噻氯匹定对2型糖尿病患者血小板膜糖蛋白表达的影响

目的：为进一步阐明糖尿病(DM)患者血小板活化状态及抗血小板药物噻氯匹定的治疗作用。方法：采用流式细胞术检测了45例2型糖尿病患者及26例健康志愿者(对照组)血小板表面血小板膜糖蛋白(GP)Ⅰb，GPⅡb，P-选择素及血小板激活复合物-1(PAG-1)表达，并对其中20例2型DM患者应用噻氯匹定治疗(0．25g，qd)2wk，观察对上述指标的影响。结果：DM患者P-选择索及PAG-1表达的荧光强度较对照组明显升高，而GPⅠb表达的荧光强度较对照组下降(P=0．014)，GPⅡb表达则无明显改变(P=0．285)。噻氯匹定治疗2wk可使DM患者P-选择素及PAC-1的表达明显下降，对GPⅡb表达则无明显影响(P=0．815)，GPⅠb表达则上升(P=0．011)。结论：2型DM患者血小板活化增强，出现高凝倾向。噻氯匹定治疗能明显缓解血栓前状态。PAG-1的表达可作为GPⅡb-Ⅲa激活更敏感的新型特异性标志。     

Association of the Platelet Glycoprotein Ia C807T Gene Polymorphism With Risk of Myocardial Infarction in Chinese

Objectives To investigate the relationship of the GPIa C807T dimorphism to the risk of myocardial infarction （MI） in Chinese. Methods We did a case-control study including 100 patients and 110 controls with same race. An allele-specific polymerase chain reaction （PCR） was used for genotyping of C807T polymorphism. Results An apparent association was found between the T807 allele and MI among individuals younger than the mean age of 60 years （odds ratio, 2. 49 ; 95 % confidence interval, 1.08 - 6.22 ）. The T807 allele remained an independent risk factor for MI when age, sex, smoking, hypertension, diabetes, bodymass index, LDL-cholesterol and HDL-cholesterol were adjusted by logistic regression. Conclusions GPIa T807 appears to be an independent risk factor for MI.     

Glycoprotein V‐specific platelet‐associated antibodies in thrombocytopenic patients

In autoimmune thrombocytopenia, platelet‐associated IgG (PA‐IgG) frequently displays specificity against glycoprotein (GP) IIbIIIa and/or GP IbIX. Because in a high proportion of patients positive PA‐IgG may not be explained by these GP specificities, studies on other target proteins are needed. We studied the presence of GP V‐specific PA‐IgG by direct monoclonal antibody‐specific immobilization of platelet antigens (MAIPA) with the monoclonal antibody SW16. We focused on 69 consecutive random patients with histories of thrombocytopenia who were strongly positive for PA‐IgG detected by the direct platelet immunofluorescence test (PIFT). PA‐IgG against GP V (ratio ≥ 1.5) was noted in 15 (22%) patients. The degree of PA‐IgG measured by PIFT, and of GP IIbIIIa‐and/or GP IbIX‐specific PA‐IgG measured by direct MAIPA, correlated directly with the GP V‐specific PA‐IgG (P < 0.001). In one patient, GP V‐specific antibodies were associated with quinidine‐induced thrombocytopenia. Although this patient had strongly positive GP V‐specific PA‐IgG, she remained negative in GP IIbIIIa‐ and GP IbIX‐specific direct MAIPA. Two patients studied because of thrombocytopenia associated with gold therapy had strongly positive GP V‐specific PA‐IgG. In one patient with rheumatoid arthritis and severe gold‐induced thrombocytopenia, the amount of GP V‐specific PA‐IgG decreased during the recovery phase. Thus, GP V may represent an important target antigen in autoimmune‐mediated thrombocytopenia, especially in drug‐induced thrombocytopenia.     

