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121.
des Portes V Boddaert N Sacco S Briault S Maincent K Bahi N Gomot M Ronce N Bursztyn J Adamsbaum C Zilbovicius M Chelly J Moraine C 《American journal of medical genetics. Part A》2004,(4):364-371
Oligophrenin-1 (OPHN-1) gene disruption is known as responsible for so called "non-specific" X-linked mental retardation (MR) Billuart et al. [1998: Nature 392:923-926]. In order to search for a possible specific clinical and radiological profile for mutation in the OPHN-1 gene, clinical and 3D brain MRI studies were performed in the two families with a known mutation in OPHN-1 reported so far: a 19-year-old female with an X;12 balanced translocation encompassing OPHN-1, and four affected males of family MRX60 sharing a frameshift mutation in OPHN-1. Clinical data shared by affected individuals were neonatal hypotonia with motor delay but no obvious ataxia, marked strabismus, early onset complex partial seizures, and moderate to severe MR. Brain MRIs performed in three individuals exhibited a specific vermian dysgenesis including an incomplete sulcation of anterior and posterior vermis with the most prominent defect in lobules VI and VII. In addition, a non-specific cerebral cortico-subcortical atrophy was also observed. These clinical and radiological features suggest a distinct clinico-radiological syndrome. These preliminary data need to be confirmed in other families and will be helpful for further targeted mutation screening of the OPHN-1 gene in male patients with similar clinico-radiological features. In addition, OPHN-1 inactivation should be considered as a relevant model of developmental vermis disorganization, leading to a better understanding of the possible role of the cerebellum in MR. 相似文献
122.
Gomot M Ronce N Dessay S Zemni R Ayrault AD Moizard MP Nivelon A Gilgenkrantz S Dourlens J Des Portes V Chelly J Moraine C 《American journal of medical genetics》2002,112(4):400-404
The TM4SF2 gene (localized at Xp11.4 between the loci DXS564 and DXS556) has been found to be mutated in one MRX family. In order to define the corresponding behavioral phenotype, global IQ and specific cognitive skills were assessed in seven males and three females of this family, independent of subject status. Mental retardation (MR) was mild in three patients and moderate in three others. Despite the broad variability of severity of MR, a cognitive profile specific to the MR in this family was documented. It was characterized by language disorder that was more marked in the articulatory component and spatial/verbal short-term memory dissociation with larger mnemonic span for spatial than for verbal cues. Linkage analysis was then performed on the basis of the cognitively determined status. Recombinations were observed with the loci DXS556 at Xp11.4 and DXS441 at Xq13.2 (maximum LOD score = 2.23 at theta = 0 for ALAS2). This localization region does not include the TM4SF2 gene that has been found mutated in both patients with MR and in one non-MR male subject of this family. The present results suggest two main hypotheses. First, TM4SF2 gene mutation could be involved in MR in this family, therefore representing accentuated intra familial phenotypic variability. Second, the structural particularity detected in the TM4SF2 gene might reflect a rare polymorphism rather than a pathogenic mutation, with the gene responsible for MR in this family being therefore more likely to be searched for in the pericentromeric region of the X chromosome. 相似文献
123.
Bienvenu T Poirier K Friocourt G Bahi N Beaumont D Fauchereau F Ben Jeema L Zemni R Vinet MC Francis F Couvert P Gomot M Moraine C van Bokhoven H Kalscheuer V Frints S Gecz J Ohzaki K Chaabouni H Fryns JP Desportes V Beldjord C Chelly J 《Human molecular genetics》2002,11(8):981-991
Investigation of a critical region for an X-linked mental retardation (XLMR) locus led us to identify a novel Aristaless related homeobox gene (ARX ). Inherited and de novo ARX mutations, including missense mutations and in frame duplications/insertions leading to expansions of polyalanine tracts in ARX, were found in nine familial and one sporadic case of MR. In contrast to other genes involved in XLMR, ARX expression is specific to the telencephalon and ventral thalamus. Notably there is an absence of expression in the cerebellum throughout development and also in adult. The absence of detectable brain malformations in patients suggests that ARX may have an essential role, in mature neurons, required for the development of cognitive abilities. 相似文献
124.
