• 【锰原卟啉IX细胞色素b5的共振拉曼光谱性质和稳定性。】 复制标题 收藏 收藏
    DOI:10.1021/bi970407p 复制DOI
    作者列表:Gruenke LD,Sun J,Loehr TM,Waskell L
    BACKGROUND & AIMS: The structure and stability of cytochrome b5 reconstituted with manganese protoporphyrin IX instead of iron protoporphyrin IX has been investigated by resonance Raman spectroscopy and stopped-flow visible spectroscopy. The resonance Raman spectrum of MnIII cytochrome b5 was consistent with a high-spin hexacoordinate MnIII protoporphyrin IX structure that converted to a high-spin pentacoordinate structure at higher laser power. The resonance Raman spectrum of MnII cytochrome b5 indicated a high-spin pentacoordinate structure which was independent of laser power. Studies of the binding of MnIII protoporphyrin IX to apocytochrome b5 indicated that the MnIII-containing porphyrin bound much less tightly to the protein than did heme. Although the second-order rate constant at 20 degrees C for the association of heme with apocytochrome b5 (4.5 x 10(7) M(-1) s(-1)) was estimated to be only 1 order of magnitude higher than that with Mn protoporphyrin IX (3.3 x 10(6) M(-1) s(-1)), the dissociation of manganese substituted cytochrome b5 into the apoprotein and free Mn protoporphyrin IX occurs with a first-order rate constant of 1.2 x 10(-2) s(-1) at 20 degrees C while the dissociation of heme from cytochrome b5 at room temperature occurs 3 orders of magnitude more slowly with a first-order rate constant of 1.67 x 10(-5) s(-1) [Vergeres, G., Chen, D. Y., Wu, F.F., & Waskell, L. (1993) Arch. Biochem. Biophys. 305, 231-241]. The equilibrium dissociation constant for manganese-substituted cytochrome b5 increased with temperature from 4 nM at 20 degrees C to 14 nM at 37 degrees C. These results suggest that, in the reconstituted cytochrome P450 metabolizing system, especially in studies done with low protein concentrations (0.1 microM), and at elevated temperatures (37 degrees C), as much as 30% of the manganese-substituted cytochrome b5 may dissociate to free Mn-protoporphyrin IX and apocytochrome b5.

    背景与目标: 用共振原拉曼光谱和停止流可见光谱研究了用锰原卟啉IX代替铁原卟啉IX重构的细胞色素b5的结构和稳定性。 MnIII细胞色素b5的共振拉曼光谱与高自旋六配位MnIII原卟啉IX结构一致,后者在更高的激光功率下转换为高自旋五配位结构。 MnII细胞色素b5的共振拉曼光谱表明高自旋五坐标结构,与激光功率无关。 MnIII原卟啉IX与脱细胞色素b5结合的研究表明,含MnIII的卟啉与蛋白质的结合比血红素少得多。虽然血红素与脱细胞色素b5(4.5 x 10(7)M(-1)s(-1))的结合在20摄氏度的二阶速率常数估计仅比其高1个数量级锰原卟啉IX(3.3 x 10(6)M(-1)s(-1)),锰取代的细胞色素b5分解为载脂蛋白和游离Mn原卟啉IX的一级速率常数为1.2 x 10( -2)在20摄氏度时为s(-1),而室温下血红素从细胞色素b5的解离发生的速度要慢3个数量级,其一阶速率常数为1.67 x 10(-5)s(-1) [Vergeres,G.,Chen,DY,Wu,FF,&Waskell,L.(1993)Arch。生化。生物物理学。 305,231-241]。锰取代的细胞色素b5的平衡解离常数随温度从20摄氏度的4 nM增加到37摄氏度的14 nM。 0.1 microM)和在升高的温度(37摄氏度)下,多达30%的锰取代的细胞色素b5可能解离成游离的Mn-原卟啉IX和载脂细胞色素b5。

  • 【表型转换导致平滑肌肌膜结构和功能的变化。】 复制标题 收藏 收藏
    DOI:10.1016/j.yexcr.2006.07.012 复制DOI
    作者列表:Matschke K,Babiychuk EB,Monastyrskaya K,Draeger A
    BACKGROUND & AIMS: :Continuous changes in the length of smooth muscles require a highly organized sarcolemmal structure. Yet, smooth muscle cells also adapt rapidly to altered environmental cues. Their sarcolemmal plasticity must lead to profound changes which affect transmembrane signal transduction as well as contractility. We have established porcine vascular and human visceral smooth muscle cultures of epithelioid and spindle-shaped morphology and determined their plasma membrane properties. Epithelioid cells from both sources contain a higher ratio of cholesterol to glycerophospholipids, and express a less diverse range of lipid-associated annexins. These findings point to a reduction in efficiency of membrane segregation in epithelioid cells. Moreover, compared to spindle-shaped cells, cholesterol is more readily extracted from epithelioid cells with methyl-beta-cyclodextrin and its synthesis is more susceptible to inhibition with lovastatin. The inability of epithelioid cells to process vasoactive metabolites, such as angiotensin or nucleotides further indicates that contractile properties are impaired. Phenotypic plasticity extends beyond the loss of smooth muscle cell marker genes. The plasma membrane has undergone profound functional changes which are incompatible with cyclic foreshortening, but might be important in the development of vascular disease.
