Effect of long-wave UV radiation on mouse melanoma: an in vitro and in vivo study

The skin cancer incidence has increased substantially over the past decades and the role of ultraviolet (UV) radiation in the etiology of skin cancer is well established. Ultraviolet B radiation (280-320 nm) is commonly considered as the more harmful part of the UV-spectrum due to its DNA-damaging potential and well-known carcinogenic effects. Ultraviolet A radiation (320-400 nm) is still regarded as a relatively low health hazard. However, UVA radiation is the predominant component in sunlight, constituting more than 90% of the environmentally relevant solar ultraviolet radiation. In the light of the recent scientific evidence, UVA has been shown to have genotoxic and immunologic effects, and it has been proposed that UVA plays a significant role in the development of skin cancer. Due to the popularity of skin tanning lamps, which emit high intensity UVA radiation and because of the prolonged sun tanning periods with the help of effective UVB blockers, the potential deleterious effects of UVA has emerged as a source of concern for public health. The possibility that UV radiation may affect melanoma metastasis has not been addressed before. UVA radiation can modulate various cellular processes, some of which might affect the metastatic potential of melanoma cells. The aim of the present study was to investigate the possible role of UVA irradiation on the metastatic capacity of mouse melanoma both in vitro and in vivo. The in vitro part of the study dealt with the enhancement of the intercellular interactions occurring either between tumor cells or between tumor cells and endothelial cells after UVA irradiation. The use of the mouse melanoma/endothelium in vitro model showed that a single-dose of UVA to melanoma cells causes an increase in melanoma cell adhesiveness to non-irradiated endothelium after 24-h irradiation. Multiple-dose irradiation of melanoma cells already increased adhesion at a 1-h time-point, which suggests the possible cumulative effect of multiple doses of UVA irradiation. This enhancement of adhesiveness might lead to an increase in binding tumor cells to the endothelial lining of vasculature in various internal organs if occurring also in vivo. A further novel observation is that UVA induced both decline in the expression of E-cadherin adhesion molecule and increase in the expression of the N-cadherin adhesion molecule. In addition, a significant decline in homotypic melanoma-melanoma adhesion (clustering) was observed, which might result in the reduction of E-cadherin expression. The aim of the in vivo animal study was to confirm the physiological significance of previously obtained in vitro results and to determine whether UVA radiation might increase melanoma metastasis in vivo. The use of C57BL/6 mice and syngeneic melanoma cell lines B16-F1 and B16-F10 showed that mice, which were i.v. injected with B16-F1 melanoma cells and thereafter exposed to UVA developed significantly more lung metastases when compared with the non-UVA-exposed group. To study the mechanism behind this phenomenon, the direct effect of UVA-induced lung colonization capacity was examined by the in vitro exposure of B16-F1 cells. Alternatively, the UVA-induced immunosuppression, which might be involved in increased melanoma metastasis, was measured by standard contact hypersensitivity assay (CHS). It appears that the UVA-induced increase of metastasis in vivo might be caused by a combination of UVA-induced systemic immunosuppression, and to the lesser extent, it might be caused by the increased adhesiveness of UVA irradiated melanoma cells. Finally, the UVA effect on gene expression in mouse melanoma was determined by a cDNA array, which revealed UVA-induced changes in the 9 differentially expressed genes that are involved in angiogenesis, cell cycle, stress-response, and cell motility. These results suggest that observed genes might be involved in cellular response to UVA and a physiologically relevant UVA dose have previously unknown cellular implications. The novel results presented in this thesis offer evidence that UVA exposure might increase the metastatic potential of the melanoma cells present in blood circulation. Considering the wellknown UVA-induced deleterious effects on cellular level, this study further supports the notion that UVA radiation might have more potential impact on health than previously suggested. The possibility of the pro-metastatic effects of UVA exposure might not be of very high significance for daily exposures. However, UVA effects might gain physiological significance following extensive sunbathing or solaria tanning periods. Whether similar UVA-induced pro-metastatic effects occur in people sunbathing or using solaria remains to be determined. In the light of the results presented in this thesis, the avoidance of solaria use could be well justified.

Memory Meanders : Place, Home and Commemoration in an Ex-Rhodesian Diaspora Community

Memory Meanders is an ethnographic analysis of a postcolonial migrant community, white former Rhodesians, who have emigrated from Zimbabwe to South Africa after Zimbabwe s independence in 1980. An estimated 100 000 whites left the country during the first years of independence. Majority of these emigrants settled in South Africa. In recent years President Mugabe s land redistribution program has inflicted forced expulsions and violence against white farmers and black farm workers, and instigated a new wave of emigration. Concerning the study of Southern Africa, my research is therefore very topical. In recent years there has been a growing concern to study postcolonialism as it unfolds in the lived realities of actual postcolonies. A rising interest has also been cast on colonial cultures and white colonials within complex power relationships. My research offers insight to these discussions by investigating the ways in which the colonial past affects and effects in the present activities and ideas of former colonials. The study also takes part in discussing fundamental questions concerning how diaspora communities socially construct their place in the world in relation to the place left behind, to their current places of dwelling and to the community in dispersal. In spite of Rhodesia s incontestable ending, it is held close by social practices; by thoughts and talks, by material displays, and by webs of meaningful relationships. Such social memory practices, I suggest, are fundamental to how the community understands itself. The vantage points from which I examine how the ex-Rhodesians reminisce about Rhodesia concern ideas and practices related to place, home and commemoration. I first focus on the processes of symbolic investment that go into understanding place and landscape in Rhodesia and ask how the once dwelled-in places, iconic landscapes and experiences within places are reminisced about in diaspora. Secondly, I examine how home both as a mundanely organized sphere of everyday lives and as an idea of belonging is culturally configured, and analyze how and if homes travel in diaspora. In the final ethnographic section I focus on commemorative practices. I first analyze how food and culturally specific festive occasions of commensality are connected to social and sensual memory, considering the unique ways in which food acts as a mnemonic trigger in a diaspora community. The second example concerns the celebration of a centenary of Rhodesia in 1990. Through this case I describe how the mnemonic power of commemoration rests on the fact that culturally meaningful experiences are bodily re-enacted. I show how habitual memory connected to performance is one example of how memory gets passed-on in non-textual ways.

