Skip to main content
Login | Suomeksi | På svenska | In English

Browsing by department "Biolääketieteen laitos"

Sort by: Order: Results:

  • Döhla, Julia Maria (2013)
    Peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) is a transcriptional coactivator involved in mitochondrial biogenesis, oxidative stress response, and energy metabolism. PGC-1α is part of an energy sensing network that translates environmental influences into alterations in gene expression of mainly mitochondrial molecular pathways. A role in neuroprotection has been implicated for PGC-1α in the context of mitochondrial expression networks. Our research group has previously established a transgenic mouse line with stable overexpression of PGC-1α in brain neurons. Transgenic overexpression of PGC-1α is associated with an enhanced functional state of mitochondrial energy production. In the context of neurodegenerative processes, brain neurons of PGC-1α transgenic mice are protected against oxidative stressors in the MPTP mouse model of Parkinson's Disease. To further characterize the transcriptional activity of PGC-1α regulated gene networks in brains of transgenic mice, a quantitative real-time PCR based system was established. Gene expression was measured for a subset of genes found to be differentially regulated in a microarray based screening of RNA obtained from hippocampus and cortex of PGC-1α transgenic mice. Increased PGC-1α gene expression was found in hippocampus and cortex of PGC-1α transgenic mice, and their translation into protein was confirmed immunohistochemically. Expression analysis revealed significant changes in mRNA levels of PGC-1α controlled molecular pathways involved in mitochondrial energy production and antioxidant responses. Furthermore, alterations in the expression of some non-mitochondrial genes with established links to neurodegeneration were observed. Furthermore, a change in GABAA receptor subunit expression was detected. In accordance with previous studies on the PGC-1α transgenic mouse line, these findings suggest that differential gene expression associated with PGC-1α overexpression contributes to an enhanced functional state of neurons in hippocampus and cortex of PGC-1α transgenic mice. Increased knowledge about the transcriptional modulation of neuronal genes regulated by PGC-1α can lead to better insights into mechanisms governing neurodegeneration and neuroprotective pathways. Pharmacological modulation of PGC-1α activity may be a feasible approach for neuroprotective treatments in neurodegenerative diseases, such as Parkinson's Disease.
  • Koskela, Ilkka (2014)
    Basilar artery occlusion (BAO) is one of the most severe neurological diseases associated with high mortality and morbidity. According to previous studies, aetiology, risk factors and outcome of BAO differ from other stroke subtypes, and little information exists on the characteristics of young adult BAO patients. This study is a retrospective observational case-control study of a large registry of consecutive young adult stroke patients (aged 15 to 49 years) treated in the Helsinki University Central Hospital between 1994 and 2007, first describing in detail the risk factors, aetiology, symptom severity and subsequent mortality and disability of young adult BAO-patients, and comparing them with other young adult stroke patients. We found that smoking is significantly less common in BAO patients than in non-BAO-patients (25% vs 45.2%, respectively), large artery atherosclerosis and vertebral or basilar artery dissection are significantly more common in BAO-patients than in non-BAO-patients (25% vs 7.8% and 32.2% vs 7.8%) whereas cardioembolisms, small vessel disease, and internal carotid artery dissection were significantly less common in BAO-patients. Stroke symptoms were significantly more difficult in BAO patients vs non-BAO patients (NIHSS medians 9 [range 0-35] vs 3 [range 0-30]) and follow-up disability defined by the modified Rankin Scale was significantly higher in BAO -patients (good outcome of mRS 0-2 in 53.6% of BAO patients vs 82.3% in non-BAO-patients at 3 months) along with mortality (BAO vs non-BAO-patients 28.6% vs 14.7%). Further development in diagnostics, treatments and rehabilitation is needed to manage BAO in young adult patients.
  • Lankinen, Christoffer (2014)
    Mål: Syftet med studien var att kartlägga behovet av akuta ambulanstjänster förorsakade av diabetes inom HUCS Peijas sjukvårdsområde under året 2012, att undersöka hur ofta patienten kunde lämnas hemma efter behandling och hur många patienter som behövde ambulanstjänster på nytt inom en tid på 4 veckor. Metoder: Denna studie är en retrospektiv, deskriptiv studie baserad på ambulans- och sjukhusjournaler. Alla fall som var kategoriserade som störning av sockerbalansen i HUCS Peijas sjukvårdsområde under året 2012 samlades in och analyserades ifall patienten hade hypo- eller hyperglykemi vid ankomst av akutvårdspersonalen. Resultat: Materialet utgjordes av 146 ambulansuppdrag. Antalet patienter totalt var 94. Hypoglykemi var den vanligaste orsaken till behov av ambulanstjänst med 130 uppdragorsakade av 79 patienter. Av dessa uppdrag orsakades 50,8% av 15patienter med 2 eller fler hypoglykemiepisoder. I 16 uppdrag hade patienten hyperglykemi och 4 av fallen hade ketoacidos. Av patienter som lämnades hemma efter behandling fick 10,9% återfall inom 4 veckors tid. 2 patienter fick återfall inom 24 h efter behandling. Slutsats: En stor del av hypoglykemierna inom akutvården uppstår hos en liten mängd patienter med relapser. Dessa patienter borde beaktas i protokollen för behandling av hypoglykemi.
