Allan Rodrigues Silva

Association of adult mastocytosis with M541L in the transmembrane domain of KIT

Editor Mastocytosis is a disorder characterized by mast cell (MC) proliferation and accumulation within various organs, most commonly the skin. Multiple KIT mutations have been reported in patients with adult mastocytosis, but the potential association of specific KIT mutations with specific subtypes of mastocytosis remains to be clarified. We present the case of a 32-year-old caucasian woman who came to the Dermatology Department complaining of a 12-year history of multiple, generalized and reddish-brown macules and papules with positive Darier’s sign. These lesions were more numerous in the trunk and limbs, and absent from face, palms and soles. She had no systemic symptoms and physical examination was unremarkable. Skin biopsy showed MC infiltrates in the dermis (Fig. 1), confirming the diagnosis of cutaneous mastocytosis. Full blood count, white blood cell differential and routine serum biochemistry tests were within normal range. Serum tryptase level was 17.9 ng ⁄ mL (normal: 0.1–11.4 ng ⁄ mL). The patient had a 46,XX karyotype. Abdominal ultrasound, PET scan and bone densitometry were all normal. Complete bone marrow study showed normal percentage of bone marrow MCs (BMMCs) (0.04%) which showed aberrant coexpression of CD25+, CD2+ and also CD33+, CD35+, CD45+, CD63+, CD69+ and CD59+. Analysis of coding exons 8, 9, 10, 11 and 17 of the KIT gene revealed the presence of a heterozygous substitution in exon 10, resulting in the substitution of leucine for methionine at codon 541 (M541L) (Fig. 2). The sequencing of KIT exon 10, using DNA extracted from oral mucosa cells, confirmed that this was a germline mutation. Human KIT is a protooncogene located at chromosome 4q12 that contains 21 exons, which encode a transmembrane receptor (kit) with tyrosine kinase (TK) activity. Binding of kit ligand stem cell factor (SCF) to kit receptor is known to activate kit TK, which results in different biological effects depending on the activated cell. In MCs, these effects include, among others, cell proliferation and suppression of apoptosis. Mutations of KIT are considered to play a key role in the pathogenesis of mastocytosis. Most frequently, KIT mutations occur at exon 11 and 17, resulting in aminoacid changes at the juxtamembrane and TK domain of kit respectively. Furitsu et al. showed that point mutations in KIT (Asp816Val and Val560Asp) are capable of inducing constitutive activation of kit. Multiple other activating KIT mutations have been reported in patients with adult mastocytosis, but few are described in the transmembrane domain of KIT, encoded by exon 10. In our patient, we detected a heterozygous substitution (germline mutation) in exon 10, resulting in the substitution of leucine for methionine at codon 541 (M541L). This mutation was described in general population, in a family with piebaldism and in two unrelated pairs of apparently identical twin children with mastocytosis. To the best of our knowledge, however, this is the first time it is reported in an adult patient with mastocytosis. According to Foster et al., cells expressing M541L displayed a significantly heightened response to low levels of SCF, suggesting that these cells may have a proliferative and ⁄ or survival advantage. Although our patient had elevated serum tryptase levels, coexpression of both CD2 and CD25 by BMMCs and a KIT Figure 2 Analysis of coding exons 8, 9, 10, 11 and 17 of the KIT gene revealed the presence of a heterozygous substitution in exon 10, resulting in the substitution of leucine for methionine at codon 541 (M541L).

MONTHLY HYDRIC BALANCE FOR TWO MUNICIPALITIES OF PARAÍBA STATE

This research aimed to analyze the monthly behavior of the Water Balance Climatological (WBC) in two different cities of Paraíba (PB): one in the city of Alhandra, located on the seafront of the PB state and the other located in the municipality of Prata. The methodology used for calculating the WBC was proposed by Thornthwaite and Matter (1957) with modifications Krishnan (1980). The results showed that the rainy season is concentrated in the months (May-July) in Alhanbra and Prata municipality in months (February to April) corresponding to about 50% of the annual total. Regarding the WBC, the results showed limitations of water resources, especially in the municipality of Prata. It was found that this city had nine months of drought. Thus affecting adversely the development of crops. Thus indicating that the Silver municipality will be insufficient to meet the basic needs of the soil, vegetation and society. Key-words: Variability, drought, water resources, water demand.

