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Dynamics of Ca2 handling in vascular smooth muscle

Intracellular Ca2+ is a key regulator of vascular contractility, and thereby of blood perfusion and pressure. Ca2+ signals are essential also for cell migration, proliferation and regulation of numerous enzymes. Besides producing vascular contraction smooth muscle cells may also modulate to a synthetic phenotype and proliferate as an initial stage in the atherosclerotic process. In this work we sh

Assessing carotid plaque structure

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

Pro- and anticoagulant mechanisms in coronary artery disease. Clinical studies on factor VII and resistance to activated protein C

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

Glucocorticosteroid effects on cytokine production: studies in a glucocorticosteroid resistance model and in allergic airway disease

Glucocorticosteroids (GCS) are potent anti-inflammatory drugs, probably due to inhibitory effects on cytokine production. However, a small number of asthma patients seem GCS-resistant. Pro-inflammatory cytokines, such as interleukin-2(IL-2) and IL-4, produced during allergic airway inflammation have been proposed to induce the resistance to GCS. IL-2 and IL-4 also induce GCS resistance in mononucl

Growth factor regulation of the urokinase plasminogen activator (uPA) system in human endometrium, and the significance of uPA receptor activation in endometrial angiogenesis.

The purpose of this thesis was to examine the role of growth factors and the urokinase plasminogen activator (uPA) system in human endometrial angiogenesis. Growth factors as well as progesterone increased expression of the main inhibitor of uPA (PAI-1) in primary cultures of endometrial stromal cells. EGF, TGF-beta1 and bFGF increased gene transcription whereas progesterone increased mRNA stabili

Alkaline Sphingomyelinase; A Potential Inhibitor in Colorectal Carcinogenesis

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

Tissue tropism among group A streptococci - importance of bacteria associated proteolytic activity

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

Solute exhange across the alveolo-capillary barrier.

The aim of this thesis was to study the transfer of solutes across the alveolo-capillary barrier in experimental models of alveolar surfactant dysfunction and lung injury as well as in smokers. Experimental studies were performed in anaesthetized, and mechanically ventilated animals. Surfactant dysfunction was induced by administration of a synthetic detergent in aerosol form. Lung injury was indu

Staphylococcal enterotoxin H - structure and function of a superantigen

The aim of this thesis was to characterise the biological functions of the superantigen staphylococcal enterotoxin H (SEH). Superantigens are highly immunostimulatory proteins, which crosslink T cells and antigen presenting cells (APCs). SEH is included in a family of staphylococcal enterotoxins (SEs) produced by certain strains of Staphylococcus aureus. The three-dimensional fold of SEH was dete

Memory Illusions and Memory Attributions : Behavioural and Electrophysiological Data

Although memory often serves us well, it can also prove highly unreliable. The study of illusions and distortions of memory unveils important information about the nature of human memory functioning and, moreover, factors affecting memory accuracy. By taking a cognitive neuroscience perspective, the present dissertation aimed at elucidating processes promoting both true and false remembering and t

Structural studies of metal-binding proteins revealing dynamic behaviour

The Mg2+ and Mn2+ structures of calbindin D9k have been determined and they reveal a conformational change compared to the structures of apo and (Ca2+)2-calbindin D9k. These findings are unique, since normally calcium and not magnesium is known to induce conformational changes of EF-hand proteins. It has also been shown that calbindin D9k binds one Mg2+ (Kd=1mM) in the regular C-terminal EF-hand c

Phase Behavior and Solution Properties of Aqueous Polyion-Surfactant Ion Systems

Polyelectrolytes and oppositely charged surfactants interact through attractive electrostatic forces, which in many cases lead to phase separation already at low total concentrations. During the past 10-15 years investigations of these systems have been simplified through the use of complex salts that consist of surfactants with polymeric counterions in a 1:1 charge stoichiometry (no excess simple

Endothelial cell seeding and the thrombogenicity of vascular grafts

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

Injury-Induced Signalling in Arterial Smooth Muscle Cells

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

Dynamic fixation of unstable trochanteric hip fractures. A clinical and radiographic evaluation of the Medoff sliding plate.

In stabilising extracapsular hip fractures, the Medoff sliding plate (MSP) differs from other screw-plates by its compression capacity along the femoral shaft (uniaxial dynamization). Additional compression along the neck of femur can be achieved by primary release of the lag screw (biaxial dynamization). 244 consecutive inter- and subtrochanteric fractures in 243 elderly patients were fixed with

Cobalamin/folate status and its relation to cognition and behaviour in psychogeriatric patients.

The aim of this study was to evaluate the diagnostic potentials of four different biochemical markers, serum cobalamin, blood folate, plasma homocysteine and serum methylmalonic acid for diagnosis of cobalamin/folate deficiency in a psychogeriatric population. The second aim was to investigate the relationship between these markers and various clinical and functional parameters of the nervous syst

Changes and tendencies in European university educations in land surveying

The European university market in land surveying and land management is diversified. In many countries MSc programmes have a strong geomatic profile. In the Nordic countries the BSc and MSc engineering programmes integrate geomatics, land legislation, land policies, planning, real estate economics and property management. Such diversity is attractive for youngsters in choosing their university stu

Fungal Lectins. Molecular structure and function of a member of a novel lectin family.

Lectins defined as non-enzyme, non-immunoglobulin carbohydrate binding proteins, have been found in a wide variety of viruses, bacteria, fungi, plants and animals. Although lectins have been purified from more than 60 different species of fungi, the structure and biological functions of these proteins are not well known. I examined the molecular structure of a lectin (designated AOL) isolated from

Role of adhesion molecules and chemokines in TNF-alpha-induced leukocyte recruitment

Migration of leukocytes from the circulating blood into the extravascular tissue is a key component in inflammatory reactions. Leukocyte extravasation (rolling-activation-adhesion-transmigration) is strictly coordinated by adhesion molecules and chemokines expressed on cell surfaces and in tissues. Tumor necrosis factor-alpha (TNF-alpha) is pleiotrophic cytokine, which plays an important role in t