• 【Papanicolaou涂片不理想的临床病理相关性。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Ransdell JS,Davey DD,Zaleski S
    BACKGROUND & AIMS: BACKGROUND:The 1991 Bethesda System for cervical/vaginal cytology reporting defined adequacy criteria for the unsatisfactory designation. Most laboratories have implemented these criteria, but clinical implications have not been established.

    METHODS:Researchers at two university hospitals retrieved by computer search all unsatisfactory Papanicolaou (Pap) smears taken between January 1994 and July 1995. Of 71,872 total Pap smears, 208 (0.3%) were unsatisfactory (corresponding atypical rate of 9% and a dysplasia/carcinoma rate of 6.5%). Time interval to follow-up and clinicopathologic outcome were determined.

    RESULTS:Approximately 26% of unsatisfactory Pap smears were from patients with a history of epithelial abnormalities. The majority (129 of 208 specimens; 62%) of follow-up Pap smears or biopsies occurred within 6 months, 5.7% within 6-12 months, and 1.4% in 12-18 months. Approximately 31% had no follow-up. The first repeat Pap smear or histologic specimen in 144 patients with follow-up was negative in 107 (74%), unsatisfactory in 6 (4%), atypical squamous cells of undetermined significance in 15 (10%), squamous intraepithelial lesion (SIL) in 13 (9%), and malignant in 3 (2%). Nonmalignant conditions contributing to the unsatisfactory smears on histologic specimens (12%) included cervicitis, endometritis, endometrial hyperplasia, and polyps. Progressive abnormalities after the first repeat specimen were noted in 7 patients (5%). A total of 23 of 144 initial unsatisfactory specimens (16% )were found to be from patients diagnosed with SIL or malignancy when all follow-up specimens were analyzed.

    CONCLUSIONS:The majority of patients with unsatisfactory Pap smears had follow-up studies within 6 months. A significant number (16%) of those with follow-up had eventual diagnoses of SIL or neoplasia. Benign pathologic conditions also contributed to unsatisfactory smears. This patient subset was more likely to have a history of abnormalities, confirming the importance of peer/hierarchical review of unsatisfactory smears.

    背景与目标: 背景:1991年用于宫颈/阴道细胞学报告的Bethesda系统定义了不合格名称的充分性标准。

    方法:1994年1月至1994年1月间,两所大学医院的研究人员通过计算机搜索检索到的所有不满意的Papanicolaou(Pap)涂片均不令人满意和1995年7月。在71,872例子宫颈抹片检查中,有208例(0.3%)不满意(相应的非典型率为9%,异型/癌变率为6.5%)。确定随访时间和临床病理结果。

    结果:约有26%的子宫颈抹片检查不满意是有上皮异常病史的患者。大部分随访检查(208个样本中的129个; 62%)在6个月内发生,在6-12个月内发生5.7%,在12-18个月内发生1.4%。大约31%的患者没有随访。 144例随访中的首次重复巴氏涂片或组织学标本阴性(107%(74%),不满意6例(4%),意义不明的非典型鳞状细胞15例(10%),鳞状上皮内病变(SIL) )在13(9%)中为恶性肿瘤,在3(2%)中为恶性肿瘤。导致组织学标本涂片不良的非恶性疾病(12%)包括宫颈炎,子宫内膜炎,子宫内膜增生和息肉。在第一个重复样本后发现有7例(5%)的进行性异常。在对所有随访标本进行分析后,总共发现144例最初不满意的标本中有23例(16%)来自被诊断为SIL或恶性肿瘤的患者。

    结论:大多数子宫颈抹片检查不满意的患者中有6个月进行了随访研究。接受随访的患者中,有很大一部分(16%)最终被诊断为SIL或瘤形成。良性病理状况也导致涂片不良。该患者亚组更可能具有异常病史,从而证实了对不满意涂片进行同行/分级检查的重要性。

