Kaksi perspektiiviä Etykiin: Viro suomalaisten ja ruotsinvirolaisten lehtien silmin 1973-1975

Suomen ja Viron välillä on ollut kontakteja tuhansien vuosien ajan. Vilkkaammiksi yhteydet muuttuivat kansallisen heräämisen ajalla ja sotien välisenä aikana. Toinen maailmansota katkaisi suomalais-virolaiset suhteet lähes 20 vuodeksi Neuvostoliiton miehitettyä Viron. Yhteydet Viroon palasivat jossakin muodossa 1960-luvulla, mutta olivat silloin ja tutkimusajankohtana 1970-luvulla tiukasti säädeltyjä. Kaikki virallisen tason yhteydenpito tapahtui Moskovan kautta ja valvonnassa, ja kansalaisyhteiskunnan tasolla tapahtuvaa toimintaa maiden välillä ei ollut. Myös lehtikirjoittelu oli Moskovan seurannassa ja Neuvostoliitto puuttui usein, mikäli Suomessa kirjoitettiin Virosta jotakin mikä ei ollut sille mieleen. Tutkielman tavoitteena on selvittää, millainen maa Viro oli 1970-luvun alkupuolella ja millainen kuva siitä oli Suomessa sekä Ruotsissa eläneen pakolaisvirolaisen yhteisön keskuudessa. Aineistona on sanomalehtiartikkeleita vuosilta 1973–1975 neljästä suomalaisesta ja kahdesta ruotsinvirolaisesta sanomalehdestä. Erityinen painopistealue on Euroopan turvallisuus- ja yhteistyökokous eli Etyk, jonka järjestelyihin Suomi otti aktiivisesti osaa. Länsivaltiot ajoivat Ety-asiakirjaan periaatteita mm. vapaammasta tiedonvälityksestä ja ihmisten liikkumisesta, Neuvostoliitto taas tavoitteli rauhansopimuksen korviketta, jolla Euroopan toisen maailmansodan jälkeiset rajat vahvistettaisiin. Etyk oli siis virolaisille monella tavalla merkittävä: he saattoivat toivoa kokouksen tuovan mahdollisuuksia ottaa Baltian asia esille ja saada Baltian maille itsenäisyys, tai ainakin suurempi itsemääräämisoikeus. Toisaalta he pelkäsivät Neuvostoliiton vain vahvistavan otettaan Virosta Etykin avulla. Etykiin liittyvässä kirjoittelussa suomalaislehtien haluttomuus ottaa Viron asiaa esille näkyy erityisen selvästi.Virosta ei muutenkaan 1970-luvulla uutisoitu usein ja Etykin yhteydessä virolaisten toiveita ja tavoitteita ei juuri julkistettu. Baltian maista paenneet pyrkivät kyllä tuomaan asiaansa julkisuuteen Helsingin 1973 ja 1975 kokousten aikaan, mutta suomalaislehdissä se ei näkynyt. Virosta myös annettiin siloiteltu kuva sanomalehdissä ja epäkohtia kuten venäläistämistoimenpiteitä, pidätyksiä tai elintarvikepulaa ei julkistettu. Samaan aikaan Ruotsissa