• 【使用iodine-123-N-(2-二乙氨基乙基) 4-碘苯甲酰胺SPECT观察眼部黑色素瘤。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Everaert H,Bossuyt A,Flamen P,Mertens J,Franken PR
    BACKGROUND & AIMS: UNLABELLED:Radiolabeled benzamides have recently been introduced for the detection of melanoma. We evaluated the potential clinical applicability of 123I-N-(2-diethylaminoethyl) 4-iodobenzamide ([123I]IDAB) for SPECT imaging of ocular melanoma.

    METHODS:Fourteen patients were studied, 10 with or suspected of malignant ocular melanoma and four with ocular naevi. All patients underwent SPECT imaging of the head and whole-body scintigraphy 4-5 hr after injection of 170 MBq [123I]IDAB.

    RESULTS:A definite tracer hyperfixation was observed in the pathological eye in 9 of 10 (90%) patients with ocular melanoma. The pathological-to-normal eye ratio averaged 1.46 (range 1.07-2.86). The melanoma nature of the scintigraphic lesions was confirmed after enucleation in eight cases and by clinical evolution in two. A false-negative scan was reported in a patient with a small and hypochromic lesion. In patients with ocular naevi, no false-positive scintigrams were documented.

    CONCLUSION:Iodine-123-IDAB scintigraphy may contribute significantly to decide about enucleation in cases where some doubt persists with conventional techniques.

    背景与目标: 未标记 : 最近已引入放射性标记的苯甲酰胺用于检测黑色素瘤。我们评估了123I-N-(2-二乙氨基乙基) 4-碘苯甲酰胺 ([123I]IDAB) 在眼部黑色素瘤SPECT成像中的潜在临床适用性。
    方法 : 研究了14名患者,10例患有或怀疑患有恶性眼部黑色素瘤,4例患有眼部恶性黑色素瘤。注射170 MBq [123I]IDAB后4-5小时,所有患者均接受了头部SPECT成像和全身闪烁显像。
    结果 : 在10例 (90% 例) 眼部黑色素瘤患者中,有9例在病理眼中观察到了明确的示踪剂超固定。病理与正常眼的比率平均为1.46 (范围1.07-2.86)。闪烁显像病变的黑色素瘤性质在8例摘除后得到证实,两例通过临床进化得到证实。在一名患有小的低色度病变的患者中报告了假阴性扫描。在患有眼痣的患者中,没有记录假阳性闪烁图。
    结论 : 在常规技术仍然存在疑问的情况下,Iodine-123-IDAB闪烁显像可能会大大有助于决定摘除。
  • 【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。
  • 【疾病机制: 2型糖尿病的肝脂肪变性-发病机制和临床意义。】 复制标题 收藏 收藏
    DOI:10.1038/ncpendmet0190 复制DOI
    作者列表:Roden M
    BACKGROUND & AIMS: :Hepatic steatosis is defined by an increased content of hepatocellular lipids (HCLs) and is frequently observed in insulin-resistant states including type 2 diabetes mellitus. A dietary excess of saturated fat contributes significantly to HCL accumulation. Elevated HCL levels mainly account for hepatic insulin resistance, which is probably mediated by partitioning of free fatty acids to the liver (fat overflow) and by an imbalance of adipocytokines (decreased adiponectin and/or increased proinflammatory cytokines). Both free fatty acids and adipocytokines activate inflammatory pathways that include protein kinase C, the transcription factor nuclear factor kappaB, and c-Jun N-terminal kinase 1 and can thereby accelerate the progression of hepatic steatosis to nonalcoholic steatohepatitis and cirrhosis. Proton magnetic resonance spectroscopy has made it possible to quantify HCL concentrations and to detect even small changes in these concentrations in clinical settings. Moderately hypocaloric, fat-reduced diets can decrease HCL levels by approximately 40-80% in parallel with loss of up to 8% of body weight. Treatment with thiazolidinediones (e.g. pioglitazone and rosiglitazone) reduces HCL levels by 30-50% by modulating insulin sensitivity and endocrine function of adipose tissue in type 2 diabetes. Metformin improves hepatic insulin action without affecting HCL levels, whereas insulin infusion for 67 h increases HCL levels by approximately 18%; furthermore, HCL levels positively correlate with the insulin dosage in insulin-treated type 2 diabetes. In conclusion, liver fat is a critical determinant of metabolic fluxes and inflammatory processes, thereby representing an important therapeutic target in insulin resistance and type 2 diabetes mellitus.
