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31.
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Analysis of K-<Emphasis Type="Italic">ras</Emphasis> Codon 12 Mutation in Flat and Nodular Variants of Serrated Adenoma in the Colon 总被引:4,自引:0,他引:4
Higashidani Y Tamura S Morita T Tadokoro T Yokoyama Y Miyazaki J Yang Y Takeuchi S Taguchi H Onishi S 《Diseases of the colon and rectum》2003,46(3):327-332
PURPOSE: The developmental process of serrated adenomas is obscure, and the importance of genetic alterations has not been elucidated clearly. The possibility that the developmental process and genetic alterations of serrated adenomas could differ from those of ordinary tubular adenomas was explored in this work.
METHODS: Serrated adenomas were obtained by endoscopic resection (n = 57) and divided into two groups: flat (n = 10) and nodular (n = 47). Mutation of the K-ras gene was analyzed by enriched polymerase chain reaction–enzyme-linked mini-sequence assay, which can detect not only the presence of a mutation but also the mutation type of K-ras codon 12 with high sensitivity. Methylation-specific polymerase chain reaction was performed with specific primers for the DNA repair gene O6-methylguanine-DNA methyltransferase.
RESULTS: Serrated adenomas located in the rectum were more likely to have a K-ras mutation (9/12, 75 percent), whereas serrated adenomas of the flat type were less likely to have one (1/10, 10 percent). Furthermore, nodular serrated adenomas that occurred in the rectum possessed a high frequency of K-ras gene codon 12 point mutation (8/10, 80 percent) despite an overall frequency of 46.8 percent (22/47). A mutation of the K-ras codon 12 gene was detected in 23 (40.4 percent) of 57 serrated adenomas. Three types of point mutations of codon 12 were detected, with the mutation of GAT being observed most frequently.
CONCLUSIONS: This study shows that development of nodular serrated adenomas may depend on the mutation of the K-ras codon 12 gene, whereas development of flat serrated adenomas may not. Additionally, serrated adenomas that occur in the rectum are closely related to the mutation of the K-ras codon 12 gene. K-ras mutations in serrated adenomas may be unaffected by the epigenetic silencing of O6-methylguanine-DNA methyltransferase by promoter hypermethylation. 相似文献
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Jarred G. Gillett Glen A. Lichtwark Roslyn N. Boyd Lee A. Barber 《Archives of physical medicine and rehabilitation》2018,99(5):900-906.e1
Objective
To investigate the relation between lower limb muscle strength, passive muscle properties, and functional capacity outcomes in adults with cerebral palsy (CP).Design
Cross-sectional study.Setting
Tertiary institution biomechanics laboratory.Participants
Adults with spastic-type CP (N=33; mean age, 25y; range, 15–51y; mean body mass, 70.15±21.35kg) who were either Gross Motor Function Classification System (GMFCS) level I (n=20) or level II (n=13).Interventions
Not applicable.Main Outcome Measures
Six-minute walk test (6MWT) distance (m), lateral step-up (LSU) test performance (total repetitions), timed up-stairs (TUS) performance (s), maximum voluntary isometric strength of plantar flexors (PF) and dorsiflexors (DF) (Nm.kg?1), and passive ankle joint and muscle stiffness.Results
Maximum isometric PF strength independently explained 61% of variance in 6MWT performance, 57% of variance in LSU test performance, and 50% of variance in TUS test performance. GMFCS level was significantly and independently related to all 3 functional capacity outcomes, and age was retained as a significant independent predictor of LSU and TUS test performance. Passive medial gastrocnemius muscle fascicle stiffness and ankle joint stiffness were not significantly related to functional capacity measures in any of the multiple regression models.Conclusions
Low isometric PF strength was the most important independent variable related to distance walked on the 6MWT, fewer repetitions on the LSU test, and slower TUS test performance. These findings suggest lower isometric muscle strength contributes to the decline in functional capacity in adults with CP. 相似文献35.
