增殖细胞核抗原在口腔鳞状细胞癌中的表达

采用鼠抗ＰＣＮＡ单克隆抗体，ＡＢＣ法，对１１例正常口腔粘膜及２９例口腔鳞癌进行了染色。结果表明：正常粘膜仅在基底层中有少量的ＰＣＮＡ阳性细胞，其阳性分级为１级。而鳞癌阳性分级主要是３～４级，随着组织学分级的升高，ＰＣＮＡ阳性表达率也相应增高。经统计学分析，正常组织与鳞癌之间及鳞癌各级均有非常显著差异（Ｐ＜００１）。提示：ＰＣＮＡ的表达与口腔鳞癌组织学分级有关。     

Down-Regulation of Estrogen Receptor Immunoreactivity by 17β-estradiol in the Guinea Pig Forebrain

Low amplitude pulses of estradiol-17β (E₂-17β) are more effective than large single bolus injections or constant exposure to E₂-17β in inducing progesterone-facilitated sex behavior in female rats and guinea pigs. The present study examined whether the increased responsiveness to E₂-17β is due to an increase in the number of estrogen receptors in the estrogen receptor rich areas of the hypothalamus and amygdala. Initial studies examined the rapid effects (20 min) of a high dose of E₂-17β (50 μg) on estrogen receptor immunostaining using either the H222 antibody or the ER 21 antiserum. ER 21 immunostaining was not affected by the E₂-17β treatment suggesting that it binds to both occupied and unoccupied estrogen receptors. Therefore the ER 21 antiserum was used to characterize the regulation of estrogen receptor immunoreactivity (ER-IR) by E₂-17β. ER-IR was examined for 48 h and serum E₂-17β for 24 h following a 2 μg s.c. injection of E₂-17β (a dose similar to that used in multiple pulse paradigms). Serum E₂-17β peaked 15 to 30 min following the injection and returned to baseline values by 1 h. In all but one area maximal suppression of ER-IR occurred at 12 h. In summary, 1) decreases in estrogen receptor immunoreactivity following E₂-17β are consistent with studies in which estrogen receptors were assayed by binding assays and estrogen receptor mRNA was determined by in situ hybridization; 2) the ER 21 antiserum is able to detect both occupied and unoccupied estrogen receptors and 3) H222 immunoreactivity is influenced by the presence of E₂-17β, so that the level of H222-IR is a reflection of ligand/receptor binding dynamics. The data suggest that up-regulation of estrogen receptors does not account for the increase in behavioral sensitivity which is observed following multiple pulses of E₂-17β.     

Inhibitory action of a conditioning procedure on visual responsive neurons of the nucleus reticularis thalami in rats

Summary In urethane anesthetized rats neuronal responses of the visual part of nucleus reticularis thalami (vTR) to light were compared with those during pairing light as a conditioned stimulus (CS) with the electrical stimulation of the rat's tail (US). The intensity of the US was adjusted to the minimum required to evoke a slight freezing behavior in the awake rat. The firing rate of most vTR neurons decreased in the period between light and US application (P < 0.01). Significant response modulations to light were observed in 39% of the units, in most of them they persisted over an extinction period of 15 min. In addition, neurons which were predominantly inhibited by conditioning sometimes changed from regular spiking to a burst pattern. The results support the hypothesis that conditioning related facilitation of geniculate neurons observed in previous experiments can be explained at least partly by disinhibition of geniculate units from vTR.     

Effects of the 5-HT1A partial agonists gepirone,ipsapirone and buspirone on local cerebral glucose utilization in the conscious rat

The azospirones gepirone (10 mg/kg), ipsapirone (10 mg/kg) and buspirone (10 mg/kg) were examined for their effect on regional cerebral glucose utilization in conscious rats using quantitative 2-deoxyglucose autoradiography. All three 5-HT_1A partial agonists reduced glucose utilization in the hippocampus and dentate gyrus by 20–25% and increased glucose utilization by 38–65% in the lateral habenular nucleus; an important relay between striatal/limbic areas and the mid-brain raphe nuclei. The findings emphasize the potential importance of the hippocampus as a site of action for 5-HT_1A receptor active drugs in vivo and also suggest that functional activity in the striatal/limbichabenular-raphe pathway may be influenced by gepirone, ipsapirone and buspirone.     

Does ageing have an effect on midbrain premotor nuclei for vertical eye movements?

