Molecular biology & medicine最新文献_第4页

Autologous fibroblast implantation. Feasibility and potential problems in gene replacement therapy. 自体成纤维细胞植入。基因替代疗法的可行性及潜在问题。

Molecular biology & medicine Pub Date : 1990-12-01

P L Chang, J P Capone, G M Brown

{"title":"Autologous fibroblast implantation. Feasibility and potential problems in gene replacement therapy.","authors":"P L Chang, J P Capone, G M Brown","doi":"","DOIUrl":"","url":null,"abstract":"Autologous implants of genetically modified fibroblasts may be an ideal approach to gene replacement therapy. However, primary fibroblasts have limited life span and their use for gene therapy is questionable. We have developed a rat model to evaluate the feasibility of this approach. Primary fibroblasts initiated from rat skin biopsies were transfected with plasmid DNA. The transkaryotic fibroblasts were implanted into the original rat donors. A plasmid-encoded gene product, human growth hormone, was detected in the donor rats' circulation but less than 1% of the expected amount was recovered. Implantation at intraperitoneal, intramuscular or subcutaneous sites were effective in delivering the novel gene product. Fluctuating levels of human growth hormone were detected for over 6 months but their determination was rendered unreliable due to interference by extremely high titers of antibodies developed against the human growth hormone. In some cases, the antibody titer continued rising for more than 6 months, indicative of the continued presence of the antigen. One of the recipients developed two intra-abdominal fibrosarcomas that were shown to be derived from the implanted cells. In conclusion, this model demonstrates that autologous fibroblast implantation is a feasible approach to delivering novel gene products lasting for several months. Strong and prolonged immuno-reaction against the gene product will occur if the recipient's immune system is naive to the replacement product, as would occur in patients with CRM- mutations. The potential for neoplastic development from the implanted fibroblasts should prompt further evaluation of the long-term safety in gene replacement therapy.","PeriodicalId":77573,"journal":{"name":"Molecular biology & medicine","volume":"7 6","pages":"461-70"},"PeriodicalIF":0.0,"publicationDate":"1990-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13232572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Frameshift mutation in exon 3 of the lipoprotein lipase gene causes a premature stop codon and lipoprotein lipase deficiency. 脂蛋白脂肪酶基因外显子3的移码突变导致过早终止密码子和脂蛋白脂肪酶缺乏。

Molecular biology & medicine Pub Date : 1990-12-01

H E Henderson, R Devlin, J Peterson, J D Brunzell, M R Hayden

引用次数: 0

Role of acrocentric cen-pter satellite DNA in Robertsonian translocation and chromosomal non-disjunction. 中心中心中心卫星DNA在罗伯逊易位和染色体不分离中的作用。

Molecular biology & medicine Pub Date : 1990-10-01

K H Choo

{"title":"Role of acrocentric cen-pter satellite DNA in Robertsonian translocation and chromosomal non-disjunction.","authors":"K H Choo","doi":"","DOIUrl":"","url":null,"abstract":"The centromeres and short arms of the human acrocentric chromosomes have in common several families of tandemly repeated DNA. Recent analyses have revealed that, within some of these families, clearly distinct subfamilies have evolved that are unique to one or a subset of the different acrocentric chromosomes. The existence and maintenance of subfamilies common to different chromosomes entail a process of regular exchange between the non-homologous chromosomes. This process is suggested for the evolution of an alpha satellite subfamily recently found on chromosomes 13, 14 and 21. The presence of this alpha subfamily may allow pairing between these chromosomes leading to the observed non-random participation of these chromosomes in t(13q14q) and t(14q21q) Robertsonian translocations. The available data also indicate a very similar molecular organisation of the cen-pter region for chromosomes 13 and 21. This latter feature may further allow the two chromosomes to undergo a relatively extensive degree of meiotic pairing (in a manner analogous to that seen in the pseudoautosomal regions of the X and Y chromosomes), thus predisposing these two chromosomes to errors in meiotic segregation and non-disjunction.","PeriodicalId":77573,"journal":{"name":"Molecular biology & medicine","volume":"7 5","pages":"437-49"},"PeriodicalIF":0.0,"publicationDate":"1990-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13250816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular regulation of 5-aminolevulinate synthase. Diseases related to heme biosynthesis. 5-氨基乙酰丙酸合成酶的分子调控。血红素生物合成相关疾病。

