人T淋巴母细胞（Jurkat）移动性的研究

利用人Ｔ淋巴母细胞（Ｊｕｒｋａｔ）细胞系作为研究对象。企图探探索细胞外基质成份及肌醇磷脂细胞信息传递系统与细胞移动的关系。研究结果表明：当细胞被伏波醇酯（ＰＭＡ）处理过后，其粘连性与移动件对纤维连结蛋白（ＦＮ）底物的反应在已是高水平的基础上有更进一步提高的作用。与ＦＮ刊相反的是，未经ＰＭＡ处理处的Ｊｕｒｋａｔ细胞对层粘连蛋白（Ｌｍ）底物却无明显的粘连性及移动性增加的反应，尽管在ＰＭＡ处理过４小时内亦无任何的增强。但是，当ＰＭＡ作用于细胞２４一４８小时后则明显池增加其Ｌｍ底物的粘连性及移动性反应，表明了其明显的协同作用。分别用抗ＦＮ、抗Ｌｍ及蛋白激酶Ｃ抑制剂Ｓｔａｕｒｏｓｐｒｉｎｅ（ＳＰ）时均起到特异性的抑制作用。可见，协同作用的产生是通过蛋白激酶Ｃ激活后的－段时间内，使细胞表面Ｌｍ受体密度增加而对底物Ｌｍ反应增强所致。     

肾康宁对肾小球肾炎治疗作用的实验及临床研究

目的:观察中药肾康宁对家兔实验性肾炎黏附分子及细胞因子表达的影响,以及临床肾小球肾炎治疗前后尿蛋白的变化.方法:检测牛血清白蛋白所致急性实验性肾炎动物肾组织ICAM-1表达、血清IL-6水平的变化,以及临床肾小球肾炎肾康宁治疗前后血清IL-6水平、尿蛋白的变化.结果:肾康宁能明显降低实验动物血清IL-6含量,降低急性实验性肾炎模型中ICAM-1阳性细胞表达率,同时减轻肾小球基底膜(GBM)增厚及炎症细胞浸润,阻止毛细血管内微血栓的形成;在临床肾小球肾炎中,肾康宁能减少肾小球肾炎患者血清IL-6水平及24 h尿蛋白含量.结论:肾康宁通过降低细胞因子IL-6水平和黏附分子ICAM-1的表达,从而抑制免疫细胞的趋化、浸润、活化和增殖、减少免疫复合物的沉积,使肾小球炎症反应减轻,有效缓解家兔急性实验性和临床肾小球肾炎,使肾功能得以改善.     

胶质瘤中LGI 1的突变及微卫星不稳定性研究

目的 为了检测人脑胶质瘤组织及胶质瘤细胞系LGI 1基因编码区中有无碱基突变及微卫星不稳定性(MSI)和杂合性缺失(LOH).方法 收集30例胶质瘤标本,2例脑膜瘤、2例瘤旁及2例颅脑损伤内减压脑组织标本及体外培养5个脑胶质瘤细胞系.提取组织标本及培养细胞基因组DNA.设计特异性引物分别扩增LGI 1各外显子序列,采用SSCP银染分析;扩增LGI 1微卫星序列,凝胶电泳银染分析;发现异常泳动条带进行DNA序列分析.结果 ①PCR-SSCP分析琼脂糖凝胶电泳检测有1例Ⅱ级胶质瘤标本未检测到第1 a外显子处扩增产物以及Ⅱ、Ⅲ级各1例胶质瘤标本均未检测到第8 c外显子处扩增产物.未在30例胶质瘤标本和4个脑胶质瘤细胞系中检测到电泳条带异常,在细胞系TJ905第5外显子处检测到电泳条带异常,经DNA测序分析证实确有突变.②在30例胶质瘤标本及5个细胞系中均未检测到MSI和LOH.结论 基因突变及MSI和LOH可能不是LGI 1在胶质瘤恶性进展过程中失活的主要原因.     

