCJD cases showed positive 14-3-3 in CSF and/or periodic sharp wave complexes (PSWC in electroencephalography (EEG. The presence of myoclonus was significantly closely related with the appearance of PSWC in EEG. Polymorphisms of codon 129 in PRNP of the notified cases revealed a highly predominant M129M genotype in Han Chinese. Among 23 genetic human prion diseases, ten were D178N/M129M Fatal familial insomnia (FFI and five were T188K genetic CJD (gCJD, possibly indicating a special distribution of gCJD-related mutations in Han Chinese. CONCLUSION: From the period of 2006 to 2010, 261 patients were diagnosed as sCJD and 23 patients were diagnosed as genetic human prion diseases in China. The epidemiological, clinical and laboratory analysis data were consistent with the characteristics of sporadic CJD, which provide insight into the features of CJD in China.

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

    Yuhai Zhao

    2015-12-01

    Full Text Available 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-κB-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.

  15. Immunohistochemical staining for p16 and BRAFV600E is useful to distinguish between sporadic and hereditary (Lynch syndrome-related) microsatellite instable colorectal carcinomas.

    Boissière-Michot, Florence; Frugier, Hélène; Ho-Pun-Cheung, Alexandre; Lopez-Crapez, Evelyne; Duffour, Jacqueline; Bibeau, Frédéric

    2016-08-01

    DNA mismatch repair (MMR) protein analysis by immunohistochemistry (IHC) can identify colorectal cancer (CRC) with microsatellite instability (MSI). As MLH1-deficient CRC can be hereditary or sporadic, markers to distinguish between them are needed. MLH1 promoter methylation assay is the reference method; however, sometimes, it is challenging on formalin-fixed paraffin-embedded tissue samples. We assessed by IHC the expression of BRAFV600E, p16, MGMT, and CDX2 in 55 MLH1-deficient MSI CRC samples (of which 8 had a germline MLH1 mutation) to determine whether this panel differentiates between sporadic and hereditary CRCs. We also analyzed MLH1 promoter methylation by methylation-specific PCR and pyrosequencing and BRAF status by genotyping. None of the hereditary CRCs showed MLH1 methylation, BRAF mutation, BRAFV600E-positive immunostaining, or loss of p16 expression. We detected MLH1 promoter methylation in 67 % and a BRAF mutation in 42 % of CRC, all showing MLH1 promoter methylation. BRAFV600E IHC and BRAF genotyping gave concordant results in all but two samples. Loss of expression of p16 was found in 30 % of CRC with methylation of the MLH1 promoter, but its expression was retained in all non-methylated and part of MLH1-methylated tumors (100 % specificity, 30 % sensitivity). CDX2 and MGMT expression was not associated with MLH1 status. Thus, BRAFV600E and p16 IHC may help in differentiating sporadic from hereditary MLH1-deficient CRC with MSI. Specifically, p16 IHC might be used as a surrogate marker for MLH1 promoter methylation, because all p16-negative CRCs displayed MLH1 methylation, whereas hereditary CRCs were all p16-positive. PMID:27220764

  16. Sporadic and familial blepharophimosis -ptosis-epicanthus inversus syndrome: FOXL2 mutation screen and MRI study of the superior levator eyelid muscle.

    Dollfus, H; Stoetzel, C; Riehm, S; Lahlou Boukoffa, W; Bediard Boulaneb, F; Quillet, R; Abu-Eid, M; Speeg-Schatz, C; Francfort, J J; Flament, J; Veillon, F; Perrin-Schmitt, F

    2003-02-01

    The analysis of the FOXL2 gene (3q23) in a series of two families and two sporadic cases affected with Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome (BPES) is presented. This study detected two novel FOXL2 mutations (missence and nonsens mutations) and confirmed the recurrence of a previously described duplication. Magnetic Resonance Imaging (MRI) of the orbit, in one family, showed absence or hypotrophy of the eyelid superior levator muscle suggesting a possible role of FOXL2 in the development of this extra-ocular muscle. PMID:12630957

  17. Cerebrospinal fluid real‐time quaking‐induced conversion is a robust and reliable test for sporadic creutzfeldt–jakob disease: An international study

    McGuire, Lynne I.; Poleggi, Anna; Poggiolini, Ilaria; Suardi, Silvia; Grznarova, Katarina; Shi, Song; de Vil, Bart; Sarros, Shannon; Satoh, Katsuya; Cheng, Keding; Cramm, Maria; Fairfoul, Graham; Schmitz, Matthias; Zerr, Inga; Cras, Patrick; Equestre, Michele; Tagliavini, Fabrizio; Atarashi, Ryuichiro; Knox, David; Collins, Steven; Haïk, Stéphane; Parchi, Piero; Pocchiari, Maurizio

    2016-01-01

    Real‐time quaking‐induced conversion (RT‐QuIC) has been proposed as a sensitive diagnostic test for sporadic Creutzfeldt–Jakob disease; however, before this assay can be introduced into clinical practice, its reliability and reproducibility need to be demonstrated. Two international ring trials were undertaken in which a set of 25 cerebrospinal fluid samples were analyzed by a total of 11 different centers using a range of recombinant prion protein substrates and instrumentation. The results show almost complete concordance between the centers and demonstrate that RT‐QuIC is a suitably reliable and robust technique for clinical practice. Ann Neurol 2016;80:160–165 PMID:27130376

  18. Risk Factors for Sporadic Non-Pregnancy Associated Listeriosis in Germany-Immunocompromised Patients and Frequently Consumed Ready-To-Eat Products.

    Karina Preußel

    Full Text Available Non-pregnancy associated (N-PA listeriosis, caused by Listeria monocytogenes, is a rare but severe disease, and is predominantly food-borne. Most cases appear sporadic and their infection vehicle remains unknown. Incidence has increased since 2008 in Germany. We aimed to identify underlying conditions and foods associated with sporadic N-PA listeriosis in Germany. We performed a nationwide case-control study from March 2012-December 2013. Cases were sporadic N-PA listeriosis patients notified to public health. Control subjects were age (40-65 years, 66-75 years, ≥ 76 years frequency-matched persons from a nationwide random telephone sample. A structured questionnaire collected information on underlying diseases, therapies and >60 food items. We conducted multivariable logistic regression analysis, adjusting for host factors identified by causal diagram theory, and calculated population attributable fractions. We enrolled 109 cases and 1982 controls. Cases' median age was 69 years, 55% were male, 44% received immunosuppressive therapy within 3 months prior to illness onset; a further 28% had at least one immunocompromising disease. In multivariable analysis, immunosuppressive therapy (OR 8.8, 95%CI 4.9-15.6, immunocompromising disease (OR 2.7; 95%CI 1.4-5.2, gastric acid suppression (OR 3.0; 95%CI 1.4-6.3, the consumption of cold cooked sausages (OR 2.6; 95%CI 1.6-4.4, the preferred consumption of packaged cheese (OR 2.1; 95%CI 1.3-3.5 and pre-sliced cheese (OR 2.2; 95%CI 1.3-3.7 were significantly associated with N-PA listeriosis. These foods accounted for 59% of all cases. Typical high risk foods, e.g. cold seafood, certain types of cheeses, tended to be negatively associated with disease. In conclusion, immunosuppressive therapy and frequently consumed ready-to-eat foods are the main risk factors for sporadic N-PA listeriosis in Germany. To reduce their risk, immunocompromised persons should consume the identified foods well before the 'use

  19. Mouse model of rare TOR1A variant found in sporadic focal dystonia impairs domains affected in DYT1 dystonia patients and animal models.

    Bhagat, Srishti L; Qiu, Sunny; Caffall, Zachary F; Wan, Yehong; Pan, Yuanji; Rodriguiz, Ramona M; Wetsel, William C; Badea, Alexandra; Hochgeschwender, Ute; Calakos, Nicole

    2016-09-01

    Rare de novo mutations in genes associated with inherited Mendelian disorders are potential contributors to sporadic disease. DYT1 dystonia is an autosomal dominant, early-onset, generalized dystonia associated with an in-frame, trinucleotide deletion (n. delGAG, p. ΔE 302/303) in the Tor1a gene. Here we examine the significance of a rare missense variant in the Tor1a gene (c. 613T>A, p. F205I), previously identified in a patient with sporadic late-onset focal dystonia, by modeling it in mice. Homozygous F205I mice have motor impairment, reduced steady-state levels of TorsinA, altered corticostriatal synaptic plasticity, and prominent brain imaging abnormalities in areas associated with motor function. Thus, the F205I variant causes abnormalities in domains affected in people and/or mouse models with the DYT1 Tor1a mutation (ΔE). Our findings establish the pathological significance of the F205I Tor1a variant and provide a model with both etiological and phenotypic relevance to further investigate dystonia mechanisms. PMID:27168150

  20. Analysis of two single nucleotide polymorphisms and loss of heterozygosity detection in the VHL gene in Chinese patients with sporadic renal cell carcinoma

    LIU Ning; GONG Kan; NA Xi; WU Guan; NA Yan-qun

    2005-01-01

    @@ Renal cell carcinoma (RCC) is the most common malignant tumour in the adult kidney.Recent studies have shown that inactivation of the tumour suppressor gene VHL located in chromosome 3p25-26 region is responsible for sporadic RCCs.1 According to Kundson's two hit theory,the mechanism of inactivation of a tumour suppressor gene involves mutation,hyper-methylation and loss of heterozygosity (LOH).Mutations and hypermethylation of the VHL gene have been well analysed in RCC,but due to the deficiency of specific gene markers in the VHL region,the exact LOH frequency of the VHL gene in RCC is still unknown.Single nucleotide polymorphisms (SNPs) are regarded as the third generation of human gene markers and are appropriate for LOH analysis.We searched the SNP database in the National Centre for Biotechnology Information,and selected two SNP sites located within the VHL gene region as gene markers.We analysed these two SNP sites in 79 Chinese sporadic RCC patients by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) to detect LOH frequency of the VHL gene and analyse the relationship between VHL LOH and the pathological parameters of RCC.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 小儿诺如病毒性肠炎的临床特征%Prevalence and Characterization of Norovirus in Children and Infants with Sporadic Acute Gastroenteritis

    夏嘉陵; 万朝敏; 朱渝

    2015-01-01

    Objective The aim of the present study was to describe the epidemiologic and clinical characteristics of hu-man noroviruses among children with symptoms of acute nonbacterial gastroenteritis. Methods Stool samples and clinical data were collected between June 2005 and December 2006 from sporadic symptomatic children. All of the specimens were detected by RT-PCR. Results With 46 HuNVs infections were identified in the 149 specimens, the prevalence of human noroviruses causing sporadic cases of acute gastroenteritis in young children was 30. 9%. The average age of children infected HuNVs was 13. 59 ± 9. 66 months. And the epidemic period of HuNVs was September-December. Conclusion Besides rotavirus, HuNVs were the second common causative viral agent in acute sporadic gastroenteritis of infant and children.%目的 了解散发性、急性婴幼儿HuNVs性肠炎临床特征和流行病学资料. 方法 采用横断面调查的研究方法,收集我院门、急诊就诊和住院婴幼儿中急性非细菌性肠炎的大便标本,通过问卷调查采集临床、流行病学资料. 检测A组轮状病毒抗原,阴性者纳入研究;对纳入标本提取病毒RNA,RT-PCR方法检测HuNVs. 分析检出率、发病年龄、发病时间、主要临床表现. 结果 婴幼儿急性非细菌性肠炎并且A组轮状病毒抗原检测为阴性的病例149份,RT-PCR方法检测有46例扩增出HuNVs条带,检出率30. 9%. HuNVs感染患儿年龄(13. 59 ± 9. 66)个月;发病时间集中在每年9~11月份,临床表现主要包括腹泻、呕吐、发热、不同程度脱水. 结论 HuNVs仅次于轮状病毒,是引起散发性、急性婴幼儿肠炎的第二位的病毒.

