The influence of HIV infection to the periodontium; a clinical, microbiological, and enzymological study

The main targets of human immunodeficiency virus (HIV) are CD4 receptors of CD4+ lymphocytes and many other cells such as monocytes/macrophages, megakaryocytes, peripheral blood dendritic cells, follicular dendritic cells (DC), epidermal Langerhans cells, and astrocytes. Infection and killing of CD4+ lymphocytes or false reaction of the body to HIV infection and the spontaneous apoptosis of CD4+ lymphocytes decrease CD4+ lymphocyte counts leading to immunosuppression, further disease progression, and appearance of opportunistic infections and malignancies. Oral manifestations are considered to be among the first signs of HIV infection. Enhanced degradation of extracellular matrix and basement membrane components in oral diseases including periodontitis is caused by Zn-dependent enzymes called matrix metalloproteinases (MMPs). The levels and degrees of activation of MMP-1, -2, -3, -7, -8, -9, -25, -26, tissue inhibitors of MMPs (TIMP)-1 and -2, and myeloperoxidase (MPO) and collagenolytic/gelatinolytic activities, and also Ig A, -G, and -M, total protein, and albumin levels in a two-year follow-up were studied from salivary samples. The expression of MMP-7, -8, -9, -25, and -26 immunoreactivities in gingival tissue specimens were studied. Healthy HIV-negative subjects served as controls. All studied clinical periodontal parameters and microbiological evaluation of the periodontopathogens showed that periodontal health of the HIV-positive patients was moderately decreased in comparison to the healthy controls. The levels of Candida in the periodontal pockets and salivary MPO increased with the severity of HIV infection. Immunoreactivities and levels of MMPs and TIMPs, and MMP activities (collagenase, gelatinase) were enhanced in the HIV-positive patient salivary samples relative to the healthy controls regardless of the phase of HIV infection. However, these parameters did not reflect periodontal status in a similar way as in the generally healthy periodontitis patients. Salivary total protein, albumin, IgA, -G, and -M levels were significantly higher in all phases of HIV infection compared to the controls, and salivary total protein, IgG and IgM levels remained higher after two years follow-up, partly correlating with the disease progression and which may reflect the leakage of serum components into the mouth and thus a decreased mucosal barrier. Salivary analyses of MMPs and TIMPs with immunohistochemical analyses showed that HIV infection could predispose to periodontal destruction when compared with healthy controls or the body s defence reactions associated with HIV infection may have been reflected or mediated by MMPs.

