Ecology, population genetics and conservation of the African violet

The ongoing rapid fragmentation of tropical forests is a major threat to global biodiversity. This is because many of the tropical forests are so-called biodiversity 'hotspots', areas that host exceptional species richness and concentrations of endemic species. Forest fragmentation has negative ecological and genetic consequences for plant survival. Proposed reasons for plant species' loss in forest fragments are, e.g., abiotic edge effects, altered species interactions, increased genetic drift, and inbreeding depression. To be able to conserve plants in forest fragments, the ecological and genetic processes that threaten the species have to be understood. That is possible only after obtaining adequate information on their biology, including taxonomy, life history, reproduction, and spatial and genetic structure of the populations. In this research, I focused on the African violet (genus Saintpaulia), a little-studied conservation flagship from the Eastern Arc Mountains and Coastal Forests hotspot of Tanzania and Kenya. The main objective of the research was to increase understanding of the life history, ecology and population genetics of Saintpaulia that is needed for the design of appropriate conservation measures. A further aim was to provide population-level insights into the difficult taxonomy of Saintpaulia. Ecological field work was conducted in a relatively little fragmented protected forest in the Amani Nature Reserve in the East Usambara Mountains, in northeastern Tanzania, complemented by population genetic laboratory work and ecological experiments in Helsinki, Finland. All components of the research were conducted with Saintpaulia ionantha ssp. grotei, which forms a taxonomically controversial population complex in the study area. My results suggest that Saintpaulia has good reproductive performance in forests with low disturbance levels in the East Usambara Mountains. Another important finding was that seed production depends on sufficient pollinator service. The availability of pollinators should thus be considered in the in situ management of threatened populations. Dynamic population stage structures were observed suggesting that the studied populations are demographically viable. High mortality of seedlings and juveniles was observed during the dry season but this was compensated by ample recruitment of new seedlings after the rainy season. Reduced tree canopy closure and substrate quality are likely to exacerbate seedling and juvenile mortality, and, therefore, forest fragmentation and disturbance are serious threats to the regeneration of Saintpaulia. Restoration of sufficient shade to enhance seedling establishment is an important conservation measure in populations located in disturbed habitats. Long-term demographic monitoring, which enables the forecasting of a population s future, is also recommended in disturbed habitats. High genetic diversities were observed in the populations, which suggest that they possess the variation that is needed for evolutionary responses in a changing environment. Thus, genetic management of the studied populations does not seem necessary as long as the habitats remain favourable for Saintpaulia. The observed high levels of inbreeding in some of the populations, and the reduced fitness of the inbred progeny compared to the outbred progeny, as revealed by the hand-pollination experiment, indicate that inbreeding and inbreeding depression are potential mechanisms contributing to the extinction of Saintpaulia populations. The relatively weak genetic divergence of the three different morphotypes of Saintpaulia ionantha ssp. grotei lend support to the hypothesis that the populations in the Usambara/lowlands region represent a segregating metapopulation (or metapopulations), where subpopulations are adapting to their particular environments. The partial genetic and phenological integrity, and the distinct trailing habit of the morphotype 'grotei' would, however, justify its placement in a taxonomic rank of its own, perhaps in a subspecific rank.

The Impact of Lifestyle and Cardiovascular Risk Factors in Midlife on the Health-Related Quality of Life among Old Men

Prevention of cardiovascular diseases is known to postpone death, but in an aging society it is important to ensure that those who live longer are neither disabled nor suffering an inferior quality of life. It is essential both from the point of view of the aging individual as well as that of society that any individual should enjoy a good physical, mental and social quality of life during these additional years. The studies presented in this thesis investigated the impact of modifiable risk factors, all of which affect cardiovascular health in the long term, on mortality and health-related quality of life (HRQoL). The data is based on the all male cohort of the Helsinki Businessmen Study. This cohort, originally of 3.490 men born between 1919 and 1934 has been followed since the 1960s. The socioeconomic status of the participants is similar, since all the men were working in leading positions. Extensive baseline examinations were conducted among 2.375 of the men in 1974 when their mean age was 48 and at this time the health, medication and cardiovascular risk factors of the participants were observed. In 2000, at the mean age of 73, the HRQoL of the survivors of the original cohort was examined using the RAND-36 mailed questionnaire (n=1.864). RAND-36, along with the equivalent SF-36, is the world s most widely used means of assessing generic health. The response rate was generally over 90%. Mortality was retrieved from national registers in 2000 and 2002. For the six substudies of this thesis, the impact of four different modifiable cardiovascular risk factors (weight gain, cholesterol, alcohol and smoking) on the HRQoL in old age was studied both independently and in combination. The follow-up time for these studies varies from 26 up to 39 years. Mortality is reported separately or included in the RAND-36 scores for HRQoL. Elevated levels of all the risk factors examined among the participants in midlife led to a diminished life expectancy. Among survivors, lower weight gain in midlife was associated with better HRQoL, both physically and mentally. Higher levels of serum cholesterol in middle age indicated both an earlier mortality and a decline in the physical component of HRQoL in a dose-response manner during the 39-year follow-up. Mortality was significantly higher in the highest baseline category of reported mean alcohol consumption (≥ 5 drinks/day), but fairly comparable in abstainers and moderate drinkers during the 29-year follow-up. When HRQoL in old age was accounted for mortality, the men with the highest alcohol consumption in midlife clearly had poorer physical and mental health in old age, but the HRQoL of abstainers and those who drank alcohol in moderation were comparatively similar. The amount of cigarette smoking in midlife was shown to have had a dose-response effect on both mortality and HRQoL in old age during the 26 year follow-up. The men smoking over 20 cigarettes daily in middle age lost about 10 years of their life-expectancy. Meanwhile, the physical functioning of surviving heavy smokers in old age was similar to men 10 years older in the general population. The impact of clustered cardiovascular risk factors was examined by comparing two subcohorts of men who were healthy in 1974, but with different baseline risk factor status. The men with low risk had a 50 % lower mortality during the 29-years follow-up. Their RAND-36 scores for the physical quality of life in old age were significantly better, and the 2002 questionnaire examining psychological well-being indicated also significantly better mental health among the low-risk group. The results indicate that different risk factor levels in midlife have a meaningful impact on life-expectancy and the quality of these extra years. Leading a healthy lifestyle improves both survival and the quality of life.

