细胞衰老与p16INK4a的转录调控

抑癌基因p16~(INK4a)可特异地抑制CDK4及CDK6,在抑制细胞生长、促进细胞衰老等方面发挥重要的生物学作用。由于p16~(INK4a)功能的重要性,近年来,针对p16~(INK4a)转录调控方面的研究取得了一系列进展,发现了一系列正性和负性调控元件和转录调控因子,如:E47、Id1、Jun B、Bmi-1、RREB等,为进一步认识细胞增殖规律以及衰老进程具有重要的理论意义。     

Producción científica en educación médica en Latinoamérica en Scopus, 2011-2015

Objective

To describe the scientific production in medical education in Latin America in Scopus, in the period 2011-2015.

氧化修饰引起脂蛋白（a）结构和生化特性变化

本文观察了体外丙二醛（ＭＤＡ），铜离子（Ｃｕ２＋氧化修饰的脂蛋白（ａ）［Ｌｐ（ａ）］结构和生物学性质的变化。氧化修饰Ｌｐ（ａ）过氧化程度增高，负电荷增加，易被巨噬细胞—清道夫受体识别和摄取。ＭＤＡ修饰Ｌｐ（ａ）出现新的ＭＤＡ－ＬＤＬ位点；同纤维蛋白溶酶原（Ｐｇ）竞争抑制试验显示氧化、修饰Ｌｐ（ａ）同Ｐｇ同源性增加。提示载脂蛋白（ａ）状态同动脉粥样硬化的病理过程有关。     

Malignant fibrous histiocytoma arising in a recurrent chordoma

Summary We present the case of a sacrococcygeal chordoma which recurred 15 years after the radical removal as a soft tissue tumor in the gluteal musculature. This tumor consisted of two parts: a chordoma without symptoms of aggressive cellular proliferation and a malignant fibrous histiocytoma. During the following 4 years several local recurrences of the malignant fibrous histiocytoma occurred in the gluteal musculature. The patient finally died of lung metastases. No chordoma tumor tissue was found in the lungs, in the gluteal musculature or in the sacrococcygeal bone area. Histology including electron microscopy revealed no proof of a transition of chordoma into malignant fibrous histiocytoma. It must be assumed that the secondary soft tissue tumor originated from residual chordoma cells which were implanted during the operation of the primary tumor. It remains unclear whether the malignant fibrous histiocytoma arose from mesenchymal stromal cells within the chordoma or directly from primitive neuroectodermal chorda cells which possess the ability to differentiate into a variety of cell types including mesenchymal cells.     

Age and sex based genetic locus heterogeneity in type 1 diabetes

BACKGROUND: Two genome scans for susceptibility loci for type 1 diabetes using large collections of families have recently been reported. Apart from strong linkage in both studies of the HLA region on chromosome 6p, clear consistent evidence for linkage was not observed at any other loci. One possible explanation for this is a high degree of locus heterogeneity in type 1 diabetes, and we hypothesised that the sex of affected offspring, age of diagnosis, and parental origin of shared alleles may be the bases of heterogeneity at some loci. METHODS: Using data from a genome wide linkage study of 356 affected sib pairs with type 1 diabetes, we performed linkage analyses using parental origin of shared alleles in subgroups based on (1) sex of affected sibs and (2) age of diagnosis. RESULTS: Among the results obtained, we observed that evidence for linkage to IDDM4 on chromosome 11q13 occurred predominantly from opposite sex, rather than same sex sib pairs. At a locus on chromosome 4q, evidence for linkage was observed in sibs where one was diagnosed above the age of 10 years and the other diagnosed below 10 years of age. CONCLUSIONS: We show that heterogeneity tests based on age of diagnosis, sex of affected subject, and parental origin of shared alleles may be helpful in reducing locus heterogeneity in type 1 diabetes. If repeated in other samples, these findings may assist in the mapping of susceptibility loci for type 1 diabetes. Similar analyses can be recommended in other complex diseases.     

Leydig cell types in primary testicular disorders

Ultrastructural study of testicular biopsy specimens from 67 adults with primary testicular disorders (Klinefelter's syndrome, XX male syndrome, Del Castillo's syndrome, and cryptorchidism) revealed the following four Leydig cell types: 1) normal or nearly normal Leydig cells with abundant smooth endoplasmic reticulum, mitochondria with tubular cristae, lipid droplets, and Reinke's crystals; 2) abnormally differentiated Leydig cells without either lipid droplets or Reinke's crystals but with altered mitochondria, concentric unfenestrated cisternae of smooth endoplasmic reticulum, and both paracrystalline and filamentous inclusions; 3) multivacuolated Leydig cells containing abundant lipid droplets; and 4) immature Leydig cells with scarce development of the smooth endoplasmic reticulum and mitochondria, and numerous cytoplasmic microfilaments. Abnormally differentiated Leydig cells might represent dysgenetic cells, whereas immature, normal, and vacuolated Leydig cells might represent three progressive stages in the Leydig cell cycle (undifferentiated, mature, and old involuting Leydig cells). An inverse correlation between the proportion of abnormal Leydig cells and testosterone levels was observed in each of these testicular disorders.     

