• 【改良的摆锤装置的生物力学-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Pendulum K引起的作用力和力矩,以在横断面和矢状面上进行磨牙远侧。专门设计的测试装置(带有锚固单元和两个电热磨牙的人工上颌,一个电子测量单元,一个带有力矩传感器的单元,一个模拟/数字转换器和一个数据读出单元)允许模拟一方面是体内条件,另一方面是精确确定力系统。所研究的器具是Pendulum K的三个标本。对最终产生的力系统进行的体外测量显示,当连续激活远端螺钉(10次激活)时,横向和矢状面的力和力矩在3 mm的测量增量内几乎保持恒定。 /毫米)。然而,在没有重新激活所结合的远端螺钉的情况下,记录了力系统的显着下降。摆K允许上颌臼齿的平移远侧移动,从而使牙弓扩张,并在需要相应指示的情况下无需拔出恒牙。这是通过不断调整内置的远端螺钉并通过对摆弹簧进行特定的预激活来实现的。
  • 【多发性骨髓瘤中热休克蛋白90(HSP90)的表达和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)是结构折叠和维持各种蛋白质(包括与细胞信号相关的几种蛋白质)构象完整性的必需。利用HSP90抑制剂17-烯丙基氨基-17-去甲氧基格尔德霉素(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是否可以靶向于多发性骨髓瘤(MM)患者,我们首先通过免疫荧光和流式细胞术分析了骨髓瘤细胞系(U266)和原发性骨髓瘤细胞中HSP90的表达。在证明HSP90在骨髓瘤细胞中表达后,通过免疫过氧化物酶染色分析了32例MM患者的档案样本。在所有患者中,骨髓瘤细胞在所有样品中均表现出强烈的HSP90细胞质表达,并且55%的患者还表现出并发的核免疫阳性。与未处理的对照细胞相比,用17AAG处理U266细胞和原代MM细胞可导致凋亡明显增加。分析与17-AAG孵育的MM细胞中的抗凋亡BCL2家族蛋白和akt,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,但是17AAG和硼替佐米治疗的组合显示出对U266细胞系的协同凋亡作用。这些数据表明,针对HSP90的靶向抑制可能被证明是开发MM患者未来治疗选择的有效且创新的策略。
  • 【卫生干预措施的优先重点设定:需要进行多标准决策分析。】 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置通常是临时的,资源没有得到最佳利用。潜在的问题是多个标准起着作用,并且决策很复杂。可以选择干预措施,以最大程度地提高总体人口健康,减少弱势或弱势群体的健康不平等,广告/或应对危及生命的情况,所有这些都涉及实际和预算方面的限制。这是决策者通常无助于理性解决的典型问题。他们倾向于使用启发式或直观的方法来简化复杂性,并且在此过程中,重要的信息将被忽略。接下来,政策制定者可能只出于政治动机选择干预措施。这表明需要采取合理和透明的方法来确定优先事项。在过去的几十年中,已经开发出许多方法,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,这些方法仅集中于单个标准,而实际上,决策者需要在选择时同时考虑多个标准。此外,它们并未涵盖与决策者相关的所有标准。因此,有必要开发一种确定优先级的多标准方法,并且最近确实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,多准则决策分析已经得到了很好的发展,已经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可以指导健康状况中的资源分配决策。我们呼吁从目前卫生领域的优先重点设定工具(倾向于只关注单一标准)转变为同时考虑所有相关标准的透明,系统的方法。
  • 【FOXP3的分析揭示了其作为转录阻遏物所需的多个结构域。】 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: 已经证明:Foxp3对于小鼠中天然产生的CD4 CD25调节性T细胞的发育和功能既必要又充分。用IPEX突变的Scurfy小鼠中的Foxp3和人类中的FOXP3突变会导致致命的早期发作的自身免疫性疾病,并证明FOXP3在维持免疫稳态方面的关键作用。 FOXP3蛋白编码几个功能域,包括C2H2锌指,亮氨酸拉链和带翼螺旋/叉头(FKH)域。先前我们已经证明FOXP3充当转录阻遏物,并抑制激活诱导的IL-2基因转录。为了表征每个预测功能结构域对FOXP3体内活性的作用,我们评估了在一大批患有免疫功能异常,多内分泌病,肠病,X连锁综合征(IPEX)的患者中鉴定出的点突变的位置,并发现它们主要聚集在FKH结构域和亮氨酸拉链中,但也存在于蛋白质的N末端定义不明确的区域。研究了每个IPEX靶向域的分子功能。我们显示FOXP3组成性地定位于原子核,并且此定位需要在其FKH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源二聚体。我们还确定了FOXP3 N末端一半内的新型功能域,这是FOXP3介导的从组成型活性启动子和NF-AT诱导型启动子转录抑制所必需的。此外,我们证明这些域中的IPEX突变与FOXP3阻遏物功能的缺陷相关,从而证实了它们的体内相关性。
