• 【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的不同。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。
  • 【所谓的“次要” ABO不相容外周血干细胞同种异体移植后的早期致命性免疫溶血。】 复制标题 收藏 收藏
    DOI:10.1038/sj.bmt.1700794 复制DOI
    作者列表:Oziel-Taieb S,Faucher-Barbey C,Chabannon C,Ladaique P,Saux P,Gouin F,Gastaut JA,Maraninchi D,Blaise D
    BACKGROUND & AIMS: A 38-year-old man, blood group A+, was allotransplanted for multiple myeloma from his fully matched sister, blood group O+. Anti-A antibodies IgG and IgM titres of the donor were low. Allogeneic peripheral blood stem cells were harvested by leukapheresis after subcutaneous administration of G-CSF. Rapid engraftment occurred since 5.6 x 10(9)/l leukocytes were achieved on day +9 post-transplant. At this time a severe immune haemolytic syndrome occurred and direct antiglobulin test was positive (IgG and C3d). Elution showed an anti-A specificity. Evolution was rapidly unfavourable related to multiorgan failure. The patient died on day +20 post-transplant.

    背景与目标: 一名38岁的男性,血型A,是从他完全匹配的姐姐的血型O中异位移植的,用于多发性骨髓瘤。供体的抗A抗体IgG和IgM滴度很低。皮下给药G-CSF后,通过白细胞分离术收集异体外周血干细胞。由于移植后第9天获得了5.6 x 10(9)/ l白细胞,因此发生了快速植入。这时发生了严重的免疫溶血综合症,直接抗球蛋白测试为阳性(IgG和C3d)。洗脱显示出抗A特异性。与多器官衰竭有关的进化迅速不利。该患者在移植后的第20天死亡。

  • 【无细胞翻译过程中的异寡聚去唾液酸糖蛋白受体复合物的组装。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.87.12.4854 复制DOI
    作者列表:Sawyer JT,Doyle D
    BACKGROUND & AIMS: :We have translated RNAs for the two rat asialoglycoprotein receptor polypeptides together in a cell-free system containing dog pancreatic microsomes and immunoprecipitated the products with antibodies that distinguish the two proteins. In this system the proteins oligomerize, as judged by their coprecipitation with either of the subunit-specific antisera. Oligomerization does not occur between subunits synthesized without microsomes or between subunits synthesized on separate microsomes mixed during detergent solubilization. Thus, oligomerization occurs within the microsomal membrane. We calculate that oligomerization proceeds with an efficiency of approximately 85%. The receptor complex appears to represent a specific oligomer because it excludes a third membrane glycoprotein synthesized in the same reaction. Oligomerization of the asialoglycoprotein receptor in vitro should provide a useful system to study the assembly of a membrane-protein complex.
    背景与目标: :我们已经在包含狗胰微粒体的无细胞系统中一起翻译了两种大鼠去唾液酸糖蛋白受体多肽的RNA,并使用区分这两种蛋白的抗体对产品进行了免疫沉淀。在该系统中,蛋白质通过与任何亚基特异性抗血清共沉淀来寡聚。在没有微粒体的情况下合成的亚基之间或在去污剂溶解过程中混合的单独微粒体上合成的亚基之间不会发生低聚。因此,低聚发生在微粒体膜内。我们计算出低聚进行的效率约为85%。受体复合物似乎代表特定的寡聚物,因为它排除了在同一反应中合成的第三膜糖蛋白。脱唾液酸糖蛋白受体的体外低聚应该提供一个有用的系统来研究膜-蛋白复合物的组装。
  • 【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50岁的男子因双侧多囊肾而导致慢性肾功能衰竭,他每周进行3次血液透析治疗5年,并于2004年12月出现呕血。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小时的紫杉醇血浆浓度在我们的患者中为0.01至0.1 micromol / L,并且这些浓度已显示出可有效抑制胃癌细胞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。
  • 【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)。本研究的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,在21名患者中有11名患者(52%)对依那西普治疗有反应,包括6名患者(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,尤其是在胃肠道受累的情况下。
  • 【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。

