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1

Neuroprotective effect of cyclooxygenase inhibitors in ICV-STZ induced sporadic Alzheimer's disease in rats.  

Science.gov (United States)

Sporadic Alzheimer's disease is an age-related neurological and psychiatric disorder characterized by impaired energy metabolism. Oxidative stress and neuroinflammation have been implicated in pathophysiology of sporadic type of dementia. The central streptozotocin administration induces behavioral and biochemical alterations resembling those in sporadic type of Alzheimer's patients. The present study was designed to investigate the effects of chronic pretreatment with cyclooxygenase-1 or cyclooxygenase-2 or cyclooxygenase-3 selective inhibitors on cognitive dysfunction and oxidative stress markers in intracerebroventricular streptozotocin-treated rats. Chronic treatment with valeryl salicylate (5 and 10 mg/kg, i.p.) and etoricoxib (5 and 10 mg/kg, i.p.) on a daily basis for a period of 21 days, beginning 1 h prior to first intracerebroventricular streptozotocin injection, significantly improved streptozotocin-induced cognitive impairment. However, phenacetin (20 and 40 mg/kg, i.p.) failed to restore the cognitive performances of streptozotocin-treated rats. Besides, improving cognitive dysfunction, chronic administration of highly selective cyclooxygenase-1 and/or cyclooxygenase-2 inhibitors (valeryl salicylate and etoricoxib, respectively), but not cyclooxygenase-3 inhibitor (phenacetin), significantly reduced elevated malondialdehyde, nitrite levels, and restored reduced glutathione and superoxide dismutase levels. Furthermore, cyclooxygenase-1 and/or cyclooxygenase-2 inhibitors significantly increased the survival of pyramidal neurons. In summary, we demonstrate for the first time that both cyclooxygenase-1 and cyclooxygenase-2 isoforms, but not cyclooxygenase-3, are involved in the progression of neuronal damage in intracerebroventricular streptozotocin-treated rats. PMID:21701788

Dhull, Dinesh Kumar; Jindal, Ankur; Dhull, Rakesh K; Aggarwal, Saurabh; Bhateja, Deepak; Padi, Satyanarayana S V

2011-06-24

2

Neuroprotective effect of cyclooxygenase inhibitors in ICV-STZ induced sporadic Alzheimer's disease in rats.  

UK PubMed Central (United Kingdom)

Sporadic Alzheimer's disease is an age-related neurological and psychiatric disorder characterized by impaired energy metabolism. Oxidative stress and neuroinflammation have been implicated in pathophysiology of sporadic type of dementia. The central streptozotocin administration induces behavioral and biochemical alterations resembling those in sporadic type of Alzheimer's patients. The present study was designed to investigate the effects of chronic pretreatment with cyclooxygenase-1 or cyclooxygenase-2 or cyclooxygenase-3 selective inhibitors on cognitive dysfunction and oxidative stress markers in intracerebroventricular streptozotocin-treated rats. Chronic treatment with valeryl salicylate (5 and 10 mg/kg, i.p.) and etoricoxib (5 and 10 mg/kg, i.p.) on a daily basis for a period of 21 days, beginning 1 h prior to first intracerebroventricular streptozotocin injection, significantly improved streptozotocin-induced cognitive impairment. However, phenacetin (20 and 40 mg/kg, i.p.) failed to restore the cognitive performances of streptozotocin-treated rats. Besides, improving cognitive dysfunction, chronic administration of highly selective cyclooxygenase-1 and/or cyclooxygenase-2 inhibitors (valeryl salicylate and etoricoxib, respectively), but not cyclooxygenase-3 inhibitor (phenacetin), significantly reduced elevated malondialdehyde, nitrite levels, and restored reduced glutathione and superoxide dismutase levels. Furthermore, cyclooxygenase-1 and/or cyclooxygenase-2 inhibitors significantly increased the survival of pyramidal neurons. In summary, we demonstrate for the first time that both cyclooxygenase-1 and cyclooxygenase-2 isoforms, but not cyclooxygenase-3, are involved in the progression of neuronal damage in intracerebroventricular streptozotocin-treated rats.

Dhull DK; Jindal A; Dhull RK; Aggarwal S; Bhateja D; Padi SS

2012-01-01

3

The Earth rotation and revolution effect on the daily and annual variation of sporadic meteor echo  

Science.gov (United States)

The Earth rotation and revolution will affect the daily and annual variation of sporadic meteor echo. We try to investigate such effect using Ham-band Radio Observation (HRO). Our system is constructed with paired two-element loop antennas (F/B ratio is 10 dB) at Nagano, Japan using the beacon signals at 53.750 MHz, 50W from Sabae, Fukui, Japan. The direction of one of this paired antenna was West toward Sagae and the other was East, so that this system could be roughly detected the direction of the reflected radio echoes. Using this system, (1) The total echo rose from midnight with the peak coming at about 6:00 and decreasing to the noon. This is well known daily variation due to the Earth rotation. (2) The peak echoes time by Eastward antenna and by Westward antennas was different; Westward was at 3:00 and Eastward was at 10:00. This daily variation is interpreted as the effect of the Earth rotation and revolution and the specular reflection property of forward meteor scattering observation.

Ohnishi, Kouji; Hattori, Shinobu; Nishimura, Osamu; Ishikawa, Toshiyuki; Aoki, Yoshie; Iijima, Yukiko; Kobayashi, Aya; Maegawa, Kimio; Abe, Shinsuke

2001-11-01

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Solar eclipse effects of 22 July 2009 on Sporadic-E  

Directory of Open Access Journals (Sweden)

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

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

2010-01-01

5

Solar eclipse effects of 22 July 2009 on Sporadic-E  

Science.gov (United States)

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

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

2010-02-01

6

The effect of sporadic solar radio emission on kinetic Alfven waves  

Science.gov (United States)

The influence of sporadic solar radio emission on the dispersion properties of kinetic Alfven waves is studied. It is shown that the electromagnetic wave changes the electron distribution function and leads to an electron drift of the related ions. If the amplitude of the electromagnetic waves is sufficiently high, the kinetic Alfven wave instability occurs. It is found that the power of the sporadic radio emission during type I and II solar radio bursts is sufficient to generate the kinetic Alfven wave excitation. It is concluded that Landau damping of the kinetic Alfven waves causes the heating of the coronal plasma.

Iukhimuk, A. K.; Kuts, S. V.

1990-04-01

7

Therapeutic effect of organoselenium dietary supplementation in a sporadic dementia of Alzheimer's type model in rats.  

UK PubMed Central (United Kingdom)

It is known that selenium (Se) might play different roles in the progression of Alzheimer's disease (AD), but there is a lack of evidence that proves whether supplementation with Se is beneficial or not for the treatment of AD. Thus, the aim of the current study was to investigate the therapeutic effect of p,p'-methoxyl-diphenyl diselenide [(MeOPhSe)(2)], an organoselenium compound, against streptozotocin (STZ)-induced sporadic dementia of Alzheimer's type (SDAT) in rats. Male Wistar rats received STZ twice daily (1.0 mg/8 ?l; 4 ?l/ventricle) for 21 days. After 21 days of STZ injection, regular-diet-fed rats were supplemented with 10 ppm of (MeOPhSe)(2) during 30 days. At the end of this period, the rats were challenged in the Morris water maze and step-down passive avoidance tasks. The activity of acetylcholinesterase (AChE), deficit in cerebral energy metabolism (measurement of adenosine 5-triphosphate and adenosine 5-diphosphate levels), and oxidative and nitrosative stress were determined in the cortex and hippocampus of rats. The results demonstrated that (MeOPhSe)(2) dietary supplementation reverted STZ-induced memory impairment of rats in both cognitive tasks. The findings also indicated that (MeOPhSe)(2) dietary supplementation reverted oxidative stress in the STZ group (decreased reactive species and tyrosine nitration levels and enhanced nonprotein thiol levels). Moreover, (MeOPhSe)(2) dietary supplementation normalized AChE activity, which was enhanced by STZ injection, but did not revert the deficit in cerebral energy metabolism caused by STZ. The results of the present study indicated the therapeutic effect of the (MeOPhSe)(2)-supplemented diet in a rat model of SDAT.

Pinton S; Brüning CA; Sartori Oliveira CE; Prigol M; Nogueira CW

2013-01-01

8

Therapeutic effect of organoselenium dietary supplementation in a sporadic dementia of Alzheimer's type model in rats.  

Science.gov (United States)

It is known that selenium (Se) might play different roles in the progression of Alzheimer's disease (AD), but there is a lack of evidence that proves whether supplementation with Se is beneficial or not for the treatment of AD. Thus, the aim of the current study was to investigate the therapeutic effect of p,p'-methoxyl-diphenyl diselenide [(MeOPhSe)(2)], an organoselenium compound, against streptozotocin (STZ)-induced sporadic dementia of Alzheimer's type (SDAT) in rats. Male Wistar rats received STZ twice daily (1.0 mg/8 ?l; 4 ?l/ventricle) for 21 days. After 21 days of STZ injection, regular-diet-fed rats were supplemented with 10 ppm of (MeOPhSe)(2) during 30 days. At the end of this period, the rats were challenged in the Morris water maze and step-down passive avoidance tasks. The activity of acetylcholinesterase (AChE), deficit in cerebral energy metabolism (measurement of adenosine 5-triphosphate and adenosine 5-diphosphate levels), and oxidative and nitrosative stress were determined in the cortex and hippocampus of rats. The results demonstrated that (MeOPhSe)(2) dietary supplementation reverted STZ-induced memory impairment of rats in both cognitive tasks. The findings also indicated that (MeOPhSe)(2) dietary supplementation reverted oxidative stress in the STZ group (decreased reactive species and tyrosine nitration levels and enhanced nonprotein thiol levels). Moreover, (MeOPhSe)(2) dietary supplementation normalized AChE activity, which was enhanced by STZ injection, but did not revert the deficit in cerebral energy metabolism caused by STZ. The results of the present study indicated the therapeutic effect of the (MeOPhSe)(2)-supplemented diet in a rat model of SDAT. PMID:22959057

Pinton, Simone; Brüning, César A; Sartori Oliveira, Carla E; Prigol, Marina; Nogueira, Cristina Wayne

2012-09-05

9

Effects of different doses of fish oil on rectal cell proliferation in patients with sporadic colonic adenomas.  

UK PubMed Central (United Kingdom)

BACKGROUND/AIMS: Fish oil supplementation can reduce cytokinetic anomalies in the flat rectal mucosa of patients with sporadic colorectal adenoma. This study attempted to identify an optimum dose for fish oil supplementation and evaluate the persistence of its effects during long-term administration. METHODS: In a double-blind study, 60 patients with sporadic adenomas received 2.5, 5.1, or 7.7 g of fish oil per day or placebo for 30 days. [3H]thymidine autoradiographic labeling indices were calculated in flat rectal mucosal biopsy specimens collected before and after supplementation. In a subsequent study, 15 patients with polyps received 2.5 g of fish oil per day. Proliferative parameters, mucosal fatty acids, and mucosal and plasma alpha-tocopherol levels were evaluated before, during, and after 6 months of supplementation. RESULTS: Mean proliferative indices and mucosal arachidonic acid levels decreased significantly (and to similar degrees) in all treated groups, whereas mucosal eicosapentaenoic and docosahexaenoic acid levels increased. Significantly reduced proliferation was observed only in patients with abnormal baseline patterns. These effects persisted during long-term, low-dose treatment. A transient reduction in mucosal (but not plasma) alpha-tocopherol levels was observed after 1 month of treatment. Side effects were insignificant. CONCLUSIONS: Low-dose fish oil supplementation has short-term and long-term normalizing effects on the abnormal rectal proliferation patterns associated with increased colon cancer risk.

Anti M; Armelao F; Marra G; Percesepe A; Bartoli GM; Palozza P; Parrella P; Canetta C; Gentiloni N; De Vitis I

1994-12-01

10

Introduction to Sporadic Groups  

Directory of Open Access Journals (Sweden)

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

Luis J. Boya

2011-01-01

11

Evaporation of high speed sporadic meteors  

Directory of Open Access Journals (Sweden)

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.

E. Murad; C. Roth

2004-01-01

12

Sporadic inclusion body myositis: an unsolved mystery  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Sporadic inclusion body myositis (sIBM) is considered to be the most common acquired muscle disease associated with aging. It is a disabling disorder still without effective treatment. sIBM causes weakness and atrophy of the distal and proximal muscles. Involvement of quadriceps and deep finger flex...

Machado, P; Miller, A; Holton, J; Hanna, M

13

Neuroprotector effect of p,p'-methoxyl-diphenyl diselenide in a model of sporadic dementia of Alzheimer's type in mice: contribution of antioxidant mechanism.  

UK PubMed Central (United Kingdom)

The present study investigated whether the antioxidant activity of p,p'-methoxyl-diphenyl diselenide [(MeOPhSe)(2)] is involved in its protective effect against cognitive impairment induced by streptozotocin (STZ) in a model of sporadic dementia of Alzheimer's type (SDAT). Swiss mice were treated with STZ or vehicle [2?µl of 2·5?mg?ml(-1) solution; intracerebroventricularly (i.c.v.)] twice, 48?h apart. (MeOPhSe)(2) (25?mg?kg(-1)) or vehicle was orally administered 30?min prior to each STZ treatment. Neuroprotector effect of (MeOPhSe)(2) on the behavioral performance of mice on spatial recognition memory consolidation was investigated in the Y-maze test. After that, mouse brains were removed for measuring antioxidant parameters. (MeOPhSe)(2) protected against the impairment in learning and memory caused by i.c.v. administration of STZ in mice. (MeOPhSe)(2) protected against the increase in reactive species and the reduction of glutathione levels, as well as, the increase in superoxide dismutase and glutathione S-transferase activities caused by STZ in whole brain. These results suggest that antioxidant property is involved, at least in part, in the neuroprotective effect of (MeOPhSe)(2) on SDAT induced by STZ in mice.

Pinton S; da Rocha JT; Gai BM; Prigol M; da Rosa LV; Nogueira CW

2011-04-01

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Neuroprotector effect of p,p'-methoxyl-diphenyl diselenide in a model of sporadic dementia of Alzheimer's type in mice: contribution of antioxidant mechanism.  

Science.gov (United States)

The present study investigated whether the antioxidant activity of p,p'-methoxyl-diphenyl diselenide [(MeOPhSe)(2)] is involved in its protective effect against cognitive impairment induced by streptozotocin (STZ) in a model of sporadic dementia of Alzheimer's type (SDAT). Swiss mice were treated with STZ or vehicle [2?µl of 2·5?mg?ml(-1) solution; intracerebroventricularly (i.c.v.)] twice, 48?h apart. (MeOPhSe)(2) (25?mg?kg(-1)) or vehicle was orally administered 30?min prior to each STZ treatment. Neuroprotector effect of (MeOPhSe)(2) on the behavioral performance of mice on spatial recognition memory consolidation was investigated in the Y-maze test. After that, mouse brains were removed for measuring antioxidant parameters. (MeOPhSe)(2) protected against the impairment in learning and memory caused by i.c.v. administration of STZ in mice. (MeOPhSe)(2) protected against the increase in reactive species and the reduction of glutathione levels, as well as, the increase in superoxide dismutase and glutathione S-transferase activities caused by STZ in whole brain. These results suggest that antioxidant property is involved, at least in part, in the neuroprotective effect of (MeOPhSe)(2) on SDAT induced by STZ in mice. PMID:21465495

Pinton, Simone; da Rocha, Juliana Trevisan; Gai, Bibiana Mozzaquatro; Prigol, Marina; da Rosa, Luiz Vinícius; Nogueira, Cristina Wayne

2011-02-24

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Effect of xixin decoction on O-linked N-acetylglucosamine glycosylation of tau proteins in rat brain with sporadic Alzheimer disease.  

UK PubMed Central (United Kingdom)

OBJECTIVE: To study the effects of Xixin decoction (XXD) on O-linked N-acetylglucosamine (O-GlcNAc) glycosylation of tau proteins in rat brain with sporadic Alzheimer disease (SAD), and discuss its possible mechanism on prevention and treatment of SAD. METHODS: The rat model of SAD was established by intracerebroventricular injection of streptozotocin. The specific pathogen free male Sprague-Dawley rats were randomly divided into sham-operation group (S), model group (M), donepezil group (D), XXD at a low dose group (XL), XXD at a medium dose group (XM) and XXD at a high dose group (XH). After treatment and praxiology test, immunohistochemistry and western blotting were used to detect O-GlcNAc glycosylation level of tau proteins in rat brain with SAD. O-GlcNAc glycosylation and expression of tau proteins were detected by O-GlcNAc-specific antibodies RL2 and CTD110.6. RESULTS: O-GlcNAc glycosylated proteins enriched by succinylated wheat germ agglutinin significantly improved in the hippocampus of SAD rats. The differences were statistically significant among XXD groups (P < 0.05, P < 0.01), while no obvious differences were observed between D group and M group (P > 0.05). CONCLUSION: XXD can significantly improve O-GlcNAc glycosylation level of tau proteins in the hippocampus of SAD rats, which maybe inhibit hyperphosphorylation of tau proteins on key sites and its toxicity, and prevent the pathological process of SAD.

Diwu Y; Tian J; Shi J

2013-06-01

16

Perceptual errors increase with movement duration and may contribute to hypokinesia in Parkinson's disease.  

UK PubMed Central (United Kingdom)

People with Parkinson's disease (PD) perceive that their movement amplitude is greater than what they actually perform. The neural mechanisms underlying one's perception of movement are believed to involve the sensorimotor integration process (SIP). How PD affects the SIP is not well understood. A previous study interrogating the SIP showed healthy adults (HAs) overestimated their limb position in the direction of movement and the error and its variance (VOE) depended on movement duration. We asked if PDs showed errors in perceived limb position and if the dependence on movement duration was different from HAs. We used an existing computational model of the SIP to explore mechanisms for the error and VOE as a function of movement duration. Twenty PDs, off medication, and 20 age-matched HAs were asked to estimate the position of their hand after performing 50, slow, non-visually guided wrist flexion or extension movements for a random period of time (<4.0 s). Both groups overestimated the amount they moved; however, the PDs' error and VOE were larger (p<0.001). HAs showed increasing error/VOE for small movement durations that reduced/stabilized for longer movement durations. PDs however showed increasing error/VOE with increasing movement duration that did not significantly improve/stabilize. The model suggested that the basis for such perceptual deficits may be abnormal proprioceptive feedback and/or processing of an abnormal internal impression (prediction) that underestimates movement amplitude. Simulation results imply that the PD's SIP could no longer effectively access sensory (proprioceptive) feedback to correct errors in other components of the SIP due to the abnormal processing of sensory feedback. We suggest from this study that an impaired perception of movement amplitude and sensory processing deficits contribute to hypokinesia in PD.

Koop MM; Hill BC; Bronte-Stewart HM

2013-07-01

17

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

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

Yong-chang Diwu

2011-01-01

18

Sporadic wind wave horse-shoe patterns  

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

S. Yu. Annenkov; V. I. Shrira

1999-01-01

19

Evaporation of high speed sporadic meteors  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 wi...

Murad, E.; Roth, C.

20

[Sporadic inclusion body myositis in Japan].  

UK PubMed Central (United Kingdom)

Sporadic inclusion body myositis (sIBM), the most common form of myopathy with inflammation in those over the age of 50 in Western countries, is an intractable and progressive skeletal muscle disease of unknown cause and without effective treatment. Muscle biopsy typically reveals endomysial inflammation, invasion of mononuclear cells into non-necrotic fibers and rimmed vacuoles, suggesting inflammation and degeneration are co-existed in the pathogenesis. We estimated the prevalence of sIBM in Japan is 9.83 per million in 2003 and an increase in the number of sIBM in Japan in the decade. In this review, we discuss the diagnostic criteria sIBM in Japan, and describe available treatments and promising new therapeutic strategies. We also provide an update on the current understanding of sIBM pathogenesis.

Aoki M; Suzuki N

2012-05-01

 
 
 
 
21

Sporadic oral angiomyolipoma: Case report  

Scientific Electronic Library Online (English)

Full Text Available Abstract in spanish El angiomiolipoma (AML) es un tumor benigno infrecuente compuesto por una proporción variable de lipocitos, músculo liso y vasos de paredes gruesas. Forma parte de la familia de tumores originados en las células epitelioides perivasculares (PEComas), y muchos casos se asocian a esclerosis tuberosa, siendo el riñón la localización más frecuente. Presentamos un caso de AML esporádico en el paladar duro de un varón de 52 años, una localización extremadamente rara (more) para este tumor. El diagnóstico diferencial con otras lesiones mesenquimales tanto benignas como malignas de la zona se basa en la identificación histológica de los 3 componentes, siendo de ayuda las tinciones inmunohistoquímicas. Los AMLs localizados en cabeza y cuello no expresan HMB-45, un anticuerpo que identifica melanosomas inmaduros, mientras que los renales y hepáticos sí lo hacen, lo que sugiere que existen diferencias entre ambos AMLs. El tratamiento de elección es la exéresis quirúrgica completa, ya que estos tumores suelen tener un comportamiento benigno. Abstract in english Angiomyolipoma (AML) is a rare, benign tumour composed of a variable proportion of lipocytes, smooth muscle and thick-walled blood vessels. AML is part of a family of tumours arising from perivascular epithelioid cells (PEComas), and many cases are associated with tuberous sclerosis, with the kidney being the most frequent site involved. We report a case of sporadic AML in the hard palate of a 52-year-old male, an extremely unusual location for this tumour. Differentiatio (more) n from other benign and malignant oral mesenchymal lesions depends on recognition of the three histologic components, and immunohistochemical techniques may be helpful. AML occurring in the head and neck do not express HMB-45, an antibody that identifies immature melanosomes, conversely to the usual immunopositivity shown in AMLs from kidney and liver, suggesting that there are differences among them. A wide surgical excision is considered curative, as this tumour usually behaves in a benign fashion.

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

2007-09-01

22

Prognostic significance of AKT/mTOR and MAPK pathways and antitumor effect of mTOR inhibitor in NF1-related and sporadic malignant peripheral nerve sheath tumors.  

UK PubMed Central (United Kingdom)

PURPOSE: Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma with poor prognosis. MPNSTs occur frequently in patients with neurofibromatosis type 1 (NF1), in which NF1 gene deficiency leads to Ras hyperactivation. Ras activation causes the subsequent activation of the AKT/mTOR and Raf/MEK/ERK pathways and regulates cellular functions. However, the activation profiles of the AKT/mTOR and MAPK pathways in MPNSTs are poorly understood. The purposes of this study are to examine the correlation between the activation of these pathways and clinicopathologic or prognostic factors and to identify candidate target molecules in MPNST. Moreover, we assessed the antitumor effects of the inhibitor of candidate target. EXPERIMENTAL DESIGN: Immunohistochemistry was conducted to evaluate the activation profiles of AKT/mTOR and MAPK pathways using 135 tumor specimens. Immunohistochemical expressions were confirmed by Western blotting. Then, an in vitro study was conducted to examine the antitumor effect of the mTOR inhibitor on MPNST cell lines. RESULTS: Phosphorylated-AKT (p-AKT), p-mTOR, p-S6RP, p-p70S6K, p-4E-BP1, p-MEK1/2, and p-ERK1/2 expressions were positive in 58.2%, 47.3%, 53.8%, 57.1%, 62.6%, 93.4%, and 81.3% of primary MPNSTs, respectively. Positivity for each factor showed no difference between NF1-related and sporadic MPNSTs. Univariate prognostic analysis revealed that p-AKT, p-mTOR, and p-S6RP expressions were associated with poor prognosis. Furthermore, activation of each p-mTOR and p-S6RP was an independent poor prognostic factor by multivariate analysis. mTOR inhibition by Everolimus showed antitumor activity on MPNST cell lines in vitro. CONCLUSION: mTOR inhibition is a potential treatment option for both NF1-related and sporadic MPNSTs.

Endo M; Yamamoto H; Setsu N; Kohashi K; Takahashi Y; Ishii T; Iida K; Matsumoto Y; Hakozaki M; Aoki M; Iwasaki H; Dobashi Y; Nishiyama K; Iwamoto Y; Oda Y

2013-01-01

23

On the variability of sporadic E  

Energy Technology Data Exchange (ETDEWEB)

The analysis of digital ionograms taken in short-time intervals shows rapid changes of sporadic E parameters. This is directly visible in the variation of the top frequency or maximum electron density of such layers. Angle of arrival data which were available with those ionograms also showed fast changes of the apparent direction and often large deviations from vertical propagation. 5 refs.

Paul, A.K. (Ocean and Atmospheric Sciences Div., San Diego, CA (USA))

1990-02-01

24

Sporadic simple groups and quotient singularities  

Science.gov (United States)

We show that if a faithful irreducible representation of a central extension of a sporadic simple group with centre contained in the commutator subgroup gives rise to an exceptional (resp. weakly exceptional but not exceptional) quotient singularity, then that simple group is the Hall-Janko group (resp. the Suzuki group).

Cheltsov, I. A.; Shramov, C. A.

2013-08-01

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Thalidomide improves clinical symptoms of primary cutaneous amyloidosis: report of familiar and sporadic cases.  

Science.gov (United States)

Primary cutaneous amyloidosis (PCA), either familial or sporadic, poses a therapeutic challenge. We conducted an open trial using thalidomide to treat three cases of familial and three cases of sporadic PCA, at initial dose of 100 mg/day. Dosage adjustment was made according to improvement of symptoms or patient's own choice. All except one sporadic case experienced moderate to significant relief on the symptoms of itching, over an observational period of 8 weeks by visual analog score (from 8.08 ± 0.88 to 1.60 ± 0.68, on average) as well as clinical amelioration of symptoms. Side effects included fatigue, drowsiness, numbness, and facial and leg edema in some of the patients. From the present observation, it seems that thalidomide is a promising drug to treat PCA. PMID:23742287

An, Qian; Zhang, Li; Zheng, Song; Lin, Junping; Hong, Yuxiao; Chen, Hong-Duo; Gao, Xing-Hua

2013-03-13

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Thalidomide improves clinical symptoms of primary cutaneous amyloidosis: report of familiar and sporadic cases.  

UK PubMed Central (United Kingdom)

Primary cutaneous amyloidosis (PCA), either familial or sporadic, poses a therapeutic challenge. We conducted an open trial using thalidomide to treat three cases of familial and three cases of sporadic PCA, at initial dose of 100 mg/day. Dosage adjustment was made according to improvement of symptoms or patient's own choice. All except one sporadic case experienced moderate to significant relief on the symptoms of itching, over an observational period of 8 weeks by visual analog score (from 8.08 ± 0.88 to 1.60 ± 0.68, on average) as well as clinical amelioration of symptoms. Side effects included fatigue, drowsiness, numbness, and facial and leg edema in some of the patients. From the present observation, it seems that thalidomide is a promising drug to treat PCA.

An Q; Zhang L; Zheng S; Lin J; Hong Y; Chen HD; Gao XH

2013-05-01

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Sporadic Medullary Microcarcinoma in a Young Patient - A Rare Case  

Directory of Open Access Journals (Sweden)

Full Text Available Sporadic medullary microcarcinoma of thyroid is a rare disease detected usually in 0.15% of all thyroid malignancy. We report a case of sporadic medullary microcarcinoma (MMC) of thyroid in a 24 year old male presenting as solitary thyroid nodule. There was no family history of medullary carcinoma of thyroid. Although medullary carcinoma in a familial setting have been reported, sporadic MMC is rare especially in a young patient.

Vijayshankar S; Amita K; Abhishek M; Manjunath D

2010-01-01

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

1995-12-18

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[Treatability of sporadic late onset nemaline myopathy].  

UK PubMed Central (United Kingdom)

Sporadic late onset nemaline myopathy (SLONM) is an extremely rare disorder which can be associated with monoclonal gammopathy of unclear significance (MGUS). Clinically SLONM appears mostly after the fourth decade of life as rapidly progressing tetraparesis, respiratory insufficiency and features, such as dropped head syndrome, facial and bulbar involvement. Diagnosis is confirmed by muscle biopsy with detection of nemaline bodies and also frequently lobulated fibres. Immunosuppressant and immunomodulating therapies have been shown to be ineffective but clinical improvement accompanied by disappearance of monoclonal gammopathy and even nemaline bodies was reported following autologous stem cell transplantation and chemotherapy with melphalan. This article presents the case of a 53-year-old man with a 4-year history of SLOMN with MGUS in which administration of intravenous immunoglobulin therapy (IVIG) was not successful in reversing gammopathy, histopathological changes or clinical symptoms.

Hanisch F; Schneider I; Müller T; Romeike BF; Stoltenburg G; Holzhausen HJ; Zierz S

2013-08-01

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Long-term observational study of sporadic inclusion body myositis.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

We describe a long-term observational study of a large cohort of patients with sporadic inclusion body myositis and propose a sporadic inclusion body myositis weakness composite index that is easy to perform during a clinic. Data collection from two groups of patients (Paris and Oxford) was complete...

Benveniste, O; Guiguet, M; Freebody, J; Dubourg, O; Squier, W

31

Percutaneous cryoablation of solitary sporadic renal cell carcinomas.  

UK PubMed Central (United Kingdom)

UNLABELLED: What's known on the subject? and What does the study add? Percutaneous renal cryoablation is a safe and effective treatment for patients with small renal masses, who are poor surgical candidates. Oncological outcomes from previous percutaneous ablation studies are difficult to interpret because of the large number of patients treated with a history of RCC (38% in our experience) and the large number of treated renal masses without a pathology-proven diagnosis. This cryoablation study addresses these issues by evaluating only solitary, sporadic biopsy-proven RCC. Oncological outcomes and complications were also evaluated by tumour T-stage, which allows some degree of comparison with previously published surgical results. OBJECTIVE: • To evaluate retrospectively our single institution experience with percutaneous cryoablation of solitary, sporadic renal cell carcinomas (RCCs), and to compare the efficacy and safety of this technique for treatment of different T-stage RCC. PATIENTS AND METHODS: • 116 patients were treated with percutaneous cryoablation for a solitary, sporadic biopsy-proven RCC in a single treatment session between November 2003 and November 2010. • The technical success of the ablation procedure, complications and evidence for local or metastatic tumour recurrence were evaluated for each patient. RESULTS: • 83 patients (72%) were treated for a stage T1a RCC, 27 patients (23%) for a stage T1b RCC, and six patients (5%) for a stage T2 RCC. • Technical success was achieved in the treatment of 115 of 116 (99%) renal tumours. The single technical failure occurred in the treatment of a 4.3-cm RCC. • Local recurrent tumour was identified in one of 88 patients (1%) with follow-up computed tomography (CT) or magnetic resonance imaging available for review >3 months from the time of ablation. The median (range) imaging follow-up in these patients was 21 (3-73) months. The local tumour recurrence was identified on CT 11 months after the ablation procedure in a patient treated for a 2.7 cm RCC. • None of the patients developed metastatic RCC. • The major complication rate was 4% for patients with stage T1a tumours, 15% for those with stage T1b tumours, and 33% for those with stage T2 tumours. There were no procedural-related deaths. CONCLUSIONS: • Percutaneous renal cryoablation of RCC can be performed with high technical success in patients with tumours up to, and beyond 7 cm in maximum diameter. • The tumour recurrence rate after percutaneous renal cryoablation was low, and recurrence was not related to tumour size in this group of patients. • Statistically significant higher complication rates were seen with treatment of larger (higher T-stage) RCCs.

Schmit GD; Thompson RH; Kurup AN; Weisbrod AJ; Carter RE; Callstrom MR; Atwell TD

2012-12-01

32

Complete genomic landscape of a recurring sporadic parathyroid carcinoma.  

UK PubMed Central (United Kingdom)

Parathyroid carcinoma is a rare endocrine malignancy with an estimated incidence of less than 1 per million population. Excessive secretion of parathyroid hormone, extremely high serum calcium level, and the deleterious effects of hypercalcaemia are the clinical manifestations of the disease. Up to 60% of patients develop multiple disease recurrences and although long-term survival is possible with palliative surgery, permanent remission is rarely achieved. Molecular drivers of sporadic parathyroid carcinoma have remained largely unknown. Previous studies, mostly based on familial cases of the disease, suggested potential roles for the tumour suppressor MEN1 and proto-oncogene RET in benign parathyroid tumourigenesis, while the tumour suppressor HRPT2 and proto-oncogene CCND1 may also act as drivers in parathyroid cancer. Here, we report the complete genomic analysis of a sporadic and recurring parathyroid carcinoma. Mutational landscapes of the primary and recurrent tumour specimens were analysed using high-throughput sequencing technologies. Such molecular profiling allowed for identification of somatic mutations never previously identified in this malignancy. These included single nucleotide point mutations in well-characterized cancer genes such as mTOR, MLL2, CDKN2C, and PIK3CA. Comparison of acquired mutations in patient-matched primary and recurrent tumours revealed loss of PIK3CA activating mutation during the evolution of the tumour from the primary to the recurrence. Structural variations leading to gene fusions and regions of copy loss and gain were identified at a single-base resolution. Loss of the short arm of chromosome 1, along with somatic missense and truncating mutations in CDKN2C and THRAP3, respectively, provides new evidence for the potential role of these genes as tumour suppressors in parathyroid cancer. The key somatic mutations identified in this study can serve as novel diagnostic markers as well as therapeutic targets.

Kasaian K; Wiseman SM; Thiessen N; Mungall KL; Corbett RD; Qian JQ; Nip KM; He A; Tse K; Chuah E; Varhol RJ; Pandoh P; McDonald H; Zeng T; Tam A; Schein J; Birol I; Mungall AJ; Moore RA; Zhao Y; Hirst M; Marra MA; Walker BA; Jones SJ

2013-07-01

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Sporadic aurorae observed in East Asia  

Directory of Open Access Journals (Sweden)

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

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

2007-01-01

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Quadriceps strength is a sensitive marker of disease progression in sporadic inclusion body myositis.  

UK PubMed Central (United Kingdom)

There are currently no effective treatments to restore the muscle function in sporadic inclusion body myositis. Natural history studies of this disease are scarce. The goal of this study consisted in defining the functional pattern of patients with sporadic inclusion body myositis and to follow its change over a 9-month period to determine the most sensitive outcome measures for future clinical trials. Twenty-two patients with definite sporadic inclusion body myositis were assessed using clinical and functional scales. Dynamometry was used to evaluate the strength for hand grip and wrist, elbow, ankle and knee flexion and extension. Among the patients, 16 were reassessed 9months later. The mean whole composite index was at 43.3±16.5% of the predicted normal values. The weakest muscle functions were hand grip, wrist flexion and elbow flexion at the upper limbs and knee extension and ankle flexion at the lower limbs. Muscle weakness was generally asymmetrical, especially for upper limbs where all tested functions were significantly stronger at the dominant side. The patient strength was correlated with the disease duration only for knee extension, which was also the only muscle function to change significantly over 9months. Knee extension strength seems to be the most relevant marker of disease progression in sporadic inclusion body myositis when measured with suitable dynamometry.

Allenbach Y; Benveniste O; Decostre V; Canal A; Eymard B; Herson S; Bloch-Queyrat C; Hogrel JY

2012-11-01

35

Genomic profiling distinguishes familial multiple and sporadic multiple meningiomas  

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

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

2009-01-01

36

A de novo mutation in sporadic nocturnal frontal lobe epilepsy.  

Science.gov (United States)

Autosomal dominant nocturnal frontal lobe epilepsy is sometimes due to mutations in CHRNA4. The commoner presentation of sporadic nocturnal frontal lobe epilepsy has not been associated with genetic defects. A 30-year-old woman diagnosed as having sporadic nocturnal frontal lobe epilepsy was found to have a de novo Ser252Leu CHRNA4 mutation. A pattern is emerging of site-specific mutation within the second transmembrane domain of CHRNA4 in association with autosomal dominant nocturnal frontal lobe epilepsy and sporadic nocturnal frontal lobe epilepsy in families with different ethnic backgrounds. PMID:10939581

Phillips, H A; Marini, C; Scheffer, I E; Sutherland, G R; Mulley, J C; Berkovic, S F

2000-08-01

37

A de novo mutation in sporadic nocturnal frontal lobe epilepsy.  

UK PubMed Central (United Kingdom)

Autosomal dominant nocturnal frontal lobe epilepsy is sometimes due to mutations in CHRNA4. The commoner presentation of sporadic nocturnal frontal lobe epilepsy has not been associated with genetic defects. A 30-year-old woman diagnosed as having sporadic nocturnal frontal lobe epilepsy was found to have a de novo Ser252Leu CHRNA4 mutation. A pattern is emerging of site-specific mutation within the second transmembrane domain of CHRNA4 in association with autosomal dominant nocturnal frontal lobe epilepsy and sporadic nocturnal frontal lobe epilepsy in families with different ethnic backgrounds.

Phillips HA; Marini C; Scheffer IE; Sutherland GR; Mulley JC; Berkovic SF

2000-08-01

38

VCP mutations in familial and sporadic amyotrophic lateral sclerosis.  

UK PubMed Central (United Kingdom)

Mutations in the valosin-containing protein (VCP) gene were recently reported to be the cause of 1%-2% of familial amyotrophic lateral sclerosis (ALS) cases. VCP mutations are known to cause inclusion body myopathy (IBM) with Paget's disease (PDB) and frontotemporal dementia (FTD). The presence of VCP mutations in patients with sporadic ALS, sporadic ALS-FTD, and progressive muscular atrophy (PMA), a known clinical mimic of inclusion body myopathy, is not known. To determine the identity and frequency of VCP mutations we screened a cohort of 93 familial ALS, 754 sporadic ALS, 58 sporadic ALS-FTD, and 264 progressive muscular atrophy patients for mutations in the VCP gene. Two nonsynonymous mutations were detected; 1 known mutation (p.R159H) in a patient with familial ALS with several family members suffering from FTD, and 1 mutation (p.I114V) in a patient with sporadic ALS. Conservation analysis and protein prediction software indicate the p.I114V mutation to be a rare benign polymorphism. VCP mutations are a rare cause of familial ALS. The role of VCP mutations in sporadic ALS, if present, appears limited.

Koppers M; van Blitterswijk MM; Vlam L; Rowicka PA; van Vught PW; Groen EJ; Spliet WG; Engelen-Lee J; Schelhaas HJ; de Visser M; van der Kooi AJ; van der Pol WL; Pasterkamp RJ; Veldink JH; van den Berg LH

2012-04-01

39

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

Directory of Open Access Journals (Sweden)

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

Nozières Cécile; Berlier Pascale; Dupuis Clémentine; Raynaud-Ravni Catherine; Morel Yves; Chazot Françoise; Nicolino Marc

2011-01-01

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SNCA polymorphisms, smoking, and sporadic Parkinson's disease in Japanese.  

UK PubMed Central (United Kingdom)

Several case-control studies and genome-wide association studies have examined the relationships between single nucleotide polymorphisms (SNPs) in the SNCA gene and Parkinson's disease (PD), and have provided inconsistent results. We investigated the relationships between SNPs rs356229, rs356219, rs356220, rs7684318, and rs2736990 and the risk of sporadic PD in Japan using data from a multicenter hospital-based case-control study. Included were 229 cases within 6 years of onset of PD as defined according to the UK PD Society Brain Bank clinical diagnostic criteria. Controls were 357 inpatients and outpatients without neurodegenerative disease. Adjustment was made for sex, age, region of residence, and smoking. Based on the recessive model, compared with subjects with the CC or CT genotype of SNP rs356220, those with the TT genotype had a significantly increased risk of sporadic PD: the adjusted OR was 1.42 (95% CI: 1.002-2.02). In the additive model, SNP rs2736990 was significantly related to the risk of sporadic PD: the adjusted OR was 1.30 (95% CI: 1.002-1.68). There were no significant relationships between SNP rs356229, rs356219, or rs7684318 and the risk of sporadic PD in any genetic model. The additive interactions between SNPs rs356219 and rs356220 and smoking with respect to sporadic PD were significant although the multiplicative interactions were not significant. This study suggests that SNCA SNPs rs356220 and rs2736990 are significantly associated with the risk of sporadic PD in Japanese. We also present new evidence for biological interactions between SNPs rs356219 and rs356220 and smoking that affect sporadic PD.

Miyake Y; Tanaka K; Fukushima W; Kiyohara C; Sasaki S; Tsuboi Y; Yamada T; Oeda T; Shimada H; Kawamura N; Sakae N; Fukuyama H; Hirota Y; Nagai M

2012-06-01

 
 
 
 
41

Association studies in late onset sporadic Alzheimer`s disease  

Energy Technology Data Exchange (ETDEWEB)

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.

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

1994-09-01

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Tocilizumab infusion therapy normalizes inflammation in sporadic ALS patients.  

Science.gov (United States)

Patients with sporadic amyotrophic lateral sclerosis (sALS) show inflammation in the spinal cord and peripheral blood. The inflammation is driven by stimulation of macrophages by aggregated superoxide dismutase 1 (SOD1) through caspase1, interleukin 1 (IL1), IL6 and chemokine signaling. Inflammatory gene activation is inhibited in vitro by tocilizumab, a humanized antibody to IL6 receptor (IL6R). Tocilizumab inhibits global interleukin-6 (IL6) signaling, a key mechanism in chronic rheumatoid disorders. Here we studied in vivo baseline inflammatory gene transcription in peripheral blood mononuclear cells (PBMCs) of 10 sALS patients, and the effects of tocilizumab (Actemra(R)) infusions. At baseline, one half of ALS subjects had strong inflammatory activation (Group 1) (8 genes up regulated >4-fold, PTocilizumab infusions in the Group 1 patients resulted in down regulation of inflammatory genes (in particular IL1?), whereas in the Group 2 patients in up regulation of inflammatory genes. Post-infusion serum and CSF concentrations of tocilizumab inhibited caspase1 activation in vitro. Three of 5 patients receiving tocilizumab infusions showed time-limited attenuation of clinical progression. In conclusion, inflammation of sALS patients at baseline is up- or down-regulated in comparison to controls, but is partially normalized by tocilizumab infusions. PMID:23844337

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

2013-06-21

43

Tocilizumab infusion therapy normalizes inflammation in sporadic ALS patients.  

UK PubMed Central (United Kingdom)

Patients with sporadic amyotrophic lateral sclerosis (sALS) show inflammation in the spinal cord and peripheral blood. The inflammation is driven by stimulation of macrophages by aggregated superoxide dismutase 1 (SOD1) through caspase1, interleukin 1 (IL1), IL6 and chemokine signaling. Inflammatory gene activation is inhibited in vitro by tocilizumab, a humanized antibody to IL6 receptor (IL6R). Tocilizumab inhibits global interleukin-6 (IL6) signaling, a key mechanism in chronic rheumatoid disorders. Here we studied in vivo baseline inflammatory gene transcription in peripheral blood mononuclear cells (PBMCs) of 10 sALS patients, and the effects of tocilizumab (Actemra(R)) infusions. At baseline, one half of ALS subjects had strong inflammatory activation (Group 1) (8 genes up regulated >4-fold, P<0.05 vs. controls) and the other half (Group 2) had weak activation. All patients showed greater than four-fold up regulation of MMP1, CCL7, CCL13 and CCL24. Tocilizumab infusions in the Group 1 patients resulted in down regulation of inflammatory genes (in particular IL1?), whereas in the Group 2 patients in up regulation of inflammatory genes. Post-infusion serum and CSF concentrations of tocilizumab inhibited caspase1 activation in vitro. Three of 5 patients receiving tocilizumab infusions showed time-limited attenuation of clinical progression. In conclusion, inflammation of sALS patients at baseline is up- or down-regulated in comparison to controls, but is partially normalized by tocilizumab infusions.

Fiala M; Mizwicki MT; Weitzman R; Magpantay L; Nishimoto N

2013-01-01

44

Is sporadic Alzheimer's disease associated with diphtheria toxin?  

UK PubMed Central (United Kingdom)

The two major aspects of Alzheimer's disease (AD) that must be considered in a search for causative agents are its association with aging and its widespread epidemiology. While a number of agents have been identified, additional factors may play a role. An association with diphtheria toxin was suggested by observations that vaccinations may provide protective effects, and the observation that decreased proteins synthesis in cortical regions from AD patients is associated with modification of elongation factor 2, the target of diphtheria toxin. While protection against diphtheria toxin is provided by vaccination, the known decline in the immune system associated with aging would result in a renewed sensitivity to the toxin. An association with diphtheria toxin would be consistent with the observations that the bacteria associated with the toxin, Corynebacterium diphtheria, is often found in the nasopharynx and an early symptom of AD is the loss of smell with a disease progression from the entorhinal cortex to the hippocampus and the neocortical areas. If diphtheria toxin is involved in sporadic AD, booster vaccinations given to elderly individuals might result in a decreased incidence of this disease. As booster DPT vaccinations are already recommended for individuals over 65, cognitive testing at the time of the booster and 5 years later, along with similar cognitive testing in age-matched individuals who decline vaccination, might provide an inexpensive method to investigate whether diphtheria toxin plays a role in AD and the efficacy of DPT booster vaccines for AD.

Merril CR

2013-01-01

45

Molecular and survival differences between familial and sporadic gastric cancers.  

UK PubMed Central (United Kingdom)

Mismatch repair (MMR) and germline E-cadherin (CDH1) mutations are two of the major pathways of carcinogenesis in familial gastric cancer (GC). A total of 260 sporadic and 66 familial GC patients were enrolled and molecular and survival differences were compared. Familial GC patients had earlier onset and were diagnosed at an earlier stage and had both a better 5-year overall survival rate and 3-year disease-free survival rate compared with sporadic GC patients. Only in diffuse type GC, the MSI-H phenotype and abnormal MMR protein expression were significantly higher in familial GC than in sporadic GC. In MSI-H GC, MLH1 promoter methylation was slightly higher in sporadic GC than familial GC (50% versus 23.1%), while the frequency of MMR gene mutation was slightly higher in familial GC than in sporadic GC (15.4% versus 3.1%). All of the patients with MMR gene mutation had diffuse type GC. Among familial GC patients with CDH1 mutation, most patients (72.3%) had diffuse type GC. In summary, for familial GC patients, we recommend screening of MSI status and CDH1 mutation especially for diffuse type GC. Because of the low incidence, mutation analysis of MMR gene might be considered in MSI-H familial GC with diffuse type only.

Fang WL; Chang SC; Lan YT; Huang KH; Lo SS; Li AF; Chi CW; Wu CW; Chiou SH

2013-01-01

46

Sporadic Jakob-Creutzfeldt disease presenting as primary progressive aphasia.  

UK PubMed Central (United Kingdom)

OBJECTIVE: To report the clinical, neuropsychological, linguistic, imaging, and neuropathological features of a unique case of sporadic Jakob-Creutzfeldt disease in which the patient presented with a logopenic variant of primary progressive aphasia. DESIGN: Case report. SETTING: Large referral center for atypical memory and aging disorders, particularly Jakob-Creutzfeldt disease. PATIENT: Patient presenting with logopenic variant primary progressive aphasia initially thought to be due to Alzheimer disease. RESULTS: Despite the long, slow 3.5-year course, the patient was shown to have pathology-proven sporadic Jakob-Creutzfeldt disease. CONCLUSIONS: These findings expand the differential of primary progressive aphasia to include prion disease.

Johnson DY; Dunkelberger DL; Henry M; Haman A; Greicius MD; Wong K; DeArmond SJ; Miller BL; Gorno-Tempini ML; Geschwind MD

2013-02-01

47

Post streptococcal acute glomerulonephritis secondary to sporadic Streptococcus equi infection.  

UK PubMed Central (United Kingdom)

Streptococcus equi subspecies zooepidemicus infection is rare in humans, but a well-known cause of pyogenic disease in cows and horses. S. zooepidemicus uncommonly causes post-strep glomerulonephritis (PSGN) in humans via epidemic outbreaks. We present a sporadic case of post S. zooepidemicus glomerulonephritis in a child most probably contracted from a horse. The 14-year-old girl presented with the typical signs of PSGN, with S. equi zooepidemicus isolated from a blood culture, together with a low C3 and raised anti-DNAse B. This is the first known report of a sporadic case of PSGN in a child caused by this organism.

Thorley AM; Campbell D; Moghal NE; Hudson S

2007-04-01

48

Post streptococcal acute glomerulonephritis secondary to sporadic Streptococcus equi infection.  

Science.gov (United States)

Streptococcus equi subspecies zooepidemicus infection is rare in humans, but a well-known cause of pyogenic disease in cows and horses. S. zooepidemicus uncommonly causes post-strep glomerulonephritis (PSGN) in humans via epidemic outbreaks. We present a sporadic case of post S. zooepidemicus glomerulonephritis in a child most probably contracted from a horse. The 14-year-old girl presented with the typical signs of PSGN, with S. equi zooepidemicus isolated from a blood culture, together with a low C3 and raised anti-DNAse B. This is the first known report of a sporadic case of PSGN in a child caused by this organism. PMID:17109135

Thorley, Anna M; Campbell, David; Moghal, Nadeem E; Hudson, Sue

2006-11-16

49

Daytime equatorial VHF radiowave scintillations and sporadic-E layer  

Science.gov (United States)

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

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

1989-08-01

50

Diagnostic value of markers of muscledegeneration in sporadic inclusionbody myositis  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 performe...