    背景与目标: : 肝脂肪变性是由肝细胞脂质 (HCLs) 含量增加定义的,在胰岛素抵抗状态 (包括2型糖尿病) 中经常观察到。饮食中过量的饱和脂肪会显着促进HCL的积累。HCL水平升高主要是导致肝胰岛素抵抗的原因,这可能是由游离脂肪酸分配到肝脏 (脂肪溢出) 和脂肪细胞因子失衡 (脂联素减少和/或促炎细胞因子增加) 介导的。游离脂肪酸和脂肪细胞因子都激活炎症途径,包括蛋白激酶C,转录因子核因子kappaB和c 6月N端激酶1,从而可以加速肝脂肪变性向非酒精性脂肪性肝炎和肝硬化的进展。质子磁共振波谱已使量化HCL浓度并在临床环境中检测到这些浓度的微小变化成为可能。中度低热量,减脂饮食可使HCL水平降低约40-80%,同时减少多达8% 的体重。噻唑烷二酮类药物 (例如吡格列酮和罗格列酮) 的治疗通过调节2型糖尿病中脂肪组织的胰岛素敏感性和内分泌功能,将HCL水平降低30-50%。二甲双胍改善肝胰岛素作用而不影响HCL水平,而胰岛素输注67小时可使HCL水平增加约18%; 此外,在胰岛素治疗的2型糖尿病中,HCL水平与胰岛素剂量呈正相关。总之,肝脏脂肪是代谢通量和炎症过程的关键决定因素,因此是胰岛素抵抗和2型糖尿病的重要治疗目标。
  • 4 bcl-2 expression in pilomatricoma. 复制标题 收藏 收藏

    【bcl-2在毛瘤中的表达。】 复制标题 收藏 收藏
    DOI:10.1097/00000372-199706000-00009 复制DOI
    作者列表:Farrier S,Morgan M
    BACKGROUND & AIMS: Pilomatricoma is a distinctive tumor characterized by a dual population of proliferating basophilic cells and diagnostic shadow cells, believed to arise from the hair matrix. The normal hair matrix undergoes defined cycles of growth (anagen), regression (catagen), and resting (telogen) that are regulated by programmed cell death (apoptosis). bcl-2 is a proto-oncogene that helps to suppress apoptosis in both benign and malignant tumors. In addition, both apoptosis and bel-2 are critical factors in normal hair follicle development. In order to clarify the role of bcl-1, we used immunohistochemical means to study 10 cases of histologically proven pilomatricoma for bcl-2 expression. The study design included both positive and negative controls. All of the pilomatricomas in our series were strongly decorated by bcl-2 immunostaining. Based on our findings of increased bcl-2 staining, we concluded that the faulty suppression of apoptosis contributes to the pathogenesis of pilomatricoma.

    背景与目标: 毛瘤瘤是一种独特的肿瘤,其特征是增殖的嗜碱性细胞和诊断阴影细胞的双重群体,据信它们是由毛发基质引起的。正常的头发基质经历了由程序性细胞死亡 (凋亡) 调节的生长 (anagen),回归 (catagen) 和静息 (telogen) 周期。bcl-2是一种原癌基因,有助于抑制良性和恶性肿瘤的细胞凋亡。此外,细胞凋亡和bel-2都是正常毛囊发育的关键因素。为了阐明bcl-1的作用,我们使用免疫组织化学手段研究了10例经组织学证实的毛瘤bcl-2表达。研究设计包括阳性和阴性对照。我们系列中的所有绒毛瘤均通过bcl-2免疫染色强烈修饰。根据我们对bcl-2染色增加的发现,我们得出结论,对细胞凋亡的错误抑制有助于毛瘤的发病机理。
  • 【鸡GATA-2和GATA-3的N端指是独立的序列特异性DNA结合结构域。】 复制标题 收藏 收藏
    DOI:10.1093/emboj/16.10.2874 复制DOI
    作者列表:Pedone PV,Omichinski JG,Nony P,Trainor C,Gronenborn AM,Clore GM,Felsenfeld G
    BACKGROUND & AIMS: The GATA family of vertebrate DNA binding regulatory proteins are expressed in diverse tissues and at different times of development. However, the DNA binding regions of these proteins possess considerable homology and recognize a rather similar range of DNA sequence motifs. DNA binding is mediated through two domains, each containing a zinc finger. Previous results have led to the conclusion that although in some cases the N-terminal finger can contribute to specificity and strength of binding, it does not bind independently, whereas the C-terminal finger is both necessary and sufficient for binding. Here we show that although this is true for the N-terminal finger of GATA-1, those of GATA-2 and GATA-3 are capable of strong independent binding with a preference for the motif GATC. Binding requires the presence of two basic regions located on either side of the N-terminal finger. The absence of one of these near the GATA-1 N-terminal finger probably accounts for its inability to bind. The combination of a single finger and two basic regions is a new variant of a motif that has been previously found in the binding domains of other finger proteins. Our results suggest that the DNA binding properties of the N-terminal finger may help distinguish GATA-2 and GATA-3 from GATA-1 and the other GATA family members in their selective regulatory roles in vivo.

