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Neurogenesis from Neural Stem Cells, Ependymal Cells and Fibroblasts

Stroke is a major cause of death and disability around the world. Stroke leads to loss of neurons and also other cells in the brain due to lack of blood supply. Currently no therapies are available to treat stroke-related disability. It has been shown that stroke leads to increased neurogenesis, birth of new neurons, within the brain. This increased neurogenesis is not sufficient to restore lost f

Targeting the hematopoietic stem cell to correct osteopetrosis

This thesis focuses on developing stem cell targeted gene therapy for the severe hereditary disorder Infantile Malignant Osteopetrosis (IMO) as well as increasing the understanding of how the genetic defect present in IMO affects the hematopoietic stem cells and hematopoiesis in general. IMO is a rare congenital disorder associated with an increased number of non-functional osteoclasts and the a

Radioimmunotherapy of Metastatic Disease - Studies of Alpha- and Beta-particle-Emitting Radionuclides in a Preclinical Model

In radioimmunotherapy, monoclonal antibodies (mAbs) are used as a targeting agent carrying a toxic payload consisting of radionuclides. This treatment allows the irradiation of small lesions, even on the microscopic level. In the present work, two radionuclides with different properties were used. Lutetium-177 (177Lu) is a beta-particle-emitting radionuclide (t½=6.7 days) and astatine-211 (211At)

Human neural stem cells: region-specific properties and prospects for cell therapy

Cell replacement by neural transplantation can, in animal models of neurodegenerative diseases, reconstruct damaged brain circuitry. In the clinical situation, the graft material used for cell therapy must, most likely, be of human origin. The human fetal brain is one potential source of neural stem cells (NSCs) for cell replacement therapy in neurodegenerative disorders such as stroke. Stroke is

Molecular Classification of Bladder Cancer

Decisions in the treatment of bladder cancer today are based on clinical and pathological risk variables such as tumor stage and tumor grade. The importance of these conventional risk variables is well documented since more than 10 years, and they are used routinely in the clinics. Over the last ten years, cancer research has seen a gradual transition towards personalized medicine, i.e. the exploi

ENHANCE YOUR WORKPLACE! A dialogue tool for workplace health promotion with a salutogenic approach

The aim of this thesis was to develop and make a quality assessment of a tool, which includes a questionnaire and a dialogue process that could be useful for workplace health promotion from a salutogenic point of view. The studies have been performed within two health care organizations between 2005 and 2009, together with hospital staff. Two questionnaire studies were conducted (n=446 n=505, resp

Prostate cancer and neuroendocrine differentiation. Molecular aspects in prostate cancer development

Hormone refractory prostate cancer occurs when androgen-deprivation therapy (ADT) fails to stop the growth of prostate cancer for any longer. Recent studies point towards a role for neuroendocrine (NE) differentiation in the development of hormone refractory disease. It has been hypothesized that NE-differentiated malignant tumor cells survive during ADT and promote development of androgen-indepen

Quantification of Fat Content and Fatty Acid Composition Using Magnetic Resonance Imaging

In obesity and several other disease scenarios, the measurement of fat accumulation in various organs and tissues has become a sought-after technique in clinical diagnostics and research. Especially, quantitative and non-invasive techniques which also provide images of accumulated fat throughout the body would be valuable. In the typical hospital, magnetic resonance imaging (MRI) is the only techn

Integrating fluvial processes into the global Si cycle

Silicon (Si) is ubiqutious in natural waters as dissolved silica (DSi) and is used as a nutrient by many plant and animal species. DSi ultimately derives from the weathering of silicate minerals, a process which also consumes atmospheric CO2 and couples the silicon and carbon cycles. These processes, among others, impart observable fractionations to the stable isotopes of silicon, which makes the

Household salt as an emergency radiation dosemeter for retrospective dose assessments using optically stimulated luminescence

