Incidence and classification of pediatric diffuse parenchymal lung diseases in Germany

<p>Abstract</p> <p>Background</p> <p>Diffuse parenchymal lung diseases (DPLD) in children represent a rare and heterogeneous group of chronic pulmonary disorders. Despite substantial advances in genetics and pathomechanisms, these often lethal diseases are still under-diagnosed. This is due to the fact that (i) the incidence is low, and (ii) clinical presentation, (iii) disease classification and (iv) specific treatment options are largely unknown.</p> <p>Methods</p> <p>Here we systematically assessed the incidence, the presentation, the diagnostic yield and treatments of pediatric DPLD in Germany, using the Surveillance Unit for Rare Paediatric Disorders (ESPED).</p> <p>Results</p> <p>The incidence of DPLD was 1.32 new cases per 1 million of children per year. The majority of these children were diagnosed within the first year of life. Overall survival was 87%. Using centralized data entry and stratification tools, the patients were categorized into an advanced classification system based on diagnostic algorithms, including clinical presentations, genetics and/or histology. Combining molecular and clinical information, this survey provides an etiological overview and specific diagnostic recommendations for children with DPLD.</p> <p>Conclusions</p> <p>Standardized surveys and systematic classifications are valuable tools for the clinical handling of children with DPLD and aim to improve the disease understanding and the prognosis of these rare detrimental lung diseases.</p

Untersuchungen zur Pathogenese viraler Atemwegsinfekte im Saeuglings- und Kleinkindesalter und ihrer Bedeutung fuer die Entwicklung einer bronchialen Hyperreagibilitaet Abschlussbericht

Acute viral infections of the respiratory tract (IRT) in infancy may lead to long lasting immunological and lung function abnormalities and can result in asthma. The aim of our prospective study was to identify risk factors for the development of asthma after a first servere IRT. We found the best prognostic value for neutrophilia during the acute episode, persistance of clinical symptoms after 1 week, and elevated ECP (Eosinophil Cationic Protein) levels 3 months after acute IRT. In an animal model (RSV-infected BALB/c-mouse) we investigated the role of alveolar macrophages (AM) during viral infection: while immunoregulatory functions like secretion of inflammatory cyctokines were upregulated, effector functions like phagocytosis and cytotoxicity were suppressed significantly. Our clinical and experimental results may provide new strategies, like antiinflammatory therapy in infants at risk and antagonization of inflammatory cytokines, for prevention of morbidity following acute IRT in infants. (orig.)SIGLEAvailable from TIB Hannover: F96B67+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

The Mating-Type Genes of the Basidiomycetes

Basidiomycete mating-type genes are encoded by two different factors resulting in a tetrapolar mating system where a cross can lead to one of four different reactions, only one of which results in a fertile state. Pairs of homeodomain transcription factors termed HD1 and HD2 classes constitute one factor (b genes in the smut fungi, A genes in the hymenomycete basidiomycetes). With the evolution of basidiomycetes, pheromone/receptor (P/R) systems (a genes in smut fungi and Bgenes in hymenomycetes) were co-opted to become independent master regulators constituting the second factor. Subsequently, the two sets of genes underwent evolutionary radiation with duplications, inversions and gene shuffling leading to the development of multiallelic HD and P/R systems, each functioning independently of the other. The multiallelic loci each developed many allelic specificities, resulting in tens of thousands of potential mating types for some species. An additional complexity of receptor gene homologues directly involved in mate discrimination has been revealed with the ready availability of genome sequences. Using examples derived from some model species, the molecular nature of the mating-type genes, the evolution of multiallelic and multispecific mating-type loci and the potential roles of newly detected receptor-like genes are discussed

Respiratory syncytial virus induced alteration of cytokine secretion by alveolar macrophages in vitro

Respiratory Syncytial Virus (RS virus) is the most common cause of lower respiratory tract disease in infants. The alveolar macrophage may contribute to the cellular immune response leading to virus elimination. Therefore, we investigated inflammatory mediators released by alveolar macrophages in response to RS virus. Supernatant of murine alveolar macrophages infected with RS virus at different multiplicities of infection have been tested at various time points for their cytokine content. In vitro infection of alveolar macrophages induced secretion of biologically active TNF alpha as well as Interleukin 6 (IL 6). In contrast, supernatant of RS virus infected alveolar macrophages contained only low amounts of Interleukin 1 (IL 1). The release of TNF, IL 6 and IL 1 by alveolar macrophages was dependent on the infectious dose of virus. We also observed a strong induction of PGE-2. However, maximal amounts of PGE-2 were released in a later stage of infection. Together these results indica te that alveolar macrophages may play a role in the regulation of the immune response to RS virus infection