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

51

Balloon Dilation in Sporadic Inclusion Body Myositis Patients with Dysphagia  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Here, we describe balloon catheter dilation at the upper esophageal sphincter (UES) in three sporadic inclusion body myositis (s-IBM) patients with dysphagia. Initially, we performed IVIg therapy, and, three months later, switched to balloon dilation therapy. A 12-Fr balloon catheter was inserted fr...

Murata, Ken-ya; Kouda, Ken; Tajima, Fumihiro; Kondo, Tomoyoshi

52

Integral group ring of the Suzuki sporadic simple group  

CERN Document Server

Using the Luthar--Passi method, we investigate the classical Zassenhaus conjecture for the normalized unit group of the integral group ring of the Suzuki sporadic simple group Suz. As a consequence, for this group we confirm the Kimmerle's conjecture on prime graphs.

Bovdi, V A; Marcos, E N

2008-01-01

53

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Background Cryptic subtelomeric rearrangements have been proposed as a significant cause of sporadic intellectual disability (ID) but the role of such aberrations in familial ID has not yet been studied. As positive family history of ID had been proposed as an important and...

Rafati Maryam; Ghadirzadeh Mohammad R; Heshmati Yaser; Adibi Homeira; Keihanidoust Zarrintaj; Eshraghian Mohammad R

54

Screening for Familial APP Mutations in Sporadic Cerebral Amyloid Angiopathy  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Background: Advances in genetic technology have revealed that variation in the same gene can cause both rare familial and common sporadic forms of the same disease. Cerebral amyloid angiopathy (CAA), a common cause of symptomatic intracerebral hemorrhage (ICH) in the elderly, can also occur in famil...

Plourde, Anna; Onofrio, Robert; Prada, Claudia M.; Biffi, Alessandro; Shen, Yiping; Smith, Eric E.; Frosch, Matthew P.

55

Olfactory dysfunction in sporadic Parkinson's Disease and LRRK2 carriers.  

UK PubMed Central (United Kingdom)

OBJECTIVE: The aim of the study was to examine the sense of smell in LRRK2 mutation carriers and in patients with sporadic PD (sPD). MATERIALS AND METHODS: A total of 343 individuals were included: 275 sPD of whom 90 were de novo patients with sPD, 17 LRRK2 PD, 36 healthy LRRK2 mutation carriers, and 15 healthy family members without mutation. All subjects underwent neurologic examination and olfactory sense testing with B-SIT (a 12-item test). Linear regression analysis was applied to build different models with B-SIT as dependent variable. RESULTS: Sporadic PD had significantly lower scores in olfaction compared with LRRK2 PD (P < 0.001). B-SIT scores were lowest in medicated sPD, and higher scores were found in de novo patients. LRRK2 PD had similar sense of smell to healthy LRRK2 mutation carriers and to healthy family members without mutation when adjusting for age. CONCLUSION: Hyposmia was pronounced already at time of diagnosis in the sPD cases but was not present in healthy LRRK2 mutation carriers and less pronounced in LRRK2 PD compared with sporadic cases. Smell testing may be a preclinical marker in sporadic PD but does not seem applicable in LRRK2 cases.

Johansen KK; Warø BJ; Aasly JO

2013-08-01

56

Role of KCNJ5 in familial and sporadic primary aldosteronism.  

UK PubMed Central (United Kingdom)

Primary aldosteronism is characterised by the dysregulation of aldosterone production and comprises both sporadic forms, caused by an aldosterone-producing adenoma or bilateral adrenal hyperplasia, and familial forms (familial hyperaldosteronism types I, II and III). The two principal physiological regulators of aldosterone synthesis are angiotensin II and serum K(+), which reverse the high resting K(+) conductance and hyperpolarized membrane potential of adrenal glomerulosa cells. The resulting membrane depolarization causes the opening of voltage-gated Ca(2+) channels and an increase in intracellular Ca(2+) that stimulates aldosterone biosynthesis. Point mutations in the KCNJ5 gene, which encodes the G-protein-activated inward rectifier K(+) channel 4 (GIRK4), have been implicated in the pathogenesis of both sporadic and familial forms of primary aldosteronism. These mutations interfere with the selectivity filter of GIRK4 causing Na(+) entry, cell depolarization and Ca(2+) channel opening, resulting in constitutive aldosterone production. Seven families with familial hyperaldosteronism caused by KCNJ5 germline mutations have so far been described, and multicentre studies have reported KCNJ5 mutations in approximately 40% of sporadic aldosterone-producing adenomas. Herein, we review the role of GIRK4 in adrenal pathophysiology and provide an overview of the clinical and biochemical phenotypes resulting from KCNJ5 mutations in patients with sporadic and familial primary aldosteronism.

Mulatero P; Monticone S; Rainey WE; Veglio F; Williams TA

2013-02-01

57

Role of KCNJ5 in familial and sporadic primary aldosteronism.  

Science.gov (United States)

Primary aldosteronism is characterised by the dysregulation of aldosterone production and comprises both sporadic forms, caused by an aldosterone-producing adenoma or bilateral adrenal hyperplasia, and familial forms (familial hyperaldosteronism types I, II and III). The two principal physiological regulators of aldosterone synthesis are angiotensin II and serum K(+), which reverse the high resting K(+) conductance and hyperpolarized membrane potential of adrenal glomerulosa cells. The resulting membrane depolarization causes the opening of voltage-gated Ca(2+) channels and an increase in intracellular Ca(2+) that stimulates aldosterone biosynthesis. Point mutations in the KCNJ5 gene, which encodes the G-protein-activated inward rectifier K(+) channel 4 (GIRK4), have been implicated in the pathogenesis of both sporadic and familial forms of primary aldosteronism. These mutations interfere with the selectivity filter of GIRK4 causing Na(+) entry, cell depolarization and Ca(2+) channel opening, resulting in constitutive aldosterone production. Seven families with familial hyperaldosteronism caused by KCNJ5 germline mutations have so far been described, and multicentre studies have reported KCNJ5 mutations in approximately 40% of sporadic aldosterone-producing adenomas. Herein, we review the role of GIRK4 in adrenal pathophysiology and provide an overview of the clinical and biochemical phenotypes resulting from KCNJ5 mutations in patients with sporadic and familial primary aldosteronism. PMID:23229280

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

2012-12-11

58

Clinical Perspective of Oxidative Stress in Sporadic ALS.  

UK PubMed Central (United Kingdom)

Sporadic amyotrophic lateral sclerosis (sALS) is one of the most devastating neurological diseases; most patients die within 3 to 4 years after symptom onset. Oxidative stress is a disturbance in the pro-oxidative/anti-oxidative balance favoring the pro-oxidative state. Autopsy and laboratory studies in ALS indicate that oxidative stress plays a major role in motor neuron degeneration and astrocyte dysfunction. Oxidative stress biomarkers in cerebrospinal fluid, plasma, and urine, are elevated, suggesting that abnormal oxidative stress is generated outside of the central nervous system. Our review indicates that agricultural chemicals, heavy metals, military service, professional sports, excessive physical exertion, chronic head trauma, and certain foods might be modestly associated with ALS risk, with a stronger association between risk and smoking. At the cellular level, these factors are all involved in generating oxidative stress. Experimental studies indicate that a combination of insults that induce modest oxidative stress can exert additive deleterious effects on motor neurons, suggesting multiple exposures in real-world environments are important. As the disease progresses, nutritional deficiency, cachexia, psychological stress, and impending respiratory failure may further increase oxidative stress. Moreover, accumulating evidence suggests that ALS is possibly a systemic disease. Laboratory, pathologic, and epidemiologic evidence clearly support the hypothesis that oxidative stress is central in the pathogenic process, particularly in genetically susceptive individuals. If we are to improve ALS treatment, well-designed biochemical and genetic epidemiological studies, combined with a multidisciplinary research approach, are needed and will provide knowledge crucial to our understanding of ALS etiology, pathophysiology, and prognosis.

D'Amico E; Factor-Litvak P; Santella RM; Mitsumoto H

2013-06-01

59

A Study Of Sporadic Adult Onset Degenerative Cerebellar Ataxias  

Directory of Open Access Journals (Sweden)

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

Sinha K K; Jha D K

1999-01-01

60

TERT promoter mutations in familial and sporadic melanoma.  

UK PubMed Central (United Kingdom)

Cutaneous melanoma occurs in both familial and sporadic forms. We investigated a melanoma-prone family through linkage analysis and high-throughput sequencing and identified a disease-segregating germline mutation in the promoter of the telomerase reverse transcriptase (TERT) gene, which encodes the catalytic subunit of telomerase. The mutation creates a new binding motif for Ets transcription factors and ternary complex factors (TCFs) near the transcription start and, in reporter gene assays, caused up to twofold increase in transcription. We then screened the TERT promoter in sporadic melanoma and observed recurrent ultraviolet signature somatic mutations in 125 of 168 (74%) of human cell lines derived from metastatic melanomas, 45 of 53 corresponding metastatic tumor tissues (85%), and 25 of 77 (33%) primary melanomas. The majority of those mutations occurred at two positions in the TERT promoter and also generated binding motifs for Ets/TCF transcription factors.

Horn S; Figl A; Rachakonda PS; Fischer C; Sucker A; Gast A; Kadel S; Moll I; Nagore E; Hemminki K; Schadendorf D; Kumar R

2013-02-01

 
 
 
 
61

Fanconi anaemia: from a monogenic disease to sporadic cancer.  

UK PubMed Central (United Kingdom)

The dissection of the molecular pathways participating in genetic instability disorders has rendered invaluable information about the mechanisms of cancer pathogenesis and progression, and is offering a unique opportunity to establish targeted anticancer therapies. Fanconi anaemia (FA) is a paradigm of cancer-prone inherited monogenic disorders. Moreover, accumulated evidence indicates that genetic and epigenetic alterations in FA genes can also play an important role in sporadic cancer in the general population. Here, we summarise current progress in the understanding of the molecular biology of FA and review the principal mechanisms accounting for a disrupted FA pathway in sporadic cancer. Additionally, we discuss the impact of these findings in the development of new anticancer therapies, particularly with DNA interstrand crosslinkers and with new inhibitors of the FA and/or alternative DNA repair pathways.

Valeri A; Martínez S; Casado JA; Bueren JA

2011-04-01

62

Critical upper airway obstruction in sporadic angioedema responding to C1-esterase inhibitor.  

UK PubMed Central (United Kingdom)

We describe a case of recurrent oropharyngeal angioedema in a 16-year-old boy with a history of sickle cell disease and thrombocytopenia and with no family history of angioedema. Emergency treatment of angioedema with C1-esterase inhibitor (C1-INH) provided immediate relief, avoiding the placement of a surgical airway. Further evaluation has shown C1-INH to be normal in quantity and function, with normal complement studies during acute attacks. Genetic testing revealed no abnormality in the factor XII gene. Our case exemplifies that even in cases of sporadic angioedema, treatment with C1-INH may be an effective and life-saving management strategy.

O'Keefe AW; McCusker C; Ben-Shoshan M

2013-01-01

63

Critical upper airway obstruction in sporadic angioedema responding to C1-esterase inhibitor.  

Science.gov (United States)

We describe a case of recurrent oropharyngeal angioedema in a 16-year-old boy with a history of sickle cell disease and thrombocytopenia and with no family history of angioedema. Emergency treatment of angioedema with C1-esterase inhibitor (C1-INH) provided immediate relief, avoiding the placement of a surgical airway. Further evaluation has shown C1-INH to be normal in quantity and function, with normal complement studies during acute attacks. Genetic testing revealed no abnormality in the factor XII gene. Our case exemplifies that even in cases of sporadic angioedema, treatment with C1-INH may be an effective and life-saving management strategy. PMID:23661661

O'Keefe, Andrew W; McCusker, Christine; Ben-Shoshan, Moshe

2013-05-08

64

Familial and sporadic hemiplegic migraine: diagnosis and treatment.  

UK PubMed Central (United Kingdom)

OPINION STATEMENT: Hemiplegic migraine (HM) is a rare subtype of migraine with aura, characterized by transient hemiparesis during attacks. Diagnosis is based on the International Classification of Headache Disorders criteria (ICHD-II). Two types of HM are recognized: familial (FHM) and sporadic hemiplegic migraine (SHM). HM is genetically heterogeneous. Three genes have been identified (CACNA1A, ATP1A2, and SCN1A) but more, so far unknown genes, are involved. Clinically, attacks of the 3 subtypes cannot be distinguished. The diagnosis can be confirmed but not ruled out by genetic testing, because in some HM patients other, not yet identified, genes are involved. The presence of additional symptoms (such as chronic ataxia or epilepsy) may increase the likelihood of identifying a mutation. Additional diagnostics like imaging, CSF analysis, or an EEG are mainly performed to exclude other causes of focal neurological symptoms associated with headache. Conventional cerebral angiography is contraindicated in HM because this may provoke an attack. Because HM is a rare condition, no clinical treatment trials are available in this specific subgroup of migraine patients. Thus, the treatment of HM is based on empirical data, personal experience of the treating neurologist, and involves a trial-and-error strategy. Acetaminophen and NSAIDs often are the first choice in acute treatment. Although controversial in HM, triptans can be prescribed when headaches are not relieved sufficiently with common analgesics. An effective treatment for the severe and often prolonged aura symptoms is more warranted, but currently no such acute treatment is available. Prophylactic treatment can be considered when attack frequency exceeds 2 attacks per month, or when severe attacks pose a great burden that requires reduction of severity and frequency. In no strictly preferred order, flunarizine, sodium valproate, lamotrigine, verapamil, and acetazolamide can be tried. While less evidence is available for prophylactic treatment with topiramate, candesartan, and pizotifen, these drugs can also be considered. The use of propranolol in HM is more controversial, but evidence of adverse effects is insufficient to contraindicate beta-blockers.

Pelzer N; Stam AH; Haan J; Ferrari MD; Terwindt GM

2013-02-01

65

Application of dopplionograms to an understanding of sporadic E  

Energy Technology Data Exchange (ETDEWEB)

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

Wright, J.W.

1982-03-01

66

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

UK PubMed Central (United Kingdom)

Mutations in parkin are the second most common known cause of Parkinson's disease (PD). Parkin is an ubiquitin E3 ligase that monoubiquitinates and polyubiquitinates proteins to regulate a variety of cellular processes. Loss of parkin's E3 ligase activity is thought to play a pathogenic role in both inherited and sporadic PD. Here, we review parkin biology and pathobiology and its role in the pathogenesis of PD.

Dawson TM; Dawson VL

2010-01-01

67

Insulin Signaling in Sporadic Alzheimer's Disease  

Science.gov (United States)

Excessive production of ?-amyloid (A?) peptides from proteolytic cleavage of amyloid precursor protein is believed to play a central role in the pathogenesis of Alzheimer’s disease (AD). In particular, accumulated intracellular A? is found in vulnerable neurons, and the soluble oligomers of A? peptides [also termed A?-derived diffusible ligands (ADDLs)] are highly toxic to neurons. Evidence shows that both extracellular and intracellular ADDLs can compromise insulin signaling. Extracellular ADDLs can bind to synapses and decrease membrane insulin receptors (IRs) through an insulin signaling–dependent mechanism. Intracellular A? inhibits IR signaling in neurons by interfering with the association between phosphoinositide-dependent kinase 1 and Akt1 to preclude Akt1 activation. Together, these findings suggest that agents that stimulate insulin signaling may have neuroprotective effects. Indeed, insulin and insulin sensitizers have been shown to improve cognitive and memory functions in animal models of AD, as well as in AD patients.

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

2009-06-09

68

Lightning-induced intensification of the ionospheric sporadic E layer.  

UK PubMed Central (United Kingdom)

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

Davis CJ; Johnson CG

2005-06-01

69

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

Directory of Open Access Journals (Sweden)

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

Emmanuel Uttah & Dominic C. Ibeh

2011-01-01

70

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

Directory of Open Access Journals (Sweden)

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

M. Gerding; M. Alpers; J. Höffner; U. von Zahn

0000-01-01

71

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

Directory of Open Access Journals (Sweden)

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

Victoria Eugenia Villegas; Fernando Velandia; Cesar Payán

2008-01-01

72

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

UK PubMed Central (United Kingdom)

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

Rafati M; Ghadirzadeh MR; Heshmati Y; Adibi H; Keihanidoust Z; Eshraghian MR; Dastan J; Hoseini A; Purhoseini M; Ghaffari SR

2012-01-01

73

Mutations in the PAX9 gene in sporadic oligodontia.  

UK PubMed Central (United Kingdom)

OBJECTIVES: Oligodontia, a congenital lack of six or more teeth, is often associated with mutations in the PAX9 gene; therefore, we searched for mutations in this gene. DESIGN: In the present work, we sequenced fragments of the PAX9 gene in individuals with sporadic oligodontia. Next, we genotyped some mutations we found in patients with oligodontia and individuals without tooth agenesis. SETTING AND SAMPLE POPULATION: DNA sequencing was performed in the material isolated from peripheral blood lymphocytes of six unrelated patients with sporadic, non-syndromic oligodontia. These patients were selected based upon explorative cluster analysis. Genotyping was performed in 38 patients with oligodontia and 100 control individuals. MATERIAL AND METHODS: Direct sequencing and restriction fragment length polymorphism PCR were employed. RESULTS: We detected two homozygotic substitutions, IVS2-109G>C and IVS2-54A>G, in intron 2 in three patients. Another homozygotic substitution in intron 2, IVS2-41A>G, was revealed in two patients. Two patients had an IVS3+40G>A homozygotic change in intron 3 and 4 patients displayed a 717C>T transition in exon 4 (silent mutation). One patient had a heterozygotic 718G>C transversion, resulting in a missense Ala240Pro substitution. We detected also several other intronic substitutions. Further genotyping of the IVS2-54A>G, IVS2-109G>C, and IVS2-41A>G mutations suggested that they can display polymorphic changes. CONCLUSION: The IVS2-54A>G, IVS2-109G>C, and IVS2-41A>G mutations of the PAX9 gene may represent polymorphism associated with sporadic oligodontia.

Pawlowska E; Janik-Papis K; Poplawski T; Blasiak J; Szczepanska J

2010-08-01

74

The influence of sporadic-E ion composition on the plasma irregularities induced by neutral turbulence in the layer  

Science.gov (United States)

Sporadic-E layers in the ionosphere can be produced by the wind-shear mechanism. This mechanism provides a redistribution of ionization through the interaction of plasma imbedded in the neutral wind with the geomagnetic field under appropriate vertical profile of the horizontal wind velocity. The mechanism is not very effective for the molecular ions which make up the greater part of the total ion content, since these have a lifetime less than the formation time of the layer; rather, the process acts on atomic metal ions. These are thought to have very long lifetimes in the E-region, since the recombination reaction for monatomic ions is very slow compared to the dissociative recombination of molecular ions. Data of observations show that the ion composition of sporadic-E differs from the normal E-region and most of ions in the layer peak are often metallic. Changes in the concentration of the ions provide changes in the mean ion mass, mi , in the layer and hence, changes in its mean parameters (e.g., the sporadic-E thickness, Ls ) and irregular structure. If a sporadic-E height is below the homopause, the neutral air turbulence exerts an essential influence on the layer and generates sporadic-E plasma irregularities. The present report is devoted to study of the influence of sporadic-E ion composition on such irregularities. The consideration was based on analytic expressions for the spectrum of the irregularities and their rms fluctuation level derived in the framework of macroscopic description of the sporadic-E plasma. The expressions were used for the case of mid-latitude sporadic-E (magnetic dip angle of 45° ) near altitude of 100 km when the layer was formed by a sinusoidal neutral wave with amplitude u0 =80 m/s and wavelength L0 =10 km, the level of turbulent mixing was unchanged and the turbulent energy dissipation rate was about 10 mW/kg. The concentrations of heavy metal ions in the layer changed so that mi increased from 31 to 51 AMU and hence the ratio of the ion gyrofrequency to the ion-neutral collision frequency decreased from 0.05 to 0.03. It was shown that the increase in the concentration of heavy metallic ions in the sporadic-E has resulted in the decrease in the level of plasma fluctuations and the increase in the power index if the irregularity spectrum is approximated by a simple power law k d . The fluctuation level has changed from 0.086 to 0.045 (for irregularity length-scales smaller 250 m) and the index d has changed from -3.0 to -2.6 (for wave-number range corresponding to the inertial range of turbulence). These changes can be mainly explained by an increase in the thickness Ls from 1.3 to 2.9 km in the present case.

Kyzyurov, Yurij

75

The monster sporadic group and a theory underlying superstring models  

International Nuclear Information System (INIS)

[en] 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

1996-01-01

76

Feasibility Analysis of Sporadic Real-Time Multiprocessor Task Systems  

CERN Multimedia

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

Bonifaci, Vincenzo

2010-01-01

77

The monster sporadic group and a theory underlying superstring models  

Energy Technology Data Exchange (ETDEWEB)

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.

Chapline, G.

1996-09-01

78

Novel BRAF Alteration in a Sporadic Pilocytic Astrocytoma.  

UK PubMed Central (United Kingdom)

Pilocytic astrocytoma (PA) is the most frequently encountered glial tumor (glioma or astrocytoma) in children. Recent studies have identified alterations in the BRAF serine/threonine kinase gene as the likely causative mutation in these childhood brain tumors. The majority of these genetic changes involve chromosome 7q34 tandem duplication, resulting in aberrant BRAF fusion transcripts. In this paper, we describe a novel KIAA1549:BRAF fusion transcript in a sporadic PA tumor associated with increased ERK activation and review the spectrum of BRAF genetic alterations in this common pediatric low-grade central nervous system neoplasm.

Dahiya S; Yu J; Kaul A; Leonard JR; Gutmann DH

2012-01-01

79

Screening of the PFN1 gene in sporadic amyotrophic lateral sclerosis and in frontotemporal dementia.  

Science.gov (United States)

Mutations in the profilin 1 (PFN1) gene, encoding a protein regulating filamentous actin growth through its binding to monomeric G-actin, have been recently identified in familial amyotrophic lateral sclerosis (ALS). Functional studies performed on ALS-associated PFN1 mutants demonstrated aggregation propensity, alterations in growth cone, and cytoskeletal dynamics. Previous screening of PFN1 gene in sporadic ALS (SALS) cases led to the identification of the p.E117G mutation, which is likely to represent a less pathogenic variant according to both frequency data in control subjects and cases, and functional experiments. To determine the effective contribution of PFN1 mutations in SALS, we analyzed a large cohort of 1168 Italian SALS patients and also included 203 frontotemporal dementia (FTD) cases because of the great overlap between these 2 neurodegenerative diseases. We detected the p.E117G variant in 1 SALS patient and the novel synonymous change p.G15G in another patient, but none in a panel of 1512 control subjects. Our results suggest that PFN1 mutations in sporadic ALS and in FTD are rare, at least in the Italian population. PMID:23063648

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

2012-10-11

80

Screening of the PFN1 gene in sporadic amyotrophic lateral sclerosis and in frontotemporal dementia.  

UK PubMed Central (United Kingdom)

Mutations in the profilin 1 (PFN1) gene, encoding a protein regulating filamentous actin growth through its binding to monomeric G-actin, have been recently identified in familial amyotrophic lateral sclerosis (ALS). Functional studies performed on ALS-associated PFN1 mutants demonstrated aggregation propensity, alterations in growth cone, and cytoskeletal dynamics. Previous screening of PFN1 gene in sporadic ALS (SALS) cases led to the identification of the p.E117G mutation, which is likely to represent a less pathogenic variant according to both frequency data in control subjects and cases, and functional experiments. To determine the effective contribution of PFN1 mutations in SALS, we analyzed a large cohort of 1168 Italian SALS patients and also included 203 frontotemporal dementia (FTD) cases because of the great overlap between these 2 neurodegenerative diseases. We detected the p.E117G variant in 1 SALS patient and the novel synonymous change p.G15G in another patient, but none in a panel of 1512 control subjects. Our results suggest that PFN1 mutations in sporadic ALS and in FTD are rare, at least in the Italian population.

Tiloca C; Ticozzi N; Pensato V; Corrado L; Del Bo R; Bertolin C; Fenoglio C; Gagliardi S; Calini D; Lauria G; Castellotti B; Bagarotti A; Corti S; Galimberti D; Cagnin A; Gabelli C; Ranieri M; Ceroni M; Siciliano G; Mazzini L; Cereda C; Scarpini E; Sorarù G; Comi GP; D'Alfonso S; Gellera C; Ratti A; Landers JE; Silani V

2013-05-01

 
 
 
 
81

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

Science.gov (United States)

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

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

2008-04-28

82

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

UK PubMed Central (United Kingdom)

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.

Salas A; Vega A; Milne RL; García-Magariños M; Ruibal A; Benítez J; Carracedo A

2008-01-01

83

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

Directory of Open Access Journals (Sweden)

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 identi?ed 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 ?anking 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 ?rst study of the ZBTB7 gene in relation to, sporadic breast cancer, we found no evidence of an association.

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

2008-01-01

84

A novel peripherin gene (PRPH) mutation identified in one sporadic amyotrophic lateral sclerosis patient.  

Science.gov (United States)

Motor neurons in amyotrophic lateral sclerosis (ALS) are characterized by the presence of inclusion bodies composed of intermediate filament (IF) proteins. Peripherin protein is as components of these inclusions and rare mutations in peripherin gene (PRPH) were identified in sporadic ALS cases. The aim of this study was to further define the spectrum of PRPH mutations in a cohort of 122 Italian ALS patients. We screened the coding sequence, the exon/intron boundaries, and the 5'-3' un-translated regions (UTRs) in 122 ALS patients. Eighteen sequence variations were detected. Seven variants were not identified in a panel of at least 245 matched controls, including 2 missense variations, namely p.R133P and p.D141Y, each identified in one heterozygous patient. p.R133P was newly identified whereas p.D141Y was previously described in one homozygous sporadic ALS patient. These 2 variants were predicted to have a deleterious effect on protein structure or function. This work contributes to determine the role of PRPH gene variants in ALS. Further studies are necessary to define the mechanisms through which the mutant peripherin could cause ALS phenotype. PMID:20363051

Corrado, Lucia; Carlomagno, Yari; Falasco, Luca; Mellone, Simona; Godi, Michela; Cova, Emanuela; Cereda, Cristina; Testa, Lucia; Mazzini, Letizia; D'Alfonso, Sandra

2010-04-03

85

A novel peripherin gene (PRPH) mutation identified in one sporadic amyotrophic lateral sclerosis patient.  

UK PubMed Central (United Kingdom)

Motor neurons in amyotrophic lateral sclerosis (ALS) are characterized by the presence of inclusion bodies composed of intermediate filament (IF) proteins. Peripherin protein is as components of these inclusions and rare mutations in peripherin gene (PRPH) were identified in sporadic ALS cases. The aim of this study was to further define the spectrum of PRPH mutations in a cohort of 122 Italian ALS patients. We screened the coding sequence, the exon/intron boundaries, and the 5'-3' un-translated regions (UTRs) in 122 ALS patients. Eighteen sequence variations were detected. Seven variants were not identified in a panel of at least 245 matched controls, including 2 missense variations, namely p.R133P and p.D141Y, each identified in one heterozygous patient. p.R133P was newly identified whereas p.D141Y was previously described in one homozygous sporadic ALS patient. These 2 variants were predicted to have a deleterious effect on protein structure or function. This work contributes to determine the role of PRPH gene variants in ALS. Further studies are necessary to define the mechanisms through which the mutant peripherin could cause ALS phenotype.

Corrado L; Carlomagno Y; Falasco L; Mellone S; Godi M; Cova E; Cereda C; Testa L; Mazzini L; D'Alfonso S

2011-03-01

86

Characteristics of the Lower Thermosphere and Ionospheric D Region Deduced From High Time-Resolution Sporadic E-Layer Data During the Solar Eclipse of August 1, 2008  

Science.gov (United States)

The digital ionosonde at Sodankylä Geophysical Observatory, Finland, is performing continuous high time resolution soundings since the beginning of IPY in 2007. During the partial solar eclipse which occurred on first of August, 2008, a stable sporadic E layer was observed with the ionosonde. Using the time development of the recorded echo power of the sporadic E trace at different frequencies as a constraint, we analyse the underlying lower thermospheric and ionospheric D-region characteristics, by applying a detailed coupled ion and neutral chemistry model SIC (Sodankyla Ion Chemistry model), together with modeling of the radio wave propagation and absorption. Use of a simplified ion chemistry model is compared with the use of the SIC model. While the expected effect of the solar eclipse on E-layer critical frequency cannot be seen due to the existence of the sporadic E layer, ionisation in the D-region is consistent with the variation of solar radiation during the eclipse.

Enell, C.; Turunen, E.; Kero, A.; Ulich, T.; Tapaninen, O.; Kaaretkoski, H.; Karppinen, T.

2008-12-01

87

Anorectal function and morphology in patients with sporadic proctalgia fugax.  

UK PubMed Central (United Kingdom)

PURPOSE: The pathophysiology of sporadic proctalgia fugax remains unknown. This study investigates whether patients with this syndrome exhibit alterations in anal function and morphology. METHODS: Eighteen patients with sporadic proctalgia fugax and 18 sex-matched and age-matched healthy controls were studied. Manometric studies investigated anal resting and squeeze pressures, the rectoanal inhibitory reflex, rectal compliance, and smooth muscle response to edrophonium chloride administration. External and internal sphincter thickness was measured endosonographically. RESULTS: Patients had slightly higher (P = 0.0291) anal resting pressures (65.5 +/- 11.4 mmHg) than controls (56 +/- 9.9 mmHg). However, anal squeeze pressure, sphincter relaxation during rectal distention, and rectal compliance were similar in both groups, and no alterations were detected in external and internal anal sphincter thickness. Edrophonium chloride administration was followed by sharp postrelaxation contractions in two patients, whereas anal function remained unaltered in controls. Acute episodes of proctalgia, which occurred in two patients while under study, were associated with a rise in anal resting tone and an increase in slow wave amplitude. CONCLUSIONS: In the resting state, patients with proctalgia fugax have normal anorectal function and morphology. However, they may exhibit a motor abnormality of the anal smooth muscle during an acute attack.

Eckardt VF; Dodt O; Kanzler G; Bernhard G

1996-07-01

88

Expression of EMSY gene in sporadic ovarian cancer.  

UK PubMed Central (United Kingdom)

The majority of familial breast and ovarian cancers arise from mutations in the BRCA1 and BRCA2 genes. Amplification at the 11q13.5 locus is commonly observed in breast and ovarian cancers. In 2003, Hughes-Davies et al. identified a novel gene (EMSY) at this locus which binds BRCA2 within a region deleted in some cancers. Although little is known about the cellular role of EMSY, indirect evidence suggests that this nuclear protein is capable of silencing the activation potential of BRCA2. In this study we aimed to investigate expression of the EMSY gene and its protein product in sporadic ovarian cancer. Real-time quantitative RT-PCR was performed in 50 ovarian cancer and 17 normal ovarian tissue samples. Overexpression of the EMSY gene was found in 6/50 cases (12%), but in none of the control samples. To determine the EMSY protein by Western blotting, semi-quantitative analysis of the EMSY protein was performed using the Scion Image Gel Analysis Program. Statistical analysis was performed using SPSS 11.5. All patients having EMSY overexpression also displayed increased levels of the EMSY protein. Sporadic ovarian cancer shows overexpression of EMSY at a prevalence similar to that found in breast cancer and the overexpression is correlated with the protein level.

Altinisik J; Karateke A; Coksuer H; Ulutin T; Buyru N

2011-01-01

89

Study of sporadic-E clouds by backscatter radar  

Directory of Open Access Journals (Sweden)

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

Z. Houminer; C. J. Russell; P. L. Dyson; J. A. Bennett

0000-01-01

90

Sporadic unilateral vestibular schwannoma with islets of meningioma: case report.  

UK PubMed Central (United Kingdom)

OBJECTIVE AND IMPORTANCE: Vestibular schwannomas with meningioma islets have been rarely reported in the literature; they have been observed only among patients with neurofibromatosis Type II. We present a case of a sporadic mixed tumor in a patient without neurofibromatosis Type II that was not suspected before surgery. CLINICAL PRESENTATION: A 59-year-old female patient presented with clinical signs of progressive loss of hearing. Her family history did not include evidence of neurological diseases. Magnetic resonance imaging scans revealed a typical unilateral vestibular schwannoma. INTERVENTION: The tumor presented with invasion of the surrounding arachnoid membrane, as well as Cranial Nerves VII and VIII. Preservation of the facial nerve with complete removal of the tumor was not possible. Therefore, Cranial Nerve VII reconstruction was performed. CONCLUSION: The concomitant occurrence of schwannomas and meningiomas infiltrating the arachnoid membrane might be related to poor clinical outcomes for patients with neurofibromatosis Type II, with respect to preservation of facial and acoustic nerves. Among sporadic schwannomas, this phenomenon is extremely rare.

Lüdemann W; Stan AC; Tatagiba M; Samii M

2000-08-01

91

Calpastatin Gene (CAST) Is Not Associated with Late Onset Sporadic Parkinson's Disease in the Han Chinese Population.  

UK PubMed Central (United Kingdom)

Recent studies point to an association between the late-onset sporadic Parkinson's disease (PD) and single nucleotide polymorphisms (SNPs) rs1559085 and rs27852 in Ca(2+)-dependent protease calpain inhibitor calpastatin (CAST) gene. This finding is of interest since loss of CAST activity could result in over activated calpain, potentially leading to Ca(2+) dysregulation and loss of substantia nigra neurons in PD. We explored the association between CAST SNPs and late-onset sporadic PD in the Han Chinese population. The study included 615 evaluable patients (363 male, 252 female) with PD and 636 neurologically healthy controls (380 male, 256 female) matched for age, gender, ethnicity, and area of residence. PD cases were identified from the PD cohort of the Chinese National Consortium on Neurodegenerative Diseases (www.chinapd.cn). A total of 24 tag-SNPs were genotyped capturing 95% of the genetic variation across the CAST gene. There was no association found between any of the polymorphisms and PD in all models tested (co-dominant, dominant-effect and recessive-effect). Similarly, none of the common haplotypes was associated with a risk for PD. Our data do not support a significant association between the CAST gene polymorphisms and late onset sporadic PD in the Han Chinese population.

Zhang L; Ding H; Wang DH; Zhang YL; Baskys A; Chan P; Zhong Y; Cai YN

2013-01-01

92

Levy diffusion as an effect of sporadic randomness  

CERN Multimedia

The Levy diffusion processes are a form of non ordinary statistical mechanics resting, however, on the conventional Markov property. As a consequence of this, their dynamic derivation is possible provided that (i) a source of randomness is present in the corresponding microscopic dynamics and (ii) that the consequent process of memory erasure is properly taken into account by the theoretical treatment.

Bologna, M; Riccardi, J; Bologna, Mauro; Grigolini, Paolo; Riccardi, Juri

1999-01-01

93

Sporadic observation of the Fleischmann-Pons heat effect  

International Nuclear Information System (INIS)

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

1989-01-01

94

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1996-11-01

95

[Functional abnormalities of complement in familial and sporadic ankylosing spondylitis  

UK PubMed Central (United Kingdom)

Levels of complement fractions of 12 patients with sporadic ankylosing Spondylitis and 6 patients with familial Ankylosing Spondylitis (N. Y. Criteria) were studied by an hemolytic and functional method (microhemolysis in plate. Cordis Lab. Miami, Fla. USA). Abnormal levels were found in 94% of them high levels of C1 and C2 (p 0.002), and C3 (p 0.05) C8 and C9 (p 0.001) deficiencies, mixed or isolated, correlated with the severity of the diseases. C9 deficiency belongs to familial Ankylosing Spondylitis. These functional deficiencies of serum complement can favor the colonization and persistence of germs, which could mediate in the genesis of Ankylosing Spondylitis.

Jiménez Balderas FJ; Rico Rosillo G; Bravo Gatica C; Mintz Spiro G

1989-01-01

96

Balloon dilation in sporadic inclusion body myositis patients with Dysphagia.  

UK PubMed Central (United Kingdom)

Here, we describe balloon catheter dilation at the upper esophageal sphincter (UES) in three sporadic inclusion body myositis (s-IBM) patients with dysphagia. Initially, we performed IVIg therapy, and, three months later, switched to balloon dilation therapy. A 12-Fr balloon catheter was inserted from the mouth under fluoroscopy and the balloon inflated at the UES. The catheter was pulled back and re-inserted several times. We examined videofluoroscopy (VF) and pressure at the oropharynx, hypopharynx and UES using computed pharyngoesophageal manometry (CPM). Before both therapies, the VF study revealed a very small amount of barium paste passing through the UES. After balloon dilation therapy, as well as IVIg, subjective complaints of dysphagia disappeared and the VF study revealed an increased amount of barium paste passing through the UES. We conclude that balloon dilation therapy is a complementary method for conventional dysphagia therapies in s-IBM patients with dysphagia.

Murata KY; Kouda K; Tajima F; Kondo T

2013-01-01

97

Sporadic inclusion body myositis presenting with severe camptocormia.  

UK PubMed Central (United Kingdom)

Sporadic inclusion body myositis (sIBM) is a slowly progressive idiopathic inflammatory myopathy. The characteristic early quadriceps and finger flexor muscle weakness often leads to the diagnosis of sIBM, especially when all canonical pathological features of sIBM are not present on muscle biopsy. Weakness of the paraspinal muscles, resulting in head drop and/or camptocormia, is a rare clinical finding along the course of sIBM, and even more rare as the presenting feature. We describe two patients with sIBM manifesting with camptocormia as the sole clinical manifestation for several years prior to the diagnosis by muscle biopsy. This observation emphasizes the role of sIBM in the etiology of camptocormia and the need to consider this common myopathy as a cause of weakness, despite the lack of classic quadriceps and finger flexor muscle weakness years after the onset of the paraspinal muscle weakness.

Ma H; McEvoy KM; Milone M

2013-09-01

98

Balloon dilation in sporadic inclusion body myositis patients with Dysphagia.  

Science.gov (United States)

Here, we describe balloon catheter dilation at the upper esophageal sphincter (UES) in three sporadic inclusion body myositis (s-IBM) patients with dysphagia. Initially, we performed IVIg therapy, and, three months later, switched to balloon dilation therapy. A 12-Fr balloon catheter was inserted from the mouth under fluoroscopy and the balloon inflated at the UES. The catheter was pulled back and re-inserted several times. We examined videofluoroscopy (VF) and pressure at the oropharynx, hypopharynx and UES using computed pharyngoesophageal manometry (CPM). Before both therapies, the VF study revealed a very small amount of barium paste passing through the UES. After balloon dilation therapy, as well as IVIg, subjective complaints of dysphagia disappeared and the VF study revealed an increased amount of barium paste passing through the UES. We conclude that balloon dilation therapy is a complementary method for conventional dysphagia therapies in s-IBM patients with dysphagia. PMID:23362370

Murata, Ken-Ya; Kouda, Ken; Tajima, Fumihiro; Kondo, Tomoyoshi

2013-01-14

99

Sporadic inclusion body myositis presenting with severe camptocormia.  

Science.gov (United States)

Sporadic inclusion body myositis (sIBM) is a slowly progressive idiopathic inflammatory myopathy. The characteristic early quadriceps and finger flexor muscle weakness often leads to the diagnosis of sIBM, especially when all canonical pathological features of sIBM are not present on muscle biopsy. Weakness of the paraspinal muscles, resulting in head drop and/or camptocormia, is a rare clinical finding along the course of sIBM, and even more rare as the presenting feature. We describe two patients with sIBM manifesting with camptocormia as the sole clinical manifestation for several years prior to the diagnosis by muscle biopsy. This observation emphasizes the role of sIBM in the etiology of camptocormia and the need to consider this common myopathy as a cause of weakness, despite the lack of classic quadriceps and finger flexor muscle weakness years after the onset of the paraspinal muscle weakness. PMID:24055211

Ma, Haihan; McEvoy, Kathleen M; Milone, Margherita

2013-09-19

100

El Nino Southern Oscillation as Sporadic Oscillations between Metastable States  

CERN Multimedia

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

Ma, Tian

2008-01-01

 
 
 
 
101

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

Science.gov (United States)

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

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

1997-06-01

102

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

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Patients with hereditary non-poliposys colorectal cancer (HNPCC) have better prognosis than sporadic colorectal cancer (CRC). Aim of our retrospective study was to compare the overall survival between sporadic CRC and HNPCC patients. Methods We analyzed a cohort of 40 (25 males and 15 females) HNPCC cases with a hospital consecutive series of 573 (312 males and 261 females) sporadic CRC observed during the period 1970–1993. In 15 HNPCC patients we performed mutational analysis for microsatellite instability. Survival rates were calculated by Kaplan-Meier method and compared with log rank test. Results The median age at diagnosis of the primary CRC was 46.8 years in the HNPCC series versus 61 years in sporadic CRC group. In HNPCC group 85% had a right cancer location, vs. 57% in the sporadic cancer group. In the sporadic cancer group 61.6% were early-stages cancer (Dukes' A and B) vs. 70% in the HNPCC group (p = ns). The crude 5-years cumulative survival after the primary CRC was 94.2% in HNPCC patients vs. 75.3% in sporadic cancer patients (p Conclusion Our results show that overall survival of colorectal cancer in patients with HNPCC is better than sporadic CRC patients. The different outcome probably relates to the specific tumorigenesis involving DNA mismatch repair dysfunction.

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

2008-01-01

103

Somatic mutations in the BRCA1 gene in Chinese sporadic breast and ovarian cancer  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Inherited mutations in the BRCA1 gene confer increased susceptibility to breast and ovarian cancer. Its role in sporadic carcinogenesis is not well defined. Somatic mutations in breast cancers have not been reported and to date there are only three reports of somatic mutations in sporadic ovarian ca...

Khoo, US; Ozcelik, H; Cheung, ANY; Chow, LWC; Ngan, HYS; Done, SJ; Liang, ACT; Chan, VWY; Au, GKH; Ng, WF; Poon, CSP; Leung, YF

104

Prevalence of Huntington's disease gene CAG repeat alleles in sporadic amyotrophic lateral sclerosis patients.  

Science.gov (United States)

A higher prevalence of intermediate ataxin-2 CAG repeats in amyotrophic lateral sclerosis (ALS) patients has raised the possibility that CAG expansions in other polyglutamine disease genes could contribute to ALS neurodegeneration. We sought to determine whether expansions of the CAG repeat of the HTT gene that causes Huntington's disease, are associated with ALS. We compared the HTT CAG repeat length on a total of 3144 chromosomes from 1572 sporadic ALS patients and 4007 control chromosomes, and also tested its possible effects on ALS-specific parameters, such as age and site of onset and survival rate. Our results show that the CAG repeat in the HTT gene is not a risk factor for ALS nor modifies its clinical presentation. These findings suggest that distinct neuronal degeneration processes are involved in these two different neurodegenerative disorders. PMID:22409360

Ramos, Eliana Marisa; Keagle, Pamela; Gillis, Tammy; Lowe, Patrick; Mysore, Jayalakshmi S; Leclerc, Ashley Lyn; Ratti, Antonia; Ticozzi, Nicola; Gellera, Cinzia; Gusella, James F; Silani, Vincenzo; Alonso, Isabel; Brown, Robert H; MacDonald, Marcy E; Landers, John E

2012-03-13

105

Prevalence of Huntington's disease gene CAG repeat alleles in sporadic amyotrophic lateral sclerosis patients.  

UK PubMed Central (United Kingdom)

A higher prevalence of intermediate ataxin-2 CAG repeats in amyotrophic lateral sclerosis (ALS) patients has raised the possibility that CAG expansions in other polyglutamine disease genes could contribute to ALS neurodegeneration. We sought to determine whether expansions of the CAG repeat of the HTT gene that causes Huntington's disease, are associated with ALS. We compared the HTT CAG repeat length on a total of 3144 chromosomes from 1572 sporadic ALS patients and 4007 control chromosomes, and also tested its possible effects on ALS-specific parameters, such as age and site of onset and survival rate. Our results show that the CAG repeat in the HTT gene is not a risk factor for ALS nor modifies its clinical presentation. These findings suggest that distinct neuronal degeneration processes are involved in these two different neurodegenerative disorders.

Ramos EM; Keagle P; Gillis T; Lowe P; Mysore JS; Leclerc AL; Ratti A; Ticozzi N; Gellera C; Gusella JF; Silani V; Alonso I; Brown RH Jr; MacDonald ME; Landers JE

2012-05-01

106

Prospective markers for early diagnosis and prognosis of sporadic pancreatic ductal adenocarcinoma.  

UK PubMed Central (United Kingdom)

BACKGROUND AND AIM: Sporadic pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer. No proven screening strategies are available and frequent cross-sectional imaging studies (CT/MRI) are impractical even in patients thought to be at higher risk than the general population. Few PDA biomarkers have been studied prospectively for screening. Here, we prospectively evaluated the Adnab-9 monoclonal antibody in stool, pancreaticobiliary secretions, and tissue for screening and prognostic value in sporadic PDA. We also evaluated the prognostic value of characterized early biomarkers in pancreaticobiliary secretions. METHODS: Adnab-9 diagnostic ability was tested in stool in 249 and 1,132 patients from China and the US, respectively. Immunohistochemistry was performed in 22 tissue samples with Adnab-9 antibody and anti-Defensin 5, a constituent of Paneth cells. Pancreatobiliary secretions were collected from 12 PDA patients and 9 controls. The enriched PCR method was performed to detect K-ras mutations. ELISA was performed with Adnab-9, anti-Her-2/neu, and monoclonal antibody D4 (anti-Reg I). RESULTS: Adnab-9 alone was diagnostic and prognostic when measured in pancreatic secretions, feces, and tissues of PDA patients compared to controls (p < 0.05). Significantly, Adnab-9 fecal binding can precede the clinical diagnosis by 2.3 years, potentially allowing earlier clinical intervention. In pancreatic secretions, a combination of K-ras and Her-2/neu when appropriately standardized can be diagnostic in 75 % of PDA. CONCLUSIONS: Our study suggests that Adnab-9 may be an effective marker for diagnosis and prognosis of PDA. Adnab-9 may be reflective of the presence of Paneth cells confirmed by Defensin-5 staining. These cells may modulate the biological activity of the cancer and confer a better prognosis.

Tobi M; Kim M; Weinstein DH; Rambus MA; Hatfield J; Adsay NV; Levi E; Evans D; Lawson MJ; Fligiel S

2013-03-01

107

Lack of association between BST1 polymorphisms and sporadic Parkinson's disease in a Japanese population.  

UK PubMed Central (United Kingdom)

Several genome-wide association studies and case-control studies have investigated the relationships between single nucleotide polymorphisms (SNPs) in the BST1 gene and Parkinson's disease (PD), but the results have been inconsistent. We examined the relationships between SNPs rs11931532, rs12645693, and rs11724635 and the risk of sporadic PD in Japan. Included were 229 cases within 6years of onset of PD as defined according to the UK PD Society Brain Bank clinical diagnostic criteria. Controls were 357 inpatients and outpatients without neurodegenerative disease. SNPs rs11931532 and rs12645693 were not significantly related to sporadic PD. Compared with a reference group of subjects with the CC genotype of SNP rs11724635, those with the AA genotype had a marginally significantly increased risk of sporadic PD: the adjusted OR was 1.57 (95% CI: 0.95-2.61, P=0.08). No significant interactions were found between BST1 SNP rs11724635 and smoking or caffeine intake with respect to sporadic PD. The current study failed to detect significant relationships between BST1 SNPs rs11931532, rs12645693, and rs11724635 and sporadic PD; however, the relationship between SNP rs11724635 and sporadic PD was of borderline significance. We do not find evidence for interactions between smoking or caffeine intake and SNP rs11724635 affecting sporadic PD.

Miyake Y; Tanaka K; Fukushima W; Kiyohara C; Sasaki S; Tsuboi Y; Yamada T; Oeda T; Shimada H; Kawamura N; Sakae N; Fukuyama H; Hirota Y; Nagai M

2012-12-01

108

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

Science.gov (United States)

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

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

2004-08-01

109

Graphical modelling of molecular networks underlying sporadic inclusion body myositis.  

