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21.
Wei SC Su YN Tsai-Wu JJ Wu CH Huang YL Sheu JC Wang CY Wong JM 《Journal of biomedical science》2004,11(2):260-265
Colorectal cancer has become the third leading cause of death from cancer in Taiwan. Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease characterized by the presence of multiple adenomatous polyps in the colon and rectum. The gene responsible for FAP(APC) was cloned in 1991. Extensive analyses of the mutation spectra in FAP kindreds have been performed in different countries, but the results have been highly variable (30–80%). In this study, we used denaturing high-performance liquid chromatography (DHPLC) followed by automatic sequencing in an effort to establish the mutation spectrum of APC from DNA of peripheral blood cells. Among the 6 FAP probands analyzed, mutations were detected in 3 (50%), 2 of which were novel. The first novel mutation was at codon 2166, with a C to T transition, resulting in a stop codon. The second novel mutation was at codon 1971, with a C to G transversion, resulting in an amino acid change from serine to cysteine. The third mutation involved an A insertion in the sequence of -AAAAAA- at codons 1554–1556, which created a downstream stop codon (codon 1558). This study is the first to report mutation analysis in Taiwanese FAP probands. 相似文献
22.
Role of Smad4 (DPC4) inactivation in human cancer 总被引:23,自引:0,他引:23
The tumor suppressor gene Smad4 (DPC4) at chromosome 18q21.1 belongs to the Smad family, which mediates the TGFbeta signaling pathway suppressing epithelial cell growth. This review summarizes the mutational events of the Smad4 gene in human cancer. The Smad4 gene is genetically responsible for familial juvenile polyposis, an autosomal dominant disease characterized by predisposition to gastrointestinal polyps and cancer. In this syndrome, polyps are formed by inactivation of the Smad4 gene through germline mutation and loss of the unaffected wild-type allele. In pancreatic and colorectal cancer, inactivation of the Smad4 gene through homozygous deletion or intragenic mutation occurs frequently in association with malignant progression. However, mutation of this gene is seen only occasionally in the rest of human cancers. The majority of Smad4 gene mutations in human cancer are missense, nonsense, and frameshift mutations at the mad homology 2 region (MH2), which interfere with the homo-oligomer formation of Smad4 protein and the hetero-oligomer formation between Smad4 and Smad2 proteins, resulting in disruption of TGFbeta signaling. Supporting evidence for the above observation was provided by genetically manipulated mice carrying either a heterozygote of the Smad4 gene or a compound heterozygote of the Smad4 and APC genes, which develop either gastrointestinal polyps/cancer mimicking familial juvenile polyposis or progressed colorectal cancer, respectively. 相似文献
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In experiments on rats under urethane anesthesia, we studied how microinjections of vasopressin into the spinal trigeminal nucleus influence jaw-opening reflexes (JOR): nociceptive JOR, induced by stimulation of the tooth pulp, and non-nociceptive JOR, evoked by stimulation of A fibers of the infraorbital nerve. It was shown that injection of 10 M vasopressin resulted in a pronounced decrease (by 45-50%) in the nociceptive JOR amplitude for 25-30 min, whereas the non-nociceptive JOR dropped only by 8-10% for 11-13 min. It is concluded that vasopressin predominantly affects the nociceptive JOR; this fact is obviously related to a central analgesic effect of this peptide. 相似文献
25.
Ferri A Gabbianelli R Casciati A Paolucci E Rotilio G Carrì MT 《Journal of neurochemistry》2000,75(2):606-613
Calcineurin (CN) is a protein phosphatase involved in a wide range of cellular responses to calcium-mobilizing signals, and a role for this enzyme in neuropathology has been postulated. We have investigated the possibility that redox modulation of CN activity is relevant to neuropathological conditions where an imbalance in reactive oxygen species has been described. We have monitored CN activity in cultured human neuroblastoma SH-SY5Y cells and obtained evidence that CN activity is promoted by treatment with ascorbate or dithiothreitol and impaired by oxidative stress. Evidence for the existence of a redox regulation of this enzyme has been also obtained by overexpression of wild-type antioxidant Cu,Zn superoxide dismutase (SOD1) that promotes CN activity and protects it from oxidative inactivation. On the contrary, overexpression of mutant SOD1s associated with familial amyotrophic lateral sclerosis (FALS) impairs CN activity both in transfected human neuroblastoma cell lines and in the motor cortex of brain from FALS-transgenic mice. These data suggest that CN might be a target in the pathogenesis of SOD1-linked FALS. 相似文献
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本文用免疫组织化学ABC法调查了4种AMPA受体亚单位(GluR1、2/3、4)和谷氨酸(Glu)在大鼠三叉神经尾侧亚核(Vc)内的分布及其匹配关系。我们发现,GluR1和2/3免疫阳性胞体和纤维密集分布于Vc的Ⅱ层和Ⅲ层外侧部,在Vc的其余各层呈散在性分布。GluR4免疫阳性胞体和纤维在Vc各层均无分布。Glu免疫阳性胞体分布于Vc各层,尤以浅层(Ⅰ、Ⅱ层)密集,Glu免疫阳性纤维及终末结构主要分布于Vc浅层。结果表明,Glu免疫阳性纤维及终末样结构与AMPA受体免疫阳性胞体和纤维在Vc浅层的分布总体上是相互匹配的,但AMPA受体各亚单位在Vc内的分布存在明显的差异。本文提示,Vc内的Glu可能通过作用于不同的AMPA受体亚单位而发挥其多种生理功能 相似文献
28.
