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Results for “Biomarker variability”

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At least 163 records · Page 9Linked to original sources

PubMed1999

MN/CA9 gene expression as a potential biomarker in renal cell carcinoma.

OBJECTIVE: To compare the levels of MN/CA9 expression with clinicopathological variables in renal cell carcinoma (RCC), and thus evaluate MN/CA9 expression as a possible biomarker for RCC. MATERIALS AND METHODS: The level of expression of MN/CA9 was evaluated in 76 surgically obtained tissue samples (49 from RCC, 22 from normal kidney and five from oncocytoma) using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. In RCC, MN/CA9 expression was compared with stage, grade and cell type. RESULTS: MN/CA9 was expressed in 42 of 49 (86%) RCC samples, but in only two of 22 (9%) normal kidney and none of five oncocytoma samples. Levels of MN/CA9 expression were significantly higher in tumours consisting only of clear cells than in those containing other cell types (P=0.0189), and MN/CA9 was expressed in 34 of 37 (92%) RCC samples consisting only of clear cells. Tumours of low clinical stage showed a striking increase in MN/CA9 expression, and high MN/CA9 expression was associated with a good patient outcome. CONCLUSION: These results suggest that MN/CA9 expression is a potential diagnostic biomarker of RCC, especially the clear-cell type, and can be targeted using molecular biological techniques.

Adult↗

PubMed2003

Effects of ventilation on the collection of exhaled breath in humans.

A computerized system has been developed to monitor tidal volume, respiration rate, mouth pressure, and carbon dioxide during breath collection. This system was used to investigate variability in the production of breath biomarkers over an 8-h period. Hyperventilation occurred when breath was collected from spontaneously breathing study subjects (n = 8). Therefore, breath samples were collected from study subjects whose breathing were paced at a respiration rate of 10 breaths/min and whose tidal volumes were gauged according to body mass. In this "paced breathing" group (n = 16), end-tidal concentrations of isoprene and ethane correlated with end-tidal carbon dioxide levels [Spearman's rank correlation test (r(s)) = 0.64, P = 0.008 and r(s) = 0.50, P = 0.05, respectively]. Ethane also correlated with heart rate (r(s) = 0.52, P < 0.05). There was an inverse correlation between transcutaneous pulse oximetry and exhaled carbon monoxide (r(s) = -0.64, P = 0.008). Significant differences were identified between men (n = 8) and women (n = 8) in the concentrations of carbon monoxide (4 parts per million in men vs. 3 parts per million in women; P = 0.01) and volatile sulfur-containing compounds (134 parts per billion in men vs. 95 parts per billion in women; P = 0.016). There was a peak in ethanol concentration directly after food consumption and a significant decrease in ethanol concentration 2 h later (P = 0.01; n = 16). Sulfur-containing molecules increased linearly throughout the study period (beta = 7.4, P < 0.003). Ventilation patterns strongly influence quantification of volatile analytes in exhaled breath and thus, accordingly, the breathing pattern should be controlled to ensure representative analyses.

Adult↗

PubMed1999

The role of metals in autoimmunity and the link to neuroendocrinology.

Current available literature indicates a risk for metal-induced autoimmunity in man. Metal pathology may be due to toxic or allergic mechanisms where both may play a role. The main factors decisive for disease induced by metals are exposure and genetics which determine the individual detoxifying capacity and sensitivity to metals. This paper reviews the possible mechanisms which may play a role in metal-induced autoimmunity with the emphasis on multiple sclerosis (MS), rheumatoid arthritis (RA) and amyotrophic lateral sclerosis (ALS). We also discuss the role of inflammation-induced changes in the hypothalamus-pituitary-adrenal (HPA) axis as a possible explanation of fatigue, depression and other psychosomatic symptoms observed in these diseases. The increased knowledge about individual sensitivity based on genotype and phenotype variability together with the use of biomarkers for the diagnosis of this individual susceptibility seems to be the key in elucidation of the operating mechanisms. Since metal-induced sensitization may be induced by chronic low-dose exposure, the conventional toxicological approach comparing concentrations of metals in brain autopsies, organ biopsies and body fluids in patients and controls may not provide answers regarding the metal-pathology connection. To address this issue, longitudinal studies of metal-sensitive patients are preferable to the traditional case-control studies.

Journal Article↗

PubMed1999

Prognostic significance of angiogenesis and Ki-67, p53, and p21 expression: a population-based endometrial carcinoma study.

