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 -
TY - JOUR
A1 - Meule, Adrian
A1 - Beck Teran, Carina
A1 - Berker, Jasmin
A1 - Gründel, Tilman
A1 - Mayerhofer, Martina
A1 - Platte, Petra
T1 - "On the differentiation between trait and state food craving: Half-year retest-reliability of the Food Cravings Questionnaire-Trait-reduced (FCQ-T-r) and the Food Cravings Questionnaire-State (FCQ-S)"
N2 - Background: Food craving refers to an intense desire to consume a specific food. The Food Cravings Questionnaires (FCQs) assess food cravings on a trait and a state level.
Method: The current study examined half-year retest-reliability of the Food Cravings Questionnaire-Trait-reduced (FCQ-T-r) and the Food Cravings Questionnaire-State (FCQ-S) and reports associations with current food deprivation in female students.
Results: The FCQ-T-r had higher retest-reliability (rtt = .74) than the FCQ-S (rtt = .39). Although trait food craving was correlated with state food craving, it was unaffected by current food deprivation.
Conclusions: Although state and trait food craving are interdependent, the FCQs are able to differentiate between the two. As scores of the FCQ-T-r represent a stable trait, but are also sensitive to changes in eating behavior, they may be useful for the investigation of the course of eating disorders and obesity.
KW - Food craving
KW - Food Cravings Questionnaires
KW - Retest-reliability
KW - University students
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110585
ER -
TY - JOUR
A1 - Buder, Kristina
A1 - Lapa, Constantin
A1 - Kreissl, Michael C.
A1 - Schirbel, Andreas
A1 - Herrmann, Ken
A1 - Schnack, Alexander
A1 - Bröcker, Eva-Bettina
A1 - Goebeler, Matthias
A1 - Buck, Andreas K.
A1 - Becker, Jürgen C.
T1 - "Somatostatin receptor expression in Merkel cell carcinoma as target for molecular imaging"
N2 - Background
Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm with increasing incidence, aggressive behavior and poor prognosis. Somatostatin receptors (SSTR) are expressed in MCC and represent a potential target for both imaging and treatment.
Methods
To non-invasively assess SSTR expression in MCC using PET and the radiotracers [68Ga]DOTA-D-Phe1-Tyr3-octreotide (DOTATOC) or -octreotate (DOTATATE) as surrogate for tumor burden. In 24 patients with histologically proven MCC SSTR-PET was performed and compared to results of computed tomography (CT).
Results
SSTR-PET detected primary and metastatic MCC lesions. On a patient-based analysis, sensitivity of SSTR-PET was 73% for nodal metastases, 100% for bone, and 67% for soft-tissue metastases, respectively. Notably, brain metastases were initially detected by SSTR-PET in 2 patients, whereas liver and lung metastases were diagnosed exclusively by CT. SSTR-PET showed concordance to CT results in 20 out of 24 patients. Four patients (17%) were up-staged due to SSTR-PET and patient management was changed in 3 patients (13%).
Conclusion
SSTR-PET showed high sensitivity for imaging bone, soft tissue and brain metastases, and particularly in combination with CT had a significant impact on clinical stage and patient management.
KW - Merkel cell carcinoma
KW - Molecular imaging
KW - Somatostatin receptor expression
KW - Positron emission tomography
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110326
ER -
TY - JOUR
A1 - Steinert, Andre F.
A1 - Rudert, Maximilian
A1 - Sieker, Jakob T.
T1 - "Symptomatic loosening of a total knee arthroplasty caused by a tibial chondrosarcoma – a case report"
N2 - Premature implant loosening following total knee arthroplasty (TKA) can have several causes. In this article we report on a rare case of a 74 year old male patient suffering tibial component loosening 14 month after primary TKA. The patient did neither have any malignancies nor joint arthroplasty before. Upon clinical examination the range of motion in the diseased knee was painfully restricted to 80° of knee flexion, with the patient increasingly suffering sleeping and resting pain, and also at weight bearing. In standard radiographs, loosening of the TKA due to a large osteolysis at the tibial component was evident. Local computed tomography (CT) of the right knee revealed loosening of the tibial component due to a presumably malign bone tumor. For determination of the final diagnosis a representative biopsy of the tumor was taken by open surgery prior to the tumor resection. Histopathologic evaluation of the biopsy revealed a periprosthetic myxoid chondrosarcoma of the proximal tibia. Pre-operative staging examination included CT scans of lung and abdomen, as well as a bone scintigraphy which revealed no signs of tumor metastasis in the body. Surgical management comprised wide tumor resection and implantation of a hinged tumor knee arthroplasty with replacements of the distal femur and proximal tibia, as well as a patella tendon replacement using a synthetic ligament. Revision surgery was necessary twice due to impaired wound healing and critical soft tissue coverage, and treatment included a gastrocnemius muscle flap with skin mesh graft covering. Unfortunately long-term follow-up examinations could not be obtained, as the patient deceased due to an alveolitis during rehabilitation. In summary, the specifics of this rare case of aseptic TKA loosening, and the unusual circumstances of chondrosarcoma diagnosis and treatment are informative for those providing surgical treatment of similar cases.
KW - Total knee arthroplasty
KW - Bone tumor
KW - Chondrosarcoma
KW - Aseptic loosening
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110341
ER -
TY - JOUR
A1 - Kestler, Thomas
A1 - Lucca, Juan Bautista
A1 - Krause, Silvana
T1 - 'Break-In Parties' and Changing Patterns of Democracy in Latin America
JF - Brazilian Political Science Review
N2 - Although Lijphart's typology of consensus and majoritarian democracy can be regarded as the most widely used tool to classify democratic regimes, it has been rarely applied to Latin America so far. We try to fill this gap by adapting Lijphart's typological framework to the Latin American context in the following way. In contrast to previous studies, we treat the type of democracy as an independent variable and include informal factors such as clientelism or informal employment in our assessment of democratic patterns. On this basis, we aim to answer the following questions. First, how did the patterns of democracy evolve in Latin America over the two decades between 1990 and 2010 and what kind of differences can be observed in the region? Second, what are the institutional determinants of the observed changes? We focus on the emergence of new parties because of their strong impact on the first dimension of Lijphart's typology. From our observations we draw the following tentative conclusions: If strong new parties established themselves in the party system but failed to gain the presidency, they pushed the system towards consensualism. Conversely, new parties that gained the presidency produced more majoritarian traits.
KW - break-in parties
KW - types of government
KW - Latin America
KW - democracy
KW - informality
Y1 - 2016
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171333
VL - 10
IS - 1
ER -
TY - JOUR
A1 - Andres, Katharina
T1 - 'Fashion's Final Frontier': The Correlation of Gender Roles and Fashion in Star Trek
JF - Culture Unbound
N2 - Since its creation in 1966, Star Trek has been a dominant part of popular culture and as thus served as the source for many cultural references. Star Trek’s creator Gene Roddenberry wanted to realize his vision of a utopia but at the same time, he used the futuristic setting of the show to comment on the present time, on actual social and political circumstances. This means that each series can be regarded as a mirror image of the time in which it was created. The clothing of the characters in the different series is one part of that image. The uniforms of The Original Se-ries show influences of the 1960s pop art movement as well as the mini-skirt trend that experienced its peak in that decade. In the course of almost 40 years, howev-er, many things changed. In the 1990s, in Deep Space Nine and Voyager, a unisex uniform replaced the mini-dresses, with few exceptions; the colorful shirts gave way to ones that were mostly black. This trend continues into the new century. This essay interprets the evolution of the female officers’ uniforms from femi-nized dresses to androgynous clothing over the development of the series as a reflection of the change of gender roles in contemporary American society. The general functions of the female characters’ uniforms are the central object of its analysis while the few, but noteworthy exceptions to this pattern are given specif-ic attention. Finally, one of the most intriguing lines of enquiry is, how the pre-quel series Enterprise, supposed to be set before The Original Series, but pro-duced and aired from 2001 to 2005, fits in the picture.
KW - Star Trek
KW - science fiction
KW - fashion
KW - women
KW - 1960s
KW - backlash
Y1 - 2013
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128827
VL - 5
ER -
TY - JOUR
A1 - Bringmann, Gerhard
A1 - Ortmann, Thomas
A1 - Zagst, Rainer
A1 - Schoener, Bernd
A1 - Assi, Laurent Ake
A1 - Burschka, Christian
T1 - +/- Dioncophyllacine A, a naphthylisoquinoline alkaloid with a 4-methoxy substituent from the leaves of Triphyophyllum peltatum
N2 - The isolation and structure elucidation of rac-dioncophyllacine A from the leaves of Triphyophyllun peltatum, is described. Unlike all other naphthylisoquinoline alkaloids, this fully dehydrogenated representative has an additional methoxy group at C-4, the position of which is deduced from NOE results. Dioncophyllacine A has a 7,1' site of the biaryl axis, as in dioncophylline A. Its constitution is confirmed by an X-ray structure analysis, which shows that the crystalline form of this new alkaloid is racemic.
KW - Dioncophyllaceae
KW - Triphyophyllum peltaturn
KW - Dioncophyllaceae leaves
KW - (± )-dioncophyllacine A
KW - naphthylisoquinoline alkaloids
KW - structure elucidation
Y1 - 1992
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31873
ER -
TY - JOUR
A1 - Christl, Manfred
A1 - Schreck, Michael
T1 - 1,2,3,5,8,8a-Hexahydronaphthalin aus 1,2-Cyclohexadien
N2 - Reaktionen von 1,3-Butadien und einigen seiner Methylderivate mit 1a und 1- Methyl-1,2-cyclohexadien 1b sowie den Übergang der [2 + 2]-Cycloaddukte 2 und 3 in das bisher unbekannte 1,2,3,5,8,8a-HexahydronaphthaJin 4a und einige seiner Methylderivate
KW - Chemie
KW - Butadien
Y1 - 1987
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31656
ER -
TY - JOUR
A1 - Christl, Manfred
A1 - Braun, Martin
A1 - Müller, Germar
T1 - 1,2,4-Cyclohexatriene, an Isobenzene, and Bicyclo[4.4.0)deca-1,3,5,7,8-pentaene, an Isonaphthalene: Generation and Trapping Reactions
N2 - No abstract available
KW - Organische Chemie
Y1 - 1992
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58639
ER -
TY - JOUR
A1 - Braunschweig, Holger
A1 - Damme, Alexander
T1 - 1,2-Bis(dimethylamino)-1,2-bis(2,4,6-triisopropylphenyl)diborane(4)
N2 - In the molecular structure of the title compound, C34H58B2N2, each B atom of the diborane(4) is connected to one dimethylamino group and one Tip ligand (Tip = 2,4,6-triisopropylphenyl). These findings indicate that the increased steric demand of the Tip groups exerts influence solely on the B—B separation but not on the overall geometry of the title compound.
KW - Anorganische Chemie
Y1 - 2010
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67639
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 - JOUR
A1 - Zapf, Ludwig
A1 - Radius, Udo
A1 - Finze, Maik
T1 - 1,3-bis(tricyanoborane)imidazoline-2-ylidenate anion - a ditopic dianionic N-heterocyclic carbene ligand
JF - Angewandte Chemie International Edition
N2 - The 1,3-bis(tricyanoborane)imidazolate anion 1 was obtained in high yield from lithium imidazolate and B(CN)\(_3\)−pyridine adduct. Anion 1 is chemically very robust and thus allowed the isolation of the corresponding H\(_5\)O\(_2\)\(^+\) salt. Furthermore, monoanion 1 served as starting species for the novel dianionic N-heterocyclic carbene (NHC), 1,3-bis(tricyanoborane)imidazoline-2-ylidenate anion 3 that acts as ditopic ligand via the carbene center and the cyano groups at boron. First reactions of this new NHC 3 with methyl iodide, elemental selenium, and [Ni(CO)\(_4\)] led to the methylated imidazolate ion 4, the dianionic selenium adduct 5, and the dianionic nickel tricarbonyl complex 6. These NHC derivatives provide a first insight into the electronic and steric properties of the dianionic NHC 3. Especially the combination of properties, such as double negative charge, different coordination sites, large buried volume and good σ-donor and π-acceptor ability, make NHC 3 a unique and promising ligand and building block.
KW - inorganic chemistry
KW - N-heterocyclic carbene
KW - anioniccarbene
KW - boron
KW - cyanoborate
KW - imidazolate
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256498
VL - 60
IS - 33
ER -
TY - JOUR
A1 - Kanal, Florian
A1 - Keiber, Sabine
A1 - Eck, Reiner
A1 - Brixner, Tobias
T1 - 100-kHz shot-to-shot broadband data acquisition for high-repetition-rate pump–probe spectroscopy
N2 - Shot-to-shot broadband detection is common in ultrafast pump–probe spectroscopy. Taking advantage of the intensity correlation of subsequent laser pulses improves the signal-to-noise ratio. Finite data readout times of CCD chips in the employed spectrometer and the maximum available speed of mechanical pump-beam choppers typically limit this approach to lasers with repetition rates of a few kHz. For high-repetition (≥ 100 kHz) systems, one typically averages over a larger number of laser shots leading to inferior signal-to-noise ratios or longer measurement times. Here we demonstrate broadband shot-to-shot detection in transient absorption spectroscopy with a 100-kHz femtosecond laser system. This is made possible using a home-built high-speed chopper with external laser synchronization and a fast CCD line camera. Shot-to-shot detection can reduce the data acquisition time by two orders of magnitude compared to few-kHz lasers while keeping the same signal-to-noise ratio.
KW - cameras
KW - CCD
KW - charge-coupled device
KW - modulators
KW - time-resolved spectroscopy
KW - ultrafast spectroscopy
KW - ultrafast measurements
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112853
ER -
TY - JOUR
A1 - Mützel, Carina
A1 - Farrell, Jeffrey M.
A1 - Shoyama, Kazutaka
A1 - Würthner, Frank
T1 - 12b,24b-Diborahexabenzo[a,c,fg,l,n,qr]pentacene: A Low-LUMO Boron-Doped Polycyclic Aromatic Hydrocarbon
JF - Angewandte Chemie International Edition
N2 - Herein we devise and execute a new synthesis of a pristine boron-doped nanographene. Our target boron-doped nanographene was designed based on DFT calculations to possess a low LUMO energy level and a narrow band gap derived from its precise geometry and B-doping arrangement. Our synthesis of this target, a doubly B-doped hexabenzopentacene (B\(_{2}\)-HBP), employs six net C−H borylations of an alkene, comprising consecutive hydroboration/electrophilic borylation/dehydrogenation and BBr\(_{3}\)/AlCl\(_{3}\)/2,6-dichloropyridine-mediated C−H borylation steps. As predicted by our calculations, B\(_{2}\)-HBP absorbs strongly in the visible region and emits in the NIR up to 1150 nm in o-dichlorobenzene solutions. Furthermore, B\(_{2}\)-HBP possesses a very low LUMO level, showing two reversible reductions at −1.00 V and −1.17 V vs. Fc\(^{+}\)/Fc. Our methodology is surprisingly selective despite its implementation of unfunctionalized precursors and offers a new approach to the synthesis of pristine B-doped polycyclic aromatic hydrocarbons.
KW - aromaticity
KW - polycycles
KW - pentacene
KW - near infrared emitter
KW - boron
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318808
VL - 61
IS - 8
ER -
TY - JOUR
A1 - Falk, W.
A1 - Ulrichs, Karin
A1 - Müller-Ruchholtz, W.
T1 - 15-Deoxyspergualin (a new guanidine-like drug) blocks T lymphocyte proliferation
N2 - No abstract available
KW - Chirurgie
Y1 - 1987
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-45215
ER -
TY - JOUR
A1 - Zhou, Xiang
A1 - Dierks, Alexander
A1 - Kertels, Olivia
A1 - Kircher, Malte
A1 - Schirbel, Andreas
A1 - Samnick, Samuel
A1 - Buck, Andreas K.
A1 - Knorz, Sebastian
A1 - Böckle, David
A1 - Scheller, Lukas
A1 - Messerschmidt, Janin
A1 - Barakat, Mohammad
A1 - Kortüm, K. Martin
A1 - Rasche, Leo
A1 - Einsele, Hermann
A1 - Lapa, Constantin
T1 - 18F-FDG, 11C-Methionine, and 68Ga-Pentixafor PET/CT in patients with smoldering multiple myeloma: imaging pattern and clinical features
JF - Cancers
N2 - This study aimed to explore the correlation between imaging patterns and clinical features in patients with smoldering multiple myeloma (SMM) who simultaneously underwent 18F-FDG, 11C-Methionine, and 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT). We retrieved and analyzed clinical characteristics and PET imaging data of 10 patients with SMM. We found a significant correlation between bone marrow (BM) plasma cell (PC) infiltration and mean standardized uptake values (SUV\(_{mean}\)) of lumbar vertebrae L2-L4 on 11C-Methionine PET/CT scans (r = 0.676, p = 0.031) and 68Ga-Pentixafor PET/CT scans (r = 0.839, p = 0.002). However, there was no significant correlation between BM involvement and SUV\(_{mean}\) of lumbar vertebrae L2-L4 on 18F-FDG PET/CT scans (r = 0.558, p = 0.093). Similarly, mean target-to-background ratios (TBR\(_{mean}\)) of lumbar vertebrae L2-L4 also correlated with bone marrow plasma cell (BMPC) infiltration in 11C-Methionine PET/CT (r = 0.789, p = 0.007) and 68Ga-Pentixafor PET/CT (r = 0.724, p = 0.018) PET/CT. In contrast, we did not observe a significant correlation between BMPC infiltration rate and TBR\(_{mean}\) in 18F-FDG PET/CT (r = 0.355, p = 0.313). Additionally, on 11C-Methionine PET/CT scans, we found a significant correlation between BMPC infiltration and TBR\(_{max}\) of lumbar vertebrae L2-L4 (r = 0.642, p = 0.045). In conclusion, 11C-Methionine and 68Ga-Pentixafor PET/CT demonstrate higher sensitivity than 18F-FDG PET/CT in detecting BM involvement in SMM.
KW - 18F-FDG PET/CT
KW - 11C-Methionine PET/CT
KW - 68Ga-Pentixafor PET/CT
KW - smoldering myeloma
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211240
SN - 2072-6694
VL - 12
IS - 8
ER -
TY - JOUR
A1 - Lückerath, Katharina
A1 - Lapa, Constantin
A1 - Malzahn, Uwe
A1 - Samnick, Samuel
A1 - Einsele, Herrmann
A1 - Buck, Andreas K.
A1 - Herrmann, Ken
A1 - Knop, Stefan
T1 - 18FDG-PET/CT for prognostic stratification of patients with multiple myeloma relapse after stem cell transplantation
N2 - The aim of this study was to investigate the prognostic value of 18F-fluoro-deoxyglucose positron emission tomography–computed tomography (18F-FDG-PET/CT) in 37 patients with a history of multiple myeloma (MM) and suspected or confirmed recurrence after stem cell transplantation (SCT). All patients had been heavily pre-treated. Time to progression (TTP) and overall survival (OS) were correlated to a number of different PET-derived as well as clinical parameters. Impact on patient management was assessed.
Absence of FDG-avid MM foci was a positive prognostic factor for both TTP and OS (p<0.01). Presence of >10 focal lesions correlated with both TTP (p<0.01) and OS (p<0.05). Interestingly, presence of >10 lesions in the appendicular skeleton proved to have the strongest association with disease progression. Intensity of glucose uptake and presence of extramedullary disease were associated with shorter TTP (p=0.037 and p=0.049, respectively). Manifestations in soft tissue structures turned out to be a strong negative predictor for both, TTP and OS (p<0.01, respectively). PET resulted in a change of management in 30% of patients.
Our data underline the prognostic value of 18F-FDG-PET/CT in MM patients also in the setting of post-SCT relapse. PET/CT has a significant impact on patient management.
KW - 18FDG-PET/CT
KW - Multiple myeloma
KW - molecular imaging
KW - FDG-PET/CT
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-113107
ER -
TY - JOUR
A1 - Plieger, Tanja
A1 - Wolf, Matthias
T1 - 18S and ITS2 rDNA sequence-structure phylogeny of Prototheca (Chlorophyta, Trebouxiophyceae)
JF - Biologia
N2 - Protothecosis is an infectious disease caused by organisms currently classified within the green algal genus Prototheca. The disease can manifest as cutaneous lesions, olecranon bursitis or disseminated or systemic infections in both immunocompetent and immunosuppressed patients. Concerning diagnostics, taxonomic validity is important. Prototheca, closely related to the Chlorella species complex, is known to be polyphyletic, branching with Auxenochlorella and Helicosporidium. The phylogeny of Prototheca was discussed and revisited several times in the last decade; new species have been described. Phylogenetic analyses were performed using ribosomal DNA (rDNA) and partial mitochondrial cytochrome b (cytb) sequence data. In this work we use Internal Transcribed Spacer 2 (ITS2) as well as 18S rDNA data. However, for the first time, we reconstruct phylogenetic relationships of Prototheca using primary sequence and RNA secondary structure information simultaneously, a concept shown to increase robustness and accuracy of phylogenetic tree estimation. Using encoded sequence-structure data, Neighbor-Joining, Maximum-Parsimony and Maximum-Likelihood methods yielded well-supported trees in agreement with other trees calculated on rDNA; but differ in several aspects from trees using cytb as a phylogenetic marker. ITS2 secondary structures of Prototheca sequences are in agreement with the well-known common core structure of eukaryotes but show unusual differences in their helix lengths. An elongation of the fourth helix of some species seems to have occurred independently in the course of evolution.
