• 【谷氨酸拮抗剂在帕金森氏病动物模型中刺激基础和L-多巴诱导的运动活动。】 复制标题 收藏 收藏
    DOI:10.1016/s0149-7634(96)00039-5 复制DOI
    作者列表:Starr MS,Starr BS,Kaur S
    BACKGROUND & AIMS: In parkinsonism, glutamate pathways within the basal ganglia become overactive, leading to the suggestion that glutamate antagonists might possess antiparkinsonian qualities. This report examines the motor properties of antagonists of NMDA and AMPA-type glutamate receptors, as well as some inhibitors of glutamate release, in animal models of idiopathic Parkinson's disease. High affinity NMDA open-channel blockers (e.g. MK 801, phencyclidine), are highly potent antagonists with inconsistent antiakinetic and strong myorelaxant activity. Other compounds are better tolerated and are capable of relieving immobility and muscular rigidity by themselves (e.g. 1-aminoadamantanes, polyamine site antagonists, kappa agonists, riluzole). Yet others do not restore movements alone (e.g. dextromethorphan, ketamine), but may interact with and strengthen the antiparkinsonian action of L-DOPA (e.g. competitive NMDA and AMPA antagonists, lamotrigine). They may do this by potentiating dopaminergic behaviours mediated by D1 or D2 receptors, or by some other mechanism.

    背景与目标: 在帕金森氏症中,基底神经节内的谷氨酸途径变得过度活跃,导致暗示谷氨酸拮抗剂可能具有抗帕金森氏症的特性。本报告研究了特发性帕金森氏病动物模型中NMDA和AMPA型谷氨酸受体拮抗剂以及谷氨酸释放抑制剂的运动特性。高亲和力的NMDA开放通道阻滞剂 (例如MK 801,苯环利定) 是具有不一致的抗肌毒性和强的肌松弛活性的高效拮抗剂。其他化合物具有更好的耐受性,并且能够自行缓解不动和肌肉僵硬 (例如1-氨基金刚烷,多胺位点拮抗剂,κ 激动剂,利鲁唑)。还有其他人不能单独恢复运动 (例如右美沙芬,氯胺酮),但可能与L-DOPA的抗帕金森病作用相互作用并加强 (例如竞争性NMDA和AMPA拮抗剂,拉莫三嗪)。他们可以通过增强D1或D2受体或其他机制介导的多巴胺能行为来做到这一点。
  • 【在细针穿刺和超快巴氏染色处理的术中涂片中,甲状腺乳头状癌的清晰核明显。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Yang GC,Greenebaum E
    BACKGROUND & AIMS: The Orphan Annie-eyed clear nucleus, defined as a large, optically clear nucleus, devoid of chromatin strands, with sharp chromatin rim, is a more specific feature than are nuclear grooves or intranuclear cytoplasmic inclusions in papillary thyroid carcinoma. In addition, this characteristic nuclear feature is detectable at low magnification. Although these clear nuclei are routinely seen in paraffin sections, they are inconspicuously seen in conventionally processed touch-imprints and fine-needle aspiration (FNA) smears. Among our two institutions, there have been 148 thyroid cases processed by Ultrafast Papanicolaou stain (UFP), including 43 papillary carcinomas, 38 cellular follicular lesions, and 67 cases of nodular hyperplasia. We observed clear nuclei in all of the cases of UFP-processed FNA and intraoperative smears of papillary carcinoma but not of other thyroid lesions. The clear nuclei are most evident in tumor cells with direct contact to the glass slide and are not seen in tumor cells soaked in cystic fluid. UFP is a valuable way to detect Orphan Annie-eyed clear nuclei of papillary thyroid carcinoma early in the diagnostic evaluation, either at immediate on-site evaluation of FNA or at intraoperative consultation and before the availability of permanent sections.

