BACKGROUND & AIMS: :Previous research showed that ferrets of both sexes rely on the perception of conspecifics' body odors to identify and motivate approach towards opposite-sex mating partners, and exposure to male body odors stimulated Fos expression in an olfactory projection circuit of female, but not male, ferrets that terminates in the ventromedial hypothalamic nucleus (VMH). We asked whether the female-typical preference of ferrets to approach male as opposed to female body odors in Y-maze tests would be disrupted by VMH lesions. Sexually experienced female ferrets were ovo-hysterectomized prior to receiving bilateral electrolytic lesions of the VMH, the preoptic area/anterior hypothalamus (POA/AH) or a sham operation. Subsequently, while receiving estradiol benzoate, females that received either complete or partial bilateral lesions of the VMH approached volatile odors from an anesthetized male on significantly fewer trials than females given POA/AH lesions or a sham operation. Both groups of ferrets with VMH lesion damage reliably discriminated between volatile anal scents as well as urinary odors from the 2 sexes in home cage habituation/dishabituation tests, suggesting that their odor-based sex discrimination remained intact. Females with complete bilateral VMH lesions showed significantly lower acceptance of neck gripping from a stimulus male (receptivity) and more aggression towards the male than all other groups of female subjects. Estrogen-sensitive neurons in the VMH appear to play a central role in female-typical neural processing of odor inputs leading to a preference to seek out a male sex partner, in addition to facilitating females' sexual receptivity.

背景与目标： : 先前的研究表明，男女雪貂都依赖于对个体体味的感知来识别和激励对异性交配伴侣的态度，暴露于男性体味会刺激女性而不是男性的嗅觉投射回路中的Fos表达，终止于腹内侧下丘脑核 (VMH) 的雪貂。我们询问，在Y迷宫测试中，雪貂对女性典型的偏爱接近男性而不是女性的体味是否会被VMH病变破坏。在接受VMH，视前区/下丘脑前部 (POA/AH) 或假手术的双侧电解病变之前，对有性经验的雌性雪貂进行了子宫切除。随后，在接受苯甲酸雌二醇的同时，接受了VMH完全或部分双侧病变的女性在麻醉的男性中获得的挥发性气味明显少于接受POA/AH病变或假手术的女性。两组患有VMH病变的雪貂在家庭笼子适应/不适应测试中可靠地区分了挥发性肛门气味以及来自2个性别的尿液气味，这表明它们基于气味的性别歧视仍然完好无损。与所有其他女性受试者相比，具有完全双侧VMH病变的女性对刺激男性的颈部抓握的接受度明显降低 (接受)，并且对男性攻击更高。VMH中的雌激素敏感神经元似乎在女性典型的气味输入的神经处理中起着核心作用，除了促进女性的性接受外，还倾向于寻找男性性伴侣。

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的Bethesda宫颈/阴道细胞学报告系统定义了不令人满意的指定的充分性标准。大多数实验室已经实施了这些标准，但尚未确定临床意义。
方法 : 两所大学医院的研究人员通过计算机搜索检索了1994年1月和1995年7月之间所有不满意的Papanicolaou (Pap) 涂片。在71,872的子宫颈抹片检查中，208 (0.3%) 不令人满意 (相应的非典型9% 率和不典型增生/癌率为6.5%)。确定了随访的时间间隔和临床病理结果。
结果 : 大约26% 的不满意的子宫颈抹片检查来自有上皮异常病史的患者。大多数 (208标本129; 62%) 的随访子宫颈抹片检查或活检发生在6个月内，5.7% 发生在6-12个月内，1.4% 发生在12-18个月内。大约31% 没有随访。144例随访患者的首次重复巴氏涂片或组织学标本阴性107例 (74% 例)，不满意6例 (4%)，非典型鳞状上皮细胞未明确意义15例 (10% 例)，鳞状上皮内病变 (SIL) 13例 (9%)，恶性3例 (2% 例)。导致组织学标本涂片不令人满意的非恶性疾病 (12%) 包括宫颈炎，子宫内膜炎，子宫内膜增生和息肉。在7例患者 (5%) 中发现了第一个重复标本后的进行性异常。在分析所有随访标本时，发现144例初始不满意标本中的23例 (16% 例) 来自诊断为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在6个月内进行了随访研究。大量 (16%) 随访的患者最终诊断为SIL或肿瘤。良性病理状况也导致涂片不令人满意。该患者子集更有可能有异常病史，这证实了对不满意的涂片进行同行/分级审查的重要性。

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：

BACKGROUND & AIMS: Several electrophysiological studies have addressed the interaction between glutamate and dopamine within the striatum. Although the results obtained from these studies were often conflicting, more recently the characterization of new forms of synaptic plasticity in the basal ganglia provided a possible integrative explanation of the different electrophysiological data regarding the interaction between these transmitters. In this review we will try to summarize and discuss the available data concerning the possible impact of the functional role of D1 and D2 receptor activation on the modulation of the glutamatergic corticostriatal pathway. Moreover, we will also describe the function of the striatum in the integration of glutamatergic and dopaminergic inputs to produce long-term changes of synaptic efficacy (long-term depression, long-term potentiation). Finally, we will consider the implication of the interaction between dopamine and glutamate in the regulation of energetic metabolism whose failure is responsible for neuronal death.

