BACKGROUND & AIMS: Interleukin-1 alpha (IL-1 alpha) induces cell motility in a variety of benign cell types and in some but not all malignant cell lines in vitro. This study characterizes the IL-1 alpha-induced motility of an aggressive human melanoma cell line that expresses both type I and type II IL-1 receptors. We tested the effect of monoclonal antibodies including function-blocking moAbs against the type I and type II IL-1 receptors on melanoma cell motility to determine which receptor is involved in signal transduction of IL-1 alpha-induced melanoma cell motility. IL-1 alpha significantly increases MM-RU melanoma cell migration in a dose-dependent manner using modified Boyden chamber assays at concentrations 10 to 100 times less than concentrations that significantly inhibit cell growth. Computer-assisted time-lapse image analysis reveals that the motility is inhibited in a dose-dependent manner by neutralizing antibodies against IL-1 alpha. Function-blocking monoclonal antibodies against either type I or type II IL-1 receptors show a significant inhibition of cytokine-induced enhanced cell migration. When both the anti-IL-1 receptor antibodies are added together, the motility-response is completely blocked to control levels. Taken together the data indicate that the IL-1 alpha-induced motility of MM-RU melanoma cells is mediated through both type I and type II IL-1 receptors. The significant inhibition of motility by neutralizing IL-1 alpha or blocking either one or both of the IL-1 receptors indicates an integration of IL-1-induced signals in the induction of melanoma cell migration.

背景与目标： 白细胞介素-1（IL-1 alpha）在多种良性细胞类型中以及某些但不是全部恶性细胞系中诱导细胞运动。这项研究的特点是表达I型和II型IL-1受体的侵略性人黑素瘤细胞系的IL-1α诱导的运动。我们测试了包括针对I型和II型IL-1受体的功能阻断性单抗的单克隆抗体对黑素瘤细胞运动性的影响，以确定哪个受体参与了IL-1α诱导的黑素瘤细胞运动性的信号转导。 IL-1α使用改良的Boyden室测定法以剂量依赖性方式显着增加MM-RU黑色素瘤细胞迁移，其浓度比明显抑制细胞生长的浓度低10至100倍。计算机辅助的延时图像分析表明，通过中和针对IL-1α的抗体，可以以剂量依赖性的方式抑制运动性。针对I型或II型IL-1受体的功能阻断性单克隆抗体显示出对细胞因子诱导的细胞迁移增强的显着抑制作用。当两种抗IL-1受体抗体一起添加时，运动反应完全被阻断至对照水平。数据合计表明，IL-1α诱导的MM-RU黑色素瘤细胞的运动是通过I型和II型IL-1受体介导的。通过中和IL-1α或阻断任何一个IL-1受体或两个IL-1受体来显着抑制运动性，这表明在黑素瘤细胞迁移的诱导中整合了IL-1诱导的信号。

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和腹膜子宫内膜异位病变的女性在位子宫内膜的微血管密度，增殖活性和血管生成之间的可能关系。还研究了是否通过血清和腹膜液中血管内皮生长因子-A（VEGF-A）的水平反映子宫内膜异位病变中这些参数的变化的问题。对子宫内膜异位症妇女（n = 25）和非子宫内膜异位症妇女（n = 14）的对位子宫内膜和腹膜子宫内膜异位病变的活检标本进行了免疫组织化学分析，涉及微血管密度，增殖活性，VEGF-A和其受体位于基质，腺体和血管中的血管内皮生长因子受体1和2（VEGFR-1和VEGFR-2）。测定腹膜液和血清中的VEGF-A浓度。子宫内膜异位症女性的分泌期异位子宫内膜比无子宫内膜异位症女性的子宫内膜微血管密度，腺上皮中的VEGF-A表达和子宫内膜血管中的VEGFR-2显着更高。与具有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，并在腹膜液和血清中具有较高的VEGFR-2血管表达以及较高的VEGF-A水平。总之，子宫内膜异位症妇女的异位子宫内膜血管新生活性似乎异常，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新生活性和血清和腹膜液中较高的VEGF水平。

BACKGROUND & AIMS: :Under normoxic conditions the alpha-subunit of hypoxia-inducible factor (HIF-1alpha) protein is targeted for degradation by the von Hippel-Lindau (VHL) tumor suppressor protein acting as an E3 ubiquitin ligase. Recently, we developed a hypoxia-targeting protein, TOP3, which consisted of procaspase-3 with the VHL-mediated protein destruction motif of HIF-1alpha. This design enables procaspase-3 to be regulated similarly with HIF-1alpha, being degraded under normoxia while stabilized under hypoxia. Furthermore, stabilized TOP3 was cleaved by the hypoxic stress-induced endogenous caspases and thus the procaspase-3 was converted to active caspase-3 specifically under hypoxic conditions. These data demonstrated that the VHL-mediated protein destruction motif of HIF-1alpha endowed procaspase-3 with hypoxia-specific cytotoxicity.