    背景与目标: :平滑肌长度的连续变化需要高度组织化的肌膜结构。然而,平滑肌细胞也能迅速适应变化的环境提示。它们的肌膜可塑性必须导致深刻的变化,从而影响跨膜信号转导和收缩。我们已经建立了上皮样和纺锤形形态的猪血管和人内脏平滑肌培养物,并确定了它们的质膜特性。来自两种来源的上皮样细胞都含有较高的胆固醇与甘油磷脂比例,并且表达的脂质相关膜联蛋白的变化范围较小。这些发现表明上皮样细胞中膜分离的效率降低。而且,与纺锤形细胞相比,胆固醇更容易用甲基-β-环糊精从上皮样细胞中提取,并且其合成更容易受到洛伐他汀的抑制。上皮样细胞不能处理血管活性代谢产物,例如血管紧张素或核苷酸,这进一步表明收缩特性受到损害。表型可塑性超出了平滑肌细胞标记基因丧失的范围。质膜已经发生了深刻的功能变化,这与循环缩短不相容,但是在血管疾病的发展中可能很重要。
  • 【对称的传感器,用于压平眼的共振断层扫描。】 复制标题 收藏 收藏
    DOI:10.1007/s11517-005-0005-1 复制DOI
    作者列表:Hallberg P,Lindén C,Bäcklund T,Eklund A
    BACKGROUND & AIMS: :Applanation resonance tonometry (ART) has been shown in a number of studies to be useful for measuring intraocular pressure (IOP). Data from in vitro laboratory bench testing, where the sensor was carefully centralised onto the cornea, has been very consistent with good precision in the determination of IOP. However, in a clinical study the unavoidable off-centre placement of the sensor against the cornea resulted in a reduced precision. The aim of this study was to evaluate a new design of the sensor with a symmetric sensor probe and a contact piece with a larger diameter. Two in vitro porcine eye experimental set-ups were used. One bench-based for examining position dependence and one biomicroscope-based set-up, simulating a clinical setting, for evaluating IOP(ART) precision at seven different pressure levels (1040 mmHg), set by connecting a saline column to the vitreous chamber. The reference IOP was recorded using a pressure transducer. There was no significant difference between four positions 1 mm off centre and the one centre position. The precision of the ART as compared with the reference pressure was +/- 1.03 mmHg (SD, n = 42). The design improvement has enhanced the precision of the ART in the biomicroscope set-up to be in parity with bench test results from a set-up using perfect positioning. This indicates that off-centre positioning was no longer a major contributor to the deviations in measured IOP. The precision was well within the limits set by ISO standard for eye tonometers. Therefore, a larger in vivo study on human eyes with the ART should be performed.
    背景与目标: :平板共振眼压计(ART)已在许多研究中显示对测量眼内压(IOP)有用。来自体外实验室工作台测试的数据(传感器被仔细地集中在角膜上)与IOP的测定精度非常一致。但是,在临床研究中,传感器不可避免地偏心放置在角膜上会导致精度降低。这项研究的目的是评估带有对称传感器探头和直径较大的接触件的传感器的新设计。使用了两个体外猪眼实验装置。一个用于检查位置依赖性的工作台,一个用于模拟临床环境的生物显微镜设置,用于通过将盐水柱连接到玻璃体腔来设置在七个不同压力水平(1040 mmHg)下评估IOP(ART)精度。使用压力传感器记录参考IOP。偏离中心1毫米的四个位置与一个中心位置之间没有显着差异。与参考压力相比,ART的精度为±1.03 mmHg(SD,n = 42)。设计上的改进提高了生物显微镜设置中ART的精度,使其与使用完美定位的设置中的基准测试结果相当。这表明偏心定位不再是导致测得的IOP偏差的主要因素。精度完全在ISO标准为眼压计设定的范围内。因此,应使用ART对人眼进行更大的体内研究。
  • 4 Functional MRI of the newborn. 复制标题 收藏 收藏

    【新生儿的功能性MRI。】 复制标题 收藏 收藏
    DOI:10.1016/j.siny.2006.07.007 复制DOI
    作者列表:Seghier ML,Lazeyras F,Huppi PS
    BACKGROUND & AIMS: :In order to provide accurate prognosis and developmental intervention to newborns, new methods of assessing cerebral functions are needed. The non-invasive technique of functional magnetic resonance imaging (fMRI) can be considered as the leading technique for functional exploration of the infant's brain. Several studies have previously applied fMRI in both healthy and diseased newborns with different sensory and cognitive tasks. In this chapter, the methodological issues that are proper to the use of fMRI in the newborn are detailed. In addition, an overview of the major findings of previous fMRI studies is provided, with a focus on notable differences from those in adult subjects. More specifically, the functional responses and the localization of cortical activations in healthy and diseased newborns are discussed. We expect a rapid expansion of this field and the establishment of fMRI as a valid clinical diagnostic tool in the newborn.
