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排序方式: 共有257条查询结果,搜索用时 15 毫秒
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AM Innes KM Boycott EG Puffenberger D Redl IM MacDonald AE Chudley C Beaulieu R Perrier T Gillan A Wade JS Parboosingh 《Clinical genetics》2010,78(5):424-431
Innes AM, Boycott KM, Puffenberger EG, Redl D, MacDonald IM, Chudley AE, Beaulieu C, Perrier R, Gillan T, Wade A, Parboosingh JS. A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders. Bardet‐Biedl syndrome (BBS) is a multisystem genetically heterogeneous disorder, the clinical features of which are largely the consequence of ciliary dysfunction. BBS is typically inherited in an autosomal recessive fashion, and mutations in at least 14 genes have been identified. Here, we report the identification of a founder mutation in the BBS2 gene as the cause for the increased incidence of this developmental disorder in the Hutterite population. To ascertain the Hutterite BBS locus, we performed a genome‐wide single nucleotide polymorphism (SNP) analysis on a single patient and his three unaffected siblings from a Hutterite family. The analysis identified two large SNP blocks that were homozygous in the patient but not in his unaffected siblings, one of these regions contained the BBS2 gene. Sequence analysis and subsequent RNA studies identified and confirmed a novel splice site mutation, c.472‐2A>G, in BBS2. This mutation was also found in homozygous form in three subsequently studied Hutterite BBS patients from two different leuts, confirming that this is a founder mutation in the Hutterite population. Further studies are required to determine the frequency of this mutation and its role, if any, in the expression of other ciliopathies in this population. 相似文献
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Tzortzaki EG Tischfield JA Sahota A Siafakas NM Gordon MK Gerecke DR 《The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology》2003,275(2):1073-1080
Collagens XII and XIV are members of a subfamily of fibril-associated collagens with interrupted triple-helices (FACITs) that facilitate the interactions of adjacent collagen fibrils. Using immunohistochemistry and in situ hybridization, we analyzed the spatial and temporal expression pattern of collagens XII and XIV during bleomycin-induced pulmonary fibrosis. C57Bl mice were treated with bleomycin (1 U, i.p., every other day for 8 days) or saline (control), and lung tissue samples were analyzed 2-12 weeks later. Collagen I protein expression was increased in the lung 2 weeks post bleomycin treatment and persisted for at least 12 weeks. In contrast, collagen XII and XIV expression was low until 4 weeks after bleomycin treatment. Whereas collagen XII expression was greatest between 4 weeks and 8 weeks, expression of collagen XIV persisted from 4 to 12 weeks, which suggests that these two proteins may play distinct roles in the fibrotic process. The mRNA for lysyl oxidase (LOX), an enzyme for cross-linking of collagens, had a delayed increase in the lung after bleomycin administration. It reached a maximum after 8 weeks, and persisted throughout the 12 weeks of the study. These data support the hypothesis that fibrosis is a multistep process that involves both collagen accumulation and changes in the molecules that modulate the biomechanical properties of fibrils. 相似文献
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Paulsson AK McMullen KP Peiffer AM Hinson WH Kearns WT Johnson AJ Lesser GJ Ellis TL Tatter SB Debinski W Shaw EG Chan MD 《中国神经肿瘤杂志》2013,(1):52-52
PURPOSE: We investigate the patterns of failure in the treatment of glioblastoma(GBM) based on clinical target volume(CTV) margin size,dose delivered to the site of initial failure,and the use of temozolomide and intensity-modulated radiotherapy(IMRT).METHODS: Between August 2000 and May 2010,161 patients with GBM were treated with radiotherapy with or without concurrent temozolomide.Patients were treated with CTV expansions that ranged from 5 to 20 mm using a shrinking field technique.Patterns of failure and time to progression and overall survival were compared based on CTV margin,use of temozolomide,and use of IMRT.Kaplan Meier analysis was used to estimate survival times,and χ test was used for comparison of cohorts.RESULTS: For patients treated with 5-,10-,and 15-to 20-mm CTV,79%,77%,and 86% experienced failures in the 60 Gy volume,respectively.Forty-eight percent,55%,and 66% of patients with 5-,10-,and 15-to 20-mm CTV experienced failures in the 46 Gy volume,respectively.There was no statistical difference between patients treated with 5-,10-,15-to 20-mm margins with regard to 60 Gy failure(P=0.76),46 Gy failure(P=0.51),or marginal failure(P=0.73).Eighty percent of patients receiving temozolomide experienced failures in the 60 Gy volume.There was no increased likelihood of marginal failures in patients receiving IMRT(P =0.97).CONCLUSIONS: Modern treatment techniques including use of concurrent temozolmide,limited CTV margin size,and IMRT have not greatly changed the patterns of failure of GBM. 相似文献
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Inhibitory synaptogenesis in mouse somatosensory cortex 总被引:4,自引:3,他引:1
It is widely believed that inhibitory synapses are not present or present
in only small numbers in the rodent cerebral cortex during the early
postnatal period when the cortex is being innervated by thalamocortical
fibers. Quantitative electron microscopy was carried out on the
posteromedial barrel subfield of mouse somatosensory cortex from postnatal
day 4 (P4) when thalamocortical innervation of the barrels is becoming
established, through to sexual maturity (>P32), and in adulthood. Both
asymmetrical (putatively excitatory) and symmetrical (putatively
inhibitory) synapses were present in all layers from P4. The symmetrical
synapses were immunoreactive for GABA at all ages. There was a progressive
increase in both asymmetrical and symmetrical synapses up to P32, density
in all layers increasing 16-fold, with the production of asymmetrical
synapses leading and greatly outstripping that of symmetrical. From P32 to
P120, the oldest age studied, synaptic numbers declined by 18% to 13 times
the P4 level, but this affected predominantly layers II/III, IV and V, and
mainly involved asymmetrical synapses. The relative percentage of
asymmetrical to symmetrical synapses from P4 to P8 was 57%/43% but at P32
it was 89.5%/10.5% and in adulthood 85.4%/14.6%. These data indicate that
inhibitory synaptogenesis in the rodent cortex begins earlier than
previously thought, a basis for inhibition being present from the earliest
period. Pruning of all synapses occurs well after thalamocortical
innervation is established and inhibitory synapses are less affected by the
pruning process.
相似文献
49.
Carmona-Bayonas A; Soler IO; Gomez FI; Billalabeitia EG; Saura HP; Tafalla MSA; Diaz MP 《Annals of oncology》2007,18(7):1281
Mitotane is often considered the front-line hormonal therapyof adrenocortical carcinoma (ACC). An illustrative case concerningthis issue and the rationale to ponder other alternatives isreported. A 69 year-old woman, diagnosed with ACC was admittedwith hypertensive crisis, supraventricular tachycardia, congestiveheart-failure, diarrhoea and rabdomyolisis. Two years earlier,she had undergone 相似文献
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