BACKGROUND: Maximal oxygen uptake (VO2max) is an important predictor for cardiovascular health. VO2max is often calculated using submaximal tests in clinic. Ekblom-Bak (EB-test) test is a new submaximal cycle ergometer test for calculating VO2max based on differences in heart frequency between two different workloads. OBJECTIVES: The aim of the study was to examine the correlation and agreement between the two methods for calculating VO2max; Åstrand cycle test (Å-test) and EB-test. A secondary aim was also to examine VO2max of physiotherapy students in Uppsala. METHODS: The study design was descriptive and comparative. 30 subjects aged 20-30 were recruited by convenience sampling. Both tests were performed during the same session. Agreement and correlation between the two tests was calculated through paired t-tests and Pearson’s correlation coefficients respectively. RESULTS: Calculated VO2max for the subjects was on average 3.65 L/min, 52.03 ml/kg/min (EB-test) and 3.38 L/min, 47.97 ml/kg/min (Å-test). The differences between the two tests were statistically significant for both L/min (p = 0.01) and ml/kg/min (p = 0.009). The correlation between the two tests was r = 0.76 (L/min) and r = 0.59 (ml/kg/min) respectively. CONCLUSION: This study shows a statistically significant difference between the two submaximal cycle ergometer tests for calculating VO2max. The difference between the two tests is clinically significant and should be considered upon use. Both tests should be used consistently upon evaluating different treatments. Further research in the area is needed.

This thesis was initiated by an awareness of the impact of low back pain in Western society in general and Australian society in particular. The studies and experiments in this thesis contribute towards an understanding of chiropractic as a professional entity in Victoria and the nature of its clinical practice. The issue of male adolescent LBP has been explored and in addition to an epidemiological description of this clinical entity, its anthropometric dimensions have been documented. The qualitative review of the literature provides ample justification for the management of patients with LBP by chiropractors, using manual or manipulative techniques. The observational study of the Victorian context in which chiropractors are educated, registered, and entitled to practice, demonstrates that Victorian chiropractors are appropriate providers of manipulative health care. They perform the role of primary contact, primary health care providers with diagnostic, treatment and management skills focussed mainly on musculoskeletal conditions, but with a small proportion of practice based in the health or preventive context, and are well placed to provide the manual and manipulative services required in the management of LBP patients. The profession is shown to have strategies in place to ensure continued legal and community acceptance. The strategies include those at entry level to the profession, such as the legislative provisions of government and the competencies required for registration as instilled during the professional education process, and those which are more of the nature to maintain the integrity of professional practice, such as the " standards of practice" concept. These are important characteristics given it is shown that the Victorian chiropractic profession is not homogenous with respect to educational standards, has a disparate gender balance, the presence of a few non-registered 'chiropractors', and a disparity in utilisation patterns with a significant tail to the right. However the chiropractic profession is shown to hold a position of strength and leadership in the Australian context with respect to the provision of manipulative health care. Indeed, it could be said that chiropractors are at the leading edge of the quality process with respect to the provision of manipulative health care in Australia. The description of chiropractic practice shows a patient base of all ages, including adolescents, presenting with a range of possible diagnoses, often funded by a third party, and with a high proportion of return visits suggestive of patient compliance and satisfaction. It is convincingly demonstrated that persons with work-related LBP attend to chiropractors in Victoria and are effectively managed with the aim being the restoration of optimal spinal function and, in the case of work-injured patients, an early return to work. This thesis includes utilisation data which suggest only a minority of Victorian chiropractors practice outside the responsible parameters described above. The case-mix data and patient profiles presented in this thesis are congruent and complement each other, suggesting a high level of patient satisfaction indicated by the high proportion of return visits by regular patients and a faster, return-to-work by work-injured claimants. The point and sample prevalence of LBP in a population of suburban male adolescents is described and shown to be similar to those found in comparable Western societies. The data for a sample of traditional Australian male adolescents describes the LBP experience for the first time in such a