NF-κB与Survivin基因在脑胶质瘤中的表达

目的 探讨细胞核因子κB和Survivin基因在胶质瘤中的表达及其与肿瘤细胞凋亡的关系.方法 分别采用原位杂交和免疫组织化学S-P法检测80例星形细胞瘤患者和10例正常脑组织Survivin mRNA和NF-κB的表达,用末端转移标记法(TUNEL)检测肿瘤组织的凋亡并计算其凋亡指数(AI).结果 星形细胞瘤组织中Survivin mRNA的阳性表达率明显高于对照组(P＜0.01),高度恶性组的阳性率明显高于低度恶性组(P＜0.01);AI在星形细胞瘤中明显高于对照组(P＜0.01),而Survivin mRNA阳性组低于阴性组(P＜0.01);NF-κB在星形细胞瘤中的表达明显高于对照组(P＜0.01),且Survivin mRNA阳性组明显高于阴性组(P＜0.05).结论 NF-κB与Survivin在星形细胞瘤中的表达密切相关,NF-κB的过表达可能通过上调Survivin mRNA的表达抑制星形细胞瘤细胞的凋亡,从而在肿瘤的发生、发展和治疗中发挥重要作用.     

人脑胶质瘤中Survivin、Ki-67的表达及其临床意义

目的探讨Survivin和Ki-67抗原在人脑胶质瘤中的表达及其临床意义。方法应用免疫组化SP法检测10倒正常脑组织和68例人脑胶质瘤中Survivin和Ki-67的表达。结果Survivin和Ki-67在正常脑组织中均不表达,而在各级别的人脑胶质瘤中均有表达,差异极显著（P％0.01）,Survivin和Ki-67的表达在高级别胶质瘤中显著高于低级别胶质瘤（P％0．01）,且Survivin和Ki-67的表达呈显著正相关（P〈0．05）。结论Ki-67可以作为评估胶质瘤细胞增殖的良好指标,Survivin和Ki-67的表达可以判断胶质瘤的恶性程度,为临床病理分级提供有意义的依据。     

Wnt信号调控因子Pygo2在人脑胶质瘤中的表达及意义

目的探讨Wnt信号重要成员Pygopus 2（Pygo 2）在人脑胶质瘤中的表达水平及与脑胶质瘤发生发展的关系。方法采用免疫组化方法检测Pygo2蛋白在80例脑胶质瘤和5例正常脑组织标本中的表达水平。结果 Pygo2在脑胶质瘤中的表达阳性率及免疫反应评分（IRS）为65.0%、3.32±2.51,正常脑组织未见染色。Ⅰ～Ⅳ级以及良、恶性脑胶质瘤Pygo2表达阳性率分别为38.5%、46.2%、78.9%、90.9%和43.6%、85.3%,在脑胶质瘤不同病理级别以及不同恶性度间Pygo2表达阳性率均有显著性差异（P〈0.01）。Ⅰ～Ⅳ级以及良、恶性脑胶质瘤Pygo2IRS分别为0.875±0.29、1.84±1.229、4.24±2.16、6.39±2.97和1.52±1.10、5.53±2.84,在脑胶质瘤不同病理级别以及不同恶性度间Pygo2IRS有极显著性差异（P〈0.01）。结论 Pygo2在脑胶质瘤中高表达,并随脑胶质瘤病理级别的增加而表达增强,可能在脑胶质瘤恶性发生发展过程中具有重要作用。     

不同病理级别胶质瘤p57^kip2/p21^cip1mRNA的表达变化

目的探讨不同病理级别人脑神经胶质瘤组织中p57^kip2/p21^cip1mRNA的表达变化及其关系。方法采用实时荧光定量PCR检测p57^kip2/p21^cip1mRNA在68例脑胶质瘤组织和16例非肿瘤脑组织中的表达水平。结果①p57^kip2mRNA在脑胶质瘤中的表达水平显著低于非肿瘤脑组织（P〈0.01）,且其表达水平与肿瘤病理级别呈显著负相关（rs=-0.495;P〈0.01）。②p21^cip1mRNA在脑胶质瘤中的表达水平与非肿瘤脑组织相比无显著差异（P〉0.05）,但其表达水平与肿瘤病理级别呈显著负相关（rs=-0.615;P〈0.01）。结论p57^kip2/p21^cip1的异常表达可能与人脑胶质瘤的发生和发展有密切相关,其表达水平可反映肿瘤的恶性程度。     

