SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Frank Christoph) "

Sökning: WFRF:(Frank Christoph)

Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Zewinger, Stephen, et al. (författare)
  • Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease : a molecular and genetic association study
  • 2017
  • Ingår i: The Lancet Diabetes and Endocrinology. - ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:7, s. 534-543
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear.</p><p>Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts.</p><p>Findings: The median follow-up was 9.9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1.44, 95% CI 1.14-1.83) and the presence of either LPA SNP (1.88, 1.40-2.53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0.95, 0.81-1.11 and either LPA SNP 1.10, 0.92-1.31) or cardiovascular mortality (0.99, 0.81-1.2 and 1.13, 0.90-1.40, respectively) or in the validation studies.</p><p>Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established.</p>
  •  
2.
  • Zewinger, Stephen, et al. (författare)
  • Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease : A molecular and genetic association study
  • 2017
  • Ingår i: The Lancet Diabetes and Endocrinology. - Elsevier. - 2213-8587. ; 5:7, s. 534-543
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14-1·83) and the presence of either LPA SNP (1·88, 1·40-2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81-1·11 and either LPA SNP 1·10, 0·92-1·31) or cardiovascular mortality (0·99, 0·81-1·2 and 1·13, 0·90-1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny.
  •  
3.
  • Boll, Rebecca, et al. (författare)
  • Imaging molecular structure through femtosecond photoelectron diffraction on aligned and oriented gas-phase molecules
  • 2014
  • Ingår i: Faraday Discussions. - Royal Society of Chemistry. - 1364-5498. ; 171, s. 57-80
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper gives an account of our progress towards performing femtosecond time-resolved photoelectron diffraction on gas-phase molecules in a pump-probe setup combining optical lasers and an X-ray free-electron laser. We present results of two experiments aimed at measuring photoelectron angular distributions of laser-aligned 1-ethynyl-4-fluorobenzene (C8H5F) and dissociating, laser-aligned 1,4-dibromobenzene (C6H4Br2) molecules and discuss them in the larger context of photoelectron diffraction on gas-phase molecules. We also show how the strong nanosecond laser pulse used for adiabatically laser-aligning the molecules influences the measured electron and ion spectra and angular distributions, and discuss how this may affect the outcome of future time-resolved photoelectron diffraction experiments.
4.
  • Breitenbuecher, Frank, et al. (författare)
  • A novel molecular mechanism of primary resistance to FLT3-kinase inhibitors in AML
  • 2009
  • Ingår i: Blood. - American Society of Hematology. - 1528-0020. ; 113:17, s. 4063-4073
  • Tidskriftsartikel (refereegranskat)abstract
    • Currently, FLT3 tyrosine kinase inhibitors (TKIs) are emerging as the most promising drug therapy to overcome the dismal prognosis of acute myelogenous leukemia (AML) patients harboring internal tandem duplications (ITDs) of FLT3. However, up-front drug resistance occurs in approximately 30% of patients, and molecular mechanisms of resistance are poorly understood. Here, we have uncovered a novel mechanism of primary resistance to FLT3 TKIs in AML: an FLT3 receptor harboring a nonjuxtamembrane ITD atypically integrating into the beta-2 sheet of the first kinase domain (FLT3_ITD627E) induces dramatic up-regulation of the anti-apoptotic myeloid cell leukemia 1 protein (MCL-1). Using RNA interference technology, deregulated MCL-1 protein expression was shown to play a major role in conferring the resistance phenotype of 32D_ITD627E cells. Enhanced and sustained binding of the adaptor protein GRB-2 to the FLT3_ITD627E receptor is involved in MCL-1 up-regulation and is independent from TKI (PKC412)-induced inhibition of the receptor kinase. Thus, we describe a new mechanism of primary resistance to TKIs, which operates by reprogramming local and distant signal transduction events of the FLT3 tyrosine kinase. The data presented suggest that particular ITDs of FLT3 may be associated with rewired signaling and differential responsiveness to TKIs. (Blood. 2009; 113: 4063-4073)
  •  
5.
  • Cossarizza, Andrea, et al. (författare)
  • Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
  • 2019
  • Ingår i: European Journal of Immunology. - WILEY. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.</p>
  •  
6.