  • Olkkonen, Juri (2015)
    Introduction: Patients with rheumatoid arthritis (RA) have disturbances in the hypothalamic-pituitary-adrenal (HPA) axis. These are reflected in altered circadian rhythm of circulating serum cortisol, melatonin and IL-6 levels and in chronic fatigue. We hypothesized that the molecular machinery responsible for the circadian timekeeping is perturbed in RA. The aim of this study was to investigate the expression of circadian clock in RA. Methods: Gene expression of thirteen clock genes was analyzed in the synovial membrane of RA and control osteoarthritis (OA) patients. BMAL1 protein was detected using immunohistochemistry. Cell autonomous clock oscillation was started in RA and OA synovial fibroblasts using serum shock. The effect of pro-inflammatory stimulus on clock gene expression in synovial fibroblasts was studied using IL-6 and TNF-a. Results: Gene expression analysis disclosed disconcerted circadian timekeeping and immunohistochemistry revealed strong cytoplasmic localization of BMAL1 in RA patients. Perturbed circadian timekeeping is at least in part inflammation independent and cell autonomous, because RA synovial fibroblasts display altered circadian expression of several clock components, and perturbed circadian production of IL-6 and IL-1b after clock resetting. However, inflammatory stimulus disturbs the rhythm in cultured fibroblasts. Throughout the experiments ARNTL2 and NPAS2 appeared to be the most affected clock genes in human immune-inflammatory conditions. Conclusion: We conclude that the molecular machinery controlling the circadian rhythm is disturbed in RA patients.
  • Miao, Zefeng (2014)
    Gemfibrozil is a fibric acid derivative used in the treatment of dyslipidemia. It activates peroxisome proliferator activated receptor α (PPARα) and alters lipoprotein metabolism gene expression. PPARα may also regulate the expression of drug disposition genes (e.g., CYP3A4). The aim of this study was to investigate possible effects of gemfibrozil on drug transporter gene expression in human whole blood. In a randomized crossover study, 10 healthy volunteers took 600 mg gemfibrozil or placebo twice daily for 6 days (Filppula et al. 2013). On the morning of day 3, a venous blood RNA sample was collected from each participant into a PaxGene® tube. The expression of 18 ABC, 24 SLC and 10 SLCO transporters was investigated using reverse transcription quantitative real-time PCR (RT-qPCR) with OpenArray® technology on a QuantStudio™ 12 K Flex Real-Time PCR system (Life Technologies, Paisley, UK). FPGS, TRAP1, DECR1 and PPIB served as reference genes. A total of 31 transporters, including 15 ABC transporters, 13 SLC transporters and 3 SLCO transporters were significantly expressed in whole blood during the placebo phase. Gemfibrozil appeared to alter the expression of three transporters. The expression of SLCO3A1 was increased by 34% by gemfibrozil (P=0.004), but gemfibrozil reduced the expression of ABCG2 and ABCC3 by 31% (P=0.018) and 50% (P=0.045), respectively. However, none of the differences remained statistically significant after correction for multiple testing. In conclusion, these data suggest that gemfibrozil might alter the gene expression of certain drug transporters in human blood.
  • Pyöriä, Lari (2014)
    In our research we studied if the overexpression of VEGF-A would save the impaired tumor growth in PROX1 silenced colorectal cancer xenografts. We conducted both small hairpin PROX1 and VEGF-A gene transfers to SW1222 colorectal cancer cells using lentiviral vectors. SW1222 cell lines were then injected to Nod scid gamma mice and grown for 14 days for analysis. We also established 3D cocultures of genetically modified SW1222 cell line together with lymphatic endothelial cells or blood endothelial cells to analyze lymphangiogenesis and angiogenesis in vitro. We found out that overexpression of VEGF-A rescues the growth of PROX1 silenced tumors. Large necrotic areas in the central of the PROX1 silenced tumors remain even though VEGF-A overexpression induces greater vascularity in these xenografts. In 3D cocultures silencing of PROX1 did not affect in vitro lymphangiogenesis or angiogenesis.
