Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Biomarkers

  • acid biomarker
  • alcohol biomarker
  • appropriate biomarker
  • bacterial biomarker
  • cancer biomarker
  • candidate biomarker
  • cardiac biomarker
  • circulating biomarker
  • diagnostic biomarker
  • disease biomarker
  • early biomarker
  • exposure biomarker
  • fatty acid biomarker
  • fluid biomarker
  • good biomarker
  • imaging biomarker
  • important biomarker
  • independent biomarker
  • inflammatory biomarker
  • lipid biomarker
  • metabolic biomarker
  • molecular biomarker
  • mri biomarker
  • new biomarker
  • non-invasive biomarker
  • noninvasive biomarker
  • novel biomarker
  • other biomarker
  • oxidative stress biomarker
  • possible biomarker
  • potential biomarker
  • predictive biomarker
  • prognostic biomarker
  • promising biomarker
  • protein biomarker
  • putative biomarker
  • relevant biomarker
  • reliable biomarker
  • salivary biomarker
  • sensitive biomarker
  • serum biomarker
  • specific biomarker
  • stress biomarker
  • surrogate biomarker
  • tumor biomarker
  • urinary biomarker
  • urine biomarker
  • used biomarker
  • useful biomarker
  • various biomarker

  • Terms modified by Biomarkers

  • biomarker analysis
  • biomarker assessment
  • biomarker candidate
  • biomarker data
  • biomarker development
  • biomarker discovery
  • biomarker distribution
  • biomarker level
  • biomarker panel
  • biomarker research
  • biomarker response
  • biomarker test

  • Selected Abstracts

    BIOMARKER: Phosphatidylethanol as a sensitive and specific biomarker,comparison with gamma-glutamyl transpeptidase, mean corpuscular volume and carbohydrate-deficient transferrin

    ADDICTION BIOLOGY, Issue 1 2007
    Susanne Hartmann
    ABSTRACT Phosphatidylethanol (PEth), a direct ethanol metabolite, is detectable in blood for more than 2 weeks after sustained ethanol intake. Our aim was to assess the usefulness of PEth [comparing sensitivity, specificity and the area under the curve (AUC)] as compared with carbohydrate-deficient transferrin (CDT), gamma-glutamyl transpeptidase (GGT) and mean corpuscular volume (MCV), calculating the results from sober patients against those from alcohol-dependent patients during withdrawal. Fifty-six alcohol-dependent patients (ICD-10 F 10.25) in detoxification, age 43 years, GGT 81 U/l, MCV 96.4 fl, %CDT 4.2, 1400 g ethanol intake in the last 7 days (median), were included in the study. Over the time of 1 year, 52 samples from 35 sober forensic psychiatric addicted in-patients [age 34 years, GGT 16 U/l, MCV 91 fl, CDT 0.5 (median)] in a closed ward were drawn and used for comparison . PEth was measured in heparinized whole blood with a high-performance liquid chromatography method. GGT, MCV and %CDT were measured using routine methods. A receiver operating characteristic curve analysis was carried out, with ,current drinking status' (sober/drinking) as the state variable and PEth, MCV, GGT and CDT as test variables. The resulting AUC was 0.974 (P < 0.0001, confidence interval 0.932,1.016) for PEth. At a cut-off of 0.36 µmol/l, the sensitivity was 94.5% and specificity 100%. The AUC for CDT, GGT and MCV were 0.931, 0.894 and 0.883, respectively. A significant Spearman's rank correlation was found between PEth and GGT (r = 0.739), CDT (r = 0.643), MVC (r = 0.639) and grams of ethanol consumed in the last 7 days (r = 0.802). Our data suggest that PEth has potential to be a sensitive and specific biomarker, having been found in previous studies to indicate longer lasting intake of higher amounts of alcohol. [source]

    BIOMARKER: The validity of the laboratory marker combinations DOVER and QUVER to detect physician's diagnosis of at-risk drinking

    ADDICTION BIOLOGY, Issue 1 2007
    Michael Bentele
    ABSTRACT Especially in situations where it might be favorable for the patient to dissimulate the existing alcohol problem, ,objective' laboratory tests can be helpful. In this study we report validation of the two combinations DOVER (DOctor VERified) and QUVER (QUestionnarie VERified) of the biological markers percent carbohydrate-deficient transferrin (%CDT) and gamma-glutamyl-transferase (,-GT) to detect patients that have been identified by their physicians with at-risk drinking behavior. Fifty-eight general practitioners (GPs) participated at two study sites in South-West Germany. Patients filled in a questionnaire that included the alcohol use disorders identification test (AUDIT) and gave a blood sample. The GP recorded his/her assessment about the presence of an alcohol-related disorder in the patient. Receiver operating characteristics (ROC) analyses of the marker combinations DOVER and QUVER were performed. A total of 2940 patients participated in the study, of which 2496 completed data sets that could be used for further analysis. The area under the curve (AUC) of 79.5% for DOVER and 77.2% (QUVER) are in a higher range than the values for gamma%CDT (75.7%) or ,-GT (72.5%) and %CDT (64.5%) and suggest superiority of the proposed marker combinations. Cross-validation results were almost identical with 76.6% and 73.3% for DOVER and QUVER, respectively. Our analysis demonstrated that the combination of the markers ,-GT and %CDT with the physician's judgement of the condition as reference was superior to the use of single markers. [source]

    Copeptin: A Biomarker of Cardiovascular and Renal Function

    Nils G. Morgenthaler MD
    Congest Heart Fail. 2010;16(4)(suppl 1):S37,S44. ©2010 Wiley Periodicals, Inc. Arginine vasopressin (AVP or antidiuretic hormone) is one of the key hormones in the human body responsible for a variety of cardiovascular and renal functions. It has so far escaped introduction into the routine clinical laboratory due to technical difficulties and preanalytical errors. Copeptin, the C-terminal part of the AVP precursor peptide, was found to be a stable and sensitive surrogate marker for AVP release. Copeptin behaves in a similar manner to mature AVP in the circulation, with respect to osmotic stimuli and hypotension. During the past years, copeptin measurement has been shown to be of interest in a variety of clinical indications, including cardiovascular diseases such as heart failure, myocardial infarction, and stroke. This review summarizes the recent progress on the diagnostic use of copeptin in cardiovascular and renal diseases and discusses the potential use of copeptin measurement in the context of therapeutic interventions with vasopressin receptor antagonists. [source]

