• 【局限性神经节神经母细胞瘤后生长激素缺乏症: 一例报告。】 复制标题 收藏 收藏
    DOI:10.1097/01.mph.0000212984.51867.88 复制DOI
    作者列表:Schiavetti A,Ingrosso A,Picone S,Boscherini B
    BACKGROUND & AIMS: :Growth hormone deficiency (GHD) related to standard dose chemotherapy has rarely been described. We report on a case of localized ganglioneuroblastoma treated by carboplatin/etoposide for 2 courses and surgery, which developed a serious GHD after 56 months. At present, the child is growing on by GH replacement therapy. We discuss about the hypothesis that GHD may be related to chemotherapy and we report a review of previous published cases.
    背景与目标: : 与标准剂量化疗相关的生长激素缺乏症 (GHD) 很少被描述。我们报告了一例经卡铂/依托泊苷治疗2个疗程和手术的局部神经节神经母细胞瘤,该病例在56个月后发展为严重的GHD。目前,这个孩子正在通过GH替代疗法成长。我们讨论了GHD可能与化疗有关的假设,并报告了以前发表的病例的回顾。
  • 【HIV-1 RNA的运输由异质核核糖核蛋白A2表达介导,并影响病毒组装。】 复制标题 收藏 收藏
    DOI:10.1111/j.1600-0854.2006.00461.x 复制DOI
    作者列表:Lévesque K,Halvorsen M,Abrahamyan L,Chatel-Chaix L,Poupon V,Gordon H,DesGroseillers L,Gatignol A,Mouland AJ
    BACKGROUND & AIMS: :Few details are known about how the human immunodeficiency virus type 1 (HIV-1) genomic RNA is trafficked in the cytoplasm. Part of this process is controlled by the activity of heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2). The role of hnRNP A2 during the expression of a bona fide provirus in HeLa cells is investigated in this study. Using immunofluorescence and fluorescence in situ hybridization techniques, we show that knockdown of hnRNP A2 expression in HIV-1-expressing cells results in the rapid accumulation of HIV-1 genomic RNA in a distinct, cytoplasmic space that corresponds to the microtubule-organizing center (MTOC). The RNA exits in the nucleus and accumulates at the MTOC region as a result of hnRNP A2 knockdown even during the expression of a provirus harboring mutations in the hnRNP A2-response element (A2RE), the expression of which results in nuclear retention of genomic RNA. We also demonstrate that hnRNP A2 expression is required for downstream trafficking of genomic RNA from the MTOC in the cytoplasm. Genomic RNA localization at the MTOC that was both the result of hnRNP A2 knockdown and the overexpression of Rab7-interacting lysosomal protein had little effect on pr55Gag synthesis but negatively influenced virus production and infectivity. These data indicate that altered HIV-1 genomic RNA localization modulates viral assembly and that the MTOC serves as a central site to which HIV-1 genomic RNA converges following its exit from the nucleus, with the host protein, hnRNP A2, playing a central role in taking it to and from this site in the cell.
    背景与目标: : 关于人类免疫缺陷病毒1型 (HIV-1) 基因组RNA如何在细胞质中运输的细节知之甚少。该过程的一部分受异质核核糖核蛋白A2 (hnRNP A2) 的活性控制。本研究研究了hnRNP A2在HeLa细胞中真正的前病毒表达中的作用。使用免疫荧光和荧光原位杂交技术,我们显示了HIV-1-expressing细胞中hnRNP A2表达的敲低导致HIV-1基因组RNA在与微管组织中心 (MTOC) 相对应的独特细胞质空间中快速积累。即使在hnRNP A2-response元件 (A2RE) 中携带突变的前病毒的表达过程中,由于hnRNP A2敲除,RNA也会在细胞核中离开并在MTOC区域积累,其表达导致基因组RNA的核保留。我们还证明hnRNP A2表达是细胞质中来自MTOC的基因组RNA下游运输所必需的。hnRNP A2敲低的结果和Rab7-interacting溶酶体蛋白的过表达在MTOC上的基因组RNA定位对pr55Gag的合成几乎没有影响,但对病毒的产生和感染性产生负面影响。这些数据表明,改变的HIV-1基因组RNA定位调节病毒组装,并且MTOC充当HIV-1基因组RNA从细胞核退出后会聚的中心位点,宿主蛋白hnrnpa2在将其带到和从细胞中的该位点中起着核心作用。
