@article{HansmannHeinzmannWrenzyckietal.2010, author = {Hansmann, T. and Heinzmann, J. and Wrenzycki, C. and Zechner, U. and Niemann, H. and Haaf, T.}, title = {Characterization of Differentially Methylated Regions in 3 Bovine Imprinted Genes: A Model for Studying Human Germ-Cell and Embryo Development}, series = {Cytogenetic and Genome Research}, volume = {132}, journal = {Cytogenetic and Genome Research}, number = {4}, issn = {1424-8581}, doi = {10.1159/000322627}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199051}, pages = {239-247}, year = {2010}, abstract = {Correct imprinting is crucial for normal fetal and placental development in mammals. Experimental evidence in animal models and epidemiological studies in humans suggest that assisted reproductive technologies (ARTs) can interfere with imprinted gene regulation in gametogenesis and early embryogenesis. Bos taurus is an agriculturally important species in which ARTs are commonly employed. Because this species exhibits a similar preimplantation development and gestation length as humans, it is increasingly being used as a model for human germ-cell and embryo development. However, in contrast to humans and mice, there is relatively little information on bovine imprinted genes. Here, we characterized the bovine intergenic IGF2-H19 imprinting control region (ICR) spanning approximately 3 kb. We identified a 300-bp differentially methylated region (DMR) approximately 6 kb upstream of the H19 promoter, containing a CpG island with CTCF-binding site and high sequence similarity with the human intergenic ICR. Additional differentially methylated CpG islands lie -6 kb to -3 kb upstream of the promoter, however these are less conserved. Both classical bisulfite sequencing and bisulfite pyrosequencing demonstrated complete methylation of the IGF2-H19 ICR in sperm, complete demethylation in parthenogenetic embryos having only the female genome, and differential methylation in placental and somatic tissues. In addition, we established pyrosequencing assays for the previously reported bovine SNRPN and PEG3 DMRs. The observed methylation patterns were consistent with genomic imprinting in all analyzed tissues/cell types. The identified IGF2-H19 ICR and the developed quantitative methylation assays may prove useful for further studies on the relationship between ARTs and imprinting defects in the bovine model.}, language = {en} } @article{StellzigEisenhauerMeyerMarcotty2010, author = {Stellzig-Eisenhauer, Angelika and Meyer-Marcotty, Philipp}, title = {Interaction between otorhinolaryngology and orthodontics: correlation between the nasopharyngeal airway and the craniofacial complex}, series = {GMS Current Topics in Otorhinolaryngology - Head and Neck Surgery}, volume = {9}, journal = {GMS Current Topics in Otorhinolaryngology - Head and Neck Surgery}, number = {Dok04}, doi = {10.3205/cto000068}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140850}, pages = {1-8}, year = {2010}, abstract = {In terms of pathophysiology, an anatomically narrow airway is a predisposing factor for obstruction of the upper respiratory tract. The correlation between the nasopharyngeal airway and the craniofacial structures is discussed in this context. Thus a mutual interaction between the pharynx and the mandibular position was demonstrated, whereby the transverse dimension of the nasopharynx was significantly larger in patients with prognathism than in patients with retrognathism. The influence of chronic obstruction of the nasal airway on craniofacial development was also discussed. The form-and-function interaction, which ought to explain the causal relationship between nasal obstruction and craniofacial growth, appears to be of a multifactorial rather than a one-dimensional, linear nature. It is not disputed, however, that expanding the maxilla improves not only nasal volume and nasal flow, but also the subjective sensation of patients, although it is not possible to make a prognostic statement about the extent of this improvement because of the differing reactions of individuals. Orthodontic appliances for advancing the mandible can also be successfully used in the treatment of mild obstructive sleep apnea syndrome. This treatment method should be considered particularly for patients who are unwilling to undergo or cannot tolerate CPAP (continuous positive airway pressure) treatment.