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Articles by U Ceglarek
Total Records ( 2 ) for U Ceglarek
  D Teupser , R Baber , U Ceglarek , M Scholz , T Illig , C Gieger , L. M Holdt , A Leichtle , K. H Greiser , D Huster , P Linsel Nitschke , A Schafer , P. S Braund , L Tiret , K Stark , D Raaz Schrauder , G. M Fiedler , W Wilfert , F Beutner , S Gielen , A Grosshennig , I. R Konig , P Lichtner , I. M Heid , A Kluttig , N. E El Mokhtari , D Rubin , A. B Ekici , A Reis , C. D Garlichs , A. S Hall , G Matthes , C Wittekind , C Hengstenberg , F Cambien , S Schreiber , K Werdan , T Meitinger , M Loeffler , N. J Samani , J Erdmann , H. E Wichmann , H Schunkert and J. Thiery
  Background—

Phytosterols are plant-derived sterols that are taken up from food and can serve as biomarkers of cholesterol uptake. Serum levels are under tight genetic control. We used a genomic approach to study the molecular regulation of serum phytosterol levels and potential links to coronary artery disease (CAD).

Methods and Results—

A genome-wide association study for serum phytosterols (campesterol, sitosterol, brassicasterol) was conducted in a population-based sample from KORA (Cooperative Research in the Region of Augsburg) (n=1495) with subsequent replication in 2 additional samples (n=1157 and n=1760). Replicated single-nucleotide polymorphisms (SNPs) were tested for association with premature CAD in a metaanalysis of 11 different samples comprising 13 764 CAD cases and 13 630 healthy controls. Genetic variants in the ATP-binding hemitransporter ABCG8 and at the blood group ABO locus were significantly associated with serum phytosterols. Effects in ABCG8 were independently related to SNPs rs4245791 and rs41360247 (combined P=1.6x10–50 and 6.2x10–25, respectively; n=4412). Serum campesterol was elevated 12% for each rs4245791 T-allele. The same allele was associated with 40% decreased hepatic ABCG8 mRNA expression (P=0.009). Effects at the ABO locus were related to SNP rs657152 (combined P=9.4x10–13). Alleles of ABCG8 and ABO associated with elevated phytosterol levels displayed significant associations with increased CAD risk (rs4245791 odds ratio, 1.10; 95% CI, 1.06 to 1.14; P=2.2x10–6; rs657152 odds ratio, 1.13; 95% CI, 1.07 to 1.19; P=9.4x10–6), whereas alleles at ABCG8 associated with reduced phytosterol levels were associated with reduced CAD risk (rs41360247 odds ratio, 0.84; 95% CI, 0.78 to 0.91; P=1.3x10–5).

Conclusion—

Common variants in ABCG8 and ABO are strongly associated with serum phytosterol levels and show concordant and previously unknown associations with CAD.

  G. M Fiedler , A. B Leichtle , J Kase , S Baumann , U Ceglarek , K Felix , T Conrad , H Witzigmann , A Weimann , C Schutte , J Hauss , M Buchler and J. Thiery
 

Purpose: Mass spectrometry–based serum peptidome profiling is a promising tool to identify novel disease-associated biomarkers, but is limited by preanalytic factors and the intricacies of complex data processing. Therefore, we investigated whether standardized sample protocols and new bioinformatic tools combined with external data validation improve the validity of peptidome profiling for the discovery of pancreatic cancer–associated serum markers.

Experimental Design: For the discovery study, two sets of sera from patients with pancreatic cancer (n = 40) and healthy controls (n = 40) were obtained from two different clinical centers. For external data validation, we collected an independent set of samples from patients (n = 20) and healthy controls (n = 20). Magnetic beads with different surface functionalities were used for peptidome fractionation followed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Data evaluation was carried out by comparing two different bioinformatic strategies. Following proteome database search, the matching candidate peptide was verified by MALDI-TOF MS after specific antibody-based immunoaffinity chromatography and independently confirmed by an ELISA assay.

Results: Two significant peaks (m/z 3884; 5959) achieved a sensitivity of 86.3% and a specificity of 97.6% for the discrimination of patients and healthy controls in the external validation set. Adding peak m/z 3884 to conventional clinical tumor markers (CA 19-9 and CEA) improved sensitivity and specificity, as shown by receiver operator characteristics curve analysis (AUROCcombined = 1.00). Mass spectrometry–based m/z 3884 peak identification and following immunologic quantitation revealed platelet factor 4 as the corresponding peptide.

Conclusions: MALDI-TOF MS-based serum peptidome profiling allowed the discovery and validation of platelet factor 4 as a new discriminating marker in pancreatic cancer.

 
 
 
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