  • 【苯巴比妥依赖性和退缩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) 依赖性和退缩大鼠大脑中谷氨酸受体的变化,即刻早期基因的表达以及AP-1的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参与。通过喂养混合药物的食物5周制备PB依赖性大鼠。放射自显影分析显示,N-甲基-d-天冬氨酸 (NMDA) 受体拮抗剂 [3H(+)-5-甲基-10,11-二氢-5H-二苯并 [a,D] cyclohepten-5,10-敏e (MK-801) 的结合,PB依赖性和24h撤回大鼠的大脑皮层显着增加。然而,[3h] MK-801在海马和 [3H]6-氰基-7-硝基喹喔啉-2结合,海马和大脑皮层中的3-二酮 (CNQX) 和 [3H] 海藻酸结合在两组中基本上没有变化。铅戒断发作后,海马和大脑皮层中c-fos mRNA的表达增加,大脑皮层中c-6月mRNA的表达增加。诱导c-MK-801可抑制fos和c-6月mRNA。此外,铅戒断增强了大脑中的AP-1 DNA结合活性。目前的发现表明,在铅戒断综合征的发展过程中,谷氨酸能神经传递的功能增强。
  • 【Dlx同源盒基因在鳃弓的远端模式中的作用: Dlx-1,Dlx-2和Dlx-1的突变,以及-2改变了源自第一和第二弓的近端骨骼和软组织结构的形态发生。】 复制标题 收藏 收藏
    DOI:10.1006/dbio.1997.8556 复制DOI
    作者列表:Qiu M,Bulfone A,Ghattas I,Meneses JJ,Christensen L,Sharpe PT,Presley R,Pedersen RA,Rubenstein JL
    BACKGROUND & AIMS: The Dlx homeobox gene family is expressed in a complex pattern within the embryonic craniofacial ectoderm and ectomesenchyme. A previous study established that Dlx-2 is essential for development of proximal regions of the murine first and second branchial arches. Here we describe the craniofacial phenotype of mice with mutations in Dlx-1 and Dlx-1 and -2. The skeletal and soft tissue analyses of mice with Dlx-1 and Dlx-1 and -2 mutations provide additional evidence that the Dlx genes regulate proximodistal patterning of the branchial arches. This analysis also elucidates distinct and overlapping roles for Dlx-1 and Dlx-2 in craniofacial development. Furthermore, mice lacking both Dlx-1 and -2 have unique abnormalities, including the absence of maxillary molars. Dlx-1 and -2 are expressed in the proximal and distal first and second arches, yet only the proximal regions are abnormal. The nested expression patterns of Dlx-1, -2, -3, -5, and -6 provide evidence for a model that predicts the region-specific requirements for each gene. Finally, the Dlx-2 and Dlx-1 and -2 mutants have ectopic skull components that resemble bones and cartilages found in phylogenetically more primitive vertebrates.

    背景与目标: Dlx同源盒基因家族在胚胎颅面外胚层和外胚间质中以复杂的模式表达。先前的研究表明,Dlx-2对于鼠第一和第二鳃弓近端区域的发育至关重要。在这里,我们描述了具有Dlx-1和-2突变的小鼠的颅面表型。对具有Dlx-1和-2突变的小鼠的骨骼和软组织分析提供了额外的证据,表明Dlx基因调节鳃弓的近端模式。此分析还阐明了Dlx-1和Dlx-2在颅面发育中的独特和重叠作用。此外,缺少Dlx-1和-2的小鼠具有独特的异常,包括缺少上颌磨牙。Dlx-1和-2在近侧和远侧第一和第二拱形中表达,但只有近侧区域是异常的。Dlx-1、-2、-3、-5和-6的嵌套表达模式为预测每个基因的区域特异性需求的模型提供了证据。最后,Dlx-2和Dlx-1和-2突变体具有异位的头骨成分,类似于在系统发育上更原始的脊椎动物中发现的骨骼和软骨。
  • 【垂体切除术前后垂体依赖性高肾上腺皮质激素,皮质醇,α-黑素细胞刺激激素和生长激素的血浆谱。】 复制标题 收藏 收藏
    DOI:10.1677/joe.1.06782 复制DOI
    作者列表:Hanson JM,Kooistra HS,Mol JA,Teske E,Meij BP
    BACKGROUND & AIMS: :The 6-h plasma profiles of adrenocorticotropic hormone (ACTH), cortisol, alpha-melanocyte-stimulating hormone (alpha-MSH), and GH were studied in 17 dogs with pituitary-dependent hyperadrenocorticism (PDH) before and after hypophysectomy. The aim of the study was to investigate the relation between the hormone profile characteristics and recurrence of PDH after surgery. The hormones were secreted in a pulsatile fashion. The basal plasma cortisol concentration and area under the curve (AUC) for cortisol were significantly higher in the PDH cases than in eight controls. The characteristics of the plasma profiles of ACTH and alpha-MSH were not significantly different between the PDH cases and the controls. In the PDH cases, less GH was secreted in pulses than in the controls, but the difference was not significant. The basal plasma