    背景与目标: 脊椎动物DNA结合调节蛋白的GATA家族在不同的组织和发育的不同时间表达。但是,这些蛋白质的DNA结合区域具有相当大的同源性,并且可以识别相当相似范围的DNA序列基序。DNA结合通过两个结构域介导,每个结构域都包含一个锌指。先前的结果得出的结论是,尽管在某些情况下,N末端手指可以促进特异性和结合强度,但它不会独立结合,而C末端手指对于结合既必要又足够。在这里,我们表明,尽管对于GATA-1的N末端手指是正确的,但GATA-2和GATA-3的手指能够强烈独立结合,并且偏爱基序GATC。结合需要存在位于N末端手指两侧的两个基本区域。在GATA-1的N末端手指附近没有这些手指之一可能是其无法结合的原因。单个手指和两个基本区域的组合是基序的新变体,以前已在其他手指蛋白的结合域中发现。我们的结果表明,N末端手指的DNA结合特性可能有助于将GATA-2和GATA-3与GATA-1和其他GATA家族成员在体内的选择性调节作用区分开。
  • 【T(2) 加权的显微mri和视觉系统的诱发电位在低髓转基因小鼠的发育过程中测量。】 复制标题 收藏 收藏
    DOI:10.1007/s11064-006-9121-z 复制DOI
    作者列表:Martin M,Reyes SD,Hiltner TD,Givogri MI,Tyszka JM,Fisher R,Campagnoni AT,Fraser SE,Jacobs RE,Readhead C
    BACKGROUND & AIMS: :Our objective was to follow the course of a dysmyelinating disease followed by partial recovery in transgenic mice using non-invasive high-resolution (117 x 117 x 70 microm) magnetic resonance (microMRI) and evoked potential of the visual system (VEP) techniques. We used JOE (for J37 golli overexpressing) transgenic mice engineered to overexpress golli J37, a product of the Golli-mbp gene complex, specifically in oligodendrocytes. Individual JOE transgenics and their unaffected siblings were followed from 21 until 75-days-old using non-invasive in vivo VEPs and 3D T2-weighted microMRI on an 11.7 T scanner, performing what we believe is the first longitudinal study of its kind. The microMRI data indicated clear, global hypomyelination during the period of peak myelination (21-42 days), which was partially corrected at later ages (>60 days) in the JOE mice compared to controls. These microMRI data correlated well with [Campagnoni AT (1995) "Molecular biology of myelination". In: Ransom B, Kettenmann H (eds) Neuroglia--a Treatise. Oxford University Press, London, pp 555-570] myelin staining, [Campagnoni AT, Macklin WB (1988) Cellular and molecular aspects of myelin protein gene-expression. Mol Neurobiol 2:41-89] a transient intention tremor during the peak period of myelination, which abated at later ages, and [Lees MB, Brostoff SW (1984) Proteins in myelin. In: Morell (ed) Myelin. Plenum Press, New York and London, pp 197-224] VEPs which all indicated a significant delay of CNS myelin development and persistent hypomyelination in JOE mice. Overall these non-invasive techniques are capable of spatially resolving the increase in myelination in the normally developing and developmentally delayed mouse brain.