Pathobiological Aspects of Nonreheumatic Aortic Valve Stenosis

Aortic valve stenosis (AS) is an active disease process akin to atherosclerosis, with chronic inflammation, lipid accumulation, extracellular matrix remodeling, fibrosis, and extensive calcification of the valves being characteristic features of the disease. The detailed mechanisms and pathogenesis of AS are still incompletely understood, however, and pharmacological treatments targeted toward components of the disease are not currently available. In this thesis project, my coworkers and I studied stenotic aortic valves obtained from 86 patients undergoing valve replacement for clinically significant AS. Non-stenotic control valves (n=17) were obtained from patients undergoing cardiac transplantation or from organ donors without cardiac disease. We identified a novel inflammatory factor, namely mast cell, in stenotic aortic valves and present evidence showing that this multipotent inflammatory cell may participate in the pathogenesis of AS. Using immunohistochemistry and double immunofluorescence stainings, we found that a considerable number of mast cells accumulate in stenotic valves and, in contrast to normal valves, the mast cells in diseased valves were in an activated state. Moreover, valvular mast cells contained two effective proteases, chymase and cathepsin G, which may participate in adverse remodeling of the valves either by inducing fibrosis (chymase and cathepsin G) or by degrading elastin fibers in the valves (cathepsin G). As chymase and cathepsin G are both capable of generating the profibrotic peptide angiotensin II, we also studied the expression and activity of angiotensin-converting enzyme (ACE) in the valves. Using RT-PCR, imunohistochemistry, and autoradiography, we observed a significant increase in the expression and activity of ACE in stenotic valves. Besides mast cell-derived cathepsin G, aortic valves contained other elastolytic cathepsins (S, K, and V). Using immunohistochemistry, RT-PCR, and fluorometric microassay, we showed that the expression and activity of these cathepsins were augmented in stenotic valves. Furthermore, in stenotic but not in normal valves, we observed a distinctive pattern of elastin fiber degradation and disorganization. Importantly, this characteristic elastin degradation observed in diseased valves could be mimicked by adding exogenous cathepsins to control valves, which initially contained intact elastin fibers. In stenotic leaflets, the collagen/elastin ratio was increased and correlated positively with smoking, a potent AS-accelerating factor. Indeed, cigarette smoke could also directly activate cultured mast cells and fibroblasts. Next, we analyzed the expression and activity of neutral endopeptidase (NEP), which parallels the actions of ACE in degrading bradykinin (BK) and thus inactivates antifibrotic mechanisms in tissues. Real-time RT-PCR and autoradiography revealed NEP expression and activity to be enhanced in stenotic valves compared to controls. Furthermore, both BK receptors (1 and 2) were present in aortic valves and upregulated in stenotic leaflets. Isolated valve myofibroblasts expressed NEP and BK receptors, and their upregulation occurred in response to inflammation. Finally, we observed that the complement system, a source of several proinflammatory mediators and also a potential activator of valvular mast cells, was activated in stenotic valves. Moreover, receptors for the complement-derived effectors C3a and C5a were expressed in aortic valves and in cultured aortic valve myofibroblasts, in which their expression was induced by inflammation as well as by cigarette smoke. In conclusion, our findings revealed several novel mechanisms of inflammation (mast cells and mast cell-derived mediators, complement activation), fibrosis (ACE, chymase, cathepsin G, NEP), and elastin fiber degradation (cathepsins) in stenotic aortic valves and highlighted these effectors as possible pathogenic contributors to AS. These results support the notion of AS as an active process with inflammation and extracellular matrix remodeling as its key features and identify possible new targets for medical therapy in AS.

Detection of renal dysfunction during and after anaesthesia and surgery - evaluation of the influence of inorganic fluoride, ketorolac and clonidine