cortisol concentration, the AUC for ACTH and cortisol, and the pulse frequency of ACTH and cortisol decreased significantly after hypophysectomy for the group of PDH cases. The basal plasma concentrations of ACTH and alpha-MSH, the AUC for alpha-MSH, and the characteristics of the plasma GH profiles of the PDH cases remained unchanged after hypophysectomy. No pulses of alpha-MSH were observed after hypophysectomy. The co-occurrence between the ACTH and cortisol pulses decreased significantly with hypophysectomy. The postoperative pulse frequency of ACTH was the only characteristic with predictive value for the recurrence of PDH after hypophysectomy. The results of this study demonstrate that ACTH, cortisol, alpha-MSH, and GH are secreted in a pulsatile fashion in dogs with PDH. Hypophysectomy effectively reduces the secretion of ACTH and cortisol. The presence of ACTH pulses after hypophysectomy is a risk factor for the recurrence of hyperadrenocorticism.
    背景与目标: : 在17只垂体切除术前后,研究了促肾上腺皮质激素 (ACTH),皮质醇,α-黑素细胞刺激激素 (alpha-MSH) 和GH的6小时血浆谱。该研究的目的是研究PDH术后激素特征与复发之间的关系。荷尔蒙以脉动的方式分泌。PDH病例的基础血浆皮质醇浓度和皮质醇曲线下面积 (AUC) 显着高于八个对照。在PDH病例和对照组之间,ACTH和 α-MSH的血浆特征没有显着差异。在PDH病例中,脉冲分泌的GH比对照组少,但差异不显着。PDH组患者垂体切除术后,基础血浆皮质醇浓度,ACTH和皮质醇的AUC以及ACTH和皮质醇的脉冲频率显着降低。垂体切除术后,PDH病例的基础血浆ACTH和 α-MSH的血浆浓度,α-MSH的AUC以及血浆GH谱的特征保持不变。垂体切除术后未观察到 α-MSH脉冲。垂体切除术后,ACTH和皮质醇脉冲之间的共存显着减少。ACTH的术后脉搏频率是垂体切除术后PDH复发的唯一特征,具有预测价值。这项研究的结果表明,患有PDH的狗以脉动方式分泌ACTH,皮质醇,α-MSH和GH。垂体切除术有效地减少了ACTH和皮质醇的分泌。垂体切除术后ACTH脉冲的存在是肾上腺皮质亢进症复发的危险因素。
  • 【interleukin-1对大鼠培养的Ito细胞的放松作用。】 复制标题 收藏 收藏
    DOI:10.1002/hep.510250618 复制DOI
    作者列表:Sakamoto M,Ueno T,Sugawara H,Torimura T,Tsuji R,Sujaku K,Sata M,Tanikawa K
    BACKGROUND & AIMS: Interleukin-1beta (IL-1beta) is closely involved in liver disorders. IL-1beta produces nitric oxide (NO) in vascular smooth muscle cells and relaxes vascular smooth muscle via cyclic guanosine 3',5'-monophosphate (cGMP). In this study, we evaluated the relaxing effect of IL-1beta on cultured Ito cells. Ito cells were isolated from the livers of male Wistar rats and cultured for 24 hours. Immunolocalization of inducible nitric oxide synthase (iNOS) and cGMP and intensity of fluorescence of cGMP were examined using a confocal laser microscope. Ito cells were treated with 0, 200, and 1,000 pmol/L IL-1beta, and the intracellular cGMP concentration was measured after 12 hours. Moreover, Ito cells treated with 200 and 1,000 pmol/L IL-1beta and not treated with IL-1beta were observed over 12 hours, and the area of the same Ito cell was compared before and after the addition of IL-1beta. Next, effects of N(G)-monomethyl-L-arginine (L-NMMA) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) on Ito cell relaxation by IL-1beta treatment were examined. In Ito cells, immunofluorescence of iNOS was observed, and fluorescent intensity of cGMP increased after addition of IL-1beta. Intracellular cGMP concentration increased dose-dependently after addition of IL-1beta. Cell area significantly increased in the IL-1beta-treated group compared with the untreated group. Relaxation of Ito cells by IL-1beta treatment was inhibited by L-NMMA in a dose-dependent manner, but was enhanced by SNAP. These results indicate that IL-1beta produces NO in cultured Ito cells and relaxes the cells via cGMP.

