BACKGROUND & AIMS: INTRODUCTION:Tissue factor (TF) has been implicated in coronary artery disease (CAD). High levels of circulating TF are found in patients with acute atherothrombotic events. Whether high serum TF levels predict risk of future CAD independent of known risk factors remains unknown. METHODS:We conducted a prospective case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population study. Cases (n=1037) were apparently healthy men and women, aged 45-79 years, who developed fatal or non-fatal CAD during follow-up. Controls (n=2005) were matched by age, sex, and enrolment time. Serum TF levels were measured using high-affinity antibodies. RESULTS:In men, median TF levels were not significant higher in cases than in controls (59.0 pg mL-1, range: 16.7-370.4 vs. 54.9 pg mL-1, range: 16.2-452.4). In women, median TF levels were not significant higher in controls than in cases (73.4 pg mL-1, range: 16.7-492.3 vs. 50.5 pg mL-1, range: 16.5-376.7). The incidence of smoking was about double in the lowest compared with the highest TF quartile. Correcting for sex, age, body mass index, smoking, diabetes, systolic blood pressure, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and C-reactive protein levels, the risk of future CAD was 1.05 (95% CI: 0.81-1.36) for people in the highest TF quartile, compared with those in the lowest (P-value for linearity=0.8). CONCLUSION:High levels of serum TF were not independently associated with an increased risk of future CAD in apparently healthy individuals.

背景与目标：

BACKGROUND & AIMS: The mammalian transcription factor LSF (CP2/LBP-1c) binds cellular promoters modulated by cell growth signals. We demonstrate here that LSF-DNA-binding activity is strikingly regulated by induction of cell growth in human peripheral T lymphocytes. Within 15 min of mitogenic stimulation of these cells, the level of LSF-DNA-binding activity increased by a factor of five. The level of LSF protein in the nucleus remained constant throughout this interval. However, a rapid decrease in the electrophoretic mobility of LSF, attributable to phosphorylation, correlated with the increase in DNA-binding activity. pp44 (ERK1) phosphorylated LSF in vitro on the same residue that was phosphorylated in vivo, specifically at amino acid position 291, as indicated by mutant analysis. As direct verification of the causal relationship between phosphorylation and DNA-binding activity, treatment in vitro of LSF with phosphatase both increased the electrophoretic mobility of the protein and decreased LSF-DNA-binding activity. This modulation of LSF-DNA-binding activity as T cells progress from a resting to a replicating state reveals that LSF activity is regulated during cell growth and suggests that LSF regulates growth-responsive promoters.

背景与目标： 哺乳动物转录因子LSF (CP2/LBP-1c) 结合由细胞生长信号调节的细胞启动子。我们在此证明，LSF-DNA结合活性通过诱导人外周血T淋巴细胞中的细胞生长而显着调节。在有丝分裂刺激这些细胞的15分钟内，lsf-dna结合活性水平增加了5倍。在整个间隔内，细胞核中LSF蛋白的水平保持恒定。然而，由于磷酸化，LSF的电泳迁移率迅速降低与DNA结合活性的增加有关。pp44 (ERK1) 在体内磷酸化的相同残基上体外磷酸化LSF，具体地在氨基酸位置291，如突变体分析所示。作为磷酸化与DNA结合活性之间因果关系的直接验证，用磷酸酶体外处理LSF既增加了蛋白质的电泳迁移率，又降低了LSF-DNA结合活性。随着T细胞从静止状态发展为复制状态，LSF-DNA结合活性的这种调节表明LSF活性在细胞生长过程中受到调节，并表明LSF调节生长反应性启动子。

