No description available.

The strategic air offensive against Germany during World War II formed a major part of Britain�s wartime military effort and it has subsequently attracted the attention of historians. Despite the attention, historians have paid little attention to the impact of the strategic air offensive on Britain. This thesis attempts to redress this situation by providing an examination of the economic impact on Britain of the offensive. The work puts the economic cost of the offensive into its historical context by describing the strategic air offensive and its intellectual underpinnings. Following this preliminary step, the economic costs are described and quantified across a range of activities using accrual accounting methods. The areas of activity examined include the expansion of the aircraft industry, the cost of individual aircraft types, the cost of constructing airfields, the manufacture and delivery of armaments, petrol and oil, and the recruitment, training and maintenance of the necessary manpower. The findings are that the strategic air offensive cost Britain �2.78 billion, equating to an average cost of �2,911.00 for every operational sortie flown by Bomber Command or �5,914.00 for every Germany civilian killed by aerial bombing. The conclusion reached is the damage inflicted upon Germany by the strategic air offensive imposed a very heavy financial burden on Britain that she could not afford and this burden was a major contributor to Britain�s post-war impoverishment.

No description available.

Durch Phosphorylierung inaktiviert GRK2 kardiale ß-Adrenorezeptoren und vermindert dadurch die Kontraktilität von neonatalen Rattenkardiomyozyten. Als natürlicher Inhibitor der GRK2 beeinflusst RKIP die Signalweiterleitung bei Stimulation von ß-Adrenorezeptoren. In dieser Arbeit konnte gezeigt werden, dass eine Überexpression von RKIP die Kontraktilität von neonatalen Rattenkardiomyozyten erhöht. Es wurde die Anzahl auftretender Spontankontraktionen vor und nach Stimulation mit Isoproterenol erfasst sowie eine zeitliche Analyse der Calciumfreisetzung und –aufnahme nach elektrischer Stimulation durchgeführt. Im unstimulierten Zustand zeigten neonatale Rattenkardiomyozyten, die Wildtyp-RKIP überexprimierten, verglichen mit der Kontrollgruppe, keine signifikanten Unterschiede hinsichtlich auftretender Spontankontraktionen. Nach Stimulation mit Isoproterenol zeigten neonatale Rattenkardiomyozyten, in denen Wildtyp-RKIP überexprimiert wurde, eine signifikant höhere Anzahl auftretender Spontankontraktionen. Eine Analyse der Calciumtransienten zeigte bei RKIP-Wildtyp überexprimierenden neonatalen Rattenkardiomyozyten eine erhöhte Calciumfreisetzung während der Systole sowie eine beschleunigte Calciumwiederaufnahme während der Diastole. Zudem wurden die RKIP-Mutanten RKIPS51V und RKIPS52V im Hinblick auf ihre Kontraktilität untersucht. Neonatale Rattenkardiomyozyten welche RKIPS51V und RKIPS52V überexprimierten zeigten weder im Hinblick auf auftretende Spontankontraktionen noch bei der Analyse der Calciumtransienten signifikante Unterschiede zur Kontrollgruppe. Da auch eine Phosphorylierung an Aminosäureposition 51 bzw. Aminosäureposition 52 ohne direkte Auswirkung auf die Kontraktilität möglich ist, wurde in einem in vitro Kinase Assay analysiert, ob neben der bekannten Phosphorylierungsstelle S153 eine weitere Phosphorylierung von RKIP durch PKA oder PKC erfolgt. Bei Einsatz der an Aminosäureposition 153 phosphorylierungsdefizienten RKIP Mutante RKIPS153A konnte keine Phosphorylierung beobachtet werden. In der vorliegenden Arbeit konnte neben einer Phosphorylierung an S153 keine weitere Phosphorylierung von RKIP durch PKC oder PKA beobachtet werden. / By phosphorylation, GRK2 inactivates cardiac ß-adrenoreceptors and thereby reduces the contractility of neonatal rat cardiomyocytes. As a natural inhibitor of GRK2, RKIP influences cell signaling when ß-adrenoreceptors are stimulated. The presented research shows that an overexpression of RKIP increases the contractility of neonatal rat cardiomyocytes. The number of spontaneous contractions occurring before and after stimulation with isoproterenol was