The DZHK research platform: maximisation of scientific value by enabling access to health data and biological samples collected in cardiovascular clinical studies

The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles. The main elements of the DZHK infrastructure are web-based and central units for data management, LIMS, IDMS, and transfer office, embedded in a framework consisting of the DZHK Use and Access Policy, and the Ethics and Data Protection Concept. This framework is characterised by a modular design allowing a high standardisation across all studies. For studies that require even tighter criteria additional quality levels are defined. In addition, the Public Open Data strategy is an important focus of DZHK. The DZHK operates as one legal entity holding all rights of data and biological sample usage, according to the DZHK Use and Access Policy. All DZHK studies collect a basic set of data and biosamples, accompanied by specific clinical and imaging data and biobanking. The DZHK infrastructure was constructed by scientists with the focus on the needs of scientists conducting clinical studies. Through this, the DZHK enables the interdisciplinary and multiple use of data and biological samples by scientists inside and outside the DZHK. So far, 27 DZHK studies recruited well over 11,200 participants suffering from major cardiovascular disorders such as myocardial infarction or heart failure. Currently, data and samples of five DZHK studies of the DZHK Heart Bank can be applied for

Translocation of particles to the pleural space and tracheobronchial lymph nodes following lung deposition

The translocation of particles from the alveolar compartment to the pleural space and tracheobronchial lymph nodes was investigated in rats over a 30 day period following the intrapulmonary instillation of 4 x 10/sup 8/ polystyrene microspheres (1.9 ..mu..m dia.). In initial studies, approx. =10/sup 4/ particles were found in the pleural space compartment on Days 1, 14 and 30 after particle deposition, and most of these were cell-associated. Subsequent pleural space studies indicated, however, that the particles found in this compartment were, at least in part, due to the pleural lavage technique, and, unlike observations reported for some fibers, the translocation of the particles used in our study to the pleural space does not represent an important lung clearance pathway. In regard to particle clearance to the tracheobronchial lymph nodes, the accumulation of particles, most of which were extracellular, kinetically was biphasic with the most rapid phase occurring within the first 24 hours. Over the Day 1-30 period, the numbers of particles in the lymph nodes increased linearly to approx. =1.2 x 10/sup 6/ microspheres. The percentages of the nodal particles that were associated with nodal mononuclear phagocytes (NMP) over the course of the study were inversely proportional to nodal particulate burdens, even though the percentage of cells with engulfed particles increased; the percentage of NMP asymptotically approached a maximum value over the range of nodal burden of 6-12 x 10/sup 5/ particles. The distributions of the microspheres in the NMP were essentially identical on Days 1, 14, and 30. Major differences in the distributions of particles in lavage alveolar macrophages and NMP were not consistent with the notion that the latter represented translocated AM. 20 refs., 7 figs., 4 tabs

Radiation-induced bystander and adaptive responses in cell and tissue models.

The use of microbeam approaches has been a major advance in probing the relevance of bystander and adaptive responses in cell and tissue models. Our own studies at the Gray Cancer Institute have used both a charged particle microbeam, producing protons and helium ions and a soft X-ray microprobe, delivering focused carbon-K, aluminium-K and titanium-K soft X-rays. Using these techniques we have been able to build up a comprehensive picture of the underlying differences between bystander responses and direct effects in cell and tissue-like models. What is now clear is that bystander dose-response relationships, the underlying mechanisms of action and the targets involved are not the same as those observed for direct irradiation of DNA in the nucleus. Our recent studies have shown bystander responses even when radiation is deposited away from the nucleus in cytoplasmic targets. Also the interaction between bystander and adaptive responses may be a complex one related to dose, number of cells targeted and time interval

GM-CSF Induction in Human Lung Fibroblasts by IL-1 β

Fibroblast-derived cytokines may play crucial roles in airway inflammation. In this study, we analyzed expression of the inflammatory cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), a major eosinophilopoietin, by normal human lung fibroblast (NHLF) cells and its regulation by monokines and macrophage contact. NHLFs were stimulated with interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) and were cocultured with the U937 myelomonocytic cell line. The expression of GM-CSF transcripts was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), and GM-CSF protein was detected by ELISA. Nuclear translocation of nuclear factor-κB (NF-κB), an important transcription factor for inflammatory gene expression, was assessed by electrophoretic mobility shift assay (EMSA). Both IL-1β and TNF-α significantly enhanced the production of GM-CSF by NHLF. Coculturing of peripheral blood mononuclear cells (PBMC) with NHLF induced GM-CSF expression. This phenomenon was also seen on coculturing U937 cells or membranes derived from U937 with NHLF but was inhibited when the two types of cells were separated, suggesting a need for cell-cell contact. U937 membranes, as well as IL-1β and TNF-α, induced nuclear translocation of NF-κB. These data support a prominent role for macrophage-fibroblast interactions in airway inflammation and fibrosis