    背景与目标: : 我们的目标是使用非侵入性高分辨率 (117x70 microm) 磁共振 (microMRI) 和视觉系统诱发电位 (VEP) 技术,跟踪畸形疾病的过程,然后在转基因小鼠中进行部分恢复。我们使用了JOE (用于J37 golli过表达) 转基因小鼠,该小鼠经过工程改造以过表达golli J37,Golli-mbp基因复合物的产物,特别是在少突胶质细胞中。从21天到75天大,在11.7 T扫描仪上使用非侵入性体内vep和3D T2-weighted显微mri跟踪了JOE transgenics及其未受影响的兄弟姐妹,我们认为这是同类研究中的首次纵向研究。microMRI数据表明,在髓鞘形成峰值期间 (21-42天),明显的整体髓鞘减少,与对照组相比,JOE小鼠在以后的年龄 (>60天) 得到了部分纠正。这些显微mri数据与 [Campagnoni在 (1995) “髓鞘形成的分子生物学” 处具有很好的相关性。In: Ransom B,Kettenmann H (eds) 神经胶质-一篇论文。牛津大学出版社,伦敦,pp 555-570] 髓磷脂染色,[Campagnoni AT,macklin WB (1988) 髓鞘蛋白基因表达的细胞和分子方面。Mol Neurobiol 2:41-89] 在髓鞘形成的高峰期短暂的意图震颤,在以后的年龄减弱,并且 [Lees MB,Brostoff SW (1984) 蛋白在髓鞘中: morell (ed) 髓鞘。纽约和伦敦的Plenum出版社,pp 197-224] VEPs,所有这些都表明乔小鼠中枢神经系统髓鞘发育和持续的低髓鞘作用显着延迟。总体而言,这些非侵入性技术能够在空间上解决正常发育和发育延迟的小鼠大脑中髓鞘形成的增加。
  • 【[分子生物学为日常医学病毒学服务。2.在病毒学诊断中的应用]。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Wattré P
    BACKGROUND & AIMS: :Molecular biology techniques are applied for the diagnosis of meningoencephalitis due to herpesviruses, enteroviruses or polyomaviruses, for the diagnosis of human cytomegalovirus, human parvovirus B19, varicella-zoster virus and rubella virus infections occurring during pregnancy, for the diagnosis and the management of retrovirus infections (HIV and HTLV) and of hepatitis (HBV and HCV), for papillomavirus typing and to detect a link between virus and clinical manifestations (cardiomyopathy or insulinodependent diabetes with coxsackievirus B: Kaposi's sarcoma with HHV 8) or to investigate an environmental contamination with viruses. These new molecular markers which are both qualitative and quantitative represent an important advance in the field of viral diagnosis research, in the monitoring of viral load during the course of infection, in the therapy control of viral disease and in the epidemiology of virus spread. Standardization and automatization are obtained using available commercial reagents and kits.
    背景与目标: : 分子生物学技术用于诊断由疱疹病毒,肠病毒或多瘤病毒引起的脑膜脑炎,用于诊断人巨细胞病毒病毒,人细小病毒B19,水痘病毒病毒和怀孕期间发生的风疹病毒病毒,用于诊断和管理复古病毒感染 (HIV和HTLV) 和肝炎 (HBV和HCV),乳头瘤病毒分型,并检测病毒与临床表现 (心肌病或胰岛素依赖型糖尿病与柯萨奇病毒B: 卡波西氏肉瘤与HHV 8) 或调查病毒es的环境污染。这些定性和定量的新分子标记物代表了病毒诊断研究领域,感染过程中病毒载量的监测,病毒性疾病的治疗控制以及病毒传播流行病学领域的重要进展。使用可用的商业试剂和试剂盒可获得标准化和自动化。
  • 【设计为MMP-3抑制剂的2-邻苯二甲酰亚胺戊二酸类似物的硅铅系列初步研究。】 复制标题 收藏 收藏
    DOI:10.1021/ci0601362 复制DOI
    作者列表:Amin EA,Welsh WJ
    BACKGROUND & AIMS: :Matrix metalloproteinases (MMPs) have been the subject of intense research because of their roles in tumor metastasis and in the rise and spread of degenerative diseases such as osteo- and rheumatoid arthritis. A preliminary class of 140 druglike, small-molecule matrix metalloproteinase-3 inhibitors, intended as starting scaffolds for optimization and synthesis, has been designed in silico using a series of highly predictive three-dimensional quantitative structure-activity relationship models, including comparative molecular field analysis and comparative molecular similarity indices analysis, with docking and scoring. Thalidomide was chosen as the skeleton on which to base the new lead series, as it moderately inhibits MMP-3, is antiangiogenic, and lends itself easily to structural modifications. Most of the new compounds demonstrate medium to high predicted biological activity and good bioavailability as estimated by the octanol-water partition coefficient ClogP. Compound 102 in particular exhibits extremely favorable predicted activity against MMP-3; is moderately bioavailable; satisfies Lipinski's Rule of Five; and shows promise for further optimization, synthesis, and experimental evaluation as a potential adjunct anticancer or antirheumatic therapeutic.
