用噬菌体表面展示技术筛选与肝癌细胞系结合的抗体模拟肽

目的:从噬菌体展示肽库中,筛选可与肝癌细胞特异性结合的抗体模拟肽。方法:通过生物淘选使噬菌体富集。利用ELISA法,鉴定噬菌体单克隆原种的亲和性,并进行统计学分析。通过竞争ELISA,分析筛选所得抗体模拟肽的结合位点,并进一步分析抗体模拟肽的序列组成。结果:随着淘选次数的增加,出现噬菌体的富集。ELISA的结果显示,相对于正常肝细胞,筛选所得环状7肽对肝癌细胞系SMMC7721和BEL7402均有良好的结合活性(P<0.05),且与SMMC7721细胞的结合活性明显优于与BEL7402细胞的亲和性(P<0.05)。在α=0.01的水平上,7肽单克隆噬菌体原种可明显与scFv竞争结合SMMC7721细胞(0.005相似文献   

Gene therapy for pituitary tumors

Pituitary tumors are the most common primary intracranial neoplasms. Although most pituitary tumors are considered typically benign, others can cause severe and progressive disease. The principal aims of pituitary tumor treatment are the elimination or reduction of the tumor mass, normalization of hormone secretion and preservation of remaining pituitary function. In spite of major advances in the therapy of pituitary tumors, for some of the most difficult tumors, current therapies that include medical, surgical and radiotherapeutic methods are often unsatisfactory and there is a need to develop new treatment strategies. Gene therapy, which uses nucleic acids as drugs, has emerged as an attractive therapeutic option for the treatment of pituitary tumors that do not respond to classical treatment strategies if the patients become intolerant to the therapy. The development of animal models for pituitary tumors and hormone hypersecretion has proven to be critical for the implementation of novel treatment strategies and gene therapy approaches. Preclinical trials using several gene therapy approaches for the treatment of anterior pituitary diseases have been successfully implemented. Several issues need to be addressed before clinical implementation becomes a reality, including the development of more effective and safer viral vectors, uncovering novel therapeutic targets and development of targeted expression of therapeutic transgenes. With the development of efficient gene delivery vectors allowing long-term transgene expression with minimal toxicity, gene therapy will become one of the most promising approaches for treating pituitary adenomas.     

兔骨髓基质细胞诱导成骨细胞复合同种异体生物衍生骨实验研究

目的探讨体外培养的骨髓基质细胞与自体来源的生物衍生骨复合后的生长特性，为进一步研究骨髓基质细胞作为种子细胞，以及探索一种良好的支架材料提供实验依据。方法分离纯化兔骨髓基质细胞并诱导成成骨细胞后与同种异体来源的生物衍生骨复合后体外培养，并在相差显微镜和扫描电镜下观察其生长情况。结果骨髓基质细胞在生物衍生骨上贴附生长、增殖良好。结论骨髓基质细胞可作为骨组织工程的理想种子细胞，与生物衍生骨复合后可作为骨组织工程的载体。     

Genetic changes in neoplasms arising in congenital melanocytic nevi: differences between nodular proliferations and melanomas

Large congenital melanocytic nevi (CMN) are at an increased risk of developing melanoma. Several forms of secondary proliferations can arise in congenital nevi on rare occasions. Although some of these closely resemble melanoma both clinically and histologically, metastasis is rare. We used comparative genomic hybridization to analyze chromosomal aberrations in different types of proliferations arising in CMN and compared them to typical congenital nevi, clear-cut melanomas arising in congenital nevi, as well as primary cutaneous melanomas that were not associated with a CMN. Cases of CMN and CMN with secondary proliferations were assigned to six groups according to the predominant histological pattern: group I, bland congenital nevi (n = 6); group II, congenital nevi with foci of increased cellularity (n = 4); group III, CMN with a proliferation simulating superficial spreading melanoma in situ (n = 3); group IV, CMN with a proliferation simulating nodular melanoma (n = 9); group V, proliferating neurocristic hamartoma (n = 1); and group VI, melanoma arising in congenital nevus (n = 6). No aberrations were found in groups I to III, whereas seven of nine cases of group IV, and one of one case of group V, showed aberrations. In group IV six of seven cases with aberrations (86%) showed numerical aberrations of whole chromosomes exclusively. This pattern differed significantly from the findings in melanoma that arose within CMN (n = 6), group VI, or independent of CMN (n = 122) in which only 5% showed numerical changes only. The single case in group V showed aberrations similar to melanoma. The finding of frequent numerical chromosomal aberrations in atypical nodular proliferations arising in CMN identifies these as clonal neoplasms with a genomic instability consistent with a mitotic spindle checkpoint defect. This difference compared to the aberration pattern found in melanoma might explain their more benign clinical behavior and may be of diagnostic value in ambiguous cases.     

