BACKGROUND & AIMS: :Studies were performed to elucidate the possible relationship between microvessel density, proliferative activity and angiogenesis in eutopic endometrium from women with and without endometriosis and peritoneal endometriotic lesions. The question whether changes in these parameters in endometriotic lesions were reflected by the level of vascular endothelial growth factor-A (VEGF-A) in serum and peritoneal fluid was also studied. Biopsy specimens of both eutopic endometrium and peritoneal endometriotic lesions from women with endometriosis (n = 25) as well as eutopic endometrium from women without endometriosis (n = 14) were analysed immunohistochemically regarding microvessel density, proliferative activity, and expression of VEGF-A and its receptors vascular endothelial growth factor receptors 1 and 2 (VEGFR-1 and VEGFR-2) in stroma, glands and blood vessels. The VEGF-A concentration was measured in peritoneal fluid and serum. Secretory phase eutopic endometrium from women with endometriosis had significantly higher microvessel density, expression of VEGF-A in glandular epithelium and VEGFR-2 in endometrial blood vessels than those from women without endometriosis. Endometriotic lesions with high proliferative activity had a higher microvessel density and showed higher vascular expression of VEGFR-2 as well as being accompanied by higher levels of VEGF-A in peritoneal fluid and serum, compared with lesions with low proliferative activity. In conclusion, there seems to be a dysregulation of angiogenic activity in the eutopic endometrium of women with endometriosis and endometriotic lesions with high proliferative activity were accompanied by higher local angiogenic activity and higher levels of VEGF in serum and peritoneal fluid.

背景与目标： : 进行了研究，以阐明患有和不患有子宫内膜异位症和腹膜子宫内膜异位病变的妇女的在位子宫内膜中微血管密度，增殖活性和血管生成之间的可能关系。还研究了血清和腹膜液中血管内皮生长因子-A (vegf-a) 的水平是否反映了子宫内膜异位病变中这些参数的变化的问题。免疫组织化学分析了子宫内膜异位症妇女 (n = 25) 的在位子宫内膜和腹膜子宫内膜异位病变的活检标本以及无子宫内膜异位症妇女 (n = 14) 的在位子宫内膜的活检标本，其微血管密度，增殖活性，并在间质、腺体和血管中表达vegf-a及其受体血管内皮生长因子受体1和2 (VEGFR-1和VEGFR-2)。在腹膜液和血清中测量vegf-a浓度。子宫内膜异位症妇女的分泌期在位子宫内膜的微血管密度，腺上皮和内膜血管VEGFR-2中vegf-a的表达明显高于无子宫内膜异位症妇女。与低增殖活性的病变相比，具有高增殖活性的子宫内膜异位病变具有更高的微血管密度，并且显示出更高的VEGFR-2血管表达，并且在腹膜液和血清中伴有较高的vegf-a水平。总之，子宫内膜异位症妇女的在位子宫内膜中似乎存在血管生成活性失调，而具有高增殖活性的子宫内膜异位病变伴有较高的局部血管生成活性以及血清和腹膜液中较高的VEGF水平。

BACKGROUND & AIMS: The effect of nutritional status on IGF-I mRNA expression in the liver and brain of juvenile barramundi (Lates calcarifer) was investigated. Fish were either fed a satiety ration (SAT) or starved (STV) for 6 weeks. Starved fish demonstrated significantly lower condition factor and hepatic IGF-I mRNA expression at 3 and 6 weeks, when compared with the SAT group. IGF-I mRNA expression in the brain was 10 fold lower than the liver and was not affected by ration size. These results suggest the liver is the major site of IGF-I mRNA synthesis and hepatic but not brain IGF-I mRNA expression is regulated by food availability in juvenile barramundi.

背景与目标： 研究了营养状况对幼年barramundi (Lates calcarifer) 肝脏和大脑中igf-i mRNA表达的影响。对鱼喂食饱腹感 (SAT) 或饥饿 (STV) 6周。与SAT组相比，饥饿的鱼在3周和6周时表现出明显较低的条件因子和肝igf-i mRNA表达。大脑中igf-i mRNA的表达比肝脏低10倍，不受日粮大小的影响。这些结果表明，肝脏是igf-i mRNA合成的主要部位，而肝脏而不是大脑igf-i mRNA的表达受幼年barramundi食物的调节。

