TY - JOUR A1 - Fröhlich, Kathrin S. A1 - Papenfort, Kai A1 - Berger, Allison A. A1 - Vogel, Jörg T1 - A conserved RpoS-dependent small RNA controls the synthesis of major porin OmpD JF - Nucleic Acids Research N2 - A remarkable feature of many small non-coding RNAs (sRNAs) of Escherichia coli and Salmonella is their accumulation in the stationary phase of bacterial growth. Several stress response regulators and sigma factors have been reported to direct the transcription of stationary phase-specific sRNAs, but a widely conserved sRNA gene that is controlled by the major stationary phase and stress sigma factor, Sigma(S) (RpoS), has remained elusive. We have studied in Salmonella the conserved SdsR sRNA, previously known as RyeB, one of the most abundant stationary phase-specific sRNAs in E. coli. Alignments of the sdsR promoter region and genetic analysis strongly suggest that this sRNA gene is selectively transcribed by Sigma(S). We show that SdsR down-regulates the synthesis of the major Salmonella porin OmpD by Hfq-dependent base pairing; SdsR thus represents the fourth sRNA to regulate this major outer membrane porin. Similar to the InvR, MicC and RybB sRNAs, SdsR recognizes the ompD mRNA in the coding sequence, suggesting that this mRNA may be primarily targeted downstream of the start codon. The SdsR-binding site in ompD was localized by 3'-RACE, an experimental approach that promises to be of use in predicting other sRNA-target interactions in bacteria. KW - shock sigma factor KW - general stress response KW - down regulation KW - stationary phase KW - salmonella enterica KW - messenger RNA KW - escherichia coli KW - enterica serovar typhimurium KW - outer-membrane proteins KW - small noncoding RNAs Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134230 VL - 40 IS - 8 ER - TY - JOUR A1 - Hagemann, Carsten A1 - Anacker, Jelena A1 - Ernestus, Ralf-Ingo A1 - Vince, Giles H. T1 - A complete compilation of matrix metalloproteinase expression in human malignant gliomas JF - World Journal of Clinical Oncology N2 - Glioblastomas are characterized by an aggressive local growth pattern, a marked degree of invasiveness and poor prognosis. Tumor invasiveness is facilitated by the increased activity of proteolytic enzymes which are involved in destruction of the extracellular matrix of the surrounding healthy brain tissue. Elevated levels of matrix metalloproteinases (MMPs) were found in glioblastoma (GBM) cell-lines, as well as in GBM biopsies as compared with low-grade astrocytoma (LGA) and normal brain samples, indicating a role in malignant progression. A careful review of the available literature revealed that both the expression and role of several of the 23 human MMP proteins is controversely discussed and for some there are no data available at all. We therefore screened a panel of 15 LGA and 15 GBM biopsy samples for those MMPs for which there is either no, very limited or even contradictory data available. Hence, this is the first complete compilation of the expression pattern of all 23 human MMPs in astrocytic tumors. This study will support a better understanding of the specific expression patterns and interaction of proteolytic enzymes in malignant human glioma and may provide additional starting points for targeted patient therapy. KW - glioblastoma cell-lines KW - matrix metalloproteinase KW - glioblastoma multiforme KW - astrocytic tumor KW - expression pattern Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123982 VL - 3 IS - 5 ER - TY - THES A1 - Platt, Christian T1 - A Common Thread in Unconventional Superconductivity: The Functional Renormalization Group in Multi-Band Systems T1 - Unkonventionelle Supraleitung in Multi-Band Systemen N2 - Die supraleitenden Eigenschaften von komplexen Materialsystemen, wie den erst kürzlich entdeckten Eisen-Pniktiden oder den Strontium-Ruthenaten, sind