Drugs and surgical techniques may have harmful renal effects during the perioperative period. Traditional biomarkers are often insensitive to minor renal changes, but novel biomarkers may more accurately detect disturbances in glomerular and tubular function and integrity. The purpose of this study was first, to evaluate the renal effects of ketorolac and clonidine during inhalation anesthesia with sevoflurane and isoflurane, and secondly, to evaluate the effect of tobacco smoking on the production of inorganic fluoride (F-) following enflurane and sevoflurane anesthesia as well as to determine the effect of F- on renal function and cellular integrity in surgical patients. A total of 143 patients undergoing either conventional (n = 75) or endoscopic (n = 68) inpatient surgery were enrolled in four studies. The ketorolac and clonidine studies were prospective, randomized, placebo controlled and double-blinded, while the cigarette smoking studies were prospective cohort studies with two parallel groups. As a sign of proximal tubular deterioration, a similar transient increase in urine N-acetyl-beta-D-glucosaminidase/creatinine (U-NAG/crea) was noted in both the ketorolac group and in the controls (baseline vs. at two hours of anesthesia, p = 0.015) with a 3.3 minimum alveolar concentration hour sevoflurane anesthesia. Uncorrelated U-NAG increased above the maximum concentration measured from healthy volunteers (6.1 units/l) in 5/15 patients with ketorolac and in none of the controls (p = 0.042). As a sign of proximal tubular deterioration, U-glutathione transferase-alpha/crea (U-GST-alpha/crea) increased in both groups at two hours after anesthesia but a more significant increase was noted in the patients with ketorolac. U-GST-alpha/crea increased above the maximum ratio measured from healthy volunteers in 7/15 patients with ketorolac and in 3/15 controls. Clonidine diminished the activation of the renin-angiotensin aldosterone system during pneumoperitoneum; urine output was better preserved in the patients treated with clonidine (1/15 patients developed oliguria) than in the controls (8/15 developed oliguria (p=0.005)). Most patients with pneumoperitoneum and isoflurane anesthesia developed a transient proximal tubular deterioration, as U-NAG increased above 6.1 units/L in 11/15 patients with clonidine and in 7/15 controls. In the patients receiving clonidine treatment, the median of U-NAG/crea was higher than in the controls at 60 minutes of pneumoperitoneum (p = 0.01), suggesting that clonidine seems to worsen proximal tubular deterioration. Smoking induced the metabolism of enflurane, but the renal function remained intact in both the smokers and the non-smokers with enflurane anesthesia. On the contrary, smoking did not induce sevoflurane metabolism, but glomerular function decreased in 4/25 non-smokers and in 7/25 smokers with sevoflurane anesthesia. All five patients with S-F- ≥ 40 micromol/L, but only 6/45 with S-F- less than 40 micromol/L (p = 0.001), developed a S-tumor associated trypsin inhibitor concentration above 3 nmol/L as a sign of glomerular dysfunction. As a sign of proximal tubulus deterioration, U-beta 2-microglobulin increased in 2/5 patients with S-F- over 40 micromol/L compared to 2/45 patients with the highest S-F- less than 40 micromol/L (p = 0.005). To conclude, sevoflurane anesthesia may cause a transient proximal tubular deterioration which may be worsened by a co-administration of ketorolac. Clonidine premedication prevents the activation of the renin-angiotensin aldosterone system and preserves normal urine output, but may be harmful for proximal tubules during pneumoperitoneum. Smoking induces the metabolism of enflurane but not that of sevoflurane. Serum F- of 40 micromol/L or higher may induce glomerular dysfunction and proximal tubulus deterioration in patients with sevoflurane anesthesia. The novel renal biomarkers warrant further studies in order to establish reference values for surgical patients having inhalation anesthesia.

Verkkomedian käyttö ja tutkiminen : Iltalehti Online 1995-2001

Marja Heinonen s dissertation Verkkomedian käyttö ja tutkiminen. Iltalehti Online 1995-2001 describes the usage of new internet based news service Iltalehti Online during its first years of existence, 1995-2001. The study focuses on the content of the service and users attitudes towards the new media and its contents. Heinonen has also analyzed and described the research methods that can be used in the research of any new media phenomenon when there is no historical perspective to do the research. Heinonen has created a process model for the research of net medium, which is based on a multidimensional approach. She has chosen an iterative research method inspired by Sudweeks and Simoff s CEDA-methodology in which qualitative and quantitative methods take turns both creating results and new research questions. The dissertation discusses and describes the possibilities of combining several research methods in the study of online news media. On general level it discusses the methodological possibilities of researching a completely new media form when there is no historical perspective. The result of these discussions is in favour for the multidimensional methods. The empiric research was built around three cases of Iltalehti Online among its users: log analysis 1996-1999, interviews 1999 and clustering 2000-2001. Even though the results of different cases were somewhat conflicting here are the central results from the analysis of Iltalehti Online 1995-2001: - Reading was strongly determined by the gender. - The structure of Iltalehti Online guided the reading strongly. - People did not make a clear distinction in content between news and entertainment. - Users created new habits in their everyday life during the first years of using Iltalehti Online. These habits were categorized as follows: - break between everyday routines - established habit - new practice within the rhythm of the day - In the clustering of the users sports, culture and celebrities were the most distinguishing contents. Users did not move across these borders as much as within them. The dissertation gives contribution to the development of multidimensional research methods in the field of emerging phenomena in media field. It is also a unique description of a phase of development in media history through an unique research material. There is no such information (logs + demographics) available of any other Finnish online news media. Either from the first years or today.