    背景与目标: : 基质金属蛋白酶 (MMPs) 由于其在肿瘤转移以及退行性疾病 (如骨关节炎和类风湿性关节炎) 的兴起和传播中的作用而成为深入研究的主题。初步设计了140类药物小分子基质metalloproteinase-3抑制剂,作为优化和合成的起始支架,使用一系列高度预测性的三维定量构效关系模型,包括比较分子场分析和比较分子相似性指数分析,对接和得分。沙利度胺被选为新铅系列的骨架,因为它适度抑制MMP-3,具有抗血管生成作用,并且易于进行结构修饰。根据辛醇-水分配系数ClogP估计,大多数新化合物表现出中等至高的预测生物活性和良好的生物利用度。化合物102尤其表现出对MMP-3极其有利的预测活性; 具有适度的生物利用度; 满足Lipinski的五法则; 并显示出有望进一步优化,合成和实验评估作为潜在的辅助抗癌或抗风湿治疗剂。
  • 【小鼠6号染色体上的2 mb YAC重叠群和自然杀伤基因复合物的物理图谱。】 复制标题 收藏 收藏
    DOI:10.1006/geno.1997.4721 复制DOI
    作者列表:Brown MG,Fulmek S,Matsumoto K,Cho R,Lyons PA,Levy ER,Scalzo AA,Yokoyama WM
    BACKGROUND & AIMS: :We have constructed a physical map of a > 2-Mb region on mouse chromosome 6 that contains the natural killer gene complex (NKC). The map comprises a contig of 14 overlapping yeast artificial chromosomes onto which we positioned 25 NKC markers. NKC genetically linked genes encode > 17 proteins that directly control innate NK cell-mediated tumor lysis and disease resistance. Herein we show that Nkrp1 genes are clustered in a region flanked by A2m and Cd69 genes and that most Ly49 genes are clustered in a distal region -1 Mb distant. Importantly, syntenic intervals of mouse chromosome 6 and human chromosome 12p that include the NKC are conserved. NKC species conservation suggests that the human NKC may contain orthologues for the mouse viral disease resistance genes, Cmv1 and Rmp1. The high-resolution NKC map will facilitate investigation of NKC gene regulation and identification of phenotypically defined gene products that confer NK cell defense against viral pathogens.
    背景与目标: : 我们已经在小鼠6号染色体上构建了一个> 2-Mb区域的物理图,其中包含自然杀伤基因复合物 (NKC)。该图谱包含14个重叠的酵母人工染色体的重叠群,我们在其上定位了25个NKC标记。NKC基因连接的基因编码> 17种直接控制先天NK细胞介导的肿瘤溶解和抗病的蛋白质。在本文中,我们显示Nkrp1基因聚集在A2m和Cd69基因两侧的区域中,并且大多数Ly49基因聚集在远端区域-1 Mb远处。重要的是,包含NKC的小鼠6号染色体和人类12p染色体的同义间隔是保守的。NKC物种保护表明,人类NKC可能包含小鼠病毒抗病基因Cmv1和rmp1的直系同源物。高分辨率NKC图谱将有助于NKC基因调控的研究和表型定义的基因产物的鉴定,这些基因产物赋予NK细胞针对病毒病原体的防御能力。
  • 【人类Achaete-Scute同源物2 (ASCL2,HASH2) 映射到11p15.5号染色体,接近IGF2,并在绒毛外滋养细胞中表达。】 复制标题 收藏 收藏
    DOI:10.1093/hmg/6.6.859 复制DOI
    作者列表:Alders M,Hodges M,Hadjantonakis AK,Postmus J,van Wijk I,Bliek J,de Meulemeester M,Westerveld A,Guillemot F,Oudejans C,Little P,Mannens M
    BACKGROUND & AIMS: Here we describe the cloning of the human Achaete Scute Homologue 2 (HASH2) gene, officially designated ASCL2 (Achaete Scute complex like 2), a homologue of the Drosophila Achaete and Scute genes. In mouse, this gene is imprinted and maps to chromosome 7. We mapped the human homologue close to IGF2 and H19 at 11p15.5, the human region syntenic with mouse chromosome 7, indicating that this imprinted region is highly conserved in mouse and man. HASH2 is expressed in the extravillus trophoblasts of the developing placenta only. The lack of HASH2 expression in non-malignant hydatidiform (androgenetic) moles indicates that HASH2 is also imprinted in man.

