CORTONESI, Leandro Masuda. Bioenergia oriental e educação física. 2011. 151 f. Tese (Doutorado em Educação) – Universidade Federal do Ceará. Faculdade de Educação, Programa de Pós-Graduação em Educação Brasileira, Fortaleza-CE, 2011. / Submitted by Raul Oliveira (raulcmo@hotmail.com) on 2012-07-05T13:39:47Z No. of bitstreams: 1 2011_Tese_LMCortonesi.pdf: 3296808 bytes, checksum: 5fa284bb066761589ef18d08115812ce (MD5) / Approved for entry into archive by Maria Josineide Góis(josineide@ufc.br) on 2012-07-19T14:04:47Z (GMT) No. of bitstreams: 1 2011_Tese_LMCortonesi.pdf: 3296808 bytes, checksum: 5fa284bb066761589ef18d08115812ce (MD5) / Made available in DSpace on 2012-07-19T14:04:47Z (GMT). No. of bitstreams: 1 2011_Tese_LMCortonesi.pdf: 3296808 bytes, checksum: 5fa284bb066761589ef18d08115812ce (MD5) Previous issue date: 2011 / Pesquisa sobre Bioenergia Oriental e suas possíveis relações com os cursos superiores de Educação Física. A tese busca a inclusão de conceitos relacionados à visão oriental da Bioenergia nos currículos dos cursos superiores de Educação Física, buscando contribuir com a percepção de corpo/mente como indissociáveis. A introdução apresenta um breve percurso pessoal de envolvimento do autor com o tema. O capítulo I fornece esclarecimentos acerca das diferenças iniciais sobre Bioenergia Ocidental e Oriental, para então ingressar em análise epistemológica ocidental. Esta análise trata do nascimento da ciência grega, problemas da medievalidade, do método cartesiano com ênfase no divórcio entre corpo e mente, e de alguns sérios problemas ainda não resolvidos: os problemas da hipótese, do controle das variáveis e da indução. O capítulo se finda com possibilidades curriculares da Educação Física. O capítulo II apresenta a epistemologia oriental, levantando as noções sobre a ciência do Extremo Oriente, e abordando os conceitos de Tao, Yin e Yang, para posteriormente ingressar no cerne da Bioenergia Oriental: o conceito de Ki. A partir do Ki, aborda-se o teste manual do círculo de energia, que é uma forma direta de analisar diminuições locais de Ki; explica-se a Teoria dos Meridianos e suas possibilidades de atuação prática, visto que a mesma serve de base para diversas terapias, como a acupuntura e shiatsu; e apresenta-se as relações da Bioenergia com a respiração, como as realizadas na arte-marcial Hapkido, uma respiração que estimula o Ki, aquecendo e energizando o organismo. Posteriormente são apresentados os estudos realizados com a energia Hado. Por fim, apresenta dificuldades epistemológicas e algumas possibilidades para a Educação Física em busca desta conexão perdida entre corpo-mente.

Knochenwachstumsfaktoren (Bone Morphogenetic Proteins, BMPs) sind ubiquitäre, sekretierte Proteine mit vielfältigen biologischen Funktionen. Die Vielfalt an zellulären Prozessen, die durch BMPs reguliert werden, von der Knochenentwicklung und Organhomöostase bis hin zur Neurogenese, erstaunt – und wirft angesichts von teils redundanten, teils spezifischen Funktionen der BMPs Fragen zu den Mechanismen ihrer Signalübermittlung auf. Die Signaltransduktion von BMPs erfolgt wie bei den strukturell verwandten TGF-βs und Activinen durch die ligandeninduzierte Oligomerisierung von transmembranen Serin/Threonin-Kinaserezeptoren, von denen zwei Typen – Typ I und Typ II – existieren. Einer Vielzahl von mehr als 18 BMP-Liganden stehen nach derzeitigem Erkenntnisstand nur vier Typ I und drei Typ II Rezeptorsubtypen für die Bildung von heteromeren Rezeptorkomplexen zur Verfügung. Ein BMP-Ligand kann hochspezifisch nur einen bestimmten Rezeptorsubtyp oder in einer promisken Art und Weise mehrere Rezeptorsubtypen binden. Trotz dieser Bindungspromiskuität üben BMPs ihre biologische Funktion überwiegend hochspezifisch aus, d.h. abhängig vom Liganden werden spezifische zelluläre Prozesse reguliert. Somit stellt sich die Frage, wie die Bildung von heteromeren Ligand-Rezeptor-Komplexen und die Aktivierung definierter intrazellulärer Signalkaskaden zusammenhängen und wie letztlich ein bestimmtes BMP-Signal durch einen „Flaschenhals“, repräsentiert durch die begrenzte Anzahl an Rezeptorsubtypen, in das Zellinnere übermittelt wird. Die Interaktionen zwischen BMP-2 / GDF-5 und den Typ I Rezeptoren BMPR-IA / BMPR-IB sind ein Paradebeispiel für Bindungspromiskuität und -spezifität. Während BMP-2 beide Rezeptoren BMPR-IA und BMPR-IB mit gleicher Bindungsaffinität bindet („promiske Interaktion“), zeigt GDF-5 eine 15-20fach höhere Bindungsaffinität zu BMPR-IB („spezifische“ Interaktion). Dieser Unterschied ist scheinbar gering, aber