BACKGROUND & AIMS: :Etanercept is a recombinant human soluble tumor necrosis factor (TNF-alpha) receptor fusion protein that inhibits TNF-alpha, a major mediator in the pathogenesis of graft-versus-host disease (GVHD). The purpose of our study was to evaluate the safety and efficacy of etanercept therapy in 21 patients with steroid-refractory acute GVHD (aGVHD) (n = 13) and chronic GVHD (cGVHD) (n = 8). Etanercept 25 mg was given subcutaneously twice weekly for 4 weeks followed by 25 mg weekly for 4 weeks. At the time of initiation of etanercept, 14 patients had skin, 13 had gastro-intestinal, 5 had liver, 5 had pulmonary, and 4 had oral involvement. Twelve patients (57%) completed 12 doses of therapy. Overall, 11 of 21 patients (52%) responded to the treatment with etanercept, including 6 patients (46%) with aGVHD [n = 4 complete response (CR), n = 2 partial response (PR)] and 5 patients (62%) with cGVHD (n = 1 CR, n = 4 PR). Clinical responses were most commonly seen in patients with refractory gut aGVHD with 55% of the patients having a CR and 9% having a PR. CMV reactivation occurred in 48% of patients, bacterial infections in 14% of patients, and fungal infections in 19% of patients. Fourteen patients (67%) were alive after a median follow-up of 429 days (range 71-1007 days) since initiation of etanercept. Seven patients died, 3 of infections, 2 of refractory aGVHD, and 2 of disease progression. In conclusion, our preliminary data indicate that etanercept is well tolerated and can induce a high response rate in patients with steroid-refractory aGVHD and cGVHD, particularly in the setting of GI involvement.

背景与目标： : 依那西普是一种重组人可溶性肿瘤坏死因子 (TNF-α) 受体融合蛋白，可抑制TNF-α，TNF-α 是移植物抗宿主病 (GVHD) 发病机理中的主要介质。我们研究的目的是评估依那西普治疗21例类固醇难治性急性GVHD (aGVHD) (n = 13) 和慢性GVHD (cGVHD) (n = 8) 患者的安全性和有效性。依那西普25 mg，每周皮下注射两次，持续4周，然后每周注射25 mg，持续4周。在开始使用依那西普时，14例患者有皮肤，13例有胃肠道，5例有肝脏，5例有肺部，4例有口腔受累。12名患者 (57%) 完成12剂治疗。总体而言，21例患者中有11例 (52%) 对依那西普治疗有反应，其中6例 (46% 例) aGVHD [n = 4完全缓解 (CR)，n = 2部分缓解 (PR)] 和5例 (62%) cGVHD (n = 1 CR，n = 4 PR)。临床反应最常见于难治性肠道aGVHD患者，其中55% 患者具有CR，9% 患者具有PR。48% 患者发生CMV再激活，14% 患者发生细菌感染，19% 患者发生真菌感染。自依那西普开始以来，中位随访429天 (范围71-1007天) 后，有14名患者 (67%) 还活着。7例患者死亡，3例感染，2例难治性aGVHD，2例疾病进展。总之，我们的初步数据表明，依那西普具有良好的耐受性，并且可以在类固醇难治性aGVHD和cGVHD患者中诱导高反应率，尤其是在GI受累的情况下。

BACKGROUND & AIMS: PURPOSE:Peptide growth factors are known accelerators of corneal wound healing, probably mediated through increased proliferation of the cells; however, information about their effect on keratocyte motility is lacking. The influence of peptide growth factors on keratocyte migratory activity was investigated, using the following growth factors: platelet derived growth factor (PDGF-BB), epidermal growth factor (EGF), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I) and transforming growth factor-beta-1 (TGF-beta 1).

METHODS:Keratocytes were seeded on gels of type 1 collagen, growth factor added, and the cells left to migrate for 72 hours. Subsequently, the number of keratocytes at the different levels in the collagen gel was evaluated by optically sectioning the gel at 20 microns, intervals, with an inverted phase contrast microscope.

RESULTS:PDGF, EGF and bFGF at 10 ng/ml, all increased the number of keratocytes at the different levels of the gel as compared to a non-stimulated control (p < 0.05 or p < 0.01, students t-test). TGF-beta proved to be a strong inhibitor of keratocyte migration, decreasing the number of keratocytes observed at every level in the gel (p < 0.05 and p < 0.01, students t-test), whereas no effect of IGF-I and aFGF was found. During the 72 hours of migration, no contraction of the collagen gels was observed. Autoradiography of histological sections of the gels showed that during the 72-hour period only TGF-beta and 10% fetal bovine serum induced an increase in keratocyte proliferation.