    背景与目标: 在这里,我们描述了人类Achaete Scute同源物2 (HASH2) 基因的克隆,该基因正式命名为ASCL2 (Achaete Scute complex like 2),这是果蝇Achaete和Scute基因的同源物。在小鼠中,该基因被印记并映射到7号染色体。我们在11p15.5处绘制了接近IGF2和H19的人类同源物,该人类区域与小鼠7号染色体同义,表明该印迹区域在小鼠和人类中高度保守。HASH2仅在发育中的胎盘的绒毛外滋养细胞中表达。HASH2在非恶性葡萄胎 (雄激素) 痣中缺乏表达,表明HASH2在人类中也有印记。
  • 【吸入类固醇/长效 β2激动剂组合产品可改善成人哮喘患者的24小时肺功能。】 复制标题 收藏 收藏
    DOI:10.1186/1465-9921-7-110 复制DOI
    作者列表:Lötvall J,Langley S,Woodcock A
    BACKGROUND & AIMS: BACKGROUND:The combination of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) is recommended by treatment guidelines for the treatment of persistent asthma. Two such combination products, salmeterol/fluticasone propionate (SFC, Seretide GSK, UK) and formoterol/budesonide (FBC, Symbicort, AstraZeneca, UK) are commercially available. OBJECTIVES:The purpose of these studies was to evaluate and compare the duration of bronchodilation of both combination products up to 24 hours after a single dose. METHODS:Two randomised, double blind, placebo-controlled, crossover studies were performed. Study A was conducted in 33 asthmatic adults receiving 400-1200 mcg of budesonide or equivalent. Serial forced expiratory volume in one second (FEV1) was measured over 24 hours to determine the duration of effect of both SFC (50/100 mcg) and FBC (4.5/160 mcg). Study B was conducted in 75 asthmatic adults receiving 800-1200 mcg of budesonide or equivalent and comprised a 4 week run-in of 400 mcg bd Becotide followed by 4 weeks treatment with either SFC 50/100 mcg bd or FBC 4.5/160 mcg bd taken in a cross-over manner. Serial 24-hour FEV1 was measured after the first dose and the last dose after each 4-weeks treatment period to determine the offset of action of each treatment. RESULTS:In study A, a single inhalation of SFC and FBC produced a sustained bronchodilation at 16 hours with an adjusted mean increase in FEV1 from pre-dose of 0.22 L (95% CI 0.19, 0.35 L) for SFC and 0.25 L (95% CI 0.21, 0.37 L) for FBC, which was significantly greater than placebo for both treatments (-0.05 L; p < 0.001). In study B, the slope of decline in FEV1 from 2-24 hours post dose was -16.0 ml/hr for SFC and -14.2 ml/hr for FBC. The weighted mean AUC over 24 hours was 0.21 Lxmin and 0.22 Lxmin and mean change from pre-dose FEV1 at 12 hours was 0.21 L for SFC and 0.20 L for FBC respectively CONCLUSION:Both SFC and FBC produced a similar sustained bronchodilator effect which was prolonged beyond 12 hours post dose and was clearly measurable at 24 h.
