• 【丝氨酸蛋白酶对前胱天蛋白酶7的激活包括非规范的特异性。】 复制标题 收藏 收藏
    DOI:10.1042/bj3240361 复制DOI
    作者列表:Zhou Q,Salvesen GS
    BACKGROUND & AIMS: :As a model to investigate the mechanism of caspase activation we have analysed the processing of pro-caspase-7 by serine proteases with varied specificities. The caspase-7 zymogen was rapidly activated by granzyme B and more slowly by subtilisin and cathepsin G, generating active enzymes with similar kinetic properties. Significantly, cathepsin G activated the zymogen by cleaving at a Gln-Ala bond, indicating that the canonical cleavage specificity at aspartic acid is not required for activation.
    背景与目标: :作为研究caspase激活机制的模型,我们分析了具有不同特异性的丝氨酸蛋白酶对pro-caspase-7的加工。胱天蛋白酶7酶原被颗粒酶B迅速激活,而枯草杆菌蛋白酶和组织蛋白酶G则更慢,从而产生具有相似动力学特性的活性酶。重要的是,组织蛋白酶G通过在Gln-Ala键处裂解激活了酶原,表明激活不需要天冬氨酸的标准裂解特异性。
  • 【体内形成SMAC的成熟免疫突触介导病毒感染的星形胶质细胞从大脑中清除。】 复制标题 收藏 收藏
    DOI:10.1084/jem.20060420 复制DOI
    作者列表:Barcia C,Thomas CE,Curtin JF,King GD,Wawrowsky K,Candolfi M,Xiong WD,Liu C,Kroeger K,Boyer O,Kupiec-Weglinski J,Klatzmann D,Castro MG,Lowenstein PR
    BACKGROUND & AIMS: :The microanatomy of immune clearance of infected brain cells remains poorly understood. Immunological synapses are essential anatomical structures that channel information exchanges between T cell-antigen-presenting cells (APC) during the priming and effector phases of T cells' function, and during natural killer-target cell interactions. The hallmark of immunological synapses established by T cells is the formation of the supramolecular activation clusters (SMACs), in which adhesion molecules such as leukocyte function-associated antigen 1 segregate to the peripheral domain of the immunological synapse (p-SMAC), which surrounds the T cell receptor-rich or central SMAC (c-SMAC). The inability so far to detect SMAC formation in vivo has cast doubts on its functional relevance. Herein, we demonstrate that the in vivo formation of SMAC at immunological synapses between effector CD8+ T cells and target cells precedes and mediates clearance of virally infected brain astrocytes.
    背景与目标: :对被感染的脑细胞免疫清除的微观解剖学知之甚少。免疫突触是必不可少的解剖结构,可在T细胞功能的启动阶段和效应阶段以及自然杀伤分子与靶细胞的相互作用期间,引导T细胞抗原呈递细胞(APC)之间的信息交换。 T细胞建立的免疫突触的标志是超分子激活簇(SMAC)的形成,其中粘附分子(如白细胞功能相关抗原1)分离到免疫突触(p-SMAC)的外围结构域,周围T细胞受体丰富或中央SMAC(c-SMAC)。迄今为止,尚无法在体内检测到SMAC的形成,对其功能相关性产生了疑问。在本文中,我们证明了在效应CD8 T细胞和靶细胞之间的免疫突触中SMAC的体内形成先于并介导了病毒感染的脑星形胶质细胞的清除。
  • 【PedsQL脑肿瘤模块:初始可靠性和有效性。】 复制标题 收藏 收藏
    DOI:10.1002/pbc.21026 复制DOI
    作者列表:Palmer SN,Meeske KA,Katz ER,Burwinkle TM,Varni JW
    BACKGROUND & AIMS: BACKGROUND:Brain tumors (BT) are second only to acute lymphoblastic leukemia as the most prevalent form of pediatric cancer, with BT 5-year survival rates approaching 70%. With increased survival, quality of life has emerged as an essential health outcome. This investigation examines the internal consistency reliability and construct validity of the Pediatric Quality of Life Inventory (PedsQL) Brain Tumor Module. METHODS:The PedsQL 4.0 Generic Core Scales, PedsQL Multidimensional Fatigue Scale, and PedsQL Brain Tumor Module were administered to 99 families. The average age of the 56 boys and 43 girls was 9.76 years (range=2-18 years). The sample included children with tumors located in the posterior fossa/brainstem (N=62, 62.6%), supratentorial (N=15, 15.2%), and midline (N=22, 22.2%). Children were on treatment (N=46, 46.5%), off treatment<12 months (N=19, 19.2%), or off treatment>12 months/long-term survivor (N=34, 34.3%). Treatment included radiation (N=61, 61.6%), surgery (N=83, 83.8%), chemotherapy (N=87, 87.9%), and bone marrow transplant (N=5, 5.1%). RESULTS:Internal consistency reliability was demonstrated for the 24-item PedsQL Brain Tumor Module (average alpha=0.78-0.92, parent proxy-report, n=99; average alpha=0.76-0.87, child self-report, n=51). Construct validity for the PedsQL Brain Tumor Module was supported through an analysis of the intercorrelations with the Generic Core Scales and Fatigue Scale. CONCLUSIONS:The findings provide support for the measurement properties of the PedsQL Brain Tumor Module.
