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101.
Lee L. Eckhardt MD Amanda L. Farley MS Esther Rodriguez MD Karen Ruwaldt BS Daniel Hammill David J. Tester BS Michael J. Ackerman MD PhD Jonathan C. Makielski MD 《Heart rhythm》2007,4(3):323-329
BACKGROUND: Loss-of-function mutations in the KCNJ2 cause approximately 50% of Andersen-Tawil Syndrome (ATS) characterized by a classic triad of periodic paralysis, ventricular arrhythmia, and dysmorphic features. Do KCNJ2 mutations occur in patients lacking this triad and lacking a family history of ATS? OBJECTIVES: The purpose of this study was to identify and characterize mutations in the KCNJ2-encoded inward rectifier potassium channel Kir2.1 from patients referred for genetic arrhythmia testing. METHODS: Mutational analysis of KCNJ2 was performed for 541 unrelated patients. The mutations were made in wild type (WT) and expressed in COS-1 cells and voltage clamped for ion currents. RESULTS: Three novel missense mutations (R67Q, R85W, and T305A) and one known mutation (T75M) were identified in 4/249 (1.6%) patients genotype-negative for other known arrhythmia genes with overall incidence 4/541 (0.74%). They had prominent U-waves, marked ventricular ectopy, and polymorphic ventricular tachycardia but no facial/skeletal abnormalities. Periodic paralysis was present in only one case. Outward current was decreased to less than 5% of WT for all mutants expressed alone. Co-expression with WT (simulating heterozygosity) caused a marked dominant negative effect for T75M and R82W, no dominant negative effect for R67Q, and a novel selective enhancement of inward rectification for T305A. CONCLUSIONS: KCNJ2 loss of function mutations were found in approximately 1% of patients referred for genetic arrhythmia testing that lacked criteria for ATS. Characterization of three new mutations identified a novel dominant negative effect selectively reducing outward current for T305A. These results extend the range of clinical phenotype and molecular phenotype associated with KCNJ2 mutations. 相似文献
102.
单宁酸处理带瓣牛颈静脉的生物学评价 总被引:1,自引:0,他引:1
目的从生物学角度评价单宁酸处理的带瓣牛颈静脉是否符合国家医用材料的要求。方法带瓣牛颈静脉经单宁酸处理后按国家医用材料的要求进行浸提液的制备、细胞毒性试验、过敏试验、皮内刺激试验、原发性皮肤刺激试验、溶血试验、急性全身毒性试验及热原试验等生物学评价试验。试验方法均参照《医用有机硅材料生物学评价试验方法》GB/T16175-1996。结果培养的L-929小鼠成纤维细胞经含浸提液的培养基培养后形态良好,增值旺盛,材料细胞毒性评级为0~1。无皮肤刺激反应和过敏反应,皮内刺激试验PⅡ(原发性刺激指数)为0.4,和阴性对照组差异无统计学意义。全身毒性实验受试动物未出现毒性症状。溶血试验溶血率0.7%,符合国家标准(〈5%)。热原试验经中国药品生物制品检定所检定,单宁酸处理后带瓣牛颈静脉无热原(样品批号:060802017)。结论单宁酸处理的带瓣牛颈静脉符合国家医用材料的要求,可以植入人体。 相似文献
103.
S. Doğru-Abbasoğlu G. Aykaç-Toker H. A. Hanagasi H. Gürvit M. Emre M. Uysal 《Neurological sciences》2007,28(1):31-34
Abstract Alzheimer's disease (AD) is defined pathologically by the presence of β-amyloid plaques, neurofibrillary tangles and extensive
neuronal loss. Evidence indicates that increased DNA damage may contribute to neuronal loss in AD. Recently, it has been shown
that in AD neurons have a reduced capacity for some types of DNA repair. Polymorphisms in DNA repair genes may be associated
with differences in repair efficiency of DNA damage. Variants of several DNA repair genes, including the base excision repair
gene XRCC1, have been described previously. We hypothesised that Arg194Trp polymorphism of XRCC1 gene may contribute to genetic susceptibility for AD. In order to test this hypothesis, we investigated
Arg194Trp polymorphism at the XRCC1 gene in the DNA samples of 98 patients with AD and 95 healthy subjects. The frequency of the Trp allele was more pronounced among cases (11.2%) compared with controls (5.8%). On combining the homozygous and heterozygous
variants of each codon, the variants seemed to be at twofold risk of AD, although the risk estimates were not statistically
significant (OR=1.95, 95% CI 0.88–4.34, p=0.09). In addition, the 194Trp allele revealed a borderline significance (OR=2.05, 95% CI 0.96–4.37, p=0.056). According to our results, it may be speculated that the polymorphic variants of XRCC1 codon 194 have a role in the
development of AD. 相似文献
104.
