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It is well-known that a majority of breast cancers are hormone-dependent, making endocrine therapy an important adjuvant treatment after surgery. Susceptibility to endocrine treatment is determined by the presence of estrogen receptors (ER) and progesterone receptors (PR) in the tumors. Tamoxifen is the most well-established endocrine treatment available, inhibiting tumor growth and improving surv
ABSTRACT In humans, synthetic vascular grafts heal with a limited ingrowth of endothelium. This fact might be responsible for inferior performance of synthetic grafts compared with native artery.Endothelial cells can be autotransplanted (seeded) into the graft in an effort to improve graft function. The attachment of endothelial cells to different graft materials was investigated in vitro (I). In
The vascular wall is an active, elastic and integrated organ made up of cellular and extracellular matrix (ECM) components. It is not a static organ; the components dynamically change and reorganize in response to physiological and pathological stimuli. Vascular injury induces a complex healing process, analogous to generalised wound healing. Subsequent to the inflammatory response, proliferation
In linkage analysis or, in a wider sense, gene mapping one searches for disease loci along a genome. This is done by observing so called marker genotypes (alleles) and phenotypes (affecteds/unaffecteds) of a pedigree set, i.e. a set of multigenerational families, in order to locate the loci corresponding to the underlying disease genes or, at least, to narrow down the interesting genome regions. I
In this thesis we explore and further develop several techniques used in the animal laboratory as well as in the clinical setting. In particular, we expand the understanding and usefulness of plethysmographic techniques in small rodents. Study I shows that the pressure signal from an un-restrained plethysmograph (UP) depends largely on heating and humidification of the inhaled air. This brings int
Atherosclerosis is a chronic inflammatory disease, characterized by the accumulation of lipids and fibrous tissue in the wall of medium and large-sized arteries. The characteristic culprit of the disease is the atheroma, or atherosclerotic plaque, a patchy thickening of the arterial wall which affects the lumen, inducing various degrees of stenosis. The rupture of the atherosclerotic plaques, foll
In this thesis, I have studied nitrogen turnover processes in watermeadows. A watermeadow is a wetland where water infiltrates through the soil of a grassland field. It is hypothesized that infiltration of water through the soil matrix promotes nutrient transformations compared to surface flow of water, by increasing the contact between water, nutrients, soil organic matter and bacteria. I have st
Atherosclerosis is the leading cause of death and disability in the western world. Its clinical complications include acute myocardial infarction, sudden death and stroke. Thirty to 40 % of all ischemic strokes are caused by a carotid stenosis. The acute clinical event is triggered by an occluding thrombosis and even more frequently by embolization. Besides the degree of stenosis, the structure of
The triggering mechanism in myocardial infarction (MI) and unstable angina involves coronary thrombus formation following plaque rupture. Coagulation is initiated by tissue factor that activates factor VII (FVII), and is inhibited by protein C and its co-factor protein S. Resistance to activated protein C (APC resistance) is a common risk factor for venous thrombosis caused by a mutation in the ge
Sphingomyelin (SM) is present both in eucaryotic cells and the diet. Sphingomyelinase (SMase) hydrolyses SM and generates ceramide that has been implicated in the regulation of cell growth, differentiation and apoptosis. Previously a SMase with alkaline pH optimum was identified in the intestinal tract. The thesis studied the distribution pattern, the species difference and the clinical implicatio
Group A streptococcus (GAS) is one of the most common of bacterial pathogens infecting humans, frequently causing throat and skin infection. Some GAS strains have surface-expressed virulence factors called M proteins that bind human plasminogen with high affinity. Plasminogen is a central component of the human fibrinolytic system, and is bound by an M protein termed PAM through defined binding mo
The main objective of this thesis was to investigate the fate of photoreceptor cells when using different strategies for retinal cell transplantation. Comparing transplantation of fragments of embryonic retina with cell suspensions of the same tissue we found that transplantation of fragments of embryonic retina result in mature transplants with a higher degree of cellular organization than transp
