Establishment and characterization of a human malignant choroids plexus papilloma cell line (HIBCPP)

A cell line designated "HIBSPP" was established from a human malignant choroids plexus papilloma of 29-year-old Japanese woman. This line grew well without interruption for 3 years and was subcultivated over 70 times. The cells were spindle, oval, and polygonal in shape, and neoplastic and pleomorphic features, a jigsaw puzzle-like arrangement, multilayering and forming papillary structures without contact inhibition. The cells proliferated slowly, and the population doubling time was about 69 hours. The chromosome number showed a wide distribution of aneuploidy. The mode was in the hypotetraploid range, and many marker chromosomes were observed. The culture cells were easily transplanted into the subcutis of nude mice and produced the tumor resembling the original tumor.     

Sympathetic denervation-induced changes in G protein expression in enteric neurons of the guinea pig colon

Chronic sympathetic denervation entails subsensitivity to alpha(2)-adrenoceptor agonists and supersensitivity to kappa- and mu-opioid receptor agonists modulating cholinergic neurons in the guinea pig colon. A possible role for signal transduction G proteins in contributing to development of these sensitivity changes was investigated. Pertussis toxin (PTX), a blocker of the G(i/o)-type family of G proteins significantly reduced the inhibitory effects of UK14,304 (alpha(2)-adrenoceptor agonist), U69593 (kappa-opioid receptor agonist) and DAMGO (mu-opioid receptor agonist) on acetylcholine (ACh) overflow in preparations obtained from normal animals, but not in those obtained from sympathetically denervated animals. In this experimental condition, immunoblot analysis revealed reduced levels of G(alphao), G(alphai2), G(alphai3) and G(beta) in myenteric plexus synaptosomes. On reverse, synaptosomal levels of G(alphai1) and G(alphaz), a PTX-insensitive G-protein, increased after chronic ablation of the sympathetic pathways. These data suggest that changes in the function and expression of inhibitory G proteins coupled to alpha(2)-adrenoceptors, kappa- and mu-opioid receptors occur in the myenteric plexus of the guinea pig colon after chronic sympathetic denervation. The possibility that regulation of G proteins represents one of the biochemical mechanisms at the basis of the changes in sensitivity of enteric cholinergic neurons to alpha(2)-adrenoceptor, kappa- and mu-opioid receptor agonists is discussed.     

不同浓度罗派卡因用于老年患者臂丛神经阻滞麻醉的临床比较研究

目的:比较不同浓度的罗派卡因对老年患者臂丛神经感觉、运动神经阻滞起效和维持时间的影响。方法:选择60例行择期上肢手术老年患者。男38例,女21例,年龄65-78岁。ASAⅠ-Ⅲ级。随机分为两组。定时记录感觉、运动神经完全阻滞起效时间和维持时间,观察并记录术中生命体征的变化和有无并发症发生。结果:两组患者感觉和运动神经阻滞的起效时间和维持时间有极显著性差异(P<0.05),术中生命体征和并发症发生率无显著性差异。结论:0.37%相较0.25%罗哌卡因用于老年患者臂丛神经阻滞麻醉起效更快,维持时间更长,副作用风险未见增加,可常规用于老年患者的上肢手术麻醉。     

Amyloid-β peptide(1-40) elimination from cerebrospinal fluid involves low-density lipoprotein receptor-related protein 1 at the blood-cerebrospinal fluid barrier

Amyloid-β peptide (Aβ) concentration in CSF is potentially a diagnostic and therapeutic target for Alzheimer's disease (AD). The purpose of this study was to clarify the elimination mechanism of human Aβ(1-40) [hAβ (1-40)] from CSF. After intracerebroventricular (ICV) administration, [(125) I]hAβ(1-40) was eliminated from the rat CSF with a half-life of 17.3 min. The elimination of [(125) I]hAβ(1-40) was significantly inhibited by human receptor-associated protein (RAP) and the elimination was attenuated in either anti-low-density lipoprotein receptor-related protein (LRP)1 antibody-treated or RAP-deficient mice, suggesting that a member(s) of the low-density lipoprotein receptor gene family is involved in the elimination of hAβ(1-40) from CSF. The amounts of LRP1 and LRP2 proteins were determined by means of liquid chromatography-tandem mass spectrometry, and the LRP1 content in rat choroid plexus was determined to be 3.7 fmol/μg protein, whereas the LRP2 content was below the detection limit (<0.2 fmol/μg protein). Conditionally, immortalized rat choroid plexus epithelial cells exhibited predominant apical-to-basal and apical-to-cell transport of [(125) I]hAβ(1-40). These results indicated that hAβ(1-40) is actively eliminated from CSF and this process is at least partly mediated by LRP1 expressed at choroid plexus epithelial cells, which therefore play a role in determining CSF concentrations of hAβ(1-40).     