P. A. da Silva M. M. S. Boffo I. G. de Mattos A. B. S. Silva J. C. Palomino A. Martin H. E. Takiff 《Clinical microbiology and infection》2006,12(3):293-296
Rapid, accurate and inexpensive methods are essential to detect drug-resistant Mycobacterium tuberculosis and allow timely application of effective treatment and precautions to prevent transmission. The proportion method, the MTT and Alamar Blue redox methods, and the D29 mycobacteriophage assay, were compared for their ability to detect resistance to isoniazid and rifampicin. When tested against a panel of known M. tuberculosis strains, the redox methods and the D29 assay showed good sensitivity and specificity compared to the proportion method, suggesting that they could be useful alternatives for identifying multidrug resistance in M. tuberculosis. 相似文献
105.
Anthony J Linz 《The Journal of asthma》2007,44(5):347-355
The differential diagnoses of persistent nonproductive cough include numerous pulmonary and nonpulmonary organic disorders as well as functional illnesses. Many diseases can cause cough, and several studies have shown asthma among the most common etiologies associated with chronic cough in adult nonsmokers, as well as children. Psychogenic cough and its relationship to asthma and other asthma-like illnesses is complex since distinct maladies with similar features may coexist individually or in combination in any given patient. While chronic cough may occur as a sole presenting manifestation of bronchial asthma in all age groups, recent findings suggest that most children with persistent cough without other respiratory symptoms do not have asthma. Since several organic, as well as functional diseases, may present with persistent cough as their sole manifestation in either adults or children, cough should not be used as a single or major determinant to diagnose and treat asthma, especially when empirically focused therapy trials fail. Given the range of illnesses causing cough, no single management guideline can be expected to be universally effective. 相似文献
106.
本文对药品检验机构建立和完善质量体系的重要性,质量体系的内涵,建立和完善质量体系应注意的主要问题进行了分析并提出了建议。 相似文献
107.
眼刺激试验替代方法研究进展 总被引:2,自引:0,他引:2
由于动物眼刺激试验 (Draizetest)本身存在的问题和“3R”运动的兴起 ,各国广泛开展了动物眼刺激试验替代方法的研究和验证试验。各种替代方法作用机制不一 ,优缺点各异 ,故需要一组互补性体外试验来对化学物质的眼刺激性进行评价 相似文献
108.
In the oomycete, Phytophthora infestans, mating type is determined by a locus that segregates in a non-Mendelian manner consistent with its linkage to a system of
balanced lethals. The significance of this unusual phenomenon was addressed by studying the segregation patterns of DNA markers
linked to mating type in the related species, P. parasitica. This was done using loci identified by either RAPD analysis of P. parasitica crosses or by cross-hybridization with RFLP markers linked to mating type in P. infestans. The resulting data revealed that, unlike P. infestans, mating type in P. parasitica was regulated by a locus displaying Mendelian segregation. An improved model for mating-type determination in Phytophthora is presented.
Received: 21 October 1996 / 7 April 1997 相似文献
109.
R Dixon AM Hughes K Nairn M Sellers JV Kemp RA Yates 《Cephalalgia : an international journal of headache》1998,18(7):468-475
Zolmitriptan (ZomigTM ) is a 5HT1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination. 相似文献
110.
钩体基因疫苗对豚鼠延髓原癌基因表达的影响 总被引:1,自引:1,他引:0
我们的研究已表明,赖型017株钩体外膜疏水蛋白OmpL39是稳定的免疫原,在此我们分别用OmpL39与钩体死菌苗和生理盐水对照免疫豚鼠,研究OmpL39的免疫保护作用和免疫机理,对OmpL39的抗原特异性刺激引起中枢原癌基因(Cfos基因)表达进行了观察。结果表明,OmpL39在豚鼠体内能产生高效价的阳性抗体,免疫保护率为100%。在OmpL39对中枢Cfos基因表达的影响中,我们观察到OmpL39免疫的豚鼠较空白和死菌苗组Cfos表达明显少于死菌苗组和空白对照组(p<005)。提示OmpL39能特异性地抑制Cfos基因的表达,减轻强毒钩体对动物体内的病理损伤,有较死菌苗强的免疫保护作用。 相似文献