| 1. |
- Steinicke, Robert, et al.
(author)
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Kidney Function and White Matter Disease in Young Stroke Patients Analysis of the Stroke in Young Fabry Patients Study Population
- 2012
-
In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 43:9, s. 2382-2388
-
Journal article (peer-reviewed)abstract
- Background and Purpose-Impaired kidney function is thought to be associated with small vessel disease, outcome, and mortality in the general stroke population. Data are limited regarding young patients. The aim of this study was to investigate the association of kidney function and white matter hyperintensities (WMHs) in young patients with first ischemic stroke. Methods-We analyzed 2500 young (18-55 years) patients with first-ever ischemic stroke from the prospective observational Stroke in Young Fabry Patients (SIFAP1) study with available MRI data on WMH. Of these, 2009 had available data concerning estimated glomerular filtration rate (eGFR). Kidney function was expressed as eGFR by the Modification of Diet in Renal Disease method. Deep WMHs on MRI were classified by the Fazekas score. Multivariate analysis was performed using a regression model with random effects. Results-Mean eGFR was 96.7 mL/min in those with WMH Grade 0 to 1 (none to mild), 90.7 mL/min in WMH Grade 2 (moderate), and 89 mL/min in WMH Grade 3 (severe). Univariate analysis revealed WMH to be associated with age (P<0.001), hypertension (P<0.001), cardiovascular disease (P=0.015), overweight (body mass index >25 kg/m(2); P=0.013), current smoking (P=0.044), and eGFR (P=0.009). In multivariate analysis, age, hypertension, and eGFR remained associated with WMH severity. Conclusions-In young patients with acute ischemic stroke, lower eGFR values in the normal range are associated with the presence of moderate to severe WMH.
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| 2. |
- Bengtsson, Staffan, et al.
(author)
-
Introduction
- 2016
-
In: Herder and Religion. - Heidelberg : Synchron. - 9783939381884 ; , s. 7-9
-
Book chapter (other academic/artistic)
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| 3. |
- Brucalassi, Anna, et al.
(author)
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Full System Test and early Preliminary Acceptance Europe results for CRIRES
- 2018
-
In: Ground-Based And Airborne Instrumentation For Astronomy VII. - : SPIE. - 9781510619586
-
Conference paper (peer-reviewed)abstract
- CRIRES+ is the new high-resolution NIR echelle spectrograph intended to be operated at the platform B of VLT Unit telescope UT3. It will cover from Y to M bands (0.95-5.3um) with a spectral resolution of R = 50000 or R = 100000. The main scientific goals are the search of super-Earths in the habitable zone of low-mass stars, the characterisation of transiting planets atmosphere and the study of the origin and evolution of stellar magnetic fields. Based on the heritage of the old adaptive optics (AO) assisted VLT instrument CRIRES, the new spectrograph will present improved optical layout, a new detector system and a new calibration unit providing optimal performances in terms of simultaneous wavelength coverage and radial velocity accuracy (a few m/s). The total observing efficiency will be enhanced by a factor of 10 with respect to CRIRES. An innovative spectro-polarimetry mode will be also offered and a new metrology system will ensure very high system stability and repeatability. Fiinally, the CRIRES+ project will also provide the community with a new data reduction software (DRS) package. CRIRES+ is currently at the initial phase of its Preliminary Acceptance in Europe (PAE) and it will be commissioned early in 2019 at VLT. This work outlines the main results obtained during the initial phase of the full system test at ESO HQ Garching.
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| 4. |
- Dand, Nick, et al.
(author)
-
Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling
- 2017
-
In: Human Molecular Genetics. - : OXFORD UNIV PRESS. - 0964-6906 .- 1460-2083. ; 26:21, s. 4301-4313
-
Journal article (peer-reviewed)abstract
- Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 x 10(-8), OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency amp;lt; 0.01) via gene-wide aggregation testing (IFIH1: p(burden) = 2.53 x 10(-7), OR = 0.707; TYK2: p(burden) = 6.17 x 10(-4), OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.