Development of regulatory T cells in the human thymus

The role of the immune system is to protect an organism against pathogens while maintaining tolerance against self. T cells are an essential component of the immune system and they develop in the thymus. The AIRE (autoimmune regulator) gene product plays an important role in T cell development, as it promotes expression of peripheral tissue antigens in the thymus. Developing T cells, thymocytes, which recognize self-antigens with high affinity are deleted. However, this deletion process is not perfect and not all autoreactive T cells are destroyed. When the distinction between self and non-self fails, tolerance breaks and the immune system attacks the host s own tissues. This results in autoimmunity. Regulatory T cells contribute to the maintenance of self-tolerance. They can actively suppress the function of autoreactive cells. Several populations of cells with regulatory properties have been described, but the best characterized population is the natural regulatory T cells (Treg cells), which develop in the thymus and express the transcription factor FOXP3. The thymic development of Treg cells in humans is the subject of this thesis. Thymocytes at different developmental stages were analyzed using flow cytometry. The CD4-CD8- double-negative (DN) thymocytes are the earliest T cell precursors in the T cell lineage. My results show that the Treg cell marker FOXP3 is up-regulated already in a subset of these DN thymocytes. FOXP3+ cells were also found among the more mature CD4+CD8+ double-positive (DP) cells and among the CD4+ and CD8+ single-positive (SP) thymocytes. The different developmental stages of the FOXP3+ thymocytes were isolated and their gene expression examined by quantitative PCR. T cell receptor (TCR) repertoire analysis was used to compare these different thymocyte populations. My data show that in humans commitment to the Treg cell lineage is an early event and suggest that the development of Treg cells follows a linear developmental pathway, FOXP3+ DN precursors evolving through the DP stage to become mature CD4+ Treg cells. Most T cells have only one kind of TCR on their cell surface, but a small fraction of cells expresses two different TCRs. My results show that the expression of two different TCRs is enriched among Treg cells. Furthermore, both receptors were capable of transmitting signals when bound by a ligand. By extrapolating flow cytometric data, it was estimated that the majority of peripheral blood Treg cells are indeed dual-specific. The high frequency of dual-specific cells among human Treg cells suggests that dual-specificity has a role in directing these cells to the Treg cell lineage. It is known that both genetic predisposition and environmental factors influence the development of autoimmunity. It is also known that the dysfunction or absence of Treg cells leads to the development of autoimmune manifestations. APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy) is a rare monogenic autoimmune disease, caused by mutations in the AIRE gene. In the absence of AIRE gene product, deletion of self-specific T cells is presumably disturbed and autoreactive T cells escape to the periphery. I examined whether Treg cells are also affected in APECED. I found that the frequency of FOXP3+ Treg cells and the level of FOXP3 expression were significantly lower in APECED patients than in controls. Additionally, when studied in cell cultures, the suppressive capacity of the patients' Treg cells was impaired. Additionally, repertoire analysis showed that the TCR repertoire of Treg cells was altered. These results suggest that AIRE contributes to the development of Treg cells in humans and the selection of Treg cells is impaired in APECED patients. In conclusion, my thesis elucidates the developmental pathway of Treg cells in humans. The differentiation of Tregs begins early during thymic development and both the cells dual-specificity and AIRE probably affect the final commitment of Treg cells.

NK-and T-cell function in chronic myeloid leukemia patients treated with interferon-? monotherapy

Chronic myeloid leukemia (CML) is one of the most studied human malignancies. It is caused by an autonomously active tyrosine kinase BCR-ABL, which is a result from a translocation between chromosomes 9 and 22 in the hematopoietic stem cell. As an outcome, a Philadelphia (Ph) chromosome is formed. BCR-ABL causes disturbed cell proliferation among other things. Although targeted tyrosine kinase inhibitor therapy has been developed in the beginning of the millenium and the survival rate has increased significantly, it is still not known why some patients benefit more from the treatment than others. Furthermore, the therapy is not considered to be curative. Before the era of tyrosine kinase inhibitors, the first-line treatment for CML was interferon-? (IFN-?). However, only a small proportion of patients benefitted from the treatment. Of these patients, a few were able to discontinue the treatment without renewal of the disease. The mechanism of IFN-? is not completely understood, but it is believed that differences in the immune system can be one of the reasons why some patients have better therapy response. Kreutzman, Rohon et al. have recently discovered that patients who have been able to stop IFN-? treatment have an increased number of NK- and T-cells. They also have a unique clonal T-cell population and more cytotoxic CD8+ T-cells and less CD4+ T-cells. The aim of this master’s thesis was to study the function of T- and NK-cells in IFN-? treated patients. Although it was shown earlier that IFN-? treated patients have increased NK-cell count, the function of these cells was unknown. Therefore, we have now investigated the killing potential of patients’ NK-cells, their activation status and cell surface antigen expression. In addition, we have also studied the activation status of patients’ T-cells and their cytotoxic properties. We observed that NK-cells from patients treated with IFN-? are unable to kill leukemic cells (K562) than NK-cells from healthy controls. In addition, patients on IFN-? treatment have more active T-cells and their NK-cells have an undifferentiated immunoregulatory phenotype. Patients that have been able to stop the treatment have anergic T-and NK-cells. As a conclusion our results suggest that IFN-? therapy induces increased NK-cell count, NK-cell immunoregulatory functions and more active T-cells. After stopping IFN-? therapy, NK- and T-cells from CML patients restore anergy typical for CML.

