			Home About us Contact

Disease Biomarkers (disease + biomarker)

Distribution by Scientific Domains

Medical Sciences	50%
Chemistry	30%
Life Sciences	20%

Selected Abstracts

Quantitative analysis of phosphopeptides in search of the disease biomarker from the hepatocellular carcinoma specimen

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 12 2009
Hyoung-Joo Lee
Abstract Reversible phosphorylation of proteins is the most common PTM in cell-signaling pathways. Despite this, high-throughput methods for the systematic detection, identification, and quantification of phosphorylated peptides have yet to be developed. In this paper, we describe the establishment of an efficient online titaniuim dioxide (TiO2)-based 3-D LC (strong cationic exchange/TiO2/C18)-MS3 -linear ion trap system, which provides fully automatic and highly efficient identification of phosphorylation sites in complex peptide mixtures. Using this system, low-abundance phosphopeptides were isolated from cell lines, plasma, and tissue of healthy and hepatocellular carcinoma (HCC) patients. Furthermore, the phosphorylation sites were identified and the differences in phosphorylation levels between healthy and HCC patient specimens were quantified by labeling the phosphopeptides with isotopic analogs of amino acids (stable isotope labeling with amino acids in cell culture for HepG2 cells) or water (HO for tissues and plasma). Two examples of potential HCC phospho-biomarkers including plectin-1(phopho-Ser-4253) and alpha-HS-glycoprotein (phospho-Ser 138 and 312) were identified by this analysis. Our results suggest that this comprehensive TiO2 -based online-3-D LC-MS3 -linear ion trap system with high-throughput potential will be useful for the global profiling and quantification of the phosphoproteome and the identification of disease biomarkers. [source]

SP-D and regulation of the pulmonary innate immune system in allergic airway changes

CLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2010
L. R. Forbes
Summary The airway mucosal surfaces are constantly exposed to inhaled particles that can be potentially toxic, infectious or allergenic and should elicit inflammatory changes. The proximal and distal air spaces, however, are normally infection and inflammation free due to a specialized interplay between cellular and molecular components of the pulmonary innate immune system. Surfactant protein D (SP-D) is an epithelial-cell-derived immune modulator that belongs to the small family of structurally related Ca2+ -dependent C-type collagen-like lectins. While collectins can be detected in mucosal surfaces of various organs, SP-A and SP-D (the ,lung collectins') are constitutively expressed in the lung at high concentrations. Both proteins are considered important players of the pulmonary immune responses. Under normal conditions however, SP-A-/- mice display no pathological features in the lung. SP-D-/- mice, on the other hand, show chronic inflammatory alterations indicating a special importance of this molecule in regulating immune homeostasis and the function of the innate immune cells. Recent studies in our laboratory and others implied significant associations between changes in SP-D levels and the presence of airway inflammation both in animal models and patients raising a potential usefulness of this molecule as a disease biomarker. Research on wild-type and mutant recombinant molecules in vivo and in vitro showed that SP-D binds carbohydrates, lipids and nucleic acids with a broad spectrum specificity and initiates phagocytosis of inhaled pathogens as well as apoptotic cells. Investigations on gene-deficient and conditional over expressor mice in addition, provided evidence that SP-D directly modulates macrophage and dendritic cell function as well as T cell-dependent inflammatory events. Thus, SP-D has a unique, dual functional capacity to induce pathogen elimination on the one hand and control of pro-inflammatory mechanisms on the other, suggesting a potential suitability for therapeutic prevention and treatment of chronic airway inflammation without compromising the host defence function of the airways. This paper will review recent findings on the mechanisms of immune-protective function of SP-D in the lung. Cite this as: L. R. Forbes and A. Haczku, Clinical & Experimental Allergy, 2010 (40) 547,562. [source]

Monoclonal antibody proteomics: Discovery and prevalidation of chronic obstructive pulmonary disease biomarkers in a single step

ELECTROPHORESIS, Issue 23 2007
Eszter Csanky
Abstract We define mAb proteomics as the global generation of disease specific antibodies that permit mass screening of biomarkers. An integrated, high-throughput, disease-specific mAb-based biomarker discovery platform has been developed. The approach readily provided new biomarker leads with the focus on large-scale discovery and production of mAb-based, disease-specific clinical assay candidates. The outcome of the biomarker discovery process was a highly specific and sensitive assay, applicable for testing of clinical validation paradigms, like response to treatment or correlation with other clinical parameters. In contrast to MS-based or systems biology-based strategies, our process produced prevalidated clinical assays as the outcome of the discovery process. By re-engineering the biomarker discovery paradigm, the encouraging results presented in this paper clearly demonstrate the efficiency of the mAb proteomics approach, and set the grounds for the next steps of studies, namely, the hunt for candidate biomarkers that respond to drug treatment. [source]

