小剂量干扰素与胸腺肽联合对慢性乙型肝炎抗病毒效应的追踪观察

本文报道小剂量干扰素与胸腺肽联合对慢性乙肝20例抗病毒效应的追踪观察结果,并与同期同批同剂量单纯干扰素治疗13例慢性乙肝作对照,追踪时间均为治后半年—2年,从HBeAg、HBcAg、DNAP、HBV DNA阴转率来看,治疗组分别为58.8％、60％、60％及66.6％、对照组分别为50％、50％、100％及50％。再从HBV四项复制指标改变来看,则治疗组4例全阴转,7例仅一项阳性,总有效率达61.1％(11/18),而对照组仅为20％(2/10),P<0.01,认为干扰素与胸腺肽联合治疗优于对照组,并扼要讨论增强干扰素抗病毒效应的各种措施,认为干扰素与胸腺肽联合,不论从前已报道近期疗效和本文远期追踪来看均较安全而有效,二者合用起到增强抗病毒效应的作用,值得进一步探索。     

Amyloid beta proteins inhibit Cl(-)-ATPase activity in cultured rat hippocampal neurons

Cl(-)-ATPase in the CNS is a candidate for an outwardly directed neuronal Cl(-) transporter requiring phosphatidylinositol-4-phosphate (PI4P) for its optimal activity. To test its pathophysiological changes in a phosphatidylinositol (PI) metabolism disorder, the effects of neurotoxic factors in Alzheimer's disease (AD), amyloid beta proteins (Abetas), on the Cl(-)-ATPase activity were examined using primary cultured rat hippocampal neurons. Amyloid beta proteins (1-40, 1-42 and 25-35) concentration-dependently (1-100 nM) and time-dependently (from 1 h to 6 day) decreased Cl(-)-ATPase activity and elevated intracellular Cl(-) concentrations ([Cl(-)]i), Abeta25-35 being the most potent. Addition of inositol or 8-Br-cyclic GMP completely reversed these Abeta-induced changes. The recoveries in enzyme activity were attenuated by an inhibitor of PI 4-kinase, 10 microM wortmannin or 20 microM quercetin, but not by a PI 3-kinase inhibitor, 50 nM wortmannin or 10 microM LY294002. The PI, PIP and PIP2 levels of the plasma membrane-rich fraction were lower in the Abeta-treated cells as compared with each control. In the Abeta-exposed culture, but not in control, stimulation by 10 microM glutamate for 10 min significantly increased fragmentation of DNA and decreased cell viability. Addition of inositol or 8-Br-cyclic GMP prevented the effect of Abeta-treatment on the neurotoxicity of glutamate. Thus, Abetas reduce neuronal Cl(-)-ATPase activity, resulting in an increase in [Cl(-)]i probably by lowering PI4P levels, and this may reflect a pre-apoptotic condition in early pathophysiological profiles of AD.     

Inhibiting Matrix Metalloproteinase 3 Ameliorates Neuronal Loss in the Ganglion Cell Layer of Rats in Retinal Ischemia/Reperfusion

It has been demonstrated that matrix metalloproteinase 3 (MMP3) is integrally involved in the neuronal degeneration of the central nervous system by promoting glial activation, neuronal apoptosis and damage to the brain–blood barrier. However, whether MMP3 also contributes to the neuronal degeneration induced by retinal ischemia/reperfusion is still uncertain. In the present study, we detected the cellular localization of MMP3 in adult rat retinae and explored the relationship of its expression with neuronal loss in the ganglion cell layer (GCL) in retinal ischemia/reperfusion. We found that MMP3 was widely expressed in many cells throughout the layers of the rat retinae, including Vertebrate neuron-specific nuclear protein (NeuN)-, parvalbumin-, calbindin-, protein kinase C-α-, glial fibrillary acidic protein-, glutamine synthetase- and CD11b-positive cells. Furthermore, all rats were treated with high intraocular pressure (HIOP) for 1 h (h) and sacrificed at 6 h, 1 day (d), 3 d, and 7 d after HIOP. Compared to the normal control, the expression of both proenzyme MMP3 and active MMP3 were significantly up-regulated after HIOP treatment without alteration of the laminar distribution pattern. Moreover, inhibiting MMP3 ameliorated the loss of NeuN-positive cells in the GCL following HIOP. In summary, our data demonstrates that MMP3 is expressed in multiple types of neurons and glial cells in normal rat retinae. Simultaneously, the up-regulation of its expression and activity are closely involved in neuronal loss in the GCL in retinal ischemia/reperfusion.     