    背景与目标:
  • 【交联聚 (1-乙烯基-2-吡咯烷酮) 凝胶对静态细胞培养中细胞生长的影响。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Hong Y,Chirila TV,Fitton JH,Ziegelaar BW,Constable IJ
    BACKGROUND & AIMS: Poly(1-vinyl-2-pyrrolidinone) (PVP) and copolymers of 1-vinyl-2-pyrrolidinone are insoluble in water when crosslinked but they can absorb very large amounts of water to become syringe-injectable hydrogels. Such gels have been investigated recently as potential substitutes for the vitreous humour in the eye. In this study, during the cytotoxic evaluation by sulforhodamine B colorimetric assay of variously crosslinked PVP gels, it was found that many of them showed protective/growth promoting effects on 3T3 mouse fibroblasts in static cultures, a phenomenon encountered previously only with aqueous solutions of a limited number of natural or synthetic polymers. Particularly, the gels crosslinked with diethylene glycol dimethacrylate (DEGDMA) induced a significant enhancement of cell proliferation, especially in serum-free cultures. No correlation between this effect and the essential gel properties (chemical composition, viscoelasticity and equilibrium water content) could be established. The study demonstrated that crosslinked PVP hydrogels showed a serum-like growth promoting effect on an anchorage-dependent cell line, which may be due to physical protection, inability of the insoluble gels to penetrate cell membranes, and their ability to mimic the extracellular matrix.

    背景与目标: 聚 (1-乙烯基-2-吡咯烷酮) (PVP) 和1-乙烯基-2-吡咯烷酮的共聚物在交联时不溶于水,但它们可以吸收大量的水,成为可注射器注射的水凝胶。最近已经研究了这种凝胶作为眼睛玻璃体液的潜在替代品。在这项研究中,在通过sulforhodamine B比色法对各种交联的PVP凝胶进行细胞毒性评估期间,发现其中许多凝胶对静态培养中的3T3小鼠成纤维细胞表现出保护/促进生长的作用,这种现象以前仅在水溶液中遇到。有限数量的天然或合成聚合物。特别是,与二甘醇二甲基丙烯酸酯 (DEGDMA) 交联的凝胶可显着增强细胞增殖,尤其是在无血清培养物中。无法建立这种作用与基本凝胶特性 (化学成分,粘弹性和平衡水含量) 之间的相关性。研究表明,交联的PVP水凝胶对锚定依赖性细胞系表现出类似血清的生长促进作用,这可能是由于物理保护,不溶性凝胶无法穿透细胞膜以及它们模仿细胞外基质的能力。
  • 【印度链球菌JCM中含2-脱氧链霉菌的抗生素的生物合成3268: 2-脱氧-scyllo-肌糖合酶的表征。】 复制标题 收藏 收藏
    DOI:10.1038/ja.2006.51 复制DOI
    作者列表:Hirayama T,Tamegai H,Kudo F,Kojima K,Kakinuma K,Eguchi T
    BACKGROUND & AIMS: :A part of the new biosynthetic gene cluster for 2-deoxystreptamine-containing antibiotics was identified from Streptoalloteichus hindustanus. The alloH gene in the gene cluster was deduced to encode 2-deoxy-scyllo-inosose synthase and the expressed protein AlloH was confirmed to have this enzyme activity. Furthermore, biochemical properties of AlloH were studied.
    背景与目标: : 从Streptoalloteichus hindustanus中鉴定出了含2-脱氧链霉菌的抗生素的新生物合成基因簇的一部分。推导了基因簇中的alloH基因编码2-脱氧-scyllo-肌糖合酶,并确认表达的蛋白AlloH具有该酶活性。此外,还研究了AlloH的生化特性。
  • 【腺病毒药物2-氨基嘌呤可防止细胞蛋白质合成的抑制。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.87.18.7115 复制DOI
    作者列表:Huang JT,Schneider RJ
    BACKGROUND & AIMS: :Adenovirus infection results in the suppression of cellular protein synthesis, but the mechanism has not been established. In this report we demonstrate that the shut-off of cellular protein synthesis by adenovirus is prevented in cells by treatment with the drug 2-aminopurine. Treatment with 2-aminopurine is shown to prevent suppression of cellular translation without disrupting the normal viral block in the transport of cellular mRNAs from the nucleus to the cytoplasm. We show that viral suppression of cellular protein synthesis occurs concomitant with activation of the interferon-induced double-stranded RNA-activated inhibitor (DAI), a protein kinase, and phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2 alpha), but that prevention of host cell shut-off by 2-aminopurine occurs without a decrease in kinase activity or a dephosphorylation of eIF-2 alpha. Results are presented that indicate that activation of DAI kinase and phosphorylation of eIF-2 alpha may be required but are not sufficient to achieve inhibition of cellular protein synthesis during adenovirus infection. We suggest that other events, in particular the modification of additional initiation factors, are likely involved in viral inhibition of cellular translation.
