Wnt signaling in axon guidance

Recent studies have identified Wnt proteins as conserved axon guidance molecules in vertebrates and invertebrates. Wnt proteins are a large family of diffusible factors that play several important roles, both in embryonic development and in adult function. The signaling mechanisms of Wnt proteins are complex and, because Wnts are newly discovered as axon guidance cues, little is known about how Wnt signaling controls the direction of growth cone navigation - a process that is crucial in development of the nervous system. This review summarizes recent work on the role of Wnts in axon guidance and discusses the possible signaling mechanisms involved in growth cone guidance. Understanding how Wnts regulate axon wiring will not only help us to understand how the nervous system is connected but also provide possible tools for axon regeneration.     

细胞色素P450 2E1基因PstⅠ多态、腌制品与大肠癌关系的病例对照研究

目的：研究代谢酶细胞色素P450 2E1基因(CYP2E1)Pst Ⅰ多态性和腌制品与大肠癌易感性的关系。方法：采用人群基础的病例对照分子流行病学研究和PCR—RFLP技术,对126例大肠癌和343名健康对照Pst Ⅰ识别的CYP2E1基因型进行检测。结果：健康对照组CYP2E1基因野生型(C1／C1)为61．8％,杂合子(C1／C2)为35．8％,突变纯合子(C2／C2)为2．4％。调整年龄性别后,结肠癌病例中突变基因型频率54．9％(52．9％ C1／C2和2．0％ C2／C2)高于对照(OR 1．979,95％ CI 1．090—3．595),但直肠癌病例与对照比较,无统计学意义。分层分析发现,突变基因型、每周1或2次和隔天或每天吃腌制品单因素作用的大肠癌OR值分别1．935、2．122和2．315,而每周1或2次 突变型、隔天或每天吃 突变型联合作用后大肠癌OR值分别为2．272和3．127。分别分析结、直肠癌,腌制品对直肠癌的危险性在食用频率为每周1或2次时,差异有统计学意义,野生型和突变型的OR值分别为2．646和2．297,两者差异无统计学意义;而结肠癌危险性只有在Pst Ⅰ突变者隔天或每天吃腌制品时才剧增,OR值4．262(1．395～13．017),为野生型的2．69倍,差异有统计学意义。结论：CYP2E1 PstⅠG→C点突变是大肠癌的遗传易感性因素,与腌制品有协同作用,该作用在结肠癌尤为明显。     

High epitope density in a single recombinant protein molecule of the extracellular domain of influenza A virus M2 protein significantly enhances protective immunity

The degree of epitope density has been shown to be a critical factor influencing the magnitude of epitope-specific responses. However, whether high epitope density in just a single protein molecule can still enhance the humoral response or, more importantly, the protective immunity, has not been determined. To test this, five glutathione-S-transferase fusion proteins bearing various numbers of copies of the M2e epitope on M2 protein of influenza virus (1, 2, 4, 8 and 16 copies) were prepared, and used to immunize mice and rabbits. Our data show clearly that M2e-specific humoral response was enhanced with increasing epitope density. By lethal challenge assay in mice, it was observed that recombinant proteins with higher M2e epitope densities resulted in higher survival rates and slower weight losses. The survival rate was directly related to the degree of epitope density in the single recombinant protein: 100% in the case of 16 M2e copies; 50% with 4 M2e epitopes; and 0% with one.     

轻链沉积病的病理诊断及研究进展

轻链沉积病(1ight chain deposition disease,LCDD)是由单克隆免疫球蛋白轻链的异常产生并沉积于全身组织而导致的一种系统性疾病,常继发于淋巴细胞增生性病变,包括多发性骨髓瘤(multiple myeloma,MM)、淋巴瘤等。同原发性淀粉样变性病(amyloidosis,AL—type)相似,肾脏为其最常见的受累器官,常导致进行性肾功能衰竭。国外自20世纪80年代以来,陆续报道了大量的病例,对其临床病理特点的认识不断提高,并对其发病机制进行了研究。国内仅有少数肾脏LCDD的报道。为加强对该病的认识,兹将其临床病理特点及研究进展综述如下。     

A novel tumorigenic human prostate epithelial cell line (M2205): molecular cytogenetic characterization demonstrates C-MYC amplification and jumping translocations

The paucity of cell lines from early-stage prostate cancer tumors has hindered the recognition of genetic and cellular changes that are associated with the acquisition of tumorigenesis. We describe the chromosomal complement of a novel tumorigenic prostate epithelial cell subline, called M2205, that acquired only three new, consistent chromosomal changes (from those present in the SV40T antigen immortalized parental cell line, P69SV40TAg) when it attained tumor-forming potential. The consistent changes, which were fully characterized using GTG-banding, CBG-banding, silver staining, fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), and spectral karyotyping (SKY), involved segmental jumping translocations and resulted in gains in the copy number of genes located on the distal long arm of chromosome 8 (8q22 to 8q24.3), including c-myc. Furthermore, the jumping translocations also resulted in ribosomal genes being present in multiple, tandem copies next to the chromatin from 8q. Given the relatively small number of cytogenetic changes present, this subline provides a means for better understanding the cellular changes associated with the acquired chromosomal imbalances. Further studies of this subline could also provide insight as to the mechanism or mechanisms leading to the formation of jumping translocations, as well as potential position effects resulting from the relocation of ribosomal genes next to other cellular genes or oncogenes.     

风湿性瓣膜病二尖瓣与主动脉瓣置换术1154例长期效果分析

目的　评价风湿性联合瓣膜病二尖瓣与主动脉瓣双瓣置换术的近期与远期疗效 ,分析影响手术疗效的因素。　方法　回顾性分析 1981年 5月～ 2 0 0 1年 5月 2 0年间 ,115 4例风湿性心脏病患者行双瓣膜置换术的临床资料和长期随访结果 ,其中二尖瓣与主动脉瓣均为狭窄病变者 2 5 3例 ,二尖瓣狭窄合并主动脉瓣关闭不全者 345例 ,二尖瓣关闭不全合并主动脉瓣狭窄者 119例 ,二尖瓣与主动脉瓣均为关闭不全者 437例 ;合并三尖瓣病变的占 5 4 0 0 %( 75 7例 ) ,其中器质性病变 7 2 7%( 84例 ) ,功能性关闭不全 5 8 31%( 6 73例 ) ;合并中度以上肺动脉高压者 339例 ;术前NYHA心功能分级Ⅲ级与Ⅳ级者分别为 873例和 186例。应用侧倾碟瓣或双叶机械瓣施行瓣膜置换术 ,合并三尖瓣功能或器质性病变者 ,同期行瓣膜成形手术。　结果　本组患者术后住院病死率为 6 5 0 %( 75 / 115 4)。早期死亡的主要原因为低心排出量综合征、顽固性心律失常、肾功能或呼吸功能衰竭 ,以及抗凝有关的出血等。长期生存 10 79例 ,随访时间为 8个月～ 2 0年 ,平均随访时间为 4 5 %病人·年。晚期死亡 6 6例 ( 0 39%病人·年 ) ;5、10与 15年累计生存率分别为 ( 89 46± 1 35 ) %、( 86 5 0± 1 91) %与 ( 6 7 86±6 16 ) %。生存的 92 9例患