    背景与目标: 孤儿安妮眼透明核,定义为一个大的,光学上透明的核,没有染色质链,具有尖锐的染色质边缘,是比甲状腺乳头状癌中核沟或核内细胞质包涵体更特异的特征。此外,这种特征性核特征在低放大倍率下是可检测到的。尽管这些清晰的核通常在石蜡切片中可见,但在常规处理的触摸印记和细针抽吸 (FNA) 涂片中却不明显。在我们的两个机构中,有148例经超快巴氏染色 (UFP) 处理的甲状腺病例,包括43例乳头状癌,38例细胞滤泡病变和67例结节性增生。我们在所有经UFP处理的FNA病例和乳头状癌的术中涂片中都观察到了清晰的核,但没有观察到其他甲状腺病变。透明的核在与载玻片直接接触的肿瘤细胞中最为明显,在浸泡在囊性液中的肿瘤细胞中未见。UFP是一种有价值的方法,可以在诊断评估的早期,无论是在FNA的现场评估还是在术中咨询以及在永久性切片之前,检测甲状腺乳头状癌的孤儿安妮眼透明核。
  • 【循环雌二醇是中年男性颈动脉内膜中层厚度进展的独立预测因子。】 复制标题 收藏 收藏
    DOI:10.1210/jc.2006-0932 复制DOI
    作者列表:Tivesten A,Hulthe J,Wallenfeldt K,Wikstrand J,Ohlsson C,Fagerberg B
    BACKGROUND & AIMS: CONTEXT:Estrogen treatment of men with prostate cancer is associated with increased cardiovascular morbidity and mortality; however, the role of endogenous estrogen levels for atherosclerotic disease in men is unknown. OBJECTIVE:The objective of the study was to determine whether endogenous serum estradiol (E2) levels predict the progression of carotid artery intima-media thickness in men. DESIGN, SETTING AND PARTICIPANTS:This was a population-based, prospective cohort study (the Atherosclerosis and Insulin Resistance study) conducted in Göteborg, Sweden, among 313 Caucasian men without cardiovascular or other clinically overt diseases. Carotid artery intima-media thickness, an index of preclinical atherosclerosis, was measured by ultrasound at baseline (58 yr of age) and after 3 yr of follow-up. Serum sex hormone levels and cardiovascular risk factors (body mass index, waist to hip ratio, systolic blood pressure, serum triglycerides, plasma c-peptide, and smoking status) were assessed at study entry. INTERVENTION:There was no intervention. MAIN OUTCOME MEASURES:Association between baseline total and free E2 levels and progression of carotid intima-media thickness over 3 yr with adjustments for cardiovascular risk factors was measured. RESULTS:In univariate analyses, both total and free E2 levels at baseline were positively associated with the annual change in intima-media thickness. In linear regression models including E2 and cardiovascular risk factors, low-density lipoprotein and high-density lipoprotein cholesterol and E2 were identified as independent predictors of progression of carotid artery intima-media thickness (total E2 beta = 0.187, P = 0.001; and free E2 beta = 0.183, P = 0.003). CONCLUSIONS:Circulating E2 is a predictor of progression of carotid artery intima-media thickness in middle-aged men. Further studies are needed to investigate the role of endogenous E2 for incident cardiovascular disease events.
    背景与目标:
  • 【外周定量计算机断层扫描 (pQCT) 可用于监测接受激素替代治疗的患者的骨矿物质密度。】 复制标题 收藏 收藏
    DOI:10.1016/j.maturitas.2006.08.006 复制DOI
    作者列表:Sawada K,Morishige K,Ohmichi M,Nishio Y,Yamamoto T,Hayakawa J,Mabuchi S,Isobe A,Sasaki H,Sakata M,Tasaka K,Murata Y
    BACKGROUND & AIMS: OBJECTIVE:A forearm fracture (Colles' fracture) is often the first sign of osteoporosis and should alert the patient and physician to the possibility of underlying skeletal fragility. Therefore, the establishment of a more accurate and reliable method for the measurement of bone mineral density (BMD) at the distal radius would be beneficial for the patients who suffer from osteoporosis. The objective of the present study was to evaluate the usefulness of peripheral quantitative computed tomography (pQCT) to assess the change of BMD at the distal radius in early postmenopausal women who receive hormone replacement therapy (HRT). METHODS:Twenty healthy early postmenopausal women who were diagnosed as osteoporosis or osteopenia were randomized to either HRT or placebo treatment. We analyzed BMD of the distal radius by pQCT, lumbar spine by dual-energy X-ray absorptiometry (DXA) and the biochemical markers of bone turn over (osteocalcin, deoxypyridinoline) every 6 months. RESULTS:The placebo group showed a significant decrease from the baseline in the trabecular BMD of the radius at 12 months (7.4+/-2.5%) (p<0.05), whereas the HRT group showed a slight increase (0.7+/-2.2%). The changes in the trabecular BMD of the radius between the HRT and placebo groups were statistically different at 12 months (p<0.05). On the other hand, in the cortical BMD of the radius, no significant differences were seen between the changes of bone densities in the HRT and control groups after 1 year of treatment. pQCT could detect a significant loss of BMD of the radius in early postmenopausal women after 1 year and HRT prevented its loss. CONCLUSION:Our preliminary clinical trial showed that pQCT might be useful for the early detection of bone loss in early postmenopausal women and for the monitoring BMD of the patients who receive HRT.