UK PubMed Central (United Kingdom)

Here we present a novel statistical methodology that allows us to analyze gene expression data that have been collected from a number of different cases or conditions in a unified framework. Using a Bayesian nonparametric framework we develop a hierarchical model wherein genes can maintain a shared set of interactions between different cases, whilst also exhibiting behaviour that is unique to specific cases, sets of conditions, or groups of data points. By doing so we are able to not only combine data from different cases but also to discern the unique regulatory interactions that differentiate the cases. We apply our method to clinical data collected from patients suffering from sporadic Inclusion Body Myositis (sIBM), as well as control samples, and demonstrate the ability of our method to infer regulatory interactions that are unique to the disease cases of interest. The method thus balances the statistical need to include as many patients and controls as possible, and the clinical need to maintain potentially cryptic differences among patients and between patients and controls at the regulatory level.

Thorne T; Fratta P; Hanna MG; Cortese A; Plagnol V; Fisher EM; Stumpf MP

2013-07-01

110

Prognosis and prognostic factors in sporadic inclusion body myositis.  

UK PubMed Central (United Kingdom)

OBJECTIVES: To describe the course of change in muscle strength sporadic inclusion body myositis (IBM) patients. MATERIAL AND METHODS: We have studied a cohort of 66 IBM pateints using a hand-held dynamometer. RESULTS: Follow-up during a mean of 61.1 months showed a deterioration of on average -0.79% per month. The 'natural course' without immunosuppressive treatment (IS), analyzed in 43 patients (mean 46.4 months) was mean -1.03% per month. Loss of muscle power was most rapid in knee extension -1.12% (P < 0.001 when compared with elbow flexion, elbow extension and hip flexion). There was a tendency towards a more rapid decline in males than females and over the first 5 years after onset, while the level of serum creatine kinase (CK), age, or region affected at onset did not predict the prognosis. The mean change during periods with any IS treatment was -0.76% per month which was significantly lower compared to the total of untreated periods -1.03% (P < 0.05). Patients (n = 13) treated with mykofenolatmofetil showed a better prognosis of -0.67% per month (P < 0.05). In this group elbow flexion and extension and hip flexion showed a positive response, while knee extension was seemingly unaffected. CONCLUSIONS: There is a mean of 1% loss in power per month in the untreated IBM patient - the rate of loss was greater in the quadriceps muscle and in untreated compared with IS-treated patients.

Lindberg C; Oldfors A

2012-05-01

111

Graphical modelling of molecular networks underlying sporadic inclusion body myositis.  

Science.gov (United States)

Here we present a novel statistical methodology that allows us to analyze gene expression data that have been collected from a number of different cases or conditions in a unified framework. Using a Bayesian nonparametric framework we develop a hierarchical model wherein genes can maintain a shared set of interactions between different cases, whilst also exhibiting behaviour that is unique to specific cases, sets of conditions, or groups of data points. By doing so we are able to not only combine data from different cases but also to discern the unique regulatory interactions that differentiate the cases. We apply our method to clinical data collected from patients suffering from sporadic Inclusion Body Myositis (sIBM), as well as control samples, and demonstrate the ability of our method to infer regulatory interactions that are unique to the disease cases of interest. The method thus balances the statistical need to include as many patients and controls as possible, and the clinical need to maintain potentially cryptic differences among patients and between patients and controls at the regulatory level. PMID:23595110

Thorne, Thomas; Fratta, Pietro; Hanna, Michael G; Cortese, Andrea; Plagnol, Vincent; Fisher, Elizabeth M; Stumpf, Michael P H

2013-04-17

112

Mid-latitude lidar observations of large sporadic sodium layers  

Energy Technology Data Exchange (ETDEWEB)

During the early morning of October 31, 1988 two large sporadic Na (Na{sub s}) layers were observed near the mesopause above Urbana, IL (40{degree}N, 88{degree}W) with a Na lidar system. The layers began forming near 102 km at 0026 LST and 0110 LST and moved downward with vertical velocities as high as 4 ms{sup {minus}1} before dissipating between 94 and 96 km. The duration of each layer was approximately 80 min. The layers were narrow ({approximately} 1 km FWHM) and dense with maximum densities approaching 7,800 cm{sup {minus}3}. The characteristics of these two Na{sub s} layers are very similar to those of similar phenomena observed recently at Andoya, Norway and Mauna Kea, Hawaii. Lidar observations of the mesospheric Na layer have been conducted routinely by several groups at mid-latitudes for almost 20 years. Although large Na{sub s} layers now appear to be relatively common at low- and high-latitudes, to our knowledge the two layers described in this letter are only the second observation of this puzzling phenomenon at mid-latitudes.

Senft, D.C.; Collins, R.L.; Gardner, C.S. (Univ. of Illinois, Urbana (USA))

1989-07-01

113

Argyrophilic grain disease is a sporadic 4-repeat tauopathy.  

UK PubMed Central (United Kingdom)

Argyrophilic grain disease (AGD) was first reported as an adult-onset dementia, but recent studies have emphasized personality change, emotional imbalance, and memory problems as clinical features of AGD. AGD is characterized by spindle- or comma-shaped argyrophilic grains in the neuropil of entorhinal cortex, hippocampus, and amygdala. Immunohistochemistry with monoclonal antibodies specific to tau isoforms with four (4R) or three (3R) repeats in the microtubule-binding domain showed immunostaining of grains with 4R, but not 3R, tau antibodies, suggesting that AGD was a 4R tauopathy. The tau isoform composition of AGD was confirmed with densitometric analysis of Western blots of sarkosyl-insoluble tau from the medial temporal lobe of AGD brains with a range of concurrent neurofibrillary pathology and compared with Alzheimer controls. The 4R/3R ratio was 1 or less for Alzheimer disease; the 4R/3R ratio was more than 1 for AGD, decreasing with increasing neurofibrillary pathology and demonstrating that insoluble tau in AGD was enriched in 4R tau. The frequency of the extended tau haplotype was not different in AGD compared to other sporadic 4R tauopathies, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Furthermore, AGD occurred in PSP and CBD more frequently than in dementia controls, including Alzheimer disease. These results suggest that AGD, PSP and CBD are 4R tauopathies that share common pathologic, biochemical, and genetic characteristics.

Togo T; Sahara N; Yen SH; Cookson N; Ishizawa T; Hutton M; de Silva R; Lees A; Dickson DW

2002-06-01

114

Clinical characteristics of hereditary and sporadic medullary thyroid carcinoma.  

UK PubMed Central (United Kingdom)

OBJECTIVE: To study the clinical characteristics and outcomes of the hereditary medullary thyroid carcinoma (HMTC) and the sporadic medullary thyroid carcinoma (SMTC). METHODS: The clinical data of 78 patients with medullary thyroid carcinoma who underwent surgery in our hospital between July 1980 and May 2011 were retrospectively analyzed. RESULTS: Of these 78 patients, there were 23 HMTC cases and 55 SMTC cases. The HMTC group was significantly younger age of onset [(36.4±13.5) years vs. (46.6±11.2) years, P<0.01] and a lower pre/post-operative serum calcitonin levels [(850.4±110.20) ng/L vs. (1450.4±118.3) ng/L, P<0.01 and (410.8±133.2) ng/L vs. (1585.4±129.5) ng/L, P<0.01] than the SMTC group. In addition, the mean tumor diameter was also significantly smaller in the HMTC group (14.3 mm vs. 21.0 mm in SMTC group, P<0.05). Tumor multifocality was seen in a significantly higher proportion of HMTC cases compared with the SMTC cases (56.6% vs. 29.1%, P<0.05). The overall 10-year survival was 100% in HMTC group and 80.2% in SMTC group (P<0.05). CONCLUSION: HMTC has a better prognosis than SMTC.

Xu L; Zhao YP; Wang WB; Zhang TP; Liao Q; Chen G; Zhou L; Shu H

2012-08-01

115

SuprimeCam Observation of Sporadic Meteors during Perseids 2004  

CERN Multimedia

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

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

2007-01-01

116

Staging of brain pathology related to sporadic Parkinson's disease.  

Science.gov (United States)

Sporadic Parkinson's disease involves multiple neuronal systems and results from changes developing in a few susceptible types of nerve cells. Essential for neuropathological diagnosis are alpha-synuclein-immunopositive Lewy neurites and Lewy bodies. The pathological process targets specific induction sites: lesions initially occur in the dorsal motor nucleus of the glossopharyngeal and vagal nerves and anterior olfactory nucleus. Thereafter, less vulnerable nuclear grays and cortical areas gradually become affected. The disease process in the brain stem pursues an ascending course with little interindividual variation. The pathology in the anterior olfactory nucleus makes fewer incursions into related areas than that developing in the brain stem. Cortical involvement ensues, beginning with the anteromedial temporal mesocortex. From there, the neocortex succumbs, commencing with high order sensory association and prefrontal areas. First order sensory association/premotor areas and primary sensory/motor fields then follow suit. This study traces the course of the pathology in incidental and symptomatic Parkinson cases proposing a staging procedure based upon the readily recognizable topographical extent of the lesions. PMID:12498954

Braak, Heiko; Del Tredici, Kelly; Rüb, Udo; de Vos, Rob A I; Jansen Steur, Ernst N H; Braak, Eva

117

Staging of brain pathology related to sporadic Parkinson's disease.  

UK PubMed Central (United Kingdom)

Sporadic Parkinson's disease involves multiple neuronal systems and results from changes developing in a few susceptible types of nerve cells. Essential for neuropathological diagnosis are alpha-synuclein-immunopositive Lewy neurites and Lewy bodies. The pathological process targets specific induction sites: lesions initially occur in the dorsal motor nucleus of the glossopharyngeal and vagal nerves and anterior olfactory nucleus. Thereafter, less vulnerable nuclear grays and cortical areas gradually become affected. The disease process in the brain stem pursues an ascending course with little interindividual variation. The pathology in the anterior olfactory nucleus makes fewer incursions into related areas than that developing in the brain stem. Cortical involvement ensues, beginning with the anteromedial temporal mesocortex. From there, the neocortex succumbs, commencing with high order sensory association and prefrontal areas. First order sensory association/premotor areas and primary sensory/motor fields then follow suit. This study traces the course of the pathology in incidental and symptomatic Parkinson cases proposing a staging procedure based upon the readily recognizable topographical extent of the lesions.

Braak H; Del Tredici K; Rüb U; de Vos RA; Jansen Steur EN; Braak E

2003-03-01

118

[The spread pattern and survival in sporadic ALS].  

Science.gov (United States)

A misfolding pathology has been suggested to spread from onset site to neighbouring areas in a prion-like manner. We examined the pattern of spread and direction of clinical lower motor neuron involvement over time until the appearance of respiratory symptom. A total of 150 patients with sporadic ALS underwent follow-up until respiratory symptoms. Symptom appearances were determined using ALSFRS-R. The interval from onset to involvement of the second region correlated significantly with survival, independent of particular combinations. No patient with a rapid spread pattern (two regions within 3 months from onset) survived >5 years. Time from onset to spread to the second site, suggesting propagation speed, is a strong predictor for survival. In terms of cumulative occurrence, symptoms spread longitudinally to adjacent regions. In most of ALS patients, the spread appears to have a contiguous pattern rather than a random pattern of progression, although the spread to non-contiguous regions was observed in 13%. This finding supports the notion that the ALS pathology gradually spreads to adjacent regions in a longitudinal manner. Although precise mechanism of symptom spread in ALS is not understood, knowledge about the pattern of onset and the anatomical direction of spread may provide valuable prognostic insights. PMID:23196516

Kimura, Fumiharu

2012-01-01

119

[The spread pattern and survival in sporadic ALS].  

UK PubMed Central (United Kingdom)

A misfolding pathology has been suggested to spread from onset site to neighbouring areas in a prion-like manner. We examined the pattern of spread and direction of clinical lower motor neuron involvement over time until the appearance of respiratory symptom. A total of 150 patients with sporadic ALS underwent follow-up until respiratory symptoms. Symptom appearances were determined using ALSFRS-R. The interval from onset to involvement of the second region correlated significantly with survival, independent of particular combinations. No patient with a rapid spread pattern (two regions within 3 months from onset) survived >5 years. Time from onset to spread to the second site, suggesting propagation speed, is a strong predictor for survival. In terms of cumulative occurrence, symptoms spread longitudinally to adjacent regions. In most of ALS patients, the spread appears to have a contiguous pattern rather than a random pattern of progression, although the spread to non-contiguous regions was observed in 13%. This finding supports the notion that the ALS pathology gradually spreads to adjacent regions in a longitudinal manner. Although precise mechanism of symptom spread in ALS is not understood, knowledge about the pattern of onset and the anatomical direction of spread may provide valuable prognostic insights.

Kimura F

2012-01-01

120

Inflammasome polymorphisms confer susceptibility to sporadic malignant melanoma.  

UK PubMed Central (United Kingdom)

Genetic variants of NLRP3 and NLRP1 are known to modulate levels of pro-inflammatory cytokine interleukin (IL)-1?. The purpose of this study was to investigate the association of NLRP3/NLRP1 polymorphisms with susceptibility and clinical features of malignant melanoma in a Swedish case-control study. Common variants in NLRP3/NLRP1 were investigated in sporadic malignant melanoma patients and healthy controls followed by analysis using logistic regression. NLRP3 variant (rs35829419) was significantly more common in male patients than in controls (OR, 2.22; CI, 1.27-3.86). Upon stratification, significant association with nodular melanoma was observed (OR, 2.89; CI, 1.33-6.30), which intensified in male patients (OR 4.03, CI 1.40-11.59). The NLRP1 variant (rs12150220) was significantly more common in fair-skinned female patients (OR, 1.85; CI, 1.04-3.33) and showed strong associations with nodular melanoma (OR, 6.03; CI, 1.33-25). Our data suggest that NLRP3/NLRP1 polymorphisms are associated with melanoma susceptibility; these findings warrant validation in other independent populations.

Verma D; Bivik C; Farahani E; Synnerstad I; Fredrikson M; Enerbäck C; Rosdahl I; Söderkvist P

2012-07-01

 
 
 
 
121

Inflammasome polymorphisms confer susceptibility to sporadic malignant melanoma.  

Science.gov (United States)

Genetic variants of NLRP3 and NLRP1 are known to modulate levels of pro-inflammatory cytokine interleukin (IL)-1?. The purpose of this study was to investigate the association of NLRP3/NLRP1 polymorphisms with susceptibility and clinical features of malignant melanoma in a Swedish case-control study. Common variants in NLRP3/NLRP1 were investigated in sporadic malignant melanoma patients and healthy controls followed by analysis using logistic regression. NLRP3 variant (rs35829419) was significantly more common in male patients than in controls (OR, 2.22; CI, 1.27-3.86). Upon stratification, significant association with nodular melanoma was observed (OR, 2.89; CI, 1.33-6.30), which intensified in male patients (OR 4.03, CI 1.40-11.59). The NLRP1 variant (rs12150220) was significantly more common in fair-skinned female patients (OR, 1.85; CI, 1.04-3.33) and showed strong associations with nodular melanoma (OR, 6.03; CI, 1.33-25). Our data suggest that NLRP3/NLRP1 polymorphisms are associated with melanoma susceptibility; these findings warrant validation in other independent populations. PMID:22524199

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

2012-06-01

122

Sporadic unilateral retinoblastoma or first sign of bilateral disease?  

UK PubMed Central (United Kingdom)

BACKGROUND: A small number of children with unilateral retinoblastoma later develop retinoblastoma in the contralateral eye (metachronous bilateral retinoblastoma). METHODS: We analysed the clinical and genetic characteristics of children with sporadic unilateral retinoblastoma to identify risk factors for the development of metachronous bilateral disease. RESULTS: Fifteen (3.1%) of 480 children with unilateral retinoblastoma later developed metachronous bilateral retinoblastoma (latency period  >30 days). The maximum latency period was 2.3 years after initial diagnosis. Nine (22.5%) of 40 children with a RB1 mutation detectable in blood developed metachronous bilateral disease while all 155 children proved to be without a germline RB1 mutation remained unilaterally affected. Clinically, the risk of developing metachronous bilateral retinoblastoma was higher for age at diagnosis ?0.5 years compared with >0.5 years (19.6% vs 1.2%), and for multifocal compared with unifocal unilateral retinoblastoma (17.1% vs 2.2%). CONCLUSIONS: This study shows that an oncogenic RB1 mutation in the blood is a risk factor for metachronous bilateral retinoblastoma. Additional clinical risk factors for metachronous bilateral disease are diagnosis at young age (?0.5 years) and multifocal unilateral retinoblastoma. Early genetic analysis may identify children at high risk of developing metachronous bilateral disease and may help to preserve vision using risk-adapted follow-up and early treatment.

Temming P; Viehmann A; Biewald E; Lohmann DR

2013-04-01

123

Nonhomologous chromatid exchange in hereditary and sporadic renal cell carcinomas  

International Nuclear Information System (INIS)

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

1991-01-01

124

Nonhomologous chromatid exchange in hereditary and sporadic renal cell carcinomas  

Energy Technology Data Exchange (ETDEWEB)

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

Kovacs, G.; Kung, Hsiangfu (National Cancer Inst., Frederick, MD (United States))

1991-01-01

125

Genetic changes in sporadic keratocystic odontogenic tumors (odontogenic keratocysts).  

Science.gov (United States)

Little is known about the genetic background of keratocystic odontogenic tumors (KCOT, odontogenic keratocysts). Our aim was to characterize genomic aberrations in sporadic KCOT using cDNA-expression arrays and array-comparative genomic hybridization. For cDNA-expression arrays, 10 KCOT specimens and 20 fetal tooth germs were studied. Quantitative real-time reverse-transcription/polymerase chain-reaction and immunohistochemical studies were also undertaken. Several genes were over-expressed in 12q13, including cytokeratin 6B (KRT6B) ( approximately 10-fold), epidermal growth factor receptor ERBB3 (approximately 4.7-fold), and glioma-associated oncogene homologue 1 (GLI1) (approximately 5- to 12-fold). One amplicon (approximately 0.7 Mega base pairs [Mbp]), covering several genes involved in the regulation of cell growth, was found in 12q13.2. Deletions were found in 3q13.1, 5p14.3, and 7q31.3, including the cell-adhesion-related gene cadherin 18 (CDH18) and leukocyte cell adhesion molecule (ALCAM, MEMD). Over-expressed and amplified genes in 12q13, also reported in several other tumors and cell lines, may contribute to the persistent growth characteristics of KCOT. PMID:17525355

Heikinheimo, K; Jee, K J; Morgan, P R; Nagy, B; Knuutila, S; Leivo, I

2007-06-01

126

Nitric oxide stress in sporadic inclusion body myositis muscle fibres: inhibition of inducible nitric oxide synthase prevents interleukin-1?-induced accumulation of ?-amyloid and cell death.  

UK PubMed Central (United Kingdom)

Sporadic inclusion body myositis is a severely disabling myopathy. The design of effective treatment strategies is hampered by insufficient understanding of the complex disease pathology. Particularly, the nature of interrelationships between inflammatory and degenerative pathomechanisms in sporadic inclusion body myositis has remained elusive. In Alzheimer's dementia, accumulation of ?-amyloid has been shown to be associated with upregulation of nitric oxide. Using quantitative polymerase chain reaction, an overexpression of inducible nitric oxide synthase was observed in five out of ten patients with sporadic inclusion body myositis, two of eleven with dermatomyositis, three of eight with polymyositis, two of nine with muscular dystrophy and two of ten non-myopathic controls. Immunohistochemistry confirmed protein expression of inducible nitric oxide synthase and demonstrated intracellular nitration of tyrosine, an indicator for intra-fibre production of nitric oxide, in sporadic inclusion body myositis muscle samples, but much less in dermatomyositis or polymyositis, hardly in dystrophic muscle and not in non-myopathic controls. Using fluorescent double-labelling immunohistochemistry, a significant co-localization was observed in sporadic inclusion body myositis muscle between ?-amyloid, thioflavine-S and nitrotyrosine. In primary cultures of human myotubes and in myoblasts, exposure to interleukin-1? in combination with interferon-? induced a robust upregulation of inducible nitric oxide synthase messenger RNA. Using fluorescent detectors of reactive oxygen species and nitric oxide, dichlorofluorescein and diaminofluorescein, respectively, flow cytometry revealed that interleukin-1? combined with interferon-? induced intracellular production of nitric oxide, which was associated with necrotic cell death in muscle cells. Intracellular nitration of tyrosine was noted, which partly co-localized with amyloid precursor protein, but not with desmin. Pharmacological inhibition of inducible nitric oxide synthase by 1400W reduced intracellular production of nitric oxide and prevented accumulation of ?-amyloid, nitration of tyrosine as well as cell death inflicted by interleukin-1? combined with interferon-?. Collectively, these data suggest that, in skeletal muscle, inducible nitric oxide synthase is a central component of interactions between interleukin-1? and ?-amyloid, two of the most relevant molecules in sporadic inclusion body myositis. The data further our understanding of the pathology of sporadic inclusion body myositis and may point to novel treatment strategies.

Schmidt J; Barthel K; Zschüntzsch J; Muth IE; Swindle EJ; Hombach A; Sehmisch S; Wrede A; Lühder F; Gold R; Dalakas MC

2012-04-01

127

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Background Few genetic factors predisposing to the sporadic form of amyotrophic lateral sclerosis (ALS) have been identified, but the pathology itself seems to be a true multifactorial disease in which complex interactions between environmental and genetic susceptibility fa...

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

128

A case of Creutzfeldt-Jakob disease following cataract surgery: sporadic versus iatrogenic cause.  

UK PubMed Central (United Kingdom)

Creutzfeldt-Jakob Disease (CJD) is a fatal neurologic disorder caused by an infectious agent called a human prion protein. CJD can be classified as sporadic CJD, familial CJD, variant CJD, and iatrogenic CJD. We report a 64-year-old man diagnosed with CJD three months after cataract surgery. Although sporadic CJD is the most common type, the patient's cataract surgery elicited the possibility of an iatrogenic transmission. It is important to consider whether visual symptoms are a manifestation of sporadic CJD, rather than cataract surgery resulting in iatrogenic CJD. Preceding cataract surgeries have been reported with CJD, but there is no proven causality. This case highlights consideration of sporadic versus iatrogenic cause when seen in association with cataract surgery.

Gnanajothy R; Umashanker D; Vega MC; Wu BJ

2013-06-01

129

Mutations of FUS gene in sporadic amyotrophic lateral sclerosis.  

UK PubMed Central (United Kingdom)

BACKGROUND: Mutations in the FUS gene have recently been discovered to be a major cause of familial amyotrophic lateral sclerosis (FALS). OBJECTIVE: To determine the identity and frequency of FUS gene mutations in a large cohort of Italian patients enriched in sporadic cases (SALS). METHODS: Exons 5, 6, 14 and 15 of the FUS gene were screened for mutations in 1009 patients (45 FALS and 964 SALS). The genetic analysis was extended to the entire coding sequence of FUS in all the FALS and 293 of the SALS patients. RESULTS: Seven missense mutations (p.G191S, p.R216C, p.G225V, p.G230C, p.R234C, p.G507D and p.R521C) were identified in nine patients (seven SALS and two FALS), and none in 500 healthy Italian controls. All mutations are novel except for the p.R521C mutation identified in one SALS and one FALS case. Both patients showed a similar unusual presentation, with proximal, mostly symmetrical, upper limb weakness, with neck and axial involvement. With the exception of p.G507D and p.R521C, the mutations identified in SALS patients are all localised in the glycine-rich region encoded by exon 6. In addition, eight different in-frame deletions in two polyglycine motifs were detected, the frequency of which was not significantly different in patients and controls. CONCLUSIONS: The results show that FUS missense mutations are present in 0.7% of Italian SALS cases, and confirm the previous mutational frequency reported in FALS (4.4%). An unusual proximal and axial clinical presentation seems to be associated with the presence of the p.R521C mutation.

Corrado L; Del Bo R; Castellotti B; Ratti A; Cereda C; Penco S; Sorarù G; Carlomagno Y; Ghezzi S; Pensato V; Colombrita C; Gagliardi S; Cozzi L; Orsetti V; Mancuso M; Siciliano G; Mazzini L; Comi GP; Gellera C; Ceroni M; D'Alfonso S; Silani V

2010-03-01

130

Molecular characterization of an Italian series of sporadic GISTs.  

Science.gov (United States)

PURPOSE: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract. Most (80 %) contain activating mutations in the KIT receptor tyrosine kinase, roughly 10 % in platelet-derived growth factor receptor-alpha (PDGFRA). In a small subset, BRAF mutations are an alternative molecular pathway. GISTs respond well to imatinib, but low response is seen in patients with wild-type KIT or PDGFRA. Resistance has also been reported as a result of mutations in downstream effectors such as BRAF. METHODS: We provide here a molecular characterization of a series of primary GISTs from Italian patients. Of 121 GIST cases diagnosed between 2000 and 2012, 83 were evaluated by PCR amplification and direct sequencing for mutations in KIT exons 8, 9, 11, 13, and 17, PDGFRA exons 12, 14, and 18, and BRAF exon 15. Eighty-one GISTs also underwent K-RAS testing. RESULTS: Sixty-four GISTs were positive: 55 had mutations in KIT and 9 in PDGFRA; 16 patients were mutation negative. Three samples came from NF1 patients and were KIT- and PDGFRA negative. Overall, we identified six novel mutations in KIT (p.K550_M552delinsL, p.Q556_W557delinsG p.Q556_G575del, p.W557_V559delinsQ p.P573_R588dup, p.G592_K593dup) and one novel mutation in PDGFRA (p.D842_N848delinsVDV), thus contributing to widening the spectrum of known mutations in GIST tumors and confirming the most frequently altered regions underlying GIST development. CONCLUSIONS: Among the 64 KIT- and PDGFRA-positive sporadic patients in our series, no BRAF or KRAS mutations were identified, suggesting that co-occurrence of these mutations is likely to be rare in the northwestern Italian population and not a frequent cause of primary resistance to imatinib in KIT-positive GIST patients. PMID:23291969

Origone, P; Gargiulo, S; Mastracci, L; Ballestrero, A; Battistuzzi, L; Casella, C; Comandini, D; Cusano, R; Dei Tos, A P; Fiocca, R; Garuti, A; Ghiorzo, P; Martinuzzi, C; Toffolatti, L; Bianchi Scarrà, G

2013-01-01

131

Distinct molecular profiles in Lynch syndrome-associated and sporadic ovarian carcinomas.  

Science.gov (United States)

Ovarian carcinoma in Lynch syndrome (LS) is associated with unexpectedly high survival; yet, beyond DNA mismatch repair (MMR) defects, the developmental mechanisms are unknown. We used established (genetic) and new (epigenetic) classifiers of ovarian cancer to explore similarities and differences between LS-associated and sporadic diseases. To this end, all available ovarian carcinomas (n = 20) from MMR gene mutation carriers ascertained through a nation-wide registry and 87 sporadic ovarian carcinomas of the main histological types were molecularly profiled. LS-ovarian carcinomas were mostly of nonserous histology (12 endometrioid, seven clear cell and one serous), diagnosed at a mean age of 45.7 years, and associated with a 10-year survival of 87%. Among LS-ovarian carcinomas, 19/20 (95%) were MMR-deficient vs. 11/87 (13%) among sporadic cases (p hypomethylation less common in LS-ovarian carcinomas compared to their sporadic counterparts. The patterns of genetic and epigenetic alterations reflected the origin as LS vs. sporadic cases on one hand and the histological type on the other hand. In conclusion, the significant molecular differences observed between LS-associated and sporadic ovarian carcinomas help explain the different behavior of these tumors and emphasize the need for tailored clinical management. PMID:23716351

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

2013-06-21

132

Familial versus sporadic cavernous malformations: differences in developmental venous anomaly association and lesion phenotype.  

UK PubMed Central (United Kingdom)

BACKGROUND AND PURPOSE: CCMs are commonly associated with DVAs, but the incidence of association in familial CCM is unknown. The presence of a DVA significantly complicates surgical management of a CCM because of the risk of compromised venous drainage. In this investigation, we compared the incidence of a DVA in the presence of a CCM in sporadic and familial CCM cases comprising predominantly familial CCM with the Southwestern US common Hispanic mutation (or Q455X mutation) of CCM1. MATERIALS AND METHODS: Retrospective review was performed of 112 patients identified with CCM. MR imaging review included the presence or absence of a DVA and number, location, size, and signal-intensity characteristics of CCMs. Record review included patient and family history and documented genetic mutations. Statistical analysis was performed by using the Fisher exact and 2-sample t tests. RESULTS: Eighty-one cases were familial, 18 were sporadic, and 13 were indeterminate. There were a total of 2212 CCMs: 2176, 21, and 15 in the familial, sporadic, and indeterminate groups, respectively. There was a close association of CCM and DVA (an apparent combined vascular lesion) in 8 of 18 (44%) sporadic cases and only 1 possible such association in the familial cases. The difference was highly statistically significant (P < .0001). CONCLUSIONS: Familial CCMs are unlikely to be associated with DVAs, and sporadic CCMs have a high rate of association with DVA. This difference in imaging features of familial and sporadic CCMs suggests the possibility of a different developmental mechanism.

Petersen TA; Morrison LA; Schrader RM; Hart BL

2010-02-01

133

Sporadic medullary thyroid carcinoma: clinical data from a university hospital  

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Full Text Available INTRODUCTION: Medullary thyroid carcinoma may occur in a sporadic (s-medullary thyroid carcinoma, 75%) or in a multiple endocrine neoplasia type 2 form (MEN2, 25%). These clinical forms differ in many ways, as s-medullary thyroid carcinoma cases are RET-negative in the germline and are typically diagnosed later than medullary thyroid carcinoma in MEN2 patients. In this study, a set of cases with s-medullary thyroid carcinoma are documented and explored. PURPOSE: To document the phenotypes observed in s-medullary thyroid carcinoma cases from a university group and to attempt to improve earlier diagnosis of s-medullary thyroid carcinoma. Some procedures for diagnostics are also recommended. METHOD: Patients (n=26) with apparent s-medullary thyroid carcinoma were studied. Their clinical data were reviewed and peripheral blood was collected and screened for RET germline mutations. RESULTS: The average age at diagnosis was 43.9 years (± 10.82 SD) and did not differ between males and females. Calcitonin levels were increased in all cases. Three patients presented values that were 100-fold greater than the normal upper limit. Most (61.54%) had values that were 20-fold below this limit. Carcinoembryonic antigen levels were high in 70.6% of cases. There was no significant association between age at diagnosis, basal calcitonin levels or time of disease onset with thyroid tumor size (0.6-15 cm). Routine thyroid cytology yielded disappointing diagnostic accuracy (46.7%) in this set of cases. After total thyroidectomy associated with extensive cervical lymph node resection, calcitonin values remained lower than 5 pg/mL for at least 12 months in eight of the cases (30.8%). Immunocyto- and histochemistry for calcitonin were positive in all analyzed cases. None of the 26 cases presented germline mutations in the classical hotspots of the RET proto-oncogene. CONCLUSION: Our cases were identified late. The basal calcitonin measurements and immunostaining for calcitonin were highly useful for diagnosing s-medullary thyroid carcinoma. The rate of complete patient recovery was low, and none of the parameters analyzed were useful predictors of the thyroid tumor size. Our findings support previous recommendations for routine serum calcitonin evaluation and immunostaining analysis involving single thyroid nodules.

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

2009-01-01

134

NF2 genetic alterations in sporadic vestibular schwannomas: clinical implications.  

UK PubMed Central (United Kingdom)

HYPOTHESIS: NF2 gene alterations may have a clinical impact in non-NF2 vestibular schwannomas (VSs). BACKGROUND: It has been suggested that NF2 mutations might correlate with clinical expression of VS in NF2 patients. The aim of this study was to analyze the impact of genetic alterations in the NF2 gene on epidemiologic, clinical, and radiologic features of patients with sporadic VS. The association between cigarette consumption and the molecular genetic findings was also studied. METHODS: The study group consisted of 51 patients who underwent surgery for removal of vestibular schwannoma in our institution between January 2006 and December 2010. Five highly polymorphic microsatellite DNA markers were used to observe the frequency of loss of heterozygosity (LOH) in chromosome 22. The NF2 gene mutations were detected using polymerase chain reaction amplification and denaturing high-performance liquid chromatography analysis (PCR/dHPLC), and direct sequencing of NF2. Multiplex ligation-dependent probe amplification (MLPA) of the NF2 gene was also performed. RESULTS: An NF2 mutation was identified in 49%, 22q LOH in 57%, and MLPA alterations in 13.7% of the cases. One mutational hit was present in 27%, and 2 hits were present in 45% of the tumors. No association was found between the type of NF2 mutation and relevant clinical parameters. The presence of NF2 mutations detected by PCR/dHPLC was associated with no complaint of hearing loss at the time of diagnosis (p = 0.023), with subjective aural fullness (p = 0.022) and with an absence of tumor involvement of the internal auditory canal (p = 0.029). Patients with NF2 mutations had lower mean corrected PTA thresholds compared with those with no NF2 mutation (p = 0.037). Inactivation of the NF2 gene by mutation, MLPA, or LOH was more frequent in smokers when compared with never smokers (p = 0.048). CONCLUSION: NF2 mutations may play a role in the pathophysiology of hearing loss as well as in the pattern of growth of VS. Cigarette smoking in patients with VS seems to play a role in both the risk of developing the tumor and also in its genetic profile. More studies are needed to corroborate these results and, more broadly, to establish links between molecular and clinical data.

Lassaletta L; Torres-Martín M; Peña-Granero C; Roda JM; Santa-Cruz-Ruiz S; Castresana JS; Gavilan J; Rey JA

2013-09-01

135

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

UK PubMed Central (United Kingdom)

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

Praline J; Blasco H; Vourc'h P; Rat V; Gendrot C; Camu W; Andres CR

2012-06-01

136

Oncologic outcomes of sporadic, neurofibromatosis-associated, and radiation-induced malignant peripheral nerve sheath tumors.  

UK PubMed Central (United Kingdom)

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) occur sporadically, after prior radiation therapy (RT), or in association with neurofibromatosis type 1 (NF1). It is controversial whether patients with NF1-associated MPNST have worse outcomes. We investigated the prognostic significance of sporadic, NF1-associated, and RT-induced MPNST. METHODS: Patients with primary high-grade MPNST from 1982 to 2011 were identified from a prospectively maintained database. Patients with sporadic MPNST were included only if the MPNST was not associated with NF1 or a neurofibroma or if it was immunohistochemically S100-positive. RESULTS: We studied 105 patients; 42 had NF1-associated tumors, 49 sporadic, and 14 RT-induced. Median age at diagnosis was 38 years. Median follow-up for surviving patients was 4 years. Mean tumor diameter was 5.5 cm for RT-induced tumors and 9.7 cm for NF1-associated and sporadic tumors (P=0.004). In multivariate analysis, factors associated with worse disease-specific survival (DSS) were larger size (HR 1.08; 95% CI 1.04-1.13; P<0.001) and positive margin (HR 3.30; 95% CI 1.74-6.28; P<0.001). Age, gender, site of disease, and S100 staining were not associated with DSS. The 3-year and median DSS were similar for NF1 and sporadic cases; combined 3-year DSS was 64% and median DSS was 8.0 years. For RT-induced tumors, 3-year DSS was 49% and median DSS was 2.4 years. The relationship between RT association and DSS approached statistical significance (HR 2.29; 95% CI 0.93-5.67; P=0.072). CONCLUSIONS: Margin status and size remain the most important predictors of DSS in patients with MPNST. NF1-associated and sporadic MPNSTs may be associated with improved DSS compared with RT-induced tumors.

LaFemina J; Qin LX; Moraco NH; Antonescu CR; Fields RC; Crago AM; Brennan MF; Singer S

2013-01-01

137

Glycoform-Selective Prion Formation in Sporadic and Familial Forms of Prion Disease  

Science.gov (United States)

The four glycoforms of the cellular prion protein (PrPC) variably glycosylated at the two N-linked glycosylation sites are converted into their pathological forms (PrPSc) in most cases of sporadic prion diseases. However, a prominent molecular characteristic of PrPSc in the recently identified variably protease-sensitive prionopathy (VPSPr) is the absence of a diglycosylated form, also notable in familial Creutzfeldt-Jakob disease (fCJD), which is linked to mutations in PrP either from Val to Ile at residue 180 (fCJDV180I) or from Thr to Ala at residue 183 (fCJDT183A). Here we report that fCJDV180I, but not fCJDT183A, exhibits a proteinase K (PK)-resistant PrP (PrPres) that is markedly similar to that observed in VPSPr, which exhibits a five-step ladder-like electrophoretic profile, a molecular hallmark of VPSPr. Remarkably, the absence of the diglycosylated PrPres species in both fCJDV180I and VPSPr is likewise attributable to the absence of PrPres glycosylated at the first N-linked glycosylation site at residue 181, as in fCJDT183A. In contrast to fCJDT183A, both VPSPr and fCJDV180I exhibit glycosylation at residue 181 on di- and monoglycosylated (mono181) PrP prior to PK-treatment. Furthermore, PrPV180I with a typical glycoform profile from cultured cells generates detectable PrPres that also contains the diglycosylated PrP in addition to mono- and unglycosylated forms upon PK-treatment. Taken together, our current in vivo and in vitro studies indicate that sporadic VPSPr and familial CJDV180I share a unique glycoform-selective prion formation pathway in which the conversion of diglycosylated and mono181 PrPC to PrPSc is inhibited, probably by a dominant-negative effect, or by other co-factors.

Xiao, Xiangzhu; Yuan, Jue; Haik, Stephane; Cali, Ignazio; Zhan, Yian; Moudjou, Mohammed; Li, Baiya; Laplanche, Jean-Louis; Laude, Hubert; Langeveld, Jan; Gambetti, Pierluigi; Kitamoto, Tetsuyuki; Kong, Qingzhong; Brandel, Jean-Philippe; Cobb, Brian A.; Petersen, Robert B.; Zou, Wen-Quan

2013-01-01

138

Estimation of Turbulent Energy Dissipation Rate from Sporadic-E Parameters  

Science.gov (United States)

Neutral air turbulence plays a very notable role in the dynamics of atmospheric layers below the ionosphere and is important for the ionospheric D and E regions too. Above an altitude of 80 km a source of the turbulence may be destruction of the atmospheric gravity waves and tides propagating from the lower atmospheric layers and also the nonlinear interaction of planetary waves and tides. These large-scale atmospheric motions are also responsible for a vertical shear of the neutral wind that is necessary for the production of mid-latitude-type sporadic-E. The sporadic-E may serve as an example of the ionosphere-atmosphere interaction. If a sporadic-E height is below the homopause level, the turbulence exerts an essential influence on sporadic-E parameters. Hence we can estimate parameters of the turbulence from parameters of the sporadic-E. A fundamental parameter of turbulence is the mean rate of turbulent energy dissipation, ?. Estimation of ? from sporadic-E parameters was the purpose of this report. Results of the windshear theory of sporadic-E formation and the Richardson-Obukhov law that describes the turbulent diffusion caused by eddies with length-scales smaller than l: DT (l) = CT ?1-3l4-3, (1) (CT ? 1 is a dimensionless constant) were used to obtain expression that connects ? with sporadic-E parameters. Under assumption of sporadic-E formation by a sinusoidal neutral wave with amplitude u0 and wavelength L0, the rate of turbulent energy dissipation can be expressed through the thickness of the layer Ls as (in (1) l = Ls): ? = L2s(2?u0?icosI-L0)3, (2) where ?i is the ratio of the ion gyrofrequency ?i to the ion-neutral collision frequency ?i, I is the magnetic dip angle. The expression (2) was used to estimate ? when the sporadic-E altitude was near 100 km (?i = 3 × 103 s-1, I = 45°, u0 = 70ms-1, L0=10 km) for two variants of the sporadic-E ion composition (the mean ion mass took values 31 and 51 a.u.m. or ?i ? 0.05 and 0.03, respectively), and the thickness Ls was changed form 1 to 3 km. It was shown that in the case of ?i ? 0.05, the rate ? changed from 4.1 × 10-3 to 3.7 × 10-2 m2s-3, and for ?i ? 0.03 from 9.2 × 10-4 to 8.3 × 10-3 m2s-3. The maximum electron density in the layer N0 was estimated also. For the background electron density in the E region NE = 3.0 × 109 m-3, N0 decreased from 1.2 × 1010 to 4.0 × 109 m-3 with increasing Ls form 1 to 3 km. If the sporadic-E is above the homopause level then the windshear theory under the chosen values of parameters predicts its thickness Ls of about 152.5 m and N0 = 7.9 × 1010 m-3. Thus, even the weak turbulence (small values of ?) is very important for the sporadic-E.

Kyzyurov, Yurij V.

2010-05-01

139

Sporadic dementia of Alzheimer's type induced by streptozotocin promotes anxiogenic behavior in mice.  

UK PubMed Central (United Kingdom)

Alzheimer disease, a form of dementia in which loss of memory is the first and the most characteristic symptom, is frequently accompanied by affective symptoms. Intracerebroventricular (i.c.v.) injection of streptozotocin (STZ) to rodents has been reported as an appropriate model for sporadic dementia of Alzheimer's type (SDAT), characterized by a progressive impairment of memory. However, very little or nothing is known about non-cognitive behavioral effects (e.g. anxiety-like behavior) in the STZ model. In this context, the hypothesis to be tested in this study is if i.c.v. injection of STZ (0.1mg/site, 4 ?l) induces anxiety-like behavior in mice. The findings of the present study indicate that i.c.v. injection of STZ in mice resulted in an anxiogenic behavior. Mice spent less time and decreased the number of entries in the open arms in the elevated plus-maze task. The latency to the first entry in the dark side in the light-dark box task was reduced by STZ. No difference was found in anxiety-like behavior between early and late time (i.e., at 7 and 21 days after infusion, respectively). These results indicate that i.c.v. STZ injection caused an anxiogenic behavior in mice.

Pinton S; da Rocha JT; Gai BM; Nogueira CW

2011-09-01

140

Sporadic dementia of Alzheimer's type induced by streptozotocin promotes anxiogenic behavior in mice.  

Science.gov (United States)

Alzheimer disease, a form of dementia in which loss of memory is the first and the most characteristic symptom, is frequently accompanied by affective symptoms. Intracerebroventricular (i.c.v.) injection of streptozotocin (STZ) to rodents has been reported as an appropriate model for sporadic dementia of Alzheimer's type (SDAT), characterized by a progressive impairment of memory. However, very little or nothing is known about non-cognitive behavioral effects (e.g. anxiety-like behavior) in the STZ model. In this context, the hypothesis to be tested in this study is if i.c.v. injection of STZ (0.1mg/site, 4 ?l) induces anxiety-like behavior in mice. The findings of the present study indicate that i.c.v. injection of STZ in mice resulted in an anxiogenic behavior. Mice spent less time and decreased the number of entries in the open arms in the elevated plus-maze task. The latency to the first entry in the dark side in the light-dark box task was reduced by STZ. No difference was found in anxiety-like behavior between early and late time (i.e., at 7 and 21 days after infusion, respectively). These results indicate that i.c.v. STZ injection caused an anxiogenic behavior in mice. PMID:21515307

Pinton, Simone; da Rocha, Juliana Trevisan; Gai, Bibiana Mozzaquatro; Nogueira, Cristina Wayne

2011-04-15

 
 
 
 
141

Everolimus treatment of abdominal lymphangioleiomyoma in five women with sporadic lymphangioleiomyomatosis.  

UK PubMed Central (United Kingdom)

OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare systemic disease of young women arising from mutations in the tuberous sclerosis complex (TSC) genes, TSC1 or TSC2. This disrupts the mammalian target of rapamycin (mTOR) pathway, affecting cellular proliferation and growth. mTOR inhibitors are a promising novel therapy in LAM. The mTOR inhibitor sirolimus is reported to produce resolution of lymphatic abnormalities in LAM, but the efficiacy of the mTOR inhibitor everolimus has not been assessed. We aimed to examine the efficacy of everolimus on lymphatic abnormalities in LAM. DESIGN, SETTING AND PARTICIPANTS: Open-label treatment of five patients with sporadic LAM (sLAM) and abdominopelvic and lung involvement at the outpatient LAM clinic of a tertiary city teaching hospital. Clinical data were collected during treatment of the women and included regular clinical reviews, everolimus levels, lung function and computed tomography assessment before and after 6 months of everolimus treatment. MAIN OUTCOME MEASURES: Symptoms and level of resolution of lymphangioleiomyomas. RESULTS: All five women experienced significant shrinkage or complete resolution of the lymphangioleiomyomas during treatment. In one woman, cessation of everolimus resulted in recurrence of symptoms. Adverse events were compatible with the known side-effect profile of everolimus, but overall the drug was well tolerated. CONCLUSIONS: This is the first report to suggest that everolimus has efficacy in the treatment of lymphangioleiomyoma and chylous ascites in sLAM.

Mohammadieh AM; Bowler SD; Silverstone EJ; Glanville AR; Yates DH

2013-07-01

142

Microarray-based mutation detection of pediatric sporadic nonsyndromic hearing loss in China.  

UK PubMed Central (United Kingdom)

OBJECTIVE: To investigate the molecular etiologic causes of sporadic nonsyndromic hearing loss in Chinese children. METHODS: 179 sporadic nonsyndromic hearing loss children were subjected to microarray-based mutation detection for nine hot spot mutations in four of the most common deafness-related genes, including GJB2, SLC26A4, GJB3, and 12s rRNA. RESULTS: The incidence of positive genetic errors was 43.58% with the current set of target genes in sporadic nonsyndromic hearing loss children. Among them, 25.14% of cases had genetic defects in GJB2, 16.76% of cases had pathogenic mutations in SLC26A4, 1.12% of cases were caused by 12s rRNA mutations, and GJB3 mutation was detected in 0.56% of this group of patients. CONCLUSIONS: Our results demonstrated that genetic factors were important causes for sporadic nonsyndromic hearing loss in Chinese pediatric cases. Mutations of GJB2 and SLC26A4 are two major genetic causes, whereas mutations of GJB3 and 12s rRNA result in the development of hearing loss in a small percentage of sporadic nonsyndromic hearing loss cases. Microarray testing is a helpful and instrumental screening method in the diagnosis of genetic hearing loss.

Qu C; Sun X; Shi Y; Gong A; Liang S; Zhao M; Chen Y; Liang F

2012-02-01

143

hMSH2 and nm23 expression in sporadic colorectal cancer and its clinical significance.  

UK PubMed Central (United Kingdom)

OBJECTIVE: To study the expression of the mismatch repair proteins hMSH2 and nm23 in sporadic colorectal cancer, determine any inter-relationship, and further investigate any clinical significance. METHODS: Expression of hMSH2 and nm23 proteins was assessed in 87 colorectal cancer tissues by SP immunohistochemistry, with analysis of survival using follow-up data. RESULTS: In the sporadic colorectal cancer tissues, nm23 protein expression appeared independent of the histological type (P > 0.05), but correlated with the invasion depth and lymphatic metastasis (P < 0.05). In contrast, hMSH2 protein expression was not significantly correlated with these clinicopathologic features (P > 0.05), although it positively correlated with that of nm23 protein in the sporadic colorectal cancers (rs=0.635, P < 0.05). Combined expression of the two was found to be related with invasion depth, lymphatic metastasis and prognosis of sporadic colorectal cancer (P < 0.05). CONCLUSION: nm23 protein level was related with the degree of malignancy, and could be used as an index to predict the invasion and metastasis potential. The expression of hMSH2 protein is positively correlated that of nm23 protein, and the combined expression of the two has certain guiding significance for the prognosis of sporadic colorectal cancer.

Wu HW; Gao LD; Wei GH

2013-01-01

144

Contribution of hepatitis E virus in acute sporadic hepatitis in north western India.  

UK PubMed Central (United Kingdom)

BACKGROUND & OBJECTIVES: Hepatitis E virus (HEV) causes acute viral hepatitis. Majority of the documented studies on hepatitis E have been focused on the incidence of this disease in northern and south central India. Limited data are available on HEV infection among acute sporadic hepatitis cases in north western India. The present study was undertaken to investigate the contribution of hepatitis E virus infection in sporadic hepatitis cases in Rajasthan and neighbouring States. METHODS: Seven hundred and thirty six patients suspected to have viral hepatitis were screened for the hepatotropic viral markers, hepatitis A, B, C and E by using commercial enzyme immunoassay kits with a high sensitivity and specificity. The acute nature of HEV infection was also confirmed by the detection of HEV RNA by nested RT-PCR. Results: Hepatitis E was found to be the major cause of acute sporadic viral hepatitis (49.7%) in this region of India. Mixed infections of HEV-HAV (1.2%), HEV-HBV (6.1%), and HEV-HCV (1.7%) were also detected. No viral marker was detected in 32 per cent cases. INTERPRETATION & CONCLUSION: HEV was found as the major aetiological agent of acute sporadic viral hepatitis in Rajasthan (north western India). It is important to screen primarily for all the common enterically and parenterally transmitted hepatotropic viral markers in acute sporadic viral hepatitis. There is a need to do additional serological and molecular tests to identify the aetiological agent in the cases of acute hepatitis.

