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91.
Dekel B Metsuyanim S Goldstein N Pode-Shakked N Kovalski Y Cohen Y Davidovits M Anikster Y 《Pediatric research》2008,63(4):398-403
Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive disorder caused by loss-of-function mutations in SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1), with clinical features of growth retardation, spondylo-epiphyseal dysplasia, nephrotic syndrome, and immunodeficiency. We report a patient with SIOD and SMARCAL1 splice mutation (IVS4-2 A>G) in a nonconsanguineous Ashkenazi family, who came to our attention at 1 mo of age due to renal malformation and only later developed signs compatible with Schimke. Interestingly, residual SMARCAL1 mRNA levels in the patient's peripheral blood were lower compared with those observed in both asymptomatic brothers' carrying the same bi-allelic mutation, whereas the latter had levels similar to those found in heterozygous carriers (parents and sister). Examination of the carrier frequency of the splice mutation in the Ashkenazi population demonstrated 1 carrier in 760 DNA samples. In situ localization of SMARCAL1 in human kidneys as well as analysis of its temporal expression during murine nephrogenesis and in the metanephric organ culture suggested a role in the early renal progenitor population and after renal maturation. Thus, disease severity within the same family might be modified by the splicing machinery. The renal expression pattern of SMARCAL1 explains a broader spectrum of renal disease in SIOD than previously described. 相似文献
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Basel-Vanagaite L Muncher L Straussberg R Pasmanik-Chor M Yahav M Rainshtein L Walsh CA Magal N Taub E Drasinover V Shalev H Attia R Rechavi G Simon AJ Shohat M 《Annals of neurology》2006,60(2):214-222
OBJECTIVE: The objective of this study was to identify the gene causing autosomal recessive infantile bilateral striatal necrosis. METHODS: We have mapped the disease gene in the candidate region to approximately 230kb on 19q13.33 in 8 interrelated families including a total of 12 patients and 39 unaffected individuals. RESULTS: Sequencing of the nup62 gene showed a missense mutation causing a change from glutamine to proline (Q391P) in all the patients, producing a substitution from a polar, hydrophilic residue to a nonpolar, neutral residue. All the other 12 candidate genes were sequenced, and no pathogenic sequence changes were found. Comparisons of p62 protein sequences from diverse species indicate that glutamine at position 391 is highly conserved. Five prenatal diagnoses were performed in three at-risk families. INTERPRETATION: This is the second example of a nuclear pore complex protein causing mendelian disease in humans (the first one is triple A syndrome). Our findings suggest that p62 has a cell type-specific role and is important in the degeneration of the basal ganglia in humans. 相似文献
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Gez E Assaf N Ashaf N Bar-Deroma R Rosenblatt E Kuten A 《International journal of radiation oncology, biology, physics》2004,60(4):1190-1194
PURPOSE: This retrospective study evaluates the results of postmastectomy electron-beam chest-wall irradiation in patients with breast cancer. METHODS AND MATERIALS: From 1980 to 1994, 144 women with localized breast cancer received postmastectomy radiotherapy. The chest wall was irradiated by electron beam, 6 to 12 MeV energy, depending on wall thickness, 2.0 Gy daily, 5 times/week for total dose of 50 Gy. Forty-one patients received 16-Gy boosts to the mastectomy scar. In addition, the supraclavicular and axilla areas were irradiated by anterior field with 6-MV photon beam. RESULTS: Median follow-up was 84 months. Fifteen patients (10%) had local-regional recurrence (LRR) and 57 patients (40%) had systemic relapse (SR). Median time from mastectomy to LRR was 20 months and median time to SR was 33 months. Axillary lymph nodes status influenced both LRR and SR. LRR rate was 0% in N0 and 12% in N1 disease; SR rate was 14% in N0 and 45% in N1 disease. Disease-free and overall survival was 58% and 67% in 10 years and 50% and 55% in 20 years, respectively. No cardiac toxicity was related to left chest-wall irradiation. CONCLUSION: Postmastectomy electron-beam chest-wall irradiation is as effective as photon-beam irradiation in breast cancer. 相似文献
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Previous studies suggest that motor recovery does not occur after spinal cord injury because reactive glia abort the natural repair processes. A permanent wound gap is left in the cord and the brain-cord circuitry consequently remains broken. Single-dose x-irradiation destroys reactive glia at the damage site in transected adult rat spinal cord. The wound then heals naturally, and a partially functional brain-cord circuitry is reconstructed. Timing is crucial; cell ablation is beneficial only within the third week after injury. Data presented here point to the possibility of translating these observations into a clinical therapy for preventing the paralysis following spinal cord injury in the human. The lesion site (at low thoracic level) in severed adult rat spinal cord was treated daily, over the third week postinjury, with protocols of fractionated radiation similar to those for treating human spinal cord tumors. This resulted, as with the single-dose protocol, in wound healing and restoration of some hindquarter motor function; in addition, the beneficial outcome was augmented. Of the restored hindlimb motor functions, weight-support and posture in stance was the only obvious one. Recovery of this motor function was partial to substantial and its incidence was 100% instead of about 50% obtained with the single-dose treatment. None of the hindlimbs, however, regained frequent stepping or any weight-bearing locomotion. These data indicate that the therapeutic outcome may be further augmented by tuning the radiation parameters within the critical time-window after injury. These data also indicate that dose-fractionation is an effective strategy and better than the single-dose treatment for targeting of reactive cells that abort the natural repair, suggesting that radiation therapy could be developed into a therapeutic procedure for repairing injured spinal cord. 相似文献
100.
Shira Yalon‐Chamovitz Tali Mano Tal Jarus Nurit Weinblatt 《British Journal of Learning Disabilities》2006,34(1):42-48
Participation in leisure activities may contribute to the development of social, motor, and language skills, and is therefore especially important for children with learning disabilities. Leisure activities of students in educational settings are performed mostly during breaks. While there have been some studies of the effect of breaks on classroom performance, none have been conducted among children with learning disabilities. Moreover, the role of breaks as a leisure agent was never addressed. The purpose of the study was to examine break activities of children with learning disabilities, through exploration of the correlation between their preferences for break activities and the activities in which they actually engaged. The study found no such correlation. It is therefore suggested that leisure education should provide students with the skills they need in order to choose leisure activities and evaluate the efficacy of the choice they had made. 相似文献