recorded and a temporal analysis of calcium release and uptake after electrical stimulation was performed. In the unstimulated state, neonatal rat cardiomyocytes which overexpressed wild-type RKIP showed no significant differences in terms of spontaneous contractions compared with the control group. After stimulation with isoproterenol, neonatal rat cardiomyocytes in which wild-type RKIP was overexpressed showed a significantly higher number of occurring spontaneous contractions. Neonatal rat cardiomyocytes overexpressing wild-type RKIP showed an increased calcium release during systole and an accelerated calcium reuptake during diastole. The RKIP mutants RKIPS51V and RKIPS52V were examined regarding their contractility. Neonatal rat cardiomyocytes which overexpressed RKIPS51V and RKIPS52V showed no significant differences compared to the control group in terms of spontaneous contractions or calcium cycling. Since phosphorylation at amino acid position 51 or amino acid position 52 could also be possible without direct effect on contractility, an in vitro kinase assay focusing on PKA and PKC was performed. In the presented work, apart from phosphorylation at S153, no further phosphorylation of RKIP by PKC or PKA could be observed.

Primary sensory axons fail to regenerate into the spinal cord following dorsal root injury leading to permanent sensory deficits. Re-entry is prevented at the dorsal root entry zone (DREZ), the CNS-PNS interface. Current approaches for promoting DR regeneration across the DREZ have had some success, but sustained, long-distance regeneration, particularly of large-diameter myelinated axons, still remains a formidable challenge. Our lab has previously shown that induced expression of constitutively active B-RAF (kaBRAF) enhanced the regenerative competence of injured DRG neurons in adult mice. In this study, I investigated whether robust intraspinal regeneration can be achieved by selective expression of kaBRAF alone or in combination with deletion of the myelin-associated inhibitors or neuron-intrinsic growth suppressors (PTEN or SOCS3). To this end, I used LSL-kaBRAF: brn3a-CreERT2 transgenic mice in which kaBRAF can be induced selectively in sensory neurons. I have also bred LSL-kaBRAF: brn3a-CreERT2 mice with triple knock-out mice lacking Nogo, Mag and OMgp or mouse lines carrying floxed alleles of PTEN or SOCS3. Single, double, and triple conditional mice were subjected to cervical DR crush and AAV2-eGFP vectors were used to selectively label regenerating axons of large-diameter neurons. I compared the extent of regeneration at 3 weeks or 2 months after DR injury using conventional anatomical and behavioral analyses. I found that kaBRAF alone promoted axon regeneration across the DREZ but did not produce significant functional recovery by two months. Supplementary deletion of Nogo, MAG, and OMgp did not improve kaBRAF-induced regeneration. Deletion of PTEN or SOCS3 individually or in combination failed to promote axon regeneration across the DREZ. In marked contrast, simultaneous deletion of PTEN, but not SOCS3, dramatically enhanced kaBRAF-mediated regeneration enabling many more axons to penetrate the DREZ and grow deep into the spinal cord. This study shows that dual activation of BRAF-MEK-ERK and PI3K-Akt signaling is an effective strategy to stimulate robust intraspinal DR regeneration and may lead to recovery of sensory function after DR injury. / Biomedical Sciences

A via RAS/RAF/MEK/ERK é frequentemente hiperativada em diversos tumores. Em leucemias sua ativação pode ocorrer, dentre outros mecanismos, a partir de mutações pontuais nos genes da família RAS, que são relevantes nas leucemias linfóide e mielóide agudas (LLA e LMA), ou a partir da atividade da tirosina-quinase BCR-ABL, que é responsável por promover a tumorigênese na leucemia mielóide crônica (LMC) e em alguns casos de LLA. A hiperativação dessa via estimula a proliferação celular e, consequentemente, a produção de espécies reativas de oxigênio (ROS), que é um dos principais mecanismos envolvidos com a indução de senescência celular em tumores. Assim sendo, as células tumorais que apresentam o gene RAS mutado são