Chandra NS; Sharma A; Rai RR; Malhotra B

2012-09-01

145

Rare copy number variants in isolated sporadic and syndromic atrioventricular septal defects.  

UK PubMed Central (United Kingdom)

Atrioventricular septal defects (AVSDs) are a frequent but not universal component of Down syndrome (DS), while AVSDs in otherwise normal individuals have no well-defined genetic basis. The contribution of copy number variation (CNV) to specific congenital heart disease (CHD) phenotypes including AVSD is unknown. We hypothesized that de novo CNVs on chromosome 21 might cause isolated sporadic AVSDs, and separately that CNVs throughout the genome might constitute an additional genetic risk factor for AVSD in patients with DS. We utilized a custom oligonucleotide arrays targeted to CNV hotspots that are flanked by large duplicated segments of high sequence identity. We assayed 29 euploid and 50 DS individuals with AVSD, and compared to general population controls. In patients with isolated-sporadic AVSD we identified two large unique deletions outside of chromosome 21 not seen in the expanded set of 8,635 controls, each overlapping with larger deletions associated with similar CHD reported in the DECIPHER database. There was a small duplication in one patient with DS and AVSD. We conclude that isolated sporadic AVSDs may be occasionally associated with large de novo genomic structural variation outside of chromosome 21. The absence of CNVs on chromosome 21 in patients with isolated sporadic AVSD suggests that sub-chromosomal duplications or deletions of greater than 150?kbp on chromosome 21 do not cause sporadic AVSDs. Large CNVs do not appear to be an additive risk factor for AVSD in the DS population.

Priest JR; Girirajan S; Vu TH; Olson A; Eichler EE; Portman MA

2012-06-01

146

Current status of molecular markers for early detection of sporadic pancreatic cancer.  

UK PubMed Central (United Kingdom)

Pancreatic cancer (PC) is a highly lethal malignancy with near 100% mortality. This is in part due to the fact that most patients present with metastatic or locally advanced disease at the time of diagnosis. Significantly, in nearly 95% of PC patients there is neither an associated family history of PC nor of diseases known to be associated with an increased risk of PC. These groups of patients who comprise the bulk of PC cases are termed as "sporadic PC" in contrast to the familial PC cases that comprise only about 5% of all PCs. Given the insidious onset of the malignancy and its extreme resistance to chemo and radiotherapy, an abundance of research in recent years has focused on identifying biomarkers for the early detection of PC, specifically aiming at the sporadic PC cohort. However, while several studies have established that asymptomatic individuals with a positive family history of PC and those with certain heritable syndromes are candidates for PC screening, the role of screening in identifying sporadic PC is still an unsettled question. The present review attempts to assess this critical question by investigating the recent advances made in molecular markers with potential use in the early diagnosis of sporadic PC - the largest cohort of PC cases worldwide. It also outlines a novel yet simple risk factor based stratification system that could be potentially employed by clinicians to identify those individuals who are at an elevated risk for the development of sporadic PC and therefore candidates for screening.

Chakraborty S; Baine MJ; Sasson AR; Batra SK

2011-01-01

147

Current status of molecular markers for early detection of sporadic pancreatic cancer.  

Science.gov (United States)

Pancreatic cancer (PC) is a highly lethal malignancy with near 100% mortality. This is in part due to the fact that most patients present with metastatic or locally advanced disease at the time of diagnosis. Significantly, in nearly 95% of PC patients there is neither an associated family history of PC nor of diseases known to be associated with an increased risk of PC. These groups of patients who comprise the bulk of PC cases are termed as "sporadic PC" in contrast to the familial PC cases that comprise only about 5% of all PCs. Given the insidious onset of the malignancy and its extreme resistance to chemo and radiotherapy, an abundance of research in recent years has focused on identifying biomarkers for the early detection of PC, specifically aiming at the sporadic PC cohort. However, while several studies have established that asymptomatic individuals with a positive family history of PC and those with certain heritable syndromes are candidates for PC screening, the role of screening in identifying sporadic PC is still an unsettled question. The present review attempts to assess this critical question by investigating the recent advances made in molecular markers with potential use in the early diagnosis of sporadic PC - the largest cohort of PC cases worldwide. It also outlines a novel yet simple risk factor based stratification system that could be potentially employed by clinicians to identify those individuals who are at an elevated risk for the development of sporadic PC and therefore candidates for screening. PMID:20888394

Chakraborty, Subhankar; Baine, Michael J; Sasson, Aaron R; Batra, Surinder K

2010-10-01

148

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

International Nuclear Information System (INIS)

[en] 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.)

1995-01-01

149

Sensitivity of the sporadic-E irregularity spectrum to the ion composition of the layer  

Science.gov (United States)

Plasma density irregularities in sporadic-E layers below the turbopause level are resulted from the action of turbulence in the neutral atmosphere. A possible dependence of the spectrum of irregularities on the sporadic-E ion composition is considered in this paper. The consideration is based on an analytic expression for the irregularity spectrum. It is shown that the rms level of the relative plasma density fluctuations caused by neutral turbulence and the shape of their spectrum should be sensitive to changes in the metal ion concentration in the layer. The rms fluctuation and the slope of the irregularity spectrum increase with increasing the concentration of metallic ions in the sporadic-E. These changes in the spectrum and in the fluctuation level are explained by the reduction in the recombination rate and by the increase in the mean ion mass.

Kyzyurov, Yu.

2000-09-01

150

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2003-02-01

151

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

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

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

2011-01-01

152

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

UK PubMed Central (United Kingdom)

Basal-like breast cancer (BLBC) appears to be characterized by a relatively unfavorable prognosis and lack of a specific therapeutic target. Estrogen receptor-alpha (ER?) has been widely accepted as a prognostic marker and a predictor for endocrine therapy response of breast cancer. This study aimed to clarify the correlation of ER? methylation with the pathogenesis and clinicopathological significance of sporadic BLBC of Chinese women without a family history of the cancer. The methylation of ER? promoter was investigated in genomic DNA of 60 sporadic BLBC with 108 cases of non-BLBC as control by methylation-specific polymerase chain reaction. We also investigated the expression of p53, breast cancer gene (BRCA)-1, and BRCA-2 by immunohistochemistry and analyzed the correlation between ER? methylation and clinicopathological features of BLBC. ER? methylation was observed in 48 of 60 (80.0%) sporadic BLBC, which was significantly higher than in sporadic non-BLBC cancer (47/108, 43.5%; ?2=20.89, p<0.01). No correlation was found between the ER? methylation and age and menopausal status, while it was significantly associated with lymph node metastasis, tumor stage, nuclear p53 accumulation, and BRCA-1 and BRCA-2 expression in sporadic BLBC. The ER? methylation status in basal-like breast cancer was significantly higher than in sporadic non-basal-like breast cancer. It was associated with the lymph node metastasis, tumor stage, p53 nuclear accumulation, and BRCA-1 and BRCA-2 expression in BLBC. It may play an important role in BLBC pathogenesis.

Jing MX; Mao XY; Li C; Wei J; Liu C; Jin F

2011-08-01

153

[Prognostic and long term follow-up analysis of sporadic bilateral renal cell carcinoma].  

UK PubMed Central (United Kingdom)

OBJECTIVE: To investigate the pathological feature, therapy and prognosis of bilateral sporadic renal cell carcinoma. METHODS: The data of 59 bilateral sporadic renal cell carcinoma patients diagnosed from Apr. 1986 to Dec. 2009 were collected. We retrospectively analyzed the treatment, pathological features, long term survival and prognosis factors of the disease. RESULTS: We found 59 patients with bilateral sporadic renal cell carcinoma (RCC) in the database diagnosed from Apr. 1986 to Dec. 2009. The median age was 56 years. Of all the cases, 37 were bilateral synchronous sporadic renal cell carcinoma and 22 bilateral metachronous sporadic renal cell carcinoma. Forty-three patients underwent bilateral surgeries, 11 unilateral surgery, and 5 no treatment. There were 122 masses in the 59 patients and 109 masses had pathological reports. All the 59 cases were RCC, and clear cell carcinomas was the main subtype (96.6%). The median follow-up time was 62.1 months (range 4-277 months). Thirty-nine patients (66.1%) survived without tumor recurrence, 4 survived with tumors recurrence, and 16 (27.1%) died. Kaplan-Meier curve revealed that the 3-year and 5-year overall survival rates were 83.5% and 81.1%, respectively; the 3-year and 5-year cancer special survival rates were 73.1% and 64.8%, respectively. The disease-free survival rates of bilateral synchronous and bilateral metachronous RCC were similar. Multivariate regression suggested that post-operative application of interferon-? and bilateral surgeries were related with a better prognosis. CONCLUSION: The main subtype of bilateral sporadic renal cell carcinoma was clear cell carcinoma (96.6%). Bilateral synchronous and bilateral metachronous RCC both had a long time disease-free survival. Interferon-? application after surgery and bilateral surgeries were related with a better prognosis.

Mu da W; Guo T; Zhang CJ; Yu W; Li XS; He ZS; Jin J; Zhou LQ

2013-08-01

154

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

Science.gov (United States)

In an Italian population of 275 unrelated men affected by adult-onset sporadic progressive cerebellar ataxia, the authors found six patients carrying an FMR1 gene premutation. Age at onset (range, 53 to 69 years) and clinical-neuropathologic findings were consistent with the fragile-X tremor ataxia syndrome (FXTAS), although tremor was not as common as previously described. FXTAS accounted for 4.2% of the cases diagnosed at >50 years, suggesting that it is a frequent genetic cause of late-onset sporadic ataxia. PMID:15642922

Brussino, A; Gellera, C; Saluto, A; Mariotti, C; Arduino, C; Castellotti, B; Camerlingo, M; de Angelis, V; Orsi, L; Tosca, P; Migone, N; Taroni, F; Brusco, A

2005-01-11

155

Prevalence of AIP mutations in a large series of sporadic Italian acromegalic patients and evaluation of CDKN1B status in acromegalic patients with multiple endocrine neoplasia.  

UK PubMed Central (United Kingdom)

BACKGROUND: Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene and the p27(KIP1) encoding gene CDKN1B have been associated with two well-defined hereditary conditions, familial isolated pituitary adenoma (FIPA) and multiple endocrine neoplasia type 4 (MEN4). Somatotropinomas are present in most AIP mutated FIPA kindreds, as well as in two-thirds of MEN4 patients who carry pituitary tumors. METHODS: Germline DNA samples of 131 Italian sporadic acromegalic patients including 38 individuals with multiple tumors, and of six FIPA families (four homogeneous for prolactinomas and two heterogeneous with prolactin/nonfunctioning pituitary adenomas) were collected in a multicentric collaborative study. The prevalence of AIP and CDKN1B gene point mutations and copy number variations were evaluated. RESULTS: Two novel (IVS3+1G>A and c.871G>A) and one previously described (c.911G>A) AIP mutations were detected in four apparently sporadic cases (3.1%) with relatively high age at diagnosis (49+/-18, range 30-67). No mutations/rearrangements were detected in FIPA families. The highly conserved c.871G>A substitution was detected in a patient who also carried a MEN1 mutation suggesting that she is a double heterozygote. The possible pathogenic effect on AIP splicing of the silent substitution c.144G>A found in another patient was ruled out using a minigene-based approach. CDKN1B mutations/rearrangements were neither identified in patients with multiple neoplasia nor in FIPA families. CONCLUSION: AIP is mutated in about 3% of apparently sporadic acromegalic patients. The relatively high age at diagnosis, as well as its sporadic presentation, suggests that these patients are carriers of mutations with reduced pathogenicity. p27(KIP1) is unlikely to represent the common unifying nonendocrine etiology for acromegaly and cancer.

Occhi G; Trivellin G; Ceccato F; De Lazzari P; Giorgi G; Demattè S; Grimaldi F; Castello R; Davì MV; Arnaldi G; Salviati L; Opocher G; Mantero F; Scaroni C

2010-09-01

156

Multilocus Analysis of Cryptosporidium hominis and Cryptosporidium parvum Isolates from Sporadic and Outbreak-Related Human Cases and C. parvum Isolates from Sporadic Livestock Cases in the United Kingdom? ‡  

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Cryptosporidium parvum and Cryptosporidium hominis isolates from sporadic, drinking water-associated, and intrafamilial human cases together with C. parvum isolates from sporadic cases in livestock were collected in the United Kingdom between 1995 and 1999. The isolates were characterized by analysi...

Leoni, Francesca; Mallon, Marianne E.; Smith, Huw V.; Tait, Andy; McLauchlin, Jim

157

Midnight variations of spreading of ionospheric sporadic E-layers before earthquakes  

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Full Text Available In the present study, ionospheric phenomena caused by earthquakes of magnitudes M >4.0 were investigated. Night-time observations of the spreading of sporadic E-layers (Es-spread) performed every 15 min by the Dushanbe and Petropavlovsk-Kamchatsky (middle Asia) vertical sounding stations were studied. The mean relative occurrence frequency of Esspread at different values of the blanketing frequency fbEs was considered, and the dependence of Es-spread on the season as well as on the year through an 11-yr solar activity cycle were studied. The fbEs characterizes the maximum plasma density of the Es-layer. The analysis shows that 1- 3 days before seismic shocks in the Earth crust at depths of h <80 km, the occurrence frequency of the Es-spread increases a few hours before midnight. This effect is characteristic of a strengthening of the turbulization of the E-layer plasma. On the basis that the radius of the earthquake preparation region (RD) is estimated by the Dobrovolsky formula RD ? exp(M) km, it was found that Es-spread is observed more often when the distance between the epicenter and the radar station is not greater than RD + 150 km. In cases of earthquakes at greater distances and depths, no midnight effect was found. The authors act on the assumption that the Es-spread might be caused by acoustic waves with periods of 20 s to 5 min. When such acoustic disturbances propagate from the Earth surface they will have maximum amplitudes if they move nearly vertically to greater altitudes.

Elena V. Liperovskaya; Alexandra S. Silina; Victor A. Liperovsky; Claudia-Veronika Meister; Dieter H.H. Hoffmann; Pier Francesco Biagi

2012-01-01

158

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

Science.gov (United States)

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

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

2013-05-31

159

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

UK PubMed Central (United Kingdom)

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

Ihnen M; zu Eulenburg C; Kolarova T; Qi JW; Manivong K; Chalukya M; Dering J; Anderson L; Ginther C; Meuter A; Winterhoff B; Jones S; Velculescu VE; Venkatesan N; Rong HM; Dandekar S; Udar N; Jänicke F; Los G; Slamon DJ; Konecny GE

2013-06-01

160

S182 and STM2 gene missense mutations in sporadic alzheimer disease  

Energy Technology Data Exchange (ETDEWEB)

The linkage of genes S182 and STM2 to early-onset or late-onset sporadic Alzheimer disease (AD) was not found in a group of 97 clinically-diagnosed AD patients and 46 autopsy-confirmed AD cases, using PCR-RFLP methods. 7 refs.

Higuchi, Susumu; Matsushita, Sachio; Hasegawa, Yoshio; Muramatsu, Taro [Kurihama National Hospital, Yokosuka (Japan)] [and others

1996-07-26

 
 
 
 
161

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

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A collaborative study of human transmissible spongiform encephalopathies has been carried out from 1993 to 2000 and includes data from 10 national registries, the majority in Western Europe. In this study, we present analyses of predictors of survival in sporadic (n = 2304), iatrogenic (n = 106) and...

Pocchiari, M; Puopolo, M; Croes, E A; Budka, H; Gelpi, E; Collins, S; Lewis, V; Sutcliffe, T; Guilivi, A; Delasnerie-Laupretre, N

162

COL11A1 in FAP polyps and in sporadic colorectal tumors.  

UK PubMed Central (United Kingdom)

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

Fischer H; Salahshor S; Stenling R; Björk J; Lindmark G; Iselius L; Rubio C; Lindblom A

2001-01-01

163

Vacuolar myopathy in a dog resembling human sporadic inclusion body myositis  

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Sporadic inclusion body myositis (sIBM) is the most common myopathy in people over the age of 50 years. While immune-mediated inflammatory myopathies are well documented in dogs, sIBM has not been described. An 11-year-old dog with chronic and progressive neuromuscular dysfunction was evaluated for ...

King, Jason; LeCouteur, Richard A.; Aleman, Monica; Williams, D. Colette; Moore, Peter F.; Guo, Ling T.; Mizisin, Andrew P.

164

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

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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 ...

Mastaglia, FL

165

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

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Muscle repair relies on coordinated activation and differentiation of satellite cells, a process that is unable to counterbalance progressive degeneration in sporadic inclusion body myositis (s-IBM). To explore features of myo regeneration, the expression of myogenic regulatory factors Pax7, MyoD an...

Wanschitz, Julia V.; Dubourg, Odile; Lacene, Emmanuelle; Fischer, Michael B.; Höftberger, Romana; Budka, Herbert

166

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

Directory of Open Access Journals (Sweden)

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

McCoy Marcia L; Mueller Christopher R; Roskelley Calvin D

2003-01-01

167

Screening of BRCA1 Mutations Using C-terminal Antibody in Sporadic non Familial Colonic Carcinoma  

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Full Text Available Background: Cancer colon is one of the most prevalent cancers in Egypt. Sporadic cancer colon is much more common than familial type; the latter accounting for not more than 30% of the reported cases in different registrations. BRCA1 is a tumor suppressor gene which is proved to be mutated in many cancer types. Limited studies tried to screen its mutation in cancer colon. Aim: This work is aimed to screen BRCA1 mutations using C-terminal antibody in sporadic non familial colonic carcinoma. Subjects and Methods: Fifty colectomy specimens were collected. Sections of paraffin blocks were cut (µm thickness), then stained with Hematoxylin and eosin and evaluated for tumor type and its nuclear grade and its stage. Immunohistochemical studies for BRCA1 were performed. Results: Positive nuclear immunostaining of BRCA1 staining was detected in 84% of the cases, with insignificant correlation with both the grade and the stage p ~ 0.42, p ~ 0.31 respectively. Conclusion: This type of staining denies a direct role of BRCA1 axon 11 mutations in sporadic colonic cancer - unlike some sporadic ovarian and breast cancers - and may point to that BRCA1 may share in the early tumorogenesis in a way other than the usual mutation of exon 11.

Reham Sh. Esmail; Walid M. Sharaf; Noha A. Helmy; Abdel Razik H. Farrag; Manal A. Badawi; Amina A. Gamal Eldin

2012-01-01

168

Kimmerle conjecture for the Held and O'Nan sporadic simple groups  

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Using the Luthar--Passi method, we investigate the Zassenhaus and Kimmerle conjectures for normalized unit groups of integral group rings of the Held and O'Nan sporadic simple groups. We confirm the Kimmerle conjecture for the Held simple group and also derive for both groups some extra information relevant to the classical Zassenhaus conjecture.

Bovdi, V; Konovalov, A

2009-01-01

169

Downregulation of fumarate hydratase is related to tumorigenesis in sporadic renal cell cancer.  

UK PubMed Central (United Kingdom)

OBJECTIVE: Although germline mutations of fumarate hydratase (FH) are a useful molecular marker of hereditary leiomyomatosis and renal cell cancer (RCC) syndrome, their clinical significance in sporadic RCC has not been studied in detail. The aim of the present study was to investigate possible correlations between the expression of FH and the clinical implications of sporadic RCC. MATERIALS AND METHODS: FH mRNA levels were evaluated in 140 tumor specimens from patients with primary RCC and in 62 specimens of corresponding normal-appearing kidney tissue using real-time quantitative polymerase chain reaction. Immunohistochemical staining was performed on 6 normal surrounding tissues and 71 RCC tissues. RESULTS: FH mRNA levels were significantly lower in tumor tissues than in matched normal-appearing kidney tissues (p = 0.031). In all normal tissues, FH staining intensity was strong. However, the expression of FH showed no significant correlation with the pathological and clinical characteristics of patients with sporadic RCC. CONCLUSIONS: Our results showed that FH mRNA expression decreased significantly in correlation with the transition from normal renal parenchyma to RCC. FH may be an indicator or tumorigenesis in sporadic RCC and could be a potential target for therapies against RCC in the future.

Ha YS; Chihara Y; Yoon HY; Kim YJ; Kim TH; Woo SH; Yun SJ; Kim IY; Hirao Y; Kim WJ

2013-01-01

170

High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas.  

UK PubMed Central (United Kingdom)

BACKGROUND: Aryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas. The prevalence of AIPmut among sporadic pituitary adenoma patients appears to be low; studies have not addressed prevalence in the most clinically relevant population. Hence, we undertook an international, multicenter, prospective genetic, and clinical analysis at 21 tertiary referral endocrine departments. METHODS: We included 163 sporadic pituitary macroadenoma patients irrespective of clinical phenotype diagnosed at <30 years of age. RESULTS: Overall, 19/163 (11.7%) patients had germline AIPmut; a further nine patients had sequence changes of uncertain significance or polymorphisms. AIPmut were identified in 8/39 (20.5%) pediatric patients. Ten AIPmut were identified in 11/83 (13.3%) sporadic somatotropinoma patients, in 7/61 (11.5%) prolactinoma patients, and in 1/16 non-functioning pituitary adenoma patients. Large genetic deletions were not seen using multiplex ligation-dependent probe amplification. Familial screening was possible in the relatives of seven patients with AIPmut and carriers were found in six of the seven families. In total, pituitary adenomas were diagnosed in 2/21 AIPmut-screened carriers; both had asymptomatic microadenomas. CONCLUSION: Germline AIPmut occur in 11.7% of patients <30 years with sporadic pituitary macroadenomas and in 20.5% of pediatric patients. AIPmut mutation testing in this population should be considered in order to optimize clinical genetic investigation and management.

Tichomirowa MA; Barlier A; Daly AF; Jaffrain-Rea ML; Ronchi C; Yaneva M; Urban JD; Petrossians P; Elenkova A; Tabarin A; Desailloud R; Maiter D; Schürmeyer T; Cozzi R; Theodoropoulou M; Sievers C; Bernabeu I; Naves LA; Chabre O; Montañana CF; Hana V; Halaby G; Delemer B; Aizpún JI; Sonnet E; Longás AF; Hagelstein MT; Caron P; Stalla GK; Bours V; Zacharieva S; Spada A; Brue T; Beckers A

2011-10-01

171

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

International Nuclear Information System (INIS)

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

2011-01-01

172

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

Science.gov (United States)

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.

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

2013-01-01

173

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

UK PubMed Central (United Kingdom)

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.

Guan WJ; Liu XJ; Tang BS; Liu YT; Zhou Y; Jiang H; Shen L; Xia K; Wang JL

2013-05-01

174

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

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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 wome...

Cassio Cardoso Filho; Gustavo Lourenço; Julia Yoriko Shinzato; Luiz Carlos Zeferino; Fernando Ferreira Costa

175

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

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AIM: To characterize aberrant crypt focus (ACF) in adjoining mucosa in sporadic colorectal carcinoma and to evaluate fragile histidine triad (Fhit) protein and Ki67. METHODS: ACF was identified grossly and classified histologically in 75 resected specimens. ACF was typed into hyperplastic ACF (HACF)...

Kim Vaiphei; Aruna Rangan; Rajinder Singh

176

[Norovirus infection in adults with sporadic gastroenteritis during 2007-2008 in Nanning Municipal].  

UK PubMed Central (United Kingdom)

OBJECTIVE: To investigate the epidemiological characteristic and genotype distribution of norovirus infection among adult patients with sporadic gastroenteritis in Nanning Municipal. METHODS: The epidemiological data of adult diarrhea patients in outpatient clinics of a hospital in Nanning City between January 2007 and December 2008 were analyzed. A total of 696 fecal specimens were collected from the patients and were screened for the presence of norovirus RNA by real-time reverse transcription-polymerase chain reaction. Some positive specimens were selected randomly and subjected for sequencing and phylogenetic analysis to identify genotypes. RESULTS: The sporadic norovirus infection in adults occurred preferentially during the cold season, and there was no statistical difference in the detection rate between age groups. 183 (26.30%) of 696 specimens were positive for norovirus RNA. Among them, 180 (98.36%) belonged to genogroup II (G II) and the other 3 (1.64%) belonged to genogroup I (G I). The sequence analysis showed that all 10 G II strains selected randomly belonged to genotype G II4, while 3 GI strains were classified into three different genotypes: G I2, G I4 and G I8. CONCLUSION: The study showed that norovirus was an important etiologic agent of sporadic gastroenteritis among adults in Nanning City. Genotype G II4 was the predominant genotype, and genotype GI existed sporadically.

Tan DM; Liu W; Deng LL

2010-04-01

177

Common polymorphisms in dystonia-linked genes and susceptibility to the sporadic primary dystonias.  

Science.gov (United States)

Genes involved in familial dystonia syndromes (DYT genes) are ideal candidates for investigating whether common genetic variants influence the susceptibility to sporadic primary dystonia. To date, there have been few candidate gene studies for primary dystonia and only two DYT genes, TOR1A and THAP1, have been assessed. We therefore employed a haplotype-tagging strategy to comprehensively assess if common polymorphisms in eight DYT genes (TOR1A, TAF1, GCH1, THAP1, MR-1 (PNKD), SGCE, ATP1A3 and PRKRA) confer risk for sporadic primary dystonia. The 230 primary dystonia cases were matched for age and gender to 228 controls, recruited from movement disorder clinics in Brisbane, Australia and the Australian electoral roll. All subjects were genotyped for 56 tagging SNPs and genotype associations were investigated. Modest genotypic associations (P<0.05) were observed for three GCH1 SNPs (rs12147422, rs3759664 and rs10483639) when comparing all cases against controls. Associations were also seen when the cases were stratified based on presentation. Overall, our findings do not support the hypothesis that common TOR1A variants affect susceptibility for sporadic primary dystonia, and that it is unlikely that common variants around the DYT genes confer substantial risk for sporadic primary dystonia. Further work is warranted to follow up the GCH1 SNPs and the subgroup analyses. PMID:22172551

Newman, Jeremy R B; Sutherland, Greg T; Boyle, Richard S; Limberg, Nicole; Blum, Stefan; O'Sullivan, John D; Silburn, Peter A; Mellick, George D

2011-12-14

178

Common polymorphisms in dystonia-linked genes and susceptibility to the sporadic primary dystonias.  

UK PubMed Central (United Kingdom)

Genes involved in familial dystonia syndromes (DYT genes) are ideal candidates for investigating whether common genetic variants influence the susceptibility to sporadic primary dystonia. To date, there have been few candidate gene studies for primary dystonia and only two DYT genes, TOR1A and THAP1, have been assessed. We therefore employed a haplotype-tagging strategy to comprehensively assess if common polymorphisms in eight DYT genes (TOR1A, TAF1, GCH1, THAP1, MR-1 (PNKD), SGCE, ATP1A3 and PRKRA) confer risk for sporadic primary dystonia. The 230 primary dystonia cases were matched for age and gender to 228 controls, recruited from movement disorder clinics in Brisbane, Australia and the Australian electoral roll. All subjects were genotyped for 56 tagging SNPs and genotype associations were investigated. Modest genotypic associations (P<0.05) were observed for three GCH1 SNPs (rs12147422, rs3759664 and rs10483639) when comparing all cases against controls. Associations were also seen when the cases were stratified based on presentation. Overall, our findings do not support the hypothesis that common TOR1A variants affect susceptibility for sporadic primary dystonia, and that it is unlikely that common variants around the DYT genes confer substantial risk for sporadic primary dystonia. Further work is warranted to follow up the GCH1 SNPs and the subgroup analyses.

Newman JR; Sutherland GT; Boyle RS; Limberg N; Blum S; O'Sullivan JD; Silburn PA; Mellick GD

2012-05-01

179

COL11A1 in FAP polyps and in sporadic colorectal tumors  

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

Fischer Heléne; Salahshor Sima; Stenling Roger; Björk Jan; Lindmark Gudrun; Iselius Lennart; Rubio Carlos; Lindblom Annika

2001-01-01

180

Thymidylate synthase gene (TYMS) polymorphisms in sporadic and hereditary breast cancer  

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Abstract Background Breast cancer (BC) is a genetic disorder characterized by growth and proliferation of breast cells in a disorderly. In Brazil, there are approximately 49.240 new cases of BC, every year. The BC etiology is still poorly understood. The BC can be sporadic (SBC) or ...

Junior José da Silva Nogueira; Marson Fernando Augusto de Lima; Bertuzzo Carmen Sílvia

 
 
 
 
181

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

UK PubMed Central (United Kingdom)

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.

D'Angelo R; Alafaci C; Scimone C; Ruggeri A; Salpietro FM; Bramanti P; Tomasello F; Sidoti A

2013-01-01

182

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

Science.gov (United States)

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

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

2013-08-22

183

Incidence of -93 MLH1 promoter polymorphism in familial and sporadic colorectal cancer.  

UK PubMed Central (United Kingdom)

AIM: The MLH1 promoter contains a common single nucleotide polymorphism (-93 guanine > adenine) located in an essential region for maximum transcriptional activity. This has been associated with an increased risk of microsatellite instability (MSI) colorectal cancer. The aim of the study was to compare the distribution of MLH1 -93G>A genotypes between patients with familial colon cancer, sporadic colon cancer and healthy subjects. METHOD: We genotyped 200 familial colon samples, 183 cases of sporadic colon cancer and 236 control subjects. MSI was analysed. RESULTS: The GA genotype was under-represented in patients with familial colon cancer, whereas the AA genotype was over-represented in cases of sporadic colon cancer. A greater frequency of the MLH1 GA genotype was found in the cancer cases with MLH1 focal immunohistochemistry (IHC) for anti-MLH1 antibody. When we compared genotype distribution in the familial colorectal cancer cases with and without MSI, we failed to detect any correlation, although the GA genotype is more frequent in cases with MSI. CONCLUSION: There is a relationship between the MLH1 -93G>A polymorphism in the homozygous state and the risk of sporadic colorectal cancer. The variant MLH1 -93G>A appears to be related to cases with focal IHC activity more than to complete absence of the MLH1 protein in the tumour tissue.

Martínez-Urueña N; Macías L; Pérez-Cabornero L; Infante M; Lastra E; Cruz JJ; Miner C; González R; Durán M

2013-03-01

184

Risks and benefits of screening for intracranial aneurysms in first-degree relatives of patients with sporadic subarachnoid hemorrhage.  

UK PubMed Central (United Kingdom)

BACKGROUND: The first-degree relatives of patients who have subarachnoid hemorrhage from ruptured intracranial aneurysms are themselves at risk for subarachnoid hemorrhage. We studied the benefits and risks of screening for aneurysms in the first-degree relatives of patients with sporadic subarachnoid hemorrhage. METHODS: We screened 626 first-degree relatives (parents, siblings, or children) of 160 patients with sporadic subarachnoid hemorrhage, from a prospective series of 193 consecutive index patients. Magnetic resonance angiography was the screening tool, and conventional angiography was used as the reference test in subjects thought to have aneurysms. Six months after elective operation, outcome was assessed by means of the modified Rankin scale of neurologic function. This observational study design was combined with a decision-analysis model to estimate the effectiveness of screening. The efficiency of screening was defined by the number of relatives who needed to be screened in order to prevent one subarachnoid hemorrhage. RESULTS: Aneurysms were found in 25 of 626 first-degree relatives (4.0 percent; 95 percent confidence interval, 2.6 to 5.8 percent). Eighteen underwent surgery, which resulted in a decrease in function in 11 (disabling in 1). Five had aneurysms that were 5 to 11 mm in diameter, 11 had aneurysms that were less than 5 mm, and 2 had both small and medium-sized aneurysms. On average, surgery increased estimated life expectancy by 2.5 years for these 18 subjects (or by 0.9 month per person screened), at the expense of 19 years of decreased function per person. The number of relatives who would need to be screened in order to prevent 1 subarachnoid hemorrhage on a lifetime basis was 149, and 298 would have to be screened in order to prevent 1 fatal subarachnoid hemorrhage. CONCLUSIONS: Implementation of a screening program for the first-degree relatives of patients with sporadic subarachnoid hemorrhage does not seem warranted at this time, since the resulting slight increase in life expectancy does not offset the risk of postoperative sequelae.

1999-10-01

185

Efficacy and safety of endoscopic treatment for nonampullary sporadic duodenal adenomas.  

UK PubMed Central (United Kingdom)

BACKGROUND: Nonampullary sporadic duodenal adenomas (NSDAs) are uncommon mucosal neoplasms with malignant potential. Recently, endoscopic treatment is used for NSDA with increasing frequency. AIMS: This study therefore aimed to evaluate the efficacy and safety of endoscopic treatment for NSDA. METHODS: A total of 36 NSDAs in 35 consecutive patients were endoscopically eradicated at Samsung Medical Center between October 1994 and May 2011. Data on patient demographics, tumor characteristics, and endoscopic treatment outcomes were obtained and retrospectively analyzed. RESULTS: Of all patients, 19 (52.8 %) were male. The mean age was 56.0 ± 12.2 (SD) years. Of the 36 NSDAs, 23 lesions were removed by endoscopic resection (ER) including endoscopic mucosal resection (EMR, n = 20) and snare polypectomy (n = 3). In the 23 cases treated with ER, en bloc resection was achieved in 20 (87.0 %). All cases undergoing en bloc resection showed tumor-free resection margins. Thirteen lesions were ablated by argon plasma coagulation (APC). During EMR, bleeding occurred in two cases and perforation occurred in one case. One patient bled during APC. All complications were successfully managed with endoscopic treatment without surgical intervention. During a median follow-up period of 11.4 months (range, 1.8-182.4 months), local recurrence occurred in one patient treated with APC (1/10, 10.0 %). Among patients undergoing ER, no local recurrence occurred but one patient treated with EMR experienced metachronous recurrence. CONCLUSIONS: Endoscopic treatment, including EMR, snare polypectomy, and APC, was an effective and safe treatment for NSDA. Further multi-center large prospective studies are warranted to establish appropriate treatment guidelines for NSDA.

Min YW; Min BH; Kim ER; Lee JH; Rhee PL; Rhee JC; Kim JJ

2013-10-01

186

Preclinical sporadic Alzheimer's disease: target for personalized diagnosis and preventive intervention.  

UK PubMed Central (United Kingdom)

The most opportune time for preventive intervention in sporadic Alzheimer's disease (spAD) is early in its preclinical stage (pcAD), when the odds of preventing or minimizing later disabling neurodegeneration are most favorable. The efficacy of promising preventive interventions should be assessed in patients in the earliest discernible phase of pcAD. This will require application of personalized medicine techniques, with use of suitable biomarkers to detect pcAD in individuals believed to be spAD-prone. This review focuses on the genetic biomarker, apolipoprotein E (apoE) ?4, and on certain neuroimaging biomarkers, such as structural MRI (sMRI), fluorodeoxyglucose-positron emission tomography (FDG-PET), and PET-amyloid tracers capable of delineating the extent and distribution of amyloid-beta (A?) deposits in the brain, that can be useful in identifying cognitively normal people who are at enhanced risk of developing spAD. Many years before AD symptoms appear, such neuroimaging procedures can disclose signature abnormalities of brain structure, function, and amyloid levels in cognitively normal apoE ?4 allele carriers and/or individuals with a family history of spAD. Although no effective treatment for spAD is yet available, there is evidence that, by taking a proactive personalized-medicine approach, the practicing physician may be able to reduce risk in AD-prone patients by attending to such modifiable AD risk factors as hypertension, obesity, type 2 diabetes, insulin resistance, hypercholesterolemia, sedentary lifestyle, and current cigarette smoking. Young patients who are ?4 positive should be advised to avoid participation in contact sports or other activities that expose them to risk of traumatic brain injury.

Vanitallie TB

2013-01-01

187

MYC overexpression and poor prognosis in sporadic breast cancer with BRCA1 deficiency.  

UK PubMed Central (United Kingdom)

Breast cancer is a complex disease; the molecular mechanisms involved in sporadic breast carcinogenesis remain to be elucidated. The present study aimed to explore the deficiency of breast cancer susceptibility gene 1 (BRCA1), including protein loss expression, promoter hypermethylation and gene copy deletion, its correlationship with other tumor markers expression (TP53, MYC, etc.), and clinical significance in sporadic breast cancer. BRCA1 protein expression was negative in 226 of 374 (60.4 %) cases of this study. Cases negative for BRCA1 protein were more often with pathological tumor-node-metastasis stage III, positive for lymph node metastasis and MYC overexpression than BRCA1-positive tumors. BRCA1 hypermethylation was detected in 16.4 % (31 of 189) breast cancers, which correlated with BRCA1 negative, ER negative, MYC overexpression, and triple-negative phenotype. In addition, the percentage of cells with BRCA1 gene copy deletion was significantly increased in BRCA1-methylated tumors. Kaplan-Meier survival analysis showed that patients with BRCA1-negative expression showed a worse overall survival (OS) than those with BRCA1-positive expression, and patients with BRCA1-methylated tumors had a significantly worse disease-free survival than did patients with unmethylated tumors. Furthermore, BRCA1 hypermethylation showed an inverse association with OS in LN-positive or p53-negative subgroup patients. Importantly, uni- and multivariate Cox regression analyses revealed that BRCA1 was an independent prognostic indicator of OS in sporadic breast cancer. Thus, we found MYC overexpression and poor prognosis in sporadic breast cancer with BRCA1 deficiency. The targeting of BRCA1 deficiency in combination with MYC-pathways inhibitors may provide a promising strategy for sporadic breast cancer care, the triple-negative subtype in particular.

Ren J; Jin F; Yu Z; Zhao L; Wang L; Bai X; Zhao H; Yao W; Mi X; Wang E; Olopade OI; Wei M

2013-07-01

188

Field-aligned current loop model on formation of sporadic metal layers  

Science.gov (United States)

This paper proposes a new mechanism for the formation of the sporadic layers by metallic ions as well as metallic atoms in the lower thermosphere and upper mesosphere. The mechanism is based on sporadic occurrence of an electric current loop consisting of the magnetic field-aligned current (FAC) and horizontal Pedersen current in the ionosphere connected with the FAC. The essential point of the present mechanism is the existence of the horizontal electric field convergence at the foot of the upward FAC region in the current loop, where the positive ions including the metallic ions may converge by the horizontal Pedersen flow. The accumulated metallic ions are reacted to the clustered metallic ions, which are transferred to the metallic atoms through the dissociative recombination with electrons. The density profile of the sporadic layer for metallic ions has been obtained in the analytical form by solving the continuity equation. The density profile of the sporadic layer for metallic atoms has been obtained also in the analytical form by assuming that 100% of the loss of the metallic ions is converted to metallic atoms. The simulation based on the present mechanism has been examined with respect to three species of metallic components: sodium, iron, and calcium. The sporadic sodium layer (SSL) derived from the present model is compared with the SSL observed by the sodium lidar installed at the European Incoherent Scatter radar site in Tromsø (69.6°N, 19.2°E), Norway, and reasonable agreement has been attained with respect to the density profile of the SSL.

Matuura, Nobuo; Tsuda, Takuo; Nozawa, Satonori

2013-07-01

189

Frequent NF2 gene transcript mutations in sporadic meningiomas and vestibular schwannomas  

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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.

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

190

Association of genetic polymorphisms in vitamin D receptor gene and susceptibility to sporadic prostate cancer.  

Science.gov (United States)

Genetic and environmental factors are involved in prostate cancer (PCa) etiology. Single nucleotide polymorphisms (SNPs) may contribute to the PCa pathogenesis. The goal of this study is to determine the role of vitamin D receptor (VDR) gene polymorphisms and haplotypes in the development and progression of sporadic PCa. One hundred and thirty-three PCa patients and 157 age-matched healthy controls were genotyped for the Apa I (rs7975232), Bsm I (rs1544410) and Taq I (rs731236) polymorphisms in VDR gene by using polymerase chain reaction-restriction fragment length polymorphism. An association was observed between the Apa I polymorphism and PCa predisposition (P = 0.03). When compared with AA genotype, there was a highly notable difference in the frequencies of the Aa (P = 0.02), aa (P = 0.026) and Apa I ''a'' allele carriers (Aa + aa) (P = 0.009) genotypes. Furthermore, we found a statistical difference in the allele frequencies of the Apa I polymorphism between the sporadic PCa patients and control subjects (P = 0.013). The genotype distribution for the Bsm I and Taq I polymorphisms were similar between cases and controls (P > 0.05). No clinically significant relationship was found between the three-locus haplotypes and development of sporadic PCa. The genotype frequencies for the three polymorphisms of the VDR gene within subgroups of PCa (defined by tumor stage, Gleason score, PSA levels) were also analyzed, but no statistically noteworthy difference was observed (P > 0.05). As far as we know, this is the first study which investigates the relationship between VDR genotypes and sporadic PCa in the Turkish population. Our findings suggest that the VDR ApaI (rs7975232) polymorphism may play a role in the development of sporadic PCa. PMID:18849534

Onen, Ilke Hacer; Ekmekci, Abdullah; Eroglu, Muzaffer; Konac, Ece; Yesil, Suleyman; Biri, Hasan

2008-10-10

191

Sporadic childhood hepatoblastomas show activation of beta-catenin, mismatch repair defects and p53 mutations.  

UK PubMed Central (United Kingdom)

Hepatoblastoma, a rare embryonic tumor that may arise sporadically or in the context of hereditary syndromes (familial adenomatous polyposis and Beckwith-Wiedemann's) is the most frequent liver cancer of childhood. Deregulation of the APC/beta-catenin pathway occurs in a consistent fraction of hepatoblastomas, with mutations in the APC and beta-catenin genes implicated in familial adenomatous polyposis-associated and sporadic hepatoblastomas, respectively. Alterations in other cancer-related molecular pathways have not been reported. We investigated a series of 21 sporadic paraffin-embedded hepatoblastoma cases for mutations in the p53 (exons 5-8) and beta-catenin (exon 3) genes, loss of heterozygosity at APC, microsatellite instability and immunohistochemical expression of beta-catenin and of the two main mismatch repair proteins, MLH1 and MSH2. No loss of heterozygosity at APC was detected. We found mutations in beta-catenin and p53 in 4/21 (19%) and 5/21 (24%) cases respectively, beta-catenin protein accumulation in 14/21 cases (67%), microsatellite instability in 17/21 cases (81%), of which eight resulted positive for high-level of microsatellite instability (in four cases associated with loss of MLH1/MSH2 immunostaining). No correlations between involved molecular pathway(s) and hepatoblastoma histotype(s) emerged. This study confirms that beta-catenin deregulation is involved in sporadic hepatoblastoma and also suggests that mismatch repair defects and p53 mutations contribute to this rare liver cancer. Sporadic hepatoblastoma appears to be molecularly and phenotypically heterogeneous and may reflect different pathways of liver carcinogenesis.

Curia MC; Zuckermann M; De Lellis L; Catalano T; Lattanzio R; Aceto G; Veschi S; Cama A; Otte JB; Piantelli M; Mariani-Costantini R; Cetta F; Battista P

2008-01-01

192

Characteristics of epidemic and sporadic strains of Acinetobacter baumannii isolated in Abu Dhabi hospitals.  

UK PubMed Central (United Kingdom)

We compared the antibiotic susceptibility, clonal lineages and resistance genes of singleton Acinetobacter baumannii strains to those of isolates representing repeatedly encountered molecular types in five Abu Dhabi hospitals. One hundred and ten clinically relevant, non-repeat strains were typed by blaOXA-51-like allele sequencing and by PFGE, and selected isolates also by MLST. Resistance was assessed by MIC determinations and by disc diffusion. Genotyping was carried out by PCR, targeting 28 genes. The 80 epidemic strains belonged to worldwide lineages 1, 2 and 7, representing 11 pulsotypes and 9 genotypes, while the 30 sporadic isolates exhibited a high level of genetic variability and, with the exception of a small subgroup, were not associated with any recognized epidemic lineages. All epidemic subtypes carried the ISAba1-linked blaOXA-23 gene, and harboured the int, the blaPER and the armA genes significantly more frequently than their sporadic counterparts. They were all multi-drug resistant, including non-susceptibility to carbepenems, and were often extensively drug resistant, a phenomenon rarely seen among sporadic strains. Epidemic strains represented 78.8 % of intensive care unit isolates, causing more respiratory infections, while sporadic strains were more frequently isolated from wound and soft tissue infections. The study showed that among strains collected at the same time and from the same region, the very heterogeneous, sensitive sporadic strains, with the exception of a few non-susceptible singleton isolates, clearly differed from the highly resistant epidemic ones, which belonged to multiple pulsotypes and genotypes clustered into three worldwide clonal lineages carrying blaOXA-64, blaOXA-66 and blaOXA-69, respectively.

Sonnevend A; Ghazawi A; Al Munthari N; Pitout M; Hamadeh MB; Hashmey R; Girgis SK; Sheikh FA; Al Haj M; Nagelkerke N; Pál T

2013-04-01

193

[Correction of metabolic changes in rats with sporadic alcoholic intoxication].  

UK PubMed Central (United Kingdom)

Faltering alcoholic intoxication is accompanied by activation of processes of lipid peroxidation in blood and a liver, and also reduction of levels of a number of amino acids in tissue. Compositions of "Tavamin" and "Neyramin" used for correction show normalizing effect on a pool of free amino acids in a liver and skeletal muscles, and also a number of biochemical characteristics in blood.

Lelevich SV; Lelevich VV; Barkovski? EV

2013-01-01

194

[Correction of metabolic changes in rats with sporadic alcoholic intoxication].  

Science.gov (United States)

Faltering alcoholic intoxication is accompanied by activation of processes of lipid peroxidation in blood and a liver, and also reduction of levels of a number of amino acids in tissue. Compositions of "Tavamin" and "Neyramin" used for correction show normalizing effect on a pool of free amino acids in a liver and skeletal muscles, and also a number of biochemical characteristics in blood. PMID:24006614

Lelevich, S V; Lelevich, V V; Barkovski?, E V

2013-01-01

195

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

Directory of Open Access Journals (Sweden)

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

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

2006-01-01

196

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

Science.gov (United States)

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.

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

2006-07-01

197

Spinocerebellar ataxia type 12 identified in two Italian families may mimic sporadic ataxia.  

Science.gov (United States)

SCA12 is an autosomal dominant cerebellar ataxia characterized by onset in the fourth decade of life with action tremor of arms and head, mild ataxia, dysmetria, and hyperreflexia. The disease is caused by an expansion of >or=51 CAGs in the 5' region of the brain- specific phosphatase 2 regulatory subunit B-beta isoform (PPP2R2B) gene. SCA12 is very rare, except for a single ethnic group in India. We screened 159 Italian ataxic patients for SCA12 and identified two families that segregated an expanded allele of 57 to 58 CAGs, sharing a common haplotype. The age at onset, phenotype, and variability of symptoms were compatible with known cases. In one family, the disease was apparently sporadic due to possible incomplete penetrance and/or late age at onset. Our data indicate that SCA12 is also present in Italian patients, and its genetic testing should be applied to both sporadic and familial ataxias. PMID:20629122

Brussino, Alessandro; Graziano, Claudio; Giobbe, Dario; Ferrone, Marina; Dragone, Elisa; Arduino, Carlo; Lodi, Raffaele; Tonon, Caterina; Gabellini, Anna; Rinaldi, Rita; Miccoli, Sara; Grosso, Enrico; Bellati, Maria Cristina; Orsi, Laura; Migone, Nicola; Brusco, Alfredo

2010-07-15

198

Electron temperature in nighttime sporadic E layer at mid-latitude  

Directory of Open Access Journals (Sweden)

Full Text Available Electron temperature in the sporadic E layer was measured with a glass-sealed Langmuir probe at a mid-latitude station in Japan in the framework of the SEEK (Sporadic E Experiment over Kyushu)-2 campaign which was conducted in August 2002. Important findings are two fold: (1) electron temperature and electron density vary in the opposite sense in the height range of 100–108 km, and electron temperature in the Es layer is lower than that of ambient plasma, (2) electron temperature in these height ranges is higher than the possible range of neutral temperature. These findings strongly suggest that the heat source that elevates electron temperature much higher than possible neutral temperature exists at around 100 km, and/or that the physical parameter values, which are used in the present theory to calculate electron temperature, are not proper.

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

2008-01-01

199

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1998-02-01

200

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

1994-09-15

 
 
 
 
201

Sporadic hemiplegic migraine in children: A report of two new cases  

Directory of Open Access Journals (Sweden)

Full Text Available Two cases of sporadic hemiplegic migraine, which fulfilled the diagnostic criteria as laid down in International Classification of Headache Disorders (ICHD)-2, are reported in children. In the first case, two unusual features were noted, namely, the occurrence of dysphsia in association with a left hemiparesis and the spread of sensory symptoms to the contralateral side during attacks. The second case is perhaps the youngest patient reported with this disorder.

Chakravarty A; Sen A

2010-01-01

202

Absence of RET proto-oncogene abnormalities in sporadic parathyroid tumors  

Energy Technology Data Exchange (ETDEWEB)

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

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

1994-09-01

203

MEN1 intragenic deletions may represent the most prevalent somatic event in sporadic primary hyperparathyroidism.  

