• 【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。

  • 【肾素-血管紧张素系统介体和雷诺现象。】 复制标题 收藏 收藏
    DOI:10.1345/aph.1H201 复制DOI
    作者列表:Wood HM,Ernst ME
    BACKGROUND & AIMS: OBJECTIVE:To review the use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) in the treatment of Raynaud's phenomenon (RP). DATA SOURCES:Biomedical literature was accessed through July 2006 via PubMed, the Iowa Drug Information System (IDIS), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus. PubMed database terms included Raynaud's disease, angiotensin-converting enzyme inhibitors, and angiotensin II type 1 receptor blockers [pharmacological action]; IDIS terms included hypotensive agents-ace inhib 24080200, raynaud's syndrome 443.0, and hypotensive agents-angioten II 24080400; and CINAHL Plus terms included Raynaud's disease, angiotensin-converting enzyme inhibitors, losartan, and irbesartan. STUDY SELECTION AND DATA EXTRACTION:All clinical trials published in English that reported both subjective and objective outcomes of efficacy were reviewed. DATA SYNTHESIS:Several small, short-term studies have evaluated captopril, enalapril, and losartan in the treatment of RP. The studies of ACE inhibitors have found conflicting results in their ability to improve digit blood flow and reduce both frequency and severity of RP attacks. Two studies have focused on the use of losartan for RP treatment, with both finding a statistically significant reduction in attacks and one showing improvement in symptoms of RP in comparison with the commonly utilized calcium-channel blocker, nifedipine. Most of the studies were short term (< or =12 wk) and included a limited number of patients (<60). CONCLUSIONS:ACE inhibitors and ARBs may provide some minor benefits in the relief of RP, although no definite evidence exists to suggest that they are superior to traditionally used treatments such as calcium-channel blockers. Larger, randomized controlled trials of longer duration are needed to compare the effectiveness of ACE inhibitors and ARBs with conventional treatment.
    背景与目标: 目的:探讨血管紧张素转换酶(ACE)抑制剂和血管紧张素II受体阻滞剂(ARBs)在治疗雷诺现象(RP)中的应用。
    数据来源:截至2006年7月,通过PubMed,爱荷华州药物信息系统(IDIS)和护理和专职健康文献累积索引(CINAHL)Plus获得了生物医学文献。 PubMed数据库中的术语包括雷诺氏病,血管紧张素转换酶抑制剂和血管紧张素II 1型受体阻滞剂[药理作用]。 IDIS术语包括降压药-王牌吸脂24080200,雷诺氏综合症443.0和降压药-血管紧张素II 24080400; CINAHL Plus术语包括雷诺氏病,血管紧张素转换酶抑制剂,氯沙坦和厄贝沙坦。
    研究选择和数据提取:审查了所有以英文发表的报告疗效的主观和客观结果的临床试验。
    数据综合:几个小型的短期研究评估了卡托普利,依那普利和氯沙坦在RP的治疗中。 ACE抑制剂的研究发现,在改善手指血流,降低RP发作的频率和严重性方面的能力存在矛盾的结果。有两项研究着眼于氯沙坦用于RP的治疗,与常用的钙通道阻滞剂硝苯地平相比,两者均发现统计学上显着降低发作次数,并且一项显示RP症状有所改善。大多数研究是短期的(<或= 12 wk),并且包括数量有限的患者(<60)。
    结论:ACE抑制剂和ARBs在缓解RP方面可能会产生一些小的益处,尽管尚无确切证据表明它们优于传统使用的治疗方法,例如钙通道阻滞剂。需要比较长时间的大型随机对照试验,以比较ACE抑制剂和ARB与常规治疗的有效性。
  • 【T(2)加权的microMRI和诱发的低髓鞘转基因小鼠的发展过程中视觉系统测量的潜力。】 复制标题 收藏 收藏
    DOI:10.1007/s11064-006-9121-z 复制DOI
    作者列表:Martin M,Reyes SD,Hiltner TD,Givogri MI,Tyszka JM,Fisher R,Campagnoni AT,Fraser SE,Jacobs RE,Readhead C
    BACKGROUND & AIMS: :Our objective was to follow the course of a dysmyelinating disease followed by partial recovery in transgenic mice using non-invasive high-resolution (117 x 117 x 70 microm) magnetic resonance (microMRI) and evoked potential of the visual system (VEP) techniques. We used JOE (for J37 golli overexpressing) transgenic mice engineered to overexpress golli J37, a product of the Golli-mbp gene complex, specifically in oligodendrocytes. Individual JOE transgenics and their unaffected siblings were followed from 21 until 75-days-old using non-invasive in vivo VEPs and 3D T2-weighted microMRI on an 11.7 T scanner, performing what we believe is the first longitudinal study of its kind. The microMRI data indicated clear, global hypomyelination during the period of peak myelination (21-42 days), which was partially corrected at later ages (>60 days) in the JOE mice compared to controls. These microMRI data correlated well with [Campagnoni AT (1995) "Molecular biology of myelination". In: Ransom B, Kettenmann H (eds) Neuroglia--a Treatise. Oxford University Press, London, pp 555-570] myelin staining, [Campagnoni AT, Macklin WB (1988) Cellular and molecular aspects of myelin protein gene-expression. Mol Neurobiol 2:41-89] a transient intention tremor during the peak period of myelination, which abated at later ages, and [Lees MB, Brostoff SW (1984) Proteins in myelin. In: Morell (ed) Myelin. Plenum Press, New York and London, pp 197-224] VEPs which all indicated a significant delay of CNS myelin development and persistent hypomyelination in JOE mice. Overall these non-invasive techniques are capable of spatially resolving the increase in myelination in the normally developing and developmentally delayed mouse brain.