Apaf-1与MODS时的细胞凋亡

细胞凋亡是一种以凋亡小体的形成为特点的,不引起周围组织的炎性反应的活体内单个细胞死亡的形态学改变,它是依赖能量的细胞内死亡程序活化而致的细胞自杀.已知细胞凋亡的途径有3条途径:死亡受体途径、线粒体途径、内质网途径.线粒体在凋亡信号传导通路中起重要作用,研究提示死亡受体和内质网通路的信号最终都汇集在线粒体通路中.线粒体介导的细胞内凋亡通路的信号传导级联反应均以Apaf-1为靶子而调节凋亡体.     

中国汉族人VKORC1 G3673A基因多态性研究

目的检测汉族人VKORC1 G3673A基因的分布情况。方法应用PCR技术对正常人外周血VKO-RC1 G3673A基因进行扩增,以Msp I进行限制性酶切图谱分析。结果219名（男112人,女107人）中国汉族人VKORC1 G3673A基因中,表现型A/A的频率是81.3%（男90人,女88人）,表现型G/A是18.7%（男22人,女19人）,表现型G/G是0。VKORC1 G3673A基因A的频率是90.6%,基因G的频率是9.4%。结论中国汉族人VKORC1 G3673A基因的分布有自己的特点,为研究VKORC1 G3673A基因在华法林个体化给药方案的制定提供了可靠的理论资料。     

Lithium and 5-HT1A receptor sensitivity: a neuroendocrine study in healthy volunteers

The effect of lithium administration (800 mg daily for 7 days) on the neuroendocrine and temperature responses to the 5-HT_1A receptor agonist, gepirone, was studied in eight healthy male volunteers. Gepirone (20 mg orally) significantly increased plasma levels of prolactin, growth hormone, corticotropin and cortisol, and lowered oral temperature. None of these responses was significantly altered by lithium treatment. The results suggest that the ability of short-term lithium treatment to increase 5-HT-mediated neuroendocrine responses in humans is unlikely to be related to changes in the sensitivity of pre- or post-synaptic 5-HT_1A receptors.     

小儿糜烂性口腔炎病毒病因及干扰素对病毒的抑制作用

本文研究了小儿糜烂性口腔炎的病毒病因,用人胚肾细胞及Hep—2细胞分离病毒,26例患儿有21例阳性(80.7％),从中取五株病毒进行鉴定,细胞病变特点属疱疹病毒,且均可被抗HSV—I抗体中和,结果表明HSV—I是本病的主要病原。体外实验证明,白细胞干扰素对新分离的HSV—I有较强的抑制病变作用,2.4～2.9Iu/ml白细胞干扰素即可抑制病毒的50％CPE。临床上试用干扰素局部治疗必获得显著的疗效。     

结构和热分析研究环戊二烯-甲萘醌加合物的逆Diels-Alder反应

晶体结构分析显示环戊二烯-甲萘醌加合物的C4-C14键被它的角甲基空间效应所弱化,热分析(TG-DSC)研究显示在130℃该加合物的逆Diels-Alder反应趋势得到加强。根据这些结果,推论并证实了环戊二烯-维生素K1加合物具有更强的逆Diels-Alder反应趋势。     

Quantitative MRI of the brain in children with sickle cell disease reveals abnormalities unseen by conventional MRI