  • 【前列腺癌放疗的四种靶标对准方法的剂量学比较。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijrobp.2006.06.044 复制DOI
    作者列表:O'Daniel JC,Dong L,Zhang L,de Crevoisier R,Wang H,Lee AK,Cheung R,Tucker SL,Kudchadker RJ,Bonnen MD,Cox JD,Mohan R,Kuban DA
    BACKGROUND & AIMS: PURPOSE:The aim of this study was to compare the dosimetric consequences of 4 treatment delivery techniques for prostate cancer patients treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS:During an 8-week course of radiotherapy, 10 patients underwent computed tomography (CT) scans 3 times per week (243 total) before daily treatment with a CT-linear accelerator. Treatment delivery was simulated by realigning a fixed-margin treatment plan on each CT scan and calculating doses. The alignment methods were those based on the following: skin marks, bony registration, ultrasonography (US), and in-room CT. For the last two methods, prostate was the alignment target. The dosimetric effects of these alignment methods on the prostate, seminal vesicles, rectum, and bladder were compared. The average daily minimum dose to 0.1 cm3 was used as the metric for target coverage. RESULTS:Skin and bone alignments provided acceptable prostate coverage for only 70% of patients, US alignment for 90%, and CT alignment for 100%. CT-based alignment of the prostate provided seminal vesicle (SV) coverage of > or = 69 Gy for all patients; US and bone alignments provided SV coverage of > or = 60 Gy. This SV coverage may be acceptable for early-stage cancer (equivalent SV dose = 55.8 Gy at 1.8 Gy per fraction), but unacceptable for late-stage cancer (SV dose = 75.6 Gy). At 75.6 Gy, the acceptable rate for SV coverage was 40% for skin and bone alignments, 70% for US, and 80% for CT. CONCLUSIONS:Direct target alignment methods (US and CT) provided better target coverage. CT-guided alignment provided the best and most consistent dosimetric coverage. A larger planning target volume margin is needed for SV coverage when the alignment target is the prostate.
    背景与目标: 目的:本研究的目的是比较四种治疗递送技术对接受强度调制放疗(IMRT)治疗的前列腺癌患者的剂量学后果。
    方法和材料:在放射治疗的8周疗程中,每天用CT线性加速器治疗的10例患者每周接受3次计算机断层扫描(CT)扫描(共243次)。通过在每次CT扫描上重新调整固定利润的治疗计划并计算剂量来模拟治疗的交付。对齐方法是基于以下方法的:皮肤标记,骨对位,超声检查(US)和室内CT。对于最后两种方法,前列腺是对准目标。比较了这些对准方法对前列腺,精囊,直肠和膀胱的剂量学影响。每日平均最小剂量为0.1 cm3,用作目标覆盖率的指标。
    结果:仅70%的患者皮肤和骨骼排列提供了可接受的前列腺覆盖率,90%的患者进行了US排列,而100%的患者进行了CT排列。对所有患者而言,基于CT的前列腺排列可提供大于或等于69 Gy的精囊(SV)覆盖率; US和骨骼比对提供SV覆盖范围>或= 60 Gy。此SV覆盖率对于早期癌症是可以接受的(等效SV剂量= 55.8 Gy,每部分1.8 Gy),但对于晚期癌症则是不可接受的(SV剂量= 75.6 Gy)。在75.6 Gy时,皮肤和骨骼排列的SV覆盖率为40%,US覆盖率为70%,CT覆盖率为80%。
    结论:直接目标对准方法(US和CT)可提供更好的目标覆盖范围。 CT引导的对准可提供最佳和最一致的剂量学覆盖范围。当对准目标是前列腺时,需要更大的计划目标体积裕度来覆盖SV。
  • 【在帕金森氏病动物模型中,谷氨酸拮抗剂刺激基础和L-DOPA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: 在帕金森病中,基底神经节内的谷氨酸途径变得过度活跃,从而提示谷氨酸拮抗剂可能具有抗帕金森病的特性。该报告检查了特发性帕金森氏病动物模型中NMDA和AMPA型谷氨酸受体的拮抗剂的运动特性,以及谷氨酸释放的某些抑制剂。高亲和力NMDA开放通道阻滞剂(例如MK 801,苯环利定)是高效抗药,具有抗运动活性不一致和强肌松活性。其他化合物具有更好的耐受性,并能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)。还有一些人不能单独恢复运动(例如右美沙芬,氯胺酮),而是可以与L-DOPA相互作用并增强其抗帕金森病作用(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受体或其他某种机制介导的多巴胺能行为来做到这一点。