physiologisch überaus relevant. Um Einblick in die Mechanismen der molekularen Erkennung zwischen den Bindungspartnern zu gewinnen, wurden binäre und ternäre Komplexe aus den Liganden BMP-2 oder GDF-5, den extrazellulären Domänen der Typ I Rezeptoren BMPR-IA oder BMPR-IB sowie der extrazellulären Domäne des Typ II Rezeptors ActR-IIB untersucht. Die hier vorliegende Arbeit beschreibt die strukturelle und funktionelle Analyse dieser Ligand-Rezeptor-Komplexe. Um den Einfluss struktureller Flexibilität auf die BMP Typ I Rezeptor Erkennung näher zu analysieren, wurde zudem die Struktur von BMPRIA in freiem Zustand mittels NMR-Spektroskopie aufgeklärt. Aus Mutagenesedaten und der Kristallstruktur des GDF-5•BMPR-IB-Komplexes lassen sich im Vergleich zu bekannten Kristallstrukturen Merkmale ableiten, mit denen die Ligand-Rezeptor-Bindung und -Erkennung charakterisiert werden kann: (1) Die Hauptbindungsdeterminanten in Komplexen von BMPR-IA und BMPR-IB mit ihren Liganden sind unterschiedlich. Während in Komplexen mit BMPR-IB ein hydrophobes Motiv die Bindungsaffinität bestimmt, trägt in Komplexen mit BMPR-IA eine polare Interaktion signifikant zur Bindungsenergie bei. Ein Vergleich der Strukturen von freien und gebundenen Liganden und Typ I Rezeptoren zeigt, dass interessanterweise diese Hauptbindemotive erst bei der Ligand-Rezeptor-Interaktion entstehen, sodass ein „induced fit“ vorliegt und die Moleküle entsprechend „aufeinander falten“. (2) Die Bindungsspezifität wird durch periphere Schleifen in den Typ I Rezeptoren bestimmt. Wie Untersuchungen von Punktmutationen in BMPR-IA zeigen, die einer krebsartigen Darmerkrankung (Juvenile Polyposis) zugrunde liegen, führt erst die „richtige“ Kombination aus Flexibilität in den Schleifen und Rigidität des Rezeptorgrundgerüsts zu signalaktiven Typ I Rezeptoren mit einer potentiell den Liganden komplementären Oberfläche. Die mangelnde sterische Komplementarität von Ligand- und Rezeptoroberflächen führt zu der niedrigeren Bindungsaffinität von GDF-5 zu BMPR-IA im Vergleich zu BMPR-IB. Interessanterweise zeigen die hier vorgestellten, hochaufgelösten Strukturdaten, dass die Orientierungen/Positionen der Typ I Rezeptoren BMPR-IA und BMPR-IB in den Bindeepitopen der Liganden BMP-2 und GDF-5 variieren. Unter der Voraussetzung, dass die extrazelluläre Domäne, das Transmembransegment und die intrazelluläre Domäne der Typ I Rezeptoren ein starres Element bilden, sollte sich die unterschiedliche Orientierung der extrazellulären Domänen der Typ I Rezeptoren in der Anordnung der Kinasedomänen widerspiegeln und sich auf die Signaltransduktion auswirken. Möglicherweise ist eine bestimmte Anordnung der Kinasedomänen der Typ I und Typ II Rezeptoren für eine effiziente Phosphorylierung bzw. Signaltransduktion erforderlich. Der Vergleich mehrerer Ligand-Typ I Rezeptor-Komplexe zeigt, dass die unterschiedliche Orientierung dieser Rezeptoren möglicherweise vom Liganden abhängt. Angesichts der Bindungspromiskuität unter BMP-Liganden und -Rezeptoren könnten so spezifische Signale übermittelt und spezifische biologische Funktionen reguliert werden. Die in dieser Arbeit vorgestellten Erkenntnisse tragen wesentlich zur strukturellen Charakterisierung der Ligand-Rezeptor-Erkennung in der BMP-Familie bei. Die Frage, warum trotz strukturell hoch homologer Liganden und Rezeptoren und weitgehend konservierten Bindeepitopen eine teils promiske und teils spezifische Interaktion möglich ist, kann nun für die Liganden BMP-2 und GDF-5 sowie den beiden Typ I Rezeptoren BMPR-IA und BMPR-IB beantwortet werden. / Bone morphogenetic proteins (BMPs) are ubiquitous, secreted cytokines involved in a manifold of biological functions. The diversity of cellular processes regulated by BMPs, from bone development to tissue homeostasis and neuronal processes, is amazing – and raises questions about the mechanisms of signal transduction in the light of redundant functions on the one hand, and specific functions on the other hand. Similar to structurally related activins and TGF-βs, the signal transduction of BMPs is accomplished by ligand-induced oligomerization of transmembrane BMP type I and type II serine/threonine receptor kinases. According to current knowledge, only four type I and three type II receptor subtypes are available for BMP signal transduction, facing a multitude of more than 18 BMP ligands. Binding of BMP ligands to their receptors can be highly specific meaning that only one specific receptor of either subtype is used for signaling. In contrast, many BMP ligands can recruit more than one