• 【择期剖宫产后新生儿死亡率和发病率与常规预期管理: 决策分析。】 复制标题 收藏 收藏
    DOI:10.1053/j.semperi.2006.07.010 复制DOI
    作者列表:Signore C,Hemachandra A,Klebanoff M
    BACKGROUND & AIMS: :A number of competing risks and benefits influence the rates of neonatal morbidity and mortality in elective cesarean delivery versus expectant management. To compare these rates, we developed complex decision trees to model the expected outcomes among hypothetical cohorts of 1,000,000 uncomplicated pregnancies undergoing elective cesarean delivery versus 1,000,000 comparable pregnancies undergoing routine pregnancy management. A separate tree was created for each complication, including neonatal death, respiratory morbidity, intracranial hemorrhage, and brachial plexus injury. We found that neonatal mortality was increased among elective cesarean deliveries, but perinatal mortality was higher with routine expectant management due to fetal deaths. Respiratory morbidity was substantially more common among infants delivered by elective cesarean delivery, whereas intracranial hemorrhage and brachial plexus injury were less common. We conclude that the fetal/neonatal impact of elective cesarean is mixed, but any improvement in perinatal health is likely to be small.
    背景与目标: : 在选择性剖宫产与预期管理中,许多竞争性风险和收益会影响新生儿的发病率和死亡率。为了比较这些比率,我们开发了复杂的决策树来模拟假设队列中的预期结果,这些队列中的1,000,000例非复杂妊娠接受选择性剖宫产,而1,000,000例可比妊娠接受常规妊娠管理。为每种并发症 (包括新生儿死亡,呼吸系统疾病,颅内出血和臂丛神经损伤) 创建了单独的树。我们发现,选择性剖宫产分娩的新生儿死亡率增加,但由于胎儿死亡,常规预期治疗的围产期死亡率更高。在择期剖宫产分娩的婴儿中,呼吸系统的发病率明显更高,而颅内出血和臂丛神经损伤则较少见。我们得出的结论是,选择性剖宫产对胎儿/新生儿的影响是混合的,但是围产期健康的任何改善都可能很小。
  • 【单极抑郁症的文献治疗: 一项荟萃分析。】 复制标题 收藏 收藏
    DOI:10.1016/s0005-7916(97)00005-0 复制DOI
    作者列表:Cuijpers P
    BACKGROUND & AIMS: In the last decades, several therapies for unipolar depression have been developed, for example cognitive therapy, behavior therapy and pharmacotherapy. A new kind of therapy is bibliotherapy. What is new in this treatment modality is not the content, because bibliotherapy usually uses a cognitive-behavioral approach. Only the form in which it is presented is new. In bibliotherapy the patient takes a standardized treatment home, in book form, and works it through more or less independently. Contacts with therapists are only supportive or facilitative. No traditional relationship between therapist and patient is developed. In this article the relevance of bibliotherapy for the clinical practice is presented and a meta-analysis of the research into bibliotherapy is described.

    背景与目标: 在过去的几十年中,已经开发了几种针对单相抑郁症的疗法,例如认知疗法,行为疗法和药物疗法。一种新的疗法是书目疗法。这种治疗方式的新内容不是内容,因为书目疗法通常使用认知行为方法。只有呈现的形式是新的。在书目疗法中,患者以书本形式接受标准化治疗,并或多或少地独立进行治疗。与治疗师的接触只是支持性或促进性的。没有发展治疗师和患者之间的传统关系。本文介绍了书目疗法与临床实践的相关性,并描述了对书目疗法研究的荟萃分析。
  • 【右精索静脉曲张和缺氧,男性不育的关键因素: 睾丸引流系统受损的流体力学分析。】 复制标题 收藏 收藏
    DOI:10.1016/s1472-6483(10)60638-4 复制DOI
    作者列表:Gat Y,Gornish M,Navon U,Chakraborty J,Bachar GN,Ben-Shlomo I
    BACKGROUND & AIMS: :Varicocele is considered a predominantly unilateral left-sided disease. However, since male fertility is preserved with only one healthy testis, infertility perforce represents bilateral testicular dysfunction. It was hypothesized that: (i) right varicocele cannot be diagnosed by palpation and therefore has not been treated in the past by the traditional treatment, and (ii) right varicocele causes impaired oxygen supply in the right testicular microcirculation, leading to germ cell degeneration. This study performed venographies of both right and left internal spermatic veins during the treatment of 840 infertile men with varicocele and analysed the results using tools of fluid mechanics. Histopathology of the right testis revealed stagnation of blood flow and degenerative changes attributed to lack of adequate oxygenation in all testicular cell types. Right varicocele was found in the vast majority of the patients. We found that due to the destruction of one-way valves, pathologic hydrostatic pressure is produced in the testicular venous microcirculatory system about five times higher than normal, exceeding arteriolar pressure. The pressure gradient between the arterioles and venules in the testicular tissue is therefore reversed, leading to persistent hypoxia. Right varicocele, although undetected, is prevalent in infertile men with varicocele, hence only bilateral occlusion of the internal spermatic veins, including the associated bypasses, eliminating the pathologic hydrostatic pressure will lead to resumption of arterial blood flow in the testicular microcirculation.