  • 【甲状腺针状乳头状癌的清晰核在细针穿刺中显着,术中涂片由超快的木瓜色素染色。】 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,光学透明的核,没有染色质链,具有清晰的染色质边缘,比乳头状甲状腺癌的核槽或核内胞浆内含物更具特异性。另外,该特征核特征在低放大倍率下是可检测的。尽管通常在石蜡切片中经常看到这些清晰的核,但在常规处理的接触印记和细针抽吸(FNA)涂片中却看不见它们。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例细胞滤泡性病变和67例结节性增生。我们在所有UFP处理的FNA病例和术中乳头状癌涂片中观察到清晰的细胞核,但其他甲状腺病变未见。透明核在直接接触载玻片的肿瘤细胞中最为明显,而在浸入囊性液体的肿瘤细胞中则未见。在诊断评估中,无论是立即进行现场FNA评估还是在术中会诊之前以及在获得永久性切片之前,UFP是一种在早期诊断评估中检测出孤儿安妮眼状乳头状甲状腺癌的宝贵方法。

  • 【循环雌二醇是中年男性颈动脉内膜中层厚度发展的独立预测因子。】 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: 背景:雌激素治疗前列腺癌的男性会增加心血管疾病的发病率和死亡率。然而,内源性雌激素水平在男性动脉粥样硬化疾病中的作用尚不清楚。
    目的:研究的目的是确定内源性血清雌二醇(E2)水平是否能预测男性颈动脉内膜中层厚度的发展。
    设计,地点和参与者:这是一项在瑞典哥德堡进行的基于人群的前瞻性队列研究(动脉粥样硬化和胰岛素抵抗研究),研究对象是313名无心血管疾病或其他临床明显疾病的白人。在基线(58岁)和随访3年后,通过超声测量颈动脉内膜中层厚度(临床前动脉粥样硬化的指标)。在研究开始时评估了血清性激素水平和心血管危险因素(体重指数,腰围与臀部的比率,收缩压,血清甘油三酸酯,血浆c肽和吸烟状况)。
    干预:没有干预。
    主要观察指标:测量基线总E2水平和游离E2水平与3年以上颈动脉内膜中层厚度进展的相关性,并调整心血管危险因素。
    结果:在单变量分析中,基线时的总E2水平和游离E2水平均与内膜中膜厚度的年度变化呈正相关。在包括E2和心血管危险因素的线性回归模型中,低密度脂蛋白和高密度脂蛋白胆固醇和E2被确定为颈动脉内膜-中膜厚度发展的独立预测因子(总E2 beta = 0.187,P = 0.001;免费) E2 beta = 0.183,P = 0.003)。
    结论:循环E2是中年男性颈动脉内膜中层厚度发展的预测指标。需要进一步的研究来研究内源性E2在心血管事件中的作用。
  • 【外围定量计算机断层扫描(pQCT)可用于监测接受激素替代疗法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: 目的:前臂骨折(Colles骨折)通常是骨质疏松症的最初征兆,应提醒患者和医生潜在的骨骼脆弱性。因此,建立一种更准确和可靠的方法来测量远端radius骨的骨矿物质密度(BMD)对于患有骨质疏松症的患者将是有益的。本研究的目的是评估外围定量计算机体层摄影术(pQCT)的有效性,以评估接受激素替代疗法(HRT)的绝经后早期女性远端radius骨BMD的变化。
    方法:将20名被诊断为骨质疏松或骨质减少的健康早期绝经后妇女随机分为HRT或安慰剂治疗组。我们每6个月通过pQCT分析远端the骨的BMD,通过双能X线吸收法(DXA)分析腰椎,并分析骨翻倒的生化标志物(骨钙蛋白,脱氧吡啶并啉)。
    结果:安慰剂组在12个月时the骨小梁BMD较基线显着降低(7.4 /-2.5%)(p <0.05),而HRT组则略有增加(0.7 /-2.2%) 。 HRT组与安慰剂组之间的radius骨小梁BMD变化在12个月时有统计学差异(p <0.05)。另一方面,在治疗1年后,HRT和对照组的骨密度变化在B骨的BMD中没有显着差异。 pQCT可以检测到绝经后早期女性在1年后B骨BMD的显着减少,而HRT可以防止这种情况的发生。
    结论:我们的初步临床试验表明,pQCT可能对早期绝经后妇女的骨丢失早期检测以及监测接受HRT的患者的BMD有用。
  • 【白介素-1α诱导的黑色素瘤细胞运动的特征:I型和II型受体阻断性单克隆抗体的抑制作用。】 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: 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。

