• 【鉴定紧凑的,疏水稳定的结构域和包含多个肽链的模块。】 复制标题 收藏 收藏
    DOI:10.1002/pro.5560060609 复制DOI
    作者列表:Zehfus MH
    BACKGROUND & AIMS: Compactness has been used to locate discontinuous structural units containing one or more polypeptide chains in proteins of known structure. Rather than exhaustively calculating the compactness of all possible units, our procedure uses a screening algorithm to find discontinuous regions that are potentially compact. Precise calculations of compactness are restricted only to units in these regions. With our procedure, compactness can be used to discover discontinuous domains with virtually any number of disjoint peptides. Small, single-domain proteins may contain several compact regionsthus, compact regions do not always correspond to folding domains.

    Because a domain is an independent folding unit and should contain a hydrophobic core, compact units were further examined for the presence of hydrophobic clusters (Zehfus MH, 1995, Protein Sci 41188-1202). This added constraint limits the number of acceptable units and helps greatly in the location of the true structural domains. The larger hydrophobically stabilized compact units correspond to domains, while the smaller units may correspond to folding intermediates.

    背景与目标: 紧密度已被用于在已知结构的蛋白质中定位包含一个或多个多肽链的不连续结构单元。我们的过程不是完全计算所有可能单元的紧凑性,而是使用筛选算法来查找可能紧凑的不连续区域。紧凑度的精确计算仅限于这些区域中的单位。通过我们的程序,紧密度可用于发现几乎任何数量的不连续肽的不连续域。小的单结构域蛋白可能包含几个紧密区域,因此,紧密区域并不总是对应于折叠结构域。

    由于结构域是一个独立的折叠单元,应该包含疏水核心,因此需要进一步研究紧密结构单元的结构疏水簇的存在(Zehfus MH,1995,Protein Sci 41188-1202)。这种增加的限制限制了可接受单元的数量,并极大地帮助确定了真正的结构域。较大的疏水稳定致密单元对应于结构域,而较小的单元可能对应于折叠中间体。

