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： 口唇瘤是一种独特的肿瘤，其特征是增殖的嗜碱性细胞和诊断性影子细胞由双重人群组成，据信这是由毛发基质引起的。正常的毛发基质经历了确定的生长（生长期），消退（生长期）和静止（休止期）周期，这些周期受程序性细胞死亡（细胞凋亡）的调节。 bcl-2是一种原癌基因，有助于抑制良性和恶性肿瘤中的细胞凋亡。此外，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，我们使用免疫组化方法研究了10例经组织学证实的pilomatricoma的bcl-2表达病例。研究设计包括阳性和阴性对照。 bcl-2免疫染色强烈修饰了我们系列中的所有pilomatricomas。根据bcl-2染色增加的发现，我们得出结论，凋亡的错误抑制是导致毛细血管瘤的发病原因。

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： GATA家族的脊椎动物DNA结合调节蛋白在不同的组织中以及在不同的发育时期表达。但是，这些蛋白质的DNA结合区具有相当的同源性，可以识别相当相似范围的DNA序列基序。 DNA结合是通过两个结构域介导的，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末端指可以有助于结合的特异性和强度，但它不能独立地结合，而C末端指对于结合既是必需的又是足够的。在这里，我们表明，尽管对于GATA-1的N端手指来说确实如此，但GATA-2和GATA-3的手指却能够强烈独立地结合，并优先选择基序GATC。结合需要在N末端指形物的两侧都存在两个基本区域。在GATA-1 N端手指附近缺少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一个基序的新变体，该变体先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区分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。

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： ：我们的目标是通过非侵入性高分辨率（117 x 117 x 70 microm）磁共振（microMRI）和视觉系统诱发电位（VEP）技术来追踪发生髓鞘异常的疾病，然后在转基因小鼠中部分恢复。我们使用经工程改造过表达Golli-mbp基因复合物产物Golli J37（特别是在少突胶质细胞中）的JOE（用于J​​37 golli过表达）转基因小鼠。从21岁到75天大，使用11.7 T扫描仪上的非侵入性体内VEP和3D T2加权显微MRI对个体JOE转基因及其未受影响的兄弟姐妹进行跟踪研究，我们认为这是同类研究中的首次纵向研究。显微MRI数据表明，在峰值髓鞘形成期（21-42天）期间出现了明显的整体性低髓鞘形成，与对照组相比，JOE小鼠在以后的年龄（> 60天）中得到了部分纠正。这些显微MRI数据与[Campagnoni AT（1995）“髓鞘形成的分子生物学”）有很好的相关性。在：Ransom B，Kettenmann H（eds）Neuroglia-专着中。牛津大学出版社，伦敦，第555-570页]髓磷脂染色，[Campagnoni AT，Macklin WB（1988）髓磷脂蛋白基因表达的细胞和分子方面。 [Mol Neurobiol 2：41-89]在髓鞘形成高峰期发生短暂的意向性震颤，此现象在以后的年龄有所减轻，[Lees MB，Brostoff SW（1984）蛋白在髓鞘中。在：莫雷尔（编辑）髓磷脂。 [Plenum Press，纽约和伦敦，第197-224页] VEP均表明JOE小鼠的CNS髓磷脂发育显着延迟和持续性髓鞘减少。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迟缓的小鼠大脑中髓鞘形成的增加。

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： ：分子生物学技术被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，人细小病毒B19，水痘-带状疱疹病毒和风疹病毒在怀孕期间发生的感染，用于诊断和管理逆转录病毒感染（HIV和HTLV）和肝炎（H​​BV和HCV），用于乳头瘤病毒分型并检测病毒与临床表现之间的联系（心肌病或胰岛素依赖型糖尿病与柯萨奇病毒B：卡波西氏肉瘤伴HHV 8）或调查环境污染病毒。这些新的定性和定量分子标记代表了病毒诊断研究领域，感染过程中病毒载量的监测，病毒疾病的治疗控制和病毒传播的流行病学的重要进展。使用可用的市售试剂和试剂盒可获得标准化和自动化。