  • Ahlsten, Manuel (2011)
    Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene were recently shown to predispose to pituitary adenomas, which are neoplasms of the anterior pituitary gland. AIP mutations were first discovered in a cluster of familial pituitary adenomas in Northern Finland and afterwards in several populations worldwide. AIP associated pituitary adenomas are predominantly growth hormone secreting, thus several patients present with acromegaly or gigantism. The aim of this study was to elucidate AIP related pituitary tumorigenesis. AIP is suggested to be involved in several cellular pathways such as the xenobiotic response. In the cytosol, AIP interacts directly with aryl hydrocarbon receptor (AHR). After interaction with xenobiotic compounds AHR translocates to the nucleus and binds aryl hydrocarbon receptor nuclear translocator (ARNT). The AHR/ARNT heterodimer regulates the expression of several xenobiotic metabolizing enzymes. The AHR pathway is linked to e.g. the hypoxia response and estrogen signaling through ARNT and possibly through ARNT2, an ARNT homolog. A previously generated heterozygous Aip (Aip+/-) mouse model was used to study the role of these pathways in AIP-mediated tumorigenesis. Immunohistochemical studies revealed that expression of either ARNT or ARNT2 protein was lost in the mouse tumors. Aip+/- mice were also crossed and pregnant mice dissected to acquire Aip knockout (Aip-/-) and Aip wildtype (Aip+/+) embryos. Mouse embryonic fibroblast cell lines were prepared from these embryos and protein extracts were used for western blot analysis. This analysis revealed that expression of ARNT and ARNT2 was uniform between Aip-/- and Aip+/+ cell lines, which suggests that aberrant ARNT/ARNT2 expression is pituitary specific. In addition, Ki-67 analysis indicated that Aip deficient tumors have higher proliferation rates as compared with Aip proficient tumors. These results suggest that mechanisms of AIP related pituitary tumorigenesis involve aberrant ARNT/ARNT2 function, possibly via the AHR, hypoxia or estrogen pathways. Furthermore, the comparatively high proliferation rates of Aip deficient tumors may correlate with a more aggressive disease. Concentration is next focused on acquiring gene expression data of early Aip-/- embryos, which will be compared with expression data of Aip+/+ embryos. Differential expression patterns in these embryos could give new insights on different pathways involving AIP. Revealing the molecular basis of AIP related pituitary tumorigenesis is important in order to develop new diagnostic and therapeutic strategies for several patients suffering with pituitary adenomas.
  • Pirinen, Jani (2009)
    Tutkimuksessa tutkittiin NR4A-ryhmän tumareseptoreiden määrän muutosta maksakudoksessa energiarajoituksen ja resveratrolin vaikutuksista. Tutkimus tehtiin hiirillä ja laboratoriomenetelmänä oli Western Blot. NR4A-tumareseptoriryhmään kuuluvat Nur77, Nurr1 ja NOR-1. Ne säätelevät useissa kudoksissa useita eri solunsisäisiä tapahtumia. Maksassa ne säätelevät eri metabolisia prosesseja, etenkin glukoneogeneesiä ja lipogeneesiä. Lipogeneesillä on merkitystä rasvamaksan syntyyn ja glukoneogeneesillä taas on merkitystä veren sokeripitoisuudelle ja lisääntynyt glukoneogeneesi on merkittävä tekijä Tyypin 2 Diabetes Mellitus-taudissa esiintyvän hyperglykemian kannalta. Saamiemme tulosten mukaan Nur77:n määrä nousee selvästi energiarajoituksen vaikutuksesta runsasrasvaista ravintoa syöneeseen kontrolliryhmään verrattuna. NOR-1:n määrä nousee selvästi suurella (4 g/kg) rehupitoisuudella resveratrolia. Nurr1:n tuloksissa ei löytynyt statistisesti merkittäviä eroja ryhmien välillä. Tulkintani mukaan resveratroli on potentiaalinen maksan rasvoittumisen estäjä ja glukoneogeneesiä lisäävä aine stimuloimalla NR4A-ryhmän tumareseptoreita maksassa. Täten resveratroli ei ainakaan hepatosyyttien NR4A-reitin kannalta selitä sitä tosiasiaa että resveratroli vähentää diabeettista hyperglykemiaa.