criticamente dependentes de mecanismos de feedback para regular a ativação da via. Jang et al. demonstraram que a ubiquitina-ligase HUWE1 atua em um mecanismo de feedback negativo que controla a ativação de ERK1/2 e apesar de amplamente estudada no contexto da tumorigênese, a atuação dessa molécula em eventos relacionados à leucemogênese ainda não foi descrita. No presente estudo, linhagens celulares leucêmicas e células tronco e progenitoras hematopoiéticas humanas (HSPCs) com mutação KRASG12V foram transduzidas com partículas lentivirais miR-E para o silenciamento gênico de HUWE1. Ensaios de proliferação celular, apoptose, análise do ciclo celular, produção de ROS e análise da expressão gênica e proteica foram realizados nas linhagens celulares; análise do crescimento cumulativo, área de formação de cobblestones, capacidade clonogênica e análise do perfil de diferenciação celular foram realizados nas HSPCs. Nas linhagens celulares observouse que o silenciamento de HUWE1 reduziu a capacidade proliferativa das linhagens Nalm-6, K562 e THP-1, porém não causou nenhum prejuízo à capacidade proliferativa da linhagem HL-60. Além disso, causou a redução da produção de ROS (p<0,05), associada à redução das taxas de apoptose (p<0,01), principalmente na linhagem K562, na qual também promoveu a ativação de ERK1/2 . Em HSPCs, observou-se a redução da capacidade proliferativa das culturas que expressavam o oncogene KRASG12V associado ao silenciamento de HUWE1. Nas mesmas condições foi observada uma drástica redução na capacidade clonogênica das HSPCs (p<0,001), em especial as do tipo BFU-E. O silenciamento de HUWE1 também alterou o perfil de diferenciação celular para a linhagem monocítica. Os resultados sugerem que HUWE1 pode participar do processo de leucemogênese e diferenciação de HSPCs humanas participando na modulação da via RAS/RAF/MEK/ERK. / The RAS/RAF/MEK/ERK pathway is frequently hyperactivated in several tumors. In leukemia, this activation can arise, among other mechanisms, from point mutations in the RAS genes, which are important in acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML), or from chromosomal translocations such as the BCR-ABL gene, which is a driver mutation in chronic myeloid leukemia (CML) and some cases of ALL. The hyperactivation of this pathway stimulates cell proliferation and, consequently, the production of reactive oxygen species (ROS), which is one of the main mechanisms involved with induction of cellular senescence in tumors. Thus, tumor cells that harbor the mutated RAS gene are critically dependent on feedback mechanisms to regulate pathway activation. Jang et al. demonstrated that the ubiquitinligase HUWE1 acts on a negative feedback mechanism that controls the activation of ERK1/2. Although widely studied in the context of tumorigenesis, the role of this molecule in events related to leukemogenesis has not yet been described. In this study, leukemia cell lines and human hematopoietic stem and progenitors cells (HSPCs) with KRASG12V mutation were transduced with miR-E lentiviral particles for HUWE1 knockdown. Cell proliferation, apoptosis, cell cycle analysis, ROS production and analysis of gene and protein expression were performed in cell lines; cumulative growth analysis, cobblestones area formations, clonogenic capacity and differentiation profile analysis were performed in HSPCs. In cell lines, it was observed that HUWE1 knockdown reduced the proliferative capacity of Nalm-6, K562 and THP-1, but not of HL-60. Besides that, it caused a reduction in ROS production (p<0,05), associated with reduction of apoptosis rates (p<0,01), especially in K562 in which it also promoted activation of ERK1/2. In HSPCs, a reduction of the proliferative capacity was observed in cultures expressing KRASG12V in combination with HUWE1 knockdown. In the same conditions, a drastic reduction of clonogenic capacity (p<0,001), especially of BFU-E colonies, was observed. HUWE1 knockdown also changed differentiation profile to the monocytic lineage. Results suggest that HUWE1 might play a role in leukemogenesis process and differentiation of human HSPCs, acting in the modulation of RAS/RAF/MEK/ERK.

