Academic and molecular matrices: a study of the transformations of connective tissue research at the University of Manchester (1947-1996)

This paper explores the different identities adopted by connective tissue research at the University of Manchester during the second half of the 20th century. By looking at the long-term redefinition of a research programme, it sheds new light on the interactions between different and conflicting levels in the study of biomedicine, such as the local and the global, or the medical and the biological. It also addresses the gap in the literature between the first biomedical complexes after World War II and the emergence of biotechnology. Connective tissue research in Manchester emerged as a field focused on new treatments for rheumatic diseases. During the 1950s and 60s, it absorbed a number of laboratory techniques from biology, namely cell culture and electron microscopy. The transformations in scientific policy during the late 70s and the migration of Manchester researchers to the US led them to adopt recombinant DNA methods, which were borrowed from human genetics. This resulted in the emergence of cell matrix biology, a new field which had one of its reference centres in Manchester. The Manchester story shows the potential of detailed and chronologically wide local studies of patterns of work to understand the mechanisms by which new biomedical tools and institutions interact with long-standing problems and existing affiliations.     

Structural characterization of chondroitin sulfate from sturgeon bone

Chondroitin sulfate (CS) was purified for the first time from the bones of sturgeon and analyzed to evaluate its structure and properties. A single polysaccharide was extracted from sturgeon bone in a concentration of 0.28-0.34% for dry tissue and characterized as CS. By means of specific chondroitinases and HPLC separation of generated unsaturated repeating disaccharides, this polymer was found to be composed of ∼55% of disaccharide monosulfated in position 6 of the GalNAc, ∼38% of disaccharide monosulfated in position 4 of the GalNAc, and ∼7% of nonsulfated disaccharide. The charge density was 0.93 and the ratio of 4:6 sulfated residues was equal to 0.69, a value confirmed by ¹³C NMR experiments. Chondroitinase B confirmed that the purified sturgeon CS contained mainly GlcA (>99.5%) as uronic acid. PAGE analysis showed a CS having a high molecular mass with an average value of 39,880 according to HPSEC values producing a weight average molecular weight (Mw) of 37,500. On the basis of the data collected, it is reasonable to assume that CS isolated from sturgeon bone might be potentially useful for scientific and pharmacological applications, making this bony fish, which is generally discarded after ovary collection, a useful source of this polymer. Finally, this newly identified source of CS would enable the production of this macromolecule having a particular repeating disaccharide composition, structure, and biological properties.     

风湿病治疗药物的药物基因组学研究及进展

风湿病的传统治疗以激素和甲氨蝶呤为代表的改善病情药物为主,随着分子水平研究的深入,以肿瘤坏死因子α阻断剂为代表的多种靶向生物制剂进入临床。药物的选择性治疗必须依靠基因组及药物遗传学的研究,对不同患者疗效及药物毒副反应作个体化的分析,从而正确的选择药物。本文就风湿病的传统的甲氨蝶呤和TNF-α阻断剂在药物基因组学预测药物的疗效及副作用等进行综述。