  • 【白人患者肺肿瘤中HER2基因的突变分析:突变主要存在于具有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: :最近在肺腺癌中,主要在东亚患者中,报道了HER2基因酪氨酸激酶结构域中的活化突变。我们的研究旨在评估白人患者肺腺癌中HER2突变的发生率和性质。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。我们发现9例(2.2%)病例中存在HER2突变。突变中的七个(78%)位于776-779位密码子(YVMA)的框架重复/插入中,另外两个为碱基取代,导致氨基酸变化。先前发现在776-779碱基处的热点突变是亚洲患者中最常见的HER2突变。在传统的肺腺癌(CLA)和具有支气管肺泡特征(ABAFs)的肺腺癌之间,突变的分布显着不同。 113个ABAF中有7个(6.2%)和290个CLA中有2个(0.7%)发生了突变(p = 0.0025)。此外,HER2突变的频率在女性(4.1%)中略高于男性(1.8%),从不吸烟者(3.1%)比吸烟者(1.9%)高,但差异无统计学意义。还研究了该系列肿瘤的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。 HER2突变在一部分肺腺癌患者中的存在增加了用HER2特异性激酶抑制剂治疗这些患者的希望。
  • 【人体冠状动脉斑块切除术标本中肝细胞生长因子的免疫组织化学分析:与转化生长因子β亚型的比较。】 复制标题 收藏 收藏
    DOI:10.1007/s004280050050 复制DOI
    作者列表:Ueda H,Imazu M,Hayashi Y,Ono K,Yasui W,Yamakido M
    BACKGROUND & AIMS: The expression and localization of hepatocyte growth factor/scatter factor (HGF/SF) were examined immunohistochemically in 59 human coronary artery lesions retrieved by directional coronary atherectomy and compared with the localization of transforming growth factor beta isoforms (TGF-beta 1, -beta 2, and -beta 3). In 21 of the 59 specimens (35.6%) HGF-like immunoreactivity (HGF-IR) was revealed. The HGF immunopositivity rate of 45% (14/31) in thrombotic tissue was significantly (P < 0.05) higher than the rates of 7.3% (4/55), 7.1% (3/42), and 0% (0/14) in fibrous tissue, neointimal hyperplasia and atheromatous gruel, respectively. Immunoreactivity for HGF was much weaker than that for TGF-beta isoforms in these components except in thrombotic tissue. These cells exhibiting strong HGF-IR were inflammatory cells such as monocytes/macrophages in thrombotic tissue, in tissue lesions adjacent to a thrombus, and outside the capillary walls in a portion of the neovascularized lesions. Smooth muscle cells (SMCs) hardly demonstrated HGF-IR. In contrast, in control coronary arteries obtained at autopsy, the HGF-IR was strongly expressed in SMCs. These findings suggest that HGF produced by macrophages play a part in the process of coronary plaque formation attributable to thrombus in man.