A via RAS/RAF/MEK/ERK é frequentemente hiperativada em diversos tumores. Em leucemias sua ativação pode ocorrer, dentre outros mecanismos, a partir de mutações pontuais nos genes da família RAS, que são relevantes nas leucemias linfóide e mielóide agudas (LLA e LMA), ou a partir da atividade da tirosina-quinase BCR-ABL, que é responsável por promover a tumorigênese na leucemia mielóide crônica (LMC) e em alguns casos de LLA. A hiperativação dessa via estimula a proliferação celular e, consequentemente, a produção de espécies reativas de oxigênio (ROS), que é um dos principais mecanismos envolvidos com a indução de senescência celular em tumores. Assim sendo, as células tumorais que apresentam o gene RAS mutado são criticamente dependentes de mecanismos de feedback para regular a ativação da via. Jang et al. demonstraram que a ubiquitina-ligase HUWE1 atua em um mecanismo de feedback negativo que controla a ativação de ERK1/2 e apesar de amplamente estudada no contexto da tumorigênese, a atuação dessa molécula em eventos relacionados à leucemogênese ainda não foi descrita. No presente estudo, linhagens celulares leucêmicas e células tronco e progenitoras hematopoiéticas humanas (HSPCs) com mutação KRASG12V foram transduzidas com partículas lentivirais miR-E para o silenciamento gênico de HUWE1. Ensaios de proliferação celular, apoptose, análise do ciclo celular, produção de ROS e análise da expressão gênica e proteica foram realizados nas linhagens celulares; análise do crescimento cumulativo, área de formação de cobblestones, capacidade clonogênica e análise do perfil de diferenciação celular foram realizados nas HSPCs. Nas linhagens celulares observouse que o silenciamento de HUWE1 reduziu a capacidade proliferativa das linhagens Nalm-6, K562 e THP-1, porém não causou nenhum prejuízo à capacidade proliferativa da linhagem HL-60. Além disso, causou a redução da produção de ROS (p<0,05), associada à redução das taxas de apoptose (p<0,01), principalmente na linhagem K562, na qual também promoveu a ativação de ERK1/2 . Em HSPCs, observou-se a redução da capacidade proliferativa das culturas que expressavam o oncogene KRASG12V associado ao silenciamento de HUWE1. Nas mesmas condições foi observada uma drástica redução na capacidade clonogênica das HSPCs (p<0,001), em especial as do tipo BFU-E. O silenciamento de HUWE1 também alterou o perfil de diferenciação celular para a linhagem monocítica. Os resultados sugerem que HUWE1 pode participar do processo de leucemogênese e diferenciação de HSPCs humanas participando na modulação da via RAS/RAF/MEK/ERK. / The RAS/RAF/MEK/ERK pathway is frequently hyperactivated in several tumors. In leukemia, this activation can arise, among other mechanisms, from point mutations in the RAS genes, which are important in acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML), or from chromosomal translocations such as the BCR-ABL gene, which is a driver mutation in chronic myeloid leukemia (CML) and some cases of ALL. The hyperactivation of this pathway stimulates cell proliferation and, consequently, the production of reactive oxygen species (ROS), which is one of the main mechanisms involved with induction of cellular senescence in tumors. Thus, tumor cells that harbor the mutated RAS gene are critically dependent on feedback mechanisms to regulate pathway activation. Jang et al. demonstrated that the ubiquitinligase HUWE1 acts on a negative feedback mechanism that controls the activation of ERK1/2. Although widely studied in the context of tumorigenesis, the role of this molecule in events related to leukemogenesis has not yet been described. In this study, leukemia cell lines and human hematopoietic stem and progenitors cells (HSPCs) with KRASG12V mutation were transduced with miR-E lentiviral particles for HUWE1 knockdown. Cell proliferation, apoptosis, cell cycle analysis, ROS production and analysis of gene and protein expression were performed in cell lines; cumulative growth analysis, cobblestones area formations, clonogenic capacity and differentiation profile analysis were performed in HSPCs. In cell lines, it was observed that HUWE1 knockdown reduced the proliferative capacity of Nalm-6, K562 and THP-1, but not of HL-60. Besides that, it caused a reduction in ROS production (p<0,05), associated with reduction of apoptosis rates (p<0,01), especially in K562 in which it also promoted activation of ERK1/2. In HSPCs, a reduction of the proliferative capacity was observed in cultures expressing KRASG12V in combination with HUWE1 knockdown. In the same conditions, a drastic reduction of clonogenic capacity (p<0,001), especially of BFU-E colonies, was observed. HUWE1 knockdown also changed differentiation profile to the monocytic lineage. Results suggest that HUWE1 might play a role in leukemogenesis process and differentiation of human HSPCs, acting in the modulation of RAS/RAF/MEK/ERK.

