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101.
《Movement disorders》2003,18(11):1240-1249
The identification of disease genes using family‐based approaches has provided important insights into the pathogenesis of Parkinson's disease (PD) demonstrating the importance of genetic studies on monogenic forms of the disease. We studied a large Cuban family with typical, late‐onset PD and probable autosomal dominant inheritance. Mean age at onset was 61.2 years (±12.53, 45–76). Other phenotypes such as essential tremor and atypical parkinsonism were observed in this family. We carried out a genome‐wide scan and linkage analyses. The genetic data were analyzed using a conservative model in which only patients with clinically definite or likely PD were considered affected, other phenotypes were regarded as “unknown.” Multipoint analyses yielded a maximum LOD of 2.26 between markers D19S221 and D19S840. Haplotype analysis showed a region on chromosome 19 shared by six of seven PD patients. The essential tremor phenotype and the atypical parkinsonism do not segregate with this haplotype, suggesting a different etiology. Our findings suggest the presence of a novel locus for PD on chromosome 19p13.3–q12. We propose that an oligogenic model with moderate contribution of two or three genes rather than a “pure” monogenic model might explain better the wide range in age at onset, the reduced penetrance and the phenotypical variability observed in PD families. © 2003 Movement Disorder Society 相似文献
102.
Platelet additive solutions (PASs) were first developed in the 1980s, and continued to be improved over the following years. The use of PASs as replacement for plasma has a number of benefits, both for the quality of the platelet concentrates and for the patients. However, some PASs have been associated with a lower platelet yield in the PCs, a shorter storage time, and a lower increment in the patient when compared to PCs in plasma. A number of reformulations of the PASs have taken place to counteract these disadvantages. Most PASs use acetate as nutrient for the platelets, which has the benefit of generating bicarbonate when oxidized by the platelets, thus supplying its own buffering capacity. Alternatively, glucose is used, but may cause deterioration of pH in the stored PCs due to the formation of lactic acid. Addition of other buffering substances, such as phosphate, can be added to ensure maintenance of neutral pH. An important finding was the inhibiting effect of potassium and magnesium on platelet activation. The initially developed PASs lacked these two ingredients and showed reduced storage times of the PCs in PAS when compared to those stored in plasma. However, when these constituents are included in the PAS, storage time is similar and even exceeds those seen for PCs in plasma. Considerable research is done in further formulating the optimal PAS. Bicarbonate is being considered as buffer for these PASs. Also, L-carnitine appears to have a favorable effect on stored platelets, including a reduction of platelet metabolism, and inhibition of apoptosis. Another area of optimization is lowering of plasma content needed for maintaining platelet quality. Where current PASs still need at least 30% residual plasma, there is a trend towards lowering the plasma content to less than 5% with the newer PASs. Preservation of purinergic platelet receptor functionality by ADP-degrading activities in plasma appears to play an important role in this respect. Development of PASs are usually based on in vitro studies alone. It is important to realize that only clinical studies can give definitive answers about the quality of platelets stored in PASs. Sofar, only limited clinical evaluations have been published that either studied the effectiveness of platelets in initially-developed PASs, or were specifically done in combination with pathogen reduction technologies. Thus, PASs seem to be an excellent replacement for (part of) the plasma when producing PCs, and allow extended storage with maintenance of quality, but more clinical studies are needed to substantiate in vitro results. 相似文献
103.
High frequency electrical stimulation by means of electrodes implanted into the brain has become an accepted technique for treatment of Parkinson's disease. The electrical field distribution normally inserted into the sub thalamic nucleus minimise abnormal brain activity. Square wave pulses of 1–3.6 V with duration of 60–90 μs at a frequency range of 130–185 pps are generally used. Every electrode unit consists of four cylindrical electrodes positioned in a row and can be switched on independently. This paper determines the contact impedance of the electrodes for different frequencies and proposes improvement to reduce the contact impedance between the electrodes and the brain. Measurements were performed by placing the electrodes in a tank filled with saline. Different frequencies were applied on two electrodes via a resistor. The current was measured through the resistor and the voltage was registered between one of the electrodes and a third non current carrying electrode. The obtained values were used to calculate the contact impedance. The result shows large contact impedance for the used frequency compared to the impedance of the treated tissue, which means that variation in contact impedance can result in variation in the electrical field applied to the tissue. 相似文献
104.
本实验将赖型钩端螺旋体(简称钩体)DNA基因库的克隆pCX7制备成 ̄(32)P-重组DNA探针,对8个不同血清群的17株问号状钩体、双曲钩体PatocⅠ株以及细螺旋体3055株DNA进行打点杂交;同时用15种DNA片断进行限制性内切酶谱分析。结果表明,该重组DNA具有问号状钩体种(Species)特异性,但与不同问号状钩体之间的同源性程度有差别;限制性内切酶谱分析发现pCX7重组DNA片段长约1.7kb,具有1个Bg1Ⅱ识别位点和3个BstB1识别位点。 相似文献
105.