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| 5. |
- de Jong, R. S., et al.
(author)
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4MOST : Project overview and information for the First Call for Proposals
- 2019
-
In: The Messenger. - : European Southern Observatory. - 0722-6691. ; 175, s. 3-11
-
Journal article (other academic/artistic)abstract
- We introduce the 4-metre Multi-Object Spectroscopic Telescope (4MOST), a new high-multiplex, wide-field spectroscopic survey facility under development for the four-metre-class Visible and Infrared Survey Telescope for Astronomy (VISTA) at Paranal. Its key specifications are: a large field of view (FoV) of 4.2 square degrees and a high multiplex capability, with 1624 fibres feeding two low-resolution spectrographs (R = λ/Δλ ~ 6500), and 812 fibres transferring light to the high-resolution spectrograph (R ~ 20 000). After a description of the instrument and its expected performance, a short overview is given of its operational scheme and planned 4MOST Consortium science; these aspects are covered in more detail in other articles in this edition of The Messenger. Finally, the processes, schedules, and policies concerning the selection of ESO Community Surveys are presented, commencing with a singular opportunity to submit Letters of Intent for Public Surveys during the first five years of 4MOST operations.
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| 6. |
- Dunkel, Mathias, et al.
(author)
-
SuperScent--a database of flavors and scents
- 2009
-
In: Nucleic Acids Research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 37, s. 291-294
-
Journal article (peer-reviewed)abstract
- Volatiles are efficient mediators of chemical communication acting universally as attractant, repellent or warning signal in all kingdoms of life. Beside this broad impact volatiles have in nature, scents are also widely used in pharmaceutical, food and cosmetic industries, so the identification of new scents is of great industrial interest. Despite this importance as well as the vast number and diversity of volatile compounds, there is currently no comprehensive public database providing information on structure and chemical classification of volatiles. Therefore, the database SuperScent was established to supply users with detailed information on the variety of odor components. The version of the database presented here comprises the 2D/3D structures of approximately 2100 volatiles and around 9200 synonyms as well as physicochemical properties, commercial availability and references. The volatiles are classified according to their origin, functionality and odorant groups. The information was extracted from the literature and web resources. SuperScent offers several search options, e.g. name, Pubchem ID number, species, functional groups, or molecular weight. SuperScent is available online at: http://bioinformatics.charite.de/superscent.
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| 7. |
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| 8. |
- Follert, Roman, et al.
(author)
-
Characterizing the cross dispersion reflection gratings of CRIRES
- 2016
-
In: Advances In Optical And Mechanical Technologies For Telescopes And Instrumentation Ii. - : SPIE. - 9781510602038 - 9781510602045
-
Conference paper (peer-reviewed)abstract
- The CRIRES+ project attempts to upgrade the CRIRES instrument into a cross dispersed echelle spectrograph with a simultaneous recording of 8-10 diffraction orders. In order to transform the CRIRES spectrograph into a cross-dispersing instrument, a set of six reflection gratings, each one optimized for one of the wavelength bands CRIRES+ will operate in (YJHKLM), will be used as cross dispersion elements in CRIRES+. Due to the upgrade nature of the project, the choice of gratings depends on the fixed geometry of the instrument. Thus, custom made gratings would be required to achieve the ambitious design goals. Custom made gratings have the disadvantage, though, that they come at an extraordinary price and with lead times of more than 12 months. To mitigate this, a set of off-the-shelf gratings was obtained which had grating parameters very close to the ones being identified as optimal. To ensure that the rigorous specifications for CRIRES+ will be fulfilled, the CRIRES+ team started a collaboration with the Physikalisch-Technische Bundesanstalt Berlin (PTB) to characterize gratings under conditions similar to the operating conditions in CRIRES+ (angle of incidence, wavelength range). The respective test setup was designed in collaboration between PTB and the CRIRES+ consortium. The PTB provided optical radiation sources and calibrated detectors for each wavelength range. With this setup, it is possible to measure the absolute efficiency of the gratings both wavelength dependent and polarization state dependent in a wavelength range from 0.9 mu m to 6 mu m.