UK PubMed Central (United Kingdom)

OBJECTIVE: Primary hyperparathyroidism (pHPT) is characterised by an inappropriate over production of parathyroid hormone and it is the most frequent pathological condition of the parathyroid glands. A minority of the cases belong to familial forms, but most of them are sporadic. The genetic alterations underlying the sporadic forms of pHPT remain poorly understood. The main goal of our study is to perform the molecular characterisation of a series of sporadic pHPT cases. DESIGN AND METHODS: We have studied matched blood and tumour from 24 patients with pHPT, who went to a medical appointment in Hospital Pedro Hispano. Informed consent was obtained from all individuals. The MEN1, RET and CDKN1B molecular study was carried out in the germline DNA by PCR/SSCP and direct sequencing. Parathyroid tumours were further analysed by the same methods for MEN1, CDKN1B and CTNNB1 genetic alterations. The multiplex ligation-dependent probe amplification technique enabled the evaluation of MEN1 gene deletions. Protein expression for menin, cyclin D1, parafibromin, p27(Kip1), ?-catenin and Ki-67 was conducted by immunohistochemistry. RESULTS: The study of parathyroid tumours detected two somatic MEN1 mutations (c.249_252delGTCT and c.115_163del49bp) and revealed the presence of MEN1 intragenic deletions in 54% (13/24) of the tumours. In RET and CDKN1B genes only previously described, non-pathogenic variants were found. Cyclin D1 protein was overexpressed in 13% (3/24) of tumours. CONCLUSIONS: These results suggest that MEN1 alterations, remarkably intragenic deletions, may represent the most prevalent genetic alteration in sporadic parathyroid tumours.

Alvelos MI; Vinagre J; Fonseca E; Barbosa E; Teixeira-Gomes J; Sobrinho-Simões M; Soares P

2013-02-01

204

Association of HPC2/ELAC2 and RNASEL non-synonymous variants with prostate cancer risk in African American familial and sporadic cases.  

UK PubMed Central (United Kingdom)

INTRODUCTION: The RNASEL and HPC2/ELAC2 genes have been implicated in hereditary prostate cancer. Further assessment of the role of these genes in sporadic prostate cancer in African American men (AAM) is warranted. METHODS: Genotyping of HPC2/ELAC2 variants (S217L, A541T), along with RNASEL variants (R462Q and E541D) was completed in 155 African American sporadic and 88 familial prostate cancer cases, and 296 healthy male controls. Logistic regression analysis was performed and odds ratios (OR) were calculated, while correcting for both age and population stratification using admixture informative markers. RESULTS: The HPC2/ELAC2 217L allele was significantly associated with risk of prostate cancer when taking all cases into account (OR = 1.6; 1.0-2.6; P = 0.03). The RNASEL 541D allele was associated with a decrease in risk of prostate cancer in sporadic cases (OR = 0.4; 0.2-0.8; P = 0.01). We did not detect an association between prostate cancer risk and the RNASEL R462Q variant. Results from haplotype analyses of the two RNASEL variants revealed highly significant differences in haplotype allele frequencies between cases and controls suggesting a synergistic effect at the RNASEL locus. One haplotype in particular (462R-541D) is far more frequent in our control population and shows a strong protective effect against prostate cancer (OR = 0.47, P = 8.1 x 10(-9)). CONCLUSIONS: These results suggest that HPC2/ELAC2 and RNASEL may play a role, however minor, in prostate cancer risk among AAM.

Robbins CM; Hernandez W; Ahaghotu C; Bennett J; Hoke G; Mason T; Pettaway CA; Vijayakumar S; Weinrich S; Furbert-Harris P; Dunston G; Powell IJ; Carpten JD; Kittles RA

2008-12-01

205

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

Energy Technology Data Exchange (ETDEWEB)

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.).

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

206

Genetic analysis of noroviruses associated with sporadic gastroenteritis during winter in guangzhou, china.  

Science.gov (United States)

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

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

2013-08-15

207

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

UK PubMed Central (United Kingdom)

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

DiGiovanni R; Serra S; Ezzat S; Asa SL

2007-01-01

208

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

UK PubMed Central (United Kingdom)

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

Fajardo-Montañana C; Daly AF; Riesgo-Suárez P; Gómez-Vela J; Tichomirowa MA; Camara-Gómez R; Beckers A

2009-08-01

209

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

Science.gov (United States)

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

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

210

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

Science.gov (United States)

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

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

2007-01-01

211

Abundant FUS-immunoreactive pathology in the skin of sporadic amyotrophic lateral sclerosis.  

UK PubMed Central (United Kingdom)

OBJECTIVES: The fused in sarcoma (FUS) protein is a 526 amino acid and its expression is ubiquitous. Recently, mutations in a gene coding FUS have been identified in familial amyotrophic lateral sclerosis (ALS). Also, FUS has been found in neuronal cytoplasmic inclusions in sporadic forms of ALS, suggesting that FUS has an important role in the neurodegeneration occurring in sporadic disease. However, there has been no study of FUS in ALS skin. MATERIAL AND METHODS: We made a quantitative immunohistochemical study of the expression of FUS in the skin from patients with sporadic ALS and controls. RESULTS: The proportion of FUS-immunoreactive (ir) cells in the epidermis in ALS patients was significantly higher (P < 0.001) than in controls. There was a significant positive relationship (r = 0.78, P < 0.001) between the proportion and duration of illness in ALS patients. The optical density of FUS-ir cells in the epidermis in ALS patients is markedly stronger (P < 0.001) than in controls. There was a significant positive relation (r = 0.49, P < 0.05) between the immunoreactivity and duration of illness in ALS patients. CONCLUSIONS: These data suggest that changes of FUS in ALS skin are related to the disease process, and that metabolic alterations of FUS may take place in the skin of patients with ALS.

Oketa Y; Higashida K; Fukasawa H; Tsukie T; Ono S

2013-03-01

212

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1993-05-01

213

Analysis of cytogenetic aberrations in sporadic vestibular schwannoma by comparative genomic hybridization.  

UK PubMed Central (United Kingdom)

Vestibular schwannomas (VS) are benign tumors of the nervous system that are usually sporadic but also occur in the inherited disorder neurofibromatosis type 2 (NF2). The NF2 gene is a tumor suppressor gene located on chromosome 22. Loss of the NF2 protein product, Merlin, is universal in both sporadic and NF2-related schwannomas and the loss or mutation of the gene is the only established causative event underlying schwannoma formation. Comparative genomic hybridization (CGH) was used to screen 20 sporadic VS to identify additional chromosomal regions that may harbor genes involved in VS-tumorigenesis. The most common change were losses on chromosome 22q. Additionally, losses were observed on chromosome 9p indicating a possible participation of the CDKN2A tumor suppressor gene in the genesis of VS. Gains were observed on 17q, 19p and 19q, which have been reported before in malignant peripheral nerve sheath tumors that are associated with neurofibromatosis type 1. Importantly, high level amplifications have been observed on 16p and 16q as well as on 9q, suggesting the possible involvement of several oncogenes in the tumorigenesis of VS. Our data suggest the involvement of various oncogenes and tumor suppressor genes might play a role in the genesis of the vestibular schwannomas apart from the inactivation of the NF2 gene.

Koutsimpelas D; Felmeden U; Mann WJ; Brieger J

2011-07-01

214

Analysis of cytogenetic aberrations in sporadic vestibular schwannoma by comparative genomic hybridization.  

Science.gov (United States)

Vestibular schwannomas (VS) are benign tumors of the nervous system that are usually sporadic but also occur in the inherited disorder neurofibromatosis type 2 (NF2). The NF2 gene is a tumor suppressor gene located on chromosome 22. Loss of the NF2 protein product, Merlin, is universal in both sporadic and NF2-related schwannomas and the loss or mutation of the gene is the only established causative event underlying schwannoma formation. Comparative genomic hybridization (CGH) was used to screen 20 sporadic VS to identify additional chromosomal regions that may harbor genes involved in VS-tumorigenesis. The most common change were losses on chromosome 22q. Additionally, losses were observed on chromosome 9p indicating a possible participation of the CDKN2A tumor suppressor gene in the genesis of VS. Gains were observed on 17q, 19p and 19q, which have been reported before in malignant peripheral nerve sheath tumors that are associated with neurofibromatosis type 1. Importantly, high level amplifications have been observed on 16p and 16q as well as on 9q, suggesting the possible involvement of several oncogenes in the tumorigenesis of VS. Our data suggest the involvement of various oncogenes and tumor suppressor genes might play a role in the genesis of the vestibular schwannomas apart from the inactivation of the NF2 gene. PMID:20872275

Koutsimpelas, Dimitrios; Felmeden, Uwe; Mann, Wolf J; Brieger, Jürgen

2010-09-26

215

Viruses Detected Among Sporadic Cases of Parotitis, United States, 2009-2011.  

UK PubMed Central (United Kingdom)

Background.?Sporadic cases of parotitis are generally assumed to be mumps, which often require a resource-intensive public health response. This project surveyed the frequency of viruses detected among such cases.Methods.?During 2009-2011, eight jurisdictions throughout the United States investigated sporadic cases of parotitis. Epidemiologic information, serum, and buccal and oropharyngeal swabs were collected. Polymerase chain reaction methods were used to detect a panel of viruses. Anti-mumps virus immunoglobulin M (IgM) antibodies were detected using a variety of methods.Results.?Of 101 specimens, 38 were positive for a single virus: Epstein-Barr virus (23), human herpesvirus (HHV) -6B (10), human parainfluenza virus (HPIV) -2 (3), HPIV-3 (1), and human bocavirus (1). Mumps virus, enteroviruses, including human parechovirus, HHV-6A, HPIV-1, and adenoviruses were not detected. Early specimen collection did not improve viral detection rate. Mumps IgM was detected in 17% of available specimens. Patients in whom a virus was detected were younger, but no difference was seen by sex or vaccination profile. No seasonal patterns were identified.Conclusions.?Considering the timing of specimen collection, serology results, patient vaccination status, and time of year may be helpful in assessing the likelihood that a sporadic case of parotitis without laboratory confirmation is mumps.

Barskey AE; Juieng P; Whitaker BL; Erdman DD; Oberste MS; Chern SW; Schmid DS; Radford KW; McNall RJ; Rota PA; Hickman CJ; Bellini WJ; Wallace GS

2013-08-01

216

C9ORF72 hexanucleotide repeat expansions in the Italian sporadic ALS population.  

UK PubMed Central (United Kingdom)

It has been recently reported that a large proportion of patients with familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are associated with a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72. We have assessed 1757 Italian sporadic ALS cases, 133 from Sardinia, 101 from Sicily, and 1523 from mainland Italy. Sixty (3.7%) of 1624 mainland Italians and Sicilians and 9 (6.8%) of the 133 Sardinian sporadic ALS cases carried the pathogenic repeat expansion. None of the 619 regionally matched control samples (1238 chromosomes) carried the expansion. Twenty-five cases (36.2%) had behavioral FTD in addition to ALS. FTD or unspecified dementia was also detected in 19 pedigrees (27.5%) in first-degree relatives of ALS patients. Cases carrying the C9ORF72 hexanucleotide expansion survived 1 year less than cases who did not carry this mutation. In conclusion, we found that C9ORF72 hexanucleotide repeat expansions represents a sizeable proportion of apparent sporadic ALS in the Italian and Sardinian population, representing by far the most common mutation in Italy and the second most common in Sardinia.

Sabatelli M; Conforti FL; Zollino M; Mora G; Monsurrò MR; Volanti P; Marinou K; Salvi F; Corbo M; Giannini F; Battistini S; Penco S; Lunetta C; Quattrone A; Gambardella A; Logroscino G; Simone I; Bartolomei I; Pisano F; Tedeschi G; Conte A; Spataro R; La Bella V; Caponnetto C; Mancardi G; Mandich P; Sola P; Mandrioli J; Renton AE; Majounie E; Abramzon Y; Marrosu F; Marrosu MG; Murru MR; Sotgiu MA; Pugliatti M; Rodolico C; Moglia C; Calvo A; Ossola I; Brunetti M; Traynor BJ; Borghero G; Restagno G; Chiò A

2012-08-01

217

Variable Somatic TIE2 Mutations in Half of Sporadic Venous Malformations.  

UK PubMed Central (United Kingdom)

Venous malformations (VMs) are the most frequent vascular malformations referred to specialized vascular anomaly centers. A rare (1-2%) familial form, termed cutaneomucosal venous malformation (VMCM), is caused by gain-of-function mutations in TIE2. More recently, sporadic VMs, characterized by the presence of large unifocal lesions, were shown to be caused by somatic mutations in TIE2. These include a frequent L914F change, and a series of double mutations in cis. All of which cause ligand-independent receptor hyperphosphorylation in vitro. Here, we expanded our study to assess the range of mutations that cause sporadic VM. To test for somatic changes, we screened the entire coding region of TIE2 in cDNA from resected VMs by direct sequencing. We detected TIE2 mutations in 17/30 (56.7%) of the samples. In addition to previously detected mutations, we identified 7 novel somatic intracellular TIE2 mutations in sporadic VMs, including 3 that cause premature protein truncation.

Soblet J; Limaye N; Uebelhoer M; Boon LM; Vikkula M

2013-04-01

218

Variable Somatic TIE2 Mutations in Half of Sporadic Venous Malformations.  

Science.gov (United States)

Venous malformations (VMs) are the most frequent vascular malformations referred to specialized vascular anomaly centers. A rare (1-2%) familial form, termed cutaneomucosal venous malformation (VMCM), is caused by gain-of-function mutations in TIE2. More recently, sporadic VMs, characterized by the presence of large unifocal lesions, were shown to be caused by somatic mutations in TIE2. These include a frequent L914F change, and a series of double mutations in cis. All of which cause ligand-independent receptor hyperphosphorylation in vitro. Here, we expanded our study to assess the range of mutations that cause sporadic VM. To test for somatic changes, we screened the entire coding region of TIE2 in cDNA from resected VMs by direct sequencing. We detected TIE2 mutations in 17/30 (56.7%) of the samples. In addition to previously detected mutations, we identified 7 novel somatic intracellular TIE2 mutations in sporadic VMs, including 3 that cause premature protein truncation. PMID:23801934

Soblet, J; Limaye, N; Uebelhoer, M; Boon, L M; Vikkula, M

2013-03-26

219

Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging.  

UK PubMed Central (United Kingdom)

The term cerebral small vessel disease (SVD) describes a range of neuroimaging, pathological, and associated clinical features. Clinical features range from none, to discrete focal neurological symptoms (eg, stroke), to insidious global neurological dysfunction and dementia. The burden on public health is substantial. The pathogenesis of SVD is largely unknown. Although the pathological processes leading to the arteriolar disease are associated with vascular risk factors and are believed to result from an intrinsic cerebral arteriolar occlusive disease, little is known about how these processes result in brain disease, how SVD lesions contribute to neurological or cognitive symptoms, and the association with risk factors. Pathology often shows end-stage disease, which makes identification of the earliest stages difficult. Neuroimaging provides considerable insights; although the small vessels are not easily seen themselves, the effects of their malfunction on the brain can be tracked with detailed brain imaging. We discuss potential mechanisms, detectable with neuroimaging, that might better fit the available evidence and provide testable hypotheses for future study.

Wardlaw JM; Smith C; Dichgans M

2013-05-01

220

Correlation of muscle biopsy, clinical course, and outcome in PM and sporadic IBM.  

UK PubMed Central (United Kingdom)

OBJECTIVE: To correlate muscle biopsy findings with prebiopsy and postbiopsy clinical course and response to therapy in polymyositis (PM) and sporadic inclusion body myositis (IBM). BACKGROUND: Existence of pure PM has recently been questioned; subsequently, the definition and criteria for diagnosing PM were debated. METHODS: Patient records, follow-up information, and muscle biopsies were analyzed in 107 patients whose biopsies were initially read as PM and IBM. RESULTS: The patients fell into three groups by combined biopsy and clinical criteria: PM, 27 patients; IBM, 64 patients; PM/IBM, 16 patients with biopsy diagnosis of PM but clinical features of IBM. For the three groups, the respective mean periods from disease onset to end of follow-up were 5.9, 8.5, and 9.6 years. Another autoimmune disease was present in 4 of 27 PM, 8 of 64 IBM, and 1 of 16 PM/IBM cases. An autoimmune serologic marker occurred in one-third of each group. Nineteen PM patients had no associated autoimmune disease or marker. Nonnecrotic fiber invasion by mononuclear cells appeared in all IBM, 17 of 27 PM, and 13 of 16 PM/IBM patients. The density of both invaded fibers and cytochrome-c oxidase-negative fibers was higher in IBM and PM/IBM than in PM. Immunotherapy improved 22 of 27 PM patients but had only transient beneficial effects in 2 of 32 IBM and 1 of 14 PM/IBM patients. CONCLUSIONS: 1) Sixteen of 43 patients (37%) with biopsy features of polymyositis (PM) had clinical features of inclusion body myositis (IBM). 2) Absence of canonical biopsy features of IBM from clinically affected muscles of IBM patients challenges biopsy criteria for IBM, or the IBM markers appear late in some patients, or their distribution in muscle is patchy and restricted compared with that of the inflammatory exudate. 3) The muscle biopsy is a reliable instrument in the diagnosis of PM and IBM in close to 85% of the patients. Errors of diagnosis in the remaining 15% can be avoided or reduced by combined evaluation of the clinical and pathologic findings.

Chahin N; Engel AG

2008-02-01

 
 
 
 
221

Analysis of the RNASEL gene in familial and sporadic prostate cancer.  

UK PubMed Central (United Kingdom)

The RNASEL gene on chromosome 1q25 was recently identified as a candidate gene for hereditary prostate cancer (PC). To confirm these findings, we screened 326 patients from 163 families with familial PC for potential germline mutations, by use of conformation-sensitive gel electrophoresis, followed by direct sequence analysis. A total of six variants were identified, including one intronic and five exonic changes (three missense and two silent alterations). There were no unequivocal pathogenic changes. To further test for potential associations between genes and increased risk for disease, the three missense polymorphisms (Ile97Leu, Arg462Gln, and Glu541Asp) were genotyped in 438 patients with familial PC and in 510 population-based control subjects. Association testing revealed no significant differences between patients and control subjects for either the Leu97 variant (chi(2) trend test = 1.42; P=.23) or the Asp541 variant (chi2=1.52; P=.22). However, significant differences were detected for the Arg462Gln genotypes (chi2=5.20; P=.02; odds ratio [OR] = 0.54; 95% confidence interval [CI] 0.32-0.91) when the genotype Gln/Gln was compared with Arg/Arg. In subset analyses, associations were also observed in the younger group (age at diagnosis sporadic PC, we genotyped an additional 499 patients with sporadic PC. Differences in frequency were not detected between patients with sporadic disease and control subjects. However, the same association was observed between patients with familial disease and patients with sporadic disease for the entire group (chi2=4.82; P=.03), as well as in the subset analyses. These results suggest that polymorphic changes within the RNASEL gene may be associated with increased risk of familial but not sporadic PC.

Wang L; McDonnell SK; Elkins DA; Slager SL; Christensen E; Marks AF; Cunningham JM; Peterson BJ; Jacobsen SJ; Cerhan JR; Blute ML; Schaid DJ; Thibodeau SN

2002-07-01

222

The Fas promoter polymorphism at position -670 is not associated with late-onset sporadic Alzheimer's disease.  

Science.gov (United States)

The Fas antigen is a cell surface receptor-mediating cell apoptosis. Recent studies have demonstrated that Fas-associated apoptosis is involved in the pathogenesis of Alzheimer's disease (AD). Moreover, the Fas gene is located on chromosome 10q24.1, a region of linkage to late-onset AD (LOAD). These two criteria, pathobiological and positional, make the Fas antigen an interesting candidate for an association with AD. We performed a case-control association study between the common A/G polymorphism at position -670 in the Fas gene (TNFSRF6) promoter and sporadic AD in Jews, investigating whether this locus acts as a risk factor or whether it has a modifying effect. An association has recently been detected by Feuk et al. in the Scottish population between this locus and the risk of early-onset AD (EOAD), but not of LOAD. In agreement with Feuk et al., we found no association between this locus and the risk of LOAD (n = 86). However, in our small sample of patients with EOAD (n = 19), no association was found either. No interactive effect was found between the Fas promoter polymorphism at position -670 and the known risk factor of LOAD, apolipoprotein E epsilon4, and no association was detected with disease progression. These findings show no evidence for an association between the Fas promoter polymorphism at position -670 and AD in our population. PMID:14739535

Rosenmann, Hanna; Meiner, Zeev; Kahana, Esther; Aladjem, Zoja; Friedman, Gideon; Ben-Yehuda, Arie; Grenader, Tal; Wertman, Eli; Abramsky, Oded

2004-01-20

223

The Fas promoter polymorphism at position -670 is not associated with late-onset sporadic Alzheimer's disease.  

UK PubMed Central (United Kingdom)

The Fas antigen is a cell surface receptor-mediating cell apoptosis. Recent studies have demonstrated that Fas-associated apoptosis is involved in the pathogenesis of Alzheimer's disease (AD). Moreover, the Fas gene is located on chromosome 10q24.1, a region of linkage to late-onset AD (LOAD). These two criteria, pathobiological and positional, make the Fas antigen an interesting candidate for an association with AD. We performed a case-control association study between the common A/G polymorphism at position -670 in the Fas gene (TNFSRF6) promoter and sporadic AD in Jews, investigating whether this locus acts as a risk factor or whether it has a modifying effect. An association has recently been detected by Feuk et al. in the Scottish population between this locus and the risk of early-onset AD (EOAD), but not of LOAD. In agreement with Feuk et al., we found no association between this locus and the risk of LOAD (n = 86). However, in our small sample of patients with EOAD (n = 19), no association was found either. No interactive effect was found between the Fas promoter polymorphism at position -670 and the known risk factor of LOAD, apolipoprotein E epsilon4, and no association was detected with disease progression. These findings show no evidence for an association between the Fas promoter polymorphism at position -670 and AD in our population.

Rosenmann H; Meiner Z; Kahana E; Aladjem Z; Friedman G; Ben-Yehuda A; Grenader T; Wertman E; Abramsky O

2004-01-01

224

Simultaneous and common-volume three-lidar observations of sporadic metal layers in the mesopause region  

Science.gov (United States)

We report on the first simultaneous three-lidar observations of sporadic metal layers in the mesopause region. The case studies indicate that the sporadic layering events can be observed generally in three neutral metal atom species (Na, Fe and Ca) or two neutral atom and one ion species (Na, Fe and Ca+). The density enhancements of all the sporadic metal atom and ion species occurred in overlapping altitude range and moved following almost the same track, indicating that the sporadic metal layers are usually a mixture of multiple metal atom and ion species, meanwhile suggesting that all these metal species in a mixture are product of the same or similar source processes. Some strong multi-metal sporadic layering events were found to manifest a regular altitude relation that the Nas is highest, the Fes is a few to tens of hundreds of meters lower than the Nas, while the Cas is a few hundred meters lower than the Fes, and the Cas+ is lowest. This altitude sequence coincides well with the boiling-point dependent differential ablation in the thermal ablation theory. For those weak multi-metal sporadic events, the altitude relation becomes complicated. Profiles from two short sequences of a single night show that the formation/variation of the Cas+ layer features appeared to follow the related Nas and Fes layer features with a delayed period of ˜5 min. At altitudes above 105 km, weak single-species Cas+ layers were occasionally observed. This appears to reflect a feature of the sputtering ablation. For the explanation of our observations the formation mechanism issues of sporadic metal layers are discussed in detail.

Yi, Fan; Zhang, Shaodong; Yu, Changming; Zhang, Yunpeng; He, Yujin; Liu, Fuchao; Huang, Kaiming; Huang, Chunming; Tan, Ying

2013-09-01

225

Aryl hydrocarbon receptor interacting protein (AIP) mutations occur rarely in sporadic parathyroid adenomas.  

UK PubMed Central (United Kingdom)

CONTEXT: The molecular pathogenesis of primary hyperparathyroidism is still largely unknown. The aryl hydrocarbon receptor interacting protein (AIP) gene has a major role in the pathogenesis of familial isolated pituitary adenoma. OBJECTIVE: We evaluated the involvement of the AIP gene in sporadic parathyroid adenomas. PATIENTS AND DESIGN: We performed direct sequencing and multiplex ligation-dependent probe amplification analyses of the AIP gene in a large series of sporadic parathyroid adenomas. Loss of heterozygosity (LOH) at the AIP locus was studied, and aryl hydrocarbon receptor interacting protein immunostaining was also performed. In addition, alterations in the MEN1 gene were studied. RESULTS: A somatic AIP mutation, substitution of arginine with glutamine at codon 304 (R304Q), was identified in 2 of 132 tumors. The mutation was germline in both cases despite the nonfamilial presentation. Heterozygous AIP large deletions were detected in 29 cases including 1 of the 2 mutated tumors, confirming a biallelic inactivation of the AIP gene. The AIP-mutated tumor with LOH showed decreased AIP immunostaining compared with normal parathyroid. LOH at the MEN1 locus, which often shared LOH at the AIP locus, was found in one third of tumors. Somatic MEN1 mutations were found in the 1 of the 2 AIP-mutated tumors and in 22 parathyroid adenomas. In addition, multiplex ligation-dependent probe amplification analysis revealed 1 large deletion of the MEN1 gene in 1 patient. CONCLUSIONS: The AIP gene is rarely involved in parathyroid adenomas, but the germline nature of the mutations suggests that it might predispose to primary hyperparathyroidism. MEN1 gene alterations occur in a substantial proportion of sporadic parathyroid adenomas.

Pardi E; Marcocci C; Borsari S; Saponaro F; Torregrossa L; Tancredi M; Raspini B; Basolo F; Cetani F

2013-07-01

226

Risk of colorectal polyps in patients with sporadic gastric polyps: A case-control study  

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Full Text Available AIM: To assess the risk of colonic polyps, adenomas and advanced neoplastic lesions (ANL) in patients with sporadic gastric polyps, especially those with fundic gland polyps (FGP). METHODS: Clinical records of patients who had performed an upper and a lower digestive endoscopy between September 2007 and August 2008 were retrospectively analyzed. A case-control study was carried out, calling patients with gastric polyps as “cases” and patients without gastric polyps as “controls”. The risk of colonic polyps, adenomas and ANL (villous component ? 25%, size ? 10 mm, or high grade dysplasia) was assessed [odds ratio (OR) and its corresponding 95%CI]. RESULTS: Two hundred and forty seven patients were analyzed: 78 with gastric polyps (cases) and 169 without gastric polyps (controls). Among the cases, the majority of gastric polyps were FGP (80%, CI: 69-88) and hyperplastic (20%, CI: 12-31); 25% had colonic polyps (25% hyperplastic and 68% adenomas, from which 45% were ANL). Among the controls, 20% had colonic polyps (31% hyperplastic and 63% adenomas, from which 41% were ANL). The patients with sporadic FGP had an OR of 1.56 (CI: 0.80-3.04) for colonic polyps, an OR of 1.78 (CI: 0.82-3.84) for colonic adenomas, and an OR of 0.80 (CI: 0.21-2.98) for ANL. Similar results were found in patients with gastric polyps in general. CONCLUSION: The results of this study did not show more risk of colorectal adenomas or ANL neither in patients with sporadic gastric polyps nor in those with FGP.

Daniel Gustavo Cimmino; José Manuel Mella; Pablo Luna; Raquel González; Lisandro Pereyra; Carolina Fischer; Adriana Mohaidle; Beatriz Vizcaino; Mario Andres Medrano; Adrián Hadad; Silvia Pedreira; Luis Boerr

2013-01-01

227

Aurora A is differentially expressed and regulated in chromosomal and microsatellite instable sporadic colorectal cancers.  

UK PubMed Central (United Kingdom)

The centrosome-associated kinase aurora A has been shown to be involved in genetic instability and to be (over)expressed in several human carcinomas. This study investigated aurora A gene copy numbers, mRNA and protein expression as well as tumour cell proliferation and aneuploidy in chromosomal and microsatellite instable sporadic colorectal cancers. Case-matched tissues of normal (n=71) and dysplastic (n=49) colorectal epithelium and invasive carcinomas (n=71) were included in this study. PCR-based microsatellite analysis classified 14/71 (20%) of carcinomas as microsatellite instable. A stepwise increase of aurora A mRNA expression (P<0.0001; quantitative RT-PCR) and aurora A protein expressing tumour cells (P=0.0141; immunohistochemistry) occurred in the adenoma-carcinoma sequence. Within invasive carcinomas, aurora A mRNA levels (P=0.0259) and aurora A positive tumour cells (P<0.0001) were closely associated with tumour cell proliferation (Ki-67 specific immunohistochemistry). Compared with chromosomal instable carcinomas, microsatellite instable carcinomas had significantly more aurora A positive tumour cells (P=0.0043) and a higher tumour cell proliferation (P=0.0335). In contrast, only chromosomal instable carcinomas exhibited marked tumour cell aneuploidy (P=0.0004, fluorescence in situ hybridization) and significantly higher aurora A gene copy numbers (P=0.0206) as compared with microsatellite instable carcinomas. This study further supports a role of aurora A in the carcinogenesis of sporadic colorectal cancers. Moreover, it demonstrates that in a minority of predominantly microsatellite instable carcinomas the presence of aurora A positive tumour cells is merely reflecting tumour cell proliferation. In contrast, the large majority of chromosomal instable carcinomas shows additional (de)regulation of aurora A by gene amplification and concomitant tumour cell aneuploidy. Thus, sporadic colorectal cancers exhibit different mechanisms of aurora A regulation and this may impact the efficacy of aurora-targeted therapies.

Lassmann S; Danciu M; Müller M; Weis R; Makowiec F; Schulte-Mönting J; Hopt UT; Werner M

2009-10-01

228

Aurora A is differentially expressed and regulated in chromosomal and microsatellite instable sporadic colorectal cancers.  

Science.gov (United States)

The centrosome-associated kinase aurora A has been shown to be involved in genetic instability and to be (over)expressed in several human carcinomas. This study investigated aurora A gene copy numbers, mRNA and protein expression as well as tumour cell proliferation and aneuploidy in chromosomal and microsatellite instable sporadic colorectal cancers. Case-matched tissues of normal (n=71) and dysplastic (n=49) colorectal epithelium and invasive carcinomas (n=71) were included in this study. PCR-based microsatellite analysis classified 14/71 (20%) of carcinomas as microsatellite instable. A stepwise increase of aurora A mRNA expression (P<0.0001; quantitative RT-PCR) and aurora A protein expressing tumour cells (P=0.0141; immunohistochemistry) occurred in the adenoma-carcinoma sequence. Within invasive carcinomas, aurora A mRNA levels (P=0.0259) and aurora A positive tumour cells (P<0.0001) were closely associated with tumour cell proliferation (Ki-67 specific immunohistochemistry). Compared with chromosomal instable carcinomas, microsatellite instable carcinomas had significantly more aurora A positive tumour cells (P=0.0043) and a higher tumour cell proliferation (P=0.0335). In contrast, only chromosomal instable carcinomas exhibited marked tumour cell aneuploidy (P=0.0004, fluorescence in situ hybridization) and significantly higher aurora A gene copy numbers (P=0.0206) as compared with microsatellite instable carcinomas. This study further supports a role of aurora A in the carcinogenesis of sporadic colorectal cancers. Moreover, it demonstrates that in a minority of predominantly microsatellite instable carcinomas the presence of aurora A positive tumour cells is merely reflecting tumour cell proliferation. In contrast, the large majority of chromosomal instable carcinomas shows additional (de)regulation of aurora A by gene amplification and concomitant tumour cell aneuploidy. Thus, sporadic colorectal cancers exhibit different mechanisms of aurora A regulation and this may impact the efficacy of aurora-targeted therapies. PMID:19648887

Lassmann, Silke; Danciu, Mihai; Müller, Matthias; Weis, Roland; Makowiec, Frank; Schulte-Mönting, Jürgen; Hopt, Ulrich T; Werner, Martin

2009-07-31

229

PTCH mutations are not mainly involved in the pathogenesis of sporadic trichoblastomas.  

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Trichoblastomas are rare, benign tumors of the appendix in human skin. The histopathology comprises elements of basal cell carcinoma and trichoepithelioma with a variable degree of follicular differentiation. Both basal cell carcinoma and trichoepithelioma reveal alterations of PTCH, the human homolog of the Drosophila segment polarity patched gene. Furthermore, heterozygous PTCH knockout mice develop trichoblastoma-like tumors. This suggests an involvement of the PTCH gene in the pathogenesis of human trichoblastomas. However, trichoblastomas arising in nevus sebaceus did not show loss of heterozygosity at the PTCH locus (9q22.3) in a previous study. Sequencing of the PTCH gene and analysis of sporadic human trichoblastomas have not been performed yet. We therefore screened 10 sporadic trichoblastomas and 1 trichoblastoma arising within a nevus sebaceus for PTCH mutations. After microdissection of the tumors, single-strand conformational polymorphism (SSCP)/heteroduplex analysis of exons 2 to 23 of PTCH was performed, and polymerase chain reaction products with aberrant band patterns were sequenced. One trichoblastoma revealed a silent mutation at codon 562 in exon 12. Another trichoblastoma showed a somatic C > T single nucleotide substitution at codon 1,315 (exon 23), which was not present in corresponding normal epidermis. This mutation at codon 1,315 represents an already described PTCH germline polymorphism and results in a heterozygous Pro to Leu substitution in the tumor. The Pro/Leu polymorphism in germline is associated with a higher risk for breast cancer, but a potential contribution to the tumorigenesis of trichoblastoma is unknown. We detected no classical PTCH mutations in the investigated trichoblastomas. Our results indicate that PTCH mutations are not mainly involved in the pathogenesis of sporadic trichoblastomas, in contrast to basal cell carcinomas and trichoepitheliomas. The genetic basis of this rare appendageal tumor remains elusive. PMID:17597182

Hafner, Christian; Schmiemann, Viola; Ruetten, Arno; Coras, Brigitte; Landthaler, Michael; Reifenberger, Julia; Vogt, Thomas

2007-06-26

230

PTCH mutations are not mainly involved in the pathogenesis of sporadic trichoblastomas.  

UK PubMed Central (United Kingdom)

Trichoblastomas are rare, benign tumors of the appendix in human skin. The histopathology comprises elements of basal cell carcinoma and trichoepithelioma with a variable degree of follicular differentiation. Both basal cell carcinoma and trichoepithelioma reveal alterations of PTCH, the human homolog of the Drosophila segment polarity patched gene. Furthermore, heterozygous PTCH knockout mice develop trichoblastoma-like tumors. This suggests an involvement of the PTCH gene in the pathogenesis of human trichoblastomas. However, trichoblastomas arising in nevus sebaceus did not show loss of heterozygosity at the PTCH locus (9q22.3) in a previous study. Sequencing of the PTCH gene and analysis of sporadic human trichoblastomas have not been performed yet. We therefore screened 10 sporadic trichoblastomas and 1 trichoblastoma arising within a nevus sebaceus for PTCH mutations. After microdissection of the tumors, single-strand conformational polymorphism (SSCP)/heteroduplex analysis of exons 2 to 23 of PTCH was performed, and polymerase chain reaction products with aberrant band patterns were sequenced. One trichoblastoma revealed a silent mutation at codon 562 in exon 12. Another trichoblastoma showed a somatic C > T single nucleotide substitution at codon 1,315 (exon 23), which was not present in corresponding normal epidermis. This mutation at codon 1,315 represents an already described PTCH germline polymorphism and results in a heterozygous Pro to Leu substitution in the tumor. The Pro/Leu polymorphism in germline is associated with a higher risk for breast cancer, but a potential contribution to the tumorigenesis of trichoblastoma is unknown. We detected no classical PTCH mutations in the investigated trichoblastomas. Our results indicate that PTCH mutations are not mainly involved in the pathogenesis of sporadic trichoblastomas, in contrast to basal cell carcinomas and trichoepitheliomas. The genetic basis of this rare appendageal tumor remains elusive.

Hafner C; Schmiemann V; Ruetten A; Coras B; Landthaler M; Reifenberger J; Vogt T

2007-10-01

231

Establishment, Characterization and Chemosensitivity of Three Mismatch Repair Deficient Cell Lines from Sporadic and Inherited Colorectal Carcinomas  

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Background Colorectal cancer (CRC) represents a morphologic and molecular heterogenic disease. This heterogeneity substantially impairs drug effectiveness and prognosis. The subtype of mismatch repair deficient (MMR-D) CRCs, accounting for about 15% of all cases, shows particular differential responses up to resistance towards currently approved cytostatic drugs. Pre-clinical in vitro models representing molecular features of MMR-D tumors are thus mandatory for identifying biomarkers that finally help to predict responses towards new cytostatic drugs. Here, we describe the successful establishment and characterization of three patient-derived MMR-D cell lines (HROC24, HROC87, and HROC113) along with their corresponding xenografts. Methodology MMR-D cell lines (HROC24, HROC87, and HROC113) were established from a total of ten clinicopathological well-defined MMR-D cases (120 CRC cases in total). Cells were comprehensively characterized by phenotype, morphology, growth kinetics, invasiveness, and molecular profile. Additionally, response to clinically relevant chemotherapeutics was examined in vitro and in vivo. Principal Findings Two MMR-D lines showing CIMP-H derived from sporadic CRC (HROC24: K-raswt, B-rafmut, HROC87: K-raswt, B-rafmut), whereas the HROC113 cell line (K-rasmut, B-rafwt) was HNPCC-associated. A diploid DNA-status could be verified by flow cytometry and SNP Array analysis. All cell lines were characterized as epithelial (EpCAM+) tumor cells, showing surface tumor marker expression (CEACAM+). MHC-class II was inducible by Interferon-? stimulation. Growth kinetics as well as invasive potential was quite heterogeneous between individual lines. Besides, MMR-D cell lines exhibited distinct responsiveness towards chemotherapeutics, even when comparing in vitro and in vivo sensitivity. Conclusions These newly established and well-characterized, low-passage MMR-D cell lines provide a useful tool for future investigations on the biological characteristics of MMR-D CRCs, both of sporadic and hereditary origin. Additionally, matched patient-derived immune cells allow for comparative genetic studies.

Maletzki, Claudia; Stier, Saskia; Gruenert, Ulrike; Gock, Michael; Ostwald, Christiane; Prall, Friedrich; Linnebacher, Michael

2012-01-01

232

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

Science.gov (United States)

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

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

2012-11-30

233

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

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

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

2008-01-01

234

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

UK PubMed Central (United Kingdom)

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

Penco S; Buscema M; Patrosso MC; Marocchi A; Grossi E

2008-01-01

235

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

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

Fernandez Bridget A; Fox George; Bhatia Rick; Sala Eric; Noble Barbara; Denic Nash; Fernandez Dzintra; Duguid Nigel; Dohey Amanda; Kamel Fady; Edwards Laura; Mahoney Krista; Stuckless Susan; Parfrey Patrick S; Woods Michael O

2012-01-01

236

Phenotypic Variability of Familial and Sporadic Progranulin p.Gln257Profs*27 Mutation.  

UK PubMed Central (United Kingdom)

The clinical phenotype of frontotemporal dementia patients carrying progranulin (GRN) mutations is known to be heterogeneous. We present a patient with corticobasal syndrome and a family with progressive aphasia and behavioral features who were found to have the same p.Gln257Profs*27 mutation. These cases depict the variability of GRN mutation carriers regarding clinical presentation and age of onset. In addition to giving a detailed report of a GRN mutation, we highlight the importance of searching for the presence of GRN mutations in selected sporadic cases and suggest a broadening of GRN genetic screening to better understand the clinical spectrum of these mutations.

Pires C; Coelho M; Valadas A; Barroso C; Pimentel J; Martins M; Duyckaerts C; de Mendonça A; Verdelho A; Miltenberger-Miltenyi G

2013-01-01

237

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

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Although rare, the chronic neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and idiopathic parkinsonism coexist to a greater degree than expected by chance. This suggests that patients with ALS may have subclinical lesions of the nigrostriatal dopaminergic pathway. To study this hypothesis, the authors did positron emission tomography with 6-fluorodopa on 16 patients with sporadic ALS and without extrapyramidal disease, and compared the results with age-matched controls. They found a significant progressive fall in 6-fluorodopa uptake with time since diagnosis, and reduced dopaminergic function in 3 patients with ALS of long duration. This supports the hypothesis that ALS and IP may share pathogenesis, and, perhaps, etiology.

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

1993-10-23

238

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

International Nuclear Information System (INIS)

Although rare, the chronic neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and idiopathic parkinsonism coexist to a greater degree than expected by chance. This suggests that patients with ALS may have subclinical lesions of the nigrostriatal dopaminergic pathway. To study this hypothesis, the authors did positron emission tomography with 6-fluorodopa on 16 patients with sporadic ALS and without extrapyramidal disease, and compared the results with age-matched controls. They found a significant progressive fall in 6-fluorodopa uptake with time since diagnosis, and reduced dopaminergic function in 3 patients with ALS of long duration. This supports the hypothesis that ALS and IP may share pathogenesis, and, perhaps, etiology

1993-10-23

239

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

Directory of Open Access Journals (Sweden)

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

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

1999-01-01

240

Evaluation of heme oxygenase-1 as a systemic biological marker of sporadic AD.  

UK PubMed Central (United Kingdom)

BACKGROUND: Heme oxygenase-1 (HO-1) is a 32-kDa stress protein that catalyzes the degradation of heme to biliverdin. HO-1 immunoreactivity is greatly increased in neurons and astrocytes of the hippocampus and cerebral cortex of individuals with AD and colocalizes to senile plaques and neurofibrillary tangles. METHODS: We investigated whether systemic HO-1 regulation is also deranged in AD patients and whether blood HO-1 measurements provide a peripheral biomarker of the disease. Plasma HO-1 protein levels were measured by competitive ELISA and lymphocyte HO-1 mRNA levels were determined by Northern analysis in patients with early probable sporadic AD, normal elderly controls (NEC), normal younger controls, individuals with age-associated cognitive decline (AACD) not meeting AD criteria, and patients with non-Alzheimer dementia, nondementing neurologic illness, and chronic medical disorders. CSF HO-1 protein concentrations were also determined by ELISA in pathologically confirmed AD and control cases. RESULTS: Mean plasma HO-1 protein concentrations were significantly lower in AD patients (0.85 +/- 0.14 microg/mL) compared with NEC (1.77 +/- 0.34 microg/mL; p < 0.05) and control patients. The AACD group exhibited plasma HO-1 concentrations (1.06 +/- 0.33 microg/mL) intermediate between, but not different from, those of the AD patients and NEC. Lymphocyte HO-1 mRNA levels were lower in the AD cohort relative to NEC (p < 0.001) and individuals with AACD, non-Alzheimer dementia, nondementing neurologic illness, and chronic medical conditions. Lymphocyte HO-1 mRNA levels were also lower in the AACD group relative to NEC (p < 0.05). In comparison with all groups excluding AACD, the sensitivity and specificity of lymphocyte HO-1 mRNA measurement for diagnosis of early sporadic AD are 88% and 75%. Mean CSF HO-1 protein concentrations were lower (p < 0.01) in AD cases (19.07 ng/mL) relative to control values (32.48 ng/mL). CONCLUSIONS: Plasma and CSF HO-1 protein and lymphocyte HO-1 mRNA levels are decreased in subjects with sporadic AD. Quantitative assay for lymphocyte HO-1 mRNA expression may serve as a useful biologic marker in early sporadic AD.

Schipper HM; Chertkow H; Mehindate K; Frankel D; Melmed C; Bergman H

2000-03-01

 
 
 
 
241

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

Directory of Open Access Journals (Sweden)

Full Text Available Creutzfeldt-Jakob disease (CJD) is a rare but fatal neurodegenerative prion disease. Classic CJD comprises a clinical triad of rapidly progressive dementia, myoclonus, and EEG abnormality. At initial presentation, this classic triad is present only in a minority of cases. Visual impairment is one of the predominant manifestations in the course of CJD, especially in Heidenhain variant phenotype. We reported a case presenting with progressive blurred vision, along with other neurological symptoms, who diagnosed as sporadic CJD with cortical blindness in China.

Guohong Tian; Lin Sun; Yunhong He; Xiaojun Zhang

2013-01-01

242

Association of apolipoprotein E epsilon 4 allele with sporadic late onset Alzheimer`s disease. A meta-analysis.  

UK PubMed Central (United Kingdom)

OBJECTIVE: To obtain a better insight into the effect of the epsilon (e) 4 allele of the apolipoprotein E gene (APOE) on the risk of late onset Alzheimer`s disease (LOAD), and assess its heterogeneity in geographic regions. METHODS: We performed a systemic review and meta-analysis of available studies. An electronic and manual search of international and local databases was conducted to identify relevant studies between January 1991 and December 2011 in the Central Library of Tabriz University of Medical Sciences, Tabriz, Iran. All articles related to patients with LOAD that evaluated APOE genotype were included in our study. Two reviewers assessed the inclusion/exclusion criteria, summarized, and analyzed the extracted data. We assessed 21 separate studies overall involving 1480 subjects; the total sample size was 6777. RESULTS: According to the results, there was no heterogeneity among the included studies. The total APOE e4 allele frequency was significantly higher in AD cases compared with control subjects (35% versus 11.43%, p<0.001). The odds ratio (OR) for APOE e4 frequency in AD and control groups was 3.98 (95% confidence interval [CI]: 3.44-4.61). This factor in various geographic regions was different. CONCLUSION: This meta-analysis is strongly supportive of the hypothesis that the APOE e4 allele increases the risk of sporadic LOAD, and determination of the e4 allele in populations may be a useful tool for monitoring demented patients and planning healthcare policies.

Sadigh-Eteghad S; Talebi M; Farhoudi M

2012-10-01

243

Amelioration of cognitive deficits and neurodegeneration by curcumin in rat model of sporadic dementia of Alzheimer's type (SDAT).  

UK PubMed Central (United Kingdom)

Recent evidence indicates that curcumin (CUR), the principal curcuminoid of turmeric, exhibits antioxidant potential and protects the brain against various oxidative stressors. The aim of the present study was to examine the modulating impacts of CUR against cognitive deficits and oxidative damage in intracerebroventricular-streptozotocin (ICV-STZ) infused rats. Rats were injected bilaterally with ICV-STZ (3 mg/kg), while sham rats received the same volume of vehicle and then supplemented with CUR (80 mg/kg) for three weeks. After two weeks of ICV-STZ infusion, rats were tested for cognitive performance using passive avoidance and water maze tasks and then sacrificed for biochemical and histopathological assays. ICV-STZ rats showed significant cognitive deficits, which were significantly improved by CUR supplementation. CUR supplementation significantly augmented increased 4-hydroxynonenal (4-HNE) and malonaldehyde (MDA), thiobarbituric reactive substances (TBARS), hydrogen peroxide (H2O2), protein carbonyl (PC) and oxidized glutathione (GSSG); decreased levels of reduced glutathione (GSH) and its dependent enzymes (Glutathione peroxidase [GPx] and glutathione reductase [GR]) in the hippocampus and cerebral cortex; and increased choline acetyltransferase (ChAT) activity in the hippocampus of ICV-STZ rats. The study suggests that CUR is effective in preventing cognitive deficits, and might be beneficial for the treatment of sporadic dementia of Alzheimer's type (SDAT).

Ishrat T; Hoda MN; Khan MB; Yousuf S; Ahmad M; Khan MM; Ahmad A; Islam F

2009-09-01

244

Amelioration of cognitive deficits and neurodegeneration by curcumin in rat model of sporadic dementia of Alzheimer's type (SDAT).  

Science.gov (United States)

Recent evidence indicates that curcumin (CUR), the principal curcuminoid of turmeric, exhibits antioxidant potential and protects the brain against various oxidative stressors. The aim of the present study was to examine the modulating impacts of CUR against cognitive deficits and oxidative damage in intracerebroventricular-streptozotocin (ICV-STZ) infused rats. Rats were injected bilaterally with ICV-STZ (3 mg/kg), while sham rats received the same volume of vehicle and then supplemented with CUR (80 mg/kg) for three weeks. After two weeks of ICV-STZ infusion, rats were tested for cognitive performance using passive avoidance and water maze tasks and then sacrificed for biochemical and histopathological assays. ICV-STZ rats showed significant cognitive deficits, which were significantly improved by CUR supplementation. CUR supplementation significantly augmented increased 4-hydroxynonenal (4-HNE) and malonaldehyde (MDA), thiobarbituric reactive substances (TBARS), hydrogen peroxide (H2O2), protein carbonyl (PC) and oxidized glutathione (GSSG); decreased levels of reduced glutathione (GSH) and its dependent enzymes (Glutathione peroxidase [GPx] and glutathione reductase [GR]) in the hippocampus and cerebral cortex; and increased choline acetyltransferase (ChAT) activity in the hippocampus of ICV-STZ rats. The study suggests that CUR is effective in preventing cognitive deficits, and might be beneficial for the treatment of sporadic dementia of Alzheimer's type (SDAT). PMID:19329286

Ishrat, Tauheed; Hoda, Md Nasrul; Khan, M Badruzzaman; Yousuf, Seema; Ahmad, Muzamil; Khan, Mohd Moshahid; Ahmad, Ajmal; Islam, Fakhrul

2009-03-28

245

The Fas gene A-670G polymorphism is not associated with sporadic Alzheimer disease in a Chinese Han population.  