receptor subtype, which results in binding promiscuity. However, even though receptor subtypes are bound in a promiscuous manner, only certain biological functions are triggered. Dependent on the BMP ligand, specific cellular processes are activated and regulated. This discrepancy between unspecific binding and specific signaling events and the biological response raises the question how the formation of heteromeric ligand-receptor complexes is linked to the activation of defined intracellular signaling cascades, and finally, how a certain BMP signal is transduced into the interior of the cell through a „bottleneck“ represented by the limited number of receptor subtypes. The interaction between BMP-2 / GDF-5 and the BMP type I receptors BMPR-IA / BMPR-IB is a prime example for binding promiscuity and binding specificity. BMP-2 binds BMPR-IA and BMPRIB with almost equal binding affinity („promiscuous interaction“) while GDF-5 exhibits a 15-20fold higher binding affinity to BMPR-IB („specific interaction“). Although this difference is seemingly small, it is however of considerable relevance for the physiological role of these ligands. To gain insight into the mechanisms of molecular recognition between the binding partners, binary and ternary ligand-receptor complexes consisting of BMP-2 or GDF-5, the extracellular domains of the type I receptors BMPR-IA or BMPR-IB, and the extracellular domain of the type II receptor ActRIIB were investigated. The thesis presented here describes the structural and functional analysis of these ligand-receptor complexes. To analyse the effect of structural flexibility on BMP type I receptor recognition in more detail, the structure of free BMPR-IA was determined using NMR spectroscopy. Based on data from a limited mutagenesis and the crystal structure of the GDF-5•BMPR-IB complex several characteristics concerning ligand-receptor binding and recognition can be deduced: (1) The main binding determinants in complexes of BMPR-IA and BMPR-IB with their ligands BMP-2 and GDF-5 differ. A hydrophobic binding motif determines binding affinity in complexes of BMPR-IB, whereas a polar interaction significantly contributes to binding energy in complexes of BMPR-IA. These main binding motifs are only formed during complex formation as demonstrated by a comparison between structures of free and bound ligands as well as type I receptors. Both ligand and receptor fold „onto each other“ which suggests an induced fit mechanism. (2) Binding specificity is encoded on loops at the periphery of the binding epitope of the type I receptors. Only the „appropriate“ combination between structural flexibility in the receptor loops and structural rigidity of the receptor backbone results in signal active type I receptors, as shown by analysis of single polymorphisms in BMPR-IA causing juvenile polyposis syndrome, a cancerous disease of the intestine. A lack of steric surface complementarity between GDF-5 and BMPR-IA, that cannot be overcome by structural flexibility, leads to the lower binding affinity in comparison to BMPR-IB. Interestingly, the high resolution structure of the GDF-5•BMPR-IB complex shows that the orientations/positions of BMPR-IA in the binding epitope of BMP-2 and of BMPR-IB in the binding epitope of GDF-5 vary. Assuming that the extracellular domain, the transmembrane segment, and the intracellular domain of the type I receptors form a rigid element, the different orientations of the extracellular domains should also reflect the assembly of the kinase domains and therefore, affect signal transduction. One can assume that a defined arrangement of the kinase domains of type I and type II receptors is required to allow for efficient phosphorylation and signal transduction, respectively. The comparison of several BMP ligand-type I receptor complexes suggests that the different orientations of these receptors are likely dependent on the ligand. Considering the binding promiscuity among BMP ligands and receptors such a mechanism would represent a possible way for the transmission of specific signals and regulation of specific biological functions. The insights into molecular structure and function of BMP ligands and receptors presented in this thesis contribute significantly to a more detailed understanding of their binding properties. The question why the interaction of BMP ligands and receptors is promiscuous on the one hand and specific on the other hand in spite of structurally highly homologous molecules can now be answered for BMP-2 and GDF-5 as well as BMPR-IA and BMPR-IB.