    背景与目标: :我们的目标是通过非侵入性高分辨率(117 x 117 x 70 microm)磁共振(microMRI)和诱发视觉系统(VEP)技术追踪转基因小鼠的运动异常,然后部分恢复。我们使用经工程改造过表达Golli-mbp基因复合物产物Golli J37(特别是在少突胶质细胞中)的JOE(用于J​​37 golli过表达)转基因小鼠。从21岁到75天大,使用11.7 T扫描仪上的非侵入性体内VEP和3D T2加权显微MRI对个体JOE转基因及其未受影响的兄弟姐妹进行跟踪研究,我们认为这是同类研究中的首次纵向研究。显微MRI数据表明,在峰值髓鞘形成期(21-42天)期间出现了明显的整体性低髓鞘形成,与对照组相比,JOE小鼠在以后的年龄(> 60天)中得到了部分纠正。这些显微MRI数据与[Campagnoni AT(1995)“髓鞘形成的分子生物学”)有很好的相关性。在:Ransom B,Kettenmann H(eds)Neuroglia-专着中。牛津大学出版社,伦敦,第555-570页]髓磷脂染色,[Campagnoni AT,Macklin WB(1988)髓磷脂蛋白基因表达的细胞和分子方面。 [Mol Neurobiol 2:41-89]在髓鞘形成高峰期发生短暂的意向性震颤,此现象在以后的年龄有所减轻,[Lees MB,Brostoff SW(1984)Proteins in髓磷脂。在:莫雷尔(编辑)髓磷脂。 [Plenum Press,纽约和伦敦,第197-224页] VEP均表明JOE小鼠的CNS髓磷脂发育显着延迟和持续性髓鞘减少。总体而言,这些非侵入性技术能够在空间上解决正常发育和发育迟缓的小鼠大脑中髓鞘形成的增加。
  • 【在使用电纺聚合物支架的三维培养系统中,鼠胚胎干细胞的成脂作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.biomaterials.2006.08.052 复制DOI
    作者列表:Kang X,Xie Y,Powell HM,James Lee L,Belury MA,Lannutti JJ,Kniss DA
    BACKGROUND & AIMS: :A mechanistic understanding of adipose tissue differentiation is critical for the treatment and prevention of obesity and type 2 diabetes. Conventional in vitro models of adipogenesis are preadipocytes or freshly isolated adipocytes grown in two-dimensional (2D) cultures. Optimal results using in vitro tissue culture models can be expected only when adipocyte models closely resemble adipose tissue in vivo. Thus the design of an in vitro three-dimensional (3D) model which faithfully mimics the in vivo environment is needed to effectively study adipogenesis. Pluripotent embryonic stem (ES) cells are a self-renewing cell type that can readily be differentiated into adipocytes. In this study, a 3D culture system was developed to mimic the geometry of adipose tissue in vivo. Murine ES cells were seeded into electrospun polycaprolactone scaffolds and differentiated into adipocytes in situ by hormone induction as demonstrated using a battery of gene and protein expression markers along with the accumulation of neutral lipid droplets. Insulin-responsive Akt phosphorylation, and beta-adrenergic stimulation of cyclic AMP synthesis were demonstrated in ES cell-derived adipocytes. Morphologically, ES cell-derived adipocytes resembled native fat cells by scanning electron and phase contrast microscopy. This tissue engineered ES cell-matrix model has potential uses in drug screening and other therapeutic developments.
    背景与目标: :对脂肪组织分化的机械理解对于肥胖症和2型糖尿病的治疗和预防至关重要。脂肪形成的常规体外模型是在二维(2D)培养物中生长的前脂肪细胞或新鲜分离的脂肪细胞。仅当脂肪细胞模型与体内脂肪组织非常相似时,才能期望使用体外组织培养模型获得最佳结果。因此,需要忠实地模拟体内环境的体外三维(3D)模型的设计才能有效地研究脂肪形成。多能胚胎干(ES)细胞是一种自我更新的细胞类型,可以很容易地分化为脂肪细胞。在这项研究中,开发了一种3D培养系统来模拟体内脂肪组织的几何形状。将鼠ES细胞接种到电纺聚己内酯支架中,并通过激素诱导原位分化为脂肪细胞,如使用一系列基因和蛋白质表达标志物以及中性脂质滴的积累所证明的。在ES细胞衍生的脂肪细胞中证实了胰岛素反应性Akt磷酸化和β-肾上腺素能刺激环状AMP合成。形态上,通过扫描电子和相差显微镜,ES细胞来源的脂肪细胞类似于天然脂肪细胞。这种组织工程化的ES细胞基质模型在药物筛选和其他治疗发展中具有潜在用途。
  • 【槲寄生制剂(伊斯卡多)在三维胶原蛋白基质系统中诱导T淋巴细胞运动的供体依赖性和剂量依赖性变异。】 复制标题 收藏 收藏
    DOI:10.1097/00001813-199704001-00014 复制DOI
    作者列表:Nikolai G,Friedl P,Werner M,Zänker KS
    BACKGROUND & AIMS: :Controlled activation of non-specific and specific immune defence mechanisms can beneficially manipulate the host's ability to attack malignant cells. In this context, migration and tissue distribution of immunocompetent cells may be prerequisites for an efficient immune surveillance. The effect of various non-cytotoxic concentrations of the Viscum album L. (mistletoe) preparation Iscadore QuFrF on the locomotory activity of immunomagnetically isolated human CD4+ and CD8+ T lymphocytes from healthy donors was investigated. Cellular migration was examined within a three-dimensional collagen matrix. Donor-dependent variations in baseline activities of spontaneously locomoting T cells were accompanied by individual response patterns of T cells from different donors in the presence of various concentrations of mistletoe preparation (0.25-2.5 micrograms/ml). Using the three-dimensional collagen matrix assay an induction of locomotory activity was detected in a highly reproducible fashion although the optimal concentration of mistletoe preparation and the time point of maximal response were individual for each donor. Our data suggest that the direct stimulation of T-cell migration by mistletoe components may modulate the system of immune surveillance and recognition in patients under mistletoe therapy.
