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排序方式: 共有751条查询结果,搜索用时 15 毫秒
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Yeo GS Lank EJ Farooqi IS Keogh J Challis BG O'Rahilly S 《Human molecular genetics》2003,12(5):561-574
Mutations in the melanocortin-4 receptor gene (MC4R) represent the commonest monogenic cause of human obesity. However, information regarding the precise effects of such mutations on receptor function is very limited. We examined the functional properties of 12 different mutations in human MC4R that result in severe, familial, early-onset obesity. Of the nine missense mutants studied, four were completely unable to generate cAMP in response to ligand and five were partially impaired. Four showed evidence of impaired cell surface expression and six of reduced binding affinity for ligand. One mutation in the C-terminal tail, I316S, showed reduced affinity for alpha-MSH but retained normal affinity for the antagonist AgRP. None of the mutations inhibited signaling through co-transfected wild-type receptors. Thus, in the most comprehensive study to date of the functional properties of naturally occurring MC4R mutations we have (1) established that defective expression on the cell surface is a common mechanism impairing receptor function, (2) identified mutations which specifically affect ligand binding affinity thus aiding the definition of receptor structure-function relationships, (3) provided evidence against the notion that these receptor mutants act as dominant-negatives, and (4) identified a potentially novel molecular mechanism of receptor dysfunction whereby a mutation alters the relative affinities of a receptor for its natural agonist versus antagonist. 相似文献
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Yeo GS Connie Hung CC Rochford J Keogh J Gray J Sivaramakrishnan S O'Rahilly S Farooqi IS 《Nature neuroscience》2004,7(11):1187-1189
An 8-year-old male with a complex developmental syndrome and severe obesity was heterozygous for a de novo missense mutation resulting in a Y722C substitution in the neurotrophin receptor TrkB. This mutation markedly impaired receptor autophosphorylation and signaling to MAP kinase. Mutation of NTRK2, which encodes TrkB, seems to result in a unique human syndrome of hyperphagic obesity. The associated impairment in memory, learning and nociception seen in the proband reflects the crucial role of TrkB in the human nervous system. 相似文献
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Anghela Z. Paredes J. Madison Hyer Diamantis I. Tsilimigras Mary Dillhoff Jordan M. Cloyd Aslam Ejaz Allan Tsung Courtney Collins Timothy M. Pawlik 《American journal of surgery》2021,221(3):492-496
IntroductionWe sought to determine the impact of payer-mix on post-operative outcomes among Medicare beneficiaries following hepatopancreatic surgery.MethodsMedicare beneficiaries who underwent hepatopancreatic surgery were identified. Hospital quality markers were obtained from the Hospital General Information dataset. Hospitals were dichotomized (low/average vs. high) based on Medicare patient days versus all patient days irrespective of payer type.ResultsHigh Medicare patient-mix hospitals were more likely to be ranked higher than the national average relative to safety of care (29.4% vs. 38.1%) and timeliness of care (15.4% vs. 26.3%) versus low burden Medicare hospitals (both p < 0.001). However, Medicare beneficiaries who had hepatopancreatic surgery at a high Medicare patient-mix hospital were at higher risk of a complication (OR = 1.13, 95%CI 1.04–1.22), and death within 30-days (OR = 1.37, 95%CI 1.23–1.53) following surgery.ConclusionWhile hospitals caring for higher numbers of Medicare beneficiaries generally performed better on CMS quality indicators, these rankings did not equate to improved post-operative outcomes. 相似文献
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Azap Rosevine A. Diaz Adrian Hyer J. Madison Tsilimigras Diamantis I. Mirdad Rayyan S. Ejaz Aslam Pawlik Timothy M. 《Annals of surgical oncology》2021,28(3):412-413
Annals of Surgical Oncology - 相似文献
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Sadaf Matiullah Mlissa Gnreux Genevive Petit 《Canadian journal of public health. Revue canadienne de santé publique》2021,112(2):253
ObjectiveA growing number of people live in urban areas. Urbanization has been associated with an increased prevalence of mental disorders, but which mechanisms cause this increase is unknown. Psychological distress is a good indicator of mental health. This study sought to examine the relationship between urbanization and distress among adults in the Eastern Townships (southern region of Quebec, Canada).MethodIn the 2014–2015 Eastern Townships Population Health Survey (N = 10,687 adults living in one of the 96 Eastern Townships communities), distress was measured with the K6 distress scale (≥ 7). Urbanization was estimated by the residential density of the community treated in quintiles. Logistic regression analyses were carried out with adjustments for individual and environmental characteristics.ResultsWomen, young people aged 18–24, single parents, those without diplomas, those without a job, those with < $20,000 in income, adults with two or more chronic physical illnesses, adults with bad perceived health, or those living in disadvantaged neighbourhoods exhibited more distress. The unadjusted estimate between density and distress is only significant for the fifth quintile when compared with the first quintile (OR 1.23; 95% CI: 1.06–1.42). The relationship is practically the same after controlling for individual characteristics but decreases considerably after controlling for environmental characteristics (lack of trees, social deprivation, intersection density, vegetation index, and land use mix).ConclusionThis study was the first to examine an association between urbanization and distress by considering individual and environmental characteristics. The latter seem to explain the relationship between these concepts. 相似文献
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Muhammad Tahir Khan Sadaf Arooj Muhammad Umer Mukhtar Rewati Raman 《Radiology Case Reports》2022,17(10):3674
Maffucci syndrome is a non-hereditary congenital condition that affects the skin and skeleton. Enchondromas (benign cartilage enlargements), bone abnormalities, and venous anomalies (hemangiomas) are all symptoms. Enchondromas occur as a result of mesodermal dysplasia and have the potential to become cancerous. They are most commonly found on the phalanges and long bones. Venous abnormalities commonly manifest themselves as soft lumps or tumors on the distal extremities. A 19-year-old boy presented with swellings on his fingers and left foot since the age of 5, along with a few bluish soft tissue swellings on his left heel. Multiple expansile lytic lesions and soft tissue swellings with phleboliths were seen on X-ray. Histology confirmed the diagnosis of hemangiomas and enchondromas. Soft tissue swellings were found to have hyper echoic areas, as well as modest marginal blood flow on Doppler, which could indicate hemangiomas. Maffucci syndrome was identified, and treatment with a multidisciplinary approach was initiated. Maffucci syndrome is a rare genetic illness reported in the literature less than 200 times. The enchondromas and hemangiomas have a strong link to malignant changes, with chondrosarcomas accounting for 30% of the associated malignancies. On X-ray, enchondromas are easily identified as osteolytic lesions with cortex thinning and endosteal scalloping while color Doppler ultrasound detects the presence of hemangiomas. Phleboliths are easily identified as small calcifications on X-rays. Radiographic examinations should be considered in patients presenting with bone or soft tissue swellings for an early diagnosis of Maffucci syndrome. 相似文献
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