    背景与目标: : 精索静脉曲张被认为是一种主要的单侧左侧疾病。但是,由于只有一个健康的睾丸可以保留男性的生育能力,因此不育表现为双侧睾丸功能障碍。假设 :( i) 无法通过触诊来诊断右精索静脉曲张,因此过去没有通过传统疗法进行治疗,并且 (ii) 右精索静脉曲张会导致右睾丸微循环中的氧气供应受损,导致生殖细胞变性。这项研究在治疗840名患有精索静脉曲张的不育男性期间对左右精索内静脉进行了静脉造影,并使用流体力学工具分析了结果。右睾丸的组织病理学显示,由于所有睾丸细胞类型缺乏足够的氧合,导致血流停滞和退行性变化。在绝大多数患者中发现了右精索静脉曲张。我们发现,由于单向阀的破坏,睾丸静脉微循环系统中产生的病理性静水压力约为正常水平的五倍,超过了小动脉压力。因此,睾丸组织中小动脉和小静脉之间的压力梯度相反,导致持续的缺氧。右精索静脉曲张虽然未被发现,但在患有精索静脉曲张的不育男性中很普遍,因此只有双侧精索内静脉 (包括相关的旁路) 闭塞,消除病理性静水压将导致睾丸微循环中动脉血流的恢复。
  • 【大鼠角膜缘和中央角膜上皮中基因表达 (SAGE) 的系列分析。】 复制标题 收藏 收藏
    DOI:10.1167/iovs.06-0216 复制DOI
    作者列表:Adachi W,Ulanovsky H,Li Y,Norman B,Davis J,Piatigorsky J
    BACKGROUND & AIMS: PURPOSE:To identify genes preferentially expressed in the stem-cell-rich limbal epithelium of the rat cornea. METHODS:The limbal and central corneal epithelial cells of 6-week-old rats were isolated by microdissection. Serial analysis of gene expression (SAGE) libraries were constructed and analyzed, and in situ hybridization, reverse transcription-polymerase chain reaction (RT-PCR) and cDNA cloning were conducted by conventional procedures. RESULTS:The rat limbal and central corneal epithelial SAGE libraries consisted of 41,894 and 40,691 tags, respectively. After annotation, this was reduced to 759 transcripts specific for the limbal library and 844 transcripts specific for the central corneal library; 2292 transcripts overlapped. Transcripts encoding proteins with metabolic functions comprised the major functional category in both libraries. In situ hybridization and/or RT-PCR results of 12 of the most abundant, highly enriched transcripts in the limbal epithelium were in general agreement with the SAGE data and showed that these proteins are also expressed in the conjunctival epithelium. Interesting limbal-enriched transcripts encode WDNM1-like protein (similar to WDNM1/Expi, a putative secreted proteinase and inhibitor of metastasis), mesothelin (a cancer marker), marapsin (a trypsin-like serine protease that may control cell growth and migration), K4 and K15 (both cytokeratins), and membrane-spanning four-domain subfamily A member 8B. WDNM1-like protein was cloned and confirmed as a member of the four-disulfide core family. CONCLUSIONS:The SAGE results extend the database of genes expressed in the rodent cornea and suggest an association between several genes preferentially expressed in the limbal epithelium with cellular proliferation and migration.
    背景与目标:
  • 【艾滋病患者的更昔洛韦耐药巨细胞病毒 (CMV) 视网膜炎病例: CMV病毒载量和血液区室病毒突变的纵向分子分析。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:1997-06-01
    来源期刊:AIDS
    DOI:10.1097/00002030-199707000-00005 复制DOI
    作者列表:Boivin G,Gilbert C,Morissette M,Handfield J,Goyette N,Bergeron MG
    BACKGROUND & AIMS: OBJECTIVE:To study the temporal relationships between cytomegalovirus (CMV) viral load and specific UL97 mutations in polymorphonuclear leukocytes (PMNL) and plasma samples from a patient with AIDS who developed ganciclovir-resistant CMV retinitis.

    METHODS:Sequential PMNL and plasma samples were analysed for determination of the CMV viral load using non-molecular methods and a quantitative polymerase chain reaction (PCR) assay. Screening of the same samples for the most common mutations conferring ganciclovir resistance was performed using nested PCR and restriction enzyme analysis.