    背景与目标: :非特异性和特异性免疫防御机制的受控激活可以有益地控制宿主攻击恶性细胞的能力。在这种情况下,免疫活性细胞的迁移和组织分布可能是有效免疫监视的先决条件。研究了Viscum album L.(槲寄生)制剂Iscadore QuFrF的各种非细胞毒性浓度对来自健康供体的免疫磁性分离的人CD4和CD8 T淋巴细胞运动功能的影响。在三维胶原蛋白基质中检查了细胞迁移。在各种浓度的槲寄生制剂(0.25-2.5微克/毫升)存在下,自发性自发性T细胞基线活动的供体依赖性变异伴随着来自不同供体的T细胞的个体反应模式。使用三维胶原蛋白基质测定法,以高度可重复的方式检测了运动活性的诱导,尽管对于每个供体而言,槲寄生制剂的最佳浓度和最大响应的时间点各不相同。我们的数据表明,槲寄生成分直接刺激T细胞迁移可能会调节槲寄生治疗下患者的免疫监视和识别系统。
  • 【社区获得性耐甲氧西林金黄色葡萄球菌对奥沙西林耐药所需的VraS / VraR两组分调节系统。】 复制标题 收藏 收藏
    DOI:10.1111/j.1574-6968.2006.00384.x 复制DOI
    作者列表:Boyle-Vavra S,Yin S,Daum RS
    BACKGROUND & AIMS: :Methicillin/oxacillin (Oxa) resistance in Staphylococcus aureus is primarily mediated by the acquired penicillin-binding protein (PBP2a) encoded by mecA. PBP2a acts together with native PBP2 to mediate oxacillin resistance by contributing complementary transpeptidase and transglycosylase activities, respectively. The VraS/VraR two-component regulatory system is inducible by cell-wall antimicrobials (beta-lactams, glycopeptides) and controls transcriptional induction of many cell-wall genes including pbp2 and itself. We investigated the role of VraS/VraR in the phenotypic expression of oxacillin resistance by inactivating vraS in community-acquired MRSA clinical isolates that lack functional genes encoding the mecA regulatory sequences mecI and mecR1. Inactivation of vraS abrogated oxacillin resistance, and complementation with the vraS operon restored the resistance phenotype. mecA transcription increased in the vraS mutants; however, PBP2a abundance was similar to that of the wild type. Although pbp2 transcription decreased in the vraS mutants, overexpression of the pbp2 operon did not restore resistance. These data demonstrate that although expressions of mecA and pbp2 are required for oxacillin resistance, they are not sufficient. Therefore, the vraS/vraR regulatory system plays a crucial role in allowing MRSA to respond to beta-lactams by regulation of a gene target other than the known effectors of methicillin resistance.