Karolinska Institutet (KI) är en kunskapsintensiv organisation som bedriver världsledande medicinsk forskning. Här blir frågor kring ägande och makt centrala då produktion av vetenskap är en bransch där det finns mycket prestige och ekonomiskt kapital att vinna. Utifrån läsning av kandidatuppsatser som gjorts på KI bildades ett intresse för att lyfta betydelsen av maktens påverkan på det vetenskapliga arbetet. Syftet med studien har varit att utöka förståelsen för hur makt manifesteras inom och mellan forskargrupper på KI. Detta har gjorts genom en kortvarig etnografisk studie under en veckas tid, då vi följt en forskargrupp i deras dagliga arbete. För att kunna styrka våra observationer har även material från tidigare studier gjorda inom samma fält, tillgodogjorts i samråd med handledaren. Forskningsfrågorna som studien utgått från är hur manifesteras makt inom och mellan forskargrupper samt vilken roll spelar kapital som valuta och medlare vid manifestation av makt. För att besvara våra forskningsfrågor har vi tillämpat Bruno Latours Actor-Network Theory (ANT) samt Pierre Bourdieus koncept kring olika kapitalformer. Genom vår observation kunde vi se hur teorierna kunde sammanföras för att förklara hur makt manifesteras och vilka aktörer som kom att spela stor roll i detta avseende. Resultatet av studien visar på att hur makt manifesteras mellan människor, till stor del formas av de så kallade icke-mänskliga aktörerna som finns inom det specifika fältet som studeras. Dessa aktörer menar vi främst är byggnadens utformning, den vetenskapliga och tekniska utrustningen, hyror och publikationer. Avslutningsvis har vi kunnat se att makt manifesteras genom att analysera den cykliska återinvesteringen av kapital.

Base teórica: doenças linfoproliferativas crônicas de linhagem B (DLPC-B) são neoplasias clonais que afetam linfócitos B maduros. A tirosina quinase de Bruton (do inglês Bruton’s tyrosine kinase, BTK) é uma proteína essencial para o desenvolvimento, diferenciação e sinalização nos linfócitos B. Ki-67 é uma proteína nuclear associada à proliferação celular. A avaliação de proteínas envolvidas nas vias de sinalização oncogênicas pode levar ao aprimoramento do diagnóstico, tratamento e definição de prognóstico das DLPC-B. Objetivo: avaliar a expressão de BTK e Ki-67 em linfócitos de portadores de DLPC-B. Métodos: para avaliação de BTK foi realizado um estudo transversal; foi avaliada a expressão de BTK em amostras de pacientes saudáveis e de pacientes com diagnóstico de DLPC-B. Para avaliação de Ki-67 foi realizado um estudo transversal. As amostras foram marcadas com CD45 FITC e CD19 APC para identificação dos linfócitos B. Após a lise das hemácias, foi realizada marcação citoplasmática de BTK PE e/ou Ki-67 PerCP-Cy5.5. O percentual de expressão e a intensidade de fluorescência média (IFM) dos marcadores avaliados foram determinados nos linfócitos B. A análise estatística foi realizada com testes de correlação de Pearson e Spearman entre BTK ou Ki-67 e as demais variáveis clínicas e laboratoriais, e ANOVA seguido por teste post hoc de Bonferroni para comparações entre grupos. Foi considerado resultado significante quando P < 0,05. Resultados: não foram observadas diferenças na expressão de BTK e não houve associação entre a expressão de BTK e as variáveis clínicas avaliadas. A expressão de Ki-67 foi maior nos grupos linfoma do manto, linfoma de Burkitt e linfoma difuso de grandes células B em relação aos demais; após análise multivariada, a IFM de Ki-67 foi associada à IFM de CD38. Conclusão: no presente trabalho, a expressão de BTK em DLPC-B foi similar a de linfócitos B normais e a expressão de Ki-67 foi maior nas DLPC-B com curso clínico mais agressivo. / Background: mature B-cell neoplasms (MBCN) are clonal neoplasms that affect mature B-cell lymphocytes. Bruton’s tyrosine kinase (BTK) is an essential protein for the development, differentiation and signaling in B-cell lymphocytes. Ki-67 is a nuclear protein associated to cellular proliferation. Evaluation of proteins involved in oncogenic signaling pathways can lead to improvement in the diagnosis, treatment and prognosis definition in MBCN. Objective: to evaluate the expression of BTK and Ki-67 in lymphocytes of MBCN patients using flow cytometry. Methods: a cross-sectional study was conducted for BTK assessment; BTK expression was assessed on healthy patients samples and MBCN samples. For evaluation of Ki-67 a cross-sectional study was conducted. Samples were stained with CD45 FITC and CD19 APC for identification of B-cell lymphocytes. After lysis of red blood cells, cytoplasmic staining of BTK PE and/or Ki-67 PerCP-Cy5.5 was performed. Percentage of expression and mean fluorescence intensity (MFI) of the markers were determined in B-cell lymphocytes. Statistical analysis was performed with Pearson and Spearman correlation tests between BTK and Ki-67 and the other clinical and laboratory variables, and ANOVA followed by post-hoc Bonferroni test for comparisons between groups. Results were considered significant when P < 0.05. Results: no differences in BTK expression were identified and there was no association between BTK expression and clinical variables evaluated. Ki-67 expression was higher in mantle cell lymphoma, Burkitt lymphoma and diffuse large B-cell lymphoma cases; after multivariate analysis, MFI of Ki-67 was associated with MFI of CD38. Conclusions: in this study, BTK expression in B-cell neoplasms was similar to that of normal B-cell lymphocytes and Ki-67 expression was higher in MBCN with more aggressive clinical courses.

