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101.
Survey of the Distribution of a Newly Characterized Receptor for Advanced Glycation End Products in Tissues 总被引:33,自引:2,他引:33
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Jerold Brett Ann Marie Schmidt Shi Du Yan Yu Shan Zou Elliott Weidman David Pinsky Roman Nowygrod Michael Neeper Craig Przysiecki Alan Shaw Antonio Migheli David Stern 《The American journal of pathology》1993,143(6):1699-1712
Advanced glycation end products (AGEs), the final products of nonenzymatic glycation and oxidation of proteins, are found in the plasma and accumulate in the tissues during aging and at an accelerated rate in diabetes. A novel integral membrane protein, termed receptor for AGE (RAGE), forms a central part of the cell surface binding site for AGEs. Using monospecific, polyclonal antibody raised to human recombinant and bovine RAGE, immunostaining of bovine tissues showed RAGE in the vasculature, endothelium, and smooth muscle cells and in mononuclear cells in the tissues. Consistent with these data, RAGE antigen and mRNA were identified in cultured bovine endothelium, vascular smooth muscle, and monocyte-derived macrophages. RAGE antigen was also visualized in bovine cardiac myocytes as well as in cultures of neonatal rat cardiac myocytes and in neural tissue where motor neurons, peripheral nerves, and a population of cortical neurons were positive. In situ hybridization confirmed the presence of RAGE mRNA in the tissues, and studies with rat PC12 pheochromocytes indicated that they provide a neuronal-related cell culture model for examining RAGE expression. Pathological studies of human atherosclerotic plaques showed infiltration of RAGE-expressing cells in the expanded intima. These results indicate that RAGE is present in multiple tissues and suggest the potential relevance of AGE-RAGE interactions for modulating properties of the vasculature as well as neural and cardiac function, prominent areas of involvement in diabetes and in the normal aging process. 相似文献
102.
Del-Favero J; Krols L; Michalik A; Theuns J; Lofgren A; Goossens D; Wehnert A; Van den Bossche D; Van Zand K; Backhovens H; van Regenmorter N; Martin JJ; Van Broeckhoven C 《Human molecular genetics》1998,7(2):177-186
Autosomal dominant cerebellar ataxia with retinal degeneration (ADCAII) was
previously mapped by linkage analysis studies to chromosome 3p12- p21.1
(SCA7). Positional cloning efforts have recently identified a novel gene,
SCA7 , containing a translated CAG repeat, expanded in SCA7 patients. We
cloned the SCA7 gene from a yeast artificial chromosome (YAC) clone contig
spanning the SCA7 candidate region. Using a combination of genomic
sequencing and cosmid-based exon trapping, two expressed sequence tags were
identified. Sequencing of the corresponding cDNA clones and RT-PCR analysis
identified the full- length SCA7 cDNA. Together, our sequence data defined
the intron/exon boundaries of the first two coding exons of the SCA7 gene,
with the first exon containing the expanded CAG repeat. Further, sequence
comparison with the published SCA7 cDNA identified one additional putative
exon in the 5'-UTR region of the SCA7 gene. The SCA7 gene was mapped on the
YAC contig in the 2.5 cM interval between D3S1600 and D3S1287. In one
extended Belgian SCA7 pedigree the expanded alleles ranged from 38 to at
least 55 repeats with allele lengths being inversely correlated with onset
age of ADCAII symptoms. The SCA7 repeats increased in length in successive
generations. Normal alleles had from four to 18 repeats, with 10 repeats
being the most common allele.
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103.
颈椎间管壁骨质增生的观察及其意义 总被引:32,自引:3,他引:32
在甘肃地区出土的成人颈椎骨骼标本390套(2730块)上,观测了钩椎关节、椎间关节、横突孔和椎体后缘的骨质增生,出现率高达22.5%。增生骨唇占据椎间管、横突孔和椎管的情况分轻、中、重三度. 相似文献
104.
钙调素对微管组装的调节作用 总被引:1,自引:1,他引:1
利用我们建成的钙调素表达可调细胞模型-RC3细胞,对CaM高表达时微管组装行为进行了研究,当用生理剂量的地塞米松处理RC3细胞,细胞内CaM水平提高,而管蛋白浓度没有变化,造成钙调素/管蛋白比值上升,MT解聚,但同时加入CaM拮抗剂三氟拉嗪处理时,则可抑制MT的解聚,C3H10T1/2转化细胞CaM含量的增加是引起MT解聚的主要因素,TFP处理可恢复MT组装。RC3细胞CaM高表达导致MT解聚的实 相似文献
105.
目的:采用磁微粒分离酶联免疫荧光(MEIF)分析技术建立一种简便、高敏感性、定量检测人血清胰岛素(insulin)的新方法.方法:选用2株识别人胰岛素不同表位的单克隆抗体(mAb).一株mAb用异硫氰酸荧光素(FITC)标记, 另一株用碱性磷酸酶(AP)标记;偶联羊抗FITC抗体的磁珠用作固相分离载体, 4-甲基磷酸伞型酮用作荧光底物.结果:成功建立了定量检测人血清胰岛素的MEIF, 灵敏度2.0 μIu/mL, 线形范围0~188.52 μIu/mL, 批内变异系数(CV)为4.3%~5.2%, 批间CV为2.6%~9.5%, 稀释回收率为93%~117%, 加标回收率为94%~113%.实际样品的测定结果与倍爱康公司商品化人insulin磁分离发光系统检测试剂盒的检测结果比较, 具有良好的相关性.结论:MEIF定量测定人insulin方法成本低、灵敏度高、稳定性好, 在临床免疫检测领域具有广阔的应用前景. 相似文献
106.