    背景与目标: 免疫组织化学方法检测了定向冠状动脉粥样斑块切除术取回的59例人类冠状动脉病变中肝细胞生长因子/分散因子(HGF / SF)的表达和定位,并与转化生长因子β同工型(TGF-beta 1,-beta 2和-beta 3)。在59个样本中的21个(35.6%)中发现了类似HGF的免疫反应性(HGF-IR)。血栓形成组织中HGF免疫阳性率为45%(14/31)显着(P <0.05)分别高于7.3%(4/55),7.1%(3/42)和0%(0/14) )分别在纤维组织,新内膜增生和粥样粥样硬化中。除了血栓形成组织外,在这些组件中,HGF的免疫反应性比TGF-β亚型的免疫反应性弱得多。这些表现出强HGF-IR的细胞是炎性细胞,例如血栓形成组织中,与血栓相邻的组织病变中,以及在部分新血管形成的病变中的毛细血管壁之外的单核细胞/巨噬细胞。平滑肌细胞(SMCs)几乎没有表现出HGF-IR。相反,在尸检时获得的对照冠状动脉中,HGF-IR在SMC中强烈表达。这些发现表明,巨噬细胞产生的HGF在可归因于人类血栓的冠状斑块形成过程中起作用。

  • 【蛋白质结构与功能关系的生物信息学分析:白细胞弹性蛋白酶(ELA2)错义突变的案例研究。】 复制标题 收藏 收藏
    DOI:10.1002/humu.20407 复制DOI
    作者列表:Thusberg J,Vihinen M
    BACKGROUND & AIMS: :Cyclic and congenital neutropenia are caused by mutations in the human neutrophil elastase (HNE) gene (ELA2), leading to an immunodeficiency characterized by decreased or oscillating levels of neutrophils in the blood. The HNE mutations presumably cause loss of enzyme activity, consequently leading to compromised immune system function. To understand the structural basis for the disease, we implemented methods from bioinformatics to analyze all the known HNE missense mutations at both the sequence and structural level. Our results demonstrate that the 32 different mutations have diverse effects on HNE structure and function, affecting structural disorder and aggregation tendencies, stability maintaining contacts, and electrostatic properties. A large proportion of the mutations are located at conserved amino acids, which are usually essential in determining protein structure and function. The majority of the disease-causing HNE missense mutations lead to major structural changes and loss of stability in the protein. A few mutations also affect functional residues, leading into decreased catalytic activity or altered ligand binding. Our analysis reveals the putative effects of all known missense mutations in HNE, thus allowing the structural basis of cyclic and congenital neutropenia to be elucidated. We have employed and analyzed a set of some 30 different methods for predicting the effects of amino acid substitutions. We present results and experience from the analysis of the applicability of these methods in the analysis of numerous genes, proteins, and diseases to reveal protein structure-function relationships and disease genotype-phenotype correlations.
    背景与目标: :循环性和先天性嗜中性白血球减少症是由人类嗜中性粒细胞弹性蛋白酶(HNE)基因(ELA2)突变引起的,导致免疫缺陷,其特征是血液中嗜中性粒细胞水平降低或振荡。 HNE突变可能导致酶活性下降,因此导致免疫系统功能受损。为了了解该疾病的结构基础,我们采用了生物信息学的方法来分析序列和结构水平上所有已知的HNE错义突变。我们的结果表明,这32种不同的突变对HNE的结构和功能具有多种影响,影响结构异常和聚集趋势,保持接触的稳定性以及静电性质。大部分突变位于保守氨基酸上,这通常是决定蛋白质结构和功能所必需的。大多数引起疾病的HNE错义突变会导致主要的结构变化和蛋白质稳定性的损失。一些突变也影响功能残基,导致催化活性降低或配体结合改变。我们的分析揭示了HNE中所有已知的错义突变的推定作用,因此可以阐明周期性和先天性中性粒细胞减少的结构基础。我们已经采用并分析了一组约30种不同的方法来预测氨基酸取代的影响。我们通过分析这些方法在分析众多基因,蛋白质和疾病中的适用性来提供结果和经验,以揭示蛋白质结构与功能的关系以及疾病的基因型与表型的相关性。
  • 【儿童实体器官移植后的脊柱:40例患者的临床,影像学和磁共振成像分析。】 复制标题 收藏 收藏
    DOI:10.1097/01.brs.0000231717.63974.f3 复制DOI
    作者列表:Helenius I,Remes V,Tervahartiala P,Salminen S,Sairanen H,Holmberg C,Palmu P,Helenius M,Peltonen J,Jalanko H
    BACKGROUND & AIMS: STUDY DESIGN:A cross-sectional study of the spine in 40 young adults after solid organ transplantation in childhood. OBJECTIVE:To evaluate the impact of organ transplantation and long-term immunosuppressive treatment on growing spine using magnetic resonance imaging (MRI). SUMMARY OF BACKGROUND DATA:A review of the current literature reveals no systematic evaluation of the spine after transplantation in childhood. METHODS:A total of 40 adult patients (mean age 22.1 years, range, 16.0-27.0), who received either kidney, liver, or heart transplant as children, were evaluated. Mean follow-up after transplantation was 11.2 years (range 3.0-18.0). All patients filled in a questionnaire, underwent an interview and physical examination, as well as had MRI of the spine. Standing spinal radiographs were taken from patients with a rib hump > or = 6 degrees. RESULTS:There were 8 (20%) patients who had a history of vertebral fracture. Eleven (28%) patients reported frequent back pain at rest. There were 15 (38%) patients who had scoliosis > 10 degrees (range 10 degrees -69 degrees ). On MRI, narrowed disc spaces were noted in 32 (80%) patients, and irregular endplates were noted in 24 (60%). There were 14 (35%) patients who had at least 1 compressed or wedged vertebra (> 20%). Patients treated for acute rejection had wedged vertebrae, speckled or black disc spaces, and irregular endplates more often than patients without rejections. Males had wedged vertebrae more often than females (P = 0.0067). CONCLUSIONS:Back pain, scoliosis, wedged vertebrae, and narrowed, degenerated disc spaces are common after solid organ transplantation in childhood.