CONCLUSION:PDGF, EGF and bFGF increase keratocyte migration, independent of proliferation in a collagen gel invasion assay and might promote corneal wound healing, not only by increasing cell proliferation, but also through increased motility.

背景与目标： 目的 : 肽生长因子是已知的角膜伤口愈合的促进剂，可能是通过细胞增殖增加介导的; 但是，缺乏有关它们对角质细胞运动的影响的信息。用以下生长因子: 血小板衍生生长因子 (pdgf-bb)，表皮生长因子 (EGF)，酸性成纤维细胞生长因子 (aFGF)，碱性成纤维细胞生长因子 (bFGF)，胰岛素样生长因子-I (igf-i) 和转化生长因子-β1 (tgf-β1)。
方法 : 将角质细胞接种在1型胶原蛋白的凝胶上，添加生长因子，细胞迁移72小时。随后，通过用倒置相差显微镜以20微米的间隔光学切片来评估胶原蛋白凝胶中不同水平的角质形成细胞的数量。
结果 :PDGF，EGF和bFGF为10 ng/ml，与未刺激的对照相比，在凝胶的不同水平下，所有这些都增加了角质细胞的数量 (p <0.05或p <0.01，学生t检验)。TGF-β 被证明是角质细胞迁移的强抑制剂，减少了在凝胶中每个水平观察到的角质细胞的数量 (p <0.05和p <0.01，学生t检验)，而没有发现igf-i和aFGF的作用。在迁移的72小时内，未观察到胶原蛋白凝胶的收缩。凝胶组织学切片的放射自显影显示，在72小时内，只有TGF-β 和10% 胎牛血清诱导角质细胞增殖增加。
结论 :PDGF，EGF和bFGF增加角质细胞迁移，在胶原蛋白凝胶侵袭试验中独立于增殖，并且可能不仅通过增加细胞增殖，而且通过增加运动性来促进角膜伤口愈合。

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。

BACKGROUND & AIMS: The present study was designed to elucidate the neurotransmitters involved in activation of the noradrenergic nucleus, locus coeruleus, by distention of the distal colon. Locus coeruleus spontaneous discharge rate was recorded from halothane-anesthetized rats before, during and after distention of the colon produced by inflation of a balloon catheter with varying volumes of water. Locus coeruleus activation by colon distention was volume-dependent and reversible. Activation of cortical electroencephalographic activity was temporally correlated with locus coeruleus activation during colon distention and prolonged distention (greater than 2 min) resulted in tachyphalaxis to both locus coeruleus and cortical electroencephalographic activation. The corticotropin-releasing factor antagonist, DPheCRF(12-41), administered intracerebroventricularly (3 microg) or microinfused into the locus coeruleus (10 ng) significantly attenuated locus coeruleus activation produced by lower, but not higher magnitudes of colon distention, implicating corticotropin-releasing factor afferents to the locus coeruleus in this response. Consistent with this, prior exposure to 30 min of footshock stress, which desensitizes locus coeruleus neurons to corticotropin-releasing factor, produced a similar attenuation of locus coeruleus activation by low, but not high magnitudes of distention. Kynurenic acid, administered intracerebroventricularly (5 micromol), significantly antagonized locus coeruleus activation by all magnitudes of colon distention. However, this excitatory amino acid antagonist was ineffective when administered directly into the locus coeruleus (0.3 nmol). Together, these findings suggest that low magnitudes of colon distention activate the locus coeruleus-noradrenergic system via corticotropin-releasing factor release within the locus coeruleus and that excitatory amino acid neurotransmission at a site distal to the locus coeruleus is necessary for this response. Activation of the locus coeruleus-noradrenergic system during colon distention may serve as a cognitive limb of the peripheral parasympathetic response. This activation may also play a role in disorders characterized by comorbidity of colonic and psychiatric symptoms, such as irritable bowel syndrome.