population and emphasises the wide variance between societies which is now being identified in the literature. The LBP experience of a typical suburban Australian male adolescent is identified and described in terms of chronicity, frequency and episode duration. Typically the male adolescent with LBP has a chronic (> 90 d) problem with frequent episodes of pain (from 2 or 3 times a month to 2 or 3 times week) which last a few hours. The pain is a little limiting but allows the performance of the Activities of Daily Living. While some limitation of general sporting activity due to pain is experienced, school attendance is generally not compromised. A particular clinical instrument, the Metrecom computerised electro-goniometer, is studied and found to be appropriate for use in gathering anthropometric dimensions to test hypotheses relating to an association between anthropometric dimensions and LBP in a male adolescent population. The applied level of uncertainty of the instrument is within acceptable limits for these dimensions. The anthropometric study tests the broad null hypothesis that the mean of specific anthropometric dimensions would be equal among samples of male adolescents drawn from the Australian population. The actual groups are a Melbourne 'Pain' group, a Melbourne 'No Pain' group, and a 'Traditional No Pain' group. The pain group reported either current LBP or a positive history of LBP, while the 'no pain' groups denied either current or historical LBP. The alternate hypothesis will be shown to be proven for the dimensions 'sitting height', 'upper body' length, 'pelvic height', and the ratio of the 'upper:lower' body segment in a population of male adolescents with idiopathic or mechanical LBP. This thesis meets its objectives of describing the chiropractic profession and its practise in the Victorian context, demonstrates the prevalence of LBP in a male adolescent population, and identifies particular anthropometric dimensions associated with those who report a LBP experience. The fact that a number of anthropometric dimensions are detectable in adolescence may allow the development of appropriate screening programs which in turn may lead to the design and introduction of suitable prophylactic interventional programs for persons found to be potentially prone to idiopathic or mechanical LBP, at the least reducing the severity and at most reducing the onset of this expensive problem in adulthood. The ratio of the upper body segment to the lower body segment would appear to be most appropriate indicator; it is robust in that it is a prime dimension, easily accessible, and with a low level of measurement uncertainty. Most importantly it would appear to hold validity throughout adolescence as it does not have a linear relationship with age.

Poxviruses are renowned for encoding proteins that modulate virtually every aspect of the host immune system. One effective barrier against virus infection is apoptosis, a form of programmed cell death. Apoptosis is controlled at the mitochondria by pro- and anti-apoptotic members of the highly conserved Bcl-2 family of proteins, and two members in particular, Bak and Bax, are absolutely critical to the induction of cell death. Although poxviruses encode an array of effective inhibitors of apoptosis, only members of the Avipoxvirus genus, of which fowlpox virus is the prototypical member, encode proteins with obvious, albeit limited, sequence identity to cellular Bcl-2 proteins. Fowlpox virus, the prototypical avipoxvirus, encodes FPV039, a protein that possesses two of the four highly conserved Bcl-2 homology (BH) domains that characterise the Bcl-2 family. Here we demonstrate that, like cellular Bcl-2 proteins, FPV039 localised to the mitochondria where it prevented apoptosis induced by a variety of cytotoxic stimuli, including virus infection itself. FPV039 inhibited apoptosis induced by Bak and Bax through an interaction with Bak and activated Bax. FPV039 also interacted with a discrete subset of BH3-only proteins, the upstream activators of Bak and Bax, to prevent Bax activation in the first place. Additionally, we have characterised the function and mechanism of action of a novel deerpox virus protein, DPV022. Intriguingly, DPV022 lacks obvious homology to cellular Bcl-2 proteins but shares limited regions of amino acid identity with two other poxviral inhibitors of apoptosis, vaccinia virus F1L and myxoma virus M11L, which are themselves unrelated. Here we demonstrate that DPV022 localised to the mitochondria where it interacted directly with Bak and Bax to inhibit apoptosis, even in the absence all cellular anti-apoptotic Bcl-2 proteins. We have also embarked on a preliminary analysis of the apical events that initially trigger apoptosis during infection with vaccinia virus, the prototypical poxvirus. Accordingly, we demonstrate that the BH3-only protein Noxa contributed to the vaccinia virus-induced apoptotic response, possibly through an involvement with dsRNA. Together, this study represents a comprehensive analysis of the ways in which poxviruses manipulate the cellular Bcl-2 family of proteins, the arbiters of cell death. / Virology

No description available.