  • 【非侵入性连续估计人pa骨的血流变化。】 复制标题 收藏 收藏
    DOI:10.1007/s11517-006-0070-0 复制DOI
    作者列表:Näslund J,Pettersson J,Lundeberg T,Linnarsson D,Lindberg LG
    BACKGROUND & AIMS: :A photoplethysmographic (PPG) technique to assess blood flow in bone tissue has been developed and tested. The signal detected by the PPG consists of a constant-level (DC) component-which is related to the relative vascularization of the tissue-and a pulsatile (AC) component-which is synchronous with the pumping action of the heart. The PPG probe was applied on the skin over the patella. The probe uses near-infrared (804 nm) and green (560 nm) light sources and the AC component of the PPG signals of the two wavelengths was used to monitor pulsatile blood flow in the patellar bone and the overlying skin, respectively. Twenty healthy subjects were studied and arterial occlusion resulted in elimination of PPG signals at both wavelengths, whereas occlusion of skin blood flow by local surface pressure eliminated only the PPG signal at 560 nm. In a parallel study on a physical model with a rigid tube we showed that the AC component of the PPG signal originates from pulsations of blood flow in a rigid structure and not necessarily from volume pulsations. We conclude that pulsatile blood flow in the patellar bone can be assessed with the present PPG technique.
    背景与目标: :已经开发并测试了用于评​​估骨组织中血流的光电容积描记(PPG)技术。 PPG检测到的信号由与组织的相对血管形成有关的恒定水平(DC)分量和与心脏的泵浦动作同步的脉动(AC)分量组成。将PPG探针施加到over骨上的皮肤上。该探头使用近红外(804 nm)和绿色(560 nm)光源,并且两个波长的PPG信号的AC分量分别用于监视the骨和周围皮肤中的脉动血流。研究了20名健康受试者,动脉阻塞导致两种波长的PPG信号均被消除,而局部表面压力阻塞皮肤血流仅消除了560 nm处的PPG信号。在具有刚性管的物理模型的并行研究中,我们显示了PPG信号的AC分量源自刚性结构中的血流脉动,而不一定源自体积脉动。我们得出的结论是,可以使用当前的PPG技术评估the骨中的搏动性血流。
  • 【非感染性空颗粒和感染性病毒上3型脊髓灰质炎病毒抗原性位点构象的差异。】 复制标题 收藏 收藏
    DOI:10.1099/0022-1317-71-6-1271 复制DOI
    作者列表:Ferguson M,Minor PD
    BACKGROUND & AIMS: :A panel of monoclonal antibodies which react with empty non-infectious type 3 poliovirus particles (C antigen) but not infectious virus (D antigen) were characterized for their reactivity with C antigen particles derived from neutralization-resistant virus strains which had single amino acid substitutions at each of the antigenic sites. Antibodies were identified which failed to bind to variant viruses with modifications at each of antigenic sites 2b, 3b and 4 indicating that the same amino acid sequences involved in the neutralization of infectious virus are also present on the surface of non-infectious particles but in different configurations.
    背景与目标: :一组与空的非感染性3型脊髓灰质炎病毒颗粒(C抗原)反应但不与感染性病毒(D抗原)反应的单克隆抗体的特征在于它们与衍生自具有单个氨基酸的中和抗性病毒株的C抗原颗粒的反应性每个抗原位点的取代。鉴定了未能结合在抗原性位点2b,3b和4处被修饰的变异病毒的抗体,这表明与感染性病毒的中和有关的相同氨基酸序列也存在于非感染性颗粒的表面,但存在差异配置。
  • 【T-T细胞相互作用是由粘附分子介导的。】 复制标题 收藏 收藏
    DOI:10.1002/eji.1830201015 复制DOI
    作者列表:Brod SA,Purvee M,Benjamin D,Hafler DA
    BACKGROUND & AIMS: :The mechanism by which T cells signal other T cells is not well defined. This was investigated by studying the ability of circulating T cells to induce the proliferation of autologous T cell clones. Peripheral blood T cells activated by cross-linking of the CD3/T cell receptor complex, which increased the expression of cell adhesion molecules LFA-1, LFA-3 and ICAM-1, induced the proliferation of autologous T cell clones. Irradiated antigen-activated peripheral blood T cells could also induce the proliferation of T cell clones which could not recognize that antigen. T-T cell activation required cell contact, was not major histocompatibility complex (MHC) restricted and was blocked by monoclonal antibodies directed against adhesion molecules CD2 and LFA-3 but was not blocked by antibody to class II MHC determinants. As CD2 is the natural ligand for LFA-3, increased expression of T cell surface adhesion molecules LFA-1, ICAM-1 and particularly LFA-3 during an inflammatory response may rapidly recruit T cells that are activated through the CD2 pathway. These results allow a simplified model to explain how relatively few antigen/MHC-specific T cells can recruit large numbers of non-antigen-specific T cells in the generation of an inflammatory response and postulates a novel role of the CD2 molecule in T cell immune function.
    背景与目标: :T细胞向其他T细胞发出信号的机制尚不明确。通过研究循环T细胞诱导自体T细胞克隆增殖的能力,对此进行了研究。通过CD3 / T细胞受体复合物交联而活化的外周血T细胞增加了细胞粘附分子LFA-1,LFA-3和ICAM-1的表达,诱导了自体T细胞克隆的增殖。辐射的抗原活化的外周血T细胞也可以诱导不能识别该抗原的T细胞克隆的增殖。 T-T细胞活化需要细胞接触,不受主要组织相容性复合物(MHC)的限制,并且被针对粘附分子CD2和LFA-3的单克隆抗体所阻断,但未被II类MHC决定簇的抗体所阻断。由于CD2是LFA-3的天然配体,因此在炎症反应期间T细胞表面粘附分子LFA-1,ICAM-1尤其是LFA-3的表达增加,可能会迅速募集通过CD2途径激活的T细胞。这些结果使简化的模型可以解释相对较少的抗原/ MHC特异性T细胞在炎症反应的产生中如何募集大量非抗原特异性T细胞,并推测CD2分子在T细胞免疫中的新作用功能。
  • 【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较高的患癌风险,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的不稳定性提供明显的保护。】 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。

