Possible role of macrophage-derived soluble mediators in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice.

Pancreatic islets from DBA/2 mice infected with the D variant of encephalomyocarditis (EMC-D) virus revealed lymphocytic infiltration with moderate to severe destruction of pancreatic beta cells. Our previous studies showed that the major population of infiltrating cells at the early stages of infection is macrophages. The inactivation of macrophages prior to viral infection resulted in the prevention of diabetes, whereas activation of macrophages prior to viral infection resulted in the enhancement of beta-cell destruction. This investigation was initiated to determine whether macrophage-produced soluble mediators play a role in the destruction of pancreatic beta cells in mice infected with a low dose of EMC-D virus. When we examined the expression of the soluble mediators interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) in the pancreatic islets, we found that these mediators were clearly expressed at an early stage of insulitis and that this expression was evident until the development of diabetes. We confirmed the expression of these mediators by in situ hybridization with digoxigenin-labelled RNA probes or immunohistochemistry in the pancreatic islets. Mice treated with antibody against IL-1beta or TNF-alpha or with the iNOS inhibitor aminoguanidine exhibited a significant decrease in the incidence of diabetes. Mice treated with a combination of anti-IL-1beta antibody, anti-TNF-alpha antibody, and aminoguanidine exhibited a greater decrease in the incidence of disease than did mice treated with one of the antibodies or aminoguanidine. On the basis of these observations, we conclude that macrophage-produced soluble mediators play an important role in the destruction of pancreatic beta cells, resulting in the development of diabetes in mice infected with a low dose of EMC-D virus.     

非酶促转氨测定蛋白质相对分子量及研究空间结构的变化

在非酶促转氨过程中测定生成甘氨酸的量,计算蛋白质的相对分子量是一种方便、节省经费和快速的方法,该方法的应用不受蛋白分子量大小的限制。非酶促转氨的另一产物２－羰化氨基酸可作为制备各种喹喔啉衍生物的原料。苯丙氨酸非酶促形成的苯丙酮酸与邻苯二胺反应生成３－苯基－２－羰基喹喔啉。该产物在３６３ｎｍ具有荧光发色性质。胰岛素及不同一级结构的短肽２－羰酰衍生物和２－喹喔啉衍生物的荧光在盐酸胍和不同ＰＨ训的变化各     

心肺压力感受器持续卸荷对前臂血流、血管阻力及心率变异性谱的影响

低压值下体负压（ＬＢＮＰ）可仅使心肺压力感受器卸荷。采用－２ｋＰａＬＢＮＰ实验结果表明：ＬＢＮＰ既不引起动脉血压变化,也不引起心率改变,但却引起基础胸阻抗（Ｚ。）从对照的２１．８±０．４升高到２２．５±０．５Ω（Ｐ＜０．０１）,前臂血管阻力（ＦＶＲ）从１２．３±０．９升高到１９．９±１．４Ｕ（Ｐ＜０．０１）,前臂血流（ＦＢＦ）从对照时７．１±０．５降低到４．３±０．３ｍｌ·ｍｉｎ￣（－１）·１００ｍｌ￣（－１）,心率变异性谱（ＨＲＶ）未发生任何变化,即心肺压力感受器卸荷时心脏自主神经活动水平与均衡性不受影响。由于ＦＶＲ和ＦＢＦ的变化可间接反映外周血管交感传出活动水平,上述实验结果提示,心肺压力感受器对外周血管及心脏自主神经活动的调节可能存在机能分化现象。     

被子植物系统发育研究的现状与展望

为植物界最大的类群—被子植物建立一个能真正反映植物的进化历史和系统发育（phylogeny）的分类系统一直是许多植物系统学家和进化学家所向往的。到目前为止,已经提出的被子植物分类系统至少有二十多个。问题在于这样的分类系统能否说已符合于系统发育的要求？要回答这个问题,首先必须弄清系统发育的真正含义是什么。     

Calcium dependent action potentials in skeletal muscle fibres of a beetle larva, Xylotrupes dichotomus

