Cationic Lipid-Based Gene Delivery Systems: Pharmaceutical Perspectives

Gene delivery systems are designed to control the location of administered therapeutic genes within a patient's body. Successful in vivo gene transfer may require (i) the condensation of plasmid and its protection from nuclease degradation, (ii) cellular interaction and internalization of condensed plasmid, (iii) escape of plasmid from endosomes (if endocytosis is involved), and (iv) plasmid entry into cell nuclei. Expression plasmids encoding a therapeutic protein can be, for instance, complexed with cationic liposomes or micelles in order to achieve effective in vivo gene transfer. A thorough knowledge of pharmaceutics and drug delivery, bio-engineering, as well as cell and molecular biology is required to design optimal systems for gene therapy. This mini-review provides a critical discussion on cationic lipid-based gene delivery systems and their possible uses as pharmaceuticals.     

Tape stripping of human stratum corneum yields cell layers that originate from various depths because of furrows in the skin

Received: 21 November 1996     

Comorbidity and social phobia: evidence from clinical,epidemiologic, and genetic studies

This paper reviews evidence from clinical, epidemiologic, and family studies regarding the association between social phobia and other syndromes. Social phobia is strongly associated with other anxiety disorders, substance abuse, and affective disorders in both clinical and community samples. An average of 80% of social phobics identified in community samples meet diagnostic criteria for another lifetime condition. Social phobia is most strongly associated with other subtypes of anxiety disorders, with an average of 50% of social phobics in the community reporting a concomitant anxiety disorder including another phobic disorder, generalized anciety, or panic disorder. Approximately 20% of subjects in the community meet lifetime criteria for a major depressive disorder. The onset of social phobia generally precedes that of all other disorders, with the exception of simple phobia. Both clinical severity and treated prevalence are consistently greater among social phobics with comorbid disorders The results of family and twin studies reveal that shared etiologic factors explain a substantial proportion of the comorbidity between social phobia and depression, whereas the association between social phobia and alcoholism derives from a nonfamilial causal relationship between the two conditions. Clinical and phenomenologic implications of these findings are discussed.     

转人GM—CSF基因人膀胱癌细胞株的建立及体外生物学特性

经逆转录病毒载体将人GM-CSF基因导入人膀胱癌细胞株BIU-87细胞中,建立了转基因细胞株BIU/GM。经流式细胞仪行细胞DNA周期分析表明GM-CSF基因的导人及表达对BIU-87细胞的增长无影响。免疫荧光测定发现转GM-CSF基因及表达不能促进BIU-87细胞表面HLA-ABC、DR、DQ抗原的表达。转基因瘤细胞株经6000rad X射线照射灭活后,丧失增殖能力,逐步死亡,但能维持一定水平的GM-CSF分泌活性达两周以上。从而为制备灭活的转基因瘤苗提供了初步经验。     

Absent chondrodysplasia punctata in a male with an Xp terminal deletion involving the putative region for CDPX1 locus

This is a follow-up report on a male patient with a 46, Y, r(X) karyotype. Although he had no clinico-radiological features of X-linked recessive chondrodysplasia punctata (CDPX1), molecular studies revealed an Xp terminal deletion involving the putative region for the CDPX1 locus (PABX-DXS31). We suspect that the absence of CDPX1 may be attributable to the nature of the disease and the extreme short stature of the patient (mean – 5.6 S.D.). © 1993 Wiley-Liss, Inc.     

人卵巢癌中肿瘤转移抑制基因nm23-H1编码蛋白的表达

目的：探讨人卵巢癌标本中，肿瘤转移抑制基因ｎｍ２３－Ｈ１编码蛋白ＮＤＰＫ－Ａ表达的临床意义及其与预后的关系。方法：应用免疫组织化学抗生蛋白链菌素－过氧化酶结合（Ｓ－Ｐ）法，检测５８例人卵巢癌标本中ｎｍ２３－Ｈ１蛋白水平。结果：ｎｍ２３－Ｈ１蛋白的表达与患者手术时是否有淋巴结及大网膜转移相关（Ｐ〈０．０５），但原发灶与转移灶间的阳性表达率相差不显著；与患者术后生存时间密切相关（Ｐ〈０．０１），术后生     

Selection of Single Nucleotide Polymorphisms for Association Studies in Candidate Genes

Comparison of polymorphic sites such as single nucleotide polymorphisms (SNPs) within a gene between cases and controls may be useful for establishing a role of this gene in disease susceptibility. The approach includes two steps: the first step is the discovery of the different SNPs within the candidate gene and the second step is the association testing per se that can be done on the entire set of sites discovered or on a subset of these sites only. Selecting a subset of sites may increase the power to detect the association with the candidate gene since a smaller number of tests would then be performed. We proposed a strategy to select sites within a candidate gene and applied it on the Genetic Analysis Workshop 12 candidate gene data. Using these selected sites, we detected an association with candidate genes 1 and 6. © 2001 Wiley‐Liss, Inc.     

干性型老年黄斑变性60例随访观察

探刊干性型老年黄斑变性（age-related macular deganeration，AMD)的病变发展特征并 寻找监测AMD病情进展的较敏感指标。 方法：用眼底彩色照相和眼底荧光血管造影(FFA)、明视视网膜电囤(ERG)、FM100-hue 色彩试验及视力检查，对60例(111眼)50~80岁、视力≤1.0的干性型AMD患者进行3～74个月(平均30.2个月)的随访观察。 结果：本组68眼经FFA检查、平均25.6个月随访，其中25%的患眼病灶损害有快慢不一的发展．全部111眼视力在平均30.2个月随访中有18%患眼的视力下降2行以下，且与病灶进展相符，FM100-hue 色彩试验的被随访者中，随访2年以后，其总错误分明显的增加(P<0.01)．63眼的明视ERG在随访过程中无明显变化。 结论：大部分干性AMD患眼的病灶损害和视力可以在较长时间内维持稳定。FM100—hue的总错误分可能为监测AMD病情进展的较敏感指标． （中华眼底病杂志，1997，13：150-152）     

抗—HCV阳性单采浆供血员HGV感染随访研究

为了解单采浆供血员庚型肝炎病毒（ＨＧＶ）感染及其转归，对１０２名抗－ＨＣＶ阳性单采浆供血员冻存血清进行抗－ＨＧＶ和ＨＧＶＲＮＡ检测，对抗－ＨＧＶ和（或）ＨＧＶＲＮＡ阳性者作３年随访研究。采用ＥＩＡ法检测抗－ＨＧＶ，包被抗原来自ＨＧＶ不同功能区的合成肽。应用ＲＴ－ＰＣＲ法检测ＨＧＶＲＮＡ，引物选自ＨＧＶＮＳ３区。结果表明，抗－ＨＣＶ阳性单采浆供血员ＨＧＶＲＮＡ阳性率为１９．６１％（２０／１０２），抗－ＨＧＶ阳性率为１７．６５％（１８／１０２），ＨＧＶ感染率（抗ＨＧＶ和／或ＨＧＶＲＮＡ阳性）为２４．５１％（２５／１０２），而对照组仅为０．９４％（１／１０６）。提示单采血浆是ＨＧＶ感染的重要危险因素。ＨＧＶＲＮＡ和抗－ＨＧＶ的３年阴转率分别为３５．００％（７／２０）和１１．１１％（２／１８），说明ＨＧＶ感染有慢性携带趋势