  • 【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,二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群相比,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少量过量的OSCC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。
  • 【ARDS的通气管理:高频振荡和肺募集!】 复制标题 收藏 收藏
    DOI:10.1186/cc5018 复制DOI
    作者列表:Kacmarek RM
    BACKGROUND & AIMS: :Many aspects of ventilatory management in patients with ARDS are still controversial and one of the major controversies is should HFO or CMV ideally be used to manage this patients. As shown by David et al. when the two approaches to ventilatory support are applied using similar principles the physiologic outcomes appear to be similar. With both approaches the use of lung recruitment maneuvers early in ARDS (1 to 3 day) after hemodynamic stabilization in patients without baratrauma is promising. The key to managing ARDS regardless of mode is to use an open lung protective ventilatory strategy. It is not the mode that makes the difference, it is the approach used to apply the mode!
    背景与目标: :ARDS患者的通气管理的许多方面仍存在争议,主要争议之一是是否应理想地使用HFO或CMV来管理该患者。如David等所示。当使用相似的原理应用两种通气支持方法时,其生理结果似乎相似。对于这两种方法,在无原发性出血的患者中,在血液动力学稳定后的ARDS早期(1至3天)使用肺募集手术是有希望的。无论采用哪种模式,管理ARDS的关键都是采用开放式肺保护性通气策略。造成差异的不是模式,而是应用模式的方法!
  • 【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。

  • 【类风湿关节炎患者中性粒细胞的肌动蛋白聚合与非甾体类抗炎药的治疗有关。】 复制标题 收藏 收藏
    DOI:10.1016/s0009-8981(96)06505-9 复制DOI
    作者列表:De Clerck LS,Mertens AV,De Gendt CM,Bridts CH,Stevens WJ
    BACKGROUND & AIMS: There is evidence that neutrophil functions such as chemotaxis and oxygen radical formation are disturbed in rheumatoid arthritis (RA). Medication might also influence these functions. Cyclic formation and depolymerisation of actin microfilaments is crucial in cell motility, but this phenomenon has not been studied in RA. The aim of this study was to investigate basal and dynamic (formyl-methionyl-leucyl-phenylalanine (fMLP)-induced) neutrophil actin polymerisation in ten RA patients (a) during therapy with non-steroidal anti-inflammatory drugs (NSAIDS) and (b) after stopping NSAIDS> The results were compared with those of ten age-matched controls. Basal F-actin content in RA patients with NSAIDS was significantly lower than in RA patients without NSAIDS and controls35.5 (25.0-49.0), 50.5 (27.0-75.0) and 52.5 (32.0-85.0), respectively. Conversely, upon stimulation with fMLP, the actin polymerisation curve of RA patients with NSAIDS was higher than for RA patients without NSAIDS and controls. These results suggest that, in RA, the effects orf NSAIDS on neutrophil functions might be related to changes in the actin polymerisation-depolymerisation cycle.

    背景与目标: 有证据表明,类风湿关节炎(RA)中性粒细胞功能(如趋化性和氧自由基的形成)受到干扰。药物治疗也可能影响这些功能。肌动蛋白微丝的循环形成和解聚对于细胞运动至关重要,但尚未在RA中研究此现象。本研究的目的是研究10名RA患者的基础和动态(甲酰基-甲硫酰基-亮氨酰-苯丙氨酸(fMLP)诱导)嗜中性白细胞肌动蛋白聚合反应(a)在使用非甾体抗炎药(NSAIDS)治疗期间和( b)停止NSAIDS后>将结果与十个年龄匹配的对照组的结果进行比较。 NSAIDS的RA患者的基础F-肌动蛋白含量显着低于非NSAIDS的RA患者和对照组,分别为35.5(25.0-49.0),50.5(27.0-75.0)和52.5(32.0-85.0)。相反,在用fMLP刺激后,患有NSAIDS的RA患者的肌动蛋白聚合曲线高于没有NSAIDS和对照的RA患者。这些结果表明,在RA中,NSAIDS对中性粒细胞功能的影响可能与肌动蛋白聚合-解聚循环的变化有关。

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