Currently, there is debate in the clinical literature as to whether defects in vertical gaze are a consequence of normal ageing or a component of an underlying neurodegenerative disorder. Although pathological changes have been demonstrated in diseased subjects, no study to date has addressed the question of normal ageing effects. In this retrospective study, we examined 23 neurologically and pathologically normal subjects (age 18-91). Using an unbiased, frame-based sampling method, we quantified neuronal and glial cell densities in 10 young (<50) and 13 aged (>65) subjects in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), the key premotor substrate in the vertical gaze pathway. We found no statistically significant difference in neuronal density, glial cell density, or neuron-to-glial cell ratios between the young and the aged. We conclude, therefore, that neuronal loss, neuronal atrophy, or gliosis in the riMLF are not consequences of normal ageing.     

Deep brain stimulation for Parkinson's disease dissociates mood and motor circuits: a functional MRI case study.

Behavioral disturbances have been reported with subthalamic (STN) deep brain stimulation (DBS) treatment in Parkinson's disease (PD). We report correlative functional imaging (fMRI) of mood and motor responses induced by successive right and left DBS. A 36-year-old woman with medically refractory PD and a history of clinically remitted depression underwent uncomplicated implantation of bilateral STN DBS. High-frequency stimulation of the left electrode improved motor symptoms. Unexpectedly, right DBS alone elicited several reproducible episodes of acute depressive dysphoria. Structural and functional magnetic resonance imaging (fMRI) imaging was carried out with sequential individual electrode stimulation. The electrode on the left was within the inferior STN, whereas the right electrode was marginally superior and lateral to the intended STN target within the Fields of Forel/zona incerta. fMRI image analysis (Analysis of Functional NeuroImages, AFNI) contrasting OFF versus ON stimulation identified significant lateralized blood oxygen level-dependent (BOLD) signal changes with DBS (P < 0.001). Left DBS primarily showed changes in motor regions: increases in premotor and motor cortex, ventrolateral thalamus, putamen, and cerebellum as well as decreases in sensorimotor/supplementary motor cortex. Right DBS showed similar but less extensive change in motor regions. More prominent were the unique increases in superior prefrontal cortex, anterior cingulate (Brodmann's area [BA] 24), anterior thalamus, caudate, and brainstem, and marked widespread decreases in medial prefrontal cortex (BA 9/10). The mood disturbance resolved spontaneously in 4 weeks despite identical stimulation parameters. Transient depressive mood induced by subcortical DBS stimulation was correlated with changes in mesolimbic cortical structures. This case provides new evidence supporting cortical segregation of motor and nonmotor cortico-basal ganglionic systems that may converge in close proximity at the level of the STN and the adjacent white matter tracts (Fields of Forel/zona incerta).     

Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease.

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow-up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off-drug/on-stimulation; off-drug/off-stimulation; on-drug/off-stimulation; and on-drug/on-stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long-term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD.     

高压氧下大鼠脑组织中氧化氮合酶阳性细胞的表达(论著)

目的：探讨高压氧（HBO）对视觉中枢的影响。方法：SD大鼠12只，随机分为3组：分别为常压对照组（NP组），高压空气对照组（HBA组），和HBO实验组（HBO组）。HBA组和HBO组动物分别给予0．25MPa高压空气和纯氧，升压20分钟，在0．25MPa下稳压4小时，然后经20分钟减至常压。动物出舱后立即灌注取脑，利用NADPH-黄递酶（NADPH-diaphorase）组织化学方法，观察氧化氮合酶（NOS）阳性细胞见脑组织外侧膝状体（LGN）、视皮层及大脑顶叶皮层的表达。结果：NOS阳性细胞存在于大鼠LGN、视皮层及大脑项叶皮层中。在0．25MPaHBO作用下，视皮层、大脑顶叶皮层中NOS阳性细胞明显增加（P＜0．05），而LGN与对照组相比无显著性差异（P＞0．05）。结论：HBO对视觉中枢的毒性作用与视皮层NOS阳性细胞增加密切相关。     

Excitatory amino acid receptor regulation after subthalamic nucleus lesions in the rat

The subthalamic nucleus plays a pivotal role in the regulation of basal ganglia output. Recent electrophysiologic, lesion and immunocytochemical studies suggest that the subthalamic nucleus uses an excitatory amino acid as a neurotransmitter. After complete ablation of the subthalamic nucleus, we have examined the NMDA, AMPA, kainate and metabotropic subtypes of excitatory amino acid receptors in two major subthalamic projection areas (globus pallidus and substantia nigra pars reticulata) with quantitative autoradiography. Two weeks after ablation, binding sites for [³H]AMPA and [³H]kainate increased in substantia nigra pars reticulata ipsilateral to the lesion. In globus pallidus on the lesioned side, [³H]glutamate binding to the NMDA recognition site decreased. The results suggest that glutamate receptors regulate after interruption of subthalamic nucleus output.