• 【异位子宫内膜和子宫内膜异位病变中微血管密度,增殖活性与血管内皮生长因子-A及其受体表达的关系。】 复制标题 收藏 收藏
    DOI:10.1530/rep.1.01110 复制DOI
    作者列表:Bourlev V,Volkov N,Pavlovitch S,Lets N,Larsson A,Olovsson M
    BACKGROUND & AIMS: :Studies were performed to elucidate the possible relationship between microvessel density, proliferative activity and angiogenesis in eutopic endometrium from women with and without endometriosis and peritoneal endometriotic lesions. The question whether changes in these parameters in endometriotic lesions were reflected by the level of vascular endothelial growth factor-A (VEGF-A) in serum and peritoneal fluid was also studied. Biopsy specimens of both eutopic endometrium and peritoneal endometriotic lesions from women with endometriosis (n = 25) as well as eutopic endometrium from women without endometriosis (n = 14) were analysed immunohistochemically regarding microvessel density, proliferative activity, and expression of VEGF-A and its receptors vascular endothelial growth factor receptors 1 and 2 (VEGFR-1 and VEGFR-2) in stroma, glands and blood vessels. The VEGF-A concentration was measured in peritoneal fluid and serum. Secretory phase eutopic endometrium from women with endometriosis had significantly higher microvessel density, expression of VEGF-A in glandular epithelium and VEGFR-2 in endometrial blood vessels than those from women without endometriosis. Endometriotic lesions with high proliferative activity had a higher microvessel density and showed higher vascular expression of VEGFR-2 as well as being accompanied by higher levels of VEGF-A in peritoneal fluid and serum, compared with lesions with low proliferative activity. In conclusion, there seems to be a dysregulation of angiogenic activity in the eutopic endometrium of women with endometriosis and endometriotic lesions with high proliferative activity were accompanied by higher local angiogenic activity and higher levels of VEGF in serum and peritoneal fluid.
    背景与目标: :进行了研究以阐明患有和不患有子宫内膜异位和腹膜子宫内膜异位病变的女性在位子宫内膜的微血管密度,增殖活性和血管生成之间的可能关系。还研究了是否通过血清和腹膜液中血管内皮生长因子-A(VEGF-A)的水平反映子宫内膜异位病变中这些参数的变化的问题。对子宫内膜异位症妇女(n = 25)和非子宫内膜异位症妇女(n = 14)的对位子宫内膜和腹膜子宫内膜异位病变的活检标本进行了免疫组织化学分析,涉及微血管密度,增殖活性,VEGF-A和其受体位于基质,腺体和血管中的血管内皮生长因子受体1和2(VEGFR-1和VEGFR-2)。测定腹膜液和血清中的VEGF-A浓度。子宫内膜异位症女性的分泌期异位子宫内膜比无子宫内膜异位症女性的子宫内膜微血管密度,腺上皮中的VEGF-A表达和子宫内膜血管中的VEGFR-2显着更高。与具有低增殖活性的病变相比,具有高增殖活性的子宫内膜异位病变具有更高的微血管密度,并且在腹膜液和血清中具有更高的VEGFR-2血管表达以及较高的VEGF-A水平。总之,子宫内膜异位症妇女的异位子宫内膜血管新生活性似乎异常,具有高增殖活性的子宫内膜异位病变伴有较高的局部血管新生活性和血清和腹膜液中较高的VEGF水平。
  • 【澳洲肺金枪鱼中肺鱼中胰岛素样生长因子-I mRNA表达的营养调控。】 复制标题 收藏 收藏
    DOI:10.1677/jme.0.0180273 复制DOI
    作者列表:Matthews SJ,Kinhult AK,Hoeben P,Sara VR,Anderson TA
    BACKGROUND & AIMS: The effect of nutritional status on IGF-I mRNA expression in the liver and brain of juvenile barramundi (Lates calcarifer) was investigated. Fish were either fed a satiety ration (SAT) or starved (STV) for 6 weeks. Starved fish demonstrated significantly lower condition factor and hepatic IGF-I mRNA expression at 3 and 6 weeks, when compared with the SAT group. IGF-I mRNA expression in the brain was 10 fold lower than the liver and was not affected by ration size. These results suggest the liver is the major site of IGF-I mRNA synthesis and hepatic but not brain IGF-I mRNA expression is regulated by food availability in juvenile barramundi.