  • 【异位子宫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。
  • 【procaspase-3的低氧特异性细胞毒性与含有Pro564的HIF-1alpha的VHL介导的蛋白质破坏基序融合的机制。】 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,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。
  • 【老年恶性神经胶质瘤患者短期疗程的前瞻性研究。】 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。

  • 【产后睾丸促性腺激素受体,血清促性腺激素和睾丸激素浓度的变化以及公牛睾丸的功能发育。】 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: :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。
  • 【子宫内膜肿瘤的侵袭性与金属蛋白酶2和金属蛋白酶2表达的组织抑制剂有关。】 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。
  • 【澳洲肺金枪鱼中肺鱼中胰岛素样生长因子-I mRNA表达的营养调控。】 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。

  • 【血红蛋白对同时放化疗的宫颈癌患者生存的影响取决于磁共振成像对淋巴结转移的发现。】 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: :这项研究的目的是确定放化疗期间的血红蛋白(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。
  • 【产前细胞因子刺激的骨髓移植可提高耐药菌株组合的早期嵌合率,但会导致长期植入不良。】 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: 目的:在缺乏免疫缺陷的情况下,子宫内造血细胞移植(IUHCT)后,人类胎儿接受者或非人类灵长类仅获得微嵌合体(<0.1%)。我们假设,如果在适应性免疫发展过程中存在较高水平的嵌合体,则在微嵌合系统中可以更可靠地实现增强的长期植入。为了评估该假设,我们在抗嵌合体的鼠类菌株组合中,在IUHCT之前用血管内皮生长因子(VEGF)和干细胞因子(SCF)刺激了供体细胞。
    方法:在IUHCT植入后的第14天(dpc)将IUBCT注入B6胎儿之前,在添加或不添加VEGF和SCF的培养基中培养供体Balb / c骨髓12小时。在短期和长期的时间点评估供体细胞的表型,归巢和嵌合,移植的动物在第8周接受皮肤同种异体移植。
    结果:在经过预处理的同种异体受体中,早期嵌合率是对照的两倍以上(71%vs 33%,p = 0.01)。这些差异与更高数量的移植前供体细胞集落形成细胞相关,而未改变供体细胞归巢。尽管与对照组相比,经过预处理的接受者的皮肤同种异体移植存活时间延长(平均存活率= 20.8 vs 8.2天,p <0.001),但长期移植并未改变。
    结论:这些发现表明,受细胞因子刺激的骨髓受体的早期嵌合水平较高,可改善短期嵌合和耐受性。需要进行进一步的研究,以确认是否存在维持长期植入所必需的“阈值”嵌合水平。

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