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Immuno Gene Therapy of Rat Brain Tumors with interferon-gamma transfected glioma cells

Immunotherapy is a new promising approach in cancer treatment. In the future, it will hopefully offer an alternative to existing brain tumors treatments, which are unable to cure. We have established an experimental, low immunogenic, brain tumor model in the rat. We have increased tumor cell immunogenicity with mutagen treatment or transfection of IFN-g. Mutagen treated glioma cells (tum-) could c

Effects of dopamine and excitotoxicity in experimental models of Huntington's disease

Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an expansion of a CAG repeat in the HD gene, that leads to dysfunction and death of striatal neurons. The pathogenetic mechanisms underlying HD are not known, but excitotoxicity and dopamine (DA) have been suggested to play a role. In this thesis, the effects of excitotoxicity and DA have been studied in striatal in vit

Molecular studies of genetic changes in myxoid and round cell liposarcoma

Chromosomal translocations commonly result in the production of fusion genes and the fusion genes are often tumor-type specific. In myxoid and round cell liposarcomas (MLS/RCLS), almost 95% of the cases carry a t(12;16)(q13;p11). In the remaining 5% of the MLS/RCLS tumors, another translocation and fusion gene can be found, i.e. the t(12;22)(q13;q12). These translocations fuse CHOP on chromosome 1

Mechanisms and time course of cell death in embryonic nigral tissue and intrastriatal transplants.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and severely affects about one in a hundred persons over the age of fifty years. In PD, there is a reduced striatal concentration of the neurotransmittor dopamine, mainly caused by a degeneration of the dopaminergic neurons in the substantia nigra. Transplantation of embryonic dopamine neurons has been developed as an al

Factors Affecting Rates of Change in Soil Bacterial Communities

The soil bacterial community is under the constant influence of its environment. Changing any of the factors affecting the bacterial community will induce a selection pressure which, with time, will change the community. In this work the effect of changing the temperature or pH on the soil bacterial community was studied. Measurements using the [3H]-thymidine incorporation technique showed that th

The EGF-like Modules of Anticoagulant Protein S. Studies of Ca2+ binding and module interactions

Protein S functions as a cofactor to activated protein C (APC) in the degradation of factors Va and VIIIa. In plasma protein S circulates in two forms; 30-40 % circulates as free protein S molecules while the remaining 60-70 % exists in a 1:1 complex with C4b-binding protein (C4BP). Only the free form of protein S functions as a cofactor to APC. Protein S is a mosaic protein composed of four discr

Ultra-fast dynamics in atoms and molecules during photoionization: from attoseconds to femtoseconds

Treating the correlated behaviour of multiple particles is challenging for both theory and experiment. This thesis reports on a variety of experimental investigations aiming to advance the understanding of fundamental processes in atoms and molecules: double ionization, isomerization and dissociation. The emphasis lies on ultra-fast processes, where multiple electrons interact or nuclei move so ra

Environmentally Responsive Surface Coatings of Polyion-Surfactant Ion Complex Salts

Complexes formed between oppositely charged polyions and surfactant ions are known to have very rich phase behaviour in bulk solution. The work in this thesis investigates the possibilites of using such complexes as surface coatings. Stoichiometric polyion-surfactant ion complexes “complex salts” (CS) consisting of alkyltrimethylammonium surfactant ions and polyacrylates are typically insoluble i

Development of a Method to Measure Plasma Levels of Activated Protein C in Complex with Protein C Inhibitor

Acute myocardial infarction (MI) and deep venous thrombosis (DVT) are conditions caused by thrombus formation with activation of the coagulation system. The plasma concentration of the complex between activated protein C (APC) and protein C inhibitor (PCI), APC–PCI complex is increased in such states. We have devised an immunofluorometric assay employing a catcher antibody (M36) that recognizes a

Functional Organization of Cerebellar Modules Controlling Forelimb Movements: Climbing and Mossy Fibre Input and Motor Output via the Red Nucleus and Motor Cortex