    背景与目标: 研究了营养状况对少年肺鱼(Lates calcarifer)肝脏和脑中IGF-I mRNA表达的影响。给鱼喂饱口粮(SAT)或饿死(STV)6周。与SAT组相比,在3周和6周时,饥饿的鱼表现出明显较低的条件因子和肝脏IGF-I mRNA表达。脑中IGF-I mRNA表达比肝脏低10倍,并且不受口粮大小的影响。这些结果表明,肝脏是IGF-I mRNA合成的主要部位,肝而不是脑IGF-I mRNA的表达受幼鱼的食物供应量的调节。

  • 【抗氧化剂对核因子-κB的抑制作用增强了紫杉醇在卵巢癌细胞系中的敏感性。】 复制标题 收藏 收藏
    DOI:10.1111/j.1525-1438.2006.00652.x 复制DOI
    作者列表:Liu GH,Wang SR,Wang B,Kong BH
    BACKGROUND & AIMS: :The objective of this study was to determine whether paclitaxel and a strong antioxidant, pyrrolidinedithiocarbamate (PDTC), can affect the activation of nuclear factor-kappa B (NF-kappaB) in SKOV-3 human ovarian cancer cell line and the effect of these two agents on the growth and apoptosis of the cancer cells. The cells were treated with various concentrations of paclitaxel and/or PDTC at various time intervals. Following treatments, cell growth and apoptosis were determined by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulphonyl)-2H-tetrazolium (WST-8) (WST) assay and flow cytometry, respectively. Western blot assay was used to determine the nuclear p65 protein and cytoplasmic IkappaB-alpha protein. High doses of PDTC significantly inhibited the growth of SKOV-3 cells and caused apoptosis. Paclitaxel and lower doses of PDTC combined demonstrated additive inhibition of cell growth and increased levels of apoptosis. Treatment of paclitaxel alone showed increased nuclear p65 protein and decreased cytoplasmic IkappaB-alpha protein expression, while pretreatment of PDTC reversed this function. PDTC blocks the paclitaxel-induced activation of NF-kappaB leading to increased chemosensitivity to paclitaxel and enhanced apoptosis. Combining antioxidants and paclitaxel has significant potential to overcome the risk of paclitaxel resistance.
    背景与目标: :这项研究的目的是确定紫杉醇和强抗氧化剂吡咯烷二硫代氨基甲酸酯(PDTC)是否会影响SKOV-3人卵巢癌细胞系中核因子-κB(NF-kappaB)的活化及其作用两种药剂对癌细胞的生长和凋亡都有影响。在不同的时间间隔用不同浓度的紫杉醇和/或PDTC处理细胞。处理后,通过2-(2-甲氧基-4-硝基苯基)-3-(4-硝基苯基)-5-(2,4-二磺酰基)-2H-四唑鎓(WST-8)(WST)测定细胞生长和凋亡)分析和流式细胞术。蛋白质印迹法用于确定核p65蛋白和细胞质IkappaB-alpha蛋白。高剂量的PDTC显着抑制SKOV-3细胞的生长并引起细胞凋亡。紫杉醇和较低剂量的PDTC联合显示可抑制细胞生长和增加细胞凋亡水平。单独使用紫杉醇的治疗显示核p65蛋白增加,而细胞质IkappaB-α蛋白表达降低,而PDTC的预处理逆转了该功能。 PDTC阻止紫杉醇诱导的NF-κB活化,从而导致对紫杉醇的化学敏感性增加和细胞凋亡增强。抗氧化剂和紫杉醇的组合具有克服紫杉醇耐药性的巨大潜力。
  • 【显然健康的男性和女性的组织因子血清水平和未来冠状动脉疾病的风险:EPIC-Norfolk前瞻性人群研究。】 复制标题 收藏 收藏
    DOI:10.1111/j.1538-7836.2006.02190.x 复制DOI
    作者列表:Keller TT,Choi D,Nagel C,Te Velthuis H,Gerdes VE,Wareham NJ,Bingham SA,Luben R,Hack CE,Reitsma PH,Levi M,Khaw KT,Boekholdt SM
    BACKGROUND & AIMS: INTRODUCTION:Tissue factor (TF) has been implicated in coronary artery disease (CAD). High levels of circulating TF are found in patients with acute atherothrombotic events. Whether high serum TF levels predict risk of future CAD independent of known risk factors remains unknown. METHODS:We conducted a prospective case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population study. Cases (n=1037) were apparently healthy men and women, aged 45-79 years, who developed fatal or non-fatal CAD during follow-up. Controls (n=2005) were matched by age, sex, and enrolment time. Serum TF levels were measured using high-affinity antibodies. RESULTS:In men, median TF levels were not significant higher in cases than in controls (59.0 pg mL-1, range: 16.7-370.4 vs. 54.9 pg mL-1, range: 16.2-452.4). In women, median TF levels were not significant higher in controls than in cases (73.4 pg mL-1, range: 16.7-492.3 vs. 50.5 pg mL-1, range: 16.5-376.7). The incidence of smoking was about double in the lowest compared with the highest TF quartile. Correcting for sex, age, body mass index, smoking, diabetes, systolic blood pressure, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and C-reactive protein levels, the risk of future CAD was 1.05 (95% CI: 0.81-1.36) for people in the highest TF quartile, compared with those in the lowest (P-value for linearity=0.8). CONCLUSION:High levels of serum TF were not independently associated with an increased risk of future CAD in apparently healthy individuals.