背景与目标： 本研究旨在阐明通过远端结肠扩张而激活去甲肾上腺素能核蓝斑的神经递质。记录了氟烷麻醉大鼠的蓝斑自然放电速率，该速率是在通过气囊导管充满不同体积的水而产生的结肠扩张之前，期间和之后。结肠扩张对蓝斑的激活是体积依赖性和可逆的。在结肠扩张期间，皮质脑电图活动的激活与蓝斑轨迹的激活在时间上相关，而长时间的扩张 (大于2分钟) 导致蓝斑轨迹和皮质脑电图激活均出现心动过速。促肾上腺皮质激素释放因子拮抗剂DPheCRF(12-41) 在脑室内给药 (3 microg) 或微注入蓝斑 (10 ng) 显着减弱了由较低但不是较高程度的结肠扩张产生的蓝斑激活，在这种反应中，促肾上腺皮质激素释放因子传入蓝斑。与此一致的是，先前暴露于30分钟的脚休克应激，使蓝斑基因座神经元对促肾上腺皮质激素释放因子脱敏，通过低但不高的扩张幅度产生了类似的蓝斑基因座激活衰减。脑室内给药 (5 micromol) 的犬尿酸可通过所有程度的结肠扩张显着拮抗蓝斑的激活。然而，当直接给予蓝斑 (0.3 nmol) 时，这种兴奋性氨基酸拮抗剂是无效的。总之，这些发现表明，低程度的结肠扩张通过在蓝斑内释放促肾上腺皮质激素释放因子来激活蓝斑-去甲肾上腺素能系统，并且在蓝斑远端的兴奋性氨基酸神经传递是这种反应所必需的。结肠扩张期间蓝斑-去甲肾上腺素能系统的激活可能是周围副交感神经反应的认知肢体。这种激活也可能在以结肠和精神症状合并症为特征的疾病中发挥作用，例如肠易激综合征。

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。

BACKGROUND & AIMS: :The growth of the pollen tube wall of Oenothera is effected by the expulsion of fibrillar material from the cytoplasm into the developing wall. This material may also be seen in the cytoplasm, contained in membrane-bound vesicles. It is not clear how the content of the vesicles is discharged, but it appears not to involve the participation of microtubules. The source of the cytoplasmic fibrillar bodies depends upon the stage of development of the pollen tube. The earilest growth is derived from the inclusion into the wall of vesicles containing pre-formed materials present in the grain on pollination. During the next stage of growth the wall is derived from the content of double-membraned inclusions also present in the pollen. The content of the former vesicles is not so similar to the wall as the latter, but intermediates between the 2 types of vesicle may be seen in the cytoplasm, indicating that the former are formed from the latter. Most of the tube wall is derived from the products of dictyosomes in the pollen grain or tube. These dicytosomes are few in number and they must be exceedingly active. This, and the observation that dictyosome vesicles are frequently associated with banked complexes of mitochondria, indicates that some steps in the metabolism of the vesicular content, perhaps phosphorylation, take place distant from the dicytosomes. These different sources of fibrillar material presumably permit the rapid starting of tube growth, without any attendant metabolism. However, it would be impossible to include enough pre-formed wall material in the grain to enable the full growth of the tube, so once started, it seems that the tube then relies on the elaboration of simple reserves for the contruction of its wall. These reserves are likely to be held in the pollen, and may be the large numbers of starch grains characteristic of the pollen cytoplasm.

背景与目标： : 卵生花粉管壁的生长是通过将原纤维物质从细胞质中排出到发育中的壁中而实现的。这种物质也可以在细胞质中看到，包含在膜结合的囊泡中。尚不清楚如何释放囊泡的含量，但似乎不涉及微管的参与。细胞质原纤维体的来源取决于花粉管的发育阶段。最早的生长来自包含在授粉时谷物中存在的包含预形成材料的囊泡壁。在生长的下一阶段，壁来自花粉中也存在的双层包裹体的含量。前者囊泡的含量不像后者那样与壁相似，但在细胞质中可能看到2种囊泡之间的中间体，表明前者是由后者形成的。大部分的管壁来源于花粉粒或管中双子体的产物。这些二胞体数量很少，它们必须非常活跃。这以及观察到dictyosome囊泡经常与线粒体的银行复合物有关，这表明囊泡含量代谢的某些步骤 (可能是磷酸化) 发生在远离二胞体的地方。这些不同的原纤维物质来源可能允许快速开始管生长，而没有任何伴随的代谢。但是，不可能在谷物中包括足够的预成型壁材料以使管完全生长，因此一旦开始，管似乎就依赖于简单的储备来构造其壁。这些储备很可能存在于花粉中，并且可能是花粉细胞质特有的大量淀粉粒。

