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排序方式: 共有1033条查询结果,搜索用时 15 毫秒
61.
Comprehensive mutational scanning of the p53 coding region by two- dimensional gene scanning 总被引:2,自引:0,他引:2
A comprehensive mutational scanning test for the p53 coding region based on
multiplex PCR and two-dimensional DNA electrophoresis was designed and
evaluated. In a 2-step multiplex PCR, the p53 coding region (exons 2-11)
was amplified as a single 8646-bp fragment by long- distance PCR in step
one. This fragment served as a template for the subsequent co-amplification
of the individual exons in two multiplex groups in step two. The multiplex
products were then separated, first on the basis of size in non-denaturant
polyacrylamide gels and then on the basis of sequence by denaturing
gradient gel electrophoresis (DGGE). Primers for optimal PCR, melting
behavior and 2-D gel distribution were designed using a recently developed
computer program. The resulting two-dimensional gene scanning (TDGS) test
was evaluated by screening, in a blinded fashion, 29 coded DNA samples from
Li- Fraumeni syndrome patients with previously identified germline
mutations. All mutations were correctly detected. This assay provides an
accurate, cost-effective and non-radioactive method for simultaneous
mutational scanning of all p53 coding exons.
相似文献
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Flecainide and sotalol: a new combination therapy for refractory supraventricular tachycardia in children <1 year of age 总被引:3,自引:0,他引:3
Price JF Kertesz NJ Snyder CS Friedman RA Fenrich AL 《Journal of the American College of Cardiology》2002,39(3):517-520
OBJECTIVES: The goal of this study was to assess the efficacy and safety of the combination therapy of flecainide and sotalol for the treatment of refractory supraventricular tachycardia (SVT) in children <1 year of age. BACKGROUND: Supraventricular tachycardia in infants can be refractory to single-drug as well as standard combination medical therapy. Radiofrequency ablation (RFA) is the definitive treatment of refractory SVT; however, interventional therapy poses a high risk of morbidity and mortality in this age group. METHODS: A retrospective review was performed identifying infants who required flecainide and sotalol to control refractory SVT. Patient age, previous drug therapy, duration of treatment, flecainide levels and corrected QT intervals were recorded; 24 h Holter monitoring was utilized to gauge efficacy of treatment. Efficacy was defined as suppression of SVT to no more than rare nonsustained episodes or slowing of SVT to a clinically tolerable rate. RESULTS: Ten patients (median age: 29 days, range: 1 to 241 days) failed at least two antiarrhythmic agents including either flecainide or sotalol as single agents before initiating combination therapy. Efficacy was achieved in all patients. The failure rate for therapy was reduced from 100% to 0% (95% confidence interval: 0% to 26%). The median doses used were: flecainide 100 mg/m(2)/day (range: 40 to 150 mg/m(2)/day) and sotalol 175 mg/m(2)/day (range: 100 to 250 mg/m(2)/day). Median duration of therapy was 16 months (range: 5 to 35 months). No proarrhythmia occurred. CONCLUSIONS: The combination of flecainide and sotalol can safely and effectively control refractory SVT and may obviate the need for RFA in children <1 year. 相似文献
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Stephenson EA Collins KK Dubin AM Epstein MR Hamilton RM Kertesz NJ Alexander ME Cecchin F Triedman JK Walsh EP Berul CI 《Journal of cardiovascular electrophysiology》2002,13(10):1009-1014
INTRODUCTION: Recent studies in adult populations have revealed seasonal variation in the frequency of acute cardiovascular events, including life-threatening arrhythmias, demonstrating increased events during winter and early spring. Trends in the time of day that arrhythmias occur also were noted. We sought to establish whether pediatric and young adult congenital heart disease implantable cardioverter defibrillator (ICD) recipients have circadian or seasonal variability in shock frequency, similar to adult populations. METHODS AND RESULTS: Data from ICD patients at six pediatric centers in North America were analyzed to assess the timing of life-threatening arrhythmias. The populations consisted of children and adults with congenital heart disease and ICDs placed for malignant arrhythmias. Data were considered in 46 patients who received appropriate therapy (total 139 episodes) for ventricular tachycardia or ventricular fibrillation. Multiple variables were analyzed, including time of day, day of week, and month of year. In contrast to previously studied adult patients, fewer events occurred in the early morning (7.5%), with the most therapies occurring between 6 P.M. and midnight (35%). An increased frequency of therapies was observed in the fall and winter (September-January), representing 60% of all appropriate shocks. Unlike adult populations, Mondays did not have an increased frequency of malignant arrhythmias. CONCLUSION: Pediatric and adult congenital heart disease populations have moderate seasonal and 24-hour variation in ICD event rate, with some distinctly different peaks than those seen in typical adult ICD populations. These findings suggest circadian variation in arrhythmia vulnerability that may differ from conventional occupational, physical, or emotional stressors. (J Cardiovasc Electrophysiol, Vol. 13, pp. 相似文献
68.