This doctorate thesis The Politics of Iwi Voice focuses on the struggle of a modern, urban iwi authority to secure political recognition from other iwi and the Crown as it attempts to assert an independent iwi voice, and exercise mana and tino rangatiratanga. The responses of the local iwi/Maori community, the Crown, and others to the re-emergence of the new iwi entity are critically examined. The thesis demonstrates how a small iwi group resists attempts to assimilate into a broader coalition of iwi, hapu, whanau and marae interests, preferring instead to maintain and develop its own distinctive identity. It uses the iwi Ngati Tama to exemplify the diaspora of an iwi, and shows how iwi identity and fortunes are buffeted by both iwi and urban contestations as well as changing political directions. The study suggests that a Ngati Tama future away from its homeland will depend primarily on the development of pragmatic adaptive and innovative strategies, and a fervent resolve to retain a distinctive identity, while participating in a dynamic and often oppressive environment. This thesis concludes that to maintain a distinctive iwi presence its members should have the right to decide who best represents them. An iwi is considered an appropriate vehicle to represent its members and manage its interests. In order to survive in a constantly changing environment, an iwi must be dynamic, flexible, relevant, and meet the needs of its membership. Further, its leadership should be focused on negotiating relationships in good faith - including third party interventions - and seeking pathways that will advance its interests into the future.

<p>The natural history of localized prostate cancer is not fully understood. In most patients the tumor will never progress to a lethal disease, while a subset of patients will ultimately die of the disease. Efficient tools to separate indolent from lethal disease is currently lacking which means that many patients will be offered treatment without any benefit, but still be at risk of experiencing treatment related side effects.</p><p>The aims of these studies were to get more insight into the natural history of untreated localized prostate cancer, to assess the prognostic value of established clinical parameters such as Gleason score, nuclear grade and tumor volume and, moreover, some new prognostic markers Ki-67, AMACR and MUC-1. We also aimed to study time trends in the detection of incidental tumors in Sweden.</p><p>Patients with localized disease (n=223) and no initial treatment were followed for 21 years. Most patients had a favorable outcome. However, a subset of patients developed lethal disease even beyond 15 years of follow-up and these patients define the group that may benefit most from treatment with curative intent. Patients with poorly differentiated tumors experienced a 9 time higher risk of dying in prostate cancer.</p><p>The studies on prognostic markers are based on a cohort of patients (n=253) with incidental prostate cancer detected by transurethral resection for presumed benign hyperplasia. All patients were left without initial treatment. Gleason grade, nuclear grade and tumor volume turned all out to be independent prognostic factors. MUC-1, AMACR and Ki-67 also carried prognostic information. However, after adjustment for Gleason grade, nuclear grade and tumor volume only MUC-1 and AMACR remained as statistically significant prognostic factors. When tested for sensitivity and specificity they all failed and, consequently, they seem to be of less value in daily practice for cancelling an individual patient regarding the choice of treatment.</p><p>Time trends in incidental prostate tumors in Sweden were analyzed in a cohort of patients with prostate tumors detected by transurethral resection (TUR-P). Through linkage of the national registration number (NRN) with several registers, e.g. the Swedish Cancer Registry, the National Inpatient registry and the Cause of Death Registry we identified, during the period 1970 through 2003, in total 23288 patients with incidental prostate cancer, who constituted the study group. As comparison group we choose all patients diagnosed with prostate cancer between 1970-2003 excluding those with incidental cancer, in total 112204 patients. Our result confirms earlier findings that there has been a dramatic change over time in incidence of incidental prostate cancers in Sweden, which parallels the introduction of prostate specific antigen. We also found that the cumulative incidence of prostate cancer death is high in the incidental group, opposing earlier findings that incidental tumours are a non-lethal disease.</p> / issn 1642-4063

<p>The incidence of breast cancer is rising steadily in Sweden and the proportion of carcinoma in situ (CIS) has increased appreciably, most likely due to mammography screening. The aim of this study was twofold: (1) to examine risk factors for subsequent invasive breast carcinoma and breast cancer death after primary ductal carcinoma in situ (DCIS) and (2) to study the biology in the progress between in situ and invasive carcinoma.</p><p> In a cohort-study based on 3,398 women with a primary CIS reported to the Swedish Cancer Registry (SCR) 1980-1992, women diagnosed in 1989-1992 ran a relative risk of 0.1 (CI 95%, 0.0-0.9) from dying of breast cancer as compared with women diagnosed in 1980-1982. Women in counties with mammography screening ran a relative risk of 0.2 (CI 95%, 0.0-2.1) for breast cancer death in comparison with women in non-screening counties.