    背景与目标: 研究设计:儿童实体器官移植后对40位年轻人的脊柱进行的横断面研究。
    目的:利用磁共振成像(MRI)评估器官移植和长期免疫抑制治疗对生长中脊柱的影响。
    背景资料摘要:对当前文献的回顾表明,儿童期移植后没有对脊柱进行系统评价。
    方法:总共评估了40名成年患者(平均年龄22.1岁,范围16.0-27.0),他们从小就接受了肾脏,肝脏或心脏移植手术。移植后的平均随访时间为11.2年(范围3.0-18.0)。所有患者均填写了问卷,接受了访谈和体格检查,并对脊柱进行了MRI检查。肋骨隆起>或= 6度的患者拍摄站立式脊柱X光片。
    结果:有8例(20%)有椎体骨折病史。 11名(28%)患者报告休息时经常出现背痛。脊柱侧弯> 10度(范围10度-69度)的患者为15(38%)。在MRI上,发现32例(80%)患者的椎间盘间隙变窄,发现24例(60%)的不规则端板。有14名(35%)患者至少有1块受压或楔入的椎骨(> 20%)。接受急性排斥反应的患者比没有排斥反应的患者更经常出现椎体楔形,斑点或黑色椎间盘间隙以及不规则的终板。男性比女性更经常楔住椎骨(P = 0.0067)。
    结论:儿童实体器官移植后,背部疼痛,脊柱侧弯,椎骨楔形和椎间盘狭窄变窄是常见的。
  • 【重症ICU患者进行即时护理和连续血糖分析的准确性和可行性。】 复制标题 收藏 收藏
    DOI:10.1186/cc5048 复制DOI
    作者列表:Corstjens AM,Ligtenberg JJ,van der Horst IC,Spanjersberg R,Lind JS,Tulleken JE,Meertens JH,Zijlstra JG
    BACKGROUND & AIMS: INTRODUCTION:To obtain strict glucose regulation, an accurate and feasible bedside glucometry method is essential. We evaluated three different types of point-of-care glucometry in seriously ill intensive care unit (ICU) patients. The study was performed as a single-centre, prospective, observational study in a 12-bed medical ICU of a university hospital. METHODS:Patients with an expected ICU stay of more than 48 hours were included. Because the reference laboratory delivers glucose values after approximately 30 to 60 minutes, which is too slow to use in a glucose regulation protocol and for calibration of the subcutaneous continuous glucose monitoring system (CGMS) (CGMS System Gold), we first validated the ICU-based blood gas/glucose analyser ABL715 (part 1 of the study). Subsequently, part 2 was performed: after inserting (and calibrating) the subcutaneous CGMS, heparinised arterial blood samples were drawn from an arterial line every 6 hours and analysed on both the Precision PCx point-of-care meter using test strips and on the blood gas/glucose analyser ABL715. CGMS glucose data were downloaded after 24 to 72 hours. The results of the paired measurements were analysed as a scatter plot by the method of Bland and Altman and were expressed as a correlation coefficient. RESULTS:Part 1: Four hundred and twenty-four blood samples were drawn from 45 critically ill ICU patients. The ICU-based blood gas/glucose analyser ABL715 provided a good estimate of conventional laboratory glucose assessment: the correlation coefficient was 0.95. In the Clarke error grid, 96.8% of the paired measurements were in the clinically acceptable zones A and B. Part 2: One hundred sixty-five paired samples were drawn from 19 ICU patients. The Precision PCx point-of-care meter showed a correlation coefficient of 0.89. Ninety-eight point seven percent of measurements were within zones A and B. The correlation coefficient for the subcutaneous CGMS System Gold was 0.89. One hundred percent of measurements were within zones A and B. CONCLUSION:The ICU-based blood glucose analyser ABL715 is a rapid and accurate alternative for laboratory glucose determination and can serve as a standard for ICU blood glucose measurements. The Precision PCx is a good alternative, but feasibility may be limited because of the blood sample handling. The subcutaneous CGMS System Gold is promising, but real-time glucose level reporting is necessary before it can be of clinical use in the ICU. When implementing a glucose-insulin algorithm in patient care or research, one should realise that the absolute glucose level may differ systematically among various measuring methods, influencing targeted glucose levels.