    RESULTS:At the time of progression of CMV retinitis (after 6 months of ganciclovir), a rapid increase in the CMV DNA load was found in both PMNL and plasma samples. This increase paralleled the emergence of a specific mutation (V594) in the same samples and recovery of ganciclovir-resistant blood isolates. In this patient, however, the only tests that substantially predicted the progression of CMV disease were the quantitative PCR assay using PMNL and to a lesser extent the pp65 antigenemia assay.

    CONCLUSIONS:Quantitative evaluation of the CMV viral load in PMNL using sensitive assays such as PCR appears to be a promising approach for monitoring antiviral therapy in subjects with AIDS. In addition, common mutations conferring ganciclovir resistance can be detected directly in PMNL and plasma samples.

    背景与目标: 目标 : 研究巨细胞病毒 (CMV) 病毒载量与多形核白细胞 (PMNL) 和血浆样本中特定UL97突变之间的时间关系,该患者患有更昔洛韦耐药的CMV视网膜炎。
    方法 : 使用非分子方法和定量聚合酶链反应 (PCR) 分析方法分析了连续的PMNL和血浆样品,以确定CMV病毒载量。使用巢式PCR和限制性内切酶分析对相同样品进行了更昔洛韦抗性最常见突变的筛选。
    结果 : 在CMV视网膜炎进展时 (更昔洛韦6个月后),在PMNL和血浆样品中发现CMV DNA载量迅速增加。这种增加与同一样品中出现特定突变 (V594) 和更昔洛韦耐药血液分离株的回收平行。但是,在该患者中,唯一可以基本预测CMV疾病进展的测试是使用PMNL的定量PCR测定,以及在较小程度上使用pp65抗原血症测定。
    结论 : 使用敏感的检测方法 (例如PCR) 定量评估PMNL中的CMV病毒载量似乎是监测艾滋病患者抗病毒治疗的有希望的方法。此外,可以直接在PMNL和血浆样品中检测到赋予更昔洛韦抗性的常见突变。
  • 【胃癌中pRb2/p130,VEGF,EZH2,p53,p16(INK4A),p27(KIP1),p21(WAF1) Ki-67表达模式的免疫组织化学分析。】 复制标题 收藏 收藏
    DOI:10.1002/jcp.20833 复制DOI
    作者列表:Mattioli E,Vogiatzi P,Sun A,Abbadessa G,Angeloni G,D'Ugo D,Trani D,Gaughan JP,Vecchio FM,Cevenini G,Persiani R,Giordano A,Claudio PP
    BACKGROUND & AIMS: :Although the considerable progress against gastric cancer, it remains a complex lethal disease defined by peculiar histological and molecular features. The purpose of the present study was to investigate pRb2/p130, VEGF, EZH2, p53, p16(INK4A), p27(KIP1), p21(WAF1), Ki-67 expressions, and analyze their possible correlations with clinicopathological factors. The expression patterns were examined by immunohistochemistry in 47 patients, 27 evaluated of intestinal-type, and 20 of diffuse-type, with a mean follow up of 56 months and by Western blot in AGS, N87, KATO-III, and YCC-2, -3, -16 gastric cell lines. Overall, stomach cancer showed EZH2 correlated with high levels of p53, Ki-67, and cytoplasmic pRb2/p130 (P < 0.05, and P < 0.01, respectively). Increased expression of EZH2 was found in the intestinal-type and correlated with the risk of distant metastasis (P < 0.05 and P < 0.01, respectively), demonstrating that this protein may have a prognostic value in this type of cancer. Interestingly, a strong inverse correlation was observed between p27(KIP1) expression levels and the risk of advanced disease and metastasis (P < 0.05), and a positive correlation between the expression levels of p21(WAF1) and low-grade (G1) gastric tumors (P < 0.05), confirming the traditionally accepted role for these tumor-suppressor genes in gastric cancer. Finally, a direct correlation was found between the expression levels of nuclear pRb2/p130 and low-grade (G1) gastric tumors that was statistically significant (P < 0.05). Altogether, these data may help shed some additional light on the pathogenetic mechanisms related to the two main gastric cancer histotypes and their invasive potentials.