</p><p> In a case-control study derived from all 4,661 women with primary CIS reported to the SCR 1960-1992, we investigated risk factors for subsequent invasive breast carcinoma (n=118) and breast cancer death (n=39). Large size and multifocality were found to increase the risk for breast cancer death. Postoperative radiotherapy and mastectomy lowered the risk for ipsilateral invasive cancer.</p><p> The standardised incidence rates (SIR) for invasive breast cancer were estimated in the cohort from 1980-1992. The SIR after primary DCIS and primary lobular carcinoma in situ (LCIS) was 4.5 (CI 95%, 3.7-5.5) and 4.0 (CI 95%, 2.1-7.5), respectively.</p><p> New histopathological classification systems for DCIS were evaluated in 195 women consecutively diagnosed with primary DCIS between 1986-1994. One group with highly differentiated lesions was defined with the EORTC classification system and had an excellent prognosis.</p><p> Histopathological grade and expression of p53, c-erbB-2, Ki 67, hormone receptors, Bcl-2 and angiogenesis were compared in 626 women with either a pure DCIS, a small invasive carcinoma or a lesion with both an invasive and in situ component. When grade was taken into account, no change in tumour markers could be detected that signalled the progression from an in situ stage to invasiveness. All tumour markers correlated to grade and their distribution was very similar in the two components of mixed lesions.</p>

The incidence of breast cancer is rising steadily in Sweden and the proportion of carcinoma in situ (CIS) has increased appreciably, most likely due to mammography screening. The aim of this study was twofold: (1) to examine risk factors for subsequent invasive breast carcinoma and breast cancer death after primary ductal carcinoma in situ (DCIS) and (2) to study the biology in the progress between in situ and invasive carcinoma. In a cohort-study based on 3,398 women with a primary CIS reported to the Swedish Cancer Registry (SCR) 1980-1992, women diagnosed in 1989-1992 ran a relative risk of 0.1 (CI 95%, 0.0-0.9) from dying of breast cancer as compared with women diagnosed in 1980-1982. Women in counties with mammography screening ran a relative risk of 0.2 (CI 95%, 0.0-2.1) for breast cancer death in comparison with women in non-screening counties. In a case-control study derived from all 4,661 women with primary CIS reported to the SCR 1960-1992, we investigated risk factors for subsequent invasive breast carcinoma (n=118) and breast cancer death (n=39). Large size and multifocality were found to increase the risk for breast cancer death. Postoperative radiotherapy and mastectomy lowered the risk for ipsilateral invasive cancer. The standardised incidence rates (SIR) for invasive breast cancer were estimated in the cohort from 1980-1992. The SIR after primary DCIS and primary lobular carcinoma in situ (LCIS) was 4.5 (CI 95%, 3.7-5.5) and 4.0 (CI 95%, 2.1-7.5), respectively. New histopathological classification systems for DCIS were evaluated in 195 women consecutively diagnosed with primary DCIS between 1986-1994. One group with highly differentiated lesions was defined with the EORTC classification system and had an excellent prognosis. Histopathological grade and expression of p53, c-erbB-2, Ki 67, hormone receptors, Bcl-2 and angiogenesis were compared in 626 women with either a pure DCIS, a small invasive carcinoma or a lesion with both an invasive and in situ component. When grade was taken into account, no change in tumour markers could be detected that signalled the progression from an in situ stage to invasiveness. All tumour markers correlated to grade and their distribution was very similar in the two components of mixed lesions.

This thesis focuses on the involvement of apoptosis and proliferation in the mechanisms of menstruation and hormonal replacement therapy, HRT, as well as in the mechanisms of progesterone therapy in endometrial carcinoma. The aim of the first study was to investigate endometrium for 4 days before and for 2 days during menstruation. In the epithelium, rapid increase in the apoptotic index, decreasing expression of estrogen receptor α (ER) and progesterone receptor (PR), and minimal proliferation were observed prior to menstruation. In the stroma, an increase in the expression of ER and PR and proliferation was seen before the final decrease, and increased apoptosis was seen during menstruation. Thus, apoptosis is involved in the remodeling of the endometrium during menstruation. Postmenopausal endometrium showed unaffected homeostasis, i.e. unchanged ratio between apoptotic index and Ki-67 index during substitution therapy. ER expression was decreased both in the epithelium and stroma, while PR showed some increase in receptor expression. The unchanged homeostasis contributes to endometrial safety during combined continuous HRT. Unchanged apoptosis and increasing proliferation were observed with increasing tumor grade in 29 patients with endometrioid endometrial carcinoma, which may contribute to greater aggression as tumor grade increases. Decreased proliferation was observed after medroxy-progesterone at 20 mg per day particularly in the foci of maximal proliferation in G1 and G2 tumors. The expression of ER was unchanged, while PR was decreased in the foci of maximal expression for PR in G1 and G2 tumors. Since high proliferation and PR expression also coexisted in the same foci, evaluated in G1 and G2 tumors, the effect of progesterone could be facilitated in these tumor groups. High expression of sex steroid receptors was also a predicting factor for good response to progesterone (= decrease in proliferation), while the amount of stroma could not predict that effect.

