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Search Results: 1 - 10 of 302088 matches for " Markus J. Maeurer "
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Increased Numbers of IL-7 Receptor Molecules on CD4+CD25?CD107a+ T-Cells in Patients with Autoimmune Diseases Affecting the Central Nervous System
Nalini Kumar Vudattu,Sharon Kuhlmann-Berenzon,Mohsen Khademi,Vicki Seyfert,Thomas Olsson,Markus J. Maeurer
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0006534
Abstract: High content immune profiling in peripheral blood may reflect immune aberrations associated with inflammation in multiple sclerosis (MS) and other autoimmune diseases affecting the central nervous system.
Pattern Recognition in Pulmonary Tuberculosis Defined by High Content Peptide Microarray Chip Analysis Representing 61 Proteins from M. tuberculosis
Simani Gaseitsiwe, Davide Valentini, Shahnaz Mahdavifar, Isabelle Magalhaes, Daniel F. Hoft, Johannes Zerweck, Mike Schutkowski, Jan Andersson, Marie Reilly, Markus J. Maeurer
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003840
Abstract: Background Serum antibody-based target identification has been used to identify tumor-associated antigens (TAAs) for development of anti-cancer vaccines. A similar approach can be helpful to identify biologically relevant and clinically meaningful targets in M.tuberculosis (MTB) infection for diagnosis or TB vaccine development in clinically well defined populations. Method We constructed a high-content peptide microarray with 61 M.tuberculosis proteins as linear 15 aa peptide stretches with 12 aa overlaps resulting in 7446 individual peptide epitopes. Antibody profiling was carried with serum from 34 individuals with active pulmonary TB and 35 healthy individuals in order to obtain an unbiased view of the MTB epitope pattern recognition pattern. Quality data extraction was performed, data sets were analyzed for significant differences and patterns predictive of TB+/?. Findings Three distinct patterns of IgG reactivity were identified: 89/7446 peptides were differentially recognized (in 34/34 TB+ patients and in 35/35 healthy individuals) and are highly predictive of the division into TB+ and TB?, other targets were exclusively recognized in all patients with TB (e.g. sigmaF) but not in any of the healthy individuals, and a third peptide set was recognized exclusively in healthy individuals (35/35) but no in TB+ patients. The segregation between TB+ and TB? does not cluster into specific recognition of distinct MTB proteins, but into specific peptide epitope ‘hotspots’ at different locations within the same protein. Antigen recognition pattern profiles in serum from TB+ patients from Armenia vs. patients recruited in Sweden showed that IgG-defined MTB epitopes are very similar in individuals with different genetic background. Conclusions A uniform target MTB IgG-epitope recognition pattern exists in pulmonary tuberculosis. Unbiased, high-content peptide microarray chip-based testing of clinically well-defined populations allows to visualize biologically relevant targets useful for development of novel TB diagnostics and vaccines.
Pattern recognition and cellular immune responses to novel Mycobacterium tuberculosis-antigens in individuals from Belarus
Raija K Ahmed, Zoyia Rohava, Kithiganahalli N Balaji, Sven E Hoffner, Hans Gaines, Isabelle Magalhaes, Alimuddin Zumla, Alena Skrahina, Markus J Maeurer
BMC Infectious Diseases , 2012, DOI: 10.1186/1471-2334-12-41
Abstract: Recombinant proteins (n = 7) and peptide pools (n = 14) from M. tuberculosis (M.tb) antigens associated with M.tb pathogenicity, modification of cell lipids or cellular metabolism, were used to compare T cell immune responses defined by IFN-γ production using a whole blood assay (WBA) from i) patients with TB, ii) individuals recovered from TB and iii) individuals exposed to TB without evidence of clinical TB infection from Minsk, Belarus.We identified differences in M.tb target peptide recognition between the test groups, i.e. a frequent recognition of antigens associated with lipid metabolism, e.g. cyclopropane fatty acyl phospholipid synthase. The pattern of peptide recognition was broader in blood from healthy individuals and those recovered from TB as compared to individuals suffering from pulmonary TB. Detection of biologically relevant M.tb targets was confirmed by staining for intracellular cytokines (IL-2, TNF-α and IFN-γ) in T cells from non-human primates (NHPs) after BCG vaccination.PBMCs from healthy individuals and those recovered from TB recognized a broader spectrum of M.tb antigens as compared to patients with TB. The nature of the pattern recognition of a broad panel of M.tb antigens will devise better strategies to identify improved diagnostics gauging previous exposure to M.tb; it may also guide the development of improved TB-vaccines.Tuberculosis (TB) is one of the major global health issue, and a serious health concern in Belarus where the prevalence and spread of multidrug-resistant (MDR) TB and extensively drug resistant (XDR) TB has increased during the last few years. About 5000 individuals are newly diagnosed each year in Belarus and the prevalence of TB is 52/100,000 individuals [1]. A recent study identified MDR TB in 35.3% of newly diagnosed patients and in 76.5% of individuals who have previously been treated. XDR TB could be identified in 14.0% among the patients diagnosed with MDR TB [2]; these are alarming levels of resistant TB in