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（MMP）由于其在肿瘤转移中以及在变性疾病（例如骨和类风湿性关节炎）的发生和扩散中的作用而受到了广泛的研究。使用一系列高度预测的三维定量结构-活性关系模型，包括比较分子场，在计算机上设计了初步的140种药物样小分子基质金属蛋白酶3抑制剂，旨在作为优化和合成的起始支架。分析和比较分子相似性指数分析，以及对接和评分。选择沙利度胺作为新铅系列的基础，因为它能适度抑制MMP-3，具有抗血管生成作用，并易于进行结构修饰。正如辛醇-水分配系数ClogP所估计的那样，大多数新化合物都具有中等至较高的预测生物活性和良好的生物利用度。特别地，化合物102对MMP-3表现出非常有利的预测活性。具有中等生物利用度；满足Lipinski的五法则；并有望进一步优化，合成和进行实验评估，作为潜在的辅助抗癌药或抗风湿药。

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： ：我们在小鼠染色体6上构建了一个大于2-Mb区域的物理图，其中包含自然杀伤基因复合体（NKC）。该图包括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遗传连锁基因编码> 17种蛋白质，这些蛋白质直接控制先天NK细胞介导的肿瘤溶解和疾病抵抗力。在本文中，我们显示Nkrp1基因聚集在A2m和Cd69基因侧翼的区域中，而大多数Ly49基因聚集在距离-1 Mb远的区域中。重要的是，保留了包含NKC的小鼠6号染色体和人类12p号染色体的同音间隔。 NKC物种保守性表明，人NKC可能含有小鼠病毒疾病抗性基因Cmv1和Rmp1的直向同源物。高分辨率的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，这些产物赋予NK细胞防御病毒病原体的能力。

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复合物类似2），是果蝇Achaete和Scute基因的同源物。在小鼠中，该基因被印迹并定位于7号染色体。我们在11p15.5处绘制了与IGF2和H19接近的人类同源基因，该区域与小鼠7号染色体呈同义关系，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。非恶性葡萄胎（雄激素性）痣中缺乏HASH2表达，这表明HASH2也被印在人体内。

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： 摘要背景：吸入性糖皮质激素（ICS）和长效β2-激动剂（LABA）的结合被治疗指南推荐用于持续性哮喘的治疗。两种这样的组合产品，沙美特罗/丙酸氟替卡松（SFC，英国Seretide GSK）和福莫特罗/布地奈德（FBC，Symbicort，阿斯利康，英国）可商购。
目的：这些研究的目的是评估和比较两种组合产品在单剂给药后直至24小时的支气管扩张持续时间。
方法：进行了两项随机，双盲，安慰剂对照，交叉研究。研究A在接受400-1200 mcg布地奈德或同等剂量的33位哮喘成人中进行。在24小时内测量一秒钟的连续呼气量（FEV1），以确定SFC（50/100 mcg）和FBC（4.5 / 160 mcg）的作用持续时间。研究B是在75名接受800-1200 mcg布地奈德或同等水平的哮喘成年人中进行的，包括4周400 mcg bd的Becotide磨合，然后用SFC 50/100 mcg bd或FBC 4.5 / 160 mcg bd进行4周治疗以交叉方式拍摄。在每4周治疗期后的第一剂和最后一剂之后，测量连续的24小时FEV1，以确定每种治疗的作用抵消。
结果：在研究A中，单次吸入SFC和FBC在16小时产生了持续的支气管扩张作用，与SFC和0.25 L（95 FBC的％CI 0.21，0.37 L），均显着高于两种治疗的安慰剂（-0.05 L; p <0.001）。在研究B中，从剂量后2-24小时开始，FEV1的下降斜率对于SFC为-16.0 ml / hr，对于FBC为-14.2 ml / hr。 24小时的加权平均AUC为0.21 Lxmin和0.22 Lxmin，与12小时前剂量前FEV1相比，SFC和FBC的平均变化分别为0.21 L和0.20 L
结论：SFC和FBC均产生相似的持续支气管扩张药作用，给药后延长至12小时以上，并且在24 h时明显可测量。

