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Results for “Biomarker testing”

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PubMed1998

A strategy for identifying biomarkers of aging: further evaluation of hematology and blood chemistry data from a calorie restriction study in rhesus monkeys.

We examined a dataset derived from a battery of hematology and blood chemistry tests to identify candidate biomarkers of aging in a sample of 33 male rhesus monkeys (Macaca mulatta) ranging in age from 4-27 years. About half this sample comprised an experimental group subjected to 30% calorie restriction for six to seven years compared to the control group fed the same nutritionally fortified diet to approximate ad lib levels. Variables that met the following criteria were selected: (1) longitudinal change within the cohorts of control monkeys; (2) cross-sectional correlation with age across the adult lifespan in the control group; (3) stability of individual differences within all groups; and (4) no obvious redundancy with other selected variables. Five variables emerged from this step-wise selection, including the percentage lymphocytes, and serum levels of alkaline phosphatase, albumin, creatinine, and calcium. These variables were then submitted to a principal component analysis, which yielded a single component accounting for about 58% of the total variance. Based on this marked degree of covariance, these candidate biomarkers of aging could be combined into a biological age score (BAS) for the control and experimental groups. When chronological age was regressed onto BAS, the slopes of the control and experimental groups could be compared. Although a trend toward a slower aging rate in calorie-restricted monkeys was apparent, this analysis did not detect a statistically significant difference in the rate of aging between these groups estimated by this index. Despite this result, a logical strategy was confirmed for expanding the search for candidate biomarkers of aging to apply to this and to other studies assessing interventions that purport to affect the rate of aging in long-lived species.

Aging↗
PubMed2000

Surrogate tests.

Explore the source record for details and available documents.

Biomarkers↗
PubMed2001

Biomarkers of polycyclic aromatic hydrocarbon-DNA damage and cigarette smoke exposures in paired maternal and newborn blood samples as a measure of differential susceptibility.

Human and experimental evidence indicates that the developing fetus may be more susceptible than the adult to the effects of certain carcinogens, including some polycyclic aromatic hydrocarbons (PAHs). Factors that can modulate susceptibility include proliferation rates, detoxification capabilities, and DNA repair capacity. Biomarkers can facilitate quantification of age-related susceptibility among human populations. In this study, we report on three biomarkers measured in paired blood samples collected at birth from 160 Polish mothers and newborns: 70 pairs from Krakow (a city with high air pollution including PAHs) and 90 pairs from Limanowa (an area with lower ambient pollution but greater indoor coal use). Biomarkers were: WBC aromatic-DNA adducts by (32)P-postlabeling and PAH-DNA adducts by ELISA (as indicators of DNA damage from PAHs and other aromatics) and plasma cotinine (as an internal dosimeter of cigarette smoke). Correlations were assessed by Spearman's rank test, and differences in biomarker levels were assessed by the Wilcoxon signed-ranks test. A significant correlation between paired newborn/maternal samples was seen for aromatic-DNA adduct levels (r = 0.3; P < 0.001) and plasma cotinine (r = 0.8; P < 0.001) but not PAH-DNA adduct levels (r = 0.14; P = 0.13). Among the total cohort, levels of the three biomarkers were higher in newborn samples compared with paired maternal samples. The difference was significant for aromatic-DNA adduct levels (16.6 +/- 12.5 versus 14.21 +/- 15.4/10(8) nucleotides; P = 0.002) and plasma cotinine (14.2 +/- 35.5 versus 8.3 +/- 24.5 ng/ml; P < 0.001) but not for PAH-DNA adduct levels (7.9 +/- 9.9 versus 5.9 +/- 8.2/10(8) nucleotides; P = 0.13). When analyses were restricted to the 80 mother/newborn pairs from whom the blood sample was drawn concurrently (within 1 h of each other), levels of all of the three biomarkers were significantly higher in the newborn compared with paired maternal blood samples (P < 0.05). Results suggest reduced detoxification capabilities and increased susceptibility of the fetus to DNA damage, especially in light of experimental evidence that transplacental exposures to PAHs are 10-fold lower than paired maternal exposures. The results have implications for risk assessment, which currently does not adequately account for sensitive subsets of the population.

Adult↗
PubMed2003

Micronucleus test in freshwater fish species: an evaluation of its sensitivity for application in field surveys.