    背景与目标: 背景:脑肿瘤(BT)仅次于急性淋巴细胞白血病,是儿童癌症的最普遍形式,其BT 5年生存率接近70%。随着生存率的提高,生活质量已成为一种必不可少的健康结果。这项研究检查了儿童生命质量量表(PedsQL)脑肿瘤模块的内部一致性可靠性和构建效度。
    方法:将PedsQL 4.0通用核心量表,PedsQL多维疲劳量表和PedsQL脑肿瘤模块应用于99个家庭。 56名男孩和43名女孩的平均年龄为9.76岁(范围= 2-18岁)。样本包括肿瘤位于后颅窝/脑干(N = 62,62.6%),幕上(N = 15,15.2%)和中线(N = 22,22.2%)的儿童。儿童接受治疗(N = 46,46.5%),不接受治疗<12个月(N = 19,19.2%)或不接受治疗> 12个月/长期幸存者(N = 34,34.3%)。治疗包括放疗(N = 61,61.6%),手术(N = 83,83.8%),化学疗法(N = 87,87.9%)和骨髓移植(N = 5,5.1%)。
    结果:24项PedsQL脑肿瘤模块具有内部一致性可靠性(平均α= 0.78-0.92,父母代理报告,n = 99;平均α= 0.76-0.87,孩子自我报告,n = 51)。通过分析通用核心量表和疲劳量表之间的相互关系,支持了PedsQL脑肿瘤模块的构建效度。
    结论:这些发现为PedsQL脑肿瘤模块的测量特性提供了支持。
  • 【鲨鱼脑中一种含有羟脯氨酸的蛋白质,与髓磷脂碱性蛋白质有关。】 复制标题 收藏 收藏
    DOI:10.1111/j.1471-4159.1990.tb04958.x 复制DOI
    作者列表:Wood DD,McLaurin J,Moscarello MA
    BACKGROUND & AIMS: :Myelin basic protein (MBP) from shark (Chondricthyes) consists of a simpler mixture of charge isomers than human MBP. About two-thirds of the total amount applied to a CM-52 cellulose cation-exchange column was recovered in the unbound fraction of the column; the remaining one-third bound to column and was eluted as a single OD280 peak. This bound material did not sow the usual pattern of charge microheterogeneity found with human or bovine MBP. The unbound fraction was composed of a high molecular weight protein (55-60 kDa), which constituted most of this protein fraction and a low molecular weight protein (approximately 18 kDa). The amino acid composition of our unbound fraction was similar to that reported earlier. The Glx (glutamic acid + glutamine) was increased about threefold whereas the Arg content was only about 25% of that of the 18.5 kDa variant of bovine or human origin. The presence of hydroxyproline (1.2 residues/100) in this protein was noteworthy, identification of which was achieved by amino acid analysis in two different systems and by mass spectrometry. In the precolumn derivatization method, hydroxyproline eluted at 2.7 min; in the postcolumn derivatization method it eluted at 12.2 min. Identification of hydroxyproline was completed by fast atom bombardment-mass spectral analysis. The effect of hydroxyproline on the secondary structure of this protein is being studied. Verification that this high molecular weight protein contained MBP sequences within its primary structure was confirmed by immunological methods.(ABSTRACT TRUNCATED AT 250 WORDS)
    背景与目标: :鲨鱼(Chondricthyes)的髓磷脂碱性蛋白(MBP)由电荷异构体组成的混合物比人MBP更简单。应用于CM-52纤维素阳离子交换柱的总量的约三分之二是在该柱的未结合馏分中回收的;剩余的三分之一与色谱柱结合,并以一个OD280峰洗脱。这种结合的材料并未播种人或牛MBP常见的电荷微异质性模式。未结合的部分由高分子量蛋白质(55-60 kDa)和低分子量蛋白质(约18 kDa)组成,其中高分子量蛋白质占该蛋白质部分的大部分。我们未结合部分的氨基酸组成与先前报道的相似。 Glx(谷氨酸谷氨酰胺)增加了约三倍,而Arg含量仅为牛或人来源的18.5 kDa变体的Arg含量的约25%。值得注意的是,该蛋白质中存在羟脯氨酸(1.2个残基/ 100个),通过在两个不同系统中进行氨基酸分析并通过质谱法进行鉴定。在柱前衍生化方法中,羟脯氨酸在2.7分钟洗脱;在柱后衍生化方法中,它在12.2分钟时洗脱。通过快速原子轰击质谱分析完成了羟脯氨酸的鉴定。羟脯氨酸对该蛋白二级结构的影响正在研究中。通过免疫学方法证实了这种高分子量蛋白质在其一级结构中包含MBP序列。(摘要截短为250字)
  • 【注意缺陷多动障碍可能与中枢性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: 注意缺陷多动障碍(ADHD)是儿童期常见的精神病。尽管进行了深入的研究,但多动症的病因仍然未知。当前证据表明,ADHD的病因是异质的,由多种因素组成。最近,已经提出,脑源性神经营养因子(BDNF),神经营养因子家族的成员,可能与ADHD的发病有关。这一假说得到了多动症最近的遗传学研究的支持。根据对ADHD药物的研究发现,该药物与中枢BDNF表达,BDNF基因敲除小鼠的过度活跃,BDNF对中脑多巴胺能功能的影响以及BDNF与多巴胺转运蛋白(ADHD发病机理的重要分子)之间的紧密联系有关,因此提出了这一建议。在这里,中央BDNF的降低,特别是在中脑区域,可能在ADHD的发病中起重要作用。该假设可能对ADHD的临床发现有一定的影响(例如,ADHD与严重抑郁症的合并症),并为ADHD治疗药物的开发提供了新的方向。
  • 【大鼠脑缺血后泛素和hsp70的基因表达】 复制标题 收藏 收藏
    DOI:10.1097/00001756-199703240-00036 复制DOI
    作者列表:Noga M,Hayashi T,Tanaka J
    BACKGROUND & AIMS: Expression of genes coding for ubiquitin and heatshock protein (hsp) 70 were examined by in situ hybridization using a rat model with permanent occlusion of the distal middle cerebral artery (MCA). Only polyubiquitin (UbC) mRNA increased markedly following ischaemia in the central zone of the MCA territory of the neocortex. UbC gene expression reached the maximum level 4 h post-occlusion and remained elevated at 24 h. UbC expression was retarded slightly compared with that of the hsp70 gene. UbB and Ub-S30 were expressed at almost similar levels in both the ischaemic and non-ischaemic hemispheres. These results indicated that UbC probably has the most stress-inducible characteristics among the three ubiquitin genes.