    Compound-specific stable-isotope (,13C) analysis in soil science

    Bruno Glaser
    Abstract This review provides current state of the art of compound-specific stable-isotope-ratio mass spectrometry (,13C) and gives an overview on innovative applications in soil science. After a short introduction on the background of stable C isotopes and their ecological significance, different techniques for compound-specific stable-isotope analysis are compared. Analogous to the ,13C analysis in bulk samples, by means of elemental analyzer,isotope-ratio mass spectrometry, physical fractions such as particle-size fractions, soil microbial biomass, and water-soluble organic C can be analyzed. The main focus of this review is, however, to discuss the isotope composition of chemical fractions (so-called molecular markers) indicating plant- (pentoses, long-chain n-alkanes, lignin phenols) and microbial-derived residues (phospholipid fatty acids, hexoses, amino sugars, and short-chain n-alkanes) as well as other interesting soil constituents such as "black carbon" and polycyclic aromatic hydrocarbons. For this purpose, innovative techniques such as pyrolysis,gas chromatography,combustion,isotope-ratio mass spectrometry, gas chromatography,combustion,isotope-ratio mass spectrometry, or liquid chromatography,combustion,isotope-ratio mass spectrometry were compared. These techniques can be used in general for two purposes, (1) to quantify sequestration and turnover of specific organic compounds in the environment and (2) to trace the origin of organic substances. Turnover times of physical (sand < silt < clay) and chemical fractions (lignin < phospholipid fatty acids < amino sugars , sugars) are generally shorter compared to bulk soil and increase in the order given in brackets. Tracing the origin of organic compounds such as polycyclic aromatic hydrocarbons is difficult when more than two sources are involved and isotope difference of different sources is small. Therefore, this application is preferentially used when natural (e.g., C3-to-C4 plant conversion) or artificial (positive or negative) 13C labeling is used. Substanzspezifische Stabilisotopenanalyse (,13C) in der Bodenforschung Dieser Artikel fasst den Stand der Forschung bezüglich der substanzspezifischen Stabilisotopenanalyse (,13C) zusammen. Innovative Anwendungen und ein Ausblick für künftige Forschungsaktivitäten werden anhand von Fallbeispielen gegeben. Zunächst wird die ökologische Bedeutung von stabilen C-Isotopen kurz erläutert. Daran schließt sich ein methodischer Teil an, in welchem die verschiedenen Techniken gegenüber gestellt werden. Analog zu ,13C-Messungen der Feinerde mittels Elementaranalysator-Isotopenverhältnis-Massenspektrometrie können physikalisch isolierte Fraktionen (z.,B. Korngrößenfraktionen, mikrobielle Biomasse, DOC) analysiert werden. Der Schwerpunkt dieses Übersichtsartikels liegt jedoch in der Diskussion der C-Isotopensignatur chemischer Fraktionen (sog. Biomarker), welche Rückschlüsse auf Herkunft und Dynamik pflanzlicher (Pentosen, langkettige n-Alkane, Ligninphenole) und mikrobieller Rückstände (Phospholipidfettsäuren, Hexosen, Aminozucker und kurzkettige n-Alkane) sowie anderer interessanter Substanzen im Boden erlaubt wie z.,B. ,Black Carbon" und polyzyklische aromatische Kohlenwasserstoffe. Zu diesem Zweck kommen innovative Techniken zum Einsatz wie z.,B. Pyrolyse-Gaschromatographie-Isotopenverhältnismassenspektrometrie, Gaschromatographie-Verbrennungs-Isotopenverhältnismassenspektrometrie und Flüssigkeitschromatographie-Oxidations-Isotopenverhältnismassenspektrometrie. Innovative ökologische Anwendungen werden erläutert, welche sich prinzipiell in zwei Kategorien einteilen lassen: (1) Quantifizierung der Sequestrierung und des Umsatzes dieser Verbindungen in der Umwelt; (2) Untersuchung der Herkunft spezifischer organischer Substanzen. Umsatzzeiten physikalischer (Sand < Schluff < Ton) und chemischer Fraktionen (Lignin < Phospholipidfettsäuren < Aminozucker , Zucker) sind generall kleiner als jene der gesamten organischen Substanz in der Feinerde und nehmen in der in Klammern angegebenen Reihenfolge zu. Die Untersuchung der Herkunft organischer Substanzen (z.,B. polyzyklischer aromatischer Kohlenwasserstoffe) ist problematisch, weil die Unterschiede der Isotopensignatur verschiedener Quellen gering sind und meist mehr als zwei Quellen zur Isotopensignatur des untersuchten Biomarkers beitragen. Deswegen sollte die Untersuchung der Herkunft organischer Substanzen auf Tracer-Experimente beschränkt werden, wie z.,B. nach natürlicher (C3-C4-Pflanzenwechsel) bzw. künstlicher (13C-An- oder -Abreicherung) Markierung. [source]

    Immunological Detection of in Vitro Formed Phosphatidylethanol,An Alcohol Biomarker,With Monoclonal Antibodies