    背景与目标: : 尽管在抗胃癌方面取得了长足的进步,但它仍然是一种由特殊的组织学和分子特征定义的复杂致死疾病。本研究的目的是调查pRb2/p130,VEGF,EZH2,p53,p16(INK4A),p27(KIP1),p21(WAF1),Ki-67表达,并分析其与临床病理因素的可能相关性。通过免疫组织化学检查了47例患者的表达模式,其中27例被评估为肠型,20例被评估为弥漫型,平均随访56个月,并通过Western blot在AGS,N87,KATO-III和YCC-2中进行了检测,-3,-16胃细胞系。总体而言,胃癌显示EZH2与高水平的p53,Ki-67和细胞质pRb2/p130相关 (分别为P <0.05和P <0.01)。在肠型中发现EZH2的表达增加,并且与远处转移的风险相关 (分别为P <0.05和P <0.01),表明该蛋白可能在此类癌症中具有预后价值。有趣的是,p27(KIP1) 表达水平与晚期疾病和转移风险之间存在很强的负相关 (P <0.05),而p21(WAF1) 表达水平与低度 (G1) 胃肿瘤之间存在正相关 (P <0.05),证实了这些肿瘤抑制基因在胃癌中的传统作用。最后,发现核pRb2/p130的表达水平与低级别 (G1) 胃肿瘤之间存在直接相关性,具有统计学意义 (P <0.05)。总之,这些数据可能有助于进一步阐明与两种主要胃癌组织类型及其侵袭潜力有关的致病机制。
  • 【葡萄膜炎患者肝素表面修饰人工晶状体与常规聚甲基丙烯酸甲酯人工晶状体的回顾性分析。】 复制标题 收藏 收藏
    DOI:10.1007/BF02583275 复制DOI
    作者列表:Lardenoye CW,van der Lelij A,Berendschot TT,Rothova A
    BACKGROUND & AIMS: BACKGROUND:Several studies described the benefits of the heparin-surface-modified intraocular tens (HSM IOL) with regard to the reduced inflammation in routine extracapsular cataract extractions. However, limited information is available about the advantages of the HSM IOL in patients with an intraocular inflammation. AIM:To assess the eventual benefits of the HSM IOL compared to the regular polymethylmethacrylate intraocular lens (PMMA IOL) in patients with uveitis. METHODS:A retrospective study of 43 patients with uveitis of various origins who underwent an extracapsular cataract extraction (24 with HSM, 19 with PMMA IOL). The activity of intraocular inflammation, visual acuity, eventual complications, and medications were examined. Standardized follow-up dates were used (before surgery, one and fourteen days, five and eleven months after surgery.) RESULTS:No difference in the inflammatory, activity was noted between HSM and PMMA groups; neither at short term clinical evaluation, nor at five months after surgery. Despite a slightly better visual acuity in the HSM group before surgery, no long term differences were observed. After surgery the increase in visual acuity was similar for both groups, as well as the frequency of cystoid macular oedema (CMO) and synechiae. Fewer patients in HSM group required Nd:YAG posterior capsulotomy, but the difference was not significant. CONCLUSION:No clinical advantage was found when the HSM IOL was compared with the regular PMMA IOL in 43 patients with uveitis.
    背景与目标:
  • 【使用口译员的跨文化访谈研究: 系统的文献综述。】 复制标题 收藏 收藏
    DOI:10.1111/j.1365-2648.2006.03963.x 复制DOI
    作者列表:Wallin AM,Ahlström G
    BACKGROUND & AIMS: AIM:This paper reviews how the interpreter's role is described in empirically based, qualitative cross-cultural interview studies and how trustworthiness is determined. BACKGROUND:Increased immigration during the past decades has created a multiethnic society in many countries. This development poses a challenge to healthcare staff, in that they need to understand how people from different cultures experience health and illness. One way to assess immigrants' experiences is through cross-cultural interview studies, involving an interpreter. Thorough knowledge of the interpreter's role is needed in order to increase the trustworthiness of this kind of nursing research. METHOD:Literature searches were conducted from October to November 2004 using PubMed, CINAHL, Psycinfo, Sociological abstract, Your Journals@ovid, and Eric databases. Qualitative interview studies written in English and performed with an interpreter were included. The Matrix Method was used to review the literature. FINDINGS:In almost all of the 13 relevant papers found, the role of the interpreter(s) in the research process was only sparsely described. In addition, all studies except one employed different techniques to established trustworthiness. The most common techniques were prolonged engagement, member check or triangulation, the latter performed either on the data, investigators or methods. CONCLUSION:Methodological issues with respect to interpreters have received only limited attention in cross-cultural interview studies. Researchers in the field of nursing need to consider (1) the interpreter's role/involvement in the research process; (2) the interpreter's competence and the style of interpreting; (3) the interpreter's impact on the findings. This information is a prerequisite when trying to determine the trustworthiness of a cross-cultural study.
