The terminal differentiation of leukemic cells is closely connected to their death. The concept of differentiation therapy originates from the idea that forced maturation of leukemic cells could induce cell death without the side-effects that are provoked by ordinary chemotherapy. The tumour suppressor protein p53 is a transcription factor, and can induce cell cycle arrest and apoptosis of maligna

The aim of this thesis is to defend a novel mechanism that triggers arthritis susceptibility in both rats and mice through reduced production of reactive oxygen species (ROS), but also to introduce a novel model for chronic relapsing arthritis. Five papers are included, all of which employ animal models for rheumatoid arthritis and one that also uses animal models for multiple sclerosis. Paper I a

The childhood malignancy neuroblastoma develops from early cells of the sympathetic nervous system (SNS), and the tumors often produce catecholamines. Neuroblastoma cells retain several characteristics of immature sympathetic cells including the expression of a number of transcription factors normally expressed during embryogenesis. The genesis of the SNS requires the correct expression pattern of

Membrane proteins are particularly important to characterize, since they are involved in cellular processes of utmost importance in control and regulation of cells, such as transport across membranes, signal transduction and photosynthesis. The word "proteome" means all proteins expressed by a e.g. a cell or a tissue, at a certain time point and "proteomics" is the large scale study of these prote

An introduction into the theory and experimental background of particle physics and the ATLAS detector is given. The transition radiation tracker (TRT) which is vital to the particle tracking and identification is then described giving particular creedence to the calibration. The automation of this calibration is explained. The second half of this thesis and the central part dwells on the analyses

The timing of the postnatal development of the gastrointestinal (GI) tract in mammals is influenced by dietary and hormonal factors. It was hypothesized that accelerated GI cell turnover during maturation would result in a precoucios conversion to more mature digestive functions. Thus, it was investigated if red kidney bean lectin, phytohaemagglutinin (PHA) - a potent gut mitogen in adult rats - c

Cholecystokinin (CCK) and the related hormone gastrin have been claimed to exert trophic effects in the pancreas and gastrointestinal tract. Two types of receptors for CCK and gastrin are known to exist, the CCK-A and the CCK-B receptor. They differ in their affinty for CCK and gastrin. The CCK-A receptor has about 500 times higher affinity for sulfated than for non-sulfated CCK and gastrin, while

N-methyl-2-pyrrolidone (NMP) is an organic solvent widely used in the industry. Irritation of the eyes and in the respiratory system has been reported after occupational exposure to low air levels of NMP. The EU has also classified it as a developmental toxicant. NMP is easily absorbed in the gastrointestinal tract and airways and through skin. The general aim of this thesis was to develop and eva

The gastrointestinal tract has two opposing functions; to effectively absorb nutrients and to act as a safety barrier against hazardous substances in the environment. After birth these functions develops gradually. The present thesis focuses on how the intestinal permeability and pancreatic secretion changes during ontogenic development of the pig, with some methodological aspects on manipulations

Ferrochelatase catalyses the terminal step in heme biosynthesis by inserting a ferrous ion into protoporphyrin IX. The reaction mechanism has in this thesis been studied by mainly crystallographic methods. The structure of ferrochelatase from Bacillus subtilis co-crystallized with N-methyl mesoporphyrin allowed for the first time a characterization of the active site of the enzyme. The structure

Malaria is a serious disease that causes around 800 000 deaths per year. Current malaria control efforts are hampered by the widespread resistance to common antimalarial drugs, such as the 4-aminoquinoline derivative called chloroquine. Previous research has shown that specific modifications of chloroquine, including inclusion of organometallic fragments into the organic framework, can result in c

Transplantation antigens encoded in the major histocompatibility complex (MHC) bind peptides and present them to T cells. We showed that mouse T cells expressing transgenic human CD8 can recognise human MHC class I. Expression on mature T cells is sufficient for activation in a mixed lymphocyte culture but expression both on thymocytes and mature T cells is necessary for peptide specific MHC restr

This thesis is based on work trying to understand the normal and pathological interactions taking place between the immune system and cartilage, specifically involving the cartilage-specific protein typ II collagen (CII). The work has been carried out in an experimental model of rheumatoid arthritis namely collagen type II induced arthritis (CIA) in mice. CIA can be triggered in mice of certain MH

Proteoglycans (PGs) is a class of highly anionic macromolecules that consist of one or more linear polysaccharide chains (glycosaminoglycans, GAGs) covalently attached to a core protein. The biological functions of PGs are mainly due to the interactions of GAG chains with various protein ligands and regulatory factors, such as cytokines and growth factors. PGs and GAGs are critical for a diverse s

Mucosal infections trigger an inflammatory response that includes the secretion of cytokines and the recruitment of neutrophils to the infected site. This thesis describes studies examining the molecular mechanisms of neutrophil migration to sites of mucosal bacterial infection. Escherichia coli (E. coli) infection of epithelial cell layers stimulates chemokine secretion and chemokine receptor ex

The aim of this thesis work was to study phase diagrams, microstructure and phase separation in alkylglucoside systems. Both alkyl glucoside/water systems and microemulsions with alkyl glucosides have been studied. The phase diagram of the ternary n -nonyl-beta-glucoside (C9G1)/ n -decyl-beta-glucoside (C10G1)/water system has been determined and is discussed in relation to the binary C9G1/water

Mantle cell lymphoma (MCL) is an aggressive form of B-cell lymphoma (BCL) with poor clinical outcome. In this thesis, which is based upon five original papers, different approaches have been used to pinpoint and investigate molecular events that promote MCL tumor growth, progression or resistance to treatment. The aim has been to identify novel targets with the potential to eradicate malignant cel

In this thesis we have used P fimbriated E. coli as a model to investigate the mechanisms of bacterial recognition and cell activation by the urinary tract (UT) epithelium. We show that Toll like receptor 4 (TLR4) is crucial for the recognition and host response to P fimbriated E. coli. This response was independent of LPS and did not require CD14. TLR4 was abundant on epithelial cells throughout

In a long-term prospective follow-up in patients randomized to an ileal or colonic conduit, with implantation of one ureter using antireflux technique and the other without, the fall in the mean total GFR exceeded the expected age-related decline. The fall in the mean separate GFR did not differ between refluxing and antirefluxing anastomosis. Patients with a continent caecal reservoir (antireflux

In the studies of this thesis, a method for automated classification of myocardial perfusion images was successfully developed and evaluated. The results show that the method, based on artificial neural networks, was equally good, or even better than human experts. It was also found that physicians interpreting myocardial perfusion images benefit from the advice of the artificial neural networks.