    背景与目标: Interleukin-1beta (IL-1beta) 与肝脏疾病密切相关。IL-1beta在血管平滑肌细胞中产生一氧化氮 (NO),并通过环鸟苷3 ',5'-单磷酸 (cGMP) 松弛血管平滑肌。在这项研究中,我们评估了IL-1beta对培养的Ito细胞的松弛作用。从雄性Wistar大鼠的肝脏中分离Ito细胞,并培养24小时。使用共聚焦激光显微镜检查诱导型一氧化氮合酶 (iNOS) 和cGMP的免疫定位以及cGMP的荧光强度。Ito细胞用0、200和1,000 pmol/L IL-1beta处理,12小时后测定细胞内cGMP浓度。此外,在12小时内观察到用200和1,000 pmol/L IL-1beta处理和不用IL-1beta处理的Ito细胞,并比较在添加IL-1beta前后相同Ito细胞的面积。接下来,通过IL-1beta处理检查了N(G)-单甲基-L-精氨酸 (L-NMMA) 和S-亚硝基-N-乙酰基-DL-青霉胺 (SNAP) 对Ito细胞松弛的影响。在Ito细胞中,观察到iNOS的免疫荧光,加入IL-1beta后cGMP的荧光强度增加。加入IL-1beta后,细胞内cGMP浓度呈剂量依赖性增加。与未处理组相比,IL-1beta-treated组的细胞面积显着增加。IL-1beta处理对Ito细胞的松弛以剂量依赖性方式被l-nmma抑制,但被SNAP增强。这些结果表明,IL-1beta在培养的Ito细胞中产生NO,并通过cGMP使细胞松弛。
  • 【谷胱甘肽缺乏症遗传模型中小脑颗粒神经元中软骨藻酸的神经毒性。】 复制标题 收藏 收藏
    DOI:10.1124/mol.106.027748 复制DOI
    作者列表:Giordano G,White CC,McConnachie LA,Fernandez C,Kavanagh TJ,Costa LG
    BACKGROUND & AIMS: :This study investigated the role of cellular antioxidant defense mechanisms in modulating the neurotoxicity of domoic acid (DomA), by using cerebellar granule neurons (CGNs) from mice lacking the modifier subunit of glutamate-cysteine ligase (Gclm). Glutamate-cysteine ligase (Glc) catalyzes the first and rate-limiting step in glutathione (GSH) biosynthesis. CGNs from Gclm (-/-) mice have very low levels of GSH and are 10-fold more sensitive to DomA-induced toxicity than CGNs from Gclm (+/+) mice. GSH ethyl ester decreased, whereas the Gcl inhibitor buthionine sulfoximine increased DomA toxicity. Antagonists of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors and of N-methyl-D-aspartate (NMDA) receptors blocked DomA toxicity, and NMDA receptors were activated by DomA-induced l-glutamate release. The differential susceptibility of CGNs to DomA toxicity was not due to a differential expression of ionotropic glutamate receptors, as evidenced by similar calcium responses and L-glutamate release in the two genotypes. A calcium chelator and several antioxidants antagonized DomA-induced toxicity. DomA caused a rapid decrease in cellular GSH, which preceded toxicity, and the decrease was primarily due to DomA-induced GSH efflux. DomA also caused an increase in oxidative stress as indicated by increases in reactive oxygen species and lipid peroxidation, which was subsequent to GSH efflux. Astrocytes from both genotypes were resistant to DomA toxicity and presented a diminished calcium response to DomA and a lack of DomA-induced L-glutamate release. Because polymorphisms in the GCLM gene in humans are associated with low GSH levels, such individuals, as well as others with genetic conditions or environmental exposures that lead to GSH deficiency, may be more susceptible to DomA-induced neurotoxicity.