BACKGROUND & AIMS: :Neurons within each layer of cerebral cortex express multiple members of the neurotrophin family and their corresponding receptors. This multiplicity could provide functional redundancy; alternatively, different neurotrophins may direct distinct aspects of cortical neuronal growth and differentiation. By neutralizing endogenous neurotrophins in organotypic slices of developing cortex with Trk receptor bodies (Trk-IgGs), we found that BDNF and NT-3 oppose one another in regulating the dendritic growth of pyramidal neurons. In layer 4, both endogenous and exogenous NT-3 inhibited the dendritic growth stimulated by BDNF. In contrast, in layer 6 both endogenous and exogenous BDNF inhibited dendritic growth stimulated by NT-3. These antagonistic actions of endogenous BDNF and NT-3 provide a mechanism by which dendritic growth and retraction can be dynamically regulated during cortical development, and suggest that the multiple neurotrophins expressed in developing cortex represent distinct components of an extracellular signaling system for regulating dendritic growth.

背景与目标： : 大脑皮层各层内的神经元表达神经营养蛋白家族的多个成员及其相应的受体。这种多样性可以提供功能冗余; 或者，不同的神经营养蛋白可能会指导皮质神经元生长和分化的不同方面。通过用Trk受体体 (Trk-igg) 中和发育中的皮层器官型切片中的内源性神经营养蛋白，我们发现BDNF和NT-3在调节锥体神经元的树突状生长方面相互对抗。在第4层中，内源性和外源性NT-3均抑制BDNF刺激的树突状生长。相反，在第6层中，内源性和外源性BDNF均抑制NT-3刺激的树突生长。内源性BDNF和NT-3的这些拮抗作用提供了一种机制，通过该机制可以在皮质发育过程中动态调节树突生长和收缩，并表明在发育中的皮质中表达的多种神经营养蛋白代表了调节树突生长的细胞外信号系统的不同成分。

BACKGROUND & AIMS: :The hypoxic environment in tumor is reported to play an important role in pancreatic cancer progression. The interaction between stromal and cancer cells also contributes to the malignant behavior of pancreatic cancer. In the present study, we investigated whether hypoxic stimulation affects stromal as well as pancreatic cancer cells. Our findings demonstrated that hypoxia remarkably elevated the HIF-1alpha expression in both pancreatic cancer (PK8) and fibroblast cells (MRC5). Hypoxic stimulation accelerated the invasive activity of PK8 cells, and invasiveness was thus further accelerated when the hypoxic PK8 cells were cultured with conditioned medium prepared from hypoxic MRC5 cells (hypoxic conditioned medium). MMP-2, MMP-7, MT1-MMP and c-Met expressions were increased in PK8 cells under hypoxia. Hypoxic stimulation also increased the hepatocyte growth factor (HGF) secretion from MRC5 cells, which led to an elevation of c-Met phosphorylation in PK8 cells. Conversely, the elevated cancer invasion, MMP activity and c-Met phosphorylation of PK8 cells were reduced by the removal of HGF from hypoxic conditioned medium. In immunohistochemical study, the HIF-1alpha expression was observed in surrounding stromal as well as pancreatic cancer cells, thus indicating hypoxia exists in both of cancer and stromal cells. Moreover, the stromal HGF expression was found to significantly correlate with not only the stromal HIF-1alpha expression but also the c-Met expression in cancer cells. These results indicate that the hypoxic environment within stromal as well as cancer cells activates the HGF/c-Met system, thereby contributing to the aggressive invasive features of pancreatic cancer.