  • 【巨噬细胞对NF-κB活化的抑制作用减少了泡沫细胞的形成。】 复制标题 收藏 收藏
    DOI:10.1016/j.atherosclerosis.2006.07.018 复制DOI
    作者列表:Ferreira V,van Dijk KW,Groen AK,Vos RM,van der Kaa J,Gijbels MJ,Havekes LM,Pannekoek H
    BACKGROUND & AIMS: :Accumulation of lipid-laden macrophages is a hallmark of atherosclerosis. The relevance of the key transcription factor nuclear factor kappaB (NF-kappaB) for macrophage-derived foam-cell formation has not been unequivocally resolved. Transgenic mice lines were generated in which NF-kappaB activation is specifically inhibited in macrophages by overexpressing a trans-dominant, non-degradable form of IkappaBalpha (IkappaBalpha (32A/36A)) under control of the macrophage-specific SR-A promoter. Alanine substitution of serines 32 and 36 prevents degradation and retains the inactive NF-kappaB/IkappaBalpha (32A/36A) complex in the cytoplasm. Similarly, stable human THP1 monocytic cell lines were generated with integrated copies of IkappaBalpha (32A/36A) cDNA. Upon treatment with oxidized low-density lipoprotein (ox-LDL), murine peritoneal macrophages from transgenic IkappaBalpha (32A/36A) mice, as well as THP1/IkappaBalpha (32A/36A) clones, display decreased lipid loading after differentiation into macrophages. This is accompanied by increased expression of the transcription factors PPARgamma and LXRalpha as well as of the major cholesterol-efflux transporter ABCA1. Paradoxically, mRNA expression of the 'lipid-uptake' receptor CD36 is also increased. Since the net result of these changes is reduction of foam-cell formation, it is proposed that under specific inhibition of NF-kappaB activation, ABCA1-mediated cholesterol efflux prevails over CD36-mediated lipid influx.
    背景与目标: :富含脂质的巨噬细胞的积累是动脉粥样硬化的标志。尚未明确解决关键转录因子核因子κB(NF-κB)与巨噬细胞衍生的泡沫细胞形成的相关性。通过在巨噬细胞特异性SR-A启动子的控制下过表达不可表达形式的IkappaBalpha(IkappaBalpha(32A / 36A)),从而在巨噬细胞中特异性抑制NF-κB活化的转基因小鼠品系。丝氨酸32和36的丙氨酸取代防止降解并在细胞质中保留无活性的NF-κB/IκBα(32A / 36A)复合物。类似地,用整合的IkappaBalpha(32A / 36A)cDNA拷贝产生稳定的人THP1单核细胞系。经氧化低密度脂蛋白(ox-LDL)处理后,转基因IkappaBalpha(32A / 36A)小鼠以及THP1 / IkappaBalpha(32A / 36A)克隆的小鼠腹膜巨噬细胞在分化为巨噬细胞后显示出降低的脂质负载。这伴随着转录因子PPARgamma和LXRalpha以及主要胆固醇外流转运蛋白ABCA1表达的增加。矛盾的是,“脂质摄取”受体CD36的mRNA表达也增加了。由于这些变化的最终结果是减少了泡沫细胞的形成,因此建议在特定抑制NF-κB活化的情况下,ABCA1介导的胆固醇外排比CD36介导的脂质内流更为普遍。
  • 【根治性膀胱切除术可改善晚期浸润性膀胱癌的疗效。】 复制标题 收藏 收藏
    DOI:10.1007/s00345-006-0111-1 复制DOI
    作者列表:Stein JP
    BACKGROUND & AIMS: :It is clear that the optimal clinical outcomes in bladder cancer patients requiring radical cystectomy are related to standard histopathologic variables of tumor grade, stage and lymph node status. However, other less well defined variables are also critical to the successful outcomes of these patients. Patients with muscle invasive bladder cancer and treating physicians should avoid unnecessary and significant treatment delays. In addition, hospital and surgeon-volume/experience are thought to be factors that may too be important components that relate to the clinical outcomes of patients following surgery. Lastly, there is a growing body of literature to support the concept of an appropriate lymphadenectomy at the time of surgery, for both node-positive and node-negative bladder cancer patients. It is becoming more obvious that there are multiple variables involved in the clinical success and outcomes of patients with bladder cancer following radical cystectomy. As treating physicians and surgeons we must be aware of these components to ensure the best outcomes for our patients.
    背景与目标: :很明显,需要根治性膀胱切除术的膀胱癌患者的最佳临床结局与肿瘤分级,分期和淋巴结状态的标准组织病理学变量有关。但是,其他定义欠佳的变量对于这些患者的成功结局也至关重要。患有肌肉浸润性膀胱癌的患者和主治医师应避免不必要和显着的治疗延迟。另外,医院和外科医生的体格/经验被认为是可能也是与手术后患者的临床结果相关的重要组成部分的因素。最后,越来越多的文献支持针对淋巴结阳性和淋巴结阴性的膀胱癌患者在手术时进行适当的淋巴结清扫术的概念。越来越明显的是,根治性膀胱切除术后膀胱癌患者的临床成功和结局涉及多个变量。作为主治医师和外科医生,我们必须意识到这些因素,以确保为我们的患者提供最佳的治疗效果。
  • 【三七能增强5-氟尿嘧啶对人大肠癌细胞的抗癌作用。】 复制标题 收藏 收藏
    DOI:10.1007/s00280-006-0350-2 复制DOI
    作者列表:Wang CZ,Luo X,Zhang B,Song WX,Ni M,Mehendale S,Xie JT,Aung HH,He TC,Yuan CS
    BACKGROUND & AIMS: PURPOSE:Panax notoginseng is a commonly used Chinese herb. Although a few studies have found that notoginseng shows anti-tumor effects, the effect of this herb on colorectal cancer cells has not been investigated. 5-Fluorouracil (5-FU) is a chemotherapeutic agent for the treatment of colorectal cancer that interferes with the growth of cancer cells. However, this compound has serious side effects at high doses. In this study, using HCT-116 human colorectal cancer cell line, we investigated the possible synergistic anti-cancer effects between notoginseng flower extract (NGF) and 5-FU on colon cancer cells. METHODS:The anti-proliferation activity of these modes of treatment was evaluated by MTS cell proliferation assay. Apoptotic effects were analyzed by using Hoechst 33258 staining and Annexin-V/PI staining assays. The anti-proliferation effects of four major single compounds from NGF, ginsenosides Rb1, Rb3, Rc and Rg3 were also analyzed. RESULTS:Both 