    背景与目标: 编码泛素和热休克蛋白(hsp)70的基因的表达通过使用大鼠模型进行了原位杂交,该模型永久性阻塞了大脑中部远端动脉(MCA)。在新皮层MCA区域的中央区域缺血后,只有多聚泛素(UbC)mRNA显着增加。 UbC基因表达在阻塞后4 h达到最高水平,并在24 h保持升高。与hsp70基因相比,UbC表达略有延迟。在缺血半球和非缺血半球中,UbB和Ub-S30的表达水平几乎相似。这些结果表明,UbC可能在三个泛素基因​​中具有最强的应激诱导特性。

  • 【使用CD63或CD203c表达对昆虫毒液过敏患者进行嗜碱性粒细胞活化测试的比较。】 复制标题 收藏 收藏
    DOI:10.1111/j.1398-9995.2006.01122.x 复制DOI
    作者列表:Eberlein-König B,Varga R,Mempel M,Darsow U,Behrendt H,Ring J
    BACKGROUND & AIMS: BACKGROUND:Flow cytometric basophil activation tests have been developed as cellular tests for in vitro diagnosis of IgE-mediated reactions. Different activation markers (CD63 or CD203c) with distinct ways of regulation have been used after stimulation with various allergens. OBJECTIVE:It was the aim of the present study to compare basophil activation tests by measuring both CD63 and CD203c upregulation in patients with insect venom allergy. MATERIALS AND METHODS:43 patients with a history of insect venom anaphylaxis were examined. A careful allergy history was taken, and skin tests and determination of specific IgE-antibodies were performed. Basophil activation tests (BAT) using CD63 or CD203c expression were done after stimulation with different concentrations of bee and wasp venom extracts. 25 healthy subjects with negative history of insect venom allergy were studied as controls. RESULTS:The CD203c protocol showed a slightly higher sensitivity than the CD63 protocol (97% vs. 89%) with regard to patients' history. The magnitude of basophil response was higher with CD203c in comparison to CD63 for both insect venoms. Specificity was 100% for the CD63 protocol and 89% for the CD203c protocol with regard to controls with negative history and negative RAST. CONCLUSION:These results support the reliability of basophil activation tests using either CD63 or CD203c as cellular tests in the in vitro diagnosis of patients with bee or wasp venom allergy with a slightly higher sensitivity for the CD203c protocol.
    背景与目标: 背景:流式细胞仪嗜碱性粒细胞活化测试已发展为用于体外诊断IgE介导的反应的细胞测试。在用各种变应原刺激后,已使用具有不同调节方式的不同激活标记(CD63或CD203c)。
    目的:本研究的目的是通过测量昆虫毒液过敏患者中的CD63和CD203c上调来比较嗜碱性粒细胞活化测试。
    材料与方法:检查43例有虫毒过敏史的患者。仔细记录过敏史,并进行皮肤测试和特定IgE抗体的测定。在用不同浓度的蜜蜂和黄蜂毒液提取物刺激后,进行了使用CD63或CD203c表达的嗜碱性粒细胞活化测试(BAT)。以25名昆虫毒液过敏史为阴性的健康受试者作为对照。
    结果:就患者病史而言,CD203c方案显示出比CD63方案更高的敏感性(97%比89%)。与两种昆虫毒液的CD63相比,CD203c的嗜碱性粒细胞反应程度更高。对于具有阴性历史和阴性RAST的对照,CD63方案的特异性为100%,CD203c方案的特异性为89%。
    结论:这些结果支持使用CD63或CD203c作为细胞测试的嗜碱性粒细胞活化测试在对蜜蜂或黄蜂毒液过敏患者的体外诊断中具有较高的敏感性,对CD203c协议的敏感性更高。
  • 8 Activation volume of DNA duplex formation. 复制标题 收藏 收藏