Notch-1mRNA在人脑胶质瘤中的表达及其意义

目的探讨Notch信号通路在人脑胶质瘤发展中的作用。方法收集脑胶质瘤组织标本60例,其中Ⅰ-Ⅱ级胶质瘤35例及Ⅲ-Ⅳ级胶质瘤25例,并取22例瘤旁正常脑组织标本作为对照。采用半定量RT-PCR方法检测这些标本中Notch-l mRNA的表达。结果Notch-1 mRNA在人脑胶质瘤中的表达显著高于正常脑组织（P〈0.01）,且在Ⅲ~Ⅳ级胶质瘤组中的表达显著高于Ⅰ-Ⅱ级组（P〈0.01）。相关性研究发现,Notch-1 mRNA的表达与人脑胶质瘤病理分级呈正相关（r=0.706,P〈0.01）。结论Notch-1mRNA在人正常脑组织和脑胶质瘤中均有表达,但其在脑胶质瘤中的表达与脑胶质瘤的病理分级呈正相关。     

IL-13Rα2在脑胶质瘤的表达及临床意义

目的研究白细胞介素13受体α2（IL-13Rα2）在脑胶质瘤中的表达及其临床意义。方法采用免疫组化SABC法检测66例胶质瘤（其中Ⅰ-Ⅱ级31例，Ⅲ-Ⅳ级35例）标本中IL-13Rα2蛋白的表达，并利用RT-PCR法检测20例胶质瘤（其中Ⅰ～Ⅱ级8例，Ⅲ-Ⅳ级12例）新鲜标本中IL-13Rα2mRNA的表达，并与5例正常脑组织对照，分析胶质瘤中IL-13Rα2的表达强度与其病理级别的关系。结果Ⅰ-Ⅱ级胶质瘤和Ⅲ-Ⅳ级胶质瘤IL-13Rα2蛋白和mRNA的表达强度均有显著性差异（P〈0.01），病理级别越高其表达越强。在5例正常脑组织中，IL-13Rα2mRNA和蛋白的表达均为阴性，与胶质瘤相比，差异显著（P〈0.01）。结论IL-13Rα2在脑恶性胶质瘤中高表达，在低级别胶质瘤和正常脑组织仅低表达或不表达。提示在某些情况下IL-13Rα2检测有助于良性与恶性胶质瘤的鉴别诊断。而IL-13Rα2也可作为脑恶性胶质瘤靶向治疗的特异性靶标。     

XRCC1在胶质瘤中的表达及意义

目的分析XRCC1在脑胶质瘤,癌旁组织和正常组织中的表达情况。方法郑州大学第五附属医院神经外科2015-07—2016-03经手术切除的脑胶质瘤标本50例,按病理类型可分级,另取因高血压所导致的脑出血行正常脑组织切除减压患者标本10例为对照组。依次检测不同级别的脑胶质瘤和正常脑组织中XRCC1的表达情况,比较XRCC1在不同级别的脑胶质瘤和正常脑组织中以及在不同年龄及性别中的阳性率和相关性。结果低度恶性组胶质瘤(Ⅰ~Ⅱ级)XRCC1阳性率低于高度恶性组胶质瘤(Ⅲ~Ⅳ级),差异无统计学意义(P0.05);在10例正常脑组织标本中XRCC1表达总阳性率为0%。XRCC1在正常脑组织与胶质瘤组织表达有显著差异(P0.05);50例胶质瘤患者组织标本中XRCC1的表达与患者年龄、性别差异无统计学意义(P0.05)。结论 XRCC1在神经胶质瘤中的表达明显高于正常脑组织;XRCC1阳性率的表达与神经胶质瘤的恶性级别无相关性。     