5-FU and NGF inhibited proliferation of HCT-116 cells. With increasing doses of 5-FU, the anti-proliferation effect was slowly increased. The combined usage of 5-FU 5 microM and NGF 0.25 mg/ml, significantly increased the anti-proliferation effect (59.4 +/- 3.3%) compared with using the two medicines separately (5-FU 5 microM, 31.1 +/- 0.4%; NGF 0.25 mg/ml, 25.3 +/- 3.6%). Apoptotic analysis showed that at this concentration, 5-FU did not exert an apoptotic effect, while apoptotic cells induced by NGF were observed, suggesting that the anti-proliferation target(s) of NGF may be different from that of 5-FU, which is known to inhibit thymidilate synthase. CONCLUSIONS:This study demonstrates that NGF can enhance the anti-proliferation effect of 5-FU on HCT-116 human colorectal cancer cells and may decrease the dosage of 5-FU needed for colorectal cancer treatment.
    背景与目标: 目的:三七是一种常用的中草药。尽管一些研究发现三七具有抗肿瘤作用,但尚未研究该药对结肠直肠癌细胞的作用。 5-氟尿嘧啶(5-FU)是一种治疗结肠直肠癌的化学治疗药物,它会干扰癌细胞的生长。但是,这种化合物在高剂量时具有严重的副作用。在这项研究中,我们使用HCT-116人结肠直肠癌细胞系,研究了三七花提取物(NGF)和5-FU对结肠癌细胞可能的协同抗癌作用。
    方法:通过MTS细胞增殖试验评估了这些治疗方式的抗增殖活性。通过使用Hoechst 33258染色和膜联蛋白-V / PI染色分析来分析细胞凋亡作用。还分析了NGF中的四种主要单一化合物,人参皂甙Rb1,Rb3,Rc和Rg3的抗增殖作用。
    结果:5-FU和NGF均抑制HCT-116细胞的增殖。随着5-FU剂量的增加,抗增殖作用缓慢增加。与分别使用两种药物(5-FU 5 microM,31.1 /-0.4%)相比,5-FU 5 microM和NGF 0.25 mg / ml的联合使用显着提高了抗增殖效果(59.4 /-3.3%); NGF 0.25 mg / ml,25.3±3.6%)。凋亡分析表明,在此浓度下,5-FU不会发挥凋亡作用,而观察到NGF诱导的凋亡细胞,这表明NGF的抗增殖靶标可能与5-FU有所不同。已知抑制胸苷酸合酶。
    结论:这项研究表明NGF可以增强5-FU对HCT-116人结肠直肠癌细胞的抗增殖作用,并可以减少治疗结肠直肠癌所需的5-FU剂量。
  • 【紫杉醇在患有晚期胃癌的血液透析患者中​​的药代动力学:一例报告。】 复制标题 收藏 收藏
    DOI:10.3748/wjg.v12.i32.5237 复制DOI
    作者列表:Kawate S,Takeyoshi I,Morishita Y
    BACKGROUND & AIMS: :We report for the first time the possibility of weekly paclitaxel chemotherapy for a patient with advanced, nonresectable gastric cancer undergoing hemodialysis. A 50-year-old man with chronic renal failure due to bilateral polycystic kidneys, who had undergone hemodialysis three times a week for 5 years, presented with hematemesis in December 2004. Based on the diagnosis of gastric cancer with lymph node metastases, surgery was performed. On the 15th postoperative day, the patient was treated with chemotherapy using paclitaxel. Paclitaxel was administered at a dose of 60 mg/m2 as a 1 h iv infusion in 250 mL of saline. Hemodialysis was started 1 h after the completion of the paclitaxel infusion and was performed for 3 h. Paclitaxel was administered weekly on d 1, 8, and 15 on a 28-d cycle. The maximum plasma concentration of paclitaxel was 1390 microg/L. The area under the curve of paclitaxel was 4398.6 microg x h/L. Grade 2 leukopenia was encountered during the first cycle. The plasma concentrations of paclitaxel from 6 to over 24 h after the infusion were 0.01 to 0.1 micromol/L in our patient, and these concentrations have been shown to be effective on inhibiting the growth of gastric cancer cells without producing adverse side effects in the patient. The plasma concentration of paclitaxel was not influenced by hemodialysis. We conclude that the pharmacokinetics of paclitaxel is not altered in a patient with renal failure, and that weekly paclitaxel is a suitable treatment regimen for hemodialysis patients with advanced gastric cancer.
    背景与目标: :我们首次报告了接受血液透析的晚期,不可切除胃癌患者每周紫杉醇化疗的可能性。一名因双侧多囊肾而导致慢性肾功能衰竭的50岁男子于5周内每周进行了3次血液透析,并于2004年12月发生了呕血。根据诊断为具有淋巴结转移的胃癌,我们进行了手术。执行。术后第15天,使用紫杉醇对患者进行化疗。紫杉醇以60 mg / m2的剂量在250 mL盐水中静脉滴注1 h。紫杉醇输注完成后1 h开始进行血液透析,并进行3 h。紫杉醇在第28天的第1、8和15天每周给药一次。紫杉醇的最大血浆浓度为1390 microg / L。紫杉醇曲线下的面积为4398.6微克×h / L。在第一个周期中遇到了2级白细胞减少症。输注后6至24小时内紫杉醇的血浆浓度在我们的患者中为0.01至0.1 micromol / L,并且这些浓度已被证明可有效抑制胃癌细胞的生长而不会对患者产生不良副作用。紫杉醇的血浆浓度不受血液透析的影响。我们得出的结论是,紫杉醇在肾衰竭患者中的​​药代动力学没有改变,并且每周紫杉醇是晚期胃癌血液透析患者的合适治疗方案。
  • 【接受放射治疗的鼻咽癌患者的口腔护理。】 复制标题 收藏 收藏
    DOI:10.1016/s0964-1955(96)00053-x 复制DOI
    作者列表:Shieh SH,Wang ST,Tsai ST,Tseng CC
    BACKGROUND & AIMS: A randomised trial was undertaken to compare the effect of three oral care protocols in delaying the onset of stomatitis and reducing oral injury in nasopharyngeal cancer patients undergoing radiotherapy, 30 eligible patients with a mean age of 56.2 years were recruited and evenly allocated to one of the three groups using a randomly permuted blocks method. Patients allocated to group E1 and group E2 were given the same instructions on oral care at 1 day, and 1 week before radiotherapy, respectively, while those allocated to the control group were given no instructions. We use the Oral Assessment Guide to assess the oral physical conditions of these patients daily. Our findings revealed that the patients in the E2 group not only had later onset of stomatitis than those in the control and the E1 groups, but also had lesser degree of oral injury measured by the overall assessment score. We thereby recommend the use of the E2 protocol for delaying the onset of stomatitis and reducing oral injury in nasopharyngeal cancer patients undergoing radiotherapy.

