| 1. |
- Johansson, Annica, 1969
(författare)
-
Susceptibility Genes in Alzheimer’s Disease: Associations and Mechanisms
- 2004
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Alzheimer’s disease (AD) is the most common form of dementia, followed by frontotemporal dementia (FTD), in the elderly. It is a genetically heterogeneous disease characterized by progressive cognitive decline and memory impairment. In the rare early-onset familial form of the disease (FAD), causative mutations have been found in three different genes, the amyloid precursor protein (APP) gene and the presenilins 1 and 2 (PSEN-1 and -2). The predominant late-onset form of AD (LOAD) is a genetically complex disorder probably involving a combination of genetic factors together with environmental influences. To date, the only genetic risk factor identified for this complex form of AD is the APOE-ε4 allele. This only account for a fraction of all AD cases, thus several susceptibility genes remain to be found. The overall aim of this thesis is to study potential candidate genes for AD and FTD, and to see how variants of these genes influence quantitative traits related to AD pathology, both in cerebrospinal fluid (CSF), and in brain tissue. In the initial investigation, a polymorphism designated Ex6+7I/D in the cell division cycle (CDC2) gene was identified. Cdc2 is a protein kinase involved in cell cycle regulation and in neuronal differentiation. In AD brain, cdc2 is expressed in neurons and is involved in the abnormal phosphorylation of tau. The polymorphism was tested for association with LOAD. A significant association between the Ex6+7II genotype and AD was found, and also an increased frequency of the Ex6+7I allele in both AD and FTD. In the second paper, variants of CYP46A1, encoding cholesterol 24-hydroxylase (CYP46), were investigated for their association with AD. The polymorphisms were tested for association with quantitative traits related to AD pathology, including cerebrospinal fluid (CSF) levels of the 42 amino-acid cleavage product of β-amyloid (β-amyloid1-42), and the tau protein. In stratified analyses, one of the polymorphisms (rs754203) significantly influenced both CSF β-amyloid1-42 and phospho-tau in elderly APOE-ε4 carriers. In the final paper, AD and FTD patients were genotyped for a polymorphism in the Saitohin (STH) gene, a previously described gene located in the intron of the human Tau gene. Numerous polymorphisms span the human tau gene and are in complete linkage disequilibrium with each other yielding two separate haplotypes, termed H1 and H2. The H1 haplotype has been associated with both AD and FTD, and our patients were also investigated for this haplotype. In all patients (AD and FTD) and controls, the STH polymorphism and the Tau haplotype were in complete disequilibrium. The Tau haplotype and STH were not associated with AD and FTD, neither did they influence CSF-levels of total-tau, phospho-tau and β-amyloid1-42, nor neuropathological scores of plaque and tangles in brain tissue.
|
|
| 2. |
- Vumma, Ravi
(författare)
-
Functional Characterization of Tyrosine Transporters in fibroblast from Healthy Controls and Schizophrenic Patients
- 2008
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cultured human fibroblasts offer an advantageous system to investigate the amino acid transport properties without confounding the affects of disease state and its treatment in many systemic psychiatric disorders. In previous studies, fibroblast cells have been used to investigate the tyrosine transport across plasma membranes in patients with schizophrenia and autism with out characterizing the particular amino acid transporters.The importance of the major tyrosine transporters (system-L and system-A) was investigated in this study. Systemic functional characterization of tyrosine transport in fibroblasts from healthy controls and patients with schizophrenia, with respect to the system-L isoforms (LAT1, LAT2, LAT3, and LAT4) was performed.Ten (n=10) fibroblast cell lines from healthy controls and ten (n=10) from patients with schizophrenia were included in this study. Transport and uptake of [14-C] L-tyrosine in fibroblasts was measured using the cluster tray method in the absence and presence of different specific inhibitors. The maximal transport capacity, Vmax and the affinity constant of the tyrosine-binding site, Km, of LAT1 isoform were determined.The results of this study showed that tyrosine transport in fibroblasts is facilitated mainly by the system-L and LAT1 isoform is involved in 90% of total tyrosine uptake. LAT2 isoform seems to be functionally weak in uptake of tyrosine, as not more than 3% could be contributed by it. LAT3 and LAT4 contributed around 7%. System-A (ATA2 isoform) contributed around 10%. Alanine consequently inhibited the tyrosine transport by up to 60%. Tyrosine uptake and kinetics did not differ between patients and controls at the LAT1 isoform. Moreover, the affinity of LAT1 isoform for tyrosine was higher when compared to system-L. LAT1 is also involved in around 51% of uptake of alanine.In conclusion, the present thesis, confirms the presence of system-L with its isoform LAT1 as a main transporter of tyrosine in human fibroblast cells. The competition between tyrosine and alanine to get transported is shown to probably exist mainly at LAT1 isoform. Aberrant tyrosine transport observed in previous studies in patients with schizophrenia is probably not linked to the LAT1 isoform. This study gave further importance and established fibroblast cells as a suitable experimental model for studying amino acid transport properties in humans.Key words: Fibroblasts, Tyrosine and alanine transport, System-L, LAT1, LAT2, LAT3, LAT4, Schizophrenia, Precursor of Dopamine.