Les formes d’adresse dans un corpus de films français et leur traduction en finnois

The use of forms of address in French films and their Finnish translations The use of forms of address constitutes an integral part of speakers’ communicative competence. In fact, they are not only used to assign to whom the speech is addressed, but also to construct the relationship between speakers. However, the choice of a suitable form is not necessarily evident in modern, pluralistic society. By the notion form of address, I refer to pronouns of address (tu vs. vous) and different nouns of address like names, titles (Monsieur, Madame, Mademoiselle), kinship terms, occupational terms, terms of endearment and insults. The purpose of the present thesis is, first, to study the semantic and pragmatic values of forms of address in dialogues of modern French films, and, second, their translation in Finnish subtitles. It is evident that film language is not spontaneous, but only a representation of authentic speech, and that subtitles are a written version of the original spoken language. Consequently, this thesis studies spoken fictive dialogues and their written translations. The methods applied in the study are the Interactional and Pragmatic Approach as well as Translatology. The role of forms of address in an interpersonal relationship is studied with dimensions of distance and power (Brown and Gilman 1960, Kerbrat-Orecchioni 1992), whereas the pragmatic dimension permits studying in particular the use of forms of address in speech acts (Kerbrat-Orecchioni 2001). The translation strategies are studied with the help of Venuti’s (1995) notions of foreignizing and domesticating strategies. The results of the thesis suggest that the pronoun use in the studied films is usually reciprocal. However, the relations of power have not disappeared, but are expressed in a more discrete manner with nouns of address (for instance vous + Docteur vs. vous + Anita). The use of the pronoun of address vous seems still to be common, but increased intimacy is expressed by accompanying familiar nouns of address like first names. The nominal forms of address accompany different speech acts, but not in a systematic manner. In a dialogue they appear usually in the first speech act, and more rarely in the response, but not in both. In addition, they have an important role in the mechanics of conversation. The translators here face multiple demands, and their translations seem mostly to be a compromise between foreignizing and domesticating strategies.

La coordination et les phrases juxtaposées en français

Coordination and juxtaposed sentences The object of this study is the examination of the relations between juxtaposed clauses in contemporary French. The matter in question is sentences which are composed of several clauses adjoined without a conjunction or other connector, as in: Je détournai les yeux, mon c ur se mit à battre. The aim of the study is to determine, which quality is the relation in these sentences and, on the other hand, what is the part of the coordination there. Furthermore, what is this relation of coordination, which, according to some grammars, manifests through a conjunction of coordination, but which, according to some others is marked in juxtaposed sentences through different features. The study is based on a corpus of written French from literary and journalistic text sources. Syntactic, semantic and textual properties in the clauses are discussed. The analysis points to differences so, it has been noted, in each case, if one of the clauses is affirmative and the other negative and if in the second clause, the subject has not been repeated. Also, an analysis has been made on the ground of the tense, mode, phrase structure type, and thematic structure, taking into account, in each case, if the clauses are identical or different. Punctuation has been one of the properties considered. The final aim has been to eliminate gradually, based on the partition of properties, subordinate sentences, so that only the hard core of coordinate sentences remains. In this way, the coordination could be defined similarly as the phoneme is defined as a group of distinctive features. The quantitative analyses have led to the conclusion that the sentences which, from a semantic point of view, are interpreted as coordinating, contain the least of these differences, while the sentences which can be considered as subordinating present the most of these differences. The conditions of coordination are, in that sense, hierarchical, so that the syntactic constraints have to make room for semantic, textual and cognitive factors. It is interesting to notice that everyone has the ability to produce correct coordinating structures and recognize incorrect coordinating structures. This can be explained by the human ability to categorize which has been widely researched in the semantic of prototype. The study suggests that coordination and subordination could be considered as prototypical cognitive categories based on different linguistic and pragmatic features.