    背景与目标:
  • 【interleukin-1 α 诱导的黑色素瘤细胞运动的表征: I型和II型受体阻断单克隆抗体的抑制。】 复制标题 收藏 收藏
    DOI:10.1097/00008390-199706000-00006 复制DOI
    作者列表:Dekker SK,Vink J,Bruijn JA,Mihm MC Jr,Vermeer BJ,Byers HR
    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: Interleukin-1 α (IL-1 α) 在体外诱导多种良性细胞类型和一些但不是全部恶性细胞系中的细胞运动。这项研究表征了表达I型和II型IL-1受体的侵袭性人类黑素瘤细胞系的IL-1 α 诱导的运动。我们测试了单克隆抗体 (包括针对I型和II型IL-1受体的功能阻断moab) 对黑色素瘤细胞运动的影响,以确定哪种受体参与IL-1 α 诱导的黑色素瘤细胞运动的信号转导。IL-1 α 以剂量依赖的方式显著增加MM-RU黑素瘤细胞迁移,使用改进的Boyden室测定法,浓度低于显著抑制细胞生长的浓度的10至100倍。计算机辅助延时图像分析表明,通过中和针对IL-1 α 的抗体,运动性以剂量依赖的方式受到抑制。针对I型或II型IL-1受体的功能阻断单克隆抗体显示出对细胞因子诱导的增强细胞迁移的显着抑制。当两种anti-IL-1受体抗体加在一起时,运动反应完全阻断到控制水平。总之,这些数据表明,IL-1 α 诱导的MM-RU黑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-1 α 或阻断一种或两种IL-1受体而显着抑制运动,表明IL-1-induced信号在诱导黑色素瘤细胞迁移中的整合。
  • 【在位内膜和子宫内膜异位病变中微血管密度,增殖活性与血管内皮生长因子-A及其受体表达的关系。】 复制标题 收藏 收藏
    DOI:10.1530/rep.1.01110 复制DOI
    作者列表:Bourlev V,Volkov N,Pavlovitch S,Lets N,Larsson A,Olovsson M
    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。
  • 【与含有pro564的HIF-1alpha的VHL介导的蛋白质破坏基序融合的procaspase-3的低氧特异性细胞毒性的机制。】 复制标题 收藏 收藏
    DOI:10.1016/j.febslet.2006.09.025 复制DOI
    作者列表:Harada H,Kizaka-Kondoh S,Hiraoka M
    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,低氧诱导因子 (HIF-1alpha) 蛋白的 α 亚基被作为E3泛素连接酶的von Hippel-Lindau (VHL) 肿瘤抑制蛋白靶向降解。最近,我们开发了一种低氧靶向蛋白TOP3,它由具有HIF-1alpha VHL介导的蛋白破坏基序的procaspase-3组成。该设计使procaspase-3能够与HIF-1alpha类似地调节,在常氧条件下降解,而在缺氧条件下稳定。此外,稳定的TOP3被低氧胁迫诱导的内源性半胱天冬酶裂解,因此procaspase-3在低氧条件下被特异性转化为活性caspase-3。这些数据表明,HIF-1alpha的VHL介导的蛋白质破坏基序赋予procaspase-3低氧特异性细胞毒性。
  • 【老年恶性胶质瘤患者短程放疗的前瞻性研究。】 复制标题 收藏 收藏
    DOI:10.1023/a:1005750111883 复制DOI
    作者列表:Hoegler DB,Davey P
    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的预后较差,标准的根治性放疗的益处是模棱两可的。在我们中心,患有恶性神经胶质瘤的成人转诊基地中有22% 的年龄在70岁或以上。进行了一项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,从而构成适当的研究性姑息治疗方案。在1988-1995之间累积了25例患者,所有这些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70-78),中位Karnofsky表现状态 (KPS) 70.40% 仅用于诊断的立体定向活检。在3周内,将放射疗法递送到有限的区域,剂量为37.5 Gy,每天15次。进行了意向性治疗分析,从初次咨询之日起确定生存率。全组的中位生存期为8.0个月 (95% CI 4.8-9.6)。表现良好的患者 (KPS > 70) 的中位生存期为10.4个月 (95% CI 9.6-14.7)。在15个每日分数中37.5 Gy似乎产生与其他系列的根治性放疗相当的中位生存期。建议对该方案进行III期研究,以研究老年恶性神经胶质瘤患者的最佳姑息治疗。
  • 【公牛睾丸促性腺激素受体,血清促性腺激素和睾丸激素浓度的产后变化以及睾丸的功能发育。】 复制标题 收藏 收藏
    DOI:10.1530/rep.1.00768 复制DOI
    作者列表:Bagu ET,Cook S,Gratton CL,Rawlings NC