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，成为可注射注射器的水凝胶。最近已经研究了这种凝胶作为眼睛中玻璃体液的潜在替代物。在这项研究中，通过磺酰罗丹明B比色法对各种交联的PVP凝胶进行细胞毒性评估时，发现它们中的许多在静态培养物中对3T3小鼠成纤维细胞均显示出保护/促生长作用，这种现象以前仅在A的水溶液中会遇到。数量有限的天然或合成聚合物。特别地，用二甘醇二甲基丙烯酸甲酯（DEGDMA）交联的凝胶诱导细胞增殖的显着增强，尤其是在无血清培养物中。在这种作用与基本的凝胶性质（化学组成，粘弹性和平衡水含量）之间没有相关性。该研究表明，交联的PVP水凝胶对锚定依赖性细胞系显示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所致。

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： ：从印度链球菌中鉴定出了一种新的生物合成基因簇，用于含有2-脱氧链胺的抗生素。推导了基因簇中的alloH基因编码2-脱氧-鞘氨醇合酶，并证实表达的蛋白AlloH具有这种酶活性。此外，研究了AlloH的生化特性。

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受到抑制，但该机制尚未建立。在本报告中，我们证明了通过用2-氨基嘌呤药物治疗可防止腺病毒关闭细胞蛋白质合成。已显示用2-氨基嘌呤处理可防止细胞翻译受到抑制，而不会破坏细胞mRNA从细胞核到细胞质的运输过程中的正常病毒阻滞。我们显示病毒抑制细胞蛋白质合成的发生与干扰素诱导的双链RNA激活的抑制剂（DAI），蛋白激酶和真核生物起始因子2（eIF-2 alpha）的α亚基的磷酸化的激活同时发生。 ，但可以防止2-氨基嘌呤阻止宿主细胞的关闭，而不会降低激酶活性或eIF-2α的去磷酸化。结果表明，可能需要DAI激酶的激活和eIF-2 alpha的磷酸化，但不足以抑制腺病毒感染期间细胞蛋白质合成。我们建议其他事件，特别是其他起始因子的修饰，可能与细胞翻译的病毒抑制有关。

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各种病因性疼痛。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试验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镇痛作用的影响，这些试验暗示了不同水平的感觉-运动在中枢神经系统（CNS）中的整合。进行活动测试以检测“假阳性”或“假阴性”结果。获得的结果表明，CGP 20712A和ICI 118551均能够在物理测试（热板和甩尾）中拮抗这些抗抑郁药的镇痛作用。但是，在化学测试（乙酸和福尔马林）中，所用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-肾上腺素能受体介导的。涉及的β-肾上腺素受体取决于伤害性刺激的类型。当刺激是物理刺激时，beta 1和beta 2都牵涉其中，但是当刺激是化学刺激时，仅涉及beta1。

BACKGROUND & AIMS: :The vascular endothelial growth factor (VEGF) family of cytokines is involved in the maintenance of existing adult blood vessels as well as in angiogenesis, the sprouting of new vessels. To study the proangiogenic activation of VEGF receptors (VEGFRs) by VEGF family members in skeletal muscle, we develop a computational model of VEGF isoforms (VEGF(121), VEGF(165)), their cell surface receptors, and the extracellular matrix in in vivo tissue. We build upon our validated model of the biochemical interactions between VEGF isoforms and receptor tyrosine kinases (VEGFR-1 and VEGFR-2) and nonsignaling neuropilin-1 coreceptors in vitro. The model is general and could be applied to any tissue; here we apply the model to simulate the transport of VEGF isoforms in human vastus lateralis muscle, which is extensively studied in physiological experiments. The simulations predict the distribution of VEGF isoforms in resting (nonexercising) muscle and the activation of VEGFR signaling. Little of the VEGF protein in muscle is present as free, unbound extracellular cytokine; the majority is bound to the cell surface receptors or to the extracellular matrix. However, interstitial sequestration of VEGF(165) does not affect steady-state receptor binding. In the absence of neuropilin, VEGF(121) and VEGF(165) behave similarly, but neuropilin enhances the binding of VEGF(165) to VEGFR-2. This model is the first to study VEGF tissue distribution and receptor activation in human muscle, and it provides a platform for the design and evaluation of therapeutic approaches.