脑胶质瘤中乙酰肝素酶mRNA的表达与微血管密度的相关性研究

目的通过对脑胶质瘤中乙酰肝素酶mRNA的检测，探讨乙酰肝素酶在脑胶质瘤中的表达及与微血管密度的相关性。方法实时荧光定量逆转录聚合酶链反应（realtime RT-PCR）检测47例各级人脑胶质瘤和8例正常脑组织中HPA mRNA的表达，并用免疫组化S—P法检测其微血管密度（MVD）情况，分析HPA mRNA的表达与其恶性程度及与MVD的相关性。结果胶质瘤HPA表达值随肿瘤病理级别增高而增高。不同级别组胶质瘤HPA mRNA相对值有显著性差异（P〈0.01）；在脑胶质瘤中HPA mRNA表达与MVD呈正相关（r=0．979，P〈0.01）。结论脑胶质瘤HPA的表达与肿瘤的恶性程度、肿瘤血管生成密切相关。HPA的高表达反映了胶质瘤的恶性生物学行为，对判断预后有重要意义。     

不同病理级别胶质瘤中EphB4和ephrinB2的表达

目的 探讨人胶质瘤中EphB4、ephrinB2的表达.方法 收集31例不同病理级别脑胶质瘤组织和4例正常脑组织,制备冰冻切片,行免疫组织化学染色,应用Image-Pro Plus5.1分析结果,并分析与病理级别的相关性.结果 EphB4、ephrinB2表达于肿瘤细胞和血管上;EphB4在胶质瘤中的表达显著高于正常脑组织,与病理级别正相关(r=0.935,P<0.01);ephrinB2在胶质瘤中表达高于正常脑组织,与病理级别正相关(r=0.922,P=0.01).结论 在人胶质瘤中EphB4、ephrinB2呈过表达及共表达,可能和肿瘤恶性进展密切相关.     

脑胶质瘤组织中BMP-7与YY1 mRNA表达的相关性研究

目的探讨骨形态形成蛋白-7（BMP-7）和Yin Yang-1（YY1）mRNA在不同级别脑胶质瘤组织中的表达及其生物学意义。方法采用定时荧光定量PCR技术检测56例胶质瘤组织及10例正常脑组织中BMP-7和YY1mRNA的表达水平,并分析其与胶质瘤病理学分级的关系。结果①BMP-7mRNA在胶质瘤标本中的表达量明显高于正常脑组织（P〈0.01）,并且其表达量随胶质瘤恶性程度的升高而增加（P〈0.01）;②YY1 mRNA在胶质瘤标本中的表达量明显高于正常脑组织（P〈0.01）,并且其表达量随胶质瘤恶性程度的升高而增加（P〈0.01）;③BMP-7和YY1mRNA表达量在胶质瘤中的表达呈正相关（r=15.831,P〈0.01）。结论BMP-7和YY1 mRNA在胶质瘤组织中表达明显升高且两者表达均与胶质瘤的病理分级呈正相关。这提示BMP-7和YY1 mRNA的表达上调可能参与了胶质瘤的发生和发展,BMP-7和YY1可能能作为胶质瘤治疗的新靶点。     

Spatial patterns of visual cortical fast EEG during conditioned reflex in a rhesus monkey

A preliminary assay was made of the existence of time-space coherence patterns of fast EEG activity in the visual cortex of a Rhesus monkey. The primary intent of the present study was to evaluate the similarities and differences in relation to the olfactory bulb, where such coherences ave been described and have been demonstrated to be associated with behavior. Segments 1.5 s in duration were recorded simultaneously without averaging from 16 of 35 subdural electrodes fixed over the left occipital lobe in an array3.6cm× 2.8cm. Each segment was taken during the delivery of a visual conditioned stimulus (CS) and the performance of a conditioned response (CR) by a well-trained Rhesus monkey. The EEGs appeared chaotic with irregular bursts lasting 75–200 ms, resembling those in the olfactory EEG but with lower peak frequencies. Fourier spectra showed broad distributions of power resembling ‘ 1/fnoise’ with multiple peaks in the range of 20–40 Hz. Time intervals were selected where coherent activity seemed to be present at a number of electrodes. A dominant component waveform that was common to all channels was extracted by principal components analysis (PCA) of each segment. The distribution of the power of this component across the electrodes (the factor loadings) was used to describe the spatial pattern of the coherent cortical activity. Statistical analyses suggested that different patterns could be associated to the CS and the CR, as has been found in the olfactory system. These patterns remained stable over a 6 week recording interval. The patterns can be better discriminated, when the factor loadings of each channel are normalized to zero mean and unit variance, to discard a basic pattern of power distribution, which may reflect anatomical and electrode positioning factors that are related to behavioral information processing by the cortex. The wide spatial distribution of the common patterns found suggests that EEG patterns that manifest differing states of the visual cortex may also be accessible with scalp electrodes.     

