Concerto no. 27 in B-flat major for Piano and Orchestra, K. 595

Soitinnus: Piano, ork.

Immunomodulation of allergic immune response during specific immunotherapy

Atopic, IgE-mediated allergies are one of the major public health problems in Finland and other Western countries. These diseases are characterized by type 2 T helper (Th2) cell predominated immune responses (interleukin-4 (IL-4), IL-5) against ubiquitous environmental allergens. Despite of adequate pharmacological treatment, more than 20% of the patients with allergic rhinitis develop asthma. Allergen specific immunotherapy (SIT) is the only treatment currently available to affect to the natural course of allergic diseases. This treatment involves repeated administration of allergens to the patients either via sublingual route (sublingual immunotherapy, SLIT) or by subcutaneous injections (subcutaneous immunotherapy, SCIT). Successful treatment with SCIT or SLIT has been shown to provide long-term remission in symptoms, and prevent disease progression to asthma, but the immunological mechanisms behind these beneficial effects are not yet completely understood. Increased knowledge of such mechanisms could not only help to improve SIT efficacy, but also provide tools to monitor the development of clinical response to SIT in individual patients, and possibly also, predict the ultimate therapeutic outcome. The aim of this work was to clarify the immunological mechanisms associated with SIT by investigating the specific allergen-induced immune responses in peripheral blood mononuclear cells (PBMC) of allergic rhinitis patients during the course of SLIT and SCIT. The results of this work demonstrate that both therapies induced increases in the protective, Th2-balancing Th1 type immune responses in PBMC, e.g. by up-regulating signaling lymphocytic activation molecule (SLAM) and interferon gamma (IFN-γ) expression, and augmented tolerogenic T regulatory (Treg) cell type responses against the specific allergens, e.g. by increasing IL-10 or Forkhead box P3 (FOXP3) expression. The induction of allergen-specific Th1 and Treg type responses during SLIT were dependent on the treatment dose, favoring high allergen dose SLIT. During SCIT, the early decrease in Th2 type cytokine production - in particular of IL-4 mRNA and IL-4/IFN-γ expression ratio - was associated with the development of good therapeutic outcome. Conversely, increases in both Th2 (IL-5) and Th1 (IFN-γ, SLAM) type responses and IL-10 mRNA production were seen in the patients with less effective outcome. In addition, increase in Th17 type cytokine (IL-17) mRNA production was found in the PBMC of patients with less effective outcome during both SLIT and SCIT. These data strengthen the current hypothesis that immunomodulation of allergen-specific immune responses from the prevailing Th2-biased responses towards a more Th1 type, and induction of tolerogenic Treg cells producing IL-10 represent the two key mechanisms behind the beneficial effects of SIT. The data also give novel insight into the mechanisms why SIT may fail to be effective in some patients by demonstrating a positive correlation between the proinflammatory IL-17 responses, Th2 type IL-5 production and clinical symptoms. Taken together, these data indicate that the analysis of Th1, Th2, Treg ja Th17-associated immune markers such as IL-10, SLAM, IL-4, IL-5 and IL-17 could provide tools to monitor the development of clinical response to SIT, and thereby, predict the ultimate clinical outcome already in the early course of the treatment.

Interleukin-4 induced leukocyte differentiation

Monocytes, macrophages and dendritic cells (DCs) are important mediators of innate immune system, whereas T lymphocytes are the effector cells of adaptive immune responses. DCs play a crucial role in bridging innate and adaptive immunity. Naïve CD4+ Th progenitors (Thp) differentiate to functionally distinct effector T cell subsets including Th1, Th2 and Th17 cells, which while being responsible for specific immune functions have also been implicated in pathological responses, such as autoimmunity, asthma and allergy. The main objective of this thesis is to dissect the signalling networks involved in the IL-4 induced differentiation of two important leukocyte subtypes, Th2 cells and DCs. Gene expression profiling lead to identification of over 200 genes which are differentially expressed during cytokine induced differentiation of human monocytes to DCs or macrophages and which are likely to be essential for the proper biological functions of these cell types. Transcriptome analysis demonstrated the dynamic regulation of gene expression by IL-12 and IL-4 during the initiation of Th cell differentiation, which was partly counteracted by an immunosuppressive cytokine, TGFβ, present in the culture media. Results from RNAi mediated gene knockdown experiments and global gene expression analysis elucidated that SATB1 regulates multiple genes important for Th cell polarization or function as well as may compete with GATA3 for the reciprocal regulation of IL-5 transcription. In conclusion, the results obtained have extended our system-level understanding of the immune cell differentiation processes and provide an excellent basis for the further functional studies which could lead to development of improved therapeutic approaches for a range of immunological conditions.