    背景与目标: : 这项研究通过使用缺乏谷氨酸-半胱氨酸连接酶修饰亚基 (Gclm) 的小鼠的小脑颗粒神经元 (CGNs),研究了细胞抗氧化防御机制在调节软骨藻酸 (DomA) 神经毒性中的作用。谷氨酸-半胱氨酸连接酶 (Glc) 催化谷胱甘肽 (GSH) 生物合成中的第一个和限速步骤。来自Gclm (-/-) 小鼠的CGNs的GSH水平非常低,并且对DomA诱导的毒性的敏感性比来自Gclm (/) 小鼠的CGNs高10倍。GSH乙酯降低,而Gcl抑制剂丁硫氨酸亚砜肟增加了DomA毒性。alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic/海藻酸盐受体和N-甲基-D-天冬氨酸 (NMDA) 受体的拮抗剂阻断了DomA毒性,并且NMDA受体被DomA诱导的l-谷氨酸释放激活。CGNs对DomA毒性的敏感性差异不是由于离子型谷氨酸受体的表达差异所致,这在两种基因型中钙反应和L-谷氨酸释放相似。钙螯合剂和几种抗氧化剂拮抗DomA诱导的毒性。DomA导致细胞GSH迅速下降,这先于毒性,并且下降主要是由于DomA诱导的GSH外排。DomA还引起了氧化应激的增加,如活性氧种类和脂质过氧化的增加所表明的,这是在GSH外排之后。两种基因型的星形胶质细胞均对DomA毒性具有抗性,并且对DomA的钙反应减弱,并且缺乏DomA诱导的L-谷氨酸释放。由于人类GCLM基因的多态性与低GSH水平相关,因此此类个体以及具有导致GSH缺乏的遗传条件或环境暴露的其他个体可能更容易受到DomA诱导的神经毒性的影响。
  • 【躁狂抑郁症与GABRbeta-1基因高度多态性标记之间的遗传关联研究。】 复制标题 收藏 收藏
    DOI:10.1002/(sici)1096-8628(19970531)74:3<342::aid-ajm 复制DOI
    作者列表:Puertollano R,Visedo G,Zapata C,Fernández-Piqueras J
    BACKGROUND & AIMS: We report on an association study between a tetranucleotide repeat polymorphism in the GABR beta1 gene and manic-depressive illness in a Spanish population. This gene may be an important candidate for bipolar affective disorders since severe GABergic alterations have been described in patients. Although our results do not reveal a clear evidence for association between manic-depressive illness and GABR beta1, we have found significant differences between patients and controls in the female subpopulation.

    背景与目标: 我们报告了一项西班牙人群中GABR beta1基因的四核苷酸重复多态性与躁狂抑郁症之间的关联研究。该基因可能是双相情感障碍的重要候选者,因为已经在患者中描述了严重的GABergic改变。尽管我们的结果并未揭示出躁狂抑郁症与GABR beta1之间存在关联的明确证据,但我们发现女性亚群的患者与对照组之间存在显着差异。
  • 【与DRA X2-box结合的NF-X2是激活蛋白1。c-6月的表达克隆】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Andersson G,Peterlin BM
    BACKGROUND & AIMS: :Human class II MHC Ag are a family of cell surface glycoproteins. Their constitutive expression is limited to B lymphocytes and thymic epithelial cells. In many other cells their expression can be induced by IFN-gamma. Conserved upstream promoter sequences regulate this tissue-specific expression of class II genes. In the DRA promoter, one of these cis-acting regulatory motifs is the X2-box to which nuclear factor X2 (NF-X2) binds. Here, we present the isolation and characterization of the full-length cDNA clone encoding NF-X2. This cDNA clone was isolated by expression cDNA cloning, and encodes the human c-Jun protein, which together with c-Fos forms the heterodimeric activator protein-1 transcription complex. Whereas c-Fos/c-Jun heterodimers do not exist in B cells, they form and bind to the X2-box in class II nonexpressing cells. Thus, c-Fos/c-Jun heterodimers might contribute to the repression of DRA gene expression.