Structure informationnelle et constructions du kabyle : Etude de trois types de phrase dans le cadre de la grammaire constructionnelle

Information structure and Kabyle constructions Three sentence types in the Construction Grammar framework The study examines three Kabyle sentence types and their variants. These sentence types have been chosen because they code the same state of affairs but have different syntactic structures. The sentence types are Dislocated sentence, Cleft sentence, and Canonical sentence. I argue first that a proper description of these sentence types should include information structure and, second, that a description which takes into account information structure is possible in the Construction Grammar framework. The study thus constitutes a testing ground for Construction Grammar for its applicability to a less known language. It constitutes a testing ground notably because the differentiation between the three types of sentences cannot be done without information structure categories and, consequently, these categories must be integrated also in the grammatical description. The information structure analysis is based on the model outlined by Knud Lambrecht. In that model, information structure is considered as a component of sentence grammar that assures the pragmatically correct sentence forms. The work starts by an examination of the three sentence types and the analyses that have been done in André Martinet s functional grammar framework. This introduces the sentence types chosen as the object of study and discusses the difficulties related to their analysis. After a presentation of the state of the art, including earlier and more recent models, the principles and notions of Construction Grammar and of Lambrecht s model are introduced and explicated. The information structure analysis is presented in three chapters, each treating one of the three sentence types. The analyses are based on spoken language data and elicitation. Prosody is included in the study when a syntactic structure seems to code two different focus structures. In such cases, it is pertinent to investigate whether these are coded by prosody. The final chapter presents the constructions that have been established and the problems encountered in analysing them. It also discusses the impact of the study on the theories used and on the theory of syntax in general.

Between Herbals et alia: Intertextuality in Medieval English Herbals

This study reports a corpus-based study of medieval English herbals, which are texts conveying information on medicinal plants. Herbals belong to the medieval medical register. The study charts intertextual parallels within the medieval genre, and between herbals and other contemporary medical texts. It seeks to answer questions where and how herbal texts are linked to each other, and to other medical writing. The theoretical framework of the study draws on intertextuality and genre studies, manuscript studies, corpus linguistics, and multi-dimensional text analysis. The method combines qualitative and quantitative analyses of textual material from three historical special-language corpora of Middle and Early Modern English, one of which was compiled for the purposes of this study. The text material contains over 800,000 words of medical texts. The time span of the material is from c. 1330 to 1550. Text material is retrieved from the corpora by using plant name lists as search criteria. The raw data is filtered through qualitative analysis which produces input for the quantitative analysis, multi-dimensional scaling (MDS). In MDS, the textual space that parallel text passages form is observed, and the observations are explained by a qualitative analysis. This study concentrates on evidence of material and structural intertextuality. The analysis shows patterns of affinity between the texts of the herbal genre, and between herbals and other texts in the medical register. Herbals are most closely linked with recipe collections and regimens of health: they comprise over 95 per cent of the intertextual links between herbals and other medical writing. Links to surgical texts, or to specialised medical texts are very few. This can be explained by the history of the herbal genre: as herbals carry information on medical ingredients, herbs, they are relevant for genres that are related to pharmacological therapy. Conversely, herbals draw material from recipe collections in order to illustrate the medicinal properties of the herbs they describe. The study points out the close relationship between medical recipes and recipe-like passages in herbals (recipe paraphrases). The examples of recipe paraphrases show that they may have been perceived as indirect instruction. Keywords: medieval herbals, early English medicine, corpus linguistics, intertextuality, manuscript studies

« Le roman est agréablement traduit » : Étude comparative sur la visibilité des traductions et des traducteurs en Finlande et en France à travers des critiques des livres