oftmals durch das Zusammenspiel vieler elektronischer Orbitale bestimmt. Um die Supraleitung in derartigen Systemen besser zu verstehen, entwickeln wir in dieser Arbeit eine Multi-Orbital-Implementierung der funktionalen Renormierungsgruppe und untersuchen die Elektronenpaarung in verschiedenen charakteristischen Materialverbindungen. In den Eisen-Pniktiden finden wir hierbei mehrere Spinfluktuationskanäle, die eine Elektronenpaarung hervorrufen, sofern die Paarwellenfunktion einen Vorzeichenwechsel zwischen den verschiedenen genesteten Bereichen der Fermifläche aufweist. Abhängig von den spezifischen Materialeigenschaften, wie der Dotierung oder der Position des Pniktogenatoms, führen diese Spinfluktuationen dann zu $s_{\pm}$-wellenartiger Paarung mit durchgängiger Energielücke oder mit Knoten auf der Fermifläche. In manchen Fällen wird zudem auch $d$-wellenartige Paarung induziert, die in der Nähe des Übergangs zur $s_{\pm}$-Symmetrie einen gemischten $(s+id)$-Zustand mit gebrochener Zeitinversionssymmetrie aufweist. Diese neuartige Phase zeigt faszinierende Eigenschaften, wie zum Beispiel das spontane Entstehen von Supraströmen am Probenrand und um nichtmagnetische Störstellen. Auf Grund der durchgängigen Energielücke ist dieser $(s+id)$-Zustand energetisch begünstigt. Im Folgenden untersuchen wir zudem auch die elektronischen Instabilitäten eines weiteren außergewöhnlichen Materials -- dotiertes Graphen. Diese rein zweidimensionale Kohlenstoffverbindung ist schon seit mehreren Jahren im Fokus der Festkörperforschung und wurde mittlerweile auch durch neuartige experimentelle Verfahren dotiert, ohne die zugrundeliegende hexagonale Gittersturktur merklich zu stören. Eine theoretische Beschreibung dieses Systems erfordert die Berücksichtigung zweier nicht-equivalenter Gitterplätze, was wiederum effektiv als Zwei-Orbital-System aufgefasst werden kann. Durch die besondere Symmetrie der hexagonalen Gitterstruktur sind beide $d$-wellenartigen Paarungskanäle entartet und ahnlich der $(s+id)$-Paarung in den Pniktiden finden wir hier eine chirale $(d+id)$-Paarung in einem weiten Dotierungsbereich um van-Hove Füllung. Des Weiteren identifizieren wir Spin-Triplet-Paarung und eine exotische Form der Spindichtewelle, welche beide durch leichte Veränderung der langreichweitigen Hüpfamplituden und Wechselwirkungensparameter realisiert werden können. Als drittes Beispiel betrachten wir die Supraleitung in dem Strontium-Ruthenat Sr$_2$RuO$_4$. Die Besonderheit dieser Materialverbindung liegt in der möglichen Realisierung einer chiralen Spin-Triplet Paarung, die wiederum faszinierende Eigenschaften wie die Existenz von halbganzzahligen Flussvortizes mit nicht-Abelscher Vertauschungsstatistik aufweisen würde. Mittels eines mikroskopischen Drei-Orbital-Modells und der Berücksichtigung von Spin-Bahn-Kopplung finden wir hierbei, dass moderate ferromagnetische Spinfluktuationen immer noch ausreichen, um diesen speziellen Paarungszustand anzutreiben. Die berechnete Energielücke zeigt im Weiteren sehr starke Anisotropien auf dem $d_{xy}$-Orbital-dominierten Bereich der Fermifläche und verschwindet nahezu vollständig auf den anderen beiden Fermiflächen. N2 - The superconducting properties of complex materials like the recently discovered iron-pnictides or strontium-ruthenate are often governed by multi-orbital effects. In order to unravel the superconductivity of those materials, we develop a multi-orbital implementation of the functional renormalization group and study the pairing states of several characteristic material systems. Starting with the iron-pnictides, we find competing spin-fluctuation channels that become attractive if the superconducting gap changes sign between the nested portions of the Fermi surface. Depending on material details like doping or pnictogen height, these spin fluctuations then give rise to $s_{\pm}$-wave pairing with or without gap nodes and, in some cases, also change the symmetry to $d$-wave. Near the transition from nodal $s_{\pm}$-wave to $d$-wave pairing, we predict the occurrence of a time-reversal symmetry-broken $(s+id)$-pairing state which avoids gap nodes and is therefore energetically favored. We further study the electronic instabilities of doped graphene, another fascinating material which has recently become accessible and which can effectively be regarded as multi-orbital system. Here, the hexagonal lattice structure assures the degeneracy of two $d$-wave pairing channels, and the system then realizes a chiral $(d+id)$-pairing state in a wide doping range around van-Hove filling. In addition, we also find spin-triplet pairing as well as an exotic spin-density wave phase which both become leading if the long-ranged hopping or interaction parameters are slightly modified, for example, by choosing different substrate materials. Finally, we consider the superconducting state of strontium-ruthenate, a possible candidate for chiral spin-triplet pairing with fascinating properties like the existence of half-quantum vortices obeying non-Abelian statistics. Using a microscopic three orbital description including spin-orbit coupling, we demonstrate that ferromagnetic fluctuations are still sufficient to induce this $\bs{\hat{z}}(p_x\pm ip_y)$-pairing state. The resulting superconducting gap reveals strong anisotropies on the $d_{xy}$-dominated Fermi-surface pocket and nearly vanishes on the other remaining two pockets. KW - Supraleitung KW - Renormierungsgruppe KW - Eisen-basierte Supraleiter KW - iron-pnictides KW - ruthenates KW - graphene KW - multi-band superconductivity KW - functional renormalization group KW - Hochtemperatursupraleitung KW - Ruthenate KW - Pnictide Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-78824 ER - TY - JOUR A1 - Homola, György A. A1 - Jbabdi, Saad A1 - Beckmann, Christian F. A1 - Bartsch, Andreas J. T1 - A Brain Network Processing the Age of Faces N2 - Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke’s understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships. KW - Medizin Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75513 ER - TY - JOUR A1 - Li, Xiang A1 - Samnick, Samuel A1 - Lapa, Constantin A1 - Israel, Ina A1 - Buck, Andreas K. A1 - Kreissl, Michael C. A1 - Bauer, Wolfgang T1 - 68Ga-DOTATATE PET/CT for the detection of inflammation of large arteries: correlation with18F-FDG, calcium burden and risk factors N2 - Background: Ga-[1,4,7,10-tetraazacyclododecane-N,N0,N00,N000-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) positron emission tomography (PET) is commonly used for the visualization of somatostatin receptor (SSTR)-positive neuroendocrine tumors. SSTR is also known to be expressed on macrophages, which play a major role in inflammatory processes in the walls of coronary arteries and large vessels. Therefore, imaging SSTR expression has the potential to visualize vulnerable plaques. We assessed 68Ga-DOTATATE accumulation in large vessels in comparison to 18F-2-fluorodeoxyglucose (FDG) uptake, calcified plaques (CPs), and cardiovascular risk factors. Methods: Sixteen consecutive patients with neuroendocrine tumors or thyroid cancer underwent both 68Ga-DOTATATE and 18F-FDG PET/CT for staging or restaging purposes. Detailed clinical data, including common cardiovascular risk factors, were recorded. For a separate assessment, they were divided into a high-risk and a low-risk group. In each patient, we calculated the maximum target-to-background ratio (TBR) of eight arterial segments. The correlation of the TBRmean of both tracers with risk factors including plaque burden was assessed. Results: The mean TBR of 68Ga-DOTATATE in all large arteries correlated significantly with the presence of CPs (r = 0.52; p < 0.05), hypertension (r = 0.60; p < 0.05), age (r = 0.56; p < 0.05), and uptake of 18F-FDG (r = 0.64; p < 0.01). There was one significant correlation between 18F-FDG uptake and hypertension (0.58; p < 0.05). Out of the 37 sites with the highest focal 68Ga-DOTATATE uptake, 16 (43.2%) also had focal 18F-FDG uptake. Of 39 sites with the highest 18F-FDG uptake, only 11 (28.2%) had a colocalized 68Ga-DOTATATE accumulation. Conclusions: In this series of cancer patients, we found a stronger association of increased 68Ga-DOTATATE uptake with known risk factors of cardiovascular disease as compared to 18F-FDG, suggesting a potential role for plaque imaging in large arteries. Strikingly, we found that focal uptake of 68Ga-DOTATATE and 18F-FDG does not colocalize in a significant number of lesions. KW - Medizin KW - Atherosclerotic plaque KW - 68Ga-DOTATATE KW - Somatostatin receptor KW - Cardiovascular risk factors KW - Macrophage Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76231 ER - TY - THES A1 - Fuchs, Andreas Rudolf T1 - 3D-Pulverdruck von Zellkulturträgern mit Magnesium-Phosphat-Chemie T1 - 3d powder printing of scaffolds with a magnesium phosphate chemistry N2 - In der vorliegenden Arbeit wurden erstmals im 3D-Pulerdruckverfahren hergestellte Struvit-Matrizes auf ihre Eignung als Trägermaterial für Knochenzellen in vitro untersucht. Hierzu wurde die Zytokompatibilität sowie die chemische Löslichkeit von gedruckten Struvit-Strukturen betrachtet. In einem zweiten Schritt wurde untersucht, ob die biologische Funktion von BMP-2-Lösungen nach Durchlaufen des Druckprozesses erhalten bleibt und ob es möglich ist, BMP-2 unter Beibehaltung seiner biologischen Wirksamkeit direkt in Struvit-Matrizes zu drucken. Als Reaktanten zur Herstellung der Struvit-Matrizes wurde modifiziertes Farringtonit-Pulver mit definierter Körnung und eine äquimolare Binder-Lösung aus DAHP und ADHP verwendet. Die untersuchten Zellkulturträger mit Magnesiumammoniumphosphatchemie zeigten eine ausreichende Zytokompatibilität in vitro. Außerdem wurde gezeigt, dass thermolabile Proteine wie BMP-2 im 3D-Pulverdruckverfahren unter weitgehender Beibehaltung ihrer biologischen Wirksamkeit in vitro grundsätzlich prozessierbar sind. Die Freisetzung direkt eingedruckter Proteine aus den Struvit-Matrizes blieb jedoch hinter den Erwartungen zurück. Mit Struvit steht ein alternatives Zementsystem für den 3D-Pulverdruck zur Verfügung, welches spezifische Vorteile gegenüber den etablierten Calciumphosphaten bietet. Weitere Untersuchungen sind erforderlich, um die Ursache für die geringe BMP-Freisetzung aus den Struvit-Matrizes zu ermitteln und die Vorteile der neutralen Abbindereaktion voll nutzen zu können. N2 - The purpose of the present study was the investigation of 3d powder printed struvite-scaffolds as a carrier material for osteoblastic cells in vitro. For this purpose, their cytocompatibility and their chemical solubility were observed. In a second step we analysed, if BMP-2 could pass through the whole printing process without losing its biological function and furthermore if it is possible to print BMP-2 directly into struvite-scaffolds without a significant loss of biological activity. As reactants for the fabrication of the struvite-scaffolds, we used a modified farringtonite-powder and a binder solution consisting of an equimolar mixture of DAHP and ADHP. The investigated struvite-scaffolds showed a sufficient cytocompatibility. It was also shown, that thermolabile proteins, such as BMP-2, could be processed in 3d powder printing without losing much of their biological activity in vitro. The release of directly imprinted proteins out of the struvite scaffolds remained unsatisfying. Struvite is an alternative hydraulic-setting cement for 3d powder printing with certain advantages over the established calcium phosphate cements. Further investigations