背景与目标： : 据报道，肿瘤中的低氧环境在胰腺癌的进展中起重要作用。基质细胞和癌细胞之间的相互作用也有助于胰腺癌的恶性行为。在本研究中，我们调查了缺氧刺激是否会影响基质细胞以及胰腺癌细胞。我们的发现表明，缺氧显着提高了胰腺癌 (PK8) 和成纤维细胞 (MRC5) 的HIF-1alpha表达。低氧刺激加速了PK8细胞的侵袭活性，因此，当用低氧MRC5细胞制备的条件培养基 (低氧条件培养基) 培养低氧PK8细胞时，其侵袭能力进一步加快。缺氧条件下PK8细胞MMP-2、MMP-7、MT1-MMP和c-Met表达增加。低氧刺激还增加了MRC5细胞的肝细胞生长因子 (HGF) 分泌，导致PK8细胞中c-Met磷酸化升高。相反，通过从低氧条件培养基中去除HGF，可以降低PK8细胞的癌症侵袭，MMP活性和c-Met磷酸化水平。在免疫组织化学研究中，在周围基质以及胰腺癌细胞中观察到HIF-1alpha表达，因此表明癌症和基质细胞中都存在缺氧。此外，发现基质HGF表达不仅与癌细胞中的基质HIF-1alpha表达显着相关，而且与c-Met表达显着相关。这些结果表明，基质和癌细胞内的缺氧环境激活了HGF/c-Met系统，从而有助于胰腺癌的侵袭性特征。

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。

BACKGROUND & AIMS: :Diabetes is associated with augmentation of prothrombogenic von Willebrand factor (vWF) content in plasma. Earlier, the author and colleagues have shown that high glucose and insulin do not appreciably influence deposition of vWF into the subendothelial extracellular matrix (SECM) produced by cultured human umbilical vein endothelial cells (HUVECs). In the present work, the author used this model to test the effects of nonenzymatically glycated albumin (Glyc-HSA) and two lectins, concanavalin A (ConA) and wheat germ agglutinin (WGA), on vWF deposition into the SECM. First-passage HUVECs were seeded into gelatin-coated 96-well plates and cultured for 6 to 7 days. HSA or Glyc-HSA (at concentrations 25, 50, and 100 microg/mL), and WGA or ConA (4, 8, and 16 microg/mL) were added 3 h after seeding. Cell viability was tested by the MTT method. To determine vWF contents in the SECM, HUVECs were detached by treatment with NH4OH and the residual material was used as a solid phase in an enzyme-linked immunosorbent assay (ELISA)-like assay with primary (anti-vWF) and secondary (peroxidase-conjugated) antibodies. Addition of Glyc-HSA did not essentially influence VWF contents in the SECM (A490 was 0.226 versus 0.268 at 0 and 100 microg/mL, respectively; p > .05, n = 16). Cultivation in the presence of WGA led to the deterioration of cell viability, which was accompanied by a significant decrease of vWF in the SECM (0.248 versus 0.128 at 0 and 16 microg/mL, respectively; p < .001, n = 16). ConA did not influence viability of HUVECs, but this lectin at all concentrations consistently increased the deposition of vWF (up to 164% relative to control, p <.001; n = 16). These data indicate that endothelial carbohydrate determinants and corresponding ligands (namely, mannose-specific lectins) may be involved in the regulation of production and deposition of vWF.

