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131.
本实验研究了甲硝唑诱导蚕豆根尖细胞微核的效应。实验表明:(1)浓度为0.1、6、12、40和500 mg/L甲硝唑均能使蚕豆根尖细胞微核率显著增加,且蚕豆根尖细胞微核率和甲硝唑浓度之间存在明显的剂量-效应关系;(2)甲硝唑能引起DNA损伤,具有分子诱变剂的性能。 相似文献
132.
D. Katie Wilkinson Edward T. Parkin Penny J. Harrison Gordon W. Stewart 《生物化学与生物物理学报:生物膜》2008,1778(1):125-132
In overhydrated hereditary stomatocytosis (OHSt), the membrane raft-associated stomatin is deficient from the erythrocyte membrane. We have investigated two aspects of raft structure and function in OHSt erythrocytes. First, we have studied the distribution of other membrane and cytoskeletal proteins in rafts by analysis of detergent-resistant membranes (DRMs). In normal erythrocytes, 29% of the actin was DRM-associated, whereas in two unrelated OHSt patients the DRM-associated actin was reduced to < 10%. In addition, there was a reduction in the amount of the actin-associated protein tropomodulin in DRMs from these OHSt cells. When stomatin was expressed in Madin-Darby canine kidney cells, actin association with the membrane was increased. Second, we have studied Ca2+-dependent exovesiculation from the erythrocyte membrane. Using atomic force microscopy and proteomics analysis, exovesicles derived from OHSt cells were found to be increased in number and abnormal in size, and contained greatly increased amounts of the raft proteins flotillin-1 and -2 and the calcium binding proteins annexin VII, sorcin and copine 1, while the concentrations of stomatin and annexin V were diminished. Together these observations imply that the stomatin-actin association is important in maintaining the structure and in modulating the function of stomatin-containing membrane rafts in red cells. 相似文献
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E.D. Weinberg 《Biometals》2002,15(4):347-350
Some heterozygote carriers of hemochromatosis HFE gene mutations become iron loaded with ensuing increased risk of disease and premature death. Contributing nutritional, behavioral and genetic factors are beginning to be identified. Carriers of HFE gene mutations should be advised to minimize contributing factors, if possible, and to have their iron values tested periodically. If values begin to rise, a schedule of phlebotomies should be considered. 相似文献
136.
遗传性血色病(Hereditary hemochromatosis,HHC)是一种罕见的常染色体隐性遗传病。本课题组招募了一个HHC的近亲婚配家系,包括一名患HHC的先证者以及同一代的4名不患HHC的成员。通过对该HHC先证者进行全外显子组测序,在目前已知的与遗传性血色病相关的5个基因(HAMP、HJV、TFR2、FPN和HFE)中,发现在铁调素调节蛋白(Hemojuvelin,HJV)的编码基因HJV上存在两个纯合突变(c.G18C和c.GC962_963AA)。其中,前者能够引起HJV蛋白发生p.Q6H的改变,但该突变的危害性较小,可能与血色病的发病无关;后者能够引起HJV蛋白发生p.C321X的改变,从而翻译出缺失糖基磷脂肌醇锚定结构域的截短型HJV蛋白。除了HJV基因上的纯合突变外,该先证者还携带了其他12个纯合突变,但这些突变的危害性均不强且其所在基因的功能与铁代谢无关。本实验室内部测序数据显示,在一般中国人群中不存在p.C321X突变,提示HJV基因上的p.C321X纯合突变可能是该HHC患者的致病性突变。与此相一致的是,4名不患HHC的家系成员中该位点为野生型纯合子或杂合子,均非p.C321X纯合子。文章首次报道了HJV p.C321X纯合突变可导致HHC,该结果将有助于遗传性血色病的基因诊断和产前咨询。 相似文献
137.
Prostate cancer is one of the most prevalent malignancies worldwide affecting the human male population. Different case-control, cohort or twin studies and segregation analyses point towards the presence of prostate cancer-susceptibility genes in the population. The studies have shown linkage of prostate susceptibility genes to multiple loci on chromosome 1 and single locus each on chromosomes 4, 8, 16, 17, 19, 20 and X chromosome. However, differences right from the mode of inheritance (autosomal dominant or X-linked recessive) to the target genes exist. There have been reports supporting no or weak linkage to these loci as well. Also, region (environmental factors), age and dietary habits have implications in different aspects of the disease. The important targets for treating prostate cancer are androgens and estrogen (synthesized from androgens by the action of enzyme aromatase) owing to their involvement in development and progression of prostate cancer. Further, prostate gland needs androgens (male hormones) for its normal maintenance and functioning. Besides, radiation therapy and surgical methods have also been used. The emerging areas include identifying and preparing successful vaccines from candidate peptides and gene therapy in several forms. This review deals with the paradox of linkage analyses and the various approaches in practice for treatment and management of prostate cancer. 相似文献
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Riccio M Di Giaimo R Pianetti S Palmieri PP Melli M Santi S 《Experimental cell research》2001,262(2):84-94
Cystatin B is an anti-protease implicated in myoclonus epilepsy, a degenerative disease of the central nervous system. In vitro, cystatin B interacts with and inhibits proteases of the cathepsin family. Confocal microscopy analysis of the subcellular localization of cystatin B and cathepsin B shows that, in vivo, the two proteins are concentrated in different cell compartments. In fact, cystatin B is found mainly in the nucleus of proliferating cells and both in the nucleus and in the cytoplasm of differentiated cells, while cathepsin B, in either case, is essentially cytoplasmic. However, colocalization of cystatin and cathepsin B is observed in the isolated cell matrix and in the nuclear scaffold of differentiated neuroblastoma cells but not of proliferating cells. This suggests that at least a fraction of cystatin B is bound to the protease in differentiated cells. The electron microscopy analysis of the cell matrix confirms the observation made with confocal microscopy. The cellular activity of cathepsin B was analyzed with a fluorogenic cytochemical assay. A fluorescent signal is observed in the cytoplasm of proliferating cells but is undetectable in the cytoplasm of differentiated cells, suggesting that cathepsin B is active mainly during the cell cycle. This result is consistent with the separate compartimentalization of cystatin B and cathepsin B that we have observed in growing cells. 相似文献
140.
Severe neurodegradative brain diseases, like Alzheimer, are tightly linked with proteolytic activity in the human brain. Proteinases expressed in the brain, such as human trypsin IV, are likely to be involved in the pathomechanism of these diseases. The observation of amyloid formed in the brain of transgenic mice expressing human trypsin IV supports this hypothesis. Human trypsin IV is also resistant towards all studied naturally occurring polypeptide inhibitors. It has been postulated that the substitution of Gly193 to arginine is responsible for this inhibitor resistance. Here we report the X-ray structure of human trypsin IV in complex with the inhibitor benzamidine at 1.7 A resolution. The overall fold of human trypsin IV is similar to human trypsin I, with a root-mean square deviation of only 0.5 A for all C(alpha) positions. The crystal structure reveals the orientation of the side-chain of Arg193, which occupies an extended conformation and fills the S2' subsite. An analysis of surface electrostatic potentials shows an unusually strong clustering of positive charges around the primary specificity pocket, to which the side-chain of Arg193 also contributes. These unique features of the crystal structure provide a structural basis for the enhanced inhibitor resistance, and enhanced substrate restriction, of human trypsin IV. 相似文献