    背景与目标: 简介:要获得严格的葡萄糖调节,准确,可行的床旁血糖测定方法必不可少。我们评估了重症重症监护病房(ICU)患者的三种不同的即时护理血糖仪。该研究是在大学医院的12张病床的ICU中进行的单中心,前瞻性,观察性研究。
    方法:包括预期ICU超过48小时的患者。由于参考实验室在大约30至60分钟后会提供葡萄糖值,这太慢了,无法用于葡萄糖调节方案以及皮下连续葡萄糖监测系统(CGMS)(CGMS System Gold)的校准,因此我们首先验证了ICU-血气/葡萄糖分析仪ABL715(研究的第1部分)。随后,执行第2部分:插入(并校准)皮下CGMS后,每6小时从一条动脉管线中抽取肝素化的动脉血样本,并在Precision PCx即时检测仪上使用试纸条和血液进行分析气体/葡萄糖分析仪ABL715。 CGMS葡萄糖数据在24到72小时后下载。配对测量的结果通过Bland和Altman方法作为散点图进行分析,并表示为相关系数。
    结果:第1部分:从45名重症ICU患者中抽取了242份血液样本。基于ICU的血气/葡萄糖分析仪ABL715提供了常规实验室葡萄糖评估的良好估计:相关系数为0.95。在Clarke误差网格中,96.8%的配对测量值在临床上可接受的区域A和B中。第2部分:从19位ICU患者中抽取了165个配对样品。 Precision PCx即时护理仪的相关系数为0.89。百分之九十八的测量值在区域A和B内。皮下CGMS系统Gold的相关系数为0.89。百分之一百的测量值在区域A和B内。
    结论:基于ICU的血糖分析仪ABL715是一种快速准确的实验室葡萄糖测定方法,可作为ICU血糖测量的标准。 Precision PCx是一个很好的选择,但由于血液样本的处理,可行性可能受到限制。皮下CGMS System Gold前景看好,但在ICU中临床应用之前,必须实时报告葡萄糖水平。在患者护理或研究中实施葡萄糖-胰岛素算法时,应认识到,各种测量方法之间的绝对葡萄糖水平可能会系统地不同,从而影响目标血糖水平。
  • 【小儿多形性肉瘤的细胞遗传学和分子遗传学分析显示与成人恶性纤维组织细胞瘤相似。】 复制标题 收藏 收藏
    DOI:10.1016/s0165-4608(96)00243-9 复制DOI
    作者列表:Palmer JL,Masui S,Pritchard S,Kalousek DK,Sorensen PH
    BACKGROUND & AIMS: Cytogenetic and molecular genetic studies were performed on a pleomorphic sarcoma removed from the left atrium of a 15-year-old girl. Histologic analysis was consistent with a storiform-pleomorphic malignant fibrous histiocytoma (MFH). Although MFH is the most common soft-tissue sarcoma of late adulthood. It is extremely rare in childhood and its existence in the pediatric population remains controversial. Cytogenetic analysis revealed several alterations previously associated with adult MFH, including abnormalities of chromosomal bands 11p11 and 19p13. Moreover, the tumor demonstrated homogeneously staining regions (HSR) and double minute chromosomes (dmin) suggestive of gene amplification. We therefore screened the case for amplification of genes localized to chromosomal bands 12q13-14, including the putative protooncogenes MDM2, CDK4, SAS, CHOP, and CLI, which are frequently amplified and overexpressed in adult MFH. Southern and Northern blot analysis confirmed the coamplification of MDM2, CDK4, SAS, and CHOP. To our knowledge, such coamplification studies of the 12q13-14 amplicon have not been previously detected in pediatric MFH. Our results provide cytogenetic and molecular genetic evidence that pediatric and adult MFH are histogenetically related entities.

