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  • 1
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Experimental dermatology 10 (2001), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Dendritic cells seem to be of major importance for the pathogenesis of psoriasis. They are increased in number in lesional psoriatic skin which is thought to be due to an increased influx from the peripheral blood regulated by chemotaxins. Using a biological/biochemical approach we have addressed the question whether psoriasis scale extracts contain proteinaceous chemotaxins for dendritic cells. Human monocytes differentiated into dendritic cells by culture with GM-CSF and IL-4 (MoDC) served as responder cells. Chemotactic activity for MoDC was purified by several HPLC-steps. The results of our study show that C5a/C5adesarg is the major chemotactic peptide for MoDC in psoriasis scale extracts. In comparison to other stimuli such as fMLP or monocyte chemotactic peptide 1 (MCP-1) C5a proved to be a most potent and efficient chemotaxin for MoDC. C5a co-eluted with MRP14/calgranulin B which is present in large amounts in psoriasis scale extracts as identified by amino acid sequencing. However, MRP14/calgranulin B did not possess any chemotactic activity for MoDC. Our results provide evidence that C5a/C5adesarg although not specific for dendritic cells seems to be the major chemoattractant for these cells in lesional psoriasis skin.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Experimental dermatology 9 (2000), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The etiology and pathogenesis of psoriasis – one of the most common chronic, inflammatory, hyperproliferative skin disorders of man – have long fascinated dermatologists, pathologists and biologists alike. Here, we have a model disease that offers to study neuroectodermal-mesenchymal interactions in the widest sense possible. Epithelial, endothelial, and hematopoietic cells as well as neurons projecting into the skin apparently all interact with each other to generate the characteristic psoriatic lesion. For decades, the ongoing controversy on the molecular nature, choreography and hierarchy of these complex interactions e.g. between epidermal keratinocytes, T cells, neurotrophils, endothelial cells and sensory nerves has served as a driving force propelling investigative dermatology to ever new horizons. This debate has not only been at the heart of our quest to develop more effective forms of therapy for this socially crippling disease, but it also has profoundly influenced how we view the skin as a whole: the numerous competing theories on the pathogenesis of psoriasis published so far also are reflections on the evolution of mainstream thought in skin biology over the last decades. These days, conventional wisdom – infatuated with a T-cell-centered approach to inflammatory skin diseases – portrays psoriasis as an autoimmune disease, where misguided T lymphocyte activities cause secondary epithelial abnormalities. And yet, as this CONTROVERSIES feature reminds us, some authoritative “pockets of academic resistance” are still quite alive, and interpret psoriasis e.g. as a genetically determined, abnormal epithelial response pattern to infectious and/or physicochemical skin insults. Weighing the corresponding lines of argumentation is not only an intriguing, clinically relevant intellectual exercise, but also serves as a wonderful instrument for questioning our own views of the skin universe and its patterns of deviation from a state of homeostasis.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Allergy 57 (2002), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: To gain insight into the mechanisms responsible for tissue neutrophil immigration in sinusitis, primary nasal fibroblasts are analyzed for synthesizing and delivering neutrophil chemokines.Methods: Primary nasal fibroblast cell culture was treated with tumor necrosis factor (TNF)-α concentrations of 20 and 200 ng/ml for 2, 8, 24 and 72 h. Chemokine concentrations in supernatants were determined by enzyme-linked immunoassay (ELISA) and chemokine mRNA expression in fibroblasts was measured by reverse transcriptase polymerase chain reaction (RT-PCR). Biological chemotactic activity was identified by three-step high-performance liquid chromatography (HPLC) and by bioassay measuring neutrophil chemotaxis in a single Boyden chamber system.Results: Interleukin (IL)-8 and growth-related oncogene (GRO)-α were induced in nasal fibroblast culture by proinflammatory stimulus. After 24 h of stimulation neutrophil chemotactic activity only was detected for IL-8. Granulocyte chemotactic protein (GCP)-2 mRNA was already significantly up-regulated after 2 h of stimulation.Conclusion: Induction of IL-8 protein dominates chemokine synthesis 24 and 72 h after stimulation, whereas induction of GCP-2 mRNA seems to have a role in the early phase after 2 h of exposition with TNF-α.