细胞色素P450 2D6缺陷型等位基因的家系分析 总被引:2,自引:1,他引:1
陈枢青 孙红颖 赵鲁杭 Peter J WedlundCHEN Shu-qing SUN Hong-ying ZHAO Lu-hang Peter J Wedlund 《遗传》1998,20(5):28-30
利用等位基因特民扩增法(ASA)为基础的基因分型法,对细胞色素P4502D6 (CYP2D6)缺陷型等位基因携带者的9个家庭共38个进行了基因分型,并与用右旋美沙芬为
探针的表型分型法进行对比,发现两种方法的结果是一致的,CYP2D6酶缺陷型等位基因呈常染色体隐性遗传。
Abstract:A genotyping method based on the principle of allele-specific amplification and a phenotyping procedure with dextromethorphan as a probe were employed in familial study of nine families with 38 members for the cytochrome P450 2D6(CYP2D6)deficient alleles——CYP2D6A,CYP2D6B,CYP2D6D and CYP2D6T.The results showed that the CYP2D6 deficient alleles were inherited as an autosomal recessive trait. 相似文献
29.
Endothelin-1 (ET-1) and bradykinin (BK) are endogenous peptides that signal through Gαq/11-protein coupled receptors (GPCRs) to produce nociceptor sensitization and pain. Both peptides activate phospholipase C to stimulate Ca2+ accumulation, diacylglycerol production, and protein kinase C activation and are rapidly desensitized via a G-protein receptor kinase 2-dependent mechanism. However, ET-1 produces a greater response and longer lasting nocifensive behavior than BK in multiple models, indicating a potentially divergent signaling mechanism in primary afferent sensory neurons. Using cultured sensory neurons, we demonstrate significant differences in both Ca2+ influx and Ca2+ release from intracellular stores following ET-1 and BK treatments. As intracellular store depletion may contribute to the regulation of other signaling cascades downstream of GPCRs, we concentrated our investigation on store-operated Ca2+ channels. Using pharmacological approaches, we identified transient receptor potential canonical channel 3 (TRPC3) as a dominant contributor to Ca2+ influx subsequent to ET-1 treatment. On the other hand, BK treatment stimulated Orai1 activation, with only minor input from TRPC3. Taken together, data presented here suggest that ET-1 signaling targets TRPC3, generating a prolonged Ca2+ signal that perpetuates nocifensive responses. In contrast, Orai1 dominates as the downstream target of BK receptor activation and results in transient intracellular Ca2+ increases and abridged nocifensive responses. 相似文献
30.
Familial Mediterranean Fever (FMF) is an autosomal recessive hereditary disease leading mostly to renal failure and nephrotic syndrome. The ultrastructure of kidney has not been fully investigated in FMF associated renal disease. The aim of this study is to provide further evidence on the ultrastructure of kidney in patients with FMF who suffer from renal disease. Renal biopsies obtained from two patients who were diagnosed with FMF renal disease complications were examined. Examination of renal tissue by light and electron microscopy identified degenerations both in tubules and the filtration barrier. Foot processes were partly effaced. Amorphous material was found in thickened glomerular basement membranes. Fibrous material deposits in thick Bowman's capsule wall were also seen. Finally, degeneration in the form of folding of plasma membrane and vacuolization as well as fusion in mitochondria cristae, was observed. Accumulation of tissue remnants in the lumen was also found in tubules. 相似文献