No description available.

La Leucémie Lymphoïde Chronique (LLC) est caractérisée par l’accumulation dans le sang de lymphocytes B/CD5+ qui sont déficients pour leur programme de mort apoptotique. Malgré les progrès thérapeutiques récents, la LLC est une maladie toujours incurable. La stratégie de rétablissement des processus apoptotiques semble pertinente pour améliorer les traitements des patients, et cette stratégie nécessite l’identification de cibles spécifiques. Dans ce but, nous avons développé une recherche du mécanisme d’action de l’hyperforine, un phloroglucinol purifié à partir de la plante Millepertuis, qui est un inducteur d’apoptose des cellules de LLC ex vivo par la voie mitochondriale dépendante des caspases. Les résultats montrent que le traitement des cellules primaires de LLC régule positivement Noxa, une protéine de la famille Bcl-2 du type « BH3-only » qui est un ligand antagoniste spécifique de Mcl-1, la protéine de survie majeure pour le défaut d’apoptose dans les LLC. Nous montrons que Noxa interagit effectivement avec Mcl-1, ce qui entraine la dissociation du complexe que Mcl-1 forme avec Bak, et l’activation de cette protéine responsable de la libération par la mitochondrie des facteurs d’activation des caspases. La régulation positive de Noxa ne résulte apparemment pas d’une activation transcriptionnelle mais plutôt d’une régulation au niveau protéique comme le suggère la capacité de l’hyperforine à inhiber l’activité protéolytique du protéasome dans les cellules de LLC. Par ailleurs, l’apoptose induite par l’hyperforine est réduite en partie par l’extinction de Noxa avec des ARN interférents. Nos résultats indiquent donc que la régulation positive de Noxa est un des mécanismes qui permet à l’hyperforine de déclencher l’apoptose des cellules de LLC. Ce mécanisme semble être commun à d’autres composés d’origine végétale, comme nous l’avons observé avec l’extrait M2Yn dans la seconde partie de notre travail qui a permis de mettre en évidence que cet extrait de plantes d’Asie centrale est capable lui aussi d’induire l’apoptose des cellules de LLC par la voie mitochondriale dépendante des caspases. Enfin, nous avons contribué à la mise en évidence des propriétés pro-apoptotiques de l’hyperforine dans un autre modèle de leucémie, la leucémie myéloïde aiguë, grâce en partie à la régulation positive de Noxa ainsi qu’à l’inhibition de l’activité kinasique de Akt-1.En conclusion, nos travaux de thèse décrivent des nouvelles étapes dans le mécanisme d’action de l’hyperforine et permettent d’établir que la protéine « BH3-only » Noxa est une cible majeure pour la stratégie thérapeutique du rétablissement d’apoptose dans les LLC, ce qui devrait susciter le développement de nouveaux agents capables d’imiter spécifiquement l’action de Noxa. / Chronic lymphocytic leukemia (CLL) is characterized by blood accumulation of CD5+/B lymphocytes which are deficient in their apoptotic program. Despite recent therapeutic advances, CLL remains an incurable disease. Treatment strategy based on the re-establishment of apoptotic processes has retained much attention, and such a strategy requires the identification of specific targets. To this aim, we have investigated the mechanism of action of hyperforin, a phloroglucinol purified from St John’s wort, capable of inducing apoptosis of CLL cells ex vivo via the caspase-dependent mitochondrial pathway. Our results show that treatment of CLL patients’ cells upregulates the BH3-only protein Noxa that is a specific antagonist ligand of Mcl-1, the crucial prosurvival protein for apoptosis deficiency in CLL. We find that hyperforin provokes both the interaction of Noxa with Mcl-1 and the dissociation of Mcl-1/Bak complex, leading to Bak activation responsible for the release of apoptogenic factors from mitochondria. Noxa upregulation does not seem to result from transcription activation but rather from a regulation at the protein level, as suggested by the ability of hyperforin to inhibit proteasome activity in CLL cells. Using siRNA, Noxa silencing partially reduces hyperforin-induced apoptosis. Our data indicate that Noxa upregulation is one of the mechanisms through which hyperforin triggers CLL cell apoptosis. This mechanism appears to be shared with other plant-derived compounds, as observed with M2Yn, an extract from central Asia plants, that we show here to be an inducer of apoptosis in CLL cells by activating the caspase-dependent mitochondrial pathway. Finally, we have participated in highlighting the proapoptotic properties of hyperforin in another leukemia model, acute myeloid leukemia, via in part Noxa upregulation and Akt1 kinase activity inhibition.In conclusion, our data describe new steps in the mechanism of action of hyperforin and favor that the BH3-only protein Noxa is a major target for the therapeutic strategy based on apoptosis induction in CLL. Thus, this thesis should prompt the development of new BH3 mimetics specific for Noxa.

