TY - THES AU - Himbergen, T.M. van PY - 2006 SN - 9090207333 UR - https://hdl.handle.net/2066/27457 AB - Paraoxonase type 1 (PON1) is an enzyme which belongs to the family of paraoxonases. Other members of the paraoxonase family are PON2 and PON3. In the human body, PON1 is located exclusively on the high-density lipoprotein (HDL) particle. As the name 'paraoxonase' indicates, PON1 can hydrolyze the highly toxic organophosphate and insecticide 'paraoxon'. Since paraoxon is a toxic chemical compound, it is not plausible that the hydrolysis of paraoxon is the primary biological function of PON1. Many research groups have previously suggested that the prevention of oxidation of low-density lipoprotein (LDL), is an important beneficial function of PON1 in the human body. Because the oxidation of LDL is one of the first steps in the development of atherosclerosis, the inhibition of LDL oxidation by PON1 may be an important step in the prevention of cardiovascular disease (CVD). There are also indications that PON1 can prevent the oxidation of the HDL particle and as a result preserve the beneficial function of HDL in the reverse cholesterol transport, i.e. the cholesterol efflux from macrophages. Since cholesterol efflux is an important function of the HDL particle, this interaction may also be an important second function of PON1. In this thesis, we have addressed the following questions regarding PON1. 1.) To what extent does PON1 inhibit the oxidation of LDL? 2.) Does PON1 influence the functioning of the HDL particle and as a result the lipid metabolism? 3.) To what extent does PON1 contribute to the onset of CVD. The main outcome of our studies is that, in contrast to what has been frequently suggested by other investigators, we cannot confirm that PON1 plays an important role in the oxidation of LDL in the human body. We do find that PON1 may have other effects which relate to CVD. We find that higher PON1 levels contribute to higher HDL-cholesterol levels in the body, demonstrating a beneficial role for PON1 in the lipid metabolism PB - [S.l. : s.n.] TI - Paraoxonase and cardiovascular disease: actions and interactions. N1 - RU Radboud Universiteit Nijmegen, 29 juni 2006 N1 - Promotor : Stalenhoef, A.F.H. Co-promotores : Tits, L.J.H. van, Roest, M., Voorbij, H.A. PS - 158 p. L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/27457/27457.pdf?sequence=1 ER - TY - THES AU - Smits-van der Graaf, C.A.A. PY - 2006 SN - 9090208917 UR - https://hdl.handle.net/2066/51060 PB - [S.l. : s.n.] TI - Pattern recognition receptors in Candida infection. N1 - RU Radboud Universiteit Nijmegen, 3 oktober 2006 N1 - Promotores : Kullberg, B.J., Meer, J.W.M. van der Co-promotor : Netea, M.G. PS - 153 p. ER - TY - THES AU - Stuyt, R.J.L. PY - 2006 SN - 9085591546 UR - https://hdl.handle.net/2066/27417 AB - Interleukin-18 (IL-18), a member of the IL-1 family, is a cytokine initially described as a co-stimulus for IFN- produced in mice injected with Propionibacterium acnes and lipopolysaccharide (LPS). It is produced by many cells of the immune system like macrophages, human peripheral blood mononuclear cells, dendritic cells, epidermal cells, osteoblastic stromal cells, and cells of the central nervous system. In the presence of secondary stimulants IL-18 is able to induce large amounts of IFN- by T cells and NK cells. IL-18 displays proinflammatory effects by inducing the production of proinflammatory cytokines and chemokines. Other proinflammatory effects of IL-18 include the upregulation of adhesion molecules. IL-18 possesses broad and potent immunomodulatory properties and therefore it plays an important role in host defenses against various infectious microbes. The aim of this thesis is to assess the position of IL-18 in the activation of the innate immunity and elimination of an invading pathogen. Several aspects have been investigated in this thesis; the place of IL-18 in the activation of the cytokine network, the direct proinflammatory properties of IL-18, and the role of IL-18 in severe infections. In our studies we have shown the importance of IL-18 (and the cytokines TNF, IL-1, and IL-12) in IFN- production induced by various microbial stimuli, such as Staphylococcus epidermidis and Staphylococcus aureus, and various staphylococcal exotoxins. Moreover, we found that IL-18 displays also proinflammatory effects by increase in expression of the adhesion molecule ICAM-1. Neutralization of IL-18 during lethal endotoxemia protects mice against lethal effects of LPS. This protection is partly mediated through inhibition of IFN- production, but mechanisms involving decreased neutrophil-mediated tissue damage due to the reduction of either chemokines (E. coli LPS) or TNF (S. typhimurium LPS) synthesis by anti-IL-18 treatment may also be involved. Furthermore, IL-18 plays a protective role in the defense against disseminated candidiasis. PB - [S.l. : s.n.] TI - The Role of Interleukin-18 in the Immune Response to Infection. N1 - RU Radboud Universiteit Nijmegen, 11 april 2006 N1 - Promotores : Meer, J.W.M. van der, Kullberg, B.J., Dinarello, C.A. Co-promotor : Netea, M.G. PS - 148 p. L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/27417/27417.pdf?sequence=1 ER - TY - THES AU - Setiati, T.E. PY - 2006 UR - https://hdl.handle.net/2066/49261 PB - [S.l. : s.n.] TI - Dengue virus infection. Clinical assessment, pathophysiology and management. N1 - RU Radboud Universiteit Nijmegen, 7 december 2006 N1 - Promotores : Meer, J.W.M. van der, Osterhaus, A.D., Soemantri, A. Co-promotor : Gorp, E. van PS - 143 p. ER - TY - THES AU - Mairuhu, A.T. PY - 2006 SN - 9036100461 UR - https://hdl.handle.net/2066/49389 PB - [S.l. : s.n.] TI - Studies on clinical and pathophysiological aspects of dengue virus infection. N1 - RU Radboud Universiteit Nijmegen, 20 september 2006 N1 - Promotores : Meer, J.W.M. van der, Osterhaus, A.D., Soemantri, A. Co-promotores : Brandjes, D.P., Gorp, E. van PS - 201 p. ER -