}, language = {en} } @article{HommersLee2010, author = {Hommers, Wilfried and Lee, Wha-Yong}, title = {Unifying Kohlberg with Information Integration: The Moral Algebra of Recompense and of Kohlbergian Moral Informers}, series = {Psicol{\´o}gica}, journal = {Psicol{\´o}gica}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85875}, year = {2010}, abstract = {In order to unify two major theories of moral judgment, a novel task is employed which combines elements of Kohlberg´s stage theory and of the theory of information integration. In contrast to the format of Kohlberg´s moral judgment interview, a nonverbal and quantitative response which makes low demands on verbal facility was used . Moral informers differing in value, i.e. high and low, are presented. The differences in effect of those two pieces of information should be substantial for a person at that specific moral stage, but small for a person at a different stage. Hence, these differences may diagnose the person's moral stage in the simplest possible way as the two levels of each of the thoughts were about typical content of the four Kohlbergian preconventional and conventional stages. The novel task allowed additionally to measure the influence of another moral concept which was about the non-Kohlbergian moral concept of recompense. After a training phase, pairs of those thoughts were presented to allow for the study of integration and individual differences. German and Korean children, 8, 10, and 12 years in age, judged deserved punishment. The patterns of means, correlations and factor loadings showed that elements of both theories can be unified, but produced unexpected results also. Additive integration of each of the two pairs of moral informers appeared, either with two Kohlbergian moral informers or with another Kohlbergian moral informer in combination with information about recompense. Also cultural independence as well as dependence, developmental changes between 8 and 10 years, and an outstanding moral impact of recompense in size and distinctiveness were observed.}, language = {en} } @article{ReisererHuangHechtetal.2010, author = {Reiserer, Andreas A. and Huang, Jer-Shing and Hecht, Bert and Brixner, Tobias}, title = {Subwavelength broadband splitters and switches for femtosecond plasmonic signals}, series = {Optics Express}, journal = {Optics Express}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85889}, year = {2010}, abstract = {Numerical simulations and an analytic approach based on transmission line theory are used to design splitters for nano-plasmonic signal processing that allow to arbitrarily adjust the ratio of transmission from an input into two different output arms. By adjusting the geometrical parameters of the structure, either a high bandwidth or a sharp transmission resonance is obtained. Switching between the two arms can be achieved by modulating the effective refractive index of the waveguide. Employing the instantaneous Kerr effect, switching rates in the THz regime are potentially feasible. The suggested devices are of interest for future applications in nanoplasmonic information processing.}, language = {en} } @article{HuenigHuenig2010, author = {Huenig, Siegfried and Huenig, Georg}, title = {Cataract Surgery With Implantation of an Artificial Lens}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85908}, year = {2010}, language = {en} } @article{JohanssenHahnerSaegeretal.2010, author = {Johanssen, Sarah and Hahner, Stefanie and Saeger, Wolfgang and Quinkler, Marcus and Beuschlein, Felix and Dralle, Henning and Haaf, Michaela and Kroiss, Matthias and Jurowich, Christian and Langer, Peter and Oelkers, Wolfgang and Spahn, Martin and Willenberg, Holger S. and Maeder, Uwe and Allolio, Bruno and Fassnacht, Martin}, title = {Deficits in the Management of Patients With Adrenocortical Carcinoma in Germany}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85897}, year = {2010}, abstract = {Background: Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Often, the physicians who first treat patients with ACC have no prior experience with the disease. The aim of our study was to evaluate the quality of medical care for patients with ACC in Germany. Methods: Data from the German ACC registry were analyzed with regard to the patients' preoperative diagnostic evaluation, histopathological reporting, and clinical followup. The findings were compared with the recommendations of the European Network for the Study of Adrenal Tumors (ENSAT). Results: Data were analyzed from 387 patients who had been given an initial diagnosis of ACC in the years 1998 to 2009. 21\% of them underwent no hormonal evaluation before surgery, and 59\% underwent an inadequate hormonal evaluation. This exposed the patients to unnecessary perioperative risks and impaired their follow-up. 48\% did not undergo CT scanning of the chest, even though the lungs are the most frequent site of metastases of ACC. For 13\% of the patients, the diagnosis of ACC was later revised by a reference pathologist. For 11\% of the patients, the histopathology report contained no information about resection status, even though this is an important determinant of further treatment and prognosis. Optimal management requires re-staging at three-month intervals, yet some patients underwent re-staging only after a longer delay, or not at all. Conclusion: We have identified significant deficits in the care of patients with ACC in Germany. We suspect that the situation is similar for other rare diseases. The prerequisite to better care is close and early cooperation of the treating physicians with specialized centers.