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781.
Morphological transformation of human keratinocytes expressing the LMP gene of Epstein-Barr virus. 总被引:40,自引:0,他引:40
The association of Epstein-Barr virus (EBV) with nasopharyngeal carcinoma (NPC) has been known for some time, but the precise role of EBV in this cancer is poorly understood, due partly to the lack of an in vitro system for studying NPC cells and the effect of EBV on epithelial cells. Biopsies of NPC tumours have revealed expression of the EBV latent membrane protein (LMP) in 65% of cases, suggesting that in at least some NPC tumours LMP may contribute to cell transformation. Here we address the question of the effect of LMP expression on epithelial cells. Transfection of an immortalized, non-tumorigenic keratinocyte cell line (RHEK-1) with the LMP gene causes a striking morphological transformation: the originally flat, polygonal colonies change to bundles of spindle-shaped cells that form multilayer foci, and cytokeratin expression is down-regulated. Our results suggest that LMP expression may be an important causal factor in the development of NPC. 相似文献
782.
A general survey of the information presently available on the osteology and myology of the hyobranchial apparatus. Included in the survey are examples of the hyobranchial skeleton of the major groups of reptiles, including the Chelonia, Crocodilia, Rhynchocephalia, and Squamata. The myology treats the muscles directly associated with the hyoid as well as those associated with the functioning of the apparatus, but not arising or inserted directly on or from the hyoid. The innervation of the hyobranchial apparatus is reviewed and briefly discussed based on the information available in a few major studies. An attempt is made to cite all pertinent literature references, and in Tables 1 and 2 the references to basic areas are indicated. Twenty - nine plates and figures are included, some of which represent original research. 相似文献
783.
G S Jimenez F Bryntesson M I Torres-Arzayus A Priestley M Beeche S Saito K Sakaguchi E Appella P A Jeggo G E Taccioli G M Wahl M Hubank 《Nature》1999,400(6739):81-83
Damage to DNA in the cell activates the tumour-suppressor protein p53, and failure of this activation leads to genetic instability and a predisposition to cancer. It is therefore crucial to understand the signal transduction mechanisms that connect DNA damage with p53 activation. The enzyme known as DNA-dependent protein kinase (DNA-PK) has been proposed to be an essential activator of p53, but the evidence for its involvement in this pathway is controversial. We now show that the p53 response is fully functional in primary mouse embryonic fibroblasts lacking DNA-PK: irradiation-induced DNA damage in these defective fibroblasts induces a normal response of p53 accumulation, phosphorylation of a p53 serine residue at position 15, nuclear localization and binding to DNA of p53. The upregulation of p53-target genes and cell-cycle arrest also occur normally. The DNA-PK-deficient cell line SCGR11 contains a homozygous mutation in the DNA-binding domain of p53, which may explain the defective response by p53 reported in this line. Our results indicate that DNA-PK activity is not required for cells to mount a p53-dependent response to DNA damage. 相似文献
784.
Epidermal growth factor receptor function is necessary for normal craniofacial development and palate closure. 总被引:19,自引:0,他引:19
P J Miettinen J R Chin L Shum H C Slavkin C F Shuler R Derynck Z Werb 《Nature genetics》1999,22(1):69-73
Craniofacial malformations are among the most frequent congenital birth defects in humans; cleft palate, that is inadequate fusion of the palatal shelves, occurs with an annual incidence of 1 in 700 to 1 in 1,000 live births among individuals of European descent. The secondary palate arises as bilateral outgrowths from the maxillary processes, and its formation depends on the coordinated development of craniofacial structures including the Meckel's cartilage and the mandible. Cleft lip and palate syndromes in humans are associated with polymorphisms in the gene (TGFA) encoding transforming growth factor-alpha (TGF-alpha), an epidermal growth factor receptor (EGFR) ligand made by most epithelia. Here we have characterized craniofacial development in Egfr-deficient (Egfr-/-) mice. Newborn Egfr-/- mice have facial mediolateral defects including narrow, elongated snouts, underdeveloped lower jaw and a high incidence of cleft palate. Palatal shelf explants from Egfr-/- mice fused, but frequently had residual epithelium in the midline. In addition, morphogenesis of Meckel's cartilage was deficient in cultured mandibular processes from Egfr-/- embryos. The secretion of matrix metalloproteinases (MMPs) was diminished in Egfr-/- explants, consistent with the ability of EGF to increase MMP secretion and with the decreased MMP expression caused by inhibition of Egfr signalling in wild-type explants. Accordingly, inactivation of MMPs in wild-type explants phenocopied the defective morphology of Meckel's cartilage seen in Egfr-/- explants. Our results indicate that EGFR signalling is necessary for normal craniofacial development and that its role is mediated in part by its downstream targets, the MMPs, and may explain the genetic correlation of human cleft palate with polymorphisms in TGFA. 相似文献
785.
Biopsies of subjects affected by ulcerous colitis were stained with ruthenium Red. Alterations of the cellular coat and glycocalyx of the epithelial cells of the colon were identified. 相似文献
786.
In rats, the vertebral artery make only a minor contribution to the blood perfusion of the ponto-medullary area. This was measured with radioactive microspheres and was confirmed by methylmetacrylate casts and local injection of a centrally acting hypotensive drug. 相似文献
787.
788.
A family of mammalian Na+-dependent L-ascorbic acid transporters. 总被引:10,自引:0,他引:10
H Tsukaguchi T Tokui B Mackenzie U V Berger X Z Chen Y Wang R F Brubaker M A Hediger 《Nature》1999,399(6731):70-75
Vitamin C (L-ascorbic acid) is essential for many enzymatic reactions, in which it serves to maintain prosthetic metal ions in their reduced forms (for example, Fe2+, Cu+), and for scavenging free radicals in order to protect tissues from oxidative damage. The facilitative sugar transporters of the GLUT type can transport the oxidized form of the vitamin, dehydroascorbic acid, but these transporters are unlikely to allow significant physiological amounts of vitamin C to be taken up in the presence of normal glucose concentrations, because the vitamin is present in plasma essentially only in its reduced form. Here we describe the isolation of two L-ascorbic acid transporters, SVCT1 and SVCT2, from rat complementary DNA libraries, as the first step in investigating the importance of L-ascorbic acid transport in regulating the supply and metabolism of vitamin C. We find that SVCT1 and SVCT2 each mediate concentrative, high-affinity L-ascorbic acid transport that is stereospecific and is driven by the Na+ electrochemical gradient. Despite their close sequence homology and similar functions, the two isoforms of the transporter are discretely distributed: SVCT1 is mainly confined to epithelial systems (intestine, kidney, liver), whereas SVCT2 serves a host of metabolically active cells and specialized tissues in the brain, eye and other organs. 相似文献
789.
E A Rogaeva S Premkumar J Grubber L Serneels W K Scott T Kawarai Y Song D L Hill S M Abou-Donia E R Martin J J Vance G Yu A Orlacchio Y Pei M Nishimura A Supala B Roberge A M Saunders A D Roses D Schmechel A Crane-Gatherum S Sorbi A Bruni G W Small P M Conneally J L Haines F Van Leuven P H St George-Hyslop L A Farrer M A Pericak-Vance 《Nature genetics》1999,22(1):19-22
790.
介绍一种对航天器的VLBI原始电压观测记录中提取多普勒频移量的方法,并用于对lunarprospector的较左VLBI观测记录的分析中,同时得到航天器的VLBI和多普勒观测数据,有利于对航天器空间位置和速度信息的同时获取。 相似文献