    ALCOHOLISM, Issue 6 2008
    Antti E. Nissinen
    Background:, Phosphatidylethanol (PEth) is a promising new marker for detecting long-term alcohol abuse with excellent sensitivity and specificity. Current methods are based on the high performance liquid chromatography,mass spectrometric method and therefore require high levels of expertise and expensive instrumentation. This study was designed to generate PEth-specific monoclonal antibodies for PEth immunoassay development. Methods:, C57/BL6 mice were immunized with PEth in 3 different carriers, mouse serum albumin, mouse high-density lipoproteins, and human low-density lipoprotein (LDL). Mouse splenocytes were fused with a mouse myeloma cell line using the hybridoma technique. Mouse IgM-producing cell lines were selected by limiting dilutions. Binding characteristics of the anti-PEth antibodies were studied using luminometric immunoassays and sequence analysis of the variable region mRNA sequences of the antibodies. Produced antibodies were purified by chromatographic methods. PEth was detected with these antibodies in fluorescence immunoassay and flow cytometric analysis. Results:, We generated monoclonal cell lines (2B1 and 2E9) that produce IgM antibodies binding specifically to PEth but not to structurally or chemically similar phospholipids, such as phosphatidylcholine, phosphatidic acid, and cardiolipin. We show here that these anti-PEth antibodies can be used to detect PEth in a fluorescent PEth assay and FACS analysis of human red blood cell samples spiked with PEth. Conclusions:, The present study shows that PEth-specific monoclonal antibodies can be generated using traditional hybridoma technique. Immunogenicity of PEth was enhanced using human LDL as an immunization carrier. The generated monoclonal anti-PEth antibodies, 2B1 and 2E9 bind to PEth in fluid phase and in biological membranes. [source]

    Analysis of Heritability of Hormonal Responses to Alcohol in Twins: Beta-Endorphin as a Potential Biomarker of Genetic Risk for Alcoholism

    ALCOHOLISM, Issue 3 2000
    J. C. Froehlich
    Background: Hormonal responses to alcohol have been reported to differ in subjects with and without a family history of alcoholism which suggests that alcohol-induced hormonal changes might be used to identify individuals who are at elevated genetic risk for developing alcoholism. However, before a biological response can be used as a marker of genetic risk for disease, it must first be demonstrated that the response is, in fact, heritable. The present study was designed to determine whether hormonal responses to alcohol are heritable. Methods: The adrenocorticotropic hormone (ACTH), beta-endorphin (,-E), cortisol (CORT), and prolactin (PRL) responses to alcohol were examined in male and female identical (monozygotic or MZ) and fraternal (dizygotic or DZ) twin pairs. Male subjects consumed 0.35g ethanol/kg body weight (BW) and female consumed 0.325 g ethanol/kg BW in each of two alcohol drinking sessions administered 1 hr apar (total dose of 0.7 g/kg BW in males and 0.65 g/kg BW in females). Plasma hormone content was analyzed in samples collected before (resting conditions) and at 15, 60, 75, 120, 180, and 240 min after onset of drinking. Hormonal responses to alcohol were examined with twin analyses using the TWINAN90 program. A separate analysis was performed for each of the four hormones. A subset of subjects from each zygosity was seen on two separate occasions to establish retest reliability. Heritability of hormonal responses to alcohol was estimated using the intraclass correlation approach before and after removing the contribution of covariates that have the potential of influencing the plasma levels of these hormones. Results: Resting plasma levels of all four hormones were within the expected range, and the ,-E, ACTH, and PRL responses to the alcohol challenge evidenced good test-retest reliability. Of the four hormones examined, the only one that showed significant heritability after alcohol drinking was ,-E. Heritability estimates were not altered for any of the four hormones after removal of the variance contributed by covariates, such as gender and age. Conclusions: Taken together with other recent findings, the results suggest that the ,-E response to alcohol may represent a new biomarker that can be used to identify individuals who are at elevated genetic risk for developing alcoholism. [source]

    Biomarker as a classifier in pharmacogenomics clinical trials: a tribute to 30th anniversary of PSI,,

    Sue-Jane Wang
    Abstract Pharmacogenetics is one of many evolving sciences that have come to the fore since the formation of the Statisticians in the Pharmaceutical Industry (PSI) 30 years ago. Following the completion of the human genome project and the HapMap in the early 21st century, pharmacogenetics has gradually focused on studies of whole-genome single-nucleotide-polymorphisms screening associating disease pathophysiology with potential therapeutic interventions. Around this time, transcription profiling aiming at similar objectives has also been actively pursued, known as pharmacogenomics. It has become increasingly apparent that treatment effects between different genomic patient subsets can be dissimilar, and the value and need for genomic biomarkers to help predict effects, particularly in cancer clinical studies, have become issues of paramount importance. Pharmacogenomics/pharmaogenetics has thus become intensely focused on the search for genomic biomarkers for use as classifiers to select patients in randomized-controlled trials. We highlight that the predictive utility of a genomic classifier has tremendous clinical appeal and that there will be growing examples in which use of a companion diagnostic will need to be considered and may become an integral part in the utilization of drugs in medical practice. The credible mechanism to test the clinical utility of a genomic classifier is to employ the study results from a prospective trial that recruits all patients. Such investigations, if well designed, will allow analysis of all relevant performance factors in the drug and diagnostic combination including the sensitivity, specificity, positive and negative predictive values of the diagnostic test and the efficacy of the drug. Published in 2007 by John Wiley & Sons, Ltd. [source]

    Biomarker Assays in Nipple Aspirate Fluid

    THE BREAST JOURNAL, Issue 6 2001
    Pamela Klein MD
    The noninvasive technique of nipple aspiration as a potential source of biomarkers of breast cancer risk was evaluated. The feasibility of performing mutagenesis assays, amplifying DNA, and performing protein electrophoresis on nipple aspirate fluid was explored. A tool was developed to measure the level of discomfort, if any, from this procedure. Twenty-five healthy women (20 premenopausal and 5 postmenopausal) were enrolled. Fluid was obtained using a modified breast pump. Premenopausal women were scheduled for four to six weekly aspirations, and postmenopausal women were scheduled for one to two weekly aspirations. Mutagenesis assays were performed using the Salmonella (Ames) assay. DNA amplification of several microsatellite regions was carried out using polymerase chain reaction. Protein was quantified, and two-dimensional protein electrophoresis was performed. Overall, fluid was obtained from 80% of the women, and the level of discomfort was minimal. Acid hydrolysis of one sample resulted in mutagenicity; all six nonhydrolyzed samples were not mutagenic. The ability to amplify DNA ranged from 34% to 96%, depending on length of the microsatellite region examined. The average protein concentration was 71 ,g/mL. Two-dimensional protein electrophoresis was successfully performed on samples from two subjects. Nipple aspiration is a simple technique and is easily learned and well tolerated, which yields a reagent useful for a variety of investigations. This technique may facilitate the identification and application of biomarkers for future breast cancer risk assessment and chemopreventive protocols. [source]