    Type of Medium: Electronic Resource
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  • 4
    Publication Date: 2015-07-09
    Print ISSN: 1045-2249
    Electronic ISSN: 1465-7279
    Topics: Biology
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  • 5
    Publication Date: 2013-01-03
    Description: The spectra of several high-redshift ( z 〉 6) quasars have shown indications for a Gunn–Peterson (GP) damping wing, suggesting a substantial mean neutral hydrogen fraction ( $\bar{x}_{\rm H\,{\scriptscriptstyle I}}^{\rm IGM}\gtrsim 0.03$ ) in the z 6 intergalactic medium (IGM). However, previous analyses assumed that the IGM was uniformly ionized outside of the quasar’s H  ii region. Here we relax this assumption and model patchy reionization scenarios for a range of IGM and quasar parameters. Compared to uniform reionization, patchy reionization imprints a different average damping wing profile with an associated sightline-to-sightline scatter. We quantify the impact of these differences on the inferred $\bar{x}_{\rm H\,{\scriptscriptstyle I}}^{\rm IGM}$ , by fitting the spectra of three quasars: SDSS J1148+5251 ( z = 6.4189), J1030+0524 ( z = 6.308) and J1623+3112 ( z = 6.247). We find that the best-fitting values of $\bar{x}_{\rm H\,{\scriptscriptstyle I}}^{\rm IGM}$ in the patchy models agree well with the uniform case. More importantly, we confirm that the observed spectra favour the presence of a GP damping wing, with peak likelihoods decreasing by factors of few–10 when the spectra are modelled without a damping wing. We also find that the Lyα absorption spectra, by themselves, cannot distinguish the damping wing in a relatively neutral IGM from a damping wing in a highly ionized IGM, caused either by an isolated neutral patch or by a damped Lyα absorber (DLA). However, neutral patches in a highly ionized universe ( $\bar{x}_{\rm H\,{\scriptscriptstyle I}}^{\rm IGM}\lesssim 10^{-2}$ ) and DLAs with the large required column densities ( $N_{\rm H\,{\small I}}\gtrsim {\rm { few}}\times 10^{20}{\rm { cm}^{-2}}$ ) are both rare. As a result, when we include reasonable prior probabilities for the line of sight (LOS) to intercept either a neutral patch or a DLA at the required distance of ~ 40-60 comoving Mpc away from the quasar, we find strong lower limits on the neutral fraction in the IGM, $\bar{x}_{\rm H\,{\scriptscriptstyle I}}^{\rm IGM}\gtrsim 0.1$ (at 95 per cent confidence). This supports earlier claims that a substantial global fraction of hydrogen in the z 6 IGM is in neutral form.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 6
    Publication Date: 2012-09-06
    Description: Nonpigmented Yersinia pestis ( pgm ) strains are defective in scavenging host iron and have been used in live-attenuated vaccines to combat plague epidemics. Recently, a Y. pestis pgm strain was isolated from a researcher with hereditary hemochromatosis who died from laboratory-acquired plague. We used hemojuvelin-knockout ( Hjv –/– ) mice to examine whether iron-storage disease restores the virulence defects of nonpigmented Y. pestis . Unlike wild-type mice, Hjv –/– mice developed lethal plague when challenged with Y. pestis pgm strains. Immunization of Hjv –/– mice with a subunit vaccine that blocks Y. pestis type III secretion generated protection against plague. Thus, individuals with hereditary hemochromatosis may be protected with subunit vaccines but should not be exposed to live-attenuated plague vaccines.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
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  • 7
    Publication Date: 2016-02-16
    Description: We employed a semi-Markov multistate model for the simultaneous analysis of various endpoints describing the course of breast cancer. Results were compared with those from standard analyses using a Cox proportional hazards model. We included 3,012 patients with invasive breast cancer newly diagnosed between 2001 and 2005 who were recruited in Germany for a population-based study, the Mamma Carcinoma Risk Factor Investigation (MARIE Study), and prospectively followed up until the end of 2009. Locoregional recurrence and distant metastasis were included as intermediate states, and deaths from breast cancer, secondary cancer, and other causes were included as competing absorbing states. Tumor characteristics were significantly associated with all breast cancer–related endpoints. Nodal involvement was significantly related to local recurrence but more strongly related to distant metastases. Smoking was significantly associated with mortality from second cancers and other causes, whereas menopausal hormone use was significantly associated with reduced distant metastasis and death from causes other than cancer. The presence of cardiovascular disease at diagnosis was solely associated with mortality from other causes. Compared with separate Cox models, multistate models allow for dissection of prognostic factors and intermediate events in the analysis of cause-specific mortality and can yield new insights into disease progression and associated pathways.