背景与目标： 在常氧条件下，缺氧诱导因子（HIF-1alpha）蛋白的α亚基被von Hippel-Lindau（VHL）肿瘤抑制蛋白作为E3泛素连接酶降解。最近，我们开发了一种低氧靶向蛋白TOP3，该蛋白由具有HIF-1alpha的VHL介导的蛋白破坏基序的procaspase-3组成。这种设计使procaspase-3与HIF-1alpha相似，在常氧下降解，而在低氧下稳定。此外，稳定化的TOP3被低氧应激诱导的内源性半胱天冬酶裂解，因此procaspase-3特别是在低氧条件下转化为活性caspase-3。这些数据表明，HIF-1α的VHL介导的蛋白质破坏基序赋予了procaspase-3具有缺氧特异性细胞毒性。

BACKGROUND & AIMS: Elderly patients with malignant glioma have a poor prognosis and the benefit of standard radical radiotherapy is equivocal. Twenty-two percent of the adult referral base with malignant glioma at our centre is of age 70 years or greater. A phase II study was undertaken to determine if a shorter course of therapy yields a comparable median survival to radical radiotherapy and thus constitutes an appropriate investigational palliative regimen. 25 patients were accrued between 1988-1995, all of whom had histologically proven malignant glioma, 23 glioblastoma multiforme and 2 anaplastic astrocytoma. The median age was 73 (range 70-78) and median Karnofsky Performance Status (KPS) was 70.40% had a stereotactic biopsy only for diagnosis. Radiotherapy was delivered to limited fields to a dose of 37.5 Gy in 15 daily fractions over 3 weeks. An intention-to-treat analysis was undertaken with survival determined from date of initial consultation. The median survival of the whole group was 8.0 months (95% CI 4.8-9.6). Patients with good performance status (KPS > 70) had a median survival of 10.4 months (95% CI 9.6-14.7). 37.5 Gy in 15 daily fractions appears to yield comparable median survival to that of other series of radical radiotherapy. A phase III study of this regimen is recommended in investigating optimal palliation of elderly malignant glioma patients.

背景与目标： 老年恶性神经胶质瘤患者预后较差，标准根治性放疗的益处是模棱两可的。我们中心的成人恶性神经胶质瘤转诊基数中有22％的年龄为70岁或更高。进行了II期研究，以确定较短的疗程是否可以产生与根治性放疗相当的中位生存期，从而构成一种适当的姑息治疗方案。 1988年至1995年期间，共有25例患者，均经组织学证实为恶性神经胶质瘤，23例多形性胶质母细胞瘤和2例间变性星形细胞瘤。中位年龄为73岁（范围为70-78岁），中位Karnofsky绩效状态（KPS）为70.40％，仅进行了立体定向活检以进行诊断。放射治疗在3周内分15天内分次以37.5 Gy的剂量传送到有限的领域。进行了意向性治疗分析，生存期从初次咨询之日起确定。整个组的中位生存期为8.0个月（95％CI 4.8-9.6）。表现良好状态（KPS> 70）的患者中位生存期为10.4个月（95％CI 9.6-14.7）。 15个每日剂量中的37.5 Gy似乎可以产生与其他系列放射疗法相当的中位生存期。建议对该方案进行III期研究，以调查老年恶性神经胶质瘤患者的最佳缓解情况。