BACKGROUND & AIMS: :The objective of this study was to determine whether paclitaxel and a strong antioxidant, pyrrolidinedithiocarbamate (PDTC), can affect the activation of nuclear factor-kappa B (NF-kappaB) in SKOV-3 human ovarian cancer cell line and the effect of these two agents on the growth and apoptosis of the cancer cells. The cells were treated with various concentrations of paclitaxel and/or PDTC at various time intervals. Following treatments, cell growth and apoptosis were determined by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulphonyl)-2H-tetrazolium (WST-8) (WST) assay and flow cytometry, respectively. Western blot assay was used to determine the nuclear p65 protein and cytoplasmic IkappaB-alpha protein. High doses of PDTC significantly inhibited the growth of SKOV-3 cells and caused apoptosis. Paclitaxel and lower doses of PDTC combined demonstrated additive inhibition of cell growth and increased levels of apoptosis. Treatment of paclitaxel alone showed increased nuclear p65 protein and decreased cytoplasmic IkappaB-alpha protein expression, while pretreatment of PDTC reversed this function. PDTC blocks the paclitaxel-induced activation of NF-kappaB leading to increased chemosensitivity to paclitaxel and enhanced apoptosis. Combining antioxidants and paclitaxel has significant potential to overcome the risk of paclitaxel resistance.

背景与目标： : 这项研究的目的是确定紫杉醇和强抗氧化剂吡咯烷二硫代氨基甲酸酯 (PDTC) 是否会影响SKOV-3人卵巢癌细胞系中核因子-κ B (NF-κ B) 的活化以及这两种药物对癌细胞生长和凋亡的影响。在不同的时间间隔用各种浓度的紫杉醇和/或PDTC处理细胞。处理后，通过2-(2-甲氧基-4-硝基苯基)-3-(4-硝基苯基)-5-(2,4-二硫酰基)-2h-四唑 (WST-8) (WST) 测定和流式细胞仪测定细胞生长和凋亡。Western blot测定法用于测定核p65蛋白和细胞质IkappaB-α 蛋白。高剂量的PDTC显著抑制SKOV-3细胞的生长并引起细胞凋亡。紫杉醇和较低剂量的PDTC组合显示出对细胞生长的加性抑制和凋亡水平的增加。单独治疗紫杉醇显示核p65蛋白增加，胞质IkappaB-α 蛋白表达降低，而PDTC的预处理逆转了这一功能。PDTC阻断紫杉醇诱导的NF-κ b激活，从而增加对紫杉醇的化学敏感性并增强细胞凋亡。结合抗氧化剂和紫杉醇具有克服紫杉醇耐药性风险的巨大潜力。

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: Thrombin activation requires assembly of a prothrombinase complex of activated coagulation factors on an anionic phospholipid surface, classically provided by activated platelets. We have previously shown that anionic phosphatidylserine is exposed by rat vascular smooth muscle cells (VSMCs) undergoing apoptosis after serum withdrawal. In this study, using a chromogenic assay, we have shown thrombin generation by apoptotic VSMCs expressing c-myc (VSMC-myc) with an area under the thrombin-generation curve (AUC) of 305 +/- 17 nmol x min/L and a peak thrombin (PT) of 154 +/- 9 nmol/L. The thrombin-generating potential of the apoptotic VSMC-myc cells was greater than that of unactivated platelets (P = .003 for AUC; P = .0002 for PT) and similar to calcium-ionophore activated platelets (AUC of 332 +/- 15 nmol x min/L, P = .3; PT of 172 +/- 8 nmol/L, P = .2). Thrombin activation was also seen with apoptotic human VSMCs (AUC of 211 +/- 8 nmol x min/L; PT of 103 +/- 4 nmol/L) and was inhibited by annexin V (P < .0001 for AUC and PT). VSMC-myc cells maintained in serum generated less thrombin than after serum withdrawal (P = .0002 for AUC and PT). VSMCs derived from human coronary atherosclerotic plaques that apoptose even in serum also generated thrombin (AUC of 260 +/- 2 nmol x min/L; PT of 128 +/- 4 nmol/L). We conclude that apoptotic VSMCs possess a significant thrombin-generating capacity secondary to phosphatidylserine exposure. Apoptotic cells within atherosclerotic plaques may allow local thrombin activation, thereby contributing to disease progression.

背景与目标： 凝血酶激活需要在阴离子磷脂表面上组装活化的凝血因子的凝血酶原复合物，通常由活化的血小板提供。我们以前已经表明，阴离子磷脂酰丝氨酸被大鼠血管平滑肌细胞 (VSMCs) 暴露，在血清戒断后发生凋亡。在这项研究中，使用显色测定法，我们已经显示表达c-myc (VSMC-myc) 的凋亡VSMC产生凝血酶，凝血酶产生曲线 (AUC) 下面积为305 +/- 17 nmol × min/L，凝血酶峰 (PT) 为154 +/- 9 nmol/L。凋亡的VSMC-myc细胞的凝血酶生成潜力大于未激活的血小板 (AUC P = .003; PT P = .0002)，与钙离子载体激活的血小板相似 (AUC为332 +/- 15 nmol x min/L，P = .3; PT为172 +/- 8 nmol/L，P = .2)。在凋亡的人VSMCs中也可以看到凝血酶活化 (AUC为211 +/- 8 nmol × min/L; PT为103 +/- 4 nmol/L)，并被膜联蛋白V抑制 (P < .0001 AUC和PT)。维持在血清中的VSMC-myc细胞产生的凝血酶少于血清戒断后 (对于AUC和PT，P = .0002)。来源于人冠状动脉粥样硬化斑块的VSMCs，即使在血清中凋亡也产生凝血酶 (AUC为260 +/- 2 nmol × min/L; PT为128 +/- 4 nmol/L)。我们得出的结论是，凋亡的VSMCs在磷脂酰丝氨酸暴露后具有显着的凝血酶生成能力。动脉粥样硬化斑块内的凋亡细胞可能会激活局部凝血酶，从而促进疾病进展。