    背景与目标: : 人类II类MHC Ag是细胞表面糖蛋白家族。它们的组成型表达仅限于B淋巴细胞和胸腺上皮细胞。在许多其他细胞中,它们的表达可以通过IFN-γ 诱导。保守的上游启动子序列调节II类基因的这种组织特异性表达。在DRA启动子中,这些顺式作用调节基序之一是核因子X2 (NF-X2) 结合的X2-box。在这里,我们介绍了编码NF-X2的全长cDNA克隆隔离和表征。通过表达cDNA克隆分离该cDNA克隆,并编码人c 6月蛋白,该蛋白与c-Fos一起形成异二聚体激活蛋白1转录复合物。尽管b细胞中不存在c-Fos/c-6月异二聚体,但它们在II类非表达细胞中形成并结合X2-box。因此,c-Fos/c-6月异二聚体可能有助于抑制DRA基因表达。
  • 【使用可生物降解的聚L-丙交酯支架进行髂吻合支架置入术: 1周和6周后的初步研究。】 复制标题 收藏 收藏
    DOI:10.1583/05-1726MR.1 复制DOI
    作者列表:Bünger CM,Grabow N,Sternberg K,Ketner L,Kröger C,Lorenzen B,Hauenstein K,Schmitz KP,Kreutzer HJ,Lootz D,Ince H,Nienaber CA,Klar E,Schareck W
    BACKGROUND & AIMS: PURPOSE:To assess the technical feasibility, thrombogenicity, and biocompatibility of a new biodegradable poly-L-lactic acid (PLLA) anastomotic stent. METHODS:A polytetrafluoroethylene bifurcated graft was implanted in 17 pigs through a midline abdominal incision. After transverse graft incision, 17 316L stainless steel stents and 17 PLLA stents were randomly implanted at both iliac anastomotic sites and deployed with a 6-mm balloon under direct vision without angiography. Intended follow-up was 1 week in 6 pigs receiving oral acetylsalicylic acid (ASA) and in 7 pigs receiving ASA/clopidogrel; 4 pigs receiving ASA/clopidogrel were followed for 6 weeks. At the end of the study, the segments containing the stents were surgically explanted and processed for histology to measure the mean luminal diameter, intimal thickness, and the vascular injury and inflammation scores. RESULTS:Initial technical success of stent placement was achieved in all animals without rupture of the suture. Two pigs died (unrelated to the stent) at 3 days after operation (1 in groups A and B). At 1 week, all PLLA stents showed thrombotic occlusion with the use of ASA alone. In contrast, all PLLA stents remained patent with concurrent administration of ASA/clopidogrel. All metal stents were patent regardless of the antiplatelet regimen. The mean luminal diameter of patent PLLA stents (4.13+/-0.17 mm) was comparable to metal stents (4.27+/-0.35 mm, p=0.78) at 1 week, but significantly diminished at 6 weeks (3.21+/-0.44 versus 4.19+/-0.18 mm, p=0.005). Histological analysis showed no signs of excessive recoil. PLLA stents induced a higher inflammation score (1.79+/-0.56) and more intimal hyperplasia (0.34+/-0.11 mm) compared to metal stents [1.27+/-0.44 mm (p<0.001) and 0.18+/-0.04 mm (p=0.006), respectively] at 6 weeks. Vascular injury was comparable between PLLA and metal stents. CONCLUSION:Biodegradable PLLA stents showed higher thrombogenicity and reduced patency compared to metal stents during early follow-up. Although ASA and clopidogrel prevented thrombotic occlusion, the increased inflammatory response and neointima formation remain major concerns of PLLA stents. A solution to this problem might be the incorporation of anti-inflammatory drugs into the PLLA stent.
    背景与目标:
  • 【图30: 一种新的HIV-1感染和复制抑制剂。】 复制标题 收藏 收藏
    DOI:10.1016/0014-5793(90)80438-o 复制DOI
    作者列表:Lee-Huang S,Huang PL,Nara PL,Chen HC,Kung HF,Huang P,Huang HI,Huang PL
    BACKGROUND & AIMS: :A new inhibitor of human immunodeficiency virus (HIV) has been isolated and purified to homogeneity from the seeds and fruits of the Momordica charantia. This compound, MAP 30 (Momordica Anti-HIV Protein), is a basic protein of about 30 kDa. It exhibits dose-dependent inhibition of cell-free HIV-1 infection and replication as measured by: (i) quantitative focal syncytium formation on CEM-ss monolayers; (ii) viral core protein p24 expression; and (iii) viral-associated reverse transcriptase (RT) activity in HIV-1 infected H9 cells. The doses required for 50% inhibition (ID50) in these assays were 0.83, 0.22 and 0.33 nM, respectively. No cytotoxic or cytostatic effects were found under the assay conditions. These data suggest that MAP 30 may be a useful therapeutic agent in the treatment of HIV-1 infections. The sequence of the N-terminal 44 amino acids of MAP 30 has been determined.