    背景与目标: 简介:组织因子(TF)与冠心病(CAD)有关。在患有急性动脉粥样硬化血栓形成事件的患者中发现高水平的循环TF。血清TF高水平是否能独立于已知的危险因素来预测未来CAD的风险仍然未知。
    方法:我们进行了一项前瞻性病例对照研究,该研究嵌套在欧洲癌症与营养前瞻性调查(EPIC)-诺福克人群研究中。病例(n = 1037)显然是健康的男性和女性,年龄在45-79岁之间,在随访期间出现了致命或非致命的CAD。对照组(n = 2005)按年龄,性别和入组时间进行匹配。使用高亲和力抗体测量血清TF水平。
    结果:在男性中,病例中的TF中位数没有显着高于对照组(59.0 pg / mL-1,范围:16.7-370.4 vs. 54.9 pg / mL-1,范围:16.2-452.4)。在女性中,对照的中位TF水平没有比病例高(73.4 pg / mL-1,范围:16.7-492.3 vs. 50.5 pg / mL-1,范围:16.5-376.7)。与最高四分位数的吸烟者相比,最低吸烟率的吸烟者约为两倍。校正性别,年龄,体重指数,吸烟,糖尿病,收缩压,低密度脂蛋白胆固醇,高密度脂蛋白胆固醇和C反应蛋白水平后,未来CAD的风险为1.05(95%CI: TF最高四分位数的人与最低TF四分位数的人(线性P值= 0.8)相比。
    结论:血清TF水平升高与明显健康的个体未来冠心病风险增加并没有独立的关系。
  • 【静止T细胞的有丝分裂刺激导致转录因子LSF迅速磷酸化,并增加了DNA结合活性。】 复制标题 收藏 收藏
    DOI:10.1101/gad.11.11.1435 复制DOI
    作者列表:Volker JL,Rameh LE,Zhu Q,DeCaprio J,Hansen U
    BACKGROUND & AIMS: The mammalian transcription factor LSF (CP2/LBP-1c) binds cellular promoters modulated by cell growth signals. We demonstrate here that LSF-DNA-binding activity is strikingly regulated by induction of cell growth in human peripheral T lymphocytes. Within 15 min of mitogenic stimulation of these cells, the level of LSF-DNA-binding activity increased by a factor of five. The level of LSF protein in the nucleus remained constant throughout this interval. However, a rapid decrease in the electrophoretic mobility of LSF, attributable to phosphorylation, correlated with the increase in DNA-binding activity. pp44 (ERK1) phosphorylated LSF in vitro on the same residue that was phosphorylated in vivo, specifically at amino acid position 291, as indicated by mutant analysis. As direct verification of the causal relationship between phosphorylation and DNA-binding activity, treatment in vitro of LSF with phosphatase both increased the electrophoretic mobility of the protein and decreased LSF-DNA-binding activity. This modulation of LSF-DNA-binding activity as T cells progress from a resting to a replicating state reveals that LSF activity is regulated during cell growth and suggests that LSF regulates growth-responsive promoters.

    背景与目标: 哺乳动物转录因子LSF(CP2 / LBP-1c)结合受细胞生长信号调节的细胞启动子。我们在这里证明,LSF-DNA结合活性是由人类外周血T淋巴细胞的细胞生长诱导来显着调节的。在这些细胞的促有丝分裂刺激的15分钟内,LSF-DNA结合活性的水平提高了五倍。在整个间隔期间,核中LSF蛋白的水平保持恒定。但是,可归因于磷酸化的LSF电泳迁移率的快速下降与DNA结合活性的增加有关。突变分析表明,pp44(ERK1)在体外磷酸化的同一残基上,特别是在氨基酸位置291处磷酸化LSF。作为磷酸化与DNA结合活性之间因果关系的直接验证,体外用磷酸酶处理LSF既增加了蛋白质的电泳迁移率,又降低了LSF-DNA结合活性。当T细胞从静止状态发展到复制状态时,对LSF-DNA结合活性的这种调节揭示了LSF活性在细胞生长过程中受到调节,并暗示LSF调节生长响应性启动子。

  • 【重组人可溶性肿瘤坏死因子受体融合蛋白作为同种异体造血干细胞移植后类固醇难治性移植物抗宿主病的治疗方法。】 复制标题 收藏 收藏
    DOI:10.1002/ajh.20752 复制DOI
    作者列表:Busca A,Locatelli F,Marmont F,Ceretto C,Falda M
    BACKGROUND & AIMS: :Etanercept is a recombinant human soluble tumor necrosis factor (TNF-alpha) receptor fusion protein that inhibits TNF-alpha, a major mediator in the pathogenesis of graft-versus-host disease (GVHD). The purpose of our study was to evaluate the safety and efficacy of etanercept therapy in 21 patients with steroid-refractory acute GVHD (aGVHD) (n = 13) and chronic GVHD (cGVHD) (n = 8). Etanercept 25 mg was given subcutaneously twice weekly for 4 weeks followed by 25 mg weekly for 4 weeks. At the time of initiation of etanercept, 14 patients had skin, 13 had gastro-intestinal, 5 had liver, 5 had pulmonary, and 4 had oral involvement. Twelve patients (57%) completed 12 doses of therapy. Overall, 11 of 21 patients (52%) responded to the treatment with etanercept, including 6 patients (46%) with aGVHD [n = 4 complete response (CR), n = 2 partial response (PR)] and 5 patients (62%) with cGVHD (n = 1 CR, n = 4 PR). Clinical responses were most commonly seen in patients with refractory gut aGVHD with 55% of the patients having a CR and 