Conventional MRI (cMRI) has shown that brain abnormalities without clinical stroke can manifest in patients with sickle cell disease (SCD). We used quantitative MRI (qMRI) and psychometric testing to determine whether brain abnormalities can also be present in patients with SCD who appear normal on cMRI. Patients 4 years of age and older with no clinical evidence of stroke were stratified by cMRI as normal (n = 17) or abnormal (n = 13). Spin-lattice relaxation time (T1) of gray and white matter structures was measured by the precise and accurate inversion recovery (PAIR) qMRI method. Patient cognitive ability was assessed with a standard psychometric instrument (WISC-III or WISC-R). In all 30 patients with SCD, qMRI T1 was lower than in 24 age- and race-matched controls, in cortical gray matter (P < .0006) and caudate (P < .0009), as well as in the ratio of gray-to-white matter T1 (P < .008). In the 17 patients who were shown to be normal by cMRI, qMRI T1 was still lower than in controls, in both cortical gray matter (P < .02) and caudate (P < .004). Histograms of voxel T1 show that the proportion of voxels with T1 values intermediate between gray and white matter (ie, consistent with encephalomalacia) was 9% higher than controls in patients shown to be normal by cMRI (P < .05) and 15% higher than controls in patients shown to be abnormal by cMRI (P < .0005). The full scale intelligence quotient (FSIQ) of all patients with SCD was 75, compared to the FSIQ of 88 in a historical control group of patient siblings (P < .001). The FSIQ of patients shown to be normal by cMRI was 79, significantly lower than the FSIQ of patient siblings (P < .04). The FSIQ of 71 in patients shown to be abnormal by cMRI was significantly lower than both the patient siblings (P < .005) and the patients shown to be normal by cMRI (P < .04). Patients shown to be abnormal by cMRI scored lower than patients shown to be normal by cMRI, specifically on the subtests of vocabulary (P = .003) and information (P = .03). Cognitive impairment is thus significant, even in patients with SCD who were shown to be normal by cMRI, suggesting that cMRI may be insensitive to subtle neurologic damage that can be detected by qMRI. Because cognitive impairment can occur in children normal by cMRI, our findings imply that prophylactic therapy may be needed earlier in the course of SCD to mitigate neurologic damage.     

Two selective 5-HT1A receptor antagonists, WAY-100 635 and NDL-249, stimulate locomotion in rats acclimatised to their environment and alter their behaviour: a behavioural analysis

The aim was to study firstly, the motor effects of a new 5-HT_1A antagonist, NDL-249 [(R)-3-(N-cyclopentyl-N-propylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide hydrochloride] and of the reference 5-HT_1A antagonist WAY-100 635 [N-(2-(1-(4-(2-methoxyphenyl)piperazinyl))ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride], in comparison to the 5-HT_1A agonist (±)-8-OH-DPAT [(8-hydroxy-2-(di-N-propylamino) tetralin, hereafter 8-OH-DPAT], in rats acclimatised to the automated activity cages; secondly, to study whether the behavioural effects of NDL-249 and 8-OH-DPAT are sensitive to the 5-HT depleting effects of p-chlorophenylalanine (PCPA); thirdly, to characterise the nature of the antagonist-induced activation seen in the automatic activity cages with the aid of a behavioural observation analysis; fourthly, to examine the interaction between the 5-HT_1Areceptors mediating the behavioural effects and dopamine (DA) receptors. NDL-249 was found to bind in vitro to rat hippocampal 5-HT_1A receptors with high affinity and selectivity. In second messenger studies, it was devoid of agonist-like effects. In the locomotor activity studies, each antagonist significantly increased the incidence of horizontal activity, peripheral activity and rearing. 8-OH-DPAT, while significantly increasing peripheral and horizontal activities, decreased the incidence of rearing. PCPA blocked the motor effects of NDL-249 but did not affect those of 8-OH-DPAT. Observational analyses indicated that NDL-249 induced significant increases at one or more doses in sniffing, rearing and locomotion together with a significant reduction in stillness. WAY-100 635 significantly increased the incidence of rearing, intense grooming and vacuous chewing. The significant increases in sniffing, grooming and intense grooming and the significant decrease in stillness induced by the DA D₁ agonist, SK&F 38393 [(±)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride], were not altered by concomitant pre-treatment with NDL-249. Pre-treatment of rats with either the DA D₁ antagonist SCH-23390 (2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol) or the DA D₂ antagonist, raclopride, blocked the reduced stillness and increased sniffing and rearing induced by NDL-249. In conclusion, 5-HT_1A antagonists including the new selective antagonist, NDL-249, induce mild behavioural activation in rats, which is mediated probably indirectly via DA systems. Received: 3 April 1997/Final version: 23 February 1998