Made available in DSpace on 2014-06-11T19:32:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-12-22Bitstream added on 2014-06-13T20:44:20Z : No. of bitstreams: 1 miranda_et_dr_arafcf.pdf: 641942 bytes, checksum: 8d27d1b81ac16fe68d939f32e284f53f (MD5) / Universidade Estadual Paulista (UNESP) / Neste trabalho foi realizado um estudo comparativo entre isolados de Pb18 e Pb265, que têm capacidades distintas de adesão às células Hela e Vero, sob influência da temperatura e diversos fatores químicos. Foram também avaliados eventos em células de epitélio pulmonar expostas à gp 43 e células de Pb18, antes e após inoculação animal, representando, respectivamente, isolados menos e mais virulentos. Os resultados mostram que as adesinas fúngicas são termo-lábeis, sugerindo sua natureza protéica. Os açúcares aminados glucosamina e galactosamina foram os mais eficientes para inibir a adesão celular, em relação à manose, glicose e galactose, indicando que esta atividade envolve mecanismos específicos tipo lectina. O estudo com componente da matriz extracelular mostrou que a laminina, assim como seus derivados sintéticos, inibiu a adesão do isolado Pb18, fato não verificado com Pb265, tanto com células Hela, quanto com a linhagem Vero, mas variável sob influência de fatores químicos. As distintas vias de sinalização foram demonstradas pelos eventos Ras-Raf, Rho e AKT verificados, sendo que o isolado menos virulento causou menos estresse citotóxico, comprovado por menor sinal Ras- Raf e AKT de proliferação. Os sinais intensos de proliferação observados nos experimentos com o isolado mais virulento e exposição à gp 43 poderiam ser associados à maior sobrevida do fungo que se internaliza mais facilmente nas células do hospedeiro, dificultando o seu reconhecimento por células do sistema monocítico-fagocitário, antes de causar apoptose, evadir e disseminar-se. A ativação das vias de sobrevida, associada a sinais citosólicos quando o Pb entra na célula epitelial, foi demonstrada de modo inédito neste trabalho. / In this work it was accomplished a comparative study between isolates Pb18 and Pb265, which have distinct capacities of adhesion to the cells Hela and Vero under influence of temperature and several chemical factors. Events in pulmonary epithelial cells exposed to gp 43 and in Pb18 cells, before and after animal inoculation, representing, respectively, isolates less and more virulent were evaluated as well. The results show that the fungal adhesins are term-labels, suggesting its proteical nature. The aminated sugars glucosamine and galactosamine were the most efficient, in comparison with manose, glycose and galactose, in inhibiting the cellular adhesion, indicating that this activity involves specific mechanisms lectin-type. The study with extracellular matrix component indicated that the laminin, as well as its synthetic derivatives, inhibited the adhesion of the isolate Pb18 to the cells Vero and Hela, what did not occur with Pb265, but it was variable under influence of chemical factors. The distinct signaling pathways were demonstrated by the Ras-Raf, Rho and AKT events, considering that the less virulent isolate caused minor cytotoxic stress, proved by minor Ras-Raf and AKT proliferation signals. The intense proliferation signals observed in the experiments with more virulent isolate and exposition to gp 43 could be associated to larger time of survival of the fungus that more easily goes inside the host cells, making it difficult to the monocyte-macrophage system cells to recognize it before the apoptosis, the evasion and the dissemination. The Ras-Raf and AKT pathways acted synergetically with the effects of the cell survival. The decrease of the AKT event implied partial loss of the survival signal that intensified, following and in a opposite way, with Ras-Raf decrease. The activation of the survival pathways, associated to citosolic signals when Pb goes inside the epithelial cell, was for the first time demonstrated in this work.