El tema principal d’aquesta tesi és considerar la noció sinojaponesa del Ki en la filosofia de Yasuo Yuasa com a fil conductor per a la seva recerca antropològica i el seu camí vers la transcendència. Calia constatar que l’aportació de Yuasa és principalment la seva determinació del lloc del Ki en la corporalitat i, per tal de fer-ho, centrar en aquest punt el tema de la present tesi. Aquesta tesi està dividida en sis capítols: En el primer capítol, tractem de Yasuo Yuasa en la seva circumstància, vida i pensament i, el seu influx i el desenvolupament del seu pensament en alguns autors actuals. En el segon capítol, abordem com Yuasa ha arribat a tenir la idea del Ki com a clau de la unitat corpòria-espiritual i l’obertura a la transcendència, mitjançant un recorregut per la seva obra. Al llarg de tota la seva obra, podem trobar les preguntes radicals sobre sí mateix, sobre el món, sobre l’origen que els transcendeix. Yuasa les anomena Ethos, els corrents filosòfics espirituals latents i fonamentals en el fons de cada tradició i cultura. En el tercer capítol, tractem una visió de conjunt al voltant de la noció del Ki i la tradició de pensament que l’acompanya per tal d’introduir el seu sentit i les seves funciones fonamentals. Per això, pretenem analitzar-la tant des de la perspectiva del seu sentit etimològic i de llurs diverses accepcions en l’ús del llenguatge, com des del punt de vista històric i de llurs diverses dimensions. En el quart capítol, considerem l’aspecte de l’ésser humà com a unitat cos-ment i el seu doble caràcter; ésser immanent i transcendent del món. En abordar la qüestió de la transcendència i de la immanència en la filosofia existencial que es troba en els filòsofs moderns japonesos, Yuasa sent la necessitat de remuntar-se a l’ontologia en la tradició occidental com ara la de Sant Tomàs. La forma d’aquest pensament ontològic (o metafísic) té uns aspectes universals i equivalents amb el pensament tradicional d’Orient que es troba en el fons de la filosofia existencial en la modernitat japonesa. A partir d’aquesta base, en el cinquè capítol, intentem analitzar si existeix la pregunta vers la transcendència en la tradició oriental, especialment la tradició xinesa japonesa representada per Yuasa. Yuasa té en compte la unitat corpòria-espiritual com a obertura a la pregunta vers la transcendència. La clau d’aquesta unitat és el Ki, el qual, segons Yuasa, és el flux que té una funció fisiològica i psicològica, així com també una funció espiritual, que fa connectar a l’ésser humà amb el món exterior. La idea del Ki ens fa abastar la visió de l’ésser humà al llarg de la història del pensament científic i antropològic i religiós o espiritual. Per això, intentarem analitzar la noció del Ki des de tres perspectives: científica, antropològica i espiritual. En el sisè capítol, finalment, tractem la pràctica del shugyô la qual té un sentit molt important a fi de poder considerar la teoria oriental de la unitat cos-ment i és una clau per tal de comprendre la transcendència en la tradició oriental. El shugyô indica l’ascesi, la pràctica o la formació del cultiu d’un mateix. Dins el concepte del shugyô Yuasa distingeix entre la praxi exterior (preceptes sîla) i la praxi interior (contemplació samâdhi). Ens fixem especialment en la praxi interior que és l’activitat que s’orienta cap a la pròpia interioritat de l’ésser humà, el significat del qual és equivalent a la vida contemplativa en el terme occidental. / El tema principal de esta tesis es considerar la noción chino-japonesa del Ki en la filosofía de Yasuo Yuasa como hilo conductor para su búsqueda antropológica y su camino hacia la trascendencia. Había que constatar que la aportación de Yuasa es principalmente su determinación del puesto del Ki en la corporalidad y, para ello, centrar en este punto el tema de la presente tesis. Esta tesis está dividida en seis capítulos: En el primer capítulo, tratamos acerca de Yasuo Yuasa en su circunstancia, vida y pensamiento y, el influjo y el desarrollo de su pensamiento en algunos autores actuales. En el segundo capítulo, abordamos sobre cómo Yuasa ha llegado a tener la idea del Ki como clave de la unidad corpóreo espiritual y apertura a la trascendencia, mediante el recorrido por su obra. A lo largo de toda su obra, podemos encontrar las preguntas radicales sobre sí mismo, sobre el mundo, sobre el origen que los trasciende. Yuasa las llama Ethos, las corrientes filosóficas espirituales latentes y fundamentales en el fondo de cada tradición y cultura. En el tercer capítulo, tratamos una visión de conjunto acerca de la noción del Ki y la tradición de pensamiento que la acompaña para introducir su sentido y sus funciones fundamentales. Por ello, pretendemos analizarla tanto desde la perspectiva de su sentido etimológico y sus diversas acepciones en el uso del lenguaje, como desde el punto de vista histórico y de sus diversas dimensiones. En el cuarto capítulo, consideramos el aspecto del ser humano como unidad cuerpo-mente y su doble carácter; ser inmanente y trascendente del mundo. Al abordar la cuestión de la trascendencia y de la inmanencia en la filosofía existencial que se encuentra en los filósofos modernos japoneses, Yuasa siente la necesidad de remontarse a la ontología medieval en la tradición occidental como la de Santo Tomas. La forma de este pensamiento ontológico (o metafísico) tiene unos aspectos universales y equivalentes con el pensamiento tradicional de Oriente que se encuentra en el fondo de la filosofía existencial en la modernidad