Tän kylän ämmät

Soitinnus: lauluääni, piano.

Nonnulla philosophice meditata perì tôn klimakterôn e etôn klimakterikôn [kreikkaa]

Invocatio: En onómati tû staurothéntos [kreikkaa].

Islet antigen-specific T cells and regulatory T cells in type 1 diabetes

T cells are the key players in the development of type 1 diabetes (T1D), mediating autoimmune reactions leading to the destruction of insulin producing beta cells in the islets. We aimed to analyze the role of different T-cell subtypes in the autoimmunity and pathogenesis of T1D. The frequency of islet antigen-specific (GAD65-, proinsulin-, and insulin-specific) CD4+ T cells was investigated in vitro in T1D patients, at-risk individuals (diabetes-associated autoantibody positive), and in controls, using MHC class II tetramers. An overall higher frequency of CD4+ T-cells recognizing the GAD65 555−567 peptide was detected in at-risk individuals. In addition, increased CD4+ T-cell responses to the same GAD65 epitope displaying a memory phenotype were observed in at-risk and diabetic children, which demonstrate a previous encounter with the antigen in vivo. Avidity and phenotypic differences were also observed among CD4+ T-cell clones induced by distinct doses of GAD65 autoantigen. T-cell clones generated at the lowest peptide dose displayed the highest avidity and expressed more frequently the TCR Vβ5.1 chain than low-avidity T cells. These findings raise attention to the antigen dose when investigating the diversity of antigen-specific T cells. Furthermore, an increased regulatory response during the preclinical phase of T1D was also found in genetically at-risk children. Higher frequencies of regulatory T (Treg) cells (CD4+CD25_high HLA-DR-/CD69-) and natural killer T (NKT) cells (CD161+Vbeta11+) were observed in children with multiple autoantibodies compared to autoantibody-negative controls. Taken together, these data showed increased frequency of islet-specific CD4+ T-cells, especially to the GAD65 555-567 epitope, and Treg and NKT cell upregulation in children at-risk for T1D, suggesting their importance in T1D pathogenesis

Free Prostate-specific Antigen Forms and Kallikrein-related Peptidase 2: Tools for Prostate Cancer Diagnostics

Prostate-specific antigen (PSA) is a marker that is commonly used in estimating prostate cancer risk. Prostate cancer is usually a slowly progressing disease, which might not cause any symptoms whatsoever. Nevertheless, some cases of cancer are aggressive and need to be treated before they become life-threatening. However, the blood PSA concentration may rise also in benign prostate diseases and using a single total PSA (tPSA) measurement to guide the decision on further examinations leads to many unnecessary biopsies, over-detection, and overtreatment of indolent cancers which would not require treatment. Therefore, there is a need for markers that would better separate cancer from benign disorders, and would also predict cancer aggressiveness. The aim of this study was to evaluate whether intact and nicked forms of free PSA (fPSA-I and fPSA-N) or human kallikrein-related peptidase 2 (hK2) could serve as new tools in estimating prostate cancer risk. First, the immunoassays for fPSA-I and free and total hK2 were optimized so that they would be less prone to assay interference caused by interfering factors present in some blood samples. The optimized assays were shown to work well and were used to study the marker concentrations in the clinical sample panels. The marker levels were measured from preoperative blood samples of prostate cancer patients scheduled for radical prostatectomy. The association of the markers with the cancer stage and grade was studied. It was found that among all tested markers and their combinations especially the ratio of fPSA-N to tPSA and ratio of free PSA (fPSA) to tPSA were associated with both cancer stage and grade. They might be useful in predicting the cancer aggressiveness, but further follow-up studies are necessary to fully evaluate the significance of the markers in this clinical setting. The markers tPSA, fPSA, fPSA-I and hK2 were combined in a statistical model which was previously shown to be able to reduce unnecessary biopsies when applied to large screening cohorts of men with elevated tPSA. The discriminative accuracy of this model was compared to models based on established clinical predictors in reference to biopsy outcome. The kallikrein model and the calculated fPSA-N concentrations (fPSA minus fPSA-I) correlated with the prostate volume and the model, when compared to the clinical models, predicted prostate cancer in biopsy equally well. Hence, the measurement of kallikreins in a blood sample could be used to replace the volume measurement which is time-consuming, needs instrumentation and skilled personnel and is an uncomfortable procedure. Overall, the model could simplify the estimation of prostate cancer risk. Finally, as the fPSA-N seems to be an interesting new marker, a direct immunoassay for measuring fPSA-N concentrations was developed. The analytical performance was acceptable, but the rather complicated assay protocol needs to be improved until it can be used for measuring large sample panels.

