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排序方式: 共有6146条查询结果,搜索用时 15 毫秒
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Emmi Helle Aldo Córdova-Palomera Tiina Ojala Priyanka Saha Praneetha Potiny Stefan Gustafsson Erik Ingelsson Michael Bamshad Deborah Nickerson Jessica X. Chong University of Washington Center for Mendelian Genomics Euan Ashley James R. Priest 《Genetic epidemiology》2019,43(2):215-226
Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes. 相似文献
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B. C. Beaudette-Zlatanova B. Whalen D. Zipris H. Yagita J. Rozing H. Groen C. D. Benjamin T. Hunig H. A. Drexhage M. J. Ansari J. Leif J. P. Mordes D. L. Greiner M. H. Sayegh A. A. Rossini 《American journal of transplantation》2006,6(5P1):894-902
Costimulatory signals regulate T-cell activation. To investigate the role of costimulation in autoimmunity and transplantation, we studied the BB rat model of type 1 diabetes. Diabetes-prone BB (BBDP) rats spontaneously develop disease when 55–120 days of age. We observed that two anti-CD28 monoclonal antibodies (mAb) with different functional activities completely prevented diabetes in BBDP rats. Anti-CD154 mAb delayed diabetes, whereas treatment with CTLA4-Ig or anti-CD80 mAb accelerated disease. Anti-CD86 or anti-CD134L mAbs had no effect. Diabetes resistant BB (BBDR) rats are disease-free, but >95% of them develop diabetes after treatment with polyinosinic-polycytidylic acid and an mAb that depletes Treg cells. In the induced BBDR model, anti-CD154 mAb delayed onset of diabetes, whereas CTLA4-Ig, anti-CD134L or either of the anti-CD28 mAbs had little or no effect. In contrast, blockade of the CD134-CD134L pathway was highly effective for preventing autoimmune recurrence against syngeneic islet grafts in diabetic BBDR hosts. Blockade of the CD40-CD154 pathway was also effective, but less so. These data suggest that the effectiveness of costimulation blockade in the treatment of type 1 diabetes is dependent on both the costimulatory pathway targeted and the mechanism of induction, stage, intensity and duration of the pathogenic process. 相似文献
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Distribution patterns of transforaminal injections in the cervical spine evaluated by multi-slice computed tomography 总被引:1,自引:1,他引:0
Transforaminal injections are sometimes used for the diagnosis and treatment of painful conditions in the lumbar and to a lesser degree in the cervical spine. The technique is most often used when investigating/treating radiculopathy caused by degenerative disease. But how selective are the nerve root blocks? What possible structures other than the intended nerve root are affected from such injections? This study was undertaken in order to try to answer these questions, as no study focusing on the possible spread from the transforaminal selective nerve root blocks in the cervical spine has been performed earlier. In three groups of patients, each group including three patients, we injected three different volumes (0.6, 1.1 and 1.7 ml) with a transforaminal technique in the cervical spine. In all the injections, a small amount of contrast media was added. The spread of the injections were then investigated using multi-slice computed tomography with reconstructions. The imaging revealed a possible effect on other nerve roots than the intended ones when a larger volume was used for the root blocks. The spread was related to the injected volume as well as to local anatomy (size of foraminal area). In this study, only 0.6-ml injections could be accepted for being selective enough for diagnostic investigations. 相似文献
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Olle Zetterström Christer Andersson Leif Eriksson ers Fredriksson Johan Friskopp Gunnar Heden Bernt Jansson Tord Lundgren Rolf Nilveus ers Olsson Stefan Renvert Lars Salonen Lars Sjöström ers Winell ers Östgren Stina Gestrelius 《Journal of clinical periodontology》1997,24(9):697-704