9% having a PR. CMV reactivation occurred in 48% of patients, bacterial infections in 14% of patients, and fungal infections in 19% of patients. Fourteen patients (67%) were alive after a median follow-up of 429 days (range 71-1007 days) since initiation of etanercept. Seven patients died, 3 of infections, 2 of refractory aGVHD, and 2 of disease progression. In conclusion, our preliminary data indicate that etanercept is well tolerated and can induce a high response rate in patients with steroid-refractory aGVHD and cGVHD, particularly in the setting of GI involvement.
    背景与目标: :Etanercept是一种重组人类可溶性肿瘤坏死因子(TNF-alpha)受体融合蛋白,可抑制TNF-alpha(一种在移植物抗宿主病(GVHD)发病机理中的主要介体)。我们的研究目的是评估依那西普治疗21例激素抵抗性急性GVHD(aGVHD)(n = 13)和慢性GVHD(cGVHD)(n = 8)患者的安全性和有效性。每周两次皮下给予Etanercept 25 mg,持续4周,然后每周25 mg,持续4周。依那西普开始治疗时,有14例皮肤,13例胃肠,5例肝,5例肺,4例经口受累。 12名患者(57%)完成了12剂治疗。总体上,21例患者中有11例(52%)对依那西普治疗有反应,其中6例(46%)患有aGVHD [n = 4完全缓解(CR),n = 2部分缓解(PR)]和5例(62 %)和cGVHD(n = 1 CR,n = 4 PR)。临床反应最常见于顽固性肠aGVHD患者,其中55%的患者为CR,9%的患者为PR。 CMV重新激活发生在48%的患者中,细菌感染发生在14%的患者中,而真菌感染发生在19%的患者中。自依那西普开始接受中位随访429天(71-1007天)后,有14名患者(67%)还活着。 7例患者死亡,3例感染,2例难治性aGVHD死亡,2例疾病进展。总之,我们的初步数据表明,依那西普耐受性好,在类固醇难治性aGVHD和cGVHD患者中可引起较高的应答率,特别是在胃肠道受累的情况下。
  • 【结肠扩张激活蓝藻:促肾上腺皮质激素释放因子和兴奋性氨基酸的作用。】 复制标题 收藏 收藏
    DOI:10.1016/s0006-8993(97)00116-9 复制DOI
    作者列表:Lechner SM,Curtis AL,Brons R,Valentino RJ
    BACKGROUND & AIMS: The present study was designed to elucidate the neurotransmitters involved in activation of the noradrenergic nucleus, locus coeruleus, by distention of the distal colon. Locus coeruleus spontaneous discharge rate was recorded from halothane-anesthetized rats before, during and after distention of the colon produced by inflation of a balloon catheter with varying volumes of water. Locus coeruleus activation by colon distention was volume-dependent and reversible. Activation of cortical electroencephalographic activity was temporally correlated with locus coeruleus activation during colon distention and prolonged distention (greater than 2 min) resulted in tachyphalaxis to both locus coeruleus and cortical electroencephalographic activation. The corticotropin-releasing factor antagonist, DPheCRF(12-41), administered intracerebroventricularly (3 microg) or microinfused into the locus coeruleus (10 ng) significantly attenuated locus coeruleus activation produced by lower, but not higher magnitudes of colon distention, implicating corticotropin-releasing factor afferents to the locus coeruleus in this response. Consistent with this, prior exposure to 30 min of footshock stress, which desensitizes locus coeruleus neurons to corticotropin-releasing factor, produced a similar attenuation of locus coeruleus activation by low, but not high magnitudes of distention. Kynurenic acid, administered intracerebroventricularly (5 micromol), significantly antagonized locus coeruleus activation by all magnitudes of colon distention. However, this excitatory amino acid antagonist was ineffective when administered directly into the locus coeruleus (0.3 nmol). Together, these findings suggest that low magnitudes of colon distention activate the locus coeruleus-noradrenergic system via corticotropin-releasing factor release within the locus coeruleus and that excitatory amino acid neurotransmission at a site distal to the locus coeruleus is necessary for this response. Activation of the locus coeruleus-noradrenergic system during colon distention may serve as a cognitive limb of the peripheral parasympathetic response. This activation may also play a role in disorders characterized by comorbidity of colonic and psychiatric symptoms, such as irritable bowel syndrome.