BACKGROUND & AIMS: :The primary objectives of this study were to follow the temporal patterns of testicular LH and FSH receptor (LH-R and FSH-R) concentrations and affinity (Ka) during sexual maturation in bulls and to see if such patterns could help explain the control of rapid testicular growth that occurs after 25 weeks of age, when serum gonadotropin concentrations are low. Separate groups of Hereford x Charolais calves (n = 6) were castrated every 4 weeks from 5 to 33 weeks of age and at 56 weeks of age. A week prior to castrations, from 5 to 33 weeks of age, blood was collected every 15 min for 10 h. The transition from indifferent supporting cells to Sertoli cells in seminiferous tubules was rapid between 13 and 25 weeks and rapid testis growth occurred after 25 weeks of age. Serum LH and FSH concentrations were transiently elevated at 12 weeks of age (P < 0.05). LH-R concentrations decreased from 13 to 25 weeks of age and increased to 56 weeks of age (P < 0.05). LH-RKa decreased from 9 to 17 weeks of age, increased to 29 weeks of age and declined to 33 weeks of age (P < 0.05). FSH-R concentrations declined from 17 to 25 weeks of age then increased to 56 weeks of age (P < 0.05). FSH-RKa increased from 17 to 25 weeks of age (P < 0.05). High concentrations of gonadotropins and their receptors may be critical to initiate testis growth postnatally and support it after 25 weeks of age in the face of low serum gonadotropin concentrations.

背景与目标： ：本研究的主要目的是追踪公牛性成熟过程中睾丸LH和FSH受体（LH-R和FSH-R）浓度和亲和力（Ka）的时间模式，并观察这种模式是否有助于解释控制因素血清促性腺激素浓度低时，在25周龄后出现睾丸快速生长的情况。从5到33周龄和56周龄每4周cast割一次赫瑞福德x夏洛来牛犊（n = 6）组。 5至33周龄weeks割前一周，每15分钟收集一次血液，持续10 h。在13至25周之间，从生精小管中的冷漠支持细胞向Sertoli细胞的过渡迅速，并且25周龄后睾丸迅速生长。血清LH和FSH浓度在12周龄时短暂升高（P <0.05）。 LH-R浓度从13周龄降低到25周龄，增加到56周龄（P <0.05）。 LH-RKa从9周龄降低到17周龄，增加到29周龄，下降到33周龄（P <0.05）。 FSH-R浓度从17周下降到25周，然后上升到56周（P <0.05）。 FSH-RKa从17周龄增加到25周龄（P <0.05）。高浓度的促性腺激素及其受体对于出生后开始睾丸生长并在25周龄后面对低血清促性腺激素浓度的情况下支持睾丸生长可能至关重要。

BACKGROUND & AIMS: :Matrix metalloproteinase (MMPs) expression has been linked to gynecological tumor aggressiveness. The objective of this study was to determine MMP-2, MMP-7, and MMP-9 and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 expression in endometrial malignancies and their relation to clinical and histologic parameters. Formalin-fixed, paraffin-embedded tumor samples from 50 patients with endometrial carcinoma treated between 1999 and 2004 were stained with specific monoclonal antibodies. The tumors were grouped according to the FIGO classification. The staining results were compared to histologic and clinical data. Semiquantitative analysis of MMP and TIMP expression showed a significant difference in TIMP-2 expression according to the histologic subtype (P = 0.03) and also a trend towards a difference in MMP-9 expression (P = 0.05). MMP-2 expression increased and TIMP-2 expression fell as the histologic grade increased (P = 0.0007, P < 0.0001, respectively). MMP-2 expression correlated with lymph node metastasis (P = 0.04), while TIMP-2 expression correlated with the depth of myometrial invasion (P = 0.01), vasculolymphatic space involvement (P = 0.02), and lymph node metastasis (P = 0.0003). These results support the involvement of MMPs and TIMPs in endometrial tumor growth and progression. High MMP-2 and low TIMP-2 expression were the most potent markers of endometrial tumors with a high risk of local and distant spread.

背景与目标： 基质金属蛋白酶（MMPs）的表达与妇科肿瘤的侵袭性有关。这项研究的目的是确定子宫内膜恶性肿瘤中MMP-2，MMP-7和MMP-9以及金属蛋白酶组织抑制剂（TIMP）-1和TIMP-2的表达及其与临床和组织学参数的关系。用特异性单克隆抗体对1999年至2004年间接受治疗的50例子宫内膜癌患者的福尔马林固定，石蜡包埋的肿瘤样品进行染色。根据FIGO分类将肿瘤分组。将染色结果与组织学和临床数据进行比较。 MMP和TIMP表达的半定量分析显示，根据组织学亚型，TIMP-2表达存在显着差异（P = 0.03），并且MMP-9表达也呈现差异的趋势（P = 0.05）。随着组织学分级的升高，MMP-2表达增加而TIMP-2表达下降（分别为P = 0.0007，P <0.0001）。 MMP-2表达与淋巴结转移相关（P = 0.04），而TIMP-2表达与肌层浸润深度（P = 0.01），血管淋巴间隙受累（P = 0.02）和淋巴结转移（P = 0.0003）相关）。这些结果支持MMP和TIMP参与子宫内膜肿瘤的生长和进展。 MMP-2的高表达和TIMP-2的低表达是子宫内膜肿瘤最有效的标志物，具有局部和远处扩散的高风险。