    Print ISSN: 0002-9262
    Electronic ISSN: 1476-6256
    Topics: Medicine
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  • 8
    Publication Date: 2012-08-15
    Description: Aims Dynamic three-dimensional-cardiac magnetic resonance (3D-CMR) perfusion proved highly diagnostic for the detection of angiographically defined coronary artery disease (CAD) and has been used to assess the efficacy of coronary stenting procedures. The present study aimed to relate significant coronary lesions as assessed by fractional flow reserve (FFR) to the volume of myocardial hypoenhancement on 3D-CMR adenosine stress perfusion imaging and to define the inter-study reproducibility of stress inducible 3D-CMR hypoperfusion. Methods and results A total of 120 patients with known or suspected CAD were examined in two CMR centres using 1.5 T systems. The protocol included cine imaging, 3D-CMR perfusion during adenosine infusion, and at rest followed by delayed enhancement (DE) imaging. Fractional flow reserve was recorded in epicardial coronary arteries and side branches with ≥2 mm luminal diameter and 〉40% severity stenosis (pathologic FFR 〈 0.75). Twenty-five patients underwent an identical repeat CMR examination for the determination of inter-study reproducibility of 3D-CMR perfusion deficits induced by adenosine. Three-dimensional CMR perfusion scans were visually classified as pathologic if one or more segments showed an inducible perfusion deficit in the absence of DE. Myocardial ischaemic burden (MIB) was measured by segmentation of the area of inducible hypoenhancement and normalized to left ventricular myocardial volume (MIB, %). Three-dimensional CMR perfusion resulted in a sensitivity, specificity, and diagnostic accuracy of 90, 82, and 87%, respectively. Substantial concordance was found for inter-study reproducibility [Lin's correlation coefficient: 0.98 (95% confidence interval: 0.96–0.99)]. Conclusion Three-dimensional CMR stress perfusion provided high diagnostic accuracy for the detection of functionally significant CAD. Myocardial ischaemic burden measurements were highly reproducible and allowed the assessment of CAD severity.
    Print ISSN: 0195-668X
    Electronic ISSN: 1522-9645
    Topics: Medicine
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  • 9
    Publication Date: 2014-04-29
    Description: Potassium (K + )-uptake transport proteins present in prokaryote and eukaryote cells are categorized into two classes; Trk/Ktr/HKT, K + channel, and Kdp belong to the same superfamily, whereas the remaining K + -uptake family, Kup/HAK/KT has no homology to the others, and neither its membrane topology nor crucial residues for K + uptake have been identified. We examined the topology of Kup from Escherichia coli . Results from the reporter fusion and cysteine labeling assays support a model with 12 membrane-spanning domains. A model for proton-coupled K + uptake mediated by Kup has been proposed. However, this study did not show any stimulation of Kup activity at low pH and any evidence of involvement of the three His in Kup-mediated K + uptake. Moreover, replacement of all four cysteines of Kup with serine did not abolish K + transport activity. To gain insight on crucial residues of Kup-mediated K + uptake activity, we focused on acidic residues in the predicted external and transmembrane regions, and identified four residues in the membrane regions required for K + uptake activity. This is different from no membrane-localized acidic residues essential for Trk/Ktr/HKTs, K + channels and Kdp. Taken together, these results demonstrate that Kup belongs to a distinct type of K + transport system.
    Print ISSN: 0021-924X
    Electronic ISSN: 1756-2651
    Topics: Biology , Chemistry and Pharmacology
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