KW - secondary structure
KW - 18S
KW - ITS2
KW - phylogeny
KW - prototheca
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-269897
SN - 1336-9563
VL - 77
IS - 2
ER -
TY - JOUR
A1 - Rackevei, Antonia S.
A1 - Karnkowska, Anna
A1 - Wolf, Matthias
T1 - 18S rDNA sequence–structure phylogeny of the Euglenophyceae (Euglenozoa, Euglenida)
JF - Journal of Eukaryotic Microbiology
N2 - The phylogeny of Euglenophyceae (Euglenozoa, Euglenida) has been discussed for decades with new genera being described in the last few years. In this study, we reconstruct a phylogeny using 18S rDNA sequence and structural data simultaneously. Using homology modeling, individual secondary structures were predicted. Sequence–structure data are encoded and automatically aligned. Here, we present a sequence–structure neighbor‐joining tree of more than 300 taxa classified as Euglenophyceae. Profile neighbor‐joining was used to resolve the basal branching pattern. Neighbor‐joining, maximum parsimony, and maximum likelihood analyses were performed using sequence–structure information for manually chosen subsets. All analyses supported the monophyly of Eutreptiella, Discoplastis, Lepocinclis, Strombomonas, Cryptoglena, Monomorphina, Euglenaria, and Colacium. Well‐supported topologies were generally consistent with previous studies using a combined dataset of genetic markers. Our study supports the simultaneous use of sequence and structural data to reconstruct more accurate and robust trees. The average bootstrap value is significantly higher than the average bootstrap value obtained from sequence‐only analyses, which is promising for resolving relationships between more closely related taxa.
KW - euglena
KW - euglenids
KW - phylogenetics
KW - secondary structure
Y1 - 2023
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311896
VL - 70
IS - 2
ER -
TY - JOUR
A1 - Wondergem, Marielle J.
A1 - Herrmann, Ken
A1 - Syrbu, Sergei
A1 - Zijlstra, Josée M.
A1 - Hoetjes, Nikie
A1 - Hoekstra, Otto S.
A1 - Cillessen, Saskia A. G. M.
A1 - Moesbergen, Laura M.
A1 - Buck, Andreas K.
A1 - Vose, Julie M.
A1 - Juweid, Malik E.
T1 - 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair
JF - EJNMMI Research
N2 - BACKGROUND:
We observed a disproportional 18 F-fluorothymidine (F-FLT) uptake in follicular lymphoma (FL) relative to its low cell proliferation. We tested the hypothesis that the 'excess' uptake of 18 F-FLT in FL is related to error-prone DNA repair and investigated whether this also contributes to 18 F-FLT uptake in diffuse large B cell lymphoma (DLBCL).
METHODS:
We performed immunohistochemical stainings to assess the pure DNA replication marker MIB-1 as well as markers of both DNA replication and repair like PCNA, TK-1 and RPA1 on lymph node biopsies of 27 FLs and 35 DLBCLs. In 7 FL and 15 DLBCL patients, 18 F-FLT-PET had been performed.
RESULTS:
18 F-FLT uptake was lower in FL than in DLBCL (median SUVmax 5.7 vs. 8.9, p = 0,004), but the ratio of 18 F-FLT-SUVmax to percentage of MIB-1 positive cells was significantly higher in FL compared with DLBCL (p = 0.001). The median percentage of MIB-1 positive cells was 10% (range, 10% to 20%) in FL and 70% (40% to 80%) in DLBCL. In contrast, the median percentages of PCNA, TK-1 and RPA1 positive cells were 90% (range, 80 to 100), 90% (80 to 100) and 100% (80 to 100) in FL versus 90% (60 to 100), 90% (60 to 100) and 100% (80 to 100) in DLBCL, respectively.
CONCLUSIONS:
This is the first demonstration of a striking discordance between 18 F-FLT uptake in FL and tumour cell proliferation. High expression of DNA replication and repair markers compared with the pure proliferation marker MIB-1 in FL suggests that this discordance might be due to error-prone DNA repair. While DNA repair-related 18 F-FLT uptake considerably contributes to 18 F-FLT uptake in FL, its contribution to 18 F-FLT uptake in highly proliferative DLBCL is small. This apparently high contribution of DNA repair to the 18 F-FLT signal in FL may hamper studies where 18 F-FLT is used to assess response to cytostatic therapy or to distinguish between FL and transformed lymphoma.
KW - 18-F-fluorothymidine uptake
KW - positron emission tomography
KW - follicular lymphoma
KW - non-Hodgkin's lymphoma
KW - DNA repair
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121233
VL - 4
ER -
TY - JOUR
A1 - Lohse, M. J.
A1 - Klotz, Karl-Norbert
A1 - Diekmann, E.
A1 - Friedrich, K.
A1 - Schwabe, U.
T1 - 2',3'-Dideoxy-N\(^6\)-cyclohexyladenosine: an adenosine derivative with antagonist properties at adenosine receptors
N2 - Tbe 2',3'-dideoxy analogue of the potent A\(_1\) receptor agonist, N\(^6\)-cyclohexyladenosine (CHA), was synthesized as a potential antagonist for the A\(_1\) adenosine receptor. In sturlies on adenylate cyclase 2',3'-dideoxy-N\(^6\)-cyclohexyladenosine (ddCHA) did not show agonist properties at A\(_1\) or at A\(_2\) receptors. However, it antagonized the inhibition by R-PIA of adenylate cyclase activity of fat cell membranes via A\(_1\) receptors with a K\(_i\) value of 13 \(\mu\)M. ddCHA competed for the binding of the selective A1 receptor antagonist, [\(^3\) HJ8-cyclopentyl-1,3-dipropylxantbine ([\(^3\)H]DPCPX), to rat brain membranes with a K\(_i\) value of 4.8 \(\mu\)M; GTP did not affect the competition curve. In contrast to the marked stereoselectivity of the A\(_1\) receptor for the cx- and the natural ß-anomer of adenosine, the cx-anomer of ddCHA showed a comparable affinity for the A\(_1\) receptor (K\(_i\) value 13.9 \8\mu\)M). These data indicate that the 2'- and 3'-hydroxy groups of adenosine and its derivatives are required foragonist activity at and high affinity binding to A\(_1\) adenosine receptors and for the distinction between the cx- and ß-forms.
KW - Toxikologie
KW - Adenosine receptors
KW - Adenylate cyclase
KW - Adenosine receptor antagonists
Y1 - 1988
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60282
ER -
TY - JOUR
A1 - Liu, Siyuan
A1 - Légaré, Marc-André
A1 - Seufert, Jens
A1 - Prieschl, Dominic
A1 - Rempel, Anna
A1 - Englert, Lukas
A1 - Dellermann, Theresa
A1 - Paprocki, Valerie
A1 - Stoy, Andreas
A1 - Braunschweig, Holger
T1 - 2,2′-Bipyridyl as a Redox-Active Borylene Abstraction Agent
JF - Inorganic Chemistry
N2 - 2,2′-Bipyridyl is shown to spontaneously abstract a borylene fragment (R–B:) from various hypovalent boron compounds. This process is a redox reaction in which the bipyridine is reduced and becomes a dianionic substituent bound to boron through its two nitrogen atoms. Various transition metal–borylene complexes and diboranes, as a well as a diborene, take part in this reaction. In the latter case, our results show an intriguing example of the homolytic cleavage of a B═B double bond.
KW - Borylene
KW - Heterocycles
KW - Boron
KW - Main-group chemistry
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215595
N1 - This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in Inorganic Chemistry, copyright © American Chemical Society after peer review. To access the final edited and published work see https://doi.org/10.1021/acs.inorgchem.0c01383.
VL - 59
IS - 15
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 - Gleiter, Rolf
A1 - Bischof, Peter
A1 - Gubernator, Klaus
A1 - Christl, Manfred
A1 - Schwager, Luis
A1 - Vogel, Pierre
T1 - 2,3-Bis(methylene)bicyclo[2.1.1]hexane and 3,4-Bis(methylene)tricyclo[3.1.0.0\(^{2,6}\)]hexane : Interaction between a π System and a Cyclobutane or Bicyclobutane Moiety
N2 - The He (I) photoelectron spectra of 2-bicyclo[2.1.l]hexene (1), 2,3-bis(methylene)bicyclo[2.1.l]hexane (3), and 3,4-bis(methylene)tricyclo[3.l.O.0\(^{2.6}\)]hexane (4) have been investigated. The assignment given is based on a ZDO model and semiempirical calculations. Tagether with the PE data of benzvalene (2), the reported data allow a comparison between 1-2 and 3-4. This yields a measure of the interactions between 8 cyclobutane or 8 bicyclobutane moiety and a double bond system within a ZDO model. The resonance integral found in the case of 1 and 3 amounts to -1.9 eV, that for 2 and 4, to -2.3 eV. The investigations furthermore reveal that the electronic factors which contribute to the higher reactivity of the bicyclobutane compounds amount to 5 kcal/mol.
KW - Chemie
Y1 - 1985
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31845
ER -
TY - JOUR
A1 - Kole, Goutam Kumar
A1 - Merz, Julia
A1 - Amar, Anissa
A1 - Fontaine, Bruno
A1 - Boucekkine, Abdou
A1 - Nitsch, Jörn
A1 - Lorenzen, Sabine
A1 - Friedrich, Alexandra
A1 - Krummenacher, Ivo
A1 - Košćak, Marta
A1 - Braunschweig, Holger
A1 - Piantanida, Ivo
A1 - Halet, Jean-François
A1 - Müller-Buschbaum, Klaus
A1 - Marder, Todd B.
T1 - 2- and 2,7-substituted para-N-methylpyridinium pyrenes: syntheses, molecular and electronic structures, photophysical, electrochemical, and spectroelectrochemical properties and binding to double-stranded (ds) DNA
JF - Chemistry - A European Journal
N2 - Two N-methylpyridinium compounds and analogous N-protonated salts of 2- and 2,7-substituted 4-pyridyl-pyrene compounds were synthesised and their crystal structures, photophysical properties both in solution and in the solid state, electrochemical and spectroelectrochemical properties were studied. Upon methylation or protonation, the emission maxima are significantly bathochromically shifted compared to the neutral compounds, although the absorption maxima remain almost unchanged. As a result, the cationic compounds show very large apparent Stokes shifts of up to 7200 cm\(^{-1}\). The N-methylpyridinium compounds have a single reduction at ca. −1.5 V vs. Fc/Fc\(^+\) in MeCN. While the reduction process was reversible for the 2,7-disubstituted compound, it was irreversible for the mono-substituted one. Experimental findings are complemented by DFT and TD-DFT calculations. Furthermore, the N-methylpyridinium compounds show strong interactions with calf thymus (ct)-DNA, presumably by intercalation, which paves the way for further applications of these multi-functional compounds as potential DNA-bioactive agents.
KW - inorganic chemistry
KW - viologens
KW - chromophores
KW - luminescent
KW - pyrenes
KW - pyridinium
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256642
VL - 27
IS - 8
ER -
TY - JOUR
A1 - Cristalli, G.
A1 - Eleuteri, A.
A1 - Vittori, S.
A1 - Volpini, R.
A1 - Lohse, M. J.
A1 - Klotz, Karl-Norbert
T1 - 2-Alkynyl derivatives of adenosine and adenosine-5'-N-ethyluronamides as selective agonists at A\(_2\) adenosine receptors
N2 - In the search for more selective A2-receptor agonists and on the basis that appropriate substitution at C2 is known to impart selectivity for A\(_2\) receptors, 2-alkynyladenosines 2a-d were resynthesized and evaluated in radioligand binding, adenylate cycla.se, and platelet aggregation studies. Binding of [\(^3\)H]NECA to A\(_2\) receptors of rat striatal membranes was inhibited by compounds 2a-d with K\(_i\) values ranging from 2.8 to 16.4 nM. 2-Alkynyladenosines also exhibited high-affmity binding at solubilized A\(_2\) receptors from human platelet membranes. Competition of 2-alkynyladenosines 2a-d for the antagonist radioligand [\(^3\)H]DPCPX and for the agonist [\(^3\)H]CCPA gave K\(_i\) values in the nanomolar range, and the compounds showed moderate A\(_2\) selectivity. In order to improve this selectivity, the correaponding 2-alkynyl derivatives of adenosine-5'-N-ethyluronamide 8a-d were synthesized and tested. A\(_1\) expected, the 5'-N-ethyluronamide derivatives retained the A\(_2\) affinity whereas the A\(_1\) affinity was attenuated, resulting in an up to 10-fold increase in A\(_2\) selectivity. A similar patternwas observed in adenylate cyclase assays andin platelet aggregation studies. A 30- to 45-fold selectivity for platelet A\(_2\) receptors compared to A\(_1\) receptors was found for compounds 8a-c in adenylate cyclase studies.
KW - Toxikologie
Y1 - 1992
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60412
ER -
TY - JOUR
A1 - Klotz, Karl-Norbert
A1 - Lohse, M. J.
A1 - Schwabe, U.
A1 - Cristalli, G.
A1 - Vittori, S.
A1 - Grifantini, M.
T1 - 2-Chloro-N\(^6\)-[\(^3\)H]cyclopentyladenosine ([\(^3\)H]CCPA) - a high affinity agonist radioligand for A\(_1\) adenosine receptors
N2 - The tritiated analogue of 2-chloro-N6-cyclopentyladenosine (CCPA), an adenosine derivative with subnanomolar affinity and a 10000-fold selectivity for A1 adenosine receptors, has been examined as a new agonist radioligand. [3H]CCP A was prepared with a specifi.c radioactivity of 1.58 TBqjmmol ( 43 Ci/mmol) and bound in a reversible manner to A1 receptors from rat brain membranes with a high affinity K0 -value of 0.2 nmol/1. In the presence of GTP a K0 -value of 13 nmol/1 was determined for the low affinity state for agonist binding. Competition of several adenosine receptor agonists and antagonists for [3H]CCPA binding to rat brain membranes confrrmed binding to an A1 receptor. Solubilized A1 receptors bound [3H]CCPA with similar affinity for the high affinity state. At solubilized receptors a reduced association rate was observed in the presence of MgC12, as has been shown for the agonist [ 3H]N6-phenylisopropyladenosine ([3H]PIA). [3H]CCPA was also used for detection of A1 receptors in rat cardio myocyte membranes, a tissue with a very low receptor density. A K0 -value of 0.4 nmol/1 and a Bmax-value of 16 fmol/ mg protein was determined in these membranes. In human platelet membranes no specific binding of [3H]CCPA was measured at concentrations up to 400 nmoljl, indicating that A2 receptors did not bind [3H]CCPA. Based on the subnanomolar affinity and the high selectivity for A1 receptors [ 3H]CCPA proved to be a useful agonist radioligand for characterization of A 1 adenosine receptors also in tissues with very low receptor density.
KW - Toxikologie
KW - Adenosine receptors
KW - Radioligauds
KW - agonists
Y1 - 1989
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60328
ER -
TY - JOUR
A1 - Lohse, M. J.
A1 - Klotz, Karl-Norbert
A1 - Schwabe, U.
A1 - Cristalli, G.
A1 - Vittori, S.
A1 - Grifantini, M.
T1 - 2-Chloro-N\(^6\)-cyclopentyladenosine: a highly selective agonist at A\(_1\) adenosine receptors
N2 - 2-Chloro-N\(^6\)-cyclopentyladenosine (CCPA) was synthesized as a potential high affinity ligand for At adenosine receptors. Binding of [\(^3\)H]PIA to A1 receptors of rat brain membranes was inhibited by CCP A with a Ki-value of 0.4 nM, compared to a Ki-value of 0.8 nM for the parent compound N\(^6\)-cyclopentyladenosine (CPA). Binding of [\(^3\)H]NECA to A\(_2\) receptors of rat striatal membranes was inhibited with a Ki-value of 3900 nM, demonstrating an almost 10,000-fold A\(_1\)-selectivity of CCPA. CCP A inhibited the activity of rat fat cell membrane adenylate cyclase, a model for the A\(_1\) receptor, with an IC\(_{50}\)-value of 33 nM, and it stimulated the adenylate cyclase activity of human platelet membranes with an EC\(_{50}\)-value of 3500 nM. The more than 100-fold A\(_1\)-selectivity compares favourably with a 38-fold selectivity of CPA. Thus, CCPA is an agonist at A\(_1\) adenosine receptors with a 4-fold higher selectivity and 2-fold higher affinity than CPA, and a considerably higher selectivity than the standard At receptor agonist R-N\(^6\) -phenylisopropyladenosine (R-PIA). CCP A represents the agonist with the highest selectivity for A\(_1\) receptors reported so far.
KW - Toxikologie
KW - Adenosine receptors
KW - Adenylate cyclase
Y1 - 1988
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60279
ER -
TY - JOUR
A1 - Meyer, Malin Tordis
A1 - Watermann, Christoph
A1 - Dreyer, Thomas
A1 - Ergün, Süleyman
A1 - Karnati, Srikanth
T1 - 2021 update on diagnostic markers and translocation in salivary gland tumors
JF - International Journal of Molecular Sciences
N2 - Salivary gland tumors are a rare tumor entity within malignant tumors of all tissues. The most common are malignant mucoepidermoid carcinoma, adenoid cystic carcinoma, and acinic cell carcinoma. Pleomorphic adenoma is the most recurrent form of benign salivary gland tumor. Due to their low incidence rates and complex histological patterns, they are difficult to diagnose accurately. Malignant tumors of the salivary glands are challenging in terms of differentiation because of their variability in histochemistry and translocations. Therefore, the primary goal of the study was to review the current literature to identify the recent developments in histochemical diagnostics and translocations for differentiating salivary gland tumors.
KW - salivary gland tumors
KW - epithelial salivary gland
KW - adenoid cystic carcinoma (ACC)
KW - pleomorphic adenoma
KW - mucoepidermoid carcinoma
KW - diagnostic markers
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261057
SN - 1422-0067
VL - 22
IS - 13
ER -
TY - JOUR
A1 - Andelovic, Kristina
A1 - Winter, Patrick
A1 - Kampf, Thomas
A1 - Xu, Anton
A1 - Jakob, Peter Michael
A1 - Herold, Volker
A1 - Bauer, Wolfgang Rudolf
A1 - Zernecke, Alma
T1 - 2D Projection Maps of WSS and OSI Reveal Distinct Spatiotemporal Changes in Hemodynamics in the Murine Aorta during Ageing and Atherosclerosis
JF - Biomedicines
N2 - Growth, ageing and atherosclerotic plaque development alter the biomechanical forces acting on the vessel wall. However, monitoring the detailed local changes in wall shear stress (WSS) at distinct sites of the murine aortic arch over time has been challenging. Here, we studied the temporal and spatial changes in flow, WSS, oscillatory shear index (OSI) and elastic properties of healthy wildtype (WT, n = 5) and atherosclerotic apolipoprotein E-deficient (Apoe\(^{−/−}\), n = 6) mice during ageing and atherosclerosis using high-resolution 4D flow magnetic resonance imaging (MRI). Spatially resolved 2D projection maps of WSS and OSI of the complete aortic arch were generated, allowing the pixel-wise statistical analysis of inter- and intragroup hemodynamic changes over time and local correlations between WSS, pulse wave velocity (PWV), plaque and vessel wall characteristics. The study revealed converse differences of local hemodynamic profiles in healthy WT and atherosclerotic Apoe\(^{−/−}\) mice, and we identified the circumferential WSS as potential marker of plaque size and composition in advanced atherosclerosis and the radial strain as a potential marker for vascular elasticity. Two-dimensional (2D) projection maps of WSS and OSI, including statistical analysis provide a powerful tool to monitor local aortic hemodynamics during ageing and atherosclerosis. The correlation of spatially resolved hemodynamics and plaque characteristics could significantly improve our understanding of the impact of hemodynamics on atherosclerosis, which may be key to understand plaque progression towards vulnerability.