pakolaisvirolaisten toimesta ilmestyneiden lehtien maailma oli aivan toisenlainen. Niiden Etyk-aiheiset kirjoitukset käsittelivät lähes pelkästään Viron asiaa ja Etykin kolmannen korin asioita eli ihmisoikeuskysymyksiä. Ne myös toivat esille aivan toisenlaisen kuvan Neuvosto-Viron oloista kuin suomalaislehdet. Muissa kuin Etykiin liittyvissä artikkeleissa suomalaislehtien välillä on kuitenkin eroja. Yhdenkään tutkituista suomalaislehdistä (Helsingin Sanomat, Hufvudstadsbladet, Kansan Uutiset ja Uusi Suomi) ei voi sanoa noudattaneen täysin horjumatta mitään tiettyä linjaa Viro-kirjoittelussa. Yhdenmukaisimmin suhtautui Kansan Uutiset, joka harvoja poikkeuksia lukuun ottamatta ei tuonut esiin kritiikkiä Neuvostoliittoa kohtaan. Vaihtelevin suhtautuminen oli Helsingin Sanomilla, jonka tapauksessa ei oikeastaan voi puhua minkäänlaisesta linjasta. Hufvudstadsbladet oli melko neutraali joskin etäinen ja maltillinen. Eniten neuvostokritiikkiä viljeli Uusi Suomi. Kuitenkin myös siinä ilmestyi esimerkiksi kaunistelevia kuvauksia elämästä Neuvosto-Virossa, eikä sekään Ety-kokousten aikaan asettunut balttipakolaisten puolelle. Yhdessäkään lehdessä ei ilmestynyt Viro-aiheisia kirjoituksia usein; kaikkiaan artikkeleita aineistossani oli 4 lehdestä 3 vuodelta 247. Monissa niistäkään Viro ei ollut pääasia vaan sitä vain sivuttiin. Ruotsinvirolaisia lehtikirjoituksia aineistossani oli 318. Lehtien (Eesti Päevaleht ja Teataja) välillä ei ollut merkittäviä sisällöllisiä eroja. Suomalaislehdistä ne taas erosivat täysin. Viron kuulumisten ja maailmanpolitiikan lisäksi ne seurasivat myös Suomen asioita ja etenkin niitä tapauksia, joissa Viro ylitti uutiskynnyksen suomalaislehdissä. Suomen lehdissä taas ei paria lähinnä Uuden Suomen poikkeusta lukuun ottamatta kirjoitettu pakolaisvirolaisista mitään, eikä etenkään heidän toiminnastaan Viron asian eteen. Pakolaisvirolaisten lisäksi myös Neuvosto-Viro oli 1970-luvulla suurimmalle osalle suomalaisista varsin tuntematon, sillä julkisessa keskustelussa se esiintyi erittäin harvoin ja oli poistettu jopa oppikirjoista. Suomalaisten yleisen käsityksen mukaan Virossa kaikki oli hyvin ja siellä asui tyytyväisiä ihmisiä. Myös Etyk nähtiin Suomessa täysin toisenlaisessa valossa kuin Pohjanlahden toisella puolella, jossa kirjoittelua leimasi pettymys Etykiin toisen maailmansodan jälkeisten rajojen vahvistajana.