Metathesin ton saleuomenon, Hebr. cap. XII: v. 27

Invocatio: I.N.J.

Ruokakerta ruumihille, Juomat hengelle hereät : 27.2.1934 Seurahuonehen salissa

E. N. Setälän 70-vuotisjuhlapäivälliset

Jousikvartetto op. 27 : 1944-1945

4. osan lopussa merkintä: Ensiesitys 23. XI 1945. Sibelius-kvartetti (Cronvall, Huttunen, Karma, Granroth.)

Gutenberg 1899:27

Gutenberg-lehti ilmestyi vuosina 1893-1915. Se oli perustettu ammattilehdeksi ja yhdyssiteeksi Suomen kirjanpainajille sekä äänenkannattajaksi Suomen kirjaltajaliitolle.

Lasten suometar : lisälehti Suomettarelle 27:1857

Lapsille tarkoitettu lisälehti Suometar-sanomalehteen.

The guards of the tomb (Matt 27:62–66 and 28:11–15) : Matthew’s apologetic legend revisited

Det har varit vanligt bland forskarna att relativt lite uppmärksamhet fästs vid Matteus berättelse om vakterna vid Jesu grav. Berättelsen har stämplats som en apologetisk legend, skapad av evangelisten eller av en okänd urkristen, mot de judiska ledare som anklagade Kristus-troende för stölden av Jesu kropp. I den här undersökningen utreddes, för det första, om de argument som har framställts när berättelsens möjliga historiska bakgrund har förkastats är hållbara. En närmare analys gav för handen att de inte är det, vilket berättigade en ny fördjupad undersökning av berättelsen. I den andra delen betraktades berättelsen med hjälp av en redaktionskritisk metod. Syftet var att klarlägga om evangelisten har utnyttjat en tradition eller själv skapat historien. Det påvisades att argumenten för det matteiska ursprunget till berättelsen inte är välgrundade i ljuset av en ändamålsenlig statistisk analys. Däremot konstaterades det att flera ord och uttryck var så otypiska för evangelistens allmänna stil att utnyttjandet av en tradition är sannolikt. I den tredje delen av undersökningen analyserades konflikten mellan judar och urkristna, som i denna undersökning kallas Kristus-troende, med hjälp av sådana socialvetenskapliga begrepp som t.ex. symboluniversum och socialt minne, tillsammans med en analys av beskrivningen om konflikten i Apostlagärningar och Pauli brev. Det föreslogs att konflikten utvecklades redan i Jesusrörelsens början i Galileen och eskalerade sedan i Jerusalem resulterande i en antagonistisk attityd mellan Jesu efterföljare och de judiska ledarna i Jerusalem. En kritisk analys av ovannämnda källor visade att antagonismen aktualiserats i flera öppna konflikter under perioden 30-70 eKr. Utifrån frågeställningen i den här undersökningen är det betydelsefullt att en lämplig kontext för den polemiska berättelsen om vakterna vid Jesu grav kan finnas i nästan vilken som helst tidspunkt under perioden. I den fjärde delen var olika teorier beträffande traditionen om Jesu tomma grav betraktade. Att en grupp kvinnor besökte Jesu grav och upptäckte att den var tom påvisades vara det mest sannolika alternativet. I analysen av den egentliga berättelsen om vakterna vid Jesu grav var de vanliga dialogmodellerna kritiskt beskådade och förkastades som för endimensionella. Det föreslogs att stöldanklagelsen var framställd av de judiska ledarna genast efter att Kristus-troendena hade påstått att Jesus är uppstånden. Efter en kritisk evaluering av de olika alternativen visade det sig sannolikt att vakterna blev introducerade till berättelsen av de judiska ledarna. Den kristna berättelsen om vakterna vid graven blev sedan formad reaktivt på grund av denna anklagelse.

Pianokonsertto 27 B, KV. 595

Soitinnus: piano, orkesteri.