|
|
| 3. |
- Wang, Chunliang, 1980-
(författare)
-
Computer Assisted Coronary CT Angiography Analysis : Disease-centered Software Development
- 2009
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The substantial advances of coronary CTA have resulted in a boost of use of this new technique in the last several years, which brings a big challenge to radiologists by the increasing number of exams and the large amount of data for each patient. The main goal of this study was to develop a computer tool to facilitate coronary CTA analysis by combining knowledge of medicine and image processing.Firstly, a competing fuzzy connectedness tree algorithm was developed to segment the coronary arteries and extract centerlines for each branch. The new algorithm, which is an extension of the “virtual contrast injection” method, preserves the low density soft tissue around the coronary, which reduces the possibility of introducing false positive stenoses during segmentation.Secondly, this algorithm was implemented in open source software in which multiple visualization techniques were integrated into an intuitive user interface to facilitate user interaction and provide good over¬views of the processing results. Considerable efforts were put on optimizing the computa¬tional speed of the algorithm to meet the clinical requirements.Thirdly, an automatic seeding method, that can automatically remove rib cage and recognize the aortic root, was introduced into the interactive segmentation workflow to further minimize the requirement of user interactivity during post-processing. The automatic procedure is carried out right after the images are received, which saves users time after they open the data. Vessel enhance¬ment and quantitative 2D vessel contour analysis are also included in this new version of the software. In our preliminary experience, visually accurate segmentation results of major branches have been achieved in 74 cases (42 cases reported in paper II and 32 cases in paper III) using our software with limited user interaction. On 128 branches of 32 patients, the average overlap between the centerline created in our software and the manually created reference standard was 96.0%. The average distance between them was 0.38 mm, lower than the mean voxel size. The automatic procedure ran for 3-5 min as a single-thread application in the background. Interactive processing took 3 min in average with the latest version of software. In conclusion, the presented software provides fast and automatic coron¬ary artery segmentation and visualization. The accuracy of the centerline tracking was found to be acceptable when compared to manually created centerlines.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Engqvist, Ulf
(författare)
-
Om samarbetet mellan barn- och ungdomspsykiatri och vuxenpsykiatri : Personalens kompetens och patienternas behov
- 2002
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Avhandlingen behandlar gränsområdet mellan barn- och ungdomspsykiatri och vuxenpsykiatri. Syfte: att beskriva hur det går för barn- och ungdomspsykiatrins patienter, vilken den patientgrupp är som blir gemensam för de båda disciplinerna och vad som krävs för att utveckla samarbetet för äldre tonåringar/unga vuxna i åldrarna 16-25 år. Metod: Journal och registerstudie. Enkätundersökning riktad till personalgrupperna inom de två psykiatriska disciplinerna. Resultat: 25 patienter, 1,8 procent avled, majoriteten på grund av självmord. Drygt var 4:e tidigare BUP-patient och nästan dubbelt så många kvinnor som män (1,7:1), har sökt vuxenpsykiatrisk kontakt efter den barn- och ungdomspsykiatriska vården. En tredjedel av de tidigare BUP-patienterna var kända i kriminalregistret. Elva personer, 0,8 procent hade utvecklat så allvarligt missbruk att LVM-vård hade skett. Resultaten av enkätundersökningen tyder på att det inom vuxenpsykiatrisk verksamhet finns brister när det gäller barn- och ungdoms kunskap i allmänhet och att det finns skillnader i syn- och arbetssätt mellan disciplinerna. Övergången för patienter från barn- och ungdomspsykiatrin till vuxenpsykiatrin sågs som ett problem av båda personalgrupperna.
|
|
| 10. |
- Flemme, Inger, 1947-
(författare)
-
Health-related quality of life in recipients with an implantable cardioverter defibrillator due to life-threatening arrhythmias : a 5 year follow-up
- 2004
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general aim of this thesis was to describe self-reported health-related quality of life (HRQoL) in recipients with an implantable cardioverter defibrillator (ICD) due to life-threatening arrhythmias over a 5-year period. The design was prospective and longitudinal. Fifty-six patients participated in Paper I, and 35 of these patients, who had survived at least five years, were included in paper II. All patients had received their ICD as a form of secondary prevention. The Quality of Life Index-Cardiac version (QLI-C), Mishel Uncertainty in Illness Scale-Community version (MUIS-C), and multiple regression analysis were used. Higher scores indicate higher HRQoL and uncertainty. The questionnaires were completed on four occasions: before implantation, at three months and at 1 year and 5 years after implantation. ICD recipients were also asked how many shocks they had perceived. At the 5-year data collection, the average ICD recipient had lived with an ICD for 6 years and 9 months. In general HRQoL was lower at year 1 than at baseline (p = 0-033). A decrease in the socioeconomic domain was observed at year 1 (p = 0.006) but improved again at year 5 (p = 0.027) although it remained below the baseline value. ICD recipients' satisfaction with the family domain decreased from the time of the ICD implantation (p < 0.001) and from year 1 (p = 0.039) to year 5 after implantation. Uncertainty related to information had decreased at year 1 in relation to baseline (p < 0.001). A decrease in overall uncertainty was observed at year 5 in relation to year 1 (p = 0.009) as well as at year 6 in relation to baseline (p = 0.009). The longer the ICD recipient had lived with the device, the greater the risk of receiving a shock. However, ICD recipients who received shocks reported being less troubled by them over time. Uncertainty was identified as a predictor of Low HRQoL. The recipients reported a higher level of HRQoL at year 5 than at year 1. HRQoL was reasonably good 5 years after implantation, and the ICD recipients felt more secure and perceived their ICD as a lifesaver.
|
|