The ionic requirement for generating action potentials in ventral longitudinal muscle fibers dissected from beetle larvae was examined by conventional electrophysiological techniques. Muscle fibers that generated only graded responses in physiological saline were able to generate an all-or-none action potential when the potassium permeability of the membrane was inhibited by tetraethylammonium⁺ added to the saline. The peak of the action potential thus elicited was intimately related to the external Ca⁺⁺ concentration. The action potential was blocked by Co⁺⁺ which is known as a competitive inhibitor of Ca-spikes. Neither tetrodotoxin (3 μM) nor a Na-free condition effectively blocked the generation of the action potential. Mg⁺⁺ induced a shift in the peak of the action potential; this was, however, due to the stabilizing action of Mg⁺⁺ but not due to the penetration of Mg⁺⁺ through the muscle membrane. No action potential was elicited in the muscle fiber when immersed in a Ca-free, EGTA saline even when a high concentration of either Mg⁺⁺, Na⁺, or tetraethylammonium⁺ was present. The action potential of the larval muscle fiber was thus concluded to be a Ca-spike, through the channel of which Na⁺ or Mg⁺⁺ did not penetrate.     

5-羟色胺诱发的主动脉区化学感受性升血压反射中某些区域性血管反应的分析

在15只麻醉开胸犬中,用在体器官恒流灌注法研究了骨胳肌、皮肤、肾和心脏的血管在5-HT 诱发的主动脉区化学感受性升血压反射中的反应,同时还观察了5-HT 对这些器官血管的直接效应。左心房注入5-HT(200μg)后,在动脉血压急剧上升的同时,股薄肌、皮肤(后爪)和肾脏的灌流压明显增加,其增值分别为43±8.47±5和56±27mmHg(P<0.01),而冠脉灌流压无明显改变。用阿托品和/或心得安阻断骨胳肌、皮肤和心脏灌流区域的 m 和同β-受体后,上述效应无进一步变动。向灌流环路直接注入5-HT(10—50μg),可引起皮肤和肾脏的血管收缩,而股薄肌和心肌的血管则扩张;后一效应不被心得安阻断。以上结果提示:1.在5-HT 诱发的主动脉区化学感受性升血压反射中,骨胳肌、皮肤和肾脏呈现明显的交感性缩血管反应,而并不伴有交感性扩血管活动;2.在外周血管可能存在两种不同的5-HT 受体,一种主要分布在皮肤和肾脏,引起缩血管效应;另一种主要分布于骨胳肌和冠状血管,引起扩血管效应。     

狗静脉注射高渗溶液后的血流动力学分析

在15只戊巴比妥钠麻醉的开胸狗身上观察高渗溶液对血流动力学的影响,主要结果如下:1.静脉内注射50%葡萄糖溶液(3m1/kg,15s 内注毕),规律地引起心动徐缓、动脉血压降低、左心室(-dp/dt)减小、左心室 dp/dt 和心输出量增加,以及肾和股薄肌的血流阻力降低。25%甘露醇溶液具有类似作用。2.切断两侧颈迷走神经后,注射高渗溶液不再能诱发动脉低血压以及肾和股薄肌血流阻力的反射性降低,提示此类效应的传入通路主要为迷走神经。3.在切断迷走神经后注射高渗溶液,还使左心室 dp/dt 进一步增加,表明高渗溶液增强心肌收缩性。根据以上结果似可认为,静脉注射高渗溶液所致动脉血压降低,实质上反映着心输出量的增加不足以抵销外周阻力的减小。     