Brown trout, Salmo trutta, European eel, Anguilla anguilla, and European minnow, Phoxinus phoxinus, three fish species inhabiting European freshwater ecosystems, were evaluated for their use as in situ pollution biomarkers using the micronucleus test in renal erythrocytes. Experimental exposure (by immersion) to different concentrations of cyclophosphamide, colchicine, and cadmium showed that brown trout are more sensitive to the three compounds than minnows and eels. In situ surveys of wild freshwater ecosystems with different levels of pollution showed that minnows and eels living in polluted sites do not present higher micronuclei averages than those caught in clean rivers systems, whereas micronuclei are induced in brown trout inhabiting polluted sites. Our results demonstrated the suitability of brown trout for in situ biomonitoring of freshwater ecosystems as well as for laboratory tests using the micronucleus test.

Anguilla↗
PubMed2003

Prospective evaluation of fecal calprotectin as a screening biomarker for colorectal neoplasia.

OBJECTIVES: Stool testing is a well established method of screening for colorectal neoplasia. Emerging data suggest that novel biomarkers may offer performance advantages over fecal occult blood. In this large, prospective study, we assessed fecal calprotectin (a leukocyte-derived protein) as a screening biomarker for colorectal neoplasia. Fecal calprotectin was directly compared to fecal hemoglobin (Hb) and colonoscopy as the existing criterion standards for stool screening and structural evaluation, respectively. METHODS: Subjects included colonoscopy patients with a personal history of colorectal neoplasia, family history of colorectal cancer, or iron deficiency anemia. Stool specimens were collected before purgation, processed appropriately, and quantitatively analyzed for calprotectin (Nycomed Pharma, Oslo, Norway) and for Hb (Mayo Medical Laboratories, Rochester, MN) by masked technicians. Colonoscopies were performed by experienced endoscopists without prior knowledge of the fecal assay results. RESULTS: Among 412 subjects, 97 (24%) subjects had one or more colorectal neoplasms (including three with adenocarcinomas). Fecal calprotectin levels did not differ significantly between subjects with versus subjects without colorectal neoplasms (p = 0.33). Neither tumor number (p = 0.85) nor tumor size (p = 0.86) significantly influenced the observed fecal calprotectin concentrations. Estimates of the sensitivity, specificity, and positive and negative predictive values of fecal calprotectin for any colorectal neoplasms were 37%, 63%, 23%, and 76%, respectively. Comparable performance estimates for fecal Hb were 3%, 97%, 27%, and 77%, respectively. CONCLUSIONS: In this cohort of colonoscopy patients at above average risk, fecal calprotectin was a poor screening biomarker for colorectal neoplasia. Further investigation of tumor-derived, rather than blood-based, biomarkers may be a more rewarding approach to stool screening for colorectal neoplasia.

Aged↗
PubMedDate not supplied

[Clinical significance of 5'-nucleotidase].

The paper deals with the current data of molecular organization, localization, activity and clinical significance of 5'-nucleotidase in the diagnosis of different illnesses. The paper also deals with the specificity and sensitivity of 5'-nucleotidase comparing to other laboratory tests.

5'-Nucleotidase↗
PubMed2004

[Biomarkers as prognostic factors in pulmonary arterial hypertension. Rationale and study design].

CURRENT SITUATION: Pulmonary arterial hypertension (PAH) is a serious disease. Its prognostic is based on the functional status quantified by the NYHA class and the 6-min walking test, and the hemodynamic data. The algorithms of treatment are solely based on the hemodynamic data and the functional status. The main objective is to test whether basal concentrations of isoprostanes, Big endotheline 1, ADMA, high sensitivity CRP, NT-Pro-BNP and cardiac troponin T are a 3-year prognostic factor in PAH using a combined criterion: death from any cause and pulmonary or cardiopulmonary transplantation. MATERIALS AND METHODS: This is a multicenter, prospective, prognostic, single blinded study (plasma and urinary samples being blinded). The study started in november 2003, running for 2 years, with a 3 year follow-up for each patient. The main inclusion criterion is PAH. The data analysis will use a multivariable Cox model, taking into account the functional and hemodynamic parameters. EXPECTED RESULTS: This study will determine whether any of the biomarkers tested provides additional prognostic information in PAH in addition to the functional and hemodynamic parameters.

