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111.
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
112.
Barnett R Maruff P Purcell R Wainwright K Kyrios M Brewer W Pantelis C 《Psychological medicine》1999,29(5):1227-1233
BACKGROUND: Olfactory identification ability has been associated with processing in the orbitofrontal cortex (OFC), an area that has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). Although olfactory sensitivity is normal in patients with OCD, no study has investigated olfactory identification in this disorder. METHODS: A group of 20 subjects with OCD and 23 age- and education-matched controls performed a standardized test of olfactory identification. They also performed computerized tests of spatial memory span, spatial working memory and spatial recognition memory that have been shown previously to be sensitive to cognitive deficits in patients with OCD. RESULTS: Performance on the olfactory identification task, spatial recognition task and spatial span task was significantly worse in the OCD group than controls. CONCLUSIONS: While impairment in spatial cognition is consistent with previous studies of OCD, its significance for brain-behaviour models of OCD is unclear. However, the finding of abnormal olfactory identification in patients with OCD is consistent with the hypothesis that there is a disruption to processing at the level of the OFC in the disorder. 相似文献
113.
NA Hanchard DR Murdock PL Magoulas M Bainbridge D Muzny YQ Wu M Wang AL McGuire JR Lupski RA Gibbs CW Brown 《Clinical genetics》2013,83(5):457-461
The advent of whole‐exome next‐generation sequencing (WES) has been pivotal for the molecular characterization of Mendelian disease; however, the clinical applicability of WES has remained relatively unexplored. We describe our exploration of WES as a diagnostic tool in a 3½‐year old female patient with a 2‐year history of episodic muscle weakness and paroxysmal dystonia who presented following a previous extensive but unrevealing diagnostic work‐up. WES was performed on the proband and her two parents. Parental exome data was used to filter potential de novo genomic events in the proband and suspected variants were confirmed using di‐deoxy sequencing. WES revealed a de novo non‐synonymous mutation in exon 21 of the calcium channel gene CACNA1S that has been previously reported in a single patient as a rare cause of atypical hypokalemic periodic paralysis. This was unexpected, as the proband's original differential diagnosis had included hypokalemic periodic paralysis, but clinical and laboratory features were equivocal, and standard clinical molecular testing for hypokalemic periodic paralysis and related disorders was negative. This report highlights the potential diagnostic utility of WES in clinical practice, with implications for the approach to similar diagnostic dilemmas in the future. 相似文献
114.
Human breast lesions: characterization with proton MR spectroscopy 总被引:31,自引:0,他引:31
115.
The locus of enterocyte effacement (LEE)-encoded regulator controls expression of both LEE- and non-LEE-encoded virulence factors in enteropathogenic and enterohemorrhagic Escherichia coli 总被引:7,自引:0,他引:7 下载免费PDF全文
Elliott SJ Sperandio V Girón JA Shin S Mellies JL Wainwright L Hutcheson SW McDaniel TK Kaper JB 《Infection and immunity》2000,68(11):6115-6126
Regulation of virulence gene expression in enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) is incompletely understood. In EPEC, the plasmid-encoded regulator Per is required for maximal expression of proteins encoded on the locus of enterocyte effacement (LEE), and a LEE-encoded regulator (Ler) is part of the Per-mediated regulatory cascade upregulating the LEE2, LEE3, and LEE4 promoters. We now report that Ler is essential for the expression of multiple LEE-located genes in both EPEC and EHEC, including those encoding the type III secretion pathway, the secreted Esp proteins, Tir, and intimin. Ler is therefore central to the process of attaching and effacing (AE) lesion formation. Ler also regulates the expression of LEE-located genes not required for AE-lesion formation, including rorf2, orf10, rorf10, orf19, and espF, indicating that Ler regulates additional virulence properties. In addition, Ler regulates the expression of proteins encoded outside the LEE that are not essential for AE lesion formation, including TagA in EHEC and EspC in EPEC. delta ler mutants of both EPEC and EHEC show altered adherence to epithelial cells and express novel fimbriae. Ler is therefore a global regulator of virulence gene expression in EPEC and EHEC. 相似文献
116.