背景与目标： : 糖尿病与血浆中血栓形成原性血管性假血友病因子 (vWF) 含量增加有关。早些时候，作者和同事已经表明，高糖和胰岛素不会明显影响vWF在培养的人脐静脉内皮细胞 (huvec) 产生的内皮下细胞外基质 (SECM) 中的沉积。在当前工作中，作者使用该模型测试了非酶促糖化白蛋白 (Glyc-HSA) 和两种凝集素，伴刀豆球蛋白A (ConA) 和小麦胚芽凝集素 (WGA) 对vWF沉积到SECM中的影响。将首次通过的huvec接种到明胶涂层的96孔板中，并培养6至7天。接种后3小时加入HSA或Glyc-HSA (浓度为25、50和100微克/毫升) 和WGA或ConA (4、8和16微克/毫升)。通过MTT方法测试细胞活力。为了确定SECM中的vWF含量，通过用NH4OH处理分离HUVECs，并将残留的物质用作一级 (抗-vWF) 和二级 (过氧化物酶结合的) 抗体的酶联免疫吸附测定 (ELISA) 样测定的固相。添加Glyc-HSA基本上不影响SECM中的VWF含量 (分别在0和100微克/毫升时A490为0.226对0.268; p> .05，n = 16)。在WGA存在下的培养导致细胞活力的恶化，其伴随着SECM中vWF的显著降低 (分别在0和16微克/毫升时0.248对0.128; p <.001，n = 16)。ConA不影响huvec的生存能力，但是在所有浓度下，这种凝集素始终增加vWF的沉积 (相对于对照高达164%，p <.001; n = 16)。这些数据表明，内皮碳水化合物决定簇和相应的配体 (即甘露糖特异性凝集素) 可能参与了vWF产生和沉积的调节。

BACKGROUND & AIMS: :Attention-deficit hyperactivity disorder (ADHD) is a common childhood psychiatric disorder. Despite intensive research efforts, the aetiology of ADHD remains unknown. Current evidence suggests that the aetiology of ADHD is heterogeneous, comprising of multiple factors. Recently, it has been proposed that brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may be implicated in the pathogenesis of ADHD. This hypothesis is supported by recent genetic studies in ADHD. Drawing on findings from studies into the drugs for ADHD relating to central BDNF expression, hyperactivity in BDNF knockout mice, BDNF effects in midbrain dopaminergic function and the close association between BDNF and the dopamine transporter (an important molecule for ADHD pathogenesis), it is proposed here that decreased central BDNF, particularly in the midbrain region, may play an important role in the pathogenesis ADHD. This hypothesis may have some implications for clinical findings in ADHD (for example, the co-morbidity between ADHD and major depression), and provide a new direction for the development of medication for ADHD treatment.

背景与目标： : 注意力缺陷多动障碍 (ADHD) 是一种常见的儿童精神疾病。尽管进行了大量研究，但ADHD的病因仍然未知。目前的证据表明，ADHD的病因是异质的，由多种因素组成。最近，有人提出，神经营养因子家族的成员脑源性神经营养因子 (BDNF) 可能与ADHD的发病机理有关。该假设得到了ADHD最近的遗传研究的支持。根据对ADHD药物的研究结果，该药物与中枢BDNF表达，BDNF基因敲除小鼠的活动过度，BDNF在中脑多巴胺能功能中的作用以及BDNF与多巴胺转运蛋白 (ADHD发病机理的重要分子) 之间的密切联系有关，在这里提出降低中枢BDNF，特别是在中脑区域，可能在ADHD的发病机理中起重要作用。该假设可能对ADHD的临床发现 (例如，ADHD与重度抑郁症之间的合并症) 具有一定的意义，并为ADHD治疗药物的发展提供了新的方向。

BACKGROUND & AIMS: :The oncoprotein LMP1 mimics an activated CD40 receptor, yet it is not known whether constitutive CD40 signaling, like LMP1, is sufficient to transform cells. Here we demonstrate that constitutive activation of the CD40 pathway by a chimeric LMP1CD40 molecule resembles the transforming function of LMP1 in inducing loss of contact inhibition and anchorage independent growth of Rat1 fibroblasts. Rat1 transformation correlates with the expression level of LMP1CD40 and depends on its ability to oligomerize. Our data provide direct evidence for the oncogenic potential of the CD40 signaling pathway, which is also established as a model-mechanism for LMP1-induced transformation.

