Lack of FasL expression in cultured human retinal pigment epithelial cells

Retinal pigment epithelial (RPE) cells have been proposed to play a part in maintaining the eye as an immune privileged organ. However, our knowledge of the implicated mechanism is still sparse. Fas ligand (FasL) expression of RPE cells is generally recognized to be essential for the immune privilege of the eye, but due to contradictory published results, it is unclear whether RPE cells express this molecule. The purpose of this study was to investigate the expression of FasL in RPE cells in vitro and in vivo. Cultured human fetal and adult RPE cells were examined by flow cytometry, Western blotting, RT-PCR and RNase Protection assay for FasL expression. Additionally, sections of ocular tissue were stained for FasL by immunohistochemistry. None of the used methods indicated FasL expression in cultured fetal or adult RPE cells of various passages. However, RPE cells in vivo, as judged from tissue sections, were positive for FasL, indicating a discrepancy between RPE cells in vitro and in vivo with regard to this molecule.     

Divergent effects of prostaglandin receptor signaling on neuronal survival

Induction of cyclooxygenase-2 (COX-2) with production of prostaglandins occurs in a wide spectrum of acute and chronic neurodegenerative diseases and is associated with neuronal death. Inhibition of the COX-2 pathway and downstream production of prostaglandins protect neurons in rodent models of cerebral ischemia and neurodegeneration. Recent studies investigating the functions of selected prostaglandin receptor pathways in mediating COX-2 neurotoxicity have demonstrated both toxic and paradoxically neuroprotective effects of several receptors in models of excitotoxicity. In this study, we investigate the functions of additional prostaglandin receptors not previously characterized in organotypic models of glutamate excitotoxicity. We find that PGD₂, PGI₂, and PGF_2α receptors protect motor neurons in an organotypic spinal cord model of amyotrophic lateral sclerosis (ALS). In addition, PGI₂ and TXA₂ receptors rescue CA1 neurons in an organotypic hippocampal model of N-methyl-d-aspartate excitotoxicity. However, in a model of inflammation induced by lipopolysaccharide, prostaglandin receptors previously found to be protective in excitotoxicity now cause CA1 neuronal death. Taken together, these studies identify novel eicosanoid receptor signaling pathways that mediate neuronal protection in excitotoxic paradigms; these data also support the emerging hypothesis that the toxic/protective effects of eicosanoid signaling on neuronal viability diverge significantly depending on whether excitotoxicity or inflammation predominates as the underlying toxic stimulus.     

阿尔茨海默氏病和帕金森氏病对老年人认知功能及日常生活能力的影响分析

目的探讨阿尔茨海默氏病(AD)和帕金森氏病(PD)对老年人认知功能及日常生活能力的影响。方法对2000～2003年就诊于我院的53例AD、68例PD和60例正常人应用简易智力量表(MMSE)和日常生活能力量表(ADL)进行分析。结果AD组与对照组相比MMSE总分及各因子分、ADL总分及各单项分均有显著性差异(P<0.01):PD组与对照组相比除MMSE的记忆力和语言因子分以及ADL第13项目(打电话)外,其余均有显著性差异(P<0.05):AD组与PD组相比除ADL第7项(穿衣)外均有显著性差异(P<0.05)。结论AD和PD对老年人的认知功能和日常生活能力均有显著的影响,两者相比,AD对老年人的影响更严重、更广泛。     

db-cAMP对转化细胞增殖抑制及其对CaM水平和PKⅡ活性的影响

目的　探讨双丁酰 环核苷酸 (db cAMP)对转化细胞增殖及细胞表型作用的机理。　方法　以流式细胞光度术 (flowcytometry ,FCM)、软琼脂集落形成、放射免疫、Northern印迹和激酶活性分析等方法观察db cAMP对转化的C3H1 0 T1 2 小鼠成纤维细胞增殖、细胞表型、钙调素 (calmodulin ,CaM)表达及蛋白激酶Ⅱ (proteinkinaseⅡ ,PKⅡ )活性的影响。　结果　db cAMP(1mmol L)使C3H1 0 T1 2 转化细胞增殖及软琼脂集落形成能力受到显著抑制 ,转化细胞中CaM的表达及PKⅡ活性明显高于正常细胞 ,经db cAMP处理后也受到明显抑制。　结论　细胞转化及cAMP的诱导分化作用与PKⅡ活性的改变有密切相关性     

