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Now showing items 13066-13085 of 25619
  • Matihaldi, Hilkka-Liisa (1973)
  • Gustafsson, Anna Maria (1990)
  • Hero, Matti (Helsingin yliopisto, 2007)
    Without estrogen action, the fusion of the growth plates is postponed and statural growth continues for an exceptionally long time. Aromatase inhibitors, blockers of estrogen biosynthesis, have therefore emerged as a new potential option for the treatment of children with short stature. We investigated the efficacy of the aromatase inhibitor letrozole in the treatment of boys with idiopathic short stature (ISS) using a randomised, placebo-controlled, double-blind research setting. A total of 30 boys completed the two-year treatment. By decreasing estrogen-mediated central negative feedback, letrozole increased gonadotrophin and testosterone secretion in pubertal boys, whereas the pubertal increase in IGF-I was inhibited. Treatment with letrozole effectively delayed bone maturation and increased predicted adult height by 5.9 cm (P0.001), while placebo had no effect on either parameter. The effect of letrozole treatment on near-final height was studied in another population, in boys with constitutional delay of puberty, who received letrozole (n=9) or placebo (n=8) for one year, in combination with low-dose testosterone for six months during adolescence. The mean near-final height of boys randomised to receive testosterone and letrozole was significantly greater than that of boys who received testosterone and placebo (175.8 vs. 169.1 cm, P=0.04). As regards safety, treatment effects on bone health, lipid metabolism, insulin sensitivity, and body composition were monitored in boys with ISS. During treatment, no differences in bone mass accrual were evident between the treatment groups, as evaluated by dual-energy x-ray absorptiometry measurements of the lumbar spine and femoral neck. Bone turnover and cortical bone growth, however, were affected by letrozole treatment. As indicated by differences in markers of bone resorption (U-INTP) and formation (S-PINP and S-ALP), the long-term rate of bone turnover was lower in letrozole-treated boys, despite their more rapid advancement in puberty. Letrozole stimulated cortical bone growth in those who progressed in puberty: the metacarpal index (MCI), a measure of cortical bone thickness, increased more in letrozole-treated pubertal boys than in placebo-treated pubertal boys (25% vs. 9%, P=0.007). The change in MCI correlated positively with the mean testosterone-to-estradiol ratio. In post-treatment radiographic evaluation of the spine, a high rate of vertebral deformities - mild anterior wedging and mild compression deformities - were found in both placebo and letrozole groups. In pubertal boys with ISS treated with letrozole, stimulated testosterone secretion was associated with a decrease in the percentage of fat mass and in HDL-cholesterol, while LDL-cholesterol and triglycerides remained unchanged. Insulin sensitivity, as evaluated by HOMA-IR, was not significantly affected by the treatment. In summary, treatment with the aromatase inhibitor letrozole effectively delayed bone maturation and increased predicted adult height in boys with ISS. Long-term follow-up data of boys with constitutional delay of puberty, treated with letrozole for one year during adolescence, suggest that the achieved gain in predicted adult height also results in increased adult height. However, until the safety of aromatase inhibitor treatment in children and adolescents is confirmed, such treatment should be considered experimental.
  • Pyöli, Jouko (1975)
  • Vuorela, Marja-Liisa (1980)
  • Sarvamaa, Pirkko (1973)
  • Laurila, Jussi (2013)
    The aim of this thesis was to improve the quality of energy wood and therefore increase the potential of forest energy. About half of the mass of a freshly-felled tree consists of water. From the point of view of energy generation this water is unwelcome. There are two main ways to dry energy wood; these are artificial drying and drying naturally. The Norway spruce (Picea abies L. Karst.) stump wood dries fairly quickly in favourable natural conditions. The average moisture content (wet basis) of a stump was about 31 % one month after stump harvesting. Small-sized whole trees did not dry well at roadside storage sites under natural conditions. About one year after harvesting the moisture content of a small-sized whole tree was still about 43 %. However, during storing a remarkable weight loss of 37 % was detected between the forest and the heating plant. The most effective and the fastest drying method found in this study was the continuous compression drying method. The lowest moisture content of 30 % was achieved for Downy birch (Betula pubescens Ehrh.) by continuous pressing using 38 MPa and with a pressing time of 30 seconds. The energy consumption for compression drying is very low compared to the energy required to vaporise water in thermal drying. The techno-economic forest energy potential of the study area was 1.6 TWh/y. The forest energy potential calculations were made using the heating value of fresh wood and therefore the real potential will be greater when using dried energy wood. For absolutely dry wood the potential was about 1.9 TWh/y. The properties of energy wood vary widely depending on its assortment, storage conditions, as well as the weather conditions and the origin of the energy wood. However, a better understanding of energy wood properties will increase forest energy s potential and the use of renewable energy and thus help mitigate climate change globally.