AimsThe aim of the literature review was to identify new and emerging out of hospital emergency care roles and to describe their activity and impact.BackgroundDemographic changes, increased demands for health services, altered working practices, and health system economic pressures have led to the development of a disparate set of new health care roles.Data sourcesMEDLINE, EMBASE and CINAHL databases, and the two search engines Google and Google Scholar were searched for contemporary studies in the identified study area.Review methodsAll publications identified through the search were assessed for relevance. Those that discussed new roles were included (n = 34) and empirical studies (n = 14) analysed in detail.ResultsEmergency care and paramedic practitioner roles (ECP & PP) are having an impact on patient care, including an average 25% reduction in the conveyance rate to hospital, improved inter-professional working, immediacy of treatment and referral, and high patient satisfaction. Limited economic data suggests savings of between £31 (USD 55) and £37 (USD 65) per case when ECPs replace standard ambulance responders. Concerns have been expressed about patient safety, recruitment and training levels, regulatory and role implementation issues.ConclusionFurther work is required to fully understand the patient safety, clinical practice, professional role and financial implications of these new roles. 相似文献
117.
The objective of this study was to determine whether the proposed Malan radiological sinusitis typing (RST) system facilitated a level of agreement and ease of use comparable with the Lund–Mackay (LM) system for chronic rhinosinusitis. Ten observers (one otolaryngologist and nine radiologists), in two separate centres (regional and tertiary), blinded to all clinical data, used these two systems to independently and randomly score and type 15 sets of scans, recording the time to score each film. Using unweighted kappa scores, both methods facilitated a moderate level of agreement, slightly better with the LM system. The Malan system is more time efficient. Preliminarily, this study shows that the Malan RST system is easy to apply with a comparable level of agreement. The Malan RST system is a focused attempt at classifying disease extent radiologically and correlating it to a surgical approach. It emphasizes that scoring systems are vulnerable and proves to be superior to the LM system as a surgical planning tool. To score sinus disease, a Quality‐of‐Life questionnaire in association with this typing method is more appropriate. 相似文献
118.
王妍 《中国实用乡村医生杂志》2007,14(7):47-49
亚临床甲状腺功能亢进和甲状腺功能减退属于试验诊断。2002年美国甲状腺协会、美国临床内分泌医师协会和内分泌腺协会的委员组成的一个专家小组,明确了亚临床甲状腺疾病的概念,回顾了涉及风险和治疗益处的文献,并且建议进行评估和人口筛查。 相似文献
119.
Almeida SS Duntas LH Dye L Nunes ML Prasad C Rocha JB Wainwright P Zaia CT Guedes RC 《Nutritional neuroscience》2002,5(5):311-320
A few months ago, the Brazilian Society for Neuroscience and Behavior (SBNeC) promoted a "virtual symposium" (by Internet, under the coordination of R.C.A. Guedes) on "Nutrition and Brain Function". The discussions generated during that symposium originated the present text, which analyzes current topics on the theme, based on the multidisciplinary experience of the authors. The way the brain could be non-homogeneously affected by nutritional alterations, as well as questions like early malnutrition and the development of late obesity and hormone abnormalities were discussed. Also, topics like the role of essential fatty acids (EFAs) on brain development, increased seizure susceptibility and changes in different neurotransmitters and in cognitive performance in malnourished animals, as well as differences between overall changes in nutrient intake and excess or deficiency of specific nutrients (e.g. iodine deficiency) were analyzed. It was pointed out that different types of neurons, possibly in distinct brain structures, might be differently affected by nutritional manipulation, including not only lack-but also excess of nutrient intake. Such differences could help in explaining discrepancies between data on humans and in animals and so, could aid in determining the basic mechanisms underlying lesions or changes in brain function and behavior. 相似文献
120.
A 7-year-old boy developed increasing cyanosis after a total cavopulmonary connection with a 3 mm fenestration in the baffle. Catheterisation performed 4 years and 7 months after the operation showed reopening of a left superior caval vein draining into the pulmonary venous atrium. Due to the large size of the left superior caval vein, and the absence of intrinsic stenosis, we chose to use an Amplatzer ductal device to occlude the reopened vein. The procedure was safe and successful. 相似文献