BACKGROUND & AIMS: The kinetic properties of wild-type rat brain IIa sodium channels in excised macropatches were studied using step depolarizations and ramp depolarizations to imitate the slow settling-time of voltage in two-electrode voltage clamp. Ramp depolarizations longer than 1 ms produce an increasing suppression of peak sodium current (I[Na]). Two rates of inactivation can be seen in macroscopic sodium current records from excised patches following both step and ramp depolarizations. During slow ramp depolarizations, reduction in peak I[Na] is associated with selective loss of the fastest rate of test-pulse inactivation. This change can be interpreted as resulting from inactivation of a separate sub-population of 'fast mode' channels. The slow rate of test-pulse inactivation is relatively unaffected by changing ramp durations. These results are sufficient to explain the typically slow inactivation kinetics seen in two-electrode voltage clamp recordings of sodium channels in Xenopus oocytes. Thus, the kinetics of sodium channels expressed in Xenopus oocytes are not readily characterizable by two-electrode clamp because of the large membrane capacitance and resulting slow clamp settling time which artifactually selects for slow mode channels.

背景与目标： 使用逐步去极化和斜坡去极化来模拟两电极电压钳位中电压的缓慢建立时间，研究了切除的大斑块中野生型大鼠脑IIa钠通道的动力学特性。长于1 ms的斜坡去极化会增加对峰值钠电流 (I[Na]) 的抑制。在阶跃和斜坡去极化之后，从切除的斑块的宏观钠电流记录中可以看到两种失活速率。在缓慢的斜坡去极化过程中，峰值I[Na] 的降低与最快的测试脉冲失活速率的选择性损失有关。此更改可以解释为由于 “快速模式” 通道的单独子种群的失活而导致。测试脉冲失活的缓慢速度相对不受斜坡持续时间变化的影响。这些结果足以解释非洲爪蟾卵母细胞中钠通道的两电极电压钳制记录中看到的典型的缓慢失活动力学。因此，非洲爪蟾卵母细胞中表达的钠通道的动力学不容易通过两电极钳来表征，因为膜电容大，并且会导致人为选择慢模式通道而产生的慢钳建立时间。

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: 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: 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: :Maternal diabetes can cause fetal macrosomia and increased risk of obesity, diabetes, and cardiovascular disease in adulthood of the offspring. Although increased transplacental lipid transport could be involved, the impact of maternal type 1 diabetes on molecular mechanisms for lipid transport in placenta is largely unknown. To examine whether maternal type 1 diabetes affects placental lipid metabolism, we measured lipids and mRNA expression of lipase-encoding genes in placentas from women with type 1 diabetes (n = 27) and a control group (n = 21). The placental triglyceride (TG) concentration and mRNA expression of endothelial lipase (EL) and hormone-sensitive lipase (HSL) were increased in placentas from women with diabetes. The differences were more pronounced in women with diabetes and suboptimal metabolic control than in women with diabetes and good metabolic control. Placental mRNA expression of lipoprotein lipase and lysosomal lipase were similar in women with diabetes and the control group. Immunohistochemistry showed EL protein in syncytiotrophoblasts facing the maternal blood and endothelial cells facing the fetal blood in placentas from both normal women and women with diabetes. These results suggest that maternal type 1 diabetes is associated with TG accumulation and increased EL and HSL gene expression in placenta and that optimal metabolic control reduces these effects.

背景与目标： : 母体糖尿病会导致胎儿巨大儿，并增加后代成年后肥胖，糖尿病和心血管疾病的风险。尽管可能涉及胎盘脂质转运增加，但母体1型糖尿病对胎盘脂质转运分子机制的影响尚不清楚。为了检查母体1型糖尿病是否影响胎盘脂质代谢，我们测量了1型糖尿病女性 (n = 27) 和对照组 (n = 21) 胎盘中脂质和脂肪酶编码基因的mRNA表达。糖尿病女性胎盘中胎盘甘油三酯 (TG) 浓度和内皮脂肪酶 (EL) 和激素敏感性脂肪酶 (HSL) 的mRNA表达增加。与糖尿病和代谢控制良好的女性相比，糖尿病和代谢控制不佳的女性的差异更为明显。糖尿病妇女和对照组的胎盘脂蛋白脂肪酶和溶酶体脂肪酶的mRNA表达相似。免疫组织化学显示，正常妇女和糖尿病妇女胎盘中面向母体血液的合体滋养层细胞中的EL蛋白和面向胎儿血液的内皮细胞。这些结果表明，母体1型糖尿病与胎盘中TG积累以及EL和HSL基因表达增加有关，而最佳的代谢控制会降低这些影响。

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: :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: 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。

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

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

BACKGROUND & AIMS: 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：

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

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

BACKGROUND & AIMS: :Several mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been identified both in familial and sporadic cases of Parkinson's disease (PD). G2019S, located at a kinase (MAPKKK) domain, is the most common mutation in the LRRK2 gene in PD, Two adjacent mutations (I2012T and I2020T) were mapped to the same domain suggesting shared pathogenic mechanism of these mutations. Since phenotypes of PD overlap with essential tremor (ET), we investigated LRRK2 G2019S, I2012T, and I2020T mutations in a cohort of 272 patients with ET. No mutations were found in our ET cohort and, therefore, we conclude that LRKK2 I2012T, G2019S and I2020T variants are rare causes of Caucasian ET.

背景与目标： : 在帕金森氏病 (PD) 的家族性和散发性病例中，已经发现了富含亮氨酸的重复激酶2基因 (LRRK2) 的几个突变。G2019S位于激酶 (MAPKKK) 结构域，是PD中LRRK2基因中最常见的突变，两个相邻的突变 (I2012T和I2020T) 被定位到同一结构域，表明这些突变的共同致病机制。由于PD的表型与原发性震颤 (ET) 重叠，我们在272例ET患者队列中研究了LRRK2 G2019S，I2012T和I2020T突变。在我们的ET队列中未发现突变，因此，我们得出结论，LRKK2 I2012T，G2019S和I2020T变体是高加索ET的罕见原因。