  • Dichgans, Martin, et al. (författare)
  • METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration : An initiative of the Joint Programme for Neurodegenerative Disease Research
  • 2016
  • Ingår i: Alzheimer's and Dementia. - Wiley. - 1552-5260. ; 12:12, s. 1235-1249
  • Tidskriftsartikel (refereegranskat)abstract
    • Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention.
7.
  • Eisenberg, Tobias, et al. (författare)
  • Cardioprotection and lifespan extension by the natural polyamine spermidine
  • 2016
  • Ingår i: Nature Medicine. - 1078-8956 .- 1546-170X. ; 22:12, s. 1428-1438
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for protection against cardiovascular disease.</p>
  •  
8.
  • Heiri, Oliver, et al. (författare)
  • Palaeoclimate records 60-8 ka in the Austrian and Swiss Alps and their forelands
  • 2014
  • Ingår i: Quaternary Science Reviews. - 0277-3791 .- 1873-457X. ; 106, s. 186-205
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The European Alps and their forelands provide a range of different archives and climate proxies for developing climate records in the time interval 60-8 thousand years (ka) ago. We review quantitative and semi-quantitative approaches for reconstructing climatic variables in the Austrian and Swiss sector of the Alpine region within this time interval. Available quantitative to semi-quantitative climate records in this region are mainly based on fossil assemblages of biota such as chironomids, cladocerans, co-leopterans, diatoms and pollen preserved in lake sediments and peat, the analysis of oxygen isotopes in speleothems and lake sediment records, the reconstruction of past variations in treeline altitude, the reconstruction of past equilibrium line altitude and extent of glaciers based on geomorphological evidence, and the interpretation of past soil formation processes, dust deposition and permafrost as apparent in loess-palaeosol sequences. Palaeoclimate reconstructions in the Alpine region are affected by dating uncertainties increasing with age, the fragmentary nature of most of the available records, which typically only incorporate a fraction of the time interval of interest, and the limited replication of records within and between regions. Furthermore, there have been few attempts to cross-validate different approaches across this time interval to confirm reconstructed patterns of climatic change by several independent lines of evidence. Based on our review we identify a number of developments that would provide major advances for palaeoclimate reconstruction for the period 60-8 ka in the Alps and their forelands. These include (1) the compilation of individual, fragmentary records to longer and continuous reconstructions, (2) replication of climate records and the development of regional reconstructions for different parts of the Alps, (3) the cross-validation of different proxy-types and approaches, and (4) the reconstruction of past variations in climate gradients across the Alps and their forelands. Furthermore, the development of downscaled climate model runs for the Alpine region 60-8 ka, and of forward modelling approaches for climate proxies would expand the opportunities for quantitative assessments of climatic conditions in Europe within this time-interval.</p>
  •  
9.
  • Lump, Edina, et al. (författare)
  • A molecular tweezer antagonizes seminal amyloids and HIV infection
  • 2015
  • Ingår i: eLIFE. - 2050-084X. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Semen is the main vector for HIV transmission and contains amyloid fibrils that enhance viral infection. Available microbicides that target viral components have proven largely ineffective in preventing sexual virus transmission. In this study, we establish that CLR01, a 'molecular tweezer' specific for lysine and arginine residues, inhibits the formation of infectivity-enhancing seminal amyloids and remodels preformed fibrils. Moreover, CLR01 abrogates semen-mediated enhancement of viral infection by preventing the formation of virion-amyloid complexes and by directly disrupting the membrane integrity of HIV and other enveloped viruses. We establish that CLR01 acts by binding to the target lysine and arginine residues rather than by a non-specific, colloidal mechanism. CLR01 counteracts both host factors that may be important for HIV transmission and the pathogen itself. These combined anti-amyloid and antiviral activities make CLR01 a promising topical microbicide for blocking infection by HIV and other sexually transmitted viruses.</p>
  •  
10.