  6. 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.

  7. The response of sporadic E-layer to the total solar eclipse of July 22, 2009 over the equatorial ionization anomaly region of the Indian zone

    Yadav, Sneha; Das, Rupesh M.; Dabas, R. S.; Gwal, A. K.

    2013-06-01

    The digital ionosonde located in Bhopal (23.2°N, 77.2°E), India has been used to investigate the responses of the Es layer in the equatorial ionization anomaly (EIA) crest to the total solar eclipse (TSE) of July 22, 2009. Results show the presence of intense Es layer during and after the eclipse period. The gravity waves induced by the solar eclipse propagated upward in the Es layer and produced the periodic disturbance. The results of the wavelet analysis display the presence of dominant oscillation of about 24-32, 16-20 and 8 min. The appearance of intense sporadic-E concomitantly with the signatures of gravity wave suggests that the wind shear introduced by the solar eclipse induced gravity wave might be the plausible mechanism behind the intensification of Es-layer ionization.

  8. SAND FLY SPECIES COMPOSITION (DIPTERA: PSYCHODIDAE: PHLEBOTOMINAE) IN THE MUNICIPALITY OF CANTAGALO , AN AREA WITH SPORADIC CASES OF HUMAN CUTANEOUS LEISHMANIASIS IN RIO DE JANEIRO STATE, BRAZIL.

    Peres-Dias, Quezia Nunes; Oliveira, Claudete Diniz; Souza, Marcos Barbosa de; Meira, Antônio de Medeiros; Villanova, Ciro Benigno

    2016-07-11

    The municipality of Cantagalo is an area with sustained transmission of American Cutaneous Leishmaniasis (ACL). Monthly sand fly collections were performed for three years (June 2012 - May 2015) using a CDC light trap. A total of 3,310 specimens belonging to 12 species were trapped: Nyssomyia intermedia, Nyssomyia whitmani, Migonemyia migonei, Evandromyia lenti, Evandromyia cortelezzii, Micropygomyia quinquefer, Brumptomyia brumpti, Psathyromyia aragaoi, Micropygomyia schreiberi, Pintomyia fischeri, Sciopemyia sordellii, and Evandromyia edwardsi. The last seven species have not been previously recorded in this area. The highest abundance of species occurred between October and March. October was the month with the highest number of captured sand flies, one month before the peak in the summer rainfall. In October the highest number of Ny. intermedia, Ny. whitmani and Mg. migonei, were also collected, the three epidemiologically most important species. The high abundance of species with epidemiological importance for ACL transmission might explain the sporadic occurrence of the disease in the area. PMID:27410910

  9. 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

  10. 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...

  11. 2012 European Thyroid Association Guidelines for the Management of Familial and Persistent Sporadic Non-Autoimmune Hyperthyroidism Caused by Thyroid-Stimulating Hormone Receptor Germline Mutations

    Paschke, R.; Niedziela, M.; Vaidya, B.; Persani, L.; Rapoport, B.; Leclere, J.

    2012-01-01

    All cases of familial thyrotoxicosis with absence of evidence of autoimmunity and all children with persistent isolated neonatal hyperthyroidism should be evaluated for familial non-autoimmune autosomal dominant hyperthyroidism (FNAH) or persistent sporadic non-autoimmune hyperthyroidism (PSNAH). First, all index patients should be analysed for the presence/absence of a thyroid-stimulating hormone (TSH) receptor (TSHR) germline mutation, and if they display a TSHR germline mutation, all other family members including asymptomatic and euthyroid family members should also be analysed. A functional characterization of all new TSHR mutations is necessary. Appropriate ablative therapy is recommended to avoid relapses of hyperthyroidism and its consequences, especially in children. Therefore, in children the diagnosis of FNAH or PSNAH needs to be established as early as possible in the presence of the clinical hallmarks of the disease. PMID:24783013

  12. The enigmatic origin of bovine mtDNA haplogroup R: sporadic interbreeding or an independent event of Bos primigenius domestication in Italy?

    Silvia Bonfiglio

    Full Text Available BACKGROUND: When domestic taurine cattle diffused from the Fertile Crescent, local wild aurochsen (Bos primigenius were still numerous. Moreover, aurochsen and introduced cattle often coexisted for millennia, thus providing potential conditions not only for spontaneous interbreeding, but also for pastoralists to create secondary domestication centers involving local aurochs populations. Recent mitochondrial genomes analyses revealed that not all modern taurine mtDNAs belong to the shallow macro-haplogroup T of Near Eastern origin, as demonstrated by the detection of three branches (P, Q and R radiating prior to the T node in the bovine phylogeny. These uncommon haplogroups represent excellent tools to evaluate if sporadic interbreeding or even additional events of cattle domestication occurred. METHODOLOGY: The survey of the mitochondrial DNA (mtDNA control-region variation of 1,747 bovine samples (1,128 new and 619 from previous studies belonging to 37 European breeds allowed the identification of 16 novel non-T mtDNAs, which after complete genome sequencing were confirmed as members of haplogroups Q and R. These mtDNAs were then integrated in a phylogenetic tree encompassing all available P, Q and R complete mtDNA sequences. CONCLUSIONS: Phylogenetic analyses of 28 mitochondrial genomes belonging to haplogroups P (N = 2, Q (N = 16 and R (N = 10 together with an extensive survey of all previously published mtDNA datasets revealed major similarities between haplogroups Q and T. Therefore, Q most likely represents an additional minor lineage domesticated in the Near East together with the founders of the T subhaplogroups. Whereas, haplogroup R is found, at least for the moment, only in Italy and nowhere else, either in modern or ancient samples, thus supporting an origin from European aurochsen. Haplogroup R could have been acquired through sporadic interbreeding of wild and domestic animals, but our data do not rule out the

  13. Communicating a Marine Protected Area Through the Local Press: The Case of the National Marine Park of Alonissos, Northern Sporades, Greece

    Dikou, Angela; Dionysopoulou, Niki

    2011-05-01

    Local distrust for Marine Protected Area (MPA) managers is emerging as an important factor obstructing the fulfillment of MPA objectives, and, thus, there is a need to develop a means of enhancing relationship building between MPA managers and local people. We used the National Marine Park of Alonissos, Northern Sporades (NMPANS), Greece, as a relevant case-study to investigate whether the local print media's framing of the marine park and its management affected locals' attitudes. We conducted a longitudinal review of local newspaper articles pertaining to the NMPANS during 1980-2008, and we conducted telephone interviews with local people. We found that salience of the NMPANS in the local print media remained limited and sporadic, the main stakeholder remained the centralized public sector, and the regional print media was rather detached, moderate, and largely supportive of the NMPANS throughout 1980-2008. The progression of the management periods of the NMPANS, however, was accompanied by increased importance of the NMPANS, increased deviance from conservation as the chief objective of the NMPANS's establishment, a shift from presenting facts to presenting reactions, and a shift from a positive to a mixed image of the NMPANS. Locals who relied on newspapers for local news were better informed about the NMPANS, more likely to accept the NMPANS, and more likely to participate in meetings regarding the NMPANS regardless of gender, age, and occupation than those who did not rely on newspapers. The local print media may be utilized as a free-choice learning vehicle to enhance the value of an MPA among local people and to enhance the development of trust between park managers and locals through a proactive, empowering, and cognitive media strategy.

  14. Occurrence of Sporadic -E layer during the Ending Phase of Solar Cycle 23rd and Rising Phase of Solar Cycle 24th over the Anomaly Crest Region Bhopal

    Bhawre, Purushottam; Gwal, Ashok Kumar; Tripathi, Sharad Chandra; Mansoori, Azad Ahmad; Aslam A., M.; Khan, Parvaiz A.; Purohit, Pramod K.; Waheed, Malik Abdul; Khatarkar, Prakash

    Ionospheric anomaly crest regions are most challenging for scientific community to understand its mechanism and investigation, for this purpose we are investigating some inospheric result for this region. The study is based on the ionogram data recorded by IPS-71 Digital Ionosonde installed over anomaly crust region Bhopal (Geo.Lat.23.2° N, Geo. Long77.4° E, Dip latitude18.4°) over a four year period from January 2007 to December 2010, covering the ending phase of 23rd Solar Cycle and starting phase of 24th solar cycle. This particular period is felt to be very suitable for examining the sunspot number and it encompasses periods of low solar activities. Quarterly ionograms are analyzed for 24 hours during these study years and have been carefully examined to note down the presence of sporadic- E. We also note down the space weather activities along with the study. The studies are divided in mainly four parts with space and geomagnetic activities during these periods. The occurrence probability of this layer is highest in summer solstice, moderate during equinox and low during winter solstice. Remarkable occurrence peaks appear from June to July in summer and from December to January in winter. The layer occurrence showed a double peak variation with distinct layer groups, in the morning (0200 LT) and the other during evening (1800 LT).The morning layer descent was associated with layer density increase indicating the strengthening of the layer while it decreased during the evening layer descent. The result indicates the presence of semi-diurnal tide over the location while the higher descent velocities could be due to the modulation of the ionization by gravity waves along with the tides. The irregularities associated with the gradient-drift instability disappear during the counter electrojet and the current flow is reversed in westward. Keyword: ionosphere, solar cycle, sporadic - E

  15. 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.

  16. 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

  17. A semi-empirical model of the contribution from sporadic meteoroid sources on the meteor input function in the MLT observed at Arecibo

    Fentzke, Jonathan T.; Janches, Diego

    2008-03-01

    In this paper, we present a modeling and observational study of the micrometeor input function with a focus on understanding how each of the extraterrestrial sporadic meteoroid sources contributes to the observed meteoric flux in the Mesosphere and Lower Thermosphere (MLT) atmospheric region. For this purpose, we expand the model presented by Janches et al. (2006) using a Monte Carlo technique and incorporating: 1) a widely accepted global mass flux, which is divided into different proportions among the known sporadic meteoroid sources as the initial input above Earth's atmosphere; 2) contemporary knowledge on the source's velocity and radiant distributions; and 3) the full integration of the canonical meteor equations that describe the meteoroid entry and ablation physics. In addition, we constrain the initial input through a comparison of our modeled results with meteor observations obtained with the 430 MHz High Power and Large Aperture (HPLA) Arecibo radar in Puerto Rico that covers all seasons. The predicted meteor rates and velocity distributions are in excellent agreement with the observed ones without the need for any additional normalization factor. Our results indicate that although the Earth's Apex centered radiant source, which is characterized by high geocentric speeds (˜55 km/s), appears to be ˜33% of the meteoroids in the Solar System at 1 AU, it accounts for ˜60% of the meteors observed by the Arecibo HPLA radar in the atmosphere. The remaining 40% of observed meteors originate mostly from the Helion and Anti-Helion sources, with a very small, but constant during the day, contribution of the South and North Toroidal sources. These results also suggest that particles smaller than ˜10-3μg with slow velocities (<30 km/s) will not significantly ablate and never become observable meteors. The motivation of this effort is to construct a new and more precise MIF model needed for the subsequent modeling of the atmospheric phenomena related to the

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

    Erhard Tietze

    Full Text Available 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.

  19. 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.)

  20. Streptozotocin Intracerebroventricular-Induced Neurotoxicity and Brain Insulin Resistance: a Therapeutic Intervention for Treatment of Sporadic Alzheimer's Disease (sAD)-Like Pathology.