肺炎克雷伯杆菌在T24细胞内存活的动态观察

目的：了解肺炎克雷伯杆菌与膀胱上皮细胞的相互关系，观察肺炎克雷伯杆菌在人膀胱上皮细胞抹T24中生存的动态变化。方法：采用肺炎克雷伯杆菌临床分离抹03138侵袭T24细胞，并用庆大霉素杀死细胞外的细菌，分别于细菌进入细胞后的4、24、48及72h裂解细胞，释放出细胞内的活细菌，用平板菌落计数法计数胞内活菌数。结果：T24细胞内的肺炎克雷伯杆菌03138抹在实验48h内有一定生长，试验72h细胞内活菌数量明显减少。加入细胞因子（TNF-αd和INF-γ）可以促进上皮细胞清除胞内细菌。结论：膀胱上皮细胞清除进入细胞内的肺炎克雷伯杆菌，可能是泌尿道天然免疫的一种防御机制，而细胞因子可以调控上皮细胞的抗菌作用。     

院外纳曲酮治疗酒精依赖的疗效观察

目的 :评估纳曲酮院外治疗酒依赖的临床疗效。方法 :采用随机对照的方法 ,分别对纳曲酮组和安慰剂组各 2 3例和 2 2例 ,作总疗程 12周的临床观察。结果 :纳曲酮显著降低病人对酒精的渴求程度 ,其疗后 4、 8、 12周的保持率分别为 91 3 %、 77 9%、 73 3 % ,明显高于安慰剂。纳曲酮的副作用与安慰剂相当 ,其主要副作用为轻度的恶心、厌食、头晕。结论 :纳曲酮是一种安全有效的治疗酒依赖的药物     

API0134对大鼠血浆和血小板血栓素B2生成与血小板聚集的影响

用放射免疫分析法和比浊法测定ＰＡＩ０１３４对大鼠血浆血栓素Ｂ２浓度，血小板ＴＸＢ２生成血小板聚集的影响。静脉注射ＡＰＩ０１３４７０ｍｇ或１００ｍｇ．ｋｇ显著降低血浆ＴＸＢ２浓度，其降低２率分别为３８．８％和５１．６％，ＡＰＩ０１３４明显抑制ＡＤＰ诱导的大鼠血小板聚集和ＴＸＢ２生成，抑制率分别为２７．８％，３９．５％，和４１．４％，５３．６％，两抑制率间呈显著正相关。     

APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD).

PURPOSE: Inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia is an adult-onset autosomal dominant illness (IBMPFD) caused by mutations in the valosin-containing protein (VCP) on chromosome 9p21.1-p12. The penetrance of the gene is 82% for myopathy, 49% for Paget's disease, but may be as low as 30% for frontotemporal dementia. Modifier genes could account for decreased frontotemporal dementia penetrance. In this study apolipoprotein-E (APOE) was evaluated for this role in IBMPFD families based on its known modifier effect in Alzheimer's disease. METHODS: From a database of 231 members of 15 families, 174 had APOE genotype available for analysis. Logistic regressions on APOE genotype and frontotemporal dementia were performed, using appropriate covariates. RESULTS AND CONCLUSION: FTD was associated with APOE 4 genotype (P=0.0002), myopathy (P=0.0006), and age (P=0.01), but not microtubule associated protein tau (MAPT) H2 haplotype (P=0.5) or gender (0.09) after adjustment for membership in pedigrees with at least one APOE 4 genotype. These data suggest a potential link between APOE 4 genotype and the specific form of frontotemporal dementia found in IBMPFD. The molecular basis of this link bears further investigation. We did not observe an association of frontotemporal dementia and H2 MAPT haplotype.