• 【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:
  • 【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细胞参与胶原疾病的发病机理仍存在争议。胶原蛋白疾病的最后阶段通常以炎症为主。因此,抗原非特异性因子 (如炎性细胞因子) 可能在这一过程中起重要作用。另一方面,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,回顾了我们的新型T细胞克隆分析系统。使用该方法,可以在体内和体外评估抗原刺激过程中T细胞克隆积累的动态变化。使用类风湿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细胞克隆在胶原疾病中的意义。
  • 【肾素-血管紧张素系统介质与雷诺现象。】 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:
  • 【T(2) 加权的显微mri和视觉系统的诱发电位在低髓转基因小鼠的发育过程中测量。】 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: : 我们的目标是使用非侵入性高分辨率 (117x70 microm) 磁共振 (microMRI) 和视觉系统诱发电位 (VEP) 技术,跟踪畸形疾病的过程,然后在转基因小鼠中进行部分恢复。我们使用了JOE (用于J37 golli过表达) 转基因小鼠,该小鼠经过工程改造以过表达golli J37,Golli-mbp基因复合物的产物,特别是在少突胶质细胞中。从21天到75天大,在11.7 T扫描仪上使用非侵入性体内vep和3D T2-weighted显微mri跟踪了JOE transgenics及其未受影响的兄弟姐妹,我们认为这是同类研究中的首次纵向研究。microMRI数据表明,在髓鞘形成峰值期间 (21-42天),明显的整体髓鞘减少,与对照组相比,JOE小鼠在以后的年龄 (>60天) 得到了部分纠正。这些显微mri数据与 [Campagnoni在 (1995) “髓鞘形成的分子生物学” 处具有很好的相关性。In: Ransom B,Kettenmann H (eds) 神经胶质-一篇论文。牛津大学出版社,伦敦,pp 555-570] 髓磷脂染色,[Campagnoni AT,macklin WB (1988) 髓鞘蛋白基因表达的细胞和分子方面。Mol Neurobiol 2:41-89] 在髓鞘形成的高峰期短暂的意图震颤,在以后的年龄减弱,并且 [Lees MB,Brostoff SW (1984) 蛋白在髓鞘中: morell (ed) 髓鞘。纽约和伦敦的Plenum出版社,pp 197-224] VEPs,所有这些都表明乔小鼠中枢神经系统髓鞘发育和持续的低髓鞘作用显着延迟。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延迟的小鼠大脑中髓鞘形成的增加。
  • 【使用电纺聚合物支架在三维培养系统中鼠胚胎干细胞的脂肪生成。】 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治疗和预防肥胖和2型糖尿病至关重要。常规的脂肪生成体外模型是在二维 (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,才能预期使用体外组织培养模型的最佳结果。因此,需要设计忠实地模仿体内环境的体外三维 (3D) 模型来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记以及中性脂质滴的积累所证明的那样。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。通过扫描电子和相差显微镜,从形态上讲,ES细胞衍生的脂肪细胞类似于天然脂肪细胞。这种组织工程的ES细胞基质模型在药物筛选和其他治疗开发中具有潜在用途。
  • 【槲寄生制剂 (Iscador) 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化。】 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利地操纵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。Viscum专辑L的各种非细胞毒性浓度的影响。(槲寄生) 制剂Iscadore QuFrF对来自健康供体的免疫磁分离的人CD4和CD8 T淋巴细胞的运动活性进行了研究。在三维胶原蛋白基质中检查细胞迁移。在存在各种浓度的槲寄生制剂 (0.25-2.5微克/毫升) 的情况下,自发运动的T细胞的基线活性的供体依赖性变化伴随着来自不同供体的T细胞的个体反应模式。使用三维胶原基质测定法,尽管槲寄生制剂的最佳浓度和最大反应的时间点对于每个供体都是单独的,但仍以高度可重复性的方式检测到运动活性的诱导。我们的数据表明,槲寄生成分对T细胞迁移的直接刺激可能会调节槲寄生治疗患者的免疫监视和识别系统。
  • 【阴道和子宫颈透明细胞腺癌。荷兰中部登记处的更新显示了双龄发病率的峰值。】 复制标题 收藏 收藏
    DOI:10.1002/(sici)1097-0142(19970601)79:11<2229::aid-c 复制DOI
    作者列表:Hanselaar A,van Loosbroek M,Schuurbiers O,Helmerhorst T,Bulten J,Bernhelm J
    BACKGROUND & AIMS: BACKGROUND:The objective of this study was to update the registry of women in the Netherlands with clear cell adenocarcinoma (CCAC) of the cervix or vagina with or without intrauterine exposure to diethylstilbestrol (DES). METHODS:From a nationwide search in PALGA, the automated pathology registry in the Netherlands, data were gathered on women with CCAC born after 1947. Information obtained from the clinical files of the patients included reported exposure to DES, patterns of complaints previous to diagnosis, the current status of the patients, and the results of cytopathologic examinations previous to histopathologic diagnosis. After review of the histopathologic slides, the specific pathologic characteristics of CCAC were determined. The age distribution of women born after 1947 was compared with that of women born before 1947. RESULTS:Information about possible exposure to DES during pregnancy was available for 73 of 88 women