Germline deletion and a somatic mutation of the PRKAR1A gene in a Carney complex-related pituitary adenoma

Objective: The objective was to assess involvement of loss of the PRKAR1A gene encoding a type 1α regulatory subunit of cAMP-dependent protein kinase A located on 17q24 in a Carney complex (CNC)-related pituitary adenoma. Design: We investigated aberrations of the PRKAR1A gene in a CNC patient with a GH-producing pituitary adenoma, whose family has 3 other members with probable CNC. Methods: A gene mutation was identified by a standard DNA sequencing method based on PCR. DNA copy number was measured to evaluate allelic loss on 17q24 by quantitative PCR. The breakpoints of deletion were determined by cloning a rearranged region in the deleted allele. Results: A PRKAR1A mutation of c.751_758del8 (p.S251LfsX16) was found in genomic DNA obtained from a pituitary adenoma, but not leukocytes from the patient. Reduced DNA copy number at loci including the PRKAR1A gene on 17q24 was detected in both the tumor and leukocytes, suggesting a deletion at the loci at the germline level. The deletion size was determined to be approximately 0.5 Mb and this large deletion was also found in other 2 family members. Conclusion: This is the first case showing a CNC-related pituitary adenoma with the combination of somatic mutation and a large inherited deletion of the PRKAR1A gene. Biallelic inactivation of PRKAR1A may be necessary for the development of CNC-related pituitary adenoma

In vitro anti-tumour activity of α-galactosylceramide-stimulated human invariant Vα24+NKT cells against melanoma

α-galactosylceramide (KRN 7000, α-GalCer) has shown potent in vivo anti-tumour activity in mice, including against melanoma and the highly specific effect of inducing proliferation and activation of human Vα24+NKT-cells. We hypothesized that human Vα24+NKT-cells activated by α-GalCer might exhibit anti-tumour activity against human melanoma. To investigate this, Vα24+NKT-cells were generated from the peripheral blood of patients with melanoma after stimulation with α-GalCer pulsed monocyte-derived dendritic cells (Mo-DCs). Vα24+NKT-cells did not exhibit cytolytic activity against the primary autologous or allogeneic melanoma cell lines tested. However, proliferation of the melanoma cell lines was markedly suppressed by co-culture with activated Vα24+NKT-cells (mean ± SD inhibition of proliferation 63.9 ± 1.3%). Culture supernatants of activated Vα24+NKT-cell cultures stimulated with α-GalCer pulsed Mo-DCs exhibited similar antiproliferative activities against melanoma cells, indicating that the majority of the inhibitory effects were due to soluble mediators rather than direct cell-to-cell interactions. This effect was predominantly due to release of IFN-γ, and to a lesser extent IL-12. Other cytokines, including IL-4 and IL-10, were released but these cytokines had less antiproliferative effects. These in vitro results show that Vα24+NKT-cells stimulated by α-GalCer-pulsed Mo-DCs have anti-tumour activities against human melanoma through antiproliferative effects exerted by soluble mediators rather than cytolytic effects as observed against some other tumours. Induction of local cytokine release by activated Vα24+NKT-cells may contribute to clinical anti-tumour effects of α-GalCer. © 2001 Cancer Research Campaign http://www.bjcancer.co

Internet and game behaviour at a secondary school and a newly developed health promotion programme: a prospective study

<p>Abstract</p> <p>Background</p> <p>This study investigated the Internet and game use of secondary school children, the compulsiveness of their use and the relationship with other health behaviours. It also evaluated the preliminary results of a recently developed school health promotion programme, implemented at a secondary school in the Netherlands in January 2008. This programme is one of the first to combine seven health behaviours in one educational programme and is a pilot project for a case-control study.</p> <p>Methods</p> <p>A total of 475 secondary school children completed an extensive questionnaire before and a year after starting the programme. Of these children, 367 were in first, second and third grade; the grades in which the lessons about internet and game behaviour were implemented. Questionnaires contained questions about personal information, Internet and game use (Compulsive Internet Use Scale), and other health behaviours (alcohol use, physical activity, psychosocial wellbeing and body mass index).</p> <p>Results</p> <p>Heavy Internet use was significantly associated with psychosocial problems, and heavy game use was significantly associated with psychosocial problems and less physical activity. No relationship was found with alcohol use or body mass index. The time spent on Internet (hours/day) and the number of pathological Internet users increased during the study. The number of game users decreased but heavy game use increased.</p> <p>Conclusion</p> <p>The association between heavy Internet use and psychosocial problems and between game use and psychosocial problems and less physical activity emphasizes the need to target different health behaviours in one health education programme. A case-control study is needed to further assess the programme-induced changes in Internet and game behaviour of school children.</p

Fatores associados a atividade fisica, comportamento sedentario e participacao na Educacao Fisica em estudantes do Ensino Medio em Santa Catarina, Brasil

Abstract published in English and Portuguese English title: Factors associated with physical activity, sedentary behavior, and participation in physical education among high school students in Santa Catarina State, BrazilThe objectives of this study were to estimate the prevalence of insufficient physical activity, sedentary behavior, and absence from physical education and associated factors. The Santa Catarina State Adolescents' Questionnaire (COMPAC, in Portuguese) was applied to a sample of 5,028 adolescents (15-19 years of age) attending public high schools in the State of Santa Catarina, Brazil. Information included demographic and socioeconomic indicators. Poisson regression analyses were used to test associations. The proportion of students with insufficient physical activity was 28.5%, associated with low consumption of fruits and vegetables (PR = 1.27; 95%CI: 1.15; 1.40) and enrollment in night classes (PR = 1.44; 95%CI: 1.34; 1.54). Absence from physical education was reported by 48.6%; employment and older age were negatively associated with absence from physical education. Sedentary behavior was reported by 38.4%, but was less frequent in rural areas (PR = 0.52; 95%CI: 0.31; 0.83) and among those enrolled in absence from physical education (RP = 0.73; 95%CI: 0.56; 0.95). The results suggest interventions with specific strategies aimed at ameliorating each contributing factor. = O objetivo deste estudo foi analisar as prevalências e fatores associados à atividade física insuficiente, comportamento sedentário e ausência nas aulas de Educação Física em escolares do Ensino Médio. O questionário COMPAC (Comportamento do Adolescente Catarinense) foi respondido por 5.028 estudantes (15 a 19 anos), de escolas públicas de Santa Catarina, Sul do Brasil. Foram analisados comportamentos de risco, informações demográficas e sócio-econômicas. Utilizou-se regressão de Poisson para análises das associações. A prevalência de atividade física insuficiente foi de 28,5% e associou-se a um menor consumo de frutas/verduras (RP = 1,27; IC95%: 1,15-1,40) e estudo noturno (RP = 1,44; IC95%: 1,34-1,54). A prevalência de ausência nas aulas de Educação Física foi de 48,6% e associou-se negativamente à idade e com estar trabalhando (RP = 1,52; IC95%: 1,18-2,19). A prevalência de comportamento sedentário foi de 38,4%, atingindo menos os residentes de áreas rurais (RP = 0,52; IC95%: 0,31-0,83) e que participavam de uma ausência nas aulas de Educação Física semanal (RP = 0,73; IC95%: 0,56-0,95). Os resultados sugerem intervenções com estratégias específicas para cada comportamento analisado.Kelly Samara da Silva, Markus Vinícius Nahas, Karen Glazer Peres, Adair da Silva Lope