    Kamat, Pradip K; Kalani, Anuradha; Rai, Shivika; Tota, Santosh Kumar; Kumar, Ashok; Ahmad, Abdullah S

    2016-09-01

    Alzheimer's disease (AD) is a neurodegenerative disorder that is remarkably characterized by pathological hallmarks which include amyloid plaques, neurofibrillary tangles, neuronal loss, and progressive cognitive loss. Several well-known genetic mutations which are being used for the development of a transgenic model of AD lead to an early onset familial AD (fAD)-like condition. However, these settings are only reasons for a small percentage of the total AD cases. The large majorities of AD cases are considered as a sporadic in origin and are less influenced by a single mutation of a gene. The etiology of sporadic Alzheimer's disease (sAD) remains unclear, but numerous risk factors have been identified that increase the chance of developing AD. Among these risk factors are insulin desensitization/resistance state, oxidative stress, neuroinflammation, synapse dysfunction, tau hyperphosphorylation, and deposition of Aβ in the brain. Subsequently, these risk factors lead to development of sAD. However, the underlying molecular mechanism is not so clear. Streptozotocin (STZ) produces similar characteristic pathology of sAD such as altered glucose metabolism, insulin signaling, synaptic dysfunction, protein kinases such as protein kinase B/C, glycogen synthase-3β (GSK-3β) activation, tau hyperphosphorylation, Aβ deposition, and neuronal apoptosis. Further, STZ also leads to inhibition of Akt/PKB, insulin receptor (IR) signaling molecule, and insulin resistance in brain. These alterations mediated by STZ can be used to explore the underlying molecular and pathophysiological mechanism of AD (especially sAD) and their therapeutic intervention for drug development against AD pathology. PMID:26298663

  1. Novel HRPT2/CDC73 gene mutations and loss of expression of parafibromin in Chinese patients with clinically sporadic parathyroid carcinomas.

    Ou Wang

    Full Text Available OBJECTIVE: It is widely recognized that the diagnosis of parathyroid carcinoma (PC is often difficult because of the overlap of characteristics between malignant and benign parathyroid tumors, especially at an early stage. Based on the identification of tumor suppressor gene HRPT2/CDC73 and its association with hereditary and sporadic PC, screening of gene mutations and detection of parafibromin immunoreactivity have been suggested as diagnostic instruments of PC in Whites. There is little information about HRPT2/CDC73 mutations and its corresponding protein expression in patients with sporadic PC in Chinese population, and the long-term follow-up data is scarce. METHODS: Paraffin-embedded tissues were obtained from 13 patients with PC, 13 patients with parathyroid adenoma (PA and 7 patients with parathyroid hyperplasia(PH, and 6 normal parathyroid (NP tissues as controls. Peripheral blood from 11 patients with PC was collected. PCR products using Genomic DNA extracted from tumor tissues or blood as template was sequenced for HRPT2/CDC73 gene. Expression of parafibromin in tumor tissues was evaluated by immunohistochemical analysis. RESULTS: Six mutations in 6 of 13 patients with PC were identified, with three being novel. Four of them were germ-line mutations. Patients with mutations were susceptible to recurrence of the PC. Complete (8/13, 61.5% or partial (5/13, 38.5% loss of parafibromin expression was observed in PC tissues. All of tissue samples from normal parathyroid or benign parathyroid tumors displayed positive immunostaining of parafibromin except one adenoma. CONCLUSIONS: The present study supplies information on the mutations and protein expression of HRPT2/CDC73 gene and phenotypes of parathyroid carcinoma in Chinese population. And the expanded mutation database of this gene may benefit patients in the diagnosis and treatment of this disease.

  2. 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.

  3. 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

  4. Array CGH identifies distinct DNA copy number profiles of oncogenes and tumor suppressor genes in chromosomal- and microsatellite-unstable sporadic colorectal carcinomas.

    Lassmann, Silke; Weis, Roland; Makowiec, Frank; Roth, Jasmine; Danciu, Mihai; Hopt, Ulrich; Werner, Martin

    2007-03-01

    DNA copy number changes represent molecular fingerprints of solid tumors and are as such relevant for better understanding of tumor development and progression. In this study, we applied genome-wide array comparative genomic hybridization (aCGH) to identify gene-specific DNA copy number changes in chromosomal (CIN)- and microsatellite (MIN)-unstable sporadic colorectal cancers (sCRC). Genomic DNA was extracted from microdissected, matching normal colorectal epithelium and invasive tumor cells of formalin-fixed and paraffin-embedded tissues of 22 cases with colorectal cancer (CIN = 11, MIN = 11). DNA copy number changes were determined by aCGH for 287 target sequences in tumor cell DNAs, using pooled normal DNAs as reference. aCGH data of tumor cell DNAs was confirmed by fluorescence in situ hybridization (FISH) for three genes on serial tissues as those used for aCGH. aCGH revealed DNA copy number changes previously described by metaphase CGH (gains 7, 8q, 13q, and 20q; losses 8p, 15q, 18q, and 17p). However, chromosomal regions 20q, 13q, 7, and 17p were preferentially altered in CIN-type tumors and included DNA amplifications of eight genes on chromosome 20q (TOP1, AIB1, MYBL2, CAS, PTPN1, STK15, ZNF217, and CYP24), two genes on chromosome 13q (BRCA2 and D13S25), and three genes on chromosome 7 (IL6, CYLN2, and MET) as well as DNA deletions of two genes on chromosome 17p (HIC1 and LLGL1). Finally, additional CIN-tumor-associated DNA amplifications were identified for EXT1 (8q24.11) and MYC (8q24.12) as well as DNA deletions for MAP2K5 (15q23) and LAMA3 (18q11.2). In contrast, distinct MIN-tumor-associated DNA amplifications were detected for E2F5 (8p22-q21.3), GARP (11q13.5-q14), ATM (11q22.3), KAL (Xp22.3), and XIST (Xq13.2) as well as DNA deletions for RAF1 (3p25), DCC (18q21.3), and KEN (21q tel). aCGH revealed distinct DNA copy number changes of oncogenes and tumor suppressor genes in CIN- and MIN-type sporadic colorectal carcinomas. The identified candidate

  5. Etiological study on sporadic viral gastroenteritis among adult in Beijing%成人散发性病毒性胃肠炎的病原学分析

    陈美芳; 魏来; 高燕; 丛旭; 孙春玲; 朱建莹; 郗萌; 郭晓琳; 杨霞; 李颖

    2008-01-01

    目的 了解北京地区成人散发性病毒性胃肠炎中诺如病毒、轮状病毒及肠道腺病毒感染情况和流行病学特点,为临床防治提供理论依据.方法 收集北京大学人民医院2005年至2006年成人肠道门诊散发非霍乱水样便腹泻患者粪便标本312份,用聚丙烯酰胺凝胶电泳(PAGE)进行轮状病毒核酸的检测;分别用德国R-Biopharm公司的酶免疫试剂盒进行诺如病毒和肠道腺病毒抗原的检测.结果 312份粪便标本中,轮状病毒核酸检测全部阴性;125份粪便标本中诺如病毒阳性22份,阳性检出率17.6%(22/125),其中10月份检出率最高,为32.4%(11/34);92份粪便标本中肠道腺病毒阳性3例,检出率3.3%(3/92),其中1例诺如病毒和腺病毒混合感染.结论 北京地区成人散发性病毒性胃肠炎病原以诺如病毒多见,秋季多发;轮状病毒感染率可能很低.%Objective To understand the infection and epidemiology of norovirus and rotavirus and enteral adenovirus among adult with sporadic viral gastroenteritis in Beijing and provide theoretical basis for clinical prevention and control.Methods Stool specimens were collected from all 312 sporadic outpatient among adult with non-cholera watery diarrhea in Infectious Disease Department of Peking University People's Hospital 2005-2006.PAGE were used for detection of rotavirus RNA in stool specimens:R-Biopharm RIDASCREEN norovirus and RIDASCREEN adenovirus were used for detection of norovirus and adenovirus.Resuits Rotavirus RNA was not present in all 312 stool specimens:Norovirus was present in 17.6%(22/125)and in 32.4%(11/34)in October;Adenovirus was present in 3.3%(3/92);Mixed infections of norovirus and adenovirus was present in 1 stool specimen.Conclusions Norovirus is more common etiologic agents of sporadic acute viral gastroenteritis among adult in Beijing.The infection peak of norovirus is in autumn.Maybe the infection of rotavirus is few.

  6. Loss of H3K27me3 Expression Is a Highly Sensitive Marker for Sporadic and Radiation-induced MPNST

    Prieto-Granada, Carlos N.; Wiesner, Thomas; Messina, Jane L.; Jungbluth, Achim A.; Chi, Ping; Antonescu, Cristina R.

    2016-01-01

    Most malignant peripheral nerve sheath tumors (MPNSTs) exhibit combined inactivation of NF1, CDKN2A, and polycomb repressive complex 2 component genes (Embryonic Ectoderm Development [EED] and Suppressor of Zeste 12 [SUZ12]). Mutations in EED and SUZ12 induce loss of trimethylation at lysine 27 of histone 3 (H3K27me3), with subsequent aberrant transcriptional activation of polycomb repressive complex 2–repressed homeobox master regulators. These findings prompted us to investigate the performance of an anti-H3K27me3 monoclonal antibody clone C36B11 as an immunohistochemical marker for MPNSTs. We assessed the C36B11 reactivity pattern in a pathologically and genetically well-characterized cohort of 68 MPNSTs, spanning various clinical presentations, such as type 1 neurofibromatosis (NF1), radiotherapy, and sporadic MPNSTs. We found that 69% (n=47) of all MPNSTs demonstrated loss of H3K27me3 expression, with 42 (61%) showing complete loss and 5 (7%) showing partial loss, whereas 31% (n = 21) retained H3K27me3 expression. Among the NF1-related high-grade MPNSTs, 60% demonstrated loss of expression. In contrast, the majority of both sporadic (95%) and radiotherapy-related (91%) MPNSTs showed loss of H3K27me3 expression. Two of the 3 low-grade MPNSTs and all neurofibromas showed retained expression. Furthermore, all 5 epithelioid MPNSTs retained H3K27me3 labeling. The specificity of H3K27me3 loss as a marker for MPNSTs was studied by testing a large spectrum of lesions included in MPNST differential diagnosis, such as spindle/desmoplastic melanomas, synovial sarcomas, myoepithelial tumors, and other mesenchymal neoplasms, all of which retained expression of H3K27me3. We conclude that immunohistochemical analysis of H3K27me3 has good sensitivity and robust specificity for the diagnosis of MPNST, particularly outside of NF1 clinical history, which represents the most challenging diagnostic setting. PMID:26645727

  7. Clinical Insights on Adult-onset Sporadic Ataxias%成人发病的散发性共济失调症临床诊疗

    张颖冬

    2015-01-01

    Adult-onset sporadic ataxias are a group of disorders manifested predominantly with ataxia, due to a variety of the potential causes including intoxication, immune-mediation, vitamins deifciencies, infections, neurodegeneration, and even some hereditary conditions. The clinical spectrum of these disorders is diverse, and their diagnosis remains a challenge. Compared with hereditary ataxias, most ataxias in this group respond the treatment well, that means the signiifcance of timely and correct diagnosis. The advanced biochemical, immune and imaging tools will help the perception and management on those ataxias. Different categories of adult-onset sporadic ataxia were elucidated with the highlight on their clinical features, neuro-imagingand diagnostic criteria.%成人发病的散发性共济失调症是由多种原因所致,临床表现以共济失调为主要的多种疾病。致病原因包括中毒、免疫介导性、维生素缺乏、感染性疾病、变性病以及遗传性疾患等。散发性共济失调临床谱具有明显异质性,临床正确诊断极具挑战性。但相比于遗传性共济失调症,此类疾患多数治疗效果较好,及时、正确诊断尤为重要。现代生化、免疫以及影像学技术有助于此类疾患的认识和诊治。文中综述并讨论可致成人发病的散发性共济失调的不同疾病分类,并着重其临床和神经影像学表现及诊断标准。

  8. Loss of H3K27me3 Expression Is a Highly Sensitive Marker for Sporadic and Radiation-induced MPNST.

    Prieto-Granada, Carlos N; Wiesner, Thomas; Messina, Jane L; Jungbluth, Achim A; Chi, Ping; Antonescu, Cristina R