Association of granulocyte-macrophage colony-stimulating factor with the crystalloid granules of human eosinophils 总被引:3,自引:1,他引:3
Levi-Schaffer F; Lacy P; Severs NJ; Newman TM; North J; Gomperts B; Kay AB; Moqbel R 《Blood》1995,85(9):2579-2586
We have previously shown that normal-density human peripheral blood eosinophils transcribe and translate mRNA for granulocyte-macrophage colony-stimulating factor (GM-CSF) and that the intracellular distribution was granular as assessed by light microscopy immunocytochemistry. The present study was conducted to confirm this apparent association between GM-CSF and the crystalloid granule using a subcellular fractionation method for human eosinophils and immunogold electron microscopy (EM). Highly purified (> 99%, by negative selection using anti-CD16 immunomagnetic microbeads) human peripheral blood eosinophils were obtained from four asthmatic subjects (not taking systemic medication), homogenized and density fractionated (5 x 10(7) cells/subject) on linear Nycodenz gradients. Twenty-four fractions were collected from each cell preparation and analyzed for marker enzyme activities as well as total protein. Dot blot analysis with specific monoclonal antibodies (MoAbs) was used to detect the eosinophil granule proteins major basic protein (MBP) and eosinophil cationic protein (ECP). An anti-CD9 MoAb was used as an eosinophil plasma membrane marker. Lactate dehydrogenase (LDH) was used as a cytosolic marker. Immunoreactivity for GM-CSF was detected by a specific enzyme-linked immunosorbent assay using a polyclonal antihuman GM-CSF antibody and confirmed by dot blot. GM-CSF coeluted with the cellular fractions containing granule markers (MBP, ECP, eosinophil peroxidase, hexosaminidase, and arylsulphatase), but not those containing cytoplasm (LDH+) or membrane (CD9+) markers. EM examination of pooled fractions associated with the peak of GM-CSF immunoreactivity confirmed that they contained crystalloid and small granules, but not plasma membrane. In addition, quantification, using immunogold labeling with an anti/GM-CSF MoAb, indicated preferential localization of gold particles over the eosinophil granule cores of intact cells. Thus, our results indicate that GM-CSF resides as a granule-associated, stored mediator in unstimulated human eosinophils. 相似文献
69.
S Desai T Diener BJ-K Tan NJ Lowry C Talukdar WM Chrusch S Wiebe 《The Canadian Journal of Infectious Diseases & Medical Microbiology》2014,25(4):227-228
The present article reports a case involving an immunocompetent, previously well child who, despite two previous doses of inactivated poliovirus vaccine, developed severe flaccid paralysis consistent with polio after receiving oral polio vaccine. 相似文献
70.
Background: Although semantic dementia (SD) is characterised by a multimodal loss of semantic knowledge, it has been demonstrated that lexical‐semantic representations are not equally disrupted in SD and that some categories may be recognised better than others. Little is known, however, about the pattern of the category‐specific comprehension deficits in SD and whether it differs from that of other forms of progressive aphasias. Aims: This exploratory study aimed to investigate the evolution of category‐specific deficits of single‐word comprehension in progressive aphasias. Methods & Procedures: A total of 19 patients with a clinical diagnosis of SD, 25 patients with primary progressive aphasia with agrammatic and relatively nonfluent speech (PPA), and 25 patients with Alzheimer's disease (AD) with aphasia were studied longitudinally with the Western Aphasia Battery (WAB). The Auditory Word Recognition subtest of the WAB was utilised to assess comprehension of words derived from different semantic categories. Outcomes & Results: The analysis revealed that, over time, category‐specific deficits of single‐word comprehension were seen in all three groups of patients. Participants with SD as well as those with PPA and AD were impaired on both pointing to fingers and the right–left orientation task. However, patients with SD were the only group that showed defective recognition of their own body parts. Interestingly, individuals with SD had no difficulties identifying colours, letters, and numbers, even during the follow‐up testing. In addition, in all three groups the extent of category‐specific deficits was associated with the severity of aphasia. Conclusions: These results indicate that category‐specific deficits of single‐word comprehension are frequently seen not only in patients with SD but also in individuals with PPA or AD, and that the extent of these deficits is associated with the severity of aphasia. However, the pattern of these deficits is often different in these three forms of neurodegenerative conditions and more dissociations between semantic categories are observed as each of these diseases progresses. 相似文献