    背景与目标:
  • 【骨髓嵌合体小鼠肿瘤浸润基质细胞的制备及功能分析。】 复制标题 收藏 收藏
    DOI:10.1111/j.1348-0421.2006.tb03830.x 复制DOI
    作者列表:Ishigaki H,Yamamoto Y,Ishida H,Kajino K,Itoh Y,Fujiyama Y,Ogasawara K
    BACKGROUND & AIMS: :Tumor-infiltrating stroma cells (TISC) as well as tumors themselves are thought to be involved in tumor-related immunosuppression, which is one of the critical mechanisms of tumor escape from immune surveillance. However, preparation of TISC is difficult because of the small proportion of TISC in established tumors. Thus, the cells thought to be involved in tumor-related immunosuppression are generally prepared from spleens or draining lymph nodes in tumor-bearing mice. In this study, we developed a method for directly preparing TISC from established tumors in order to analyze their function. Using green fluorescent protein (GFP) transgenic (Tg) mice and C57BL/6 mice transplanted with bone marrow (BM) cells of GFPTg mice, we detected three subpopulations of TISC: one is compatible with immature myeloid cells (ImC) derived from BM and the two other subpopulations, CD11b(+) cells and CD11b(-) cells, do not originate from BM. The TISC including these subpopulations but not each subpopulation independently after culturing with tumors in the presence of GM-CSF could suppress T cell proliferation induced by anti-CD3. In our system, tumors did not inhibit T cell responses directly, but unknown factors from tumors affected immunosuppression by TISC.
    背景与目标: : 肿瘤浸润的基质细胞 (TISC) 以及肿瘤本身被认为与肿瘤相关的免疫抑制有关,这是肿瘤逃避免疫监视的关键机制之一。然而,由于TISC在已建立的肿瘤中的比例较小,因此很难制备TISC。因此,被认为与肿瘤相关的免疫抑制有关的细胞通常是从荷瘤小鼠的脾脏或引流淋巴结中制备的。在这项研究中,我们开发了一种从已建立的肿瘤中直接制备TISC的方法,以分析其功能。使用绿色荧光蛋白 (GFP) 转基因 (Tg) 小鼠和C57BL/6小鼠移植了GFPTg小鼠的骨髓 (BM) 细胞,我们检测到了TISC的三个亚群: 一个与BM衍生的未成熟髓样细胞 (ImC) 相容,另外两个亚群,CD11b(+) 细胞和CD11b(-) 细胞不起源于BM。在gm-csf存在下用肿瘤培养后,包括这些亚群但不是每个亚群的TISC可以抑制anti-CD3诱导的T细胞增殖。在我们的系统中,肿瘤没有直接抑制T细胞反应,但是肿瘤的未知因素会影响TISC的免疫抑制。
  • 【改良摆锤器具的生物力学-力系统的理论考虑和体外分析。】 复制标题 收藏 收藏
    DOI:10.1093/ejo/cjl028 复制DOI
    作者列表:Kinzinger GS,Diedrich PR
    BACKGROUND & AIMS: :The aim of this study was to analyse the acting forces and moments induced by a special orthodontic appliance, the Pendulum K, for molar distalization in the transverse and sagittal planes. The purpose-designed test set-up (artificial maxilla with anchorage unit and two electrothermodynamic molars, an electronic measuring unit, a unit with force-moment sensor, an analogue/digital converter, and a data read-out unit) allowed simulation of in vivo conditions on the one hand and precise determination of the force systems on the other. The appliances investigated were three specimens of the Pendulum K. In vitro measurement of the resulting force systems revealed that the forces and moments in the transverse and sagittal planes remained almost constant over a 3 mm measuring increment when the distal screw was continuously activated (10 activations/mm). Without reactivation of the incorporated distal screw, however, a marked decline in the force systems was recorded. The Pendulum K allows translatory distalization of the upper molars and thus dental arch expansion, dispensing with the need for permanent teeth to be extracted, subject to a corresponding indication. This is achieved by continuous adjustment of an incorporated distal screw and by specific pre-activations of the Pendulum springs.
