Signaling pathways of hypocretin-1 actions on pyramidal neurons in the rat prefrontal cortex

We have investigated the direct excitatory effects of hypocretin-1 on acutely isolated prefrontal cortical pyramidal neurons and explored the signaling mechanisms of these actions. Puff application of hypocretin-1 caused an excitation in the recorded neurons. These effects of hypocretin-1 were abolished by a phospholipase C inhibitor D609, demonstrating that phospholipase C mediates the actions of hypocretin-1. A specific protein kinase C inhibitor, bisindolylmaleimide II, blocked the excitatory actions of hypocretin-1, suggesting that protein kinase C plays a key role. Finally, protein kinase A inhibitor applied intracellularly did not affect the responses. These results indicate that hypocretin-1 excites prefrontal neurons by activation of phospholipase C and protein kinase C pathways, but not protein kinase A.     

Role of active movement in place-specific firing of hippocampal neurons

The extent of external and internal factors contributing to location-specific firing of hippocampal place cells is currently unclear. We investigated the role of active movement in location-specific firing by comparing spatial firing patterns of hippocampal neurons, while rats either ran freely or rode a motorized cart on the same circular track. Most neurons changed their spatial firing patterns across the two navigation conditions ("remapping"), and they were stably maintained across repeated active or passive navigation sessions. These results show that active movement is a critical factor in determining place-specific firing of hippocampal neurons. This could explain why passive displacement is not an effective way of acquiring spatial knowledge for subsequent active navigation in an unfamiliar environment.     

Using automated morphometry to detect associations between ERP latency and structural brain MRI in normal adults

Despite the clinical significance of event-related potential (ERP) latency abnormalities, little attention has focused on the anatomic substrate of latency variability. Volume conduction models do not identify the anatomy responsible for delayed neural transmission between neural sources. To explore the anatomic substrate of ERP latency variability in normal adults using automated measures derived from magnetic resonance imaging (MRI), ERPs were recorded in the visual three-stimulus oddball task in 59 healthy participants. Latencies of the P3a and P3b components were measured at the vertex. Measures of local anatomic size in the brain were estimated from structural MRI, using tissue segmentation and deformation morphometry. A general linear model was fitted relating latency to measures of local anatomic size, covarying for intracranial vault volume. Longer P3b latencies were related to contractions in thalamus extending superiorly into the corpus callosum, white matter (WM) anterior to the central sulcus on the left and right, left temporal WM, the right anterior limb of the internal capsule extending into the lenticular nucleus, and larger cerebrospinal fluid volumes. There was no evidence for a relationship between gray matter (GM) volumes and P3b latency. Longer P3a latencies were related to contractions in left temporal WM, and left parietal GM and WM near the interhemispheric fissure. P3b latency variability is related chiefly to WM, thalamus, and lenticular nucleus, whereas P3a latency variability is not related as strongly to anatomy. These results imply that the WM connectivity between generators influences P3b latency more than the generators themselves do.     

A brief history of studies on anti-tumor remedies in China

This paper gives a general introduction to the studies on the formulation and invention of anti-tumor remedies from 1950s-1980s. Beginning from 50s, antitumor antibiotics were investigated. New alkylicompoun and antibiotics were found in the 60s, while more new natural compounds were found in the 70s. Researches were proceeded in the 80s based on the former achievements. Through the process of about 30 years, nearly 80 new species were produced, many anti-tumor pharmaceutical corporations established, and a contigent of high level research workers was formed. However, there still exist a rather large gap between the urgent clinical needs for clinical chemotherapeutics and the actual status. Based on some 30 years of experience in China, the following points were summarized, i.e., shifting from merely imitation to invention, developing the spirit of massive cooperation, investigating the thesaurus of TCM, developing China's plant resources, and traditional Chinese preventive idea, so that the stress point for research be laid on the invention of preventive anti-tumor remedies.     

准分子激光原位角膜磨镶术后角膜瓣下上皮细胞植入的临床及病理学研究

目的探讨准分子激光原位角膜磨镶术（ｅｘｃｉｍｅｒｌａｓｅｒｉｎｓｉｔｕｋｅｒａｔｏｍｉｌｅｕｓｉｓ,ＬＡＳＩＫ）后角膜瓣下上皮细胞植入的临床细胞学、病理学特点及术后并发症的处理方法。方法对ＬＡＳＩＫ术后１５～６５天发生角膜瓣下上皮细胞增生的４只患眼行向鼻侧撕开角膜瓣,刮除植入及增生的有形物质,冲洗层间,重新将角膜瓣复位。结果术后１～１２个月,无新的上皮细胞植入。将刮除的植入及增生的有形物质行临床细胞学、病理学检查,可见较多变性、坏死且呈散在或小团状分布的角膜上皮细胞及部分细长形的纤维细胞样细胞。膜样有形成分行组织学ＨＥ染色,可见淡蓝色的细颗粒状无结构物质,其中夹杂少量变性坏死的细胞。结论ＬＡＳＩＫ术后角膜上皮瓣下植入增生可出现瓣下乳白色有形物质,主要由细颗粒状无结构物质构成,夹杂变性坏死的细胞成分。具有不规则、匍匐性进展的特征,应尽早清除。     