    【DNA双链体形成的激活量。】 复制标题 收藏 收藏
    DOI:10.1021/bi963175n 复制DOI
    作者列表:Lin MC,Macgregor RB Jr
    BACKGROUND & AIMS: The denaturation-renaturation thermal hysteresis was used to investigate the kinetics of the helix-coil equilibrium of four 22-base pair homopurine-homopyrimidine duplex oligonucleotides with fractional G x C base pair content (f(G x C)) between 0.14 and 0.5. In 20 mM NaCl and 20 mM Tris-HCl at pH 7.0 and at hydrostatic pressures up to 200 MPa, a two-state bimolecular reaction mechanism adequately described the observed kinetics. At 1 MPa and 47 degrees C, the rate constant for helix formation, k1, increased by a factor of 210, and the reverse rate constant, k(-1), decreased by a factor of 420 upon increasing f(G x C) from 0.14 to 0.5. The activation energies for formation of the duplexes were negative and relatively insensitive to f(G x C). The pressure-induced change in the rate constants is related to the activation volume of the reaction step. Pressure causes k1 to become larger, and the magnitude of the change in k1 with pressure increases the lower the f(G x C) value. Thus, when f(G x C) = 0.14, the activation volume for forward reaction, delta V++(1), equals -20 mL/mol, while when f(G x C) = 0.5, delta V++(1) = -6.7 mL/mol. The rate constant for strand separation, k(-1), decreases at high pressure. The activation volume for this step, delta V++(1), varies from 17 to 1.6 mL/mol when f(G x C) = 0.14 and 0.5, respectively. The delta V for helix formation calculated from the activation parameters changed from -23 mL/mol when f(G x C) = 0.14 to -5.8 mL/mol when f(G x C) = 0.5. From extrapolation, it is estimated that the molar volume change for formation of G x C base pairs in homopurine-homopyrimidine sequences is approximately 0 mL/mol. Parameters calculated from kinetics of other two duplex molecules, when f(G x C) = 0.23 and 0.32, lie between these extremes.