Molecular biology & medicine Pub Date : 1990-10-01

B K May, C R Bhasker, M J Bawden, T C Cox

{"title":"Molecular regulation of 5-aminolevulinate synthase. Diseases related to heme biosynthesis.","authors":"B K May, C R Bhasker, M J Bawden, T C Cox","doi":"","DOIUrl":"","url":null,"abstract":"All nucleated animal cells synthesize heme to provide the prosthetic group of respiratory cytochromes. Large amounts of heme are synthesized by erythroid cells for hemoglobin production and by liver cells for drug-induced cytochromes P450. This review focuses on the first enzyme of the heme biosynthetic pathway, 5-aminolevulinate synthase (ALAS), which catalyzes the rate-controlling step in liver and possibly other tissues. We report that there are two distinct human genes for ALAS: one, a housekeeping gene, is probably ubiquitously expressed while the other is active only in erythroid tissue. By contrast it has been reported that, for porphobilinogen deaminase, the third enzyme of the heme pathway, there is a single human gene with two promoters; one functional in all tissues, the other erythroid specific. In liver, transcription of the housekeeping ALAS gene is induced by drugs and repressed by heme. Heme also acts in a novel way to prevent transport of ALAS into mitochondria, its site of function. Porphyrias result from inherited defects in enzymes of the heme pathway subsequent to ALAS and the molecular abnormality is now known for the most common subtype of acute intermittent porphyria. In developing red cells, levels of ALAS are regulated by increased gene transcription and by a post-transcriptional mechanism, in which iron most probably controls translation of erythroid ALAS mRNA through an iron-responsive element identified in the 5' untranslated region of the mRNA. The human erythroid ALAS gene is located on the X-chromosome, suggesting that a defect in this gene may be responsible for X-linked sideroblastic anemias.","PeriodicalId":77573,"journal":{"name":"Molecular biology & medicine","volume":"7 5","pages":"405-21"},"PeriodicalIF":0.0,"publicationDate":"1990-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13250814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Non-radioactive in situ hybridization of DNA probes to chromosomes and nuclei. A comparison of techniques. DNA探针对染色体和细胞核的非放射性原位杂交。技术的比较。

Molecular biology & medicine Pub Date : 1990-10-01

S S Habeebu, D H Spathas, M A Ferguson-Smith

引用次数: 0

The mucopolysaccharidoses. Diagnosis, molecular genetics and treatment. 黏多醣症。诊断、分子遗传学和治疗。

Molecular biology & medicine Pub Date : 1990-10-01

J J Hopwood, C P Morris

引用次数: 0

Methods of detection of single base substitutions in clinical genetic practice. 临床遗传学实践中单碱基置换的检测方法。

Molecular biology & medicine Pub Date : 1990-10-01

S Forrest, R G Cotton

{"title":"Methods of detection of single base substitutions in clinical genetic practice.","authors":"S Forrest, R G Cotton","doi":"","DOIUrl":"","url":null,"abstract":"The ability to diagnose human diseases at the DNA level has become possible because of a rapid development in DNA technology, particularly in the area of detection of single base substitutions. Mutations in the genomic DNA of a particular gene may be inferred indirectly using linkage analysis and restriction fragment length polymorphisms. However, direct detection of the mutation is the more favourable approach. The advent of the polymerase chain reaction to amplify specific regions of genomic DNA or mRNA has enhanced the speed and sensitivity of many of the screening and diagnostic procedures. Screening methods have been developed that will detect at least 70% and, with some methods, close to 100% of all mutations. The methods include ribonuclease A cleavage, denaturing gradient gel electrophoresis, chemical cleavage of mismatch and direct sequencing. Choice of method is based on a number of factors and will depend on the structure of the gene to be analysed. Following identification of a mutation using one of the screening procedures, prenatal diagnosis and carrier testing can be offered. The overall aim is to develop a method that has the potential to determine the mutation present in an index case of a previously untested family in a few days, thus allowing any other relevant family member to be tested.","PeriodicalId":77573,"journal":{"name":"Molecular biology & medicine","volume":"7 5","pages":"451-9"},"PeriodicalIF":0.0,"publicationDate":"1990-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13250817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

T cell recognition of stress proteins. A link between infectious and autoimmune disease. T细胞识别应激蛋白。传染病和自身免疫性疾病之间的联系

Molecular biology & medicine Pub Date : 1990-08-01

J R Lamb, D B Young

引用次数: 0

Sequence of a cDNA encoding human galactose-1-phosphate uridyl transferase. 编码人半乳糖-1-磷酸尿苷转移酶的cDNA序列。

Molecular biology & medicine Pub Date : 1990-08-01

J E Flach, J K Reichardt, L J Elsas

引用次数: 0

Direct gene diagnosis of cystic fibrosis by allele-specific polymerase chain reactions. 应用等位基因特异性聚合酶链反应直接诊断囊性纤维化。

Molecular biology & medicine Pub Date : 1990-08-01

M Wagner, M Schloesser, J Reiss

引用次数: 0