}, language = {en} } @article{Dietl2010, author = {Dietl, Johannes}, title = {The Marketing Effect}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85868}, year = {2010}, language = {en} } @article{ZollnerRehnDietl2010, author = {Zollner, Ursula and Rehn, Monika and Dietl, Johannes}, title = {Perinatal Problems in Multiple Births Inconsistent Terminology}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85850}, year = {2010}, language = {en} } @article{RueschEberhartWallenbornetal.2010, author = {Ruesch, Dirk and Eberhart, Leopold H. J. and Wallenborn, Jan and Kranke, Peter}, title = {Nausea and Vomiting After Surgery Under General Anesthesia An Evidence-Based Review Concerning Risk Assessment, Prevention, and Treatment}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85847}, year = {2010}, abstract = {Background: The German-language recommendations for the management of postoperative nausea and vomiting(PONV) have been revised by an expert committee. Major aspects of this revision are presented here in the form of an evidence-based review article. Methods: The literature was systematically reviewed with the goal of revising the existing recommendations. New evidence-based recommendations for the management of PONV were developed, approved by consensus, and graded according to the scheme of the Scottish Intercollegiate Guidelines Network (SIGN). Results: The relevant risk factors for PONV include female sex, nonsmoker status, prior history of PONV, motion sickness, use of opioids during and after surgery, use of inhalational anesthetics and nitrous oxide, and the duration of anesthesia. PONV scoring systems provide a rough assessment of risk that can serve as the basis for a riskadapted approach. Risk-adapted prophylaxis, however, has not been shown to provide any greater benefit than fixed (combination) prophylaxis, and PONV risk scores have inherent limitations; thus, fixed prophylaxis may be advantageous. Whichever of these two approaches to manage PONV is chosen, high-risk patients must be given multimodal prophylaxis, involving both the avoidance of known risk factors and the application of multiple validated and effective antiemetic interventions. PONV should be treated as soon as it arises, to minimize patient discomfort, the risk of medical complications, and the costs involved. Conclusion: PONV lowers patient satisfaction but is treatable. The effective, evidence-based measures of preventing and treating it should be implemented in routine practice.}, language = {en} } @article{SchuppHeidlandStopper2010, author = {Schupp, Nicole and Heidland, August and Stopper, Helga}, title = {Genomic Damage in Endstage Renal Disease - Contribution of Uremic Toxins}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68653}, year = {2010}, abstract = {Patients with end-stage renal disease (ESRD), whether on conservative, peritoneal or hemodialysis therapy, have elevated genomic damage in peripheral blood lymphocytes and an increased cancer incidence, especially of the kidney. The damage is possibly due to accumulation of uremic toxins like advanced glycation endproducts or homocysteine. However, other endogenous substances with genotoxic properties, which are increased in ESRD, could be involved, such as the blood pressure regulating hormones angiotensin II and aldosterone or the inflammatory cytokine TNF-. This review provides an overview of genomic damage observed in ESRD patients, focuses on possible underlying causes and shows modulations of the damage by modern dialysis strategies and vitamin upplementation.}, subject = {Toxin}, language = {en} } @article{SchenkelUhlemann2010, author = {Schenkel, Alexander and Uhlemann, Christoph F.}, title = {Field Theory on Curved Noncommutative Spacetimes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68648}, year = {2010}, abstract = {We study classical scalar field theories on noncommutative curved spacetimes. Following the approach of Wess et al. [Classical Quantum Gravity 22 (2005), 3511 and Classical Quantum Gravity 23 (2006), 1883], we describe noncommutative spacetimes by using (Abelian) Drinfel'd twists and the associated ?-products and ?-differential geometry. In particular, we allow for position dependent noncommutativity and do not restrict ourselves to the Moyal-Weyl deformation. We construct action functionals for real scalar fields on noncommutative curved spacetimes, and derive the corresponding deformed wave equations. We provide explicit examples of deformed Klein-Gordon operators for noncommutative Minkowski, de Sitter, Schwarzschild and Randall-Sundrum spacetimes, which solve the noncommutative Einstein equations. We study the construction of deformed Green's functions and provide a diagrammatic approach for their perturbative calculation. The leading noncommutative corrections to the Green's functions for our examples are derived.