    背景与目标: 金黄色葡萄球菌对甲氧西林/奥沙西林(Oxa)的耐药性主要由mecA编码的获得性青霉素结合蛋白(PBP2a)介导。 PBP2a与天然PBP2共同发挥作用,通过分别贡献互补的转肽酶和转糖基酶活性来介导奥沙西林抗性。 VraS / VraR两组分调节系统可通过细胞壁抗微生物剂(β-内酰胺,糖肽)诱导,并控制包括pbp2及其本身在内的许多细胞壁基因的转录诱导。我们通过灭活社区获得的MRSA临床分离株中的vraS而失活,研究了VraS / VraR在奥沙西林耐药性表型表达中的作用,该分离株缺乏编码mecA调控序列mecI和mecR1的功能基因。 vraS的失活消除了奥沙西林的耐药性,与vraS操纵子的互补恢复了耐药性表型。在vraS突变体中,mecA转录增加;但是,PBP2a的丰度与野生型相似。尽管在vraS突变体中pbp2转录降低,但是pbp2操纵子的过表达不能恢复抗性。这些数据表明,尽管抗mecA和pbp2的表达是奥沙西林耐药性所必需的,但它们还不够。因此,vraS / vraR调节系统在允许MRSA通过调节除已知的甲氧西林抗性效应子以外的基因靶标而对β-内酰胺作出响应中起着至关重要的作用。
  • 【人类前脑神经母细胞对成年大鼠中枢神经系统长轴突通路的改造。】 复制标题 收藏 收藏
    DOI:10.1038/347556a0 复制DOI
    作者列表:Wictorin K,Brundin P,Gustavii B,Lindvall O,Björklund A
    BACKGROUND & AIMS: :The failure of lesioned axons to regenerate over long distances in the mammalian central nervous system (CNS) is not due to an inability of central neurons to regenerate, but rather to the non-permissive nature of the CNS tissue environment. Regenerating CNS axons, which grow well within a peripheral nerve, for example, fail to penetrate mature CNS tissue by more than about 1 mm. Recent evidence indicates that this may be due to inhibitory membrane proteins associated with CNS oligodendrocytes and myelin. We report here that human telencephalic neuroblasts implanted into the excitotoxically lesioned striatum of adult rats can escape or neutralize this inhibitory influence of the adult CNS environment and extend axons along major myelinated fibre tracts for distances of up to approximately 20 mm. The axons were seen to elongate along the paths of the striato-nigral and cortico-spinal tracts to reach the substantia nigra, the pontine nuclei and the cervical spinal cord, which are the normal targets for the striatal and cortical projection neurons likely to be present in these implants.
    背景与目标: :损伤的轴突在哺乳动物中枢神经系统(CNS)中无法长距离再生的原因不是由于中枢神经元无法再生,而是由于CNS组织环境的非许可性质。例如,在周围神经中生长良好的再生中枢神经轴突不能穿透成熟的中枢神经系统组织超过约1毫米。最近的证据表明,这可能是由于与CNS少突胶质细胞和髓磷脂相关的抑制性膜蛋白所致。我们在这里报告说,植入成年大鼠兴奋毒性损伤的纹状体的人类端脑神经母细胞可以逃避或中和成年中枢神经系统环境的这种抑制作用,并沿主要有髓纤维束延伸轴突的距离可达约20 mm。看到轴突沿纹状体-黑色和皮质-脊髓束的路径伸长,到达黑质,桥脑核和颈脊髓,它们是可能存在的纹状体和皮质投射神经元的正常靶标在这些植入物中。
  • 【流域可持续水质管理框架和战略规划系统。】 复制标题 收藏 收藏
    DOI:10.1007/s00267-005-0304-1 复制DOI
    作者列表:Chen CH,Liu WL,Leu HG
    BACKGROUND & AIMS: :In Taiwan, the authorities have spent years working on remedying polluted rivers. Generally, the remediation planning works are divided into two phases. During the first phase, the allowed pollution discharge quantity and abatement quantity of each drainage zone, including the assimilative capacity, are generated based on the total river basin. In the second phase, the abatement action plans for each pollution source in each drainage zone are respectively devised by the related organizations based on the strategies generated during the first phase. However, the effectiveness of linking the two phases is usually poor. Highly integrated performances are not always achieved because the separate two-phase method does not take system and management thinking into consideration in the planning stage. This study pioneers the use of the Managing for Results (MFR) method in planning strategies and action plans for river water quality management. A sustainable management framework is proposed based on the concept and method of MFR, Management Thinking, and System Analysis. The framework, consisting of planning, implementation, and controlling stages, systematically considers the relationships and interactions among four factors: environment, society, economy, and institution, based on the principles of sustainable development. Based on the framework, the Modified Bounded Implicit Enumeration algorithm, which is used as a solving method, is combined with Visual Basic software and MS Excel to develop a computer system for strategy planning. The Shetzu River, located in northern Taiwan, is applied as a case study. According to the theoretical, practical, and regulatory considerations, the result-oriented objectives are defined to first improve the pollution length of the Shetzu River in specific remediation periods to finally meet regulated water quality standards. The objectives are then addressed as some of the constraints for the strategy planning model. The model objective is to pursue the maximum assimilative capacity (environmental phase) subjected to the constraints of water quality standards (institutional phase), social equity (social phase), and proper available technology (economic phase). The pollution quantity abatement and allocation, which are named the top strategies, of each drainage zone for different scenarios can be obtained based on each water quality standard. The middle as well as lower strategies and action plans, which consist of pollution quantity abatement and allocation of each class (domestic, industrial, livestock, and non-point pollution sources) and their individual pollution sources in each drainage zone, are then generated based on the top strategies. The performance indicators and measure plans are proposed based on the action plans to promote the comprehensive effectiveness of river water quality management. The authorities have begun to develop a budget based on the strategies and action plans developed in this study. The analytical results indicate that the objectives, strategies, and action plans developed based on the sustainable management framework and strategy planning system can effectively help the related authorities to fulfill the tasks of water quality management for a river basin.