Interleukin-18 Primes the Oxidative Burst of Neutrophils in Response to Formyl-Peptides: Role of Cytochrome b558 Translocation and N-Formyl Peptide Receptor Endocytosis
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Carole Elbim Cécile Guichard Pham M. C. Dang Michèle ?Fay Eric Pedruzzi Hélène Demur Cécile Pouzet Jamel El Benna Marie-Anne Gougerot-Pocidalo 《Clinical and Vaccine Immunology : CVI》2005,12(3):436-446
Using flow cytometry, we observed that interleukin-18 (IL-18) primed human neutrophils (PMNs) in whole blood to produce superoxide anion (O2°−) in response to N-formyl peptide (fMLP) stimulation, whereas IL-18 alone had no significant effect. In contrast to tumor necrosis factor alpha (TNF-α), which is a cytokine known to strongly prime O2°− production, IL-18 did not induce either p47phox phosphorylation or its translocation from the cytosol to the plasma membrane. However, IL-18 increased PMN degranulation, as shown by increased levels of cytochrome b558 and CD11b expression at the PMN surface. Moreover, addition of IL-18 to whole blood for 45 min reduced the ability of PMNs to bind to fMLP, suggesting endocytosis of fMLP receptors, as visualized by confocal microscopy. 2,3-Butanedione 2-monoxime, which inhibits endosomal recycling of plasma membrane components back to the cell surface, concomitantly accentuated the diminution of fMLP binding at the PMN surface and increased IL-18 priming of O2°− production by PMNs in response to fMLP. This suggests that fMLP receptor endocytosis could account, at least in part, for the priming of O2°− production. In addition, genistein, a tyrosine kinase inhibitor, and SB203580, a p38 mitogen-activated protein kinase (p38MAPK) inhibitor, completely reversed the decreased level of fMLP binding and increased the level of CD11b expression after IL-18 treatment. Flow cytometric analysis of intact PMNs in whole blood showed that IL-18 increased p38MAPK phosphorylation and tyrosine phosphorylation. In particular, IL-18 induced phosphorylation of focal adhesion kinase (p125FAK), which has been implicated in cytoskeleton reorganization. Taken together, our findings suggest several mechanisms that are likely to regulate cytokine-induced priming of the oxidative burst in PMNs in their blood environment. 相似文献
125.
Bndicte Grard Jamel El Benna Franoise Alcain Marie‐Anne Gougerot‐Pocidalo Bernard Grandchamp Sylvie Chollet‐Martin 《Human mutation》2001,18(2):163-163
The most frequent form of chronic granulomatous disease (CGD) is caused by inactivation of the CYBB gene, which encodes the gp91‐phox subunit of phagocyte NADPH oxidase. This defect prevents phagocytes from producing reactive oxygen species and thus from eradicating bacterial and fungal infections. We investigated 16 unrelated male patients with suspected X‐linked CGD and gp91‐phox deficiency. A mutation was found in the CYBB gene of all 16 patients, and 11 of these mutations were novel. Eleven patients (69%) had a point mutation (84G>A in two unrelated patients, and 177C>G, 217C>T, 388C>T, 676C>T, 691C>T, 868C>T, 919A>C, 1384G>T and T1514G in one case each, yielding W28X, C59W, R73X, R130X, R226X, Q231X, R290X, T307P, E462X, L505R gp‐91phox). One patient had an in‐frame deletion removing two amino acids (R54 and A55). Finally, insertions or duplications were found in four patients (from +1 to +31 bases). Overall, 12 (75%) of the mutations led to the production of a truncated protein. No clear correlation was found between clinical manifestations and genomic/biochemical alterations. Thirteen mothers could be tested, and all were carriers. Hum Mutat 18:163, 2001. © 2001 Wiley‐Liss, Inc. 相似文献
126.
Loss of parental-specific methylation at the IGF2 locus in human hepatocellular carcinoma 总被引:5,自引:0,他引:5
Poirier K Chalas C Tissier F Couvert P Mallet V Carrié A Marchio A Sarli D Gicquel C Chaussade S Beljord C Chelly J Kerjean A Terris B 《The Journal of pathology》2003,201(3):473-479
Significant production of the growth factor IGF2 has been reported in human hepatocellular carcinomas (HCCs). Disturbances associated with changes in methylation at this locus or affecting the 11p15.5 imprinting domain as a whole can be postulated in HCCs. In the present study, the methylation status of differentially methylated regions of the imprinted genes TSSC5, LIT1, and IGF2, which span the 11p15 domain, was analysed in 71 liver tissues from virus-associated and non-virus-associated HCCs compared with six normal liver tissues. Altered methylation of TSSC5 and LIT1 was observed in only 6% and 8% of HCCs, respectively, compared with 89% at the IGF2 locus, suggesting that these loci were not concomitantly dysregulated. These observations suggest that loss of parental-specific methylation at the IGF2 locus may be specifically associated with HCC, whether virus-associated or non-virus-associated, and arising in cirrhotic or non-cirrhotic livers. 相似文献
127.