Havupuiden erikoismuotojen lisäysmenetelmät

Havupuiden erikoismuotoja on käytetty koristekasveina jo vuosisatoja ympäri maailmaa. Niitä on lisätty pääsääntöisesti pistokkaista ja varttamalla. Suomessa kotimaisten metsäpuidemme erikois-muotoja on kartoitettu ja kerätty kokoelmiin järjestelmällisemmin 1960-luvulta alkaen. Taimisto-viljelijät, puutarhasuunnittelijat ja kotipuutarhurit ovat olleet enenevässä määrin kiinnostuneita näistä kotimaisista kestävistä havukasveista. Yli 90 prosenttia markkinoillamme olevista havukas-veista tuodaan ulkomailta, joten on selvää, että niiden talvenkestävyydessä on ongelmia. Tämän tutkimuksen tavoitteena oli selvittää kotimaisille erikoismuodoille sopivia lisäysmene-telmiä ja siten edistää kotimaisen havukasvituotannon mahdollisuuksia. Aineistona kokeissa oli kotimaisia erikoismuotoja metsäkuusesta (Picea abies (L.) Karsten) ja kotikatajasta (Juniperus communis L.), tavallisia metsäkuusia sekä kahdeksan ulkomaista havupuutaksonia. Lisäysmene-telmistä tutkittiin varttamista ja pistokaslisäystä ja kokeet suoritettiin Metsäntutkimuslaitoksen toimipaikoissa Lopen Haapastensyrjässä sekä Punkaharjulla. Varttamiskokeessa vertailtiin koti-maisen kuusen erikoismuotokloonien varttamisen onnistumista. Pistokaskokeissa tutkittiin geno-tyypin, emopuun iän, pistokasoksan sijainnin sekä hormonikäsittelyn vaikutusta havukasvien pis-tokkaiden juurtumiseen. Tavalliset metsäkuuset toimivat kontrolleina. Tutkimus osoitti, että varttaminen onnistui erinomaisesti kaikilla erikoismuotoklooneilla. Ovat-ko vartteet esteettisesti katsottuna koristekäyttöön sopivia, jää vielä seurattavaksi. Pistokaskokeis-sa havaittiin, että juveniilisuus vaikutti pistokkaiden juurtumiseen, mutta iäkkäistäkin puista lisää-minen onnistuu, kunhan genotyyppi on sopiva. Keskimäärin alaoksat juurtuivat paremmin kuin latvuksen yläosista otetut pistokasoksat, mutta vain yhdellä kloonilla ero oli tilastollisesti merkit-sevä. Hormonikäsittely heikensi selvästi kotimaisen kuusen ja katajan pistokkaiden juurtumista, mutta ulkomaisiin havupuulajeihin käsittelyllä ei ollut vaikutusta. Kotimaisen havukasvituotannon pohjaksi pitäisi tehdä kloonivalintaa, jossa koristearvon lisäksi otettaisiin huomioon myös kloonin lisättävyys. Taimien tuottaminen pistokkaista on selvästi edul-lisempaa kuin vartteiden tuottaminen, joskin varte kasvaa myyntikuntoon nopeammin kuin pisto-kastaimi. Pistokastaimi on kuitenkin omajuurinen ja stabiilimpi kasvutavaltaan kuin varte. Tämä korostuu etenkin kääpiömuotoja tuotettaessa.

Tupakka, luokka ja terveyskäyttäytymisen ongelma

Smoking has decreased significantly over the last few decades, but it still remains one of the most serious public health problems in all Western countries. Smoking has decreased especially in upper socioeconomic groups, and this differentiation is an important factor behind socioeconomic health differentials. The study examines smokers risk perceptions, justifications and the meaning of smoking in different occupational groups. The starting point of the research is that the concept of health behaviour and the individualistic orientation it implies is too narrow a viewpoint with which to understand the current cultural status of smoking and to explain its association with social class. The study utilizes two kinds of data. Internet discussions are used to examine smokers risk perceptions and counter-reactions to current public health discourses. Interviews of smokers and ex-smokers (N=55) from different occupations are utilized to analyse the process of giving up smoking, social class differences in the justifications of smoking and the role of smoking in manual work. The continuing popularity of smoking is not a question of lacking knowledge of or concern about health risks. Even manual workers, in whom smoking is more prevalent, consider smoking a health risk. However, smokers have several ways of dealing with the risk. They can equate it with other health risks confronted in everyday life or question the adequacy of expert knowledge. Smoking can be seen as signifying the ability to make independent decisions and to question authorities. Regardless of the self-acknowledged dependency, smoking can be understood as a choice. This seemingly contradictory viewpoint was central especially for non-manual workers. They emphasized the pleasures and rules of smoking and the management of dependency. In contrast, manual workers did not give positive justifications for their smoking, thus implying the self-evident nature of the habit. Still, smoking functions as a resource in manual work as it increases the autonomy of workers in terms of their daily tasks. At the same time, smoking is attached to other routines and practices at workplaces. The study shows that in order to understand current trends in smoking, differing perceptions of risk and health as well as ways of life and their social and economic determinants need to be taken into account. Focussing on the social contexts and environments in which smoking is most prevalent is necessary in order to explain the current association of smoking with the working class.