As teorias científicas surgiram da necessidade do homem entender o funcionamento das coisas. Novos métodos e técnicas são então criados com o objetivo não só de melhor compreender, mas também de desenvolver essas próprias teorias. Nesta dissertação, vamos estudar várias dessas técnicas (aqui chamadas de algoritmos) com o objetivo de obter estados fundamentais em sistemas de spin e de revelar suas possíveis propriedades de auto-organização crítica. No segundo capítulo desta dissertação, apresentamos os algoritmos de otimização: simulated annealing, algoritmo genético, otimização extrema (EO) e evolutivo de Bak-Sneppen (BS). No terceiro capítulo apresentamos o conceito de criticalidade auto-organizada (SOC), usando como exemplo o modelo da pilha de areia. Para uma melhor compreensão da importância da criticalidade auto-organizada, apresentamos vários outros exemplos de onde o fenômeno é observado. No quarto capítulo apresentamos o modelo de relógio quiral de p-estados que será nosso sistema de testes. No caso unidimensional, determinamos a matriz de transferência e utilizamos o teorema de Perron-Frobenius para provar a inexistência de transição de fase a temperaturas finitas a temperaturas finitas. Esboçamos os diagramas de fases dos estados fundamentais que obtivemos de maneira analítica e numérica para os casos de p = 2, 3, 4, 5 e 6, no caso numérico fazendo uso do algoritmo de Bak-Sneppen com sorteio (BSS). Apresentamos ainda um breve estudo do número de mínimos locais para o modelo de relógio quiral de p-estados, para os casos de p = 3 e 4. Por último, no quinto capítulo, propomos uma dinâmica Bak-Sneppen com ruído (BSR) como uma nova técnica de otimização para tratar sistemas discretos. O ruído é introduzido diretamente no espaço de configuração de spins. Conseqüentemente, o fitness (adaptabilidade) passa a assumir valores contínuos, num pequeno intervalo em torno do seu valor original (discreto). Os resultados dessa dinâmica indicam a presença de criticalidade auto-organizada, evidenciada pelo decaimento em leis de potências das correlações espacial e temporal. Também estudamos o método EO e obtivemos uma confirmação numérica de que sua dinâmica exibe um comportamento não crítico com alcance espacial infinito e decaimento exponencial das avalanches. Finalmente, para o modelo de relógio quiral, comparamos a eficiência das três dinâmicas (EO, BSS e BSR) no que tange às suas habilidades de encontrar o estado fundamental do sistema. / In order to understand how things work, man has formulated scientific theories. New methods and techniques have been created not only to increase our understanding on the subject but also to develop and even expand those theories. In this thesis, we study several techniques (here called algorithms) designed with the objective to get the ground states of some spin systems and eventually to reveal possible properties of critical self-organization. In the second chapter, we introduce four fundamental optimization algorithms: simulated annealing, genetics algorithms, extremal optimization (EO) and Bak-Sneppen (BS). In the third chapter we present the concept of self-organized criticality (SOC), using as an example the sandpile model. To understand the importance of the self-organized criticality, we show many other situations where the phenomenon can be observed. In the fourth chapter, we introduce the p-states chiral clock model. This will be our test or toy system. For the one-dimensional case, we first determined the corresponding transfer-matrix and then proved the nonexistence of phase transitions by using the Perron-Frobenius theorem. We calculate the ground state phase diagrams both analytically and numerically in the cases of p = 2, 3, 4, 5 and 6. We also present a brief study of the number of local minima for the cases p = 3 and 4 of the chiral clock model. Finally, in the fifth chapter, we propose a Bak-Sneppen dynamics with noise (BSN) as a new technique of optimization to treat discrete systems. The noise is directly introduced into the spin configuration space. Consequently, the fitness now take values in a continuum but small interval around its original value (discrete). The results of this dynamics indicate the presence of self-organized criticality, which becomes evident with the power law scaling of the spacial and temporal correlations. We also study the EO algorithm and found a numerical con_rmation that it does not show a critical behavior since it has an in_nite space range and an exponential decay of the avalanches. At the end, we compare the e_ciency of the three dynamics (EO, BSD and BSN) for the chiral clock model, concerning their abilities to _nd the system\'s ground state.