    背景与目标: :为了给新生儿提供准确的预后和发育干预,需要评估脑功能的新方法。功能性磁共振成像(fMRI)的非侵入性技术可以被认为是婴儿大脑功能性探索的主要技术。先前有几项研究将功能磁共振成像应用于具有不同感觉和认知任务的健康和患病新生儿。在本章中,将详细介绍适合于新生儿使用fMRI的方法学问题。此外,提供了以前的功能磁共振成像研究的主要发现的概述,重点是与成人受试者的显着差异。更具体地说,讨论了健康和患病新生儿的功能反应和皮质激活的定位。我们期望这一领域的快速发展和功能磁共振成像作为新生儿有效的临床诊断工具的建立。
  • 【皮肤病变功能评估的表征策略。】 复制标题 收藏 收藏
    DOI:10.1016/j.burns.2006.03.022 复制DOI
    作者列表:Rodrigues LM,Roberto MA
    BACKGROUND & AIMS: :Assessment of wound healing is a complex task, especially when the lesion is associated to significant (full thickness) loss of the skin. The clinical observation, essentially subjective and highly dependent on the observer's experience, creates difficulties in the comparison of results. Scoring scales were introduced in the clinical practice to create comparable semi-quantitative data and promote better management of resources, but its usefulness in a clinical perspective is still limited. New non-invasive biometric methodologies, although infrequently used, have opened new possibilities. While complementing the clinical observation and contributing to therapeutic decisions and prognosis, they may also help to look further into the pathophysiological mechanisms of scarring drugs rehabilitation. Following previous work in this arena, the authors review, the state-of-the-art of cutaneous wound healing clinical and biometric follow up, proposing a diagnosis correlation for the most relevant descriptors found in both strategies in order to fully characterise the different stages of the healing process.
    背景与目标: :伤口愈合的评估是一项复杂的任务,尤其是当病变与皮肤的严重(全层)损失有关时。临床观察本质上是主观的,并且高度依赖观察者的经验,因此在比较结果时会遇到困难。在临床实践中引入了评分量表,以创建可比较的半定量数据并促进更好的资源管理,但其在临床上的实用性仍然有限。新的非侵入性生物识别方法学虽然很少使用,但开辟了新的可能性。在补充临床观察并有助于治疗决策和预后的同时,它们还可能有助于进一步研究疤痕药物康复的病理生理机制。在此领域的先前工作之后,作者回顾了最新的皮肤伤口愈合临床和生物测定学随访情况,提出了两种策略中最相关的描述符的诊断相关性,以全面表征不同的阶段愈合过程。
  • 【在非常接近高压传输线的家庭中,短期住宅测量在预测72 h暴露于工频磁场中的准确性。】 复制标题 收藏 收藏
    DOI:10.1038/sj.jes.7500522 复制DOI
    作者列表:Ger WJ,Chang WP,Sung FC,Li CY
    BACKGROUND & AIMS: :Between February and April 2003, a total of 80 single-dwelling households close (< 70 m) to high-tension (161 or 345 kV) power lines in a northern community of Taiwan received measurements of indoor extremely low-frequency (ELF) magnetic field for 72 h. Measurements were performed with EMDEX II meter at a sampling rate of every 300 s, yielding some 860 readings of ELF magnetic field for each household. In addition to the 72-h mean ELF magnetic field, we also calculated arithmetic means of the first 2, 6, 12, and 288 readings taken in each household to represent the information on spot, 30-min, 60-min, and 24-h exposures, respectively. The mean 72-h exposure to ELF magnetic field for the 80 study households was estimated at 0.80 micro-Tesla (microT) with a standard deviation (SD) of 1.13 microT. The mean for pot, 30-min, 60-min, and 24-h exposure was 0.88 (SD 1.38), 0.90 (SD 1.40), 0.9 (SD 1.17), and 0.83 (SD 1.17) microT, respectively. There were high agreements, indicated by a nearly perfect intra-class correlation coefficient, between 72-h mean exposure and those short-term exposure measures. Additionally, the sensitivity and specificity of various short-term exposures in the prediction of 72-h exposure greater than 0.4 microT were similar at values of 0.82-0.87 and 0.93-0.95, respectively. This study indicates that short-term measurements of indoor ELF magnetic field seem adequate to represent the mean 72-h exposure, but tended to overpredict 72-h exposure greater than 0.4 microT. Further investigation is needed to assess whether these findings can be replicated in households far away from high-tension power lines.