Familial aggregation of type 1 diabetes and diabetic nephropathy in Finland

Type 1 diabetes (T1D) is a common, multifactorial disease with strong familial clustering. In Finland, the incidence of T1D among children aged 14 years or under is the highest in the world. The increase in incidence has been approximately 2.4% per year. Although most new T1D cases are sporadic the first-degree relatives are at an increased risk of developing the same disease. This study was designed to examine the familial aggregation of T1D and one of its serious complications, diabetic nephropathy (DN). More specifically the study aimed (1) to determine the concordance rates of T1D in monozygotic (MZ) and dizygotic (DZ) twins and to estimate the relative contributions of genetic and environmental factors to the variability in liability to T1D as well as to study the age at onset of diabetes in twins; (2) to obtain long-term empirical estimates of the risk of T1D among siblings of T1D patients and the factors related to this risk, especially the effect of age at onset of diabetes in the proband and the birth cohort effect; (3) to establish if DN is aggregating in a Finnish population-based cohort of families with multiple cases of T1D, and to assess its magnitude and particularly to find out whether the risk of DN in siblings is varying according to the severity of DN in the proband and/or the age at onset of T1D: (4) to assess the recurrence risk of T1D in the offspring of a Finnish population-based cohort of patients with childhood onset T1D, and to investigate potential sex-related effects in the transmission of T1D from the diabetic parents to their offspring as well as to study whether there is a temporal trend in the incidence. The study population comprised of the Finnish Young Twin Cohort (22,650 twin pairs), a population-based cohort of patients with T1D diagnosed at the age of 17 years or earlier between 1965 and 1979 (n=5,144) and all their siblings (n=10,168) and offspring (n=5,291). A polygenic, multifactorial liability model was fitted to the twin data. Kaplan-Meier analyses were used to provide the cumulative incidence for the development of T1D and DN. Cox s proportional hazards models were fitted to the data. Poisson regression analysis was used to evaluate temporal trends in incidence. Standardized incidence ratios (SIRs) between the first-degree relatives of T1D patients and background population were determined. The twin study showed that the vast majority of affected MZ twin pairs remained discordant. Pairwise concordance for T1D was 27.3% in MZ and 3.8% in DZ twins. The probandwise concordance estimates were 42.9% and 7.4%, respectively. The model with additive genetic and individual environmental effects was the best-fitting liability model to T1D, with 88% of the phenotypic variance due to genetic factors. The second paper showed that the 50-year cumulative incidence of T1D in the siblings of diabetic probands was 6.9%. A young age at diagnosis in the probands considerably increased the risk. If the proband was diagnosed at the age of 0-4, 5-9, 10-14, 15 or more, the corresponding 40-year cumulative risks were 13.2%, 7.8%, 4.7% and 3.4%. The cumulative incidence increased with increasing birth year. However, SIR among children aged 14 years or under was approximately 12 throughout the follow-up. The third paper showed that diabetic siblings of the probands with nephropathy had a 2.3 times higher risk of DN compared with siblings of probands free of nephropathy. The presence of end stage renal disease (ESRD) in the proband increases the risk three-fold for diabetic siblings. Being diagnosed with diabetes during puberty (10-14) or a few years before (5-9) increased the susceptibility for DN in the siblings. The fourth paper revealed that of the offspring of male probands, 7.8% were affected by the age of 20 compared with 5.3% of the offspring of female probands. Offspring of fathers with T1D have 1.7 times greater risk to be affected with T1D than the offspring of mothers with T1D. The excess risk in the offspring of male fathers manifested itself through the higher risk the younger the father was when diagnosed with T1D. Young age at onset of diabetes in fathers increased the risk of T1D greatly in the offspring, but no such pattern was seen in the offspring of diabetic mothers. The SIR among offspring aged 14 years or under remained fairly constant throughout the follow-up, approximately 10. The present study has provided new knowledge on T1D recurrence risk in the first-degree relatives and the risk factors modifying the risk. Twin data demonstrated high genetic liability for T1D and increased heritability. The vast majority of affected MZ twin pairs, however, remain discordant for T1D. This study confirmed the drastic impact of the young age at onset of diabetes in the probands on the increased risk of T1D in the first-degree relatives. The only exception was the absence of this pattern in the offspring of T1D mothers. Both the sibling and the offspring recurrence risk studies revealed dynamic changes in the cumulative incidence of T1D in the first-degree relatives. SIRs among the first-degree relatives of T1D patients seems to remain fairly constant. The study demonstrates that the penetrance of the susceptibility genes for T1D may be low, although strongly influenced by the environmental factors. Presence of familial aggregation of DN was confirmed for the first time in a population-based study. Although the majority of the sibling pairs with T1D were discordant for DN, its presence in one sibling doubles and presence of ESRD triples the risk of DN in the other diabetic sibling. An encouraging observation was that although the proportion of children to be diagnosed with T1D at the age of 4 or under is increasing, they seem to have a decreased risk of DN or at least delayed onset.

Context-dependent mate choice in the sand goby, Pomatoschistus minutus

The results presented in this thesis show that all females of a given population do not necessarily choose similar mating partners. Specifically, partner preferences of a fish, the sand goby (Pomatoschistus minutus), varied among individual females and depended on the social context at the time of choice. I also show that females assess multiple mate choice cues simultaneously; partner preferences were based more strongly on an interaction effect between different choice cues than on any individual cue. Furthermore, I found that preferred matings involved fitness benefits in the form of increased offspring success, but these benefits were not significantly affected by mate compatibility. Hence, mate choice for partner compatibility does not appear to be an important determinant of the observed variation in female mate preferences in this species. The context-dependency of female mating preferences revealed is relevant to how genetic variation in sexually selected traits might be maintained: as the mating success of a certain male type varies according to the choice context, directional sexual selection on male traits is shown to be less intense than generally thought making for a slower loss of genetic variation in these traits. Mating preferences of sand gobies were assessed by giving females a binary choice between males that differed in body size and/or other focus traits. These association preferences were found to be sexually motivated, repeatable and to correspond to actual mating decisions.