背景与目标： ：细胞因子的血管内皮生长因子（VEGF）家族与现有成人血管的维护以及血管生成，新血管的萌发有关。为了研究骨骼肌中VEGF家族成员对VEGF受体（VEGFRs）的促血管生成激活作用，我们建立了VEGF同种型（VEGF（121），VEGF（165）），它们的细胞表面受体和细胞外基质的计算模型。体内组织。我们建立在我们的体外VEGF同工型和受体酪氨酸激酶（VEGFR-1和VEGFR-2）和非信号神经pilin-1共受体之间的生化相互作用的验证模型的基础上。该模型是通用模型，可以应用于任何组织。在这里，我们应用该模型来模拟VEGF同工型在人股外侧肌中的运输，这在生理实验中已得到广泛研究。模拟预测了静息（非运动）肌肉中VEGF亚型的分布和VEGFR信号的激活。肌肉中很少有VEGF蛋白以游离的，未结合的细胞外细胞因子的形式存在。大多数与细胞表面受体或细胞外基质结合。但是，间质隔离VEGF（165）不会影响稳态受体结合。在没有神经纤毛蛋白的情况下，VEGF（121）和VEGF（165）的行为相似，但是神经纤毛蛋白会增强VEGF（165）与VEGFR-2的结合。该模型是第一个研究人肌肉中VEGF组织分布和受体激活的模型，它为设计和评估治疗方法提供了平台。

BACKGROUND & AIMS: BACKGROUND:A few prospective controlled trials comparing early functional rehabilitation after Achilles tendon repair and non-operative immobilization have been reported. HYPOTHESES:There is no difference in Achilles tendon elongation between early motion and immobilization after Achilles tendon repair. Tendon elongation does not correlate with the clinical outcome. STUDY DESIGN:Randomized clinical trial; Level of evidence, 2. METHODS:Fifty patients with acute Achilles tendon rupture were randomized postoperatively to receive either early movement of the ankle between neutral and plantar flexion in a brace for 6 weeks or immobilization in tension using a below-knee cast with the ankle in a neutral position for 6 weeks. Full weightbearing was allowed after 3 weeks in both groups. Standardized radiographs to measure previously placed radiographic markers were taken on the first day postoperatively and at 1, 3, 6, 12, 24 weeks postoperatively, with the final radiograph a mean of 60 (SD, 6.4) weeks postoperatively. The outcome was assessed at the 3-month and final checkups by the clinical scoring method described by Leppilahti et al and included subjective factors and objective factors. RESULTS:Tendon elongation occurred in both groups but was somewhat less in the early motion group (median 2 mm in the early motion group vs median 5 mm in the cast group a mean of 60 weeks postoperatively, P = .054). The elongation curves first rose and then slowly fell in both groups. The patients who had less elongation achieved a better clinical outcome (rho = -.42, P = .017). Tendon elongation did not correlate significantly with age, body mass index, or isokinetic peak torques. CONCLUSION:Achilles tendon elongation was somewhat less in the early motion group and correlated with the clinical outcome scores. We recommend early functional postoperative treatment after Achilles rupture repair.

