• 【巨噬细胞对NF-κB活化的抑制作用减少了泡沫细胞的形成。】 复制标题 收藏 收藏
    DOI:10.1016/j.atherosclerosis.2006.07.018 复制DOI
    作者列表:Ferreira V,van Dijk KW,Groen AK,Vos RM,van der Kaa J,Gijbels MJ,Havekes LM,Pannekoek H
    BACKGROUND & AIMS: :Accumulation of lipid-laden macrophages is a hallmark of atherosclerosis. The relevance of the key transcription factor nuclear factor kappaB (NF-kappaB) for macrophage-derived foam-cell formation has not been unequivocally resolved. Transgenic mice lines were generated in which NF-kappaB activation is specifically inhibited in macrophages by overexpressing a trans-dominant, non-degradable form of IkappaBalpha (IkappaBalpha (32A/36A)) under control of the macrophage-specific SR-A promoter. Alanine substitution of serines 32 and 36 prevents degradation and retains the inactive NF-kappaB/IkappaBalpha (32A/36A) complex in the cytoplasm. Similarly, stable human THP1 monocytic cell lines were generated with integrated copies of IkappaBalpha (32A/36A) cDNA. Upon treatment with oxidized low-density lipoprotein (ox-LDL), murine peritoneal macrophages from transgenic IkappaBalpha (32A/36A) mice, as well as THP1/IkappaBalpha (32A/36A) clones, display decreased lipid loading after differentiation into macrophages. This is accompanied by increased expression of the transcription factors PPARgamma and LXRalpha as well as of the major cholesterol-efflux transporter ABCA1. Paradoxically, mRNA expression of the 'lipid-uptake' receptor CD36 is also increased. Since the net result of these changes is reduction of foam-cell formation, it is proposed that under specific inhibition of NF-kappaB activation, ABCA1-mediated cholesterol efflux prevails over CD36-mediated lipid influx.
    背景与目标: :富含脂质的巨噬细胞的积累是动脉粥样硬化的标志。尚未明确解决关键转录因子核因子κB(NF-κB)与巨噬细胞衍生的泡沫细胞形成的相关性。通过在巨噬细胞特异性SR-A启动子的控制下过表达不可表达形式的IkappaBalpha(IkappaBalpha(32A / 36A)),从而在巨噬细胞中特异性抑制NF-κB活化的转基因小鼠品系。丝氨酸32和36的丙氨酸取代防止降解并在细胞质中保留无活性的NF-κB/IκBα(32A / 36A)复合物。类似地,用整合的IkappaBalpha(32A / 36A)cDNA拷贝产生稳定的人THP1单核细胞系。经氧化低密度脂蛋白(ox-LDL)处理后,转基因IkappaBalpha(32A / 36A)小鼠以及THP1 / IkappaBalpha(32A / 36A)克隆的小鼠腹膜巨噬细胞在分化为巨噬细胞后显示出降低的脂质负载。这伴随着转录因子PPARgamma和LXRalpha以及主要胆固醇外流转运蛋白ABCA1表达的增加。矛盾的是,“脂质摄取”受体CD36的mRNA表达也增加了。由于这些变化的最终结果是减少了泡沫细胞的形成,因此建议在特定抑制NF-κB活化的情况下,ABCA1介导的胆固醇外排比CD36介导的脂质内流更为普遍。
  • 【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。

  • 【结肠扩张激活蓝藻:促肾上腺皮质激素释放因子和兴奋性氨基酸的作用。】 复制标题 收藏 收藏
    DOI:10.1016/s0006-8993(97)00116-9 复制DOI
    作者列表:Lechner SM,Curtis AL,Brons R,Valentino RJ
    BACKGROUND & AIMS: The present study was designed to elucidate the neurotransmitters involved in activation of the noradrenergic nucleus, locus coeruleus, by distention of the distal colon. Locus coeruleus spontaneous discharge rate was recorded from halothane-anesthetized rats before, during and after distention of the colon produced by inflation of a balloon catheter with varying volumes of water. Locus coeruleus activation by colon distention was volume-dependent and reversible. Activation of cortical electroencephalographic activity was temporally correlated with locus coeruleus activation during colon distention and prolonged distention (greater than 2 min) resulted in tachyphalaxis to both locus coeruleus and cortical electroencephalographic activation. The corticotropin-releasing factor antagonist, DPheCRF(12-41), administered intracerebroventricularly (3 microg) or microinfused into the locus coeruleus (10 ng) significantly attenuated locus coeruleus activation produced by lower, but not higher magnitudes of colon distention, implicating corticotropin-releasing factor afferents to the locus coeruleus in this response. Consistent with this, prior exposure to 30 min of footshock stress, which desensitizes locus coeruleus neurons to corticotropin-releasing factor, produced a similar attenuation of locus coeruleus activation by low, but not high magnitudes of distention. Kynurenic acid, administered intracerebroventricularly (5 micromol), significantly antagonized locus coeruleus activation by all magnitudes of colon distention. However, this excitatory amino acid antagonist was ineffective when administered directly into the locus coeruleus (0.3 nmol). Together, these findings suggest that low magnitudes of colon distention activate the locus coeruleus-noradrenergic system via corticotropin-releasing factor release within the locus coeruleus and that excitatory amino acid neurotransmission at a site distal to the locus coeruleus is necessary for this response. Activation of the locus coeruleus-noradrenergic system during colon distention may serve as a cognitive limb of the peripheral parasympathetic response. This activation may also play a role in disorders characterized by comorbidity of colonic and psychiatric symptoms, such as irritable bowel syndrome.