    背景与目标: : 这项研究的目的是分析由特殊的正畸矫治器摆K引起的作用力和力矩,以在横向和矢状平面中使磨牙远侧。目的设计的测试装置 (带有锚固单元和两个电热磨牙的人造上颌骨,一个电子测量单元,一个带力-力矩传感器的单元,一个模拟/数字转换器,和数据读出单元) 一方面可以模拟体内条件,另一方面可以精确确定力系统。所研究的器具是摆锤K的三个样本。所得力系统的体外测量表明,当远端螺钉连续激活 (10个激活/mm) 时,在3毫米测量增量内,横向和矢状平面中的力和力矩几乎保持恒定。但是,如果不重新激活合并的远端螺钉,则记录到力系统明显下降。摆锤K允许上磨牙的平移远端化,从而使牙弓扩张,从而无需拔出恒牙,但要有相应的指示。这是通过连续调节结合的远端螺钉和通过摆簧的特定预激活来实现的。
  • 【热休克蛋白-90 (HSP90) 在多发性骨髓瘤中的表达及HSP90抑制剂 (17-AAG) 的作用分析。】 复制标题 收藏 收藏
    DOI:10.1080/10428190500472123 复制DOI
    作者列表:Duus J,Bahar HI,Venkataraman G,Ozpuyan F,Izban KF,Al-Masri H,Maududi T,Toor A,Alkan S
    BACKGROUND & AIMS: :Heat shock protein 90 (HSP90) is required for structural folding and maintenance of conformational integrity of various proteins, including several associated with cellular signaling. Recent studies utilizing 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90, demonstrated an antitumor effect in solid tumors. To test whether HSP90 could be targeted in multiple myeloma (MM) patients, we first investigated expression of HSP90 by immunofluorescence and flow cytometric analysis in a myeloma cell line (U266) and primary myeloma cells. Following demonstration of HSP90 expression in myeloma cells, archival samples of 32 MM patients were analysed by immunoperoxidase staining. Myeloma cells in all patients showed strong cytoplasmic expression of HSP90 in all samples and 55% also demonstrated concurrent nuclear immunopositivity. Treatment of U266 and primary MM cells with 17AAG resulted in significantly increased apoptosis compared to untreated control cells. Analysis of anti-apoptotic BCL2 family proteins and akt in MM cells incubated with 17-AAG revealed down-regulation of BCL-2, BCL-XL, MCL-1 and akt. Furthermore, although a low concentration of bortezomib resulted in no cell death, a combination of 17AAG and bortezomib treatment revealed a synergistic apoptotic effect on the U266 cell line. These data suggest that targeted inhibition of HSP90 may prove to be a valid and innovative strategy for the development of future therapeutic options for MM patients.
    背景与目标: : 热休克蛋白90 (HSP90) 是各种蛋白质的结构折叠和构象完整性维持所必需的,包括与细胞信号传导相关的几种。利用HSP90抑制剂17-allylamino-17-demethoxygeldanamycin (17-AAG) 的最新研究表明,在实体瘤中具有抗肿瘤作用。为了测试HSP90是否可以靶向多发性骨髓瘤 (MM) 患者,我们首先通过免疫荧光和流式细胞仪分析研究了HSP90在骨髓瘤细胞系 (U266) 和原发性骨髓瘤细胞中的表达。在证明骨髓瘤细胞中HSP90表达后,通过免疫过氧化物酶染色分析了32 MM患者的档案样本。所有患者的骨髓瘤细胞在所有样品中均显示出HSP90的强细胞质表达,并且55% 还显示出同时的核免疫阳性。与未处理的对照细胞相比,用17AAG处理U266和原代MM细胞可显着增加细胞凋亡。对与17-aag孵育的MM细胞中抗凋亡BCL2家族蛋白和akt的分析表明,BCL-2,BCL-XL,MCL-1和akt下调。此外,尽管低浓度的硼替佐米不会导致细胞死亡,但17AAG和硼替佐米的组合治疗显示出对U266细胞系的协同凋亡作用。这些数据表明,靶向抑制HSP90可能被证明是开发MM患者未来治疗选择的有效且创新的策略。
  • 【CROPPER: 用于跨平台和跨物种汇编研究的metagene creator资源。】 复制标题 收藏 收藏
    DOI:10.1186/1471-2105-7-418 复制DOI
    作者列表:Paananen J,Storvik M,Wong G
    BACKGROUND & AIMS: BACKGROUND:Current genomic research methods provide researchers with enormous amounts of data. Combining data from different high-throughput research technologies commonly available in biological databases can lead to novel findings and increase research efficiency. However, combining data from different heterogeneous sources is often a very arduous task. These sources can be different microarray technology platforms, genomic databases, or experiments performed on various species. Our aim was to develop a software program that could facilitate the combining of data from heterogeneous sources, and thus allow researchers to perform genomic cross-platform/cross-species studies and to use existing experimental data for compendium studies. RESULTS:We have developed a web-based software resource, called CROPPER that uses the latest genomic information concerning different data identifiers and orthologous genes from the Ensembl database. CROPPER can be used to combine genomic data from different heterogeneous sources, allowing researchers to perform cross-platform/cross-species compendium studies without the need for complex computational tools or the requirement of setting up one's own in-house database. We also present an example of a simple cross-platform/cross-species compendium study based on publicly available Parkinson's disease data derived from different sources. CONCLUSION:CROPPER is a user-friendly and freely available web-based software resource that can be successfully used for cross-species/cross-platform compendium studies.