背景与目标： 一些电生理研究已经解决了纹状体内谷氨酸和多巴胺之间的相互作用。尽管从这些研究中获得的结果通常是相互矛盾的，但最近对基底神经节中突触可塑性的新形式的表征为有关这些递质之间相互作用的不同电生理数据提供了可能的综合解释。在这篇综述中，我们将尝试总结和讨论有关D1和D2受体激活的功能作用对谷氨酸能皮质纹状体途径调节的可能影响的可用数据。此外，我们还将描述纹状体在整合谷氨酸能和多巴胺能输入以产生突触功效的长期变化 (长期抑郁，长期增强) 中的功能。最后，我们将考虑多巴胺和谷氨酸之间的相互作用在调节能量代谢中的意义，而能量代谢的失败是导致神经元死亡的原因。

BACKGROUND & AIMS: :A 43-year-old man developed a skin eruption characterized by 'macules with blisters' typical to Stevens-Johnson syndrome, as well as erosions of the lips and buccal mucosa, 2 weeks after he had started treatment with lamotrigine. He had a fever (39.6 degrees C), elevated liver enzymes and atypical lymphocytes in the peripheral blood. This undoubtedly reflects a case of Stevens-Johnson syndrome induced by lamotrigine, but it can also fulfill the criteria of anticonvulsant hypersensitivity syndrome or drug rash with eosinophilia and systemic signs. A case that precisely fits the definition of two syndromes that have different characteristics, different treatments and different prognoses indicates that there is a flaw in the classification.

背景与目标： : 一名43岁的男子在开始使用拉莫三嗪治疗2周后，出现了以史蒂文斯-约翰逊综合征典型的 “带水疱的斑疹” 以及嘴唇和颊粘膜糜烂为特征的皮肤喷发。发热 (39.6 ℃)，肝酶升高，外周血淋巴细胞不典型。这无疑反映了拉莫三嗪诱发的史蒂文斯-约翰逊综合征，但它也可以满足抗惊厥超敏反应综合征或伴有嗜酸性粒细胞增多和全身体征的药疹的标准。一个精确地符合具有不同特征，不同治疗方法和不同预后的两种综合征的定义的案例表明，分类存在缺陷。

BACKGROUND & AIMS: :A number of competing risks and benefits influence the rates of neonatal morbidity and mortality in elective cesarean delivery versus expectant management. To compare these rates, we developed complex decision trees to model the expected outcomes among hypothetical cohorts of 1,000,000 uncomplicated pregnancies undergoing elective cesarean delivery versus 1,000,000 comparable pregnancies undergoing routine pregnancy management. A separate tree was created for each complication, including neonatal death, respiratory morbidity, intracranial hemorrhage, and brachial plexus injury. We found that neonatal mortality was increased among elective cesarean deliveries, but perinatal mortality was higher with routine expectant management due to fetal deaths. Respiratory morbidity was substantially more common among infants delivered by elective cesarean delivery, whereas intracranial hemorrhage and brachial plexus injury were less common. We conclude that the fetal/neonatal impact of elective cesarean is mixed, but any improvement in perinatal health is likely to be small.

背景与目标： : 在选择性剖宫产与预期管理中，许多竞争性风险和收益会影响新生儿的发病率和死亡率。为了比较这些比率，我们开发了复杂的决策树来模拟假设队列中的预期结果，这些队列中的1,000,000例非复杂妊娠接受选择性剖宫产，而1,000,000例可比妊娠接受常规妊娠管理。为每种并发症 (包括新生儿死亡，呼吸系统疾病，颅内出血和臂丛神经损伤) 创建了单独的树。我们发现，选择性剖宫产分娩的新生儿死亡率增加，但由于胎儿死亡，常规预期治疗的围产期死亡率更高。在择期剖宫产分娩的婴儿中，呼吸系统的发病率明显更高，而颅内出血和臂丛神经损伤则较少见。我们得出的结论是，选择性剖宫产对胎儿/新生儿的影响是混合的，但是围产期健康的任何改善都可能很小。

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。

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。

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：

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：

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。

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: :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。

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。

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。