KW - atherosclerosis
KW - mouse
KW - 4D flow MRI
KW - aortic arch
KW - flow dynamics
KW - WSS
KW - mapping
KW - PWV
KW - plaque characteristics
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252164
SN - 2227-9059
VL - 9
IS - 12
ER -
TY - JOUR
A1 - Thurner, Annette
A1 - Augustin, Anne Marie
A1 - Bley, Thorsten Alexander
A1 - Kickuth, Ralph
T1 - 2D-perfusion angiography for intra-procedural endovascular treatment response assessment in chronic mesenteric ischemia: a feasibility study
JF - BMC Medical Imaging
N2 - Background
Endovascular revascularization has become the first-line treatment of chronic mesenteric ischemia (CMI). The qualitative visual analysis of digital subtraction angiography (DSA) is dependent on observer experience and prone to interpretation errors. We evaluate the feasibility of 2D-Perfusion Angiography (2D-PA) for objective, quantitative treatment response assessment in CMI.
Methods
49 revascularizations in 39 patients with imaging based evidence of mesenteric vascular occlusive disease and clinical signs of CMI were included in this retrospective study. To assess perfusion changes by 2D-PA, DSA-series were post-processed using a dedicated, commercially available software. Regions of interest (ROI) were placed in the pre- and post-stenotic artery segment. In aorto-ostial disease, the inflow ROI was positioned at the mesenteric artery orifice. The ratios outflow to inflow ROI for peak density (PD), time to peak and area-under-the-curve (AUC) were computed and compared pre- and post-interventionally. We graded motion artifacts by means of a four-point scale. Feasibility of 2D-PA and changes of flow parameters were evaluated.
Results
Motion artifacts due to a mobile vessel location beneath the diaphragm or within the mesenteric root, branch vessel superimposition and inadequate contrast enhancement at the inflow ROI during manually conducted DSA-series via selective catheters owing to steep vessel angulation, necessitated exclusion of 26 measurements from quantitative flow evaluation. The feasibility rate was 47%. In 23 technically feasible assessments, PD\(_{outflow}\)/PD\(_{inflow}\) increased by 65% (p < 0.001) and AUC\(_{outflow}\)/AUC\(_{inflow}\) increased by 85% (p < 0.001). The time to peak density values in the outflow ROI accelerated only minimally without reaching statistical significance. Age, BMI, target vessel (celiac trunk, SMA or IMA), stenosis location (ostial or truncal), calcification severity, plaque composition or the presence of a complex stenosis did not reach statistical significance in their distribution among the feasible and non-feasible group (p > 0.05).
Conclusions
Compared to other vascular territories and indications, the feasibility of 2D-PA in mesenteric revascularization for CMI was limited. Unfavorable anatomic conditions contributed to a high rate of inconclusive 2D-PA results.
KW - 2D-perfusion angiography
KW - chronic mesenteric ischemia
KW - endovascular treatment
KW - mesenteric stenting
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301131
VL - 22
ER -
TY - JOUR
A1 - Lanzendörfer, Franz
A1 - Christl, Manfred
T1 - 3,4-Bismethylentricyclo[3.1.0.02,6]hexan - Synthese und Diels-Alder-Addition an Tetracyanethylen
N2 - No abstract available
Y1 - 1983
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-30263
ER -
TY - JOUR
A1 - Grunz, Jan-Peter
A1 - Wenig, Andreas Max
A1 - Kunz, Andreas Steven
A1 - Veyhl-Wichmann, Maike
A1 - Schmitt, Rainer
A1 - Gietzen, Carsten Herbert
A1 - Pennig, Lenhard
A1 - Herz, Stefan
A1 - Ergün, Süleyman
A1 - Bley, Thorsten Alexander
A1 - Gassenmaier, Tobias
T1 - 3D cone-beam CT with a twin robotic x-ray system in elbow imaging: comparison of image quality to high-resolution multidetector CT
JF - European Radiology Experimental
N2 - Background
Elbow imaging is challenging with conventional multidetector computed tomography (MDCT), while cone-beam CT (CBCT) provides superior options. We compared intra-individually CBCT versus MDCT image quality in cadaveric elbows.
Methods
A twin robotic x-ray system with new CBCT mode and a high-resolution clinical MDCT were compared in 16 cadaveric elbows. Both systems were operated with a dedicated low-dose (LD) protocol (equivalent volume CT dose index [CTDI\(_{vol(16 cm)}\)] = 3.3 mGy) and a regular clinical scan dose (RD) protocol (CTDI\(_{vol(16 cm)}\) = 13.8 mGy). Image quality was evaluated by two radiologists (R1 and R2) on a seven-point Likert scale, and estimation of signal intensity in cancellous bone was conducted. Wilcoxon signed-rank tests and intraclass correlation coefficient (ICC) statistics were used.
Results
The CBCT prototype provided superior subjective image quality compared to MDCT scans (for RD, p ≤ 0.004; for LD, p ≤ 0.001). Image quality was rated very good or excellent in 100% of the cases by both readers for RD CBCT, 100% (R1) and 93.8% (R2) for LD CBCT, 62.6% and 43.8% for RD MDCT, and 0.0% and 0.0% for LD MDCT. Single-measure ICC was 0.95 (95% confidence interval 0.91–0.97; p < 0.001). Software-based assessment supported subjective findings with less “undecided” pixels in CBCT than dose-equivalent MDCT (p < 0.001). No significant difference was found between LD CBCT and RD MDCT.
Conclusions
In cadaveric elbow studies, the tested cone-beam CT prototype delivered superior image quality compared to high-end multidetector CT and showed a potential for considerable dose reduction.
KW - Cancellous bone
KW - Cone-beam computed tomography
KW - Elbow
KW - Elbow joint
KW - Multidetector computed tomography
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229877
VL - 4
ER -
TY - JOUR
A1 - Gensler, Marius
A1 - Leikeim, Anna
A1 - Möllmann, Marc
A1 - Komma, Miriam
A1 - Heid, Susanne
A1 - Müller, Claudia
A1 - Boccaccini, Aldo R.
A1 - Salehi, Sahar
A1 - Groeber-Becker, Florian
A1 - Hansmann, Jan
T1 - 3D printing of bioreactors in tissue engineering: A generalised approach
JF - PLoS One
N2 - 3D printing is a rapidly evolving field for biological (bioprinting) and non-biological applications. Due to a high degree of freedom for geometrical parameters in 3D printing, prototype printing of bioreactors is a promising approach in the field of Tissue Engineering. The variety of printers, materials, printing parameters and device settings is difficult to overview both for beginners as well as for most professionals. In order to address this problem, we designed a guidance including test bodies to elucidate the real printing performance for a given printer system. Therefore, performance parameters such as accuracy or mechanical stability of the test bodies are systematically analysed. Moreover, post processing steps such as sterilisation or cleaning are considered in the test procedure. The guidance presented here is also applicable to optimise the printer settings for a given printer device. As proof of concept, we compared fused filament fabrication, stereolithography and selective laser sintering as the three most used printing methods. We determined fused filament fabrication printing as the most economical solution, while stereolithography is most accurate and features the highest surface quality. Finally, we tested the applicability of our guidance by identifying a printer solution to manufacture a complex bioreactor for a perfused tissue construct. Due to its design, the manufacture via subtractive mechanical methods would be 21-fold more expensive than additive manufacturing and therefore, would result in three times the number of parts to be assembled subsequently. Using this bioreactor we showed a successful 14-day-culture of a biofabricated collagen-based tissue construct containing human dermal fibroblasts as the stromal part and a perfusable central channel with human microvascular endothelial cells. Our study indicates how the full potential of biofabrication can be exploited, as most printed tissues exhibit individual shapes and require storage under physiological conditions, after the bioprinting process.
KW - stem cells
KW - technology
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231368
VL - 15
IS - 11
ER -
TY - JOUR
A1 - Westermaier, Thomas
A1 - Linsenmann, Thomas
A1 - Homola, György A.
A1 - Loehr, Mario
A1 - Stetter, Christian
A1 - Willner, Nadine
A1 - Ernestus, Ralf-Ingo
A1 - Soymosi, Laszlo
A1 - Vince, Giles H.
T1 - 3D rotational fluoroscopy for intraoperative clip control in patients with intracranial aneurysms – assessment of feasibility and image quality
JF - BMC Medical Imaging
N2 - Background
Mobile 3D fluoroscopes have become increasingly available in neurosurgical operating rooms. In this series, the image quality and value of intraoperative 3D fluoroscopy with intravenous contrast agent for the evaluation of aneurysm occlusion and vessel patency after clip placement was assessed in patients who underwent surgery for intracranial aneurysms.
Materials and methods
Twelve patients were included in this retrospective analysis. Prior to surgery, a 360° rotational fluoroscopy scan was performed without contrast agent followed by another scan with 50 ml of intravenous iodine contrast agent. The image files of both scans were transferred to an Apple PowerMac® workstation, subtracted and reconstructed using OsiriX® free software. The procedure was repeated after clip placement. Both image sets were compared for assessment of aneurysm occlusion and vessel patency.
Results
Image acquisition and contrast administration caused no adverse effects. Image quality was sufficient to follow the patency of the vessels distal to the clip. Metal artifacts reduce the assessability of the immediate vicinity of the clip. Precise image subtraction and post-processing can reduce metal artifacts and make the clip-site assessable and depict larger neck-remnants.
Conclusion
This technique quickly supplies images at adequate quality to evaluate distal vessel patency after aneurysm clipping. Significant aneurysm remnants may be depicted as well. As it does not require visual control of all vessels that are supposed to be evaluated intraoperatively, this technique may be complementary to other intraoperative tools like indocyanine green videoangiography and micro-Doppler, especially for the assessment of larger aneurysms. At the momentary state of this technology, it cannot replace postoperative conventional angiography. However, 3D fluoroscopy and image post-processing are young technologies. Further technical developments are likely to result in improved image quality.
KW - aneurysm surgery
KW - clip control
KW - angiography
KW - 3D fluoroscopy
KW - image quality
KW - intraoperative
KW - vessel patency
KW - contrast
KW - post-processing
Y1 - 2016
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146381
VL - 16
IS - 30
ER -
TY - JOUR
A1 - Dietl, Alexander
A1 - Prieschenk, Christine
A1 - Eckert, Franziska
A1 - Birner, Christoph
A1 - Luchner, Andreas
A1 - Maier, Lars S.
A1 - Buchner, Stefan
T1 - 3D vena contracta area after MitraClip© procedure: precise quantification of residual mitral regurgitation and identification of prognostic information
JF - Cardiovascular Ultrasound
N2 - Background
Percutaneous mitral valve repair (PMVR) is increasingly performed in patients with severe mitral regurgitation (MR). Post-procedural MR grading is challenging and an unsettled issue. We hypothesised that the direct planimetry of vena contracta area (VCA) by 3D–transoesophageal echocardiography allows quantifying post-procedural MR and implies further prognostic relevance missed by the usual ordinal scale (grade I-IV).
Methods
Based on a single-centre PMVR registry containing 102 patients, the association of VCA reduction and patients’ functional capacity measured as six-minute walk distance (6 MW) was evaluated. 3D–colour-Doppler datasets were available before, during and 4 weeks after PMVR.
Results
Twenty nine patients (age 77.0 ± 5.8 years) with advanced heart failure (75.9% NYHA III/IV) and severe degenerative (34%) or functional (66%) MR were eligible. VCA was reduced in all patients by PMVR (0.99 ± 0.46 cm\(^2\) vs. 0.22 ± 0.15 cm\(^2\), p < 0.0001). It remained stable after median time of 33 days (p = 0.999). 6 MW improved after the procedure (257.5 ± 82.5 m vs. 295.7 ± 96.3 m, p < 0.01). Patients with a decrease in VCA less than the median VCA reduction showed a more distinct improvement in 6 MW than patients with better technical result (p < 0.05). This paradoxical finding was driven by inferior results in very large functional MR.
Conclusions
VCA improves the evaluation of small residual MR. Its post-procedural values remain stable during a short-term follow-up and imply prognostic information for the patients’ physical improvement. VCA might contribute to a more substantiated estimation of treatment success in the heterogeneous functional MR group.
KW - percutaneous mitral valve repair
KW - MitraClip
KW - 3D echocardiography
KW - vena contracta area
KW - six-minute walk test
KW - NT-proBNP
KW - prognosis
KW - functional mitral regurgitation
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225318
VL - 16
ER -
TY - JOUR
A1 - Sollfrank, Teresa
A1 - Hart, Daniel
A1 - Goodsell, Rachel
A1 - Foster, Jonathan
A1 - Tan, Tele
T1 - 3D visualization of movements can amplify motor cortex activation during subsequent motor imagery
JF - Frontiers in Human Neuroscience
N2 - A repetitive movement practice by motor imagery (MI) can influence motor cortical excitability in the electroencephalogram (EEG). This study investigated if a realistic visualization in 3D of upper and lower limb movements can amplify motor related potentials during subsequent MI. We hypothesized that a richer sensory visualization might be more effective during instrumental conditioning, resulting in a more pronounced event related desynchronization (ERD) of the upper alpha band (10–12 Hz) over the sensorimotor cortices thereby potentially improving MI based brain-computer interface (BCI) protocols for motor rehabilitation. The results show a strong increase of the characteristic patterns of ERD of the upper alpha band components for left and right limb MI present over the sensorimotor areas in both visualization conditions. Overall, significant differences were observed as a function of visualization modality (VM; 2D vs. 3D). The largest upper alpha band power decrease was obtained during MI after a 3-dimensional visualization. In total in 12 out of 20 tasks the end-user of the 3D visualization group showed an enhanced upper alpha ERD relative to 2D VM group, with statistical significance in nine tasks.With a realistic visualization of the limb movements, we tried to increase motor cortex activation during subsequent MI. The feedback and the feedback environment should be inherently motivating and relevant for the learner and should have an appeal of novelty, real-world relevance or aesthetic value (Ryan and Deci, 2000; Merrill, 2007). Realistic visual feedback, consistent with the participant’s MI, might be helpful for accomplishing successful MI and the use of such feedback may assist in making BCI a more natural interface for MI based BCI rehabilitation.
KW - 3-dimensional visualization
KW - motor cortex activation
KW - EEG
KW - brain-computer interfaces
Y1 - 2015
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126058
VL - 9
IS - 463
ER -
TY - JOUR
A1 - Houben, Roland
A1 - Alimova, Pamela
A1 - Sarma, Bhavishya
A1 - Hesbacher, Sonja
A1 - Schulte, Carolin
A1 - Sarosi, Eva-Maria
A1 - Adam, Christian
A1 - Kervarrec, Thibault
A1 - Schrama, David
T1 - 4-[(5-methyl-1H-pyrazol-3-yl)amino]-2H-phenyl-1-phthalazinone inhibits MCPyV T antigen expression in Merkel cell carcinoma independent of Aurora kinase A
JF - Cancers
N2 - Merkel cell carcinoma (MCC) is frequently caused by the Merkel cell polyomavirus (MCPyV), and MCPyV-positive tumor cells depend on expression of the virus-encoded T antigens (TA). Here, we identify 4-[(5-methyl-1H-pyrazol-3-yl)amino]-2H-phenyl-1-phthalazinone (PHT) — a reported inhibitor of Aurora kinase A — as a compound inhibiting growth of MCC cells by repressing noncoding control region (NCCR)-controlled TA transcription. Surprisingly, we find that TA repression is not caused by inhibition of Aurora kinase A. However, we demonstrate that β-catenin — a transcription factor repressed by active glycogen synthase kinase 3 (GSK3) — is activated by PHT, suggesting that PHT bears a hitherto unreported inhibitory activity against GSK3, a kinase known to function in promoting TA transcription. Indeed, applying an in vitro kinase assay, we demonstrate that PHT directly targets GSK3. Finally, we demonstrate that PHT exhibits in vivo antitumor activity in an MCC xenograft mouse model, suggesting a potential use in future therapeutic settings for MCC.
KW - Merkel cell carcinoma
KW - polyomavirus
KW - large T antigen
KW - phthalazinone pyrazole
KW - glycogen synthase kinase 3
KW - GSK3
Y1 - 2023
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313547
SN - 2072-6694
VL - 15
IS - 9
ER -
TY - JOUR
A1 - Wiedenmann, J.
A1 - Bocquillon, E.
A1 - Deacon, R.S.
A1 - Hartinger, S.
A1 - Herrmann, O.
A1 - Klapwijk, T.M.
A1 - Maier, L.
A1 - Ames, C.
A1 - Brüne, C.
A1 - Gould, C.
A1 - Oiwa, A.
A1 - Ishibashi, K.
A1 - Tarucha, S.
A1 - Buhmann, H.
A1 - Molenkamp, L.W.
T1 - 4π-periodic Josephson supercurrent in HgTe-based topological Josephson junctions
JF - Nature Communications
N2 - The Josephson effect describes the generic appearance of a supercurrent in a weak link between two superconductors. Its exact physical nature deeply influences the properties of the supercurrent. In recent years, considerable efforts have focused on the coupling of superconductors to the surface states of a three-dimensional topological insulator. In such a material, an unconventional induced p-wave superconductivity should occur, with a doublet of topologically protected gapless Andreev bound states, whose energies vary 4π-periodically with the superconducting phase difference across the junction. In this article, we report the observation of an anomalous response to rf irradiation in a Josephson junction made of a HgTe weak link. The response is understood as due to a 4π-periodic contribution to the supercurrent, and its amplitude is compatible with the expected contribution of a gapless Andreev doublet. Our work opens the way to more elaborate experiments to investigate the induced superconductivity in a three-dimensional insulator.
KW - Josephson effect
KW - supercurrent
KW - superconductors
Y1 - 2016
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175353
VL - 7
ER -
TY - JOUR
A1 - Stopper, Helga
A1 - Pechan, R.
A1 - Schiffmann, D.
T1 - 5-azacytidine induces micronuclei in and morphological transformation of Syrian hamster embryo fibroblasts in the absence of unscheduled DNA synthesis
N2 - lt is known that 5-azacytidine (5-AC) induces tumors in several organs of rats and mice. The mechanisms of these effects are still poorly understood although it is known that 5-AC can be incorporated into DNA. Furthermore, it can inhibit DNA methylation. The known data on its clastogenic andjor gene mutation-inducing potential are still controversial. Therefore, we have investigated the kinds of genotoxic effects caused by 5-AC in Syrian hamster embryo (SHE) fibroblasts. Three different endp6ints (micronucleus formation, unscheduled DNA synthesis (UDS) and cell transforrnation) were assayed under similar conditions of metabolism and dose at target in this cell system. 5-AC induces morphological transformation of SHE cells, but not UDS. Therefore, 5-AC does not seem to cause repairable DNA lesions. Furthermore, our studies revealed that 5-AC is a potent inducer of mkronuclei in the SHE system. Immunocytochemical analysis revealed that a certain percentage of these contain kinetochores indicating that 5-AC may induce both clastogenic events and numerical chromosome changes.
KW - Toxikologie
KW - 5-Azacytidine
KW - Micronuclei
KW - Kinetochores
KW - Unscheduled DNA synthesis
KW - Cell transformation
Y1 - 1992
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63443
ER -
TY - JOUR
A1 - Karabeg, Margherita M.
A1 - Grauthoff, Sandra
A1 - Kollert, Sina Y.
A1 - Weidner, Magdalena
A1 - Heiming, Rebecca S.
A1 - Jansen, Friederike
A1 - Popp, Sandy
A1 - Kaiser, Sylvia
A1 - Lesch, Klaus-Peter
A1 - Sachser, Norbert
A1 - Schmitt, Angelika G.
A1 - Lewejohann, Lars
T1 - 5-HTT Deficiency Affects Neuroplasticity and Increases Stress Sensitivity Resulting in Altered Spatial Learning Performance in the Morris Water Maze but Not in the Barnes Maze
JF - PLoS ONE
N2 - The purpose of this study was to evaluate whether spatial hippocampus-dependent learning is affected by the serotonergic system and stress. Therefore, 5-HTT knockout (-/-), heterozygous (+/-) and wildtype (+/+) mice were subjected to the Barnes maze (BM) and the Morris water maze (WM), the latter being discussed as more aversive. Additionally, immediate early gene (IEG) expression, hippocampal adult neurogenesis (aN), and blood plasma corticosterone were analyzed.
While the performance of 5-HTT-/- mice in the BM was undistinguishable from both other genotypes, they performed worse in the WM. However, in the course of the repeated WM trials 5-HTT-/- mice advanced to wildtype level. The experience of a single trial of either the WM or the BM resulted in increased plasma corticosterone levels in all genotypes. After several trials 5-HTT-/- mice exhibited higher corticosterone concentrations compared with both other genotypes in both tests. Corticosterone levels were highest in 5-HTT-/- mice tested in the WM indicating greater aversiveness of the WM and a greater stress sensitivity of 5-HTT deficient mice.
Quantitative immunohistochemistry in the hippocampus revealed increased cell counts positive for the IEG products cFos and Arc as well as for proliferation marker Ki67 and immature neuron marker NeuroD in 5-HTT-/- mice compared to 5-HTT+/+ mice, irrespective of the test. Most differences were found in the suprapyramidal blade of the dentate gyrus of the septal hippocampus. Ki67-immunohistochemistry revealed a genotype x environment interaction with 5-HTT genotype differences in naïve controls and WM experience exclusively yielding more Ki67-positive cells in 5-HTT+/+ mice. Moreover, in 5-HTT-/- mice we demonstrate that learning performance correlates with the extent of aN.