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: These experiments were designed to determine whether glycogenolysis was influenced by the glycogen concentration of vascular smooth muscle. Segments of hog carotid artery smooth muscle were allowed to synthesize variable amounts of 1-[13C]glucosyl units of glycogen. Artery segments were then isometrically contracted in the presence of 2-[13C]glucose. Prior to and after isometric contraction, measurements were made of tissue glycogen content and superfusate glucose and lactate concentrations. 2-[13C]Lactate and 3-[13C]lactate peak intensities in the superfusate were measured using 13C-NMR spectroscopy. The tissue glycogen content decreased exponentially during the 4.5 h of isometric contraction (R2 = 0.990), despite more than a 3-fold range of glycogen concentration prior to contraction. The extent of glycogen utilization during a 3 h isometric contraction varied linearly with the precontraction glycogen concentration (R2 = 0.727). Lactate production specifically from glycogen breakdown increased with an increase in precontraction glycogen concentration (R2 = 0.620). During a 3 h isometric contraction neither the glucose utilization (R2 = 0.007) nor lactate production specifically produced from glucose (R2 = 0.00002) varied with the precontraction glycogen concentration. It is concluded that the rate of glycogenolysis is determined by the content of glycogen during prolonged contractions. In addition, precontraction glycogen levels influence the pathway for glycogen utilization but not the pathway for glucose utilization. Therefore, glycolysis and glycogenolysis behave independently in vascular smooth muscle.

背景与目标： 这些实验旨在确定糖原分解是否受血管平滑肌糖原浓度的影响。允许猪颈动脉平滑肌段合成可变量的1-[13C] 糖原葡萄糖单元。然后在2-[13C] 葡萄糖存在下等距收缩动脉段。在等距收缩之前和之后，测量组织糖原含量和超融合物葡萄糖和乳酸浓度。使用13C-NMR光谱测量超融合物中的2-[13C] 乳酸和3-[13C] 乳酸峰强度。组织糖原含量在等距收缩的4.5小时内呈指数下降 (R2 = 0.990)，尽管收缩前糖原浓度超过3倍。在3 h等距收缩期间糖原利用的程度随收缩前糖原浓度线性变化 (R2 = 0.727)。糖原分解产生的乳酸产量随着收缩前糖原浓度的增加而增加 (R2 = 0.620)。3小时的等距收缩葡萄糖利用率 (R2 = 0.007) 和特别由葡萄糖产生的乳酸产量 (R2 = 0.00002) 都不随收缩前糖原浓度而变化。结论是糖原分解速率由长期收缩期间糖原含量决定。此外，收缩前糖原水平会影响糖原利用的途径，但不会影响葡萄糖利用的途径。因此，糖酵解和糖原分解在血管平滑肌中独立运作。

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: CONTEXT:In animal models, estrogen inhibits atherogenesis by inhibiting many of the early steps of atherosclerotic plaque formation. However, the lack of cardioprotective effect by postmenopausal hormone replacement therapy and possible increase in cardiovascular events observed during the first year after the initiation of hormone replacement therapy may suggest that once the plaque is formed, estrogen may have additional effects that may counteract its beneficial outcomes. Indeed, the effect of estrogen on plaque stability has not been identified. OBJECTIVE:We hypothesized that 17beta-estradiol (E2) may cause increased apoptosis in human coronary artery endothelial cells (HCAECs). This effect would explain an adverse effect on plaque stability in vivo. INTERVENTION(S) AND MAIN OUTCOME MEASURE(S):The effect of E2 on apoptosis, cell proliferation, and expression of proapoptotic molecules Fas and Fas ligand (FasL) in cultured HCAECs was evaluated. RESULTS:HCAECs in culture treated with E2 showed an increase in DNA strand breaks and nuclear fragmentation indicative of apoptosis. E2 treatment also induced a significant concentration-dependent increase in Fas mRNA and protein expressions in HCAECs. Moreover, the expression of FasL mRNA and secretion of FasL protein by HCAECs were enhanced in response to E2 treatments. CONCLUSIONS:E2 increases the apoptosis in cultured HCAECs. Enhanced Fas and FasL expressions in response to E2 suggest that activation of the Fas/FasL pathway may be a mediator of the proapoptotic effects of E2 in these cells.

背景与目标：

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。