    背景与目标: :在台湾,当局花费了多年的时间来修复受污染的河流。通常,修复计划工作分为两个阶段。在第一阶段,每个流域的允许污染排放量和减排量(包括同化能力)是基于总流域产生的。在第二阶段,相关组织根据第一阶段产生的策略分别制定每个流域每个污染源的减排行动计划。但是,连接两个阶段的有效性通常很差。由于分离的两阶段方法在计划阶段没有考虑系统和管理思想,因此无法始终实现高度集成的性能。这项研究开创了在河流水质管理的规划策略和行动计划中使用“结果管理”(MFR)方法的方法。基于MFR,管理思想和系统分析的概念和方法,提出了一种可持续的管理框架。该框架由规划,实施和控制阶段组成,根据可持续发展的原则,系统地考虑了四个因素之间的关系和相互作用:环境,社会,经济和制度。在此框架的基础上,将改进的有界隐式枚举算法(作为一种求解方法)与Visual Basic软件和MS Excel相结合,以开发用于战略规划的计算机系统。以台湾北部的神社河为例。根据理论,实践和监管方面的考虑,确定了以结果为导向的目标,即首先在特定的修复时期内改善Shetzu河的污染长度,以最终达到规定的水质标准。然后,将目标作为战略计划模型的一些约束条件加以解决。该模型的目标是在水质标准(机构阶段),社会公平(社会阶段)和适当的可用技术(经济阶段)的约束下,追求最大同化能力(环境阶段)。可以根据每个水质标准获得不同情景下每个流域的污染量减免和分配,这是最重要的策略。然后基于每个流域生成中等和较低的战略和行动计划,其中包括减少污染量和分配每个类别(家庭,工业,牲畜和非点源污染源)及其各自的污染源。在最重要的策略上。根据行动计划提出绩效指标和措施计划,以提高河流水质管理的综合有效性。当局已开始根据本研究制定的策略和行动计划制定预算。分析结果表明,基于可持续管理框架和战略计划系统制定的目标,战略和行动计划可以有效地帮助有关部门完成流域水质管理的任务。
  • 【将CT图像集成到电解剖标测系统中对心房纤颤导管消融的临床结果的影响。】 复制标题 收藏 收藏
    DOI:10.1111/j.1540-8167.2006.00594.x 复制DOI
    作者列表:Kistler PM,Rajappan K,Jahngir M,Earley MJ,Harris S,Abrams D,Gupta D,Liew R,Ellis S,Sporton SC,Schilling RJ
    BACKGROUND & AIMS: BACKGROUND:A detailed appreciation of left atrial/pulmonary vein (LA/PV) anatomy may be important in improving the safety and success of catheter ablation (CA) for atrial fibrillation (AF). OBJECTIVES:The aim of this nonrandomized study was to determine the impact of computerized tomography (CT) image integration into a 3-dimensional (3D) mapping system on the clinical outcome of patients undergoing CA for AF. METHODS:Ninety-four patients (age: 56 +/- 10 years) with AF (paroxysmal 46, persistent 48) underwent wide encirclement of ipsilateral PV pairs using irrigated radiofrequency ablation with the endpoint of electrical isolation. Ablation was guided by 3D mapping alone (electroanatomic 24, noncontact 23) in 47 (3DM group) patients and by CT image integration (Cartomerge) in 47 (CT group). In persistent AF, a combination of linear ablation and targeted ablation of complex fractionated electrograms was also performed. RESULTS:Successful PV electrical isolation did not differ between the two groups. A significant reduction in fluoroscopy times was demonstrated in the CT group (49 +/- 27 minutes vs 3DM group 62 +/- 26 minutes, P = 0.03). Arrhythmia recurrence was reduced in the CT group (32% vs 51% in the 3DM group, P < 0.01). In 30 symptomatic patients (12 CT and 18 3DM), repeat procedures for AF (13 in 3DM and 5 CT, P < or = 0.10) and AT (5 in 3DM and 7 CT, P = NS) were performed. Overall success on 7-day monitor off antiarrhythmic drugs was achieved in 60% in the 3DM group when compared with 83% in the CT group (P < 0.05) at a follow-up of 25 +/- 5 weeks. CONCLUSION:CA for AF guided by CT integration was associated with reduced fluoroscopy times, arrhythmia recurrence, and increased restoration of sinus rhythm. Improved visualization of complex LA geometries might improve the safety and success of CA for AF.
    背景与目标: 背景:详细了解左心房/肺静脉(LA / PV)解剖结构对于提高房颤(AF)导管消融(CA)的安全性和成功率可能很重要。
    目的:这项非随机研究的目的是确定将计算机断层扫描(CT)图像集成到3维(3D)制图系统中对接受CA房颤的患者的临床结局的影响。
    方法:94例房颤(阵发性46例,持续性48例)(年龄56 /-10岁)采用射频消融冲洗并以电隔离为终点,对同侧PV对进行了大包围。 47例(3DM组)患者仅通过3D映射(电解剖学24,非接触式23)进行消融,47例(CT组)通过CT图像积分(Cartomerge)进行消融。在持续性房颤中,还执行了复杂的电描记图的线性消融和靶向消融的组合。
    结果:两组之间成功的PV电气隔离没有差异。在CT组中,荧光检查时间显着减少(49 /-27分钟,而3DM组62 /-26分钟,P = 0.03)。 CT组心律失常复发率降低(3DM组为32%,而51%为P <0.01)。在30例有症状的患者中(12 CT和18 3DM),重复进行AF(3DM和5 CT中13例,P <或= 0.10)和AT(3DM和7 CT中5例,P = NS)的重复手术。在25 /-5周的随访中,3DM组60%的抗心律失常药物获得了总体成功,而CT组为83%(P <0.05)。
    结论:CT整合引导的房颤CA与减少的透视时间,心律失常的复发和窦性心律的恢复增加有关。改善复杂的LA几何图形的可视化可能会提高CA用于AF的安全性和成功性。
  • 【用反向四环素调节的逆转录病毒载体(RTRV)系统控制基因的表达。】 复制标题 收藏 收藏
    DOI:10.1006/bbrc.1997.6705 复制DOI
    作者列表:Watsuji T,Okamoto Y,Emi N,Katsuoka Y,Hagiwara M
    BACKGROUND & AIMS: :A retroviral vector was constructed with an autoregulatory cassette to allow expression of the gene of interest in response to oral administration of doxycycline (Dox) in vivo. The cassette contains all the components of the reverse tetracycline-regulated (rtTA) system, a drug selectable marker with the internal ribosome entry site and the gene of interest (GFP). FACS analyses showed an induction of GFP-fluorescence of two orders of magnitude in retrovirus-infected 208F cells dependent on the amount of Dox in the medium. Furthermore, oral administration of Dox resulted in GFP expression in transplanted 208F cells in the peritoneal cavity of nude mice. Thus this reverse tetracycline-regulated retroviral vector (RTRV) system simplifies the delivery of controllable genes to cultured and implanted cells. It is hoped that this approach may pave the way to controlled gene expression during a particular window of time in gene therapy applications.
