Genomic analysis of the nuclear receptor family: new insights into structure, regulation, and evolution from the rat genome

Completion of the Rattus norvegicus genome sequence enabled a global inventory and analysis of the nuclear receptors (NRs) in three mammalian species. Forty-nine NR members were found in mouse, 48 in human. Forty-seven were found in the rat, with gaps at the locations expected for the other two. Pairwise comparisons of their distribution in rat, mouse, and human identified 11 syntenic NR gene blocks, including three small clusters of two or three closely related genes, each spanning 40 kb to 1700 kb. The exon structure of the ligand-binding domain suggests that exon shuffling has played a role in the evolution of this family. An invariant splice junction in all members of the NR family except LXRbeta suggests a functional role for the intron. The ligand-binding domains of PXR and CAR are among the most divergent in the family. Their higher nucleotide substitution rates may be related to the central role played by these two NRs in the metabolism of the foreign compounds and may have resulted from limited positive selection.     

采用高脂饲料加空气干燥术建立颈动脉粥样硬化动物模型

目的:利用高脂饮食加空气干燥术建立一种稳定、重复性好、有较典型动脉粥样硬化病理改变的动物模型。方法:32只日本大耳白兔随机分为模型组(n=24)、对照组(n=8)。模型组给予高脂饲料喂养加空气干燥术,术中结扎左侧颈动脉分支血管,对照组正常饲料喂养,分别于术后第2、4、8、12周处死动物。取颈动脉组织切片HE染色,光镜下观察。结果:(1)75%兔颈总动脉存在细小血管分支,暂时结扎侧支血管后干燥效果更好。(2)对双侧颈动脉实施手术,结扎左侧分支,成模率更高。部分斑块显示出不稳定性。结论:采用改进后高脂饮食加空气干燥术可成功建立兔颈动脉粥样硬化模型,其病理特点适合于目前临床研究。     

促甲状腺素释放激素对荷瘤鼠NK和IL－2活性的影响

本文采用中性红和噻唑蓝比色法，观察了促甲状腺素释放激素（ＴＲＨ）对荷瘤小鼠脾细胞ＮＫ活性和ＩＬ－２产生能力的影响，并研究其抑瘤效应及机理。结果表明：ＴＲＨ能够明显抑制小鼠Ｓ１８０腹水瘤移植物的生长，抑瘤率为５４．６％；并能明显提高荷瘤鼠ＮＫ活性和ＩＬ－２产生能力。这一结果提示ＴＲＨ是一种重要的抗肿瘤免疫调节因子。     

先天性三尖瓣畸形及其功能影响

在１５６例先天性心血管畸形标本的观察和测量中，检出先天性三尖瓣畸形２５例（１６．０２％），其中Ｅｂｓｔｅｉｎ＇ｓ畸形６例，三尖瓣发育不良１４例，三尖瓣缺如１例，三尖瓣瓣叶或／和腱索骑跨４例。用测量及比较解剖学的方法探求三尖瓣畸形与其功能的影响。结果显示：Ｅｂｓｔｅｉｎ＇ｓ畸形和三尖瓣发育不良的心脏构筑都有明显的变化，而且两者存在一定的差异，同时明确了Ｅｂｓｔｅｉｎ＇ｓ畸形的病理诊断标准和三尖瓣发育不良的分类。     

冰冻切片免疫过氧化物酶染色法在抗细胞性单克隆抗体筛选和鉴定中的应用

本文介绍一种快速准确地筛选和鉴定抗细胞性单克隆抗体(单抗)的冰冻切片免疫过氧化物酶染色技术。它既能筛选融合后的大量单抗(一般在3小时以内能筛选200～400孔杂交瘤细胞上清液);又可根据组织固有结构及细胞分区分布的特性,作为全面鉴定单抗的重要方法。我们运用此法从12次融合中,筛选并经克隆化获得291个单抗,进一步全面鉴定后得到抗T细胞等101个单抗。此外还讨论了消除非特异性染色的体会。     