    2016-04-01

    Most malignant peripheral nerve sheath tumors (MPNSTs) exhibit combined inactivation of NF1, CDKN2A, and polycomb repressive complex 2 component genes (Embryonic Ectoderm Development [EED] and Suppressor of Zeste 12 [SUZ12]). Mutations in EED and SUZ12 induce loss of trimethylation at lysine 27 of histone 3 (H3K27me3), with subsequent aberrant transcriptional activation of polycomb repressive complex 2-repressed homeobox master regulators. These findings prompted us to investigate the performance of an anti-H3K27me3 monoclonal antibody clone C36B11 as an immunohistochemical marker for MPNSTs. We assessed the C36B11 reactivity pattern in a pathologically and genetically well-characterized cohort of 68 MPNSTs, spanning various clinical presentations, such as type 1 neurofibromatosis (NF1), radiotherapy, and sporadic MPNSTs. We found that 69% (n=47) of all MPNSTs demonstrated loss of H3K27me3 expression, with 42 (61%) showing complete loss and 5 (7%) showing partial loss, whereas 31% (n=21) retained H3K27me3 expression. Among the NF1-related high-grade MPNSTs, 60% demonstrated loss of expression. In contrast, the majority of both sporadic (95%) and radiotherapy-related (91%) MPNSTs showed loss of H3K27me3 expression. Two of the 3 low-grade MPNSTs and all neurofibromas showed retained expression. Furthermore, all 5 epithelioid MPNSTs retained H3K27me3 labeling. The specificity of H3K27me3 loss as a marker for MPNSTs was studied by testing a large spectrum of lesions included in MPNST differential diagnosis, such as spindle/desmoplastic melanomas, synovial sarcomas, myoepithelial tumors, and other mesenchymal neoplasms, all of which retained expression of H3K27me3. We conclude that immunohistochemical analysis of H3K27me3 has good sensitivity and robust specificity for the diagnosis of MPNST, particularly outside of NF1 clinical history, which represents the most challenging diagnostic setting. PMID:26645727

  9. Study on the clinicpathologic features of female sporadic basal-like breast cancer%女性散发性基底细胞型乳腺癌临床病理特征的研究

    毛晓韵; 王欢; 范垂锋; 魏晶; 姚凡; 刘崇; 金锋

    2012-01-01

    目的:筛选女性散发性基底细胞型乳腺癌,探讨其临床病理特征.方法:用免疫组化结合荧光原位杂交的方法从500例女性散发性乳腺癌中筛选出基底细胞型乳腺癌,结合形态学及临床病理参数分析散发性基底细胞型乳腺癌的临床病理特征.结果:在500例乳腺癌中共筛出三阴性乳腺癌77例(15.4%),基底细胞型乳腺癌60例(12.0%).基底细胞型乳腺癌的病理组织学形态学与非基底细胞型乳腺癌并无明显差异.基底细胞型乳腺癌与非基底细胞型乳腺癌相比,其在发病年龄、发病时月经状态及肿瘤TNM分期并无明显统计学差异,二者在肿瘤大小及淋巴结转移上有统计学差异.结论:散发型基底细胞型乳腺癌倾向于原发灶较大,淋巴结转移多.%Objective: To screen female sporadic basal - like breast cancer and investigate the clinicopathological characters of basal - like breast cancer. Methods: To screen female sporadic basal - like breast cancer from 500 sporadic breast cancer by immunohistochemistry and fluorescence in situ hybridization and analyze the clinicopathological characters of basal - like breast cancer combined with morphological and clinicopathological factors. Results: Total of 77 cases of triple - negative breast cancer were screened out in 500 sporadic breast caner ( 77/500, 15. 4% ), 60 cases of sporadic basal - like breast cancer ( 60/500, 12. 0% ). There were no significant difference in morphology, age, menopausal status and tumor stage between basal - like breast cancer and non basal - like breast cancer. Statistical analysis revealed a significant difference in tumor size and lymph node metastasis between basal - like breast cancer and non basal - like breast cancer. Conclusion: Sporadic basal - like breast cancer associated with big tumor size and lymph node metastasis.

  10. 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

  11. Protease-sensitive conformers in broad spectrum of distinct PrPSc structures in sporadic Creutzfeldt-Jakob disease are indicator of progression rate.

    Chae Kim

    2011-09-01

    Full Text Available The origin, range, and structure of prions causing the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD, are largely unknown. To investigate the molecular mechanism responsible for the broad phenotypic variability of sCJD, we analyzed the conformational characteristics of protease-sensitive and protease-resistant fractions of the pathogenic prion protein (PrP(Sc using novel conformational methods derived from a conformation-dependent immunoassay (CDI. In 46 brains of patients homozygous for polymorphisms in the PRNP gene and exhibiting either Type 1 or Type 2 western blot pattern of the PrP(Sc, we identified an extensive array of PrP(Sc structures that differ in protease sensitivity, display of critical domains, and conformational stability. Surprisingly, in sCJD cases homozygous for methionine or valine at codon 129 of the PRNP gene, the concentration and stability of protease-sensitive conformers of PrP(Sc correlated with progression rate of the disease. These data indicate that sCJD brains exhibit a wide spectrum of PrP(Sc structural states, and accordingly argue for a broad spectrum of prion strains coding for different phenotypes. The link between disease duration, levels, and stability of protease-sensitive conformers of PrP(Sc suggests that these conformers play an important role in the pathogenesis of sCJD.

  12. 儿童散发性伯基特淋巴瘤的研究进展%Research evolution of children with sporadic Burkitt' s lymphoma

    徐红艳

    2012-01-01

    Children with sporadic Burkitt's lymphoma (BL) is a highly aggressive lymphoma.It partly overlaps with diffuse large B cell lymphoma (DLBCL) and unclassified B cell lymphoma (DLBCL/BL) which is between DLBCL and BL in the morphological,immunophenotypic and molecular genetic aspects,but it has its unique.characterization. Enhancing awareness of the disease based on the BL pathology, pathogenesis and prognosis of understanding,at the time of diagnosis and identificate with DLBCL and DLBCL/BL at the tine of diagnosis will be beneficial to clinical correct treatment and prognosis.%儿童散发性伯基特淋巴瘤(BL)属于高度侵袭性淋巴瘤,在形态学、免疫表型和分子遗传学等方面与弥漫性大B细胞淋巴瘤( DLBCL)及介于DLBCL和BL之间的未分类B细胞淋巴瘤( DLBCL/BL)有部分重叠,但亦有其独特的表征.通过对BL病理、发病机制及预后的了解,增强对该病的认识,并在诊断时与DLBCL、DLBCL/BL进行鉴别,有利于临床正确的治疗及预后判断.

  13. The Alterations of Cortical Volume, Thickness, Surface, and Density in the Intermediate Sporadic Parkinson's Disease from the Han Population of Mainland China

    Deng, Xia; Zhou, Meihong; Tang, Chunyan; Zhang, Jie; Zhu, Lei; Xie, Zunchun; Gong, Honghan; Xiao, Xiangzuo; Xu, Renshi

    2016-01-01

    Many symptoms of sporadic Parkinson's disease (sPD) can't be completely explained by the lesion of simple typical extrapyramidal circuit between striatum and substantia nigra. Therefore, we investigated the alteration of cortical volume, thickness, surface, and density in the intermediate sPD from the Han population of Mainland China in order to find the new pathological brain regions associated with the complex clinical manifestations of sPD. The cortical volume, thickness, surface and density were examined using the voxel-based cortical morphometry and corticometry on magnetic resonance image (MRI) in 67 intermediate sPD and 35 controls, the multiple adjusted comparisons analysis of all MRI data were employed to assess the relationships between the cortical morphometric alteration in the specific brain regions and sPD. Results showed that a significantly shrunk volume, thinned thickness and enlarged or reduced surface of cortex in some specific brain regions were closely associated with sPD, but all cortical densities were not different. The majority of morphometric alteration of hemisphere cortex was symmetric, but that in the left hemisphere was more significant. The cortical morphometric alterations in the frontal, temporal, parietal, occipital and limbic lobe, cerebellum, caudate, and thalamus were closely related to the clinical neural dysfunction (Clinical manifestations) of sPD. Our data indicated that the deficits of extensive brain regions involved in the development of sPD, resulted in a series of correspondent complex clinical manifestations in the disease. PMID:27536237

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

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

    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 were novel. Genotype-phenotype correlation analysis suggested that the maximum aortic diameter in the disruptive mutation group was significantly larger than that in the non-Cys missense mutation group. Interestingly, the variant Ala27Thr at −1 position, which is predicted to change the cleavage site of the signal peptidase of fibrillin-1, was detected in two unrelated patients. Furthermore, genotyping analysis of this variant detected 10 heterozygous Ala27Thr from additional 666 unrelated patients (1.50%), versus 7 from 1500 controls (0.47%), indicating a significant association of this variant with STAAD. Collectively, the identification of the variant Ala27Thr may represent a relatively common genetic predisposition and a novel pathogenetic mechanism for STAAD. Also, expansion of the mutation spectrum in FBN1 will be helpful in genetic counselling for Chinese patients with STAAD. PMID:26272055

  15. Clonality Analysis of Immunoglobulin Gene Rearrangement by Next-Generation Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of BCR as Opposed to Sporadic Burkitt Lymphoma

    Amato, Teresa; Abate, Francesco; Piccaluga, Pierpaolo; Iacono, Michele; Fallerini, Chiara; Renieri, Alessandra; De Falco, Giulia; Ambrosio, Maria Raffaella; Mourmouras, Vaselious; Ogwang, Martin; Calbi, Valeria; Rabadan, Roul; Hummel, Michael; Pileri, Stefano; Bellan, Cristiana

    2016-01-01

    Objectives: Recent studies using next-generation sequencing (NGS) analysis disclosed the importance of the intrinsic activation of the B-cell receptor (BCR) pathway in the pathogenesis of sporadic Burkitt lymphoma (sBL) due to mutations of TCF3/ID3 genes. Since no definitive data are available on the genetic landscape of endemic Burkitt (eBL), we first assessed the mutation frequency of TCF3/ID3 in eBL compared with sBL and subsequently the somatic hypermutation status of the BCR to answer whether an extrinsic activation of BCR signaling could also be demonstrated in Burkitt lymphoma. Methods: We assessed the mutations of TCF3/ID3 by RNAseq and the BCR status by NGS analysis of the immunoglobulin genes (IGs). Results: We detected mutations of TCF3/ID3 in about 30% of the eBL cases. This rate is significantly lower than that detected in sBL (64%). The NGS analysis of IGs revealed intraclonal diversity, suggesting an active targeted somatic hypermutation process in eBL compared with sBL. Conclusions: These findings support the view that the antigenic pressure plays a key role in the pathogenetic pathways of eBL, which may be partially distinct from those driving sBL development. PMID:26712879

  16. Mutation analysis of the gene encoding Bruton`s tyrosine kinase in a family with a sporadic case of X-linked agammaglobulinemia reveals three female carriers

    Hagemann, T.L.; Kwan, Sau-Ping [Rush Medical School, Chicago, IL (United States); Assa`ad, A.H. [Children`s Hospital Medical Center, Cincinnati, OH (United States)

    1995-11-06

    Bruton`s tyrosine kinase (Btk) has been identified as the protein responsible for the primary immunodeficiency X-linked agammaglobulinemia (XLA). We and others have cloned the gene for Btk and recently reported the genomic organization. Nineteen exons were positioned within the 37 kb gene. With the sequence data derived from our genomic map, we have designed a PCR based assay to directly identify mutations of the Btk gene in germline DNA of patients with XLA. In this report, the assay was used to analyze a family with a sporadic case of XLA to determine if other female relatives carry the disease. A four base-pair deletion was found in the DNA of the affected boy and was further traced through three generations. With the direct identification of the mutations responsible for XLA, we can now diagnose conclusively the disease and identify the immunologically normal female carriers. This same technique can easily be applied to prenatal diagnosis in families where the mutation can be identified. 34 refs., 3 figs.