Melanoma cutâneo ainda constitui a principal causa de morte por câncer de pele nos países desenvolvidos. A variabilidade do comportamento clínico dessa neoplasia tem sido apenas parcialmente explicada pelos aspectos clínicos e histológicos, e a identificação de variáveis biológicas pode vir a ser importante na determinação de grupos de risco específicos. Foram estudados 69 pacientes com melanoma cutâneo primário de diversos graus de gravidade, tratados entre 1990 e 2007, com o intuito de verificar aspectos clínicos e epidemiológicos, preparar Tissue microarray (TMA) para estudo dos melanomas cutâneos primários com espessura maior que 1,0 mm, avaliar por análise imuno-histoquímica a expressão das proteínas da apoptose celular Bcl2, Bax, Bak, Apaf-1, Caspase 3, Caspase 9, Caspase 8, FasL e Fas em nevos-controle e em melanomas primários com espessuras menores e maiores que 1mm, e correlacionar a expressão dessas proteínas da apoptose com a evolução de melanomas cutâneos primários. Os resultados ratificaram tanto dados epidemiológicos já publicados em relação a sexo, idade e local da lesão, quanto a correlação entre a evolução da doença e os índices de Breslow. A análise dos escores compostos relativos à expressão das proteínas da apoptose revelou que o perfil imuno-histoquímico dessas proteínas parece não ter significado prognóstico, uma vez que não houve diferenças de expressão entre pacientes com e sem doença disseminada. Não foram encontradas alterações na expressão das proteínas da apoptose estudadas que pudessem sugerir o seu envolvimento tanto na gênese quanto na progressão de melanoma primário. O perfil imuno-histoquímico com tendência pró-apoptótica parece indicar que outros fatores seriam responsáveis pelo crescimento e disseminação da neoplasia / Cutaneous melanoma still constitutes the main cause of skin cancer death in developed world. Clinical behavior variability of this neoplasia has been only partially explained by clinical and histological aspects, and identification of biological variables can be important for determining specific risk groups. Sixty nine (69) patients with mild to severe primary cutaneous melanoma treated in 1990-2007 were studied aiming at (a) verifying clinical epidemiological aspects, (b) generating a Tissue microarray (TMA) for characterizing proteins expression of cutaneous melanoma > 1.0 mm, (c) analyzing the immunohistochemical expression of the apoptosis proteins Bcl2, Bax, Bak, Apaf-1, Caspase 3, Caspase 9, Caspase 8, FasL e Fas in 10 control nevi and in primary melanomas with thickness 1mm, (d) and correlating these proteins expression with the disease prognosis. Results have ratified known epidemiological date on gender, age and lesion localization as well as the correlation between the disease prognosis and the Breslow\'s indexes. Analysis of the composite scores relating to apoptosis proteins has revealed that their immunohistochemical profile seems to be not significant for determining the disease prognosis, since no differences in proteins expression were found when compared patients with and without disease dissemination. Alterations in proteins expression suggesting their role in the genesis as well as in the prognosis of primary melanoma were not evidenced. Immunohistochemical profile with pro-apoptosis trend seems to indicate other factor as responsible for the neoplasia growth and dissemination

