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31.
目的 观察巯基化合物对内毒素诱导大鼠枯否细胞(KC)NF-kB活性和肿瘤坏死因子-a(TNF-a)释放的影响。方法采用胶原酶灌注和percoll密度梯度离心法分离得到高纯度大鼠KC,在过夜培养后冲洗两遍(不含血清),加入内毒素(LPS)10ng/ml刺激原代培养的KC,观察不同浓度谷胱甘肽乙基酯(GSHEE)及N-乙酰半胱氨酸(NAC)对大鼠KCTNF-a释放和KC内谷胱甘肽(GSH)及NF-kB活性的影响。并观察使用谷胱甘肽合成抑制剂BSO后,对NAC抑制炎症因子的影响,采用凝胶滞留电泳法测NF-kB活性,采用高效液相色谱分析法测GSH水平。结果 LPS诱导KC中GSH水平无变化;GSHEE和NAC可提高KC中GSH水平(P〈0.05),降低NF-kB活性和TNF-a释放(P〈0.05)。NAC与BSO合用时KC中GSH水平无变化,TNF-a释放降低(P〈0.05)。结论 NAC通过抑制KC中NF-kB的激活和TNF-a的释放调节KC功能,但这种抑制作用并非通过增加GSH介导。 相似文献
32.
M. RAUVALA K. AGLUND† U. PUISTOLA T. TURPEENNIEMI-HUJANEN‡ G. HORVATH§ R. WILLÉN & U. STENDAHL† 《International journal of gynecological cancer》2006,16(3):1297-1302
The incidence of uterine cervical cancer has increased slightly in Western countries, with an increase in relatively young women. Overexpression of matrix metalloproteinases (MMPs)-2 and -9 has turned out as a prognostic factor in many cancers. We compared the expression of the proteins MMP-2 and MMP-9 in cervical primary tumors with clinical outcome and risk factors of cervical cancer. One hundred sixty-one patients with cervical cancer treated in Ume? University Hospital or Sahlgrenska University Hospital, Sweden, between 1991 and 1995 were included in the study. Paraffin-embedded tissue samples obtained prior to treatment were examined immunohistochemically by specific antibodies for MMP-2 and MMP-9. Forty-two percent of the tumors were intensively positive for MMP-2 and 31% for MMP-9. Nineteen percent of the samples were intensively positive for both proteinases and 47% negative or weak for both. Overexpression of MMP-2 seemed to predict unfavorable survival under Kaplan-Meier analysis and in the multivariate analysis. Early sexual activity and low parity seemed to correlate to overexpression of MMP-2. MMP-9 was not associated with survival or sexual behavior. Intensive MMP-9 was noted in grade 1 tumors. We conclude that MMP-2 and MMP-9 have different roles in uterine cervical cancer. MMP-2 could be associated with aggressive behavior, but MMP-9 expression diminishes in high-grade tumors. 相似文献
33.
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
34.
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
35.
The B cell functional response following ligation of surface(s) lgM is dependent upon the differentiation stage of the populationstudied: cross-linking slgM promotes proliferation of restingtonsillar follicular mantle (FM) B lymphocytes but induces apoptosisin the susceptible Epstein- Barr virus genome-negative Burkittlymphoma (BL) cell line Ramos (Ramos-BL). This study investigateswhether phosphatidylinositol-3-kinase (Pl3-kinase), which hasbeen reported to be intimately involved in the regulation ofcellular growth, plays a role in the regulation of these sig-promoted B cell responses, and uses the selective and irreversibleinhibitor of Pl3-kinase activity, wortmannin (Wm). In Ramos-BLB cells, at 8 h post-treatment, Wm triggers a transient increasein apoptosis of 16 ± 6.9% with a concomitant cellularloss of 16 ± 6.1% from the G1 phase of cell cycle; [3H]thymidineincorporation also decreases by 33 ± 5.0%, from 37,274c.p.m. ± 10% to 25,127 c.p.m. ± 4.0%. Moreover,at 72 h culture, Wm inhibits anti-lgM-induced FM B lymphocytelevels of [3H]thymidine incorporation typically by 47% and triggers80% apoptosis from the G0G1 phase of cell cycle. Ramos-BL Bcells exhibit high basal levels of Pl3-kinase activity, as determinedby immunoprecipitation with antibody to the p85 regulatory subunitof Pl3-kinase and 32P incorporation into phosphatidylinositol,which is not significantly affected by anti-lgM stimulation;by contrast, anti-lgM stimulates significant Pl3-kinase activityover negligible basal levels in FM B lymphocytes. Pre-treatmentwith Wm inhibits Pl3-kinase activity in both cell types. Takentogether these data indicate that in Ramos-BL B cells slgM-triggeredgrowth arrest and apoptosis is Pl3- kinase independent, whereasPl3-kinase activity is critical for slgM-triggered mitogenesisof FM B lymphocytes. Thus Pl3-kinase plays a pivotal role inthe regulation of both normal and neoplastic B lymphocyte progressionthrough the cell cycle, such that if this Pl3-kinase-dependentpathway is inhibited these cells default to apoptosis. 相似文献
36.