    背景与目标: :在2003年2月至2003年4月之间,台湾北部一个社区中共有80个单户家庭靠近(<70 m)高压(161或345 kV)电力线,他们接受了室内极低频(ELF)的测量磁场72小时。使用EMDEX II仪表以每300 s的采样速率进行测量,每个家庭可获得约860个ELF磁场读数。除了平均72小时的ELF磁场外,我们还计算了每个家庭中头2、6、12和288个读数的算术平均值,以表示当场,30分钟,60分钟和24点的信息。 -h曝光。 80个研究家庭平均暴露在ELF磁场下72小时的时间为0.80微特斯拉(microT),标准偏差(SD)为1.13 microT。锅暴露30分钟,60分钟和24小时的平均值分别为microT的0.88(SD 1.38),0.90(SD 1.40),0.9(SD 1.17)和0.83(SD 1.17)。在72小时平均暴露量与那些短期暴露量之间,存在接近一致的类内相关系数,表明存在高度一致性。此外,预测72 h暴露大于0.4 microT时,各种短期暴露的敏感性和特异性分别为0.82-0.87和0.93-0.95。这项研究表明,室内ELF磁场的短期测量似乎足以代表72小时的平均暴露量,但往往会高估大于0.4 microT的72小时暴露量。需要进一步调查以评估这些发现是否可以在远离高压电线的家庭中复制。
  • 【胎儿小脑发育的磁共振成像。】 复制标题 收藏 收藏
    DOI:10.1080/14734220600589210 复制DOI
    作者列表:Triulzi F,Parazzini C,Righini A
    BACKGROUND & AIMS: :In the last few years fetal magnetic resonance imaging (MRI) has been proposed as a second level technique in the evaluation of fetal brain anomalies. It has been demonstrated that MRI is highly accurate in illustrating the morphologic changes of developing brain and fetal brain abnormalities being a useful procedure when ultrasonography is inconclusive or doubtful. Starting from the 19-20 weeks gestational age (GA), MRI can reliably depict fetal brain anatomy and locating pathology, offering a robust and reliable tool in the assessment of fetal CNS diseases. In this review both in vivo MRI quantitative and qualitative data about fetal cerebellar development are presented and compared with ultrasonography data. Fetal cerebellar development is gradual, steady, and largely comparable to the development of the supratentorial brain. Archicerebellar (flocculo-nodular lobe) and paleocerebellar (vermis) structures develop first, whereas neocerebellum (cerebellar hemispheres) develop slowly and largely after birth.
    背景与目标: :在最近几年中,胎儿磁共振成像(MRI)已被提出作为评估胎儿脑异常的第二级技术。已经证明,当超声检查不确定或值得怀疑时,MRI可以高度准确地说明发育中的大脑和胎儿脑部异常的形态变化,这是一种有用的方法。从19-20周胎龄(GA)开始,MRI可以可靠地描绘胎儿的大脑解剖结构和定位病理,从而为评估胎儿CNS疾病提供了强大而可靠的工具。在这篇综述中,提出了关于胎儿小脑发育的体内MRI定量和定性数据,并将其与超声检查数据进行了比较。胎儿小脑发育是渐进的,稳定的,并且在很大程度上可与上脑上脑的发育相媲美。先生小脑(结节状结节状)和小脑((状)结构,而新小脑(小脑半球)出生后缓慢且大部分发育。
  • 【骨髓嵌合体小鼠的肿瘤浸润基质细胞的制备和功能分析。】 复制标题 收藏 收藏
    DOI:10.1111/j.1348-0421.2006.tb03830.x 复制DOI
    作者列表:Ishigaki H,Yamamoto Y,Ishida H,Kajino K,Itoh Y,Fujiyama Y,Ogasawara K
    BACKGROUND & AIMS: :Tumor-infiltrating stroma cells (TISC) as well as tumors themselves are thought to be involved in tumor-related immunosuppression, which is one of the critical mechanisms of tumor escape from immune surveillance. However, preparation of TISC is difficult because of the small proportion of TISC in established tumors. Thus, the cells thought to be involved in tumor-related immunosuppression are generally prepared from spleens or draining lymph nodes in tumor-bearing mice. In this study, we developed a method for directly preparing TISC from established tumors in order to analyze their function. Using green fluorescent protein (GFP) transgenic (Tg) mice and C57BL/6 mice transplanted with bone marrow (BM) cells of GFPTg mice, we detected three subpopulations of TISC: one is compatible with immature myeloid cells (ImC) derived from BM and the two other subpopulations, CD11b(+) cells and CD11b(-) cells, do not originate from BM. The TISC including these subpopulations but not each subpopulation independently after culturing with tumors in the presence of GM-CSF could suppress T cell proliferation induced by anti-CD3. In our system, tumors did not inhibit T cell responses directly, but unknown factors from tumors affected immunosuppression by TISC.