    背景与目标: 进行一项随机试验以比较三种口腔护理方案在接受放射治疗的鼻咽癌患者中延迟口腔炎和减少口腔损伤的效果,招募了30名平均年龄为56.2岁的合格患者,并平均分配给其中一名患者。三组使用随机排列的块方法。分配给E1组和E2组的患者分别在放疗前1天和1周接受相同的口腔护理指导,而分配给对照组的患者则没有给予指导。我们使用《口腔评估指南》每天评估这些患者的口腔身体状况。我们的研究结果表明,E2组患者不仅比对照组和E1组患者发生口腔炎的时间要晚,而且通过总体评估得分来衡量其口腔损伤的程度也较小。因此,我们建议在接受放射治疗的鼻咽癌患者中使用E2方案延迟口腔炎的发作并减少口腔损伤。

  • 【角质形成细胞迁移和肽生长因子:PDGF,bFGF,EGF,IGF-I,aFGF和TGF-β对胶原凝胶中人角膜细胞迁移的影响。】 复制标题 收藏 收藏
    DOI:10.1076/ceyr.16.6.605.5081 复制DOI
    作者列表:Andresen JL,Ledet T,Ehlers N
    BACKGROUND & AIMS: PURPOSE:Peptide growth factors are known accelerators of corneal wound healing, probably mediated through increased proliferation of the cells; however, information about their effect on keratocyte motility is lacking. The influence of peptide growth factors on keratocyte migratory activity was investigated, using the following growth factors: platelet derived growth factor (PDGF-BB), epidermal growth factor (EGF), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I) and transforming growth factor-beta-1 (TGF-beta 1).

    METHODS:Keratocytes were seeded on gels of type 1 collagen, growth factor added, and the cells left to migrate for 72 hours. Subsequently, the number of keratocytes at the different levels in the collagen gel was evaluated by optically sectioning the gel at 20 microns, intervals, with an inverted phase contrast microscope.

    RESULTS:PDGF, EGF and bFGF at 10 ng/ml, all increased the number of keratocytes at the different levels of the gel as compared to a non-stimulated control (p < 0.05 or p < 0.01, students t-test). TGF-beta proved to be a strong inhibitor of keratocyte migration, decreasing the number of keratocytes observed at every level in the gel (p < 0.05 and p < 0.01, students t-test), whereas no effect of IGF-I and aFGF was found. During the 72 hours of migration, no contraction of the collagen gels was observed. Autoradiography of histological sections of the gels showed that during the 72-hour period only TGF-beta and 10% fetal bovine serum induced an increase in keratocyte proliferation.

    CONCLUSION:PDGF, EGF and bFGF increase keratocyte migration, independent of proliferation in a collagen gel invasion assay and might promote corneal wound healing, not only by increasing cell proliferation, but also through increased motility.

    背景与目标: 目的:肽生长因子是已知的角膜伤口愈合促进剂,可能是通过细胞增殖的增加来介导的。但是,缺乏有关它们对角膜细胞运动性影响的信息。使用以下生长因子研究了肽生长因子对角膜细胞迁移活性的影响:血小板衍生生长因子(PDGF-BB),表皮生长因子(EGF),酸性成纤维细胞生长因子(aFGF),碱性成纤维细胞生长因子(bFGF) ),胰岛素样生长因子I(IGF-I)和转化生长因子β-1(TGF-beta 1)。

    方法:将角质形成细胞接种在1型胶原蛋白,添加了生长因子,细胞迁移了72小时。随后,通过倒置相差显微镜以20微米的间隔对凝胶进行光学切片,评估胶原蛋白凝胶中不同水平的角质形成细胞的数量。

    结果:PDGF与未刺激的对照组相比,10 ng / ml的EGF和bFGF均增加了凝胶水平不同时的角膜细胞数量(p <0.05或p <0.01,学生t检验)。 TGF-β被证明是一种强烈的角膜细胞迁移抑制剂,可减少凝胶中各个水平上观察到的角膜细胞数量(p <0.05和p <0.01,学生t检验),而IGF-I和aFGF则没有作用成立。在迁移的72小时内,未观察到胶原凝胶的收缩。凝胶组织学切片的放射自显影显示,在72小时内,只有TGF-β和10%的胎牛血清诱导了角膜细胞增殖的增加。

    结论:PDGF,EGF bFGF和bFGF可增加角膜细胞迁移,而不受胶原凝胶入侵试验中的增殖的影响,并且不仅可以通过增加细胞增殖,而且可以通过增加运动性来促进角膜伤口愈合。

  • 【环己胺添加剂可增强反相液相色谱中的肽分离效果。】 复制标题 收藏 收藏
    DOI:10.1002/(SICI)1099-0801(199705)11:3<167::AID-BMC67 复制DOI
    作者列表:Cole SR,Dorsey JG
    BACKGROUND & AIMS: While the choice of stationary phase, organic modifier, and gradient strength can have significant effects on biomolecule separations, mobile phase additives can also have a significant effect on the chromatographic selectivity, recovery, efficiency and resolution. Given the importance of stationary phase coverage, the beneficial, silanol-masking properties of amines, and the potential for selectivity modification through ion-pair interactions, cyclohexylamine was examined as a mobile phase additive and compared with triethylamine and trifluoroacetic acid. Greatly improved separation was possible when cyclohexylamine was used as compared with phosphate buffer, and cyclohexylamine did not require purification before use, while triethylamine required distillation before 'clean' chromatograms were obtained.