    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: : 这项研究的主要目的是跟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25周龄后睾丸快速生长的控制,当血清促性腺激素浓度较低时。从5到33周龄和56周龄,每4周对不同的Hereford x Charolais小牛 (n = 6) 进行cast割。阉割前一周,从5到33周龄,每15分钟收集一次血液,持续10小时。在13至25周之间,生精小管中从冷漠的支持细胞向Sertoli细胞的过渡迅速,并且在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至25周龄降低,并增加至56周龄 (P <0.05)。Lh-rka从9周龄下降到17周龄,增加到29周龄,下降到33周龄 (P <0.05)。Fsh-r浓度从17至25周龄下降,然后增加至56周龄 (P <0.05)。Fsh-rka从17周增加到25周龄 (P <0.05)。面对低血清促性腺激素浓度,高浓度的促性腺激素及其受体对于启动出生后睾丸生长并在25周龄后支持睾丸生长可能至关重要。
  • 【子宫内膜肿瘤的侵袭性与金属蛋白酶2和金属蛋白酶2的组织抑制剂的表达有关。】 复制标题 收藏 收藏
    DOI:10.1111/j.1525-1438.2006.00717.x 复制DOI
    作者列表:Graesslin O,Cortez A,Uzan C,Birembaut P,Quereux C,Daraï E
    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金属蛋白酶 (TIMP)-1和TIMP-2的MMP-2,MMP-7,MMP-9和组织抑制剂及其与临床和组织学参数的关系。用特异性单克隆抗体对来自50例1999年和2004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分类对肿瘤进行分组。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表达存在差异的趋势 (P = 0.05)。随着组织学分级的增加,MMP-2表达增加,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相关 (P = 0.01),血管淋巴间隙受累 (P = 0.02) 和淋巴结转移 (P = 0.0003)。这些结果支持MMPs和TIMPs参与子宫内膜肿瘤的生长和进展。高MMP-2和低TIMP-2表达是子宫内膜肿瘤的最有效标志物,具有局部和远处扩散的高风险。
  • 【barramundi,Lates calcarifer中胰岛素样生长因子-I mRNA表达的营养调节。】 复制标题 收藏 收藏
    DOI:10.1677/jme.0.0180273 复制DOI
    作者列表:Matthews SJ,Kinhult AK,Hoeben P,Sara VR,Anderson TA
    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,而肝而非脑igf-i mRNA表达受幼年barramundi食物供应的调节。
  • 【血红蛋白对同期放化疗治疗的宫颈癌患者生存的影响取决于磁共振成像的淋巴结转移发现。】 复制标题 收藏 收藏
    DOI:10.1111/j.1525-1438.2006.00666.x 复制DOI
    作者列表:Choi YS,Yi CM,Sin JI,Ye GW,Shin IH,Lee TS
    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: : 本研究的目的是确认放化疗期间血红蛋白 (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。回顾性分析了85例同期放化疗治疗的宫颈癌患者。疾病的阶段介于FIGO IB期和IVA期之间。通过单变量和多变量分析评估无病生存率和总体生存率。中位随访35.7个月后,24例患者出现疾病复发,14例患者死于疾病。分期、LN转移、放化疗期间鳞状细胞癌抗原和Hb水平与生存率显著相关 (P <0.05)。Hb维持在10.0g/dL以上与较好的生存率相关 (P <0.05)。然而,通过磁共振成像 (MRI) 在LN转移患者中未观察到这种益处。多因素Cox回归风险模型显示,放化疗期间的Hb水平是MRI无LN转移患者的独立预后因素。化疗期间维持血红蛋白对无LN转移但无LN转移的宫颈癌患者有好处。
  • 【细胞因子刺激的骨髓的产前移植可改善耐药菌株组合中的早期嵌合,但导致长期移植不良。】 复制标题 收藏 收藏
    DOI:10.1016/j.exphem.2006.05.007 复制DOI
    作者列表:Shaaban AF,Kim HB,Gaur L,Liechty KW,Flake AW
    BACKGROUND & AIMS: OBJECTIVE:In the absence of immunodeficiency, only microchimerism (<0.1%) has been achieved in human fetal recipients or nonhuman primates following in utero hematopoietic cell transplantation (IUHCT). We hypothesized that enhanced long-term engraftment might be more reliably achieved in microchimeric systems if higher levels of chimerism existed during development of adaptive immunity. To evaluate this hypothesis, we