    背景与目标: 细胞遗传学和分子遗传学研究是从一个15岁女孩的左心房切除的多形性肉瘤。组织学分析与星形样多形性恶性纤维组织细胞瘤(MFH)一致。尽管MFH是成年后期最常见的软组织肉瘤。它在儿童时期极为罕见,其在儿科人群中的存在仍然引起争议。细胞遗传学分析揭示了以前与成人MFH相关的几种改变,包括染色体条带11p11和19p13的异常。此外,肿瘤表现出均一的染色区(HSR)和双分钟染色体(dmin),提示基因扩增。因此,我们筛选了扩增位于染色体12q13-14的基因的案例,包括推定的原癌基因MDM2,CDK4,SAS,CHOP和CLI,这些基因在成年MFH中经常被扩增和过表达。 Southern和Northern印迹分析证实了MDM2,CDK4,SAS和CHOP的共扩增。据我们所知,这种12q13-14扩增子的共扩增研究以前未在儿科MFH中检测到。我们的研究结果提供了细胞遗传学和分子遗传学证据,表明小儿和成人MFH是组织遗传学相关的实体。

  • 【植物繁殖对生境破碎化的敏感性:通过荟萃分析进行综述和综合。】 复制标题 收藏 收藏
    DOI:10.1111/j.1461-0248.2006.00927.x 复制DOI
    作者列表:Aguilar R,Ashworth L,Galetto L,Aizen MA
    BACKGROUND & AIMS: :The loss and fragmentation of natural habitats by human activities are pervasive phenomena in terrestrial ecosystems across the Earth and the main driving forces behind current biodiversity loss. Animal-mediated pollination is a key process for the sexual reproduction of most extant flowering plants, and the one most consistently studied in the context of habitat fragmentation. By means of a meta-analysis we quantitatively reviewed the results from independent fragmentation studies throughout the last two decades, with the aim of testing whether pollination and reproduction of plant species may be differentially susceptible to habitat fragmentation depending on certain reproductive traits that typify the relationship with and the degree of dependence on their pollinators. We found an overall large and negative effect of fragmentation on pollination and on plant reproduction. The compatibility system of plants, which reflects the degree of dependence on pollinator mutualism, was the only reproductive trait that explained the differences among the species' effect sizes. Furthermore, a highly significant correlation between the effect sizes of fragmentation on pollination and reproductive success suggests that the most proximate cause of reproductive impairment in fragmented habitats may be pollination limitation. We discuss the conservation implications of these findings and give some suggestions for future research into this area.
    背景与目标: :人类活动造成的自然栖息地的丧失和破碎化是遍及地球的陆地生态系统中普遍存在的现象,也是当前生物多样性丧失的主要驱动力。动物介导的授粉是大多数现存开花植物有性繁殖的关键过程,也是在栖息地破碎化背景下研究最一致的一个过程。通过荟萃分析,我们定量评估了过去二十年中独立破碎研究的结果,目的是检验植物的授粉和繁殖是否可能根据代表该关系的某些生殖性状而不同地易受生境破碎的影响。以及对传粉媒介的依赖程度。我们发现碎裂对授粉和植物繁殖总体上产生了很大的负面影响。植物的相容性系统反映了对传粉媒介共生的依赖程度,是唯一可以解释物种效应大小差异的繁殖性状。此外,片段化对授粉的影响大小与繁殖成功之间的高度显着相关性表明,片段化生境中繁殖受损的最直接原因可能是授粉限制。我们讨论了这些发现的保护意义,并为该领域的未来研究提供了一些建议。
  • 【冷暴露对大鼠肾上腺酪氨酸羟化酶的影响:RNA,蛋白质,酶活性和辅因子水平的分析。】 复制标题 收藏 收藏
    DOI:10.1111/j.1471-4159.1990.tb01232.x 复制DOI
    作者列表:Baruchin A,Weisberg EP,Miner LL,Ennis D,Nisenbaum LK,Naylor E,Stricker EM,Zigmond MJ,Kaplan BB
    BACKGROUND & AIMS: :Long-term cold exposure (5-7 days) is known to induce concomitant increases in the levels of adrenomedullary tyrosine hydroxylase (TH) RNA, protein, and enzyme activity. In this report, we compare the time courses of these changes and investigate the effects of cold exposure on the levels of biopterin, the cofactor required for tyrosine hydroxylation. After only 1 h of cold exposure, TH mRNA abundance increased 71% compared with nonstressed controls. Increases in total cellular TH RNA levels were maximal (threefold over control values) within 3-6 h of cold exposure and remained elevated throughout the duration of the experiment (72 h). TH protein levels increased rapidly after 24 h of cold exposure and reached a maximal value threefold above that of controls at 48-72 h. Despite the relatively rapid and large elevations in TH RNA and protein content, only modest increases in TH activity were detected during the initial 48 h of cold exposure. Adrenomedullary biopterin increased rapidly after the onset of cold exposure, rising to a level approximately twofold that of the nonstressed controls at 24 h, and remained at this level throughout the duration of the stress period. Taken together, the results of this time course study indicate that cold-induced alterations in adrenal TH activity are mediated by multiple cellular control mechanisms, which may include pre- and posttranslational regulation. Our findings also suggest that cold stress-induced increases in the levels of the TH cofactor may represent another key event in the sympathoadrenal system's response to cold stress.