Whole CMV Proteome Pattern Recognition Analysis after HSCT Identifies Unique Epitope Targets Associated with the CMV Status
Lena Pérez-Bercoff, Davide Valentini, Simani Gaseitsiwe, Shahnaz Mahdavifar, Mike Schutkowski, Thomas Poiret, ?sa Pérez-Bercoff, Per Ljungman, Markus J. Maeurer
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089648
Abstract: Cytomegalovirus (CMV) infection represents a vital complication after Hematopoietic Stem Cell Transplantation (HSCT). We screened the entire CMV proteome to visualize the humoral target epitope-focus profile in serum after HSCT. IgG profiling from four patient groups (donor and/or recipient +/? for CMV) was performed at 6, 12 and 24 months after HSCT using microarray slides containing 17174 of 15mer-peptides overlapping by 4 aa covering 214 proteins from CMV. Data were analyzed using maSigPro, PAM and the ‘exclusive recognition analysis (ERA)’ to identify unique CMV epitope responses for each patient group. The ‘exclusive recognition analysis’ of serum epitope patterns segregated best 12 months after HSCT for the D+/R+ group (versus D?/R?). Epitopes were derived from UL123 (IE1), UL99 (pp28), UL32 (pp150), this changed at 24 months to 2 strongly recognized peptides provided from UL123 and UL100. Strongly (IgG) recognized CMV targets elicited also robust cytokine production in T-cells from patients after HSCT defined by intracellular cytokine staining (IL-2, TNF, IFN and IL-17). High-content peptide microarrays allow epitope profiling of entire viral proteomes; this approach can be useful to map relevant targets for diagnostics and therapy in patients with well defined clinical endpoints. Peptide microarray analysis visualizes the breadth of B-cell immune reconstitution after HSCT and provides a useful tool to gauge immune reconstitution.
A Broad Profile of Co-Dominant Epitopes Shapes the Peripheral Mycobacterium tuberculosis Specific CD8+ T-Cell Immune Response in South African Patients with Active Tuberculosis
Rebecca Axelsson-Robertson, André G. Loxton, Gerhard Walzl, Marthie M. Ehlers, Marleen M. Kock, Alimuddin Zumla, Markus Maeurer
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0058309
Abstract: We studied major histocompatibility complex (MHC) class I peptide-presentation and nature of the antigen-specific CD8+ T-cell response from South African tuberculosis (TB) patients with active TB. 361 MHC class I binding epitopes were identified from three immunogenic TB proteins (ESAT-6 [Rv3875], Ag85B [Rv1886c], and TB10.4 [Rv0288], including amino acid variations for Rv0288, i.e., A10T, G13D, S27N, and A71S for MHC allotypes common in a South African population (e.g., human leukocyte antigen [HLA]-A*30, B*58, and C*07). Inter-allelic differences were identified regarding the broadness of the peptide-binding capacity. Mapping of frequencies of Mycobacterium tuberculosis (M. tb) antigen-specific CD8+ T-cells using 48 different multimers, including the newly constructed recombinant MHC class I alleles HLA-B*58:01 and C*0701, revealed a low frequency of CD8+ T-cell responses directed against a broad panel of co-dominant M. tb epitopes in the peripheral circulation of most patients. The antigen-specific responses were dominated by CD8+ T-cells with a precursor-like phenotype (CD45RA+CCR7+). The data show that the CD8+ T-cell response from patients with pulmonary TB (prior to treatment) is directed against subdominant epitopes derived from secreted and non-secreted M. tb antigens and that variant, natural occurring M. tb Rv0288 ligands, have a profound impact on T-cell recognition.
Immune Responses to ESAT-6 and CFP-10 by FASCIA and Multiplex Technology for Diagnosis of M. tuberculosis Infection; IP-10 Is a Promising Marker
Emilie Borgstr?m,Peter Andersen,Fredrik Atterfelt,Inger Julander,Gunilla K?llenius,Markus Maeurer,Ida Rosenkrands,Maria Widfeldt,Judith Bruchfeld,Hans Gaines
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043438
Abstract: There is a need for reliable markers to diagnose active and latent tuberculosis (TB). The interferon gamma release assays (IGRAs) are compared to the tuberculin skin test (TST) more specific, but cannot discriminate between recent or remote TB infection. Here the Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA), which quantifies expanded T-lymphoblasts by flow-cytometric analysis after long-term antigen stimulation of whole blood, is combined with cytokine/chemokine analysis in the supernatant by multiplex technology for diagnosis of Mycobacterium tuberculosis (Mtb) infection.