  • Ahokas, Lauri Juhani (2011)
    The Hodgkin and Huxley (HH) model of action potential has become a central paradigm of neuroscience. Despite its ability to predict action potentials with remarkable accuracy, it fails to explain several biophysical findings related to the initiation and propagation of the nerve impulse. The isentropic heat release and optical phenomena demonstrated by various experiments suggest that action potential is accompanied by a transient phase change in the axonal membrane. In this study a method was developed for preparing a giant axon from the crayfish abdominal cord for studying the molecular mechanisms of action potential simultaneously by electrophysiological and optical methods. Also an alternative setup using a single-cell culture of an Aplysia sensory neuron is presented. In addition to the description of the method, the preliminary results on the effect of phloretin, a dipole potential lowering compound, on the excitability of a crayfish giant axon are presented.
  • Kuusanmäki, Heikki (2013)
    Recently, our research group together with the Hematology Research Unit Helsinki, found that 31 of 77 patients (40%) with T-cell large granular lymphocytic leukemia have somatic point mutations in the Src Homology 2 (SH2) domain of the STAT3 gene. LGL leukemia is a rare and indolent disease characterized by the clonal expansion of large granular lymphocytes of unknown etiology. The aim of this master's thesis study was to elucidate whether the identified Y640F and D661V mutations can cause hyperactivity of the STAT3 protein and excessive proliferation of T-cells. STAT3 is a transcription factor that is known to have a key role in cell proliferation and apoptosis, and which is activated by the phosphorylation of receptor-associated kinases. The phosphorylation of tyrosine residue 705 in STAT3 induces dimerization and localization of the STAT3 dimer to the nucleus. In several cancers STAT3 protein has been reported to be constitutively active. Furthermore, previously published data strongly support our hypothesis that the mutations identified in LGL patients might cause STAT3 to be hyperactive resulting in inhibition of apoptotic pathways in cytotoxic T cells. In order to evaluate the function of the novel mutations, expression constructs of STAT3 containing the D661V and Y640F mutations were generated. In addition, lentiviral vectors were produced to establish a T-cell line (Jurkat) with stable expression of mutant STAT3. After the successful generation of STAT3 constructs and cell line models, several functional assays were performed. Transcriptional activity of STAT3 was measured by luciferase reporter assay and immunocytochemistry was used to determine whether the mutations promote nuclear localization of STAT3. STAT3 phosphorylation was examined by immunoblotting. In addition, quantitative RT-PCR was used to detect differential expression of five STAT3 target genes from patient samples. The results, particularly the luciferase reporter assay, indicated a significant difference between the mutant and wild type STAT3 providing strong evidence that the STAT3 mutants are transcriptionally more active. The localization assay, imaged by fluorescence microscopy, showed more STAT3 D661V and Y640F protein present in the nucleus when compared to wild type STAT3. However, the proliferation rate of mutant STAT3 expressing Jurkat cells was not increased. In addition, STAT3 target gene expression levels of two patient samples did not show large differences when compared to healthy LGL cells. As a result of these findings, it can be strongly hypothesized that aberrant STAT3 signaling underlies the cause of T-cell LGL leukemia. Understanding the molecular basis of LGL leukemia is important in order to develop diagnostic and therapeutic strategies for patients suffering from the disease. Since constitutively active STAT3 is common amongst many cancers and autoimmune disorders, activating mutations could possibly be found in these diseases. More careful sequencing studies of STAT3 upstream molecules are warranted as well, and will be performed in the future from leukemic LGL samples.
  • Perttula, Antti (2012)
    Gliasoluperäinen hermokasvutekijä (GDNF) aiheuttaa muutoksen n. 300 geenin ilmentymisessä munuaisen kehityksen aikana. Geenien paikantaminen auttaa käsittämään solujen toimintaa elinten kehittymisen aikana. Lisäksi GDNFn toiminnan ymmärtäminen voi mahdollistaa Parkinsonin taudin uusien hoitomuotojen kehittämisen. Tässä työssä geenien ilmentymistä tutkittiin in situ –hybridisaatiomenetelmällä ja siten pyrittiin selvittämään viiden geenin merkitystä munuaisen kehityksessä. Visninlike-protein-1 (VSNL-1) lienee tutkituista geeneistä olennaisin, ja se saattaa olla uusi munuaisen kehitykselle välttämättön induktori, joka ilmentyy Wolffin tiehyessä ja uretersilmussa. Plakofilin ilmentyy Wolffin tiehyessä sekä uretersilmussa epiteelien välisissä liitoksissa. Kondroitiini-sulfaatti proteoglykaani (CSPG) ilmentyy myös Wolffin tiehyessä sekä virtsanjohtimessa. Dixed-2 ja Mrlp2 ilmentyvät hiiren sikiökehityksen aikana koko munuaisessa ilman erityistä sijaintia.
