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。

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。

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。

BACKGROUND & AIMS: :By screening a pigeon genomic DNA library, we isolated a recombinant phage clone containing the alpha(A)-globin gene. The DNA sequence of the approximately 6kbp-long insert fragment of the phage clone was determined. The sequence suggested the existence of pigeon alpha(D)-globin gene located 3.1 kbp upstream from the alpha(A)-globin gene. The expression of the alpha(D)-globin in late embryo was also shown by the N-terminal amino-acid sequence of the intact globin chain. These results show that two adult alpha-globin genes, alpha(A) and alpha(D), exist in the pigeon genome, and the alpha(D)-globin is expressed at the late embryo stage. The stage-specific expression suggests the existence of regulatory elements and factors interacting to inhibit transcription at the adult stage.

背景与目标： : 通过筛选鸽子基因组DNA文库，我们分离出含有 α (a)-珠蛋白基因的重组噬菌体克隆。确定了噬菌体克隆的约6kbp长的插入片段的DNA序列。该序列表明存在位于 α (A)-珠蛋白基因上游3.1 kbp的鸽子 α (D)-珠蛋白基因。完整珠蛋白链的N端氨基酸序列也显示了 α (D)-珠蛋白在晚期胚胎中的表达。这些结果表明，鸽子基因组中存在两个成年的 α-珠蛋白基因 α (A) 和 α (D)，并且 α (D)-珠蛋白在胚胎晚期表达。阶段特异性表达表明存在调节元件和因子相互作用以抑制成年阶段的转录。

BACKGROUND & AIMS: :In this study, the contribution of the CD5+ B cell to the preferential expression of VH 7183 and Q52 observed early in development was determined. CD5+ and CD5- B cells from BALB/c mice were isolated by fluorescence-activated cell sorter and the expression of particular VH gene families was determined directly by in situ hybridization. The results indicate that CD5+ B cells obtained from both adult and neonatal animals express Q52 at increased levels compared with CD5- B cells. Preferential expression of VH 7183 was observed only in the neonatal CD5- B cell subset. Thus, the increased expression of VH 7183 early in development is caused by the CD5- subset whereas increased Q52 expression is caused by the CD5+ subset. These results indicate that the fetal/neonatal conventional B cell is distinct from conventional adult B cells in terms of Ig gene repertoire expression.

背景与目标： : 在这项研究中，确定了CD5 b细胞对发育早期观察到的VH 7183和Q52的优先表达的贡献。通过荧光激活细胞分选仪分离BALB/c小鼠的CD5和CD5-b细胞，并通过原位杂交直接确定特定VH基因家族的表达。结果表明，与CD5-b细胞相比，从成年动物和新生动物获得的CD5 b细胞表达Q52的水平更高。仅在新生儿cd5-b细胞亚群中观察到VH 7183的优先表达。因此，VH 7183在发育早期的表达增加是由CD5-子集引起的，而Q52表达增加是由CD5 + 子集引起的。这些结果表明，就Ig基因库表达而言，胎儿/新生儿常规b细胞与常规成人b细胞不同。

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。

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：

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。

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。

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。

BACKGROUND & AIMS: The exact mechanism for the decrease in intestinal calcium absorption with age is not yet understood. A decrease with age in serum 1,25-dihydroxyvitamin D (1,25(OH)2D) or a decrease in the intestinal vitamin D receptor (VDR) protein concentration are possible causes. The objective of this study was to examine the effect of age on these factors. Fifty-nine young women age 25-35 years were compared with 41 elderly women age 65-83 years who underwent measurements of VDR, calcium absorption using a 20 mg and 100 mg calcium carrier, and calciotropic hormones. Calcium absorption by both tests was lower in the elderly women compared with the young women (p < 0.05). Serum 1,25(OH)2D and duodenal VDR protein concentration were not significantly different between the two age groups. Serum 1,25(OH)2D correlated with the 20 mg calcium absorption test in both young (r = 0.35, p < 0.007) and elderly women (r = 0.58, p < 0.0001) and with the 100 mg calcium absorption in the elderly (r = 0.32; p < 0.05). VDR did not correlate with calcium absorption in young women or elderly women, nor did VDR correlate with serum 1,25(OH)2D and serum 25-hydroxyvitamin D. In summary, the decrease in calcium absorption cannot be explained by a decrease in intestinal VDR. The correlation between serum 1,25(OH)2D and both calcium absorption tests only accounts for 12-30% of the variance in the age-related change in the calcium absorption tests. Other factors, not yet understood, are responsible for the decline in calcium absorption with age.