    背景与目标: 变性-复性热滞后作用用于研究四个G-C碱基对含量(f(G x C))在0.14至0.5之间的22个碱基对的高嘌呤-高嘧啶双链体寡核苷酸的螺旋-螺旋平衡动力学。在pH 7.0和最高200 MPa的静水压力下的20 mM NaCl和20 mM Tris-HCl中,两态双分子反应机理充分描述了所观察到的动力学。在1 MPa和47摄氏度时,随着f(G x C)的增加,螺旋形成的速率常数k1增加了210倍,反向速率常数k(-1)减小了420倍。从0.14到0.5。形成双链体的活化能为负,对f(G x C)相对不敏感。速率常数的压力诱导变化与反应步骤的活化体积有关。压力导致k1变大,并且f(G x C)值越低,k1随压力变化的幅度就越大。因此,当f(G x C)= 0.14时,正向反应的活化体积δV(1)等于-20 mL / mol,而当f(G x C)= 0.5时,δV(1)=- 6.7毫升/摩尔。股线分离的速率常数k(-1)在高压下降低。当f(G x C)分别为0.14和0.5时,此步骤的活化体积delta V(1)从17到1.6 mL / mol不等。由活化参数计算的螺旋形成的δV从当f(G×C)= 0.14时的-23mL / mol变为当f(G×C)= 0.5时的-5.8mL / mol。通过外推,估计在高嘌呤-高嘧啶序列中形成G x C碱基对的摩尔体积变化约为0mL / mol。当f(G x C)= 0.23和0.32时,由其他两个双链体分子的动力学计算得出的参数位于这些极端之间。