VEGFR-2 and VEGFR-3 Specific Signaling in Lymphangiogenesis and Angiogenesis

The circulatory system consists of the blood and lymphatic vessels. While blood vessels transport oxygen, cells, and nutrients to tissues, the lymphatic vessels collect fluid, cells, and plasma proteins from tissues to return back to the blood circulation. Angiogenesis, the growth of new blood vessels from pre-existing ones, is an important process involved in several physiological conditions such as inflammation, wound healing, and embryonic development. Furthermore, angiogenesis is found in many pathological conditions such as atherosclerosis and the growth and differentiation of solid tumors. Many tumor types spread via lymphatic vessels to form lymph node metastasis. The elucidation of the molecular players coordinating development of the vascular system has provided an array of tools for further insight of the circulatory system. The discovery of the Vascular Endothelial Growth Factor (VEGF) family members and their tyrosine kinase receptors (VEGFRs) has facilitated the understanding of the vasculature in different physiological and pathological situations. The VEGFRs are expressed on endothelial cells and mediate the growth and maintenance of both the blood and lymphatic vasculatures. This study was undertaken to address the role of VEGFR-2 specific signaling in maturation of blood vessels during neoangiogenesis and in lymphangiogenesis. We also wanted to differentiate between VEGFR-2 and VEGFR-3 specific signaling in lymphangiogenesis. We found that specific VEGFR-2 stimulation alone by gene therapeutic methods is not sufficient for production of mature blood vessels. However, VEGFR-2 stimulation in combination with expression of platelet-derived growth factor D (PDGF-D), a recently identified member of the PDGF growth factor family, was capable of stabilizing these newly formed vessels. Signaling through VEGFR-3 is crucial during developmental lymphangiogenesis, but we showed that the lymphatic vasculature becomes independent of VEGFR-3 signaling after the postnatal period. We also found that VEGFR-2 specific stimulation cannot rescue the loss of lymphatic vessels when VEGFR-3 signaling is blocked and that VEGFR-2 specific signals promote lymphatic vessel enlargement, but are not involved in vessel sprouting to generate new lymphatic vessels in vivo, in contrast to the VEGFR-2 dependent sprouting observed in blood vessels. In addition, we compared the inhibitory effects of a small molecular tyrosine kinase inhibitor of VEGFR-2 vs. VEGFR-3 specific signaling in vitro and in vivo. Our results showed that the tyrosine kinase inhibitor could equally affect physiological and pathological processes dependent on VEGFR-2 and VEGFR-3 driven angiogenesis or lymphangiogenesis. These results provide new insights into the VEGFR specific pathways required for pre- and postnatal angiogenesis as well as lymphangiogenesis, which could provide important targets and therapies for treatment of diseases characterized by abnormal angiogenesis or lymphangiogenesis.

Venous thromboembolism during pregnancy and the impact of thrombophilia in pregnancy complications