  17. 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

  18. Sporadic Fibrodysplasia Ossificans Progressiva in an Egyptian Infant with c.617G > A Mutation in ACVR1 Gene: A Case Report and Review of Literature

    Mohammad Al-Haggar

    2013-01-01

    Full Text Available Fibrodysplasia ossificans progressiva (FOP is an autosomal dominant severe musculoskeletal disease characterized by extensive new bone formation within soft connective tissues and unique skeletal malformations of the big toes which represent a birth hallmark for the disease. Most of the isolated classic cases of FOP showed heterozygous mutation in the ACVR1 gene on chromosome 2q23 that encodes a bone morphogenetic protein BMP (ALK2. The most common mutation is (c.617G > A leading to the amino acid substitution of arginine by histidine (p.Arg206His. We currently report on an Egyptian infant with a sporadic classic FOP in whom c.617G > A mutation had been documented. The patient presented with the unique congenital malformation of big toe and radiological evidence of heterotopic ossification in the back muscles. The triggering trauma was related to the infant's head, however; neither neck region nor sites of routine intramuscular vaccination given during the first year showed any ossifications. Characterization of the big toe malformation is detailed to serve as an early diagnostic marker for this rare disabling disease.

  19. 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 ...

  20. 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.

  1. Pseudo-obstrucción intestinal por miopatía visceral esporádica Intestinal pseudo-obstruction due to sporadic visceral myopathy

    Pedro Montalvo

    2004-12-01

    Full Text Available Se presenta el caso infrecuente de un paciente con miopatía visceral esporádica y afectación de la totalidad del tracto gastrointestinal y de la vía urinaria. La miopatía visceral es una forma de pseudo-obstrucción intestinal crónica idiopática caracterizada por degeneración vacuolar, atrofia y fibrosis de la capa muscular propia de la pared intestinal, sin células inflamatorias. Se puede presentar en niños y adolescentes afectando la musculatura visceral digestiva y urinaria. La manifestación familiar se encuentra en aproximadamente el 30% de los casos y se transmite de forma autosómica recesiva en la mayoría de las familias. Es fundamental descartar causas secundarias de pseudo-obstrucción intestinal crónica y la realización de biopsia de todo el espesor de la pared gastrointestinal para poder arribar al diagnóstico. El tratamiento quirúrgico sólo es eficaz en los que tienen afectación de porciones aisladas del tubo digestivo.We report an unusual case of a patient with sporadic visceral myopathy and involvement of the entire gastrointestinal and urinary tract. Visceral myopathy is a form of chronic idiophatic intestinal pseudo-obstruction characterized by vacuolar degeneration, atrophy and fibrosis of the intestinal propia muscle layer without inflammatory cells. It can be found in childhood and adolescence affecting the gastrointestinal and urinary visceral muscle. The familial occurrence can be found in about 30% of cases and the mode of transmission is autosomal recessive in most families. It is crucial to exclude secondary forms of chronic intestinal pseudo-obstruction and to obtain full thickness intestinal biopsy for the diagnosis. Surgical treatment is only beneficial in cases with isolated segmental involvement of the gastrointestinal tract.

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

    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

  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. Dynamics of HEV viremia, fecal shedding and its relationship with transaminases and antibody response in patients with sporadic acute hepatitis E

    Chandra Nidhi S

    2010-09-01

    Full Text Available Abstract Background There is paucity of data regarding duration of fecal excretion and viremia on sequential samples from individual patients and its correlation with serum transaminases and antibody responses in patients with acute hepatitis E. This prospective study was undertaken at a tertiary care center in Northern India over 15 months. Only those patients of sporadic acute hepatitis E who were in their first week of illness and followed up weekly for liver function tests, IgM anti HEV antibody and HEV RNA in sera and stool were included. HEV RNA was done by RT - nPCR using two pairs of primers from RdRp region of ORF 1 of the HEV genome. Results Over a period of 15 months 60 patients met the inclusion criterion and were enrolled for the final analysis. The mean age of the patients was 29.2 ± 8.92 years, there were 39 males. The positivity of IgM anti HEV was 80% at diagnosis and 18.3% at 7th week, HEV RNA 85% at diagnosis and 6.6% at 7th week and fecal RNA 70% at the time of diagnosis and 20% at 4th week. The maximum duration of viremia detected was 42 days and fecal viral shedding was 28 days after the onset of illness. Conclusion Present study reported HEV RNA positivity in sera after normalization of transaminases. Fecal shedding was not seen beyond normalization of transaminases. However, viremia lasted beyond normalization of transaminases suggesting that liver injury is independent of viral replication.

  5. The effect of anakinra, an IL1 receptor antagonist, in patients with sporadic inclusion body myositis (sIBM): a small pilot study.

    Kosmidis, Michalis L; Alexopoulos, Harry; Tzioufas, Athanasios G; Dalakas, Marinos C

    2013-11-15

    In sIBM, an inflammatory process mediated by cytotoxic T cells and cytokines in conjunction with a degenerative process, deposits of beta amyloid and misfolded proteins appear to be the main culprits in disease pathogenesis. IL-1β may play a key role because it is upregulated in sIBM myofibers, co-localizes with Amyloid Precursor Protein (APP) and promotes the production of APP and amyloid deposits. We performed a small, pilot study to examine whether anakinra, an IL1 receptor antagonist could benefit sIBM patients. Four patients with biopsy-proven sIBM received anakinra for a mean period of 7.7 months. No improvement in muscle strength or stabilization was noted in any of the patients based on grip strength and MRC measurements. The treatment failure may be due to insufficiency of anakinra to suppress the intramuscular IL1, the short study period, or the irrelevance of IL1 in the disease process. PMID:23998706

  6. 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;

    2016-01-01

    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...

  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. 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.

  9. A Pooling Genome-Wide Association Study Combining a Pathway Analysis for Typical Sporadic Parkinson's Disease in the Han Population of Chinese Mainland.

    Hu, Yakun; Deng, Libing; Zhang, Jie; Fang, Xin; Mei, Puming; Cao, Xuebing; Lin, Jiari; Wei, Yi; Zhang, Xiong; Xu, Renshi

    2016-09-01

    Genome-wide association studies (GWAS) on sporadic Parkinson's disease (sPD) are mainly conducted in European and American populations at present, and the Han populations of Chinese mainland (HPCM) almost have not been studied yet. Here, we conducted a pooling GWAS combining a pathway analysis with 862,198 autosomal single nucleotide polymorphisms of IlluminaHumanOmniZhongHua-8 in 250 sPD and 250 controls from HPCM precluded toxicant exposure, age, and heavy coffee drinking habit interference. We revealed that among the 22 potential loci implicated, PRDM2/KIAA1026 (kgp8090149), TSG1/MANEA (kgp154172), PDE10A (kgp8130520), MDGA2 (rs9323124), ATPBD4/LOC100288892 (kgp11333367), ZFP64/TSHZ2 (kgp4156164), PAQR3/ARD1B (kgp9482779), FLJ23172/FNDC3B (kgp760898), C18orf1 (kgp348599), FLJ43860/NCRNA00051 (kgp4105983), CYP1B1/C2orf58 (kgp11353523), WNT9A/LOC728728 (rs849898), ANXA1/LOC100130911 (rs10746953), FLJ35379/LOC100132423 (kgp9550589), PLEKHN1 (kgp7172368), DMRT2/SMARCA2 (kgp10769919), ZNF396/INO80C (rs1362858), C3orf67/LOC339902 (rs6783485), LOC285194/IGSF11 (rs1879553), FGF10/MRPS30 (rs13153459), BARX1/PTPDC1 (kgp6542803), and COL5 A2 (rs11186), the peak significance was at the kgp4105983 of FLJ43860 gene in chromosome 8, the first top strongest associated locus with sPD was PRDM2 (kgp8090149) in chromosome 1, and the 24 pathways including 100 significantly associated genes were strongly associated with sPD from HPCM. The 40 genes were shared by at least two pathways. The most possible associated pathways with sPD were axon guidance, ECM-receptor interaction, neuroactive ligand-receptor interaction, tight junction, focal adhesion, gap junction, long-term depression, drug metabolism-cytochrome P450, adherens junction, endocytosis, and protein digestion and absorption. Our results indicated that these loci, pathways, and their related genes might be involved in the pathogenesis of sPD from HPCM and provided some novel evidences for further searching the genetic

  10. Two major histocompatibility complex haplotypes influence susceptibility to sporadic inclusion body myositis: critical evaluation of an association with HLA-DR3.

    Price, P; Santoso, L; Mastaglia, F; Garlepp, M; Kok, C C; Allcock, R; Laing, N

    2004-11-01

    Previous studies of sporadic inclusion body myositis (sIBM) have shown a strong association with HLA-DR3 and other components of the 8.1 ancestral haplotype (AH) (HLA-A1, B8, DR3), where the susceptibility locus has been mapped to the central major histocompatibility complex (MHC) region between HLA-DR and C4. Here, the association with HLA-DR3 and other genes in the central MHC and class II region was further investigated in a group of 42 sIBM patients and in an ethnically similar control group (n = 214), using single-nucleotide polymorphisms and microsatellite screening. HLA-DR3 (marking DRB1*0301 in Caucasians) was associated with sIBM (Fisher's test). However, among HLA-DR3-positive patients and controls, carriage of HLA-DR3 without microsatellite and single-nucleotide polymorphism alleles of the 8.1AH (HLA-A1, B8, DRB3*0101, DRB1*0301, DQB1*0201) was marginally less common in patients. Patients showed no increase in carriage of the 18.2AH (HLA-A30, B18, DRB3*0202, DRB1*0301, DQB1*0201) or HLA-DR3 without the central MHC of the 8.1AH, further arguing against HLA-DRB1 as the direct cause of susceptibility. Genes between HLA-DRB1 and HOX12 require further investigation. BTL-II lies in this region and is expressed in muscle. Carriage of allele 2 (exon 6) was more common in patients. BTL-II(E6)*2 is characteristic of the 35.2AH (HLA-A3, B35, DRB1*01) in Caucasians and HLA-DR1, BTL-II(E6)*2, HOX12*2, RAGE*2 was carried by several patients. The 8.1AH and 35.2AH may confer susceptibility to sIBM independently or share a critical allele. PMID:15496200

  11. Measurements of mid-latitude E-region, sporadic-E, and TID-related drifts using HF Doppler-sorted interferometry

    Parkinson, M. L.; Dyson, P. L.