Biomarkers↗
PubMed2005

Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons. We tested the hypothesis that proteomic analysis will identify protein biomarkers that provide insight into disease pathogenesis and are diagnostically useful. To identify ALS specific biomarkers, we compared the proteomic profile of cerebrospinal fluid (CSF) from ALS and control subjects using surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS). We identified 30 mass ion peaks with statistically significant (p < 0.01) differences between control and ALS subjects. Initial analysis with a rule-learning algorithm yielded biomarker panels with diagnostic predictive value as subsequently assessed using an independent set of coded test subjects. Three biomarkers were identified that are either decreased (transthyretin, cystatin C) or increased (carboxy-terminal fragment of neuroendocrine protein 7B2) in ALS CSF. We validated the SELDI-TOF-MS results for transthyretin and cystatin C by immunoblot and immunohistochemistry using commercially available antibodies. These findings identify a panel of CSF protein biomarkers for ALS.

Adult↗
PubMed1996

The lipid membrane hypothesis of schizophrenia: implications for possible clinical breath tests.

The diagnosis of disease on the basis of an altered profile of breath volatiles is a new area of clinical biochemistry. The membrane hypothesis of schizophrenia leads to a number of predictions about possible volatile biochemical markers for this condition. These molecules would arise from autoxidation of arachidonic acid and possibly other unsaturated fatty acids. Preliminary experimental studies in this area are reviewed. The results are encouraging and developments in analytical methodology, especially mass spectrometry and electronic nose technology, hold promise for an objective test for monitoring the progress of the disease and possibly for diagnosis.

Biomarkers↗
PubMed2005

Exploratory Bayesian model selection for serial genetics data.

Characterizing the process by which molecular and cellular level changes occur over time will have broad implications for clinical decision making and help further our knowledge of disease etiology across many complex diseases. However, this presents an analytic challenge due to the large number of potentially relevant biomarkers and the complex, uncharacterized relationships among them. We propose an exploratory Bayesian model selection procedure that searches for model simplicity through independence testing of multiple discrete biomarkers measured over time. Bayes factor calculations are used to identify and compare models that are best supported by the data. For large model spaces, i.e., a large number of multi-leveled biomarkers, we propose a Markov chain Monte Carlo (MCMC) stochastic search algorithm for finding promising models. We apply our procedure to explore the extent to which HIV-1 genetic changes occur independently over time.

Algorithms↗
PubMed2006

Myeloperoxidase and C-reactive protein augment the specificity of B-type natriuretic peptide in community screening for systolic heart failure.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (N-BNP) is elevated in left ventricular systolic dysfunction (LVSD) and may be cost-effective for screening in the community but is relatively nonspecific. We sought to improve specificity using inflammatory markers such as C-reactive protein (CRP) and myeloperoxidase (MPO), which have been implicated in cardiovascular disease. METHODS: A total of 1360 subjects (45-80 years) were invited in this prospective screening study for undiagnosed LVSD (defined as wall motion score >1.8 [ejection fraction < or = 40%]), and 1331 had analyzable echocardiographic scans and plasma specimens. Peptides were measured using immunoluminometric assays. RESULTS: Twenty-eight patients with LVSD had elevated plasma N-BNP, CRP, and MPO levels compared with healthy subjects (P < .0005). Receiver operating characteristic curve areas for N-BNP, CRP, and MPO were 0.839, 0.824, and 0.909, respectively. All tests had high negative predictive values (>99%). Specificity was maximized to 88.4% in a logistic model with all 3 markers (all independent predictors, accounting for 44.8% of the variance). This reduced the number of cases to scan to detect 1 case of LVSD from 29.7 (using N-BNP alone) to 6.6. Using plasma MPO (at 33.9 ng/mL) or urinary N-BNP (at 10.7 fmol/mL) as initial screening tests, combinations of plasma N-BNP, MPO, and CRP can achieve specificities up to a maximum of 94.3%. Costs were minimized by using urinary N-BNP as the initial screening test, followed by plasma biomarkers. CONCLUSIONS: Plasma CRP and MPO increased the specificity of N-BNP in LVSD screening. Screening is optimized by urinary N-BNP as an initial test, followed by plasma CRP, N-BNP, and MPO.

Aged↗
PubMed2006

Monitoring the mycotoxins in food and their biomarkers in the Czech Republic.

Testing of the presence of toxigenic microfungi and mycotoxins in foodstuffs in the food chain is an important part of the food safety strategy in The Czech Republic. At the national level, control of their presence in the entire food chain is assured by Public Health Protection Agencies, by the Veterinary Administration and by the Czech Agriculture and Food Inspection Authority. This article summarizes surveillance activities of Public Health Protection Agencies and mycotoxins findings in dietary raw materials and foodstuffs from the 1990s to 2004 in the Czech Republic. At present, the health risk from the mycotoxins exposure from foodstuffs is assessed to be relatively low in the Czech Republic, especially as far as the foodstuffs of the Czech origin are concerned. It may result in late toxic effects (e. g., carcinogenic risk) following a single or repeated ingestion of low mycotoxins doses from foodstuffs. Nevertheless, the overall situation may change due to the globalization of the food market. In order to minimize the risk associated with mycotoxins and eliminate their impact on Czech public health, continuous monitoring of the presence of toxigenic moulds, mycotoxins, and their biomarkers is necessary, in conjunction with strict respect to European Union legislation.

Aflatoxin B1↗
PubMed2006

A simple method to combine multiple molecular biomarkers for dichotomous diagnostic classification.

BACKGROUND: In spite of the recognized diagnostic potential of biomarkers, the quest for squelching noise and wringing in information from a given set of biomarkers continues. Here, we suggest a statistical algorithm that--assuming each molecular biomarker to be a diagnostic test--enriches the diagnostic performance of an optimized set of independent biomarkers employing established statistical techniques. We validated the proposed algorithm using several simulation datasets in addition to four publicly available real datasets that compared i) subjects having cancer with those without; ii) subjects with two different cancers; iii) subjects with two different types of one cancer; and iv) subjects with same cancer resulting in differential time to metastasis. RESULTS: Our algorithm comprises of three steps: estimating the area under the receiver operating characteristic curve for each biomarker, identifying a subset of biomarkers using linear regression and combining the chosen biomarkers using linear discriminant function analysis. Combining these established statistical methods that are available in most statistical packages, we observed that the diagnostic accuracy of our approach was 100%, 99.94%, 96.67% and 93.92% for the real datasets used in the study. These estimates were comparable to or better than the ones previously reported using alternative methods. In a synthetic dataset, we also observed that all the biomarkers chosen by our algorithm were indeed truly differentially expressed. CONCLUSION: The proposed algorithm can be used for accurate diagnosis in the setting of dichotomous classification of disease states.

Algorithms↗
PubMed2004

Critical analysis of soil invertebrate biomarkers: a field case study in Avonmouth, UK.

During the period 1996-1999 a joint field research programme (BIOPRINT-II) funded by the European Union was undertaken. The main objective of this project was the deployment of biochemical fingerprint techniques of soil invertebrate biomarkers for assessing the exposure and effect of toxicants on soil invertebrates in the field. The aim was to apply these techniques in the field focusing on a a chronically polluted field near a lead and zinc smelter in Avonmouth (UK). Therefore six sites were selected from which organisms were either sampled or transplanted to or from the laboratory. The project has provided a unique opportunity to apply a series of biological test methodologies in order to determine the hazard posed to soil sustainability and by inference soil biodiversity and function. This work has attempted to understand the linkage between effects measured at the molecular or cellular level and relate these to changes at higher levels of biological organisation. Here we evaluated the links between biomarkers and soil function parameters. The paper aims to summarize and explore the necessary caveats that must be understood before soil biomarker test systems may be used to strengthen the risk assessment process.

Animals↗
PubMedDate not supplied

Myocardial necrosis biomarkers after different cardiac surgical operations.

AIM: A high postoperative peak of cardiac Troponin I is associated to an increased risk of morbidity and mortality after cardiac operations. The aim of this study was to investigate the release of cardiac Troponin I in different cardiac surgical procedures. METHODS: This was a prospective, single-centre study performed at the IRCCS San Raffaele Hospital in Milan, Italy. The study group consisted of 194 consecutive patients undergoing cardiac surgery. For each of them creatinkinase MB and cardiac Troponin I were assayed preoperatively, at ICU arrival, 4 h and 18 h postoperatively. RESULTS: Different cardiac surgical procedures were characterized by different release of cardiac biomarkers (P<0.001, ANOVA test). Off-pump coronary artery bypass grafting (CABG) was associated to the smallest amount of myocardial injury while mitral valve replacement produced the largest amount of biomarkers release. Patients who suffered a postoperative cardiac event released more myocardial necrosis biomarkers than those with an uneventful course (P=0.01). CONCLUSION: We showed that each type of cardiac operation has a peculiar amount of myocardial necrosis biomarkers: mitral valve replacement in particular is associated to the highest release of cardiac biomarkers.

Aged↗