CD2 and other surface molecules in the regulation of non-MHC-restricted cytolytic function.

The effect of anti-CD2 and Fc receptor binding molecules on the cytolytic function of a highly enriched population of CD3- large granular lymphocytes (LGL) was studied. These cells could mediate natural killer (NK) activity, antibody-dependent cellular cytotoxicity (ADCC) and lectin-dependent cellular cytotoxicity (LDCC). Both ADCC and LDCC were enhanced by anti-CD2. The enhanced LDCC could also be observed with IL-2-activated LGL. However, NK cell activity was usually slightly diminished or unaffected by anti-CD2 binding. Immune complex and aggregated human IgG had no effect on ADCC but an anti-CD16 showed a dose-dependent inhibition of ADCC, reversible by anti-HLA-ABC and anti-CD2. Cross-linking of LGL surface-bound anti-CD2 caused an almost complete inhibition of LDCC and ADCC but had much less effect on NK activity. These experiments show that ADCC and LDCC mediated by CD3- LGL can be influenced by perturbing the CD2 molecule. NK activity was, however, affected differently, suggesting some basic differences in the pathway of ADCC and NK function.     

Sequence analysis of cDNAs for the human and bovine ATP synthase β subunit: mitochondrial DNA genes sustain seventeen times more mutations

We have cloned and sequenced human and bovine cDNAs for the subunit of the ATP synthase (ATP-synß), a nuclear DNA (nDNA) encoded oxidative phosphorylation (OXPHOS) gene. The two cDNAs were found to share 99% amino acid homology and 94% nucleotide homology. The evolutionary rate of ATPsynß was then compared with that of two mitochondrial DNA (mtDNA) ATP synthase genes (ATPase 6 and 8), seven other mtDNA OXPHOS genes, and a number of nuclear genes. The synonymous substitution rate for ATPsynß proved to be 1.9 × 10^–9 substitutions per site per year (substitutions × site^–1 × year^–1) (SSY). This is less than 1/2 that of the average nDNA gene, 1/12 the rate of ATPase 6 and 8, and 1/17 the rate of the average mtDNA gene. The synonymous and replacement substitution rates were used to calculate a new parameter, the selective constraint ratio. This revealed that even the most variable mtDNA protein was more constrained than the average nDNA protein. Thus, the high substitution mutation rate and strong selective constraints of mammalian mtDNA proteins suggest that mtDNA mutations may result in a disproportionately large number of human hereditary diseases of OXPHOS.     

ST2作为Th2细胞亚群标志以及其与支气管哮喘的关系的研究

各自主要分泌IFN γ和IL 4的Th1和Th2亚群 ,与临床疾病的关系十分密切。如何从表面标志上加以区分是一项迫切需要解决的问题。ST2是近年来提出的Th2细胞的稳定标志物。本工作在体外成功地诱导人脐带血T细胞向Th1或Th2分化的基础上 ,应用逆转录PCR分析了ST2mRNA的表达特点。证实ST2在人Th2细胞上的选择性表达。为了探索ST2、Th2与支气管哮喘的关系 ,本工作进一步检测了正常人和支气管哮喘患者外周血单个核细胞中 β actin、ST2以及IFN γ和IL 4的mRNA水平。结果显示 :支气管哮喘患者ST2mRNA水平升高 ,IL 4水平也明显升高 ,但IFN γ无变化。这提示ST2作为Th2细胞的标志物 ,有可能成为Th2极化性疾病如哮喘发病机制研究的一个参考性标志 ,至于ST2是否有可能作为治疗的靶分子 ,有待进一步探讨     

69,XXY伴严重生长迟缓及眼球突出病例的产前诊断

目的分析孕中期血清筛查数据和胎儿彩色多普勒与染色体异常之间的关系。方法对一孕中期血清产前筛查18三体风险1:10,血清Free-hCGβ异常减低(值为1.29ng/ml即0.08MOM),胎儿系统结构检查提示胎儿小于孕周,头腹围比(1.63)大于正常(1.25),上唇连续性中断延至鼻底的孕妇进行羊膜腔穿刺,抽取羊水进行细胞遗传学检查。结果羊水细胞染色体核型:69,XXY。结论中孕期妇女血清Free-hCGβ异常减低和胎儿头胸围发育不同步、胎儿唇腭裂提示胎儿染色体畸变可能,血清和超声联合筛查有助于染色体疾病的检出。     