are necessary to identify the reasons for the low BMP-release out of the struvite-scaffolds and to take full advantage of the neutral setting reaction of struvite-cements. KW - Struvit KW - Rapid Prototyping KW - Knochen-Morphogenese-Proteine KW - 3D-Pulverdruck KW - BMP KW - Scaffold KW - 3d powder printing KW - scaffold KW - BMP KW - struvite Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-77415 ER - TY - JOUR A1 - Finze, Maik A1 - Reiss, Guido J. A1 - Frohn, Hermann-Josef T1 - 2,3,5,6-Tetrafluoro-1,4-bis(trimethylsilyl)benzene N2 - no abstract available KW - Chemie KW - single-crystal X-ray study KW - T = 199 K KW - R factor = 0.027 KW - wR factor = 0.068 KW - data-to-parameter ratio = 14.0. Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75401 ER - TY - JOUR A1 - Klotz, Barbara A1 - Mentrup, Birgit A1 - Regensburger, Martina A1 - Zeck, Sabine A1 - Schneidereit, Jutta A1 - Schupp, Nicole A1 - Linden, Christian A1 - Merz, Cornelia A1 - Ebert, Regina A1 - Jakob, Franz T1 - 1,25-Dihydroxyvitamin D3 Treatment Delays Cellular Aging in Human Mesenchymal Stem Cells while Maintaining Their Multipotent Capacity JF - PLoS ONE N2 - 1,25-dihydroxyvitamin D3 (1,25D3) was reported to induce premature organismal aging in fibroblast growth factor-23 (Fgf23) and klotho deficient mice, which is of main interest as 1,25D3 supplementation of its precursor cholecalciferol is used in basic osteoporosis treatment. We wanted to know if 1,25D3 is able to modulate aging processes on a cellular level in human mesenchymal stem cells (hMSC). Effects of 100 nM 1,25D3 on hMSC were analyzed by cell proliferation and apoptosis assay, beta-galactosidase staining, VDR and surface marker immunocytochemistry, RT-PCR of 1,25D3-responsive, quiescence-and replicative senescence-associated genes. 1,25D3 treatment significantly inhibited hMSC proliferation and apoptosis after 72 h and delayed the development of replicative senescence in long-term cultures according to beta-galactosidase staining and P16 expression. Cell morphology changed from a fibroblast like appearance to broad and rounded shapes. Long term treatment did not induce lineage commitment in terms of osteogenic pathways but maintained their clonogenic capacity, their surface marker characteristics (expression of CD73, CD90, CD105) and their multipotency to develop towards the chondrogenic, adipogenic and osteogenic pathways. In conclusion, 1,25D3 delays replicative senescence in primary hMSC while the pro-aging effects seen in mouse models might mainly be due to elevated systemic phosphate levels, which propagate organismal aging. KW - perspectives KW - bone marrow KW - mutant mice KW - oxidative stress KW - transcription factors KW - vitamin-D-receptor KW - differentiation KW - tissue KW - 2',7'-dichlorofluorescin KW - homeostasis Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133392 VL - 7 IS - 1 ER - TY - THES A1 - Zimmerer, Daniel Johannes T1 - "Plasmodium falciparum - changes under treatment" : Eine lichtmikroskopische Studie morphologischer Änderungen von Plasmodium falciparum unter Therapie T1 - "Plasmodium falciparum - changes under treatment" : A light microscopic study of morphological changes from Plasmodium falciparum under treatment N2 - Die Hälfte der Weltbevölkerung lebt mit dem Risiko, an einer schweren Malaria tropica zu erkranken. Zunehmende Resistenzen von Plasmodium falciparum gegen gängige Therapeutika erschweren eine Behandlung, und es existiert keine Möglichkeit frühzeitig die Wirksamkeit der angewandten Medikation festzustellen. Die Bestimmung der Parasitämie als einzig verfügbarer Parameter kann auch bei erfolgreicher Therapie noch über den ersten Tag ansteigen. Das Ziel dieser Studie war, lichtmikroskopische Parameter zu finden, mit denen der Erfolg einer Therapie frühzeitig festgestellt werden kann. So wurden im Rahmen einer Fallstudie die Plasmodien eines an einer schweren Malaria tropica erkrankten Patienten auf morphologische Veränderungen im Verlauf der Chinin-Therapie untersucht. Die Beurteilung der Plasmodien erfolgte durch eine Einteilung nach ihrer Lage im Erythrozyten und der Kern-Plasma-Relation der Ringformen, anschliessend wurden die Ergebnisse durch eine Vermessung der Plasmodien am Computer verifiziert. Es zeigte sich, dass ein Therapieerfolg anhand der Veränderung in der Morphologie der Ringformen bereits in den ersten Stunden nach Therapiebeginn festgestellt werden kann. So lässt sich innerhalb der ersten drei Stunden ein Wechsel von kleinen Ringformen mit dünnem, homogenem Zytoplasmaband zu vergrösserten Ringformen mit einem verbreiterten und inhomogenen Zytoplasma finden. Im weiteren konnten ab der 7. Therapiestunde eine zunehmende Lageveränderungen der Plasmodien im Erythrozyten aufgezeigt werden. So waren ab diesem Zeitpunkt zunehmend Plasmodien, die die Erythrozyten-Membran hervorwölben (Arbeitstitel „Accentué“-Formen), im peripheren Blutausstrich des Patienten zu sehen. Dass die Änderung der Kern-Plasma-Relation der Ringformen ursächlich einer direkten Medikamentenwirkung zuzuschreiben sind, konnte in einem abschliessenden „in vitro“-Studienteil gezeigt werden, in welchem Plasmodien-Kulturen unter Chinin-Einfluss mit Kontrollkulturen ohne Medikamenteneinfluss verglichen wurden. N2 - This case study examines early morphological changes of Plasmodium falciparum under treatment, visible by light microscopy. A transition from small thin ring shapes to thick rings during the early hours of treatment could be demonstrated, as well as an increase in erythrocyte surface distorsion by the plasmodia, beginning after 7 hours of treatment. These findings could help to recognise resistances to medication within hours of beginning treatment and may save crucial time for patients. KW - Malaria tropica KW - Plasmodium falciparum KW - Morphologie KW - Therapie KW - Änderung KW - plasmodium falciparum KW - treatment KW - morphology KW - changes Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76597 ER - TY - JOUR A1 - Güder, Gülmisal A1 - Brenner, Susanne A1 - Angermann, Christiane E. A1 - Ertl, Georg A1 - Held, Matthias A1 - Sachs, Alfred P. A1 - Lammers, Jan Willem A1 - Zanen, Peter A1 - Hoes, Arno W. A1 - Störk, Stefan A1 - Rutten, Frans H. T1 - "GOLD or lower limit of normal definition? a comparison with expert-based diagnosis of chronic obstructive pulmonary disease in a prospective cohort-study" N2 - Background: The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed postbronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7. Agedependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative. We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis. Methods: In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner’s diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years. Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated. The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography. Results: Compared to the expert panel diagnosis, ‘GOLD-COPD’ misclassified 69 (28%) patients, and the three LLNs misclassified 114 (46%), 96 (39%), and 98 (40%) patients, respectively. The GOLD classification led to more false positives, the LLNs to more false negative diagnoses. The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 % predicted, and the residual volume/total lung capacity ratio (RV/TLC). Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50% of the number of misdiagnoses. The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN. Conclusions: GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis. Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice. KW - Medizin KW - COPD diagnosis KW - lower limit of normal KW - GOLD KW - validation Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75193 ER -