Science.gov (United States)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by excessive neuronal loss, intracellular neurofibrillary tangles and extracellular deposition of amyloid beta-peptide (Abeta). The Fas antigen is a cell surface receptor-mediating cell apoptosis. Several lines of evidence have made Fas/Fas ligand induced apoptosis play an important role in the pathogenesis of AD. Moreover, the Fas gene is located on chromosome 10q24.1, a region of linkage to late-onset AD. Several reports have investigated the association between a single nucleotide polymorphism (SNP) that is located at position -670 of Fas gene and AD, but yielded ambiguous results. To figure out the association of this SNP with sporadic AD in Chinese Han population, we have analyzed 509 patients with AD and 561 controls for the genetic association studies. Our results indicate that the distribution of the Fas genotypes (chi(2) = 0.66, P = 0.72) and alleles (chi(2) = 0.70, P = 0.40) did not differ significantly. The similar results were observed when AD and control groups were stratified by age/age at onset and sex (P > 0.10). The present data revealed no significant effect of the genotypes on the age of onset for developing AD, and no significant association between the genotypes and the severity of the disease. PMID:16703675

He, Xiao-ming; Zhang, Zhen-xin; Zhang, Jun-wu; Zhou, Yong-tao; Tang, Mou-ni; Wu, Cheng-bin; Hong, Zhen

2006-04-12

246

The Fas gene A-670G polymorphism is not associated with sporadic Alzheimer disease in a Chinese Han population.  

UK PubMed Central (United Kingdom)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by excessive neuronal loss, intracellular neurofibrillary tangles and extracellular deposition of amyloid beta-peptide (Abeta). The Fas antigen is a cell surface receptor-mediating cell apoptosis. Several lines of evidence have made Fas/Fas ligand induced apoptosis play an important role in the pathogenesis of AD. Moreover, the Fas gene is located on chromosome 10q24.1, a region of linkage to late-onset AD. Several reports have investigated the association between a single nucleotide polymorphism (SNP) that is located at position -670 of Fas gene and AD, but yielded ambiguous results. To figure out the association of this SNP with sporadic AD in Chinese Han population, we have analyzed 509 patients with AD and 561 controls for the genetic association studies. Our results indicate that the distribution of the Fas genotypes (chi(2) = 0.66, P = 0.72) and alleles (chi(2) = 0.70, P = 0.40) did not differ significantly. The similar results were observed when AD and control groups were stratified by age/age at onset and sex (P > 0.10). The present data revealed no significant effect of the genotypes on the age of onset for developing AD, and no significant association between the genotypes and the severity of the disease.

He XM; Zhang ZX; Zhang JW; Zhou YT; Tang MN; Wu CB; Hong Z

2006-04-01

247

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

Science.gov (United States)

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.

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

2010-09-01

248

Formation of gelsolin amyloid fibrils in the rough endoplasmic reticulum of skeletal muscle in the gelsolin mouse model of inclusion body myositis: comparative analysis to human sporadic inclusion body myositis.  

UK PubMed Central (United Kingdom)

Abstract Sporadic inclusion body myositis has a significant impact on the life of the elderly. Despite some similarities to other myopathies with established genetic defects, little is known about mechanisms of its development and no effective treatment is available. Therefore, there is a need for animal models that can faithfully reconstitute important aspects of this human disease. The authors recently expressed a mutant form of human gelsolin in mice under the control of a muscle-specific promoter. This induced myopathic changes reminiscent of human inclusion body myositis. In this study, immunogold labeling is used to further characterize this model. The study demonstrates a presence of gelsolin amyloid deposits within the rough endoplasmic reticulum. It further compares this mouse model to human sporadic inclusion body myositis.

Bannykh SI; Balch WE; Kelly JW; Page LJ; Shelton GD

2013-10-01

249

Formation of gelsolin amyloid fibrils in the rough endoplasmic reticulum of skeletal muscle in the gelsolin mouse model of inclusion body myositis: comparative analysis to human sporadic inclusion body myositis.  

Science.gov (United States)

Abstract Sporadic inclusion body myositis has a significant impact on the life of the elderly. Despite some similarities to other myopathies with established genetic defects, little is known about mechanisms of its development and no effective treatment is available. Therefore, there is a need for animal models that can faithfully reconstitute important aspects of this human disease. The authors recently expressed a mutant form of human gelsolin in mice under the control of a muscle-specific promoter. This induced myopathic changes reminiscent of human inclusion body myositis. In this study, immunogold labeling is used to further characterize this model. The study demonstrates a presence of gelsolin amyloid deposits within the rough endoplasmic reticulum. It further compares this mouse model to human sporadic inclusion body myositis. PMID:24047347

Bannykh, Sergei I; Balch, William E; Kelly, Jeffery W; Page, Lesley J; Shelton, G Diane

2013-10-01

250

A new germline VHL gene mutation in three patients with apparently sporadic pheochromocytoma.  

UK PubMed Central (United Kingdom)

CONTEXT: Germline mutations in four genes (RET, VHL, SDHB and SDHD) are detected in about 17% of patients with apparently sporadic pheochromocytoma. Thus, genetic screening of all patients with this disease is suggested for a rational diagnostic approach and management. OBJECTIVE: To report the clinical, biochemical and genetic analysis of three unrelated patients affected by pheochromocytoma. DESIGN AND PATIENTS: All the coding regions and exon-intron boundaries of RET, VHL, SDHB and SDHD genes were sequenced in three unrelated patients with intra-adrenal pheochromocytoma: a 17-year-old girl, a 15-year-old boy and a 73-year-old man. The family history of all three cases was negative for von Hippel-Lindau lesions or other types of endocrine tumours. Structural modelling of the VHL protein was then performed. RESULTS: We identified a novel germline VHL gene point mutation, a G to A nucleotide substitution in exon 3, leading to an aspartate to asparagine amino acid change in codon 197 (D197N). No mutations were found in RET, SDHB and SDHD genes. Structural modelling of the VHL protein suggests that the D197N mutation could have a functional role. CONCLUSIONS: Our study expands the number of VHL gene known mutations and indicates the usefulness of performing the genetic analysis in all patients with apparently sporadic pheochromocytoma.

D'Elia AV; Grimaldi F; Pizzolitto S; De Maglio G; Bregant E; Passon N; Franzoni A; Verrienti A; Tamburrano G; Durante C; Filetti S; Fogolari F; Russo D; Damante G

2013-03-01

251

[Sporadic adenoma and colitis-associated intraepithelial neoplasia: a difficult differential diagnosis  

UK PubMed Central (United Kingdom)

The differential diagnosis between sporadic adenoma and colitis-associated neoplasia is difficult. Clinical, histological and molecular genetic methods are available to recognise a difference between these two entities. The aim of the present analysis was to check known criteria in a large series of patients and 352 patients with ulcerative colitis and concomitant intraepithelial neoplastic lesions [149 adenomas (A), 123 colitis-associated intraepithelial neoplasias (N), 80 carcinomas (K)] were investigated. Clinical history helped to identify patients with sporadic adenoma since patients with colitis-associated neoplastic lesions presented with different data such as age (A: 61.3+/-13 years, N: 48.4+/-16.4 years, K: 53.9+/-16.9 years), duration of disease (A: 6.9+/-8.1 years, N: 11.9+/-10 years, K: 13.6+/-9.6 years), frequency of pancolitis (A: 28.6%, N: 56.3%, K: 48.3%) and frequency of solitary lesions (A: 83.7%, N: 23.1%, K: 51.9%). The differential diagnosis between adenoma and colitis-associated neoplasia in patients with ulcerative colitis appears to be possible but the diagnosis should only be made in the remission phase. Furthermore the patients need a careful endoscopic and bioptic follow-up. If in doubt one should consider colitis-associated neoplasia especially when there are multiple intraepithelial neoplastic lesions. Long-term follow-up studies are urgently needed.

Vieth M; Behrens H; Stolte M

2003-02-01

252

Ultrasound-guided unilateral neck exploration for sporadic primary hyperparathyroidism: is it worthwhile?  

UK PubMed Central (United Kingdom)

The role of preoperative localisation tests before initial neck exploration for primary hyperparathyroidism (PHP) remains controversial, as does the optimal surgical approach. We report our experience with preoperative ultrasound (US) and the operative management of sporadic PHP between 1990 and 1995. Preoperative US was carried out by an experienced radiologist. Three surgeons adopted a policy of 'selective' US-guided unilateral neck exploration (UNE); the fourth surgeon performed routine bilateral neck exploration (BNE). There were 72 patients: 26 men and 46 women, with a mean age of 57.4 +/- 12.5 years (range 21-80 years). All patients underwent initial neck exploration for 'sporadic' PHP, of whom 63 had preoperative US. This was positive in 52 patients; 27 of whom underwent a UNE, 23 had a BNE, and two patients had a UNE converted to a BNE. Patients with 'negative' US (n = 11), and those receiving no preoperative localisation test (n = 90) underwent a BNE. The sensitivity, specificity and accuracy of US were 80% (52/65), 100% (61/61), and 90% (113/126), respectively. Comparable success rates were achieved (BNE: 97% (33/34) vs UNE: 93% (27/29), P < 0.05), with very low morbidity. Failures with the scan-guided UNE were caused by missed contralateral adenomas. An experienced radiologist and a low incidence of multiglandular disease (MGD) are essential prerequisites for the scan-guided unilateral approach. An experienced surgeon, on the other hand, is the only prerequisite for the 'gold standard' bilateral approach.

Ammori BJ; Madan M; Gopichandran TD; Price JJ; Whittaker M; Ausobsky JR; Antrum RM

1998-11-01

253

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

UK PubMed Central (United Kingdom)

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

Craggs LJ; Hagel C; Kuhlenbaeumer G; Borjesson-Hanson A; Andersen O; Viitanen M; Kalimo H; McLean CA; Slade JY; Hall RA; Oakley AE; Yamamoto Y; Deramecourt V; Kalaria RN

2013-09-01

254

Longitudinal observational study of sporadic inclusion body myositis: implications for clinical trials.  

UK PubMed Central (United Kingdom)

Sporadic inclusion body myositis (IBM) is the most common acquired myopathy occurring in adults aged over 50 years. The aim of the study was to assess prospectively the clinical features and functional impact of sporadic inclusion body myositis (IBM). Clinical data, manual muscle testing (MMT), quantitative muscle testing (QMT) of quadriceps muscle and IBM functional rating scale (IBM-FRS) were collected according to a standardised protocol at baseline (n=51) and one-year follow-up (n=23). MMT, quadriceps QMT and IBM-FRS significantly declined after one year (by 5.2%, 27.9%, and 13.8%, respectively). QMT of the quadriceps muscle and IBM-FRS were the most sensitive measures of disease progression. After a median time of seven years of disease duration, 63% of patients had lost independent walking. Disease onset after 55 years of age, but not sex or treatment, is predictive of a shorter time to requirement of a walking stick. We detected no differences in disease presentation and progression between clinically and pathologically defined IBM patients. The study provides evidence that quadriceps QMT and IBM-FRS could prove helpful as outcome measures in future therapeutic trials in IBM.

Cortese A; Machado P; Morrow J; Dewar L; Hiscock A; Miller A; Brady S; Hilton-Jones D; Parton M; Hanna MG

2013-05-01

255

Longitudinal observational study of sporadic inclusion body myositis: implications for clinical trials.  

Science.gov (United States)

Sporadic inclusion body myositis (IBM) is the most common acquired myopathy occurring in adults aged over 50 years. The aim of the study was to assess prospectively the clinical features and functional impact of sporadic inclusion body myositis (IBM). Clinical data, manual muscle testing (MMT), quantitative muscle testing (QMT) of quadriceps muscle and IBM functional rating scale (IBM-FRS) were collected according to a standardised protocol at baseline (n=51) and one-year follow-up (n=23). MMT, quadriceps QMT and IBM-FRS significantly declined after one year (by 5.2%, 27.9%, and 13.8%, respectively). QMT of the quadriceps muscle and IBM-FRS were the most sensitive measures of disease progression. After a median time of seven years of disease duration, 63% of patients had lost independent walking. Disease onset after 55 years of age, but not sex or treatment, is predictive of a shorter time to requirement of a walking stick. We detected no differences in disease presentation and progression between clinically and pathologically defined IBM patients. The study provides evidence that quadriceps QMT and IBM-FRS could prove helpful as outcome measures in future therapeutic trials in IBM. PMID:23489664

Cortese, A; Machado, P; Morrow, J; Dewar, L; Hiscock, A; Miller, A; Brady, S; Hilton-Jones, D; Parton, M; Hanna, M G

2013-03-11

256

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

UK PubMed Central (United Kingdom)

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

Rafati M; Seyyedaboutorabi E; Ghadirzadeh MR; Heshmati Y; Adibi H; Keihanidoust Z; Eshraghian MR; Javadi GR; Dastan J; Mosavi-Jarrahi A; Hoseini A; Purhoseini M; Ghaffari SR

2012-01-01

257

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

UK PubMed Central (United Kingdom)

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

Akelma AZ; Cizmeci MN; Kanburoglu MK; Mete E; Bozkaya D; Tufan N; Catal F

2013-08-01

258

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

Science.gov (United States)

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

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

2013-05-06

259

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

Directory of Open Access Journals (Sweden)

Full Text Available Cerebral amyloid angiopathy (CAA) refers to the specific deposition of amyloid fibrils in the leptomeningeal and cerebral blood vessel walls, often causing secondary vascular degenerative changes. Although many kinds of peptides are known to be deposited as vascular amyloid, amyloid-? (A?)-CAA is the most common type associated with normal aging, sporadic CAA, Alzheimer’s disease (AD) and Down’s syndrome. Moreover, A?-CAA is also associated with rare hereditary cerebrovascular amyloidosis due to mutations within the A? domain of the amyloid precursor protein (APP) such as Dutch and Flemish APP mutations. Genetics and clinicopathological studies on these familial diseases as well as sporadic conditions have already shown that CAA not only causes haemorrhagic and ischemic strokes, but also leads to progressive dementia. Transgenic mouse models based on familial AD mutations have also successfully reproduced many of the features found in human disease, providing us with important insights into the pathogenesis of CAA. Importantly, such studies have pointed out that specific vastopic A? variants or an unaltered A?42/A?40 ratio favor vascular A? deposition over parenchymal plaques, but higher than critical levels of A?40 are also observed to be anti-amyloidogenic. These data would be important in the development of therapies targeting amyloid in vessels.

Samir Kumar-Singh

2009-01-01

260

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

Directory of Open Access Journals (Sweden)

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

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

2012-01-01

 
 
 
 
261

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

Science.gov (United States)

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

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

2010-06-01

262

Lidar observations of sporadic Na layers over Gadanki (13.5° N, 79.2° E)  

Directory of Open Access Journals (Sweden)

Full Text Available We studied the characteristics of sporadic sodium layers (SSLs) observed with the sodium (Na) resonance scattering lidar at Gadanki (13.5° N, 79.2° E). The SSLs were observed on a total of 63 occasions during 464 h of Na lidar observations from January 2005 to February 2006. The observations showed that one SSL event occurred, on average, every 7 h. The most prominent sporadic layer, which formed on 12 February 2005, exhibited a peak density of 60 722 Na atoms/cm³ around 92 km and it was nearly twice the peak density reported from elsewhere using ground-based observations. In general, the SSLs exhibited the following characteristics: (1) they developed at heights between 88 and 98 km with an average height around 94 km; (2) maximum density occurred during the early morning hours between 02:00 and 05:00 IST; (3) the ratio of the maximum peak Na density to the average density was normally around 3 to 5 and it exceeded even 10 in some cases; (4) the events lasted from a few minutes to several hours. The formation period of the SSLs was longer compared to the decay period of the SSLs. Most of the SSL events showed downward motions.

P. Vishnu Prasanth; S. Sridharan; Y. Bhavani Kumar; D. Narayana Rao

2007-01-01

263

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

DEFF Research Database (Denmark)

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

Coutinho Calado Domingues, Ana Rita; Pires, Sara Monteiro

264

Loss of heterozygosity at the BRCA1 locus in Tunisian women with sporadic breast cancer.  

Science.gov (United States)

Breast cancer in Tunisia is characterized by a much higher incidence of aggressiveness compared with Western countries. The pattern of allelic loss at the BRCA1 locus in Tunisian women with breast carcinoma has not been studied. Therefore, the aim of this present preliminary study was mainly focused on loss of heterozygosity (LOH) analysis of the BRCA1 gene to determine if this tumor suppressor gene is involved in sporadic breast carcinoma among Tunisian women. We investigate allelic losses by analyzing three microsatellite markers in the BRCA1 region, in a panel of 21 human breast tumors. D17S1322 marker had the highest frequency of LOH (59%), followed by the D17S1323 (35%), and EDH-17B (20%). Collectively out of 21 informative cases 13 (62%) showed LOH at at least one BRCA1 locus. This data provides evidence that allelic loss at BRCA1 is a frequent event in sporadic breast tumorigenesis among Tunisian women, and suggests that the BRCA1 gene might play an important role as a tumor suppressor gene. PMID:15914269

Charef-Hamza, Sameh; Trimeche, Mounir; Ziadi, Sonia; Amara, Khaled; Gaddas, Naim; Mokni, Moncef; Sriha, Badreddine; Yacoubi, Tahar; Korbi, Sadok

2004-12-15

265

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

Directory of Open Access Journals (Sweden)

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

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

2006-01-01

266

Synchronous sporadic gastrointestinal stromal tumors in the stomach and jejunum: report of a case.  

UK PubMed Central (United Kingdom)

This report describes a patient with synchronous sporadic gastrointestinal stromal tumors (GISTs) in the stomach and jejunum. A 71-year-old Japanese male presented with a 2-year history of occasional melena and general fatigue. Computed tomography of the abdomen demonstrated an enhanced extramural gastric tumor, 4 cm in diameter. Endoscopic examination revealed a jejunal submucosal tumor. He was referred to the surgical outpatient clinic for surgical treatment of an extramural gastric tumor and a jejunal submucosal tumor. Laparotomy allowed the identification of a nut-sized extramural tumor at the stomach and a thumb's head-sized tumor on the jejunum. Partial resections of the stomach and jejunum were performed. Histopathological and immunohistochemical examination revealed that these tumors were GISTs. Although no molecular analysis was performed, the immunohistochemical staining patterns of these two tumors were different from each other. Therefore, the final diagnosis was synchronous sporadic GISTs in the stomach and jejunum. This patient has survived without recurrence for approximately 12 years since complete resection.

Nakayama Y; Kadowaki K; Higure A; Hisaoka M; Yamaguchi K

2013-01-01

267

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

UK PubMed Central (United Kingdom)

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

Laczmanska I; Karpinski P; Bebenek M; Sedziak T; Ramsey D; Szmida E; Sasiadek MM

2013-01-01

268

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

Science.gov (United States)

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

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

2012-10-25

269

Genetic alterations of Carney complex are not present in sporadic cardiac myxomas.  

Science.gov (United States)

Cardiac myxomas are the most frequent cardiac tumors and cause for significant morbidity and mortality. Recent evidence indicates that cardiac myxomas are, in fact, neoplasms rather than organized thrombi. Cardiac myxomas may present as solitary lesions or in association with the Carney complex. Carney complex has been linked to chromosome 2p16 and the PRKAR1A gene at 17q22-24. In this study, we analyzed sporadic cardiac myxomas to evaluate whether the genetic alterations seen in Carney complex are present in non Carney complex associated cardiac myxomas as well. We analyzed microdissected material from 13 patients with cardiac myxomas for the markers PRKAR1 9CA, D2S2153, D2S2251 and D2S123. None of the cases demonstrated loss of heterozygosity or definite band changes suggestive of microsatellite instability for any of the markers used. We conclude that sporadic cardiac myxomas are genetically not related to Carney complex and most likely do not represent an incomplete form of Carney complex. PMID:11744997

Fogt, Franz; Zimmerman, Robert L; Hartmann, Christopher J; Brown, Charlotte A; Narula, Navneet

2002-01-01

270

Genetic alterations of Carney complex are not present in sporadic cardiac myxomas.  

UK PubMed Central (United Kingdom)

Cardiac myxomas are the most frequent cardiac tumors and cause for significant morbidity and mortality. Recent evidence indicates that cardiac myxomas are, in fact, neoplasms rather than organized thrombi. Cardiac myxomas may present as solitary lesions or in association with the Carney complex. Carney complex has been linked to chromosome 2p16 and the PRKAR1A gene at 17q22-24. In this study, we analyzed sporadic cardiac myxomas to evaluate whether the genetic alterations seen in Carney complex are present in non Carney complex associated cardiac myxomas as well. We analyzed microdissected material from 13 patients with cardiac myxomas for the markers PRKAR1 9CA, D2S2153, D2S2251 and D2S123. None of the cases demonstrated loss of heterozygosity or definite band changes suggestive of microsatellite instability for any of the markers used. We conclude that sporadic cardiac myxomas are genetically not related to Carney complex and most likely do not represent an incomplete form of Carney complex.

Fogt F; Zimmerman RL; Hartmann CJ; Brown CA; Narula N

2002-01-01

271

A cellular model for sporadic ALS using patient-derived induced pluripotent stem cells.  

UK PubMed Central (United Kingdom)

Development of therapeutics for genetically complex neurodegenerative diseases such as sporadic amyotrophic lateral sclerosis (ALS) has largely been hampered by lack of relevant disease models. Reprogramming of sporadic ALS patients' fibroblasts into induced pluripotent stem cells (iPSC) and differentiation into affected neurons that show a disease phenotype could provide a cellular model for disease mechanism studies and drug discovery. Here we report the reprogramming to pluripotency of fibroblasts from a large cohort of healthy controls and ALS patients and their differentiation into motor neurons. We demonstrate that motor neurons derived from three sALS patients show de novo TDP-43 aggregation and that the aggregates recapitulate pathology in postmortem tissue from one of the same patients from which the iPSC were derived. We configured a high-content chemical screen using the TDP-43 aggregate endpoint both in lower motor neurons and upper motor neuron like cells and identified FDA-approved small molecule modulators including Digoxin demonstrating the feasibility of patient-derived iPSC-based disease modelling for drug screening.

Burkhardt MF; Martinez FJ; Wright S; Ramos C; Volfson D; Mason M; Garnes J; Dang V; Lievers J; Shoukat-Mumtaz U; Martinez R; Gai H; Blake R; Vaisberg E; Grskovic M; Johnson C; Irion S; Bright J; Cooper B; Nguyen L; Griswold-Prenner I; Javaherian A

2013-07-01

272

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

UK PubMed Central (United Kingdom)

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

Qi X; Luu DT; Yang Q; Maës O; Matton DP; Morse D; Cappadocia M

2001-02-01

273

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

Science.gov (United States)

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 presentation A 36-year-old Asian woman was referred complaining of an abdominal tumor. She had no history of familial adenomatous polyposis, abdominal surgery, trauma or pregnancy. A laparoscopy-assisted right hemicolectomy with a minilaparotomy was conducted for resection of her right-side colon and the anterior wall of her duodenum. The histopathological diagnosis was a desmoid tumor that grew from the transverse mesocolon. Mutational analysis indicated a mutation of the ?-catenin gene (CTNNB1), consisting of a substitution of threonine for alanine at codon 41. The patient has been followed postoperatively for more than 3 years without any sign of recurrence. Conclusion We report a case of sporadic colonic desmoid tumor which was resected by laparoscopic surgery. A successful outcome was achieved because there has been no local recurrence for more than 3 years. The tumor grew from the transverse mesocolon, and harbored a mutation of the CTNNB1 gene. Mutational analysis of CTNNB1 gene may play an important role as a prognostic marker of desmoid tumors.

2013-01-01

274

Characterisation of persistent and sporadic Listeria monocytogenes strains by pulsed-field gel electrophoresis (PFGE) and amplified fragment length polymorphism (AFLP).  

UK PubMed Central (United Kingdom)

This study was set up to evaluate the genetic similarity or dissimilarity of persistent and sporadic Listeria monocytogenes strains existing in eleven food processing facilities, including fish, dairy, meat and poultry processing plants. In each plant persistent and sporadic strains were selected on the basis of PFGE typing results. A total of 17 strains representing persistent strains and 38 sporadic strains originating from eleven food processing plants were included in the study. PFGE macrorestriction patterns of persistent and sporadic strains from different processing plants were compared and the strains were further studied by amplified fragment length polymorphism (AFLP), being a characterisation method giving more whole genome based information. The 17 persistent and 38 sporadic strains showed 14 and 35 pulsotypes, 14 and 28 AFLP types, respectively. The combination of PFGE and AFLP typing results yielded a total of 48 genotypes. Thirteen of 15 genotypes presented by persistent strains were only associated with persistent strains and similarly 94% (33/35) of genotypes showed by sporadic strains were recovered among sporadic strains only. Our results showed that L. monocytogenes strains causing persistent contamination differ from sporadic strains. In AFLP analysis persistent strains did not, however, form any specific clusters and neither was there any difference between the known two genomic groups. These results indicate that even though persistent strains differ from sporadic strains there seems not to be any specific evolutional lineage of persistent strains.

Autio T; Keto-Timonen R; Lundén J; Björkroth J; Korkeala H

2003-11-01

275

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

Science.gov (United States)

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 (< 16) or cytosine-adenine-guanine (< 18) repeats appears to increase the AR activity, resulting in a raising PC 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, as it is mainly shown in African-American populations. Also VDR gene, that is a component of ligand (steroid)-dependent nuclear transcription factor superfamily, shows various polymorphisms which appear to be associated with PC risk. Except an earlier age of onset, no anatomo-clinical and tumor progression peculiarities between hereditary and sporadic PC have been generally identified. Indeed, tumor progression and metastasis, both in hereditary and sporadic PC, are mainly influenced by a variety of biochemical and immune-mediated tumor microenvironmental conditions rather than by the hereditary genetic factors, thus gene expression associated with invasive ability representing a newly acquired genetic variant rather than a selection of pre-existent gene abnormalities in PC cells. It's questionable whether genetic testing of unaffected men of hereditary PC families might be actually useful. Nevertheless a suitable counselling must be proposed. Family history and/or gene profiling-guided preventive strategies for men at high risk of familial PC, range from dietary to drug measures. Cancer chemopreventive approaches may include 5-alpha-reductase inhibitors, histone deacetylase inhibitors, antioxidans, non-steroidal anti-inflammatory drugs, cholesterol-lowering statins, vitamin D analogues. PMID:20184087

Alberti, C

2010-01-01

276

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

UK PubMed Central (United Kingdom)

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 (< 16) or cytosine-adenine-guanine (< 18) repeats appears to increase the AR activity, resulting in a raising PC 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, as it is mainly shown in African-American populations. Also VDR gene, that is a component of ligand (steroid)-dependent nuclear transcription factor superfamily, shows various polymorphisms which appear to be associated with PC risk. Except an earlier age of onset, no anatomo-clinical and tumor progression peculiarities between hereditary and sporadic PC have been generally identified. Indeed, tumor progression and metastasis, both in hereditary and sporadic PC, are mainly influenced by a variety of biochemical and immune-mediated tumor microenvironmental conditions rather than by the hereditary genetic factors, thus gene expression associated with invasive ability representing a newly acquired genetic variant rather than a selection of pre-existent gene abnormalities in PC cells. It's questionable whether genetic testing of unaffected men of hereditary PC families might be actually useful. Nevertheless a suitable counselling must be proposed. Family history and/or gene profiling-guided preventive strategies for men at high risk of familial PC, range from dietary to drug measures. Cancer chemopreventive approaches may include 5-alpha-reductase inhibitors, histone deacetylase inhibitors, antioxidans, non-steroidal anti-inflammatory drugs, cholesterol-lowering statins, vitamin D analogues.

Alberti C

2010-01-01

277

Screening for NLRP7 mutations in familial and sporadic recurrent hydatidiform moles: report of 2 Tunisian families.  

Science.gov (United States)

A familial or sporadic recurrent hydatidiform mole is a rare autosomal recessive condition that has been associated with biallelic mutations in the nucleotide-binding, leucine-rich repeat, pyrin domain 7 (NLRP7) gene (19q13.42). Cases from different ethnic origins have been reported earlier. Here we report the first Tunisian patients: 2 sisters with homozygous NLRP7 mutations (p.E570X) and 1 sporadic case with no mutation in NLRP7. Our results extend the number of familial recurrent reproductive wastages due to mutations in NLRP7. We suggest that mutations screening of NLRP7 could be proposed more systematically in women with recurrent pathologic pregnancy outcomes of unknown origin. The rare cases with a typical clinical picture, which were not related to NLRP7 mutation as in our sporadic case, should be investigated more to identify the causative gene. PMID:21623199

Landolsi, Hanène; Rittore, Cécile; Philibert, Laurent; Missaoui, Nabiha; Hmissa, Sihem; Touitou, Isabelle; Gribaa, Moez; Yacoubi, Mohamed Tahar

2011-07-01

278

Reduced expression of the Kinesin-Associated Protein 3 (KIFAP3) gene increases survival in sporadic amyotrophic lateral sclerosis.  

UK PubMed Central (United Kingdom)

Amyotrophic lateral sclerosis is a degenerative disorder of motor neurons that typically develops in the 6th decade and is uniformly fatal, usually within 5 years. To identify genetic variants associated with susceptibility and phenotypes in sporadic ALS, we performed a genome-wide SNP analysis in sporadic ALS cases and controls. A total of 288,357 SNPs were screened in a set of 1,821 sporadic ALS cases and 2,258 controls from the U.S. and Europe. Survival analysis was performed using 1,014 deceased sporadic cases. Top results for susceptibility were further screened in an independent sample set of 538 ALS cases and 556 controls. SNP rs1541160 within the KIFAP3 gene (encoding a kinesin-associated protein) yielded a genome-wide significant result (P = 1.84 x 10(-8)) that withstood Bonferroni correction for association with survival. Homozygosity for the favorable allele (CC) conferred a 14.0 months survival advantage. Sequence, genotypic and functional analyses revealed that there is linkage disequilibrium between rs1541160 and SNP rs522444 within the KIFAP3 promoter and that the favorable alleles of rs1541160 and rs522444 correlate with reduced KIFAP3 expression. No SNPs were associated with risk of sporadic ALS, site of onset, or age of onset. We have identified a variant within the KIFAP3 gene that is associated with decreased KIFAP3 expression and increased survival in sporadic ALS. These findings support the view that genetic factors modify phenotypes in this disease and that cellular motor proteins are determinants of motor neuron viability.

Landers JE; Melki J; Meininger V; Glass JD; van den Berg LH; van Es MA; Sapp PC; van Vught PW; McKenna-Yasek DM; Blauw HM; Cho TJ; Polak M; Shi L; Wills AM; Broom WJ; Ticozzi N; Silani V; Ozoguz A; Rodriguez-Leyva I; Veldink JH; Ivinson AJ; Saris CG; Hosler BA; Barnes-Nessa A; Couture N; Wokke JH; Kwiatkowski TJ Jr; Ophoff RA; Cronin S; Hardiman O; Diekstra FP; Leigh PN; Shaw CE; Simpson CL; Hansen VK; Powell JF; Corcia P; Salachas F; Heath S; Galan P; Georges F; Horvitz HR; Lathrop M; Purcell S; Al-Chalabi A; Brown RH Jr

2009-06-01

279

Reduced expression of the Kinesin-Associated Protein 3 (KIFAP3) gene increases survival in sporadic amyotrophic lateral sclerosis.  

Science.gov (United States)

Amyotrophic lateral sclerosis is a degenerative disorder of motor neurons that typically develops in the 6th decade and is uniformly fatal, usually within 5 years. To identify genetic variants associated with susceptibility and phenotypes in sporadic ALS, we performed a genome-wide SNP analysis in sporadic ALS cases and controls. A total of 288,357 SNPs were screened in a set of 1,821 sporadic ALS cases and 2,258 controls from the U.S. and Europe. Survival analysis was performed using 1,014 deceased sporadic cases. Top results for susceptibility were further screened in an independent sample set of 538 ALS cases and 556 controls. SNP rs1541160 within the KIFAP3 gene (encoding a kinesin-associated protein) yielded a genome-wide significant result (P = 1.84 x 10(-8)) that withstood Bonferroni correction for association with survival. Homozygosity for the favorable allele (CC) conferred a 14.0 months survival advantage. Sequence, genotypic and functional analyses revealed that there is linkage disequilibrium between rs1541160 and SNP rs522444 within the KIFAP3 promoter and that the favorable alleles of rs1541160 and rs522444 correlate with reduced KIFAP3 expression. No SNPs were associated with risk of sporadic ALS, site of onset, or age of onset. We have identified a variant within the KIFAP3 gene that is associated with decreased KIFAP3 expression and increased survival in sporadic ALS. These findings support the view that genetic factors modify phenotypes in this disease and that cellular motor proteins are determinants of motor neuron viability. PMID:19451621

Landers, John E; Melki, Judith; Meininger, Vincent; Glass, Jonathan D; van den Berg, Leonard H; van Es, Michael A; Sapp, Peter C; van Vught, Paul W J; McKenna-Yasek, Diane M; Blauw, Hylke M; Cho, Ting-Jan; Polak, Meraida; Shi, Lijia; Wills, Anne-Marie; Broom, Wendy J; Ticozzi, Nicola; Silani, Vincenzo; Ozoguz, Aslihan; Rodriguez-Leyva, Ildefonso; Veldink, Jan H; Ivinson, Adrian J; Saris, Christiaan G J; Hosler, Betsy A; Barnes-Nessa, Alayna; Couture, Nicole; Wokke, John H J; Kwiatkowski, Thomas J; Ophoff, Roel A; Cronin, Simon; Hardiman, Orla; Diekstra, Frank P; Leigh, P Nigel; Shaw, Christopher E; Simpson, Claire L; Hansen, Valerie K; Powell, John F; Corcia, Philippe; Salachas, François; Heath, Simon; Galan, Pilar; Georges, Franck; Horvitz, H Robert; Lathrop, Mark; Purcell, Shaun; Al-Chalabi, Ammar; Brown, Robert H

2009-05-18

280

De novo expression of CD44 variants in sporadic and hereditary gastric cancer.  

UK PubMed Central (United Kingdom)

CD44 is the major ubiquitously expressed cell surface receptor for hyaluronate. The CD44 gene encodes several protein isoforms due to extensive alternative splicing and post-translational modifications. Some of these CD44 variable isoforms have been foreseen as key players in malignant transformation and their expression is highly restricted and highly specific, unlike the canonical CD44 standard isoform. In this study, we aimed at dissecting the mRNA splicing pattern of CD44 in normal stomach and gastric cancer (GC) cell lines (n=9) using cloning and quantitative mRNA amplification assays. Moreover, we assessed the RNA levels and protein expression pattern of relevant splicing forms in distinct premalignant and malignant gastric lesions (sporadic (n=43) and hereditary (n=3) forms) using real-time RT-PCR and immunohistochemistry. We also explored the association of CD44 and E-cadherin expression by immunohistochemistry, as E-cadherin has a pivotal functional role in GC. We established the pattern of CD44 variant forms in normal stomach and gastric malignancy. We observed that although exon v6-containing isoforms were rarely expressed in normal gastric mucosa, they became increasingly expressed both in gastric premalignant (hyperplastic polyps, complete and incomplete intestinal metaplasia, low- and high-grade dysplasia) and malignant lesions (cell lines derived from GCs, primary sporadic GCs and hereditary diffuse GCs (HDGCs)). Moreover, we verified that whenever E-cadherin expression was absent, exon v6-containing CD44 isoforms were overexpressed. The lack of expression of CD44 isoforms containing exon v6 in the surface and foveolar epithelia of normal stomach and, its de novo expression in premalignant, as well as in sporadic and hereditary malignant lesions of the stomach, pinpoint CD44 v6-containing isoforms as potential biomarkers for early transformation of the gastric mucosa. Further, our results raise the hypothesis of using CD44v6 as a marker of early invasive intramucosal carcinoma in HDGC CDH1 mutation carriers that lack CDH1 expression in their tumors.

da Cunha CB; Oliveira C; Wen X; Gomes B; Sousa S; Suriano G; Grellier M; Huntsman DG; Carneiro F; Granja PL; Seruca R

2010-11-01

 
 
 
 
281

Molecular epidemiology of Vibrio cholerae causing outbreaks & sporadic cholera in northern India.  

UK PubMed Central (United Kingdom)

BACKGROUND & OBJECTIVES: Several outbreaks of cholera have been reported in Chandigarh region during a span of seven years from 2002-2008. The genetic characteristics of Vibrio cholerae isolates obtained during these outbreaks have not been adequately studied. The aim of this study was to do molecular typing of V. cholerae isolated from the sporadic and outbreak cases by pulsed-field gel electrophoresis (PFGE), Rep-PCR and ribotyping. METHODS: Fifty representative isolates of V. cholerae from outbreak as well as sporadic cases were subjected to molecular typing by PFGE, 173 isolates (163 clinical and 10 environmental) were typed by rep-PCR and ribotyping. Ribotyping was done by determination of rRNA restriction pattern of BglI restriction digestion and hybridization with 7.2 kb rRNA probe of pKK3535 plasmid using DIG DNA labelling and detection kit. Universal VC1 primer was used for rep-PCR. RESULTS: PFGE generated 15 pulsotypes, of which four matched the published pulsotypes and there were 11 new pulsotypes. PFGE was the most discriminatory method that could differentiate between isolates belonging to single ribotype. Pulsotype P1 corresponding to known pulsotype H1 was the major pulsotype till 2003. Pulsotype P3 corresponding to known pulsotype L emerged in 2004. The 2007 outbreaks in Punjab and Haryana were caused by P5 though P1 and P3 were isolated from the sporadic cases from the same region. The 2008 outbreak was caused by pulsotypes P6 and P7. Ribotype IV was the most predominant followed by RIII. This ribotype was not isolated after 2003 and ribotype IV became the most predominant 2004 onwards. Of the two unknown ribotypes (UNI and UN2), UNI was more common (27 isolates). Rep-PCR was the least discriminatory and divided all clinical isolates into four major profiles. The dendrogram analysis of PFGE revealed similarity of some clinical isolates with environmental isolates indicating the genetic relatedness. INTERPRETATION & CONCLUSION: Our findings showed that Rep-PCR was least discriminatory method. Ribotyping was a reliable and reproducible method. Ribotype IV was predominant ribotype followed by RIII. A total of 15 pulsotypes were generated and 11 of these were not reported earlier. Genetic relatedness was shown by clinical and environmental isolates which needs to be confirmed in future studies.

Taneja N; Sangar G; Chowdhury G; Ramamurthy T; Mishra A; Singh M; Sharma M

2012-10-01

282

GATA2 mutations in sporadic and familial acute myeloid leukaemia patients with CEBPA mutations.  

Science.gov (United States)

GATA2 mutations have recently been reported in acute myeloid leukaemia (AML) patients with CEBPA-double mutations. To explore their impact on this favourable-risk disease, we determined GATA2 status in 153 sporadic AML patients and three members of a germ-line CEBPA-mutant family at AML presentation. Overall, 27% (15/55) CEBPA-double, 16% (7/43) CEBPA-single and 0% (0/55) normal karyotype/CEBPA-wild-type patients were GATA2-mutant. All familial AML patients acquired both a second CEBPA and a GATA2 mutation. CEBPA and GATA2 mutant levels indicated that both mutations were likely to be early events in leukaemogenesis. GATA2 status did not impact on the favourable outcome of CEBPA-double/FLT3-inernal tandem duplication-negative patients. PMID:23560626

Green, Claire L; Tawana, Kiran; Hills, Robert K; Bödör, Csaba; Fitzgibbon, Jude; Inglott, Sarah; Ancliff, Phil; Burnett, Alan K; Linch, David C; Gale, Rosemary E

2013-04-05

283

GATA2 mutations in sporadic and familial acute myeloid leukaemia patients with CEBPA mutations.  

UK PubMed Central (United Kingdom)

GATA2 mutations have recently been reported in acute myeloid leukaemia (AML) patients with CEBPA-double mutations. To explore their impact on this favourable-risk disease, we determined GATA2 status in 153 sporadic AML patients and three members of a germ-line CEBPA-mutant family at AML presentation. Overall, 27% (15/55) CEBPA-double, 16% (7/43) CEBPA-single and 0% (0/55) normal karyotype/CEBPA-wild-type patients were GATA2-mutant. All familial AML patients acquired both a second CEBPA and a GATA2 mutation. CEBPA and GATA2 mutant levels indicated that both mutations were likely to be early events in leukaemogenesis. GATA2 status did not impact on the favourable outcome of CEBPA-double/FLT3-inernal tandem duplication-negative patients.

Green CL; Tawana K; Hills RK; Bödör C; Fitzgibbon J; Inglott S; Ancliff P; Burnett AK; Linch DC; Gale RE

2013-06-01

284

Primary generalized familial and sporadic glucocorticoid resistance (Chrousos syndrome) and hypersensitivity.  

UK PubMed Central (United Kingdom)

Familial or sporadic primary generalized glucocorticoid resistance or Chrousos syndrome is a rare genetic condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids and a consequent hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis. Primary generalized glucocorticoid hypersensitivity (PGGH) represents the mirror image of the former, and is characterized by generalized, partial, target-tissue hypersensitivity to glucocorticoids, and compensatory hypoactivation of the HPA axis. The molecular basis of both conditions has been ascribed to mutations in the human glucocorticoid receptor (hGR) gene, which impair the molecular mechanisms of hGR action and alter tissue sensitivity to glucocorticoids. This review summarizes the pathophysiology, molecular mechanisms and clinical aspects of Chrousos syndrome and PGGH.

Charmandari E; Kino T; Chrousos GP

2013-01-01

285

A dysphagia study in patients with sporadic inclusion body myositis (s-IBM).  

UK PubMed Central (United Kingdom)

The nature of the swallowing impairment in patients with sporadic inclusion body myositis (s-IBM) has not been well characterized. In this study, we examined ten consecutive s-IBM patients using videofluoroscopy (VF) and computed pharyngoesophageal manometry (CPM). The patients were divided into two groups: patients with complaint and without complaint of dysphagia. VF results indicated pharyngeal muscle propulsion (PP) at the hypopharyngeal and upper esophagus sphincter (UES) in all s-IBM patients. Patients without complaint of dysphagia showed a mild degree of PP, whereas a severe form of PP was observed in patients with complaint of dysphagia. CPM revealed that negative pressure during UES opening was not observed in the s-IBM patients with complaint of dysphagia. Incomplete opening and PP at the UES were observed in all s-IBM patients. These results indicate that the dysphagic processes occur subclinically in s-IBM patients who may not report swallowing impairments.

Murata KY; Kouda K; Tajima F; Kondo T

2012-08-01

286

Knee extensor strength exhibits potential to predict function in sporadic inclusion-body myositis.  

UK PubMed Central (United Kingdom)

INTRODUCTION: In this study we address the challenging issue of potential use of muscle strength to predict function in clinical trials. This has immediate relevance to translational studies that attempt to improve quadriceps strength in sporadic inclusion-body myositis (sIBM). METHODS: Maximum voluntary isometric contraction testing as a measure of muscle strength and a battery of functional outcomes were tested in 85 ambulatory subjects with sIBM. RESULTS: Marked quadriceps weakness was noted in all patients. Strength was correlated with distance walked at 2 and 6 minutes. Additional correlations were found with time to get up from a chair, climb stairs, and step up on curbs. CONCLUSIONS: Quadriceps (knee extensor) strength correlated with performance in this large cohort of sIBM subjects, which demonstrated its potential to predict function in this disease. These data provide initial support for use of muscle strength as a surrogate for function, although validation in a clinical trial is required.

Lowes LP; Alfano L; Viollet L; Rosales XQ; Sahenk Z; Kaspar BK; Clark KR; Flanigan KM; Mendell JR; McDermott MP

2012-02-01

287

Sporadic Creutzfeldt-Jakob disease: a clinico-neuropathological analysis of nine definite cases  

Directory of Open Access Journals (Sweden)

Full Text Available The authors have analyzed clinico-neuropathologically nine cases of the definite sporadic form of Creutzfeldt-Jakob disease (CJD). All cases were female, with mean age of 62.7 years. Eighty-nine percent of the patients exhibited prodromal and initial psychiatric symptoms; definite signs of dementia, and myoclonus were present in 100% of cases. The EEG was abnormal in all cases and pseudoperiodic paroxysms were present in 56% of the patients. Their evolution time ranged from 3 to 19 months. Neuropathologically, brain and cerebellar atrophy, spongiosis, astrocytosis and neuronal loss were present in 100% of the patients. In 5 (56%) of these 9 cases, prion protein (PrP) amyloid plaques were detected in the cerebellum, by optical- and electronmicroscopy. There was a positive correlation between the number of plaques and the evolution time. The authors outline the similarities of their cases in the elderly with the new variant of CJD described in young people.

COSTA CARLOS M. DE CASTRO; BRUCHER JEAN MARIE; LATERRE CHRISTIAN

1998-01-01

288

Endplate structure and parameters of neuromuscular transmission in sporadic centronuclear myopathy associated with myasthenia.  

UK PubMed Central (United Kingdom)

Centronuclear myopathy is a pathologically diagnosed congenital myopathy. The disease genes encode proteins with membrane modulating properties (MTM1, DNM2, and BIN1) or alter excitation-contraction coupling (RYR1). Some patients also have myasthenic symptoms but electrodiagnostic and endplate studies in these are limited. A sporadic patient had fatigable weakness and a decremental EMG response. Analysis of centronuclear myopathy disease- and candidate-genes identified no mutations. Quantitative endplate electron microscopy studies revealed simplified postsynaptic regions, endplate remodeling with normal nerve terminal size, normal synaptic vesicle density, and mild acetylcholine receptor deficiency. The amplitude of the miniature endplate potential was decreased to 60% of normal. Quantal release by nerve impulse was reduced to 40% of normal due to a decreased number of releasable quanta. The safety margin of neuromuscular transmission is compromised by decreased quantal release by nerve impulse and by a reduced postsynaptic response to the released quanta.

Liewluck T; Shen XM; Milone M; Engel AG

2011-06-01

289

Endplate structure and parameters of neuromuscular transmission in sporadic centronuclear myopathy associated with myasthenia.  

Science.gov (United States)

Centronuclear myopathy is a pathologically diagnosed congenital myopathy. The disease genes encode proteins with membrane modulating properties (MTM1, DNM2, and BIN1) or alter excitation-contraction coupling (RYR1). Some patients also have myasthenic symptoms but electrodiagnostic and endplate studies in these are limited. A sporadic patient had fatigable weakness and a decremental EMG response. Analysis of centronuclear myopathy disease- and candidate-genes identified no mutations. Quantitative endplate electron microscopy studies revealed simplified postsynaptic regions, endplate remodeling with normal nerve terminal size, normal synaptic vesicle density, and mild acetylcholine receptor deficiency. The amplitude of the miniature endplate potential was decreased to 60% of normal. Quantal release by nerve impulse was reduced to 40% of normal due to a decreased number of releasable quanta. The safety margin of neuromuscular transmission is compromised by decreased quantal release by nerve impulse and by a reduced postsynaptic response to the released quanta. PMID:21482111

Liewluck, Teerin; Shen, Xin-Ming; Milone, Margherita; Engel, Andrew G

2011-04-08

290

Sporadic ALS with compound heterozygous mutations in the SQSTM1 gene.  

UK PubMed Central (United Kingdom)

Accumulating evidence suggests that heterozygous mutations in the SQSTM1 gene, which encodes p62 protein, are associated with amyotrophic lateral sclerosis (ALS). Here, we report a Japanese patient with sporadic, late-onset ALS who harbored compound heterozygous SQSTM1 mutations (p.[Val90Met];[Val153Ile]). Autopsy examination revealed that although TDP-43 pathology was rather widespread, the selective occurrence of p62-positive/TDP-43-negative cytoplasmic inclusions in the lower motor neurons (LMNs) was a characteristic feature. No Bunina bodies were found. Ultrastructurally, p62-positive cytoplasmic inclusions observed in the spinal anterior horn cells were composed of aggregates of ribosome-like granules and intermingled bundles of filamentous structures. Another feature of interest was concomitant Lewy body pathology. The occurrence of distinct p62 pathology in the LMNs in this patient indicates the pathogenic role of SQSTM1 mutations in the development of a subset of ALS.

