子宫腺肌症病变中雌激素、孕激素、癌基因、凋亡抑制基因的表达研究

目的 研究雌激素（ER）、孕激素（PR）及癌基因（cerbB-2）、凋亡抑制基因（Bcl-2）在子宫腺肌症病变中的表达和子宫腺肌症发病的相关性。方法 用免疫组化方法检测40例子宫腺肌症病变组织中ER及其他生物学指标的表达。结果 ER、PR与CerbB．2、Bcl-2在子宫腺肌症病变中均有不同程度的阳性表达，子宫肌层异位内膜ER阳性表达率97．5％，PR阳性率97．5％，cerbB-2阳性率82．5％，Bcl-2阳性率62．5％。在位内膜和异位内膜ER、PR均呈阳性，阳性率比较差异无统计学意义（P〉0．05）。异位内膜cerbB-2的强阳性率高于在位内膜，差异有统计学意义（P〈0．05）。ER、PR与cerbB-2、Bcl-2阳性率相比具有相关性（P〈0．05）。结论 ER、PR与cerbB．2、Bcl-2在异位内膜高表达，提示这些生物学指标在子宫腺肌症发生发展中发挥作用。     

Severe hypoglycaemia in a person with insulin autoimmune syndrome accompanied by insulin receptor anomaly type B.

AIMS: A rare case of the insulin autoimmune syndrome (IAS) accompanied by insulin receptor anomaly is reported. METHODS: Antibodies to insulin and insulin receptor were determined in the patient with severe hypoglycaemia before and after the treatment with prednisolone. RESULTS: Titers of antibody to insulin and insulin receptors were 73.0% and 41.5%, respectively. Drug-induced lymphocyte stimulation tests were all negative for the suspicious drugs. Her HLA-DR was DRB1*0403/04051. Following steroid therapy, the formation of antibodies was suppressed and alleviated her symptoms. Scatchard analysis yielded findings specific to polyclonal antibodies. CONCLUSIONS: The changes in autoantibodies resulted in alleviation of the hypoglycemic symptoms as a result of steroid therapy.     

Activation of 5-HT3 receptor by 1-phenylbiguanide increases dopamine release in the rat nucleus accumbens

The serotonin-3 (5-HT₃) agonist 1-phenylbuguanide (0.1–1.0 mM in perfusate) caused a robust, dose-dependent enhancement of extracellular dopamine content in nucleus accumbens as measured by in vivo microdialysis. This action was antagonized by co-perfusion of the 5-HT₃ antagonists zacopride and GR38032F (1 mM in perfusate). Similar effects were observed in 5-HT-denervated rats. These findings suggest that there is a potent modulation of dopamine (DA) release in the nucleus accumbens mediated via 5-HT₃ receptors, which appear to be located presynaptically on DA terminals of the mesolimbic DA pathway.     

Bacterial ghosts (BGs)—Advanced antigen and drug delivery system

Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system (ADDS) for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. Uptake of BGs loaded with Doxorubicin (Dox) by CaCo2 cells led to effective Dox release from endo-lysosomal compartments and accumulation in the nucleus. Viability and proliferative capacity of the cells were significantly decreased (2–3 orders of magnitude) after internalization of Dox loaded BGs as compared to cells incubated with free Dox. The same effect was observed with leukemia cells. Melanoma cells also revealed a high capability to internalize BGs. These results indicate that BGs are able to target a range of types of cancer. BGs have also been investigated as DNA delivery vectors. Studies show DNA loaded BGs are efficiently phagocytosed and internalized by both professional APCs and tumor cells with up to 82% of cells expressing the plasmid-encoded reporter gene. Our studies with BGs as an ADDS system contribute (i) to optimize drug delivery for the treatment of cancer; (ii) define specific conditions for selection and preparation of BG formulations; (iii) and provide a background for the clinical application of BGs in cancer therapy.     

多发性骨髓瘤患者血浆尿激酶型纤溶酶原激活物及其可溶性受体的检测与临床意义

目的 :研究多发性骨髓瘤 ( MM)患者血浆尿激酶型纤溶酶原激活物 ( u- PA )及其可溶性受体 ( su PAR )的水平变化 ,并探讨其临床意义。方法 :用 ELISA法检测 34例 MM患者血浆 u- PA及 su PA R的浓度 ,同时观察其中6例 MM患者化疗前后血浆 u- PA及 su PAR的浓度变化。结果 :MM患者血浆 u- PA及 su PA R水平均明显高于正常对照组 ,其中进展期 MM患者血浆 u- PA及 su PAR水平明显高于正常对照组和稳定期 MM患者 ( P <0 .0 1) ,而稳定期 MM患者血浆 u- PA及 su PA R水平与正常对照组无显著性差异 ( P>0 .0 5)。 6例 MM患者化疗后血浆 u- PA及 su PA R水平 ,明显低于化疗前血浆 u- PA及 su PAR水平 ( P<0 .0 5)。骨髓涂片瘤细胞比例 >2 0 %的 MM患者血浆 u- PA及 su PA R水平 ,明显高于瘤细胞比例≤ 2 0 % M M患者 ( P<0 .0 5;P<0 .0 1)。M M患者血浆 u- PA及su PA R水平均与骨髓瘤细胞百分比及血清球蛋白呈正相关 ,而与血清白蛋白呈负相关。结论 :血浆 u- PA及 su PA R水平升高可能与多发性骨髓瘤的发生、发展有密切关系 ;其水平可作为临床分期、判断疗效、了解疾病进展情况及预后的一个重要指标。     