Health consequences of acute and chronic marihuana use

Chemical content, assay procedures, and pharmacokinetics of cannabis sativa are discussed briefly. Cannabinoid cellular effects relating to chromosomes and immunity including cellular metabolism and allergic reactions are presented. Gross and microscopic brain pathology due to cannabis use is reviewed involving EEG alterations, psychopathology including aggressive behaviour as well as properties of psychomotor impairment, tolerance and dependence. Cardiopulmonary effects of marihuana are recorded under pulmonary pharmacological effects including the macrophage defense system and effects of smoke constituents; under cardiovascular effects cardiac toxicity and possible mechanism of action are discussed. Alterations of reproductive hormonal production and maturation of reproductive cells by marihuana in males and females with attendant impairment of reproductive function or fertility including reproductive outcome are reported. Field studies with healthy chronic cannabis users in Jamaica, Greece and Costa Rica are related as to observed medical alterations. Potential clinical effects are summarized in point form.     

Toward noninvasive monitoring of ongoing electrical activity of human uterus and fetal heart and brain

Objective

To evaluate whether a full-coverage fetal-maternal scanner can noninvasively monitor ongoing electrophysiological activity of maternal and fetal organs.

Concentration of antiepileptic drugs in persons with epilepsy: a comparative study in serum and saliva

Aim of the study: The monitoring of antiepileptic drugs (AEDs) in clinical setting is important for measuring the efficacy of drugs and their safety and in personalizing drug therapy. We investigated the levels of AED, carbamazepine (CBZ), phenytoin (PHT) and phenobarbital (PHB), to understand their association in saliva compared with those in serum during the therapy. Materials and methods: In this study, we performed a prospective study of 116 persons with epilepsy (PWE; mean age 26.90 ± 11.83 years). Serum and saliva samples were collected at trough levels from the patients, who were under the treatment of CBZ, PHT and PHB either alone or in combination of these drugs for at least three months. The drug levels were assessed by high-performance liquid chromatography. Results and conclusions: The number of males (n = 88; 75.86%) was higher than females (n = 28; 24.14%) among the recruited patients. The intake of CBZ, PHT and PHB was observed in 49.14%, 68.10% and 38.79% of PWE, respectively. The levels of these AEDs showed a significant correlation (p < 0.05) between serum and saliva. Interestingly, the levels of mono-therapy or bi-therapy showed a significant association (p < 0.05) between serum and saliva, however, there was no significant association in case of poly-therapy. This is the first report in the Indian population on simultaneous estimation of the three commonly used AEDs, such as CBZ, PHT and PHB in serum and saliva implicating their associations, either in mono-therapy or bi-therapy in PWE.     

Do scalp-recorded slow potentials during neuro-feedback training reflect the cortical activity?

Objective

Neuro-feedback (NFB) training by the self-regulation of slow potentials (SPs) <0.5?Hz recorded from the vertex scalp has been applied for seizure suppression in patients with epilepsy. However, SP is highly susceptible to artifact contamination, such as the galvanic skin response (GSR). This study aimed to evaluate the correlation between SPs recorded from the scalp and intracranial electroencephalography (EEG) by event-related coherence analysis.

脑红蛋白在脑梗死大鼠表达及丁苯酞干预效应

目的探讨脑红蛋白在脑梗死大鼠中的表达和丁苯酞干预在氧化应激损伤中作用。方法将90只雄性SD大鼠随机分为假手术组、模型组、治疗组。每组再分为3个亚组:1 d组、3 d组和7 d组,每亚组10只。模型组和治疗组采用线栓法制作大鼠大脑中动脉闭塞模型(MCAO),假手术组只分离不结扎。治疗组在动物苏醒后以丁苯酞植物油灌胃,假手术组和模型组同法给予等量植物油灌胃。每只大鼠在术后3h和处死前行神经功能评分,应用RT-PCR和免疫组化检测脑组织脑红蛋白(NGB)表达,化学比色法检测超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果 (1)神经功能评分,模型组和治疗组术后3 h评分差异无统计学意义(P>0.05),各时间点处死前评分差异均有统计学意义(P<0.05)。(2)NGB mRNA和免疫组化表达随时间延长逐渐降低,各时间点模型组较假手术组、治疗组较模型组高,差异均有统计学意义(P<0.05)。(3)SOD活性和MDA含量随时间延长逐渐减少。SOD活性假手术组较治疗组、治疗组较模型组高,差异均有统计学意义(P<0.05);MDA含量假手术组较治疗组、治疗组较模型组低,差异均有统计学意义(P<0.05)。结论丁苯酞促进脑缺血大鼠脑红蛋白表达,减少氧化应激损伤。     