中国疫霉属异宗配合种的交配型

在疫霉属真菌中,很多种是重要的经济植物的病原菌,寄主范围广泛,包括乔木、灌木和各种农作物;为害性大,常带来严重的经济损失。本文主要研究疫霉异宗配合种的交配型。根据疫霉在纯培养和成对培养(dual culture)中产生有性器官的能力,疫霉属可分为同宗配合种和异宗配合种两大类群。异宗配合种的A~1交配型与同一种或其它种的A~2交配型进行成对培养时,可以形成有性器官。两个可亲合菌系配合而形成有性器官时,可能发生基因重组,其结果将使病原菌具有更强的生存能力、致病力以及更广泛的寄主范围。因此,研究疫霉两种不同的交配型的分布,不仅对认识病害的发生发展规律,进一步设计防治措施有着重要意义,而且对疫霉属的起源、演化和移栖也有着深远的理论意义。作者对收集到的7个异宗配合种:Phytophthora capsici,P.cinnamomi,P.citrophthora,P.colocasiae,P.infestans,P.nicotianae,P.palmivora的38个分离物进行了交配型的研究,测定工作使用澄清的Campbell蔬菜汁琼脂培养基(V8C),用于确定交配型的菌系有P.nicotianae var.parasitica A~1,P.nicotianae var.parasitica A~2,P.cinnamomi A~1,P.cinnamomi A~2,P.palmivora A~1,P.palmivora A~2.每个分离物分别与已知种的A~1和A~2两个菌系成对接种于同一V8C平板上,放入25℃温箱中培养,2周后在两个菌落的连线上检查有性器官的产生情况。实验结果表明,中国疫霉属异宗配合种的这些分离物的交配型与寄主或地理分布似无相关性,同一种植物上分离到的同种疫霉可以是A~1交配型,也可以为A~2交配型;同一地区可以出现两种交配型,不同地区又有相同的交配型。云南西双版纳橡胶园中的分离物(P.citrophthora,P.colocasiae,P.palmivora)都表现为中性。     

MIXED MODEL APPROACHES FOR ESTIMATING GENETIC VARIANCES AND COVARIANCES

The limitations of methods for analysis of variance(ANOVA)in estimating genetic variances are discussed. Among the three methods(maximum likelihood ML, restricted maximum likelihood REML, and minimum norm quadratic unbiased estimation MINQUE)for mixed linear models, MINQUE method is presented with formulae for estimating variance components and covariances components and for predicting genetic effects. Several genetic models, which cannot be appropriately analyzed by ANOVA methods, are introduced in forms of mixed linear models. Genetic models with independent random effects can be analyzed by MINQUE(1)method whieh is a MINQUE method with all prior values setting 1. MINQUE(1)method can give unbiased estimation for variance components and covariance components, and linear unbiased prediction (LUP) for genetic effects. There are more complicate genetic models for plant seeds which involve correlated random effects. MINQUE(0/1)method, which is a MINQUE method with all prior covariances setting 0 and all prior variances setting 1, is suitable for estimating variance and covariance components in these models. Mixed model approaches have advantage over ANOVA methods for the capacity of analyzing unbalanced data and complicated models. Some problems about estimation and hypothesis test by MINQUE method are discussed.     

Inhibitors of Urokinase and Thrombin in Cultured Neural Cells

Recent studies have suggested important roles for certain proteases and protease inhibitors in the growth and development of the CNS. In the present studies, inhibitors of urokinase or thrombin in cultured neural cells and serum-free medium from the cells were identified by screening for components that formed sodium dodecyl sulfate-stable complexes with 125I-urokinase or 125I-thrombin. Rinsed glioblastoma possessed two components that complexed 125I-urokinase. One was type 1 plasminogen activator inhibitor (PAI-1), because the 125I-urokinase-containing complexes were immunoprecipitated with anti-PAI-1 antibodies. The other component formed complexes with 125I-urokinase that were not recognized by antibodies to PAI-1 or protease nexin-1 (PN-1). Its identity is unknown. In addition to these cell-bound components, the glioblastoma cells also secreted two inhibitors that formed complexes with 125I-urokinase; one was PAI-1, and the other was PN-1. The secreted PN-1 also formed complexes with 125I-thrombin. It was the only thrombin inhibitor detected in these studies. Human neuroblastoma cells did not contain components that formed detectable complexes with either 125I-urokinase or 125I-thrombin. However, human neuroblastoma cells did contain very low levels of PN-1 mRNA and PN-1 protein. Added PN-1 bound to the surface of both glioblastoma and neuroblastoma cells. This interaction accelerated the inhibition of thrombin by PN-1 and blocked the ability of PN-1 to form complexes with 125I-urokinase. Thus, cell-bound PN-1 was a specific thrombin inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)