    1998-03-01

    Modern HF digital ionosondes have been used for Doppler-sorted interferometry (DSI) to automatically measure F-region plasma drifts by detecting the Doppler shift and angle-of-arrival of echoes. We report on the use of a Digisonde 256 receiving on a seven-element antenna array located at the Australian mid-latitude station Beveridge (37.5° S, 144.9° E, -48.0°CGM latitude) to extend the routine application of drift measurements to the E-region, and especially sporadic-E (Es). Obtaining good quality E-region drift measurements required many more soundings independent in the frequency and time domains than are usually made for F-region measurements. This is because the E-region isoionic surfaces were usually more horizontally stratified than those in the more disturbed F-region, and so did not return as many of the oblique echoes upon which the accuracy of the technique depends. Smoothness of the ionosphere was less of a problem when performing Es measurements because of the patchy, cloud-like property of the layers. When making F-region drift measurements the motions are usually thought of as being uniform throughout the volume of ionosphere sampled for echoes. Application of the technique to E-region measurements is interesting because of the enhanced irregular neutral winds associated with gravity waves which grow in amplitude with height. These irregular winds control the motion of the plasma via high collision frequencies, and lead to the formation of Es layers at mid-latitudes. Therefore, the possibility of sharp vertical gradients in plasma drifts must be considered when making and analysing measurements. During numerous campaigns conducted throughout 1994/95, horizontal drifts in the range of ≈ 30-250 m/s were measured for Es patches lasting up to 6 h. The drift measurements sometimes indicated the presence of wave-like motions in the ionosphere with periods in the range 5-90 min. A TID was observed to propagate towards the station from the south, and

  12. 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

  13. Comprehensive genetic and epigenetic analysis of sporadic meningioma for macro-mutations on 22q and micro-mutations within the NF2 locus

    Jarbo Caroline

    2007-01-01

    Full Text Available Abstract Background Meningiomas are the most common intracranial neoplasias, representing a clinically and histopathologically heterogeneous group of tumors. The neurofibromatosis type 2 (NF2 tumor suppressor is the only gene known to be frequently involved in early development of meningiomas. The objective of this study was to identify genetic and/or epigenetic factors contributing to the development of these tumors. A large set of sporadic meningiomas were analyzed for presence of 22q macro-mutations using array-CGH in order to identify tumors carrying gene dosage aberrations not encompassing NF2. The NF2 locus was also comprehensively studied for point mutations within coding and conserved non-coding sequences. Furthermore, CpG methylation within the NF2 promoter region was thoroughly analyzed. Results Monosomy 22 was the predominant finding, detected in 47% of meningiomas. Thirteen percent of the tumors contained interstitial/terminal deletions and gains, present singly or in combinations. We defined at least two minimal overlapping regions outside the NF2 locus that are small enough (~550 kb and ~250 kb to allow analysis of a limited number of candidate genes. Bialleinactivationo the NF2 gne was detected in 36% of meningiomas. Among the monosomy 22 cases, no additional NF2 mutations could be identified in 35% (17 out of 49 of tumors. Furthermore, the majority of tumors (9 out of 12 with interstitial/terminal deletions did not have any detectable NF2 mutations. Methylation within the NF2 promoter region was only identified at a single CpG site in one tumor sample. Conclusion We confirmed previous findings of pronounced differences in mutation frequency between different histopathological subtypes. There is a higher frequency of biallelic NF2 inactivation in fibroblastic (52% compared to meningothelial (18% tumors. The presence of macro-mutations on 22q also shows marked differences between fibroblastic (86% and meningothelial (39% subtypes

  14. 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

  15. Epidemiology of sporadic (non-epidemic) cases of Trichophyton tonsurans infection in Japan based on PCR-RFLP analysis of non-transcribed spacer region of ribosomal RNA gene.

    Mochizuki, Takashi; Kawasaki, Masako; Anzawa, Kazushi; Fujita, Jun; Ushigami, Tsuyoshi; Takeda, Kiminobu; Sano, Ayako; Takahashi, Yoko; Kamei, Katsuhiko

    2008-05-01

    A number of cases of Trichophyton tonsurans infection have been reported among sportsmen and women participating in wrestling, judo, and sumo wrestling in Japan, but there have also been sporadic reports of cases with no history of contact with these sports. A molecular method using restriction enzyme analysis of PCR-amplified fragments targeting the non-transcribed spacer region (NTS) of ribosomal RNA gene in fungal nuclei was applied to T. tonsurans strains isolated from sporadic cases in Japan. Five of 6 molecular types recorded in Japan, i.e., NTS types I, II, IV, V, and VI, and two new types, designated NTS VII and NTS VIII, were observed among 10 strains isolated from sporadic cases. The NTS IV strains, considered not to be related to the present epidemic, were found to be the most prevalent molecular type accounting for 4 of the 10 strains isolated. NTS I was the most prevalent type in the current epidemic in Japan, but it was cultured from only one patient who was later noted to be the daughter of a retired judo practitioner. Four subjects had histories of living abroad and were considered to have been infected outside Japan. The strains in these cases were NTS II, V, VI, and VII. The results of this study suggested that the NTS IV strains were originally present in Japan at a low incidence, but that there has been a recent influx of NTS I, II, V, VI, and VII from abroad, which has been accompanied by the secondary spread of strains from wrestlers and practitioners of martial arts to the general community. PMID:18503175

  16. 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 ...

  17. Mutation of PARK2 gene in sporadic early-onset Parkinson's disease and its clinical characteristics%散发性早发帕金森病PARK2基因突变及其临床特征

    陈思; 刘艺鸣; 任楠楠; 陈良; 李佳珍; 宁翔; 王京

    2012-01-01

    目的 探讨42例散发性早发性帕金森病(EOPD)PARK2基因突变情况及突变患者的临床特点.方法 采用SYBR GreenⅠ实时荧光定量以及DNA直接测序方法,对42例EOPD患者进行PARK2基因突变分析.结果 在42例EOPD患者中共发现5例PARK2基因突变,外显子杂合缺失突变、外显子纯合双重重复突变、复合杂合点突变各1例,另外2例存在相同的杂合小片段缺失突变.c.850G>C和c.968-973delGTGTCC为已经报道的突变,c.925G>T为未报道新突变.PARK2基因突变EOPD患者发病年龄比无PARK2基因突变者小.但是在统一帕金森病评定量表(UPDRS)3.0版第Ⅲ部分关期评分和Hoehr-Yahr关期评分上无差异.结论 散发性EOPDPARK2基因突变率为11.9%;点突变是散发性EOPD的主要突变类型;PARK2基因突变组和无突变组的EOPD患者在临床症状上和病情严重程度上无明显差异,但PARK2基因突变组发病年龄小,病程长,病情进展缓慢.%Objective To investigate PARK2 gene mutations in 42 patients with sporadic early-onset Parkinson's disease ( EOPD) and to explore their clinical characteristics. Methods A total of 42 sporadic EOPD patients were screened for mutations in PARK2 gene by using SYBR GreenI real-time VCR and DNA direct sequencing methods. Results 5 patients carried PARK1 gene mutations in the 42 sporadic EOPD, including 1 heterozygous deletions mutation, 1 homo-zygous duplication mutation, 1 compound heterozygous point mutation and 2 identical heterozygous small sequence deletion mutations. Two of the mutations (c. 850G > C and c. 968-973delGTGTCC) were reported previously. The c. 925G > T was a novel mutation. The patients with PARK2 mutations showed an earlier onset age than those without PARK2 mutations. But they showed no significant difference in the score of UPDRS( Unified Parkinson's Disease Rating Scale) 3.0 and Hoehr-Yahr. Conclusion The frequency of mutations in PARK! gene is 11.9% in sporadic EOPD. Point

  18. 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.

  19. 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.

  20. Clinical analysis of 1489 cases of sporadic acute hepatitis E in Beijing, China%1489例散发性戊型肝炎患者临床分析

    朱冰; 游绍莉; 刘鸿凌; 荣义辉; 李晨; 臧红; 万志红; 辛绍杰

    2015-01-01

    目的 总结分析大宗散发性急性戊型病毒性肝炎(hepatitis E)的临床特点,为散发性戊型肝炎的防治提供依据.方法 收集解放军第三○二医院2003-2012年所有急性戊型病毒性肝炎的临床资料,对患者临床分型、转归等采用SPSS 21.0统计软件进行统计分析,计量资料以均数±标准差((x)±s)表示,组间均数比较符合正态分布、方差齐性者用t检验和方差分析;不符合正态分布、方差齐性者用秩和检验.P<0.05为差异有统计学意义.结果 2003-2012年解放军第三○二医院共收治急性戊型肝炎患者1 489例,主要来自华北地区,以冬春季节多发,常见于青中年患者,占急性戊型肝炎患者总数的73.81%.急性黄疸型(总胆红素值≥17.1 μmol/L)1 376例,占92.41%,急性无黄疸型113例,占7.59%.普通型戊型肝炎患者最多,占78.64%(1 171/1 489);淤胆型戊型肝炎患者186例,占12.49%;戊型肝衰竭患者132例,占8.87%.治疗好转率在普通肝炎组、淤胆型肝炎组、肝衰竭组分别为97.78%(1 145/1 171)、97.31% (181/186)、39.39% (52/132),肝衰竭组明显比其他两组转归差(P<0.05),同时重叠感染在肝衰竭组占50.00%,与其他两组之间比较差异均有统计学意义(P<0.05).老年戊型肝炎患者(年龄≥60岁)376例(25.25%),青少年戊型肝炎(年龄<18岁)14例(0.94%).老年治愈好转率92.29%;青少年治愈好转率100.00%.结论 散发性戊型肝炎一般预后较好,但是发展为肝衰竭者预后较差,年龄大、重叠感染、肝硬化基础是病情危重的危险因素.%Objective To analyze the clinical characteristics of patients with sporadic acute hepatitis E in Beijing,China.Methods The clinical characteristics of all sporadic acute hepatitis E patients were collected in the 302th Military Hospital in Beijing of China from 2003 to 2012,and the clinical classifications and outcomes of those patients were analyzed.Results A total of 1

  1. 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.

  2. Prospective comparison of {sup 68}Ga-DOTATATE and {sup 18}F-FDOPA PET/CT in patients with various pheochromocytomas and paragangliomas with emphasis on sporadic cases

    Archier, Aurelien; Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Inserm UMR1068 Marseille Cancerology Research Center, Institut Paoli-Calmettes, Marseille (France); Varoquaux, Arthur; Beschmout, Eva [Aix-Marseille University, Department of Medical Imaging, Conception Hospital, Marseille (France); Garrigue, Philippe; Guillet, Benjamin [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, Department of Radiopharmacy, La Timone and North University Hospital, Marseille (France); Montava, Marion; Fakhry, Nicolas [Aix-Marseille University, Department of Otorhinolaryngology-Head and Neck Surgery, Conception Hospital, Marseille (France); Guerin, Carole; Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, Conception Hospital, Marseille (France); Gabriel, Sophie [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Morange, Isabelle; Castinetti, Frederic [Aix-Marseille University, Department of Endocrinology, Conception Hospital, Marseille (France); Barlier, Anne [Aix-Marseille, University, Laboratory of Biochemistry and Molecular Biology, Conception Hospital, Marseille (France); Loundou, Anderson [Aix-Marseille University, Department of Public Health, Marseille (France); Pacak, Karel [National Institutes of Health, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD (United States)

    2016-07-15

    Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress somatostatin receptors and recent studies have already shown excellent results in the localization of these tumors using {sup 68}Ga-labeled somatostatin analogs ({sup 68}Ga-DOTA-SSA), especially in patients with germline succinate dehydrogenase subunit B gene (SDHB) mutations and head and neck PGLs (HNPGLs). The value of {sup 68}Ga-DOTA-SSA has to be established in sporadic cases, including PHEOs. Thus, the aim of this study was to compare {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging in patients with various PHEOs/PGLs with a special emphasis on sporadic cases, including those located in the adrenal gland. {sup 68}Ga-DOTATATE, {sup 18}F-FDOPA PET/CT, and conventional imaging (contrast-enhanced CT and MRI with MR angiography sequences) were prospectively performed in 30 patients (8 with SDHD mutations, 1 with a MAX mutation and 21 sporadic cases) with PHEO/PGL at initial diagnosis or relapse. The patient-based sensitivities were 93 % (28/30), 97 % (29/30), and 93 % (28/30) for {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging, respectively. The lesion-based sensitivities were 93 % (43/46), 89 % (41/46), and 76 % (35/46) for {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging respectively (p = 0.042). {sup 68}Ga-DOTATATE PET/CT detected a higher number of HNPGLs (30/30) than {sup 18}F-FDOPA PET/CT (26/30; p = 0.112) and conventional imaging (24/30; p = 0.024). {sup 68}Ga-DOTATATE PET/CT missed two PHEOs of a few millimeters in size and a large recurrent PHEO. One lesion was considered false-positive on {sup 68}Ga-DOTATATE PET/CT and corresponded to a typical focal lesion of fibrous dysplasia on MRI. Among the 11 lesions missed by conventional imaging, 7 were detected by conventional imaging with knowledge of the PET results (4 HNPGLs, 2 LNs, and 1 recurrent PHEO). {sup 68}Ga-DOTATATE PET/CT is the most sensitive tool in the

  3. Polymorphisms and haplotypes of the NBS1 gene are associated with risk of sporadic breast cancer in non-Hispanic white women

    LU, JIACHUN; Wei, Qingyi; Bondy, Melissa L.; Li, Donghui; Brewster, Abenaa; Shete, Sanjay; Yu, Tse-Kuan; Sahin, Aysegul; Meric-Bernstam, Funda; Kelly K Hunt; Singletary, S Eva; Ross, Merrick I.; Wang, Li-E

    2006-01-01

    Biomarker: three Nijmegen breakage syndrome 1 (NBS1) protein haplotype-tagging polymorphisms (i.e. 924T>C, 8360G>C and 30537G>C) of Effect studied: breast cancer risk; DNA damage. Tissue/biological material/sample size: 30 ml of blood. Method of analysis: PCR-RFLP assay. Study design: case-control study. Study size: 421 cases and 423 controls Impact on outcome (including dose-response): compared with 924TT homozygotes the variant homozygote 924CC carriers had a 4.55-fold increased risk of bre...