Overall, higher baseline IEG expression and increased an in the hippocampus of 5-HTT-/- mice together with increased stress sensitivity may constitute the neurobiological correlate of raised alertness, possibly impeding optimal learning performance in the more stressful WM.
KW - immediate early genes
KW - learning curves
KW - animal performance
KW - animal behavior
KW - serotonin
KW - learning
KW - mice
KW - hippocampus
Y1 - 2013
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129978
VL - 8
IS - 10
ER -
TY - JOUR
A1 - Popp, Sandy
A1 - Schmitt-Böhrer, Angelika
A1 - Langer, Simon
A1 - Hofmann, Ulrich
A1 - Hommers, Leif
A1 - Schuh, Kai
A1 - Frantz, Stefan
A1 - Lesch, Klaus-Peter
A1 - Frey, Anna
T1 - 5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction
JF - Journal of Clinical Medicine
N2 - Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Cardiological evaluation of experimentally naïve male mice revealed a mild cardiac dysfunction in ≥4-month-old 5-HTT knockout (−/−) animals. Following induction of chronic cardiac dysfunction (CCD) by MI vs. sham operation 5-HTT−/− mice with infarct sizes >30% experienced 100% mortality, while 50% of 5-HTT+/− and 37% of 5-HTT+/+ animals with large MI survived the 8-week observation period. Surviving (sham and MI < 30%) 5-HTT−/− mutants displayed reduced exploratory activity and increased anxiety-like behavior in different approach-avoidance tasks. However, CCD failed to provoke a depressive-like behavioral response in either 5-Htt genotype. Mechanistic analyses were performed on mice 3 days post-MI. Electrocardiography, histology and FACS of inflammatory cells revealed no abnormalities. However, gene expression of inflammation-related cytokines (TGF-β, TNF-α, IL-6) and MMP-2, a protein involved in the breakdown of extracellular matrix, was significantly increased in 5-HTT−/− mice after MI. This study shows that 5-HTT deficiency leads to age-dependent cardiac dysfunction and disrupted early healing after MI probably due to alterations of inflammatory processes in mice.
KW - chronic heart failure
KW - myocardial infarction
KW - serotonin transporter deficient mice
KW - anxiety
KW - depression
KW - behavior
KW - inflammation
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242739
SN - 2077-0383
VL - 10
IS - 14
ER -
TY - JOUR
A1 - Chen, Y.
A1 - Palm, F.
A1 - Lesch, K. P.
A1 - Gerlach, M.
A1 - Moessner, R.
A1 - Sommer, C.
T1 - 5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, is responsible for complete Freund's adjuvant-induced thermal hyperalgesia in mice
N2 - Background: The role of serotonin (5-hydroxytrptamine, 5-HT) in the modulation of pain has been widely studied. Previous work led to the hypothesis that 5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, might by itself influence pain thresholds. Results: In the present study, we investigated the role of 5-HIAA in inflammatory pain induced by intraplantar injection of complete Freund’s adjuvant (CFA) into the hind paw of mice. Wild-type mice were compared to mice deficient of the 5-HT transporter (5-HTT-/- mice) using behavioral tests for hyperalgesia and high-performance liquid chromatography (HPLC) to determine tissue levels of 5-HIAA. Wild-type mice reproducibly developed thermal hyperalgesia and paw edema for 5 days after CFA injection. 5-HTT-/- mice treated with CFA had reduced thermal hyperalgesia on day 1 after CFA injection and normal responses to heat hereafter. The 5-HIAA levels in spinal cord and sciatic nerve as measured with HPLC were lower in 5-HTT-/- mice than in wild-type mice after CFA injection. Pretreatment of wild-type mice with intraperitoneal injection of para-chlorophenylalanine (p-CPA), a serotonin synthesis inhibitor, resulted in depletion of the 5-HIAA content in spinal cord and sciatic nerve and decrease in thermal hyperalgesia in CFA injected mice. The application of exogenous 5-HIAA resulted in potentiation of thermal hyperalgesia induced by CFA in 5-HTT-/- mice and in wild-type mice pretreated with p- CPA, but not in wild-type mice without p-CPA pretreatment. Further, methysergide, a broad-spectrum serotonin receptor antagonist, had no effect on 5-HIAA-induced potentiation of thermal hyperalgesia in CFA-treated wildtype mice. Conclusion: Taken together, the present results suggest that 5-HIAA plays an important role in modulating peripheral thermal hyperalgesia in CFA induced inflammation, probably via a non-serotonin receptor mechanism.
KW - Medizin
Y1 - 2011
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68858
ER -
TY - JOUR
A1 - Blömer, Nadja
A1 - Pachel, Christina
A1 - Hofmann, Urlich
A1 - Nordbeck, Peter
A1 - Bauer, Wolfgang
A1 - Mathes, Denise
A1 - Frey, Anna
A1 - Bayer, Barbara
A1 - Vogel, Benjamin
A1 - Ertl, Georg
T1 - 5-Lipoxygenase facilitates healing after myocardial infarction
JF - Basic Research in Cardiology
N2 - Early healing after myocardial infarction (MI) is characterized by a strong inflammatory reaction. Most leukotrienes are pro-inflammatory and are therefore potential mediators of healing and remodeling after myocardial ischemia. The enzyme 5-lipoxygenase (5-LOX) has a key role in the transformation of arachidonic acid in leukotrienes. Thus, we tested the effect of 5-LOX on healing after MI. After chronic coronary artery ligation, early mortality was significantly increased in 5-LOX\(^{−/−}\) when compared to matching wildtype (WT) mice due to left ventricular rupture. This effect could be reproduced in mice treated with the 5-LOX inhibitor Zileuton. A perfusion mismatch due to the vasoactive potential of leukotrienes is not responsible for left ventricular rupture since local blood flow assessed by magnetic resonance perfusion measurements was not different. However, after MI, there was an accentuation of the inflammatory reaction with an increase of pro-inflammatory macrophages. Yet, mortality was not changed in chimeric mice (WT vs. 5-LOX\(^{−/−}\) bone marrow in 5-LOX\(^{−/−}\) animals), indicating that an altered function of 5-LOX\(^{−/−}\) inflammatory cells is not responsible for the phenotype. Collagen production and accumulation of fibroblasts were significantly reduced in 5-LOX\(^{−/−}\) mice in vivo after MI. This might be due to an impaired migration of 5-LOX\(^{−/−}\) fibroblasts, as shown in vitro to serum. In conclusion, a lack or inhibition of 5-LOX increases mortality after MI because of healing defects. This is not mediated by a change in local blood flow, but through an altered inflammation and/or fibroblast function.
KW - lipoxygenase
KW - myocardial infarction
KW - extracellular matrix remodeling
KW - inflammation
Y1 - 2013
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132602
VL - 108
IS - 4
ER -
TY - JOUR
A1 - Schmid, Michael
A1 - Steinlein, Claus
A1 - Lomb, Christian
A1 - Sperling, Karl
A1 - Neitzel, Heidemarie
T1 - 5-Methylcytosine-Rich Heterochromatin in the Indian Muntjac
JF - Cytogenetic and Genome Research
N2 - Two 5-methylcytosine (5-MeC)-rich heterochromatic regions were demonstrated in metaphase chromosomes of the Indian muntjac by indirect immunofluorescence using a monoclonal anti-5-MeC antibody. The metaphases were obtained from diploid and triploid cell lines. A major region is located in the ‘neck' of the 3;X fusion chromosome and can be detected after denaturation of the chromosomal DNA with UV-light irradiation for 1 h. It is located exactly at the border of the X chromosome and the translocated autosome 3. A minor region is found in the centromeric region of the free autosome 3 after denaturing the chromosomal DNA for 3 h or longer. The structure and possible function of the major hypermethylated region as barrier against spreading of the X-inactivation process into the autosome 3 is discussed.
KW - heterochromatin
KW - immunofluorescence
KW - Indian muntjac
KW - 5-Methylcytosine
Y1 - 2016
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196701
SN - 1424-8581
SN - 1424-859X
N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL - 147
IS - 4
ER -
TY - JOUR
A1 - Christl, Manfred
A1 - Leß, Roland
A1 - Müller, Heinrich
T1 - 6,7-Dimethylene-2,4-diphenylbicyclo[3.2.l]oct-3-en-2-yl Anion : A Test for the Origin of the Unusual Properties of the Bicyclo[3.2.l]octa-3,6-dien-2-yl Anion
N2 - No abstract available
Y1 - 1994
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31547
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 - JOUR
A1 - Christl, Manfred
A1 - Brunn, E.
A1 - Roth, W. R.
A1 - Lennartz, H.-W.
T1 - 7-Methyl- and 7-Phenylcyclohepta-1,3,5-trienes from Benzvalene Via 3,3a,4,5,6,6a-Hexahydro-4,5,6-methenocyclopentapyrazoles and Tetracyclo[4.1.0.0\(^{2,4}\).0\(^{3,5}\)]heptanes
N2 - No abstract available
KW - Organische Chemie
Y1 - 1989
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58471
ER -
TY - JOUR
A1 - Gunesch, Sandra
A1 - Hoffmann, Matthias
A1 - Kiermeier, Carolina
A1 - Fischer, Wolfgang
A1 - Pinto, Antonio F. M.
A1 - Maurice, Tangui
A1 - Maher, Pamela
A1 - Decker, Michael
T1 - 7-O-Esters of taxifolin with pronounced and overadditive effects in neuroprotection, anti-neuroinflammation, and amelioration of short-term memory impairment in vivo
JF - Redox Biology
N2 - Alzheimer's disease (AD) is a multifactorial disease and the most common form of dementia. There are no treatments to cure, prevent or slow down the progression of the disease. Natural products hold considerable interest for the development of preventive neuroprotectants to treat neurodegenerative disorders like AD, due to their low toxicity and general beneficial effects on human health with their anti-inflammatory and antioxidant features. In this work we describe regioselective synthesis of 7-O-ester hybrids of the flavonoid taxifolin with the phenolic acids cinnamic and ferulic acid, namely 7-O-cinnamoyltaxifolin and 7-O-feruloyltaxifolin. The compounds show pronounced overadditive neuroprotective effects against oxytosis, ferroptosis and ATP depletion in the murine hippocampal neuron HT22 cell model. Furthermore, 7-O-cinnamoyltaxifolin and 7-O-feruloyltaxifolin reduced LPS-induced neuroinflammation in BV-2 microglia cells as assessed by effects on the levels of NO, IL6 and TNFα. In all in vitro assays the 7-O-esters of taxifolin and ferulic or cinnamic acid showed strong overadditive activity, significantly exceeding the effects of the individual components and the equimolar mixtures thereof, which were almost inactive in all of the assays at the tested concentrations. In vivo studies confirmed this overadditive effect. Treatment of an AD mouse model based on the injection of oligomerized Aβ\(_{25-35}\) peptide into the brain to cause neurotoxicity and subsequently memory deficits with 7-O-cinnamoyltaxifolin or 7-O-feruloyltaxifolin resulted in improved performance in an assay for short-term memory as compared to vehicle and mice treated with the respective equimolar mixtures. These results highlight the benefits of natural product hybrids as a novel compound class with potential use for drug discovery in neurodegenerative diseases due to their pharmacological profile that is distinct from the individual natural components.
KW - Alzheimer's disease
KW - Natural product hybrids
KW - Flavonoids
KW - Phenolic acids
KW - Microglia
KW - In vivo studies
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202718
VL - 29
ER -
TY - JOUR
A1 - Grunicke, H.
A1 - Pyerin, W.
A1 - Eisenbrand, G.
A1 - Havemann, K.
A1 - Rabes, H. M.
A1 - Molling, K.
A1 - Schwab, M.
A1 - Lutz, Werner K.
A1 - Wahrendorf, J.
A1 - Schirrmacher, V.
T1 - 7th International Symposium of the Division of Experimental Cancer Research (AEK) of the German Cancer Society : [Meeting report]
N2 - No abstract available
KW - Toxikologie
Y1 - 1994
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60651
ER -
TY - JOUR
A1 - Lohse, M. J.
A1 - Klotz, Karl-Norbert
A1 - Lindenborn Fotinos, J.
A1 - Reddington, M.
A1 - Schwabe, U.
A1 - Olsson, R. A.
T1 - 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) - a selective high affinity antagonist radioligand for A\(_1\) adenosine receptors
N2 - The properties of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as an antagonist ligand for A\(_1\) adenosirre receptors were examined and conipared with other radioligands for this receptor. DPCPX competitively antagonized both the inhibition of adenylate cyclase activity via A\(_1\) adenosirre receptors and the stimulationvia A\(_2\) adenosirre receptors. The K\(_i\)-values of this antagonism were 0.45 nM at the A\(_1\) receptor of rat fat cells, and 330 nM at the A\(_2\) receptor of human platelets, giving a more than 700-fold A\(_1\)-selectivity. A similar A\(_1\)-selectivity was determined in radioligand binding studies. Even at high concentrations, DPCPX did not significantly inhibit the soluble cAMPphosphodiesterase activity of human platelets. [\(^3\)H]DPCPX (105 Ci/mmol) bound in a saturable manner with high affinity to A\(_1\) receptors in membranes of bovine brain and heart, and rat brain and fat cells (K\(_D\) -values 50-190 pM). Its nonspecific binding was about 1% of total at K\(_D\) , except in bovine myocardial membranes (about 10%). Binding studies with bovine myocardial membranes allowed the analysis of both the high and low agonist affinity states of this receptor in a tissue with low receptor density. The binding properties of [\(^3\)H]DPCPX appear superior to those of other agonist and antagonist radioligands for the A\(_1\) receptor.
KW - Toxikologie
KW - Adenosine receptors
KW - Adenylate cyclase
KW - Phosphodiesterase
KW - Xanthines
KW - Radioligands
Y1 - 1987
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60246
ER -
TY - JOUR
A1 - Gerhard-Hartmann, Elena
A1 - Goergen, Helen
A1 - Bröckelmann, Paul J.
A1 - Mottok, Anja
A1 - Steinmüller, Tabea
A1 - Grund, Johanna
A1 - Zamò, Alberto
A1 - Ben-Neriah, Susana
A1 - Sasse, Stephanie
A1 - Borchmann, Sven
A1 - Fuchs, Michael
A1 - Borchmann, Peter
A1 - Reinke, Sarah
A1 - Engert, Andreas
A1 - Veldman, Johanna
A1 - Diepstra, Arjan
A1 - Klapper, Wolfram
A1 - Rosenwald, Andreas
T1 - 9p24.1 alterations and programmed cell death 1 ligand 1 expression in early stage unfavourable classical Hodgkin lymphoma: an analysis from the German Hodgkin Study Group NIVAHL trial
JF - British Journal of Haematology
N2 - High programmed cell death 1 ligand 1 (PD-L1) protein expression and copy number alterations (CNAs) of the corresponding genomic locus 9p24.1 in Hodgkin- and Reed–Sternberg cells (HRSC) have been shown to be associated with favourable response to anti-PD-1 checkpoint inhibition in relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In the present study, we investigated baseline 9p24.1 status as well as PD-L1 and major histocompatibility complex (MHC) class I and II protein expression in 82 biopsies from patients with early stage unfavourable cHL treated with anti-PD-1-based first-line treatment in the German Hodgkin Study Group (GHSG) NIVAHL trial (ClinicalTrials.gov Identifier: NCT03004833). All evaluated specimens showed 9p24.1 CNA in HRSC to some extent, but with high intratumoral heterogeneity and an overall smaller range of alterations than reported in advanced-stage or r/r cHL. All but two cases (97%) showed PD-L1 expression by the tumour cells in variable amounts. While MHC-I was rarely expressed in >50% of HRSC, MHC-II expression in >50% of HRSC was found more frequently. No obvious impact of 9p24.1 CNA or PD-L1 and MHC-I/II expression on early response to the highly effective anti-PD-1-based NIVAHL first-line treatment was observed. Further studies evaluating an expanded panel of potential biomarkers are needed to optimally stratify anti-PD-1 first-line cHL treatment.
KW - fluorescence in situ hybridisation
KW - major histocompatibility complex
KW - immune checkpoint blockade
KW - classical Hodgkin lymphoma
KW - CD274
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258358
VL - 196
IS - 1
ER -
TY - JOUR
A1 - Hesselbach, Robert
T1 - <> – A Corpus-based Approach of Official French, Italian, and Spanish Social Media Discourse in the Light of the Coronavirus Crisis
JF - promptus - Würzburger Beiträge zur Romanistik
N2 - France, Italy, and Spain are three Romance-speaking countries which – at least in Europe – have been affected to a very high degree by the consequences of the Corona pandemic. This paper examines discursive strategies on social media (Twitter and Facebook) by the three heads of government/state of the aforementioned countries – namely Emmanuel Macron (France), Giuseppe Conte (Italy), and Pedro Sánchez (Spain)- from a corpuslinguistic point of view. For this purpose, a corpus was created which contains all Twitter and Facebook messages posted by these heads of government/state from the beginning of February until the end of April 2020. By applying corpus-linguistic methods we find that all three politicians consciously use social media to sensitize, inform, and – in view of a dramatic pandemic situation – unite their respective populations behind them.
KW - corpus linguistics
KW - coronavirus
KW - Covid-19
KW - political discourse
KW - social media
KW - lexical co-occurrences
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244251
VL - 6
ER -
TY - JOUR
A1 - Nose, Naoko
A1 - Nogami, Suguru
A1 - Koshino, Kazuhiro
A1 - Chen, Xinyu
A1 - Werner, Rudolf A.
A1 - Kashima, Soki
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Fukuchi, Kazuki
A1 - Higuchi, Takahiro
T1 - [18F]FDG-labelled stem cell PET imaging in different route of administrations and multiple animal species
JF - Scientific Reports
N2 - Stem cell therapy holds great promise for tissue regeneration and cancer treatment, although its efficacy is still inconclusive and requires further understanding and optimization of the procedures. Non-invasive cell tracking can provide an important opportunity to monitor in vivo cell distribution in living subjects. Here, using a combination of positron emission tomography (PET) and in vitro 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) direct cell labelling, the feasibility of engrafted stem cell monitoring was tested in multiple animal species. Human mesenchymal stem cells (MSCs) were incubated with phosphate-buffered saline containing [18F]FDG for in vitro cell radiolabelling. The pre-labelled MSCs were administrated via peripheral vein in a mouse (n=1), rats (n=4), rabbits (n=4) and non-human primates (n=3), via carotid artery in rats (n=4) and non-human primates (n=3), and via intra-myocardial injection in rats (n=5). PET imaging was started 10 min after cell administration using a dedicated small animal PET system for a mouse and rats. A clinical PET system was used for the imaging of rabbits and non-human primates. After MSC administration via peripheral vein, PET imaging revealed intense radiotracer signal from the lung in all tested animal species including mouse, rat, rabbit, and non-human primate, suggesting administrated MSCs were trapped in the lung tissue. Furthermore, the distribution of the PET signal significantly differed based on the route of cell administration. Administration via carotid artery showed the highest activity in the head, and intra-myocardial injection increased signal from the heart. In vitro [18F]FDG MSC pre-labelling for PET imaging is feasible and allows non-invasive visualization of initial cell distribution after different routes of cell administration in multiple animal models. Those results highlight the potential use of that imaging approach for the understanding and optimization of stem cell therapy in translational research.
KW - biomarkers
KW - molecular medicine
KW - stem-cell research
KW - stem cells
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260590
VL - 11
IS - 1
ER -
TY - JOUR
A1 - Breun, Maria
A1 - Monoranu, Camelia M.
A1 - Kessler, Almuth F.
A1 - Matthies, Cordula
A1 - Löhr, Mario
A1 - Hagemann, Carsten
A1 - Schirbel, Andreas
A1 - Rowe, Steven P.
A1 - Pomper, Martin G.
A1 - Buck, Andreas K.
A1 - Wester, Hans-Jürgen
A1 - Ernestus, Ralf-Ingo
A1 - Lapa, Constantin
T1 - [\(^{68}\)Ga]-Pentixafor PET/CT for CXCR4-mediated imaging of vestibular schwannomas
JF - Frontiers in Oncology
N2 - We have recently demonstrated CXCR4 overexpression in vestibular schwannomas (VS). This study investigated the feasibility of CXCR4-directed positron emission tomography/computed tomography (PET/CT) imaging of VS using the radiolabeled chemokine ligand [\(^{68}\)Ga]Pentixafor.
Methods: 4 patients with 6 primarily diagnosed or pre-treated/observed VS were enrolled. All subjects underwent [\(^{68}\)Ga]Pentixafor PET/CT prior to surgical resection. Images were analyzed visually and semi-quantitatively for CXCR4 expression including calculation of tumor-to-background ratios (TBR). Immunohistochemistry served as standard of reference in three patients.