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| 9. |
- Franke, W W, et al.
(author)
-
Desmosomes--dual junctional principles of intra- and supracellular order in epithelial differentiation and tissue formation
- 1994
-
In: Verhandlungen der Deutschen Gesellschaft fur Pathologie. - 0070-4113. ; 78, s. 8-14
-
Journal article (peer-reviewed)abstract
- The cells of most normal and malignantly growing tissues are connected by "adhering junctions", i.e. distinct sites of "homotypic" contact between the plasma membranes of two cells of the same or a similar kind, associated on the cytoplasmic side by a dense plaque at which often bundles of cytoskeletal filaments anchor. Of the various types of adhering junctions desmosomes are characteristic of epithelia and carcinomas but also occur in some other cell types. Their molecular components have recently been identified and characterized by cDNA-cloning and sequencing. Unexpectedly, the molecular complement of desmosomes has been found to show certain differences in different epithelia, with particularly complex patterns in stratified squamous epithelia as well as in tumors and cultured cell lines derived therefrom. In addition, molecular principles important in the assembly of desmosomes and in the specific anchorage of intermediate-sized filaments (IFs) at desmosomal plaques have been elucidated. The possible value of cell type-specific isoforms of desmosomal components as markers for the subtyping of carcinomas and the role of desmosomal cadherins during invasion and metastasis of carcinomas are discussed.
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| 10. |
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| 11. |
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| 12. |
- Howes, Louise, et al.
(author)
-
The Gaia-ESO Survey: the most metal-poor stars in the Galactic bulge
- 2014
-
In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 1365-2966 .- 0035-8711. ; 445:4, s. 4241-4246
-
Journal article (peer-reviewed)abstract
- We present the first results of the EMBLA survey (Extremely Metal-poor BuLge stars with AAOmega), aimed at finding metal-poor stars in the Milky Way bulge, where the oldest stars should now preferentially reside. EMBLA utilizes SkyMapper photometry to pre-select metal-poor candidates, which are subsequently confirmed using AAOmega spectroscopy. We describe the discovery and analysis of four bulge giants with -2.72 <= [Fe/H] <= -2.48, the lowest metallicity bulge stars studied with high-resolution spectroscopy to date. Using FLAMES/UVES spectra through the Gaia-ESO Survey we have derived abundances of twelve elements. Given the uncertainties, we find a chemical similarity between these bulge stars and halo stars of the same metallicity, although the abundance scatter may be larger, with some of the stars showing unusual [alpha/Fe] ratios.
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| 13. |
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| 14. |
- Kattge, Jens, et al.
(author)
-
TRY plant trait database - enhanced coverage and open access
- 2020
-
In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
-
Journal article (peer-reviewed)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 15. |
- Lange, Leslie A, et al.
(author)
-
Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol.
- 2014
-
In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 233-245
-
Journal article (peer-reviewed)abstract
- Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.
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| 16. |
- Locke, Adam E, et al.
(author)
-
Genetic studies of body mass index yield new insights for obesity biology.
- 2015
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
-
Journal article (peer-reviewed)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 17. |
- Nuber, Ulrike, et al.