    背景与目标: 本研究旨在阐明远端结肠扩张引起的去甲肾上腺素能核激活的神经递质。记录了氟烷麻醉大鼠在用不同体积的水充胀球囊导管充盈结肠之前,期间和之后自发排出蓝藻的频率。结肠扩张引起的蓝斑轨迹激活是体积依赖性的和可逆的。皮质脑电图活动的激活在时间上与结肠扩张期间脑蓝素的激活相关,而长期扩张(大于2分钟)会导致脑脊髓蓝素和皮质脑电图的速动性。皮质激素释放因子拮抗剂DPheCRF(12-41),经脑室内(3微克)或微输注到蓝斑(10 ng)时,可显着减弱由较低但不是较高程度的结肠扩张产生的蓝斑激活,这暗示促肾上腺皮质激素-在这种反应中,释放因子传入蓝斑。与此相一致,事先暴露于30分钟的足底震荡中,使蓝斑蓝皮病的神经元对促肾上腺皮质激素释放因子不敏感,通过低但不高的扩张程度,蓝斑蓝皮病的激活也有类似的减弱。脑室内(5微摩尔)施用的犬尿酸通过各种程度的结肠扩张显着拮抗蓝斑轨迹激活。但是,这种兴奋性氨基酸拮抗剂当直接施用于蓝斑(0.3 nmol)时无效。总之,这些发现表明低水平的结肠扩张通过蓝藻中的促肾上腺皮质激素释放因子释放来激活蓝藻-去甲肾上腺素能系统,并且在蓝藻远侧的部位,兴奋性氨基酸神经传递对于该反应是必需的。结肠扩张期间蓝斑-去甲肾上腺素能系统的激活可能充当外周副交感反应的认知肢体。这种活化作用还可能在以结肠和精神症状合并症为特征的疾病中起作用,例如肠易激综合症。

  • 【即将进入二十世纪的职业医学:对预防方法中已完成和预期发生的变化的评估。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Indulski JA
    BACKGROUND & AIMS: The World Bank in its document under the title 'Investing in Health' (1993) states that the health status of the population, including the working population, and working conditions in individual countries depend essentially on the value of gross national product per capita. The attitudes towards the role and objectives of occupational medicine have changed significantly over the last three decades. A high priority given to primary prevention reflects the mainstream of a new approach to preventive measures. Advancements in technology, production and services, common use of computers and flattening of work organisation structures have brought about the need for workers' active participation in planning of activities and shaping working conditions in own enterprise. At the same time, workers are required to possess much higher qualifications facilitating their participation in applying new technologies and using new information systems, which resulted in a fierce competition on the labour market. In the countries in the political, social and economic transition, the conditions for introducing a new system of sustained development, described by Gustavsen at the 25th International Congress on Occupational Health have not as yet been established. A procedure-based system involving negotiations between employers and workers' representatives failed to be successful in improving working conditions as the roles of the state, employers and trade unions had not been defined precisely. It is expected that further health promotion at the worksites in these countries will depend mainly on the economic progress and the reformed system of education.

    背景与目标: 世界银行在其题为“投资卫生”(1993年)的文件中指出,人口的健康状况,包括劳动人口,以及各个国家的劳动条件,基本上取决于人均国民生产总值。在过去的三十年中,人们对职业医学的作用和目标的态度发生了巨大变化。对初级预防的高度重视反映了预防措施新方法的主流。技术,生产和服务的进步,计算机的普遍使用以及工作组织结构的扁平化带来了工人积极参与活动计划和塑造本企业工作条件的需求。同时,要求工人具有更高的资格,以促进他们参与应用新技术和使用新信息系统,从而导致劳动力市场上的激烈竞争。在政治,社会和经济转型国家中,古斯塔夫森在第25届国际职业卫生大会上描述的引入新的可持续发展系统的条件尚未建立。涉及雇主和工人代表之间的谈判的基于程序的系统未能成功改善工作条件,因为国家,雇主和工会的角色尚未得到准确界定。预计这些国家在工作场所进一步促进健康将主要取决于经济进步和教育体制的改革。

  • 【通过纵隔镜下方法对胸骨下甲状腺肿进行甲状腺切除术。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Tsai VW,Cameron RB,Wang MB
    BACKGROUND & AIMS: :We report an unusual case in which a patient presented with a large posterior mediastinal goiter that extended to the level of the aorta. The goiter was resected through a standard Kocher neck incision with mediastinoscopic assistance. The large goiter was completely excised without the need for a sternotomy.