Results: [\(^{68}\)Ga]Pentixafor PET/CT was visually positive in all cases. SUV\(_{mean}\) and SUV\(_{max}\) were 3.0 ± 0.3 and 3.8 ± 0.4 and TBR\(_{mean}\) and TBR\(_{max}\) were 4.0 ± 1.4 and 5.0 ± 1.7, respectively. Histological analysis confirmed CXCR4 expression in tumors.
Conclusion: Non-invasive imaging of CXCR4 expression using [\(^{68}\)Ga]Pentixafor PET/CT of VS is feasible and could prove useful for in vivo assessment of CXCR4 expression.
KW - vestibular schwannoma
KW - CXCR4
KW - PET/CT
KW - molecular imaging
KW - Pentixafor
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201863
VL - 9
IS - 503
ER -
TY - JOUR
A1 - Lapa, Constantin
A1 - Schreder, Martin
A1 - Schirbel, Andreas
A1 - Samnick, Samuel
A1 - Kortüm, Klaus Martin
A1 - Herrmann, Ken
A1 - Kropf, Saskia
A1 - Einsele, Herrmann
A1 - Buck, Andreas K.
A1 - Wester, Hans-Jürgen
A1 - Knop, Stefan
A1 - Lückerath, Katharina
T1 - [\(^{68}\)Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma - comparison to [\(^{18}\)F]FDG and laboratory values
JF - Theranostics
N2 - Chemokine (C-X-C motif) receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer including multiple myeloma (MM). Proof-of-concept of CXCR4-directed radionuclide therapy in MM has recently been reported. This study assessed the diagnostic performance of the CXCR4-directed radiotracer [\(^{68}\)Ga]Pentixafor in MM and a potential role for stratifying patients to CXCR4-directed therapies.
Thirty-five patients with MM underwent [\(^{68}\)Ga]Pentixafor-PET/CT for evaluation of eligibility for endoradiotherapy. In 19/35 cases, [\(^{18}\)F]FDG-PET/CT for correlation was available. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with standard clinical parameters of disease activity.
[\(^{68}\)Ga]Pentixafor-PET detected CXCR4-positive disease in 23/35 subjects (66%). CXCR4-positivity at PET was independent from myeloma subtypes, cytogenetics or any serological parameters and turned out as a negative prognostic factor. In the 19 patients in whom a comparison to [\(^{18}\)F]FDG was available, [\(^{68}\)Ga]Pentixafor-PET detected more lesions in 4/19 (21%) subjects, [\(^{18}\)F]FDG proved superior in 7/19 (37%). In the remaining 8/19 (42%) patients, both tracers detected an equal number of lesions. [\(^{18}\)F]FDG-PET positivity correlated with [\(^{68}\)Ga]Pentixafor-PET positivity (p=0.018).
[\(^{68}\)Ga]Pentixafor-PET provides further evidence that CXCR4 expression frequently occurs in advanced multiple myeloma, representing a negative prognostic factor and a potential target for myeloma specific treatment. However, selecting patients for CXCR4 directed therapies and prognostic stratification seem to be more relevant clinical applications for this novel imaging modality, rather than diagnostic imaging of myeloma.
KW - medicine
KW - multiple myeloma
KW - FDG
KW - molecular imaging
KW - CXCR4
KW - PET
KW - radionuclide therapy
KW - theranostics
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172106
VL - 7
IS - 1
ER -
TY - JOUR
A1 - Ewing, William C.
A1 - Dellermann, Theresa
A1 - Angel Wong, Y. T.
A1 - Mattock, James D.
A1 - Vargas, Alfredo
A1 - Bryce, David L.
A1 - Dewhurst, Rian D.
A1 - Braunschweig, Holger
T1 - \(\pi\)‐Complexes of Diborynes with Main Group Atoms
JF - Chemistry – An Asian Journal
N2 - We present herein an in‐depth study of complexes in which a molecule containing a boron‐boron triple bond is bound to tellurate cations. The analysis allows the description of these salts as true π complexes between the B−B triple bond and the tellurium center. These complexes thus extend the well‐known Dewar‐Chatt‐Duncanson model of bonding to compounds made up solely of p block elements. Structural, spectroscopic and computational evidence is offered to argue that a set of recently reported heterocycles consisting of phenyltellurium cations complexed to diborynes bear all the hallmarks of \(\pi\)‐complexes in the \(\pi\)‐complex/metallacycle continuum envisioned by Joseph Chatt. Described as such, these compounds are unique in representing the extreme of a metal‐free continuum with conventional unsaturated three‐membered rings (cyclopropenes, azirenes, borirenes) occupying the opposite end.
KW - boron
KW - main group elements
KW - solid-state NMR
KW - \(\pi\) interactions
KW - multiple bonds
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214677
VL - 15
IS - 10
SP - 1553
EP - 1557
ER -
TY - JOUR
A1 - Lapa, Constantin
A1 - Garcia-Velloso, Maria J.
A1 - Lückerath, Katharina
A1 - Samnick, Samuel
A1 - Schreder, Martin
A1 - Otero, Paula Rodriguez
A1 - Schmid, Jan-Stefan
A1 - Herrmann, Ken
A1 - Knop, Stefan
A1 - Buck, Andreas K.
A1 - Einsele, Hermann
A1 - San-Miguel, Jesus
A1 - Kortüm, Klaus Martin
T1 - \(^{11}\)C-methionine-PET in multiple myeloma: a combined study from two different institutions
JF - Theranostics
N2 - \(^{11}\)C-methionine (MET) has recently emerged as an accurate marker of tumor burden and disease activity in patients with multiple myeloma (MM). This dual-center study aimed at further corroboration of the superiority of MET as positron emission tomography (PET) tracer for staging and re-staging MM, as compared to \(^{18}\)F-2`-deoxy-2`-fluoro-D-glucose (FDG).
78 patients with a history of solitary plasmacytoma (n=4), smoldering MM (SMM, n=5), and symptomatic MM (n=69) underwent both MET- and FDG-PET/computed tomography (CT) at the University Centers of Würzburg, Germany and Navarra, Spain. Scans were compared on a patient and on a lesion basis. Inter-reader agreement was also evaluated. In 2 patients, tumor biopsies for verification of discordant imaging results were available.
MET-PET detected focal lesions (FL) in 59/78 subjects (75.6%), whereas FDG-PET/CT showed lesions in only 47 patients (60.3%; p<0.01), accordingly disease activity would have been missed in 12 patients. Directed biopsies of discordant results confirmed MET-PET/CT results in both cases.
MET depicted more FL in 44 patients (56.4%; p<0.01), whereas in two patients (2/78), FDG proved superior. In the remainder (41.0%, 32/78), both tracers yielded comparable results. Inter-reader agreement for MET was higher than for FDG (κ = 0.82 vs κ = 0.72).
This study demonstrates higher sensitivity of MET in comparison to standard FDG to detect intra- and extramedullary MM including histologic evidence of FDG-negative, viable disease exclusively detectable by MET-PET/CT. MET holds the potential to replace FDG as functional imaging standard for staging and re-staging of MM.
KW - medicine
KW - PET/CT
KW - \(^{11}\)C-methionine
KW - multiple myeloma
KW - FDG
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172038
VL - 7
IS - 11
ER -
TY - JOUR
A1 - Lückerath, Katharina
A1 - Lapa, Constantin
A1 - Albert, Christa
A1 - Herrmann, Ken
A1 - Jörg, Gerhard
A1 - Samnick, Samuel
A1 - Einsele, Herrmann
A1 - Knop, Stefan
A1 - Buck, Andreas K.
T1 - \(^{11}\)C-Methionine-PET: a novel and sensitive tool for monitoring of early response to treatment in multiple myeloma
JF - Oncotarget
N2 - Multiple myeloma (MM) remains an essentially incurable hematologic malignancy. However, new treatment modalities and novel drugs have been introduced and thus additional tools for therapy monitoring are increasingly needed. Therefore, we evaluated the radiotracers \(^{11}\)C-Methionine (paraprotein-biosynthesis) and \(^{18}\)F-FDG (glucose-utilization) for monitoring response to anti-myeloma-therapy and outcome prediction. Influence of proteasome-inhibition on radiotracer-uptake of different MM cell-lines and patient-derived CD138\(^{+}\) plasma cells was analyzed and related to tumor-biology. Mice xenotransplanted with MM. 1S tumors underwent MET- and FDG-\(\mu\)PET. Tumor-to-background ratios before and after 24 h, 8 and 15 days treatment with bortezomib were correlated to survival. Treatment reduced both MET and FDG uptake; changes in tracer-retention correlated with a switch from high to low CD138-expression. In xenotransplanted mice, MET-uptake significantly decreased by 30-79% as early as 24 h after bortezomib injection. No significant differences were detected thus early with FDG. This finding was confirmed in patient-derived MM cells. Importantly, early reduction of MET-but not FDG-uptake correlated with improved survival and reduced tumor burden in mice. Our results suggest that MET is superior to FDG in very early assessment of response to anti-myeloma-therapy. Early changes in MET-uptake have predictive potential regarding response and survival. MET-PET holds promise to individualize therapies in MM in future.
KW - positron emission tomography
KW - imaging techniques
KW - experience
KW - \(^{11}\)C-Methionine-PET
KW - treatment response
KW - molecular imaging
KW - multiple myeloma
KW - management
KW - \(^{18}\)F-FDG PET/CT
KW - bone disease
KW - stem-cell transplantation
KW - esophagogastric junction
Y1 - 2015
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148688
VL - 6
IS - 10
ER -
TY - JOUR
A1 - Christl, Manfred
A1 - Warren, J. D.
A1 - Hawkins, B. L.
A1 - Roberts, J. D.
T1 - \(^{13}\)C and \(^{15}\)N Nuclear Magnetic Resonance Spectroscopy of Nitrile Oxides and Related Reaction Products : Unexpected \(^{13}\)C and \(^{15}\)N Nuclear Magnetic Resonance Parameters of 2,4,6-Trimethylbenzonitrile Oxide
N2 - No abstract available
KW - Organische Chemie
Y1 - 1973
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-57894
ER -
TY - JOUR
A1 - Beykan, Seval
A1 - Dam, Jan S.
A1 - Eberlein, Uta
A1 - Kaufmann, Jens
A1 - Kjærgaard, Benedict
A1 - Jødal, Lars
A1 - Bouterfa, Hakim
A1 - Bejot, Romain
A1 - Lassmann, Michael
A1 - Jensen, Svend Borup
T1 - \(^{177}\)Lu-OPS201 targeting somatostatin receptors: in vivo biodistribution and dosimetry in a pig model
JF - EJNMMI Research
N2 - Background
\(^{177}\)Lu is used in peptide receptor radionuclide therapies for the treatment of neuroendocrine tumors. Based on the recent literature, SST2 antagonists are superior to agonists in tumor uptake. The compound OPS201 is the novel somatostatin antagonist showing the highest SST2 affinity. The aim of this study was to measure the in vivo biodistribution and dosimetry of \(^{177}\)Lu-OPS201 in five anesthetized Danish Landrace pigs as an appropriate substitute for humans to quantitatively assess the absorbed doses for future clinical applications.
Results
\(^{177}\)Lu-OPS201 was obtained with a specific activity ranging from 10 to 17 MBq/μg. Prior to administration, the radiochemical purity was measured as s > 99.7 % in all cases. After injection, fast clearance of the compound from the blood stream was observed. Less than 5 % of the injected activity was presented in blood 10 min after injection. A series of SPECT/CT and whole-body scans conducted until 10 days after intravenous injection showed uptake mostly in the liver, spine, and kidneys. There was no visible uptake in the spleen. Blood samples were taken to determine the time-activity curve in the blood. Time-activity curves and time-integrated activity coefficients were calculated for the organs showing visible uptake. Based on these data, the absorbed organ dose coefficients for a 70-kg patient were calculated with OLINDA/EXM. For humans after an injection of 5 GBq \(^{177}\)Lu-OPS201, the highest predicted absorbed doses are obtained for the kidneys (13.7 Gy), the osteogenic cells (3.9 Gy), the urinary bladder wall (1.8 Gy), and the liver (1.0 Gy). No metabolites of 177Lu-OPS201 were found by radio HPLC analysis. None of the absorbed doses calculated will exceed organ toxicity levels.
Conclusions
The \(^{177}\)Lu-OPS201 was well tolerated and caused no abnormal physiological or behavioral signs. In vivo distributions and absorbed doses of pigs are comparable to those observed in other publications. According to the biodistribution data in pigs, presented in this work, the expected radiation exposure in humans will be within the acceptable range.
KW - lutetium-177
KW - JR11
KW - antagonist
KW - dosimetry
KW - neuroendocrine tumor (NET)
KW - OPS201
KW - pig model
KW - PRRT
Y1 - 2016
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146888
VL - 6
IS - 50
ER -
TY - JOUR
A1 - Morales-Lozano, Maria I.
A1 - Viering, Oliver
A1 - Samnick, Samuel
A1 - Rodriguez-Otero, Paula
A1 - Buck, Andreas K.
A1 - Marcos-Jubilar, Maria
A1 - Rasche, Leo
A1 - Prieto, Elena
A1 - Kortüm, K. Martin
A1 - San-Miguel, Jesus
A1 - Garcia-Velloso, Maria J.
A1 - Lapa, Constantin
T1 - \(^{18}\)F-FDG and \(^{11}\)C-methionine PET/CT in newly diagnosed multiple myeloma patients: comparison of volume-based PET biomarkers
JF - Cancers
N2 - \(^{11}\)C-methionine (\(^{11}\)C-MET) is a new positron emission tomography (PET) tracer for the assessment of disease activity in multiple myeloma (MM) patients, with preliminary data suggesting higher sensitivity and specificity than \(^{18}\)F-fluorodeoxyglucose (\(^{18}\)F-FDG). However, the value of tumor burden biomarkers has yet to be investigated. Our goals were to corroborate the superiority of \(^{11}\)C-MET for MM staging and to compare its suitability for the assessment of metabolic tumor burden biomarkers in comparison to \(^{18}\)F-FDG. Twenty-two patients with newly diagnosed, treatment-naïve symptomatic MM who had undergone \(^{11}\)C-MET and \(^{18}\)F-FDG PET/CT were evaluated. Standardized uptake values (SUV) were determined and compared with total metabolic tumor volume (TMTV) for both tracers: total lesion glycolysis (TLG) and total lesion \(^{11}\)C-MET uptake (TLMU). PET-derived values were compared to Revised International Staging System (R-ISS), cytogenetic, and serologic MM markers such as M component, beta 2 microglobulin (B2M), serum free light chains (FLC), albumin, and lactate dehydrogenase (LDH). In 11 patients (50%), \(^{11}\)C-MET detected more focal lesions (FL) than FDG (p < 0.01). SUVmax, SUVmean, SUVpeak, TMTV, and TLMU were also significantly higher in \(^{11}\)C-MET than in \(^{18}\)F-FDG (p < 0.05, respectively). \(^{11}\)C-MET PET biomarkers had a better correlation with tumor burden (bone marrow plasma cell infiltration, M component; p < 0.05 versus p = n.s. respectively). This pilot study suggests that \(^{11}\)C-MET PET/CT is a more sensitive marker for the assessment of myeloma tumor burden than \(^{18}\)F-FDG. Its implications for prognosis evaluation need further investigation.
KW - multiple myeloma
KW - methionine
KW - total lesion glycolysis (TLG)
KW - metabolic tumor volume (MTV)
KW - total lesion methionine uptake (TLMU)
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203686
SN - 2072-6694
VL - 12
IS - 4
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Derlin, Thorsten
A1 - Lapa, Constantin
A1 - Sheikbahaei, Sara
A1 - Higuchi, Takahiro
A1 - Giesel, Frederik L.
A1 - Behr, Spencer
A1 - Drzezga, Alexander
A1 - Kimura, Hiroyuki
A1 - Buck, Andreas K.
A1 - Bengel, Frank M.
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Rowe, Steven P.
T1 - \(^{18}\)F-labeled, PSMA-targeted radiotracers: leveraging the advantages of radiofluorination for prostate cancer molecular imaging
JF - Theranostics
N2 - Prostate-specific membrane antigen (PSMA)-targeted PET imaging for prostate cancer with \(^{68}\)Ga-labeled compounds has rapidly become adopted as part of routine clinical care in many parts of the world. However, recent years have witnessed the start of a shift from \(^{68}\)Ga- to \(^{18}\)F-labeled PSMA-targeted compounds. The latter imaging agents have several key advantages, which may lay the groundwork for an even more widespread adoption into the clinic. First, facilitated delivery from distant suppliers expands the availability of PET radiopharmaceuticals in smaller hospitals operating a PET center but lacking the patient volume to justify an onsite \(^{68}\)Ge/\(^{68}\)Ga generator. Thus, such an approach meets the increasing demand for PSMA-targeted PET imaging in areas with lower population density and may even lead to cost-savings compared to in-house production. Moreover, \(^{18}\)F-labeled radiotracers have a higher positron yield and lower positron energy, which in turn decreases image noise, improves contrast resolution, and maximizes the likelihood of detecting subtle lesions. In addition, the longer half-life of 110 min allows for improved delayed imaging protocols and flexibility in study design, which may further increase diagnostic accuracy. Moreover, such compounds can be distributed to sites which are not allowed to produce radiotracers on-site due to regulatory issues or to centers without access to a cyclotron. In light of these advantageous characteristics, \(^{18}\)F-labeled PSMA-targeted PET radiotracers may play an important role in both optimizing this transformative imaging modality and making it widely available. We have aimed to provide a concise overview of emerging \(^{18}\)F-labeled PSMA-targeted radiotracers undergoing active clinical development. Given the wide array of available radiotracers, comparative studies are needed to firmly establish the role of the available \(^{18}\)F-labeled compounds in the field of molecular PCa imaging, preferably in different clinical scenarios.
KW - Radiofluorine
KW - prostate-specific membrane antigen
KW - prostate cancer
KW - \(^{18}\)F
KW - PSMA
KW - \(^{68}\)Ga
KW - theranostics
KW - radioligand therapy
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202559
SN - 1838-7640
VL - 10
IS - 1
ER -
TY - JOUR
A1 - Hertlein, Tobias
A1 - Sturm, Volker
A1 - Jakob, Peter
A1 - Ohlsen, Knut
T1 - \(^{19}\)F Magnetic Resonance Imaging of Perfluorocarbons for the Evaluation of Response to Antibiotic Therapy in a Staphylococcus aureus Infection Model
JF - PLoS ONE
N2 - Background
The emergence of antibiotic resistant bacteria in recent decades has highlighted the importance of developing new drugs to treat infections. However, in addition to the design of new drugs, the development of accurate preclinical testing methods is essential. In vivo imaging technologies such as bioluminescence imaging (BLI) or magnetic resonance imaging (MRI) are promising approaches. In a previous study, we showed the effectiveness of \(^{19}\)F MRI using perfluorocarbon (PFC) emulsions for detecting the site of Staphylococcus aureus infection. In the present follow-up study, we investigated the use of this method for in vivo visualization of the effects of antibiotic therapy.
Methods/Principal findings
Mice were infected with S. aureus Xen29 and treated with 0.9% NaCl solution, vancomycin or linezolid. Mock treatment led to the highest bioluminescence values during infection followed by vancomycin treatment. Counting the number of colony-forming units (cfu) at 7 days post-infection (p.i.) showed the highest bacterial burden for the mock group and the lowest for the linezolid group. Administration of PFCs at day 2 p.i. led to the accumulation of \(^{19}\)F at the rim of the abscess in all mice (in the shape of a hollow sphere), and antibiotic treatment decreased the \(^{19}\)F signal intensity and volume. Linezolid showed the strongest effect. The BLI, cfu, and MRI results were comparable.
Conclusions
\(^{19}\)F-MRI with PFCs is an effective non-invasive method for assessing the effects of antibiotic therapy in vivo. This method does not depend on pathogen specific markers and can therefore be used to estimate the efficacy of antibacterial therapy against a broad range of clinically relevant pathogens, and to localize sites of infection.
KW - staphylococcus aureus
KW - abscesses
KW - vancomycin
KW - antibiotics
KW - magnetic resonance imaging
KW - emulsions
KW - bioluminescence imaging
KW - in vivo imaging
Y1 - 2013
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130113
VL - 8
IS - 5
ER -
TY - JOUR
A1 - Lapa, Constantin
A1 - Lückerath, Katharina
A1 - Kleinlein, Irene
A1 - Monoranu, Camelia Maria
A1 - Linsenmann, Thomas
A1 - Kessler, Almuth F.
A1 - Rudelius, Martina
A1 - Kropf, Saskia
A1 - Buck, Andreas K.
