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41.
Claudia Gedlicka Gudrun Hager Martina Weissenböck Wilhelm Gedlicka Birgit Knerer Johannes Kornfehl Michael Formanek 《Journal of oral pathology & medicine》2006,35(8):472-478
BACKGROUND: 1Alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2) Vitamin D(3)] induces growth inhibition in squamous cell carcinoma (SCC) cell lines of the head and neck by arresting the cells in the G0/G1 phase of the cell cycle, probably due to an enhanced expression of p21, which could be demonstrated in other cell lines (JPPA, SCC9) before. In SCC25, a SCC cell line isolated from tongue, growth inhibition but no overexpression of p21 was detected. The retinoblastoma gene, as a direct target of G1 cyclin-CDK complexes, showed an obvious shift from the hyperphosphorylated to the hypophosphorylated form under 1,25(OH)(2)Vitamin D(3), which indicates that the growth inhibition takes place in the G0/G1 phase. To explore the possible pathway of growth inhibition in SCC25 we investigated other cell cycle inhibitors (p18, p19, p27). METHODS: Synchronized cells were treated with 1,25(OH)(2)Vitamin D(3) over 96 h. The cell cycle status and expression of cell cycle-regulating proteins was determined by fluorescence-activated cell sorting (FACS) and Western blotting. An overexpression of p18 in 1,25(OH)(2)Vitamin D(3) vs. ethanol-treated cells was determined until 30 h in SCC25. No influence was detectable on the expression of p27 and p19. CONCLUSION: One mechanism by which 1,25(OH)(2)Vitamin D(3) controls cell growth might be the upregulation of p21. As p21 was unsusceptible to 1,25(OH)(2)Vitamin D(3) in SCC25, other inhibiting proteins were necessary to be tested. The proven upregulation of p18 seems to be the responsible step for growth inhibition of 1,25(OH)(2)Vitamin D(3) in SCC25. 相似文献
42.
AKIKO TANAKA MASAHIRO MATSUMOTO YUJIRO HAYASHI KOJI TAKEUCHI 《Journal of gastroenterology and hepatology》2006,20(1):38-45
Background and Aim: We recently reported that cyclooxygenase (COX)-2 is upregulated in the rat small intestine after administration of indomethacin, and this may be the key to non-steroidal anti-inflammatory drug (NSAID)-induced intestinal damage. The present study investigated the mechanism for COX-2 expression induced in the rat small intestine by indomethacin, in relation with ulcerogenic processes.
Methods: Animals were given indomethacin or SC-560 p.o., and the intestinal mucosa was examined 24 h later.
Results: Indomethacin caused hemorrhagic lesions in the small intestine, accompanied with an increase in intestinal motility, bacterial invasion and inducible nitric oxide synthase (iNOS) activity, as well as the expression of COX-2 mRNA in the mucosa. Although SC-560 did not cause any damage, this agent caused intestinal hypermotility, the bacterial invasion and the upregulation of COX-2 expression. The mucosal PGE2 content was decreased by SC-560 at 3 h but recovered 12 h later, and this recovery of PGE2 was attenuated by both atropine and ampicillin, in addition to rofecoxib. The intestinal hypermotility response to indomethacin was prevented by both 16,16-dimethyl PGE2 and atropine, but not ampicillin. Yet all these agents inhibited not only the bacterial invasion but also the expression of COX-2 and iNOS activity in the intestinal mucosa following indomethacin treatment, resulting in the prevention of intestinal lesions.
Conclusion: These results suggest that COX-2 expression in the intestinal mucosa following the administration of indomethacin is associated with intestinal hypermotility and bacterial invasion. The intestinal hypermotility caused by COX-1 inhibition may be a key to COX-2 expression after administration of NSAIDs and their intestinal ulcerogenic properties. 相似文献
Methods: Animals were given indomethacin or SC-560 p.o., and the intestinal mucosa was examined 24 h later.
Results: Indomethacin caused hemorrhagic lesions in the small intestine, accompanied with an increase in intestinal motility, bacterial invasion and inducible nitric oxide synthase (iNOS) activity, as well as the expression of COX-2 mRNA in the mucosa. Although SC-560 did not cause any damage, this agent caused intestinal hypermotility, the bacterial invasion and the upregulation of COX-2 expression. The mucosal PGE
Conclusion: These results suggest that COX-2 expression in the intestinal mucosa following the administration of indomethacin is associated with intestinal hypermotility and bacterial invasion. The intestinal hypermotility caused by COX-1 inhibition may be a key to COX-2 expression after administration of NSAIDs and their intestinal ulcerogenic properties. 相似文献
43.