La polyarthrite rhumatoïde (PR) est le rhumatisme inflammatoire chronique le plus fréquent. La PR est une maladie génétique où il existe plusieurs allèles de susceptibilité HLA-DRB1. Les auto-anticorps anti-protéines citrullinées sont les plus spécifiques de la PR. Ils sont détectés par les tests anti-peptides cycliques citrullinés (anti-CCP). 1/L’objectif de notre premier travail était de montrer l’influence des allèles susceptibilité HLA-DR sur la présence d’anti-CCP dans notre population marseillaise de PR. Nous avons montré que les allèles de susceptibilité HLA-DR ne sont pas nécessaires à la présence des anticorps anti-CCP. Nous avons mis en évidence une association entre l’allèle HLA-DRB1*04:04 et la présence des anti-CCP.2/Environ un tiers des patients présentant une PR n’ont pas d’anticorps anti-CCP. Nous avons donc recherché des nouveaux auto-anticorps pour le diagnostic de la maladie.Les auto-anticorps dirigés contre le domaine catalytique de la protéine B-Raf (v raf murine sarcoma viral oncogen homologue B1) ont été identifiés par la technique des puces à protéines chez les patients PR. B-Raf est une sérine-thréonine kinase qui est impliquée dans la voie des MAP-kinases. Nous avons montré que les auto-anticorps anti-B-Raf activent B-Raf. Nous avons montré que le peptide p25 de B-Raf est spécifiquement reconnu par les auto-anticorps des PR. Les auto-anticorps anti-p25 identifient 21% des patients PR sans anticorps anti-CCP.3/En utilisant des puces à protéines, nous avons identifié 24 nouveaux auto-antigènes associés aux PR débutantes. Quatre de ces auto-antigènes ont été validés par ELISA : GABA(A) receptor associated protein like, zinc finger protein 706, tropomyosin 2 et WIBG (within BGCN homolog (Drosophila)). Les auto-anticorps anti-WIBG identifient exclusivement les PR.Ces nouveaux auto-antigènes pourront être utilisés dans le diagnostic des PR débutantes et des PR sans anticorps anti-CCP. / Rheumatoid arthritis (RA) is a chronic inflammatory disease with a prevalence of 0.5% wordwilde. HLA-DR genes are the strongest genetic prevalence in RA. The sera of RA patients contain many auto-antibodies. The most characteristic are directed at citrullinated proteins (ACPA). ACPA can be detected by commercially available enzyme-linked immune-absorbent assays using synthetic cyclic citrullinated peptides (CCP).1/In the first work we tested whether the presence of RA associated HLA-DRB1 alleles individually influences anti-CCP production in a population of RA from Marseille. We showed RA associated HLA-DR alleles are not mandatory for the production of anti-CCP. HLA-DRB1*04:04 was the most strongly associated with the presence of anti-CCP in RA sera. 2/ Anti-CCP antibodies are detected in 65% of RA patients. We wanted to detect new auto-antibodies for the diagnosis of RA.By screening protein arrays we found that B-Raf (v raf murine sarcoma viral oncogen homologue B1) is a major non-citrullinated auto-antigen recognized by 35% of RA patients’sera. B-Raf encodes a serine threonine-kinase involved in the MAPK signaling pathway. We showed that anti-B-Raf auto-antibodies activate the in vitro phosphorylation of MEK1 mediated by B-Raf.We found that one peptide of B-Raf, p25, is specifically recognized by auto-antibodies from RA patients. Of interest, anti-p25 auto-antibodies are detected in 21% of anti-CCP negative RA patients.3/We identified 24 new auto-antigens associated with RA patients with disease duration less than one year using 8000 human protein arrays. We identified four auto-antigens recognized almost uniquely by sera of early RA patients: GABA(A) receptor associated protein like, zinc finger protein 706, tropomyosin 2 and WIBG (within BGCN homolog (Drosophila)). These reactivities were confirmed by ELISA on purified proteins. Auto-antibodies to anti-WIBG identify exclusively RA patients’sera. These new auto-antigens could be used for the diagnosis of anti-CCP negative RA patients and in early RA.