    背景与目标: 逆转录病毒载体用自动调节盒构建,以响应体内口服强力霉素(Dox)来表达目的基因。该盒包含逆四环素调节(rtTA)系统的所有组件,具有内部核糖体进入位点和目的基因(GFP)的药物选择标记。 FACS分析显示,在逆转录病毒感染的208F细胞中,取决于培养基中Dox的量,诱导GFP荧光的数量级为两个数量级。此外,口服Dox导致裸鼠腹膜腔内移植的208F细胞表达GFP。因此,这种反向四环素调节的逆转录病毒载体(RTRV)系统简化了可控基因向培养和植入细胞的传递。希望这种方法可以为基因治疗应用中特定时间段内控制基因表达铺平道路。
  • 11 Tachykinins and the cardiovascular system. 复制标题 收藏 收藏

    【速激肽和心血管系统。】 复制标题 收藏 收藏
    DOI:10.2174/138945006778019291 复制DOI
    作者列表:Walsh DA,F McWilliams D
    BACKGROUND & AIMS: :The tachykinin family of vasoactive peptides comprises the neuropeptides substance P, neurokinin A and neurokinin B, and the newly discovered endokinins and hemokinins. Their cardiovascular effects are predominantly mediated by the family of neurokinin receptors. This review summarises the most recent advances in understanding the effects of tachykinins on the vasculature, and summarises their therapeutic potential. Tachykinins stimulate plasma extravasation, particularly acting through neurokinin-1 receptors in an endothelium-dependent manner. They therefore play prominent roles in tissue oedema and inflammation (called neurogenic inflammation). Pro-inflammatory effects of tachykinins are enhanced by their capacity to stimulate inflammatory cell recruitment, and to initiate angiogenesis. Tachykinins also regulate vascular tone and blood flow, although differences between species and between different vascular beds make this a highly complex area of research. They may relax vessels in some scenarios whilst inducing vasoconstriction in other situations, the state of the endothelium appearing to be of key importance. Tachykinins also modulate blood pressure and heart rate, acting both peripherally, and on the central nervous system. Cardiovascular effects of tachykinins and neurokinin receptors may be important therapeutic targets in diverse disorders such as pulmonary oedema, hypertension, pre-eclampsia, complex regional pain syndrome type 2, stroke and chronic inflammatory diseases such as arthritis. Sophisticated modelling of human disease is required to enable neurokinin receptor antagonists to achieve this therapeutic potential.