    背景与目标: : 已从苦瓜的种子和果实中分离并纯化出一种新的人类免疫缺陷病毒 (HIV) 抑制剂,使之同质。该化合物MAP 30 (苦味子抗HIV蛋白) 是约30 kDa的碱性蛋白。它表现出对无细胞HIV-1感染和复制的剂量依赖性抑制,通过以下方式测量 :( i) cem-ss单层上的定量局灶性合胞体形成; (ii) 病毒核心蛋白p24表达; 和 (iii) HIV-1感染的H9细胞中的病毒相关逆转录酶 (RT) 活性。在这些测定中50% 抑制所需的剂量 (ID50) 分别为0.83、0.22和0.33 nM。在测定条件下未发现细胞毒性或细胞抑制作用。这些数据表明,MAP 5月30日是治疗HIV-1感染的有用治疗剂。已确定MAP 30的N端44个氨基酸的序列。
  • 【山羊 α-乳白蛋白中单个Trp残基的荧光贡献。】 复制标题 收藏 收藏
    DOI:10.1016/j.bbapap.2006.07.011 复制DOI
    作者列表:Vanhooren A,Illyes E,Majer Z,Hanssens I
    BACKGROUND & AIMS: :Goat alpha-lactalbumin (GLA) contains four tryptophan (Trp) residues. In order to obtain information on the fluorescence contribution of the individual Trp residues in native GLA, we recorded the fluorescence spectra of four GLA mutants, W26F, W60F, W104F, and W118F, in each of which a single Trp residue was replaced with phenylalanine (Phe). Comparison of the fluorescence spectra of the four mutants with that of wild-type GLA indicated that, in native GLA, three Trp residues (Trp60, Trp104, and Trp118) are strongly quenched and account for the partial indirect quenching of Trp26. As a consequence, the fluorescence of wild-type GLA and of the mutants W60F, W104F, and W118F mainly results from Trp26. An inspection of the crystal structure indicated that, in addition to the disulfide bonds that are in direct contact with the indole groups of Trp60 and Trp118, backbone peptide bonds that are in direct contact with the indole groups of Trp60, Trp104, and Trp118, contribute to the direct quenching effects. Interestingly, the lack of direct quenching of Trp26 explains why the cleavage of disulfide bonds by UV light is mediated more by the highly fluorescent Trp26 than by the less fluorescent Trp104 and Trp118.
    背景与目标: : 山羊 α-乳白蛋白 (GLA) 含有四个色氨酸 (Trp) 残基。为了获得有关天然GLA中单个Trp残基的荧光贡献的信息,我们记录了四个GLA突变体W26F,W60F,W104F和W118F的荧光光谱,其中每个单个Trp残基被替换为苯丙氨酸 (Phe)。将四个突变体的荧光光谱与野生型GLA的荧光光谱进行比较表明,在天然GLA中,三个Trp残基 (Trp60,Trp104和Trp118) 被强烈淬灭,并解释了trp26的部分间接猝灭。因此,野生型GLA和突变体W60F,W104F和W118F的荧光主要来自trp26。对晶体结构的检查表明,除了与Trp60和Trp118的吲哚基团直接接触的二硫键外,与Trp60,Trp104和Trp118的吲哚基团直接接触的骨架肽键有助于直接猝灭作用。有趣的是,缺乏Trp26的直接猝灭解释了为什么高荧光的Trp26比低荧光的Trp104和trp118更多地介导紫外光对二硫键的裂解。
  • 【根据哌唑嗪的亲和力,人类良性前列腺肥大组织中的 α-1肾上腺素受体亚型 (高,低)。】 复制标题 收藏 收藏
    DOI:10.1002/(sici)1097-0045(19970601)31:4<216::aid-pro 复制DOI
    作者列表:Takeda M,Hatano A,Komeyama T,Koizumi T,Mizusawa T,Kanai T,Tomita Y,Maruyama K,Nagatomo T
    BACKGROUND & AIMS: BACKGROUND:A novel classification of alpha-1 adrenoceptor subtypes (High, Low) was applied to human benign prostatic hypertrophy (BPH) tissue. METHODS:Human BPH specimens were examined by a radioligand binding assay method using 3H-prazosin, and those data were compared with preoperative therapies. RESULTS:(1) Scatchard analysis showed a high-affinity site (Kd:27.18 +/- 6.41 pM; Bmax:9.29 +/- 0.98 fM/mg protein; mean +/- SE) as alpha 1H, and a low-affinity site (Kd: 4088.0 +/- 744.34 pM, Bmax: 140.81 +/- 19.98 fM/mg protein) as alpha 1L subtype, for prazosin. (2) The Kd and Bmax were not different in the nontreated group (n = 5), alpha 1 blocker group (n = 5), and antiandrogen group (n = 5), in either alpha 1-high affinity or alpha 1-low affinity subtype. (3) Phenoxybenzamine had different pKi values for the above two adrenoceptor subtypes. Scatchard analysis showed that alpha 1-high affinity binding site disappeared in the presence of 1 microM of phenoxybenzamine, and the Kd and Bmax values in the presence of 1 microM of phenoxybenzamine were almost identical to the alpha 1-low affinity site of the two subtypes. CONCLUSIONS:Human BPH tissue possesses both alpha 1H- and alpha 1L-adrenoceptor subtypes according to the affinities for prazosin, and only the alpha 1H subtype can be completely inhibited by some concentration of phenoxybenzamine. Treatment by alpha 1 blocker may not change the conditions of alpha 1-adrenoceptors in prostatic tissue.