Muitos pacientes submetidos à tireoidectomia por Carcinoma Papilífero da Tireoide (CPT) têm doença linfonodal subclínica no momento da cirurgia. A mutação BRAF T17799A (V600E) é um evento comum no CPT e alguns estudos demonstram correlação entre a mutação e características de maior agressividade tumoral, incluindo a presença de metástases linfonodais. O esvaziamento eletivo do compartimento central ganha aceitação, uma vez que alguns estudos evidenciam que a presença de metástases linfonodais aumenta o risco de recidiva e mortalidade. Devido ao grande potencial de complicações do esvaziamento do compartimento central, o objetivo deste trabalho foi avaliar a associação entre a presença da mutação BRAF T17799A (V600E), a presença de metástases linfonodais e fatores clínicos e histopatológicos de pior prognóstico. Métodos: 51 casos consecutivos de pacientes com CPT foram submetidos à tireoidectomia total e ao esvaziamento eletivo ou terapêutico do compartimento central. Em todos os pacientes foi pesquisada a mutação BRAF T17799A (V600E) no tecido tireoidiano com Carcinoma Papilífero de Tireoide. Resultados: Cinquenta e quatro por cento (54,9%) dos pacientes apresentaram metástases linfonodais. Seis pacientes apresentaram metástases laterais confirmadas por punção aspirativa por agulha fina no pré-operatório e 22 pacientes (43%) apresentaram metástases não detectadas no pré ou no intra operatório A mutação BRAF T17799A (V600E) foi encontrada em 15 pacientes portadores de CPT (29,4%). A presença da mutação não teve associação estatisticamente significante para sexo, idade, tamanho do tumor, extensão extratireoidiana, multicentricidade, embolização angiolinfática e metástases linfonodais. As metástases linfonodais se associaram à multifocalidade (p = 0,005) e invasão angiolinfática (p = 0,003) na análise univariada. Conclusão: A presença da mutação BRAF T17799A (V600E) não se associou à metástases linfonodais em nosso estudo. A multifocalidade e a detecção de invasão angiolinfática no CPT foram os fatores mais importantes na predição de metástases linfonodais / Background: Many patients undergoing thyroidectomy for Papillary Thyroid Carcinoma (PTC) have subclinical node disease at the time of surgery. The BRAF T17799A (V600E) mutation is a common event in PTC and some studies have demonstrated a correlation between the mutation and aggressive characteristics including lymph node metastasis. Prophylactic Central Node Dissection (CND) is gaining acceptance in the treatment of PTC as studies have shown nodal disease increases local recurrence and may alter mortality. Given the potential complications of CND, the aim of this study was to determine the correlation among BRAF mutation, lymph node metastasis and clinical and histopathological factors of worse prognosis. Methods: A total of 51 consecutive cases of patients with PTC underwent total thyroidectomy and routine prophylactic (CND) or therapeutic neck dissection when metastases were found. All patients were tested for the BRAF mutation. Results: Overall, positive lymph nodes were found in Fifty four per cent9% of patients. Six patients had lateral metastases confirmed by fine needle aspirative cytology and 22 patients (43%) had occult metastases. The BRAF mutation was found in 15 patients (29.4%). BRAF was not correlated with sex, age, size of tumor, multifocality, extrathyroid extension or lymph node metastases. Lymph node metastases were correlated with multifocality (p = 0.005) and angiolymphatic invasion (p = 0.003) in univariate. Conclusions: The BRAF mutation was not correlated with lymph node metastases in our study. Multifocality and angiolymphatic invasion were important factors for predicting lymph node metastases