  • Sandell, Katarin (2013)
    Unverricht-Lundborg disease (EPM1/ULD, OMIM 254800) is an autosomal recessive inherited severe type of epilepsy with myoclonus and progressive neurological degeneration. The incidence of EPM1 in Finland is 1:20.000 births per year, and there are about 200 diagnosed cases. The age of disease onset is between 6 and 16 years. The symptoms start with epileptic seizures, stimulus sensitive myoclonus, and generalized tonic-clonic seizures, and progress within a few years to ataxia, incoordination, and dysarthria. Fourteen EPM1-associated loss-of-function mutations in the gene cystatin B (CSTB) have been described. CSTB is a ubiquitously expressed intracellular cysteine proteinase inhibitor, counteracting i.e. cathepsins B, L, and K. The expression levels of CSTB are higher in cerebellar Purkinje cells and in Bergmann glia of the adult central nervous system. There is a Cstb-deficient mouse model for EPM1, which shows progressive death of neurons and widespread gliosis. It has been earlier shown that Cstb knockdown sensitizes cerebellar granule neurons to cathepsin B mediated oxidative stress, resulting in cell death. This master's thesis is based on a previously done gene expression profiling of primary microglia of Cstb-/- mice, which revealed a downregulation of type I and type II interferon-regulated genes on the Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) –signaling pathway. The two aims of this study were to create an in vitro disease model for EPM1 in the human cervical adeno-carcinoma cell line HeLa, and in the murine leukemic cell line RAW264.7 by siRNA mediated RNA inhibition, and to study the effects of Cstb knockdown in selected interferon regulated genes of the JAK/STAT signaling pathway. Cystatin B was successfully knocked down in both cell lines HeLa and RAW264.7, and the obtained kinetics of Cstb knockdown in the cell line RAW264.7 provided with valuable information for the sec-ond part of the study. In the cell line HeLa, downregulation of CSTB did not change the expression lev-els of the genes of the JAK/STAT signaling pathway. In the cell line RAW264.7, CSTB knockdown on protein level was followed by a downregulation of the genes Stat1, Stat2, and Irf9. These results were in concordance with the results that had been obtained from the previously performed gene expression profiling of Cstb-/- microglia.
  • Pöyhönen, Julia Rosanna Hellin (2013)
    Charcot-Marie-Tooth (CMT) neuropathy is phenotypically and genetically a very heterogeneous disease. It can be inherited as an autosomal recessive, dominant or X-linked trait. CMT is characterized by distal muscle weakness, atrophy and deformity of the feet as well as clumsiness of gait. The onset of CMT varies and also the symptoms of the disease can vary even among the members of a single family. So far more than 40 genes have been identified for CMT and the list is estimated to grow by 30-50 genes. Whole exome sequencing (WES) is a new next generation sequencing technique, which targets the protein-coding area of the genome. Through WES analysis it is possible to search for disease causing mutations with all kinds of inheritance patterns. Patients suffering from CMT are good candidates for WES analysis because of the genetic heterogeneity of their disease. WES can be used for diagnosing Mendelian disorders with atypical symptoms as well as diseases, which are difficult to confirm using clinical criteria alone and which require costly evaluation, e.g. CMT. In this master study new disease causing mutations for early-onset neuropathies are identified by whole exome sequencing (WES). The aims of this study include using WES for the molecular diagnosis of four patients suffering from early-onset axonal neuropathies, the functional analysis of possible causative variants and improving and developing the process of analyzing variants from whole exome sequencing data, especially the analyzing steps of insertion and deletion variants. Finding causative variants among the insertion and deletion variants has previously been often left out from the WES analysis because of the lack of systematic analysis technique. As a result of the WES data analysis a new candidate disease gene, tripartite motif containing 2 (TRIM2) was identified. A missense mutation c.761T>A (p.E254V) and a deletion c.1779delA (p.K594Rfs7X) were found in patient 2, who suffers from severe CMT type 2. The carrier frequency was analysed to see whether the variants are present in the general population or not. The functional analysis of TRIM2 was started by preparing constructs carrying the missense mutation and the deletion and by setting up conditions for western blotting.