    Ratiometric Fluorescent Detection of an Anthrax Biomarker at Molecular Printboards,

    ANGEWANDTE CHEMIE, Issue 34 2010
    Deniz Yilmaz
    Hochempfindlich und -selektiv: Ein neuartiges oberflächengestütztes fluoreszenzbasiertes Sensorsystem ermöglicht den ratiometrischen Nachweis des Anthraxbiomarkers Dipicolinsäure (DPA, schwarz, siehe Bild) auf einer molekularen Platine. Das System bietet eine Empfindlichkeit im Nanomolbereich und eine hohe Selektivität für DPA. [source]

    Stress im Boden: Früherkennung ökotoxikologischer Effekte durch Biomarker

    Bevor Kontaminationen von Böden mit Chemikalien ökosystemare Veränderungen nach sich ziehen, ist die Präsenz oder die Wirkung dieser Schadstoffe mittels Biomarkerreaktionen bei wirbellosen Bodentieren nachweisbar. Zu etablierten Biomarkern bei diesen Tieren zählen die Induktion von metallbindenden Proteinen und Stressproteinen sowie die lysosomale Stabilität und histo- beziehungweise cytopathologische Reaktionen. Unterschiedliche Sensitivitäten, Indikationsspektren und Konzentrations-Wirkungs-Kinetiken dieser subzellulären Marker erfordern eine Kombination derselben in einer "Biomarker-Batterie" zur Frühdiagnostik auftretender Schäden. Molekulare und zelluläre Effektmarker gewährleisten, ähnlich wie in der Humanmedizin, verlässliche Aussagen über den Gesundheitszustand der untersuchten Organismen. [source]

    Biotec Visions 2010, May,June

    Article first published online: 3 MAY 2010
    News:Ethanol biofuels from orange peels , Targeting leukaemia's gene addiction , Pea-derived solar cells , HIV is a kick in the head , Nano-scale DNA reader , Membrane in black , Cheese improves the immune response of elderly , Synthetic proteins built from standard parts , Therapeutic proteins produced in algae , Biosensor detects 100 mycoplasma cells , Protecting maggots against bacteria , Advanced biofuels from microbes , Fluorescent bacterial uptake , Two disparate stem cell states , Brachypodium genome sequenced Encyclopedia of Life Sciences: Nuclear transfer for cell lines WIREs Nanomedicine and Nanobiotechnology: Nanoparticle detection of respiratory infection Journal Highlights: Biocatalysis , Synthetic Biology In the news: Nanobiotech to detect cancer Most Read Industry News: Biomarker assays for personalized medicine , Bioplastic industry defies economic crisis , SDS-PAGE monitoring of mAB Awards: BTJ Editors elected members of the US National Academy of Engineering (NAE) Meeting highlight Writing tips: Figure preparation made simple , Some useful tutorials on the web Book Highlights:Molecular Biotechnology , Bacterial Signaling , Yeast Test your knowledge:Do you recognize this? WIREs Authors Spotlight:Nanotechnology and orthopedics [source]

    In Vitro and In Silico Analysis of Annexin V Binding to Lymphocytes as a Biomarker in Emergency Department Sepsis Studies

    Colin F. Greineder
    Background: Peripheral blood lymphocyte apoptosis is a recognized feature of serious infection and sepsis and can be easily quantified by flow cytometric measurement of annexin V binding to the cell surface. Use of apoptosis as a biomarker in emergency department (ED) studies of sepsis is potentially difficult because of sample processing requirements and limited availability of a research cytometer with which to measure patient samples. Objectives: To assess, in vitro and in simulation, the relationship between sample stability, timing of patient enrollment, and diagnostic performance of a flow cytometric assay for sepsis in patients evaluated in EDs. Methods: Assuming any clinical trial would require daily sample batching, the authors measured the stability of lymphocyte samples over time, noting the rate at which annexin V,negative cells became positive as ED processing delays increased. With these data, they then optimized a study design that could evaluate lymphocyte apoptosis as a sepsis biomarker by using a series of Monte Carlo,based simulated clinical trials. Results: The authors found that annexin V,negative lymphocytes become positive during storage delays that would be encountered in an ED sepsis trial. The extent of this deterioration was least among cells left as whole blood at room temperature until just before analysis or when lymphocytes were isolated early and stored in culture media at 4°C until analysis. When the expected rate of sample deterioration was considered in simulated clinical trials, an inverse relationship was found between the rate at which patients are enrolled and the best achievable receiver operating characteristic curve a study could produce. Conclusions: Peripheral blood samples being analyzed for lymphocyte apoptosis degrade at a rate relevant to the design of ED trials of sepsis. Because of sample processing delays inherent in studying unscheduled septic patients, the performance of annexin V binding as a biomarker for sepsis can approach, but not be expected to exceed, its performance in a comparable intensive care unit,based study. [source]

    Nanoparticle-Based Electrochemical Immunosensor for the Detection of Phosphorylated Acetylcholinesterase: An Exposure Biomarker of Organophosphate Pesticides and Nerve Agents