Evaluation of the Burden of Unsuspected Pulmonary Tuberculosis and Co-Morbidity with Non-Communicable Diseases in Sputum Producing Adult Inpatients
Matthew Bates, Justin O’Grady, Peter Mwaba, Lophina Chilukutu, Judith Mzyece, Busiku Cheelo, Moses Chilufya, Lukundo Mukonda, Maxwell Mumba, John Tembo, Mumba Chomba, Nathan Kapata, Andrea Rachow, Petra Clowes, Markus Maeurer, Michael Hoelscher, Alimuddin Zumla
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0040774
Abstract: Background A high burden of tuberculosis (TB) occurs in sub-Saharan African countries and many cases of active TB and drug-resistant TB remain undiagnosed. Tertiary care hospitals provide an opportunity to study TB co-morbidity with non-communicable and other communicable diseases (NCDs/CDs). We evaluated the burden of undiagnosed pulmonary TB and multi-drug resistant TB in adult inpatients, regardless of their primary admission diagnosis, in a tertiary referral centre. Methodology/Principal Findings In this prospective study, newly admitted adult inpatients able to produce sputum at the University Teaching Hospital, Lusaka, Zambia, were screened for pulmonary TB using fluorescent smear microscopy and automated liquid culture. The burden of pulmonary TB, unsuspected TB, TB co-morbidity with NCDs and CDs was determined. Sputum was analysed from 900 inpatients (70.6% HIV infected) 277 (30.8%) non-TB suspects, 286 (31.8%) TB suspects and 337 (37.4%) were already receiving TB treatment. 202/900 (22.4%) of patients had culture confirmed TB. TB co-morbidity was detected in 20/275 (7.3%) NCD patients, significantly associated with diabetes (P = 0.006, OR 6.571, 95%CI: 1.706–25.3). 27/202 (13.4%) TB cases were unsuspected. There were 18 confirmed cases of MDR-TB, 5 of which were unsuspected. Conclusions/Significance A large burden of unsuspected pulmonary TB co-morbidity exists in inpatients with NCDs and other CDs. Pro-active sputum screening of all inpatients in tertiary referral centres in high TB endemic countries is recommended. The scale of the problem of undiagnosed MDR-TB in inpatients requires further study.
Clinical application of biochemical markers of bone turnover
Seibel, Markus J.;
Arquivos Brasileiros de Endocrinologia & Metabologia , 2006, DOI: 10.1590/S0004-27302006000400006
Abstract: with the ageing population in most countries, disorders of bone and mineral metabolism are becoming increasingly relevant to every day clinical practice. consequently, the interest in, and the need for effective measures to be used in the screening, diagnosis and follow-up of such pathologies have markedly grown. together with clinical and imaging techniques, biochemical tests play an important role in the assessment and differential diagnosis of metabolic bone disease. in recent years, the isolation and characterisation of cellular and extracellular components of the skeletal matrix have resulted in the development of molecular markers that are considered to reflect either bone formation or bone resorption. these biochemical indices are non-invasive, comparatively inexpensive and, when applied and interpreted correctly, helpful tools in the diagnostic and therapeutic assessment of metabolic bone disease. this review provides an overview of the current evidence regarding the clinical use of biochemical markers of bone remodelling in bone disease, with an emphasis on osteoporosis.
Solar Stereoscopy and Tomography
Markus J. Aschwanden
Living Reviews in Solar Physics , 2011,
Abstract: We review stereoscopic and tomographic methods used in the solar corona, including ground-based and space-based measurements, using solar rotation or multiple spacecraft vantage points, in particular from the STEREO mission during 2007--2010. Stereoscopic and tomographic observations in the solar corona include large-scale structures, streamers, active regions, coronal loops, loop oscillations, acoustic waves in loops, erupting filaments and prominences, bright points, jets, plumes, flares, CME source regions, and CME-triggered global coronal waves. Applications in the solar interior (helioseismic tomography) and reconstruction and tracking of CMEs from the outer corona and into the heliosphere (interplanetary CMEs) are not included.
4D Modeling of CME expansion and EUV dimming observed with STEREO/EUVI
Markus J. Aschwanden
Physics , 2009, DOI: 10.5194/angeo-27-3275-2009
Abstract: This is the first attempt to model the kinematics of a CME launch and the resulting EUV dimming quantitatively with a self-consistent model. Our 4D-model assumes self-similar expansion of a spherical CME geometry that consists of a CME front with density compression and a cavity with density rarefaction, satisfying mass conservation of the total CME and swept-up corona. The model contains 14 free parameters and is fitted to the 2008 March 25 CME event observed with STEREO/A and B. Our model is able to reproduce the observed CME expansion and related EUV dimming during the initial phase from 18:30 UT to 19:00 UT. The CME kinematics can be characterized by a constant acceleration (i.e., a constant magnetic driving force). While the observations of EUVI/A are consistent with a spherical bubble geometry, we detect significant asymmetries and density inhomogeneities with EUVI/B. This new forward-modeling method demonstrates how the observed EUV dimming can be used to model physical parameters of the CME source region, the CME geometry, and CME kinematics.
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