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Bussiere F.I.,Institute Pasteur Paris | Michel V.,Institute Pasteur Paris | Memet S.,Institute Pasteur Paris | Memet S.,French National Center for Scientific Research | And 4 more authors.
Cellular Microbiology | Year: 2010

Summary: Helicobacter pylori infection is associated with the development of gastric adenocarcinoma. Upstream stimulatory factors USF1 and USF2 regulate the transcription of genes related to immune response, cell cycle and cell proliferation. A decrease in their expression is observed in human gastric epithelial cells infected with H. pylori, associated to a lower binding to their DNA E-box recognition site as shown by electrophoretic mobility shift assay. DNA methylation leads to gene silencing. The treatment of cells with 5'-azacytidine, an inhibitor of DNA methylation, restored the USF1 and USF2 gene expression in the presence of infection. Using promoter PCR methylation assay, a DNA hypermethylation was shown in the promoter region of USF1 and USF2 genes, in infected cells. The inhibition of USF1 and USF2 expression by H. pylori and the DNA hypermethylation in their gene promoter region was confirmed in gastric tissues isolated from 12 to 18 months infected mice. Our study demonstrated the involvement of USF1 and USF2 as molecular targets of H. pylori and the key role of DNA methylation in their regulation. These mechanisms occurred in the context of metaplastic lesions, suggesting that alteration of USF1 and USF2 levels could participate in the promotion of neoplastic process during H. pylori infection. © 2010 Blackwell Publishing Ltd.

Palomero T.,Columbia University | Couronne L.,Columbia University | Khiabanian H.,Columbia University | Kim M.-Y.,Columbia University | And 22 more authors.
Nature Genetics | Year: 2014

Peripheral T cell lymphomas (PTCLs) are a heterogeneous and poorly understood group of non-Hodgkin lymphomas. Here we combined whole-exome sequencing of 12 tumor-normal DNA pairs, RNA sequencing analysis and targeted deep sequencing to identify new genetic alterations in PTCL transformation. These analyses identified highly recurrent epigenetic factor mutations in TET2, DNMT3A and IDH2 as well as a new highly prevalent RHOA mutation encoding a p.Gly17Val alteration present in 22 of 35 (67%) angioimmunoblastic T cell lymphoma (AITL) samples and in 8 of 44 (18%) PTCL, not otherwise specified (PTCL-NOS) samples. Mechanistically, the RHOA Gly17Val protein interferes with RHOA signaling in biochemical and cellular assays, an effect potentially mediated by the sequestration of activated guanine-exchange factor (GEF) proteins. In addition, we describe new and recurrent, albeit less frequent, genetic defects including mutations in FYN, ATM, B2M and CD58 implicating SRC signaling, impaired DNA damage response and escape from immune surveillance mechanisms in the pathogenesis of PTCL. © 2014 Nature America, Inc.

Fernandez-Torre J.L.,University of Cantabria | Fernandez-Torre J.L.,Institute Formacion E Investigacion Marques Of Valdecilla Ifimav | Kaplan P.W.,Johns Hopkins University
Seizure | Year: 2014

Purpose The aim of this paper is to describe two additional cases of subacute encephalopathy with seizures in alcoholics (SESA syndrome), and to propose that this entity now should be considered as a subtype of nonconvulsive status epilepticus (NCSE). Methods We retrospectively analyzed the clinical characteristics, electroencephalography (EEG), neuroimaging data, and prognosis of these two further cases of SESA syndrome. In addition, we compare our findings with the cases previously described in the English literature in order to propose new diagnostic criteria. Results Two adults with history of chronic alcohol abuse were admitted because of confusion and seizures. A routine EEG showed frequent periodic lateralized epileptiform discharges (PLEDs) localized over the right temporal regions. In one case, we captured two complex partial seizures (CPSs) arising from the right hemisphere. Neuroimaging studies revealed subjacent chronic vascular pathology. Following transfer to the intensive care unit (ICU), both improved to antiepileptic treatment and were discharged with full recovery. Conclusion On the basis of our findings and a review of the literature, we suggest that SESA syndrome represents a subtype of partial or localization-related NCSE given its particular clinical, electroencephalographic, neuroimaging and prognostic characteristics. © 2014 British Epilepsy Association.