  • Quandt, Jasmin, et al. (författare)
  • Long-peptide vaccination with driver gene mutations in p53 and Kras induces cancer mutation-specific effector as well as regulatory T cell responses
  • 2018
  • Ingår i: OncoImmunology. - Landes Bioscience. - 2162-4011. ; 7:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Mutated proteins arising from somatic mutations in tumors are promising targets for cancer immunotherapy. They represent true tumor-specific antigens (TSAs) as they are exclusively expressed in tumors, reduce the risk of autoimmunity and are more likely to overcome tolerance compared to wild-type (wt) sequences. Hence, we designed a panel of long peptides (LPs, 28–35 aa) comprising driver gene mutations in TP35 and KRAS frequently found in gastrointestinal tumors to test their combined immunotherapeutic potential. We found increased numbers of T cells responsive against respective mutated and wt peptides in colorectal cancer patients that carry the tested mutations in their tumors than patients with other mutations. Further, active immunization of HLA(-A2/DR1)-humanized mice with mixes of the same mutated LPs yielded simultaneous, polyvalent CD8+/CD4+ T cell responses against the majority of peptides. Peptide-specific T cells possessed a multifunctional cytokine profile with CD4+ T cells showing a TH1-like phenotype. Two mutated peptides (Kras[G12V], p53[R248W]) induced significantly higher T cell responses than corresponding wt sequences and comprised HLA-A2/DR1-restricted mutated epitopes. However, vaccination with the same highly immunogenic LPs strongly increased systemic regulatory T cells (Treg) numbers in a syngeneic sarcoma model over-expressing these mutated protein variants and resulted in accelerated tumor outgrowth. In contrast, tumor outgrowth was delayed when vaccination was directed against tumor-intrinsic Kras/Tp53 mutations of lower immunogenicity. Conclusively, we show that LP vaccination targeting multiple mutated TSAs elicits polyvalent, multifunctional, and mutation-specific effector T cells capable of targeting tumors. However, the success of this therapeutic approach can be hampered by vaccination-induced, TSA-specific Tregs.
Skapa referenser, mejla, bekava och länka
Åtkomst
fritt online (25)
Typ av publikation
tidskriftsartikel (121)
konferensbidrag (5)
forskningsöversikt (5)
annan publikation (1)
bokkapitel (1)
Typ av innehåll
refereegranskat (130)
övrigt vetenskapligt (10)
Författare/redaktör
Bostedt, Christoph (16)
Barty, Anton (15)
Bajt, Saša (15)
Erk, Benjamin, (13)
Rudenko, Artem, (13)
Rolles, Daniel, (13)
visa fler...
Aquila, Andrew (13)
Foucar, Lutz (13)
Rudek, Benedikt (13)
Chapman, Henry N. (13)
Frank, Matthias (13)
Gumprecht, Lars (13)
Schlichting, Ilme (13)
Schulz, Joachim (13)
Ullrich, Joachim (13)
Hemminki, Kari, (12)
Hartmann, Robert (12)
Coppola, Nicola (12)
Holl, Peter (12)
Kimmel, Nils (12)
Reich, Christian (12)
Soltau, Heike (12)
Bogan, Michael J (11)
Krasniqi, Faton (11)
Marchesini, Stefano (11)
Schmidt, Carlo (11)
Graafsma, Heinz, (10)
Hirsemann, Helmut, (10)
Hajdu, Janos, (10)
Messerschmidt, Marc (10)
Martin, Andrew V. (10)
Barthelmess, Miriam (10)
Epp, Sascha W. (10)
Lomb, Lukas (10)
Starodub, Dmitri (10)
Shoeman, Robert L (9)
Caleman, Carl (9)
Maia, Filipe R. N. C ... (9)
White, Thomas A. (9)
Hampton, Christina Y ... (9)
Hartmann, Andreas (9)
Stern, Stephan (9)
Ludwig, Frank, (8)
Gustavsson, Anders, (8)
Allgulander, Christe ... (8)
Alonso, Jordi (8)
Melin, Beatrice, (8)
Bozek, John D. (8)
Liang, Mengning (8)
Nass, Karol (8)
visa färre...
Lärosäte
Lunds universitet (36)
Uppsala universitet (24)
Luleå tekniska universitet (14)
Stockholms universitet (13)
Göteborgs universitet (8)
Umeå universitet (8)
visa fler...
Kungliga Tekniska Högskolan (8)
Chalmers tekniska högskola (6)
Linköpings universitet (5)
Karolinska Institutet (4)
RISE (4)
Högskolan i Jönköping (3)
Örebro universitet (2)
Karlstads universitet (2)
Högskolan Kristianstad (1)
swepub_uni:mau_t (1)
visa färre...
Språk
Engelska (131)
Forskningsämne (UKÄ/SCB)
Naturvetenskap (54)
Medicin och hälsovetenskap (54)
Teknik (23)
Samhällsvetenskap (6)
Lantbruksvetenskap (1)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy