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Waiczies H.,Max Delbruck Center for Molecular Medicine | Waiczies H.,Physikalisch - Technische Bundesanstalt | Lepore S.,Max Delbruck Center for Molecular Medicine | Janitzek N.,Max Delbruck Center for Molecular Medicine | And 12 more authors.

The development of cellular tracking by fluorine ( 19F) magnetic resonance imaging (MRI) has introduced a number of advantages for following immune cell therapies in vivo. These include improved signal selectivity and a possibility to correlate cells labeled with fluorine-rich particles with conventional anatomic proton ( 1H) imaging. While the optimization of the cellular labeling method is clearly important, the impact of labeling on cellular dynamics should be kept in mind. We show by 19F MR spectroscopy (MRS) that the efficiency in labeling cells of the murine immune system (dendritic cells) by perfluoro-15-crown-5-ether (PFCE) particles increases with increasing particle size (560>365>245>130 nm). Dendritic cells (DC) are professional antigen presenting cells and with respect to impact of PFCE particles on DC function, we observed that markers of maturation for these cells (CD80, CD86) were also significantly elevated following labeling with larger PFCE particles (560 nm). When labeled with these larger particles that also gave an optimal signal in MRS, DC presented whole antigen more robustly to CD8+ T cells than control cells. Our data suggest that increasing particle size is one important feature for optimizing cell labeling by PFCE particles, but may also present possible pitfalls such as alteration of the immunological status of these cells. Therefore depending on the clinical scenario in which the 19F-labeled cellular vaccines will be applied (cancer, autoimmune disease, transplantation), it will be interesting to monitor the fate of these cells in vivo in the relevant preclinical mouse models. © 2011 Waiczies et al. Source

Witt H.,TU Munich | Beer S.,Boston University | Rosendahl J.,University of Leipzig | Chen J.-M.,French Institute of Health and Medical Research | And 80 more authors.
Nature Genetics

Chronic pancreatitis is an inflammatory disorder of the pancreas. We analyzed CPA1, encoding carboxypeptidase A1, in subjects with nonalcoholic chronic pancreatitis (cases) and controls in a German discovery set and three replication sets. unctionally impaired variants were present in 29/944 (3.1%) German cases and 5/3,938 (0.1%) controls (odds ratio (OR) = 24.9, P = 1.5 X 10-16). The association was strongest in subjects aged =10 years (9.7%; OR = 84.0, P = 4.1 X 10-24). In the replication sets, defective CPA1 variants were present in 8/600 (1.3%) cases and 9/2,432 (0.4%) controls from Europe (P = 0.01), 5/230 (2.2%) cases and 0/264 controls from India (P = 0.02) and 5/247 (2.0%) cases and 0/341 controls from Japan (P = 0.013). The mechanism by which CPA1 variants confer increased pancreatitis risk may involve misfolding-induced endoplasmic reticulum stress rather than elevated trypsin activity, as is seen with other genetic risk factors for this disease. © 2013 Nature America, Inc. All rights reserved. Source

Dames C.,Charite - Medical University of Berlin | Akyuz L.,Charite - Medical University of Berlin | Reppe K.,Charite - Medical University of Berlin | Tabeling C.,Charite - Medical University of Berlin | And 8 more authors.
American Journal of Respiratory Cell and Molecular Biology

Lung diseases, including pneumonia and asthma, are among the most prevalent human disorders, and murine models have been established to investigate their pathobiology and develop novel treatment approaches. Whereas bronchoscopy is valuable for diagnostic and therapeutic procedures in patients, no equivalent for small rodents has been established. Here, we introduce a miniaturized video-bronchoscopy system offering new opportunities in experimental lung research. With an outer diameter of 0.75 mm, it is possible to advance the optics into the main bronchi of mice. An irrigation channel allows bronchoalveolar lavage and unilateral application of substances to one lung. Even a unilateral infection is possible, enabling researchers to use the contralateral lung as internal control. Copyright © 2014 by the American Thoracic Society. Source

Ruckert J.C.,Charite - Medical University of Berlin | Ismail M.,Charite - Medical University of Berlin | Badakhshi H.,Charite - Medical University of Berlin | Meisel A.,NeuroCure Clinical Research Center | Swierzy M.,Charite - Medical University of Berlin
Zentralblatt fur Chirurgie - Zeitschrift fur Allgemeine, Viszeral- und Gefasschirurgie

Thymectomy, the surgical removal of the thymic gland, is essential in cases of thymoma. The majority of cases of a myasthenia gravis (MG) represent a relative indication for thymectomy which requires cooperation with specialized neurologists. Patients with MG may present with a tumor of the thymic gland. In case of suspicious thymoma, the resectability of the tumor has to be evaluated in the preoperative diagnostic. The clinical condition of patients with MG has to be stabilized preoperatively. The aim of thymectomy is the radical removal of thymoma and/or maximal improvement of MG symptoms. This requires the complete extirpation of the thymic gland including all ectopic thymic tissue in the anterior mediastinum. There is a variety of surgical techniques for performing a complete thymectomy. In addition to the conventional techniques with sternotomy, the significance of minimally-invasive approaches is increasing rapidly. Despite the ongoing scarcity of data of higher evidence concerning the procedure of thymectomy an increasing number of equivalent results with minimally-invasive operation techniques for MG and for thymoma are available. The successful surgical performance of a thymectomy is part of an interdisciplinary cooperation in the perioperative treatment of MG as well as the postoperative long-term care for patients with MG and/or thymoma.©Georg Thieme Verlag KG Stuttgart. Source

Alten F.,University of Muenster Medical Center | Motte J.,University of Muenster Medical Center | Ewering C.,University of Muenster Medical Center | Osada N.,University of Munster | And 6 more authors.

Methods: 28 eyes of fourteen CADASIL patients and an equal number of control subjects underwent confocal scanning laser ophthalmoscopy (cSLO), spectral-domain optical coherence tomography (SD-OCT), retinal nerve fibre layer (RNFL) measurements, fluorescein and indocyanine angiography. Three vessel measurement techniques were applied: RNFL thickness, a semiautomatic software tool based on cSLO images and manual vessel outlining based on SD-OCT.Results: Mean age of patients was 56.2±11.6 years. Arteriovenous nicking was present in 22 (78.6%) eyes and venous dilation in 24 (85.7%) eyes. Retinal volume and choroidal volume were 8.77±0.46 mm3 and 8.83±2.24 mm3. RNFL measurements showed a global increase of 105.2 μm (Control group: 98.4 μm; p = 0.015). Based on semi-automatic cSLO measurements, maximum diameters of arteries and veins were 102.5 μ m (106.0 μm; p = 0.21) and 128.6 μm (124.4 μm; p = 0.27) respectively. Manual SD-OCT measurements revealed significantly increased mean arterial 138.7 μm (125.4 mm; p〈 0.001) and venous 160.0 μm (146.9; p = 0.003) outer diameters as well as mean arterial 27.4 mm (19.2 μm; p〈0.001) and venous 18.3 μm (15.7 μm; p〈0.001) wall thicknesses in CADASIL patients.Conclusions: The findings reflect current knowledge on pathophysiologic changes in vessel morphology in CADASIL patients. SD-OCT may serve as a complementary tool to diagnose and follow-up patients suffering from cerebral smallvessel diseases.Purpose: To further elucidate retinal findings and retinal vessel changes in Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients by means of high resolution retinal imaging. © 2014 Alten et al. Source

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