In the event of a radiation accident, it is crucial to make rapid estimates of the absorbed dose received by both emergency workers, so-called first responders, and members of the public. Today, only personnel in rescue teams responding to nuclear emergencies have access to individual dosemeters. To make accurate assessments of the radiological consequences of an emergency situation, methods of re

A systematic approach to improving pharmacotherapy in the elderly

The aim of this thesis was to investigate whether a structured and systematic approach on improving pharmacotherapy in the elderly (the LIMM-model) would lead to a more appropriate and accurate drug use in the elderly. The elderly use many drugs and are more prone to suffer from adverse drug reaction. It is therefore important to address the quality of their drug therapy. The first study presente

Redistribution of moisture and ions in cement based materials

There were two principal objectives for this thesis. The first was to develop a methodology and evaluation model of moisture redistribution in order to make the future relative humidity in a screeded concrete slab predictable. The second objective was to develop a method to determine the critical humidity for ion transport in concrete. Residual moisture in screeded concrete slabs may be redistrib

FLT3 receptor in normal and malignant hematopoiesis

All hematopoietic cells originate from hematopoietic stem cells (HSCs) residing in the bone marrow (BM). The classical model of hematopoietic lineage commitment, that has been the prevailing model for hematopoiesis, proposes that the first lineage commitment step of HSCs and progenitors results in a strict separation of myelopoiesis and lymphopoiesis. However, an alternative model has already been

Involvement of non-dopaminergic systems in L-DOPA-induced dyskinsia

Parkinson's disease and L-DOPA-induced dyskinesia (LID) does not merely involve the dopamine (DA) system but also include non-dopaminergic systems such as glutamate and serotonin (5-HT). An aberrant glutamate transmission at the corticostriatal synapse, has been linked to LID. Pharmacological agents to glutamate receptors at this synapse, (of which some are already clinically tested), could preve

Brain plasticity and hand function

The aim of this thesis was to investigate the effects of cortical reorganisational changes following experimental deafferentation and peripheral nerve injury and apply the concept of brain plasticity to enhance sensory re-education following peripheral nerve injury and repair in the hand. In the first two papers the effects on hand function of contralateral deafferentation was investigated. Tourn

Assessment of myocardial viability using magnetic resonance imaging

Myocardial infarction (MI) following an acute coronary occlusion is a leading cause of morbidity and mortality. During revascularization, microemboli may complicate treatment and affect cardiac function. The long-term effects of microembolization are not fully elucidated. Following an MI it is important to accurately determine the size of the infarction, as it can be used for guidance in terms of

Analysis and Modelling of Desalination Brines

Seawater desalination constitutes an important water supply to the population bordering the Arabian Gulf, the Mediterranean Sea and the Red Sea. The three regions represent about 11.8% of the world land area and the countrieshosted approximately 9% of the world population in 1950 and 2008 and are also projected to do so in 2050. The results obtained for desalination capacity in the study area were

PET in the evaluation of head and neck cancer treatment - management of the neck

The treatment for head and neck squamous cell carcinoma (HNSCC) is surgery or (chemo)radiotherapy +/- surgery. Side effects related to therapy are long lasting and adversely affects quality of life. The incidence of oropharyngeal cancer is increasing and patients commonly present an advanced tumour stage with neck metastases at the time of diagnosis. The treatment protocol previously comprised rad

Neuroimmune Interactions of Enteric Neurons and Mast Cells: Friends or Foes?

Psychological distress or physical strain lead to reduced blood flow in the intestine since other organs are prioritised. One aim of this thesis was to investigate how ischemia followed by reperfusion affects the large intestine and the enteric nervous system (ENS). To do so an experimental ischemia/reperfusion (I/R) model was set up using rat large intestine. In order to study how the ENS reacts

Escalation: Explorative studies of high-risk situations from the theoretical perspectives of complexity and joint cognitive systems

The main aim of the research is to explore different aspects of organisational resilience in escalating situations, with an investigation of both theoretical and practical implications. From the platform of an explorative approach, this study makes use of naturalistic research in the domain of health care and experimental simulation studies, in order to establish a broad theoretical framework vis-