    背景与目标: :我们报告了一个不寻常的病例,其中患者出现了一个较大的后纵隔甲状腺肿,延伸至主动脉水平。甲状腺肿通过标准的Kocher颈部切口在纵隔镜下切除。大甲状腺肿完全切除,不需要胸骨切开术。
  • 【缺氧条件下的肿瘤基质细胞相互作用通过肝细胞生长因子/ c-Met途径增加了胰腺癌细胞的侵袭性。】 复制标题 收藏 收藏
    DOI:10.1002/ijc.22178 复制DOI
    作者列表:Ide T,Kitajima Y,Miyoshi A,Ohtsuka T,Mitsuno M,Ohtaka K,Koga Y,Miyazaki K
    BACKGROUND & AIMS: :The hypoxic environment in tumor is reported to play an important role in pancreatic cancer progression. The interaction between stromal and cancer cells also contributes to the malignant behavior of pancreatic cancer. In the present study, we investigated whether hypoxic stimulation affects stromal as well as pancreatic cancer cells. Our findings demonstrated that hypoxia remarkably elevated the HIF-1alpha expression in both pancreatic cancer (PK8) and fibroblast cells (MRC5). Hypoxic stimulation accelerated the invasive activity of PK8 cells, and invasiveness was thus further accelerated when the hypoxic PK8 cells were cultured with conditioned medium prepared from hypoxic MRC5 cells (hypoxic conditioned medium). MMP-2, MMP-7, MT1-MMP and c-Met expressions were increased in PK8 cells under hypoxia. Hypoxic stimulation also increased the hepatocyte growth factor (HGF) secretion from MRC5 cells, which led to an elevation of c-Met phosphorylation in PK8 cells. Conversely, the elevated cancer invasion, MMP activity and c-Met phosphorylation of PK8 cells were reduced by the removal of HGF from hypoxic conditioned medium. In immunohistochemical study, the HIF-1alpha expression was observed in surrounding stromal as well as pancreatic cancer cells, thus indicating hypoxia exists in both of cancer and stromal cells. Moreover, the stromal HGF expression was found to significantly correlate with not only the stromal HIF-1alpha expression but also the c-Met expression in cancer cells. These results indicate that the hypoxic environment within stromal as well as cancer cells activates the HGF/c-Met system, thereby contributing to the aggressive invasive features of pancreatic cancer.
    背景与目标: :据报道肿瘤中的低氧环境在胰腺癌的进展中起重要作用。基质细胞与癌细胞之间的相互作用也有助于胰腺癌的恶性行为。在本研究中,我们调查了低氧刺激是否影响基质以及胰腺癌细胞。我们的发现表明,低氧显着提高了胰腺癌(PK8)和成纤维细胞(MRC5)中HIF-1alpha的表达。低氧刺激加速了PK8细胞的侵袭活性,因此,当用由低氧MRC5细胞制备的条件培养基(低氧条件培养基)培养低氧PK8细胞时,侵袭性进一步加快。在缺氧条件下,PK8细胞中的MMP-2,MMP-7,MT1-MMP和c-Met表达增加。缺氧刺激还增加了MRC5细胞的肝细胞生长因子(HGF)分泌,从而导致PK8细胞中c-Met磷酸化的升高。相反,通过从低氧条件培养基中去除HGF,可以降低PK8细胞的癌浸润,MMP活性和c-Met磷酸化水平的升高。在免疫组织化学研究中,在周围的基质细胞和胰腺癌细胞中均观察到了HIF-1alpha的表达,因此表明在癌细胞和基质细胞中均存在缺氧。此外,发现基质HGF表达不仅与癌细胞中的基质HIF-1α表达而且与c-Met表达显着相关。这些结果表明基质以及癌细胞内的低氧环境激活了HGF / c-Met系统,从而促进了胰腺癌的侵袭性侵袭性。
  • 【内窥镜经膀胱-经尿道瘘管修复阴道阴道瘘:初诊病例报告。】 复制标题 收藏 收藏
    DOI:10.1089/end.1997.11.203 复制DOI
    作者列表:Okamura K,Kanai S,Kurokawa T,Kondo A
    BACKGROUND & AIMS: :Through an endoscopic transvesico-transurethral approach, we closed a vesicovaginal fistula that occurred after hysterectomy in a patient with uterine leiomyoma. The 3-mm fistula, located in the midportion of retrotrigone, was resected transurethrally and sutured in two layers through two 5-mm suprapubic trocars placed into the bladder and the urethral route under pneumobladder. The patient had no urine leakage from the vagina after surgery.
