Browsing by discipline "Sisätaudit"

Typ 1 diabetiker har en betydligt högre risk att insjukna i ett slaganfall än vad typ 2 diabetiker och icke-diabetiker har. Dock saknas studier som försöker utreda de självständiga riskfaktorerna för slaganfall vid typ 1 diabetes och därmed var syftet med denna studie att klarlägga dessa riskfaktorer. Studien är en del av FinnDiane-studien, vars mål är att undersöka riskfaktorer för följdsjukdomar vid typ 1 diabetes. Studiepopulationen bestod av 2285 patienter, varav 75 fick sitt första slaganfall under uppföljningstiden på 5,3 år. Information på slaganfall insamlades genom att sjukjournaler av ifrågavarande patient lästes igenom. Detta sammanställdes i en data-bas och analyserades med hjälp av SPSS. De självständiga riskfaktorerna för slaganfall visade sig vara diabetisk nefropati, diabetisk retinopati, dålig blodsockerbalans, högre ålder och lägre BMI. Studien har en betydande roll i utvärderingen av risken för att insjukna i ett slaganfall och av behovet av vård hos patienter med typ 1 diabetes.

Somatic mutations contribute to tumorigenesis. Although these mutations occur in all proliferating cells, their accumulation under non-malignant conditions, such as in autoimmune disorders, has not been investigated. Here, we show that patients with newly diagnosed rheumatoid arthritis have expanded CD8+ T-cell clones; in 20% (5/25) of patients CD8+ T cells, but not CD4+ T cells, harbour somatic mutations. In healthy controls (n=20), only one mutation is identified in the CD8+ T-cell pool. Mutations exist exclusively in the expanded CD8+ effector-memory subset, persist during follow-up, and are predicted to change protein functions. Some of the mutated genes (SLAMF6, IRF1) have previously been associated with autoimmunity. RNA sequencing of mutation-harbouring cells shows signatures corresponding to cell proliferation. Our data provide evidence of accumulation of somatic mutations in expanded CD8+ T cells, which may have pathogenic significance for RA and other autoimmune diseases.

MicroRNAs are small single-stranded RNA molecules that regulate gene expression by silencing the translation of messenger RNAs. They have the ability to silence translation of multiple different messenger RNAs simultaniously and have been shown to have an important role in the formation and maintaining homeostatsis of several tissue types. The regenerative ability of the human heart after myocardial injury is limited, which often leads to adverse changes in cardiac structure and function. This is why molecules that enhance the regenerative and reparative abilities of cardiomyocytes, such as carbon monoxide, are of special interest. Carbon monoxide protects cardiomyocytes from apoptosis and prevents their proliferation. One proposed modulator of these effects is the p38 mitogen-activated protein kinase (p38 MAPK). We studied the effects of carbon monoxide releasing molecule-3 (CORM-3) on cardiac recovery after myocardial infarction in adult rats and how it effects the expression of microRNAs miR-133a, miR-133b, miR-206 and miR-208. In addition, we studied the effects of carbon monoxide releasing molecule-A1 (CORM-A1) and inhibition of p38 MAPK on neonatal rat cardiomyocyte proliferation and apoptosis. We showed that CORM-3 improves cardiac recovery after myocardial infarction by increasing the amount of cardiomyocytes in the infarct area and improving the cardiac function of the left ventricle. Additionally, we showed that inhibiting p38 MAPK increases proliferation in neonatal rat cardiomyocytes. The beneficial effects of carbon monoxide on cardiac recovery after myocardial injury are well known. However, the exact mechanisms of its actions in cardiomyocytes remain poorly known. MicroRNAs might at least partly mediate these effects as CORM-3 increased their expression in rat hearts. The potential pathways between carbon monoxide and microRNA require still further research.

Background: Common variable immunodeficiency (CVID) is the most common primary immunodeficiency. Prevalence varies greatly between countries and studies. Most diagnostic criteria include hypogammaglobulinemia and impaired vaccine response. Aim: To evaluate the minimum prevalence as well as the clinical and immunological phenotypes of CVID in Southern Finland. Methods: We performed a cross-sectional study to assess all adult CVID patients followed-up in three hospital districts in Southern and South-Eastern Finland between April 2007 and August 2015. CVID diagnosis was based, with a minor modification, on the ESID/PAGID criteria for primary CVID. Antipolysaccharide responses to Pneumovax® were defined as impaired only if 50% or more of the serotypes did not reach a level of 0.35 μg/mL after vaccination. We further characterized the patients’ B cell phenotypes and complications associated with CVID. Results: In total, nine patients were excluded due to potential secondary causes before diagnosis. ESID/PAGID criteria were met by 132 patients (males 52%), of whom 106 had “probable” and 26 “possible CVID”. Based on the population statistics in the three hospital districts, the minimum adult prevalence per 100 000 inhabitants in Finland for all CVID (“probable CVID”, respectively) patients was 6.9 (5.5). In the highest prevalence district (Helsinki and Uusimaa), the prevalence was 7.7 (6.1). CVID patients suffer from frequent complications. Ten patients died during follow up. Of probable CVID patients, 73% had more than one clinical phenotype. Intriguingly, gradual B cell loss from peripheral blood during follow up was seen in as many as 16% of “probable CVID” patients. Patients with possible CVID displayed somewhat milder clinical and laboratory phenotypes than probable CVID patients. We also confirm that large granular lymphocyte lymphoproliferation is a CVID-associated complication. Conclusion: The prevalence of CVID in Finland appears the highest recorded, likely reflecting the genetic isolation and potential founder effects in the Finnish population. Studies to discover potential gene variants responsible for the high prevalence in Finland thus seem warranted. Increased awareness of CVID among physicians would likely lead to earlier diagnosis and improved quality of care.