Chul-Su Yang Hye-Mi Lee Ji-Yeon Lee Jeong-Ah Kim Sung Joong Lee Dong-Min Shin Young-Ho Lee Dong-Seok Lee Jamel El-Benna Eun-Kyeong Jo 《Journal of neuroinflammation》2007,4(1):27-16
Background
Activated microglia elicits a robust amount of pro-inflammatory cytokines, which are implicated in the pathogenesis of tuberculosis in the central nervous system (CNS). However, little is known about the intracellular signaling mechanisms governing these inflammatory responses in microglia in response to Mycobacterium tuberculosis (Mtb). 相似文献128.
J M Casillas V Gremeaux S Damak A Feki D Pérennou 《Annales de Réadaptation et de Médecine Physique》2007,50(6):403-18, 386-402
This review surveys effort training, a validated and recommended therapy, in patients with atheromatous cardiovascular disease. This true therapy reduces mortality by 25-35%, reduces clinical manifestations and complications (rhythm problems, thrombosis) and improves physical capacity, reintegration and quality of life. The effects are essentially linked to improved metabolic performance of muscles and reduced endothelial dysfunction, insulin resistance and neurohormonal abnormalities. Training also has an impact on the evolution of major risk factors, especially diabetes and arterial hypertension. The risks are limited as long as the contraindications are respected and the programmes supervised. The indications (stable angina, chronic heart failure, peripheral arterial disease) should be described more precisely by taking into account functional criteria: physical deconditioning, exclusion, compliance, mood swings, and seriousness of risk factors. The training programme should be tailor made and based on evaluation of the patient's adaptation to effort, in terms of frequency, intensity and duration of the exercises. Various types of exercise include overall or segmental physical training; concentric, eccentric, even isokinetic muscle contraction exercises; and proprioceptive rehabilitation. However, knowledge is lacking about the molecular mechanisms of the effects of training, the most effective intensity of effort, and strategies to develop physical activity in this ever-growing population for both primary and secondary prevention. 相似文献
129.
Jamel Daoud Nabil Toumi Wissem Siala Abdelmonem Ghorbel Mohamed Mokthar Drira Mounir Frikha 《Radiotherapy and oncology》2007,85(1):17-23
BACKGROUND AND PURPOSE: Nasopharyngeal carcinoma (NPC) is generally responsive to radiation therapy. However therapeutic results after conventional radiotherapy remain relatively poor especially for patients with locoregional advanced NPC. The aim of this study was to evaluate the impact of a split course bifractionated radiotherapy regimen in a phase III randomised trial. PATIENTS AND METHODS: From January 1997 to September 2003, 154 patients with M0 histologically proven NPC were treated in our institution. They were staged according to the American Joint Committee on Cancer - International Union Against Cancer (AJCC-UICC) 1986 TNM classification. Patients with locally advanced nodal disease (N2-N3) received induction chemotherapy. All patients were randomised to receive either conventional radiotherapy at 2 Gy/fraction/day, 5 days/week to 70 Gy/7 weeks or split course bifractionated radiotherapy at 1.6 Gy/fraction, twice daily, 5 days/week to 70.4 Gy/6 weeks. Response and toxicity were evaluated according to the WHO and RTOG criteria. RESULTS: Patients were well balanced between the two arms. The complete remission rate was 91% in conventional radiotherapy arm and 93% in bifractionated radiotherapy arm (p=0.3). There was more grade II-III skin fibrosis in experimental arm with a 5 year actuarial probability of 66% vs 52% (p=0.04). Locoregional and distant relapses occurred in 34% of cases in conventional arm and 38% in experimental arm (p=0.28). With a median follow-up of 56 months, the 5 year overall survival and the disease free survival rates were, respectively (71% and 61%), in conventional arm and (62% and 60%) in bifractionated arm, the difference being statistically non significant. COMMENTS: The present trial comparing conventional radiotherapy to a split course bifractionated radiation therapy failed to demonstrate significant improvement in locoregional control and survival in experimental arm which was associated with more grade II-III skin fibrosis. 相似文献
130.
Kochbati L Besbes M Frikha H Sellami D Gargouri W Ben Ammar CN Ben Aissia R Benna F Damak H Maalej M 《La Tunisie médicale》2005,83(10):581-585
The radiotherapy department at Salah Aza?z institute had started, in March 2000, a new sophisticated technique of irradiation consisting in total body irradiation (TBI). TBI is used in many preparative regimens before bone marrow transplantation in the treatment of haematological malignancies. TBI aims to destroy immunocompetent tissues in order to avoid graft rejection and to eradicate residual tumor cells. In this article, we review different TBI techniques and its main indications. We also describe the acute and late effects of TBI. 相似文献