  • Myllynen, Mikko (2013)
    Epithelial tissue is characterized by close cell-cell and cell-extracellular matrix (ECM) contacts as well as by apico-basal polarization. Integrity of these two features is important for functionality of epithelium. Additionally, proteins regulating polarity and cell junctions have been linked to cell cycle and apoptosis control. Consequently, defects in many of the polarity proteins have been linked to oncogenic events and loss of polarity is a hallmark of advanced cancers but whether it is causal to tumorigenesis is yet unknown. However, large body of knowledge on apico-basal polarity regulation and its connection on homeostasis control is derived from studies in Drosophila. This is mainly due to fact that efficient high throughput organotypic three dimensional (3D) culture methods enabling apico-basal polarization have not been available until the last decade. Large screens for epithelial polarity regulators have not been carried out in mammalian cells. Moreover, as cancer is the leading cause of death in developed countries and most of the cancers originate from epithelial tissues, knowledge of polarity regulation can be medically relevant. Oncogene MYC is overexpressed or amplified in variety of human cancers. The tumorigenic function of MYC is mainly due to its ability to drive cell cycle. We have previously shown that intact epithelial architecture is protective from cell cycle deregulating activities of MYC in 3D MCF10A mammary epithelial cell model and in vivo. This resistance can be overcome by inactivating LKB1 which is the human homologue of the polarity protein PAR4 implying a tumour suppressive role for epithelial architecture in mammalian cells. To identify regulators of epithelial architecture in mammalian cells, we have established lentiviral shRNA library (human epithelial architecture library, hEAL) encompassing 219 constructs targeting 77 genes associated with polarity regulation in Drosophila. We have previously screened the shRNA constructs for downregulation and quantified their effects on acinar morphology in the MCF10A 3D model. In this Master's Thesis I have validated the downregulation and phenotypes observed in a subset of the shRNAs during primary screening of the constructs of the library. Additionally, the possible co-operation with downregulation of the polarity regulators and conditional activation of MYC was determined. Most dramatically, downregulation of Wnt pathway gene DVL3 was shown to cause formation of enlarged multiacinar structures, which have increased proliferation. Additionally, downregulation of another Wnt pathway gene, GSK3β, resulted in acini with increased size and filled lumens. Thus these results propose a role for these genes in epithelial architecture regulation and tumour suppression in the used model even though apico-basal polarization of the acini was intact and no synergy with MYC was observed. Interestingly, no role in epithelial architecture regulation for Hippo pathway related genes FAT4 and MOBKL1A was found. Importantly, this study was able to validate primary screen showing relevance of the pipeline. Lastly, the study characterized the synthetic lethality phenotype found in the primary screen caused by downregulation of GTPase RHOA and chronic MYC activation. The shRHOA acini exhibited perturbed α6-integrin localization. When combined with MYC activation, the percentage of apoptotic acini was significantly increased. Importantly, the results suggest the observed synthetic lethality to be specific for the 3D context and to be associated with MEK/ERK and ROCK pathways. Taken together, in this study I have validated the role of novel epithelial architecture regulators and candidate tumour suppressors in MCF10A cells which may have medical relevance by helping to characterize tumorigenic processes. Furthermore, I characterized a novel 3D specific RHOA-MYC synthetic lethal interaction, which may prove to have therapeutic significance in MYC-driven cancers in future.
  • Masar, Robert (2011)
    Inledning Diabetisk nefropati är den mest fruktade diabeteskomplikationen. Utvecklingen av nefropati har redan länge undersökts genom mätning av mängden albuminutsöndring i urinen. Nyligen har man upptäckt att njurfunktionen kan vara nedsatt oberoende av albuminuri. Mål Att undersöka prevalensen samt associationer av kronisk njursvikt utan albuminuri (nonalbuminuric renal disease eller NARD) hos typ 1 diabetiker. Betydelsen av blodtrycksmedicinering, speciellt ACE-/AT2-inhibitorer, behandlas också. Material och metoder Studien ingår i den nationella multicenterstudien FinnDiane. En population på ca. 4000 typ 1 diabetiker har analyserats. Patienter med nefropati utan albuminuri identifierades. Statistiska analyser gjordes med SPSS 19.0. Njurfunktionen (eGFR) estimerades med CKD-EPI ekvationen. Resultat Prevalensen av NARD inom den normoalbuminura gruppen var 3,5%, prevalensen hos män 1,0% samt hos kvinnor 5,4%. Sammanlagt 79 patienter med NARD (12 män och 67 kvinnor) identifierades. ACE-/AT2-inhibitorer kan påverka prevalensen av NARD men inte statistiskt signifikant (p=0,067). Risken för progression av NARD till mikroalbuminuri var betydligt större hos denna grupp (p=0,006) i jämförelse med den normoalbuminura gruppen med normal njurfunktion. I en överlevnadsanalys framkom att mortaliteten var högre inom mikroalbuminuri-gruppen än inom NARD-gruppen (p<0,001, ålders- samt könskorrigerat). Diskussion Prevalensen av NARD var lägre än i motsvarande studier utomlands på typ 2 diabetiker. NARD patienterna hade en ökad risk för progression till mikroalbuminuri men inte en ökad mortalitet. ACE-/AT2-inhibitorerna kan delvis förklara NARD fenomenet. Nya studier med ett större antal NARD patienter behövs för en noggrannare utredning.
