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KJ Champion C Bunag AL Estep JR Jones CH Bolt RC Rogers KA Rauen DB Everman 《Clinical genetics》2011,79(5):468-474
Champion KJ, Bunag C, Estep AL, Jones JR, Bolt CH, Rogers RC, Rauen KA, Everman DB. Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome. BRAF, the protein product of BRAF, is a serine/threonine protein kinase and one of the direct downstream effectors of Ras. Somatic mutations in BRAF occur in numerous human cancers, whereas germline BRAF mutations cause cardio‐facio‐cutaneous (CFC) syndrome. One recurrent somatic mutation, p.V600E, is frequently found in several tumor types, such as melanoma, papillary thyroid carcinoma, colon cancer, and ovarian cancer. However, a germline mutation affecting codon 600 has never been described. Here, we present a patient with CFC syndrome and a de novo germline mutation involving codon 600 of BRAF, thus providing the first evidence that a pathogenic germline mutation involving this critical codon is not only compatible with development but can also cause the CFC phenotype. In vitro functional analysis shows that this mutation, which replaces a valine with a glycine at codon 600 (p.V600G), leads to increased ERK and ELK phosphorylation compared to wild‐type BRAF but is less strongly activating than the cancer‐associated p.V600E mutation. 相似文献
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Intracranial meningiomas: high-field MR imaging 总被引:6,自引:0,他引:6
Spagnoli MV; Goldberg HI; Grossman RI; Bilaniuk LT; Gomori JM; Hackney DB; Zimmerman RA 《Radiology》1986,161(2):369
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The purpose of this study was to evaluate the gait responses of individuals with low vision compared to those of normal-visioned individuals when their vision is challenged by extreme levels of light. Twenty subjects with age-related maculopathy (ARM) and 20 subjects with normal vision first walked along a flat, unobstructed path immediately after the ambient light level was changed from low (5 lux) to high (2500 lux). The procedure was repeated after the light was reduced from the high to the low level. Muscle activity, temporal and kinematic variables, and ground reaction forces were used to detect gait characteristics because of ambient light level changes. Data suggested that ARM subjects walked slower and with more caution than normal subjects but that these differences were not related to ambient light level. Head angle, an estimate of gaze direction, was lower for ARM subjects during high light, but the gaze direction for both groups was low during low light. Among these ARM subjects, extreme levels of ambient light did not affect gait; subjects made adaptations that were reasonable to encourage safe ambulation, despite the direction of light change. Normal-visioned individuals in this study experienced more difficulty in low light than high light situations. 相似文献
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Toxins produced by staphylococci and enterobacteria isolated from the nasopharynx of cases of sudden infant death syndrome (SIDS) have a lethal effect when injected into chick embryos. If the toxins are progressively diluted the lethal effect disappears, but certain combinations of toxins show synergy so that if sublethal doses are mixed a highly lethal effect is produced. In this paper it is shown that nicotine at very low concentrations (less than that produced in man by 0.05 cigarettes) potentiates the lethal action of certain SIDS associated bacterial toxins and markedly potentiates the lethal action of synergistic combinations of bacterial toxins. These results could explain, at least in part, why parental smoking increases the risk of SIDS. They also provide further support for the common bacterial toxin hypothesis of cot death. 相似文献