    背景与目标: 固定相,有机改性剂和梯度强度的选择可能对生物分子分离产生重大影响,而流动相添加剂也可能对色谱的选择性,回收率,效率和分离度产生重大影响。考虑到固定相覆盖的重要性,胺的有益硅烷醇掩蔽特性以及通过离子对相互作用进行选择性修饰的潜力,我们将环己胺作为流动相添加剂进行了研究,并将其与三乙胺和三氟乙酸进行了比较。与磷酸盐缓冲液相比,使用环己胺可以大大提高分离度,并且在使用前不需要纯化环己胺,而在获得“干净”色谱图之前,需要对三乙胺进行蒸馏。

  • 【幽门螺杆菌和胃癌:转移了全球负担。】 复制标题 收藏 收藏
    DOI:10.3748/wjg.v12.i34.5458 复制DOI
    作者列表:Prinz C,Schwendy S,Voland P
    BACKGROUND & AIMS: :Infection with H pylori leads to a persistent chronic inflammation of the gastric mucosa, thereby increasing the risk of distal gastric adenocarcinoma. Numerous studies have determined a clear correlation between H pylori infection and the risk of gastric cancer; however, general eradication is not recommended as cancer prophylaxis and time points for treatment remain controversial in different areas of the world. Prevalence rates in Western countries are decreasing, especially in younger people (< 10%); and a decline in distal gastric adenocarcinoma has been observed. Risk groups in Western countries still show considerably higher risk of developing cancer, especially in patients infected with cagA+ strains and in persons harboring genetic polymorphism of the IL-1B promoter (-511T/T) and the corresponding IL-1 receptor antagonist (IL-1RN*2). Thus, general eradication of all infected persons in Western countries not recommended and is limited to risk groups in order to achieve a risk reduction. In contrast, infection rates and cancer prevalence are still high in East Asian countries. A prevention strategy to treat infected persons may avoid the development of gastric cancer to a large extent and with enormous clinical importance. However, studies in China and Japan indicate that prevention of gastric cancer is effective only in those patients that do not display severe histological changes such as atrophy and intestinal metaplasia. Thus, prophylactic strategies to prevent gastric cancer in high risk populations such as China should therefore especially aim at individuals now at younger age when the histological alterations caused by the bacterial infection was still reversible. In countries with a low prevalence of gastric cancer, risk groups carrying cagA+ strains and IL-1 genetic polymorphisms should be identified and treated.
    背景与目标: 幽门螺杆菌感染导致胃粘膜持续性慢性炎症,从而增加了远端胃腺癌的风险。大量研究已确定幽门螺杆菌感染与胃癌风险之间存在明显的相关性。但是,不建议普遍根除,因为在世界不同地区,癌症的预防和治疗时间仍然存在争议。西方国家的患病率正在下降,尤其是在年轻人中(<10%);并且已经观察到远端胃腺癌的下降。西方国家的风险人群仍然显示出罹患癌症的高得多的风险,尤其是在感染cagA株的患者以及具有IL-1B启动子(-511T / T)和相应的IL-1受体拮抗剂(IL- 1RN * 2)。因此,不建议在西方国家全面消灭所有感染者,并且仅限于风险人群,以实现降低风险的目的。相反,东亚国家的感染率和癌症患病率仍然很高。治疗感染者的预防策略可以在很大程度上避免胃癌的发展,并且具有巨大的临床意义。但是,在中国和日本的研究表明,胃癌的预防仅对那些没有表现出严重的组织学改变(例如萎缩和肠化生)的患者有效。因此,在中国这样的高风险人群中,预防胃癌的预防策略应特别针对年龄较小的人群,因为这些年龄段的细菌感染引起的组织学改变仍然是可逆的。在胃癌患病率较低的国家,应识别和治疗携带cagA毒株和IL-1遗传多态性的危险人群。
  • 【在复制错误阳性胃肠道癌症中,针对癌症相关基因中重复序列不稳定的明显保护。】 复制标题 收藏 收藏
    DOI:10.1038/sj.onc.1201094 复制DOI
    作者列表:Simms LA,Zou TT,Young J,Shi YQ,Lei J,Appel R,Rhyu MG,Sugimura H,Chenevix-Trench G,Souza RF,Meltzer SJ,Leggett BA
    BACKGROUND & AIMS: Genomic instability at simple repeated sequences has been observed in various types of human cancers and is considered an important mechanism in tumorigenesis. Alterations at microsatellite loci have been reported scattered throughout the genome. Recently, the transforming growth factor-beta receptor type II (TGF-beta RII) and the insulin-like growth factor II receptor (IGF-IIR) genes were shown to have inactivating mutations within coding microsatellite sequences. The demonstration of mutations in two growth regulatory genes supports the idea that other regulatory genes with repeat sequences may also be targets in tumours with defective mismatch repair. We examined genes involved in tumour suppression, cell adhesion and cell cycle regulation for mutations at small repeat sequences in replication error positive gastrointestinal cancers. Several polymorphisms were found which exhibited instability, but no other instability was present in the regions examined.