    背景与目标: :肿瘤浸润基质细胞(TISC)以及肿瘤本身都被认为与肿瘤相关的免疫抑制有关,这是肿瘤逃避免疫监视的关键机制之一。然而,由于在已建立的肿瘤中TISC的比例很小,因此TISC的制备是困难的。因此,通常被认为与肿瘤相关的免疫抑制有关的细胞是从荷瘤小鼠的脾脏或引流淋巴结中制备的。在这项研究中,我们开发了一种从已建立的肿瘤中直接制备TISC的方法,以分析其功能。使用绿色荧光蛋白(GFP)转基因(Tg)小鼠和移植有GFPTg小鼠骨髓(BM)细胞的C57BL / 6小鼠,我们检测到TISC的三个亚群:一个与源自BM的未成熟髓样细胞(ImC)相容。其他两个亚群CD11b()细胞和CD11b(-)细胞并非源自BM。在存在GM-CSF的情况下与肿瘤培养后,TISC包括这些亚群,但并非每个亚群独立地抑制由抗CD3诱导的T细胞增殖。在我们的系统中,肿瘤并未直接抑制T细胞反应,但来自肿瘤的未知因素影响了TISC的免疫抑制。
  • 【丛枝菌根真菌分离株的功能多样性与根外菌丝网络有关。】 复制标题 收藏 收藏
    DOI:10.1111/j.1469-8137.2006.01839.x 复制DOI
    作者列表:Avio L,Pellegrino E,Bonari E,Giovannetti M
    BACKGROUND & AIMS: :We investigated the functional significance of extraradical mycorrhizal networks produced by geographically different isolates of the arbuscular mycorrhizal fungal (AMF) species Glomus mosseae and Glomus intraradices. A two-dimensional experimental system was used to visualize and quantify intact extraradical mycelium (ERM) spreading from Medicago sativa roots. Growth, phosphorus (P) and nitrogen (N) nutrition were assessed in M. sativa plants grown in microcosms. The AMF isolates were characterized by differences in extent and interconnectedness of ERM. Phenotypic fungal variables, such as total hyphal length, hyphal density, hyphal length per mm of total or colonized root length, were positively correlated with M. sativa growth response variables, such as total shoot biomass and plant P content. The utilization of an experimental system in which size, growth rate, viability and interconnectedness of ERM extending from mycorrhizal roots are easily quantified under realistic conditions allows the simultaneous evaluation of different isolates and provides data with a predictive value for selection of efficient AMF.
    背景与目标: :我们调查了丛枝菌根真菌(AMF)物种Glomus mosseae和Glomus intraradices的地理上不同的分离物产生的自由基外菌根网络的功能意义。二维实验系统用于可视化和量化从紫花苜蓿根部传播的完整的根外菌丝体(ERM)。在微观世界中评估了苜蓿植物的生长,磷(P)和氮(N)营养。 AMF分离株的特征是ERM的程度和相互连接性不同。表型真菌变量,例如总菌丝长度,菌丝密度,每毫米总或定殖根长度的菌丝长度,与苜蓿生长反应变量(如总枝生物量和植物P含量)呈正相关。在实际条件下容易量化从菌根根延伸的ERM的大小,生长速度,生存力和相互连接性的实验系统,可以同时评估不同的分离物,并为选择有效AMF提供具有预测价值的数据。
  • 【在流感血凝素的相同抗原位点具有特异性的辅助T细胞之间存在很大程度的功能多样性。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Haberman AM,Moller C,McCreedy D,Gerhard WU
    BACKGROUND & AIMS: :The site-1 determinant of the hemagglutinin molecule of influenza virus (A/PR/8/34) is one of several immunodominant sites in the BALB/c Th cell response to Ha. A synthetic peptide comprising this T cell site (HA110-120), a panel of analogs containing single substitutions in this determinant, and homologs truncated at the amino- or carboxyl-terminal were used to examine the fine specificities of 15 T cells specific for site-1 in the context of I-Ed. The results indicate that every residue within the minimal determinant plays a role in the T cell recognition process, as single substitutions at any of these positions affected the ability of the peptide to stimulate at least some site 1-specific T cells. For the majority of the residues examined, substitutions had dissimilar effects on distinct T cells, indicating that the substituted residues were affecting recognition in a receptor-specific manner. Each of the 15 T cells examined had a distinct fine specificity pattern, suggesting that the BALB/c T cell repertoire for this site is likely to exceed 100 distinct clonotypes.