A homozygous MITF mutation leads to familial Waardenburg syndrome type 4

Waardenburg syndrome (WS) is a genetic disorder characterized by hearing loss and pigmentary abnormalities with variable penetrance. Though heterozygous mutations in MITF are a major cause for Waardenburg syndrome type 2 (WS2), homozygous mutations in this gene and the associated phenotype have been rarely characterized. In this study, we identified a novel p.R223H mutation in MITF in a Chinese Han family with variable WS features. Both parents carried a heterozygous p.R223H mutation. They had normal hearing, and premature greying of the hair is their only pigmentary abnormality. In contrast, their two children both carried a homozygous p.R223H mutation and had classic WS features including profound hearing loss, heterochromia irides and marked pigmentary abnormalities in hair and skin. Interestingly, the two affected children also have persistent chronic constipation since the neonatal period, symptoms suggestive of Waardenburg syndrome type 4 (WS4). Our study revealed a likely association between homozygous mutations in MITF and WS4, which implies a dosage effect for the underlying pathogenesis mechanism.     

Cytotoxicity against human peripheral blood mononuclear cells and T cell lines mediated by anti-T cell immunotoxins in the absence of added potentiator.

Several in vitro assays have indicated that anti-T cell immunotoxins (IT), composed of monoclonal antibodies (MoAbs) conjugated to ricin A chain (RTA), are maximally effective against T cells only in the presence of potentiators. It was thought that such IT might not be sufficiently cytotoxic to deplete T cells in vivo upon administration to patients. Therefore, we have re-evaluated the in vitro assays and report herein that even with a short exposure time (2 h), the two anti-T cell IT, H65-RTA (anti-CD5 MoAb coupled to RTA) and 4MRTA (anti-CD7 MoAb coupled to RTA30), were specifically cytotoxic for peripheral blood mononuclear cells (PBMC) in the absence of potentiators. Moreover, as has been reported for IT when tested against T cell lines, prolonging the exposure time of the IT with PBMC from 2 h to as long as 90 h, without added potentiators, enhanced their cytotoxicity from 2- to 40-fold. In contrast, most T cell lines were more sensitive to IT in the presence of potentiator, and IT cytotoxicity was much less enhanced by prolonging the exposure time. Thus, T cell lines may not serve as accurate models to determine the efficacy of IT against PBMC in vitro or in vivo. We conclude that IT-induced cytotoxicity of PBMC can be demonstrated in vitro at pharmacologically achievable concentrations in the absence of added potentiators.     

Insertion/deletion mutations of type I oculocutaneous albinism in chinese patients from Taiwan

Type I oculocutaneous albinism (OCA1) is an autosomal recessive disorder, which is caused by the reduction or the absence of tyrosinase activity in melanocytes of the skin, hair and eyes. Although tyrosinase mutations of OCA1 have been extensively analyzed in most populations worldwide, there is no systemic study of OCA1 mutation in Chinese patients. By use of single strand conformation polymorphism and direct sequencing, we had detected 21 mutant alleles out of 24 OCA1 chromosomes screened (87.5%). Detected mutant alleles include one splicing site, three insertion/deletion and five missense mutations, of which the splicing site nucleotide alteration (IVS 1-3C>G) and two each of the insertion/deletion (232-233 ins GGG and 861-862 del TT) and missense mutations (Cys 289 Gly and Trp 400 Leu) are novel. The ins/del mutations accounts for about 37.5% in Chinese OCA1 alleles. The 232-233 ins GGG, one of the novel mutations, was found to be most frequent (25%) among the OCA1 alleles in Chinese. Through this study, we found that while some of the OCA mutant alleles were identified in other populations, ethnic difference still exists. Hum Mutat 14:542, 1999.     

人心连续组织切片的计算机三维重建

用表面重建法对人心连续组织切片进行了三维重建，重建中应用了火棉胶断面切片技术及图像拟合与插值处理，与以往的解剖断面重建比较，图像更加清晰、逼真，可从不同观察心脏的外部轮廓与内部结构。作为三维重建的基础性研究，可为心血管影像诊断提供解剖形态学依据和可靠的三维软件。     

Safety and efficacy of oral nemonoxacin versus levofloxacin in treatment of community-acquired pneumonia: A phase 3, multicenter,randomized, double-blind,double-dummy,active-controlled,non-inferiority trial

Background/Purpose

Nemonoxacin is a novel nonfluorinated quinolone with excellent in vitro activity against most pathogens in community-acquired pneumonia (CAP), especially Gram-positive isolates. The purpose of this study was to assess the efficacy and safety of nemonoxacin compared with levofloxacin in patients with CAP.