  • 【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,以及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。
  • 【IFN-γ诱导的溶酶体硫醇还原酶在T细胞活化中的抑制作用。】 复制标题 收藏 收藏
    DOI:10.4049/jimmunol.177.7.4369 复制DOI
    作者列表:Barjaktarević I,Rahman A,Radoja S,Bogunović B,Vollmer A,Vukmanović S,Marić M
    BACKGROUND & AIMS: :IFN-gamma-inducible lysosomal thiol reductase (GILT) is a unique thiol reductase with optimal enzymatic activity at low pH. GILT plays a crucial role in unfolding the antigenic proteins in preparation for their proteolytic cleavage and presentation of resulting peptides by MHC class II. In this study, we demonstrate that GILT is expressed in T lymphocytes and that it has an APC-nonrelated role in the regulation of T cell activation. Surprisingly, comparison of wild-type and GILT-deficient T cell activation in vitro revealed stronger responsiveness in the absence of GILT. The effect of GILT in reducing the proliferative and cytotoxic responses was endogenous to T cells and resulted from decreased sensitivity at the individual cell level. Therefore, a molecule with primarily lysosomal localization suppresses T cell activation, a process characterized by signal transmission from plasma membrane to cytoplasm and nucleus.
    背景与目标: :IFN-γ诱导的溶酶体硫醇还原酶(GILT)是独特的硫醇还原酶,在低pH值下具有最佳的酶促活性。 GILT在展开抗原蛋白以进行蛋白水解切割和通过MHC II类呈递所得肽的过程中起着至关重要的作用。在这项研究中,我们证明了GILT在T淋巴细胞中表达,并且在T细胞活化的调节中具有APC无关的作用。出人意料的是,在体外比较野生型和GILT缺陷型T细胞的激活情况显示,在没有GILT的情况下,其反应性更强。 GILT减少增殖和细胞毒性反应的作用是T细胞内源性的,是由于单个细胞水平的敏感性降低所致。因此,主要具有溶酶体定位的分子可抑制T细胞活化,该过程的特征是信号从质膜传递到细胞质和细胞核。
  • 【新的胆囊收缩素类似物(JMV 236)对大鼠食物摄入和脑单胺的影响。】 复制标题 收藏 收藏
    DOI:10.1016/0143-4179(90)90158-u 复制DOI
    作者列表:Gourch A,Orosco M,Rodriguez M,Martinez J,Cohen Y,Jacquot C
    BACKGROUND & AIMS: :JMV 236, a new cholecystokinin-octapeptide-sulfate (CCK 8 S) derivative (Boc-Tyr (SO3)-Nle-Gly-Trp-Nle-Asp-Phe-NH2) has been synthesized in the Centre de Pharmacologie-Endocrinologie (Montpellier). This peptide has been shown to present the same activity as CCK 8 S on pancreatic amylase secretion and has the advantage of a better chemical stability. With a view to further characterization, the effect of JMV 236 on food intake and brain monoamine and metabolite variations was assayed in the rat after intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administrations. JMV 236 decreased food intake 2 and 3 hours after i.p. administration of 12.5 and 50 micrograms/kg but was inactive after i.c.v. injection. Its global action was similar to that of CCK 8 S, but was less marked with delayed onset of response. As in our previous work with CCK 8 S, JMV 236 was more potent in inducing monoaminergic variations after i.p. than after i.c.v. administration. The main effects were decreases in striatal dopamine metabolite levels and increases in hypothalamic and striatal serotonin metabolite (5-HIAA) levels. These effects are classically observed with CCK 8 S and are described in our previous reports. The interesting peptide will require further characterization and may serve as a possible reference compound for studies on CCK derivatives.
    背景与目标: :JMV 236是一种新的胆囊收缩素-八肽硫酸盐(CCK 8 S)衍生物(Boc-Tyr(SO3)-Nle-Gly-Trp-Nle-Asp-Phe-NH2),已在药理学-内分泌中心(蒙彼利埃)。已显示该肽在胰腺淀粉酶分泌方面具有与CCK 8 S相同的活性,并且具有更好的化学稳定性的优点。为了进一步表征,在大鼠腹膜内(i.p.)和脑室内(i.c.v.)给药后,在大鼠中测定了JMV 236对食物摄入以及脑单胺和代谢产物变化的影响。腹腔注射后2和3小时,JMV 236的食物摄入量减少。静脉注射12.5和50微克/公斤,但在静脉内注射后无效。注射。它的整体作用与CCK 8 S相似,但反应迟缓的症状较少。就像我们以前使用CCK 8 S所做的一样,JMV 236腹腔内注射后在诱导单胺能变化方面更有效。比在i.c.v.之后行政。主要影响是纹状体多巴胺代谢物水平降低,下丘脑和纹状体5-羟色胺代谢物(5-HIAA)水平升高。这些效应在CCK 8 S上得到了经典观察,并在我们以前的报告中进行了描述。令人感兴趣的肽将需要进一步表征,并可能用作研究CCK衍生物的可能参考化合物。
  • 【鸡巨噬细胞中溶菌酶基因的发育活化与其增强子上的核心组蛋白乙酰化有关。】 复制标题 收藏 收藏
    DOI:10.1093/nar/gkl543 复制DOI
    作者列表:Myers FA,Lefevre P,Mantouvalou E,Bruce K,Lacroix C,Bonifer C,Thorne AW,Crane-Robinson C
    BACKGROUND & AIMS: :Native chromatin IP assays were used to define changes in core histone acetylation at the lysozyme locus during developmental maturation of chicken macrophages and stimulation to high-level expression by lipo-polysaccharide. In pluripotent precursors the lysozyme gene (Lys) is inactive and there is no acetylation of core histones at the gene, its promoter or at the upstream cis-control elements. In myeloblasts, where there is a very low level of Lys expression, H4 acetylation appears at the cis-control elements but not at the Lys gene or its promoter: neither H3 nor H2B become significantly acetylated in myeloblasts. In mature macrophages, Lys expression increases 5-fold: H4, H2B and H2A.Z are all acetylated at the cis-control elements but H3 remains unacetylated except at the -2.4 S silencer. Stimulation with LPS increases Lys expression a further 10-fold: this is accompanied by a rise in H3 acetylation throughout the cis-control elements; H4 and H2B acetylation remain substantial but acetylation at the Lys gene and its promoter remains low. Acetylation is thus concentrated at the cis-control elements, not at the Lys gene or its immediate promoter. H4 acetylation precedes H3 acetylation during development and H3 acetylation is most directly linked to high-level Lys expression.
    背景与目标: :天然染色质IP分析用于确定鸡巨噬细胞发育成熟和脂多糖刺激高水平表达期间溶菌酶基因座核心组蛋白乙酰化的变化。在多能的前体中,溶菌酶基因(Lys)是无活性的,并且在该基因,其启动子或上游顺式控制元件上没有核心组蛋白的乙酰化。在成纤维细胞中,Lys表达水平非常低,H4乙酰化出现在顺式控制元件上,而没有出现在Lys基因或其启动子上:H3和H2B在成纤维细胞中都没有被显着乙酰化。在成熟的巨噬细胞中,Lys表达增加5倍:H4,H2B和H2A.Z在顺式控制元件上均被乙酰化,但H3除外-2.4 S沉默子上保持未乙酰化。用LPS刺激可将Lys表达进一步提高10倍:伴随着整个顺式控制元件中H3乙酰化的增加; H4和H2B的乙酰化作用仍然很强,但Lys基因及其启动子的乙酰化作用仍然很低。因此,乙酰化作用集中在顺式控制元件上,而不是Lys基因或其直接启动子上。在发育过程中,H4乙酰化先于H3乙酰化,而H3乙酰化与高水平Lys表达最直接相关。
  • 【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。