亮氨酸脑啡肽样和P物质样免疫反应物在大鼠延髓迷走神经背核簇和网状结构内的分布

用PAP法研究亮氨酸脑啡肽样(L—ENK—LI)和P物质样(SP—LI)免疫反应物在大鼠延髓迷走神经背核簇和网状结构内的分布。证明在孤束核、迷走神经背核、外侧网状核外侧部及其外侧的区域内有大量的L-ENK样终末和纤维,在背侧和腹侧网状核之间的移行区内有中等量的分布,其余区内为少量。L-ENK样胞体在孤束核、咀侧腹外侧网状核、巨细胞网状核的腹侧部和α部、外侧旁巨细胞核以及中缝大核内均有许多分布,在迷走神经背核的尾侧部、背侧和腹侧网状核之间的移行区有中等量,其余区内为少量。SP样反应物的分布与L-ENK样物类似,但其终末和纤维的数量较L-ENK者略少,阳性胞体的数量除了在中缝核及外侧旁巨细胞核内侧端中的量较L-ENK样胞体多以外,在其余区内均较少。     

脑缺血大鼠海马超微结构的形态定量研究

对大鼠双侧颈总动脉夹闭2小时,经透射电镜观察海马,用Weibel氏形态定量法分别测量了海马1区和3区的线粒体和突触的表面积密度(Svi)、表面积—体积比(Si/Vi),并与对照组进行了比较。结果表明:缺血时海马1区受损较严重,表现为线粒体体积缩小,数量减少,Svi下降;突触数量有增多的趋势,但突触的Svi与Si/Vi变化不明显。缺血组海马3区受损较轻,线粒体和突触的结构基本正常,其Svi、Si/Vi与对照组差别不显著,提示了3区对缺血有较强的耐受性。     

老年大鼠的海马神经元对微量注射Ach的敏感性

本工作观察了老年大鼠海马神经元对微量注射Ach(10μg/0.5μl)的敏感性。 实验在6只老年大鼠(大于30月龄)和5只年青大鼠(4～5月龄)上进行。结果表明:年青大鼠和老年大鼠的海马神经元对Ach的主要反应模式有所不同,前者多出现神经元放电明显增加的兴奋反应。后者多出现抑制反应,神经元的放电明显减少。此外,老年大鼠的海马神经元对Ach反应的持续时间(包括兴奋和抑制反应)也明显长于年青大鼠。本文对海马神经元敏感性和适应能力的改变可能是影响老年记忆的重要因素进行了讨论。     

淋巴细胞经TCR－CD3活化增殖作用的分析

本文探讨了抗ＣＤ３单抗诱导的淋巴细胞活化增殖及有关影响因素。实验结果表明：①淋巴细胞内钙升高是淋巴细胞活化增殖的重要条件，ＣＤ３ＭｃＡｂ引起的早期胞浆游离钙迅速升高主要由内质网释放钙离子所致，而淋巴细胞增殖不仅需要细胞内钙释放，还需要细胞外钙内流；②ＧＴＰ结合蛋白是淋巴细胞激活过程的一重要环节，经Ｇ蛋白作用物霍乱毒素作用后，淋巴细胞ＤＮＡ合成显著降低；③新霉素和ＰＳＳ可抑制ＰＬＣ和ＰｋＣ的活性，对淋巴细胞ＮＤＡ合成造成剂量依赖性抑制作用。此外，抗ＣＤ３ＭｃＡｂ诱导的淋巴细胞ＤＮＡ合成需要辅佐细胞的存在，高度纯化的Ｔ细胞对ＣＤ３ＭｃＡｂ的刺激不发生增殖反应。     

Two dinucleotide repeat polymorphisms at the D8S1442 and D8S1443 loci

Two polymorphic dinucleotide (CA) repeat clones were isolated from cosmids, cCI8-1121 and cCI8-1199, mapped to chromosome 8p11.2-p12.