• 【钳位上升时间对非洲爪蟾卵母细胞中大鼠脑IIA钠通道的影响。】 复制标题 收藏 收藏
    DOI:10.1016/s0165-0270(96)02216-9 复制DOI
    作者列表:Ruben PC,Fleig A,Featherstone D,Starkus JG,Rayner MD
    BACKGROUND & AIMS: The kinetic properties of wild-type rat brain IIa sodium channels in excised macropatches were studied using step depolarizations and ramp depolarizations to imitate the slow settling-time of voltage in two-electrode voltage clamp. Ramp depolarizations longer than 1 ms produce an increasing suppression of peak sodium current (I[Na]). Two rates of inactivation can be seen in macroscopic sodium current records from excised patches following both step and ramp depolarizations. During slow ramp depolarizations, reduction in peak I[Na] is associated with selective loss of the fastest rate of test-pulse inactivation. This change can be interpreted as resulting from inactivation of a separate sub-population of 'fast mode' channels. The slow rate of test-pulse inactivation is relatively unaffected by changing ramp durations. These results are sufficient to explain the typically slow inactivation kinetics seen in two-electrode voltage clamp recordings of sodium channels in Xenopus oocytes. Thus, the kinetics of sodium channels expressed in Xenopus oocytes are not readily characterizable by two-electrode clamp because of the large membrane capacitance and resulting slow clamp settling time which artifactually selects for slow mode channels.

    背景与目标: 使用逐步去极化和斜坡去极化来模拟在两电极电压钳中电压的缓慢建立时间,研究了切除的大斑块中野生型大鼠脑IIa钠通道的动力学特性。超过1 ms的斜坡去极化会产生对钠电流峰值(I [Na])的越来越大的抑制。在阶跃和斜波去极化后,从切下的小片的宏观钠电流记录中可以看到两种失活速率。在缓慢的斜坡去极化期间,峰值I [Na]的降低与最快的测试脉冲失活速率的选择性损失有关。可以将这种变化解释为是由于“快速模式”通道的单独子群体未激活而导致的。测试脉冲失活的缓慢速率相对不受斜坡持续时间变化的影响。这些结果足以解释爪蟾卵母细胞中钠通道的两电极电压钳记录中典型的缓慢失活动力学。因此,非洲爪蟾卵母细胞中表达的钠通道的动力学不易通过两电极钳夹来表征,因为膜电容大且钳夹建立时间慢,这是人为地选择慢模式通道的原因。
  • 【氨基末端脑钠肽:一种诊断,预后和管理心力衰竭的生物标志物。】 复制标题 收藏 收藏
    DOI:10.1586/14737159.6.5.649 复制DOI
    作者列表:Morello AM,Januzzi JL
    BACKGROUND & AIMS: :There is a substantial need for a diagnostic tool to aid in the early diagnosis of heart failure and in the recognition of those at risk for its development, as well as in guidance of therapy. Testing for amino-terminal pro-brain natriuretic peptide (NT-proBNP) has been recognized to have utility in the diagnosis, prognosis and management of heart failure. In addition, numerous other applications for NT-proBNP testing are now recognized, such as evaluation of patients with heart disease in the absence of heart failure, as well as the diagnostic and prognostic evaluation of patients with acute coronary syndromes or pulmonary thromboembolism.
    背景与目标: :非常需要一种诊断工具来辅助心力衰竭的早期诊断,并认识到可能发展为心力衰竭的人,以及指导治疗。氨基末端脑钠肽(NT-proBNP)的检测已被认为可用于心力衰竭的诊断,预后和管理。此外,现在还认可了NT-proBNP测试的许多其他应用,例如在没有心力衰竭的情况下对心脏病患者的评估以及对急性冠状动脉综合征或肺血栓栓塞患者的诊断和预后评估。
  • 【人脑中的微透析:其应用综述。】 复制标题 收藏 收藏
    DOI:10.1080/01616412.1997.11740814 复制DOI
    作者列表:Hamani C,Luer MS,Dujovny M
    BACKGROUND & AIMS: The analysis of brain extracellular fluid can provide essential information about both the physiology and the pathology of the human nervous system. The introduction of microdialysis into the clinical sciences has provided a new opportunity to study this environment. Using microdialysis, endogenous substances can be obtained and drugs can be delivered in very close proximity to the receptors and ion channels on neuronal membranes. In this sense, microdialysis can be regarded as a novel technique since it can continuously measure interstitial brain activity in living tissue while causing minimal adverse effects. Although it has been well established as an experimental technique for neurochemistry, the true utility of microdialysis as a clinical tool is still being defined. The potential clinical applications of microdialysis to characterize the human brain extracellular environment in patients with pathologic conditions has grown rapidly. The number of publications in which microdialysis has been performed in clinical studies has been increasing during recent years and this article gives a summary of those reports where microdialysis was applied in the study of human brain disorders.