A1 - Ernestus, Ralf-Ingo
A1 - Wester, Hans-Jürgen
A1 - Löhr, Mario
A1 - Herrmann, Ken
T1 - \(^{68}\)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma
JF - Theranostics
N2 - Chemokine receptor-4 (CXCR4) has been reported to be overexpressed in glioblastoma (GBM) and to be associated with poor survival. This study investigated the feasibility of non-invasive CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine receptor ligand \(^{68}\)Ga-Pentixafor.
15 patients with clinical suspicion on primary or recurrent glioblastoma (13 primary, 2 recurrent tumors) underwent \(^{68}\)Ga-Pentixafor-PET/CT for assessment of CXCR4 expression prior to surgery. O-(2-\(^{18}\)F-fluoroethyl)-L-tyrosine (\(^{18}\)F-FET) PET/CT images were available in 11/15 cases and were compared visually and semi-quantitatively (SUV\(_{max}\), SUV\(_{mean}\)). Tumor-to-background ratios (TBR) were calculated for both PET probes. \(^{68}\)Ga-Pentixafor-PET/CT results were also compared to histological CXCR4 expression on neuronavigated surgical samples.
\(^{68}\)Ga-Pentixafor-PET/CT was visually positive in 13/15 cases with SUV\(_{mean}\) and SUV\(_{max}\) of 3.0±1.5 and 3.9±2.0 respectively. Respective values for \(^{18}\)F-FET were 4.4±2.0 (SUV\(_{mean}\)) and 5.3±2.3 (SUV\(_{max}\)). TBR for SUV\(_{mean}\) and SUV\(_{max}\) were higher for \(^{68}\)Ga-Pentixafor than for \(^{18}\)F-FET (SUV\(_{mean}\) 154.0±90.7 vs. 4.1±1.3; SUV\(_{max}\) 70.3±44.0 and 3.8±1.2, p<0.01), respectively. Histological analysis confirmed CXCR4 expression in tumor areas with high \(^{68}\)Ga-Pentixafor uptake; regions of the same tumor without apparent \(^{68}\)Ga-Pentixafor uptake showed no or low receptor expression.
In this pilot study, \(^{68}\)Ga-Pentixafor retention has been observed in the vast majority of glioblastoma lesions and served as readout for non-invasive determination of CXCR4 expression. Given the paramount importance of the CXCR4/SDF-1 axis in tumor biology, \(^{68}\)Ga-Pentixafor-PET/CT might prove a useful tool for sensitive, non-invasive in-vivo quantification of CXCR4 as well as selection of patients who might benefit from CXCR4-directed therapy.
KW - imaging
KW - chemokine receptor-4
KW - glioblastoma
KW - positron emission tomography/computed tomography
KW - \(^{68}\)Ga-Pentixafor
Y1 - 2016
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168174
VL - 6
IS - 3
ER -
TY - JOUR
A1 - Goettel, James T.
A1 - Gao, Haopeng
A1 - Dotzauer, Simon
A1 - Braunschweig, Holger
T1 - \(^{Me}\)CAAC=N\(^{-}\): A Cyclic (Alkyl)(Amino)Carbene Imino Ligand
JF - Chemistry – A European Journal
N2 - A cyclic (alkyl)(amino)carbene (CAAC) has been shown to react with a covalent azide similar to the Staudinger reaction. The reaction of \(^{Me}\)CAAC with trimethylsilyl azide afforded the N‐silylated 2‐iminopyrrolidine (\(^{Me}\)CAAC=NSiMe\(_{3}\)), which was fully characterized. This compound undergoes hydrolysis to afford the 2‐iminopyrrolidine and trimethylsiloxane which co‐crystallize as a hydrogen‐bonded adduct. The N‐silylated 2‐iminopyrrolidine was used to transfer the novel pyrrolidine‐2‐iminato ligand onto both main‐group and transition‐metal centers. The reaction of the tetrabromodiborane bis(dimethyl sulfide) adduct with two equivalents of \(^{Me}\)CAAC=NSiMe\(_{3}\) afforded the disubstituted diborane. The reaction of \(^{Me}\)CAAC=NSiMe\(_{3}\) with TiCl\(_{4}\) and CpTiCl\(_{3}\) afforded \(^{Me}\)CAAC=NTiCl\(_{3}\) and \(^{Me}\)CAAC=NTiCl\(_{2}\)Cp, respectively.
KW - boron
KW - carbenes
KW - imide ligands
KW - nitrogen ligands
KW - titanium
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212662
VL - 26
IS - 5
ER -
TY - JOUR
A1 - Zopf, Kathrin
A1 - Frey, Kathrin R.
A1 - Kienitz, Tina
A1 - Ventz, Manfred
A1 - Bauer, Britta
A1 - Quinkler, Marcus
T1 - \(Bcl\)I polymorphism of the glucocorticoid receptor and adrenal crisis in primary adrenal insufficiency
JF - Endocrine Connections
N2 - Context: Patients with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) are at a high risk of adrenal crisis (AC). Glucocorticoid sensitivity is at least partially genetically determined by polymorphisms of the glucocorticoid receptor (GR).
Objectives: To determine if a number of intercurrent illnesses and AC are associated with the GR gene polymorphism \(Bcl\)I in patients with PAI and CAH.
Design and patients: This prospective, longitudinal study over 37.7 ± 10.1 months included 47 PAI and 25 CAH patients. During the study period, intercurrent illness episodes and AC were documented.
Results: The study period covered 223 patient years in which 21 AC occurred (9.4 AC/100 pat years). There were no significant differences between \(Bcl\)I polymorphisms (CC (n=29), CG (n=34) and GG (n=9)) regarding BMI, hydrocortisone equivalent daily dose and blood pressure. We did not find a difference in the number of intercurrent illnesses/patient year among \(Bcl\)I polymorphisms (CC (1.5±1.4/pat year), CG (1.2±1.2/pat year) and GG (1.6±2.2/pat year)). The occurrence of AC was not significantly different among the homozygous (GG) genotype (32.5 AC/100 pat years), the CC genotype (6.7 AC/100 pat years) and the CG genotype (4.9 AC/100 pat years). Concomitant hypothyroidism was the highest in the GG genotype group (5/9), compared to others (CC (11/29) and CG (11/34)).
Conclusions: Although sample sizes were relatively small and results should be interpreted with caution, this study suggests that the GR gene polymorphism \(Bcl\)I may not be associated with the frequencies of intercurrent illnesses and AC.
KW - medicine
KW - adrenal crisis
KW - adrenal insufficiency
KW - cortisol
KW - hydrocortisone
KW - polyglandular autoimmune syndrome
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173276
VL - 6
IS - 8
ER -
TY - JOUR
A1 - Allert, Stefanie
A1 - Förster, Toni M.
A1 - Svensson, Carl-Magnus
A1 - Richardson, Jonathan P.
A1 - Pawlik, Tony
A1 - Hebecker, Betty
A1 - Rudolphi, Sven
A1 - Juraschitz, Marc
A1 - Schaller, Martin
A1 - Blagojevic, Mariana
A1 - Morschhäuser, Joachim
A1 - Figge, Marc Thilo
A1 - Jacobsen, Ilse D.
A1 - Naglik, Julian R.
A1 - Kasper, Lydia
A1 - Mogavero, Selene
A1 - Hube, Bernhard
T1 - \(Candida\) \(albicans\)-Induced Epithelial Damage Mediates Translocation through Intestinal Barriers
JF - mBio
N2 - Life-threatening systemic infections often occur due to the translocation of pathogens across the gut barrier and into the bloodstream. While the microbial and host mechanisms permitting bacterial gut translocation are well characterized, these mechanisms are still unclear for fungal pathogens such as Candida albicans, a leading cause of nosocomial fungal bloodstream infections. In this study, we dissected the cellular mechanisms of translocation of C. albicans across intestinal epithelia in vitro and identified fungal genes associated with this process. We show that fungal translocation is a dynamic process initiated by invasion and followed by cellular damage and loss of epithelial integrity. A screen of >2,000 C. albicans deletion mutants identified genes required for cellular damage of and translocation across enterocytes. Correlation analysis suggests that hypha formation, barrier damage above a minimum threshold level, and a decreased epithelial integrity are required for efficient fungal translocation. Translocation occurs predominantly via a transcellular route, which is associated with fungus-induced necrotic epithelial damage, but not apoptotic cell death. The cytolytic peptide toxin of C. albicans, candidalysin, was found to be essential for damage of enterocytes and was a key factor in subsequent fungal translocation, suggesting that transcellular translocation of C. albicans through intestinal layers is mediated by candidalysin. However, fungal invasion and low-level translocation can also occur via non-transcellular routes in a candidalysin-independent manner. This is the first study showing translocation of a human-pathogenic fungus across the intestinal barrier being mediated by a peptide toxin. IMPORTANCE Candida albicans, usually a harmless fungus colonizing human mucosae, can cause lethal bloodstream infections when it manages to translocate across the intestinal epithelium. This can result from antibiotic treatment, immune dysfunction, or intestinal damage (e.g., during surgery). However, fungal processes may also contribute. In this study, we investigated the translocation process of C. albicans using in vitro cell culture models. Translocation occurs as a stepwise process starting with invasion, followed by epithelial damage and loss of epithelial integrity. The ability to secrete candidalysin, a peptide toxin deriving from the hyphal protein Ece1, is key: C. albicans hyphae, secreting candidalysin, take advantage of a necrotic weakened epithelium to translocate through the intestinal layer.
KW - Candida albicans
KW - candidalysin
KW - host cell damage
KW - host cell invasion
KW - intestinal barrier
KW - necrosis
KW - translocation
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221084
VL - 9
IS - 3
ER -
TY - JOUR
A1 - Kühlhorn, Franziska
A1 - Rath, Matthias
A1 - Schmoeckel, Katrin
A1 - Cziupka, Katharina
A1 - Nguyen, Huu Hung
A1 - Hildebrandt, Petra
A1 - Hünig, Thomas
A1 - Sparwasser, Tim
A1 - Huehn, Jochen
A1 - Pötschke, Christian
A1 - Bröker, Barbara M.
T1 - \(Foxp3^+\) Regulatory T Cells Are Required for Recovery from Severe Sepsis
JF - PLoS ONE
N2 - The role of regulatory T cells (Tregs) in bacterial sepsis remains controversial because antibody-mediated depletion experiments gave conflicting results. We employed DEREG mice (DEpletion of REGulatory T cells) and a caecal ligation and puncture model to elucidate the role of \(CD4^+Foxp3^+\) Tregs in sepsis. In DEREG mice natural Tregs can be visualized easily and selectively depleted by diphtheria toxin because the animals express the diphtheria toxin receptor and enhanced green fluorescent protein as a fusion protein under the control of the foxp3 locus. We confirmed rapid Treg-activation and an increased ratio of Tregs to Teffs in sepsis. Nevertheless, 24 h after sepsis induction, Treg-depleted and control mice showed equally strong inflammation, immune cell immigration into the peritoneum and bacterial dissemination. During the first 36 h of disease survival was not influenced by Treg-depletion. Later, however, only Treg-competent animals recovered from the insult. We conclude that the suppressive capacity of Tregs is not sufficient to control overwhelming inflammation and early mortality, but is a prerequisite for the recovery from severe sepsis.
KW - CD4(+)CD25(+)
KW - toll-like receptors
KW - TGF-BETA
KW - mediated suppression
KW - polymicrobial sepsis
KW - improves survival
KW - adoptive transfer
KW - infected mice
KW - in-vivo
KW - CD4(+)
Y1 - 2013
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130940
VL - 8
IS - 5
ER -
TY - JOUR
A1 - Breyer, Maximilian
A1 - Grüner, Julia
A1 - Klein, Alexandra
A1 - Finke, Laura
A1 - Klug, Katharina
A1 - Sauer, Markus
A1 - Üçeyler, Nurcan
T1 - \(In\) \(vitro\) characterization of cells derived from a patient with the GLA variant c.376A>G (p.S126G) highlights a non-pathogenic role in Fabry disease
JF - Molecular Genetics and Metabolism Reports
N2 - Highlights
• The GLA variant S126G is not associated with Fabry symptoms in the presented case
• S126G has no effect on α-GAL A activity or Gb3 levels in this patient
• S126G sensory neurons show no electrophysiological abnormalities
Abstract
Fabry disease (FD) is a life-limiting disorder characterized by intracellular globotriaosylceramide (Gb3) accumulations. The underlying α-galactosidase A (α-GAL A) deficiency is caused by variants in the gene GLA. Variants of unknown significance (VUS) are frequently found in GLA and challenge clinical management. Here, we investigated a 49-year old man with cryptogenic lacunar cerebral stroke and the chance finding of the VUS S126G, who was sent to our center for diagnosis and initiation of a costly and life-long FD-specific treatment. We combined clinical examination with in vitro investigations of dermal fibroblasts (HDF), induced pluripotent stem cells (iPSC), and iPSC-derived sensory neurons. We analyzed α-GAL A activity in iPSC, Gb3 accumulation in all three cell types, and action potential firing in sensory neurons. Neurological examination and small nerve fiber assessment was normal except for reduced distal skin innervation. S126G iPSC showed normal α-GAL A activity compared to controls and no Gb3 deposits were found in all three cell types. Baseline electrophysiological characteristics of S126G neurons showed no difference compared to healthy controls as investigated by patch-clamp recordings. We pioneer multi-level cellular characterization of the VUS S126G using three cell types derived from a patient and provide further evidence for the benign nature of S126G in GLA, which is of great importance in the management of such cases in clinical practice.
KW - Fabry disease
KW - variants of unknown significance
KW - C.376A>G (p.S126G)
KW - globotriaosylceramide
KW - induced pluripotent stem cells
KW - sensory neurons
KW - disease model
KW - α-Galactosidase A
Y1 - 2024
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350295
SN - 22144269
VL - 38
ER -
TY - JOUR
A1 - Jannasch, Maren
A1 - Weigel, Tobias
A1 - Engelhardt, Lisa
A1 - Wiezoreck, Judith
A1 - Gaetzner, Sabine
A1 - Walles, Heike
A1 - Schmitz, Tobias
A1 - Hansmann, Jan
T1 - \({In}\) \({vitro}\) chemotaxis and tissue remodeling assays quantitatively characterize foreign body reaction
JF - ALTEX - Alternatives to Animal Experimentation
N2 - Surgical implantation of a biomaterial triggers foreign-body-induced fibrous encapsulation. Two major mechanisms of this complex physiological process are (I) chemotaxis of fibroblasts from surrounding tissue to the implant region, followed by (II) tissue remodeling. As an alternative to animal studies, we here propose a process-aligned \({in}\) \({vitro}\) test platform to investigate the material dependency of fibroblast chemotaxis and tissue remodeling mediated by material-resident macrophages.
Embedded in a biomimetic three-dimensional collagen hydrogel, chemotaxis of fibroblasts in the direction of macrophage-material-conditioned cell culture supernatant was analyzed by live cell imaging. A combination of statistical analysis with a complementary parameterized random walk model allowed quantitative and qualitative characterization of the cellular walk process. We thereby identified an increasing macrophage-mediated chemotactic potential ranking of biomaterials from glass over polytetrafluorethylene to titanium. To address long-term effects of biomaterial-resident macrophages on fibroblasts in a three-dimensional microenvironment, we further studied tissue remodeling by applying macrophage-material-conditioned medium on fibrous \({in}\) \({vitro}\) tissue models. A high correlation of the \({in}\) \({vitro}\) tissue model to state of the art \({in}\) \({vivo}\) study data was found. Titanium exhibited a significantly lower tissue remodeling capacity compared to polytetrafluorethylene. With this approach, we identified a material dependency of both chemotaxis and tissue remodeling processes, strengthening knowledge on their specific contribution to the foreign body reaction.
KW - medicine
KW - foreign body reaction
KW - fibroblast chemotaxis
KW - tissue remodeling
KW - in vitro
KW - quanititative characterization
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172080
VL - 34
IS - 2
ER -
TY - JOUR
T1 - \({ZZ}\) -> l(+)l(-)l '(+)l '(-) cross-section measurements and search for anomalous triple gauge couplings in 13 TeV \({pp}\) collisions with the ATLAS detector
JF - Physical Review D
N2 - Measurements of ZZ production in the l(+)l(-)l'(+)l'(-) channel in proton-proton collisions at 13 TeV center-of-mass energy at the Large Hadron Collider are presented. The data correspond to 36.1 fb(-1) of collisions collected by the ATLAS experiment in 2015 and 2016. Here l and l ' stand for electrons or muons. Integrated and differential ZZ -> l(+)l(-)l'(+)l'(-) cross sections with Z -> l(+)l(-) candidate masses in the range of 66 GeV to 116 GeV are measured in a fiducial phase space corresponding to the detector acceptance and corrected for detector effects. The differential cross sections are presented in bins of twenty observables, including several that describe the jet activity. The integrated cross section is also extrapolated to a total phase space and to all standard model decays of Z bosons with mass between 66 GeV and 116 GeV, resulting in a value of 17.3 +/- 0.9 [+/- 0.6(start) +/- 0.5 (syst) +/- 0.6 (lumi)] pb. The measurements are found to be in good agreement with the standard model. A search for neutral triple gauge couplings is performed using the transverse momentum distribution of the leading Z boson candidate. No evidence for such couplings is found and exclusion limits are set on their parameters.
KW - Parton Distributions
KW - Events
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225844
VL - 97
IS - 3
ER -
TY - JOUR
A1 - Massih, Bita
A1 - Veh, Alexander
A1 - Schenke, Maren
A1 - Mungwa, Simon
A1 - Seeger, Bettina
A1 - Selvaraj, Bhuvaneish T.
A1 - Chandran, Siddharthan
A1 - Reinhardt, Peter
A1 - Sterneckert, Jared
A1 - Hermann, Andreas
A1 - Sendtner, Michael
A1 - Lüningschrör, Patrick
T1 - A 3D cell culture system for bioengineering human neuromuscular junctions to model ALS
JF - Frontiers in Cell and Developmental Biology
N2 - The signals that coordinate and control movement in vertebrates are transmitted from motoneurons (MNs) to their target muscle cells at neuromuscular junctions (NMJs). Human NMJs display unique structural and physiological features, which make them vulnerable to pathological processes. NMJs are an early target in the pathology of motoneuron diseases (MND). Synaptic dysfunction and synapse elimination precede MN loss suggesting that the NMJ is the starting point of the pathophysiological cascade leading to MN death. Therefore, the study of human MNs in health and disease requires cell culture systems that enable the connection to their target muscle cells for NMJ formation. Here, we present a human neuromuscular co-culture system consisting of induced pluripotent stem cell (iPSC)-derived MNs and 3D skeletal muscle tissue derived from myoblasts. We used self-microfabricated silicone dishes combined with Velcro hooks to support the formation of 3D muscle tissue in a defined extracellular matrix, which enhances NMJ function and maturity. Using a combination of immunohistochemistry, calcium imaging, and pharmacological stimulations, we characterized and confirmed the function of the 3D muscle tissue and the 3D neuromuscular co-cultures. Finally, we applied this system as an in vitro model to study the pathophysiology of Amyotrophic Lateral Sclerosis (ALS) and found a decrease in neuromuscular coupling and muscle contraction in co-cultures with MNs harboring ALS-linked SOD1 mutation. In summary, the human 3D neuromuscular cell culture system presented here recapitulates aspects of human physiology in a controlled in vitro setting and is suitable for modeling of MND.
KW - NMJ–neuromuscular junction
KW - motoneuron (MN)
KW - skeletal muscle
KW - iPSC (induced pluripotent stem cells)
KW - 3D cell culture
Y1 - 2023
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304161
SN - 2296-634X
VL - 11
ER -
TY - JOUR
A1 - Schneider, Verena
A1 - Kruse, Daniel
A1 - Bernardelli de Mattos, Ives
A1 - Zöphel, Saskia
A1 - Tiltmann, Kendra-Kathrin
A1 - Reigl, Amelie
A1 - Khan, Sarah
A1 - Funk, Martin
A1 - Bodenschatz, Karl
A1 - Groeber-Becker, Florian
T1 - A 3D in vitro model for burn wounds: monitoring of regeneration on the epidermal level
JF - Biomedicines
N2 - Burns affect millions every year and a model to mimic the pathophysiology of such injuries in detail is required to better understand regeneration. The current gold standard for studying burn wounds are animal models, which are under criticism due to ethical considerations and a limited predictiveness. Here, we present a three-dimensional burn model, based on an open-source model, to monitor wound healing on the epidermal level. Skin equivalents were burned, using a preheated metal cylinder. The healing process was monitored regarding histomorphology, metabolic changes, inflammatory response and reepithelialization for 14 days. During this time, the wound size decreased from 25% to 5% of the model area and the inflammatory response (IL-1β, IL-6 and IL-8) showed a comparable course to wounding and healing in vivo. Additionally, the topical application of 5% dexpanthenol enhanced tissue morphology and the number of proliferative keratinocytes in the newly formed epidermis, but did not influence the overall reepithelialization rate. In summary, the model showed a comparable healing process to in vivo, and thus, offers the opportunity to better understand the physiology of thermal burn wound healing on the keratinocyte level.