He-Ne激光对小麦属间杂交影响的研究

1988年以来,作者采用He-Ne激光辐照黑麦花粉与杂交相结合的新方法,对小麦属间杂交(普通小麦×黑麦)进行了研究,获得了较好的效应.试验采用随机区组排列,重复三次,单粒条播.辐照方法,采用He-Ne激光分别以100秒、200秒、300秒辐照三个黑麦品种的花粉,与普通小麦授粉,配制成9个(普通小麦×黑麦)属间杂交组合.所得结果,采用方差分析、新复极差测验法,测定了组合与对照组合相比的差异显著性,也测定了各组合间相互比较的差异显著性.激光辐照小麦属间杂交所获种子的结实率极显著高于对照,为113.52～341.60%.籽粒千粒重和饱满度均超过对照,分别为84.07～295.43%、30.30～127.27%,差异均极显著.L1代籽粒出苗率和植株成活率分别比对照提高58.18～83.06%、41.35～87.78%,差异达到极显著水平.He-Ne激光的诱变作用,在于促进了小麦属间杂交的可交配性,提高了杂交籽粒的结实率,改善了籽粒的饱满度,提高了籽粒的千粒重,因而促进了杂种种子的出苗率和成活率.并且,在L1代植株中均获得了染色体自然加倍的双二倍体即小黑麦种子.现已获得L1～L8代的小黑麦后代材料和稳定株系.高科技的激光诱变育种,为小麦属间杂交育种工作开辟了新的简便途径.     

百日咳杆菌去内毒素及保护性抗原的纯化

内毒素(Endotoxin,简称ET)是百日咳全菌苗(Bordetellapertussis vaccine)产生副作用的主要毒素之一,且不易除去。现有的分离方法,如蔗糖密度梯度离心法,较繁琐,成本高。本文采用Sepha-cryl S-300凝胶层折法可以简便有效的去除大部分内毒素。初步毒素试验结果表明:已达到日本生物制品规格的要求。两种保护性抗原FHA和LPF-HA也得到进一步分离纯化,为今后研制高效的百日咳组分菌苗提供了实验条件。     

Morphological Alteration of Golgi Apparatus and Subcellular Compartmentalization of TGF-β1 in Golgi Apparatus in Gerbils Following Transient Forebrain Ischemia

Golgi apparatus (GA) is a very important organelle involved in the metabolism of numerous proteins. TGF-β1 plays an important role in supporting neuronal survival after ischemic insults. Little is known, however, about the morphological alteration of GA and subcellular compartmentalization of TGF-β1 in brain after ischemia. Therefore, our present study was designed to check for GA morphological alterations and TGF-β1 subcellular localization. GA immunoreactivities were examined in the somatosensory cortex of gerbils after 10 min transient forebrain ischemia. Confocal Immunofluorographs of TGF-β1 and TGN38 were also taken. Results indicated that no fragmentation of GA was found in gerbils of norm, shams and 6, 24 and 72 h postocclusion, but some of the cortical cells showed fragmentation of GA in gerbils 7 days postocclusion. TGF-β1 was colocalized with TGN38, a marker molecule for the GA. We conclude that there was morphological alterations of GA and TGF-β1 was present in GA in the somatosensory cortex after 10 min ischemia.     

Signaling function of PSGL-1 in neutrophil: tyrosine-phosphorylation-dependent and c-Abl-involved alteration in the F-actin-based cytoskeleton

P-selectin glycoprotein ligand-1 (PSGL-1) is the best-characterized selectin ligand that has been demonstrated to mediate leukocytes rolling on endothelium and leukocytes recruitment into inflamed tissue in vivo. In addition to its direct role in leukocyte capturing, PSGL-1 also functions as a signal-transducing receptor. The present work showed that after cross-linking of PSGL-1 with KPL1, an anti-PSGL-1 monoclonal antibody, PSGL-1 linked to the cytoskeleton and became a detergent-insoluble component in activated neutrophils. The antibody cross-linking led to the polymerization and redistribution of F-actin-based cytoskeleton, and this alteration of cytoskeleton was spatiotemporally related to the polarization of PSGL-1. PSGL-1's polarization was cytoskeleton-dependent because it was eliminated by cytochalasin B. Furthermore, the polymerization and redistribution of F-actin filaments were tyrosine-phosphorylation-dependent since the alteration of F-actin-based cytoskeleton was severely blocked by genistein, a universal tyrosine kinase inhibitor. STI571, a small molecule inhibitor for cytoplasmic tyrosine kinase c-Abl, also inhibited the alteration of F-actin-based cytoskeleton, and c-Abl was redistributed to where F-actin concentrated in the activated neutrophils. The results suggested that cross-linking of PSGL-1 induces the phosphorylation-dependent and c-Abl-involved alteration of F-actin-based cytoskeleton in neutrophils.     

Mamu-B genes and their allelic repertoires in different populations of Chinese-origin rhesus macaques

Since rhesus monkeys of Chinese origin have gained greater utilization in recent years, it is urgent to investigate the major histocompatibility complex (MHC) immunogenetics of Chinese rhesus macaques. In this study, we identified 81 Mamu-B sequences using complementary DNA cloning and sequencing on a cohort of 58 rhesus monkeys derived from three local populations of China. Twenty of these Mamu-B alleles are novel and four of them represent new lineages. Although more alleles are shared among different populations than Mamu-A locus, the Mamu-B allelic repertoires found in these three populations of Chinese macaques are largely independent, which underscores the MHC polymorphism among different populations of Chinese rhesus macaques. Our results are an important addition to the limited MHC immunogenetic information available for rhesus macaques of Chinese origin.