The general aim of this thesis was to molecularly characterize urothelial carcinoma (UC) at the transcriptional level using gene expression microarrays to improve the classification and pathogenetic understanding of this disease. In the first two studies (Articles I and II), gene expression profiling was used to study dysregulated transcriptional networks in a large cohort of UCs. We also investig

The chemokine receptors CCR5 and CXCR4 are required, together with CD4, for the entry of HIV-1 into target cells. CCR5 using HIV-1 dominates during transmission and the asymptomatic phase of infection. During progression, virus phenotypes with the ability to use CXCR4 emerge in about 50% of infected individuals. Individuals continuously harbouring CCR5-restricted isolates still progress to AIDS. D

Abstract Adrenocorticotrophic hormone (ACTH) has strong and direct lipid-lowering effects in man. All apoB-containing lipoproteins, i.e. VLDL, LDL, Lp(a), are reduced by 25-30%. In contrast, levels of HDL increase about 10%. In hepatic cell cultures, ACTH inhibits expression and secretion of apoB. In this thesis we corroborate that the reduced apoB synthesis, seen in hepatic cell systems, is als

Introduction: The mechanism of post ischemic reactive hyperemia is still unknown but now thought to be multifactorial and perhaps involving purinergic signalling. Purines such as ATP and ADP have recently been discovered to play a vital role in the regulation of vascular tone. We postulated that ADP could play a vital role in the mechanism of coronary post ischemic reactive hyperemia and that incr

The operational core of firefighting operations was examined. The effects of various firefighting procedures on the fire ground, their impact upon conditions on the fire ground in which decisions by commanding officers are made and the effects of allocating resources in time and space on the fire ground were explored. In addition, various approaches for modelling firefighting operations were discu

This thesis examines the microvascular inflammatory response in the skin. The microvascular response includes vasodilatation and plasma exudation. In the first three studies, the combined response was measured in guinea pig skin with a technique based on detection of radiolabelled protein. Transferrin was labelled in vivo by injection of 113mIn and the conversion electrons detected over the skin u

The present thesis aimed to examine how ischemic stroke affects the vascular endothelin and angiotensin systems in cerebral arteries. To study vascular receptor changes in ischemic stroke transient focal ischemia was induced in rats. In addition, rat cerebral arteries and arterial smooth muscle cells were cultured for further analysis of cerebrovascular receptor regulation. For functional studies

This study explores the role of brain-derived neurotrophic factor (BDNF) for neuronal vulnerability and neurogenesis following cerebral ischemia in the rat. Cerebral ischemia results in selective neuronal cell loss in specific brain regions. We here demonstrate the rank order of vulnerability in two regions affected by global forebrain ischemia, i.e., hippocampus and striatum, by combining specifi

The relationship between intracellular free calcium ([Ca2+]i) and force in smooth muscle was investigated in receptor-coupled permeabilized preparations and by fluorimetry of the calcium indicator Fura 2 in intact smooth muscle. The time integral of spontaneous [Ca2+]i transients in the intact rat portal vein was decreased by cyanide and, during tonic contraction, cyanide reduced force without cha

Food chain theory is based on consumption; that is, presupposing that the only important interaction between organisms is that they actually meet in an unstructured environment and that one of them is consumed. Recently, studies, including biomanipulation projects, have indicated that trophic interactions are more complex than predicted by food chain theory. In this thesis I examine the role of yo

Systems for on-line monitoring of bioprocesses were developed, consisting of a membrane-based sampling unit, a liquid chromatographic (LC) separation step, and a detector. Two sampling units, a tangential flow filtration (TFF) module and a microdialysis probe, were characterised and evaluated for use in different types of bioprocesses. When using the TFF module, an additional sample clean-up step

The sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) are present in human cerebral, meningeal and temporal arteries, as are peptides associated with the sympathetic (neuropeptide Y, NPY) and parasympathetic (vasoactive intestinal peptide, VIP) nervous system. NPY is a vasoconstrictor in cerebral and meningeal arteries and potentiates noradrenaline (NA) as a vasocon

Each Ig V-region has its own upstream promoter and the promoter of a mature Ig gene is thereby selected during the V(D)J recombination process. Upon comparison, it is evident that only one transcription factor binding site, the octamer, is preserved within all promoters. The octamer motif and the binding Oct-proteins are crucial for Ig promoter function, but not sufficient for a high level of tran

Mucosal inflammation and airway hyperreactivity are regulated by hundreds of different mediators. The recent discovery of gaseous mediators, produced and active within the airways, opens new possibilities for identification of therapeutic targets and ways to monitor airway inflammation. This thesis is focused on two such mediators, nitric oxide (NO) and carbon monoxide (CO) along with their role i

The aquaporins (AQPs) belong to a family of water permeable membrane channels found in virtually all living organisms. Thirteen isoforms of mammalian AQPs are found, whereas in Arabidopsis thaliana 35 genes encoding AQPs are found. The AQPs are distributed in different organs, cell types and in different subcellular membranes. The aquaporins form homotetramers where each monomer functions as an in

Controversies exist regarding both what is required for a proper diagnosis of chronic venous disease (CVD), and what treatment to offer patients. An objective evaluation is mandatory to individualize treatment. This thesis deals with the evaluation of patients with CVD with specific emphasis on CEAP classification (C; clinical, E; etiological, A; anatomical, P; pathophysiological), symptoms and si

With the goal to study the mechanisms of dinuclear metalloenzymes, a new line of synthetic and computational models were prepared and studied. Mixed imidazole and carboxylate multidentate complexes were synthesized to better simulate carboxylate-rich ligand environments. Of the compounds, which showed to be the most useful, were one symmetric and the other one asymmetric and in both cases they wer

Peripheral arterial disease (PAD) is the manifestation of atherosclerotic lesions in arteries supplying blood to the legs. Atherosclerosis is now recognized as an inflammatory disease of the vessel wall and important features in the pathophysiology are activation of WBC, endothelial cells and increased levels of inflammatory mediators. The inflammatory response in PAD is further influenced in case

Detta är den sjätte årsrapporten från Svensk Dagfjärilsövervakning, ett nationelltmiljöövervakningsprogram som koordineras av Lunds universitet på uppdrag avNaturvårdsverket sedan 2010. Svensk Dagfjärilsövervakning är ett samarbete mellan Sveriges Entomologiska Förening, Naturvårdsverket, Lunds universitet, Sveriges lantbruksuniversitet och Länsstyrelserna. Verksamheten möjliggörs av frivilliga la

Risk assessment of suicidal behaviour is one of the most important tasks in clinical psychiatry and a major determinant of subsequent care and treatment selections. To date, suicide risk assessment is based solely on clinical evaluations, which inevitably leads to subjective interpretations and decisions by the psychiatrist. In order to find more robust instruments in the evaluation of suicidality