KW - skin models
KW - open-source epidermis
KW - wound model
KW - impedance spectroscopy
KW - wound physiology
KW - burn wound
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246068
SN - 2227-9059
VL - 9
IS - 9
ER -
TY - JOUR
A1 - Kiesel, Matthias
A1 - Beyers, Inga
A1 - Kalisz, Adam
A1 - Joukhadar, Ralf
A1 - Wöckel, Achim
A1 - Herbert, Saskia-Laureen
A1 - Curtaz, Carolin
A1 - Wulff, Christine
T1 - A 3D printed model of the female pelvis for practical education of gynecological pelvic examination
JF - 3D Printing in Medicine
N2 - Background
Pelvic palpation is a core component of every Gynecologic examination. It requires vigorous training, which is difficult due to its intimate nature, leading to a need of simulation. Up until now, there are mainly models available for mere palpation which do not offer adequate visualization of the concerning anatomical structures. In this study we present a 3D printed model of the female pelvis. It can improve both the practical teaching of gynecological pelvic examination for health care professionals and the spatial understanding of the relevant anatomy.
Methods
We developed a virtual, simplified model showing selected parts of the female pelvis. 3D printing was used to create a physical model.
Results
The life-size 3D printed model has the ability of being physically assembled step by step by its users. Consequently, it improves teaching especially when combining it with commercial phantoms, which are built solely for palpation training. This is achieved by correlating haptic and visual sensations with the resulting feedback received.
Conclusion
The presented 3D printed model of the female pelvis can be of aid for visualizing and teaching pelvic anatomy and examination to medical staff. 3D printing provides the possibility of creating, multiplying, adapting and sharing such data worldwide with little investment of resources. Thus, an important contribution to the international medical community can be made for training this challenging examination.
KW - gynecology
KW - pelvic examination
KW - pelvic palpation
KW - 3D printing
KW - FDM
KW - SLA
KW - teaching
KW - visualization
KW - education
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313347
VL - 8
ER -
TY - JOUR
A1 - Schmitt, Joachim
A1 - Lindner, Nathalie
T1 - A 3‐week multimodal intervention involving high‐intensity interval training in female cancer survivors: a randomized controlled trial
JF - Physiological Reports
N2 - To compare the effects of a 3‐week multimodal rehabilitation involving supervised high‐intensity interval training (HIIT) on female breast cancer survivors with respect to key variables of aerobic fitness, body composition, energy expenditure, cancer‐related fatigue, and quality of life to those of a standard multimodal rehabilitation program. A randomized controlled trial design was administered. Twenty‐eight women, who had been treated for cancer were randomly assigned to either a group performing exercise of low‐to‐moderate intensity (LMIE; n = 14) or a group performing high‐intensity interval training (HIIT; n = 14) as part of a 3‐week multimodal rehabilitation program. No adverse events related to the exercise were reported. Work economy improved following both HIIT and LMIE, with improved peak oxygen uptake following LMIE. HIIT reduced mean total body fat mass with no change in body mass, muscle or fat‐free mass (best P < 0.06). LMIE increased muscle and total fat‐free body mass. Total energy expenditure (P = 0.45) did not change between the groups, whereas both improved quality of life to a similar high extent and lessened cancer‐related fatigue. This randomized controlled study demonstrates that HIIT can be performed by female cancer survivors without adverse health effects. Here, HIIT and LMIE both improved work economy, quality of life and cancer‐related fatigue, body composition or energy expenditure. Since the outcomes were similar, but HIIT takes less time, this may be a time‐efficient strategy for improving certain aspects of the health of female cancer survivors.
KW - high-intensity interval training
Y1 - 2016
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146455
VL - 4
IS - 3
ER -
TY - JOUR
A1 - Sperlich, Billy
A1 - Hahn, Lea-Sofie
A1 - Edel, Antonia
A1 - Behr, Tino
A1 - Helmprobst, Julian
A1 - Leppich, Robert
A1 - Wallmann-Sperlich, Birgit
A1 - Holmberg, Hans-Christer
T1 - A 4-week intervention involving mobile-based daily 6-minute micro-sessions of functional high-intensity circuit training improves strength and quality of life, but not cardio-respiratory fitness of young untrained adults
JF - Frontiers in Physiology
N2 - The present study was designed to assess the psycho-physiological responses of physically untrained individuals to mobile-based multi-stimulating, circuit-like, multiple-joint conditioning (Circuit\(_{HIIT}\)) performed either once (1xCircuitHIIT) or twice (2xCircuit\(_{HIIT}\)) daily for 4 weeks. In this single-center, two-arm randomized, controlled study, 24 men and women (age: 25 ± 5 years) first received no training instructions for 4 weeks and then performed 4 weeks of either 1xCircuitHIIT or 2xCircuit\(_{HIIT}\) (5 men and 7 women in each group) daily. The 1xCircuitHIIT and 2xCircuit\(_{HIIT}\) participants carried out 90.7 and 85.7% of all planned training sessions, respectively, with average heart rates during the 6-min sessions of 74.3 and 70.8% of maximal heart rate. Body, fat and fat-free mass, and metabolic rate at rest did not differ between the groups or between time-points of measurement. Heart rate while running at 6 km⋅h\(^{-1}\) declined after the intervention in both groups. Submaximal and peak oxygen uptake, the respiratory exchange ratio and heart rate recovery were not altered by either intervention. The maximal numbers of push-ups, leg-levers, burpees, 45°-one-legged squats and 30-s skipping, as well as perception of general health improved in both groups. Our 1xCircuit\(_{HIIT}\) or 2xCircuit\(_{HIIT}\) interventions improved certain parameters of functional strength and certain dimensions of quality of life in young untrained individuals. However, they were not sufficient to enhance cardio-respiratory fitness, in particular peak oxygen uptake.
KW - aerobic fitness
KW - body composition
KW - functional training
KW - mHealth
KW - power training
KW - V800
KW - wearable
KW - web-based apps
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176565
VL - 9
IS - 423
ER -
TY - JOUR
A1 - Gilmore, Michael S.
A1 - Cruz-Rodz, Armando L.
A1 - Leimeister-Wächter, Michaela
A1 - Kreft, Jürgen
A1 - Goebel, Werner
T1 - A Bacillus cereus cytolytic determinant, cereolysin AB, which comprises the phospholipase C and sphingomyelinase genes: nucleotide sequence and genetic linkage
N2 - A cloned cytolytic determinant from the genome of Bacillus cereus GP-4 has been characterized at the molecular Ievel. Nucleotide sequence determination revealed the presence of two open reading frames. 8oth open reading frames were found by deletion and complementation analysis to be necessary for expression of the hemolytic phenotype by Bacillus subtilis and Escherichia coli hosts. The 5' open reading frame was found to be nearly identical to a recently reported phospholipase C gene derived from a mutant B. cereus strain which overexpresses the respective protein, and it conferred a lecithinase-positive phenotype to the B. subtilis host. The 3' open reading frame encoded a sphingomyelinase. The two tandemly encoded activities, phospholipase C and sphingomyelinase, constitute a biologically functional cytolytic determinant of B. cereus termed cereolysin AB.
KW - Biologie
Y1 - 1989
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60588
ER -
TY - JOUR
A1 - Vona, Barbara
A1 - Mazaheri, Neda
A1 - Lin, Sheng-Jia
A1 - Dunbar, Lucy A.
A1 - Maroofian, Reza
A1 - Azaiez, Hela
A1 - Booth, Kevin T.
A1 - Vitry, Sandrine
A1 - Rad, Aboulfazl
A1 - Rüschendorf, Franz
A1 - Varshney, Pratishtha
A1 - Fowler, Ben
A1 - Beetz, Christian
A1 - Alagramam, Kumar N.
A1 - Murphy, David
A1 - Shariati, Gholamreza
A1 - Sedaghat, Alireza
A1 - Houlden, Henry
A1 - Petree, Cassidy
A1 - VijayKumar, Shruthi
A1 - Smith, Richard J. H.
A1 - Haaf, Thomas
A1 - El-Amraoui, Aziz
A1 - Bowl, Michael R.
A1 - Varshney, Gaurav K.
A1 - Galehdari, Hamid
T1 - A biallelic variant in CLRN2 causes non-syndromic hearing loss in humans
JF - Human Genetics
N2 - Deafness, the most frequent sensory deficit in humans, is extremely heterogeneous with hundreds of genes involved. Clinical and genetic analyses of an extended consanguineous family with pre-lingual, moderate-to-profound autosomal recessive sensorineural hearing loss, allowed us to identify CLRN2, encoding a tetraspan protein, as a new deafness gene. Homozygosity mapping followed by exome sequencing identified a 14.96 Mb locus on chromosome 4p15.32p15.1 containing a likely pathogenic missense variant in CLRN2 (c.494C > A, NM_001079827.2) segregating with the disease. Using in vitro RNA splicing analysis, we show that the CLRN2 c.494C > A variant leads to two events: (1) the substitution of a highly conserved threonine (uncharged amino acid) to lysine (charged amino acid) at position 165, p.(Thr165Lys), and (2) aberrant splicing, with the retention of intron 2 resulting in a stop codon after 26 additional amino acids, p.(Gly146Lysfs*26). Expression studies and phenotyping of newly produced zebrafish and mouse models deficient for clarin 2 further confirm that clarin 2, expressed in the inner ear hair cells, is essential for normal organization and maintenance of the auditory hair bundles, and for hearing function. Together, our findings identify CLRN2 as a new deafness gene, which will impact future diagnosis and treatment for deaf patients.
KW - deafness
KW - CLRN2
KW - gene
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-267740
SN - 1432-1203
VL - 140
IS - 6
ER -
TY - JOUR
A1 - Doryab, Ali
A1 - Taskin, Mehmet Berat
A1 - Stahlhut, Philipp
A1 - Schröppel, Andreas
A1 - Orak, Sezer
A1 - Voss, Carola
A1 - Ahluwalia, Arti
A1 - Rehberg, Markus
A1 - Hilgendorff, Anne
A1 - Stöger, Tobias
A1 - Groll, Jürgen
A1 - Schmid, Otmar
T1 - A Bioinspired in vitro Lung Model to Study Particokinetics of Nano-/Microparticles Under Cyclic Stretch and Air-Liquid Interface Conditions
JF - Frontiers in Bioengineering and Biotechnology
N2 - Evolution has endowed the lung with exceptional design providing a large surface area for gas exchange area (ca. 100 m\(^{2}\)) in a relatively small tissue volume (ca. 6 L). This is possible due to a complex tissue architecture that has resulted in one of the most challenging organs to be recreated in the lab. The need for realistic and robust in vitro lung models becomes even more evident as causal therapies, especially for chronic respiratory diseases, are lacking. Here, we describe the Cyclic In VItro Cell-stretch (CIVIC) “breathing” lung bioreactor for pulmonary epithelial cells at the air-liquid interface (ALI) experiencing cyclic stretch while monitoring stretch-related parameters (amplitude, frequency, and membrane elastic modulus) under real-time conditions. The previously described biomimetic copolymeric BETA membrane (5 μm thick, bioactive, porous, and elastic) was attempted to be improved for even more biomimetic permeability, elasticity (elastic modulus and stretchability), and bioactivity by changing its chemical composition. This biphasic membrane supports both the initial formation of a tight monolayer of pulmonary epithelial cells (A549 and 16HBE14o\(^{-}\)) under submerged conditions and the subsequent cell-stretch experiments at the ALI without preconditioning of the membrane. The newly manufactured versions of the BETA membrane did not improve the characteristics of the previously determined optimum BETA membrane (9.35% PCL and 6.34% gelatin [w/v solvent]). Hence, the optimum BETA membrane was used to investigate quantitatively the role of physiologic cyclic mechanical stretch (10% linear stretch; 0.33 Hz: light exercise conditions) on size-dependent cellular uptake and transepithelial transport of nanoparticles (100 nm) and microparticles (1,000 nm) for alveolar epithelial cells (A549) under ALI conditions. Our results show that physiologic stretch enhances cellular uptake of 100 nm nanoparticles across the epithelial cell barrier, but the barrier becomes permeable for both nano- and micron-sized particles (100 and 1,000 nm). This suggests that currently used static in vitro assays may underestimate cellular uptake and transbarrier transport of nanoparticles in the lung.
KW - lung cell model
KW - cyclic stretch
KW - ALI culture
KW - bioinspired membrane
KW - particle study
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223830
SN - 2296-4185
VL - 9
ER -
TY - JOUR
A1 - Doryab, Ali
A1 - Taskin, Mehmet Berat
A1 - Stahlhut, Philipp
A1 - Schröppel, Andreas
A1 - Wagner, Darcy E.
A1 - Groll, Jürgen
A1 - Schmid, Otmar
T1 - A Biomimetic, Copolymeric Membrane for Cell‐Stretch Experiments with Pulmonary Epithelial Cells at the Air‐Liquid Interface
JF - Advanced Functional Materials
N2 - Chronic respiratory diseases are among the leading causes of death worldwide, but only symptomatic therapies are available for terminal illness. This in part reflects a lack of biomimetic in vitro models that can imitate the complex environment and physiology of the lung. Here, a copolymeric membrane consisting of poly(ε‐)caprolactone and gelatin with tunable properties, resembling the main characteristics of the alveolar basement membrane is introduced. The thin bioinspired membrane (≤5 μm) is stretchable (up to 25% linear strain) with appropriate surface wettability and porosity for culturing lung epithelial cells under air–liquid interface conditions. The unique biphasic concept of this membrane provides optimum characteristics for initial cell growth (phase I) and then switch to biomimetic properties for cyclic cell‐stretch experiments (phase II). It is showed that physiologic cyclic mechanical stretch improves formation of F‐actin cytoskeleton filaments and tight junctions while non‐physiologic over‐stretch induces cell apoptosis, activates inflammatory response (IL‐8), and impairs epithelial barrier integrity. It is also demonstrated that cyclic physiologic stretch can enhance the cellular uptake of nanoparticles. Since this membrane offers considerable advantages over currently used membranes, it may lead the way to more biomimetic in vitro models of the lung for translation of in vitro response studies into clinical outcome.
KW - alveolar‐capillary barrier
KW - cyclic mechanical stretch
KW - hybrid polymers
KW - in vitro cell‐stretch model
KW - tunable ultra‐thin biphasic membrane
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225645
VL - 31
IS - 10
ER -
TY - JOUR
A1 - Schmidt, Sven
A1 - Alt, Yvonne
A1 - Deoghare, Nikita
A1 - Krüger, Sarah
A1 - Kern, Anna
A1 - Rockel, Anna Frederike
A1 - Wagner, Nicole
A1 - Ergün, Süleyman
A1 - Wörsdörfer, Philipp
T1 - A blood vessel organoid model recapitulating aspects of vasculogenesis, angiogenesis and vessel wall maturation
JF - Organoids
N2 - Blood vessel organoids are an important in vitro model to understand the underlying mechanisms of human blood vessel development and for toxicity testing or high throughput drug screening. Here we present a novel, cost-effective, and easy to manufacture vascular organoid model. To engineer the organoids, a defined number of human induced pluripotent stem cells are seeded in non-adhesive agarose coated wells of a 96-well plate and directed towards a lateral plate mesoderm fate by activation of Wnt and BMP4 signaling. We observe the formation of a circular layer of angioblasts around days 5–6. Induced by VEGF application, CD31\(^+\) vascular endothelial cells appear within this vasculogenic zone at approximately day 7 of organoid culture. These cells arrange to form a primitive vascular plexus from which angiogenic sprouting is observed after 10 days of culture. The differentiation outcome is highly reproducible, and the size of organoids is scalable depending on the number of starting cells. We observe that the initial vascular ring forms at the interface between two cell populations. The inner cellular compartment can be distinguished from the outer by the expression of GATA6, a marker of lateral plate mesoderm. Finally, 14-days-old organoids were transplanted on the chorioallantois membrane of chicken embryos resulting in a functional connection of the human vascular network to the chicken circulation. Perfusion of the vessels leads to vessel wall maturation and remodeling as indicated by the formation of a continuous layer of smooth muscle actin expressing cells enwrapping the endothelium. In summary, our organoid model recapitulates human vasculogenesis, angiogenesis as well as vessel wall maturation and therefore represents an easy and cost-effective tool to study all steps of blood vessel development and maturation directly in the human setting without animal experimentation.
KW - organoid
KW - blood vessel
KW - vasculogenesis
KW - angiogenesis
KW - induced pluripotent stem cells
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284043
SN - 2674-1172
VL - 1
IS - 1
SP - 41
EP - 53
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 - Würthner, Frank
A1 - Noll, Niklas
T1 - A Calix[4]arene‐Based Cyclic Dinuclear Ruthenium Complex for Light‐Driven Catalytic Water Oxidation
JF - Chemistry - A European Journal
N2 - A cyclic dinuclear ruthenium(bda) (bda: 2,2’‐bipyridine‐6,6’‐dicarboxylate) complex equipped with oligo(ethylene glycol)‐functionalized axial calix[4]arene ligands has been synthesized for homogenous catalytic water oxidation. This novel Ru(bda) macrocycle showed significantly increased catalytic activity in chemical and photocatalytic water oxidation compared to the archetype mononuclear reference [Ru(bda)(pic)\(_2\)]. Kinetic investigations, including kinetic isotope effect studies, disclosed a unimolecular water nucleophilic attack mechanism of this novel dinuclear water oxidation catalyst (WOC) under the involvement of the second coordination sphere. Photocatalytic water oxidation with this cyclic dinuclear Ru complex using [Ru(bpy)\(_3\)]Cl\(_2\) as a standard photosensitizer revealed a turnover frequency of 15.5 s\(^{−1}\) and a turnover number of 460. This so far highest photocatalytic performance reported for a Ru(bda) complex underlines the potential of this water‐soluble WOC for artificial photosynthesis.
KW - water
KW - oxidation
KW - ruthenium
KW - dinuclear
KW - catalytic
KW - artificial photosynthesis
KW - homogenous catalysis
KW - photocatalysis
KW - ruthenium complexes
KW - water oxidation
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230030
UR - https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202004486
VL - 27
IS - 1
ER -
TY - JOUR
A1 - Eulalio, Ana
A1 - Fröhlich, Kathrin S.
A1 - Mano, Miguel
A1 - Giacca, Mauro
A1 - Vogel, Jörg
T1 - A Candidate Approach Implicates the Secreted Salmonella Effector Protein SpvB in P-Body Disassembly
N2 - P-bodies are dynamic aggregates of RNA and proteins involved in several post-transcriptional regulation processes. Pbodies have been shown to play important roles in regulating viral infection, whereas their interplay with bacterial pathogens, specifically intracellular bacteria that extensively manipulate host cell pathways, remains unknown. Here, we report that Salmonella infection induces P-body disassembly in a cell type-specific manner, and independently of previously characterized pathways such as inhibition of host cell RNA synthesis or microRNA-mediated gene silencing. We show that the Salmonella-induced P-body disassembly depends on the activation of the SPI-2 encoded type 3 secretion system, and that the secreted effector protein SpvB plays a major role in this process. P-body disruption is also induced by the related pathogen, Shigella flexneri, arguing that this might be a new mechanism by which intracellular bacterial pathogens subvert host cell function.
KW - Salmonella
KW - RNS
Y1 - 2011
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68928
ER -
TY - JOUR
A1 - Bischoff, Joakim M.
A1 - Ringsted, Thomas K.
A1 - Petersen, Marian
A1 - Sommer, Claudia
A1 - Üçeyler, Nurcan
A1 - Werner, Mads U.
T1 - A Capsaicin (8%) Patch in the Treatment of Severe Persistent Inguinal Postherniorrhaphy Pain: A Randomized, Double-Blind, Placebo-Controlled Trial
JF - PLOS ONE
N2 - Background: Persistent pain after inguinal herniorrhaphy is a disabling condition with a lack of evidence-based pharmacological treatment options. This randomized placebo-controlled trial investigated the efficacy of a capsaicin 8% cutaneous patch in the treatment of severe persistent inguinal postherniorrhaphy pain. Methods: Forty-six patients with persistent inguinal postherniorrhaphy pain were randomized to receive either a capsaicin 8% patch or a placebo patch. Pain intensity (Numerical Rating Scale [NRS 0-10]) was evaluated under standardized conditions (at rest, during movement, and during pressure) at baseline and at 1, 2 and 3 months after patch application. Skin punch biopsies for intraepidermal nerve fiber density (IENFD) measurements were taken at baseline and 1 month after patch application. Quantitative sensory testing was performed at baseline and at 1, 2, and 3 months after patch application. The primary outcome was comparisons of summed pain intensity differences (SPIDs) between capsaicin and placebo treatments at 1, 2 and 3 months after patch application (significance level P<0.01). Results: The maximum difference in SPID, between capsaicin and placebo treatments, was observed at 1 month after patch application, but the pain reduction was not significant (NRS, mean difference [95% CI]: 5.0 [0.09 to 9.9]; P=0.046). No differences in SPID between treatments were observed at 2 and 3 months after patch application. Changes in IENFD on the pain side, from baseline to 1 month after patch application, did not differ between capsaicin and placebo treatment: 1.9 [-0.1 to 3.9] and 0.6 [-1.2 to 2.5] fibers/mm, respectively (P=0.32). No significant changes in sensory function, sleep quality or psychological factors were associated with capsaicin patch treatment. Conclusions: The study did not demonstrate significant differences in pain relief between capsaicin and placebo treatment, although a trend toward pain improvement in capsaicin treated patients was observed 1 month after patch application.