    背景与目标: 对大脑细胞外液的分析可以提供有关人类神经系统生理和病理的基本信息。将微透析技术引入临床科学为研究这种环境提供了新的机会。使用微透析,可以获得内源性物质,并且药物可以非常靠近神经元膜上的受体和离子通道递送。从这个意义上讲,微透析可以被视为一种新颖的技术,因为它可以连续测量活组织中的间质性大脑活动,同时将不良影响降到最低。尽管已经将其很好地确立为神经化学的实验技术,但微透析作为临床工具的真正用途仍在定义中。微透析在表征病理状况患者中表征人脑细胞外环境的潜在临床应用迅速增长。近年来,在临床研究中进行微透析的出版物数量不断增加,本文总结了在人类脑部疾病研究中应用微透析的那些报道。

  • 【苯巴比妥依赖和戒断大鼠脑中谷氨酸受体,c-fos mRNA表达和激活蛋白-1(AP-1)DNA结合活性的变化。】 复制标题 收藏 收藏
    DOI:10.1016/s0006-8993(97)00134-0 复制DOI
    作者列表:Tanaka S,Kiuchi Y,Numazawa S,Oguchi K,Yoshida T,Kuroiwa Y
    BACKGROUND & AIMS: We studied changes in glutamate receptors, expression of immediate early genes, and AP-1 DNA binding activity in the brains of phenobarbital (PB)-dependent and -withdrawn rats to investigate the possible involvement of activation of glutamate receptors in PB withdrawal syndrome. PB-dependent rats were prepared by feeding drug-admixed food for 5 weeks. Autoradiographic analysis showed that binding of [3H(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imin e (MK-801), an antagonist of N-methyl-D-aspartic acid (NMDA) receptors, increased significantly in the cerebral cortices of PB-dependent and 24-h-withdrawn rats. However, [3H]MK-801 binding in the hippocampus and [3H]6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and [3H]kainic acid binding in the hippocampus and cerebral cortex were essentially unchanged in both groups. PB withdrawal seizures were followed by increased expression of c-fos mRNA in the hippocampus and cerebral cortex and of c-jun mRNA in the cerebral cortex. The induction of c-fos and c-jun mRNA was suppressed by administration of MK-801. Furthermore, PB withdrawal enhanced AP-1 DNA binding activity in the brain. The present findings suggest functional enhancement of glutamatergic neurotransmission during the development of PB withdrawal syndrome.

    背景与目标: 我们研究了苯巴比妥(PB)依赖和戒断大鼠大脑中谷氨酸受体的变化,立即早期基因的表达以及AP-1 DNA结合活性,以研究谷氨酸受体激活在PB戒断综合征中的可能。通过喂食药物混合的食物5周来制备PB依赖的大鼠。放射自显影分析表明,[3H()-5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺e(MK-801)与N-甲基- D-天冬氨酸(NMDA)受体,在PB依赖和24小时戒断大鼠的大脑皮层中显着增加。然而,在海马中的[3H] MK-801结合以及在海马和大脑皮层中的[3H] 6-氰基-7-硝基喹喔啉-2,3-二酮(CNQX)和[3H]海藻酸结合基本上没有变化。组。 PB抽搐发作后,海马和大脑皮层中c-fos mRNA的表达增加,大脑皮层中c-jun mRNA的表达增加。通过施用MK-801抑制了c-fos和c-jun mRNA的诱导。此外,PB撤离可增强大脑中AP-1 DNA的结合活性。目前的发现表明,在PB戒断综合征的发展过程中,谷氨酸能神经传递的功能增强。