48例非霍奇金淋巴瘤中的p53基因突变 总被引:1,自引:0,他引:1
采用ABC和PCR-SSCP法在48例NHL中研究p53基因外显子5~8中发生突变的类型、频率与突变型p53蛋白的表达以及它们与病理分型、恶性程度的相关性。结果:突变型p53蛋白在NHL中的阳性率为41.7%,其中在弥漫型大细胞性淋巴瘤(DLCL)为75%,在非DLCL为35%,两者差异显著(P<0.05);在p53蛋白表达阳性的NHL中PCRSSCP阳性主要见于DLCL,检出率为15%,在非DLCL中PCR-SSCP均为阴性(P<0.05)。表明国人NHL,尤其在恶性程度很高的DLCL中存在p53基因突变,各型NHL都有不同程度的突变型p53蛋白表达 相似文献
106.
癌基因c-fos、c-jun蛋白在鳞状细胞癌皮损中的表达及意义 总被引:3,自引:0,他引:3
目的 探讨癌基因c fos、c jun的表达与皮肤鳞癌发生和发展的关系。 方法 采用免疫组化法对 6 0例皮肤鳞癌的c fos、c jun的表达情况进行检测 ,并与正常皮肤组织进行对照。 结果 c fos、c jun在正常皮肤组织不表达 ,在皮肤鳞癌中的表达阳性率分别为 6 1.7%和 4 8.3% ,其表达水平与癌组织的分化程度有关 (P <0 .0 5 ) ,肿瘤的分化程度越高其表达水平越高。 结论 c fos、c jun的表达水平可作为判定皮肤鳞癌分化的指标。 相似文献
107.
S H Jee S Y Won J E Yun J E Lee J S Park S S Ji 《International journal of gynaecology and obstetrics》2004,85(3):301-308
OBJECTIVES: Although some studies have reported that the arginine isoform on codon 72 of p53 increases the susceptibility to invasive cervical cancer, such data remain controversial. The objective of this study was to quantitatively summarize the evidence for such a relationship. METHODS: Our data sources consisted of a MEDLINE search of the literature published before December 2002, bibliography review, and expert consultation. Thirty-seven studies met the inclusion criteria. Information on sample size, study design, Hardy-Weinberg equilibrium, and method of genotype determination was abstracted by two reviewers using a standardized protocol. The overall odds ratio (OR) of the p53 gene on invasive cervical cancer was estimated using the Mantel-Haenzel method. RESULTS: The overall OR (95% confidence interval) for cervical cancer among those with the homozygous mutant (Arg/Arg) was 1.2 (1.1-1.3, P=0.001) compared with those with the heterozygous mutant (Arg/Pro). By a cellular type of cervical cancer, the overall OR among those with Arg/Arg was statistically significant in adenocarcinomas (1.7, 1.1-2.6, P=0.024), but not in squamous cell carcinomas (1.1, 0.9-1.2, P=0.960), compared with Pro/Pro. Compared with Arg/Pro, the OR among those with Arg/Arg was statistically significant in HPV types 16 (1,5, 1.2-2.0, P=0.002). CONCLUSIONS: Overall, the p53 gene was associated with increased risk for invasive cervical cancer. However, the risk varied by country, cellular, and HPV type. 相似文献
108.
检测25例脑肿瘤中抑制癌基因P53突变情况。突用复合PCR,聚合酶链反应-=单链构象多态性分析法,统计学处理采用X^2检验。结果:P53基因总的突变率为44.0%,其中第5外显子突变率为28.0%,第6外显子突变率12.0%,第7外显子突变率为12.0%,第8外显子突变率16.0%;病理分级Ⅱ级及其以上突变为72.7%, 相似文献
109.
石棉相关肿瘤p53基因突变的免疫组化及PCR—SSCP研究 总被引:3,自引:0,他引:3
为了分析石棉相关肿瘤p53基因的突变特点,对石蜡包埋的石棉相关肿瘤p53基因突变体蛋白的表达进行了免疫组化观察,提取染色体DNA,对p53基因的第5、7、8外显子进行PCR-SSCP及测序分析。免疫组化观察发现:在分析的10例病例中有5例阳性。PCR-SSCP分析发现7例(8处)发生突变,其中4处集中在第8外显子上。5例腺癌中有4例发生p53基因突变。测序发现热点区突变。提示:石棉相关肿瘤p53基因突变率高。 相似文献
110.