Promotion of S-phase entry and cell growth under serum starvation by SAG/ROC2/Rbx2/Hrt2, an E3 ubiquitin ligase component: association with inhibition of p27 accumulation

The sensitive-to-apoptosis gene (SAG) was initially identified as a redox-inducible, apoptosis-protective protein and subsequently found to be the second family member of regulator of cullins (ROC)/RING box protein (Rbx)/Hrt, which acts as a component of E3 ubiquitin ligase. We report here that SAG promoted cell growth under serum starvation. Microinjection of SAG mRNA into quiescent NIH/3T3 cells induced S-phase entry as determined by [(3)H]-thymidine incorporation. Likewise, overexpression of SAG by either adenovirus infection of immortalized human epidermal keratinocytes (Rhek-1) or DNA transfection of SY5Y human neuroblastoma cells induced cell proliferation under serum starvation. Because cyclin-dependent kinase inhibitors (CKIs), including p21, p27, and p57, are degraded through the ubiquitin pathway, we tested whether SAG-induced cell growth is associated with CKI degradation. Although there was no significant difference in the levels of p21 and p57 between the vector controls and SAG-overexpressing cells, serum starvation induced 10- to 18-fold accumulation of p27 in control Rhek-1 cells. Accumulation of p27 was remarkably inhibited (only 2 to 5-fold) in SAG-infected cells. Inhibition of p27 accumulation was also observed in stably SAG-overexpressing SY5Y cells. Significantly, SAG-associated inhibition of p27 accumulation was largely abolished by the treatment with a proteasome inhibitor. In vivo binding of SAG and Skp2, an F-box protein that promotes p27 ubiquitination, was detected, and the binding was enhanced in SAG-overexpressing cells grown under serum starvation. Thus, SAG-induced growth with serum withdrawal appears to be associated with SAG-mediated p27 degradation. Mol. Carcinog. 30:37-46, 2001.     

Regulation of Laloo by the Xenopus C-terminal Src kinase (Xcsk) during early vertebrate development

Mesoderm formation in the frog, Xenopus laevis, is dependent on the activity of one or more members of the Src family kinases; the molecular interactions underlying this requirement are not well understood. The C-terminal Src Kinase (Csk) is a potent inhibitor of Src activity, and is required for normal mammalian development; here we report the characterization of Xenopus Csk (Xcsk). Xcsk is widely expressed during early development, physically interacts with the Src kinase Laloo, and inhibits the generation of mesoderm by the Src kinases. Xcsk activity requires a functional kinase domain; furthermore, a kinase-inactive Xcsk mutant potently synergizes with Laloo during early vertebrate development, suggesting a fundamental role for the Src kinase-Csk regulatory circuit during mesoderm induction, in vivo.     

细胞外基质和细胞粘附分子在细支气管肺泡癌中的表达与意义

目的：研究细胞外基质（ECM）中层粘连蛋白（LN）、Ⅳ型胶原（CollⅣ）、纤粘连蛋白（FN）和细胞粘附分子A－CAM在细支气管肺泡癌（BAC）及其三个亚型和肺腺癌（CPA）间的表达下及意义。方法：采用免疫组化LSAB法,检测50例BAC（包括14例粘液型、22型非粘液型和14例硬化型）和6例CPA中ECM分布和A－CAM表达情况。结果：在LN、Coll Ⅳ、FN分布上,粘液型BAC与癌旁肺实质相同,为在基底膜水平只不过连续单层窄线性染色;非粘液型BAC则呈连续、不规则增宽的双层轨道样;硬化型BAC外周区域同非粘液型,中央区域与CPA相似,其内癌性腺体基底膜水平处表现为中继或缺如;A－CAM在BAC和CPA中的阳性率分别为605（30／50）和83％（5／6）（P＞0．05）,在BAC三个亚型中则分别为43％（6／14）、55％（12／22）和865（12／14）,呈递增趋势,粘液型显著低于硬化型（P＜0．05）,硬化型BAC则与CAP十分接近,结论从ECM分布和A－CAM的表达来看,BAC整体应视为CAP的一种亚型,粘液型BAC是真正意义上的BAC;BAC三个亚型间及与CAP间可能存在某种分化关系。