    背景与目标:
  • 【健康干预的优先级设置: 多标准决策分析的必要性。】 复制标题 收藏 收藏
    DOI:10.1186/1478-7547-4-14 复制DOI
    作者列表:Baltussen R,Niessen L
    BACKGROUND & AIMS: :Priority setting of health interventions is often ad-hoc and resources are not used to an optimal extent. Underlying problem is that multiple criteria play a role and decisions are complex. Interventions may be chosen to maximize general population health, to reduce health inequalities of disadvantaged or vulnerable groups, ad/or to respond to life-threatening situations, all with respect to practical and budgetary constraints. This is the type of problem that policy makers are typically bad at solving rationally, unaided. They tend to use heuristic or intuitive approaches to simplify complexity, and in the process, important information is ignored. Next, policy makers may select interventions for only political motives. This indicates the need for rational and transparent approaches to priority setting. Over the past decades, a number of approaches have been developed, including evidence-based medicine, burden of disease analyses, cost-effectiveness analyses, and equity analyses. However, these approaches concentrate on single criteria only, whereas in reality, policy makers need to make choices taking into account multiple criteria simultaneously. Moreover, they do not cover all criteria that are relevant to policy makers. Therefore, the development of a multi-criteria approach to priority setting is necessary, and this has indeed recently been identified as one of the most important issues in health system research. In other scientific disciplines, multi-criteria decision analysis is well developed, has gained widespread acceptance and is routinely used. This paper presents the main principles of multi-criteria decision analysis. There are only a very few applications to guide resource allocation decisions in health. We call for a shift away from present priority setting tools in health--that tend to focus on single criteria--towards transparent and systematic approaches that take into account all relevant criteria simultaneously.
    背景与目标: : 卫生干预措施的优先级设定通常是临时性的,资源的使用没有达到最佳程度。潜在的问题是,多个标准发挥作用,决策很复杂。可以选择干预措施,以最大程度地提高总体人口健康水平,减少弱势或弱势群体的健康不平等,ad/或应对威胁生命的情况,所有这些都涉及实际和预算方面的限制。这是政策制定者通常不善于理性地、没有帮助地解决的问题。他们倾向于使用启发式或直观的方法来简化复杂性,在此过程中,重要的信息被忽略。接下来,政策制定者可能只出于政治动机选择干预措施。这表明需要合理和透明的方法来确定优先级。在过去的几十年中,已经开发了许多方法,包括循证医学,疾病负担分析,成本效益分析和公平性分析。但是,这些方法仅集中在单个标准上,而实际上,决策者需要同时考虑多个标准来做出选择。此外,它们并未涵盖与决策者相关的所有标准。因此,有必要开发一种多标准方法来确定优先级,并且最近确实已将其确定为卫生系统研究中最重要的问题之一。在其他科学学科中,多准则决策分析得到了很好的发展,得到了广泛的认可,并被常规使用。本文介绍了多准则决策分析的主要原理。只有很少的应用程序来指导健康中的资源分配决策。我们呼吁从目前的卫生优先事项设定工具 (往往侧重于单一标准) 转向透明和系统的方法,同时考虑到所有相关标准。
  • 【对FOXP3的分析揭示了其作为转录阻遏物的功能所需的多个结构域。】 复制标题 收藏 收藏
    DOI:10.4049/jimmunol.177.5.3133 复制DOI
    作者列表:Lopes JE,Torgerson TR,Schubert LA,Anover SD,Ocheltree EL,Ochs HD,Ziegler SF
    BACKGROUND & AIMS: :Foxp3 has been shown to be both necessary and sufficient for the development and function of naturally arising CD4+ CD25+ regulatory T cells in mice. Mutation of Foxp3 in Scurfy mice and FOXP3 in humans with IPEX results in fatal, early onset autoimmune disease and demonstrates the critical role of FOXP3 in maintaining immune homeostasis. The FOXP3 protein encodes several functional domains, including a C2H2 zinc finger, a leucine zipper, and a winged-helix/forkhead (FKH) domain. We have shown previously that FOXP3 functions as a transcriptional repressor and inhibits activation-induced IL-2 gene transcription. To characterize the role of each predicted functional domain on the in vivo activity of FOXP3, we have evaluated the location of point mutations identified in a large cohort of patients with the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) and found them to cluster primarily within the FKH domain and the leucine zipper, but also present within the poorly defined N-terminal portion of the protein. The molecular functions of each of the IPEX-targeted domains were investigated. We show that FOXP3 is constitutively localized to the nucleus and this localization requires sequences at both the amino and C-terminal ends of its FKH domain. Moreover, FOXP3 was found to homodimerize through its leucine zipper. We also identify a novel functional domain within the N-terminal half of FOXP3, which is required for FOXP3-mediated repression of transcription from both a constitutively active and a NF-AT-inducible promoter. Furthermore, we demonstrate that IPEX mutations in these domains correlate with deficiencies in FOXP3 repressor function, corroborating their in vivo relevance.