    背景与目标: 流感病毒血凝素分子(A / PR / 8/34)的1位点决定簇是BALB / c Th细胞对Ha的免疫应答中的几个免疫优势位点之一。包含该T细胞位点的合成肽(HA110-120),在该决定簇中包含单个取代基的一组类似物以及在氨基或羧基端截短的同源物用于检查15个对该位点特异性的T细胞的精细特异性在I-Ed中为-1。结果表明,最小决定簇内的每个残基都在T细胞识别过程中起作用,因为这些位置中任何一个的单取代都会影响肽刺激至少一些位点1特异性T细胞的能力。对于所检查的大多数残基,取代对不同的T细胞的影响不同,表明取代的残基以受体特异性方式影响识别。检查的15个T细胞中的每一个都有独特的精细特异性模式,表明该位点的BALB / c T细胞库可能超过100种不同的克隆型。
  • 【黄色荧光蛋白变体YFP-H148Q / I152L的碘化钠转运蛋白活性的基于细胞的成像。】 复制标题 收藏 收藏
    DOI:10.1152/ajpcell.00291.2006 复制DOI
    作者列表:Rhoden KJ,Cianchetta S,Stivani V,Portulano C,Galietta LJ,Romeo G
    BACKGROUND & AIMS: :The sodium iodide symporter (NIS) mediates iodide (I(-)) transport in the thyroid gland and other tissues and is of increasing importance as a therapeutic target and nuclear imaging reporter. NIS activity in vitro is currently measured with radiotracers and electrophysiological techniques. We report on the development of a novel live cell imaging assay of NIS activity using the I(-)-sensitive and genetically encodable yellow fluorescent protein (YFP) variant YFP-H148Q/I152L. In FRTL-5 thyrocytes stably expressing YFP-H148Q/I152L, I(-) induced a rapid and reversible decrease in cellular fluorescence characterized by 1) high affinity for extracellular I(-) (35 muM), 2) inhibition by the NIS inhibitor perchlorate, 3) extracellular Na(+) dependence, and 4) TSH dependence, suggesting that fluorescence changes are due to I(-) influx via NIS. Individual cells within a population of FRTL-5 cells exhibited a 3.5-fold variation in the rate of NIS-mediated I(-) influx, illustrating the utility of YFP-H148Q/I152L to detect cell-to-cell difference in NIS activity. I(-) also caused a perchlorate-sensitive decrease in YFP-H148Q/I152L fluorescence in COS-7 cells expressing NIS but not in cells lacking NIS. These results demonstrate that YFP-H148Q/I152L is a sensitive biosensor of NIS-mediated I(-) uptake in thyroid cells and in nonthyroidal cells following gene transfer and suggest that fluorescence detection of cellular I(-) may be a useful tool by which to study the pathophysiology and pharmacology of NIS.
    背景与目标: :碘化钠共转运蛋白(NIS)介导碘化物(I(-))在甲状腺和其他组织中的运输,并作为治疗靶标和核成像报告者越来越重要。目前,使用放射性示踪剂和电生理技术测量了NIS的体外活性。我们报告了使用I(-)敏感和遗传可编码的黄色荧光蛋白(YFP)变体YFP-H148Q / I152L对NIS活性进行新型活细胞成像测定的发展报告。在稳定表达YFP-H148Q / I152L的FRTL-5甲状腺细胞中,I(-)诱导了细胞荧光的快速和可逆下降,其特征在于1)对细胞外I(-)(35 muM)的高度亲和力,2)NIS抑制剂的抑制作用高氯酸盐,3)细胞外Na()依赖性和4)TSH依赖性,表明荧光变化是由于I(-)通过NIS流入所致。 FRTL-5细胞群中的单个细胞在NIS介导的I(-)流入速率中表现出3.5倍的变化,说明了YFP-H148Q / I152L可用于检测NIS活性中的细胞间差异。 I(-)还在表达NIS的COS-7细胞中引起高氯酸盐敏感的YFP-H148Q / I152L荧光下降,但在缺乏NIS的细胞中不引起高氯酸盐敏感性下降。这些结果表明,YFP-H148Q / I152L是基因转移后甲状腺细胞和非甲状腺细胞中NIS介导的I(-)摄取的灵敏生物传感器,并表明细胞I(-)的荧光检测可能是一种有用的工具,研究NIS的病理生理学和药理学。
  • 【氟化分子在中枢神经系统中作为药物和显像剂。】 复制标题 收藏 收藏
    DOI:10.2174/156802606777951046 复制DOI
    作者列表:Sun S,Adejare A
    BACKGROUND & AIMS: :The strategic use of fluorine substitution in drug discovery and drug development is well documented. The small size and high electronegativity of fluorine are among properties of this element that lend special advantages. Applications in drugs targeted to the central nervous system (CNS) have been particularly fruitful in addition to favorable properties seen in many peripherally acting drugs. Fluorine substitution can be used to solve problems unique to the CNS, such as blood brain barrier (BBB) penetration. Likewise, use of the positron emitting isotope, (18)F, provides a unique tool for non-invasive imaging and diagnoses in the CNS. In this review, fluorine in CNS drugs and drug discovery are discussed.