    Guodong Liu Dr.
    Abstract A nanoparticle-based electrochemical immunosensor has been developed for the detection of phosphorylated acetylcholinesterase (AChE), which is a potential biomarker of exposure to organophosphate (OP) pesticides and chemical warfare nerve agents. Zirconia nanoparticles (ZrO2 NPs) were used as selective sorbents to capture the phosphorylated AChE adduct, and quantum dots (ZnS@CdS, QDs) were used as tags to label monoclonal anti-AChE antibody to quantify the immunorecognition events. The sandwich-like immunoreactions were performed among the ZrO2 NPs, which were pre-coated on a screen printed electrode (SPE) by electrodeposition, phosphorylated AChE and QD-anti-AChE. The captured QD tags were determined on the SPE by electrochemical stripping analysis of its metallic component (cadmium) after an acid-dissolution step. Paraoxon was used as the model OP insecticide to prepare the phosphorylated AChE adducts to demonstrate proof of principle for the sensor. The phosphorylated AChE adduct was characterized by Fourier transform infrared spectroscopy (FTIR) and mass spectroscopy. The binding affinity of anti-AChE to the phosphorylated AChE was validated with an enzyme-linked immunosorbent assay. The parameters (e.g., amount of ZrO2 NP, QD-anti-AChE concentration,) that govern the electrochemical response of immunosensors were optimized. The voltammetric response of the immunosensor is highly linear over the range of 10,pM to 4,nM phosphorylated AChE, and the limit of detection is estimated to be 8.0,pM. The immunosensor also successfully detected phosphorylated AChE in human plasma. This new nanoparticle-based electrochemical immunosensor provides an opportunity to develop field-deployable, sensitive, and quantitative biosensors for monitoring exposure to a variety of OP pesticides and nerve agents. [source]

    Dynamic Changes in Lymphocyte GRK2 Levels in Cardiac Transplant Patients: A Biomarker for Left Ventricular Function

    Raphael E. Bonita M.D., Sc.M.
    Abstract G protein-coupled receptor kinase 2 (GRK2), which is upregulated in the failing human myocardium, appears to have a role in heart failure (HF) pathogenesis. In peripheral lymphocytes, GRK2 expression has been shown to reflect myocardial levels. This study represents an attempt to define the role for GRK2 as a potential biomarker of left ventricular function in HF patients. We obtained blood from 24 HF patients before and after heart transplantation and followed them for up to 1 year, also recording hemodynamic data and histological results from endomyocardial biopsies. We determined blood GRK2 protein by Western blotting and enzyme-linked immunosorbent assay. GRK2 levels were obtained before transplant and at first posttransplant biopsy. GRK2 levels significantly declined after transplant and remained low over the course of the study period. After transplantation, we found that blood GRK2 signifi cantly dropped and remained low consistent with improved cardiac function in the transplanted heart. Blood GRK2 has potential as a biomarker for myocardial function in end-stage HF. Clin Trans Sci 2010; Volume #: 1,5 [source]

    Treatment of Anemia With Darbepoetin Alfa in Heart Failure

    William T. Abraham MD
    Anemia is common in heart failure (HF) patients. A prespecified pooled analysis of 2 randomized, double-blind, placebo-controlled studies evaluated darbepoetin alfa (DA) in 475 anemic patients with HF (hemoglobin [Hb], 9.0,12.5 g/dL). DA was administered subcutaneously every 2 weeks and titrated to achieve and maintain a target Hb level of 14.0±1.0 g/dL. By week 27, mean (SD) Hb concentrations did not increase with placebo but increased with DA from 11.5 (0.7) to 13.3 (1.3) g/dL. Hazard ratios (HRs) for DA compared with placebo for all-cause death or first HF hospitalization (composite end point), all-cause death, and HF hospitalization by month 12 were 0.67 (95% confidence interval [CI], 0.44,1.03; P=.067), 0.76 (95% CI, 0.39,1.48; P=.419), and 0.66 (95% CI, 0.40,1.07; P=.093), respectively. Incidence of adverse events was similar in both groups. In post hoc analyses, improvement in the composite end point was significantly associated with the mean Hb change from baseline (adjusted HR, 0.40; P=.017) with DA treatment. There was no increased risk of all-cause mortality or first HF hospitalization with DA in patients with reduced renal function or elevated baseline B-type natriuretic peptide, a biomarker of worse HF. These results suggest that DA is well tolerated, corrects HF-associated anemia, and may have favorable effects on clinical outcomes., Congest Heart Fail. 2010;16:87,95. © 2010 Wiley Periodicals, Inc. [source]

    The Role of Natriuretic Peptides in Patients With Chronic Complex (Mixed or Multiple) Heart Valve Disease

    FRACP, Naylin Bissessor MBChB
    N-terminal prohormone B-type natriuretic peptide (NT-proBNP) is an important biomarker of prognosis in heart failure and single valve disease. There are limited studies of complex valve disease. Patients with complex valve disease adopt a sedentary lifestyle, so symptoms may be difficult to detect. The authors aimed to determine whether NT-proBNP correlates with the severity of the valve lesion and underlying cardiac function and whether resting NT-proBNP predicts impaired peak VO2 in patients with complex valve disease. Forty-five patients with complex moderate to severe stenosis or regurgitation of the heart valves underwent a clinical assessment, echocardiography, resting NT-proBNP assessment, and formal cardiopulmonary exercise testing. In a multivariate analysis, the log NT-proBNP (,=,9.3, SE=1.9, P<.0001) and lean body weight (,=0.59, SE=0.22, P=.01) were dominant independent predictors of peak VO2. An NT-proBNP value of 84 pmol/L had 77% sensitivity and 70% specificity to predict impaired functional capacity, peak VO2 <60% (predicted), area under the curve=0.80. Resting NT-proBNP was the best predictor of peak VO2 in patients with complex valve disease, while symptoms and ejection fraction are a less reliable guide. Congest Heart Fail. 2010;16:50,54. © 2009 Wiley Periodicals, Inc. [source]

    Up-and-Coming Markers: Myeloperoxidase, a Novel Biomarker Test for Heart Failure and Acute Coronary Syndrome Application?