Pro gradu -työssä tutkitaan ja vertaillaan käännöskirjallisuuden arvosteluja Ranskassa ja Suomessa. Empiirinen aineisto koostuu kaikista Helsingin Sanomien ja Le Monden vuonna 2003 julkaisemista arvosteluista. Lehdissä oli yhteensä 2691 arvosteltua kirjaa, joista 845 oli käännöksiä. Päätavoite on ollut selvittää näiden valtasanomalehtien kritiikkejä tutkimalla, kummassa maassa kääntäjän ja käännöksen asema on näkyvämpi ja minkälaisia julkaistut käännöskritiikit ovat. Lisäksi tavoitteena on ollut tutkia, kumpi lehdistä on avoimempi vieraskielisiä kirjoja ja käännöksiä kohtaan. Kirja-arvostelujen lähemmälle tutkimiselle luodaan pohjaa perehtymällä kääntäjän ja käännöksen näkyvyyteen liittyviin seikkoihin. Tässä käytetään hyväksi Koskisen (2000) tutkimusta. Tutkimuksessa tarkastellaan myös, millainen on hyvä käännös eri kääntäjien ja tutkijoiden mielestä, sekä muita saman aihepiirin tutkimuksia ja aiheesta vallalla ollutta keskustelua. Lisäksi selvitetään, miksi laadukkaat käännösarvostelut ovat harvinaisia ja mistä tämä johtuu. Analyysivaiheen kvantitatiivisessa osassa perehdytään käännösten määrälliseen osuuteen sekä aineistossa että Ranskan ja Suomen kokonaisjulkaisumäärissä. Aineiston käännösarvostelut luokitellaan niiden sisällön mukaan. Tässä on käytetty soveltuvin osin Gullinin (1998) kehittelemää mallia. Käännösarvostelujen sisältöanalyysissa kiinnitetään huomiota niiden käännöstä ja kääntäjää koskeviin kommentteihin. Arvostelujen laadun ja kriitikkojen käyttämien arvosteluperusteiden pohdinta nojautuu aiheesta aikaisemmin tehtyihin teoreettisiin sekä empiirisiin tutkimuksiin. Pro gradu -työ sisältää myös erillisen katsauksen käännettyjen lastenkirjojen arvosteluihin sekä arvostelujen ulkopuolisiin kääntäjiin ja kääntämiseen liittyviin artikkeleihin. Koko tutkimuksen ajan lähestymistapa on vertaileva Le Monden ja Helsingin Sanomien välillä. Tutkimuksesta selviää, että Le Monde julkaisee huomattavasti enemmän kirja-arvosteluja. Molemmat lehdet sisältävät kuitenkin suhteellisesti yhtä paljon arvosteluja käännöskirjoista. Helsingin Sanomissa on enemmän vieraskielisten teosten arvosteluja, ja käännösten ja kääntäjän asema on huomattavasti näkyvämpi lehden kritiikeissä. Suurin osa Le Monden käännösarvosteluista sisältää vain kääntäjän nimen bibliografisissa tiedoissa. Helsingin Sanomissa vain alle puolet käännöskirjoista on arvosteltu tällä tavoin. Myös kritiikit, joissa kääntäjän nimeä ei mainita ollenkaan, ovat yleisempiä ranskalaislehdessä. Suhteellisen pieni osa käännösarvosteluista arvioi käännöksen laatua. Näille arvioille on ominaista perustelujen ja analyysin puuttuminen ja ne ovat usein lyhyitä. Arviot ovat sävyltään enimmäkseen positiivisia tai neutraaleja. Hyvin yleistä on myös se, että kriitikko sekoittaa kaksi eri asiaa: kääntäjän ja kirjailijan tyylin. Yleisin kriitikkojen käyttämä arviointikriteeri on tutkia käännöksen ja kohdekielen tai käännöksen ja lähtötekstin suhdetta. Monesti arviointikriteeri jää täysin epäselväksi. Helsingin Sanomien kritiikeissä kääntäjiin viitataan huomattavasti useammin myös itse arvostelutekstissä. Lehti tuo näkyvästi esille kääntäjiä muissakin kuin kirja-arvosteluartikkeleissaan. Sen sijaan Le Mondessa ei ole pelkästään kääntäjiä käsitteleviä tekstejä.

Acta Societatis pro fauna et flora Fennica

Kielet saksa ja ruotsi. Nimiösivulla teksti Helsingforsiae 1924-27.

Acta Societatis pro fauna et flora Fennica

Kielet saksa ja ruotsi. Nimiösivulla teksti Helsingforsiae 1924-29.

Acta Societatis pro fauna et flora Fennica

Kielet suomi ja saksa. Nimiösivulla teksti Helsingforsiae 1935-36.

Acta Societatis pro fauna et flora Fennica

Kielet saksa ja ruotsi.

Acta Societatis pro fauna et flora Fennica

Kielet saksa ja ruotsi.