Shimizu H; Toyoshima Y; Shiga A; Yokoseki A; Arakawa K; Sekine Y; Shimohata T; Ikeuchi T; Nishizawa M; Kakita A; Onodera O; Takahashi H

2013-09-01

291

Sporadic ALS with compound heterozygous mutations in the SQSTM1 gene.  

Science.gov (United States)

Accumulating evidence suggests that heterozygous mutations in the SQSTM1 gene, which encodes p62 protein, are associated with amyotrophic lateral sclerosis (ALS). Here, we report a Japanese patient with sporadic, late-onset ALS who harbored compound heterozygous SQSTM1 mutations (p.[Val90Met];[Val153Ile]). Autopsy examination revealed that although TDP-43 pathology was rather widespread, the selective occurrence of p62-positive/TDP-43-negative cytoplasmic inclusions in the lower motor neurons (LMNs) was a characteristic feature. No Bunina bodies were found. Ultrastructurally, p62-positive cytoplasmic inclusions observed in the spinal anterior horn cells were composed of aggregates of ribosome-like granules and intermingled bundles of filamentous structures. Another feature of interest was concomitant Lewy body pathology. The occurrence of distinct p62 pathology in the LMNs in this patient indicates the pathogenic role of SQSTM1 mutations in the development of a subset of ALS. PMID:23812289

Shimizu, Hiroshi; Toyoshima, Yasuko; Shiga, Atsushi; Yokoseki, Akio; Arakawa, Keiko; Sekine, Yumi; Shimohata, Takayoshi; Ikeuchi, Takeshi; Nishizawa, Masatoyo; Kakita, Akiyoshi; Onodera, Osamu; Takahashi, Hitoshi

2013-06-28

292

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

UK PubMed Central (United Kingdom)

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

Rampini M; Russo CD; Taylan MS; Gelosa A; Cobolli M

2012-01-01

293

Exome sequencing to identify de novo mutations in sporadic ALS trios.  

UK PubMed Central (United Kingdom)

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease whose causes are still poorly understood. To identify additional genetic risk factors, we assessed the role of de novo mutations in ALS by sequencing the exomes of 47 ALS patients and both of their unaffected parents (n = 141 exomes). We found that amino acid-altering de novo mutations were enriched in genes encoding chromatin regulators, including the neuronal chromatin remodeling complex (nBAF) component SS18L1 (also known as CREST). CREST mutations inhibited activity-dependent neurite outgrowth in primary neurons, and CREST associated with the ALS protein FUS. These findings expand our understanding of the ALS genetic landscape and provide a resource for future studies into the pathogenic mechanisms contributing to sporadic ALS.

Chesi A; Staahl BT; Jovi?i? A; Couthouis J; Fasolino M; Raphael AR; Yamazaki T; Elias L; Polak M; Kelly C; Williams KL; Fifita JA; Maragakis NJ; Nicholson GA; King OD; Reed R; Crabtree GR; Blair IP; Glass JD; Gitler AD

2013-07-01

294

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

Directory of Open Access Journals (Sweden)

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

Qi Li; Wei Ba

2010-01-01

295

ATL1 and REEP1 mutations in hereditary and sporadic upper motor neuron syndromes.  

UK PubMed Central (United Kingdom)

SPAST mutations are the most common cause of autosomal dominant hereditary spastic paraplegias (AD-HSPs), but many spastic paraplegia patients are found to carry no mutations in this gene. In order to assess the contribution of ATL1 and REEP1 in AD-HSP, we performed mutational analysis in 27 SPAST-negative AD-HSP families. We found three novel ATL1 mutations and one REEP1 mutation in five index-patients. In 110 patients with sporadic adult-onset upper motor neuron syndromes, a novel REEP1 mutation was identified in one patient. Apart from a significantly younger age at onset in ATL1 patients and restless legs in some, the clinical phenotype of ATL1 and REEP1 was similar to other pure AD-HSPs.

de Bot ST; Veldink JH; Vermeer S; Mensenkamp AR; Brugman F; Scheffer H; van den Berg LH; Kremer HP; Kamsteeg EJ; van de Warrenburg BP

2013-03-01

296

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

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

Koshitani, Shigeo; Noeske, Felix

2010-01-01

297

Sporadic re-emergence of enzootic porcine transmissible gastroenteritis in Hungary.  

UK PubMed Central (United Kingdom)

Transmissible gastroenteritis (TGE) is a coronavirus-induced disease of pigs, characterised by diarrhoea and vomiting. The incidence of the disease had been decreasing since the late 1980s when deletion mutant variants (porcine respiratory coronavirus, PRCoV) of the virus emerged, repressing TGE gradually. Although disease manifestations are infrequent, the virus is still present in pig herds, causing sporadic outbreaks in a milder form. Identification and characterisation of the spike genes from TGEV and PRCoV, detected in such outbreaks, were performed in Hungary. Analysis of the amplified partial gene sequences showed that TGEV was present in herds with TGE clinical signs together with PRCoV. The sequences, apart from the deletions in PRCoV, were identical and at least two types of PRCoV spike proteins could be identified based on the length of the deleted sequence.

L?rincz M; Biksi I; Andersson S; Cságola A; Tuboly T

2013-07-01

298

A disturbance in the neuronal insulin receptor signal transduction in sporadic Alzheimer's disease.  

UK PubMed Central (United Kingdom)

Disturbances of glucose and energy metabolism are hypothesized as pathogenetic factors in sporadic dementia of Alzheimer type (SDAT). Insulin and is receptors play an important role in the regulation of brain glucose metabolism and neuronal growth. In postmortem brain cortex in SDAT, the densities of brain insulin receptors were decreased compared to adult controls, but were increased in relation to aged controls. Tyrosine kinase activity, a signal transduction mechanism common to insulin and IGF-1 receptors, was reduced in SDAT in comparison to middle-aged and age-matched control groups. The data are consistent with a neurotrophic role of insulin in the human brain and an upregulation of insulin receptors is SDAT brain as a compensatory mechanism, possibly due to impaired signal transduction mechanism.

Frölich L; Blum-Degen D; Riederer P; Hoyer S

1999-01-01

299

A disturbance in the neuronal insulin receptor signal transduction in sporadic Alzheimer's disease.  

Science.gov (United States)

Disturbances of glucose and energy metabolism are hypothesized as pathogenetic factors in sporadic dementia of Alzheimer type (SDAT). Insulin and is receptors play an important role in the regulation of brain glucose metabolism and neuronal growth. In postmortem brain cortex in SDAT, the densities of brain insulin receptors were decreased compared to adult controls, but were increased in relation to aged controls. Tyrosine kinase activity, a signal transduction mechanism common to insulin and IGF-1 receptors, was reduced in SDAT in comparison to middle-aged and age-matched control groups. The data are consistent with a neurotrophic role of insulin in the human brain and an upregulation of insulin receptors is SDAT brain as a compensatory mechanism, possibly due to impaired signal transduction mechanism. PMID:10672251

Frölich, L; Blum-Degen, D; Riederer, P; Hoyer, S

1999-01-01

300

Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum.  

Science.gov (United States)

Sporadic cerebral amyloid angiopathy (CAA) is a common age related cerebral small vessel disease, characterised by progressive deposition of amyloid-? (A?) in the wall of small to medium sized arteries, arterioles and capillaries of the cerebral cortex and overlying leptomeninges. Previously considered to be a rare neurological curiosity, CAA is now recognised as an important cause of spontaneous intracerebral haemorrhage and cognitive impairment in the elderly, two fundamental challenges in the field of cerebrovascular disease. Our understanding of the pathophysiology and clinical manifestations of CAA continues to evolve rapidly, with the use of transgenic mouse models and advanced structural and/or molecular neuroimaging techniques. Yet, despite remarkable recent interest, CAA remains under-recognised by neurologists and stroke physicians. In this review, a fresh look at key developments in understanding the complex pathophysiology, important clinical and radiological features, diagnostic approaches and prospects for rational therapies for this enigmatic small vessel disorder is provided. PMID:22056963

Charidimou, Andreas; Gang, Qiang; Werring, David J

2011-11-05

 
 
 
 
301

Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum.  

UK PubMed Central (United Kingdom)

Sporadic cerebral amyloid angiopathy (CAA) is a common age related cerebral small vessel disease, characterised by progressive deposition of amyloid-? (A?) in the wall of small to medium sized arteries, arterioles and capillaries of the cerebral cortex and overlying leptomeninges. Previously considered to be a rare neurological curiosity, CAA is now recognised as an important cause of spontaneous intracerebral haemorrhage and cognitive impairment in the elderly, two fundamental challenges in the field of cerebrovascular disease. Our understanding of the pathophysiology and clinical manifestations of CAA continues to evolve rapidly, with the use of transgenic mouse models and advanced structural and/or molecular neuroimaging techniques. Yet, despite remarkable recent interest, CAA remains under-recognised by neurologists and stroke physicians. In this review, a fresh look at key developments in understanding the complex pathophysiology, important clinical and radiological features, diagnostic approaches and prospects for rational therapies for this enigmatic small vessel disorder is provided.

Charidimou A; Gang Q; Werring DJ

2012-02-01

302

Sporadic Legionnaires' disease: the role of domestic electric hot-water tanks.  

UK PubMed Central (United Kingdom)

Sporadic community-acquired legionellosis (SCAL) can be acquired through contaminated aerosols from residential potable water. Electricity-dependent hot-water tanks are widely used in the province of Quebec (Canada) and have been shown to be frequently contaminated with Legionella spp. We prospectively investigated the homes of culture-proven SCAL patients from Quebec in order to establish the proportion of patients whose domestic potable hot-water system was contaminated with the same Legionella isolate that caused their pneumonia. Water samples were collected in each patient's home. Environmental and clinical isolates were compared using pulsed-field gel electrophoresis. Thirty-six patients were enrolled into the study. Legionella was recovered in 12/36 (33%) homes. The residential and clinical isolates were found to be microbiologically related in 5/36 (14%) patients. Contaminated electricity-heated domestic hot-water systems contribute to the acquisition of SCAL. The proportion is similar to previous reports, but may be underestimated.

Dufresne SF; Locas MC; Duchesne A; Restieri C; Ismaïl J; Lefebvre B; Labbé AC; Dion R; Plante M; Laverdière M

2012-01-01

303

Sporadic colon cancer murine models demonstrate the value of autoantibody detection for preclinical cancer diagnosis  

Science.gov (United States)

Although autoantibody detection has been proposed for diagnosis of colorectal cancer, little is known about their initial production and development correlation with cancer progression. Azoxymethane/dextran sodium sulfate (AOM/DSS)-treated mice developed colon adenocarcinoma in the distal colon similar to human sporadic colon cancer. We assessed this model together with AOM and DSS-only models for their applicability to early detection of cancer. All AOM/DSS-treated mice produced autoantibodies to tumor-associated antigens analogous to those observed in human colon cancer patients. Autoantibody response was related to tumor antigen overexpression. Cancer autoantibodies were detected 21 days after starting treatment, when no malignant histopathological features were detectable, and they increased according to tumor progression. When carcinogenesis was induced separately by AOM or DSS, only those mice that developed malignant lesions produced significant levels of autoantibodies. These findings demonstrate that autoantibody development is an early event in tumorigenesis and validates its use for preclinical colon cancer diagnosis.

Barderas, Rodrigo; Villar-Vazquez, Roi; Fernandez-Acenero, Maria Jesus; Babel, Ingrid; Pelaez-Garcia, Alberto; Torres, Sofia; Casal, J. Ignacio

2013-01-01

304

Attributing sporadic and outbreak-associated infections to sources: blending epidemiological data.  

UK PubMed Central (United Kingdom)

SUMMARY Common sources of shiga toxin-producing Escherichia coli (STEC) O157 infection have been identified by investigating outbreaks and by case-control studies of sporadic infections. We conducted an analysis to attribute STEC O157 infections ascertained in 1996 and 1999 by the Foodborne Diseases Active Surveillance Network (FoodNet) to sources. Multivariable models from two case-control studies conducted in FoodNet and outbreak investigations that occurred during the study years were used to calculate the annual number of infections attributable to six sources. Using the results of the outbreak investigations alone, 27% and 15% of infections were attributed to a source in 1996 and 1999, respectively. Combining information from both data sources, 65% of infections in 1996 and 34% of infections in 1999 were attributed. The results suggest that methods to incorporate data from multiple surveillance systems and over several years are needed to improve estimation of the number of illnesses attributable to exposure sources.

Cole D; Griffin PM; Fullerton KE; Ayers T; Smith K; Ingram LA; Kissler B; Hoekstra RM

2013-04-01

305

Sporadic amyotrophic lateral sclerosis of long duration mimicking spinal progressive muscular atrophy: a clinicopathological study.  

UK PubMed Central (United Kingdom)

We report an autopsy case of amyotrophic lateral sclerosis (ALS) clinically diagnosed as spinal progressive muscular atrophy (SPMA). The patient was a Japanese woman without hereditary burden. She developed muscle weakness of the distal part of the left lower extremity at age 42, followed by muscle weakness and atrophy of the right lower extremity and upper extremities. At age 57, she needed transient ventilatory support. Slight weakness in the facial muscles and fasciculation of the tongue appeared at age 60. At age 61, she died of sudden respiratory arrest. During the clinical course, neurological examination revealed neither Babinski signs nor hyperreflexia. The neuropathological examination revealed not only neuronal loss with gliosis in the facial nucleus, hypoglossal nucleus, and anterior horns of the spinal cord, but also loss of Betz cells and degeneration of the pyramidal tracts. Based on these clinicopathological findings and review of literature, we conclude that sporadic ALS mimicking SPMA is present.

Tsuchiya K; Shintani S; Kikuchi M; Kondo H; Kamaya T; Ohbu S; Kato S; Hayashi H; Ikeda K; Nakano I

1999-01-01

306

Sporadic amyotrophic lateral sclerosis of long duration mimicking spinal progressive muscular atrophy: a clinicopathological study.  

Science.gov (United States)

We report an autopsy case of amyotrophic lateral sclerosis (ALS) clinically diagnosed as spinal progressive muscular atrophy (SPMA). The patient was a Japanese woman without hereditary burden. She developed muscle weakness of the distal part of the left lower extremity at age 42, followed by muscle weakness and atrophy of the right lower extremity and upper extremities. At age 57, she needed transient ventilatory support. Slight weakness in the facial muscles and fasciculation of the tongue appeared at age 60. At age 61, she died of sudden respiratory arrest. During the clinical course, neurological examination revealed neither Babinski signs nor hyperreflexia. The neuropathological examination revealed not only neuronal loss with gliosis in the facial nucleus, hypoglossal nucleus, and anterior horns of the spinal cord, but also loss of Betz cells and degeneration of the pyramidal tracts. Based on these clinicopathological findings and review of literature, we conclude that sporadic ALS mimicking SPMA is present. PMID:10202983

Tsuchiya, K; Shintani, S; Kikuchi, M; Kondo, H; Kamaya, T; Ohbu, S; Kato, S; Hayashi, H; Ikeda, K; Nakano, I

1999-01-15

307

Corneal Confocal Microscopy Findings in Sporadic Cases of Pre-Descemet Corneal Dystrophy.  

UK PubMed Central (United Kingdom)

PURPOSE:: To present corneal confocal microscopy (CCM) findings in a series of patients with pre-Descemet corneal dystrophy (PDCD). METHODS:: A 28-year-old man, a 50-year-old man, a 30-year-old woman, and a 31-year-old man were clinically diagnosed with PDCD on slit lamp microscopic evaluation. All patients were evaluated by means of CCM. The parents of the patients were clinically evaluated. Two of the patients underwent photorefractive keratectomy. RESULTS:: In all the patients, CCM revealed highly reflective stromal particles and pleomorphic structures that included particles in the deep stroma, immediately anterior to the Descemet membrane extending up to 60 ?m from endothelium. No evidence of PDCD was observed clinically in the parents of the patients. Postoperative course of photorefractive keratectomy was uneventful for both of the patients. CONCLUSIONS:: With the use of CCM, a specific pattern of findings seemed to be related with PDCD in this series of sporadic cases.

Kontadakis GA; Kymionis GD; Kankariya VP; Papadiamantis AG; Pallikaris AI

2013-02-01

308

BRCA1 expression is epigenetically repressed in sporadic ovarian cancer cells by overexpression of C-terminal binding protein 2.  

UK PubMed Central (United Kingdom)

INTRODUCTION: Ovarian cancer is the leading cause of mortality from gynecological malignancy despite advancements in novel therapeutics. We have recently demonstrated that the transcriptional co-repressor C-terminal binding protein 2 (CtBP2) is overexpressed in epithelial ovarian carcinoma. MATERIALS AND METHODS: Reverse-transcribed cDNA from CtBP2 wild-type and knockdown ovarian cancer cell lines was hybridized to Affymetrix Gene 1.0 ST microarrays, and differentially expressed genes were studied. Immunohistochemical analysis of CtBP2 and BRCA1 staining of ovarian tissues was performed. Chromatin immunoprecipitation (ChIP) and luciferase assays were carried out. The effect of the drugs 4-methylthio-2-oxobutyric acid (MTOB) and poly(ADP-ribose) polymerase (PARP) inhibitor Olaparib on CtBP2 wild-type and knockdown cell lines was examined using methylthiazol tetrazolium assays and an xCELLigence System. RESULTS: Eighty-five genes involved in DNA repair, mitotic checkpoint, nucleosome assembly, and the BRCA1 network were differentially regulated by CtBP2 expression. ChIP and luciferase reporter assays using a BRCA1 promoter-regulated luciferase construct indicated that the CtBP2 complex binds the BRCA1 promoter and represses BRCA1 transcription. Immunohistochemistry illustrated a significant inverse CtBP2 and BRCA1 expression in a panel of malignant ovarian tumor tissues. The CtBP2 inhibitor MTOB suppressed ovarian cancer cell survival in a CtBP2-dependent manner. Ovarian cancer cells with CtBP2 knockdown did not display increased sensitivity to the PARP inhibitor Olaparib. CONCLUSION: CtBP2 is an ovarian cancer oncogene that may play a significant role in epigenetically silencing BRCA1 function in sporadic epithelial ovarian cancer. CtBP2-specific inhibitors, such as MTOB, may be effective adjunct therapies in the management of patients with CtBP2-positive ovarian carcinoma.

May T; Yang J; Shoni M; Liu S; He H; Gali R; Ng SK; Crum C; Berkowitz RS; Ng SW

2013-06-01

309

The neurotensin receptor-1 promotes tumor development in a sporadic but not an inflammation-associated mouse model of colon cancer.  

Science.gov (United States)

Neurotensin receptor-1 (NTR-1) is overexpressed in colon cancers and colon cancer cell lines. Signaling through this receptor stimulates proliferation of colonocyte-derived cell lines and promotes inflammation and mucosal healing in animal models of colitis. Given the causal role of this signaling pathway in mediating colitis and the importance of inflammation in cancer development, we tested the effects of NTR-1 in mouse models of inflammation-associated and sporadic colon cancer using NTR-1-deficient (Ntsr1(-) (/-)) and wild-type (Ntsr1(+/+)) mice. In mice treated with azoxymethane (AOM) to model sporadic cancer, NTR-1 had a significant effect on tumor development with Ntsr1(+/+) mice developing over twofold more tumors than Ntsr1(-) (/-) mice (p = 0.04). There was no effect of NTR-1 on the number of aberrant crypt foci or tumor size, suggesting that NT/NTR-1 signaling promotes the conversion of precancerous cells to adenomas. Interestingly, NTR-1 status did not affect tumor development in an inflammation-associated cancer model where mice were treated with AOM followed by two cycles of 5% dextran sulfate sodium (DSS). In addition, colonic molecular and histopathologic analyses were performed shortly after a single cycle of DSS. NTR-1 status did not affect colonic myeloperoxidase activity or histopathologic scores for damage and inflammation. However, Ntsr1(-) (/-) mice were more resistant to DSS-induced mortality (p = 0.01) and had over twofold higher colonic expression levels of Il6 and Cxcl2 (p < 0.04), cytokines known to promote tumor development. These results represent the first direct demonstration that targeted disruption of the Ntsr1 gene reduces susceptibility to colon tumorigenesis. PMID:21630261

Bugni, James M; Rabadi, Leina Al-; Jubbal, Kevin; Karagiannides, Iordanis; Lawson, Gregory; Pothoulakis, Charalabos

2011-11-17

310

Association of hereditary prostate cancer gene polymorphic variants with sporadic aggressive prostate carcinoma.  

UK PubMed Central (United Kingdom)

BACKGROUND: ELAC2, MSR1, and RNASEL are candidate genes for hereditary prostate carcinoma (HPC). While, studies have demonstrated that single nucleotide polymorphisms (SNPs) in these genes are associated with sporadic disease as well as HPC, these results are often not replicated in follow-up studies. Given that the majority of patients studied had localized disease and up to 50% of localized prostate cancer is clinically insignificant, the inability to replicate the initial findings may reflect that some subjects had indolent tumors. Herein, we examine patients with metastatic disease to determine if an association exists between HPC SNPs and unambiguously significant prostate cancer. METHODS: We examined polymorphisms within ELAC2 (S217L, A541T, E622V), MSR1 (P275A, R293X, aIVS5-59c), and RNASEL (E265X, R462Q, D541E) in 150 European-Americans with metastatic prostate cancer and 170 prostate cancer-free controls using pyrosequencing assays. RESULTS: Only ELAC2 217L (37% cases vs. 29% controls (P=0.034)) and RNASEL 541E (61% cases vs. 53% controls (P=0.045)) were over-represented. Analysis of genotypes revealed that presence of the leucine ELAC2 allele (OR 1.54: 95% CI=0.99-2.41, SS vs. SL, LL) and homozygosity for the glutamic acid RNASEL allele (OR 1.68: 95% CI=1.04-2.70, EE vs. DE, DD) were associated with increased risk. Patients with both genotypes were of particularly high-risk (OR 2.66: 95% CI=1.36-5.19). CONCLUSIONS: These results suggest that, in a European-American population, ELAC2 217L and RNASEL 541E are associated with metastatic sporadic disease. ELAC2 and RNASEL SNP analysis may prove useful in determining which patients are at risk for developing clinically significant prostate carcinoma.

Noonan-Wheeler FC; Wu W; Roehl KA; Klim A; Haugen J; Suarez BK; Kibel AS

2006-01-01

311

Ultrasound-guided unilateral neck exploration for sporadic primary hyperparathyroidism: is it worthwhile?  

Science.gov (United States)

The role of preoperative localisation tests before initial neck exploration for primary hyperparathyroidism (PHP) remains controversial, as does the optimal surgical approach. We report our experience with preoperative ultrasound (US) and the operative management of sporadic PHP between 1990 and 1995. Preoperative US was carried out by an experienced radiologist. Three surgeons adopted a policy of 'selective' US-guided unilateral neck exploration (UNE); the fourth surgeon performed routine bilateral neck exploration (BNE). There were 72 patients: 26 men and 46 women, with a mean age of 57.4 +/- 12.5 years (range 21-80 years). All patients underwent initial neck exploration for 'sporadic' PHP, of whom 63 had preoperative US. This was positive in 52 patients; 27 of whom underwent a UNE, 23 had a BNE, and two patients had a UNE converted to a BNE. Patients with 'negative' US (n = 11), and those receiving no preoperative localisation test (n = 90) underwent a BNE. The sensitivity, specificity and accuracy of US were 80% (52/65), 100% (61/61), and 90% (113/126), respectively. Comparable success rates were achieved (BNE: 97% (33/34) vs UNE: 93% (27/29), P < 0.05), with very low morbidity. Failures with the scan-guided UNE were caused by missed contralateral adenomas. An experienced radiologist and a low incidence of multiglandular disease (MGD) are essential prerequisites for the scan-guided unilateral approach. An experienced surgeon, on the other hand, is the only prerequisite for the 'gold standard' bilateral approach. PMID:10209415

Ammori, B J; Madan, M; Gopichandran, T D; Price, J J; Whittaker, M; Ausobsky, J R; Antrum, R M

1998-11-01

312

Prevalence of BRCA1 mutations in familial and sporadic greek ovarian cancer cases.  

UK PubMed Central (United Kingdom)

Germline mutations in the BRCA1 and BRCA2 genes contribute to approximately 18% of hereditary ovarian cancers conferring an estimated lifetime risk from 15% to 50%. A variable incidence of mutations has been reported for these genes in ovarian cancer cases from different populations. In Greece, six mutations in BRCA1 account for 63% of all mutations detected in both BRCA1 and BRCA2 genes. This study aimed to determine the prevalence of BRCA1 mutations in a Greek cohort of 106 familial ovarian cancer patients that had strong family history or metachronous breast cancer and 592 sporadic ovarian cancer cases. All 698 patients were screened for the six recurrent Greek mutations (including founder mutations c.5266dupC, p.G1738R and the three large deletions of exon 20, exons 23-24 and exon 24). In familial cases, the BRCA1 gene was consequently screened for exons 5, 11, 12, 20, 21, 22, 23, 24. A deleterious BRCA1 mutation was found in 43/106 (40.6%) of familial cancer cases and in 27/592 (4.6%) of sporadic cases. The variant of unknown clinical significance p.V1833M was identified in 9/698 patients (1.3%). The majority of BRCA1 carriers (71.2%) presented a high-grade serous phenotype. Identifying a mutation in the BRCA1 gene among breast and/or ovarian cancer families is important, as it enables carriers to take preventive measures. All ovarian cancer patients with a serous phenotype should be considered for genetic testing. Further studies are warranted to determine the prevalence of mutations in the rest of the BRCA1 gene, in the BRCA2 gene, and other novel predisposing genes for breast and ovarian cancer.

Stavropoulou AV; Fostira F; Pertesi M; Tsitlaidou M; Voutsinas GE; Triantafyllidou O; Bamias A; Dimopoulos MA; Timotheadou E; Pectasides D; Christodoulou C; Klouvas G; Papadimitriou C; Makatsoris T; Pentheroudakis G; Aravantinos G; Karydakis V; Yannoukakos D; Fountzilas G; Konstantopoulou I

2013-01-01

313

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

DEFF Research Database (Denmark)

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

Larsen, Nicolai Balle; Rasmussen, Merete

2009-01-01

314

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

UK PubMed Central (United Kingdom)

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.

Garcia-Vidal C; Labori M; Viasus D; Simonetti A; Garcia-Somoza D; Dorca J; Gudiol F; Carratalà J

2013-01-01

315

Role of poultry meat in sporadic Campylobacter infections in Bosnia and Herzegovina: laboratory-based study.  

UK PubMed Central (United Kingdom)

AIM: To investigate genetic diversity and specificity of Campylobacter jejuni and Campylobacter coli strains isolated from humans, retail poultry meat, and live farm chickens in Zenica-Doboj Canton, Bosnia and Herzegovina, and identify the role of poultry meat in sporadic Campylobacter infections. METHODS: We determined the type of Campylobacter species using standard microbiological methods and multiplex polymerase chain reaction (PCR), and performed pulsed field gel-electrophoresis (PFGE) and restriction fragment length polymorphism (RFLP) typing of the flaA gene to investigate genetic diversity among the isolates. RESULTS: We isolated C jejuni and C coli from 75 (5.2%) of 1453 samples of consecutive outpatients with sporadic diarrhea; from 51 (34.7%) of 147 samples of poultry meat; and from 15 out of 23 farm chicken samples. The proportion of C coli found among human (30.1%), poultry meat (56.9%), and farm chicken isolates (53.3%), was greater than the proportion of C jejuni. Fourteen and 24 PFGE genotypes were identified among 20 C coli and 37 C jejuni isolates, respectively. Identical PFGE genotypes were found in two cases of human and poultry meat isolates and two cases of poultry meat and farm chicken isolates. CONCLUSION: Only a minority of human Campylobacter isolates shared identical PFGE type with poultry meat isolates. Although poultry is the source of a certain number of human infections, there may be other more important sources. Further research is required to identify the environmental reservoir of Campylobacter spp responsible for causing human disease and the reason for the high prevalence of C coli human infections in this region.

Uzunovi?-Kamberovi? S; Zorman T; Heyndrickx M; Smole Mozina S

2007-12-01

316

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

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

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

2008-01-01

317

Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease.  

UK PubMed Central (United Kingdom)

The search for the causes of neurodegenerative disorders is a major theme in brain research. Acquired disturbances of several aspects of cellular metabolism appear pathologically important in sporadic Alzheimer's disease (SDAT). Among these brain glucose utilisation is reduced in the early stages of the disease and the regulatory enzymes important for glucose metabolism are reduced. In the brain, insulin, insulin-like growth factors and their receptors regulate glucose metabolism and promote neuronal growth. To detect changes in the functional activity of the brain insulin neuromodulatory system of SDAT patients, we determined the concentrations of insulin and c-peptide as well as insulin receptor binding and IGF-I receptor binding in several regions of postmortem brain cortex during aging and Alzheimer's disease. Additionally, we performed immunohistochemical staining with antibodies against insulin in neocortical brain areas in SDAT and controls. We show for the first time that insulin and c-peptide concentration in the brain are correlated and decrease with aging, as do brain insulin receptor densities. Weak insulin-immunoreactivity could be demonstrated histochemically in pyramidal neurons of controls, whereas in SDAT a stronger insulin-immunoreactivity was found. On a biochemical level, insulin and c-peptide levels were reduced compared to middle-aged controls, but were unchanged compared to age-matched controls. Brain insulin receptor densities in SDAT were decreased compared to middle-aged controls, but increased in comparison to age-matched controls. IGF-I receptor densities were unchanged in aging and in SDAT. Tyrosine kinase activity, a signal transduction mechanism common to both receptor systems, was reduced in SDAT in comparison to middle-aged and age-matched control groups. These data are consistent with a neurotrophic role of insulin in the human brain and a disturbance of insulin signal transduction in SDAT brain and favor the hypothesis that insulin dependent functions may be of pathogenetic relevance in sporadic SDAT.

Frölich L; Blum-Degen D; Bernstein HG; Engelsberger S; Humrich J; Laufer S; Muschner D; Thalheimer A; Türk A; Hoyer S; Zöchling R; Boissl KW; Jellinger K; Riederer P

1998-01-01

318

Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease.  

Science.gov (United States)

The search for the causes of neurodegenerative disorders is a major theme in brain research. Acquired disturbances of several aspects of cellular metabolism appear pathologically important in sporadic Alzheimer's disease (SDAT). Among these brain glucose utilisation is reduced in the early stages of the disease and the regulatory enzymes important for glucose metabolism are reduced. In the brain, insulin, insulin-like growth factors and their receptors regulate glucose metabolism and promote neuronal growth. To detect changes in the functional activity of the brain insulin neuromodulatory system of SDAT patients, we determined the concentrations of insulin and c-peptide as well as insulin receptor binding and IGF-I receptor binding in several regions of postmortem brain cortex during aging and Alzheimer's disease. Additionally, we performed immunohistochemical staining with antibodies against insulin in neocortical brain areas in SDAT and controls. We show for the first time that insulin and c-peptide concentration in the brain are correlated and decrease with aging, as do brain insulin receptor densities. Weak insulin-immunoreactivity could be demonstrated histochemically in pyramidal neurons of controls, whereas in SDAT a stronger insulin-immunoreactivity was found. On a biochemical level, insulin and c-peptide levels were reduced compared to middle-aged controls, but were unchanged compared to age-matched controls. Brain insulin receptor densities in SDAT were decreased compared to middle-aged controls, but increased in comparison to age-matched controls. IGF-I receptor densities were unchanged in aging and in SDAT. Tyrosine kinase activity, a signal transduction mechanism common to both receptor systems, was reduced in SDAT in comparison to middle-aged and age-matched control groups. These data are consistent with a neurotrophic role of insulin in the human brain and a disturbance of insulin signal transduction in SDAT brain and favor the hypothesis that insulin dependent functions may be of pathogenetic relevance in sporadic SDAT. PMID:9720972

Frölich, L; Blum-Degen, D; Bernstein, H G; Engelsberger, S; Humrich, J; Laufer, S; Muschner, D; Thalheimer, A; Türk, A; Hoyer, S; Zöchling, R; Boissl, K W; Jellinger, K; Riederer, P

1998-01-01

319

A distinct DNA methylation profile associated with microsatellite and chromosomal stable sporadic colorectal cancers.  

Science.gov (United States)

Aberrant DNA methylation, microsatellite instability (MSI) and chromosomal instability (CIN) are well-characterised molecular features of sporadic colorectal cancers (CRCs). In addition to CpG island methylator phenotype (CIMP) associated with MSI, an intermediate methylation subgroup is also a feature of non-MSI cancers. A large proportion of CRCs have no evidence of either MSI or CIN, here called Microsatellite and Chromosomal Stable (MACS), and require their methylation profile to be established. The clinical and molecular features of 170 sporadic CRC patients were investigated and stratified into MSI, CIN and MACS groups. MACS were most often found in the left colon and had a significantly lower BRAF mutation frequency (p < 0.001) compared with MSI. MACS had better survival [hazard ratio (HR) = 0.244, p = 0.017] compared with CIN, but were similar to MSI. The methylation status of 1,505 CpG loci from cancer-related genes was analysed in a subset of CRCs (n = 44 normal-tumour pairs) and compared with CIN, MSI and MACS status. Using two-way hierarchical clustering, three subgroups were identified, which associated with CIN, MSI and MACS status. Using significance analysis of microarray, 16 CpG loci demonstrating methylation changes associated with MACS were identified. A combination of six loci identified MACS with 81% sensitivity and 93% specificity. This result now requires independent validation. Hypomethylation of a CpG locus within the sonic hedgehog (SHH) promoter correlated with increased gene expression and was associated significantly with MACS cancers. In conclusion, we propose that MACS have distinct clinicopathological features and can be distinguished from other CRCs by a specific set of methylation loci. PMID:21455990

Silver, Andrew; Sengupta, Neel; Propper, David; Wilson, Peter; Hagemann, Thorsten; Patel, Asif; Parker, Alexandra; Ghosh, Anil; Feakins, Roger; Dorudi, Sina; Suraweera, Nirosha

2011-08-03

320

Clinical, demographic and prognostic features of sporadic amyotrophic lateral sclerosis in Northern Turkey.  

UK PubMed Central (United Kingdom)

Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease for which progression cannot be prevented. In this study, we evaluated 37 patients diagnosed with sporadic definitive-probable ALS who were monitored in our Neurology clinic between 2002 and 2012 in terms of age, gender, profession, onset, and clinical course within the disease process. The hospital ethics committee approved the study. Nineteen female and 18 male patients diagnosed with sporadic definitive or probable ALS were evaluated for age, gender, level of education, residence, onset of disease, the time between the first symptom and diagnosis, and average lifetime after diagnosis. Twenty-eight of the patients had graduated from primary-secondary school, 6 were illiterate, and 3 of them were college graduates. Eighteen patients were living in city center, 19 were living in the country. Fourteen patients were farmers, 11 were housewives, and the remaining were working in various different occupations. The age of onset was 62.13. The men and women were diagnosed 10.27 months and 17.91 months after the first symptom, respectively (p = 0.001). The average survival time after diagnosis was 36.70 months for males and 49.80 months for females (p<0.05). This difference was particularly evident among patients from rural areas. In addition, our female patients required interventions such as ventilation at a later period than did males. In conclusion, female gender seems to be one of the good prognostic factors for our ALS patients. This may be due to the protection by hormonal mechanisms in women or differences in their responses to exogenous toxins.

Aksoy D; Cevik B; Solmaz V; Kurt SG

2013-07-01

 
 
 
 
321

Alterations of MEN1 and E-cadherin/?-catenin complex in sporadic pulmonary carcinoids.  

UK PubMed Central (United Kingdom)

Pulmonary carcinoids, distinct in typical and atypical, represent 2-5% of all primary lung tumors. The aim of this study was to investigate the molecular alterations correlated with the development of this form of neoplasms. A collection of 38 paraffin-embedded apparently sporadic carcinoids was investigated, through a combined study, for protein expression/localization of menin, p53, ?-catenin and E-cadherin and for mutational analysis of the MEN1, TP53 and CTNNB1 genes. Menin was expressed in 71% of cases, with a prevalent cytoplasmic (c) localization, ?-catenin was expressed in 68.4% of cases, of which 36.8% with a membranous (m) and 31.6% with a cytoplasmic localization. Membranous E-cadherin immunoreactivity was detected in 84.2% cases, nuclear p53 expression in 5.3% of cases. Positive correlation was found between c-menin and c-?-catenin expression (rho=0.439, P=0.008). In addition, m-?-catenin showed a positive correlation with both c-?-catenin and E-cadherin expression (rho=0.380, P=0.022 and rho=0.360, P=0.040, respectively). With regard to the E-cadherin/?-catenin complex, we found also a significant positive correlation between c-menin and 'disarrayed' ?-catenin expression (rho=0.481, P=0.007). MEN1 gene variants were characterized in 34% of cases. c-menin was more highly expressed in tumors with MEN1 variants, compared to tumors without MEN1 variants (P=0.023). Three nucleotide variants of TP53 were also detected. This study confirms the involvement of the MEN1 gene in the development of sporadic pulmonary carcinoids, demonstrates the accumulation of menin in the cytoplasm, and indicates that the disarrayed pattern of the complex significantly correlates with c-menin accumulation.

Veschi S; Lattanzio R; Aceto GM; Curia MC; Magnasco S; Angelucci D; Cama A; Piantelli M; Battista P

2012-10-01

322

Alterations of MEN1 and E-cadherin/?-catenin complex in sporadic pulmonary carcinoids.  

Science.gov (United States)

Pulmonary carcinoids, distinct in typical and atypical, represent 2-5% of all primary lung tumors. The aim of this study was to investigate the molecular alterations correlated with the development of this form of neoplasms. A collection of 38 paraffin-embedded apparently sporadic carcinoids was investigated, through a combined study, for protein expression/localization of menin, p53, ?-catenin and E-cadherin and for mutational analysis of the MEN1, TP53 and CTNNB1 genes. Menin was expressed in 71% of cases, with a prevalent cytoplasmic (c) localization, ?-catenin was expressed in 68.4% of cases, of which 36.8% with a membranous (m) and 31.6% with a cytoplasmic localization. Membranous E-cadherin immunoreactivity was detected in 84.2% cases, nuclear p53 expression in 5.3% of cases. Positive correlation was found between c-menin and c-?-catenin expression (rho=0.439, P=0.008). In addition, m-?-catenin showed a positive correlation with both c-?-catenin and E-cadherin expression (rho=0.380, P=0.022 and rho=0.360, P=0.040, respectively). With regard to the E-cadherin/?-catenin complex, we found also a significant positive correlation between c-menin and 'disarrayed' ?-catenin expression (rho=0.481, P=0.007). MEN1 gene variants were characterized in 34% of cases. c-menin was more highly expressed in tumors with MEN1 variants, compared to tumors without MEN1 variants (P=0.023). Three nucleotide variants of TP53 were also detected. This study confirms the involvement of the MEN1 gene in the development of sporadic pulmonary carcinoids, demonstrates the accumulation of menin in the cytoplasm, and indicates that the disarrayed pattern of the complex significantly correlates with c-menin accumulation. PMID:22825745

Veschi, Serena; Lattanzio, Rossano; Aceto, Gitana Maria; Curia, Maria Cristina; Magnasco, Salvatore; Angelucci, Domenico; Cama, Alessandro; Piantelli, Mauro; Battista, Pasquale

2012-07-20

323

Clinical features and outcome of sporadic serogroup W135 disease Taiwan  

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

Wang Jiun-Ling; Liu Ding-Ping; Yen Jer-Jea; Yu Chia-Jung; Liu Hsi-Chen; Lin Ching-Yuang; Chang Shan-Chwen

2006-01-01

324

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

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

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

2008-01-01

325

Survival of patients with Stage III colon cancer is improved in hereditary non-polyposis colorectal cancer compared with sporadic cases. A Danish registry based study.  

UK PubMed Central (United Kingdom)

AIM: Patients with hereditary non-polyposis colorectal cancer (HNPCC) seem to have a better prognosis than those with sporadic colorectal cancer (CRC). The aim was to compare survival after Stage III CC in patients with HNPCC with those having sporadic CC. METHOD: A total of 230 patients with hereditary cancer from the Danish HNPCC Register and 3557 patients with sporadic CC from the Danish Colorectal Cancer Database, diagnosed during May 2001-December 2008, were included. HNPCC patients were classified according to mismatch repair mutation status and family pedigree. Sporadic cases had no known family history of cancer. Patient characteristics, geographical differences and survival data were analysed. RESULTS: The overall survival (OS) was better in HNPCC patients compared with sporadic CC after stratification for sex and age (P = 0.02; CI 1.04-1.7). The 5-year survival was 70% in HNPCC patients compared with 56% in sporadic CC (P < 0.001). No survival difference was found between HNPCC subgroups but a tendency to better OS was seen in patients with Lynch syndrome. No geographical differences in OS were found. The median follow-up was 3.9 (0-9.5) years for HNPCC vs 3.2 (0-9.6) years for sporadic CC. CONCLUSION: HNPCC patients with Stage III CC have a better OS compared with sporadic CC. No significant difference in OS was found within HNPCC subgroups.

Brixen LM; Bernstein IT; Bülow S; Ehrnrooth E

2013-07-01

326

Transforming growth factor-beta receptor type 2 mutations and microsatellite instability in sporadic colorectal adenomas and carcinomas.  

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Frame-shift mutations in a run of 10 adenines (A10) of the transforming growth factor-beta receptor type 2 gene (TGF-beta RII) are commonly seen in inherited and sporadic colonic cancers that exhibit microsatellite instability. A10 mutations and instability also are commonly seen in hereditary nonpo...

Samowitz, W. S.; Slattery, M. L.

327

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

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Sporadic inclusion body myositis (s-IBM) is a chronic inflammatory myopathy of unknown pathogenesis. The common findings of ragged red fibres, cytochrome c oxidase-negative fibres and multiple mitochondrial DNA deletions in the muscle of patients with s-IBM have suggested that a deficit of energy me...

Lodi, R; Taylor, DJ; Tabrizi, SJ; Hilton-Jones, D; Squier, MV

328

Sporadic Inclusion Body Myositis: Inflammatory and Degenerative Disease Mechanisms Die sporadische Inclusion body myositis: entzündliche und degenerative Mechanismen  

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Sporadic inclusion body myositis (sIBM) is an enigmatic disease resistant to immunomodulatory treatment and featuring autoimmune and degenerative aspects: clonally expanded CD8+ T cells focally infiltrate uniformly HLA-I+ myofibers that harbor beta-amyloid deposits. In a non-hypothesis-driven approa...

Ivanidze, Jana

329

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

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The hallmark pathologies of sporadic inclusion-body myositis (s-IBM) muscle fibers are autophagic vacuoles and accumulation of ubiquitin-positive multiprotein aggregates that contain amyloid-? or phosphorylated tau in a ?-pleated sheet amyloid configuration. Endoplasmic reticulum stress (ERS) and 26...

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

330

Sporadic, Nontrauma-Related, Desmoid Tumor of the Pancreas: A Rare Disease—Case Report and Literature Review  

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Desmoid tumors (DTs) are neoplasms of fibroblastic origin characterized by lack of a capsule. They are nonmetastatic and locally aggressive. Intraabdominal DTs are often observed in familial adenomatous polyposis and Gardner syndrome or subsequent to localized traumatic injury. Sporadic forms are de...

Polistina, F.; Costantin, G.; D'Amore, E.; Ambrosino, G.

331

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

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Papillary thyroid cancers (PTCs) incidence dramatically increased in the vicinity of Chernobyl. The cancer-initiating role of radiation elsewhere is debated. Therefore, we searched for a signature distinguishing radio-induced from sporadic cancers. Using microarrays, we compared the expression profi...

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

332

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

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Multidrug-resistant strains of Shigella dysenteriae type 1 were implicated in three outbreaks and sporadic cases of dysentery in eastern India in 2002 and 2003. After a hiatus of 14 years, this pathogen reemerged with an altered antibiotic resistance pattern. In addition to ampicillin, co-trimoxazol...

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

333

Mutation in CDKN2C (p18) and CDKN2D (p19) may cause sporadic parathyroid adenoma.  

UK PubMed Central (United Kingdom)

Extract: Hyperparathyroidism can arise from germline mutation of MEN1, CASR, or HRPT (Marx 2011). Recent studies also suggest that germline mutation of several cyclin-dependent kinase inhibitors is an uncommon cause of hyperparathyroidism (Pellegata et al, 2006; Agarwal, et al. 2009). A gene that predisposes to tumor via germline mutation also may predispose to similar tumor by somatic mutation; in fact, the MEN1 gene is mutated in about 30% of sporadic parathyroid tumors (Marx 2011). Screening a small number of sporadic parathyroid tumors by others, using whole exome analysis, did not show any CDKI gene mutation (Cromer, et al. 2012; Newey, et al. 2012). In a recent study, all 7 CDKI genes were sequenced in 81 sporadic parathyroid adenomas. There were 5 novel DNA missense changes in p15, p18, and p21. 3-4 of these were also in the germline, and none of the five was unequivocally a pathological mutation, such as a truncation change (Costa-Guda 2013). We evaluated further whether some cases of sporadic parathyroid adenoma are caused by somatic mutation in CDKI genes ...

Gluick T; Yuan Z; Libutti SK; Marx SJ

2013-10-01

334

Nuclear DNA content of isolated crypts of background colonic mucosa from patients with familial adenomatous polyposis and sporadic colorectal cancer.  

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The DNA content of the upper one third of the crypt epithelium was compared with that of the lower two thirds in the background colorectal mucosa of eight cases of familial adenomatous polyposis (FAP) and eight control cases of sporadic colorectal cancer (SCRC). Intact crypts were isolated by incuba...

Nakamura, S; Kino, I; Baba, S

335

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

UK PubMed Central (United Kingdom)

In Listeria monocytogenes serotype 4b isolates from sporadic listeriosis, heavy metal resistance was primarily encountered in certain clonal groups (ECI, ECII, and ECIa). All arsenic-resistant isolates harbored the arsenic resistance cassette previously identified in pLI100; ECIa harbored additional arsenic resistance genes and a novel cadmium resistance determinant in a conserved chromosomal locus.

Lee S; Rakic-Martinez M; Graves LM; Ward TJ; Siletzky RM; Kathariou S

2013-04-01

336

The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial.  

UK PubMed Central (United Kingdom)

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) is implicated in DNA repair and transcription regulation. Niraparib (MK4827) is an oral potent, selective PARP-1 and PARP-2 inhibitor that induces synthetic lethality in preclinical tumour models with loss of BRCA and PTEN function. We investigated the safety, tolerability, maximum tolerated dose, pharmacokinetic and pharmacodynamic profiles, and preliminary antitumour activity of niraparib. METHODS: In a phase 1 dose-escalation study, we enrolled patients with advanced solid tumours at one site in the UK and two sites in the USA. Eligible patients were aged at least 18 years; had a life expectancy of at least 12 weeks; had an Eastern Cooperative Oncology Group performance status of 2 or less; had assessable disease; were not suitable to receive any established treatments; had adequate organ function; and had discontinued any previous anticancer treatments at least 4 weeks previously. In part A, cohorts of three to six patients, enriched for BRCA1 and BRCA2 mutation carriers, received niraparib daily at ten escalating doses from 30 mg to 400 mg in a 21-day cycle to establish the maximum tolerated dose. Dose expansion at the maximum tolerated dose was pursued in 15 patients to confirm tolerability. In part B, we further investigated the maximum tolerated dose in patients with sporadic platinum-resistant high-grade serous ovarian cancer and sporadic prostate cancer. We obtained blood, circulating tumour cells, and optional paired tumour biopsies for pharmacokinetic and pharmacodynamic assessments. Toxic effects were assessed by common toxicity criteria and tumour responses ascribed by Response Evaluation Criteria in Solid Tumors (RECIST). Circulating tumour cells and archival tumour tissue in prostate patients were analysed for exploratory putative predictive biomarkers, such as loss of PTEN expression and ETS rearrangements. This trial is registered with ClinicalTrials.gov, NCT00749502. FINDINGS: Between Sept 15, 2008, and Jan 14, 2011, we enrolled 100 patients: 60 in part A and 40 in part B. 300 mg/day was established as the maximum tolerated dose. Dose-limiting toxic effects reported in the first cycle were grade 3 fatigue (one patient given 30 mg/day), grade 3 pneumonitis (one given 60 mg/day), and grade 4 thrombocytopenia (two given 400 mg/day). Common treatment-related toxic effects were anaemia (48 patients [48%]), nausea (42 [42%]), fatigue (42 [42%]), thrombocytopenia (35 [35%]), anorexia (26 [26%]), neutropenia (24 [24%]), constipation (23 [23%]), and vomiting (20 [20%]), and were predominantly grade 1 or 2. Pharmacokinetics were dose proportional and the mean terminal elimination half-life was 36·4 h (range 32·8-46·0). Pharmacodynamic analyses confirmed PARP inhibition exceeded 50% at doses greater than 80 mg/day and antitumour activity was documented beyond doses of 60 mg/day. Eight (40% [95% CI 19-64]) of 20 BRCA1 or BRCA2 mutation carriers with ovarian cancer had RECIST partial responses, as did two (50% [7-93]) of four mutation carriers with breast cancer. Antitumour activity was also reported in sporadic high-grade serous ovarian cancer, non-small-cell lung cancer, and prostate cancer. We recorded no correlation between loss of PTEN expression or ETS rearrangements and measures of antitumour activity in patients with prostate cancer. INTERPRETATION: A recommended phase 2 dose of 300 mg/day niraparib is well tolerated. Niraparib should be further assessed in inherited and sporadic cancers with homologous recombination DNA repair defects and to target PARP-mediated transcription in cancer. FUNDING: Merck Sharp and Dohme.