  • 【ROS形成对依赖NADH的底物支持的孤立的脑线粒体中DeltaPsim的中等依赖性。】 复制标题 收藏 收藏
    DOI:10.1007/s11064-006-9130-y 复制DOI
    作者列表:Tretter L,Adam-Vizi V
    BACKGROUND & AIMS: :The membrane potential (DeltaPsim) dependence of the generation of reactive oxygen species (ROS) in isolated guinea-pig brain mitochondria respiring on NADH-linked substrates (glutamate plus malate) was addressed. Depolarization by FCCP was without effect on H(2)O(2) formation in the absence of bovine serum albumin (BSA). Addition of BSA (0.025%) to the assay medium hyperpolarized mitochondria by 6.1 +/- 0.9 mV (from 169 +/- 3 to 175.1 +/- 2.1 mV) and increased the rate of H(2)O(2) formation from 207 +/- 4.5 to 312 +/- 12 pmol/min/mg protein. Depolarization by FCCP (5-250 nM) in the presence of BSA decreased H(2)O(2) formation but only to the level observed in the absence of BSA. Rotenone stimulated the formation of H(2)O(2) both in the absence and presence of BSA. It is suggested that H(2)O(2) formation in mitochondria supported by NADH-linked substrates is sensitive to changes in DeltaPsim only when mitochondria are highly polarized and even then, 60% of ROS generation is independent of DeltaPsim. This is in contrast to earlier reports on the highly DeltaPsim sensitive ROS formation related to reverse electron flow observed in well-coupled succinate-supported mitochondria.
    背景与目标: :膜电位(DeltaPsim)依赖于在NADH相连的底物(谷氨酸加苹果酸)上呼吸的豚鼠脑线粒体中分离的活性氧(ROS)的产生。在没有牛血清白蛋白(BSA)的情况下,通过FCCP去极化对H(2)O(2)的形成没有影响。将BSA(0.025%)添加到测定介质超极化线粒体的6.1 /-0.9 mV(从169 /-3到175.1 /-2.1 mV),并将H(2)O(2)的形成速率从207 /-增加4.5至312 /-12 pmol / min / mg蛋白质。在BSA存在下由FCCP(5-250 nM)进行的去极化降低了H(2)O(2)的形成,但仅达到了在没有BSA的情况下观察到的水平。鱼藤酮在没有和存在BSA的情况下刺激H(2)O(2)的形成。建议仅在线粒体高度极化并且即使那时,60%的ROS生成独立于DeltaPsim时,由NADH链接的底物支持的线粒体中的H(2)O(2)形成对DeltaPsim的变化敏感。这与早先报道的关于高度DeltaPsim敏感的ROS形成相反,后者与在耦合良好的琥珀酸负载的线粒体中观察到的反向电子流有关。
  • 【正常成年大鼠的血脑屏障缺陷区域的免疫环境增强。】 复制标题 收藏 收藏
    DOI:10.1016/s0165-5728(97)00038-6 复制DOI
    作者列表:Pedersen EB,McNulty JA,Castro AJ,Fox LM,Zimmer J,Finsen B
    BACKGROUND & AIMS: The circumventricular organs (CVOs) in the brain are without a blood-brain barrier (BBB) and as such directly exposed to blood plasma constituents and blood-borne pathogens. In light of previous studies showing discrepancies regarding the immunocompetence of these organs, we initiated the present study to provide a comprehensive immunohistochemical analysis of the cellular expression of immune-associated antigens within the pineal gland, area postrema and the subfornical organ. In all CVOs, subpopulations of cells morphologically similar to complement receptor type 3 immunoreactive microglial/macrophage cells expressed major histocompatibility complex (MHC) class II antigen, leucocyte common antigen (LCA/CD45), as well as CD4 and ED1 antigen. Based on morphological criteria the MHC class II antigen expressing cells could be grouped into a major population of classical parenchymal and perivascular ramified microglial cells and a minor population presenting itself as scattered or small groups of rounded macrophage-like cells. CD4 and ED1 antigen were expressed by both cell types. CD45 was preferentially expressed by macrophage-like cells. MHC class I antigen was expressed by the vascular endothelium in both BBB-protected and BBB-deficient areas and was additionally present as a lattice-like network throughout the BBB-deficient parenchyma in all CVOs. The results suggest that the BBB-free areas of the brain besides being constantly surveyed by blood-borne macrophages, possess an intrinsic immune surveillance system based on resting and activated microglial cells, which may function as a non-endothelial, cellular barrier against blood-borne pathogens.

    背景与目标: 大脑中的室间隔器官(CVO)没有血脑屏障(BBB),因此直接暴露于血浆成分和血源性病原体。鉴于先前的研究表明这些器官的免疫能力存在差异,我们启动了本研究,以提供对松果体,视网膜后区域和分支下器官内免疫相关抗原的细胞表达的全面免疫组织化学分析。在所有CVO中,与补体受体3型免疫反应性小胶质细胞/巨噬细胞细胞形态相似的细胞亚群表达了主要的组织相容性复合物(MHC)II类抗原,白细胞常见抗原(LCA / CD45)以及CD4和ED1抗原。根据形态学标准,可以将表达MHC II类抗原的细胞分为经典的实质和血管周围分枝的小神经胶质细胞的主要群体,以及表现为散在的或成团的圆形巨噬细胞样细胞的少数群体。 CD4和ED1抗原通过两种细胞类型表达。 CD45优先由巨噬细胞样细胞表达。 MHC I类抗原在BBB保护区和BBB缺失区均由血管内皮表达,并在所有CVO中的整个BBB缺失实质中均呈格子状网络存在。结果表明,除了大脑中无血脑屏障的区域不断被血源性巨噬细胞检查外,还具有基于静止和活化的小胶质细胞的内在免疫监视系统,该系统可能起非内皮细胞屏障的作用。传播的病原体。

  • 【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。

  • 【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。
  • 【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。
  • 【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。

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