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： 研究了营养状况对少年肺鱼（Lates calcarifer）肝脏和脑中IGF-I mRNA表达的影响。给鱼喂饱口粮（SAT）或饿死（STV）6周。与SAT组相比，在3周和6周时，饥饿的鱼表现出明显较低的条件因子和肝脏IGF-I mRNA表达。脑中IGF-I mRNA表达比肝脏低10倍，并且不受口粮大小的影响。这些结果表明，肝脏是IGF-I mRNA合成的主要部位，肝而不是脑IGF-I mRNA的表达受幼鱼的食物供应量的调节。

BACKGROUND & AIMS: BACKGROUND AND PURPOSE:The purpose of this project was to create guidelines for 13 types of physical rehabilitation interventions used in the management of adult patients (>18 years of age) presenting with hemiplegia or hemiparesis following a single clinically identifiable ischemic or hemorrhagic cerebrovascular accident (CVA). METHOD:Using Cochrane Collaboration methods, the Ottawa Methods Group identified and synthesized evidence from comparative controlled trials. The group then formed an expert panel, which developed a set of criteria for grading the strength of the evidence and the recommendation. Patient-important outcomes were determined through consensus, provided that these outcomes were assessed with a validated and reliable scale. RESULTS:The Ottawa Panel developed 147 positive recommendations of clinical benefit concerning the use of different types of physical rehabilitation interventions involved in post-stroke rehabilitation. DISCUSSION AND CONCLUSION:The Ottawa Panel recommends the use of therapeutic exercise, task-oriented training, biofeedback, gait training, balance training, constraint-induced movement therapy, treatment of shoulder subluxation, electrical stimulation, transcutaneous electrical nerve stimulation, therapeutic ultrasound, acupuncture, and intensity and organization of rehabilitation in the management of post stroke.

背景与目标： 背景与目的：本项目的目的是为在临床上可识别的缺血性或出血性脑血管意外（单发或偏瘫）后出现偏瘫或偏瘫的成年患者（> 18岁）的治疗中使用的13种类型的物理康复干预措施创建指南。 CVA）。
方法：渥太华方法小组使用Cochrane协作方法，从比较对照试验中鉴定并合成了证据。然后，该小组成立了一个专家小组，为评估证据和推荐的强度制定了一套标准。通过共识确定患者重要的结局，但前提是这些结局必须以经过验证的可靠量表进行评估。
结果：渥太华专家组针对涉及卒中后康复的各种类型的物理康复干预措施的使用提出了147项临床有益的积极建议。
讨论与结论：渥太华小组建议使用治疗性锻炼，任务导向训练，生物反馈，步态训练，平衡训练，约束性运动疗法，肩关节半脱位治疗，电刺激，经皮电神经刺激，超声治疗，针灸，以及中风后管理中康复的强度和组织。

BACKGROUND & AIMS: :The objective of this study was to confirm whether hemoglobin (Hb) levels during chemoradiotherapy are associated with survival in patients with locally advanced cervical carcinoma and to assess impact of the Hb level on survival according to lymph node (LN) metastasis. A retrospective review of 85 cervical carcinoma patients treated with concurrent chemoradiotherapy was conducted. The stage of disease ranged between FIGO stage IB and stage IVA. Disease-free and overall survivals were evaluated by univariate and multivariate analyses. After median follow-up of 35.7 months, 24 patients developed recurrence of disease and 14 patients died from their disease. Stage, LN metastasis, and squamous cell carcinoma antigen and Hb levels during chemoradiation were correlated significantly with survival (P < 0.05). Maintenance of Hb above 10.0 g/dL was associated with better survival (P < 0.05). However, no such benefits were observed in patients with LN metastasis by magnetic resonance imaging (MRI). Multivariate Cox regression hazard model showed that Hb levels during chemoradiation were an independent prognostic factor in patients without LN metastasis by MRI. Maintenance of Hb during chemoradiation is of benefit in cervical carcinoma patients without LN metastasis but not with LN metastasis by MRI.