Abstract The aim of the present clinical trial was to test tolerability during 2 treatments with EMDOGAIN® in a large number of patients. An open, controlled study design in 10 Swedish specialist clinics was chosen, with a test group of 107 patients treated with EMDOGAIN® in connection with periodontal surgery at 2 surgical test sites per patient. The procedures were performed 2 to 6 weeks apart on one-rooted teeth with at least 4 mm deep intraosseous lesions. A control group of 33 patients underwent flap surgery without EMDOGAIN® at I comparable site. In total 214 test and 33 control surgeries were performed. Serum samples were obtained from test patients for analysis of total and specific antibody levels. 10 of the patients had samples taken before and after the first surgery. 56 other samples were taken after one treatment with EMDOGAIN®, and 63 after 2 treatments. None of the samples, not even from allergy-prone patients after 2 treatments, indicated deviations from established baseline ranges. This indicates that the immunogenic potential of EMDOGAIN® is extremely low when applied in conjunction with periodontal surgery. Comparison between the test and control groups demonstrated the same type and frequency of post-surgical experiences, i.e., reactions caused by the surgical procedure itself. Clinical probing and radiographic evaluation was performed at baseline and 8 months postsurgery. About half of the patients (44 test and 21 control) were also evaluated after 3 years. There was a significant difference between the test and control results at 8 months post surgery. and this difference had increased further at the 3 year follow-up. The 2.5–3 mm increase in attachment and bone level after treatment with EMDOGAIN® was of the same magnitude as seen in the studies with split-mouth design aiming for lest of effectiveness of EMDOGAIN®. 相似文献
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We present some important current applications of reconstructive microsurgery. This field is expanding rapidly and the techniques are finding application in many branches of surgery. There is a pressing need for educational programs and training in microsurgery, as well as for continued research.
Many of the procedures reviewed here have already been shown to substantially reduce costs, shorten hospitalization, and lessen patient disability; and as a result, several conventional procedures have been out-dated. We have stressed the concept that this is team surgery. To cover the needs of replantation and emergency free flaps around the clock, several micro-surgeons must work together in established centers, and the team must possess expertise from all the involved surgical specialities. This may imply revision of many organizational aspects of patient care. Replantation centers would provide the necessary educational bases and give an impetus to the development of microsurgery. 相似文献
Many of the procedures reviewed here have already been shown to substantially reduce costs, shorten hospitalization, and lessen patient disability; and as a result, several conventional procedures have been out-dated. We have stressed the concept that this is team surgery. To cover the needs of replantation and emergency free flaps around the clock, several micro-surgeons must work together in established centers, and the team must possess expertise from all the involved surgical specialities. This may imply revision of many organizational aspects of patient care. Replantation centers would provide the necessary educational bases and give an impetus to the development of microsurgery. 相似文献
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Endothelin modulation of neuroeffector transmission in rat and guinea pig vas deferens 总被引:4,自引:0,他引:4
N P Wiklund A Ohlén C U Wiklund P Hedqvist L E Gustafsson 《European journal of pharmacology》1990,185(1):25-33
The effects of endothelin-1 (human, porcine) on contractions induced by transmural nerve stimulation, exogenous ATP or noradrenaline, and on the release of [3H]noradrenaline were studied in guinea pig and rat vas deferens. Endothelin enhanced nerve-induced contractile responses, increased basal muscle tone and increased the contractile response to exogenous ATP in both guinea pig and rat vas deferens. Endothelin did not affect the contractile responses to exogenous noradrenaline. The calcium channel blocker felodipine antagonized the stimulating effects of endothelin in the rat vas deferens, whereas blockade of lipoxygenase and cyclooxygenase pathways by a combination of BW 755C and indomethacin was without effect. In rat vas deferens preparations preincubated with [3H]noradrenaline, endothelin inhibited the 3H overflow induced by transmural stimulation, although the contractile responses were enhanced by endothelin. Pretreatment with forskolin or felodipine did not abolish the endothelin inhibition of radiotracer overflow. In conclusion, endothelin can modulate adrenergic and purinergic neuroeffector transmission in both guinea pig and rat vas deferens via inhibitory prejunctional and stimulant postjunctional mechanisms. The stimulant postjunctional effect seemed to predominate in our experiments. 相似文献