  • 【早期大剂量左甲状腺素治疗对先天性甲状腺功能减退症儿童入学时听性脑事件相关电位的影响。】 复制标题 收藏 收藏
    DOI:10.1159/000095069 复制DOI
    作者列表:Marti S,Alvarez M,Simoneau-Roy J,Leroux S,Van Vliet G,Robaey P
    BACKGROUND & AIMS: AIMS:We tested whether brain event-related potentials (ERPs) are normal in children with congenital hypothyroidism (CH) after early high-dose levothyroxine treatment. METHODS:Auditory ERPs were recorded in 33 normal controls and in 15 children with CH at 5 years 9/12. Based on bone maturation at diagnosis, the CH group was divided into severe (n = 8) and moderate (n = 7) subgroups. CH patients were treated at a median age of 14 days with a mean initial dose of levothyroxine of 11.6 microg/kgxday. Two ERP components (N100 and N200) were measured and clinical follow-up variables collected. RESULTS:The functional anatomical and cognitive organisation of the auditory system, as revealed by the analyses of ERP measures, did not differ between CH and controls, or between severe and moderate CH subjects. However, N200 latency was globally longer in the CH than in the control group (p = 0.01) and was positively correlated with the over-treatment index (r = 0.61; p < 0.05) and verbal IQ. N200 amplitude was negatively correlated with initial dose (r = -0.74; p < 0.005). CONCLUSION:These data suggest that sensitive tools such as ERPs can reveal differences between CH and controls and relate these differences to the adequacy of treatment of CH.
    背景与目标: 目的:我们测试了大剂量左甲状腺素早期治疗后先天性甲状腺功能减退症(CH)儿童的脑事件相关电位(ERP)是否正常。
    方法:在33名正常对照者和15名5岁9/12的CH儿童中记录了听诊ERP。根据诊断时的骨成熟度,将CH组分为严重(n = 8)和中度(n = 7)亚组。 CH患者的中位年龄为14天,左甲状腺素的平均初始剂量为11.6 microg / kgxday。测量了两个ERP组件(N100和N200),并收集了临床随访变量。
    结果:ERP措施的分析显示,听觉系统的功能解剖和认知组织在CH和对照之间,或在重度和中度CH患者之间没有差异。但是,CH中的N200潜伏期总体上比对照组长(p = 0.01),并且与过度治疗指数(r = 0.61; p <0.05)和言语智商呈正相关。 N200振幅与初始剂量呈负相关(r = -0.74; p <0.005)。
    结论:这些数据表明,诸如ERPs之类的敏感工具可以揭示CH与对照之间的差异,并将这些差异与CH的治疗充分性联系起来。
  • 【立体定向脑活检的冰冻切片评估:188例立体定向靶位的诊断率。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Brainard JA,Prayson RA,Barnett GH
    BACKGROUND & AIMS: OBJECTIVE:Use of the image-guided stereotactic brain biopsy has facilitated the diagnosis of previously inaccessible lesions with both safety and reliability. However, few studies have assessed the diagnostic yield of frozen section evaluation of the initial stereotactic target (FS-0). We describe our experience with 188 stereotactic brain biopsies in order to evaluate the diagnostic yield of FS-0.