    背景与目标: :已知长期冷暴露(5-7天)会引起肾上腺髓质酪氨酸羟化酶(TH)RNA,蛋白质和酶活性的同时升高。在本报告中,我们比较了这些变化的时程,并研究了冷暴露对生物蝶呤水平的影响,生物蝶呤是酪氨酸羟化所需的辅助因子。低温暴露仅1小时后,与未受压力的对照组相比,TH mRNA的丰度增加了71%。在冷暴露的3-6小时内,总细胞TH RNA水平的增加最大(比对照值高三倍),并且在整个实验过程中(72小时)保持升高。在冷暴露24小时后,TH蛋白水平迅速升高,在48-72 h时达到最大值,是对照的三倍。尽管TH RNA和蛋白质含量的升高相对较快且幅度较大,但在冷暴露的最初48小时内仅检测到TH活性的适度增加。冷暴露开始后,肾上腺髓质生物蝶呤迅速增加,在24 h时升高至非应激对照组的两倍,并在整个应激期一直保持在该水平。两者合计,此时间过程研究的结果表明,冷诱导的肾上腺TH活性的改变是由多种细胞控制机制介导的,其中可能包括翻译前和翻译后调控。我们的发现还表明,冷应激诱导的TH辅助因子水平升高可能代表交感肾上腺系统对冷应激反应的另一个关键事件。
  • 13 A multivariate model for ordinal trait analysis. 复制标题 收藏 收藏

    【序数特征分析的多元模型。】 复制标题 收藏 收藏
    DOI:10.1038/sj.hdy.6800885 复制DOI
    作者列表:Xu S,Xu C
    BACKGROUND & AIMS: :Many economically important characteristics of agricultural crops are measured as ordinal traits. Statistical analysis of the genetic basis of ordinal traits appears to be quite different from regular quantitative traits. The generalized linear model methodology implemented via the Newton-Raphson algorithm offers improved efficiency in the analysis of such data, but does not take full advantage of the extensive theory developed in the linear model arena. Instead, we develop a multivariate model for ordinal trait analysis and implement an EM algorithm for parameter estimation. We also propose a method for calculating the variance-covariance matrix of the estimated parameters. The EM equations turn out to be extremely similar to formulae seen in standard linear model analysis. Computer simulations are performed to validate the EM algorithm. A real data set is analyzed to demonstrate the application of the method. The advantages of the EM algorithm over other methods are addressed. Application of the method to QTL mapping for ordinal traits is demonstrated using a simulated baclcross (BC) population.