  4. 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

  5. Identification and characterization of CDH1 germline variants in sporadic gastric cancer patients and in individuals at risk of gastric cancer.

    Marica Garziera

    Full Text Available OBJECTIVE: To screen and characterize germline variants for E-cadherin (CDH1 in non-hereditary gastric cancer (GC patients and in subjects at risk of GC. METHODS: 59 GCs, 59 first degree relatives (FDRs of GC, 20 autoimmune metaplastic atrophic gastritis (AMAGs and 52 blood donors (BDs were analyzed for CDH1 by direct sequencing, structural modelling and bioinformatics. Functional impact on splicing was assessed for intronic mutations. E-cadherin/β-catenin immunohistochemical staining and E-cadherin mRNA quantification using RT-PCR were performed. RESULTS: In GCs, 4 missense variants (p.G274S; p.A298T; p.T470I; p.A592T, 1 mutation in the 5'UTR (-71C>G and 1 mutation in the intronic IVS12 (c.1937-13T>C region were found. First pathogenic effect of p.A298T mutation was predicted by protein 3D modelling. The novel p.G274S mutation showed a no clear functional significance. Moreover, first, intronic IVS12 (c.1937-13T>C mutation was demonstrated to lead to an aberrant CDH1 transcript with exon 11 deletion. This mutation was found in 2 GCs and in 1 BD. In FDRs, we identified 4 variants: the polymorphic (p.A592T and 3 mutations in untranslated regions with unidentified functional role except for the 5'UTR (-54G>C that had been found to decrease CDH1 transcription. In AMAGs, we detected 2 alterations: 1 missense (p.A592T and 1 novel variant (IVS1 (c.48+7C>T without effect on CDH1 splicing. Several silent and polymorphic substitutions were found in all the groups studied. CONCLUSIONS: Overall our study improves upon the current characterization of CDH1 mutations and their functional role in GC and in individuals at risk of GC. Mutations found in untranslated regions and data on splicing effects deserve a particular attention like associated with a reduced E-cadherin amount. The utility of CDH1 screening, in addition to the identification of other risk factors, could be useful for the early detection of GC in subjects at risk (i.e. FDRs and AMAGs, and

  6. Detection of CD4+/CD8+T Lymphocyte Ratio and CD4+CD25+ Treg in Peripheral Blood of Patients with Sporadic Vitiligo%散发型白癜风患者外周血CD4+/CD8+T细胞比值及CD4+CD25+T细胞的检测

    叶蓉; 马刚; 胡小平; 彭曦

    2012-01-01

    目的 检测散发型白癜风患者外周血CD4+/CD8+T细胞比值及CD4+CD25+调节性T细胞水平,探讨其与散发型白癜风发病的关系.方法 散发型白癜风患者29例,男13例,女16例.通过流式细胞仪对散发型白癜风患者外周血CD4+/CD8+T细胞比值及CD4+CD25+调节性T细胞水平进行检测,并与20例健康人相比较.结果 与健康对照组相比,散发型白癜风患者外周血中CD4+/CD8+T细胞比值的差异无统计学意义(P>0.05),而CD4+CD25+调节性T细胞水平明显减少,差异有统计学意义(P<0.05),但在不同病程的患者中CD4+CD25+调节性T细胞数量的差异无统计学意义(P>0.05).结论 散发型白癜风患者外周血中存在CD4+CD25+调节性T细胞水平下降,可能与散发型白癜风的发生发展有一定关系.%Objective To detect the CD4+/CD8+ T lymphocyte ratio and the CD4+CD25+ Treg level in peripheral blood of patients with sporadic vitiligo, and to investigate its role in the pathogenesis of sporadic vitiligo. Methods Peripheral blood samples were taken from 29 outpatients with sporadic vitiligo, including 13 males and 16 females. The CD4+/CD8+ T lymphocyte ratio and the CD4+CD25+ Treg level was detected in peripheral blood of patients with sporadic vitiligo by flow cytometry, as well as controlled samples from 20 healthy human. Results There was no difference on the ratio of CD4+/CD8+ T lymphocyte between the patients with sporadic vitiligo and healthy people (P>0.05). Compared to the controlled group, the proportion of CD4+CD25+ Treg was significantly lower in sporadic vitiligo patients(P0.05). Conclusion The level of CD4+CD25+ Treg is lower in peripheral blood of sporadic vitiligo patients, which might play a role in the pathogenesis and development of sporadic vitiligo.

  7. Structured exploratory data analysis (SEDA) for determining mode of inheritance of quantitative traits. I. Simulation studies on the effect of background distributions.

    Karlin, S; Williams, P T; Carmelli, D

    1981-03-01

    We examine through simulations the effectiveness of a new methodology to help distinguish among monogenic, multifactorial, and sporadic trait transmission from parents to offspring in nuclear family data sets. The major gene index (MGI), which compares the deviation of the offspring from the midparental value with a function of the individual deviations between parents and offspring, aids in the discrimination of multifactorial from sporadic and monogenic models. In contrast with other methodologies, the ability of the MGI to separate multifactorial, monogenic, and sporadic models improves with increased skewness in the trait distribution. The midparental correlation coefficient serves as a further guide for indicating mode of inheritance. A new class of techniques, the offspring between parents function (OBP), is introduced that provides a more sensitive tool to help in assessing mode of transmission through the analysis of the level, shape, and undulation characteristics of the curves. Four data examples are used to illustrate the methodology: erythrocyte catechol-O-methyltransferase (COMT) activity, height, weight, and triglyceride measurements. Height appears largely multifactorial, and weight appears to be mostly sporadic, while COMT and triglyceride measurements suggest the presence of some major gene influences. PMID:7211841

  8. Food- and water-borne disease: using case control studies to estimate the force of infection that accounts for primary, sporadic cases.

    Smith, G

    2013-06-01

    Disease models which take explicit account of heterogeneities in the risk of infection offer significant advantages over models in which the risk of infection is assumed to be uniform across all hosts. However, estimating the incidence rate (force of infection) in the different at-risk (exposure) groups is no easy matter. Classically, epidemiologists differentiate groups of hosts with different infection-risks according to their exposure to putative explanatory risk factors. The importance of these risk factors is assessed by case-control studies, in which the measure of effect (the difference in disease occurrence between one population and another) is the odds ratio. This paper describes for the first time how - and under what circumstances - the incidence in these different exposure groups can be estimated from odds ratios derived from case control studies in which controls have been selected by density sampling. This new estimation technique can be applied to any transmission modality but is especially useful in the case of models of food- and water-borne disease for which the case control literature represents a vast and, as yet, untapped resource. The paper finishes with a worked example using one of the most common of all food- and water-borne pathogens, Toxoplasma gondii. PMID:23746800

  9. Effects of the Leadership Style on the Employees’ Job Satisfaction and Organizational Commitment from the Hotel Industry

    ANDREIA ISPAS; CARMEN BABAITA

    2013-01-01

    The study of leadership in the context of the hotel industry and hospitality industry in Romania was characterized by sporadic attempts to identify the optimal and effective leadership style and also the most desired by the employees. Few researches were focused on identifying the positive or negative effects of the leadership style on the level of job satisfaction and organizational commitment of the employees. According with this lack of empirical research, the first objective of this paper...

  10. THE EFFECTS OF LEADERSHIP STYLE ON THE EMPLOYEES’ JOB SATISFACTION AND ORGANIZATIONAL COMMITMENT FROM THE HOTEL INDUSTRY

    ANDREIA ISPAS; CARMEN BÃBÃI?Ã

    2012-01-01

    The study of leadership in the context of the hotel industry and hospitality industry in Romania was characterized by sporadic attempts to identify the optimal and effective leadership style and also the most desired by the employees. Few researches were focused on identifying the positive or negative effects of the leadership style on the level of job satisfaction and organizational commitment of the employees. According with this lack of empirical research, the first objective of this paper...

  11. Interactive effect of water stress and nitrogen on plant height and root length of wheat (Triticum aestivum L.)

    Abdul Ghani; Abid Nisar Ahmad; Anwar-ul-Hassan; Iqbal, M.; Yasin, G.; Naeem Iqbal

    2000-01-01

    Interactive effect of water stress and nitrogen on plant height and root length of wheat varieties inqulab-91 and Parwaz-94 were investigated. Urea as nitrogen fertilizer was applied before imposition of water stress in plots and water stress was imposed 25, 35 and 45 days after germination. The data reveal that sporadic stress and urea fertilizer have highly significant response. The effects of water stress were mostly reduced to greater extent at high nitrogen level (98 gm / plot) Nitrogen ...

  12. Novel graphene papers with sporadic alkyl brushes on the basal plane as a high-capacity flexible anode for lithium ion batteries

    Graphene paper that exhibits an excellent stabilized capacity, as high as 1300 mAh g−1 at a current rate of 60 mA g−1, as a lithium ion battery anode is fabricated and evaluated. The few-layer graphene used to make the graphene paper is prepared via the thermal reduction of graphite oxide. The graphene is then modified by a novel method utilizing inherent defects, namely epoxy groups, on the graphene as active sites for a reaction with methanol, 1-butanol, 1-hexanol, and 1-octanol. The density values and X-ray diffraction patterns obtained for the graphene paper demonstrate that the alkyl brushes on the graphene sheets expand the d-spacing and hinder close restacking of the sheets, thereby inducing the formation of extra cavities within the paper. This loose packing due to the alkyl brushes increases sensitively as the alkyl chain length of the alcohol becomes longer. The lithium ion insertion capacity of a graphene paper electrode at the first cycle also increases with the alkyl chain length. However, fading of the capacity at early charge/discharge cycles is accelerated by the modification process because of electrolyte penetration into the gallery and the acceleration of protective solid electrolyte interface film formation due to looser packing. The paper composed of graphene modified with 1-butanol rather than shorter or longer alcohols exhibits the best reversible storage capacity, more than two-fold higher when compared to that of pristine graphene paper, due to a compromise between two conflicting effects on the reversible storage capacity by long alkyl brushes. The tensile properties and electrical conductivity of the graphene papers are also examined

  13. Familial prostate cancer has a more aggressive course than sporadic prostate cancer after treatment for localized disease, mainly due to a higher rate of distant metastases