stimulated the donor cells with vascular endothelial growth factor (VEGF) and stem cell factor (SCF) prior to IUHCT in a chimerism-resistant murine strain combination. METHODS:Donor Balb/c marrow was cultured in media with or without VEGF and SCF supplementation for 12 hours prior to IUHCT into B6 fetuses at 14 days postcoitum (dpc). Donor cell phenotype, homing, and chimerism were assessed at short and long-term time points and transplanted animals received skin allografts at 8 weeks. RESULTS:In pretreated allogeneic recipients, early chimerism rates were more than double that of controls (71% vs 33%, p = 0.01). These differences were associated with higher numbers of pretransplant donor cell colony-forming cells without change in donor cell homing. Despite prolonged skin allograft survival for pretreated recipients compared with controls (mean survival = 20.8 vs 8.2 days, p < 0.001), long-term engraftment was unchanged. CONCLUSIONS:These findings demonstrate that higher levels of early chimerism in recipients of cytokine-stimulated marrow result in improved short-term chimerism and tolerance. Future studies are needed to confirm the existence of a "threshold" level of chimerism necessary to sustain long-term engraftment.
    背景与目标:
  • 【抗氧化剂抑制核因子-kappaB可增强卵巢癌细胞系中紫杉醇的敏感性。】 复制标题 收藏 收藏
    DOI:10.1111/j.1525-1438.2006.00652.x 复制DOI
    作者列表:Liu GH,Wang SR,Wang B,Kong BH
    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。
  • 【植入结果: 采用混合方法评估成人人工耳蜗植入方案的疗效。】 复制标题 收藏 收藏
    DOI:10.3109/09638289709166533 复制DOI
    作者列表:Hogan A
    BACKGROUND & AIMS: Studies concerned with the efficacy of cochlear implants have traditionally focused on measuring enhancements in speech perception associated with implantation. This paper reports the findings of a study concerned with qualitative and quantitative measures of psychosocial benefit associated with the adult cochlear implant programme. Cochlear implants enhanced implantees' interpersonal communication skills and social confidence, and were associated with a reduction in the user's social anxiety. Broader socioeconomic gains were not achieved by implantees, mainly because of an absence of adequate employment and community education programmes associated with implant programmes.

    背景与目标: 传统上,与人工耳蜗的功效有关的研究集中在测量与植入相关的语音感知的增强。本文报告了一项研究的结果,该研究涉及与成人人工耳蜗计划相关的社会心理益处的定性和定量测量。人工耳蜗增强了植入者的人际沟通技巧和社交信心,并与减少用户的社交焦虑有关。植入者没有实现更广泛的社会经济收益,这主要是因为缺乏与植入计划相关的适当就业和社区教育计划。

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