”Hei, mä opin tän asian enkuks!” Toimintatutkimus ympäristötiedon ainesisältöjen ja vieraan kielen oppimisesta sekä opettamisesta englanninkielissä oppituokioissa

Tämä kvalitatiivinen toimintatutkimus sai lähtökipinän opettajan tarpeesta kehittää englannin kielen opetustaan suuntaan, joka innostaisi oppijoita opiskelemaan ja tuottamaan vierasta kieltä rohkeasti. Tutkimuksen tarkoituksena oli selvittää, mitä muutoksia oppijoissa ilmenee, kun perinteiseen vieraan kielen opetukseen sisällytetään kahden lukuvuoden ajan oppituokioita, joissa ympäristötiedon ainesisältöjä opetetaan vieraalla kielellä. Kiinnostuksen kohteena oli tutkia, ilmeneekö oppijoilla muutoksia ainesisältöjen hallinnassa, englanninkielisen ympäristötiedon sanavaraston karttumisessa, kielitaidon kehittymisessä sekä asenteessa oppituokioita ja englannin kieltä kohtaan yleensä. Tutkimuksen tarkoituksena oli myös luoda toimivaa käytäntöä opettajalle toteuttaa ainesisältöjen opettamista vieraalla kielellä, josta kansainvälisesti käytetään termiä Content and language integrated learning (CLIL). Tutkimus oli kahden vuoden pitkittäistutkimus, joka toteutettiin lukuvuosina 2008–2010. Tutkimusjoukko koostui 18:sta (11 poikaa ja 7 tyttöä) neljättä luokkaa aloittavasta oppijasta. Vertailuryhmään kuului 22 musiikkiluokan oppijaa (6 poikaa ja 16 tyttöä). Tutkija opetti molemmille ryhmille englannin kieltä kaksi viikkotuntia. Englanninkieliset oppituokiot toteutettiin englannin tuntien yhteydessä noin kerran viikossa. Kerrallaan tuokio kesti 15–20 minuuttia. Tutkimusaineistoa, joka koostuu sekä kvalitatiivisesta että kvantitatiivisesta aineistosta, kerättiin eri tavoin: tutkija keräsi havaintomateriaalia päiväkirjaansa koko tutkimuksen ajan, oppijoita testattiin kuusi kertaa tutkimuksen aikana sekä itsearvio- ja asennekyselyjä toteutettiin kahdesti. Tutkimusaineiston pohjalta saatiin selviä tutkimustuloksia, joiden mukaan CLIL-opetus vaikutti oppijoihin positiivisesti: ympäristötiedon ainesisältöjä opittiin, englanninkielinen ympäristötiedon sanavarasto laajeni ja vierasta kieltä käytettiin rohkeammin kuin aiemmin. Kommunikoidessa huomio kiinnitettiin kielen tarkkailun sijasta asiasisältöön. Oppijat suhtautuivat englanninkielisiin oppituokioihin positiivisesti ja englannin osaaminen koettiin tärkeäksi. Tässäkin kokeilussa CLIL osoittautui joustavaksi metodiseksi lähestymistavaksi, joka taipuu käyttökelpoiseksi käytännön teoriaksi soveltuen monenlaisille oppijoille.

Tukholmaan tänä kesänä

kuv., 12 x 26 cm

Tänä vuonna liikkukaa ulkona luonnossa ajelkaa komeasti ja hauskasti

kuv., 22 x 13 cm

Täten saan pyytämättänne ilmoittaa, että tänä keväänä liikkeeltänne ostamallani "Cleveland" (urheilumalli) autolla tein ensimäisen suuremman matkan

11 x 15 cm

Modulation of Signaling Molecules by Human Leucocyte Antigen B27; Special Reference to STAT1

Reactive arthritis (ReA) is an inflammatory joint disease, which belongs to the group of Spondyloarthritis (SpA). It may occur after infections with certain gram-negative bacteria such as Salmonella and Yersinia. SpAs are strongly associated with the human leucocyte antigen (HLA)-B27. Despite active research, the mechanism by which HLA-B27 causes disease susceptibility is still unknown. However, HLA-B27 has a tendency to misfold during assembly. It is possible that the misfolding of HLA-B27 could alter signaling pathways and/or molecules involved in inflammatory response in cells. We have earlier discovered that in HLA-B27-positive cells the interaction between the host and causative bacteria is disturbed. Our recent studies indicate that the expression of HLA-B27 may alter certain signaling molecules by disturbing their activation. The aim of this study was to investigate whether the expression of HLA-B27 disturbs the signaling molecules, especially the phosphorylation of transcription factor STAT1. STAT1 is an important mediator of inflammatory responses. Our results show that the phosphorylation of the STAT1 is significantly altered in HLA-B27-expressing U937 monocytic cells compared with control cells. STAT1 tyrosine 701 is more strongly phosphorylated in HLAB27- expressing cells; whereas the phosphorylation of STAT1 serine 727 is prolonged. Phosphorylation of STAT1 was discovered to be dependent on protein kinase PKR. Furthermore, we found out that the expression of posttranscriptional gene regulator HuR was altered in HLA-B27-expressing cells. We also detected that HLA-B27-positive cells secrete more interleukin 6, which is an important mediator of inflammation. These results help to understand how HLA-B27 may confer susceptibility to SpAs.