背景与目标： ：本研究的目的是确定化学放疗期间血红蛋白（Hb）水平是否与局部晚期宫颈癌患者的生存相关，并根据淋巴结（LN）转移评估Hb水平对生存的影响。回顾性回顾了85例同时放化疗的宫颈癌患者。疾病的阶段在FIGO的IB阶段和IVA阶段之间。通过单因素和多因素分析评估无病生存期和总生存期。在中位随访35.7个月后，有24例患者复发疾病，有14例患者死于疾病。化学放疗期间的分期，LN转移，鳞状细胞癌抗原和血红蛋白水平与生存率显着相关（P <0.05）。维持Hb高于10.0 g / dL与更好的生存率相关（P <0.05）。但是，通过磁共振成像（MRI）在LN转移患者中未观察到此类益处。多元Cox回归风险模型显示，放化疗期间Hb水平是无LN转移的患者（通过MRI）的独立预后因素。对于没有LN转移但没有MRI的LN转移的宫颈癌患者，放化疗期间维持Hb有益。

BACKGROUND & AIMS: OBJECTIVE:To assess the effect of preoperative local anaesthesia with ropivacaine and find out if there was a dose-response relationship with postoperative pain after inguinal hernia repair.

DESIGN:Randomised, double-blind, placebo-controlled trial.

SETTING:Two Swedish and two Norwegian hospitals.

SUBJECTS:131 Male patients undergoing elective inguinal hernia repair.

INTERVENTION:Infiltration of the inguinal field before operation with 0.5% ropivacaine 40 ml (200 mg), 0.25% ropivacaine 40 ml (100 mg) or saline 40 ml.

MAIN OUTCOME MEASURES:Wound pain at rest and during mobilisation, pressure exerted to reach pain threshold and maximum pain tolerance after 3, 6, 10, and 24 hours, and after 7 days; consumption of analgesics; and Quality of Life assessed by two independent questionnaires before and after operation.

RESULTS:Pain scores after 3 hours were significantly lower in the ropivacaine groups compared with the saline group for all variables (p < 0.05). At 6 hours pain scores were significantly lower for ropivacaine 0.5% compared with saline for wound pain during mobilisation and pressure exerted to reach maximum pain tolerance. Patients given saline made their first request for analgesics significantly sooner than in the other two groups (p < 0.05), and a significantly larger percentage of them requested analgesics during the first 24 hours (p < 0.05). Evaluation of the Quality of Life questionnaires showed no significant differences between the groups.

CONCLUSION:Ropivacaine has a significant, dose-related pain-reducing effect in the immediate postoperative period but we could find no support for the theory that preoperative infiltration analgesia reduces long term pain.

背景与目标： 目的：评估罗哌卡因术前局部麻醉的效果，并确定腹股沟疝修补术后是否与术后疼痛存在剂量反应关系。

DESIGN ：随机，双盲，安慰剂对照试验。

设置：两家瑞典医院和两家挪威医院。

受试者 ：131接受择期腹股沟疝修补术的男性患者。

干预：术前用0.5％罗哌卡因40 ml（200 mg），0.25％罗哌卡因40 ml（100毫克或盐水40毫升。

主要观察指标：静止和运动时的伤口疼痛，施加压力以达到疼痛阈值，并在3、6、10和10分钟后达到最大疼痛耐受性24小时及7天后；止痛药的消费；术前和术后通过两份独立的问卷对生活质量和生活质量进行评估。

结果：与所有生理变量相比，罗哌卡因组3小时后的疼痛评分明显低于生理盐水组（ p ＜0.05）。在6小时时，罗哌卡因0.5％的疼痛评分显着低于动员期间伤口疼痛的生理盐水，并且施加压力以达到最大的疼痛耐受性。接受盐水治疗的患者比其他两组患者明显更快地提出了首次镇痛剂的使用要求（p <0.05），并且在开始的24小时内有更大比例的患者要求进行镇痛剂使用（p <0.05）。生活质量调查问卷的评估显示两组之间无显着差异。没有发现支持术前浸润镇痛可减轻长期疼痛的理论。