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991.
玻璃体出血是由全身性疾病、眼底病,眼外伤、手术所致的眼科常见病。笔者采用增视冲剂治疗玻璃体出血84例,现报告如下。 相似文献
992.
Muñoz-Martínez F Lu P Cortés-Selva F Pérez-Victoria JM Jiménez IA Ravelo AG Sharom FJ Gamarro F Castanys S 《Cancer research》2004,64(19):7130-7138
Overexpression of ABCB1 (MDR1) P-glycoprotein, a multidrug efflux pump, is one mechanism by which tumor cells may develop multidrug resistance (MDR), preventing the successful chemotherapeutic treatment of cancer. Sesquiterpenes from Celastraceae family are natural compounds shown previously to reverse MDR in several human cancer cell lines and Leishmania strains. However, their molecular mechanism of reversion has not been characterized. In the present work, we have studied the ability of 28 dihydro-beta-agarofuran sesquiterpenes to reverse the P-glycoprotein-dependent MDR phenotype and elucidated their molecular mechanism of action. Cytotoxicity assays using human MDR1-transfected NIH-3T3 cells allowed us to select the most potent sesquiterpenes reversing the in vitro resistance to daunomycin and vinblastine. Flow cytometry experiments showed that the above active compounds specifically inhibited drug transport activity of P-glycoprotein in a saturable, concentration-dependent manner (K(i) down to 0.24 +/- 0.01 micromol/L) but not that of ABCC1 (multidrug resistance protein 1; MRP1), ABCC2 (MRP2), and ABCG2 (breast cancer resistance protein; BCRP) transporters. Moreover, sesquiterpenes inhibited at submicromolar concentrations the P-glycoprotein-mediated transport of [(3)H]colchicine and tetramethylrosamine in plasma membrane from CH(R)B30 cells and P-glycoprotein-enriched proteoliposomes, supporting that P-glycoprotein is their molecular target. Photoaffinity labeling in plasma membrane and fluorescence spectroscopy experiments with purified protein suggested that sesquiterpenes interact with transmembrane domains of P-glycoprotein. Finally, sesquiterpenes modulated P-glycoprotein ATPase-activity in a biphasic, concentration-dependent manner: they stimulated at very low concentrations but inhibited ATPase activity as noncompetitive inhibitors at higher concentrations. Sesquiterpenes from Celastraceae are promising P-glycoprotein modulators with potential applications in cancer chemotherapy because of their MDR reversal potency and specificity for P-glycoprotein. 相似文献
993.
Homozygous deletion and expression of PTEN and DMBT1 in human primary neuroblastoma and cell lines 总被引:5,自引:0,他引:5
Muñoz J Lázcoz P Inda MM Nistal M Pestaña A Encío IJ Castresana JS 《International journal of cancer. Journal international du cancer》2004,109(5):673-679
Neuroblastoma is the most common pediatric solid tumor. Although many allelic imbalances have been described, a bona fide tumor suppressor gene for this disease has not been found yet. In our study, we analyzed 2 genes, PTEN and DMBT1, mapping 10q23.31 and 10q25.3-26.1, respectively, which have been found frequently altered in other kinds of neoplasms. We screened both genes for homozygous deletions in 45 primary neuroblastic tumors and 12 neuroblastoma cell lines. Expression of these genes in cell lines was assessed by RT-PCR analysis. We could detect 2 of 41 (5%) primary tumors harboring PTEN homozygous deletions. Three of 41 (7%) primary tumors and 2 of 12 cell lines presented homozygous losses at the g14 STS on the DMBT1 locus. All cell lines analyzed expressed PTEN, but lack of DMBT1 mRNA expression was detected in 2 of them. We tried to see whether epigenetic mechanisms, such as aberrant promoter hypermethylation, had any role in DMBT1 silencing. The 2 cell lines lacking DMBT1 expression were treated with 5-aza-2'-deoxycytidine; DMBT1 expression was restored in only one of them (MC-IXC). From our work, we can conclude that PTEN and DMBT1 seem to contribute to the development of a small fraction of neuroblastomas, and that promoter hypermethylation might have a role in DMBT1 gene silencing. 相似文献
994.
Muñoz A Samet J 《Journal of the National Cancer Institute》2004,96(5):411; author reply 411-411; author reply 412
995.
996.