    背景与目标: : Foxp3已被证明对于小鼠中自然产生的CD4 CD25调节性T细胞的发育和功能既必要又充分。在患有pex的Scurfy小鼠中Foxp3和人类中FOXP3的突变会导致致命的,早发性自身免疫性疾病,并证明了FOXP3在维持免疫稳态中的关键作用。FOXP3蛋白编码几个功能结构域,包括C2H2锌指,亮氨酸拉链和有翼螺旋/叉头 (FKH) 结构域。我们先前已经证明FOXP3作为转录阻遏物起作用并抑制激活诱导的IL-2基因转录。为了表征每个预测的功能域对FOXP3体内活性的作用,我们评估了在免疫失调,多内分泌病,肠病,X连锁综合征 (IPEX),发现它们主要聚集在FKH结构域和亮氨酸拉链内,但也存在于蛋白质定义不明确的N端部分。研究了每个pex靶向域的分子功能。我们证明FOXP3组成性地定位于细胞核,并且这种定位需要在其FKH结构域的氨基和C末端都具有序列。此外,发现FOXP3通过其亮氨酸拉链同向二聚。我们还在FOXP3的N末端一半内鉴定了一个新的功能结构域,这是FOXP3-mediated抑制组成型活性和NF-AT诱导启动子转录所必需的。此外,我们证明了这些域中的IPEX突变与FOXP3阻遏物功能的缺陷相关,从而证实了它们在体内的相关性。
  • 【白种人患者肺肿瘤中HER2基因的突变分析: 突变主要存在于具有细支气管肺泡特征的腺癌中。】 复制标题 收藏 收藏
    DOI:10.1002/ijc.22143 复制DOI
    作者列表:Buttitta F,Barassi F,Fresu G,Felicioni L,Chella A,Paolizzi D,Lattanzio G,Salvatore S,Camplese PP,Rosini S,Iarussi T,Mucilli F,Sacco R,Mezzetti A,Marchetti A
    BACKGROUND & AIMS: :Activating mutations in the tyrosine kinase domain of the HER2 gene have recently been reported in lung adenocarcinomas, mainly in East Asian patients. Our study was devised to evaluate the prevalence and nature of HER2 mutations in lung adenocarcinomas from Caucasian patients. The mutational status of the HER2 gene was evaluated in 403 lung adenocarcinomas by PCR-single strand conformation polymorphism analysis and direct sequencing of Exons 19 and 20. We found HER2 mutations in 9 (2.2%) cases. Seven (78%) of the mutations were in frame duplications/insertions at codons 776-779 (YVMA), the other 2 were base substitutions resulting in aminoacid changes. The hotspot mutation at bases 776-779 was previously found to be the most frequent HER2 mutation in Asiatic patients. The distribution of mutations was significantly different between conventional lung adenocarcinomas (CLAs) and lung adenocarcinomas with bronchioloalveolar features (ABAFs). Seven (6.2%) of 113 ABAFs and 2 (0.7%) of 290 CLA were mutated (p = 0.0025). In addition, the frequency of HER2 mutations was slightly higher in females (4.1%) than in males (1.8%) and in never smokers (3.1%) than in smokers (1.9%), but differences were not statistically significant. This series of tumors was also investigated for EGFR and K-ras mutations. EGFR mutations were observed in 43 (10.7%) cases, and K-ras mutations in 110 (27.3%) cases. EGFR, HER2 and K-ras mutations were found to be mutually exclusive events. The presence of HER2 mutations in a subset of patients with lung adenocarcinoma raise hope to treat these patients with HER2 specific kinase inhibitors.
    背景与目标: : 最近在肺腺癌 (主要是东亚患者) 中报道了HER2基因酪氨酸激酶结构域的激活突变。我们的研究旨在评估白种人肺腺癌中HER2突变的患病率和性质。通过PCR-单链构象多态性分析和外显子19和20的直接测序,评估了403例肺腺癌中HER2基因的突变状态。我们在9 (2.2%) 例病例中发现HER2突变。7 (78%) 个突变在密码子776-779 (YVMA) 的帧重复/插入中,另外2个是导致氨基酸变化的碱基取代。先前发现776-779碱基的热点突变是亚洲患者中最常见的HER2突变。在常规肺腺癌 (cras) 和具有细支气管肺泡特征的肺腺癌 (ABAFs) 之间,突变的分布显着不同。113 ABAFs中的7个 (6.2%) 和290 CLA中的2个 (0.7%) 发生突变 (p = 0.0025)。此外,女性 (4.1%) 的HER2突变频率略高于男性 (1.8%),从不吸烟者 (3.1%) 高于吸烟者 (1.9%),但差异无统计学意义。还研究了这一系列肿瘤的EGFR和K-ras突变。在43 (10.7%) 例中观察到EGFR突变,在110 (27.3%) 例中观察到K-ras突变。发现EGFR,HER2和K-ras突变是相互排斥的事件。在一部分肺腺癌患者中存在HER2突变,这使人们希望用HER2特异性激酶抑制剂治疗这些患者。

+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