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51.
The bleeding diathesis associated with hereditary factor XI (fXI) deficiency is prevalent in Ashkenazi Jews, in whom the disorder appears to be an autosomal recessive condition. The homodimeric structure of fXI implies that the product of a single mutant allele could confer disease in a dominant manner through formation of heterodimers with wild-type polypeptide. We studied 2 unrelated patients with fXI levels less than 20% of normal and family histories indicating dominant disease transmission. Both are heterozygous for single amino acid substitutions in the fXI catalytic domain (Gly400Val and Trp569Ser). Neither mutant is secreted by transfected fibroblasts. In cotransfection experiments with a wild-type fXI construct, constructs with mutations common in Ashkenazi Jews (Glu117Stop and Phe283Leu) and a variant with a severe defect in dimer formation (fXI-Gly350Glu) have little effect on wild-type fXI secretion. In contrast, cotransfection with fXI-Gly400Val or fXI-Trp569Ser reduces wild-type secretion about 50%, consistent with a dominant negative effect. Immunoprecipitation of cell lysates confirmed that fXI-Gly400Val forms intracellular dimers. The data support a model in which nonsecretable mutant fXI polypeptides trap wild-type polypeptides within cells through heterodimer formation, resulting in lower plasma fXI levels than in heterozygotes for mutations that cause autosomal recessive fXI deficiency. 相似文献
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Giant cell tumour (GCT) of bone is a benign but locally aggressive tumour and accounts for 20 % of all benign bone tumours and 5 % of all bone tumours. Multicentric GCT of bone is a rare entity and has increased prevalence of involvement of the small bones of hands and feet in multicentric GCT. The clinical behaviour in multicentric GCTs tends to be aggressive as in recurrent GCTs. En-bloc resection remains the most successful surgical technique for treating both multicentric and solitary lesions. We report a 14-year-old female patient presenting with metachronous benign GCT located at the right proximal humerus and subsequent lesions in left hand and left proximal humerus. The case was treated with multimodality therapy including en-bloc resection along with bisphosphonate therapy over a period of 5 years. 相似文献
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Jay Simhan Daniel Ramirez Steven J. Hudak Allen F. Morey 《Translational andrology and urology》2014,3(2):214-220
Bladder neck contracture (BNC) is a well-described complication of the surgical treatment of benign and malignant prostate conditions. Nevertheless, etiologies of BNC development are highly dependent on the primary treatment modality undertaken with BNC also occurring after pelvic radiation. The treatment options for BNC can range from simple, office-based dilation procedures to more invasive, complex abdomino-perineal reconstructive surgery. Although numerous strategies have been described, a patient-specific approach is usually necessary in the management of these complex patients. In this review, we highlight various therapeutic maneuvers described for the management of BNC and further delineate a tailored approach utilized at our institution in these complicated patients. 相似文献
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Differential developmental trajectories of magnetic susceptibility in human brain gray and white matter over the lifespan
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Wei Li Bing Wu Anastasia Batrachenko Vivian Bancroft‐Wu Rajendra A. Morey Vandana Shashi Christian Langkammer Michael D. De Bellis Stefan Ropele Allen W. Song Chunlei Liu 《Human brain mapping》2014,35(6):2698-2713
As indicated by several recent studies, magnetic susceptibility of the brain is influenced mainly by myelin in the white matter and by iron deposits in the deep nuclei. Myelination and iron deposition in the brain evolve both spatially and temporally. This evolution reflects an important characteristic of normal brain development and ageing. In this study, we assessed the changes of regional susceptibility in the human brain in vivo by examining the developmental and ageing process from 1 to 83 years of age. The evolution of magnetic susceptibility over this lifespan was found to display differential trajectories between the gray and the white matter. In both cortical and subcortical white matter, an initial decrease followed by a subsequent increase in magnetic susceptibility was observed, which could be fitted by a Poisson curve. In the gray matter, including the cortical gray matter and the iron‐rich deep nuclei, magnetic susceptibility displayed a monotonic increase that can be described by an exponential growth. The rate of change varied according to functional and anatomical regions of the brain. For the brain nuclei, the age‐related changes of susceptibility were in good agreement with the findings from R2* measurement. Our results suggest that magnetic susceptibility may provide valuable information regarding the spatial and temporal patterns of brain myelination and iron deposition during brain maturation and ageing. Hum Brain Mapp 35:2698–2713, 2014. © 2013 Wiley Periodicals, Inc . 相似文献
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Dubin-Johnson综合征是一种先天性非溶血性黄疸,在临床中较罕见,需与其他原因所导致的黄疸相鉴别.本文报告了我院1例Dubin- Johnson综合征的诊治情况,有助于加深对该病的认识. 相似文献
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