Absorption,distribution, metabolism and excretion of novel phosphodiesterase type 4 inhibitor ASP3258 in rats 下载免费PDF全文
Yoshiaki Ohtsu Takuya Sonoda Yoko Susaki Toshifumi Tohda Yasuhisa Fukunaga Takafumi Iwatsubo Kiyoshi Noguchi 《Biopharmaceutics & drug disposition》2015,36(1):34-48
The potent and selective phosphodiesterase 4 inhibitor ASP3258 is a novel therapeutic agent for asthma and chronic obstructive pulmonary disease (COPD). After a single oral administration to rats, ASP3258 is rapidly absorbed with a bioavailability of 106%. In situ absorption data indicated that ASP3258 is mainly absorbed in the small intestine. Tissue distribution data after oral administration of 14C‐ASP3258 showed rapid and extensive distribution to various tissues. Excluding the gastrointestinal tract, the tissues with the highest concentrations were liver, heart and plasma. Liquid chromatography‐nuclear magnetic resonance spectroscopy data revealed that O‐glucuronidation of the carboxylic acid moiety of ASP3258 (formation of an acyl glucuronide) plays a key role in metabolism. No indication was found that the acyl glucuronide reacted with proteins in plasma or tissues. When 14C‐ASP3258 was orally administered to intact rats, urinary and fecal excretion accounted for 1.3% and 100.6% of the administered radioactivity, respectively. After a single oral administration of 14C‐ASP3258 to bile‐cannulated rats, urinary and biliary excretion accounted for 0.7% and 93.8% of the administered radioactivity, respectively. These findings suggest that fecal excretion via bile plays an important role in the elimination of ASP3258‐derived radioactivity. In vitro metabolic profiles were relatively similar among the species examined, suggesting that our findings in rats may help us to understand pharmacokinetics, efficacy and safety profiles in humans and other species. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
36.
目的分析深圳地区人群的αβ复合型地贫及非缺失型α-地贫的常见基因突变类型及血液学特征。方法收集2012年7月-2013年1月来我院中心实验室进行地贫基因检测的地贫疑似患者。检测中国人群中最常见的17种β-地贫突变、3种α-地贫点突变及3种缺失型β-地贫基因改变。并对阳性病例进行血液学分析。结果236例经基因确诊为地贫的患者中有非缺失型α基因突变12例,WS位点突变频率最高;αβ复合型地贫11例,CD41—42杂合突变合并-^SEA/αα最常见。结论深圳地区αβ复合型地贫发生率为4.7%,略高于全省平均水平;最常见的非缺失型α地贫突变为WS位点突变,与先前文献报道略有不同。 相似文献
37.
《The British journal of oral & maxillofacial surgery》2020,58(1):25-33
Tumour necrosis factor-α (TNF-α) inhibitors are increasingly being used as immunomodulators to manage inflammatory conditions such as rheumatoid arthritis and Crohn’s disease. Reported serious side effects include an increased incidence of lymphoma and greater susceptibility to infections such as tuberculosis. The aim of this systematic review was to find out whether there is an associated risk of medication-related osteonecrosis of the jaw (MRONJ). Three authors independently searched PubMed, MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials for published reports of oral osteonecrosis (ONJ) or osteomyelitis (OM) in patients who took anti TNF-α drugs and had no history of antiangiogenic agents or antiresorptive treatment. All types of studies on humans treated with TNF-α inhibitors were considered. Only six were eligible for analysis, and all were independently assessed for risk of bias. They included six patients with ONJ or OM that was attributed solely to TNF-α inhibitors. The most common site of ONJ was the posterior mandible (n = 5). The mean (SD) duration of anti-TNF-α treatment before the development of bony lesions was 62.5 (47.4) months. Invasive surgery was reported as a precipitating factor in five cases, and the ONJ/OM resolved with conservative management in five. Although all the studies were judged to be at high risk of bias, the limited data suggest that some patients will potentially develop ONJ/OM as a result of treatment with TNF-α inhibitors. Studies of higher quality are now needed to establish the relative risk of MRONJ in patients who take them. 相似文献
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Byung Sun Lee Young Gyu Kim Dong Ho Kim Mou Seop Lee 《Journal of Korean Neurosurgical Society》2013,54(3):261-264
We report a long-term survival case of a primary malignant intracerebral nerve sheath tumor (MINST) occurring in the right frontal lobe of a 13-year old boy. After the gross total resection (GTR), we have performed radiation therapy but it recurred 50 months after the surgery, so the second GTR was performed. Later, second tumor recurrence was found 4 months after the second surgery. Subsequently the third GTR, radiotherapy, and chemotherapy were carried out. At present, the patient has been remaining alive for 77 months without evidence of tumor recurrence. According to the previous reports, the primary MINST is very rare : there are only 8 cases reported. It is also a fast-growing, invasive tumor with poor outcome. This is the first case that had no recurrence for 50 months after the surgery among the reported cases that had been followed up for more than 5 years. It is supposed that a period of recurrence free survival after GTR and low mitotic activity are associated with the patient''s prognosis. A GTR followed by adjuvant radiation therapy and chemotherapy will be recommended to patients of MINST. 相似文献