National Institute of Neurological Disorders and Stroke (NINDS): Advances in understanding and treating neuropathy, 24,25 October 2006; Bethesda, Maryland

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2008
Eva L. Feldman
Abstract National Institute of Neurological Disorders and Stroke sponsored a meeting to explore the current status of basic and clinical research in peripheral neurobiology and clinical neuropathy. The goal of the workshop was to identify areas where additional research could lead to the development of new therapeutics in the next 5 years. Participants discussed the current understanding of disease mechanisms of axonal and demyelinating neuropathies, existing techniques in research, disease biomarkers, and assessment of neuropathy. Painful neuropathies were discussed at the basic scientific and clinical levels in relation to new insights into etiology and treatment. The meeting concluded with a discussion on therapeutic development in neuropathy and the need for a unified approach to multicenter trials. Short-term goals of the workshop were to form a working group for neuropathy, the Peripheral Neuropathy Study Group, and to translate new scientific findings into therapies and complete clinical trials. [source]

Quantitative analysis of phosphopeptides in search of the disease biomarker from the hepatocellular carcinoma specimen

Dynamic urinary proteomic analysis reveals stable proteins to be potential biomarkers

PROTEOMICS - CLINICAL APPLICATIONS, Issue 3 2009
Wei Sun
Abstract Human urinary proteome analysis is a convenient and efficient approach for understanding disease processes affecting the kidney and urogenital tract. Many potential biomarkers have been identified in previous differential analyses; however, dynamic variations of the urinary proteome have not been intensively studied, and it is difficult to conclude that potential biomarkers are genuinely associated with disease rather then simply being physiological proteome variations. In this paper, pooled and individual urine samples were used to analyze dynamic variations in the urinary proteome. Five types of pooled samples (first morning void, second morning void, excessive water-drinking void, random void, and 24,h void) collected in 1,day from six volunteers were used to analyze intra-day variations. Six pairs of first morning voids collected a week apart were used to study inter-day, inter-individual, and inter-gender variations. The intra-day, inter-day, inter-individual, and inter-gender variation analyses showed that many proteins were constantly present with relatively stable abundances, and some of these had earlier been reported as potential disease biomarkers. In terms of sensitivity, the main components of the five intra-day urinary proteomes were similar, and the second morning void is recommended for clinical proteome analysis. The advantages and disadvantages of pooling samples are also discussed. The data presented describe a pool of stable urinary proteins seen under different physiological conditions. Any significant qualitative or quantitative changes in these stable proteins may mean that such proteins could serve as potential urinary biomarkers. [source]

Use of activated graphitized carbon chips for liquid chromatography/mass spectrometric and tandem mass spectrometric analysis of tryptic glycopeptides

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 4 2009
William R. Alley Jr.
Protein glycosylation has a significant medical importance as changes in glycosylation patterns have been associated with a number of diseases. Therefore, monitoring potential changes in glycan profiles, and the microheterogeneities associated with glycosylation sites, are becoming increasingly important in the search for disease biomarkers. Highly efficient separations and sensitive methods must be developed to effectively monitor changes in the glycoproteome. These methods must not discriminate against hydrophobic or hydrophilic analytes. The use of activated graphitized carbon as a desalting media and a stationary phase for the purification and the separation of glycans, and as a stationary phase for the separation of small glycopeptides, has previously been reported. Here, we describe the use of activated graphitized carbon as a stationary phase for the separation of hydrophilic tryptic glycopeptides, employing a chip-based liquid chromatographic (LC) system. The capabilities of both activated graphitized carbon and C18 LC chips for the characterization of the glycopeptides appeared to be comparable. Adequate retention time reproducibility was achieved for both packing types in the chip format. However, hydrophilic glycopeptides were preferentially retained on the activated graphitized carbon chip, thus allowing the identification of hydrophilic glycopeptides which were not effectively retained on C18 chips. On the other hand, hydrophobic glycopeptides were better retained on C18 chips. Characterization of the glycosylation sites of glycoproteins possessing both hydrophilic and hydrophobic glycopeptides is comprehensively achieved using both media. This is feasible considering the limited amount of sample required per analysis (<1,pmol). The performance of both media also appeared comparable when analyzing a four-protein mixture. Similar sequence coverage and MASCOT ion scores were observed for all proteins when using either stationary phase. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Exercise and Alzheimer's disease biomarkers in cognitively normal older adults