    背景与目标: 在各种类型的人类癌症中已经观察到简单重复序列的基因组不稳定性,并且被认为是肿瘤发生的重要机制。据报道,微卫星基因座的改变分散在整个基因组中。最近,研究表明转化生长因子β受体II型(TGF-βRII)和胰岛素样生长因子II受体(IGF-IIR)基因在编码微卫星序列中具有失活突变。两个生长调节基因突变的证明支持了这样的想法,即具有重复序列的其他调节基因也可能是错配修复缺陷的肿瘤的靶标。我们检查了涉及复制抑制阳性胃肠道癌中小重复序列突变的肿瘤抑制,细胞粘附和细胞周期调控的基因。发现了几个表现出不稳定性的多态性,但在检查的区域中没有其他不稳定性。

  • 【Xanthomonas campestris pv的特异结合。 vesicatoria AraC型转录激活因子HrpX到植物诱导型启动子盒。】 复制标题 收藏 收藏
    DOI:10.1128/JB.00795-06 复制DOI
    作者列表:Koebnik R,Krüger A,Thieme F,Urban A,Bonas U
    BACKGROUND & AIMS: :The pathogenicity of the plant-pathogenic bacterium Xanthomonas campestris pv. vesicatoria depends on a type III secretion system which is encoded by the 23-kb hrp (hypersensitive response and pathogenicity) gene cluster. Expression of the hrp operons is strongly induced in planta and in a special minimal medium and depends on two regulatory proteins, HrpG and HrpX. In this study, DNA affinity enrichment was used to demonstrate that the AraC-type transcriptional activator HrpX binds to a conserved cis-regulatory element, the plant-inducible promoter (PIP) box (TTCGC-N(15)-TTCGC), present in the promoter regions of four hrp operons. No binding of HrpX was observed when DNA fragments lacking a PIP box were used. HrpX also bound to a DNA fragment containing an imperfect PIP box (TTCGC-N(8)-TTCGT). Dinucleotide replacements in each half-site of the PIP box strongly decreased binding of HrpX, while simultaneous dinucleotide replacements in both half-sites completely abolished binding. Based on the complete genome sequence of Xanthomonas campestris pv. vesicatoria, putative plant-inducible promoters consisting of a PIP box and a -10 promoter motif were identified in the promoter regions of almost all HrpX-activated genes. Bioinformatic analyses and reverse transcription-PCR experiments revealed novel HrpX-dependent genes, among them a NUDIX hydrolase gene and several genes with a predicted role in the degradation of the plant cell wall. We conclude that HrpX is the most downstream component of the hrp regulatory cascade, which is proposed to directly activate most genes of the hrpX regulon via binding to corresponding PIP boxes.
    背景与目标: :植物致病性细菌Xanthomonas campestris pv的致病性。 vesicatoria依赖于由23-kb hrp(过敏反应和致病性)基因簇编码的III型分泌系统。 hrp操纵子的表达在植物和特殊的基本培养基中强烈诱导,并依赖于两种调节蛋白HrpG和HrpX。在这项研究中,DNA亲和力富集用于证明AraC型转录激活因子HrpX与保守的顺式调控元件,即植物诱导型启动子(PIP)框(TTCGC-N(15)-TTCGC)结合,四个hrp操纵子的启动子区域。当使用缺少PIP盒的DNA片段时,未观察到HrpX的结合。 HrpX还绑定到包含不完整的PIP盒(TTCGC-N(8)-TTCGT)的DNA片段。 PIP盒每个半位中的二核苷酸替换强烈降低了HrpX的结合,而两个半位中同时进行的二核苷酸替换则完全消除了结合。基于Xanthomonas campestris pv的完整基因组序列。在几乎所有的HrpX激活基因的启动子区域中,鉴定出了由vesptoria组成的假定的植物诱导型启动子,该启动子由PIP框和-10个启动子组成。生物信息学分析和逆转录-PCR实验揭示了新的HrpX依赖性基因,其中包括NUDIX水解酶基因和几个在植物细胞壁降解中具有预测作用的基因。我们得出的结论是,HrpX是hrp调节级联的最下游组件,建议通过与相应的PIP盒结合直接激活hrpX regulon的大多数基因。
  • 【在胃十二指肠溃疡住院的患者中,通过组织学检查发现食道癌的风险。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:2007-04-01
    来源期刊:Gut
    DOI:10.1136/gut.2006.109082 复制DOI
    作者列表:Bahmanyar S,Zendehdel K,Nyrén O,Ye W