JNK activation is critical for Aplidin-induced apoptosis 总被引:4,自引:0,他引:4
Aplidin is an antitumor drug that induces apoptosis and activates EGFR, Src, JNK and p38MAPK. Here, we show that Aplidin induces c-JUN, JUN B, JUN D, c-FOS, FRA-1 and FOS B genes of the activator-protein (AP)-1 family, and also p65/RELA, a major component of nuclear factor-kappa B (NF-kappaB). Concordantly, Aplidin increases AP-1 and NF-kappaB activity. c-FOS induction depends on EGFR, Src and JNK/p38MAPK. In contrast, induction of c-JUN does not require EGFR activity and p65/RELA induction is only partially dependent on these kinases. We used several genetically deficient cells to identify the critical target of Aplidin. Mouse embryo fibroblasts (MEFs) deficient for src, yes and fyn, and those lacking all p38MAPK isoforms displayed normal Aplidin sensitivity (IC50=12 nM). In contrast, MEFs lacking jnk1 and jnk2, which do not express any JNK isoform, were much less sensitive (IC50>500 nM). Furthermore, cells lacking c-jun or expressing a c-Jun protein in which JNK targets Ser(63/73) were mutated (c-JunAA) showed intermediate sensitivity (IC50=60 nM). Additionally, Aplidin has higher cytotoxic activity against proliferating than quiescent cells, which is reflected in higher JNK activation. We conclude that phosphorylation by JNK of c-Jun and additional substrate(s) is crucial for Aplidin activity. 相似文献
997.
Kumru H Santamaria J Tolosa E Valldeoriola F Muñoz E Marti MJ Iranzo A 《Annals of neurology》2004,56(4):599-603
Rapid eye movement sleep behavior disorder (RBD) in the setting of parkinsonism or dementia often reflects an underlying synucleinopathy. Lewy bodies, intraneuronal aggregates containing abnormal alpha-synuclein, are absent in most cases of parkinsonism with parkin mutations (Park2). We performed clinical history and video-polysomnography in 10 Park2 patients (seven men; age, 51.2 +/- 11.6 years; parkinsonism duration, 18.3 +/- 11.2 years) and found RBD in 6. In all instances, RBD followed the onset of motor symptoms by several years. Our study shows that RBD is frequent in Park2, suggesting that mechanisms other than synuclein deposition can cause RBD in neurodegenerative disorders. 相似文献
998.
Cebrián-Carretero JL Pérez-López C Alvarez F Sarmiento MA del Castillo JL Muñoz-Caro JM 《Neurocirugía (Asturias, Spain)》2004,15(6):571-5; discussion 575-7
We report the case of a 45 year old patient who was affected by an infectious disease of the temporal bone, after the surgical treatment of a meningioma in the greater sphenoid wing. This infection healed after the resection of the craniotomy flap. The remaining bone defect was reconstructed using a titanium mesh covered by hydroxyapatite cement (Norian). The result was excellent due to the strength of the titanium mesh and the volume and contour offered by the hydroxyapatite cement. 相似文献
999.
Effect of tetramethylpyrazine on acute nociception mediated by signaling of P2X receptor activation in rat 总被引:7,自引:0,他引:7
Tetramethylpyrazine (TMP) has been used in traditional Chinese medicine as an analgesic for dysmenorrhea. In the present study, we try to investigate the effects of TMP on acute nociception mediated by P2X receptor activation of rat hindpaw and the membrane depolarization of rat dorsal root ganglion (DRG) neurons induced by P2X receptor agonists. The subcutaneous administration of TMP (0.1-10 mmol) into rat hindpaw in a dose-dependent manner decreased acute paw flinching responses mediated by adenosine 5'-triphosphate (ATP, 1000 nmol) or alpha,beta-methylene ATP (alpha,beta-meATP, 600 nmol). The subcutaneous administration of TMP (5 or 10 mmol) into rat hindpaw inhibited significantly the first phase of nociceptive behaviors induced by 5% formalin and attenuated slightly the second phase of nociceptive behaviors induced by 5% formalin. The subcutaneous administration of TMP (10 mmol) into rat hindpaw reduced the nociceptive responses induced by alpha,beta-meATP (200 nmol) co-injected with Prostaglandin E2 (PGE2), 5 micromol). The membrane depolarization induced by ATP (200 micromol) or alpha,beta-meATP (50 micromol) in DRG neurons was inhibited by TMP (300 micromol). The data suggest that the antinociceptive effect of TMP is involved in blocking the signaling of P2X3 receptor activation in rat. 相似文献
1000.
Correlation of neuron-specific enolase and S100B with histological cerebral damage in fetal sheep after severe asphyxia 总被引:2,自引:0,他引:2
Fujii EY Kozuki M Mu J Ino Y Ushioda N Tomimatsu T Fukuda H Kanzaki T Nakayama M Murata Y 《Brain research》2004,1018(1):136-140
Experimental brain damage was induced in 16 fetal sheep by umbilical cord occlusion, and the correlation of neuron-specific enolase (NSE) or S100B with the damage grade was investigated in seven fetuses. Significant correlations of damage degree with NSE (p = 0.016) and S100B (p = 0.018) in serum 2 h after insult were shown by Spearman's test. These findings suggest that they represent potentially useful markers for detecting brain damage at early stage after ischemic insult. 相似文献