背景与目标： 背景：一些前瞻性对照试验比较了跟腱修复和非手术固定后的早期功能康复。
假设：跟腱修复后的早期运动和固定之间的跟腱伸长没有差异。肌腱伸长与临床结果无关。
研究设计：随机临床试验；证据水平2。
方法：将50例急性跟腱断裂患者术后随机接受踝关节在中性和足底屈曲之间的早期运动，持续6周，或使用膝下石膏将踝关节置于中性位置，以固定不动的张力，持续6周。周。两组均在3周后允许完全负重。术后第一天和术后1、3、6、12、24周拍摄标准化的X线照片以测量先前放置的X线标记，最后的X射线照片平均在术后60（SD，6.4）周。结果通过Leppilahti等人描述的临床评分方法在3个月及最终体检时进行评估，其中包括主观因素和客观因素。
结果：两组的肌腱伸长均发生，但早期运动组则有所减少（早期运动组中位2 mm，而石膏组中位5 mm，平均术后60周，P = .054）。两组的伸长率曲线先上升，然后缓慢下降。伸长率较低的患者获得较好的临床预后（rho = -.42，P = .017）。肌腱伸长率与年龄，体重指数或等速运动峰值扭矩无显着相关性。
结论：早期运动组跟腱伸长率略低，且与临床结果评分相关。我们建议跟腱断裂修复后尽早进行术后功能治疗。

BACKGROUND & AIMS: AIM:To evaluate photodynamic therapy (PDT) combined with the preferential the cyclooxygenase-2 (COX-2) inhibitor, nabumetone in the treatment of the neovascular age-related macular degeneration (ARMD). METHODS:A prospective, double-blind, randomized study on 60 patients with subfoveal CNV secondary to ARMD without any previous treatment. Patients were divided into a nabumetone or placebo group. The main endpoints were the change of best-corrected visual acuity (BCVA), central macular thickness (CRT) and number of required PDT treatments. RESULTS:In the nabumetone group, 27 patients (90%) and 28 (93%) in the placebo group completed the follow-up of 12 months. In the nabumetone group, the mean CRT decreased from 332 μm (SD 68 μm) to 220 μm (SD 46 μm). In the placebo group, CRT decreased from 331 μm (SD 72 μm) to 254 μm (SD 61 μm). The mean BCVA was 0.68 log MAR (SD 0.22 log MAR) in the nabumetone group and 0.62 log MAR (SD 0.23 log MAR) in the placebo group at baseline. This stabilised in the placebo group to 0.66 log MAR (SD 0.33) but deteriorated in the nabumetone group to 0.86 log MAR (SD 0.41 log MAR). There was a significant reduction in the number of required PDTs in the nabumetone group, but significant progression of the RPE atrophy area. CONCLUSION:Combined PDT with oral intake of the COX-2 inhibitor, nabumetone reduced the number of required PDT retreatments, but worsening BCVA caused by macular atrophy progression. Therefore the combination of the PDT with the nabumetone is not recommended.

背景与目标： 目的：评估光动力疗法（PDT）与优先使用环氧合酶-2（COX-2）抑制剂萘丁美酮的组合，以治疗新生血管性年龄相关性黄斑变性（ARMD）。
方法：一项前瞻性，双盲，随机对照研究，对60例继发于ARMD继发于中央凹下的CNV患者而未进行任何治疗。将患者分为萘丁美酮或安慰剂组。主要终点是最佳矫正视力（BCVA），中央黄斑厚度（CRT）和所需PDT治疗次数的改变。
结果：萘丁美通组中，安慰剂组27例（90％）和28例（93％）完成了12个月的随访。在萘丁美酮组中，平均CRT从332μm（SD 68μm）降至220μm（SD 46μm）。在安慰剂组中，CRT从331μm（SD 72μm）降至254μm（SD 61μm）。萘丁美tone组的平均BCVA为0.68 log MAR（SD 0.22 log MAR），而安慰剂组的基线BCVA为0.62 log MAR（SD 0.23 log MAR）。这在安慰剂组中稳定至0.66 log MAR（SD 0.33），但在萘丁美通组中恶化至0.86 log MAR（SD 0.41 log MAR）。萘丁美通组中所需PDT的数量显着减少，但RPE萎缩区域进展明显。
结论：萘丁美酮与PDT结合口服摄入COX-2抑制剂相结合，减少了所需的PDT再治疗次数，但由于黄斑萎缩的进展而使BCVA恶化。因此，不建议将PDT与萘丁美酮组合使用。