    背景与目标: 速激肽的血管活性肽家族包括神经肽物质P,神经激肽A和神经激肽B,以及新发现的内皮激肽和血红素。它们的心血管作用主要由神经激肽受体家族介导。这篇综述总结了了解速激肽对脉管系统的影响的最新进展,并总结了其治疗潜力。速激肽刺激血浆外渗,特别是以内皮依赖性方式通过神经激肽-1受体起作用。因此,它们在组织水肿和炎症(称为神经源性炎症)中起重要作用。速激肽的促炎作用通过其刺激炎性细胞募集和启动血管生成的能力而增强。速激肽还调节血管张力和血流量,尽管物种之间和不同血管床之间的差异使这成为一个高度复杂的研究领域。在某些情况下,它们可能使血管松弛,而在其他情况下,它们会引起血管收缩,内皮的状态似乎是至关重要的。速激肽还调节血压和心率,作用于外周和中枢神经系统。速激肽和神经激肽受体的心血管作用可能是多种疾病(例如肺水肿,高血压,先兆子痫,2型复杂区域性疼痛综合征),中风和慢性炎性疾病(例如关节炎)的重要治疗靶标。要使神经激肽受体拮抗剂能够实现这种治疗潜力,就需要对人类疾病进行复杂的建模。
  • 【肌肉骨骼系统的磁共振成像。第8部分。脊柱,第1节。】 复制标题 收藏 收藏
    DOI:10.1097/00003086-199705000-00037 复制DOI
    作者列表:Gundry CR,Fritts HM
    BACKGROUND & AIMS: Magnetic resonance has assumed a preeminent role in the imaging evaluation of the spine. Owing to its multiplanar capability and superior soft tissue contrast, magnetic resonance imaging is the procedure of choice for a host of spinal disorders including degenerative disc disease, tumor evaluation, trauma, and spinal deformities. It represents the most accurate means of distinguishing between recurrent disc herniation and epidural fibrosis, and it excels at the assessment of many postoperative abnormalities such as infection, adjacent segment disc degeneration, and arachnoiditis. Magnetic resonance imaging is also helpful in the evaluation of numerous diagnostic challenges that are less well resolved by other means. This includes the distinction between disc herniation and epidural hematoma, synovial cyst from nonspecific fibrous thickening of a facet capsule, and the evaluation of numerous other soft tissue abnormalities. Computed tomography, computed tomography myelography, and scintigraphy continue to be useful for numerous specific disorders and in those patients with metal hardware or contraindications to magnetic resonance scanning. Overall, however, magnetic resonance is the imaging procedure preferred for many spinal disorders. This article is the first installment of a 3-part series discussing the role of magnetic resonance imaging of spinal disorders. Section 1 will describe the varying imaging modalities available and their relative advantages and disadvantages. A consideration of magnetic resonance imaging techniques will follow, followed by a discussion of the imaging manifestations of early degenerative disc disease. Section 2 will be devoted to an in depth discussion of specific pathologic processes encountered in patients with degenerative disc disease. Section 3 will end the series with a consideration of postoperative imaging followed by a discussion of spinal deformities, trauma, and neoplasms.

    背景与目标: 磁共振在脊柱的成像评估中发挥了重要作用。由于其多平面能力和出色的软组织对比度,磁共振成像是许多脊柱疾病(包括退行性椎间盘疾病,肿瘤评估,创伤和脊柱畸形)的首选程序。它代表了区分复发性椎间盘突出症和硬膜外纤维化的最准确方法,并且擅长评估许多术后异常,例如感染,邻近节段性椎间盘退变和蛛网膜炎。磁共振成像还有助于评估许多诊断挑战,而这些挑战很难通过其他方式解决。这包括区分椎间盘突出症和硬膜外血肿,小囊囊的非特异性纤维增厚引起的滑膜囊肿,以及许多其他软组织异常的评估。计算机体层摄影术,计算机体层摄影术脊髓造影和闪烁显像术继续对许多特定疾病以及那些具有金属硬件或磁共振扫描禁忌症的患者有用。但是,总的来说,磁共振是许多脊柱疾病首选的成像方法。本文是由三部分组成的系列文章的第一部分,该系列讨论了磁共振成像对脊柱疾病的作用。第1节将描述可用的各种成像方式及其相对优缺点。随后将考虑磁共振成像技术,然后讨论早期退行性椎间盘疾病的成像表现。第2节将专门讨论变性椎间盘疾病患者遇到的特定病理过程。第三部分将在结束本系列文章时考虑术后影像学,然后讨论脊柱畸形,创伤和肿瘤。

  • 【肾对肾素-血管紧张素系统阻滞反应的性别差异。】 复制标题 收藏 收藏
    DOI:10.1681/ASN.2005101095 复制DOI
    作者列表:Miller JA,Cherney DZ,Duncan JA,Lai V,Burns KD,Kennedy CR,Zimpelmann J,Gao W,Cattran DC,Scholey JW
    BACKGROUND & AIMS: :Evidence suggests that gender differences exist in renin-angiotensin system (RAS) function. It was hypothesized that women may differ also in their response to RAS blockade. The renal and peripheral hemodynamic responses to incremental dosages of an angiotensin receptor blocker and the degree of angiotensin II (AngII) insensitivity achieved during 8 wk were examined in men and women. Participants were 30 young healthy men (n = 15; mean age 27 +/- 2) and women (n = 15; mean age 28 +/- 2) who were on a controlled sodium and protein diet for 1 wk before each study. The humoral, renal, and systemic response to incremental dosages of irbesartan (75 mg for 4 wk, then 150 mg for 4 wk) was assessed, as was the pressor response to AngII (3 ng/kg per min), at 2-wk intervals. AngII type 1 receptor expression in skin biopsies was assessed at baseline and after 8 wk by a real-time PCR protocol. Men and women both exhibited significant declines in BP. Women achieved significantly reduced AngII sensitivity compared with men at lower dosages, showing no pressor response at 4 wk of 75 mg/d irbesartan, whereas men continued to exhibit a pressor response at 4 wk of 150 mg/d. Receptor expression at baseline did not differ between men and women but by 8 wk was significantly decreased in women and unchanged in men. Our findings indicate that men may require larger dosages of angiotensin receptor blocker than do women and that the BP response cannot be used as a surrogate marker for adequate RAS blockade of the renal microvasculature.