(author)
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The widespread human desmocollin Dsc2 and tissue-specific patterns of synthesis of various desmocollin subtypes
- 1995
-
In: European Journal of Cell Biology. - 0171-9335. ; 66:1, s. 69-74
-
Journal article (peer-reviewed)abstract
- By comparison of the cDNA-derived amino acid sequences and the cell type-specific patterns of synthesis we have identified desmocollin Dsc2 as the most widespread, perhaps ubiquitous desmocollin subtype. Using Northern blot analyses and ribonuclease protection assays we have found an approximately 5.6 kb mRNA encoding Dsc2 in all the diverse human tissues, tumors and cell lines examined that are known to possess desmosomes, i.e. not only epithelial cells but also myocardiac cells and lymph nodes. By contrast, desmocollin subtypes Dsc1 and Dsc3 have been detected only in certain stratified squamous epithelia, with the most conspicuous restriction of Dsc1 to epidermis and--remarkably, but unexplained--lymph nodes, and in certain carcinomas and cell lines derived therefrom. We have also determined that both Dsc2 mRNA splice forms, the one encoding the larger polypeptide a and the one coding for the shorter Dsc2b, occur in all the diverse tissues and cell lines examined. We also show that certain cells such as the epidermal keratinocyte line HaCaT and the vulvar carcinoma-derived line A-431 continually synthesize more than one Dsc subtype. The cell type-specific patterns of synthesis of the various Dsg and Dsc subtypes are discussed in relation to tissue development during embryogenesis and to malignant transformations, and the utilization of reagents for the specific Dsg and Dsc subtypes in tumor diagnosis is proposed.
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| 18. |
- Papadopoulos, Nikolaos G, et al.
(author)
-
Research needs in allergy: an EAACI position paper, in collaboration with EFA.
- 2012
-
In: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 2:1
-
Journal article (peer-reviewed)abstract
- ABSTRACT: In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.
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| 19. |
- Park, Julien H., et al.
(author)
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The motor system is exceptionally vulnerable to absence of the ubiquitously expressed superoxide dismutase-1
- 2023
-
In: Brain Communications. - : Oxford University Press. - 2632-1297. ; 5:1
-
Journal article (peer-reviewed)abstract
- Superoxide dismutase-1 is a ubiquitously expressed antioxidant enzyme. Mutations in SOD1 can cause amyotrophic lateral sclerosis, probably via a toxic gain-of-function involving protein aggregation and prion-like mechanisms. Recently, homozygosity for loss-of-function mutations in SOD1 has been reported in patients presenting with infantile-onset motor neuron disease. We explored the bodily effects of superoxide dismutase-1 enzymatic deficiency in eight children homozygous for the p.C112Wfs∗11 truncating mutation. In addition to physical and imaging examinations, we collected blood, urine and skin fibroblast samples. We used a comprehensive panel of clinically established analyses to assess organ function and analysed oxidative stress markers, antioxidant compounds, and the characteristics of the mutant Superoxide dismutase-1. From around 8 months of age, all patients exhibited progressive signs of both upper and lower motor neuron dysfunction, cerebellar, brain stem, and frontal lobe atrophy and elevated plasma neurofilament concentration indicating ongoing axonal damage. The disease progression seemed to slow down over the following years. The p.C112Wfs∗11 gene product is unstable, rapidly degraded and no aggregates were found in fibroblast. Most laboratory tests indicated normal organ integrity and only a few modest deviations were found. The patients displayed anaemia with shortened survival of erythrocytes containing decreased levels of reduced glutathione. A variety of other antioxidants and oxidant damage markers were within normal range. In conclusion, non-neuronal organs in humans show a remarkable tolerance to absence of Superoxide dismutase-1 enzymatic activity. The study highlights the enigmatic specific vulnerability of the motor system to both gain-of-function mutations in SOD1 and loss of the enzyme as in the here depicted infantile superoxide dismutase-1 deficiency syndrome.
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| 20. |
- Piller, Gunther, et al.
(author)
-
Digital Enterprise Architectures
- 2015
-
In: 45. Jahrestagung der Gesellschaft für Informatik, Informatik 2015, Informatik, Energie und Umwelt, 28. September - 2. Oktober 2015 in Cottbus, Deutschland. - 9783885796404
-
Conference paper (peer-reviewed)
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| 21. |
- Rauch, Alexander, et al.
(author)
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Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor.