    背景与目标:
  • 【产气荚膜梭菌的 α 毒素不是鸡坏死性肠炎的必需毒力因子。】 复制标题 收藏 收藏
    DOI:10.1128/IAI.00806-06 复制DOI
    作者列表:Keyburn AL,Sheedy SA,Ford ME,Williamson MM,Awad MM,Rood JI,Moore RJ
    BACKGROUND & AIMS: :The Clostridium perfringens alpha-toxin has previously been implicated as the major virulence factor in necrotic enteritis in chickens, although definitive proof has not been reported. In this study an alpha-toxin mutant was constructed in a virulent chicken isolate and shown to retain full virulence in a chicken disease model. These results demonstrated that alpha-toxin is not an essential virulence factor in the pathogenesis of necrotic enteritis in chickens.
    背景与目标: : 尽管尚未报道明确的证据,但以前曾将产气荚膜梭菌 α 毒素作为鸡坏死性肠炎的主要毒力因子。在这项研究中,在强毒鸡分离株中构建了一个 α 毒素突变体,并显示在鸡疾病模型中保留了完全的毒力。这些结果表明,在鸡坏死性肠炎的发病机理中,α-毒素不是必需的毒力因子。
  • 【巴巴多斯黑人中的严重原发性HIV-1感染。】 复制标题 收藏 收藏
    DOI:10.1258/0956462971920325 复制DOI
    作者列表:Hudson CP,Levett PN,Edwards CN,Moosai R,Roach TC
    BACKGROUND & AIMS: :Descriptions of primary HIV-1 infection have so far been based on Caucasians living in industrialized nations. Due to studies of leptospirosis in the predominantly black population of Barbados, serum was available for patients admitted with acute febrile illnesses to the Queen Elizabeth Hospital (QEH). By searching the medical records of 510 adult patients with known HIV-1 infection we identified 10 patients who had stored serum from an admission for an acute febrile illness that predated or coincided with their first HIV-1-positive test. Serological testing confirmed primary HIV-1 infection in 9 and was suggestive in the 10th patient. The clinical features of these 10 patients were in keeping with previous descriptions of primary HIV-1 infection but differed from leptospirosis cases seen at the QEH. One patient died during his seroconversion illness and another died 3 months after seroconversion. The findings suggest that severe primary HIV-1 infection could be a relatively uncommon occurrence, that the condition may be misdiagnosed, and that cases may not occur until the AIDS epidemic is established. :A retrospective review was conducted of the medical records of 510 HIV-1-positive adult patients who had attended the Queen Elizabeth Hospital (QEH) to determine whether any had been admitted for an illness compatible with a diagnosis of primary HIV-1 infection. A serum bank, created from patients who had been admitted with acute febrile illnesses and investigated for leptospirosis, provided serological evidence for primary HIV-1 infection in 10 patients. Serological testing of the serum samples confirmed primary HIV-1 infection in nine patients and was suggestive in the tenth. The clinical features of the 10 patients fit the earlier descriptions of primary HIV-1 infection, but differed from the leptospirosis cases seen at the QEH. One patient died during his seroconversion illness and another died 3 months after seroconversion. These findings suggest that severe primary HIV-1 infection could be a relatively uncommon occurrence, that the condition may be misdiagnosed, and that cases may not occur until the AIDS epidemic is established.
    背景与目标:

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