    背景与目标: : 腺病毒感染导致细胞蛋白质合成的抑制,但机制尚未建立。在本报告中,我们证明了通过用药物2-氨基嘌呤处理可防止细胞中腺病毒对细胞蛋白质合成的切断。显示用2-氨基嘌呤处理可防止抑制细胞翻译,而不会破坏细胞mrna从细胞核到细胞质转运中的正常病毒阻滞。我们显示,细胞蛋白合成的病毒抑制与干扰素诱导的双链RNA激活抑制剂 (DAI),蛋白激酶的激活以及真核起始因子2 (eIF-2 α) 的 α 亚基的磷酸化同时发生,但是,通过2-氨基嘌呤阻止宿主细胞关闭而不会降低激酶活性或eIF-2 α 的去磷酸化。结果表明DAI激酶的活化和eIF-2 α 的磷酸化可能是必需的,但不足以在腺病毒感染期间实现细胞蛋白合成的抑制。我们建议其他事件,尤其是其他起始因子的修饰,可能与病毒对细胞翻译的抑制有关。
  • 【Β1-和 β2-肾上腺素能受体在三环抗抑郁药的抗伤害感受作用中的意义。】 复制标题 收藏 收藏
    DOI:10.1016/s0924-977x(97)00411-2 复制DOI
    作者列表:Micó JA,Gibert-Rahola J,Casas J,Rojas O,Serrano MI,Serrano JS
    BACKGROUND & AIMS: Tricyclic antidepressants have been shown to be useful for the treatment of pain of varying etiology. Monoaminergic systems seem to be implicated in this phenomenon. In this study, the influence of the selective beta 1- (CGP 20712A) and beta 2- (ICI 118551) adrenergic blockers on the antinociceptive effect of desipramine and nortriptyline was studied in mice using physical and chemical nociceptive tests that implicate different levels of sensory-motor integration in the central nervous system (CNS). An activity test was performed to detect "false positive" or "false negative" results. Results obtained show that both CGP 20712A and ICI 118551 are able to antagonize the antinociceptive effect of these antidepressants in physical tests (hot-plate and tail-flick). However, in chemical tests (acetic acid and formalin), the analgesic effect of the antidepressants used was only antagonized by CGP 20712A. These results suggest that the analgesic effect of desipramine and nortriptyline is mediated by beta-adrenoceptors. The beta-adrenoceptor involved depends on the type of nociceptive stimulusbeta 1 and beta 2 are both implicated when the stimulus is physical, but only beta 1 is involved when the stimulus is chemical.

    背景与目标: 三环抗抑郁药已被证明可用于治疗不同病因的疼痛。单胺能系统似乎与这种现象有关。在这项研究中,使用物理和化学伤害性测试在小鼠中研究了选择性 β1- (CGP 20712A) 和 β2- (ICI 118551) 肾上腺素能阻滞剂对地昔帕明和去甲替林的抗伤害感受作用的影响,该测试涉及中枢神经系统 (CNS) 中不同水平的感觉-运动整合。进行活性测试以检测 “假阳性” 或 “假阴性” 结果。获得的结果表明,CGP 20712A和ICI 118551都能够在物理测试 (热板和甩尾) 中拮抗这些抗抑郁药的抗伤害感受作用。然而,在化学测试 (乙酸和福尔马林) 中,所使用的抗抑郁药的镇痛作用仅被CGP 20712A拮抗。这些结果表明,地昔帕明和去甲替林的镇痛作用是由 β-肾上腺素受体介导的。涉及的 β-肾上腺素能受体取决于伤害性刺激的类型,当刺激是物理刺激时,β1和 β2都涉及,但当刺激是化学刺激时,只有 β1涉及。

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