  • Pietilä, Markus (Helsingfors universitetUniversity of HelsinkiHelsingin yliopisto, 2015)
    Apotti on Helsingin ja Uudenmaan sairaanhoitopiirin sekä alueen kuntien potilastietojärjestelmähanke. Helsingin kaupungin terveyslautakunta kokoontui ensimmäisen kerran ottamaan kantaa Apottiin 11.9.2012. Ennen kokousta sosiaalisessa mediassa oli virinnyt vilkas keskustelu, jossa lähinnä kritisoitiin hanketta. (Hanketta kritisoitiin muun muassa sen korkeasta kustannusarviosta ja siitä, että hankkeessa oltaisiin ajautumassa niin sanottuun toimittajaloukkuun.) Keskustelun keskiössä oli 9.7.2012 perustettu Facebook-ryhmä Terveydenhuollon tietojärjestelmät korjattava. Keskusteluun osallistuivat suoraan ja välillisesti myös perinteisempi media ja potilastietojärjestelmähankkeen vastuuhenkilöt. Keskustelun tärkeimmät pitkät puheenvuorot ja lyhyemmät kommentit ovat hajallaan ja sekavassa järjestyksessä eri internetsivustoilla. Tämän tutkielman ensisijaisena tavoitteena on etsiä nämä keskustelun tärkeimmät puheenvuorot ja esitellä ne kronologisessa järjestyksessä (luvut 2-7 ja 13-29). Tutkielman toissijaisena tavoitteena on pohtia joitakin keskustelussa esiinnousseita teemoja (luvut 8-12 ja 30).
  • Vesala, Tommi (2014)
    Alaviisaudenhampaan poistoa suunniteltaessa selvitetään panoraamatomografiatutkimuksen (PTG) perusteella juurten lukumäärä ja morfologia sekä juurten ja nervus alveolaris inferiorin (NAI) suhde. Tämä tehdään ennen toimenpidettä poiston vaikeusasteen selvittämiseksi. Tietyt vaaranmerkit PTG:ssa kertovat suurentuneesta NAI:n vaurioriskistä, jolloin kartiokeilatietokonetomografiatutkimus (KKTT) on aiheellinen. Tutkimustietoa KKTT:n luotettavuudesta viisaudenhampaan morfologian ja juurten lukumäärän suhteen on niukasti. Tutkimuksessa määritettiin 22 alaviisaudenhampaan juurten lukumäärä ja juurimorfologia PTG- ja KKTT-kuvista ja verrattiin näin saatua tulosta poistetun viisaudenhampaan todelliseen morfologiaan. Aineiston tulokset analysoitiin Excel-taulukointiohjelmalla. Tilastollisen merkitsevyyden P-arvot saatiin chi-squared testin avulla. Yatesin korjauskerrointa käytettiin, koska chi-squared testin odotusarvoissa oli alle kymmenen suuruisia arvoja. KKTT-tutkimuksella voitiin tunnistaa juurten lukumäärä useammin oikein kuin PTG-kuvauksella (87 % ja 67 % vastaavasti), ja juurten taipuminen useammin oikein verrattuna PTG-kuvaukseen (73 % ja 60 % vastaavasti). Johtopäätöksenä tästä tutkimuksesta oli, että KKTT-tutkimus näytti olevan luotettavampi kuin PTG-tutkimus viisaudenhampaiden juurten lukumäärän ja ulkoisen juurimorfologian arvioinnissa.