PURPOSE: For endometrial carcinoma patients, there is a need for improved identification of high-risk groups that may benefit from postoperative adjuvant therapy. We therefore studied the prognostic impact of markers for cell proliferation, cell-cycle regulation, and angiogenesis among endometrial carcinoma patients in a population-based setting. PATIENTS AND METHODS: All patients diagnosed with endometrial carcinoma between 1981 and 1985 in Hordaland County, Norway, were studied. The median follow-up for the survivors was 11.5 years (range, 8 to 15 years), with no patient lost because of insufficient follow-up information. Paraffin-embedded tumor tissue, available in 96% of the cases (n = 142), was studied immunohistochemically for microvessel density (MVD) and expression of Ki-67, p53, and p21 proteins. We used the hot spot method for calculation of MVD, and expression of Ki-67 and p21 protein, because this approach may increase the probability of detecting small aggressive clones of possible prognostic relevance. The importance of these tumor markers was investigated in univariate survival analyses and Cox regression analysis. RESULTS: The majority of traditional clinicopathologic variables was significantly associated with the tumor biomarkers. Age, International Federation of Gynecology and Obstetrics (FIGO) stage, histologic type, histologic grade, MVD, as well as Ki-67, p53, and p21 protein expression, all significantly influenced survival in univariate analyses (P < or = .05). In the Cox regression analysis, age, FIGO stage, MVD, Ki-67 expression, and p53 expression were the only variables with independent prognostic impact (P < or = .05), whereas histologic type, histologic grade, and p21 expression had no independent influence. A group of high-risk patients with more than one unfavorable marker was identified. CONCLUSION: In addition to age and FIGO stage, MVD, Ki-67, and p53 protein expression showed an independent prognostic impact. Thus, information derived from routine histologic specimens identified a subgroup of high-risk endometrial carcinoma patients in this population-based study.

Aged↗

PubMed1989

Improving the precision of biological age determinations. Part 2: Automatic human tests, age norms and variability.

In order to eliminate variability due to test operators, procedures for measuring 12 physiological functions that are candidate biomarkers of aging have been automated. Data was collected from a norm group of 2462 male and female office workers using an instrument which requires no test operators, administers all 12 tests in about 45 min. per subject, computes biological age, prints out results, and stores data on floppy disks for transfer to other computers for analysis. This report a) describes the instrumentation and test procedures, b) presents normal age/sex standards for each of the 12 biomarkers, c) reports the variance of the data for each biomarker by sex, d) lists sources of biomarker variance, e) discusses criteria for biomarker selection and f) examines implications for information loss when biomarker data is combined to calculate biological age. After eliminating chronological age as a variable, the standard deviations of the frequency distributions of predicted age for individual biomarkers were found to vary from .226 to 1.075, a range of more than 4 to 1. Procedures are discussed for improving the ratio of useful-to-useless variance in calculating biological age.

Accommodation, Ocular↗

PubMed2025

Methylation-based droplet digital polymerase chain reaction shows high concordance with chronic lymphocytic leukemia IGHV somatic mutation status.

OBJECTIVE: Somatic hypermutation at immunoglobulin heavy chain variable (IGHV) genes, an established prognostic and predictive biomarker for chronic lymphocytic leukemia (CLL), is assessed by gene sequencing. We developed a single methylation-specific droplet digital polymerase chain reaction (methyl-ddPCR) to predict IGHV status in patients with CLL. METHODS: The CLL methylation array and IGHV data from the International Cancer Genome Consortium (ICGC) were used for biomarker discovery. Top-ranked candidate regions were manually screened for PCR primer and probe binding sites. A single methyl-ddPCR was evaluated on an internal cohort of CLLs with mutated (M), unmutated (U), and inconclusive IGHV results originally determined by next-generation sequencing (NGS). RESULTS: Analysis of ICGC data identified array probe cg23844018 as a candidate for the PCR. The corresponding CpG site showed high methylation levels in U-CLL and lower levels in M-CLL. On the internal cohort, a single optimal cutoff correctly classified 104 of 115 U- and M-CLLs (90.4%; area under the curve = 0.96). The PCR data correlated with some prognostic fluorescence in situ hybridization and CLL subset groupings. Limited analysis suggests that the PCR may be able to stratify some patients with CLL who have inconclusive results on IGHV NGS testing. CONCLUSIONS: The methyl-ddPCR showed high concordance with CLL IGHV status in an internal cohort.

Humans↗

PubMed2003

Greater dietary variety is associated with better biochemical nutritional status in Spanish children: the Four Provinces Study.