    Christoph Sinning MD
    Myeloperoxidase (MPO) is a mammalian enzyme responsible for generation of hypochlorite. The advantage of myeloperoxidase for use as a biomarker in the setting of heart failure and acute coronary syndrome is the early increase of MPO concentration in response to the acute event. In the setting of heart failure the reported independency of coronary artery disease and general inflammation, as indicated by MPO concentration in comparison to other inflammatory markers or in subgroups of patients with ischemic and non-ischemic cardiomyopathy, has to be highlighted. In terms of ACS, inclusion of MPO into a multiple marker strategy might add to enhance diagnosis and therapy decision making. Therefore, MPO is a biomarker worthwhile of further evaluation in the setting of cardiovascular disease. Congest Heart Fail. 2008;14(4 suppl 1):46,48. ©2008 Le Jacq [source]

    Mechanisms of fibrinogen-induced microvascular dysfunction during cardiovascular disease

    ACTA PHYSIOLOGICA, Issue 1 2010
    D. Lominadze
    Abstract Fibrinogen (Fg) is a high molecular weight plasma adhesion protein and a biomarker of inflammation. Many cardiovascular and cerebrovascular disorders are accompanied by increased blood content of Fg. Increased levels of Fg result in changes in blood rheological properties such as increases in plasma viscosity, erythrocyte aggregation, platelet thrombogenesis, alterations in vascular reactivity and compromises in endothelial layer integrity. These alterations exacerbate the complications in peripheral blood circulation during cardiovascular diseases such as hypertension, diabetes and stroke. In addition to affecting blood viscosity by altering plasma viscosity and erythrocyte aggregation, growing experimental evidence suggests that Fg alters vascular reactivity and impairs endothelial cell layer integrity by binding to its endothelial cell membrane receptors and activating signalling mechanisms. The purpose of this review is to discuss experimental data, which demonstrate the effects of Fg causing vascular dysfunction and to offer possible mechanisms for these effects, which could exacerbate microcirculatory complications during cardiovascular diseases accompanied by increased Fg content. [source]

    Connective tissue growth factor and cardiac fibrosis

    ACTA PHYSIOLOGICA, Issue 3 2009
    A. Daniels
    Abstract Cardiac fibrosis is a major pathogenic factor in a variety of cardiovascular diseases and refers to an excessive deposition of extracellular matrix components in the heart, which leads to cardiac dysfunction and eventually overt heart failure. Evidence is accumulating for a crucial role of connective tissue growth factor (CTGF) in fibrotic processes in several tissues including the heart. CTGF orchestrates the actions of important local factors evoking cardiac fibrosis. The central role of CTGF as a matricellular protein modulating the fibrotic process in cardiac remodelling makes it a possible biomarker for cardiac fibrosis and a potential candidate for therapeutic intervention to mitigate fibrosis in the heart. [source]

    Flow cytometric measurement of circulating endothelial cells: The effect of age and peripheral arterial disease on baseline levels of mature and progenitor populations

    CYTOMETRY, Issue 2 2006
    Rebecca Gusic Shaffer
    Abstract Background: Age and cardiovascular disease status appear to alter numbers and function of circulating endothelial progenitor cells (EPCs). Despite no universal phenotypic definition, numerous studies have implicated progenitors with apparent endothelial potential in local responses to vascular injury and with cardiovascular disease in general. To further define the role of this lineage in peripheral artery disease (PAD), we developed a multiparameter flow cytometry assay to analyze multiple phenotypic definitions of progenitor cells (PCs), EPCs, and mature endothelial cells (ECs) and evaluate effects of age and PAD on baseline levels of each subset. Methods: Blood was collected from young healthy subjects (N = 9, mean age 33 ± 8 years), older healthy subjects (N = 13, mean age 66 ± 8 years), and older subjects with PAD (N = 15, mean age 69 ± 8 years). After ammonium chloride lysis, cells were stained and analyzed on a Becton-Dickinson LSR II with a 5-color antibody panel: FITC-anti-CD31, PE-anti-CD146, PE-anti-CD133, PerCP-Cy5.5-anti-CD3,-CD19,-CD33 (lineage panel), PE-Cy7-anti-CD34, and APC-anti-VEGF-R2. Viability was assessed by propidium iodide exclusion, and only viable, low to medium side scatter lineage-negative singlets were analyzed. In some studies, cells were sorted for morphological studies. Subsets were defined as indicated later. Results: Our results, using a comprehensive flow cytometric panel, indicate that CD133+, CD34+, and CD133+/CD34+ PCs are elevated in younger healthy individuals compared to older individuals, both healthy and with PAD. However, the number of EPCs and mature ECs did not significantly differ among the three groups. Assessment of endothelial colony forming units and dual acLDL-lectin staining supported the flow cytometric findings. Conclusions: We describe a comprehensive flow cytometric method to detect circulating mature and progenitor endothelial populations confirmed by conventional morphological and functional assays. Our findings suggest that aging may influence circulating levels of PCs, but not EPCs or ECs; PAD had no effect on baseline levels of any populations investigated. This study provides the basis for evaluating the potential effects of acute stress and therapeutic intervention on circulating progenitor and endothelial populations as a biomarker for cardiovascular status. © 2005 International Society for Analytical Cytology [source]

    Human Papillomavirus and Overexpression of P16INK4a in Nonmelanoma Skin Cancer

    Ingo Nindl PhD
    Background. P16INK4a overexpression has been identified as a specific biomarker in high-risk human papillomavirus (HPV),infected cervical (pre)cancer lesions. Objective. To evaluate the overexpression of this cyclin-dependent kinase inhibitor in skin tumors depending on HPV infections, we analyzed normal skin, benign skin disease, and skin cancer specimens. Methods. Biopsies of 23 patients with normal histology (3), psoriasis (2), verrucae vulgaris (2), actinic keratoses (5), squamous cell carcinoma (SCC) in situ (3), Bowen's carcinoma (1), and SCC (7) were analyzed. Specimens of 23 patients were immunostained using the monoclonal antibody E6H4 specific for p16INK4a. HPV status was assessed by a polymerase chain reaction (PCR) system to detect all currently known HPV types. MY (MY09/MY11 and MYN9/MYN10)-, CP (CP65/CP70 and CP66/CP69)-nested PCR, and three single PCR methods CN1, CN3, and CN4 were used in a first step, and HPV typing was performed by restriction fragment length polymorphism analysis. Only ,-globin,positive patients were included in this study. Results. HPV DNA was detected in all actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC, in 50% (one of two) of verrucae vulgaris, in 66% (two of three) of normal skin, and in none of two psoriasis. P16INK4a expression was not detected in normal skin, psoriasis, and verrucae vulgares. Overexpression of p16INK4a was detected in a subset of dysplastic cells (10% to 80%) of all skin (pre)cancer lesions such as actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC infected with HPV independent of sun exposure. Conclusion. P16INK4a appears to be overexpressed in a portion of dysplastic cells from actinic keratoses and SCC. Further studies to examine the association of HPV infection and the overexpression of p16INK4a are warranted. [source]