    背景与目标: :氟取代在药物发现和药物开发中的战略用途已得到充分证明。氟的小尺寸和高电负性是该元素的特性之一,具有特殊的优势。除了在许多外围作用药物中看到的有利特性外,在针对中枢神经系统(CNS)的药物中的应用也特别富有成果。氟取代可用于解决CNS独有的问题,例如血脑屏障(BBB)渗透。同样,正电子发射同位素(18)F的使用为CNS中的非侵入性成像和诊断提供了独特的工具。在这篇综述中,讨论了中枢神经系统药物中的氟和药物发现。
  • 【膜联蛋白V磁激活细胞分选分离后的精子回收率评估。】 复制标题 收藏 收藏
    DOI:10.1016/s1472-6483(10)61437-x 复制DOI
    作者列表:Said TM,Agarwal A,Grunewald S,Rasch M,Glander HJ,Paasch U
    BACKGROUND & AIMS: :Magnetic-activated cell sorting (MACS) using paramagnetic annexin V-conjugated microbeads eliminates spermatozoa with externalized phosphatidylserine, which is considered one of the features of apoptosis. The objective of this study was to evaluate sperm recovery following the use of MACS as a sperm preparation technique. Mature spermatozoa were separated and divided into two fractions: the first was prepared by density gradient centrifugation (DGC) and MACS, while the second was prepared by DGC only. Following MACS, the percentage of cells collected in the annexin-negative fraction was significantly higher than the annexin-positive fraction and the sperm recovery rate was 73.8 +/- 12.1%. In conclusion, the integration of MACS with DGC can be considered as an effective sperm preparation technique that does not lead to significant cell loss. Separating a distinctive population of non-apoptotic spermatozoa with intact membranes may optimize the outcome of assisted reproduction.
    背景与目标: :使用顺磁性膜联蛋白V偶联的微珠进行磁激活细胞分选(MACS),消除了带有外部磷脂酰丝氨酸的精子,这被认为是细胞凋亡的特征之一。这项研究的目的是评估使用MACS作为精子制备技术后的精子回收率。将成熟的精子分离并分为两部分:第一部分通过密度梯度离心(DGC)和MACS制备,而第二部分仅通过DGC制备。进行MACS后,在膜联蛋白阴性组分中收集的细胞百分比显着高于膜联蛋白阳性组分,精子回收率为73.8 / 12.1%。总之,MACS与DGC的整合可以被认为是一种有效的精子制备技术,不会导致明显的细胞损失。用完整的膜分离非凋亡性精子的独特群体可以优化辅助生殖的结果。
  • 【螺旋CT血管造影术对腹部主动脉瘤进行完整的术前影像学评估。】 复制标题 收藏 收藏
    DOI:10.1016/s0009-9260(97)80132-8 复制DOI
    作者列表:Errington ML,Ferguson JM,Gillespie IN,Connell HM,Ruckley CV,Wright AR
    BACKGROUND & AIMS: PURPOSE:A prospective evaluation of spiral CT angiography (SCTA) as the sole pre-operative imaging modality for abdominal aortic aneurysm repair.

    MATERIALS AND METHODS:Spiral CT angiography was compared with conventional transfemoral angiography in 30 patients and results correlated with surgical findings in 22 patients. The following features were assessed: renal artery number and disease; upper and lower aneurysm extent; aneurysm size; perianeurysmal inflammation; iliac artery disease; radiation dose; and contrast usage.