Fernandez-Torre J.L.,University of Cantabria | Fernandez-Torre J.L.,Institute Formacion E Investigacion Marques Of Valdecilla Ifimav | Rebollo M.,University of Cantabria | Gutierrez A.,University of Cantabria | And 3 more authors.
Clinical Neurophysiology | Year: 2012

Objective: Nonconvulsive status epilepticus (NCSE) represents an important percentage of status epilepticus in adults, but detailed studies of both NCSE proper and comatose NCSE are lacking. We retrospectively analyzed a prospectively collected series of 50 adult patients with a diagnosis of NCSE whose electroencephalograms (EEGs) have been interpreted for a period of 10. years by the same investigator. Methods: Two groups, NCSE proper and comatose NCSE were considered. All clinical, EEGs, neuroimaging data, antiepileptic treatment and outcome were analyzed. Results: Thirty-two patients (64%) had NCSE proper and 18 patients (36%) comatose NCSE. The mean age was 56. years (range 19-89. years). Fourteen (44%) were diagnosed with absence status epilepticus (ASE), one had simple partial status epilepticus (SPSE) and 17 (53%) had complex partial status epilepticus (CPSE). The mean episode duration (33.2. ±. 13.9 versus 60.6. ±. 34.0), mean number of antiepileptic drugs (AEDs) (1.46. ±. 0.5 versus 2.77. ±. 1.39) and neuroimaging anomalies (50% versus 16%) was significantly greater in the partial/focal NCSE proper subgroup than in the ASE subgroup. The mean age (56.0. ±. 19.9 versus 69.4. ±. 12.1), number of elderly individuals (46% versus 77%), mean duration of the episode (49.1. ±. 30.4 versus 153.3. ±. 142.6), mortality rate (6% versus 61%) and admission at ICU (18% versus 83%) was significantly higher in the comatose NCSE group than in the NCSE proper group (p<.05). Conversely, a previous history of chronic epilepsy was significantly more frequent (62% versus 5.6%) in the NCSE proper group. The mean duration of comatose NCSE was significantly greater in the surviving subgroup (102.5. ±. 29.1 versus 233.1. ±. 65.3; p<. .05). Conclusions: Our study demonstrates that there are sufficient differences regarding age of onset, history of previous epilepsy, episode duration, mortality rate and clinical presentation between NCSE proper and comatose NCSE to recommend adoption in clinical practice. These results should be taken into account when developing future classifications and therapeutic trials on NCSE. Significance: A distinction between NCSE proper (ambulatory forms of NCSE) and comatose NCSE is useful in the clinical practice and, therefore, it should taken in account in the design of future investigations on this heterogeneous epileptic condition. © 2011 International Federation of Clinical Neurophysiology.

Fernandez-Torre J.L.,University of Cantabria | Fernandez-Torre J.L.,Institute Formacion E Investigacion Marques Of Valdecilla Ifimav | Hernandez-Hernandez M.A.,University of Cantabria | Hernandez-Hernandez M.A.,Institute Formacion E Investigacion Marques Of Valdecilla Ifimav
Seizure | Year: 2012

We report the case of a patient with an extensive right cerebral hematoma complicated by focal nonconvulsive status epilepticus (NCSE) in whom the use of the new bilateral BIS-Vista™ monitor was helpful in managing profound sedation and antiepileptic treatment in the absence of continuous EEG monitoring (CEEG). The analysis of color density spectral array (CDSA) showed stereotyped changes indicative of recurrent focal nonconvulsive seizures (NCSz) and NCSE. We noted a close correlation between NCSz and BIS value changes. EEGs during working hours always confirmed the persistence of focal NCSE. After several days of sedation, CDSA disclosed a gradual resolution of NCSE that was also confirmed by electroencephalography. The patient died of cardiorespiratory complications a few days later. © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

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