A modular organization has recently been described for the cerebellar control system comprising the forelimb areas of the C1/C3/Y zones in the cerebellar cortex and nucleus interpositus anterior (NIA) of the cat. A module is a group of cells in NIA which receives homogenous climbing fibre input via Purkinje cells that belong to the same set of microzones in the C1/C3/Y zones. The organization of i

Influence of cisplatin on RNA structure in solution Escherichia coli tRNA(Ala) and human Wnt-5a 3' UTR model system studies

RNA molecules in the cellular environment have several important functions. In many cases, proper RNA function is intimately linked to proper three-dimensional structure of the molecule. Thus, it seems reasonable to assume that structural changes caused by external influence can strongly inhibit important cellular functions maintained by RNAs. Studies in this thesis have had a focus on the influen

Molecular analysis of Streptococcus pyogenes and its interactions with the human host

Streptococcus pyogenes causes infections only in humans, from trivial tonsillitis to life-threatening conditions. One of its most important virulence factors is the M-like protein family conferring resistance to phagocytosis to the bacterium. The M-like proteins are surface exposed rod-like molecules attached to the cell wall. Each strain of S. pyogenes expresses unique M-like proteins that bind t

Avian MHC: variation and selection in the wild

In vertebrates the Major Histocompatibility Complex (MHC) plays a central role in the specific immune defence against various pathogens. Compared with other coding genes the MHC genes exhibit an extremely high level of polymorphism that is maintained by balancing selection. The importance in the immune defence and the polymorphism make these genes interesting to study from an ecological and evolut

Endothelial and cardiac effects of 5-fluorouracil. An experimental and clinical study.

The cytostatic drug 5-fluorouracil (5-FU) has been shown to affect both morphology and function of vascular endothelium. These effects could be part of the pathophysiology for 5-FU induced cardiotoxicity. The present thesis explores the mechanisms of this endothelial toxicity. In an animal model, treatment with thromboprophylactic doses of the low-molecular weight heparin (LMWH) dalteparin could

A study of potassium channel activation as a pharmacological principle for vasodilation of cerebral blood vessels

Increasing [K+]o is intimately coupled to progressive ischemia and reduced CBF. In isolated cerebral and mesenteric arteries, it was found that significant differences in the vascular responses to [K+]o exist. Among the species studied, human cerebral arteries were the most sensitive artery to increasing [K+]o. Rabbit basilar arteries, denuded from the endothelium, showed increased sensitivity to

Hand-arm vibration syndrome; Consequences for hand function and quality of life

Workers exposed to hand-held vibrating machines may risk developing a hand-arm vibration syndrome (HAVS), a condition which can cause chronic impairment and disability. The aims of this thesis were 1) to obtain deeper insight and further knowledge of HAVS and the consequences for hand function, and aspects of quality of life (QoL); 2) to investigate the usefulness of clinical assessments in diagno

Gene description, activity quantification and physiological responses of mitochondrial alternative NAD(P)H dehydrogenases

In addition to proton-pumping complex I, the plant respiratory chain contains type II NAD(P)H dehydrogenases. These extra enzymes do not pump protons and consequently do not contribute to the electrochemical proton gradient. Database screening of the Arabidopsis genome identified seven type II NAD(P)H dehydrogenase homologues of which two and four genes were closely related to potato (Solanum tube

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

Regulation of lipid metabolism in rat and 3T3-L1 adipocytes; Cross-talk between Insulin, the neuro-peptides PACAP/VIP and with B1-integrins

Type 2 Diabetes is a disorder that increases globally, but mainly in the western world. One of the hallmarks of Type 2 diabetes is insulin resistance in the target tissues of insulin action (adipose tissue, liver and skeletal muscle). In addition, most patients with Type 2 diabetes are obese. Increased release of free fatty acids from the enlarged and/or dysfunctional adipose tissue is suggested t

Methods of Multi-Conjugate Adaptive Optics for Astronomy

This work analyses several aspects of multi-conjugate adaptive optics (MCAO) for astronomy. The research ranges from fundamental and technical studies for present-day MCAO projects, to feasibility studies of high-order MCAO instruments for the extremely large telescopes (ELTs) of the future. The first part is an introductory exposition on atmospheric turbulence, adaptive optics (AO) and MCAO, esta