    Purpose: We had already established that familial prostate cancer, defined as prostate cancer diagnosed in a father or brother, was an independent predictor of biochemical failure after treatment for localized disease. Our aim was to determine whether differences in outcome could be observed with respect to clinical failures (either local or distant) between the two forms of prostate cancer. Methods: Of the 1685 consecutive cases with localized prostate carcinoma treated between 1986 and 1996, patients with the following were excluded from the present study: no pretreatment Prostatic Specific Antigen (iPSA) level (n=54), no biopsy Gleason score (bGS) (n=25), adjuvant or neoadjuvant treatment (n=234), no available follow-up PSA level (n=30). We also excluded 617 patients who did not have a minimum of 3 years potential follow-up. The analysis was performed on 725 cases. Radiotherapy (RT) was the primary treatment in 330 patients and radical prostatectomy (RP) in 395 patients. Five percent had clinical stage T3 disease (n=37). Positive family history was defined as the presence of prostate cancer in a first degree relative (father or brother). The outcomes of interest were biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), local relapse-free survival (locRFS), distant relapse-free survival (dRFS). We used proportional hazards to analyze the effect of family history and other potential confounding variables (i.e. age, race, treatment modality, stage, biopsy GS, and iPSA levels) on treatment outcome. We included pathologic findings (extracapsular extension, seminal vesicle involvement, surgical margin involvement, and lymph node metastases) in a separate analysis for RP patients. Results: The median follow-up was 45 months. Eight percent of all cases (n=57) had a positive family history. The 5-year bRFS rates for patients with negative and positive family history were 54% and 38%, respectively (p<0.001). The 5-year cRFS rates for patients

  14. 散发性视网膜色素变性视紫红质基因突变筛查%Screening for mutation in rhodopsin gene among Chinese sporadic retinitis pigmentosa

    管涛; 麻张伟; 丁世萍

    2008-01-01

    目的 研究中国人散发性视网膜色素变性(sporadic retinitis pigmentosa,SRP)患者视紫红质(rhodopsin,RHO)基因突变频率及特征,揭示其在SRP发病机制中的潜在作用.方法 运用聚合酶链反应-单链构象多态性(polymerase chain reaction-single-strand conformation polymorphism,PCR-SSCP)结合DNA测序技术,对80例SRP患者和80例健康对照者进行RHO基因5个外显子的突变筛查.结果 SRP患者RHO基因5个外显子PCR扩增产物经SSCP分析后,发现其电泳带型与对照组一致,均包括2条单链带和1条双链带,且电泳迁移率相同,即在患者和对照组中均未检测到RHO基因突变.结论 中国人SRP患者RHO基因外显子的突变率较低;PCR-SSCP分子遗传学方法快速、简单、灵敏,适用于大批量RP患者的基因变异筛查.(中国眼耳鼻喉科杂志,2008,8:351-353)

  15. True hermaphroditism in a 46, XY individual, caused by a postzygotic somatic point mutation in the male gonadal sex-determining locus (SRY): Molecular genetics and histological findings in a sporadic case

    Braun, A.; Kammerer, S.; Cleve, H.; Loehrs, U.; Schwarz, H.P.; Kuhnle, U. (Univ. of Munich (Germany))

    1993-03-01

    Recently, the gene for the determination of maleness has been identified in the sex-determining region on the short arm of the Y chromosome (SRY) between the Y-chromosomal pseudoautosomal boundary (PABY) and the ZFY gene locus. Experiments with transgenic mice confirmed that SRY is a part of the testis-determining factor (TDF). The authors describe a sporadic case of a patient with intersexual genitalia and the histological finding of ovotestes in the gonad, which resembles the mixed type of gonadal tissue without primordial follicle structures. The karyotype of the patient was 46,XY. By PCR amplification, they tested for the presence of SRY by using DNA obtained from histological gonadal slices. The SRY products of both DNA preparations were further analyzed by direct sequencing. All three parts of the sex-determining region of the Y chromosome could be amplified from leukocytic DNA. The patient's and the father's SRY sequences were identical with the published sequence. In the SRY PCR product of gonadal DNA, the wild-type and two point mutations were present in the patient's sequence, simulating a heterozygous state of a Y-chromosomal gene: one of the mutations was silent, while the other encoded for a nonconservative amino acid substitution from leucine to histidine. Subcloning procedures showed that the two point mutations always occurred together. The origin of the patient's intersexuality is a postzygotic mutation of the SRY occurring in part of the gonadal tissue. This event caused the loss of the testis-determining function in affected cells. 37 refs., 6 figs.

  16. 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

    2012-10-01

    Full Text Available 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 by genotyping 13 nuclear short tandem repeat loci (namely, D2S123, TPOX, D3S1358, D3S1611, FGA, D7S820, TH01, D13S317, D13S790, D16S539, D17S796, intron 12 BRCA1 and intron 1 TP53 that were amplified with the fluorescent AmpFlSTR Identifiler Genotyping system (Applied Biosystems, USA and by silver nitrate staining following 6% denaturing polyacrylamide gel electrophoresis. Somatic mtDNA mutations in the D-loop site were assessed with direct sequencing of the hypervariable HVI and HVII mitochondrial regions. RESULTS: Half of the cancer tissues presented some nuclear instability. Interestingly, the D13S790 locus was the most frequently affected (36%, while the D2S123 locus presented no alterations. Forty-two percent of the cases showed somatic mitochondrial mutations, the majority at region 303-315 poly-C. We identified associations between Elston grade III, instabilities at 13q31 region (p = 0.0264 and mtDNA mutations (p = 0.0041. Furthermore, instabilities at 13q31 region were also associated with TP53 mutations in the invasive ductal carcinoma cases (p= 0.0207. CONCLUSION: Instabilities at 13q31 region and the presence of somatic mtDNA mutations in a D-loop site correlated with tumor aggressiveness.

  17. Ezrin expression and its translocation in human primary sporadic colorectal carcinoma and prognostic significance%Ezrin在散发性结直肠癌中的表达及意义

    Ge Yan; Xiaoyan Zhou; Xiuying Xiao; Hongfen Lu; Xiang Du

    2007-01-01

    Objective:The membrane-linking protein Ezrin is highly expressed in several types of human cancers.The correlations between its immunoreactivtv and histopathological data as well as patient outcome have previously been shown.However,the role played by Ezrin in the carcinogenesis,progression and metastasis of primary sporadic colorectal carcinoma (SCRC)is still under investigation.This study assessed Ezrin protein expression in a series of clinical specimens.Methods:lmmunohistochemical analysis was used to characterize paRerns of Ezrin expression in 132 cases of SCRC.including 74 metastatic cases and 58 non-metastatic cases and 43 adjacent normal colorectal mucosa.Results:(1)The expression rate of Ezrinin SCRC(79.5%)was significantly higher than in adjacent normal colorectal mucosa (11.6%)(P<0.001):(2)The total expression rate of Ezrin was 86.5%and 70.7%in metastatic group and non-metastatic group.respectively(P=0.026);the membrane expression rate of Ezrin was 31.1%and 6.9%in the two groups,respectively(P<0.01):(3)Therewas no relationship between the expression of Ezrin with age,gender,tumor size,location,degree of differentiation and invasive depth;(4)In the cases with followed-up data.univariate analysis demonstrated that Ezrin expression and its membrane translocation was correlated with worse patient's disease-free survival(DFS)(Puni<0.05).Conclusion:Ezrin was expressed in lhe majority of SCRC and associated with adverse prognostic factors.The increase expression and the switch of Ezrin localization from the cytoplasm to the membrane were closely correlated with metastasis in SCRC.It might be served as an important parameter for determining tumor biological behavior.

  18. Autosomal dominant transmission of a Goldenhar-like syndrome: Description of a family and report of a sporadic case with a de novo 4p16;8q24.11 translocation

    Graganm H.N. Jr.; Hixon, H.; Bacino, C.A. [Univ. of Iowa, Iowa City, IA (United States)] [and others

    1994-09-01

    We report vertical transmission of a Goldenhar-like syndrome, including a father and 5 offspring, with male-to-male transmission and variable features that include hearing loss, ear anomalies (microtia, ear tags/pits), branchial cysts, ocular/periocular dermoids, micrognathia and seizures. We also report an individual with an apparently balanced de novo reciprocal translocation with breakpoints at 4p16 and 8q24.11. This individual has unilateral microtia, an epibulbar dermoid cyst, facial asymmetry with a small chin, and seizures. In addition to these features resembling those seen in the family above, she has multiple exostoses, supraventricular tachycardia, hypoglycemia and mild developmental delays. Based on the overlap in physical findings between this family and the individual with the de novo reciprocal translocation, linkage studies on the family were intiated. Preliminary results exclude linkage to HOX 7 at 4p16.1 but not to 8q. The brancho-oto-renal syndrome has previously been localized to 8q11-8q13, but linkage to this region appears unlikely. Although most cases of Goldenhar syndrome appear to be sporadic, there are a few reports of autosomal dominant inheritance (MIM No. 164210). One such family showed vertical transmission of dermoids, ear anomalies, hearing loss, micrognathia and vertebral anomalies, but no branchial cysts. Another family showed sensorineural deafness, preauricular pits, and branchial fistulae, and other families reveal ear anomalies, branchial fistulas, and hearing loss. These latter families appear to lack ocular/periocular dermoids, and appear to be affected by a different disorder (MIM No. 125100). Further clinical delineation of such families, combined with genetic linkage analysis, should help to sort out this heterogeneity.

  19. 散发性皮肤非结核分枝杆菌感染37例回顾研究%Sporadic cutaneous infections due to nontuberculous mycobacteria: a retrospective study of 37 cases

    金江; 贾军; 丁晓岚; 陈雪; 孙青苗; 徐健楠; 薛晨红; 杜娟; 蔡林

    2015-01-01

    Objective:To study the clinical and pathological characteristics of sporadic cutaneous in-fections due to nontuberculous mycobacteria ( NTM) , and investigate the diagnostic criteria and therapeu-tic principal. Methods:Totally 37 cases of sporadic cutaneous infections due to NTM were confirmed in the Department of Dermatology, Peking University People's Hospital from January 2000 to March 2014. The microbiologic and clinical data were reviewed, and their skin biopsy specimens were reassessed. Re-sults:Of all the 37 patients, 30 cases were Mycobacterium marinum infection, 6 were Mycobacterium ab-scessus infection, and one was Mycobacterium chelonea and Mycobacterium fortuitum infection. Identifica-tion of mycobacterial species by analysis of hsp65 gene in tissue DNA was more sensitive than traditional bacterial culture. The most common risk factors were traumatic injuries ( 21 of 37 ) and aquarium or fish-related job (21 of 37). One case of Mycobacterium abscessus infection occurred after autologous fat filling. Nodule and plaque were most common lesions in Mycobacterium marinum infection. Twenty-four of the 30 cases of Mycobacterium marinum infection presented with multiple lesions or sporotrichoid spread lesions. Ulceration, papules, abscess, and purulent discharge were observed in cases of Mycobac-terium abscessus infection. Infective granuloma was most common histopathological appearance. For the treatment of Mycobacterium marinum infection, rifampin, ethambutol, and clarithromycin were commonly used (combination of two antibiotics, or three antibiotics), with the cure rate 90. 00%. Four of the six Mycobacterium abscessus infections cases were cured, and one patient died. Conclusion:The most com-mon species of sporadic cutaneous infections due to NTM is Mycobacterium marinum. Traumatic injuries, aquarium or fish-related job, and cosmetic surgeries are common risk factors. Mycobacterium marinum in-fection often presents with nodules, plaques, and sometimes

  20. Deregulated genes in sporadic vestibular schwannomas

    Cayé-Thomasen, Per; Helweg-Larsen, Rehannah Holga Andrea; Stangerup, Sven-Eric;

    2010-01-01

    In search of genes associated with vestibular schwannoma tumorigenesis, this study examines the gene expression in human vestibular nerve versus vestibular schwannoma tissue samples using microarray technology.......In search of genes associated with vestibular schwannoma tumorigenesis, this study examines the gene expression in human vestibular nerve versus vestibular schwannoma tissue samples using microarray technology....