    VMAT2 quantitation by PET as a biomarker for ,-cell mass in health and disease

    M. Freeby
    The common pathology underlying both type 1 and type 2 diabetes (T1DM and T2DM) is insufficient ,-cell mass (BCM) to meet metabolic demands. An important impediment to the more rapid evaluation of interventions for both T1DM and T2DM lack of biomarkers of pancreatic BCM. A reliable means of monitoring the mass and/or function of ,-cells would enable evaluation of the progression of diabetes as well as the monitoring of pharmacologic and other interventions. Recently, we identified a biomarker of BCM that is quantifiable by positron emission tomography (PET). PET is an imaging technique which allows for non-invasive measurements of radioligand uptake and clearance, is sensitive in the pico- to nanomolar range and of which the results can be deconvoluted into measurements of receptor concentration. For BCM estimates, we have identified VMAT2 (vesicular monoamine transporter type 2) as a biomarker and [11C] DTBZ (dihydrotetrabenazine) as the transporter's ligand. VMAT2 is highly expressed in ,-cells of the human pancreas relative to other cells of the endocrine and exocrine pancreas. Thus measurements of [11C] DTBZ in the pancreas provide an indirect measurement of BCM. Here we summarize our ongoing efforts to validate the clinical utility of this non-invasive approach to real-time BCM measurements [source]

    Application of flow cytometry for biomarker-based cervical cancer cells detection

    Jian Ling Ph.D.
    Abstract The Pap test used for cervical cancer screening is subjective, labor-intensive, and has relatively low sensitivity and specificity for the detection of underlying clinically significant lesions. The objective of this study is to develop a biomarker/flow cytometry-based approach for cervical cancer screening. Immunofluorescence technology to quantify cervical cell expression of two biomarkers p16INK4A and Mcm5 was developed and evaluated by both microcopy and flow cytometry. The capability of using biomarker/flow cytometry approach to detect rare-event dysplastic cells in a large background of benign epithelial and inflammatory cells was evaluated. The results indicate that flow cytometry could detect 0.01% dysplastic cells in a background of normal cervical epithelial cells with the combination of the two biomarkers. Thirty-two clinical specimens were used to test the biomarker/flow cytometry-based approach and the results were compared with the liquid-based cervical cytology. The experiment yielded 100% sensitivity and 93% specificity with reference to the liquid-based cervical cytology. This study indicates the promise of using multi-color fluorescence flow cytometry for biomarker-based cervical cancer screening. This molecular-based, potentially high-throughput and automated method is expected to provide an alternative/auxiliary means of cervical cancer screening. Diagn. Cytopathol. 2008;36:76,84. © 2008 Wiley-Liss, Inc. [source]

    Microbiotic crusts as biomarkers for surface stability and wetness duration in the Negev Desert

    Giora J. Kidron
    Abstract Microbiotic crusts play an important role in arid and semi-arid regions. Yet, very little information exists regarding the factors that impact their development. In an attempt to assess the main factors that may determine their growth, measurements of the amount of fines (silt and clay), rain, moisture content, wetness duration and wind erosion and deposition were carried out along a 12 station transect within a partially crusted dune field in the western Negev Desert and compared to the crust cover and chlorophyll content. Surface stability was the only variable that exhibited significant relationship with crust cover while daylight wetness duration exhibited strong positive relationship (r2 = 0·92,0·99) with the crust's chlorophyll content. The data point out that microbiotic crusts may serve as a useful biomarker for surface stability. While wetness duration and wind will control crust cover and the crust chlorophyll content in semi-stable habitats (with absolute annual change in sand level of 2,3 mm), stable habitats (absolute change <1 mm) will be controlled primarily by moisture, while habitats with low surface stability (absolute change of tens and hundreds of millimeters) will be primarily controlled by wind. Furthermore, owing to the strong positive relationship between daylight wetness duration and the crust's chlorophyll content, the crust may serve as a useful biomarker for the quantification of surface wetness duration. Copyright © 2009 John Wiley & Sons, Ltd. [source]

    Estimating driver risk using alcohol biomarkers, interlock blood alcohol concentration tests and psychometric assessments: initial descriptives

    ADDICTION, Issue 2 2010
    Paul Marques
    ABSTRACT Aim To identify alcohol biomarker and psychometric measures that relate to drivers' blood alcohol concentration (BAC) patterns from ignition interlock devices (IIDs). Design, setting, participants, measurements In Alberta, Canada, 534 drivers, convicted of driving under the influence of alcohol (DUI), installed IIDs and agreed to participate in a research study. IID BAC tests are an established proxy for predicting future DUI convictions. Three risk groups were defined by rates of failed BAC tests. Program entry and follow-up blood samples (n = 302, 171) were used to measure phosphatidyl ethanol (PETH), carbohydrate deficient transferrin (%CDT), gamma glutamyltransferase (GGT) and other biomarkers. Program entry urine (n = 130) was analyzed for ethyl glucuronide (ETG) and ethyl sulphate (ETS). Entry hair samples were tested for fatty acid ethyl esters (FAEE) (n = 92) and ETG (n = 146). Psychometric measures included the DSM-4 Diagnostic Interview Schedule Alcohol Module, Alcohol Use Disorders Identification Test (AUDIT), the time-line follow-back (TLFB), the Drinker Inventory of Consequences (DRINC) and the Temptation and Restraint Inventory (TRI). Findings Except for FAEE, all alcohol biomarkers were related significantly to the interlock BAC test profiles; higher marker levels predicted higher rates of interlock BAC test failures. PETH, the strongest with an overall analysis of variance F ratio of 35.5, had significant correlations with all nine of the other alcohol biomarkers and with 16 of 19 psychometric variables. Urine ETG and ETS were correlated strongly with the IID BAC tests. Conclusions The findings suggest that several alcohol biomarkers and assessments could play an important role in the prediction and control of driver alcohol risk when re-licensing. [source]