    RESULTS:Spiral CT angiography agreed with conventional angiography in all cases of severe stenosis or occlusion of renal arteries and had 90% agreement overall for renal artery disease. Two of nine accessory renal arteries seen at conventional angiography were missed. For showing aneurysm extent SCTA was 100% sensitive, and performed better than conventional angiography. Aneurysm size was better shown with SCTA. In iliac disease SCTA, as performed in this study, was poor for mild-moderate disease, but detected four of six severely stenosed/occluded iliac arteries seen at conventional angiography. Prospective sensitivity for perianeurysmal inflammation was 33%. Radiation dose for SCTA was approximately twice and contrast dose approximately three times that for conventional angiography.

    CONCLUSION:Spiral CT angiography can provide all the necessary imaging information to plan aneurysm repair in the non-claudicant.

    背景与目标: 目的:前瞻性评价螺旋CT血管造影(SCTA)作为腹主动脉瘤修复术前唯一的影像学检查方法。

    材料与方法:螺旋CT血管造影与常规经股动脉血管造影在30例患者中进行了比较,结果与22例患者的手术结果相关。评估以下特征:肾动脉数量和疾病;上下动脉瘤程度;动脉瘤大小;动脉瘤周围炎;动脉疾病;辐射剂量

    结果:在所有严重狭窄或肾动脉阻塞的病例中,螺旋CT血管造影与常规血管造影相符,并且总体上90%符合肾动脉疾病。在常规血管造影术中发现的9条辅助肾动脉中有2条漏诊了。为了显示动脉瘤的程度,SCTA是100%敏感的,并且比常规的血管造影术表现更好。使用SCTA可以更好地显示动脉瘤的大小。在这项研究中进行的动脉疾病中,SCTA对于轻度中度疾病较差,但在常规血管造影术中发现了6条严重狭窄/闭塞的动脉中的4条。对动脉瘤周围炎症的预期敏感性为33%。 SCTA的放射剂量约为常规血管造影的两倍,对比剂量约为传统血管造影的三倍。

    结论:螺旋CT血管造影可以提供所有必要的影像学信息,以计划在非-claudicant。

  • 【神经放射学专业专家对脑CT成像研究进行重新解释的质量结果。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Jordan MJ,Lightfoote JB,Jordan JE
    BACKGROUND & AIMS: PURPOSE:To determine the clinical importance and relative value of reinterpreting brain CT imaging studies by subspecialty experts regarding changes in clinical management. METHODS:Computerized records were queried at two institutions during the years 2002-2003 for both primary interpretation by board-certified nonneuroradiologists and secondary interpretation by three neuroradiologists. A total of 1,081 cases were reviewed. Each case was initially interpreted as an emergent or urgent study. The reinterpreted studies were scored as concordant or discordant by the subspecialty experts. The discordant studies were then categorized as a "major discordance" if there was a change in clinical management, or as a "minor discordance" if there was no impact or change in clinical management. RESULTS:Of the 1,081 studies reviewed, 14 studies were identified as discordant (1.3%). Of those discordant studies, four were categorized as major discrepancies necessitating a change in clinical management (0.4 %). Ten were categorized as minor discrepancies (0.9%). There were no permanent adverse outcomes with respect to morbidity and mortality as a result of any discrepancy. CONCLUSION:The vast majority of interpreted head CT cases read by board-certified general radiologists do not result in discordant interpretations as verified by subspecialty experts. Discordant interpretations did not result in changes in clinical management in most cases. Double reading of head CTs by subspecialty experts appears to be an inefficient method of substantially improving imaging health quality outcomes.
    背景与目标: 目的:确定亚专业专家对临床管理变化进行重新解释脑CT成像研究的临床重要性和相对价值。
    方法:在2002年至2003年期间,在两家机构中查询了计算机记录,以获取由董事会认证的非神经放射科医生进行的主要解释和由三位神经放射科医生进行的次要解释。总共审查了1,081例。最初,每个案例都被解释为紧急研究。重新解释的研究被专业专家评定为一致或不一致。如果临床管理发生变化,则将不一致的研究分类为“重大不一致”,如果临床管理没有影响或发生变化,则将其分类为“轻微不一致”。
    结果:在所审查的1,081项研究中,有14项研究被确定为不一致(1.3%)。在这些不一致的研究中,有四项被归类为需要改变临床管理的主要差异(0.4%)。十个分类为轻微差异(0.9%)。任何差异都不会在发病率和死亡率方面带来永久性的不良后果。
    结论:经董事会认证的一般放射科医生阅读的绝大多数解释性头部CT病例,经专科专家验证,并不会导致不一致的解释。在大多数情况下,不一致的解释并不会导致临床管理的改变。专科专家对头颅CT进行双重读取似乎是一种实质上改善影像健康质量结果的无效方法。

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