Ruokauskomukset Mosambikin maaseudun raskaana olevilla ja imettävillä naisilla

Ihmisille ympäri maailmaa on tyypillistä valita tiettyjä ruokia suuremmasta valikoimasta syömäkelpoista ruokaa ja luoda mieltymyksiä sekä kieltoja joitakin ruokia kohtaan. Näitä ilmiöitä kutsutaan ruokauskomuksiksi ja ne ovat tärkeä osa kulttuuria. Niiden taustalla on usein terveydelliset perustelut tai sosiaalinen arvostus yhteisössä. Afrikassa on todettu olevan paljon erilaisia ruokauskomuksia, jotka kohdistuvat usein raskaana oleviin ja imettäviin naisiin sekä lapsiin, ryhmään, joka on fysiologisesti erityisen herkässä elämänvaiheessa. Ravitsemustilan tai ruokaturvan ollessa heikko, mahdollisilla ruokauskomuksilla voi olla merkittävät seuraukset erityisesti tämän väestönosan terveydentilaan. Aliravitsemus ja virheravitsemus ovat edelleen suuria ongelmia Afrikassa ja muissa kehittyvissä maissa. Tämän työn tavoitteena oli tutkia laadullisin menetelmin, onko erityisesti raskaana olevilla ja imettävillä naisilla Keski-Mosambikin maaseudulla, Zambézian maakunnassa, ruokauskomuksia, mitä ne mahdollisesti ovat, sekä arvioida voiko ruokauskomuksilla olla ravitsemuksellista merkitystä. Menetelminä oli 5 ryhmähaastattelua kolmessa kylässä ja 10 yksilöhaastattelua kahdessa kylässä. Tutkittavat olivat 12–78-vuotiaita naisia ja heitä oli yhteensä 27. Tulkkaus, tutkimusaiheen sensitiivisyys ja haastattelijan kokemattomuus aiheuttivat haasteita haastatteluiden toteutukseen. Tämän vuoksi menetelmää muokattiin ja se vaihdettiin ryhmähaastattelusta yksilöhaastatteluun tutkimuksen aikana. Ruokauskomukset vaihtelivat sekä kylien välillä että kylien sisällä, joskin niistä löytyi samantyyppisiä pääpiirteitä. Työssä todettiin, että raskaana oleviin ja imettäviin naisiin kohdistui tutkimusalueella ruokauskomuksia. Raskauden aikana tuli välttää pääasiassa proteiinipitoisia ruokia, kuten lihaa ja kalaa ja puolestaan suosia kasvisten, hedelmien ja viljatuotteiden käyttöä. Linnun munien syöntiä sekä suositeltiin että kehotettiin välttämään raskauden aikana. Raskauden aikana ilmeni lisäksi tietoinen tapa vähentää kassavapuuron tai ruuan syömistä kokonaisuudessaan. Imetyksen aikana ei vältetty juuri mitään ruokia, vaan suositeltiin kookosta ja kasviksia. Suurin osa perusteluista liittyi äidin ja lapsen terveyteen. Perustelut voitiin jakaa seuraaviin ryhmiin: lisää äidinmaidon tuotantoa; aiheuttaa vatsakipua äidillä; pitää yllä kuntoa ja estää vatsan kasvua; äidistä tulee vahva, terve ja hän saa vitamiineja; lapsen ulkonäkö muuttuu; lapsesta tulee terve ja vahva; lapsen käyttäytyminen muuttuu; aiheuttaa keskenmenon; aiheuttaa vaikean tai helpon synnytyksen. Ruokauskomukset ja terveysviranomaisilta tullut valistus oli osittain sekoittunut keskenään. Lähes kaikki naiset kertoivat noudattavansa näitä ruokauskomuksia. Muutamat naiset kertoivat suositeltavien ruokien kohdalla, että ruokien saatavuus tekee noudattamisen joskus vaikeaksi. Proteiinipitoisten ruokien välttäminen voi lisätä proteiinialiravitsemuksen riskiä ja syömisen vähentäminen saattaa lisätä riskiä saada riittämättömästi energiaa raskauden aikana. Suositeltavat ruuat todennäköisesti edistävät terveyttä. Tutkielman perusteella voitiin todeta, että vieraassa kulttuurissa tutkiminen vaatii tutkimusmenetelmältä paljon. Tärkeää on menetelmän joustavuus, jotta sitä voi muuttaa tutkimuskentällä toimivampaan ja luotettavampaan muotoon. Johtopäätöksenä todettiin, että suositeltavin menetelmä tutkittaessa ruokauskomuksia tällä tutkimusalueella olisi ollut yksilöhaastattelut, jossa olisi ollut mahdollisimman vähän osallistujia ja osallistujat olisivat olleet samaa sukupuolta ja saman ikäisiä. Terveyden ja ravitsemuksen kannalta on tärkeää, että ruokauskomuksista ollaan tietoisia ja väestön ruokauskomuksia tutkitaan alueittain, koska ne voivat vaihdella merkittävästi jopa kylien tai ihmisryhmien sisällä.

Non-small cell lung cancer : studies on pathogenesis, tumour targeting and treatment outcomes

Lung cancer accounts for more cancer-related deaths than any other cancer. In Finland, five-year survival ranges from 8% to 13%. The main risk factor for lung cancer is long-term cigarette smoking, but its carcinogenesis requires several other factors. The aim of the present study was to 1) evaluate post-operative quality of life, 2) compare clinical outcomes between minimally invasive and conventional open surgery, 3) evaluate the role of oxidative stress in the carcinogenesis of non-small lung cancer (NSCLC), and 4) to identify and characterise targeted agents for therapeutic and diagnostic use in surgery. For study I, pneumonectomy patients replied to 15D quality of life and baseline dyspnea questionnaires. Study III involved a prospective quality of life assessment using the 15D questionnaire after lobectomy or bi-lobectomy. Study IV was a retrospective comparison of clinical outcomes between 212 patients treated with open thoracotomy and 116 patients who underwent a minimally invasive technique. Study II measured parameters of oxidative metabolism (myeloperoxidase activity, glutathione content and NADPH oxidase activity) and DNA adducts. Study V employed the phage display method and identified a core motif for homing peptides. This method served in cell-binding, cell-localisation, and biodistribution studies. Following both pneumonectomy and lobectomy, NSCLC patients showed significantly decreased long-term quality of life. No significant correlation was noted between post-operative quality of life and pre-operative pulmonary function tests. Women suffered more from increased dyspnea after pneumonectomy which was absent after lobectomy or bi-lobectomy. Patients treated with video-assisted thoracoscopy showed significantly decreased morbidity and shorter periods of hospitalization than did open surgery patients. This improvement was achieved even though the VATS patients were older and suffered more comorbid conditions and poorer pulmonary function. No significant differences in survival were noted between these two groups. An increase in NADPH oxidase activity was noted in tumour samples of both adenocarcinoma and squamous cell carcinoma. This increase was independent from myeloperoxidase activity. Elevated glutathione content was noted in tumour tissue, especially in adenocarcinoma. After panning the clinical tumour samples with the phage display method, an amino acid sequence of ARRPKLD, the Thx, was chosen for further analysis. This method proved selective of tumour tissue in both in vitro and in vivo cell-binding assay, and biodistribution showed tumour accumulation. Because of the significantly reduced quality of life following pneumonectomy, other operative strategies should be implemented as an alternative (e.g. sleeve-lobectomy). To treat this disease, implementation of a minimally invasive surgical technique is safe, and the results showed decreased morbidity and a shorter period of hospitalisation than with thoracotomy. This technique may facilitate operative treatment of elderly patients with comorbid conditions who might otherwise be considered inoperable. Simultaneous exposure to oxidative stress and altered redox states indicates the important role of oxidative stress in the pathogenesis and malignant transformation of NSCLC. The studies showed with great specificity and with favourable biodistribution that Thx peptide is specific to NSCLC tumours. Thx thus shows promise in imaging, targeted therapy, and monitoring of treatment response.