    Detection of C Reactive Protein (CRP) in Serum by an Electrochemical Aptamer-Based Sandwich Assay

    ELECTROANALYSIS, Issue 11 2009
    Sonia Centi
    Abstract A disposable electrochemical assay involving magnetic particles and carbon-based screen-printed electrodes (SPCEs) was developed for the detection of C Reactive Protein (CRP). CRP is a plasma protein and is among the most expressed proteins in acute phase inflammation cases, being a known biomarker for inflammatory states. The assay was based on a sandwich format in which a RNA aptamer was coupled to a monoclonal antibody and alkaline phosphatase (AP) was used as enzymatic label. After the sandwich assay, the modified magnetic beads were captured by a magnet on the surface of a graphite working electrode and the electrochemical detection was thus achieved through the addition of the AP substrate (,-naphthyl-phosphate) and ,-naphthol produced during the enzymatic reaction was detected using differential pulse voltammetry (DPV). The parameters influencing the different steps of the assay were optimized in order to reach the best sensitivity and specificity. With the optimized conditions, the assay was applied to the analysis of CRP free serum and serum samples. [source]

    Precautions to improve the accuracy of quantitative determinations of biomarkers in clinical diagnostics

    ELECTROPHORESIS, Issue 16 2010
    Nasim Ghasemzadeh
    Abstract Although protein biomarkers have a great potential as biomarkers for diagnosis of diseases, they are seldom used in hospitals. There are many reasons for this, for instance, the difficulties to (i) find a biomarker for which the concentration in body fluids clearly differs between patients and healthy subjects, (ii) attain purification of the biomarker close to 100%, which is required for production of conventional protein antibodies as well as artificial gel antibodies for selective capture of a biomarker, (iii) design a standard curve for rapid and accurate determination of the concentration of the biomarker in the body fluid because of adsorption of the biomarker onto vials, pipettes, etc., (iv) determine accurately the sample volume delivered by a pipette, (v) avoid polymerization of the biomarker upon storage and to decide whether it is in the form not only of monomers, but also of dimers, trimers, etc., in the native state, (vi) determine the degree of possible glycosylation and amidation of the biomarker and (vii) decide whether glycosylation and amidation positively or negatively affects the possibilit to use the protein as a biomarker. In this article, we discuss in quantitative terms the difficulties (iii,vii) and how to overcome them, which also may help to overcome the difficulty (ii), which in turn minimizes difficulty (i). [source]

    Development of a CE-MS method to analyze components of the potential biomarker vascular endothelial growth factor 165

    ELECTROPHORESIS, Issue 13 2009
    Angel Puerta
    Abstract The vascular endothelial growth factor 165 (VEGF165) is the predominant form of the complex VEGF-A family. Its angiogenic effect is involved in many physiological and pathological events. For this reason, its roles as a potential biomarker and as a therapeutic drug have been considered. Nevertheless, very little is known about the existence of different forms of VEGF165 arising from glycosylation and potentially from other PTMs. This aspect is important because different forms may differ in biological activity (therapeutic drug application) and the pattern of the different forms can vary with pathological changes (biomarker application). In this work a CE-MS method to separate up to seven peaks containing, at least, 19 isoforms of intact VEGF165 is described. Comparison between human VEGF165 expressed in a glycosylating system, i.e. insect cells, and in a non-glycosylating system, i.e. E. coli cells, has been carried out. The method developed provides structural information (mass fingerprint) about the different forms of VEGF165 and after the deconvolution and the analysis of the MS spectra, PTMs pattern of VEGF165 including glycosylation and loss of amino acids at the N- and C-terminus was identified. Glycans involved in PTMs promoting different glycoforms observed in the CE-MS fingerprint were confirmed by MALDI-MS after deglycosylation with peptide N-glycosidase F. This approach is a starting point to study the role of VEGF165 as a potential biomarker and to perform quality control of the drug during manufacturing. To our knowledge this is the first time that a CE-MS method for the analysis of VEGF165 has been developed. [source]

    The role of electrophoresis in disease biomarker discovery

    ELECTROPHORESIS, Issue 12 2007
    Haleem J. Issaq Dr.
    Abstract There has been increased activity in the last few years in the search for disease markers using fractionation of complex biological fluids combined with MS. While electrophoretic and chromatographic separations have played a major role in this endeavor, this manuscript is limited to a review of electrophoretic methods that have been established for disease biomarker discovery. These methods include 2-DE, difference gel electrophoresis (DIGE), and CE. We define what constitutes a biomarker, identify the steps required for establishing a biomarker, and describe the parameters needed in the design of an ideal diagnostic test. The application, advantages, and limitations of CE, DIGE, and 2-DE in meeting the goal of discovering novel biomarkers is discussed in detail, along with a few selected examples that illustrate the search for biomarkers for cancer and neurological diseases. [source]

    Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene

    Shyra J. Miller
    Abstract Understanding the biological pathways critical for common neurofibromatosis type 1 (NF1) peripheral nerve tumours is essential, as there is a lack of tumour biomarkers, prognostic factors and therapeutics. We used gene expression profiling to define transcriptional changes between primary normal Schwann cells (n,=,10), NF1-derived primary benign neurofibroma Schwann cells (NFSCs) (n,=,22), malignant peripheral nerve sheath tumour (MPNST) cell lines (n,=,13), benign neurofibromas (NF) (n,=,26) and MPNST (n,=,6). Dermal and plexiform NFs were indistinguishable. A prominent theme in the analysis was aberrant differentiation. NFs repressed gene programs normally active in Schwann cell precursors and immature Schwann cells. MPNST signatures strongly differed; genes up-regulated in sarcomas were significantly enriched for genes activated in neural crest cells. We validated the differential expression of 82 genes including the neural crest transcription factor SOX9 and SOX9 predicted targets. SOX9 immunoreactivity was robust in NF and MPSNT tissue sections and targeting SOX9 , strongly expressed in NF1-related tumours , caused MPNST cell death. SOX9 is a biomarker of NF and MPNST, and possibly a therapeutic target in NF1. [source]