  • Turunen, Rigina (1997)
  • Nymark, Penny (Helsingin yliopisto, 2010)
    Background: Asbestos is a well known cancer-causing mineral fibre, which has a synergistic effect on lung cancer risk in combination with tobacco smoking. Several in vitro and in vivo experiments have demonstrated that asbestos can evoke chromosomal damage and cause alterations as well as gene expression changes. Lung tumours, in general, have very complex karyotypes with several recurrently gained and lost chromosomal regions and this has made it difficult to identify specific molecular changes related primarily to asbestos exposure. The main aim of these studies has been to characterize asbestos-related lung cancer at a molecular level. Methods: Samples from asbestos-exposed and non-exposed lung cancer patients were studied using array comparative genomic hybridization (aCGH) and fluorescent in situ hybridization (FISH) to detect copy number alterations (CNA) as well as microsatellite analysis to detect allelic imbalance (AI). In addition, asbestos-exposed cell lines were studied using gene expression microarrays. Results: Eighteen chromosomal regions showing differential copy number in the lung tumours of asbestos-exposed patients compared to those of non-exposed patients were identified. The most significant differences were detected at 2p21-p16.3, 5q35.3, 9q33.3-q34.11, 9q34.13-q34.3, 11p15.5, 14q11.2 and 19p13.1-p13.3 (p<0.005). The alterations at 2p and 9q were validated and characterized in detail using AI and FISH analysis in a larger study population. Furthermore, in vitro studies were performed to examine the early gene expression changes induced by asbestos in three different lung cell lines. The results revealed specific asbestos-associated gene expression profiles and biological processes as well as chromosomal regions enriched with genes believed to contribute to the common asbestos-related responses in the cell lines. Interestingly, the most significant region enriched with asbestos-response genes was identified at 2p22, close to the previously identified region showing asbestos-related CNA in lung tumours. Additionally, in this thesis, the dysregulated biological processes (Gene Ontology terms) detected in the cell line experiment were compared to dysregulated processes identified in patient samples in a later study (Ruosaari et al., 2008a). Commonly affected processes such as those related to protein ubiquitination, ion transport and surprisingly sensory perception of smell were identified. Conclusions: The identification of specific CNA and dysregulated biological processes shed some light on the underlying genes acting as mediators in asbestos-related lung carcinogenesis. It is postulated that the combination of several asbestos-specific molecular alterations could be used to develop a diagnostic method for the identification of asbestos-related lung cancer.
  • Hienonen, Tuija (Helsingin yliopisto, 2005)
  • Hristozova, Nevena (2012)
    The white rot fungus Heterobasidion annosum s.l. is a basidiomycete which is considered to be the most economical important pathogen of conifer trees (Pinus, Picea and Abies) in the northern hemisphere. Presently, the knowledge on the biology and molecular aspects of the Heterobasidion pathosystem is still poor and this is the major set-back in preventing the spread of the pathogen. A deeper investigation at the molecular level of the pathogenicity factors involved during the infection process is very important to better control the disease. Intra-cellular signal-transduction pathways, and in particular the Mitogen Activated Protein Kinases (MAPKs), have been shown to play key roles in the infection cycle in many fungal pathogens, being pivotal in survival, appressorial formation, sporulation and response to various biotic and abiotic stresses. The aim of this study is to characterize a specific H. annosum MAPK, with high sequence homology to FUS3 gene (involved in mating) in S. cerevisiae and with PMK1 gene (involved in appressoria formation) in Magnaporthe grisea. In order to study the function of this MAPK in H. annosum, we performed a complementation experiment in the S. cerevisiae fus3􀂨 mutant. Expression level profiles, proteomics and immunology studies were used to distinguish between phosphorylated/active and non-phosphorylated/inactive form of the MAPK. Some valuable insights on this kinase cascade in Heterobasidion were discovered, but further studies are required to fully understand its role in the lifecycle of this fungus.
  • Luiro, Kaisu (Helsingin yliopisto, 2006)
    Neurodegenerative disorders are chronic, progressive, and often fatal disorders of the nervous system caused by dysfunction, and ultimately, death of neuronal cells. The underlying mechanisms of neurodegeneration are poorly understood, and monogenic disorders can be utilised as disease models to elucidate the pathogenesis. Juvenile neuronal ceroid-lipofuscinosis (JNCL, Batten disease) is a recessively inherited lysosomal storage disorder with progressive neurodegeneration and accumulation of autofluorescent storage material in most tissues. It is caused by mutations in the CLN3 gene; however, the exact function of the corresponding CLN3 protein, as well as the molecular mechanisms of JNCL pathogenesis have remained elusive. JNCL disease exclusively affects the central nervous system leaving other organs unaffected, and therefore it is of a particular importance to conduct studies in brain tissue and neuronal cells. The aim of this thesis project was to elucidate the molecular and cell biological mechanisms underlying JNCL. This was the first study to describe the endogenous Cln3 protein, and it was shown that Cln3 localised to neuronal cells in the mouse brain. At a subcellular level, endogenous Cln3 was localised to the presynaptic terminals and to the synaptosome compartment, but not to the synaptic vesicles. Studies with the CLN3-deficient cells demonstrated an impaired endocytic membrane trafficking, and established an interconnection between CLN3, microtubulus-binding Hook1 and Rab proteins. This novel data was not only important in characterising the roles of CLN3 in cells, but also provided significant information delineating the versatile role of the Rab proteins. To identify affected cellular pathways in JNCL, global gene expression profiling of the knock-out mouse Cln3-/- neurons was performed and systematically analysed; this revealed a slight dysfunction of the mitochondria, cytoskeletal abnormality in the microtubule plus-end, and an impaired recovery from depolarizing stimulus when specific N-type Ca2+ channels were inhibited, thus leading to a prolonged time of higher intracellular calcium. All these defective pathways are interrelated, and may together be sufficient to initiate the neurodegenerative process. Results of this thesis also suggest that in neuronal cells, CLN3 most likely functions at endocytic vesicles at the presynaptic terminal, potentially involved in the regulation of the calcium-mediated synaptic transmission.