}, subject = {Physik}, language = {en} } @article{ConradFritschZeidleretal.2010, author = {Conrad, Christopher and Fritsch, Sebastian and Zeidler, Julian and R{\"u}cker, Gerd and Dech, Stefan}, title = {Per-Field Irrigated Crop Classification in Arid Central Asia Using SPOT and ASTER Data}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68630}, year = {2010}, abstract = {The overarching goal of this research was to explore accurate methods of mapping irrigated crops, where digital cadastre information is unavailable: (a) Boundary separation by object-oriented image segmentation using very high spatial resolution (2.5-5 m) data was followed by (b) identification of crops and crop rotations by means of phenology, tasselled cap, and rule-based classification using high resolution (15-30 m) bi-temporal data. The extensive irrigated cotton production system of the Khorezm province in Uzbekistan, Central Asia, was selected as a study region. Image segmentation was carried out on pan-sharpened SPOT data. Varying combinations of segmentation parameters (shape, compactness, and color) were tested for optimized boundary separation. The resulting geometry was validated against polygons digitized from the data and cadastre maps, analysing similarity (size, shape) and congruence. The parameters shape and compactness were decisive for segmentation accuracy. Differences between crop phenologies were analyzed at field level using bi-temporal ASTER data. A rule set based on the tasselled cap indices greenness and brightness allowed for classifying crop rotations of cotton, winter-wheat and rice, resulting in an overall accuracy of 80 \%. The proposed field-based crop classification method can be an important tool for use in water demand estimations, crop yield simulations, or economic models in agricultural systems similar to Khorezm.}, subject = {Geologie}, language = {en} } @article{LandmannSchrammColditzetal.2010, author = {Landmann, Tobias and Schramm, Matthias and Colditz, Rene R. and Dietz, Andreas and Dech, Stefan}, title = {Wide Area Wetland Mapping in Semi-Arid Africa Using 250-Meter MODIS Metrics and Topographic Variables}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68628}, year = {2010}, abstract = {Wetlands in West Africa are among the most vulnerable ecosystems to climate change. West African wetlands are often freshwater transfer mechanisms from wetter climate regions to dryer areas, providing an array of ecosystem services and functions. Often wetland-specific data in Africa is only available on a per country basis or as point data. Since wetlands are challenging to map, their accuracies are not well considered in global land cover products. In this paper we describe a methodology to map wetlands using well-corrected 250-meter MODIS time-series data for the year 2002 and over a 360,000 km2 large study area in western Burkina Faso and southern Mali (West Africa). A MODIS-based spectral index table is used to map basic wetland morphology classes. The index uses the wet season near infrared (NIR) metrics as a surrogate for flooding, as a function of the dry season chlorophyll activity metrics (as NDVI). Topographic features such as sinks and streamline areas were used to mask areas where wetlands can potentially occur, and minimize spectral confusion. 30-m Landsat trajectories from the same year, over two reference sites, were used for accuracy assessment, which considered the area-proportion of each class mapped in Landsat for every MODIS cell. We were able to map a total of five wetland categories. Aerial extend of all mapped wetlands (class "Wetland") is 9,350 km2, corresponding to 4.3\% of the total study area size. The classes "No wetland"/"Wetland" could be separated with very high certainty; the overall agreement (KHAT) was 84.2\% (0.67) and 97.9\% (0.59) for the two reference sites, respectively. The methodology described herein can be employed to render wide area base line information on wetland distributions in semi-arid West Africa, as a data-scarce region. The results can provide (spatially) interoperable information feeds for inter-zonal as well as local scale water assessments.}, subject = {Geologie}, language = {en} } @article{KoetschanFoersterKelleretal.2010, author = {Koetschan, Christian and Foerster, Frank and Keller, Alexander and Schleicher, Tina and Ruderisch, Benjamin and Schwarz, Roland and Mueller, Tobias and Wolf, Matthias and Schultz, Joerg}, title = {The ITS2 Database III-sequences and structures for phylogeny}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68390}, year = {2010}, abstract = {The internal transcribed spacer 2 (ITS2) is a widely used phylogenetic marker. In the past, it has mainly been used for species level classifications. Nowadays, a wider applicability becomes apparent. Here, the conserved structure of the RNA molecule plays a vital role. We have developed the ITS2 Database (http://its2.bioapps .biozentrum.uni-wuerzburg.de) which holds information about sequence, structure and taxonomic classification of all ITS2 in GenBank. In the new version, we use Hidden Markov models (HMMs) for the identification and delineation of the ITS2 resulting in a major redesign of the annotation pipeline. This allowed the identification of more than 160 000 correct full ength and more than 50 000 partial structures. In the web interface, these can now be searched with a modified BLAST considering both sequence and structure, enabling rapid taxon sampling. Novel sequences can be annotated using the HMM based approach and modelled according to multiple template structures. Sequences can be searched for known and newly identified motifs. Together, the database and the web server build an exhaustive resource for ITS2 based phylogenetic analyses.