    背景与目标: :证据表明,肾素-血管紧张素系统(RAS)功能存在性别差异。据推测,妇女对RAS阻滞的反应也可能有所不同。在男性和女性中,检查了在8周内达到的肾血管和外周血流动力学对血管紧张素受体阻滞剂递增剂量的反应以及血管紧张素II(AngII)不敏感的程度。参加研究的是30名年轻健康男性(n = 15;平均年龄27/2)和女性(n = 15;平均年龄28/2),他们在每次研究前均接受钠和蛋白质的控制饮食1周。评估了对依贝沙坦递增剂量的体液,肾脏和全身反应(75 mg,4 wk,然后150 mg,4 wk),以及在2周时对AngII的升压反应(3 ng / kg / min)。间隔。在基线和8周后通过实时PCR方案评估皮肤活检中AngII 1型受体的表达。男性和女性的血压均显着下降。与较低剂量的男性相比,女性的AngII敏感性大大降低,厄贝沙坦在4 wk时未显示升压反应,而在150 mg / d的4 wk时,男性仍表现出升压反应。男性和女性在基线时的受体表达没有差异,但女性8周时显着降低,男性则保持不变。我们的发现表明,与女性相比,男性可能需要更大剂量的血管紧张素受体阻滞剂,并且BP反应不能用作肾微血管系统RAS充分阻断的替代指标。
  • 【细胞质基因表达系统提高了阳离子脂质体介导的体内基因向小鼠脑内转移的效率。】 复制标题 收藏 收藏
    DOI:10.1006/bbrc.1997.6568 复制DOI
    作者列表:Mizuguchi H,Nakagawa T,Morioka Y,Imazu S,Nakanishi M,Kondo T,Hayakawa T,Mayumi T
    BACKGROUND & AIMS: Development of methodologies for gene transfer into the central nervous system (CNS) is important for fundamental research as well as clinical studies for gene therapy. Cationic liposomes (CL) are attractive vectors because of their safety and ease of use. However, to date only low rates of success have been reported. We succeeded in obtaining high transfection efficiencies into the newborn mouse brain in vivo by CL and a cytoplasmic gene expression system based on T7 RNA polymerase and T7 RNA polymerase- and the luciferase-gene with the T7 promoter sequence. This system showed an efficiency rate 2 orders of magnitude higher than the standard system, which used CL and luciferase genes with a Rous sarcoma virus promoter, pRSVL. In addition, in vitro experiments using LLCMK2 cells showed that cytoplasmic gene expression occurred rapidly (within 6 h) after transfection. In contrast, pRSVL required 24-48 h for induction of luciferase expression. Our results suggest that the cytoplasmic gene expression system is useful for gene delivery into the CNS.

    背景与目标: 基因转移到中枢神经系统(CNS)的方法学的发展对于基础研究以及基因治疗的临床研究都很重要。由于阳离子脂质体(CL)的安全性和易用性,它们是有吸引力的载体。然而,迄今为止,仅报道了低成功率。我们成功地通过CL和基于T7 RNA聚合酶和T7 RNA聚合酶以及荧光素酶基因(具有T7启动子序列)的细胞质基因表达系统,成功地在体内获得了新生小鼠大脑的高转染效率。该系统的效率比标准系统高2个数量级,后者使用带有Rous肉瘤病毒启动子pRSVL的CL和荧光素酶基因。此外,使用LLCMK2细胞的体外实验显示,转染后(6小时内)细胞质基因表达迅速发生。相比之下,pRSVL需要24-48小时才能诱导萤光素酶表达。我们的结果表明,胞质基因表达系统可用于将基因传递到中枢神经系统。

  • 【恶臭假单胞菌(Pseudomonas putida)U对D-葡萄糖的分解代谢通过细胞外转化为D-葡萄糖酸和诱导特定的葡萄糖酸盐转运系统而发生。】 复制标题 收藏 收藏
    DOI:10.1099/00221287-143-5-1595 复制DOI
    作者列表:Schleissner C,Reglero A,Luengo JM
    BACKGROUND & AIMS: Pseudomonas putida U does not degrade D-glucose through the glycolytic pathway but requires (i) its oxidation to D-gluconic acid by a peripherally located constitutive glucose dehydrogenase (insensitive to osmotic shock), (ii) accumulation of D-gluconic acid in the extracellular medium, and (iii) the induction of a specific energy-dependent transport system responsible for the uptake of D-gluconic acid. This uptake system showed maximal rates of transport at 30 degrees C in 50 mM potassium phosphate buffer, pH 7.0. Under these conditions the K(m) calculated for D-gluconic acid was 6.7 microM. Furthermore, a different transport system, specific for the uptake of glucose, was also identified. It is active and shows maximal uptake rates at 35 degrees C in 50 mM potassium phosphate buffer, pH 6.0, with a K(m) value of 8.3 microM.

    背景与目标: 恶臭假单胞菌U不会通过糖酵解途径降解D-葡萄糖,但需要(i)通过位于外围的组成型葡萄糖脱氢酶(对渗透压休克不敏感)将其氧化为D-葡萄糖酸,(ii)D-葡萄糖酸在D.葡萄糖中的积累(iii)诱导负责摄取D-葡萄糖酸的特定能量依赖性转运系统。该摄取系统显示了在30 mC,pH 7.0的50 mM磷酸钾缓冲液中的最大运输速率。在这些条件下,D-葡萄糖酸的K(m)计算值为6.7 microM。此外,还发现了一个专门针对葡萄糖吸收的不同转运系统。它是有活性的,在35 m的50 mM磷酸钾缓冲液(pH 6.0)中显示最大吸收速率,K(m)值为8.3 microM。

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