    DESIGN:Retrospective study of 188 stereotactic brain biopsies from 185 patients.

    SETTING:Tertiary referral center with a high volume of neurosurgical cases including image-guided stereotactic brain biopsies.

    PATIENTS:One hundred eighty-five patients who underwent imaged-guided stereotactic brain biopsy over a 58-month period.

    RESULTS:The patients studied included 107 males and 78 females (mean age 48 years). Eleven (6%) biopsies were nondiagnostic. Diagnoses from FS-0 included a neoplastic condition in 96 (73%) of 131 cases and a nonneoplastic condition in 23 (50%) of 46 cases. In 119 (67%) of 177 cases, a diagnosis was reached at FS-0. A correct diagnosis was made on subsequent frozen section in 28 (16%) of cases, including 21 (16%) of 131 neoplasms and 7 (15%) of nonneoplastic conditions. In 15 (54%) of 28 cases, the correct diagnosis was made on the second frozen section; in 25 (89%) of 28, the correct diagnosis was made by the fourth frozen section. In 14 (11%) of 131 neoplastic cases, a sampling error relative to the lesion resulted in an inaccurate diagnosis at FS-0. A significant error in diagnosis occurred in three cases (1.7%).

    CONCLUSIONS:We conclude that (1) because 58 (33%) of 177 diagnosed cases in our series would have been potentially misdiagnosed if only one biopsy had been taken at the stereotactic target, frozen section evaluation or cytologic examination of material at the time of surgery should be performed routinely to ensure that adequate tissue has been obtained for purposes of diagnosis; (2) taking up to four biopsies increases the diagnostic yield (from 67% to 89% in this series); and (3) neoplastic lesions are more likely to be definitively diagnosed at FS-0 than non-neoplastic lesions.

    背景与目标: 目标:使用图像引导的立体定向脑活检技术,既安全又可靠,有助于诊断先前难以接近的病变。但是,很少有研究评估初始立体定位目标(FS-0)的冷冻切片评估的诊断率。我们描述了188例立体定向脑活检的经验,以评估FS-0的诊断率。

    DESIGN :对185例患者的188例立体定向脑活检的回顾性研究。
    设置:拥有大量神经外科病例的三级转诊中心,包括图像引导的立体定向脑活检。

    患者:一百八十五

    结果:接受影像引导的立体定向脑活检的患者。研究的患者包括107例男性和78例女性(平均年龄48岁)。 11例(6%)活检未确诊。 FS-0的诊断包括131例中的96例(73%)为肿瘤性疾病和46例中23例(50%)为非肿瘤性疾病。在177例病例中,有119例(67%)达到了FS-0的诊断。在随后的冰冻切片中,有28例(16%)做出了正确的诊断,包括131例肿瘤中的21例(16%)和7例(15%)的非肿瘤性疾病。在28例病例中,有15例(54%)对第二个冷冻切片做出了正确的诊断。 28例中有25例(89%)通过第四次冰冻切片做出了正确的诊断。在131例肿瘤病例中,有14例(11%)相对于病变的采样错误导致FS-0诊断不准确。结论3例诊断错误(1.7%)。

    结论:我们得出结论:(1)因为本系列177例诊断病例中有58例(33%)如果仅在立体定向目标上进行了一次活检,可能会被误诊,在手术时应常规进行冰冻切片评估或材料的细胞学检查,以确保获得足够的组织用于诊断; (2)最多进行四次活检可以提高诊断率(在本系列中从67%增至89%); (3)FS-0比非肿瘤性病变更有可能明确诊断出肿瘤性病变。

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