  • Halonen, Lauri (2011)
    γ-Aminobutyric acid type A (GABAA) receptors are ligand gated ion channels mediating most inhibitory signals in the brain. GABAA receptor consists of five subunits, and there are 16 different subunits known. This forms base to pharmacological diversity of GABAA receptors. In this study autoradiography on subunit gene knock out mouse models was used to visualize the meaning of different subunits in forming GABAA receptors exhibiting special kinds of pharmacology, ie. GABA-insensitive [35S]TBPS-binding and high-affinity [3H]muscimol binding. In receptors exhibiting GABA-insensitive TBPS-binding GABA fails to cause full dissociation of TBPS from the ionophore, which means that the receptors are not fully activated by GABA. This study revealed, that contrary to what was previously believed, the forebrain GABA-insensitive [35S]TBPS binding is most likely caused by GABAA receptors consisting of α1 and β subunits or α1, β and δ subunits. High-affinity muscimol binding in the α1 KO mice was found to be unaltered, whereas α4 KO, δ KO and α4 + δ KO mice exhibited diminished high-affinity [3H]muscimol binding. Contrary to what was previously considered, this study points out that α1β GABAA receptors are mediating GIS-binding in the forebrain. Changes in high-affinity [3H]muscimol binding has also been found to correlate with changes of muscimols effects in vivo in knock out mouse models.
  • Immonen, Anastasia (2010)
    Tutkimuksen tavoitteena oli ensisijaisesti oppia kanan alkion manipuloinnin tekniikka ja tutkia sen avulla hermostopienan solujen vaellusta kehittyvässä alkiossa. Toinen tavoite oli tarkastella Ret-geenin mutaation (C634R) vaikutusta hermostopienan migraatiokaavaan. Tutkittu Ret-geenin mutaatio aikaansaa geenin tuotteen uudenlaisen toiminnankuvan, jolloin tuloksena voi olla syöpäsairaus. Tutkimus suoritettiin käyttämällä kanan alkiota. Kananmunia haudottiin inkubaattorissa sopivaan kehitysvaiheeseen, minkä jälkeen alkiota käsiteltiin kuoreen tehdyn aukon kautta. Mikroskoopin avulla alkion kehittyvään hermostoputkeen ruiskutettiin plasmidi-Dna:ta, joka sisälsi gfp-geenin sekä joko tutkittavan geenimutaation tai villityypin geenin. Plasmidin siirron jälkeen alkio elektroporoitiin, jotta siirretty perimäaines pääsisi alkion solujen sisään proteiinisynteesin alkamiseksi. Gfp:n fluoresoivan ominaisuuden avulla voitiin jälkitarkastelussa seurata plasmidin geenien ilmentymistä. Tutkimustulosten perusteella voidaan todeta tarkastellun Ret-geenin mutaation aiheuttavan hermostopienan solujen vaelluskaavioon häiriöitä verrattuna kontrolliin. Häiriöitä olivat mm. solujen rykelmäinen ryhmittyminen sekä hermostopienan solujen vaelluksen paikoittainen katkeaminen ja hajanaisuus. Tutkimusaineiston suppeuden vuoksi, mitään varmoja johtopäätöksiä suoritetun tutkimuksen perusteella ei voida vielä tehdä, vaan asia vaatii lisää tutkimuksia.
  • Lempiäinen, Juha (2011)
    Lihavuus on kasvava ongelma länsimaissa. Siihen liittyy useita metabolisia muutoksia, jotka johtavat erilaisiin kohde-elinvaurioihin. Vaurioiden mekanismien tunnistaminen on tärkeää, jotta niiden ehkäisyyn voidaan kehittää uusia elintapa- ja lääkehoitoja. Tämän tutkimuksen tarkoituksena oli selvittää ravinnon rasvamäärän, resveratrolin ja kalorirajoituksen vaikutuksia hiirten sydämissä ja maksoissa sekä määrittää näiden vaikutus SIRT1 – proteiinin määrään kyseisissä kudoksissa. Tutkimuksessa vertailtiin Western Blot – menetelmän avulla SIRT1:n pitoisuutta hiirten sydämissä ja maksoissa. SIRT1:n lokalisaatio osoitettiin immunohistokemiallisen värjäyksen avulla. Sydänlihassolujen hypertrofiaa arvioitiin mikroskoopin avulla HE – värjätyistä leikkeistä. Resveratrolin vaikutus sydänlihassolujen hypertrofian asteeseen jäi vähäiseksi. Kalorirajoitus lisäsi SIRT1:n määrää sekä sydämessä että maksassa ja esti sydänlihassolujen hypertrofian. Tutkimus tarjoaa hyvän pohjan selvittää laajemmin resveratrolin vaikutusta SIRT1:n aktivaatioon ja sitä kohde-elinvaurioiden estoon.