Critical leg ischaemia with tissue loss : a challenge for the vascular surgeon

There is a widespread reporting habit of combining the outcomes for patients with rest pain (Fontaine III) and tissue loss (Fontaine IV) under the single category of critical leg ischaemia (CLI). This study focused on patients with ischaemic tissue loss treated with infrainguinal bypass surgery (IBS). All patients included in the study were treated at Helsinki University Central Hospital in 2000-2007. First, ulcer healing time after IBS and factors influencing healing time were prospectively assessed in 2 studies including 148 and 110 patients, respectively. Second,the results of redo IBS were retrospectively evaluated in 593 patients undergoing primary IBS for CLI with tissue loss . Third,long-term outcome were retrospectively analysed in 636 patients who underwent IBS for CLI with tissue loss . Fourth, the outcome of IBS was retrospectively compared with endovascular treatment (PTA) of the infrapopliteal arteries in 1023 CLI patients. Fifth, the influence multidrug resistant Pseudomans aeruginosa (MDR Pa) bacteria contamination in CLI patients treated with IBS was retropectively assessed. Sixty-four patients with positive MDR Pa -culture were matched with 64 MDR Pa - negative controls. Complete ulcer healing rate, including the ischemic ulcers and incisional wounds, was 40% at 6 months after IBS and 75% at one year. Diabetes was a risk factor for prolonged complete ulcer healing time. Ischaemic tissue lesions located in mid-and hindfoot healed poorly. At one year after IBS 50% of the patients were alive with salvaged leg and completely healed ulcers. The absence of gap between tertiary graft patency and leg salvage rates indicates the importance of a patent infrainguinal graft to save a leg with ischaemic tissue loss. Long-term survival for patients with ischaemic tissue loss was poor, 38% at 5 years. Only 30% of the patients were alive without amputation at 5 years. Several of the patient comorbidities increased independently the mortality risk; coronary artery disease, renal insufficiency, chronic obstructive lung disease and high age. When both PTA and bypass is feasible, infrapopliteal PTA as a first-line strategy is expected to achieve similar long-term results to bypass surgery in CLI when redo surgery is actively utilized. MDR Pa in a patient with CLI should be considered as a serious event with increased risk of early major amputation or death. Conclusion: Despite a successful infrainguinal bypass healing of the ischaemic ulcers and incisional wounds ulcer healing is a slow process especially in diabetics. Bypass surgery and PTA improve the outcome of the ischaemic leg but the mortality rate of the patients is high due to their severe comorbidities.

The Biocontrol Agent Phlebiopsis gigantea: Efficacy and Impacts on the Stump Bacterial Biota and Conifer tree Defences

Phlebiopsis gigantea has been for a long time known as a strong competitor against Heterobasidion annosum and intensively applied as a biological control agent on stump surfaces of Picea abies in Fennoscandia. However, the mechanism underlying its antagonistic activity is still unknown. A primary concern is the possible impact of P. gigantea treatment on resident non-target microbial biota of conifer stumps. Additional risk factor is the potential of P. gigantea to acquire a necrotrophic habit through adaptation to living wood tissues. This study focused on the differential screening of several P. gigantea isolates from diverse geographical sources as well as the use of breeding approach to enhance the biocontrol efficacy against H. annosum infection. The results showed a significant positive correlation between growth rate in wood and high biocontrol efficacy. Furthermore, with aid of breeding approach, several progeny strains were obtained that had better growth rate and control efficacy than parental isolates. To address the issue of the potential of P. gigantea to acquire necrotrophic capability, a combination of histochemical, molecular and transcript profiling (454 sequencing) were used to investigate the interactions between these two fungi and ten year old P. sylvestris seedlings. The results revealed that both P. gigantea and H. annosum provoked strong necrotic lesions, but after prolonged incubation, P. gigantea lesions shrank and ceased to expand further. Tree seedlings pre-treated with P. gigantea further restricted H. annosum-induced necrosis and had elevated transcript levels of genes important for lignification, cell death regulation and jasmonic acid signalling. These suggest that induced localized resistance is a contributory factor for the biocontrol efficacy of P.gigantea, and it has a comparatively limited necrotrophic capability than H. annosum. Finally, to investigate the potential impact of P. gigantea on the stump bacterial biota, 16S rDNA isolated from tissue samples from stumps of P. abies after 1-, 6- and 13-year post treatment was sequenced using bar-coded 454 Titanium pyrosequencing. Proteobacteria were found to be the most abundant at the initial stages of stump decay but were selectively replaced by Acidobacteria at advanced stages of the decay. Moreover, P. gigantea treatment significantly decreased the bacterial richness at initial decay stage in the stumps. Over time, the bacterial community in the stumps gradually recovered and the negative effects of P. gigantea was attenuated.