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
37.
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
38.
目的 评价单克隆IgH基因重排检测在恶性淋巴瘤 (B NHL)临床中的应用价值。方法 用半巢式PCR检测单克隆IgH基因重排。病例组为B NHL ,包括 6 9例石蜡包埋组织切片、治疗前 16例骨髓和 2 9例外周血、阳性者治疗后复查骨髓和外周血 ;对照组为 10例慢性淋巴结炎、3例T NHL和 2例HD。结果 对照组均阴性。病例组 :切片中单克隆IgH基因重排阳性率为 6 3.8% (44 / 6 9) ;骨髓和外周血阳性率分别为 43 .8%(7/ 16 )和 41.4% (12 / 2 9) ,细胞形态学检查未见异常细胞者阳性率分别为 33 .3% (3/ 9)和 31.3% (5 / 16 )。 16例同时采集骨髓和外周血者 ,阳性率分别为 43 .8% (7/ 16 )和 37.5 % (6 / 16 ) ,两者无统计学差异。治疗前单克隆IgH重排阳性者 ,6例完全缓解 (CR)后转阴 ,处于持续缓解状态 ,1例临床缓解后 13个月仍阳性 ,现在继续随访中 ,另 1例CR后持续阳性者 ,6个月后复发。结论 切片、骨髓和外周血中检测单克隆IgH基因重排可以作为B NHL诊断和随访微小残留病灶的辅助手段 相似文献
39.
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
40.
W. Nörenberg Ernst Schöffel Bela Szabo Klaus Starke 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(2):159-165
The aim of the study was to subclassify the soma-dendritic α2-autoreceptors in the locus coeruleus (LC) of the rat by means of antagonists. To this end, the frequency of spontaneous action
potentials was recorded extracellularly from single LC neurones in brain slices. The neurones fired spontaneously at an average
rate of 1 Hz. The selective α2-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) and noradrenaline decreased the action potential
discharge with IC50 values of 5 and 510 nM, respectively. The concentration-inhibition curves of UK 14,304 and noradrenaline were shifted to the
right by phentolamine (0.15 μM) and rauwolscine (0.15 μM) but not by prazosin (1 μM). Apparent K
d values of phentolamine were 17 nM (against UK 14,304) and 20 nM (against noradrenaline). Apparent K
d values of rauwolscine were 47 nM (against UK 14,304) and 70 nM (against noradrenaline). (+)-Oxaprotiline (1 μM) suppressed
the firing of the neurones within 10 to 33 min. In the continued presence of oxaprotiline, phentolamine and rauwolscine restored
firing with EC50 values of 120 and 250 nM, respectively. Prazosin (1 μM) again was ineffective. All three antagonist affinity estimates –
against UK 14,304, exogenous noradrenaline and endogenous noradrenaline (that accumulates in the extracellular space in the
presence of oxaprotiline) – yield an affinity order phentolamine > rauwolscine >> prazosin, prazosin being ineffective even
at a concentration of 1 μM. These findings identify the soma-dendritic α2-autoreceptors of the LC as the rat variant of the α2A/D-adrenoceptor, i.e. α2D. Not only presynaptic but also soma-dendritic α2-autoreceptors may at least predominantly be α2A/D throughout the nervous system.
Received: 3 March 1997 / Accepted: 21 April 1997 相似文献