    背景与目标: :通过内窥镜经膀胱-经尿道入路,我们关闭了子宫平滑肌瘤患者子宫切除术后发生的膀胱阴道瘘。将3毫米瘘管(位于逆行三角骨的中部)经尿道切开,并通过两根5毫米耻骨上套管针将其缝合在两层中,然后将其插入膀胱和在气囊下的尿道。病人术后没有尿液从阴道漏出。
  • 【产气荚膜梭菌的α-毒素不是鸡坏死性肠炎的必需毒力因子。】 复制标题 收藏 收藏
    DOI:10.1128/IAI.00806-06 复制DOI
    作者列表:Keyburn AL,Sheedy SA,Ford ME,Williamson MM,Awad MM,Rood JI,Moore RJ
    BACKGROUND & AIMS: :The Clostridium perfringens alpha-toxin has previously been implicated as the major virulence factor in necrotic enteritis in chickens, although definitive proof has not been reported. In this study an alpha-toxin mutant was constructed in a virulent chicken isolate and shown to retain full virulence in a chicken disease model. These results demonstrated that alpha-toxin is not an essential virulence factor in the pathogenesis of necrotic enteritis in chickens.
    背景与目标: 产气荚膜梭菌α毒素以前被认为是鸡坏死性肠炎的主要毒力因子,尽管尚未有确切的证据报道。在这项研究中,在有毒的鸡隔离株中构建了α-毒素突变体,并显示在鸡疾病模型中保留了全部毒力。这些结果表明,α-毒素不是鸡坏死性肠炎发病机理中必不可少的毒力因子。
  • 【经腋窝入路无气内镜甲状腺切除术:经验30例。】 复制标题 收藏 收藏
    DOI:10.1097/00129689-200608000-00006 复制DOI
    作者列表:Yoon JH,Park CH,Chung WY
    BACKGROUND & AIMS: :Surgery for thyroid disease requires skin incisions that can result in postsurgical problems such as prominent scars, adhesions, hypesthesia, and paresthesia in the neck. To overcome these problems we performed gasless endoscopic thyroidectomy via an axillary approach. Between May 2004 and April 2005, 30 patients underwent gasless endoscopic thyroidectomy via an axillary approach. The mean operating time was 126.8+/-32.4 minutes, and the mean length of hospital stay was 4.3+/-1.1 days. No cases required conversion to open surgery and none involved significant intraoperative complications. Three patients (10.0%) complained of slight hypesthesia or paresthesia in the anterior chest wall, and only 2 patients (6.7%) complained of discomfort while swallowing 4 months after surgery. All patients were satisfied with the cosmetic results. Gasless endoscopic thyroidectomy via an axillary approach is feasible and safe and provides excellent cosmetic results with a minimal degree of postoperative complaints.
    背景与目标: :甲状腺疾病的手术需要皮肤切口,这可能导致术后问题,例如明显的疤痕,粘连,感觉异常和颈部感觉异常。为了克服这些问题,我们通过腋窝入路进行了无气内镜甲状腺切除术。在2004年5月至2005年4月之间,有30例患者通过腋窝入路行无气内镜甲状腺切除术。平均手术时间为126.8 /-32.4分钟,平均住院时间为4.3 /-1.1天。没有病例需要转换为开放手术,也没有涉及重大的术中并发症。 3例患者(10.0%)抱怨前胸壁轻度感觉异常或感觉异常,而只有2例患者(6.7%)吞咽术后4个月吞咽不适。所有患者对美容效果均满意。通过腋窝入路的无气内镜甲状腺切除术是可行且安全的,并能以极少的术后不适程度提供出色的美容效果。
  • 【伴刀豆球蛋白A,但不是糖化白蛋白,可增加体外血管性假血友病因子的内皮下沉积。】 复制标题 收藏 收藏
    DOI:10.1080/10623320600903916 复制DOI
    作者列表:Nizheradze K
    BACKGROUND & AIMS: :Diabetes is associated with augmentation of prothrombogenic von Willebrand factor (vWF) content in plasma. Earlier, the author and colleagues have shown that high glucose and insulin do not appreciably influence deposition of vWF into the subendothelial extracellular matrix (SECM) produced by cultured human umbilical vein endothelial cells (HUVECs). In the present work, the author used this model to test the effects of nonenzymatically glycated albumin (Glyc-HSA) and two lectins, concanavalin A (ConA) and wheat germ agglutinin (WGA), on vWF deposition into the SECM. First-passage HUVECs were seeded into gelatin-coated 96-well plates and cultured for 6 to 7 days. HSA or Glyc-HSA (at concentrations 25, 50, and 100 microg/mL), and WGA or ConA (4, 8, and 16 microg/mL) were added 3 h after seeding. Cell viability was tested by the MTT method. To determine vWF contents in the SECM, HUVECs were detached by treatment with NH4OH and the residual material was used as a solid phase in an enzyme-linked immunosorbent assay (ELISA)-like assay with primary (anti-vWF) and secondary (peroxidase-conjugated) antibodies. Addition of Glyc-HSA did not essentially influence VWF contents in the SECM (A490 was 0.226 versus 0.268 at 0 and 100 microg/mL, respectively; p > .05, n = 16). Cultivation in the presence of WGA led to the deterioration of cell viability, which was accompanied by a significant decrease of vWF in the SECM (0.248 versus 0.128 at 0 and 16 microg/mL, respectively; p < .001, n = 16). ConA did not influence viability of HUVECs, but this lectin at all concentrations consistently increased the deposition of vWF (up to 164% relative to control, p <.001; n = 16). These data indicate that endothelial carbohydrate determinants and corresponding ligands (namely, mannose-specific lectins) may be involved in the regulation of production and deposition of vWF.