with CCAC born after 1947. Exposure to DES was reported for 47 (64%) of these women. The DES medication was most often reported as having started before the 18th week of pregnancy. Cytopathologic examination was informative in 81% of the cases of CCAC of the cervix, but only in 41% of the cases of CCAC of the vagina. Most patients had Stage I or II tumors at diagnosis. Tumor Stage III and IV and a high grade of nuclear atypia were related to unfavorable outcome. The age distribution of all patients with CCAC showed two distinct peaks; one at young age, (a mean age of 26 years), and one at older age (a mean age of 71 years). This bimodal age distribution still applied when the cases in which DES exposure was reported had been excluded. CONCLUSIONS:Despite the fact that DES has not been prescribed to pregnant women in the Netherlands in the last 20 years, CCAC is still relevant in our times. It is important to stay alert and periodically to update and evaluate the data of this registry, including data on women born outside the DES exposure period. The bimodal age distribution in this study of women without intrauterine exposure to DES suggests a carcinogenesis-promoting role of menarche and menopause and/ or the existence of a subpopulation with genetic risk factors or exogenous risk factors other than exposure to DES. Postmenopausal observation of women exposed to DES must be encouraged for clinical reasons and may help facilitate differentiation between these two hypotheses. If these risk factors of CCAC were better documented and their interrelationships better defined, CCAC could become an important model of multistep carcinogenesis in tissues sensitive to sex hormones.
    背景与目标:
  • 【社区获得性耐甲氧西林金黄色葡萄球菌对苯唑西林耐药所需的VraS/VraR双组分调节系统。】 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/苯唑西林 (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PBP2一起通过分别贡献互补的转肽酶和转糖基化酶活性来介导苯唑西林抗性。VraS/VraR两组分调节系统可由细胞壁抗菌剂 (β-内酰胺,糖肽) 诱导,并控制许多细胞壁基因 (包括pbp2及其自身) 的转录诱导。我们通过在缺乏编码mecA调节序列mecI和mecr1的功能基因的社区获得性MRSA临床分离株中灭活VraS,研究了vraS/VraR在苯唑西林抗性表型表达中的作用。vraS的失活消除了苯唑西林的抗性,并与vraS操纵子互补恢复了抗性表型。vraS突变体中的mecA转录增加; 然而,PBP2a的丰度与野生型相似。尽管vraS突变体中的pbp2转录降低,但pbp2操纵子的过表达并不能恢复抗性。这些数据表明,尽管mecA和pbp2的表达对于苯唑西林抗性是必需的,但它们还不够。因此,vraS/vraR调节系统在允许MRSA通过调节除甲氧西林抗性的已知效应子以外的基因靶标来响应 β-内酰胺方面起着至关重要的作用。
  • 【人前脑成神经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: : 受损的轴突在哺乳动物中枢神经系统 (CNS) 中无法长距离再生不是由于中枢神经元无法再生,而是由于CNS组织环境的非宽松性质。例如,在周围神经内良好生长的再生CNS轴突不能穿透成熟的CNS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。我们在此报告,植入成年大鼠兴奋性毒性病变纹状体的人类端脑神经母细胞可以逃避或中和成年CNS环境的这种抑制作用,并沿主要有髓纤维束延伸轴突,距离可达约20毫米。可以看到轴突沿着纹状体-黑质和皮质-脊髓束的路径伸长,到达黑质,桥脑核和颈脊髓,这是纹状体和皮质投射神经元的正常目标。这些植入物。
  • 【流域的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,当局花了数年时间对污染的河流进行补救。通常,补救计划工作分为两个阶段。在第一阶段,根据整个流域产生每个流域的允许排污量和减排量,包括同化能力。在第二阶段,相关组织根据第一阶段产生的策略,分别为每个排水区的每个污染源制定减排行动计划。然而,将这两个阶段联系起来的有效性通常很差。并非总是能够实现高度集成的性能,因为在计划阶段,单独的两阶段方法并未考虑系统和管理思想。这项研究率先在河流水质管理的规划策略和行动计划中使用了结果管理 (MFR) 方法。基于MFR的概念和方法,管理思想和系统分析,提出了可持续管理框架。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,系统地考虑了环境,社会,经济和制度四个因素之间的关系和相互作用。基于该框架,将作为求解方法的改进的有界隐式枚举算法与Visual Basic软件和MS Excel相结合,开发了用于策略规划的计算机系统。以台湾北部的Shetzu河为例。根据理论,实践和法规方面的考虑,定义了以结果为导向的目标,以首先在特定的整治时期改善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规划模型的一些约束条件来解决。模型目标是在水质标准 (制度阶段),社会公平 (社会阶段) 和适当的可用技术 (经济阶段) 的约束下,追求最大的同化能力 (环境阶段)。根据每个水质标准,可以获得每个排水区针对不同情况的污染量减少和分配 (称为顶级策略)。然后生成中间和较低的策略和行动计划,其中包括减少和分配每一类 (家庭,工业,牲畜和面源污染源) 及其在每个排水区中的单个污染源根据顶级策略。根据促进河流水质管理综合成效的行动计划,提出了绩效指标和措施计划。当局已开始根据本研究中制定的战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规划系统制定的目标,战略和行动计划可以有效地帮助相关当局完成流域水质管理的任务。