Texts "Con and Pro" : The Early Modern Medical Controversy over Tobacco

The habit of "drinking smoke" , meaning tobacco smoking, caused a true controversy in early modern England. The new substance was used both for its alleged therapeutic properties as well as its narcotic effects. The dispute over tobacco continues the line of written controversies which were an important means of communication in the sixteenth and seventeenth century Europe. The tobacco controversy is special among medical controversies because the recreational use of tobacco soon spread and outweighed its medicinal use, ultimately causing a social and cultural crisis in England. This study examines how language is used in polemic discourse and argumentation. The material consists of medical texts arguing for and against tobacco in early modern England. The texts were compiled into an electronic corpus of tobacco texts (1577 1670) representing different genres and styles of writing. With the help of the corpus, the tobacco controversy is described and analyzed in the context of early modern medicine. A variety of methods suitable for the study of conflict discourse were used to assess internal and external text variation. The linguistic features examined include personal pronouns, intertextuality, structural components, and statistically derived keywords. A common thread in the work is persuasive language use manifested, for example, in the form of emotive adjectives and the generic use of pronouns; the latter is especially pronounced in the dichotomy between us and them. Controversies have not been studied in this manner before but the methods applied have supplemented each other and proven their suitability in the study of conflictive discourse. These methods can also be applied to present-day materials.

Smoking patterns and lung function : A longitudinal twin study

In many countries, the prevalence of smoking and smokers average cigarette consumption have decreased, with occasional smoking and daily light smoking (1-4 cigarettes per day, CPD) becoming more common. Despite these changes in smoking patterns, the prevalence of chronic obstructive pulmonary disease (COPD), a disorder characterized by a progressive decline in lung function, continues to rise globally. Smoking is the most important factor causing COPD, however, not all smokers develop the disease. Genetic factors partly explain the inter-individual differences in lung function and susceptibility of some smokers to COPD. No earlier research on the genetic and environmental determinants of lung function or on the phenomenon of light smoking exists in the Finnish population. Further, the association between low-rate smoking patterns and COPD remains partly unknown. This thesis aimed to study the prevalence and consistency of light smoking longitudinally in the Finnish population, to assess the characteristics of light smokers, and to examine the risks of chronic bronchitis and COPD associated with changing smoking patterns over time. A further aim was to estimate longitudinally the proportions of genetic and environmental factors that explain the inter-individual variances in lung function. Data from the Older Finnish Twin Cohort, including same-sex twin pairs born in Finland before 1958, were used. Smoking patterns and chronic bronchitis symptoms were consistently assessed in surveys conducted in 1975, 1981, and 1990. National registry data on reimbursement eligibilities and medication purchases were used to define COPD. Lung function data were obtained from a subsample of the cohort, 217 female twin pairs, who attended spirometry in 2000 and 2003 as part of the Finnish Twin Study on Ageing. The genetic and environmental influences on lung function were estimated by using genetic modeling. This thesis found that light smokers are more often female, well-educated, and exhibit a healthier lifestyle than heavy smokers. At individual level, light smoking is rarely a constant pattern. Light smoking, reducing from heavier smoking to light smoking, and relapsing to light smoking after quitting, are among patterns associated with an increased risk of chronic bronchitis and COPD. Constant light smoking is associated with an increased use of inhaled anticholinergics, a medication for CODP. In addition to smoking, other environmental factors influence lung function in the older age. During a three-year follow-up, new environmental effects influencing spirometry values were observed, whereas the genes affecting lung function remained mostly the same. In conclusion, no safe level of daily smoking exists with regard to pulmonary diseases. Even daily light smoking in middle-age is associated with increased respiratory morbidity later in life. Smoking reduction does not decrease the risk of COPD, and should not be recommended as an alternative to quitting smoking. In elderly people, attention should also be drawn to other factors that can prevent poor lung function.