瘦素受体在条件性厌味大鼠脑的表达

目的 :观察瘦素受体 (LR)在条件性厌味 (CTA)大鼠脑的表达 .方法 :采用高度特异的抗瘦素受体血清 ,用免疫组化ABC法观察LR在CTA和对照大鼠脑的分布与表达 .结果 :与对照组大鼠相比 ,CTA大鼠皮层Ⅲ层、视交叉上核、弓状核、杏仁基底外侧核、海马CA3、下丘脑外侧区等核团瘦素受体表达增加 (14 6vs 12 0 ,138vs 92 ,118vs 78,10 7vs70 ,85vs 38cells·mm-2 ,P <0 .0 5 ) ,而下丘脑前区、脑桥臂旁核、杏仁中央核瘦素受体表达减弱 (13vs2 6 ,70vs5 5 ,12 2vs 16 2cells·mm-2 ,P <0 .0 5 ) ,孤束核瘦素受体的表达与对照大鼠无显著性差异 (5 0vs 5 7cells·mm-2 ,P >0 .0 5 ) .结论 :瘦素可能通过杏仁核、臂旁核、海马、皮层的瘦素受体参与CTA的形成与维持     

雌激素对穹隆海马伞切断大鼠脑内nAchR的干预作用

目的以双侧穹隆-海马伞切断制作阿尔茨海默病(AD)大鼠模型,观察脑内海马CA1区和皮层区烟碱型乙酰胆碱受体(nAchR)表达的变化,探讨与AD相关的发病机制,并观察雌激素的干预作用。方法健康雌性W istar大鼠,随机分为3组:(1)穹隆-海马伞切断组;(2)雌激素治疗组;(3)假手术对照组;每组大鼠5只。在脑立体定位仪上切断穹隆-海马伞,建立模拟AD动物模型。应用免疫组织化学技术观察AD大鼠海马CA1区和皮层区的nAchR阳性细胞表达的变化,以及应用外源性雌激素的干预作用。结果与对照组大鼠脑内nAchR表达比较,穹隆-海马伞切断组大鼠脑内海马CA1区、皮层区nAchR表达显著减少(P<0.05);与穹隆-海马伞切断组比较,雌激素治疗组海马CA1区、皮层区nAchR表达显著增加(P<0.01),但与对照组比较无显著差异(P>0.05)。结论穹隆-海马伞切断组大鼠脑内海马CA1区、皮层区nAchR的阳性细胞显著减少,补充外源性雌激素治疗后,上述各脑区内的nAchR表达显著增加。nAchR的变化与AD的病理变化过程密切相关,补充雌激素可以干预这种病理过程。     

Ramatroban (BAY u 3405): A Novel Dual Antagonist of TXA2 Receptor and CRTh2, a Newly Identified Prostaglandin D2 Receptor

It is known that thromboxane A₂ (TXA₂) contributes to various diseases such as bronchial asthma, ischemic heart disease, cerebrovascular disorders and allergic rhinitis. A number of TXA₂ synthase inhibitors and TXA₂ receptor (TP receptor) antagonists have been developed to treat these diseases. Ramatroban (BAY u 3405) was developed as a potent TP receptor antagonist with excellent efficacy against allergic rhinitis in many animal models and patients. Recent studies also revealed that ramatroban can block the newly identified PGD₂ receptor, chemoattractant receptor‐homologous molecule expressed on Th2 cells (CRTh2). PGD₂ induces migration and degranulation of eosinophils through CRTh2 and contributes to late‐phase inflammation and cell damage. Accordingly, it was considered that ramatroban suppresses the late‐phase inflammation via TP receptor and CRTh2 blockade. In terms of the efficacy on vascular systems, it was revealed that ramatroban can suppress the expression of monocyte chemoattractant protein‐1 (MCP‐1) and adhesion molecules in endothelial cells and prevent exacerbation of inflammation by blocking these responses. According to our recent studies in hypercholesterolemic rabbits ramatroban prevents macrophage infiltration through MCP‐1 downregulation and neointimal formation after balloon injury and attenuates vascular response to acetylcholine. Therefore, ramatroban may be beneficial in the treatment of atherosclerosis.     

运用siRNA建立稳定低表达IGF1R基因的肝癌细胞株的实验研究

目的运用siRNA技术在肝癌细胞株中建立稳定低表达人胰岛素样生长因子1类受体(IGF1R)基因的细胞株。方法构建包含封闭IGF1R基因的真核表达载体pSUPER-IGF1R-siRNA,转染SMMC7721和Hep3B细胞,G418筛选表达稳定的细胞株。通过RT-PCR、Western-blot分析与鉴定IGF1R mRNA和蛋白及cyclin D1、cyclinB1蛋白的表达,并绘制细胞生长曲线。结果在SMMC7721和Hep3B细胞中成功建立低表达IGF1R基因的细胞株,其生长明显减慢(P<0.05),且其cyclinD1表达亦明显下降(P<0.05)。结论pSUPER-IGF1R-siRNA能抑制SMMC7721和Hep3B细胞的生长。