- 2010
-
In: Cell metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 11:6, s. 517-31
-
Journal article (peer-reviewed)abstract
- Development of osteoporosis severely complicates long-term glucocorticoid (GC) therapy. Using a Cre-transgenic mouse line, we now demonstrate that GCs are unable to repress bone formation in the absence of glucocorticoid receptor (GR) expression in osteoblasts as they become refractory to hormone-induced apoptosis, inhibition of proliferation, and differentiation. In contrast, GC treatment still reduces bone formation in mice carrying a mutation that only disrupts GR dimerization, resulting in bone loss in vivo, enhanced apoptosis, and suppressed differentiation in vitro. The inhibitory GC effects on osteoblasts can be explained by a mechanism involving suppression of cytokines, such as interleukin 11, via interaction of the monomeric GR with AP-1, but not NF-kappaB. Thus, GCs inhibit cytokines independent of GR dimerization and thereby attenuate osteoblast differentiation, which accounts, in part, for bone loss during GC therapy.
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| 22. |
- Rolfs, Arndt, et al.
(author)
-
Acute Cerebrovascular Disease in the Young The Stroke in Young Fabry Patients Study
- 2013
-
In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 44:2, s. 340-349
-
Journal article (peer-reviewed)abstract
- Background and Purpose-Strokes have especially devastating implications if they occur early in life; however, only limited information exists on the characteristics of acute cerebrovascular disease in young adults. Although risk factors and manifestation of atherosclerosis are commonly associated with stroke in the elderly, recent data suggests different causes for stroke in the young. We initiated the prospective, multinational European study Stroke in Young Fabry Patients (sifap) to characterize a cohort of young stroke patients. Methods-Overall, 5023 patients aged 18 to 55 years with the diagnosis of ischemic stroke (3396), hemorrhagic stroke (271), transient ischemic attack (1071) were enrolled in 15 European countries and 47 centers between April 2007 and January 2010 undergoing a detailed, standardized, clinical, laboratory, and radiological protocol. Results-Median age in the overall cohort was 46 years. Definite Fabry disease was diagnosed in 0.5% (95% confidence interval, 0.4%-0.8%; n=27) of all patients; and probable Fabry disease in additional 18 patients. Males dominated the study population (2962/59%) whereas females outnumbered men (65.3%) among the youngest patients (18-24 years). About 80.5% of the patients had a first stroke. Silent infarcts on magnetic resonance imaging were seen in 20% of patients with a first-ever stroke, and in 11.4% of patients with transient ischemic attack and no history of a previous cerebrovascular event. The most common causes of ischemic stroke were large artery atherosclerosis (18.6%) and dissection (9.9%). Conclusions-Definite Fabry disease occurs in 0.5% and probable Fabry disease in further 0.4% of young stroke patients. Silent infarcts, white matter intensities, and classical risk factors were highly prevalent, emphasizing the need for new early preventive strategies.
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| 23. |
- Rolfs, Arndt, et al.
(author)
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Protocol and Methodology of the Stroke in Young Fabry Patients (sifap1) Study: A Prospective Multicenter European Study of 5,024 Young Stroke Patients Aged 18-55 Years
- 2011
-
In: Cerebrovascular Diseases. - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 31:3, s. 253-262
-
Journal article (peer-reviewed)abstract
- Background: Stroke in the young has not been thoroughly investigated with most previous studies based on a small number of patients from single centers. Furthermore, recent reports indicate that Fabry disease may be a significant cause for young stroke. The primary aim of our study was to determine the prevalence of Fabry disease in young stroke patients, while the secondary aim was to describe patterns of stroke in young patients. Methods: We initiated the Stroke in Young Fabry Patients (sifap1) study as a multinational prospective European study of stroke patients aged 18-55 years and collected a broad range of clinical, laboratory, and radiological data using stringent standardized methods. All patients were tested for Fabry disease and blood was stored for future genetic testing. Results: We managed to enroll 5,024 eligible young stroke patients in 15 countries and 47 centers across Europe between April 2007 and January 2010. The median number of patients included per center was 98 with a range between 8 and 315. The average duration of patient recruitment per center was 22 months, ranging between 5 and 33 months. The database was closed in July 2010. This paper describes protocol and methodology of the sifap1 study. Conclusion: The sifap1 study included the largest series of young stroke patients so far and will allow for analyses on a large number of aspects of stroke in the young. Copyright (C) 2010 S. Karger AG, Basel
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| 24. |
- Schmidt, A, et al.