Diversity in the surface morphology of adjacent epithelial cells of the choroid plexus: an ultrastructural analysis

It is generally known that the luminal surface of the choroidal epithelial cells is covered with a luxuriant coat of slender microvilli and cilia. However, extensive ultrastructural studies on the surface morphology of choroidal epithelial cells are lacking. This study, therefore, is focused on the detailed surface morphology of the choroid plexus of the lateral ventricle of adult Wistar rats using transmission and scanning electron microscopy. The animals were anesthetized, perfused with 0.9% oxygenated saline followed by 3% gluteraldehyde and the choroid plexus was processed for routine electron microscopy. The results of the ultrastructural observations presented in this study show that even the neighboring choroidal epithelial cells may express distinct morphology. In addition to the usually described morphology of choroidal epithelial cells, in this study, the presence of cells with uniform small blebs, crenulated or doughnut shaped structures, large mature blebs, or cells with an extensive network of fibers were observed. Although, dissimilar surface morphology of adjacent choroidal epithelial cells may indicate their distinct functional status, further studies are necessary to understand the physiological relevance of the varied surface morphology of choroidal epithelial cells.     

Neural invasion in pancreatic cancer: a mutual tropism between neurons and cancer cells

Neural invasion by pancreatic cancer cells (PCC) worsens the prognosis and frequently limits curative resection. We established a novel in-vitro model in which T3M4-PCCs were co-cultured with either isolated myenteric plexus cells (MP) or dorsal root ganglia (DRG) of newborn rats within a three-dimensional extracellular matrix gel. The close vicinity of MP or DRG to T3M4-PCCs induced early morphologic changes on T3M4-PCCs at the migration front prior to the migration process with elongated and neurite-targeting PCCs, compared to round and non-grouping at the non-migrating front. T3M4-PCCs built cancer-cell clusters around the DRG or MP, a process which was accelerated by increasing number of T3M4-PCCs or neurons. These findings indicate that neuro-cancer interactions start prior to PCC migration and induce evident changes in cancer and nerve biology. These findings can be reproduced within the introduced 3D in-vitro migration assay which allows investigation in the early pathogenesis of neural PCC invasion.     

臂丛神经撕脱伤后慢性疼痛患者脑区葡萄糖代谢的研究

臂丛神经撕脱伤后慢性疼痛是一种临床上顽固性神经病理性疼痛.然而,对于其潜在的中枢机制还知之甚少.为了进一步探讨臂丛神经撕脱伤后慢性疼痛的相关脑区活动,利用18F-脱氧葡萄糖(FDG)正电子断层扫描(PET)技术观察臂丛神经撕脱后慢性疼痛患者的脑葡萄糖代谢.选择左侧臂丛神经撕脱伤后慢性疼痛行脊髓后根入髓区(DREZ)切开术后疼痛减轻>75%的患者,共5例,分别在术前和术后14天行PET扫描采集数据,同时行视觉模拟评分(VAS),汉密尔顿(Hamilton)抑郁和焦虑评分.用统计参数图(SPM2)软件分析数据.与术前疼痛状态下相比,术后葡萄糖代谢明显减低的脑区有双侧尾状核,眶额回(OFC)(BA11),对侧扣带下回(BA25)和同侧前额叶背外侧区域(DLPFC)(BA46/47).葡萄糖代谢明显增高的脑区有对侧丘脑,枕核和同侧项叶(BA7).研究结果提示,涉及情绪、注意和疼痛内在调节的脑区在臂丛神经撕脱伤后慢性疼痛的调制中发挥重要作用.     

Purinergic receptors and gastrointestinal secretomotor function

Secretomotor reflexes in the gastrointestinal (GI) tract are important in the lubrication and movement of digested products, absorption of nutrients, or the diarrhea that occurs in diseases to flush out unwanted microbes. Mechanical or chemical stimulation of mucosal sensory enterochromaffin (EC) cells triggers release of serotonin (5-HT) (among other mediators) and initiates local reflexes by activating intrinsic primary afferent neurons of the submucous plexus. Signals are conveyed to interneurons or secretomotor neurons to stimulate chloride and fluid secretion. Inputs from myenteric neurons modulate secretory rates and reflexes, and special neural circuits exist to coordinate secretion with motility. Cellular components of secretomotor reflexes variably express purinergic receptors for adenosine (A1, A2a, A2b, or A3 receptors) or the nucleotides adenosine 5'-triphosphate (ATP), adenosine diphosphate (ADP), uridine 5'-triphosphate (UTP), or uridine diphosphate (UDP) (P2X(1-7), P2Y(2), P2Y(4), P2Y(6), P2Y(12) receptors). This review focuses on the emerging concepts in our understanding of purinergic regulation at these receptors, and in particular of mechanosensory reflexes. Purinergic inhibitory (A(1), A(3), P2Y(12)) or excitatory (A(2), P2Y(1)) receptors modulate mechanosensitive 5-HT release. Excitatory (P2Y(1), other P2Y, P2X) or inhibitory (A(1), A(3)) receptors are involved in mechanically evoked secretory reflexes or "neurogenic diarrhea." Distinct neural (pre- or postsynaptic) and non-neural distribution profiles of P2X(2), P2X(3), P2X(5), P2Y(1), P2Y(2), P2Y(4), P2Y(6), or P2Y(12) receptors, and for some their effects on neurotransmission, suggests their role in GI secretomotor function. Luminal A(2b), P2Y(2), P2Y(4), and P2Y(6) receptors are involved in fluid and Cl(-), HCO(3) (-), K(+), or mucin secretion. Abnormal receptor expression in GI diseases may be of clinical relevance. Adenosine A(2a) or A(3) receptors are emerging as therapeutic targets in inflammatory bowel diseases (IBD) and gastroprotection; they can also prevent purinergic receptor abnormalities and diarrhea. Purines are emerging as fundamental regulators of enteric secretomotor reflexes in health and disease.