Brain endothelial cell production of a neuroprotective cytokine, interleukin-6, in response to noxious stimuli

Brain endothelial cells (BECs), specialized cells of the blood–brain barrier (BBB), are ideally positioned to monitor and respond to events in the periphery. The present study examined their potential role in transducing immune signals to the brain and in responding to noxious stimuli. BECs were isolated from rhesus monkeys at 3 age points (fetal/neonatal, adult, and very old animals). Cells were then challenged in vitro with either an immune stimulus (interleukin-1β (IL-1β), or lipopolysaccharide (LPS)) or an oxidative challenge (hypoxia). BECs released interleukin-6 (IL-6), which is known to have neurotrophic and neuroprotective functions. Furthermore, higher amounts of IL-6 were released in both baseline and stimulated conditions by BECs derived from aged animals. This research indicates a pathway whereby immune signals may be communicated to the CNS and has revealed one way that the BBB may protect neuronal survival under challenge conditions.     

Pharmacologically evoked fictive motor patterns in the acutely spinalized marmoset monkey (Callithrix jacchus)

The existence of a spinal network capable of generating rhythmic alternating activity resembling locomotion still has not been firmly established in primates, including man, although evidence for one is accumulating. The present study investigated whether it is possible to activate such a network by administration of a variety of pharmacological agents to acutely spinalized marmoset monkeys (Callithrix jacchus) in the absence of phasic afferent input to the spinal cord. Fourteen marmoset monkeys were decerebrated, spinalized, and paralyzed. The nerves supplying both hindlimbs were cut and recorded from. In 5 monkeys the effect of electrical stimulation of the brainstem was investigated before spinalization. In 3 of these monkeys, rhythmic activity alternating between extensors and flexor nerves was seen. In the 2 other monkeys only synchronized activity was elicited. In acutely spinalized monkeys, administration of l-3,4-dihydroxyphenylalanine (l-dopa; 3–4 h after treatment with nialamide) failed to evoke any rhythmic alternating activity. In contrast, administration of clonidine elicited alternating activity in all of 8 monkeys tested. In 4 of these monkeys, the activity was restricted to alternation between ipsilateral and contralateral flexor nerves, whereas alternating activity between ipsilateral flexors and extensors was also seen in the other 4 monkeys. Administration of excitatory amino acids (NMDA or NMA) also elicited rhythmic alternating activity in 7 of 10 spinalized monkeys. In 4, rhythmic alternating activity was seen between extensors and flexors on one limb as well as between ipsilateral and contralateral flexors. In 3 monkeys NMDA/NMA produced alternation between extensors and flexors of one limb without alternation between the ipsilateral and contralateral sides. Administration of noradrenaline failed to elicit any rhythmic activity, but rather completely depressed already existing activity. Administration of serotonin (5-HT) was ineffective in facilitating alternating activity in 6 of 8 monkeys and was facilitatory to rhythmic activity in the other 2. We suggest that these data provide further evidence of a network capable of eliciting rhythmic alternating activity resembling locomotion in the primate spinal cord. The network, however, seems to be more difficult to activate pharmacologically in those conditions than in other mammals. This may especially be the case in higher primates, including man. Received: 6 November 1997 / Accepted: 21 April 1998     

超声根管预备效果的猴牙实验研究

４只猴的６４个牙，造成实验性尖周炎后，随机分２组进行超声或手持器械预备极管。分别于治疗后３、６、９、１２个月将猴处死，每个牙根经根尖孔制６μｍ厚的牙颌组织切片，１式３份，经不同染色显示尖周的炎症状况和根管系统内细菌的存在状况，结果表明，不论哪一种方法都不能彻底去除极管系统内的细菌和牙髓组织；所有切片均显示不同程度的尖周炎症。     

Attention-related neurons in the supplementary eye field of the macaque monkey

This study investigated whether the neuronal activity of a cortical area involved in the control of eye fixation is affected by the covert orienting of attention. We recorded single-unit activity from the supplementary eye field (SEF) of two macaque monkeys performing fixation and peripheral-attention tasks. Ninety-nine out of four hundred and fifteen cells were related to eye movements. The other neurons showed relationship with postural adjustments, and arm and ear movements. Fifty-five neurons were active during fixation (fixation cells) and 44 discharged in relation to saccades. The experiments reported here primarily concern the fixation cells. The activity of 64% (35/55) of fixation cells started with the onset of visual stimulus, before the visual input reached the fovea, and continued during active fixation. The activity of 27% (15/55) of fixation cells started with the onset of fixation. The activity of 9% (5/55) of fixation cells modified their timing trial by trial. Sixty-four percent of the fixation cells (35/55) were position-dependent, showing a selective spatial field of activity, 36% (20/55) were position-independent and characterized by a full spatial field. None of the 55 cells showed a visual receptive field. We tested both types of fixation cells by means of a peripheral attention task. When attention was oriented peripherally toward a target located in the selective spatial field, the cells discharged as if the gaze was held toward it. When attention was oriented peripherally toward a target, lying outside the selective spatial field, the cells were inactive as if gaze was held in that position. These results suggest that the supplementary eye field neurons may code for oriented attention in space and might be involved in the preparation of motor action. Preliminary results were presented at the 1994 ENA meeting in abstract form     

Stimulus specific adaptation in excited but not in inhibited cells in inferotemporal cortex of Macaque

Many cells in inferotemporal cortex respond more actively to a novel presentation than to a subsequent re-presentation of the same image, exhibiting stimulus specific adaptation (SSA). Previously, analysis of this adaptation was limited to visually excited cells, excluding visually inhibited cells. In the present experiment we studied 654 cells in four macaques performing visual tasks. Strong SSA (P < 0.0001) was observed in those cells which were excited by visual stimuli. This adaptation was also seen in the subset of such cells which, though excited by visual stimuli, failed to show visual specificity in their responses. Interestingly, no SSA (P > 0.1) was observed in the group of cells inhibited by visual stimuli. Furthermore, most inhibited cells failed to show visual specificity. This lack of visual specificity and SSA suggest that the visually inhibited cells have a limited role in the detailed information processing of visual perception and memory activated by the tasks used in the present experiments.     