Rapid‐acting antidepressant ketamine,its metabolites and other candidates: A historical overview and future perspective

Major depressive disorder (MDD) is one of the most disabling psychiatric disorders. Approximately one‐third of the patients with MDD are treatment resistant to the current antidepressants. There is also a significant therapeutic time lag of weeks to months. Furthermore, depression in patients with bipolar disorder (BD) is typically poorly responsive to antidepressants. Therefore, there exists an unmet medical need for rapidly acting antidepressants with beneficial effects in treatment‐resistant patients with MDD or BD. Accumulating evidence suggests that the N‐methyl‐D‐aspartate receptor (NMDAR) antagonist ketamine produces rapid and sustained antidepressant effects in treatment‐resistant patients with MDD or BD. Ketamine is a racemic mixture comprising equal parts of (R)‐ketamine (or arketamine) and (S)‐ketamine (or esketamine). Because (S)‐ketamine has higher affinity for NMDAR than (R)‐ketamine, esketamine was developed as an antidepressant. On 5 March 2019, esketamine nasal spray was approved by the US Food and Drug Administration. However, preclinical data suggest that (R)‐ketamine exerts greater potency and longer‐lasting antidepressant effects than (S)‐ketamine in animal models of depression and that (R)‐ketamine has less detrimental side‐effects than (R,S)‐ketamine or (S)‐ketamine. In this article, the author reviews the historical overview of the antidepressant actions of enantiomers of ketamine and its major metabolites norketamine and hydroxynorketamine. Furthermore, the author discusses the other potential rapid‐acting antidepressant candidates (i.e., NMDAR antagonists and modulators, low‐voltage‐sensitive T‐type calcium channel inhibitor, potassium channel Kir4.1 inhibitor, negative modulators of γ‐aminobutyric acid, and type A [GABA_A] receptors) to compare them with ketamine. Moreover, the molecular and cellular mechanisms of ketamine’s antidepressant effects are discussed.     

Update of the original HDLS kindred: divergent clinical courses

Sundal C, Ekholm S, Nordborg C, Jönsson L, Börjesson‐Hanson A, Lindén T, Zetterberg H, Viitanen M, Andersen O. Update of the original HDLS kindred: divergent clinical courses.
Acta Neurol Scand: 2012: 126: 67–75.
© 2011 John Wiley & Sons A/S. Background – Hereditary diffuse leukoencephalopathy with spheroids (HDLS) was first identified among a Swedish kindred with 17 cases. The average age of onset was 36 years. Autopsy in four cases revealed the presence of axonal spheroids. The causative gene is unknown. Methods – We performed genealogical and longitudinal observations of the original kindred. Forty members were examined, five telephone‐interviewed, and one of the original HDLS cases from 1984 was neuropathologically examined. The clinical course was documented. The cerebrospinal fluid (CSF) findings of two recently affected cases were examined, and one of those autopsied. Results – Of those examined, two developed HDLS during our survey and 38 were healthy. Those interviewed by telephone were healthy. One had symptoms suggestive of HDLS in 1984, but autopsy during our survey showed no spheroids. This patient, two relatives healthy at our examination and one without symptoms at telephone interview had HDLS diagnoses in the 1984 report. Thus, four HDLS diagnoses were unconfirmed. The number of identified patients amounts to 15 among 75 individuals in four generations, including two recent cases who demonstrated a subacute multisystem encephalopathy in Case 1 and an insidious course in Case 2. CSF showed signs of neurodegeneration without inflammation, and autopsy verified HDLS in Case 1. Conclusions – Some HDLS cases were misdiagnosed with unspecified psychiatric diagnoses in affected relatives from the original 1984 publication. However, HDLS is an encephalopathy dominated by a frontal lobe syndrome with an inexorably progressive and fatal course, where the different symptomatology in two recent cases confirmed the existence of acute and chronic variants.