    背景与目标: 糖尿病与血浆中促血栓性血管性血友病因子(vWF)含量的增加有关。早前,作者和同事已经表明,高葡萄糖和胰岛素不会明显影响vWF在培养的人脐静脉内皮细胞(HUVEC)产生的内皮下细胞外基质(SECM)中的沉积。在目前的工作中,作者使用该模型测试了非酶促糖基化白蛋白(Glyc-HSA)和两种凝集素,伴刀豆球蛋白A(ConA)和小麦胚芽凝集素(WGA)对vWF沉积到SECM中的影响。将第一代HUVEC接种到明胶包被的96孔板中,并培养6至7天。播种后3小时,添加HSA或Glyc-HSA(浓度分别为25、50和100微克/毫升)和WGA或ConA(4、8和16微克/毫升)。细胞存活力通过MTT方法测试。为了确定SECM中的vWF含量,通过用NH4OH处理将HUVEC分离,并将残留的物质作为固相用于类似酶联免疫吸附测定(ELISA)的类似测定中,该测定具有一级(抗vWF)和二级(过氧化物酶-偶联的)抗体。添加Glyc-HSA基本上不影响SECM中的VWF含量(0和100 microg / mL时A490分别为0.226和0.268; p> .05,n = 16)。在存在WGA的情况下进行培养会导致细胞活力下降,并伴有SECM中的vWF显着下降(0和16 microg / mL分别为0.248和0.128; p <.001,n = 16)。 ConA不会影响HUVEC的生存力,但是该凝集素在所有浓度下均会持续增加vWF的沉积(相对于对照,高达164%,p <.001; n = 16)。这些数据表明内皮糖决定簇和相应的配体(即,甘露糖特异性凝集素)可能参与vWF的产生和沉积的调节。
  • 【注意缺陷多动障碍可能与中枢性脑源性神经营养因子活性降低有关:临床和治疗意义。】 复制标题 收藏 收藏
    DOI:10.1016/j.mehy.2006.06.025 复制DOI
    作者列表:Tsai SJ
    BACKGROUND & AIMS: :Attention-deficit hyperactivity disorder (ADHD) is a common childhood psychiatric disorder. Despite intensive research efforts, the aetiology of ADHD remains unknown. Current evidence suggests that the aetiology of ADHD is heterogeneous, comprising of multiple factors. Recently, it has been proposed that brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may be implicated in the pathogenesis of ADHD. This hypothesis is supported by recent genetic studies in ADHD. Drawing on findings from studies into the drugs for ADHD relating to central BDNF expression, hyperactivity in BDNF knockout mice, BDNF effects in midbrain dopaminergic function and the close association between BDNF and the dopamine transporter (an important molecule for ADHD pathogenesis), it is proposed here that decreased central BDNF, particularly in the midbrain region, may play an important role in the pathogenesis ADHD. This hypothesis may have some implications for clinical findings in ADHD (for example, the co-morbidity between ADHD and major depression), and provide a new direction for the development of medication for ADHD treatment.
    背景与目标: 注意缺陷多动障碍(ADHD)是儿童期常见的精神病。尽管进行了深入的研究,但多动症的病因仍然未知。当前证据表明,ADHD的病因是异质的,由多种因素组成。最近,已经提出,脑源性神经营养因子(BDNF),神经营养因子家族的成员,可能与ADHD的发病有关。这一假说得到了多动症最近的遗传学研究的支持。根据对ADHD药物的研究发现,该药物与中枢BDNF表达,BDNF基因敲除小鼠的过度活跃,BDNF对中脑多巴胺能功能的影响以及BDNF与多巴胺转运蛋白(ADHD发病机理的重要分子)之间的紧密联系有关,因此提出了这一建议。在这里,中央BDNF的降低,特别是在中脑区域,可能在ADHD的发病中起重要作用。该假设可能对ADHD的临床发现有一定的影响(例如,ADHD与严重抑郁症的合并症),并为ADHD治疗药物的开发提供了新的方向。

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