This thesis describes several topics on angiogenesis and screening in uveal melanoma, the most frequent eye tumour in adults. The expression of vascular endothelial growth factor and other... Show moreThis thesis describes several topics on angiogenesis and screening in uveal melanoma, the most frequent eye tumour in adults. The expression of vascular endothelial growth factor and other angiostimulating factors in this tumour are described. In a second part, the use of different screening tests in screening for metastases of uveal melanoma is investigated. Show less
There is a fundamental difference between mammals and fish in how hypoxia affects the lipid metabolism by means of the stress hormone noradrenaline. In mammals, hypoxia induces an increase in lipid... Show moreThere is a fundamental difference between mammals and fish in how hypoxia affects the lipid metabolism by means of the stress hormone noradrenaline. In mammals, hypoxia induces an increase in lipid metabolism, which can eventually lead to tissue damage due to elevated plasma fatty acid levels, e.g. in case of a heart attack. However, hypoxia is not a normally occurring situation in healthy mammals as opposed to many fish species, because water is a relative poor source of oxygen. In hypoxic fish therefore, noradrenaline mediates a decrease in lipid metabolism, and we believe that this is a general protection mechanism in fish against lipid poisoning. There is a clear difference in the mode of breathing between mammals and fish, namely air- vs. water-breathing. Hence, we hypothesise that this difference is the cause for the opposing effects of noradrenaline. Therefore, we studied the effects of hypoxia on an air-breathing fish, the African catfish. However, physiologically this species reacted the same as other water-breathing fish, namely by means of a reduced lipid metabolism. Additionally, we demonstrated that, despite the opposing effects on the lipid metabolism, the transduction pathways in fish and mammals are very alike, and thus only a minor change has occurred in the course of evolution. This research has aided in a better understanding of the evolutionary changes in lipid metabolism.|Er is een fundamenteel verschil tussen zoogdieren en vissen in hoe het vetmetabolisme onder hypoxie (=zuurstoftekort) wordt veranderd door het stresshormoon noradrenaline. In zoogdieren leidt hypoxie tot een verhoogd vetmetabolisme, wat uiteindelijk zelfs weefselschade kan veroorzaken door te hoge vetzuurgehaltes, b.v. bij een hartaanval. Gezonde zoogdieren komen normaliter niet in zuurstofnood, in tegenstelling tot veel vissoorten, omdat water een relatief arme zuurstofbron is. In hypoxische vissen daalt dan ook het vetmetabolisme door noradrenaline, en wij denken dat dit een beschermingsmechanisme is tegen een vetzuurvergiftiging. Er is een duidelijk verschil in de manier van ademhalen van zoogdieren en vissen, respectievelijk lucht- en waterademhaling, en dit verschil ligt mogelijkerwijs ten grondslag aan deze verschillende effecten van noradrenaline; dit is de centrale hypothese van het onderzoek. Daarom is gekeken naar het effect van zuurstoftekort bij een luchtademhalende vissoort, de Afrikaanse meerval. Deze vis bleek echter fysiologisch hetzelfde te reageren als waterademhalende vissen, namelijk een verlaagd vetmetabolisme. Daarnaast is aangetoond dat, ondanks tegenovergestelde effecten op het vetmetabolisme, de aansturingmechanismen in vissen en zoogdieren vergelijkbaar zijn, en dat er dus maar een minimale verandering in de evolutie heeft plaatsgevonden. Dit onderzoek heeft bijgedragen tot een beter begrip van de evolutionaire veranderingen in het vetmetabolisme. Show less
The thesis deals with certain aspects of Katz modular forms over finite fields, in particular of weight one. A special case of Serre's conjecture is proved and the faithfulness of the Hecke module... Show moreThe thesis deals with certain aspects of Katz modular forms over finite fields, in particular of weight one. A special case of Serre's conjecture is proved and the faithfulness of the Hecke module of modular symbols is studied. Show less
The formation of snow and ice has always intrigued humans and challenged them to study these phenomena. Every snowflake has its own unique history of formation, but no two are alike. Like snow... Show moreThe formation of snow and ice has always intrigued humans and challenged them to study these phenomena. Every snowflake has its own unique history of formation, but no two are alike. Like snow-crystals, interstellar ices consist predominantly of water (H2O), but also contain significant fractions of other molecules such as carbon monoxide (CO), carbon dioxide (CO2), and methanol (CH3OH), and traces of dinitrogen (N2) and ammonia (NH3). The presence, or absence, of a molecule in the ice strongly depends on the environmental conditions. Vice versa, these molecules have an influence on their environment as well. Hence, the chemical composition and the structure of interstellar ices are thought to contain valuable information about the past and the future of interstellar regions, and it is for this reason that interstellar ices are simulated and studied under laboratory conditions. The present thesis contains a study of laboratory analogs of interstellar ices and presents a newly developed apparatus that provides a novel laboratory route to investigate the properties of these ices in more detail than has previously been possible. Show less
Finite temperature instantons - so called calorons - are considered in 4-dimensional pure Yang-Mills theory. Exact solutions are found along with zero-modes of the associated Dirac operator and the... Show moreFinite temperature instantons - so called calorons - are considered in 4-dimensional pure Yang-Mills theory. Exact solutions are found along with zero-modes of the associated Dirac operator and the moduli space of all solutions is described. Show less
Immune responsiveness is carefully regulated. Cells of the immune system have to respond adequately to invading micro-organisms and possibly to transformed cells, but tolerance for the own body... Show moreImmune responsiveness is carefully regulated. Cells of the immune system have to respond adequately to invading micro-organisms and possibly to transformed cells, but tolerance for the own body constituents needs to be preserved. Dendritic cells (DC) comprise a family of professional antigen presenting cells (APC) that play a central role in the regulation of the immune response. Immature DC, located in the periphery, can efficiently take up Ag, but lack the co-stimulatory signals for effective T-cell activation. Upon maturation, DC migrate to secondary lymphoid organs and increase the expression of co-stimulatory molecules and MHC molecules. Mature DC are very efficient in priming na____ve T-cells. In contrast to their T-cell priming capacity, DC in peripheral tissues constitutively process and present Ag in the absence of pathogen-related or endogenous inflammatory stimuli, and make a major contribution to peripheral tolerance by inducing unresponsiveness or deletion of specific T-cells. The central role of DC in controlling immunity makes these cells attractive tools for many clinical situations that involve T-cells: induction of tolerance in case of transplantation, allergy and autoimmune disease and induction of efficient T-cell responsiveness in case of infection and tumors. Many tumor components do not elicit Ag-specific T-cell responses in patients, which may be due to the absence of functional DC in tumors or the secretion of factors by tumor cells that reduce DC development and function. Application of tumor Ag to DC ex vivo and reinfusion of these DC leads to induction of specific immunity. In animals this strategy can lead to protection against tumors and even a reduction in size of established tumors. At present similar studies are carried out in patients. The research described in this thesis focuses on the requirements for induction of efficient cytotoxic T lymphocyte (CTL)- responses and tumor immunity by DC. Different modes of Ag presentation were studied for the induction of CTL-responses and tumor protection. Show less