Mapping the platelet profile for functional genomic studies and demonstration of the effect size of the GP6 locus

BACKGROUND: Evidence suggests the wide variation in platelet response within the population is genetically controlled. Unraveling the complex relationship between sequence variation and platelet phenotype requires accurate and reproducible measurement of platelet response. OBJECTIVE: To develop a methodology suitable for measuring signaling pathway-specific platelet phenotype, to use this to measure platelet response in a large cohort, and to demonstrate the effect size of sequence variation in a relevant model gene. METHODS: Three established platelet assays were evaluated: mobilization of [Ca(2+)](i), aggregometry and flow cytometry, each in response to adenosine 5'-diphosphate (ADP) or the glycoprotein (GP) VI-specific crosslinked collagen-related peptide (CRP). Flow cytometric measurement of fibrinogen binding and P-selectin expression in response to a single, intermediate dose of each agonist gave the best combination of reproducibility and inter-individual variability and was used to measure the platelet response in 506 healthy volunteers. Pathway specificity was ensured by blocking the main subsidiary signaling pathways. RESULTS: Individuals were identified who were hypo- or hyper-responders for both pathways, or who had differential responses to the two agonists, or between outcomes. 89 individuals, retested three months later using the same methodology, showed high concordance between the two visits in all four assays (r(2) = 0.872, 0.868, 0.766 and 0.549); all subjects retaining their phenotype at recall. The effect of sequence variation at the GP6 locus accounted for approximately 35% of the variation in the CRP-XL response. CONCLUSION: Genotyping-phenotype association studies in a well-characterized, large cohort provides a powerful strategy to measure the effect of sequence variation in genes regulating the platelet response.     

单纯疱疹病毒糖蛋白C模拟表位mgC真核表达载体的构建和表达

目的为鉴定单纯疱疹病毒(HSV)糖蛋白C(gC)一个短肽模拟表位mgC基因作为HSVDNA表位疫苗的可能性 ,需构建含此表位的真核载体。方法合成编码该表位的单链DNA ,经不对称PCR扩增后 ,克隆入真核表达载体pcD NA3.1中 ,并在CHO细胞中表达。用RT PCR法鉴定mRNA的表达。结果含mgC基因的真核表达载体在哺乳动物细胞中可以在mRNA水平表达外源蛋白。结论成功地构建了HSVgC中短肽模拟表位mgC基因的真核表达载体 ,为进一步探讨该HSV模拟表位的功能奠定了基础。     

丹参对大鼠乙酸慢性胃溃疡的影响

以传统的抗溃疡药甲氰咪胍为标准对比药,探讨了丹参对大鼠乙酸慢性胃溃疡急性期和复发期(1～35天为急性期,36～140天为复发期,我们只在溃疡制作后的1～30天用丹参和甲氰咪胍进行治疗)的影响.结果发现:在溃疡制作后的5、30、126天,丹参组的溃疡指数明显低于对照组和甲氰咪胍组(P<0.01),其溃疡抑制率和腺胃粘液糖蛋白含量明显高于对照组和甲氰咪胍组(P<0.01).表明丹参具有促进急性期溃疡愈合,并有抑制溃疡复发的作用,此作用与腺胃粘液糖蛋白的含量有关.     

Simultaneous existence of galactose-containing glycoprotein and several neuropeptides in DRG of the rat

Summary By use of light microscopic immunohistochemical and leetin histochemical methods, the interrelation of galactose-containing glycoprotein (GC-GP), calcitonin gene-related peptide (CGRP)-like, leu-enkephalin (L-ENK)-like, and substance P (SP)-like peptides has been evaluated on consecutive sections of dorsal root ganglia from colchicine-treated rats. The results showed that GCGP, CGRP, L-ENK and SP exist simultaneously in individual neurons of the dorsal root ganglia in rats. Almost all small neurons in dorsal root ganglion contained both GCGP and CGRP. The stronger peanut lectin affinity with small neurons, the weaker CGRP immunoreactivity, and vice versa. Some neurons of medium size were of strong CGRP-like immunoreactivity; however, they lacked in affinity with peanut lectin. The large spinal ganglionic cells rarely showed CGRP immunoreactivity and affinity with peanut leetin. The results suggested that there was a negative interrelation between GCGP and CGRP in small primary sensory neurons. From the above it may be suggested that the GCGP plays an important role in recognizing and transmitting information in primary sensory neurons.     