japonesa. A partir de esta base, en el quinto capítulo, intentamos analizar si existe la pregunta hacia la trascendencia en la tradición oriental, especialmente la tradición china japonesa representado por Yuasa. Yuasa tiene en cuenta la unidad corpóreo espiritual como apertura a la pregunta hacia la trascendencia. La clave de esta unidad es el Ki, que según Yuasa, es el flujo que tiene una función fisiológica y psicológica, así como también una función espiritual, que hace conectar al ser humano con el mundo exterior. La idea del Ki nos hace abarcar la visión del ser humano a lo largo de la historia del pensamiento científico y antropológico y religioso o espiritual. Por ello, intentaremos analizar la noción del Ki desde tres perspectivas: científica, antropológica y espiritual. En el sexto capítulo, finalmente, tratamos la práctica del shugyô que tiene un sentido muy importante para poder considerar la teoría oriental de la unidad cuerpo-mente y es una clave para comprender la trascendencia en la tradición oriental. El shugyô indica la ascesis, la práctica o la formación del autocultivo. Dentro del concepto del shugyô Yuasa distingue entre la praxis exterior (preceptos sîla) y la praxis interior (contemplación samâdhi). Nos fijamos especialmente en la praxis interior que es la actividad que se orienta hacia la propia interioridad del ser humano, cuyo significado es equivalente a la vida contemplativa en el término occidental. / The main purpose of this dissertation is to study the Chino-Japanese thought about Ki in the philosophy of Yuasa as a key for his anthropological search and as a way toward transcendance. We had to clarify the contribution of Yuasa to both the anthropological and the metaphysical question. The main contribution of Yuasa to this problem is the determination of the role of Ki within the Mind-Body theory. That is why we had to focus our research upon this point as the main subject of our dissertation. Our research follows the steps of the following chapters: In the first chapter we present the thought of Yuasa within the context of his biographical circumstances, as well as the influence of further developments of his thought in other contemporary thinkers. In the second chapter we go through the whole complete works of Yuasa in order to find the development of his thought about Ki and the way he has arrived to the conclusion of setting the idea of Ki as the leading thread to grasp both the Mind-body unity and the openness toward transcendence. Throughout his work we find him seeking to answer the basic questions about himself, about the world and about the tarscendental origins of both the human being and the cosmos. Yuasa sees these basic questions as the Ethos of the philosophical and spiritual currents in the bottom of each tradition and culture. In the third chapter we present an overall view about the idea of Ki and the tradition of thought developed around this fundamental concept of Eastern philosophy, trying to show its meaning and its role for the understanding of both the human being and the cosmos. For that purpose we analyse the notion of Ki from the viewpoint of its etimological, historical and other dimensions. In the fourth chapter we deal with the Mind-body unity of the human being and the two characteristics of his way of being in the world, namely, inmanence and transcendance. Yuasa studied the problem of inmanence and transcendence in the existential philosophy of the modern Japanese thinkers, and the roots of their thought in the Eastern tradition. Then, in order to compare them with Western thought, he felt the need to seek the roots of contemporary existential Western philosophy in the tradition of ontology in the Middle Age, as in Thomas Aquinas. Yuasa arrived at the conclusion that this ontological (or metaphysical thinking) has some universal aspects which can be related to the traditional Eastern thought as we find it within the existential philosophy of some modern Japanese thinkers. Taking into account this comparative approach, we ask in our analysis of the fifth chapter, whether the question toward transcendence can be found in the Eastern tradition, especially in the tradition represented by Yuasa. Yuasa gives a great importance to the unity of mind and body as a key toward the question about transcendence. The key of the Mind and body unity is, according to Yuasa, the Ki, which plays not only a physiological and psychological role, but also an spiritual one in order to connect the human being with the world outside. The idea of Ki helps us to reach an overall perspective about human being along the history of anthropological, scientific, and religious or spiritual thought. Therefore, it was important for us to analyse the notion of Ki from the viewpoint of its three main dimensions, namely, scientific, anthropological and spiritual dimensions. Finally, in the sixth chapter we deal with the practice of shugyô or cultivation, which has a very important meaning for the understanding of the Eastern Mind-Body theory, and which is a key for the understanding of transcendence in that tradition. The meaning of shugyô points to ascesis or practices of self-cultivation. Within the concept of shugyô Yuasa makes a distinction between external practices (precepts, sîla) and internal practices (contemplation samâdhi). We concentrate our analysis in the internal practices, orientated toward the interiority of the human being. These practices can be related to the Western tradition of contemplative life.