As teorias científicas surgiram da necessidade do homem entender o funcionamento das coisas. Novos métodos e técnicas são então criados com o objetivo não só de melhor compreender, mas também de desenvolver essas próprias teorias. Nesta dissertação, vamos estudar várias dessas técnicas (aqui chamadas de algoritmos) com o objetivo de obter estados fundamentais em sistemas de spin e de revelar suas possíveis propriedades de auto-organização crítica. No segundo capítulo desta dissertação, apresentamos os algoritmos de otimização: simulated annealing, algoritmo genético, otimização extrema (EO) e evolutivo de Bak-Sneppen (BS). No terceiro capítulo apresentamos o conceito de criticalidade auto-organizada (SOC), usando como exemplo o modelo da pilha de areia. Para uma melhor compreensão da importância da criticalidade auto-organizada, apresentamos vários outros exemplos de onde o fenômeno é observado. No quarto capítulo apresentamos o modelo de relógio quiral de p-estados que será nosso sistema de testes. No caso unidimensional, determinamos a matriz de transferência e utilizamos o teorema de Perron-Frobenius para provar a inexistência de transição de fase a temperaturas finitas a temperaturas finitas. Esboçamos os diagramas de fases dos estados fundamentais que obtivemos de maneira analítica e numérica para os casos de p = 2, 3, 4, 5 e 6, no caso numérico fazendo uso do algoritmo de Bak-Sneppen com sorteio (BSS). Apresentamos ainda um breve estudo do número de mínimos locais para o modelo de relógio quiral de p-estados, para os casos de p = 3 e 4. Por último, no quinto capítulo, propomos uma dinâmica Bak-Sneppen com ruído (BSR) como uma nova técnica de otimização para tratar sistemas discretos. O ruído é introduzido diretamente no espaço de configuração de spins. Conseqüentemente, o fitness (adaptabilidade) passa a assumir valores contínuos, num pequeno intervalo em torno do seu valor original (discreto). Os resultados dessa dinâmica indicam a presença de criticalidade auto-organizada, evidenciada pelo decaimento em leis de potências das correlações espacial e temporal. Também estudamos o método EO e obtivemos uma confirmação numérica de que sua dinâmica exibe um comportamento não crítico com alcance espacial infinito e decaimento exponencial das avalanches. Finalmente, para o modelo de relógio quiral, comparamos a eficiência das três dinâmicas (EO, BSS e BSR) no que tange às suas habilidades de encontrar o estado fundamental do sistema. / In order to understand how things work, man has formulated scientific theories. New methods and techniques have been created not only to increase our understanding on the subject but also to develop and even expand those theories. In this thesis, we study several techniques (here called algorithms) designed with the objective to get the ground states of some spin systems and eventually to reveal possible properties of critical self-organization. In the second chapter, we introduce four fundamental optimization algorithms: simulated annealing, genetics algorithms, extremal optimization (EO) and Bak-Sneppen (BS). In the third chapter we present the concept of self-organized criticality (SOC), using as an example the sandpile model. To understand the importance of the self-organized criticality, we show many other situations where the phenomenon can be observed. In the fourth chapter, we introduce the p-states chiral clock model. This will be our test or toy system. For the one-dimensional case, we first determined the corresponding transfer-matrix and then proved the nonexistence of phase transitions by using the Perron-Frobenius theorem. We calculate the ground state phase diagrams both analytically and numerically in the cases of p = 2, 3, 4, 5 and 6. We also present a brief study of the number of local minima for the cases p = 3 and 4 of the chiral clock model. Finally, in the fifth chapter, we propose a Bak-Sneppen dynamics with noise (BSN) as a new technique of optimization to treat discrete systems. The noise is directly introduced into the spin configuration space. Consequently, the fitness now take values in a continuum but small interval around its original value (discrete). The results of this dynamics indicate the presence of self-organized criticality, which becomes evident with the power law scaling of the spacial and temporal correlations. We also study the EO algorithm and found a numerical con_rmation that it does not show a critical behavior since it has an in_nite space range and an exponential decay of the avalanches. At the end, we compare the e_ciency of the three dynamics (EO, BSD and BSN) for the chiral clock model, concerning their abilities to _nd the system\'s ground state.