    背景与目标: 本研究旨在阐明远端结肠扩张引起的去甲肾上腺素能核激活的神经递质。记录了氟烷麻醉大鼠在用不同体积的水充入球囊导管使结肠扩张之前,期间和之后自发排出蓝藻的频率。结肠扩张引起的蓝斑轨迹激活是体积依赖性的和可逆的。皮质脑电图活动的激活在时间上与结肠扩张期间脑蓝素的激活相关,而长期扩张(大于2分钟)会导致脑脊髓蓝素和皮质脑电图的速动性。皮质激素释放因子拮抗剂DPheCRF(12-41),经脑室内(3微克)或微输注到蓝斑(10 ng)时,可显着减弱由较低但不是较高程度的结肠扩张产生的蓝斑激活,这暗示促肾上腺皮质激素-在这种反应中,释放因子传入蓝斑。与此相一致,事先暴露于30分钟的足底震荡中,使蓝斑蓝皮病的神经元对促肾上腺皮质激素释放因子不敏感,通过低但不高的扩张程度,蓝斑蓝皮病的激活也有类似的减弱。脑室内(5微摩尔)施用的犬尿酸通过各种程度的结肠扩张显着拮抗蓝斑轨迹激活。但是,这种兴奋性氨基酸拮抗剂当直接施用于蓝斑(0.3 nmol)时无效。在一起,这些发现表明低程度的结肠扩张通过蓝藻中的促肾上腺皮质激素释放因子释放来激活蓝藻-去甲肾上腺素能系统,并且在蓝藻远侧的部位,兴奋性氨基酸神经传递对于该反应是必需的。结肠扩张期间蓝斑-去甲肾上腺素能系统的激活可能充当外周副交感反应的认知肢体。这种活化作用还可能在以结肠和精神症状合并症为特征的疾病中起作用,例如肠易激综合症。

  • 【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。
  • 【细胞外钙敏感受体的激活启动了朗格汉斯人胰岛的胰岛素分泌:蛋白激酶的参与。】 复制标题 收藏 收藏
    DOI:10.1677/joe.1.06891 复制DOI
    作者列表:Gray E,Muller D,Squires PE,Asare-Anane H,Huang GC,Amiel S,Persaud SJ,Jones PM
    BACKGROUND & AIMS: :The extracellular calcium-sensing receptor (CaR) is usually associated with systemic Ca(2+) homeostasis, but the CaR is also expressed in many other tissues, including pancreatic islets of Langerhans. In the present study, we have used human islets and an insulin-secreting cell line (MIN6) to investigate the effects of CaR activation using the calcimimetic R-568, a CaR agonist that activates the CaR at physiological concentrations of extracellular Ca(2+). CaR activation initiated a marked but transient insulin secretory response from both human islets and MIN6 cells at a sub-stimulatory concentration of glucose, and further enhanced glucose-induced insulin secretion. CaR-induced insulin secretion was reduced by inhibitors of phospholipase C or calcium-calmodulin-dependent kinases, but not by a protein kinase C inhibitor. CaR activation was also associated with an activation of p42/44 mitogen-activated protein kinases (MAPK), and CaR-induced insulin secretion was reduced by an inhibitor of p42/44 MAPK activation. We suggest that the beta-cell CaR is activated by divalent cations co-released with insulin, and that this may be an important mechanism of intra-islet communication between beta-cells.
    背景与目标: :细胞外钙敏感受体(CaR)通常与全身性Ca(2)稳态相关,但该CaR在许多其他组织中也表达,包括Langerhans的胰岛。在本研究中,我们已经使用人类胰岛和胰岛素分泌细胞系(MIN6)来研究使用拟钙剂R-568(CaR激动剂在生理浓度的细胞外Ca(2)激活CaR的CaR激活)的作用。 。 CaR激活在葡萄糖的亚刺激浓度下启动了来自人胰岛和MIN6细胞的显着但短暂的胰岛素分泌反应,并进一步增强了葡萄糖诱导的胰岛素分泌。 CaR诱导的胰岛素分泌通过磷脂酶C或钙钙调蛋白依赖性激酶的抑制剂降低,但不通过蛋白激酶C抑制剂降低。 CaR激活还与p42 / 44丝裂原激活的蛋白激酶(MAPK)激活相关,并且CaR诱导的胰岛素分泌被p42 / 44 MAPK激活的抑制剂减少。我们建议β细胞CaR被与胰岛素共释放的二价阳离子激活,这可能是β细胞之间胰岛内通讯的重要机制。
  • 【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。

  • 【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。
  • 15 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。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录