ANNALS OF NEUROLOGY, Issue 3 2010
Kelvin Y. Liang BS
Objective In addition to the increasingly recognized role of physical exercise in maintaining cognition, exercise may influence Alzheimer's disease (AD) pathology, as transgenic mouse studies show lowered levels of AD pathology in exercise groups. The objective of this study was to elucidate the association between exercise and AD pathology in humans using Pittsburgh compound-B (PIB), amyloid-, (A,)42, tau, and phosphorylated tau (ptau)181 biomarkers. Methods Sixty-nine older adults (17 males, 52 females) aged 55 to 88 years, were recruited and confirmed to be cognitively normal. A questionnaire on physical exercise levels over the past decade was administered to all. Cerebrospinal fluid samples were collected from 56 participants, and amyloid imaging with PIB was performed on 54 participants. Results Participants were classified based on biomarker levels. Those with elevated PIB (p = 0.030), tau (p = 0.040), and ptau181 (p = 0.044) had significantly lower exercise, with a nonsignificant trend for lower A,42 (p = 0.135) to be associated with less exercise. Results were similar for PIB after controlling for covariates; tau (p = 0.115) and ptau181 (p = 0.123) differences were reduced to nonsignificant trends. Additional analyses also demonstrated that active individuals who met the exercise guidelines set by the American Heart Association had significantly lower PIB binding and higher A,42 levels with and without controlling for covariates (PIB: p = 0.006 and p = 0.001; A,42: p = 0.042 and p = 0.046). Last, the associations between exercise engagement and PIB levels were more prominent in APOE epsilon 4 noncarriers. Interpretation Collectively, these results are supportive of an association between exercise engagement and AD biomarkers in cognitively normal older adults. Ann Neurol 2010;68:311,318 [source]

Ligands for retinoic acid receptors are elevated in osteoarthritis and may contribute to pathologic processes in the osteoarthritic joint

ARTHRITIS & RHEUMATISM, Issue 6 2009
Mark R. Davies
Objective Vitamin A derivatives, including all- trans -retinoic acid (ATRA), have a well-established role during skeletal development and limb formation and have been shown to have profound effects on chondrocyte phenotype. The aim of this study was to elucidate the effects of retinoids and components of the retinoid metabolic pathway on chondrocyte phenotype in the tibiofemoral joints of patients with osteoarthritis (OA), to show that the retinoids can have multiple effects relevant to the OA disease process. Methods Human explant tissue and a chondrocyte-like cell line were treated with ATRA, and the responses of 4 key markers of chondrocyte phenotype were analyzed. In addition, the effects of ATRA on a number of novel genes associated with OA were assessed using a low-density microarray containing 80 disease marker genes. Results Vitamin A metabolite levels were elevated in synovial fluid, serum, and cartilage from patients with OA. Expression profiling of a retinoic acid receptor , coactivator protein, P/CAF, demonstrated elevated expression in patients with OA, suggesting the potential for increased signaling via the retinoid receptors in the disease. ATRA increased the levels of matrix metalloproteinase 13 and aggrecanase activity in human cartilage explants and in a human chondrocyte cell line. Furthermore, ATRA altered the expression of a wide range of relevant genes, including the types I, II, IX, and XI collagen genes, toward a nonchondrogenic and OA-like phenotype. Conclusion These results suggest that retinoid signaling could have a central role in OA, and that components of the pathway may provide potential disease biomarkers or targets for therapeutic intervention. [source]

An overview of proteomic and metabolomic technologies and their application to pregnancy research

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 2 2009
RP Horgan
,Omic' technologies represent a strategy towards high-throughput, simultaneous analysis of thousands of biological molecules. Their development has been accelerated in the post-genomic era since these molecules represent the interaction of genes and environment or the ,functional genome'. Omic domains are of particular interest in the search for predictive disease biomarkers and have additional relevance in understanding pathophysiology and the development of molecularly targeted therapeutics. This review examines the fields of proteomics and metabolomics in the context of obstetrics and gynaecology, including a discussion of methodology, challenges, potential applications and current research. [source]