背景与目标： 随着年龄的增长，肠道钙吸收减少的确切机制尚不清楚。血清1,25-二羟基维生素d (1,25(OH)2D) 随着年龄的增长而降低或肠道维生素d受体 (VDR) 蛋白浓度降低是可能的原因。这项研究的目的是检查年龄对这些因素的影响。将59名年龄在25-35岁之间的年轻女性与41名年龄在65-83岁之间的老年女性进行了比较，这些女性接受了VDR，使用20 mg和100 mg钙载体的钙吸收以及钙促激素的测量。与年轻女性相比，老年女性两种测试对钙的吸收均较低 (p <0.05)。血清1,25(OH)2D和十二指肠VDR蛋白浓度在两个年龄组之间没有显着差异。血清1,25(OH)2D与青年 (r = 0.35，p <0.007) 和老年妇女 (r = 0.58，p <0.0001) 的20 mg钙吸收试验相关，与老年人的100 mg钙吸收相关 (r = 0.32; p <0.05)。VDR与年轻女性或老年女性的钙吸收无关，也与血清1,25(OH)2D和血清25-羟基维生素d无关。总而言之，钙吸收的减少不能用肠道VDR的减少来解释。血清1,25(OH)2D与两种钙吸收测试之间的相关性仅占钙吸收测试中年龄相关变化的12-30%。其他尚未了解的因素是钙吸收随年龄下降的原因。

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。

BACKGROUND & AIMS: Pseudomonas putida U does not degrade D-glucose through the glycolytic pathway but requires (i) its oxidation to D-gluconic acid by a peripherally located constitutive glucose dehydrogenase (insensitive to osmotic shock), (ii) accumulation of D-gluconic acid in the extracellular medium, and (iii) the induction of a specific energy-dependent transport system responsible for the uptake of D-gluconic acid. This uptake system showed maximal rates of transport at 30 degrees C in 50 mM potassium phosphate buffer, pH 7.0. Under these conditions the K(m) calculated for D-gluconic acid was 6.7 microM. Furthermore, a different transport system, specific for the uptake of glucose, was also identified. It is active and shows maximal uptake rates at 35 degrees C in 50 mM potassium phosphate buffer, pH 6.0, with a K(m) value of 8.3 microM.

背景与目标： 恶臭假单胞菌U不会通过糖酵解途径降解D-葡萄糖，但需要 (i) 通过位于外周的组成型葡萄糖脱氢酶将其氧化为D-葡萄糖酸 (对渗透休克不敏感)，(ii) D-葡萄糖酸在细胞外培养基中的积累，(iii) 诱导负责吸收D-葡萄糖酸的特定能量依赖性转运系统。该吸收系统在50 mM磷酸钾缓冲液 (pH 7.0) 中显示了在30 ℃ 下的最大转运速率。在这些条件下，计算的D-葡萄糖酸的K(m) 为6.7微米。此外，还确定了特定于葡萄糖摄取的不同转运系统。它具有活性，并在50 mM磷酸钾缓冲液 (pH 6.0) 中的35摄氏度下显示出最大的吸收速率，K(m) 值为8.3微米。

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) 家族参与现有成人血管的维持以及血管生成，新血管的萌发。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，我们建立了VEGF同工型 (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。我们建立在我们验证的VEGF同工型与受体酪氨酸激酶 (VEGFR-1和VEGFR-2) 之间的生化相互作用的模型，以及体外非信号neuropilin-1共受体。该模型是通用的，可以应用于任何组织; 在这里，我们应用该模型来模拟人外侧肌中VEGF同工型的运输，这在生理实验中得到了广泛的研究。模拟预测了静息 (非运动) 肌肉中VEGF亚型的分布以及VEGFR信号传导的激活。肌肉中几乎没有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。然而，VEGF(165) 的间质隔离不影响稳态受体结合。在不存在神经菌毛蛋白的情况下，VEGF(121) 和VEGF(165) 表现相似，但是神经菌毛蛋白增强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，它为治疗方法的设计和评估提供了平台。

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.

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