KW - postherpetic neuralgia
KW - long-term pain
KW - crossover trial
KW - neuropathic pain
KW - risk factors
KW - cutaneous patch
KW - scale
KW - hernia repair
KW - interference
KW - validation
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115198
SN - 1932-6203
VL - 9
IS - 10
ER -
TY - JOUR
A1 - Bommakanti, R. K.
A1 - Klotz, Karl-Norbert
A1 - Dratz, E. A.
A1 - Jesaitis, A. J.
T1 - A carboxyl-terminal tail peptide of neutrophil chemotactic receptor disrupts its physical complex with G protein
N2 - No abstract available
KW - Toxikologie
Y1 - 1993
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60456
ER -
TY - JOUR
A1 - Rosenfeldt, Mathias T.
A1 - Hartmann, Elena M.
A1 - Leng, Corinna
A1 - Rosenwald, Andreas
A1 - Anagnostopoulos, Ioannis
T1 - A case of nodular lymphocyte predominant Hodgkin lymphoma with unexpected EBV-latency type
JF - Annals of Hematology
N2 - No abstract available.
KW - nodular lymphcyte
KW - Hodgkin lymphoma
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232571
SN - 0939-5555
VL - 100
ER -
TY - JOUR
A1 - Baur, Johannes
A1 - Schedelbeck, Ulla
A1 - Pulzer, Alina
A1 - Bluemel, Christina
A1 - Wild, Vanessa
A1 - Fassnacht, Martin
A1 - Steger, U.
T1 - A case report of a solitary pancreatic metastasis of an adrenocortical carcinoma
JF - BMC Surgery
N2 - Background
Solitary metastases to the pancreas are rare. Therefore the value of resection in curative intention remains unclear. In the literature there are several promising reports about resection of solitary metastasis to the pancreas mainly of renal origin.
Case presentation
Here we report for the first time on the surgical therapy of a 1.5 cm solitary pancreatic metastasis of an adrenocortical carcinoma. The metastasis occurred almost 6 years after resection of the primary tumor. A partial pancreatoduodenectomy was performed and postoperatively adjuvant mitotane treatment was initiated. During the follow-up of 3 years after surgery no evidence of tumor recurrence occurred.
Conclusion
Resection of pancreatic tumors should be considered, even if the mass is suspicious for metastatic disease including recurrence of adrenocortical cancer.
KW - surgical treatment
KW - adrenocortical
KW - carcinoma metastases to pancreas
Y1 - 2015
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126130
VL - 15
IS - 93
ER -
TY - JOUR
A1 - Lorenz, Delia
A1 - Musacchio, Thomas
A1 - Kunstmann, Erdmute
A1 - Grauer, Eva
A1 - Pluta, Natalie
A1 - Stock, Annika
A1 - Speer, Christian P.
A1 - Hebestreit, Helge
T1 - A case report of Sanfilippo syndrome - the long way to diagnosis
JF - BMC Neurology
N2 - Background
Mucopolysaccharidosis type III (Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in the heparan-N-sulfatase enzyme involved in the catabolism of the glycosaminoglycan heparan sulfate. It is characterized by early nonspecific neuropsychiatric symptoms, followed by progressive neurocognitive impairment in combination with only mild somatic features. In this patient group with a broad clinical spectrum a significant genotype-phenotype correlation with some mutations leading to a slower progressive, attenuated course has been demonstrated.
Case presentation
Our patient had complications in the neonatal period and was diagnosed with Mucopolysaccharidosis IIIa only at the age of 28 years. He was compound heterozygous for the variants p.R245H and p.S298P, the latter having been shown to lead to a significantly milder phenotype.
Conclusions
The diagnostic delay is even more prolonged in this patient population with comorbidities and a slowly progressive course of the disease.
KW - Mucopolysaccharidosis IIIa
KW - diagnostic delay
KW - genotype-phenotype correlation
KW - p.S298P
KW - p.R245H
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300465
VL - 22
IS - 1
ER -
TY - JOUR
A1 - May-Mederake, Birgit
A1 - Shehata-Dieler, Wafaa
T1 - A Case Study Assessing the Auditory and Speech Development of Four Children Implanted with Cochlear Implants by the Chronological Age of 12 Months
JF - Case Reports in Otolaryngology
N2 - Children with severe hearing loss most likely receive the greatest benefit from a cochlear implant (CI) when implanted at less than 2 years of age. Children with a hearing loss may also benefit greater from binaural sensory stimulation. Four children who received their first CI under 12 months of age were included in this study. Effects on auditory development were determined using the German LittlEARS Auditory Questionnaire, closed- and open-set monosyllabic word tests, aided free-field, the Mainzer and Göttinger speech discrimination tests, Monosyllabic-Trochee-Polysyllabic (MTP), and Listening Progress Profile (LiP). Speech production and grammar development were evaluated using a German language speech development test (SETK), reception of grammar test (TROG-D) and active vocabulary test (AWST-R). The data showed that children implanted under 12 months of age reached open-set monosyllabic word discrimination at an age of 24 months. LiP results improved over time, and children recognized 100% of words in the MTP test after 12 months. All children performed as well as or better than their hearing peers in speech production and grammar development. SETK showed that the speech development of these children was in general age appropriate. The data suggests that early hearing loss intervention benefits speech and language development and supports the trend towards early cochlear implantation. Furthermore, the data emphasizes the potential benefits associated with bilateral implantation.
KW - Otolaryngolgy
Y1 - 2013
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128750
VL - 2013
IS - 359218
ER -
TY - JOUR
A1 - Dütting, Sebastian
A1 - Gaits-Iacovoni, Frederique
A1 - Stegner, David
A1 - Popp, Michael
A1 - Antkowiak, Adrien
A1 - van Eeuwijk, Judith M.M.
A1 - Nurden, Paquita
A1 - Stritt, Simon
A1 - Heib, Tobias
A1 - Aurbach, Katja
A1 - Angay, Oguzhan
A1 - Cherpokova, Deya
A1 - Heinz, Niels
A1 - Baig, Ayesha A.
A1 - Gorelashvili, Maximilian G.
A1 - Gerner, Frank
A1 - Heinze, Katrin G.
A1 - Ware, Jerry
A1 - Krohne, Georg
A1 - Ruggeri, Zaverio M.
A1 - Nurden, Alan T.
A1 - Schulze, Harald
A1 - Modlich, Ute
A1 - Pleines, Irina
A1 - Brakebusch, Cord
A1 - Nieswandt, Bernhard
T1 - A Cdc42/RhoA regulatory circuit downstream of glycoprotein Ib guides transendothelial platelet biogenesis
JF - Nature Communications
N2 - Blood platelets are produced by large bone marrow (BM) precursor cells, megakaryocytes (MKs), which extend cytoplasmic protrusions (proplatelets) into BM sinusoids. The molecular cues that control MK polarization towards sinusoids and limit transendothelial crossing to proplatelets remain unknown. Here, we show that the small GTPases Cdc42 and RhoA act as a regulatory circuit downstream of the MK-specific mechanoreceptor GPIb to coordinate polarized transendothelial platelet biogenesis. Functional deficiency of either GPIb or Cdc42 impairs transendothelial proplatelet formation. In the absence of RhoA, increased Cdc42 activity and MK hyperpolarization triggers GPIb-dependent transmigration of entire MKs into BM sinusoids. These findings position Cdc42 (go-signal) and RhoA (stop-signal) at the centre of a molecular checkpoint downstream of GPIb that controls transendothelial platelet biogenesis. Our results may open new avenues for the treatment of platelet production disorders and help to explain the thrombocytopenia in patients with Bernard–Soulier syndrome, a bleeding disorder caused by defects in GPIb-IX-V.
KW - megakaryocytes
KW - blood platelets
KW - regulatory circuit downstream
KW - glycoprotein Ib
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170797
VL - 8
IS - 15838
ER -
TY - JOUR
A1 - Philipp, Marius
A1 - Dietz, Andreas
A1 - Ullmann, Tobias
A1 - Kuenzer, Claudia
T1 - A circum-Arctic monitoring framework for quantifying annual erosion rates of permafrost coasts
JF - Remote Sensing
N2 - This study demonstrates a circum-Arctic monitoring framework for quantifying annual change of permafrost-affected coasts at a spatial resolution of 10 m. Frequent cloud coverage and challenging lighting conditions, including polar night, limit the usability of optical data in Arctic regions. For this reason, Synthetic Aperture RADAR (SAR) data in the form of annual median and standard deviation (sd) Sentinel-1 (S1) backscatter images covering the months June–September for the years 2017–2021 were computed. Annual composites for the year 2020 were hereby utilized as input for the generation of a high-quality coastline product via a Deep Learning (DL) workflow, covering 161,600 km of the Arctic coastline. The previously computed annual S1 composites for the years 2017 and 2021 were employed as input data for the Change Vector Analysis (CVA)-based coastal change investigation. The generated DL coastline product served hereby as a reference. Maximum erosion rates of up to 67 m per year could be observed based on 400 m coastline segments. Overall highest average annual erosion can be reported for the United States (Alaska) with 0.75 m per year, followed by Russia with 0.62 m per year. Out of all seas covered in this study, the Beaufort Sea featured the overall strongest average annual coastal erosion of 1.12 m. Several quality layers are provided for both the DL coastline product and the CVA-based coastal change analysis to assess the applicability and accuracy of the output products. The predicted coastal change rates show good agreement with findings published in previous literature. The proposed methods and data may act as a valuable tool for future analysis of permafrost loss and carbon emissions in Arctic coastal environments.
KW - permafrost
KW - coastal erosion
KW - circum-Arctic
KW - deep learning
KW - change vector analysis
KW - Google Earth Engine
KW - synthetic aperture RADAR
Y1 - 2023
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304447
SN - 2072-4292
VL - 15
IS - 3
ER -
TY - JOUR
A1 - White, P. Lewis
A1 - Springer, Jan
A1 - Wise, Matt P.
A1 - Einsele, Hermann
A1 - Löffler, Claudia
A1 - Seif, Michelle
A1 - Prommersberger, Sabrina
A1 - Backx, Matthijs
A1 - Löffler, Jürgen
T1 - A clinical case of COVID-19-associated pulmonary aspergillosis (CAPA), illustrating the challenges in diagnosis (despite overwhelming mycological evidence)
JF - Journal of Fungi
N2 - The COVID-19 pandemic has resulted in large numbers of patients requiring critical care management. With the established association between severe respiratory virus infection and invasive pulmonary aspergillosis (7.6% for COVID-19-associated pulmonary aspergillosis (CAPA)), the pandemic places a significant number of patients at potential risk from secondary invasive fungal disease. We described a case of CAPA with substantial supporting mycological evidence, highlighting the need to employ strategic diagnostic algorithms and weighted definitions to improve the accuracy in diagnosing CAPA.
KW - COVID-19
KW - CAPA
KW - diagnostics
KW - Aspergillus
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-302438
SN - 2309-608X
VL - 8
IS - 1
ER -
TY - JOUR
A1 - Lutz, Werner K.
A1 - Schlatter, C.
T1 - A closed inhalation system for pharmacokinetic and metabolism studies of volatile compounds with small laboratory animals
N2 - In the inhalation system described an animal can be kept in the same atmosphere of a 2-liter desiccator for up to 24 h. The expired carbon dioxide is adsorbed with soda lime and the resulting reduced pressure is balanced by a supply of oxygen also used for the inflow of the chemical to be investigated. Urine and faeces can be collected ~eparately and the system allows a periodical control of the concentration of the chemical by sampling the air with needle and syringe.
KW - Toxikologie
Y1 - 1978
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-80145
ER -
TY - JOUR
A1 - Drescher, Nora
A1 - Klein, Alexandra-Maria
A1 - Schmitt, Thomas
A1 - Leonhardt, Sara Diana
T1 - A clue on bee glue: New insight into the sources and factors driving resin intake in honeybees (Apis mellifera)
JF - PLoS ONE
N2 - Honeybees (Apis mellifera) are threatened by numerous pathogens and parasites. To prevent infections they apply cooperative behavioral defenses, such as allo-grooming and hygiene, or they use antimicrobial plant resin. Resin is a chemically complex and highly variable mixture of many bioactive compounds. Bees collect the sticky material from different plant species and use it for nest construction and protection. Despite its importance for colony health, comparatively little is known about the precise origins and variability in resin spectra collected by honeybees. To identify the botanical resin sources of A. mellifera in Western Europe we chemically compared resin loads of individual foragers and tree resins. We further examined the resin intake of 25 colonies from five different apiaries to assess the effect of location on variation in the spectra of collected resin. Across all colonies and apiaries, seven distinct resin types were categorized according to their color and chemical composition. Matches between bee-collected resin and tree resin indicated that bees used poplar (Populus balsamifera, P. x canadensis), birch (Betula alba), horse chestnut (Aesculus hippocastanum) and coniferous trees (either Picea abies or Pinus sylvestris) as resin sources. Our data reveal that honeybees collect a comparatively broad and variable spectrum of resin sources, thus assuring protection against a variety of antagonists sensitive to different resins and/or compounds. We further unravel distinct preferences for specific resins and resin chemotypes, indicating that honeybees selectively search for bioactive resin compounds.
KW - Honey bees
KW - Poplars
KW - Trees
KW - Forests
KW - Chemical composition
KW - Bees
KW - Conifers
KW - Phenols
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200935
VL - 14
IS - 2
ER -
TY - JOUR
A1 - Marcus, U.
A1 - Vogel, U.
A1 - Schubert, A.
A1 - Claus, H.
A1 - Baetzing-Feigenbaum, J.
A1 - Hellenbrand, W.
A1 - Wichmann, O.
T1 - A cluster of invasive meningococcal disease in young men who have sex with men in Berlin, October 2012 to May 2013
JF - Eurosurveillance
N2 - No abstract available.
KW - meningococcal disease
Y1 - 2013
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131711
VL - 18
IS - 28
ER -
TY - JOUR
A1 - Schuhmann, Antonia
A1 - Scheiner, Ricarda
T1 - A combination of the frequent fungicides boscalid and dimoxystrobin with the neonicotinoid acetamiprid in field-realistic concentrations does not affect sucrose responsiveness and learning behavior of honeybees
JF - Ecotoxicology and Environmental Safety
N2 - The increasing loss of pollinators over the last decades has become more and more evident. Intensive use of plant protection products is one key factor contributing to this decline. Especially the mixture of different plant protection products can pose an increased risk for pollinators as synergistic effects may occur. In this study we investigated the effect of the fungicide Cantus® Gold (boscalid/dimoxystrobin), the neonicotinoid insecticide Mospilan® (acetamiprid) and their mixture on honeybees. Since both plant protection products are frequently applied sequentially to the same plants (e.g. oilseed rape), their combination is a realistic scenario for honeybees. We investigated the mortality, the sucrose responsiveness and the differential olfactory learning performance of honeybees under controlled conditions in the laboratory to reduce environmental noise. Intact sucrose responsiveness and learning performance are of pivotal importance for the survival of individual honeybees as well as for the functioning of the entire colony. Treatment with two sublethal and field relevant concentrations of each plant protection product did not lead to any significant effects on these behaviors but affected the mortality rate. However, our study cannot exclude possible negative sublethal effects of these substances in higher concentrations. In addition, the honeybee seems to be quite robust when it comes to effects of plant protection products, while wild bees might be more sensitive.
Highlights
• Mix of SBI fungicides and neonicotinoids can lead to synergistic effects for bees.
• Combination of non-SBI fungicide and neonicotinoid in field-realistic doses tested.
• Synergistic effect on mortality of honeybees.
• No effects on sucrose responsiveness and learning performance of honeybees.
• Synergistic effects by other pesticide mixtures or on wild bees cannot be excluded.
KW - Apis mellifera
KW - non-SBI fungicide
KW - insecticide
KW - pesticide mixture
KW - synergistic effect
KW - sublethal effect
Y1 - 2023
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350047
VL - 256
ER -
TY - JOUR
A1 - Richter, Gesa M.
A1 - Kruppa, Jochen
A1 - Munz, Matthias
A1 - Wiehe, Ricarda
A1 - Häsler, Robert
A1 - Franke, Andre
A1 - Martins, Orlando
A1 - Jockel-Schneider, Yvonne
A1 - Bruckmann, Corinna
A1 - Dommisch, Henrik
A1 - Schaefer, Arne S.
T1 - A combined epigenome- and transcriptome-wide association study of the oral masticatory mucosa assigns CYP1B1 a central role for epithelial health in smokers
JF - Clinical Epigenetics
N2 - Background
The oral mucosa has an important role in maintaining barrier integrity at the gateway to the gastrointestinal and respiratory tracts. Smoking is a strong environmental risk factor for the common oral inflammatory disease periodontitis and oral cancer. Cigarette smoke affects gene methylation and expression in various tissues. This is the first epigenome-wide association study (EWAS) that aimed to identify biologically active methylation marks of the oral masticatory mucosa that are associated with smoking.
Results
Ex vivo biopsies of 18 current smokers and 21 never smokers were analysed with the Infinium Methylation EPICBeadChip and combined with whole transcriptome RNA sequencing (RNA-Seq; 16 mio reads per sample) of the same samples. We analysed the associations of CpG methylation values with cigarette smoking and smoke pack year (SPY) levels in an analysis of covariance (ANCOVA). Nine CpGs were significantly associated with smoking status, with three CpGs mapping to the genetic region of CYP1B1 (cytochrome P450 family 1 subfamily B member 1;best p=5.5x10(-8)) and two mapping to AHRR (aryl-hydrocarbon receptor repressor; best p=5.9x10(-9)). In the SPY analysis, 61 CpG sites at 52 loci showed significant associations of the quantity of smoking with changes in methylation values. Here, the most significant association located to the gene CYP1B1, with p=4.0x10(-10). RNA-Seq data showed significantly increased expression of CYP1B1 in smokers compared to non-smokers (p=2.2x10(-14)), together with 13 significantly upregulated transcripts. Six transcripts were significantly downregulated. No differential expression was observed for AHRR. In vitro studies with gingival fibroblasts showed that cigarette smoke extract directly upregulated the expression of CYP1B1.
Conclusion
This study validated the established role of CYP1B1 and AHRR in xenobiotic metabolism of tobacco smoke and highlights the importance of epigenetic regulation for these genes. For the first time, we give evidence of this role for the oral masticatory mucosa.
KW - EWAS
KW - Methylation
KW - Expression
KW - Masticatory mucosa
KW - CYP1B1
KW - AHRR
KW - Cytochrome P 450 pathway
KW - OSCC
KW - Smoking
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226175
VL - 11
ER -
TY - JOUR
A1 - El-Kareh, Lydia
A1 - Bihlmayer, Gustav
A1 - Buchter, Arne
A1 - Bentmann, Hendrik
A1 - Blügel, Stefan
A1 - Reinert, Friedrich
A1 - Bode, Matthias
T1 - A combined experimental and theoretical study of Rashba-split surface states on the ( √3x√3) Pb/Ag (111)R30° surface
N2 - We report on a combined low-temperature scanning tunneling spectroscopy (STS), angle-resolved photoemission spectroscopy (ARPES), and density functional theory (DFT) investigation of the ( √3x√3) Pb/Ag (111)R30° surface alloy which provides a giant Rashba-type spin splitting. With STS we observed spectroscopic features that are assigned to two hole-like Rashba-split bands in the unoccupied energy range. By means of STS and quantum interference mapping we determine the band onsets, splitting strengths, and dispersions for both bands. The unambiguous assignment of scattering vectors is achieved by comparison to ARPES measurements. While intra-band scattering is found for both Rashba bands, inter-band scattering is only observed in the occupied energy range. Spin- and orbitally-resolved band structures were obtained by DFT calculations. Considering the scattering between states of different spin- and orbital character, the apparent deviation between experimentally observed scattering events and the theoretically predicted spin polarization could be resolved.
KW - Rashba effect
KW - spin–orbit coupling
KW - scanning tunneling microscopy
KW - angle resolved photo emission spectroscopy
KW - density functional theory
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112786
ER -