Venous thromboembolism (VTE) is the greatest single cause of maternal mortality in pregnant women in developed countries. Pregnancy is a hypercoagulable state and brings about an enhanced risk of deep venous thrombosis (DVT) in otherwise healthy women. Traditionally, unfractionated heparin (UFH) has been used for treatment of DVT during pregnancy. We showed in our observational study that low molecular weight heparin (LMWH) is as effective and safe as UFH in the treatment of DVT during pregnancy. Although DVT during pregnancy is often massive, increasing the risk of developing long-term consequences, namely post-thrombotic syndrome (PTS), only 11% of all patients had confirmed PTS 3 4 years after DVT. In our studies the prevalence of PTS was not dependent on treatment (UFH vs LMWH). Low molecular weight heparin is more easily administered, few laboratory controls are required and the hospital stay is shorter, factors that lower the costs of treatment. Cervical insufficiency is defined as repeated very preterm delivery during the second or early third trimester. Infection is a well-known risk factor of preterm delivery. We found overpresentation of thrombophilic mutations (FV Leiden, prothrombin G20210A)among 42 patients with cervical insufficiency compared with controls (OR 6.7, CI 2.7 18.4). Thus, thrombophilia might be a risk factor of cervical insufficiency possibly explained by interaction of coagulation and inflammation processes. The presence of antiphospholipid (aPL) antibodies increases the risk for recurrent miscarriage (RM). Annexins are proteins which all bind to anionic phospholipids (PLs) preventing clotting on vascular phospholipid surfaces. Plasma concentrations of circulating annexin IV and V were investigated in 77 pregnancies at the beginning of pregnancy among women with a history of RM, and in connection to their aPL antibody status. Control group consisted unselected pregnant patients (n=25) without history of adverse pregnancy outcome. Plasma levels of annexin V were significantly higher at the beginning (≤5th week) of pregnancy in women with aPL antibodies compared with those without aPL antibodies (P=0.03). Levels of circulating annexin V were also higher at the 6th (P= 0.01) and 8th week of pregnancy in subjects with aPL antibodies (P=0.01). Results support the hypothesis that aPL could displace annexin from anionic phospholipid surfaces of syncytiotrophoblasts (STBs) and may exert procoagulant activities on the surfaces of STBs Recurrent miscarriage (RM) has been suggested to be caused by mutations in genes coding for various coagulation factors resulting in thrombophilia. In the last study of my thesis were investigated the prevalence of thrombomodulin (TM) and endothelial protein C receptor polymorphism EPCR among 40 couples and six women suffering RM. This study showed that mutations in the TM or EPCR genes are not a major cause of RM in Finnish patients.

HDL subspecies : association with low HDL-C, obesity, and metabolic syndrome

AIMS An independent, powerful coronary heart disease (CHD) predictor is a low level of high-density lipoprotein cholesterol (HDL-C). Discoidal preβ-HDL particles and large HDL2 particles are the primary cholesterol acceptors in reverse cholesterol transport, a key anti-atherogenic HDL mechanism. The quality of HDL subspecies may provide better markers of HDL functionality than does HDL-C alone. We aimed I) to study whether alterations in the HDL subspecies profile exist in low-HDL-C subjects II) to explore the relationship of any changes in HDL subspecies profile in relation to atherosclerosis and metabolic syndrome; III) to elucidate the impact of genetics and acquired obesity on HDL subspecies distribution. SUBJECTS The study consisted of 3 cohorts: A) Finnish families with low HDL-C and premature CHD (Study I: 67 subjects with familial low HDL-C and 64 controls; Study II: 83 subjects with familial low HDL-C, 65 family members with normal HDL-C, and 133 controls); B) a cohort of 113 low- and 133 high-HDL-C subjects from the Health 2000 Health Examination Survey carried out in Finland (Study III); and C) a Finnish cohort of healthy young adult twins (52 monozygotic and 89 dizygotic pairs) (Study IV). RESULTS AND CONCLUSIONS The subjects with familial low HDL-C had a lower preβ-HDL concentration than did controls, and the low-HDL-C subjects displayed a dramatic reduction (50-70%) in the proportion of large HDL2b particles. The subjects with familial low HDL-C had increased carotid atherosclerosis measured as intima-media-thickness (IMT), and HDL2b particles correlated negatively with IMT. The reduction in both key cholesterol acceptors, preβ-HDL and HDL2 particles, supports the concept of impaired reverse cholesterol transport contributing to the higher CHD risk in low-HDL-C subjects. The family members with normal HDL-C and the young adult twins with acquired obesity showed a reduction in large HDL2 particles and an increase in small HDL3 particles, which may be the first changes leading to the lowering of HDL-C. The low-HDL-C subjects had a higher serum apolipoprotein E (apoE) concentration, which correlated positively with the metabolic syndrome components (waist circumference, TG, and glucose), highlighting the need for a better understanding of apoE metabolism in human atherosclerosis. In the twin study, the increase in small HDL3b particles was associated with obesity independent of genetic effects. The heritability estimate, of 73% for HDL-C and 46 to 63% for HDL subspecies, however, demonstrated a strong genetic influence. These results suggest that the relationship between obesity and lipoproteins depends on different elements in each subject. Finally, instead of merely elevating HDL-C, large HDL2 particles and discoidal preβ-HDL particles may provide beneficial targets for HDL-targeted therapy.