    BACKGROUND & AIMS: OBJECTIVE:The mechanism behind the epidemiologically evident inverse relation between Helicobacter pylori seropositivity and risk of oesophageal adenocarcinoma (OAC) remains obscure. Severe corpus gastritis is unlikely to be in the causal pathway. With the hypothesis of a uniformly low risk, the associations of OAC with duodenal ulcer and gastric ulcer were explored, both linked to H pylori infection but with different patterns of bacterial colonisation and intragastric acidity. Possible associations of oesophageal squamous cell carcinoma (OSCC) with these ulcer types were also addressed. DESIGN AND PATIENTS:Retrospective cohorts of 61,548 and 81,379 unoperated patients with duodenal ulcer and gastric ulcer, respectively, recorded in the Swedish Inpatient Register since 1965, were followed from the first hospitalisation until the date of any cancer, death, emigration, definitive surgery, or 31 December 2003. Standardised incidence ratios (SIRs), with 95% CIs, expressed relative risk of oesophageal cancer, compared with the Swedish population matched for age, sex and calendar period. RESULTS:Contrary to expectation, patients with duodenal ulcer had a significant 70% excess risk of OAC (SIR 1.7, 95% CI 1.1 to 2.5). Gastric ulcer was unrelated to OAC (SIR 1.1, 95% CI 0.6 to 1.7). Although duodenal ulcer was non-significantly associated with a small excess of OSCC (SIR 1.3, 95% CI 0.96 to 1.8), gastric ulcer was linked to 80% increased risk (SIR 1.8, 95% CI 1.4 to 2.3). CONCLUSION:The inverse association between H pylori and OAC does not pertain to all infections. The pattern of gastric colonisation and/or impact on acidity may be important. With the reservation for the possibility of confounding, this study also provides some support for the importance of intragastric environment in the aetiology of OSCC.
    背景与目标: 目的:幽门螺杆菌血清阳性与食管腺癌(OAC)风险之间的流行病学证据呈负相关。严重的胃炎胃炎不太可能在因果关系中。假设风险均一,探讨了OAC与十二指肠溃疡和胃溃疡的相关性,两者均与幽门螺杆菌感染有关,但细菌定植和胃内酸度不同。食管鳞状细胞癌(OSCC)与这些溃疡类型的可能关联也得到了解决。
    设计和患者:自1965年以来在瑞典住院患者登记表中记录的分别有61,548和81,379例未手术的十二指肠溃疡和胃溃疡患者的回顾性队列,从首次住院治疗直至癌症,死亡,移民,定型手术,或2003年12月31日。与年龄,性别和日历时期相匹配的瑞典人口相比,具有95%CI的标准发生率(SIR)表示食道癌的相对风险。
    结果:与预期相反,十二指肠溃疡患者发生OAC的风险显着增加70%(SIR 1.7,95%CI 1.1至2.5)。胃溃疡与OAC无关(SIR 1.1,95%CI 0.6至1.7)。尽管十二指肠溃疡与OSCC的少量过量无显着相关性(SIR 1.3,95%CI 0.96至1.8),但胃溃疡与80%的风险增加相关(SIR 1.8,95%CI 1.4至2.3)。
    结论:幽门螺杆菌与OAC之间的负相关并不适用于所有感染。胃定植的模式和/或对酸度的影响可能很重要。由于保留了混淆的可能性,本研究还为胃内环境在OSCC病因中的重要性提供了一些支持。
  • 【抗原特异性T细胞克隆在胶原疾病中的意义:用新型T细胞克隆性评估系统进行分析。】 复制标题 收藏 收藏
    DOI:10.2169/internalmedicine.36.242 复制DOI
    作者列表:Yamamoto K
    BACKGROUND & AIMS: The involvement of antigen-specific T cells in the pathogenesis of collagen diseases is still controversial. The final stages of collagen diseases are usually characterized by the dominance of inflammation. Therefore, antigen non-specific factors, such as inflammatory cytokines, probably play an important role in this process. On the other hand, the methods available to analyze the antigen-specific aspects of the immune response are still limited. Here we review our novel system of T cell clonality analysis based on the idea that activated antigen-specific T cells should form accumulating clones among the lymphocyte population. Using this method, dynamic changes of clonal accumulation of T cells could be evaluated during antigenic stimulation in vivo and in vitro. The significance of antigen-specific T cell clones in collagen diseases is discussed using data obtained from patients with rheumatoid arthritis and systemic lupus erythematosus.