}, subject = {Biologie}, language = {en} } @article{AlbrechtSharmaReinhardtetal.2010, author = {Albrecht, Marco and Sharma, Cynthia M. and Reinhardt, Richard and Vogel, Joerg and Rudel, Thomas}, title = {Deep sequencing-based discovery of the Chlamydia trachomatis transcriptome}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68389}, year = {2010}, abstract = {Chlamydia trachomatis is an obligate intracellular pathogenic bacterium that has been refractory to genetic manipulations. Although the genomes of several strains have been sequenced, very little information is available on the gene structure of these bacteria. We used deep sequencing to define the transcriptome of purified elementary bodies (EB) and reticulate bodies (RB) of C. trachomatis L2b, respectively. Using an RNAseq approach, we have mapped 363 transcriptional start sites (TSS) of annotated genes. Semiquantitative analysis of mapped cDNA reads revealed differences in the RNA levels of 84 genes isolated from EB and RB, respectively. We have identified and in part confirmed 42 genome- and 1 plasmid-derived novel non-coding RNAs. The genome encoded non-coding RNA, ctrR0332 was one of the most abundantly and differentially expressed RNA in EB and RB, implying an important role in the developmental cycle of C. trachomatis. The detailed map of TSS in a thus far unprecedented resolution as a complement to the genome sequence will help to understand the organization, control and function of genes of this important pathogen.}, subject = {Biologie}, language = {en} } @article{SchneiderPliushchElHajjetal.2010, author = {Schneider, Eberhard and Pliushch, Galyna and El Hajj, Nady and Galetzka, Danuta and Puhl, Alexander and Schorsch, Martin and Frauenknecht, Katrin and Riepert, Thomas and Tresch, Achim and Mueller, Annette M. and Coerdt, Wiltrud and Zechner, Ulrich and Haaf, Thomas}, title = {Spatial, temporal and interindividual epigenetic variation of functionally important DNA methylation patterns}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68371}, year = {2010}, abstract = {DNA methylation is an epigenetic modification that plays an important role in gene regulation. It can be influenced by stochastic events, environmental factors and developmental programs. However, little is known about the natural variation of genespecific methylation patterns. In this study, we performed quantitative methylation analyses of six differentially methylated imprinted genes (H19, MEG3, LIT1, NESP55, PEG3 and SNRPN), one hypermethylated pluripotency gene (OCT4) and one hypomethylated tumor suppressor gene (APC) in chorionic villus, fetal and adult cortex, and adult blood samples. Both average methylation level and range of methylation variation depended on the gene locus, tissue type and/or developmental stage. We found considerable variability of functionally important methylation patterns among unrelated healthy individuals and a trend toward more similar methylation levels in monozygotic twins than in dizygotic twins. Imprinted genes showed relatively little methylation changes associated with aging in individuals who are >25 years. The relative differences in methylation among neighboring CpGs in the generally hypomethylated APC promoter may not only reflect stochastic fluctuations but also depend on the tissue type. Our results are consistent with the view that most methylation variation may arise after fertilization, leading to epigenetic mosaicism.}, subject = {Medizin}, language = {en} } @article{RotheReinthalerLiuetal.2010, author = {Rothe, D. G. and Reinthaler, R. W. and Liu, C-X and Molenkamp, L. W. and Zhang, S-C and Hankiewicz, E. M.}, title = {Fingerprint of different spin-orbit terms for spin transport in HgTe quantum wells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68362}, year = {2010}, abstract = {Using k · p theory, we derive an effective four-band model describing the physics of the typical two-dimensional topological insulator (HgTe/CdTe quantum well (QW)) in the presence of an out-of-plane (in the z-direction) inversion breaking potential and an in-plane potential. We find that up to third order in perturbation theory, only the inversion breaking potential generates new elements to the four-band Hamiltonian that are off-diagonal in spin space. When this new effective Hamiltonian is folded into an effective twoband model for the conduction (electron) or valence (heavy hole) bands, two competing terms appear: (i) a Rashba spin-orbit interaction originating from inversion breaking potential in the z-direction and (ii) an in-plane Pauli term as a consequence of the in-plane potential. Spin transport in the conduction band is further analysed within the Landauer-B{\"u}ttiker formalism. We find that for asymmetrically doped HgTe QWs, the behaviour of the spin-Hall conductance is dominated by the Rashba term.