Anne-Catherine Bachoud-Lévi Philippe Hantraye Marc Peschanski 《Movement disorders》2002,17(3):439-444
Intrastriatal transplantation of striatal neuroblasts from human fetuses is a promising approach for treatment of Huntington's disease, on the basis of many experimental animal studies and, most recently, pilot clinical trials. Technically, several issues remain to be resolved (e.g., the precise site of dissection of the fetal tissue; the number and location of the fetal striatal implants; or the use of immunosuppressive therapy), and await larger-scale trials and purposely designed protocols. Further clinical data must also be obtained, and preliminary promising results must be replicated in a patient group large enough to provide conclusive results. It is important to establish (1) the amount of clinical benefit provided to the patient by the grafted cells; (2) the anticipated duration of clinical benefits; and (3) the secondary rate of decline after the benefit of the graft has been overbalanced. Evaluation of these parameters will require very long-term follow-up of the patients involved, over several years after grafting, before the technique can eventually be proposed widely to patients. 相似文献
44.
β-胡萝卜素立体异构体对环磷酰胺处理小鼠免疫功能的比较研究 总被引:3,自引:0,他引:3
就β-胡萝卜素立体异构体对环磷酰胺处理小鼠的免疫功能影响进行了比较研究。结果显示β-胡萝卜素立体异构体对外磷酰胺造成的免疫功能低下具有不同程度的改善作用,提高胸腺和脾脏指数,增强脾脏细胞对刀豆素A(ConA)的反应性和NK活性,血清溶菌酶含量也有所增加。综合各项指标,9-顺式和全反式混合物的作用最明显,提示一定浓度的9-顺式对于提高β-胡萝卜素对机体的总体作用是有一定意义的。 相似文献
45.
表皮生长因子对牛眼小梁细胞c—fos基因表达的诱导 总被引:4,自引:0,他引:4
目的研究表皮生长因子(epidermalgrowthfactor,EGF)对小梁细胞的作用。方法应用分子杂交技术研究EGF对体外培养的牛眼小梁细胞c-fos基因表达的诱导和3H胸腺核苷酸(3H-thymidineincorparation,3H-TdR)掺入法观察细胞DNA的合成。结果小梁细胞的3H-TdR掺入率随着EGF浓度不同而变化,浓度为20~150ng/ml时,细胞掺入率随浓度增加升高(P<0.01)。与对照组相比,EGF刺激停止生长的小梁细胞0.5小时后,c-fos基因开始表达,1小时后达高峰,至2小时后消失。不同浓度EGF刺激小梁细胞1小时后,c-fos基因表达呈浓度依赖性。结论实验结果表明EGF刺激小梁细胞增殖或进入生长状态,可能与c-fos基因产物的信号传递作用有关。 相似文献
46.
Large granular lymphocyte expansions in patients with Felty's syndrome: analysis using anti-T cell receptor V beta-specific monoclonal antibodies. 总被引:5,自引:0,他引:5 下载免费PDF全文
S J Bowman M Bhavnani G C Geddes V Corrigall A W Boylston G S Panayi J S Lanchbury 《Clinical and experimental immunology》1995,101(1):18-24
Felty's syndrome (FS), the association of rheumatoid arthritis (RA) and idiopathic neutropenia, remains an unexplained phenomenon. HLA-DR4 is found in over 90% of cases. Patients with FS may have a T cell lymphocytosis of CD3+CD8+CD57+ large granular lymphocytes (LGL syndrome). In this study of 47 patients with FS, 19% had clear evidence for LGL expansions, while in total 42% had variable evidence for the LGL syndrome using currently available techniques. Of these T cell expansions, 76% were clonal, as demonstrated by Southern blotting and analysis with T cell receptor (TCR) beta chain constant region probes. This technique may fail to detect clonal populations in some patients. Cytofluorographic analysis using antibodies specific for TCR V beta chains identified patients with clonal LGL expansions with results comparable to those obtained with Southern blotting. No evidence for shared V beta usage among expansions from different patients was seen. The role of LGL in RA and FS is currently unclear, but this technique offers a practical and accessible means of identifying patients with LGL expansions, as a starting point for further investigation. 相似文献
47.