    背景与目标: 抗原特异性T细胞是否参与胶原蛋白疾病的发病机制仍存在争议。胶原蛋白疾病的最后阶段通常以炎症占优势为特征。因此,抗原非特异性因子,例如炎性细胞因子,可能在此过程中起重要作用。另一方面,可用于分析免疫应答的抗原特异性方面的方法仍然有限。在这里,我们基于激活的抗原特异性T细胞应在淋巴细胞群体中形成累积克隆的想法,回顾了我们的T细胞克隆性分析的新系统。使用这种方法,可以在体内和体外抗原刺激过程中评估T细胞克隆积累的动态变化。利用类风湿性关节炎和系统性红斑狼疮患者获得的数据,讨论了抗原特异性T细胞克隆在胶原蛋白疾病中的重要性。

  • 【罕见的母体mRNA编码调控蛋白,这些蛋白控制着海胆胚胎中谱系特异性基因的表达。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.87.20.7953 复制DOI
    作者列表:Cutting AE,Höög C,Calzone FJ,Britten RJ,Davidson EH
    BACKGROUND & AIMS: :The prevalence of mRNAs coding for the sea urchin embryo regulatory factors P3A1 and P3A2 was measured by single-strand probe excess solution hybridization. P3A1 and P3A2 are not homologous proteins, though they both bind specifically to a particular cis-regulatory sequence. Interaction at this target site is known to be required for lineage-specific expression of an aboral ectoderm-specific gene and probably for several other genes as well. Genome blot hybridizations show that both factors are encoded by single-copy genes. Maternal mRNAs for both factors are present at less than 10(3) molecules per egg, which places them in the rare mRNA class. During development to the mesenchyme blastula stage, the amount of P3A1 mRNA (per embryo) increases severalfold while that of P3A2 remains approximately constant. Specification of the aboral ectoderm founder cells and of their initial patterns of gene expression must occur during early to mid-cleavage stage. Therefore, the regulatory proteins needed for this process must be produced by this stage. We show that the quantities of the P3A proteins that can be synthesized from the numbers of mRNA molecules present in the large blastomeres of the early embryo are sufficient to be functional, because these proteins will be accumulated in the nuclei. Thus maternal P3A1 or P3A2 proteins asre not required, nor were these detected in earlier studies. Furthermore, differential spatial (as well as temporal) distribution of both of these newly synthesized factor species could result from the unequal cleavage pattern utilized in the sea urchin egg.
    背景与目标: :通过单链探针过量溶液杂交测量编码海胆胚胎调节因子P3A1和P3A2的mRNA的发生率。尽管P3A1和P3A2都与特定的顺式调控序列特异性结合,但它们不是同源蛋白。已知该靶标位点的相互作用是特定于宗族的外胚层特异性基因的谱系表达所必需的,并且可能还需要其他几个基因。基因组印迹杂交显示这两个因子均由单拷贝基因编码。每个鸡蛋的母体mRNA均少于10(3)个分子,这使它们处于罕见的mRNA类中。在发育到间充质囊阶段期间,P3A1 mRNA(每个胚胎)的数量增加了几倍,而P3A2的数量则保持大致恒定。胎盘外胚层基础细胞及其基因表达的初始模式的规范必须在卵裂早期至中期进行。因此,必须在该阶段生产该过程所需的调节蛋白。我们表明,可以从早期胚胎的大型卵裂球中存在的mRNA分子数量合成的P3A蛋白数量足以发挥功能,因为这些蛋白将积聚在细胞核中。因此,不需要母体P3A1或P3A2蛋白,也不需要在早期研究中检测到这些蛋白。此外,这两种新合成的因子物种在空间(以及时间)上的差异分布可能是由于海胆卵中使用的不均等卵裂模式造成的。
  • 【连续静脉和皮下注射吗啡治疗慢性癌症疼痛的前瞻性,在患者内交叉研究。】 复制标题 收藏 收藏
    DOI:10.1016/s0885-3924(96)00329-6 复制DOI
    作者列表:Nelson KA,Glare PA,Walsh D,Groh ES
    BACKGROUND & AIMS: The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

    背景与目标: 比较了慢性癌症疼痛患者中吗啡连续静脉输注(CIVI)与吗啡连续皮下输注(CSCI)的剂量,疗效和副作用。符合条件的患者被转到姑息治疗计划,并接受稳定剂量的吗啡CIVI。该设计是患者内部的单向交叉。其中每个患者提供了从吗啡从CIVI切换到CSCI之前和之后的数据。 “救援”剂量是根据需要每2小时给予的每小时剂量的50%。吗啡通过McGaw / AccuPro容量输注泵静脉内(i.v.)和皮下(s.c.)输注。获得包括副作用和疼痛评估在内的基线数据后,每天对患者进行两次毒性和止痛效果评估。连续48个小时具有稳定CIVI剂量的患者以与静脉内(i.v.)阶段相同的剂量转入CSCI。稳定剂量定义为无剂量变化,在过去24小时内有四个或更少的急救剂量,疼痛等级为无或轻度。如果连续96个小时保持这些标准,则认为CIVI等于CSCI。入组患者57例,其中40例可评估(女性15例,男性25例)。中位年龄为67岁(范围为30-83岁)。在整个静脉内维持稳定剂量后,所有40位参与者阶段,跨到南卡罗来纳州相并保持在s.c.至少持续48小时。在整个静脉内,有32名患者维持了稳定的剂量。和s.c.阶段。平均稳定i.v.剂量(第2天)为5.05 mg / hr,平均稳定s.c.剂量(第4天)为5.7 mg / hr(P = 0.01)。第2天的平均急救剂量为每24小时0.83,而第4天为每24小时0.80(P = 0.6)。第2天的平均类别疼痛评分为0.83,第4天的平均疼痛评分为0.85(P = 0.7)。第2天的平均视觉模拟量表(VAS)为22.9毫米,而第4天为17.6毫米(P = 0.1)。第2天的副作用的平均发生率为1.7,而第4天的平均发生率为2.0(P = 0.2)。没有患者因不可接受的毒性而退出或剂量减少。有两份关于SC针插入点的局部毒性(轻度红斑)的报道,需要进行部位改变。我们所有的40名患者均通过CIVI和CSCI吗啡可以很好地控制疼痛。在没有保持相同i.v.的八位参与者中和s.c.剂量较高时,所有患者均具有足够的疼痛控制能力,并且在较高的s.c.下具有相似的副作用。吗啡剂量。这些数据表明和s.c.当以连续输注方式给药时,对于大多数患者而言,这两种途径均具有镇痛作用。疼痛控制和副作用状况非常相似且可以接受。南卡罗来纳州吗啡是静脉注射的绝佳替代品。需要胃肠外吗啡治疗的住院患者和门诊患者中的吗啡疼痛。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录