(author)
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Desmosomes and cytoskeletal architecture in epithelial differentiation: cell type-specific plaque components and intermediate filament anchorage
- 1994
-
In: European Journal of Cell Biology. - 0171-9335. ; 65:2, s. 229-245
-
Journal article (peer-reviewed)abstract
- Among the diverse kinds of intercellular, plaque-bearing, cadherin-containing junctions, desmosomes (maculae adhaerentes) represent a major type characterized by the presence of specific transmembrane glycoproteins, i.e. desmosomal cadherins of the desmoglein and desmocollin categories, and the cytoplasmic plaque proteins, desmoplakin I and plakoglobin. Recent studies, however, have shown that the composition of desmosomes is not identical in the various normal and tumorous desmosome-forming tissues and cell cultures, including diverse forms of epithelia and carcinomas, meningothelia and meningiomas, myocardium and the lymph node follicle reticulum. Desmosomes can differ in their specific complement of desmogleins, Dsg1-3, and desmocollins, Dsc1a-3b, as well as in the additional presence and in their relative amounts of certain accessory plaque proteins such as desmoplakin II and plakophilin 1, a basic member of the larger plakoglobin family of proteins ("band 6 protein"). Assembly and function of desmosomes are effected by the interaction of the specific complement of desmosomal cadherins with certain cytoplasmic proteins. In particular, the cytoplasmic portions ("tails") of the desmosomal cadherins contain certain domains and amino acid sequence motifs, identified by mutagenesis and transfection assays, that are essential elements in desmosome formation, notably the assembly of plaque proteins, and in the site-specific anchorage of intermediate-sized filaments (IFs) of the cytoskeleton, thereby contributing to the specific intracellular as well as supracellular, i.e. tissue, architecture.
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| 25. |
- Schmidt, Sarah, et al.
(author)
-
The Role of Donor Lymphocyte Infusion (DLI) in Post-Hematopoietic Cell Transplant (HCT) Relapse for Chronic Myeloid Leukemia (CML) in the Tyrosine Kinase Inhibitor (TKI) Era
- 2020
-
In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 26:6, s. 1137-1143
-
Journal article (peer-reviewed)abstract
- Treatment for relapse of chronic myeloid leukemia (CML) following hematopoietic cell transplantation (HCT) includes tyrosine kinase inhibitors (TKIs) with or without donor lymphocyte infusions (DLIs), but the most effective treatment strategy is unknown. This study was performed through the Center for International Blood and Marrow Transplant Research (CIBMTR) database. We retrospectively reviewed all patients reported to the CIBMTR registry from 2002 to 2014 who underwent HCT for CML and were alive 30 days postrelapse. A total of 215 HCT recipients relapsed and were analyzed in the following groups: (1) TKI alone (n = 128), (2) TKI with DLI (n = 48), and (3) DLI without TKI (n = 39). In multivariate analysis, disease status prior to HCT had a significant effect on overall survival (OS). Patients who received a DLI alone compared with a TKI with a DLI had inferior survival (hazard ratio, 2.28; 95% confidence interval, 1.23 to 4.24; P= .009). Those who received a TKI alone had similar survival compared with those who received a TKI with a DLI (P = .81). These data support that despite use of TKIs pretransplantation, TKI salvage therapy continues to provide significant survival following relapse in patients with CML following HCT. These data do not suggest that adding a DLI to a TKI adds an improvement in OS.
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