背景与目标： : 癌蛋白LMP1模仿活化的CD40受体，但尚不清楚组成型CD40信号传导 (如LMP1) 是否足以转化细胞。在这里，我们证明了嵌合LMP1CD40分子对CD40途径的组成型激活类似于LMP1在诱导Rat1成纤维细胞的接触抑制丧失和锚定独立生长方面的转化功能。Rat1转化与LMP1CD40的表达水平相关，并取决于其寡聚能力。我们的数据为CD40信号通路的致癌潜力提供了直接证据，CD40信号通路也被确立为LMP1-induced转化的模型机制。

BACKGROUND & AIMS: :A novel procaryotic transcriptional regulatory element, AlgP, with a histone H1-like carboxy-terminal domain was identified in Pseudomonas aeruginosa. AlgP is required for transcription of the key biosynthetic gene algD, which is necessary for production of the exopolysaccharide alginate causing mucoidy in P. aeruginosa. Mucoidy is a critical virulence determinant of P. aeruginosa invariably associated with the respiratory infections causing high mortality in cystic fibrosis. Here we show that AlgP and histones H1 both have repeated units of the Lys-Pro-Ala-Ala motif (KPAA) and its variations within their long (over 100 amino acids) carboxy-terminal domains. This region of histone H1 tails has been shown to bind to the linker DNA in eucaryotic chromatin fibers. A synthetic 50-mer peptide consisting of repeats from the AlgP carboxy-terminal domain was found to bind DNA in a mobility shift DNA-binding assay. AlgP is encoded by a gene that contains multiple direct repeats organized as tandem, head-to-tail, 12-base-pair (bp) units overlapping with six highly conserved 75-bp units. The repetitive structure of the algP gene appears to participate in the processes underlying the metastable character of mucoidy in P. aeruginosa. Relatively large DNA rearrangements spanning the region with tandem direct repeats encoding the carboxy-terminal histone H1-like structure of AlgP were detected in several strains upon conversion from the mucoid to the nonmucoid phenotype. The frequency of the detectable algP rearrangements associated with the transition into the nonmucoid state varied from strain to strain and ranged from 0 to 50%. The nonmucoid derivatives with the clearly rearranged chromosomal copy of algP were complemented to mucoidy with plasmids containing algP from P. aeruginosa PAO. When a random collection of mucoid strains, isolated from different cystic fibrosis patients, was analyzed by using polymerase chain reaction, an additional level of strain-dependent sequence variation in algP was observed. Variations in the number of the 12-bp repeats were found; however, they did not appear to influence the mucoid status of the strains examined. Thus, the repeated region of algP appears to be a hot spot for DNA rearrangements and strain-dependent variability.

背景与目标： : 在铜绿假单胞菌中鉴定了一种新型的原核转录调节元件AlgP，其具有组蛋白H1-like羧基末端结构域。AlgP是关键生物合成基因algD转录所必需的，这对于产生引起铜绿假单胞菌粘液的胞外多糖藻酸盐是必需的。粘液症是铜绿假单胞菌的关键毒力决定因素，总是与导致囊性纤维化高死亡率的呼吸道感染相关。在这里，我们显示了AlgP和组蛋白H1都具有Lys-Pro-Ala基序 (KPAA) 的重复单元及其在其长 (超过100个氨基酸) 羧基末端结构域中的变化。已显示组蛋白H1尾巴的该区域与真核染色质纤维中的接头DNA结合。在迁移率转移DNA结合试验中，发现由来自AlgP羧基末端结构域的重复序列组成的合成50聚体肽结合DNA。AlgP由一个基因编码，该基因包含多个直接重复序列，组织为串联，头对尾，12碱基对 (bp) 单元，与六个高度保守的75 bp单元重叠。algP基因的重复结构似乎参与了铜绿假单胞菌黏液的亚稳态特征的潜在过程。从粘液样转化为非粘液样表型后，在几个菌株中检测到跨越编码AlgP羧基末端组蛋白H1-like结构的串联直接重复序列的区域的相对较大的DNA重排。与过渡到非粘液状态相关的可检测的algP重排的频率因菌株而异，范围为0至50%。具有明显重排的algP染色体拷贝的非粘液衍生物与含有铜绿假单胞菌PAO的algP的质粒互补为粘液。当使用聚合酶链反应分析从不同的囊性纤维化患者中分离出的粘液样菌株的随机集合时，观察到algP中菌株依赖性序列变异的额外水平。发现12 bp重复序列的数量有所变化; 但是，它们似乎并未影响所检查菌株的粘液状态。因此，algP的重复区域似乎是DNA重排和应变依赖性变异性的热点。