猴自体椎间盘移植的组织学研究

本实验观察了猴自体椎间盘移植术的不同时期间盘组织学变化。结果表明大体形态移植间盘髓核的含水景减少，呈较粘稠胶状，光镜下纤维环和终板软骨结构无明显变化，髓核中有部分细胞退变，同时亦有成软骨样纤维细胞再生。透射电镜发现间盘髓核中仍有脊索细胞存在，移植后不同时间组髓与纤维环中均可见部分细胞变性坏死。本实验成功地建立了椎间盘移植动物模型，为进上步深入研究提供了依据。     

猴B病毒囊膜蛋白gD的B细胞表位预测及鉴定

目的鉴定猴B病毒囊膜蛋白gD的抗原表位。方法利用生物信息学分析猴B病毒囊膜蛋白gD的二级结构、亲水性、表面可及性、抗原性指数以及柔韧性,得到可能的表位肽段;再利用合成肽与B病毒阳性血清进行ELlSA验证,评价表位肽段的特异性和敏感性。结果在异D蛋白上预测得到7个表位肽段;ELISA测定结果显示,4个肽段（序列分别为^46 LPPLEQKTD^54、^106 RGAPEATRSDA^126、^291291PELAPEERGTSRFPGD＾３０６和＾３６１AVYLVRRRGR＾３７０可与B病毒阳性血清发生免疫学反应,敏感性在40％～70％之间。结论B病毒gD蛋白上至少存在4个线性化表位。     

常用实验动物不同组织部位肥大细胞异质性的组织学特点比较

目的 探讨并比较六种常用实验动物不同部位肥大细胞异质性的形态学特点.方法 应用麻醉后处死的方法,取小鼠、大鼠、豚鼠、兔、犬和猴的皮肤、肺脏、乙状结肠和脾脏组织,经4%中性缓冲甲醛溶液或Bouin''s液固定后,制作常规组织切片,分别作HE、甲苯胺蓝、阿尔新蓝-藏红和P物质免疫组织化学染色,镜下观察并应用彩色病理图像分析软件进行形态学分析;另取皮肤组织固定于磷酸缓冲戊二醛溶液,制作常规超薄切片,透射电镜下观察肥大细胞超微结构. 结果 六种动物不同组织中肥大细胞各有其分布特点,且在形态大小、异染性及染色特性等方面表现各异,肥大细胞密度和形态学参数差异有显著性(P<0.05);豚鼠、犬和猴皮肤肥大细胞颗粒具有特殊亚微结构;小鼠皮肤组织内可见P物质免疫阳性肥大细胞和神经纤维,犬脾脏内可见P物质免疫阳性肥大细胞. 结论 在六种实验动物的同一组织中以及同一种动物不同组织中,肥大细胞具有明显的异质性,此异质性对采用实验动物开展与肥大细胞功能相关的动物实验研究具有重要参考价值.     

甲型肝炎病毒在恒河猴中连续传代的实验观察

本文报告了用人HAV直接感染恒河猴并连续传代的结果。三代共四只恒河猴感染HAV后SGPT反应曲线相似,有两个异常高峰。四只猴感染前及恢复期的双份血清测定抗-HAV,结果恢复期血清抗-HAV均阳转。抗-HAV阳转的时间,三代猴都在接种HAV后7~10周之间。第一代和第二代猴的粪便经放射免疫和IEM检查证明HAAg阳性。传代感染的成功,证明了此第1、2代猴粪便排泄HAV的事实。另外,三只人工饲养2~8个月的恒河猴抗-HAV阳性,说明还能获得自然感染。     

The glycine/NMDA receptor antagonist HA-966 impairs visual recognition memory in rhesus monkeys

Recent studies have shown that strychnine-insensitive glycine binding sites positively modulate the N-methyl-d-aspartate (NMDA) subclass of glutamate receptors, which are important in neural pathways involved in cognitive function. We examined the effect of (±)-3-amino-1-hydroxy-2-pyrrolidone (HA-966), a highly specific antagonist of this glycine modulatory site on the NMDA receptor, on visual recognition memory in four rhesus monkeys performing a computer-automated version of delayed nonmatching-to-sample (DNMS) with a list length of 20 trial-unique graphic symbols. In addition, the effect of HA-966 was compared with that of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine; MK-801), a noncompetitive NMDA channel blocker. Administration of HA-966 (0.1–10 mg/kg, i.m.) 30 min before testing impaired DNMS performance dose-dependently, starting at doses of 3.2 mg/kg; the memory deficit following the highest dose (10 mg/kg) was associated with prolonged response latencies. Similar impairments in recognition memory were observed following treatment with MK-801, though at much lower doses (3.2–32 μg/kg) than those at which HA-966 was effective. Administration of low doses of HA-966 (1 mg/kg) and MK-801 (10 μg/kg), each of which had no significant effect on performance when given alone, also failed to impair performance when given concurrently. Combined administration of both drugs, each at amnesia-producing doses (3.2 mg/kg of HA-966 plus 32 μg/kg of MK-801), markedly impaired performance in an additive, not a synergistic, manner. From these results, we propose that the recognition memory impairment observed in our monkeys following HA-966 administration is via an action on the glycine modulatory site of the NMDA receptor complex.