Clima e Doenças: Análise dos Elementos Meteorológicos e Infecções Respiratórias Agudas nas Capitais do Nordeste Brasileiro (Climate and Diseases: Analysis of Elements Meteorological and Respiratory Infections Acute in the Capitals of Northeast of Brazil)

Estudos demonstram que o clima influencia de forma tambem danosa ao meio ambiente, bem como manifestacao de determinados agravos a saude. Procurou-se analisar as capitais do Nordeste Brasileiro. O objetivo deste estudo e detectar possiveis associacoes entre as infeccoes respiratorias agudas em criancas e o clima nas capitais. Utilizaram-se dados mensais do Sistema Unico de Saude – SUS de internacoes por infeccoes agudas do sistema respiratorio; dados mensais de variaveis meteorologicas (temperatura do ar, umidade relativa do ar, Precipitacao pluvial acumulada), disponibilizados pelo Instituto Nacional de Meteorologia, no periodo de 2000 a 2011. Foi utilizado o modelo marginal das Equacoes de Estimacoes Generalizadas, a fim de obter estimativas confiaveis para as variaveis, levando em consideracao os dados de contagem e uma estrutura de correlacao para detectar associacoes entre os indicadores climaticos e os numeros de internacoes. Os resultados constatam que Fortaleza apresentou o maior numero de casos, totalizando 72.670 internacoes. Constatando tambem associacoes significativas, do numero de internacoes de criancas, com a temperatura e a umidade relativa do ar (ambos os valores-p<0,001) na cidade do Recife-PE. Em Fortaleza-CE e Natal-RN as associacoes significativas, entre numero de internacoes de criancas foram captadas apenas com a temperatura (ambos os valores-p<0,001). Salvador-BA e Teresinha-PI mostraram associacoes significativas com a umidade relativa do ar (valor-p=0,019 e 0,033 respectivamente). Aracaju-SE, Joao Pessoa-PB e Sao Luis-MA as associacoes significativas ocorreram apenas com a precipitacao (valor-p<0,001, 0,050 e 0,001 respectivamente). Esses resultados preliminares podem ser indicadores para que gestores possam focar em medidas que possam minimizar os efeitos danosos da variabilidade climatica na saude.

ANÁLISE DO POTENCIAL EÓLICO NA REGIÃO METROPOLITANA DE NATAL – RN

This work aimed to make a wind potential analysis in the metropolitan region of Natal in the State of Rio Grande do Norte, thus obtaining the characteristic of wind power and wind power generation using the weibull distribution.

INFLUÊNCIA DE UM VÓRTICE CICLÔNICO DE ALTOS NÍVEIS, NO REGIME DE CHUVAS EM NATAL – RN EM JUNHO DE 2013 (ESTUDO DE CASO)

Objetivo principal e prever, com alguma antecedencia, as possibilidades de ocorrencia das precipitacoes, bem como sua quantidade e intensidade em areas urbanas. Com isso, permitir a preparacao de medidas preventivas contra eventos extremos.

EVOLUÇÃO DIURNA DA CAMADA LIMITE PLANETÁRIA DURANTE UM EVENTO DE FRIAGEM EM RONDÔNIA

Neste trabalho, foi feita a analise dos perfis da temperatura potencial durante a intrusao de um evento de friagem na regiao sudeste da Amazonia, durante a estacao de transicao entre a estacao seca e chuvosa. Este evento, apesar da curta duracao apresentou variacao significativa no perfil da CLP, tanto em relacao a altura quanto em relacao a estabilizacao da camada.

MODELAGEM DE INTERNAÇÕES POR DOENÇAS RESPIRATÓRIAS EM IDOSOS PELA SENSAÇÃO TÉRMICA NO MUNICÍPIO DE NATAL-RN

Este trabalho teve por objetivo captar associacoes significativas entre internacoes e variaveis meteorologicas no municipio de Natal-RN, situado em uma regiao litorânea do nordeste brasileiro. Foram utilizados dados de velocidade do vento e temperatura do ar e de internacoes por doencas respiratorias em idosos (60 anos ou mais), no periodo de 2002 a 2010. O modelo marginal das equacoes de estimacao generalizada nao conseguiu captar associacoes significativas quando levou em consideracao o efeito direto das variaveis meteorologicas, porem quando ajustado com o efeito em conjunto das mesmas, captou a relacao existente com significância estatistica.