Hyvän kuntoutuskäytännön perusta.Käytännön ja tutkimustiedon analyysistä suosituksiin vaikeavammaisten kuntoutuksen kehittämishankkeessa.

Laki Kelan kuntoutuksesta määrittää, että kuntoutuksen tulee olla hyvän kuntoutuskäytännön mukaista. Tämän Vaikeavammaisten kuntoutuksen kehittämishankkeeseen (VAKE) kuuluvan tutkimuksen tavoitteena oli kolmen diagnoosiryhmän – aivoverenkiertohäiriön (AVH), multippeliskleroosin (MS) ja Cerebral Palsyn (CP) – avulla kuvata Kelan järjestämän vaikeavammaisten lääkinnällisen kuntoutuksen nykytilaa, sen kehittämistarpeita ja eri kuntoutustoimenpiteiden vaikuttavuutta sekä laatia suositukset hyvästä kuntoutuskäytännöstä. Tutkimus toteutettiin laajassa tutkimusyhteistyössä vuosina 2007–2009. Kirjan toisessa osassa kuvataan AVH-, MS- ja CP-kuntoutuksen nykykäytännöt, jotka perustuvat kuntoutusalan ammattilaisille ja asiantuntijoille tehtyihin kysely- ja haastattelututkimuksiin, sekä esitellään Kelalle lähetettyjen kuntoutussuunnitelmien analyysit. Kirjan kolmas osa käsittelee kuntoutuksen arviointikäytäntöjä. Tulokset perustuvat nykykäytäntöjä selvittäneisiin kysely- ja haastatteluaineistoihin sekä vaikuttavuustutkimuksissa käytettyihin arviointimenetelmiin. Neljännessä osassa esitetään järjestelmällisiin katsauksiin perustuva vaikuttavuusnäyttö AVH-, MS- ja CP-kuntoutujien fysio-, puhe- ja toimintaterapiasta sekä MS:n osalta neuropsykologisesta kuntoutuksesta. Näytön asteen määrittely perustuu Käypä hoito -suosituksen kriteereihin. Kirjan viidennessä osassa esitetään tunnistettujen ongelmien sekä tutkimustulosten perusteella laaditut suositukset hyvistä kuntoutuskäytännöistä Kelan järjestämisvelvollisuuteen kuuluvan vaikeavammaisten lääkinnällisen kuntoutuksen osalta. Suositukset perustuvat edellä mainittuihin tutkimuksiin ja Asiakkaan äänellä -tutkimukseen. Suositusten tavoitteena on mahdollistaa tämänhetkisen tiedon mukainen asiakaslähtöinen, oikea-aikainen, oikein kohdennettu ja vaikuttava kuntoutus vaikeavammaisille kuntoutujille. Kuntoutujan sujuva ja yksilöllinen kuntoutusprosessi edellyttää suomalaisessa kuntoutusjärjestelmässä eri organisaatioiden välistä, moniammatillista sekä osaavaa yhteistyötä, kuntoutujan näkemyksen ja elämän kokonaistilanteen ymmärtämistä, joustavaa tiedonvälitystä sekä pitkäaikaista ohjausta, tukea ja seurantaa. Kuntoutuksen viitekehyksenä tulee käyttää ICF-luokitusta. Hyvien kuntoutuskäytäntöjen edelleen kehittämiseksi on saatava lisätietoa nykyisistä kuntoutuskäytännöistä, kuntoutuksen vaikuttavuudesta ja sen osoittamiseen soveltuvista arviointimenetelmistä.

Denitrification in the River Estuaries of the Northern Baltic Sea

Estuaries have been suggested to have an important role in reducing the nitrogen load transported to the sea. We measured denitrification rates in six estuaries of the northern Baltic Sea. Four of them were river mouths in the Bothnian Bay (northern Gulf of Bothnia), and two were estuary bays, one in the Archipelago Sea (southern Gulf of Bothnia) and the other in the Gulf of Finland. Denitrification rates in the four river mouths varied between 330 and 905 mu mol N m(-2) d(-1). The estuary bays at the Archipelago Sea and the Gulf of Bothnia had denitrification rates from 90 mu mol N m(-2) d(-1) to 910 mu mol N m(-2) d(-1) and from 230 mu mol N m(-2) d(-1) to 320 mu mol N m(-2) d(-1), respectively. Denitrification removed 3.6-9.0% of the total nitrogen loading in the river mouths and in the estuary bay in the Gulf of Finland, where the residence times were short. In the estuary bay with a long residence time, in the Archipelago Sea, up to 4.5% of nitrate loading and 19% of nitrogen loading were removed before entering the sea. According to our results, the sediments of the fast-flowing rivers and them estuary areas with short residence times have a limited capacity to reduce the nitrogen load to the Baltic Sea.