    背景与目标: :许多农作物的重要经济特征都是按序性状衡量的。对序性状遗传基础的统计分析似乎与常规的定量性状完全不同。通过Newton-Raphson算法实现的广义线性模型方法在分析此类数据时提供了更高的效率,但并未充分利用线性模型领域开发的广泛理论。相反,我们开发了用于序性状分析的多元模型,并实现了用于参数估计的EM算法。我们还提出了一种计算估计参数的方差-协方差矩阵的方法。事实证明,EM方程与标准线性模型分析中的公式极为相似。执行计算机仿真以验证EM算法。分析实际数据集以演示该方法的应用。解决了EM算法相对于其他方法的优点。使用模拟的baclcross(BC)群体证明了该方法在序性状QTL定位中的应用。
  • 【肝移植受者巨细胞病毒感染危险因素的多因素分析。】 复制标题 收藏 收藏
    DOI:10.1016/0016-5085(90)90352-2 复制DOI
    作者列表:Gorensek MJ,Carey WD,Vogt D,Goormastic M
    BACKGROUND & AIMS: :Thirty-three consecutive liver-transplant recipients were prospectively studied over a 37-mo period for evidence of cytomegalovirus infection. Sixteen (48%) episodes of cytomegalovirus infection were identified; 9 were primary infections and 7 were recurrent infections. Beginning with patient 8, gamma-globulin prophylaxis was routinely administered to most patients. Twelve potential risk factors for cytomegalovirus infection were evaluated and included pretransplant cytomegalovirus serological status of donor and recipient; recipient's age, sex, race, and liver disease; number and type of blood products transfused; type and intensity of immunosuppression; and occurrence of rejection. The Cox proportional hazards model identified positive donor cytomegalovirus serology as the single most important risk factor for subsequent development of cytomegalovirus infection, regardless of recipient cytomegalovirus serological status. In addition, use of gamma-globulin prophylaxis seemed to be protective against the occurrence of disseminated cytomegalovirus disease.
    背景与目标: :在37个月内对33例连续肝移植接受者进行了前瞻性研究,以发现巨细胞病毒感染的迹象。鉴定出十六例(48%)巨细胞病毒感染; 9例是原发性感染,7例是复发性感染。从患者8开始,常规对大多数患者进行了γ-球蛋白的预防。对巨细胞病毒感染的十二种潜在危险因素进行了评估,包括供体和受体移植前巨细胞病毒的血清学状况。接受者的年龄,性别,种族和肝脏疾病;输血产品的数量和类型;免疫抑制的类型和强度;和拒绝的发生。 Cox比例风险模型将阳性供体巨细胞病毒血清学确定为随后发展成巨细胞病毒感染的唯一最重要的危险因素,而与受体巨细胞病毒血清学状况无关。另外,使用γ-球蛋白预防似乎可以预防弥漫性巨细胞病毒病的发生。
  • 【I型糖尿病易感性候选基因的分析:2q31-35号染色体上基因的病例对照和家庭关联研究。】 复制标题 收藏 收藏
    DOI:10.2337/diab.46.6.1069 复制DOI
    作者列表:Owerbach D,Naya FJ,Tsai MJ,Allander SV,Powell DR,Gabbay KH
    BACKGROUND & AIMS: Recent genome searches suggest a putative linkage of many loci to susceptibility to type I diabetes. The chromosome 2q31-35 region is reported to be linked to susceptibility to type I diabetes and is thought to contain several diabetes susceptibility loci. These candidate genes include the HOXD gene cluster, BETA2, CTLA4, CD28, IGFBP2, and IGFBP5. Association studies in populations and families are required to confirm and/or identify the actual susceptibility loci. We hereby report several previously unknown DNA polymorphisms for HOXD8, BETA2, and IGFBP5, which we have used along with previously known polymorphisms of HOXD8 and CTLA4 to test whether these candidate loci are the susceptibility genes on chromosome 2q31-35. Using a case-control design with a subsequent family-association approach to confirm associations, we find no evidence that these candidate genes are associated with susceptibility to type I diabetes.

    背景与目标: 最近的基因组搜索表明,许多基因位点与I型糖尿病易感性的推测联系。据报道,染色体2q31-35与I型糖尿病易感性相关,并被认为含有几个糖尿病易感性基因座。这些候选基因包括HOXD基因簇,BETA2,CTLA4,CD28,IGFBP2和IGFBP5。需要在人群和家庭中进行协会研究,以确认和/或识别实际的易感基因座。我们在此报告了HOXD8,BETA2和IGFBP5的几种先前未知的DNA多态性,并将其与HOXD8和CTLA4的先前已知多态性一起用于测试这些候选基因座是否为2q31-35染色体上的易感性基因。使用病例对照设计和随后的家庭关联方法来确认关联,我们没有发现这些候选基因与I型糖尿病易感性相关的证据。

+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