No abstract

Evidence-based medicine is critically dependent on three sources of information: a medical knowledge base, the patient's medical record and knowledge of available resources, including where appropriate, clinical protocols. Patient data is often scattered in a variety of databases and may, in a distributed model, be held across several disparate repositories. Consequently addressing the needs of an evidencebased medicine community presents issues of biomedical data integration, clinical interpretation and knowledge management. This paper outlines how the Health-e-Child project has approached the challenge of requirements specification for (bio-) medical data integration, from the level of cellular data, through disease to that of patient and population. The approach is illuminated through the requirements elicitation and analysis of Juvenile Idiopathic Arthritis (JIA), one of three diseases being studied in the EC-funded Healthe-Child project.

Through the analysis of genetically modified mice a hierarchy of transcription factors regulating pancreas specification, endocrine destiny as well as endocrine subtype specification and differentiation has been established. In addition to conventional approaches such as transgenic technologies and gene targeting, recombinase fate mapping in mice has been key in establishing the lineage relationship between progenitor cells and their progeny in understanding pancreas formation. Moreover, the design of specific mouse models to conditionally express transcription factors in different populations of progenitor cells has revealed to what extent transcription factors required for islet cell development are also sufficient to induce endocrine differentiation and the importance of the competence of progenitor cells to respond to the genetic program implemented by these factors. Taking advantage of this basic science knowledge acquired in rodents, immature insulin-producing cells have recently been differentiated in vitro from human embryonic stem cells. Taken together these major advances emphasize the need to gain further in-depth knowledge of the molecular and cellular mechanisms controlling beta-cell differentiation in mice to generate functional beta-cells in the future that could be used for cell therapy in diabetes.

Since ageing is accompanied by various alterations of the immune system, the aim of the present study was to investigate the effect of age on the expression of surface markers in peripheral blood monocytes. We studied 28 healthy young subjects and 28 elderly subjects fulfilling the criteria of the SENIEUR protocol. Peripheral blood mononuclear cells were isolated and the expression of various surface markers was analysed by double colour flow cytometry. The mean fluorescence intensity of the intercellular adhesion molecule- (CD54), CD29, CD45RO and CD32 was increased significantly in CD14+ cells of elderly people when compared with the young subjects. No significant differences were found in the expression of CD11a, CD11b, CD15, CD26, CD27, CD33, CD45RA, CD45RB, CD49d, HLA-DR and CD65. In summary, we demonstrated significant increase in four monocyte surface markers in subjects of old age; this finding may be related to certain immune phenomena observed in ageing subjects such as auto-immunity.