Noninvasive biomarkers for early smoking related lung disease

Chronic obstructive pulmonary disease (COPD) is a slowly progressive disease characterized by airway inflammation and largely irreversible airflow limitation. One major risk factor for COPD is cigarette smoking. Since the inflammatory process starts many years prior to the onset of clinical symptoms and still continues after smoking cessation, there is an urgent need to find simple non-invasive biomarkers that can be used in the early diagnosis of COPD and which could help in predicting the disease progression. The first aim of the present study was to evaluate the involvement of different oxidative/nitrosative stress markers, matrix metalloproteinases (MMPs) and their tissue inhibitor-1 (TIMP-1) in smokers and in COPD. Elevated numbers of inducible nitric oxide synthase (iNOS), nitrotyrosine, myeloperoxidase (MPO) and 4-hydroxy-2-nonenal (4-HNE) positive cells and increased levels of 8-isoprostane and lactoferrin were found in sputum of non-symptomatic smokers compared to non-smokers, and especially in subjects with stable mild to moderate COPD, and they correlated with the severity of airway obstruction. This suggests that an increased oxidant burden exists already in the airways of smokers with normal lung function values. However, none of these markers could differentiate healthy smokers from symptomatic smokers with normal lung function values i.e. those individuals who are at risk of developing COPD. In contrast what is known about asthma exhaled nitric oxide (FENO) was lower in smokers than in non-smokers, the reduced FENO value was significantly associated with neutrophilic inflammation and the elevated oxidant burden (positive cells for iNOS, nitrotyrosine and MPO). The levels of sputum MMP-8 and plasma MMP-12 appeared to differentiate subjects who have a risk for COPD development but these finding require further investigations. The levels of all studied MMPs correlated with the numbers of neutrophils, and MMP-8 and MMP-9 with markers of neutrophil activation (MPO, lactoferrin) suggesting that especially neutrophil derived oxidants may stimulate the tissue destructive MMPs already in lungs of smokers who are not yet experiencing any airflow limitation. When investigating the role of neutrophil proteases (neutrophil elastase, MMP-8, MMP-9) during COPD exacerbation and its recovery period, we found that levels of all these proteases were increased in sputum of patients with COPD exacerbation as compared to stable COPD and controls, and decreased during the one-month recovery period, giving evidence for a role of these enzymes in COPD exacerbations. In the last study, the effects of subject`s age and smoking habits were evaluated on the plasma levels of surfactant protein A (SP-A), SP-D, MMP-9 and TIMP-1. Long-term smoking increased the levels of all of these proteins. SP-A most clearly correlated with age, pack years and lung function decline (FEV1/FVC), and based on the receiver operating characteristic curve analysis, SP-A was the best marker for discriminating subjects with COPD from controls. In conclusion, these findings support the hypothesis that especially neutrophil derived oxidants may activate MMPs and induce an active remodeling process already in the lungs of smokers with normal lung function values. The marked increase of sputum levels of neutrophil proteases in smokers, stable COPD and/or during its exacerbations suggest that these enzymes play a role in the development and progression of COPD. Based on the comparison of various biomarkers, SP-A can be proposed to serve as sensitive biomarker in COPD development.

Timotein (Phleum pratense ssp. pratense L.) alkuperän vaikutus kylmänkestävyyteen, vernalisaatiovaatimukseen sekä kasvuun ja kehitykseen

Nurmiheinien merkitys maailmanlaajuisesti on merkittävä, sillä noin 69 % maapallon peltopinta-alasta on pysyvää laidunmaata tai niittyä. Suomessa nurmien osuus on noin 29 %, ja tuotanto perustuu pääosin intensiiviseen säilörehuntuotantoon. Yleisin nurmiheinälaji Suomessa on timotei (Phleum pratense ssp. pratense L.). Timotei on talvenkestävä ja soveltuu siksi pohjoisiin kasvuoloihin. Timoteilajikkeita jalostettaessa pohjoista alkuperää olevia vanhempaislinjoja käytetään hyvän talvenkestävyyden varmistamiseksi, eteläisiä tavoiteltaessa nopeaa kasvurytmiä. Ilmaston muutoksen ennustetaan lisäävän erilaisia äärioloja kuten myrskyjä ja sateita. Vuorokauden keskilämpötila nousee ja kasvukausi pidentyy. Lisäksi talvet muuttuvat sateisemmiksi. Muutokset näkyvät erityisesti pohjoisissa kasvuympäristöissä. Tutkimuksessa haluttiinkin selvittää eri alkuperää edustavien timoteilajikkeiden ja linjojen kylmänkestävyyttä, kasvu-, ja kehitysnopeutta sekä vernalisaation vaikutusta. Lisäksi tutkittiin syysviljojen vernalisaatiovasteen mittaamiseen käytettyjen menetelmien soveltuvuutta nurmille. Tutkimukseen kuului kaksivuotinen peltokoe sekä kasvatuskaappikoe. Vernalisaatio nopeutti timotein kasvua ja kehitystä. Tutkimuksen perusteella eteläistä alkuperää olevilla lajikkeilla kasvu- ja kukintavalmius oli olemassa ilman vernalisaatiota. Pohjoisilla lajikkeilla oli suurempi vernalisaatiovaste ja niiden kukkiminen ja kasvu nopeutui vernalisaation myötä. Vernalisaatiolla oli vaikutusta myös kasvuston rakenteeseen. Generatiivisten versojen määrä lisääntyi vernalisaation myötä, kun taas vegetatiivisten versojen määrä väheni. Kylmänkestävyys oli tutkimuksen perusteella riippuvainen syksyn karaistumisjakson pituudesta sekä jakson lämpösummasta (FH-COLD). Korkea keskilämpötila ja lyhyt karaistumisjakso heikensivät kylmänkestävyyttä. Vastaavasti karaistumiskauden lämpötilan ollessa välillä 0 °C:ta ja + 5 °C:ta ja jakson pituuden kasvaessa kylmänkestävyys lisääntyi. Tutkimuksen perusteella vernalisaatiolla oli selvä vaikutus timotein kasvuun ja kehitykseen. Pohjoista alkuperää olevat timoteit reagoivat vernalisaatioon eteläisiä enemmän. Osa pohjoisista linjoista vaati vernalisaation generatiivisten versojen muodostumiseen. Syysviljojen vernalisaatiovasteen mittausmenetelmät soveltuvat osin myös puhtaiden timoteilajikkeiden vernalisaation seurantaan.