Abraham Nudelman Yitschak Binnes Naomi Shmueli-Broide Yael Odessa J. Paul Hieble Anthony C. Sulpizio 《Archiv der Pharmazie》1996,329(3):125-132
Vinylogous (Groups III and V ) and acetylenologous (Group IV ) analogs of the classical β-adrenergic agents — stimulants and blockers — were prepared in order to evaluate the effect of degree of saturation, position of unsaturation and rigidity of the chain linking the aromatic ring and the amino containing functional group on biological activity. Derivatives from Group III , which represent 4-aryl-3-butenyl-2-ol-amine analogs of Group II , retained β1-adrenoceptor antagonist activity albeit substantially less potent (50–200-fold) than that possessed by their aryloxy counterparts. Consistent with the SAR for Group II compounds, substitution at position 2 of the aromatic ring yielded the most potent antagonists ( 5a, 5d, 5g ), with KB's ranging from 73–93 nM while 3,4-dichloro substitution ( 5e ) markedly reduced antagonist potency (KB = 2,400 nM). Agonist activity was also noted for 5b and 5d , suggesting that these compounds may be best classified as partial agonists. Representatives from Groups IV and V were inactive as antagonists at the β1-adrenoceptor confirming the importance of the spatial relationship between the hydroxyl and the amino nitrogen. 相似文献
48.
P. A. Milligan P. E. McGill C. W. Howden A. W. Kelman B. Whiting 《European journal of clinical pharmacology》1993,45(6):507-512
Summary A randomised crossover study was performed in subjects with rheumatoid arthritis (or other arthropathies) to investigate if any alteration in the steady pharmacokinetics of the NSAID piroxicam (a drug which is extensively metabolised via cytochrome P450) or its major metabolites occurred as a result of coadministering either cimetidine or nizatidine.Twelve females and 2 males with mean age, weight, and albumin concentrations of 58 years, 61 kg, and 40 g·L–1 respectively, completed the study. Comparisons were made between the following parameters: plasma piroxicam AUCs [AUC0-24(P)], plasma 5-hydroxypiroxicam AUCs [AUC0-24(5-OHP)], the ratio of these i.e. AUC0-24(5-OHP):AUC0-24(p), the % piroxicam daily dose excreted in urine as 5-hydroxypiroxicam (before and after glucuronidase incubation); and the mean of the steady state trough piroxicam, and 5-hydroxypiroxicam concentrations (obtained during each study phase in addition to the wash-out period).A statistically significant difference as a result of initiating either cimetidine or nizatidine was obtained only for the ratio AUC0-23(5-OHP):AUC0-24(P). This was indicative of a weak potential to inhibit piroxicam hydroxylation.No clinically significant alteration in the steady state pharmacokinetics of piroxicam occurred in these subjects as a result of cimetidine or nizatidine coadministration. Consequently it is unlikely that any adverse events would arise from these combinations. 相似文献
49.
Sarah A. Taylor Jacqueline Benedetti David Schuller Stephen P. Richman Goronwy O. Broun Alexander Hantel 《Investigational new drugs》1993,11(2-3):227-229
Summary Twenty-two patients with recurrent or metastatic squamous cell carcinoma of the head and neck were treated with piroxantrone 150 mg/m2 intravenously every 21 days. There were no objective responses. The 95% upper confidence bound for response is 15%. Primary toxicity was hematologic. 相似文献
50.
中国汉坦病毒H82O5株G2糖蛋白基因的克隆及在真核细胞中的瞬时表达 总被引:2,自引:1,他引:1
从感染病毒乳鼠脑组织提取总RNA,采用RT-PCR和分子克隆技术将扩增到的G2糖蛋白基因插入含CMV启动子的pcDNA3.1/His质粒载体中,通过脂质体介导转染COS-7细胞,用SDS-PAGE、Western-blot及IFIA方法分别测定表达产物的相对分子量及特异性。结果证明获得正向插入的G2-pcDNA3.1/His重组表达质粒,表达产物的相对分子量为56ku,与理论预期大小一致,并且可与汉坦病毒H8205株的腹水抗体起特异反应。表明构建的G2-pcDNA3.1/His重组质粒所表达的蛋白为中国汉坦病毒株特有,能在哺乳动物细胞中表达并具有抗原性,重组质粒可应用于汉坦病毒的DNA疫苗研究。 相似文献