New immunocytochemical evidence for a neuronal/oligodendroglial origin for corpora amylacea

New immunocytochemical evidence for a neuronal/oligodendroglial origin for corpora amylaceaStudies employing a bank of antisera applied to sections of LR White embedded AD and normal ageing brain tissue, may throw new light on the derivation of CA. Conspicuous levels of immunoreactivity were found in the CA of both tissues with markers for oligodendrocytic proteins such as antisera against myelin basic proteolipid protein, galacto–cerebroside and myelin/oligodendrocyte glycoprotein. CA were unreactive with MRC OX–42, a marker for microglia and macrophages. In a previous publication [22] we demonstrated that the much more abundant CA in the brains of Alzheimer's disease (AD) sufferers, although slightly more varied in their immunoreactivity than those found in normally ageing controls, were universally immunoreactive with anti–tau, a neuronally derived protein and often also contained amyloid. The cores of CA were not immunoreactive with anti–GFAP, suggesting a lack of involvement with astrocytes. Our results now show that in addition to amyloid and neuronal proteins, a significant proportion of the content of CA is derived from oligodendrocytes and/or myelin. The substantial Fe peak previously reported [22] following X–ray microanalysis of CA was probably due to ferritin. However, immuno–staining with antisera to ferritin showed that high ferritin immunoreactivity was common to both micro– and macroglia as well as CA. More significantly, the immunoreactivity of CA with anti–ubiquitin [22] suggests that degeneration of neuronal/oligodendrocytic elements may precede CA formation.     

管角螺肌肉中性糖蛋白的化学组成及抗肿瘤活性研究

目的:研究海洋软体动物管角螺Hemifusus tuba(Gmelin)肌肉中糖蛋白的化学组成、理化性质及抗肿瘤活性。方法:管角螺肌肉用盐水浸提,水提取液再经DEAE-cellulose、Sephadex G-100柱层析分离,冷冻干燥得到1种中性糖蛋白(Neutral Glycoprotein of H.tuba,NGH)和3种酸性糖蛋白(Acidic Glycoprotein ofH.tuba,AGH);HPLC对NGH进行了纯度检测及相对分子质量测定,改良的苯酚-浓硫酸和Folin酚法测总糖、总蛋白质的含量,气相色谱法测定糖组成,IR和NMR法确定糖苷键类型。结果:NGH为均一性组分,相对分子质量为7.66×10~5,其总糖含量为89.6％,蛋白质含量为7.2％;糖组成分析表明:糖链部分主要由半乳糖及少量的甘露糖和葡萄糖组成,其物质的量比为23.5:2.6:1.0;IR及~1HNMR谱分析表明:其单糖残基为α-吡喃构型。初步药理实验表明:NGH对小鼠S_(180)肿瘤具有显著的抑制作用。     

小鼠实验性自身免疫性脑脊髓炎的病理变化

目的用髓鞘少突胶质细胞糖蛋白多肽(MOG35-55)诱发实验性自身免疫性脑脊髓炎(experi-m ental autoimmune encephalomyelitis,EAE)小鼠模型。方法应用MOG35-55抗原加完全弗氏佐剂免疫C57BL/6小鼠,利用光镜、电镜观察小鼠组织学改变。结果光镜下可见小血管周围炎细胞浸润,呈袖套状改变、血管周围明显脱髓鞘及神经元变性,B ieschowsky银染显示大量轴索肿胀和轴索卵形体的形成,电镜下可见髓鞘结构松散、断裂或融合,包括不同程度的髓鞘重建,脊髓病变广泛,程度重于脑部。结论EAE的病理改变为血管周围炎性细胞浸润、白质脱髓鞘及髓鞘重建。