Genetic alterations in primary and secondary hyperparathyroidism

Hyperparathyroidism refers to a term representing a wide spectrum of parathyroid disorders that are characterized by the increased production of parathyroid hormone. Hyperparathyroidism was once thought to be tare but is now more commonly recognized, aifecting 1 in 500 women over 40 years of age. Yet the interpretation of parathyroid pathology is still controversial and confusing. Over the past 10 years, genetic changes ( ret and menin genes) involved in the pathogenesis of MEN 2 and MEN 1 have been discovered in succession. Different mutations of the calcium-sensing receptor gene have been identified in neonatal severe hyperparathyroidism and familial hypocalciuric hypercal-cemia, respectively. The HRPT 2 gene responsible for the development of heredltaty hyperparathyroidism and jaw tumors has been localized on the 1q21–31 locus. Several genetic alterations have also been characterized in primary and secondary hyperparathyroidism. Different genetic alterations appear to involve the development of different types of hyperparathyroidism. These novel advances give us new insights into the pathogenesis of hyperparathyroidism and allow better differentiation between the different types of parathyroid disorders.     

Cell lines that support replication of a novel herpes simplex virus 1 UL31 deletion mutant can properly target UL34 protein to the nuclear rim in the absence of UL31

Previous results indicated that the herpes simplex virus 1 (HSV-1) U(L)31 gene is necessary and sufficient for localization of the U(L)34 protein exclusively to the nuclear membrane of infected Hep2 cells. In the current studies, a bacterial artificial chromosome containing the entire HSV-1 strain F genome was used to construct a recombinant viral genome in which a gene encoding kanamycin resistance was inserted in place of 262 codons of the 306 codon U(L)31 open reading frame. The deletion virus produced virus titers approximately 10- to 50-fold lower in rabbit skin cells, more than 2000-fold lower in Vero cells, and more than 1500-fold lower in CV1 cells, compared to a virus bearing a restored U(L)31 gene. The replication of the U(L)31 deletion virus was restored on U(L)31-complementing cell lines derived either from rabbit skin cells or CV1 cells. Confocal microscopy indicated that the majority of U(L)34 protein localized aberrantly in the cytoplasm and nucleoplasm of Vero cells and CV1 cells, whereas U(L)34 protein localized at the nuclear membrane in rabbit skin cells, and U(L)31 complementing CV1 cells infected with the U(L)31 deletion virus. We conclude that rabbit skin cells encode a function that allows proper localization of U(L)34 protein to the nuclear membrane. We speculate that this function partially complements that of U(L)31 and may explain why U(L)31 is less critical for replication in rabbit skin cells as opposed to Vero and CV1 cells.     

吗氯贝胺与米帕明治疗抑郁症多中心双盲对照试验

目的 :以经典抗抑郁药物米帕明为阳性对照药采用随机双盲双模拟方法对吗氯贝胺和米帕明治疗抑郁症的疗效和安全性进行研究。方法 :共纳入病人 2 0 0例 ,分别口服吗氯贝胺 3 0 0 -60 0mg d或米帕明75 -2 5 0mg d。结果 :两组病人Hamilton抑郁量表 (HAMD)以及Hamilton焦虑量表 (HAMA)总分在治疗结束时均显著下降 (P <0 0 0 1)。两组之间疗效无显著差异 (p >0 0 5 )。治疗结束时HAMD减分率分别为吗氯贝胺组 0 74± 0 2 4,米帕明组 0 74± 0 2 4(P >0 0 5 ) ;有效率吗氯贝胺组 79 4% ,米帕明组 85 4% (P >0 0 5 )。吗氯贝胺组有 10种不良反应发生频率显著低于米帕明组 ,主要是抗胆碱能、中枢神经系统及心血管系统不良反应。吗氯贝胺的疗效指数也显著高于米帕明组。结论 :吗氯贝胺是一种安全有效的抗抑郁药物