Postnatal development of somatostatin-containing neurons in the visual cortex of normal and dark-reared rats

Summary The distribution of somatostatin (SRIF)-immunoreactive neurons in the visual cortical areas 17, 18 and 18a of Wistar rats from birth to adulthood was followed in both normal and dark-reared animals. The SRIF neurons show difference in distribution amongst the three cortical areas studied as early as the first postnatal week. Area 17 was distinguished by fewer SRIF cells in the upper layers (I–III), which results in a lower overall density. The SRIF neurons in all areas appeared to increase in numbers up to about 3 weeks and then decline dramatically to adult levels, which were 14–19% of the peak levels. Although this decline was still obvious, it moderated to 25–31% in dark-reared animals. The greatest effect was seen in area 18 where, at 60 days of age, there were twice as many SRIF cells in darkreared as in normal controls. It is suggested that, under conditions of dark rearing, the overall pattern of development of SRIF neurons, being uninfluenced by extrinsic factors, reveals the cells' genetic potential.     

鼠巨细胞病毒抑制神经干细胞分化及分化基因表达的体外研究

目的 研究鼠巨细胞病毒(MCMV)感染对体外培养神经干细胞(NSCs)分化及分化基因表达的影响,探讨CMV先天感染致神经损伤的机制.方法 体外分离培养和鉴定BALB/c胎鼠NSCs并检测其分化潜能,用感染复数(MOI)为5、1和0.1的MCMV Smith毒株感染NSCs并进行分化培养,倒置显微镜下观察细胞形态学改变,流式细胞术检测分化细胞比率,免疫荧光法观察NSCs及其分化细胞标记物Nestin、胶质纤维酸性蛋白(GFAP)和神经元特异性烯醇化酶(NSE)表达的变化,采用MCMV早期抗原(EA)示踪感染过程(MOI=1),real-time RT-PCR检测分化早期NSCs Wnt信号途径关键分化基因Wnt-3和Wnt-Ta mRNA水平的动态变化.结果 体外培养的NSCs呈球样生长,神经干细胞特异性标记Nestin表达阳性,并可进一步诱导分化为NF-200阳性的神经元和GFAP阳性的星形胶质细胞;分化培养后,感染组NSCs不能贴壁分化生长并逐渐出现肿胀,细胞Nestin表达下调缓慢并显著高于正常对照组,而GFAP和NSE表达显著低于正常对照组(P<0.05),可检测到MCMV EA的阳性表达;分化培养3-9 d,感染组Nestin阳性细胞比率显著高于正常对照组,GFAP和NSE阳性细胞比率显著低于正常对照组(P<0.05);感染组Wnt-3 mRNA水平在分化培养后第1～2天显著低于正常对照组(P<0.05),感染组Wnto-7a mRNA水平在第0.5～2天明显低于正常对照组(P<0.05);感染组和正常对照组的差异随病毒MOI的增加而更加明显.结论 MCMV感染可明显抑制NSCs向神经元和星形胶质细胞方向分化,导致分化细胞比率减少;下调或干扰NSCs wnt信号途径分化基因wnt-3和Wnt-7a的表达;抑制NSCs分化及其分化基因表达的效应与MOI大小存在一定量效依赖关系;MCMV可能通过抑制NSCs分化基因的表达来抑制其分化,这可能是CMV先天感染致脑发育异常的重要机制之一.     

B族链球菌C5a肽酶蛋白表位的克隆、表达和免疫学分析

目的应用生物信息学方法预测B族链球菌C5a肽酶蛋白表位，结合基因工程手段进行表位重组、表达和免疫原性分析。方法用预测程序ProPred和ANTIGENIC预测B族链球菌C5a肽酶蛋白的表位，应用PCR技术扩增出编码该表位基因片段，克隆PCR产物构建重组质粒，测序验证。在大肠杆菌BL21（DE3）中诱导表达融合蛋白。表达的蛋白经质谱分析和Western blot鉴定。纯化该融合蛋白并免疫C57／BL小鼠，萃取GBS表面蛋白，双向琼脂扩散试验检测抗体水平。结果在SCPB中预测到1个既具有MHC结合肽特性又具有B细胞表位特征的肽段。重组和表达了这一肽段，质谱得出与SCPB蛋白的相似性分数为79，Western-blot证实能与抗SCPB的抗体反应，纯化后融合蛋白纯度〉90％。动物实验证实融合蛋白能产生特异性的抗GBS抗体。结论重组表位具有一定免疫原性。为相关蛋白的毒力机制研究和亚单位疫苗等方面的研究打下了良好的基础。     

During active viscerocutaneous leishmaniasis the anti-P2 humoral response is specifically triggered by the parasite P proteins.

In this work we show that in the sera from dogs naturally infected with the protozoan parasite Leishmania infantum there are antibodies that react specifically against the parasite acidic ribosomal proteins LiP2a and LiP2b, and that each one of the Leishmania P proteins elicits a specific humoral immune response. Using synthetic peptides, the antigenic epitope of these proteins has been mapped in a single region located adjacent to the C-terminal domain highly conserved among the eukaryotic P proteins. The anti-P antibodies elicited during the Leishmania infection do not recognize the conserved C-terminal domain of the parasite P proteins, in contrast with the findings reported in Chagas' disease or systemic lupus erythematosus. The antigenic epitopes of the LiP2a and LiP2b are almost identical in amino acid sequence. No reactivity against Trypanosoma cruzi and human P proteins was found in sera from L. infantum-infected dogs.