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Bianconi SE Conley SK Keil MF Sinaii N Rother KI Porter FD Stratakis CA 《American journal of medical genetics. Part A》2011,(11):2732-2738
Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation syndrome due to mutations of the 7-dehydrocholesterol reductase gene (DHCR7), which leads to a deficiency of cholesterol synthesis and an accumulation of 7-dehydrocholesterol. The SLOS clinical spectrum ranges from multiple major malformations to a mild phenotype with minor anomalies and intellectual disability. Several children with SLOS and adrenal insufficiency have been described. We performed ovine corticotropin (oCRH) testing in 35 SLOS patients and 16 age- and gender-matched controls. We reviewed prior adrenocorticotropin (ACTH) stimulation tests of our SLOS patients (19 of 35 available) and reviewed results of ACTH stimulation tests from 10 additional SLOS patients. Results from oCRH testing showed that patients with SLOS had significantly higher ACTH baseline values than healthy controls (24.8 ± 15.3 pg/ml vs. 17.8 ± 7.5 pg/ml, P = 0.034). However, no statistically significant differences were noted for peak ACTH values (74.4 ± 35.0 pg/ml vs. 64.0 ± 24.9 pg/ml, P = 0.303) and for baseline (14.2 ± 7.8 mcg/dl vs. 14.2 ± 6.3 mcg/dl, P = 0.992) and peak cortisol values (28.2 ± 7.9 mcg/dl vs. 24.8 ± 8.1 mcg/dl, P = 0.156). The area-under-the-curve (AUC) was not significantly different in SLOS patients compared to controls for both ACTH (250.1 ± 118.7 pg/ml vs. 195.3 ± 96.6 pg/ml, P = 0.121) as well as cortisol secretion (83.1 ± 26.1 mcg/dl vs. 77.8 ± 25.9 mcg/dl, P = 0.499). ACTH stimulation test results were normal in 28 of 29 tests. The individual with the abnormal test results had subsequent normal oCRH tests. The slightly increased baseline ACTH level seen during oCRH testing may be due to compensated adrenocortical insufficiency. However, we were able to show that our patients with SLOS had an adequate glucocorticoid response, and thus, in mild to moderate cases of SLOS stress steroid coverage may not be warranted. 相似文献
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Emmett Hegarty Ciara Campbell Ektor Grammatopoulos Martyn Sherriff Martyn T. Cobourne 《Journal of orthodontics》2017,44(2):90-96
Objective: To investigate video content on YouTube? related to orthognathic surgery.Materials and methods: YouTube? was searched using the terms: orthognathic surgery; orthodontic surgery; jaw surgery; jaw corrective surgery. Inclusion criteria included English language; primary content orthognathic surgery and acceptable audio-visual quality. Videos were sorted into the top 50 for each search term by view-count and into an overall top 60 from the four searches. The following parameters were recorded for each video: number of views; likes; dislikes; source; primary intention. Each was classified according to information content as ‘excellent’, ‘moderate’ or ‘poor’. A pre-determined list of orthognathic surgery-related information domains was also evaluated.Results: The top 60 videos had a combined total of 6,986,141 views. Videos predominantly involved patients describing their personal experience (41.67%) with the majority positively biased (61.67%). Only 9.17% of videos were classified as having excellent general information content and 55.83% were rated as poor. Surgical procedures were described in 45% whilst the need for pre- and post-surgical orthodontics was discussed in 33% and 16%, respectively. Post-operative paraesthesia was discussed in 17.5% of videos outcome.Conclusions: Video content on YouTube? relating to orthognathic surgery is substandard and patients should be advised to view it with caution. 相似文献
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Lucianne Groenink Elisabeth Y. Bijlsma Meg J. V. van Bogaert Ronald S. Oosting Berend Olivier 《Psychopharmacology》2011,214(1):353-365
Rationale
Early life stress is a risk factor for the development of psychopathology in later life. Consequences of adverse life events, however, may depend on the genetic makeup of an individual. Reduced serotonin1A receptor function may predispose to the development of anxiety disorders. 相似文献69.
Nan Zhang Rebecca E Sadun Robyn S Arias Meg L Flanagan Suzanne M Sachsman Yu-Chih Nien Leslie A Khawli Peisheng Hu Alan L Epstein 《Clinical cancer research》2007,13(9):2758-2767
Introduction: CD137L is a member of the tumor necrosis factor superfamily that provides a costimulatory signal to T cells. In this study, two novel CD137L fusion proteins were produced and compared with the CD137 agonist antibody 2A. Materials and Methods: Murine CD137L was linked to the COOH terminus of either the Fc fragment of immunoglobulin (untargeted version) or TNT-3 (targeted version), an antibody that binds to necrotic regions of tumors. Groups of mice bearing established Colon 26 tumors were then treated daily x 5 with each fusion protein or 2A to determine their immunotherapeutic potential. RESULTS: Both fusion proteins retained CD137L activity in vitro and TNT-3/CD137L showed tumor-binding activity by biodistribution analysis in tumor-bearing mice. The fusion proteins also produced similar responses in vivo at the 1 nmol per dose range and showed a 60% (TNT-3/CD137L) or 40% (Fc/CD137L) survival of treated mice at 150 days after tumor implantation, similar to the effects of 2A. Morphologic and immunohistochemical analyses showed massive central necrosis and infiltration of granzyme B-positive cells in necrotic areas and viable peripheral regions of treated tumors. Finally, cell depletion studies showed that CD137L-mediated tumor regression was CD8(+) T cell dependent. CONCLUSIONS: From these studies, it was determined that both targeted and untargeted CD137L fusion proteins showed effective antitumor activity, but that the targeted version was more potent. Therefore, the use of the natural CD137 ligand is a promising approach to the treatment of solid tumors by virtue of its ability to produce physiologic costimulation within the tumor, limiting side effects often seen with agonist antibody therapies. 相似文献
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Expansion of peripheral blood CD5+ B cells is associated with mild disease in chronic hepatitis C virus infection 总被引:6,自引:0,他引:6
Curry MP Golden-Mason L Nolan N Parfrey NA Hegarty JE O'Farrelly C 《Journal of hepatology》2000,32(1):121-125
BACKGROUND/AIMS: Hepatitis C virus (HCV) infection is associated with the development of chronic liver disease and extra-hepatic manifestations, which include autoantibody production, immune-mediated diseases such as cryoglobulinaemia and B-cell lymphoproliferation. Recent identification of intra-hepatic clonal B cells capable of rheumatoid factor production, selective infection of B cells over T cells and of an HCV receptor on B lymphocytes strongly supports a central role for these cells in the immune response to HCV infection. In particular, CD5+ B cells which are capable of producing natural antibodies with autoreactive specificities are likely to be important in the development of HCV-associated autoimmunity and lymphoproliferation. METHODS: We have investigated the presence of CD5+ B cells in a unique cohort of HCV-infected women who were infected with a single inoculum of HCV genotype 1b following immunisation with contaminated anti-D immunoglobulin in 1977. RESULTS: CD5+ B cells are significantly increased in chronic HCV infection (37.66+/-1.92%) as compared with those with resolved infection (25.33+/-1.90%). High levels of CD5+ B cells were associated with the production of rheumatoid factor. The number of peripheral blood CD5+ B cells correlated negatively with histological activity index. CONCLUSIONS: The expansion of this B cell population in patients with active HCV infection may give rise to immune-mediated sequelae associated with HCV infection. This expanded population of CD5+ B cells may protect against the development of progressive liver disease. 相似文献