Sandhu SK; Schelman WR; Wilding G; Moreno V; Baird RD; Miranda S; Hylands L; Riisnaes R; Forster M; Omlin A; Kreischer N; Thway K; Gevensleben H; Sun L; Loughney J; Chatterjee M; Toniatti C; Carpenter CL; Iannone R; Kaye SB; de Bono JS; Wenham RM

2013-08-01

337

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

UK PubMed Central (United Kingdom)

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

Sabatelli M; Eusebi F; Al-Chalabi A; Conte A; Madia F; Luigetti M; Mancuso I; Limatola C; Trettel F; Sobrero F; Di Angelantonio S; Grassi F; Di Castro A; Moriconi C; Fucile S; Lattante S; Marangi G; Murdolo M; Orteschi D; Del Grande A; Tonali P; Neri G; Zollino M

2009-10-01

338

Three novel human sporadic melanoma cell lines: signaling pathways controlled by MC1R, BRAF and ?-catenins.  

UK PubMed Central (United Kingdom)

We studied the behaviour of three novel human sporadic melanoma cell lines (hmel1, hmel9, hmel11) extracted from tumors with different degrees of malignancy, concerning the cell signalling pathways controlled by MC1R, BRAF, NRAS and ?-catenins. The novel cell lines were compared to metastatic cell lines (HBL, LND1), wild type (wt) for MC1R and BRAF genes, that have been extensively characterised and were used as control. All the novel cell lines have silent or no MC1R mutations even though MC1R signalling is severely impaired. Conversely, they harbour BRAF mutations at the V600 residue. These mutations determine a constitutive ERK phosphorylation in all the three cell lines. Our new melanoma cell lines were BRAF mutated in hetero- and homozygosis, even with a wild type MC1R, and unresponsive to NDP-MSH treatment. Quantity and subcellular localization of ?-catenin were analyzed in both novel and control cell lines. In HBL and LND1 there were high levels of beta-catenin distributed in the cytoplasm/nucleus, while in the novel melanoma cell lines ?-catenins were less abundant and seemed to be located at the plasma membrane/cytoplasm and absent in the nucleus. We sequenced beta-catenin cDNA for all the melanoma cell lines, and found mutations in HBL, LND1 and hmel1, while hmel9 and hmel11 were wt. We found that beta-catenin levels were not influenced by the RAS/RAF/MAPK pathway because inhibition with PD98059 (a MEK inhibitor) did not produce any effect on beta-catenin stability and/or localization.

Zanna P; Maida I; Grieco C; Guida S; Turpin Sevilla MC; De Summa S; Tommasi S; Vena GA; Filotico R; Guida G

2013-01-01

339

Rutin prevents cognitive impairments by ameliorating oxidative stress and neuroinflammation in rat model of sporadic dementia of Alzheimer type.  

Science.gov (United States)

The objective of the present study was to assess the neuroprotective role of rutin (vitamin P) and delineate the mechanism of action. Recent evidence indicates that rutin exhibits antioxidant potential and protects the brain against various oxidative stressors. More precisely, the aim of the present study was to examine the modulating impacts of rutin against cognitive deficits and oxidative damage in intracerebroventricular-streptozotocin (ICV-STZ)-infused rats. Rats were injected bilaterally with ICV-STZ (3 mg/kg), whereas sham rats received the same volume of vehicle. After 2 weeks of streptozotocin (STZ) infusion, rats were tested for cognitive performance using Morris water maze tasks and thereafter euthanized for further biochemical, histopathological, and immunohistochemical studies. Rutin pretreatment (25 mg/kg, orally, once daily for 3 weeks) significantly attenuated thiobarbituric acid reactive substances (TBARS), activity of poly ADP-ribosyl polymerase, and nitrite level and decreased level of reduced glutathione (GSH) and activities of its dependent enzymes (glutathione peroxidase [GPx] and glutathione reductase [GR]) and catalase in the hippocampus of ICV-STZ rats. ICV-STZ rats showed significant cognitive deficits, which was improved significantly by rutin supplementation. The results indicate that rutin attenuates STZ-induced inflammation by reducing the expression of cyclooxygenase-2 (COX-2), glial fibrillary acidic protein (GFAP), interleukin-8 (IL-8), inducible nitric oxide synthase (iNOS), nuclear factor-kB, and preventing the morphological changes in hippocampus. The study thereby suggests the effectiveness of rutin in preventing cognitive deficits and might be beneficial for the treatment of sporadic dementia of Alzheimer type (SDAT). PMID:22441036

Javed, H; Khan, M M; Ahmad, A; Vaibhav, K; Ahmad, M E; Khan, A; Ashafaq, M; Islam, F; Siddiqui, M S; Safhi, M M; Islam, F

2012-03-06

340

Rutin prevents cognitive impairments by ameliorating oxidative stress and neuroinflammation in rat model of sporadic dementia of Alzheimer type.  

UK PubMed Central (United Kingdom)

The objective of the present study was to assess the neuroprotective role of rutin (vitamin P) and delineate the mechanism of action. Recent evidence indicates that rutin exhibits antioxidant potential and protects the brain against various oxidative stressors. More precisely, the aim of the present study was to examine the modulating impacts of rutin against cognitive deficits and oxidative damage in intracerebroventricular-streptozotocin (ICV-STZ)-infused rats. Rats were injected bilaterally with ICV-STZ (3 mg/kg), whereas sham rats received the same volume of vehicle. After 2 weeks of streptozotocin (STZ) infusion, rats were tested for cognitive performance using Morris water maze tasks and thereafter euthanized for further biochemical, histopathological, and immunohistochemical studies. Rutin pretreatment (25 mg/kg, orally, once daily for 3 weeks) significantly attenuated thiobarbituric acid reactive substances (TBARS), activity of poly ADP-ribosyl polymerase, and nitrite level and decreased level of reduced glutathione (GSH) and activities of its dependent enzymes (glutathione peroxidase [GPx] and glutathione reductase [GR]) and catalase in the hippocampus of ICV-STZ rats. ICV-STZ rats showed significant cognitive deficits, which was improved significantly by rutin supplementation. The results indicate that rutin attenuates STZ-induced inflammation by reducing the expression of cyclooxygenase-2 (COX-2), glial fibrillary acidic protein (GFAP), interleukin-8 (IL-8), inducible nitric oxide synthase (iNOS), nuclear factor-kB, and preventing the morphological changes in hippocampus. The study thereby suggests the effectiveness of rutin in preventing cognitive deficits and might be beneficial for the treatment of sporadic dementia of Alzheimer type (SDAT).

Javed H; Khan MM; Ahmad A; Vaibhav K; Ahmad ME; Khan A; Ashafaq M; Islam F; Siddiqui MS; Safhi MM; Islam F

2012-05-01

 
 
 
 
341

Estrogen receptor alpha, BRCA1, and FANCF promoter methylation occur in distinct subsets of sporadic breast cancers.  

Science.gov (United States)

Estrogen receptor alpha (ER) and its ligand estrogen play vital roles in the development, progression and treatment of breast cancer. An increasing number of studies have also provided evidence linking disruption of the Fanconi anemia/BRCA cascade to breast cancer. Our objectives were to examine the methylation status and expression profiles of ER, correlate the findings with BRCA1 and FANCF methylation and map the critical CpGs for ER expression. We found that the CpG islands in the 5' region of the ER gene are methylated in 59 of 120 (49.2%) primary breast cancers, including 45 of 59 ER-negative tumors (76.3%, P < 0.00001). In addition, we observed a strong correlation between ER promoter and BRCA1 promoter methylation (odds ratio 3.12, 95% confidence interval 1.10-9.68, P = 0.02). In contrast, FANCF methylation was rare in breast tumors: one of 120 (0.8%). ER methylation was associated with high tumor grade (60.4% methylated vs. 39.6% unmethylated in grade 3 tumors, P = 0.04) and tumor subtype (P = 0.03). Though small in number, all tumors of the medullary subtype were ER methylated. In contrast, the lobular subtype had the least methylation (23.1% methylated vs. 76.9% unmethylated). After treatment of MDA-MB-231 cells with 5-aza-cytidine (5-aza-dC) and trichostatin, which resulted in re-expression of ER mRNA, we localized dramatic demethylation effects to CpG islands in positions +68, +165, +192, +195, +337, +341 and +405 from transcription start site of the ER promoter. These data suggest that unlike FANCF, both ER and BRCA1 are specifically targeted for methylation in sporadic breast cancers, a phenomenon that should be explored for development of novel diagnostic and therapeutic approaches. PMID:17932744

Wei, Minjie; Xu, Jinhua; Dignam, James; Nanda, Rita; Sveen, Lise; Fackenthal, James; Grushko, Tatyana A; Olopade, Olufunmilayo I

2007-10-12

342

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

Directory of Open Access Journals (Sweden)

Full Text Available AIM: To analyze ?-methylacyl CoA racemase (AMACR) expression in relation to various dysplasia phenotypes and clinicopathological parameters of sporadic colorectal adenomas.METHODS: Fifty-five cases of sporadic colorectal adenomas were categorized according to the Vienna classification for Gastrointestinal Neoplasia. These corresponded to a total of 98 different intra-lesion microscopic fields that were further independently assigned a histological grade based on the old nomenclature (mild, moderate, severe dyplasia and carcinoma in situ). AMACR expression was evaluated by immunohistochemistry and statistical analysis was performed to investigate possible associations with various clinicopathologic parameters of adenomas i.e. gender, age, localization, grade of dysplasia, size and configuration.RESULTS: Patient age ranged from 41 to 84 years (mean 65 ± 13.2 years); 37 patients were males and 18 were females. Adenomas ranged in size between 0.5 and 30 cm (mean 2 ± 1.3 cm), including 18 tubular, 16 villous, 20 mixed or tubulovillous, and 1 giant sessile villous adenoma. AMACR expression was observed in 3 out of 16 (18.8%) of low-grade vs 23 out of 35 (62.8%) of high-grade lesions (P = 0.002). Most adenomas exhibiting high grade dysplasia with in situ carcinoma-like areas stained positive for AMACR (15/17 or 88.2%) as compared to adenomas with high grade dysplasia which contained severe dysplasia-like foci (6/15 or 40%), (P = 0.005). In AMACR positive adenomas featuring severe dysplasia-like or in situ carcinoma-like areas, AMACR staining was not necessarily observed in the in situ component. Positivity in intra-lesion of mild, moderate or severe dysplasia-like foci was more often encountered in adenomas harboring in situ, intramucosal or infiltrative carcinoma [21/33 (63.6%) vs 9/40 (22.5%), P 1 cm stained more frequently for AMACR than smaller ones [27/45 (60%) vs 2/10 (20%), P = 0.02]. Overall, AMACR expression was associated with the grade of dysplasia, as well as with the size and configuration of adenomas, i.e. the consensus risk factors applied to colorectal adenoma patient surveillance.CONCLUSION: It may be worthy to further evaluate the possible use of AMACR as an additional risk factor for the assessment of colorectal adenoma patients.

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

2010-01-01

343

Mutations in COQ2 in familial and sporadic multiple-system atrophy.  

UK PubMed Central (United Kingdom)

BACKGROUND: Multiple-system atrophy is an intractable neurodegenerative disease characterized by autonomic failure in addition to various combinations of parkinsonism, cerebellar ataxia, and pyramidal dysfunction. Although multiple-system atrophy is widely considered to be a nongenetic disorder, we previously identified multiplex families with this disease, which indicates the involvement of genetic components. METHODS: In combination with linkage analysis, we performed whole-genome sequencing of a sample obtained from a member of a multiplex family in whom multiple-system atrophy had been diagnosed on autopsy. We also performed mutational analysis of samples from members of five other multiplex families and from a Japanese series (363 patients and two sets of controls, one of 520 persons and one of 2383 persons), a European series (223 patients and 315 controls), and a North American series (172 patients and 294 controls). On the basis of these analyses, we used a yeast complementation assay and measured enzyme activity of parahydroxybenzoate-polyprenyl transferase. This enzyme is encoded by the gene COQ2 and is essential for the biosynthesis of coenzyme Q10. Levels of coenzyme Q10 in lymphoblastoid cells and brain tissue were measured on high-performance liquid chromatography. RESULTS: We identified a homozygous mutation (M78V-V343A/M78V-V343A) and compound heterozygous mutations (R337X/V343A) in COQ2 in two multiplex families. Furthermore, we found that a common variant (V343A) and multiple rare variants in COQ2, all of which are functionally impaired, are associated with sporadic multiple-system atrophy. The V343A variant was exclusively observed in the Japanese population. CONCLUSIONS: Functionally impaired variants of COQ2 were associated with an increased risk of multiple-system atrophy in multiplex families and patients with sporadic disease, providing evidence of a role of impaired COQ2 activities in the pathogenesis of this disease. (Funded by the Japan Society for the Promotion of Science and others.).

2013-07-01

344

The initiation and progression of neoplasia in inherited and sporadic colorectal cancer.  

UK PubMed Central (United Kingdom)

This dissertation describes investigations into aspects of neoplastic initiation and progression in the gut, in the context of inherited and sporadic gastrointestinal cancer. In familial adenomatous polyposis, there is marked locoregional variation in polyp density. This work investigated the relationship between gut location and somatic inactivation of APC. It demonstrated that the frequency of APC loss of heterozygosity (LOH) varied along the colon, suggesting a colonic gradient in "just right" signalling. It investigated adenomas of the ileoanal pouch, where small bowel functions as rectum. A longitudinal study revealed the largely indolent natural history of these polyps, while mutational analysis demonstrated that they differed from polyps arising in colon, by usually retaining 2-3 remaining 20-amino-acid repeats. A comparison of pouch and rectal polyps showed differences in their histogenesis. Neoplastic initiation was investigated arising in the context of a new phenotype of young-onset colorectal cancer, with multiple adenomas and neurological deficit. A novel homozygous mutation involving PMS2 and FSCJV was found. Although neoplastic lesions showed nuclear beta-catenin expression, no mutated wnt pathway genes were identified. No evidence was found that PMS2 or FSCN mutation was causative in other patients with related multiple adenoma or neurological phenotypes. Key stepwise events in the adenoma-carcinoma sequence were investigated in sporadically occurring adenomas with contiguous carcinoma. Laser microdissection allowed crypt-by-crypt analysis of APC, TP53, KRAS2, and LOH at 17p and 18q, in order to establish the presence of cryptal heterogeneity and the inferred order of genetic alterations. Using similar contiguous paired lesions, a further study investigated neoplastic aneuploidy using image cytometry, genome-wide LOH analysis and individual SNP analysis for LOH 5q, 17p, and 18q. Aneuploidy did not cluster as tetraploidy. The degree of aneuploidy correlated well with the degree of LOH ascertained by genome-wide analysis, with LOH at 17p and 18q (but not 5q), and with nuclear beta-catenin accumulation.

Will OCC

345

Glycemic control in familial vs. sporadic type 1 diabetes patients over 5 years.  

UK PubMed Central (United Kingdom)

Abstract Background: Studies have shown that familial type 1 diabetes patients (FTID) have less severe metabolic derangement at presentation compared to sporadic patients (ST1D), but data on long-term metabolic control are lacking. Objective/Hypothesis: (1) FT1D will have less severe presentation and better HbA1c over 5 years compared to ST1D; (2) HbA1c in the offspring will correlate with parent HbA1c in parent-offspring group; and (3) HbA1c of the second affected sibling (SP2) will correlate with the first affected sibling (SP1) in sib-pairs. Methods: Cohort of 33 parent-offspring and 19 sib-pairs; controls included 33 sporadic subjects matched by age, sex, ethnicity, puberty, and insulin regimen. Paired t-test and Pearson's correlation were used for statistical analysis. Results: At diagnosis, mean age in FT1D vs. matched ST1D (7.7±4.9 vs. 7.6±4.5 years), mean HbA1c (9.6% vs. 10.7%), HCO3 (21 vs. 18 meq/L), glucose (428 vs. 463 mg/dL) and pH (7.35 vs. 7.36; p=ns) were not different. At 5 years, HbA1c (8.9% vs. 8.8%; p=0.81), clinic visits (12 vs. 12.5, p=0.68) and emergency room visits (0.48 vs. 0.24, p=0.10) were not different. In affected siblings, only HCO3 was different (SP1:18 vs. SP2: 24 meq/L; p<0.01). HbA1c for SP2 correlated positively with SP1 (r=0.67, p<0.01). Offspring HbA1c correlated positively with affected parents (9.3% vs. 8.6%, r=0.57, p=0.18) but was not significant. Conclusion: Metabolic control at diagnosis and at 5 years was similar in FT1D and ST1D. In sib-pairs, the second affected sibling had milder clinical presentation compared to the first affected sibling.

Reddy S; Reinert SE; Gopalakrishnan G; Plante W; Boney CM; Quintos JB

2013-08-01

346

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

Directory of Open Access Journals (Sweden)

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

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

2005-01-01

347

Deactivating germline mutations in LEMD3 cause osteopoikilosis and Buschke-Ollendorff syndrome, but not sporadic melorheostosis.  

UK PubMed Central (United Kingdom)

UNLABELLED: Autosomal dominant OPK and BOS feature widespread foci of osteosclerotic trabeculae without or with skin lesions, respectively. Occasionally, a larger area of dense bone in OPK or BOS resembles MEL, a sporadic sclerosing disorder primarily involving cortical bone. Others, finding deactivating germline LEMD3 mutations in OPK or BOS, concluded such defects explain all three conditions. We found germline LEMD3 mutations in OPK and BOS but not in sporadic MEL. INTRODUCTION: In 2004, others discovered that heterozygous, loss-of-function, germline mutations in the LEMD3 gene (LEMD3 or MAN1) cause both osteopoikilosis (OPK) and Buschke-Ollendorff syndrome (BOS). OPK is an autosomal dominant, usually benign, skeletal dysplasia featuring multiple, small, especially metaphyseal, oval or round, dense trabecular foci distributed symmetrically throughout the skeleton. BOS combines OPK with connective tissue nevi comprised of collagen and elastin. In some OPK and BOS families, an individual may have relatively large, asymmetric areas of dense cortical bone interpreted as melorheostosis (MEL). MEL, however, classically refers to a sporadic, troublesome skeletal dysostosis featuring large, asymmetric, "flowing hyperostosis" of long bone cortices often with overlying, constricting soft tissue abnormalities. However, a heterozygous germline mutation in LEMD3 was offered to explain MEL. MATERIALS AND METHODS: We studied 11 unrelated individuals with sclerosing bone disorders where LEMD3 mutation was a potential etiology: familial OPK (1), familial BOS (2), previously reported familial OPK with MEL (1), sporadic MEL (3), sporadic MEL with mixed-sclerosing-bone dystrophy (1), and patients with other unusual sclerosing bone disorders (3). All coding exons and adjacent mRNA splice sites for LEMD3 were amplified by PCR and sequenced using genomic DNA from leukocytes. We did not study lesional tissue from bone or skin. RESULTS: In the OPK family, a heterozygous nonsense mutation (c.1433T>A, p.L478X) was discovered in exon 1. In the two BOS families, a heterozygous nonsense mutation (exon 1, c.1323C>A, p.Y441X) and a heterozygous frame-shift mutation (exon 1, c.332_333insTC) were identified. In the individual with MEL and familial OPK, a heterozygous nonsense mutation (c.1963C>T, p.R655X) was detected in exon 7. However, no LEMD3 mutation was found for any other patient, including all four with sporadic MEL. CONCLUSIONS: We confirm that OPK and BOS individuals, including those with MEL-like lesions, have heterozygous, deactivating, germline LEMD3 mutations. However, MEL remains of unknown etiology.

Mumm S; Wenkert D; Zhang X; McAlister WH; Mier RJ; Whyte MP

2007-02-01

348

A Complex Association of ABCA7 Genotypes With Sporadic Alzheimer Disease in Chinese Han Population.  

UK PubMed Central (United Kingdom)

PURPOSE:: Recently, a large genome-wide association study has revealed that polymorphism of alleles and genotypes in rs3,764,650 within ABCA7 gene is associated with Alzheimer disease in whites. We conducted a case-control study to investigate whether these susceptible genetic variants are risk factors for sporadic Alzheimer disease (SAD) in Chinese Han population. DESIGN AND METHODS:: A total of 633 participants consisting of 350 SAD and 283 nondemented elderly controls matched for sex and age were recruited and genetic variants in ABCA7 (rs3,764,650) were genotyped using DNA sequencing. RESULTS:: On the basis of allele and genotype frequencies in both groups, we found a significant association (P=0.004) between ABCA7 genotypes and SAD in Chinese Han population, and the results were influenced by age and ApoE?4 status. ApoE?4-carrier and aging are linked to enhancing ABCA7 risk-associated SAD. However, the prevalence of the minor allele G in rs3,764,650 within ABCA7 showed no significant difference between the 2 groups in this study. CONCLUSIONS:: ABCA7 (rs3,764,650) was associated with SAD in the Chinese population, with both ApoE?4-carrier and aging being factors enhancing its risk.

Liu LH; Xu J; Deng YL; Tang HD; Wang Y; Ren RJ; Xu W; Ma JF; Wang G; Chen SD

2013-10-01

349

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

Science.gov (United States)

Muscle repair relies on coordinated activation and differentiation of satellite cells, a process that is unable to counterbalance progressive degeneration in sporadic inclusion body myositis (s-IBM). To explore features of myo regeneration, the expression of myogenic regulatory factors Pax7, MyoD and Myogenin and markers of regenerating fibers was analyzed by immunohistochemistry in s-IBM muscle compared with polymyositis, dermatomyositis, muscular dystrophy and age-matched controls. In addition, the capillary density and number of interstitial CD34+ hematopoietic progenitor cells was determined by double-immunoflourescence staining. Satellite cells and regenerating fibers were significantly increased in s-IBM similar to other inflammatory myopathies and correlated with the intensity of inflammation (R > 0.428). Expression of MyoD, visualizing activated satellite cells and proliferating myoblasts, was lower in s-IBM compared to polymyosits. In contrast, Myogenin a marker of myogenic cell differentiation was strongly up-regulated in s-IBM muscle. The microvascular architecture in s-IBM was distorted, although the capillary density was normal. Notably, CD34+ hematopoietic cells were significantly increased in the interstitial compartment. Our findings indicate profound myo-endothelial remodeling of s-IBM muscle concomitant to inflammation. An altered expression of myogenic regulatory factors involved in satellite cell activation and differentiation, however, might reflect perturbations of muscle repair in s-IBM.

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

2013-01-01

350

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

UK PubMed Central (United Kingdom)

Muscle repair relies on coordinated activation and differentiation of satellite cells, a process that is unable to counterbalance progressive degeneration in sporadic inclusion body myositis (s-IBM). To explore features of myo regeneration, the expression of myogenic regulatory factors Pax7, MyoD and Myogenin and markers of regenerating fibers was analyzed by immunohistochemistry in s-IBM muscle compared with polymyositis, dermatomyositis, muscular dystrophy and age-matched controls. In addition, the capillary density and number of interstitial CD34(+) hematopoietic progenitor cells was determined by double-immunoflourescence staining. Satellite cells and regenerating fibers were significantly increased in s-IBM similar to other inflammatory myopathies and correlated with the intensity of inflammation (R>0.428). Expression of MyoD, visualizing activated satellite cells and proliferating myoblasts, was lower in s-IBM compared to polymyosits. In contrast, Myogenin a marker of myogenic cell differentiation was strongly up-regulated in s-IBM muscle. The microvascular architecture in s-IBM was distorted, although the capillary density was normal. Notably, CD34(+) hematopoietic cells were significantly increased in the interstitial compartment. Our findings indicate profound myo-endothelial remodeling of s-IBM muscle concomitant to inflammation. An altered expression of myogenic regulatory factors involved in satellite cell activation and differentiation, however, might reflect perturbations of muscle repair in s-IBM.

Wanschitz JV; Dubourg O; Lacene E; Fischer MB; Höftberger R; Budka H; Romero NB; Eymard B; Herson S; Butler-Browne GS; Voit T; Benveniste O

2013-01-01

351

Overexpression of autophagic proteins in the skeletal muscle of sporadic inclusion body myositis.  

UK PubMed Central (United Kingdom)

AIMS: Sporadic inclusion body myositis (s-IBM) is characterized by rimmed vacuole formation and misfolded protein accumulation. Intracellular protein aggregates are cleared by autophagy. When autophagy is blocked aggregates accumulate, resulting in abnormal rimmed vacuole formation. This study investigated the autophagy-lysosome pathway contribution to rimmed vacuole accumulation. METHODS: Autophagy was studied in muscle biopsy specimens obtained from 11 s-IBM patients, 1 suspected hereditary IBM patient, 9 patients with other inflammatory myopathies and 9 non myopathic patients as controls. The analysis employed morphometric methods applied to immunohistochemistry using the endosome marker Clathrin, essential proteins of the autophagic cascade such as AuTophaGy-related protein ATG5, splicing variants of microtubule-associated protein light chain 3a (LC3a) and LC3b, compared with Beclin 1, the major autophagy regulator of both the initiation phase and late endosome/lysosome fusion of the autophagy-lysosome pathway. RESULTS: In muscle biopsies of s-IBM patients, an increased expression of Clathrin, ATG5, LC3a, LC3b and Beclin 1 was shown. Moreover, the inflammatory components of the disease, essentially lymphocytes, were preferentially distributed around the Beclin 1(+) myofibres. These affected myofibres also showed a moderate sarcoplasmic accumulation of SMI-31(+) phospho-tau paired helical filaments. CONCLUSION: The overexpression of autophagy markers linked to the decreased clearance of misfolded proteins, including SMI-31, and rimmed vacuoles accumulation may exhaust cellular resources and lead to cell death.

Girolamo F; Lia A; Amati A; Strippoli M; Coppola C; Virgintino D; Roncali L; Toscano A; Serlenga L; Trojano M

2013-03-01

352

Contrasting echogenicity in FDP-FCU: A diagnostic ultrasound pattern in sporadic inclusion body myositis.  

UK PubMed Central (United Kingdom)

Introduction: We aimed to clarify whether muscle ultrasound (US) of the forearm can be used to differentiate between patients with sporadic inclusion body myositis (s-IBM) and those with s-IBM-mimicking diseases. Methods: We compared the echo intensity (EI) of the flexor digitorum profundus (FDP) muscle and the flexor carpi ulnaris (FCU) muscles in patients with s-IBM (n = 6), polymyositis/dermatomyositis (PM/DM) (n = 6), and amyotrophic lateral sclerosis (ALS) (n = 6). Results: We identified EI abnormalities in 100% of patients with s-IBM, 33% of those with PM/DM, and 33% of those with ALS. An "FDP-FCU echogenicity contrast", a US pattern involving a higher EI in the FDP than in the FCU, was observed in all patients with s-IBM, but in none of those with PM/DM or ALS. Conclusions: "FDP-FCU echogenicity contrast" in muscle US is a sensitive diagnostic indicator of s-IBM. © 2013 Wiley Periodicals, Inc.

Noto YI; Shiga K; Tsuji Y; Kondo M; Tokuda T; Mizuno T; Nakagawa M

2013-08-01

353

Invasive fibroblasts: Fundamental difference between sporadic inclusion body myositis and polymyositis.  

UK PubMed Central (United Kingdom)

Introduction: Sporadic inclusion body myositis (sIBM) is a progressive disease that leads to extensive muscle weakness. The aim of this study was to determine whether the number and distribution of fibroblasts differ in sIBM when compared with polymyositis. Methods: Immunofluorescence double labelling was performed on 35 biopsies with antibodies directed against perlecan and CD90, procollagen I, CD34, and CD105. In addition, non-serial ultrathin sections were studied from 3 biopsies of each condition. Results: Fibroblasts expressing CD90 and CD34 accumulated in the endomysial compartment in polymyositis and sIBM. In addition, cells expressing CD90 were found beneath the basal lamina in both conditions. At the ultrastructural level in polymyositis, fibroblasts invaded the myofiber, with focal destruction of the basement membrane. In sIBM, by contrast, invasive fibroblasts were ensheathed by the intact myofiber basement membrane. Discussion: The impact of intruding fibroblasts on satellite cells remains to be established. © 2013 Wiley Periodicals, Inc.

Doppler K; Pantazis G; Lindner A; Mack A; Bornemann A

2013-05-01

354

Investigation of splicing changes and post-translational processing of LMNA in sporadic inclusion body myositis.  

Science.gov (United States)

Some features of sporadic inclusion body myositis (s-IBM) suggest that there is acceleration of the normal ageing process in muscle tissue. LMNA encodes the nuclear lamina proteins lamin A/C through alternative splicing, and aberrant splicing of exon 11 leads to the premature ageing disease, Hutchinson-Gilford progeria syndrome. Progerin, the pathogenic isoform expressed in HGPS tissues, has also been detected at low levels in tissues of normal individuals with aging. We therefore investigated the alternative splicing of LMNA gene transcripts, and the post-translational processing of prelamin A, in s-IBM and control muscle samples. Age-related low level expression of the progerin transcript was detected in both s-IBM and control muscles, but was not increased in s-IBM and there was no increase in progerin protein or demonstrable accumulation of intermediate prelamin isoforms in the s-IBM muscles. However, an age-related shift in the balance of splicing towards lamin A-related transcripts, which was present in normal muscles, was not found in s-IBM. Our findings indicate that while there are changes in the patterns of LMNA splicing in s-IBM muscle which are probably secondary to the underlying pathological process, it is unlikely that aberrant splicing of exon 11 or defective post-translational processing of prelamin A are involved in the pathogenesis of the disease. PMID:24040437

Luo, Yue-Bei; Mitrpant, Chalermchai; Johnsen, Russell; Fabian, Vicki; Needham, Merrilee; Fletcher, Sue; Wilton, Steve D; Mastaglia, Frank L

2013-08-15

355

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

Science.gov (United States)

Muscle repair relies on coordinated activation and differentiation of satellite cells, a process that is unable to counterbalance progressive degeneration in sporadic inclusion body myositis (s-IBM). To explore features of myo regeneration, the expression of myogenic regulatory factors Pax7, MyoD and Myogenin and markers of regenerating fibers was analyzed by immunohistochemistry in s-IBM muscle compared with polymyositis, dermatomyositis, muscular dystrophy and age-matched controls. In addition, the capillary density and number of interstitial CD34(+) hematopoietic progenitor cells was determined by double-immunoflourescence staining. Satellite cells and regenerating fibers were significantly increased in s-IBM similar to other inflammatory myopathies and correlated with the intensity of inflammation (R>0.428). Expression of MyoD, visualizing activated satellite cells and proliferating myoblasts, was lower in s-IBM compared to polymyosits. In contrast, Myogenin a marker of myogenic cell differentiation was strongly up-regulated in s-IBM muscle. The microvascular architecture in s-IBM was distorted, although the capillary density was normal. Notably, CD34(+) hematopoietic cells were significantly increased in the interstitial compartment. Our findings indicate profound myo-endothelial remodeling of s-IBM muscle concomitant to inflammation. An altered expression of myogenic regulatory factors involved in satellite cell activation and differentiation, however, might reflect perturbations of muscle repair in s-IBM. PMID:23058947

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

2012-10-09

356

Investigation of splicing changes and post-translational processing of LMNA in sporadic inclusion body myositis.  

UK PubMed Central (United Kingdom)

Some features of sporadic inclusion body myositis (s-IBM) suggest that there is acceleration of the normal ageing process in muscle tissue. LMNA encodes the nuclear lamina proteins lamin A/C through alternative splicing, and aberrant splicing of exon 11 leads to the premature ageing disease, Hutchinson-Gilford progeria syndrome. Progerin, the pathogenic isoform expressed in HGPS tissues, has also been detected at low levels in tissues of normal individuals with aging. We therefore investigated the alternative splicing of LMNA gene transcripts, and the post-translational processing of prelamin A, in s-IBM and control muscle samples. Age-related low level expression of the progerin transcript was detected in both s-IBM and control muscles, but was not increased in s-IBM and there was no increase in progerin protein or demonstrable accumulation of intermediate prelamin isoforms in the s-IBM muscles. However, an age-related shift in the balance of splicing towards lamin A-related transcripts, which was present in normal muscles, was not found in s-IBM. Our findings indicate that while there are changes in the patterns of LMNA splicing in s-IBM muscle which are probably secondary to the underlying pathological process, it is unlikely that aberrant splicing of exon 11 or defective post-translational processing of prelamin A are involved in the pathogenesis of the disease.

Luo YB; Mitrpant C; Johnsen R; Fabian V; Needham M; Fletcher S; Wilton SD; Mastaglia FL

2013-01-01

357

Clinical, pathological, and genetic mutation analysis of sporadic inclusion body myositis in Japanese people.  

UK PubMed Central (United Kingdom)

Previous studies have identified several genetic loci associated with the development of familial inclusion body myopathy. However, there have been few genetic analyses of sporadic inclusion body myositis (sIBM). In order to explore the molecular basis of sIBM and to investigate genotype-phenotype correlations, we performed a clinicopathological analysis of 21 sIBM patients and screened for mutations in the Desmin, GNE, MYHC2A, VCP, and ZASP genes. All coding exons of the five genes were sequenced directly. Definite IBM was confirmed in 14 cases, probable IBM in three cases, and possible IBM in four cases. No cases showed missense mutations in the Desmin, GNE, or VCP genes. Three patients carried the missense mutation c.2542T>C (p.V805A) in the MYHC2A gene; immunohistochemical staining for MYHC isoforms in these three cases showed atrophy or loss of muscle fibers expressing MYHC IIa or IIx. One patient harbored the missense mutation c.1719G>A (p.V566M) in the ZASP gene; immunohistochemical studies of Z-band-associated proteins revealed Z-band abnormalities. Both of the novel heterogeneous mutations were located in highly evolutionarily conserved domains of their respective genes. Cumulatively, these findings have expanded our understanding of the molecular background of sIBM. However, we advocate further clinicopathology and investigation of additional candidate genes in a larger cohort.

Cai H; Yabe I; Sato K; Kano T; Nakamura M; Hozen H; Sasaki H

2012-09-01

358

Overexpression of autophagic proteins in the skeletal muscle of sporadic inclusion body myositis.  

Science.gov (United States)

AIMS: Sporadic inclusion body myositis (s-IBM) is characterized by rimmed vacuole formation and misfolded protein accumulation. Intracellular protein aggregates are cleared by autophagy. When autophagy is blocked aggregates accumulate, resulting in abnormal rimmed vacuole formation. This study investigated the autophagy-lysosome pathway contribution to rimmed vacuole accumulation. METHODS: Autophagy was studied in muscle biopsy specimens obtained from 11 s-IBM patients, 1 suspected hereditary IBM patient, 9 patients with other inflammatory myopathies and 9 non myopathic patients as controls. The analysis employed morphometric methods applied to immunohistochemistry using the endosome marker Clathrin, essential proteins of the autophagic cascade such as AuTophaGy-related protein ATG5, splicing variants of microtubule-associated protein light chain 3a (LC3a) and LC3b, compared with Beclin 1, the major autophagy regulator of both the initiation phase and late endosome/lysosome fusion of the autophagy-lysosome pathway. RESULTS: In muscle biopsies of s-IBM patients, an increased expression of Clathrin, ATG5, LC3a, LC3b and Beclin 1 was shown. Moreover, the inflammatory components of the disease, essentially lymphocytes, were preferentially distributed around the Beclin 1(+) myofibres. These affected myofibres also showed a moderate sarcoplasmic accumulation of SMI-31(+) phospho-tau paired helical filaments. CONCLUSION: The overexpression of autophagy markers linked to the decreased clearance of misfolded proteins, including SMI-31, and rimmed vacuoles accumulation may exhaust cellular resources and lead to cell death. PMID:23452291

Girolamo, Francesco; Lia, Anna; Amati, Angela; Strippoli, Maurizio; Coppola, Cristiana; Virgintino, Daniela; Roncali, Luisa; Toscano, Antonio; Serlenga, Luigi; Trojano, Maria

2013-03-01

359

Molecular epidemiology of Vibrio cholerae O1 isolated from sporadic cholera cases in Okinawa, Japan.  

Science.gov (United States)

In July 1994, 6 cholera cases due to Vibrio cholerae O1 El Tor Ogawa sporadically appeared in Okinawa. All 6 patients had no history of traveling abroad. In the period of this cholera outbreak, a strain of V. cholerae O1 El Tor Ogawa was detected from an imported fish at the Naha port quarantine station. The isolates were characterized to clarify whether or not, they belonged to a common clone. Phenotypes were identical except that one strain revealed cured Celebes and the others were original Celebes in kappa phage typing. The restriction fragment patterns of DNA of the isolates hybridized with an enzyme-labeled oligonucleotide probe for cholera toxin gene (ctx) were identical. Randomly amplified polymorphic DNA of the isolates were identical when a primer was used, but 2 patterns were seen when another primer was used. Pulsed-field gel electrophoresis of the chromosomal DNA digested with NotI restriction enzyme showed 3 patterns. The DNA fragment pattern of the strain isolated from the imported fish was different from the clinical isolates. These results suggested that there was no epidemiological relation among the strains of V. cholerae O1 isolated during this period. PMID:9444327

Iwanaga, M; Honma, Y; Enami, M

1997-01-01

360

Molecular epidemiology of Vibrio cholerae O1 isolated from sporadic cholera cases in Okinawa, Japan.  

UK PubMed Central (United Kingdom)

In July 1994, 6 cholera cases due to Vibrio cholerae O1 El Tor Ogawa sporadically appeared in Okinawa. All 6 patients had no history of traveling abroad. In the period of this cholera outbreak, a strain of V. cholerae O1 El Tor Ogawa was detected from an imported fish at the Naha port quarantine station. The isolates were characterized to clarify whether or not, they belonged to a common clone. Phenotypes were identical except that one strain revealed cured Celebes and the others were original Celebes in kappa phage typing. The restriction fragment patterns of DNA of the isolates hybridized with an enzyme-labeled oligonucleotide probe for cholera toxin gene (ctx) were identical. Randomly amplified polymorphic DNA of the isolates were identical when a primer was used, but 2 patterns were seen when another primer was used. Pulsed-field gel electrophoresis of the chromosomal DNA digested with NotI restriction enzyme showed 3 patterns. The DNA fragment pattern of the strain isolated from the imported fish was different from the clinical isolates. These results suggested that there was no epidemiological relation among the strains of V. cholerae O1 isolated during this period.

Iwanaga M; Honma Y; Enami M

1997-01-01

 
 
 
 
361

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

DEFF Research Database (Denmark)

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

MØlbak, Kåre; Neimann, Jacob

2002-01-01

362

PICALM and CR1 variants are not associated with sporadic Alzheimer's disease in Chinese patients.  

Science.gov (United States)

Alzheimer's disease (AD) is the most common form of senile dementia, and the overall prevalence increases exponentially with age. It is well known that genetic variants may play an important role in the pathogenesis of this disorder. Recently, two independent large-scale genome-wide association studies (GWAS) identified 3 novel single nucleotide polymorphisms (SNPs) (rs11136000 within CLU, rs3851179 within PICALM and rs6656401 within CR1) that are associated with late-onset AD (LOAD), and these results have been replicated by other studies performed in the Caucasian population. Recently, an independent study failed to verify the association for the SNP within CLU in a Han Chinese population, indicating that there may be genetic heterogeneity in this association. In the present study, we studied the SNPs within PICALM and CR1 in 474 sporadic AD patients (SAD) and 591 unrelated age- and sex-matched healthy controls of Han Chinese descent. Our data revealed that the frequencies of both of these SNPs were not significantly difference between the SAD and control groups. Thus, the association between SNPs within PICALM, CR1, and SAD should be studied further in different ethnic groups. PMID:21358043

Li, Hong-Lei; Shi, Sheng-Sheng; Guo, Qi-Hao; Ni, Wang; Dong, Yi; Liu, Ying; Sun, Yi-Min; Bei-Wang; Lu, Shen-Ji; Hong, Zhen; Wu, Zhi-Ying

2011-01-01

363

PICALM and CR1 variants are not associated with sporadic Alzheimer's disease in Chinese patients.  

UK PubMed Central (United Kingdom)

Alzheimer's disease (AD) is the most common form of senile dementia, and the overall prevalence increases exponentially with age. It is well known that genetic variants may play an important role in the pathogenesis of this disorder. Recently, two independent large-scale genome-wide association studies (GWAS) identified 3 novel single nucleotide polymorphisms (SNPs) (rs11136000 within CLU, rs3851179 within PICALM and rs6656401 within CR1) that are associated with late-onset AD (LOAD), and these results have been replicated by other studies performed in the Caucasian population. Recently, an independent study failed to verify the association for the SNP within CLU in a Han Chinese population, indicating that there may be genetic heterogeneity in this association. In the present study, we studied the SNPs within PICALM and CR1 in 474 sporadic AD patients (SAD) and 591 unrelated age- and sex-matched healthy controls of Han Chinese descent. Our data revealed that the frequencies of both of these SNPs were not significantly difference between the SAD and control groups. Thus, the association between SNPs within PICALM, CR1, and SAD should be studied further in different ethnic groups.

Li HL; Shi SS; Guo QH; Ni W; Dong Y; Liu Y; Sun YM; Bei-Wang; Lu SJ; Hong Z; Wu ZY

2011-01-01

364

Cyclooxygenase-1 and -2 in brains of patients who died with sporadic Creutzfeldt-Jakob disease.  

Science.gov (United States)

Cyclooxygenases (COXs) mediate inflammation, immunomodulation, blood flow, apoptosis, and fever in various diseases of the brain. Whereas COX-2 is cytokine inducible, COX-1 is expressed by macrophages/microglial cells that accumulate in pathological foci. We analyzed the localization of COX-1 and COX-2 in postmortem cortex slices of eight patients who died with sporadic Creutzfeldt-Jakob disease (CJD) and four neuropathologically unaltered controls by immunohistochemical double-labeling, reverse transcriptase polymerase chain reaction (RT-PCR), and Western blotting experiments. In healthy brains, COX-1 was expressed by single macrophages/microglial cells and COX-2 by disseminated neurons. In patients with CJD, significantly (p = 0.0195) more COX-1-expressing macrophages/microglial cells were detected adjacent to neurons. COX-2 expression was predominantly observed in neurons, and their number was significantly higher (p < 0.0001) compared to controls. RT-PCR and Western blotting revealed more COX-1 and COX-2 mRNA and protein in one CJD patient than in one control patient. These data show that accumulation of COX-1-expressing macrophages/microglial cells and COX-2-expressing neurons might represent important regulatory mechanisms in the complex process of neuronal degeneration in CJD patients. PMID:12663931

Deininger, Martin H; Bekure-Nemariam, Kubrom; Trautmann, Katrin; Morgalla, Matthias; Meyermann, Richard; Schluesener, Hermann J

2003-02-01

365

Brain sterol dysregulation in sporadic AD and MCI: relationship to heme oxygenase-1.  

Science.gov (United States)

The objective of this study was to ascertain the impact of aging and Alzheimer's disease (AD) on brain cholesterol (CH), CH precursors, and oxysterol homeostasis. Altered CH metabolism and up-regulation of heme oxygenase-1 (HO-1) are characteristic of AD-affected neural tissues. We recently determined that HO-1 over-expression suppresses total CH levels by augmenting liver X receptor-mediated CH efflux and enhances oxysterol formation in cultured astroglia. Lipids and proteins were extracted from postmortem human frontal cortex derived from subjects with sporadic AD, mild cognitive impairment (MCI), and no cognitive impairment (n = 17 per group) enrolled in the Religious Orders Study, an ongoing clinical-pathologic study of aging and AD. ELISA was used to quantify human HO-1 protein expression from brain tissue and gas chromatography-mass spectrometry to quantify total CH, CH precursors, and relevant oxysterols. The relationships of sterol/oxysterol levels to HO-1 protein expression and clinical/demographic variables were determined by multivariable regression and non-parametric statistical analyses. Decreased CH, increased oxysterol and increased CH precursors concentrations in the cortex correlated significantly with HO-1 levels in MCI and AD, but not no cognitive impairment. Specific oxysterols correlated with disease state, increasing neuropathological burden, neuropsychological impairment, and age. A model featuring compensated and de-compensated states of altered sterol homeostasis in MCI and AD is presented based on the current data set and our earlier in vitro work. PMID:19522732

Hascalovici, Jacob R; Vaya, Jacob; Khatib, Soliman; Holcroft, Christina A; Zukor, Hillel; Song, Wei; Arvanitakis, Zoe; Bennett, David A; Schipper, Hyman M

2009-06-09

366

Brain sterol dys-regulation in sporadic AD and MCI: Relationship to heme oxygenase-1  

Science.gov (United States)

The objective of this study was to ascertain the impact of aging and Alzheimer disease (AD) on brain cholesterol (CH), CH precursors and oxysterol homeostasis. Altered CH metabolism and up-regulation of heme oxygenase-1 (HO-1) are characteristic of AD-affected neural tissues. We recently determined that HO-1 over-expression suppresses total CH levels by augmenting liver X receptor-mediated CH efflux and enhances oxysterol formation in cultured astroglia. Lipids and proteins were extracted from post-mortem human frontal cortex derived from subjects with sporadic AD, mild cognitive impairment (MCI) and no cognitive impairment (NCI; n=17 per group) enrolled in the Religious Orders Study, an ongoing clinical-pathologic study of aging and AD. ELISA was used to quantify human HO-1 protein expression from brain tissue and GC-MS to quantify total CH, CH precursors and relevant oxysterols. The relationships of sterol/oxysterol levels to HO-1 protein expression and clinical/demographic variables were determined by multivariable regression and non-parametric statistical analyses. Decreased CH, increased oxysterol and increased CH precursors concentrations in the cortex correlated significantly with HO-1 levels in MCI and AD, but not NCI. Specific oxysterols correlated with disease state, increasing neuropathological burden, neuropsychological impairment and age. A model featuring compensated and de-compensated states of altered sterol homeostasis in MCI and AD are presented based on the current data set and our earlier in vitro work.

Hascalovici, Jacob R.; Vaya, Jacob; Khatib, Soliman; Holcroft, Christina A.; Zukor, Hillel; Song, Wei; Arvanitakis, Zoe; Bennett, David A.; Schipper, Hyman M.

2009-01-01

367

Brain sterol dysregulation in sporadic AD and MCI: relationship to heme oxygenase-1.  

UK PubMed Central (United Kingdom)

The objective of this study was to ascertain the impact of aging and Alzheimer's disease (AD) on brain cholesterol (CH), CH precursors, and oxysterol homeostasis. Altered CH metabolism and up-regulation of heme oxygenase-1 (HO-1) are characteristic of AD-affected neural tissues. We recently determined that HO-1 over-expression suppresses total CH levels by augmenting liver X receptor-mediated CH efflux and enhances oxysterol formation in cultured astroglia. Lipids and proteins were extracted from postmortem human frontal cortex derived from subjects with sporadic AD, mild cognitive impairment (MCI), and no cognitive impairment (n = 17 per group) enrolled in the Religious Orders Study, an ongoing clinical-pathologic study of aging and AD. ELISA was used to quantify human HO-1 protein expression from brain tissue and gas chromatography-mass spectrometry to quantify total CH, CH precursors, and relevant oxysterols. The relationships of sterol/oxysterol levels to HO-1 protein expression and clinical/demographic variables were determined by multivariable regression and non-parametric statistical analyses. Decreased CH, increased oxysterol and increased CH precursors concentrations in the cortex correlated significantly with HO-1 levels in MCI and AD, but not no cognitive impairment. Specific oxysterols correlated with disease state, increasing neuropathological burden, neuropsychological impairment, and age. A model featuring compensated and de-compensated states of altered sterol homeostasis in MCI and AD is presented based on the current data set and our earlier in vitro work.

Hascalovici JR; Vaya J; Khatib S; Holcroft CA; Zukor H; Song W; Arvanitakis Z; Bennett DA; Schipper HM

2009-08-01

368

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

DEFF Research Database (Denmark)

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

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

2009-01-01

369

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

Science.gov (United States)

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