  • 【CT图像整合到电解剖标测系统对房颤导管消融临床结果的影响。】 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:
  • 【注意缺陷多动障碍可能与中枢脑源性神经营养因子活性降低有关: 临床和治疗意义。】 复制标题 收藏 收藏
    DOI:10.1016/j.mehy.2006.06.025 复制DOI
    作者列表:Tsai SJ
    BACKGROUND & AIMS: :Attention-deficit hyperactivity disorder (ADHD) is a common childhood psychiatric disorder. Despite intensive research efforts, the aetiology of ADHD remains unknown. Current evidence suggests that the aetiology of ADHD is heterogeneous, comprising of multiple factors. Recently, it has been proposed that brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may be implicated in the pathogenesis of ADHD. This hypothesis is supported by recent genetic studies in ADHD. Drawing on findings from studies into the drugs for ADHD relating to central BDNF expression, hyperactivity in BDNF knockout mice, BDNF effects in midbrain dopaminergic function and the close association between BDNF and the dopamine transporter (an important molecule for ADHD pathogenesis), it is proposed here that decreased central BDNF, particularly in the midbrain region, may play an important role in the pathogenesis ADHD. This hypothesis may have some implications for clinical findings in ADHD (for example, the co-morbidity between ADHD and major depression), and provide a new direction for the development of medication for ADHD treatment.
    背景与目标: : 注意力缺陷多动障碍 (ADHD) 是一种常见的儿童精神疾病。尽管进行了大量研究,但ADHD的病因仍然未知。目前的证据表明,ADHD的病因是异质的,由多种因素组成。最近,有人提出,神经营养因子家族的成员脑源性神经营养因子 (BDNF) 可能与ADHD的发病机理有关。该假设得到了ADHD最近的遗传研究的支持。根据对ADHD药物的研究结果,该药物与中枢BDNF表达,BDNF基因敲除小鼠的活动过度,BDNF在中脑多巴胺能功能中的作用以及BDNF与多巴胺转运蛋白 (ADHD发病机理的重要分子) 之间的密切联系有关,在这里提出降低中枢BDNF,特别是在中脑区域,可能在ADHD的发病机理中起重要作用。该假设可能对ADHD的临床发现 (例如,ADHD与重度抑郁症之间的合并症) 具有一定的意义,并为ADHD治疗药物的发展提供了新的方向。
  • 【用反向四环素调节的逆转录病毒载体 (RTRV) 系统控制基因表达。】 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: : 用自动调节盒构建逆转录病毒载体,以响应体内口服强力霉素 (Dox) 的目的基因表达。该盒包含反向四环素调节 (rtTA) 系统的所有成分,该系统是具有内部核糖体进入位点和目标基因 (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,诱导了两个数量级的GFP荧光。此外,口服Dox导致裸鼠腹膜腔中移植的208F细胞中GFP表达。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在基因治疗应用中的特定时间窗口内控制基因表达铺平道路。
  • 14 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: : 血管活性肽的速激肽家族包括神经肽p物质,神经激肽A和神经激肽B,以及新发现的内收缩素和血收缩素。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影响的最新进展,并总结了它们的治疗潜力。速激肽刺激血浆外渗,特别是通过neurokinin-1受体以内皮依赖性方式起作用。因此,它们在组织水肿和炎症 (称为神经源性炎症) 中起着重要作用。速激肽的促炎作用通过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,尽管物种之间以及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,它们可能会放松血管,而在其他情况下会引起血管收缩,内皮状态似乎至关重要。速激肽还调节血压和心率,既作用于外周,又作用于中枢神经系统。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型复杂区域疼痛综合征,中风和慢性炎症性疾病 (例如关节炎) 的重要治疗靶标。需要对人类疾病进行复杂的建模,以使神经激肽受体拮抗剂能够实现这种治疗潜力。
  • 【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) 的首选方法。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,相邻节段椎间盘退变和蛛网膜炎。磁共振成像也有助于评估许多诊断难题,而其他方法无法很好地解决这些难题。这包括椎间盘突出症和硬膜外血肿之间的区别,关节突囊的非特异性纤维增厚引起的滑膜囊肿,以及对许多其他软组织异常的评估。计算机断层扫描,计算机断层扫描脊髓造影和闪烁显像对于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仍然有用。然而,总的来说,磁共振是许多脊柱疾病首选的成像程序。本文是由3部分组成的系列文章的第一部分,讨论了脊柱疾病的磁共振成像的作用。第1节将描述可用的各种成像方式及其相对的优缺点。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节将致力于深入讨论退行性椎间盘疾病患者遇到的特定病理过程。第3节将在系列结束时考虑术后影像学,然后讨论脊柱畸形,创伤和肿瘤。

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