CD69 is a TGF-β/1α,25-dihydroxyvitamin D3 target gene in monocytes

CD69 is a transmembrane lectin that can be expressed on most hematopoietic cells. In monocytes, it has been functionally linked to the 5-lipoxygenase pathway in which the leukotrienes, a class of highly potent inflammatory mediators, are produced. However, regarding CD69 gene expression and its regulatory mechanisms in monocytes, only scarce data are available. Here, we report that CD69 mRNA expression, analogous to that of 5-lipoxygenase, is induced by the physiologic stimuli transforming growth factor-β (TGF-β) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in monocytic cells. Comparison with T- and B-cell lines showed that the effect was specific for monocytes. CD69 expression levels were increased in a concentration-dependent manner, and kinetic analysis revealed a rapid onset of mRNA expression, indicating that CD69 is a primary TGF-β/1α,25(OH)2D3 target gene. PCR analysis of different regions of the CD69 mRNA revealed that de novo transcription was initiated and proximal and distal parts were induced concomitantly. In common with 5-lipoxygenase, no activation of 0.7 kb or ~2.3 kb promoter fragments by TGF-β and 1α,25(OH)2D3 could be observed in transient reporter assays for CD69. Analysis of mRNA stability using a transcription inhibitor and a 3′UTR reporter construct showed that TGF-β and 1α,25(OH)2D3 do not influence CD69 mRNA stability. Functional knockdown of Smad3 clearly demonstrated that upregulation of CD69 mRNA, in contrast to 5-LO, depends on Smad3. Comparative studies with different inhibitors for mitogen activated protein kinases (MAPKs) revealed that MAPK signalling is involved in CD69 gene regulation, whereas 5-lipoxygenase gene expression was only partly affected. Mechanistically, we found evidence that CD69 gene upregulation depends on TAK1-mediated p38 activation. In summary, our data indicate that CD69 gene expression, conforming with 5-lipoxygenase, is regulated monocyte-specifically by the physiologic stimuli TGF-β and 1α,25(OH)2D3 on mRNA level, although different mechanisms account for the upregulation of each gene

The intrafamilial transmission of rheumatoid arthritis--III : The lack of support for a genetic hypothesis

This report does not support a conclusion that heredity is an important feature of the etiology of rheumatoid arthritis. Errors that might have contributed to earlier conclusions have been discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32906/1/0000286.pd

A Computational Fluid-Dynamics Assessment of the Improved Performance of Aerodynamic Rain Gauges

The airflow surrounding any catching-type rain gauge when impacted by wind is deformed by the presence of the gauge body, resulting in the acceleration of wind above the orifice of the gauge, which deflects raindrops and snowflakes away from the collector (the wind-induced undercatch). The method of mounting a gauge with the collector at or below the level of the ground, or the use of windshields to mitigate this effect, is often not practicable. The physical shape of a gauge has a significant impact on its collection efficiency. In this study, we show that appropriate \u201caerodynamic\u201d shapes are able to reduce the deformation of the airflow, which can reduce undercatch. We have employed computational fluid-dynamic simulations to evaluate the time-averaged airflow realized around \u201caerodynamic\u201d rain gauge shapes when impacted by wind. Terms of comparison are provided by the results obtained for two standard \u201cconventional\u201d rain gauge shapes. The simulations have been run for different wind speeds and are based on a time-averaged Reynolds-Averaged Navier-Stokes model. The shape of the aerodynamic gauges is shown to have a positive impact on the time-averaged airflow patterns observed around the orifice compared to the conventional shapes. Furthermore, the turbulent air velocity fields for the aerodynamic shapes present \u201crecirculating\u201d structures, which may improve the particle-catching capabilities of the gauge collector

Improving guideline adherence for cardiac rehabilitation in the Netherlands

Background In 2004, the Netherlands Society of Cardiology released the current guideline on cardiac rehabilitation. Given its complexity and the involvement of various healthcare disciplines, it was supplemented with a clinical algorithm, serving to facilitate its implementation in daily practice. Although the algorithm was shown to be effective for improving guideline adherence, several shortcomings and deficiencies were revealed. Based on these findings, the clinical algorithm has now been updated. This article describes the process and the changes that were made. Methods The revision consisted of three phases. First, the reliability of the measurement instruments included in the 2004 Clinical Algorithm was investigated by evaluating between-centre variations of the baseline assessment data. Second, based on the available evidence, a multidisciplinary expert advisory panel selected items needing revision and provided specific recommendations. Third, a guideline development group decided which revisions were finally included, also taking practical considerations into account. Results A total of nine items were revised: three because of new scientific insights and six because of the need for more objective measurement instruments. In all revised items, subjective assessment methods were replaced by more objective assessment tools (e.g. symptom-limited exercise instead of clinical judgement). In addition, four new key items were added: screening for anxiety/depression, stress, cardiovascular risk profile and alcohol consumption. Conclusion Based on previously determined shortcomings, the Clinical Algorithm for Cardiac Rehabilitation was thoroughly revised mainly by incorporating more objective assessment methods and by adding several new key area

How the Mid-Victorians Worked, Ate and Died†

Analysis of the mid-Victorian period in the U.K. reveals that life expectancy at age 5 was as good or better than exists today, and the incidence of degenerative disease was 10% of ours. Their levels of physical activity and hence calorific intakes were approximately twice ours. They had relatively little access to alcohol and tobacco; and due to their correspondingly high intake of fruits, whole grains, oily fish and vegetables, they consumed levels of micro- and phytonutrients at approximately ten times the levels considered normal today. This paper relates the nutritional status of the mid-Victorians to their freedom from degenerative disease; and extrapolates recommendations for the cost-effective improvement of public health today

Prevalência de angina do peito pelo questionário de Rose na população brasileira: análise da Pesquisa Nacional de Saúde, 2013

RESUMO: Objetivo: Estimar a prevalência de angina do peito na população adulta brasileira com a aplicação do questionário de Rose para angina na Pesquisa Nacional de Saúde (PNS-2013). Métodos: Inquérito populacional representativo da população brasileira acima de 18 anos de idade, com amostragem probabilística conglomerada em três estágios. Foram obtidos registros de entrevistas de 60.202 indivíduos no território nacional. Apresentou-se ao entrevistado o questionário de Rose curto com três questões, adaptado por Lawlor em 2003 e validado no Brasil, para identificar angina do peito grau I (leve) e II (moderada/grave). Calcularam-se os valores de prevalência com intervalo de confiança de 95% (IC95%) segundo sexo, faixa etária, escolaridade e raça/cor. Resultados: A prevalência de angina leve (grau I) foi de 7,6% (IC95% 7,2 - 8,0) para toda população, com frequência maior em mulheres - 9,1% (IC95% 8,5 - 9,7) - do que em homens - 5,9% (5,3 - 6,4). A frequência de angina moderada/grave (grau II) foi 4,2 (IC95% 3,9 - 4,5), também mais frequente em mulheres - 5,2% (IC95% 4,7 - 5,6) - do que em homens - 3,0% (IC95% 2,7 - 3,4). A prevalência de angina por faixa etária aumentou progressivamente com a idade. A prevalência de angina, de qualquer tipo, foi inversa aos anos de estudo formal. Apesar do valor maior da presença de angina em negros, não houve diferença significativa por raça/cor da pele. Conclusão: Os valores de prevalência elevada de angina do peito na população brasileira acima de 18 anos foram compatíveis com estudos em outros países, revelando a importância da doença coronariana como problema de saúde pública