Melanoma cutâneo ainda constitui a principal causa de morte por câncer de pele nos países desenvolvidos. A variabilidade do comportamento clínico dessa neoplasia tem sido apenas parcialmente explicada pelos aspectos clínicos e histológicos, e a identificação de variáveis biológicas pode vir a ser importante na determinação de grupos de risco específicos. Foram estudados 69 pacientes com melanoma cutâneo primário de diversos graus de gravidade, tratados entre 1990 e 2007, com o intuito de verificar aspectos clínicos e epidemiológicos, preparar Tissue microarray (TMA) para estudo dos melanomas cutâneos primários com espessura maior que 1,0 mm, avaliar por análise imuno-histoquímica a expressão das proteínas da apoptose celular Bcl2, Bax, Bak, Apaf-1, Caspase 3, Caspase 9, Caspase 8, FasL e Fas em nevos-controle e em melanomas primários com espessuras menores e maiores que 1mm, e correlacionar a expressão dessas proteínas da apoptose com a evolução de melanomas cutâneos primários. Os resultados ratificaram tanto dados epidemiológicos já publicados em relação a sexo, idade e local da lesão, quanto a correlação entre a evolução da doença e os índices de Breslow. A análise dos escores compostos relativos à expressão das proteínas da apoptose revelou que o perfil imuno-histoquímico dessas proteínas parece não ter significado prognóstico, uma vez que não houve diferenças de expressão entre pacientes com e sem doença disseminada. Não foram encontradas alterações na expressão das proteínas da apoptose estudadas que pudessem sugerir o seu envolvimento tanto na gênese quanto na progressão de melanoma primário. O perfil imuno-histoquímico com tendência pró-apoptótica parece indicar que outros fatores seriam responsáveis pelo crescimento e disseminação da neoplasia / Cutaneous melanoma still constitutes the main cause of skin cancer death in developed world. Clinical behavior variability of this neoplasia has been only partially explained by clinical and histological aspects, and identification of biological variables can be important for determining specific risk groups. Sixty nine (69) patients with mild to severe primary cutaneous melanoma treated in 1990-2007 were studied aiming at (a) verifying clinical epidemiological aspects, (b) generating a Tissue microarray (TMA) for characterizing proteins expression of cutaneous melanoma > 1.0 mm, (c) analyzing the immunohistochemical expression of the apoptosis proteins Bcl2, Bax, Bak, Apaf-1, Caspase 3, Caspase 9, Caspase 8, FasL e Fas in 10 control nevi and in primary melanomas with thickness 1mm, (d) and correlating these proteins expression with the disease prognosis. Results have ratified known epidemiological date on gender, age and lesion localization as well as the correlation between the disease prognosis and the Breslow\'s indexes. Analysis of the composite scores relating to apoptosis proteins has revealed that their immunohistochemical profile seems to be not significant for determining the disease prognosis, since no differences in proteins expression were found when compared patients with and without disease dissemination. Alterations in proteins expression suggesting their role in the genesis as well as in the prognosis of primary melanoma were not evidenced. Immunohistochemical profile with pro-apoptosis trend seems to indicate other factor as responsible for the neoplasia growth and dissemination