}, subject = {Physik}, language = {en} } @article{UeceylerBikoSommer2010, author = {Ueceyler, Nurcan and Biko, Lydia and Sommer, Claudia}, title = {MDL-28170 Has No Analgesic Effect on CCI Induced Neuropathic Pain in Mice}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68359}, year = {2010}, abstract = {The calpain inhibitor MDL-28710 blocks the early local pro-inflammatory cytokine gene expression in mice after chronic constriction nerve injury (CCI). Onehundred- thirteen wild type mice of C57Bl/6J background received CCI of the right sciatic nerve. Mechanical paw withdrawal thresholds and thermal withdrawal latencies were investigated at baseline and at 1, 3, and 7 days after CCI. Three application regimens were used for MDL-28170: a) single injection 40 min before CCI; b) serial injections of MDL- 28170 40 min before and up to day three after CCI; c) sustained application via intraperitoneal osmotic pumps. The control animals received the vehicle DMSO/PEG 400. The tolerable dose of MDL-28170 for mice was 30 mg/kg body weight, higher doses were lethal within the first hours after application. Mechanical withdrawal thresholds and thermal withdrawal latencies were reduced after CCI and did not normalize after single or serial injections, nor with application of MDL-28170 via osmotic pumps. Although the calpain inhibitor MDL-28170 inhibits the early local cytokine upregulation in the sciatic nerve after CCI, pain behavior is not altered. This finding implies that local cytokine upregulation after nerve injury alone is only one factor in the induction and maintenance of neuropathic pain.}, subject = {Medizin}, language = {en} } @article{ChenBoettgerReifetal.2010, author = {Chen, Yong and Boettger, Michael K. and Reif, Andreas and Schmitt, Angelika and Ueceyler, Nurcan and Sommer, Claudia}, title = {Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68349}, year = {2010}, abstract = {Background: Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. Results: Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1b), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1b. The increase of the antiinflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-1b, and IL-10 following CFA, overall corroborating the inhibitor data. Conclusion: These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.}, subject = {Medizin}, language = {en} } @article{MeierjohannHufnagelWendeetal.2010, author = {Meierjohann, Svenja and Hufnagel, Anita and Wende, Elisabeth and Kleinschmidt, Markus A. and Wolf, Katarina and Friedl, Peter and Gaubatz, Stefan and Schartl, Manfred}, title = {MMP13 mediates cell cycle progression in melanocytes and melanoma cells: in vitro studies of migration and proliferation}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68335}, year = {2010}, abstract = {Background: Melanoma cells are usually characterized by a strong proliferative potential and efficient invasive migration. Among the multiple molecular changes that are recorded during progression of this disease, aberrant activation of receptor tyrosine kinases (RTK) is often observed. Activation of matrix metalloproteases goes along with RTK activation and usually enhances RTK-driven migration. The purpose of this study was to examine RTKdriven three-dimensional migration of melanocytes and the pro-tumorigenic role of matrix metalloproteases for melanocytes and melanoma cells. Results: Using experimental melanocyte dedifferentiation as a model for early melanomagenesis we show that an activated EGF receptor variant potentiates migration through three-dimensional fibrillar collagen. EGFR stimulation also resulted in a strong induction of matrix metalloproteases in a MAPK-dependent manner. However, neither MAPK nor MMP activity were required for migration, as the cells migrated in an entirely amoeboid mode. Instead, MMPs fulfilled a function in cell cycle regulation, as their inhibition resulted in strong growth inhibition of melanocytes. The same effect was observed in the human melanoma cell line A375 after stimulation with FCS. Using sh- and siRNA techniques, we could show that MMP13 is the protease responsible for this effect. Along with decreased proliferation, knockdown of MMP13 strongly enhanced pigmentation of melanocytes. Conclusions: Our data show for the first time that growth stimuli are mediated via MMP13 in melanocytes and melanoma, suggesting an autocrine MMP13-driven loop. Given that MMP13-specific inhibitors are already developed, these results support the evaluation of these inhibitors in the treatment of melanoma.}, subject = {Medizin}, language = {en} }