107.
Matrix metalloproteinase expression in basal cell carcinoma: relationship between enzyme profile and collagen fragmentation pattern 总被引:2,自引:0,他引:2
Yucel T Mutnal A Fay K Fligiel SE Wang T Johnson T Baker SR Varani J 《Experimental and molecular pathology》2005,79(2):151-160
Matrix metalloproteinases (MMPs) with collagenolytic and gelatinolytic activities are up-regulated in basal cell carcinoma. In the present study we demonstrate that the major collagenolytic enzyme detected is MMP-1 (interstitial collagenase) while gelatinolytic enzymes include both MMP-2 (72-kDa gelatinase A) and MMP-9 (92-kDa gelatinase B). Significant fractions of all three enzymes are present as active forms. In spite of the fact that high levels of gelatinolytic enzymes are present, the major fragmentation products resulting from digestion of intact type I collagen are the 1/4 and 3/4 fragments (products of MMP-1-mediated digestion). Thus, it appears that the gelatinolytic enzymes are not capable of degrading the collagen fragments as rapidly as they are produced. Since previous studies have demonstrated that interaction of interstitial fibroblasts with high molecular weight fragments of type I collagen leads to increased MMP production, the present results suggest a mechanism underlying altered function of stromal elements in the connective tissue adjacent to the growing neoplasm. 相似文献
108.
Absence of proteinase-activated receptor-1 signaling affords protection from bleomycin-induced lung inflammation and fibrosis
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Howell DC Johns RH Lasky JA Shan B Scotton CJ Laurent GJ Chambers RC 《The American journal of pathology》2005,166(5):1353-1365
Activation of the coagulation cascade is commonly observed in the lungs of patients with both acute and chronic inflammatory and fibrotic lung disorders, as well as in animal models of these disorders. The aim of this study was to examine the contribution of the major thrombin receptor, proteinase-activated receptor-1 (PAR-1), during the acute inflammatory and chronic fibrotic phases of lung injury induced by intratracheal instillation of bleomycin in mice. Inflammatory cell recruitment and increases in bronchoalveolar lavage fluid (BALF) protein were attenuated by 56 +/- 10% (P < 0.05) and 53 +/- 12% (P < 0.05), respectively, in PAR-1-deficient (PAR-1-/-) mice compared with wild-type (WT) mice. PAR-1-/- mice were also protected from bleomycin-induced pulmonary fibrosis with total lung collagen accumulation reduced by 59 +/- 5% (P < 0.05). The protection afforded by PAR-1 deficiency was accompanied by significant reductions in pulmonary levels of the potent PAR-1-inducible proinflammatory and profibrotic mediators, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-beta-1 (TGF-beta1), and connective tissue growth factor/fibroblast-inducible secreted protein-12 (CTGF/FISP12). In addition, PAR-1 was highly expressed in inflammatory and fibroproliferative lesions in lung sections obtained from patients with fibrotic lung disease. These data show for the first time that PAR-1 signaling plays a key role in experimentally induced lung injury, and they further identify PAR-1 as one of the critical receptors involved in orchestrating the interplay between coagulation, inflammation, and remodeling in response to tissue injury. 相似文献
109.
目的:探讨人乳头瘤病毒(HPV)的E6E7基因在细胞恶性转化中所起的作用。方法:将人乳头瘤病毒(HPV)的E6E7基因克隆至腺病毒伴随病毒表达载体中,通过包装的重组病毒感染,将E6E7基因导入并整合到永生293细胞的基因组中。结果:本研究成功地构建了HPV18 E6E7 AAV病毒并感染了永生293细胞,PCR/Southern杂交分析表明E6E7基因在转化细胞293TL中确有表达,转化细胞293TC和293TL具有明显的转化表型,和亲本293细胞相比,生长速度快,接触抑制消失,集落形成率提高20倍,且集落明显增大,形成时间短。结论:成功地构建了HPV18 E6E7 AAV病毒,HPV18 E6E7基因引起永生化人上皮细胞293的恶性转化。此病毒可用于感染正常上皮细胞,研究其致癌机制。 相似文献
110.
目的:探讨脑出血血肿周围局部病理改变及细胞免疫机制。方法:用免疫组化方法及组织HE染色法观察20只大鼠尾壳核脑出血24 h,3天、7天血肿周围区域的组织病变及CD3 、CD8 T淋巴细胞的分布形式和表达时程。结果:①在脑出血后24 h血肿周围即可见明显血管源性水肿,大量炎性细胞浸润,以中性粒细胞为主,少量散在淋巴细胞、小胶质细胞、星形细胞、少突胶质细胞弥漫浸润;出血3天、7天以淋巴细胞、巨噬细胞浸润为主,小胶质细胞、星形细胞、少突胶质细胞增生明显,双侧半球皮层下和血管周围出现小胶质细胞结节;②出血灶周围CD3 和CD8 T淋巴细胞浸润在出血后24 h已可见,出血后3天组和出血后7天组,CD3 和CD8 阳性细胞数明显高于出血后24 h组。结论:①脑出血期以中性粒细胞反应为主,以后以淋巴细胞反应为主,胶质细胞反应在出血后24 h已发生,持续一周以上;②CD3 、CD8 阳性细胞的出现提示它们参与了出血后脑损伤的病理过程,在出血7天内, CD3 和CD8-阳性细胞反应呈增强趋势。 相似文献