BACKGROUND AND AIM: Although dietary variety has been associated with a better nutritional profile, its possible role in obesity raises doubts about its overall health benefits. In this study, we examined the association between dietary variety and anthropometric variables, food intake and various food intake biomarkers in Spanish children. METHODS AND RESULTS: This was a cross-sectional study of 1112 children aged 6-7 years from Cadiz, Murcia, Orense and Madrid, who were selected by means of the random cluster-sampling of schools. Information concerning food and nutrient intake was obtained using a food frequency questionnaire, and a dietary variety index (DVI) was calculated on the basis of the number of different foods consumed more than once a month. The anthropometric variables (weight and height), and plasma lipid and vitamin levels were determined using standardised methods. Our results show that the body mass index (BMI) did not vary substantially as a function of DVI: it was 16.9 in the lowest DVI tertile and 17.2 in the highest (p=0.20). Unlike BMI, the DVI positively correlated (p<0.05) with the plasma levels of alpha and beta-carotene, lycopene, retinol, alpha-tocopherol and vitamin E, with energy intake, and with most of the foods, particularly vegetables, fruit and sausages (respective correlation coefficients of 0.43, 0.26 and 0.23). CONCLUSIONS: Dietary variety is associated with a better food and nutritional profile in Spanish children. Nevertheless, the presence of a positive association between the DVI and energy intake, and the consumption of sausages and pre-cooked products calls for the recommendation of a varied diet of healthy foods, such as cereals (especially whole grains), fruits and vegetables.

Biomarkers↗

PubMed2003

Dietary patterns associated with risk factors for cardiovascular disease in healthy US adults.

BACKGROUND: Certain nutrients are well established as dietary risk factors for cardiovascular disease (CVD), but dietary patterns may be a better predictor of CVD risk. OBJECTIVE: This study tested the hypothesis that the complex dietary behaviors of US adults can be grouped into major dietary patterns that are related to risk factors for CVD. DESIGN: With the use of food-frequency questionnaire data from the third National Health and Nutrition Examination Survey, dietary patterns of healthy US adults (>/or =20 y old; n = 13 130) were identified by factor analysis. Log-transformed biomarker data were associated with major dietary patterns after control for confounding variables in regression analyses. All statistical analyses accounted for the survey design and sample weights. RESULTS: Of 6 dietary patterns identified, 2 patterns emerged as the most predominant: the Western pattern was characterized by high intakes of processed meats, eggs, red meats, and high-fat dairy products, and the American-healthy pattern was characterized by high intakes of green, leafy vegetables; salad dressings; tomatoes; other vegetables (eg, peppers, green beans, corn, and peas); cruciferous vegetables; and tea. The Western pattern was associated (P < 0.05) positively with serum C-peptide, serum insulin, and glycated hemoglobin and inversely with red blood cell folate concentrations after adjustment for confounding variables. The American-healthy pattern had no linear relation with any of the biomarkers examined. CONCLUSIONS: The identification of common dietary patterns among free-living persons is promising for characterizing high-risk groups at the US population level. The dietary patterns identified here are similar to those reported in other nonrepresentative samples and are associated with biomarkers of CVD risk, which confirms that dietary pattern analysis can be a valuable method for assessing dietary intakes when predicting CVD risk.

Adult↗

PubMed2005

Design issues and outcomes in IBD clinical trials.

Successful clinical trials in inflammatory bowel disease are based on precise definitions of study populations, standardized and well-defined interventions, reliable indices of disease activity, and clearly stipulated outcome measures. Interpretation of research results is often complicated by the differentiation of goals of therapy (remission induction and maintenance, quality of life) and the multitude of patient subsets. Choosing the correct patient subtype to enroll in a clinical trial is critical to the results of a study, its conclusions, and its applicability to the clinical setting. Validated, easy-to-use disease activity indices allow interpretation of results across trials. The use of biomarkers as surrogate clinical endpoints provides reproducibility, ease of statistical handling as a continuous variable, and consistent measurement of response to treatment. Despite these potential advantages, biomarkers of disease activity lack specificity and will need to be validated against clinically meaningful outcomes. Careful subject selection, standardization of disease activity indices, and precise outcome measurement are the keys to continued improvement of the inflammatory bowel disease research process.

Biomarkers↗

PubMed1994

Application of reliability models to studies of biomarker validation.

We present a model of biomarker validation developed in our laboratory, the results of the validation study, and the impact of the estimation of the variance components on the design of future molecular epidemiologic studies. Four different biomarkers of exposure are illustrated: DNA-protein cross-link (DNA-PC), DNA-amino acid cross link (DNA-AA), metallothionein gene expression (MT), and autoantibodies to oxidized DNA bases (DNAox). The general scheme for the validation experiments involves n subjects measured on k occasions, with j replicate samples analyzed on each occasion. Multiple subjects, occasions, and replicates provide information on intersubject, intrasubject, and analytical measurement variability, respectively. The analysis of variance showed a significant effect of batch variability for DNA-PC and MT gene expression, whereas DNAox showed a significant between-subject variability. Among the amino acids tested, cysteine and methionine showed a significant contribution of both batch and between-subject variability, threonine showed between-subject variability only, and tyrosine showed between-batch and between-subject variability. The total variance estimated through the experiment was used to calculate the minimum sample size required for a future epidemiologic study including the same biomarkers used for the reliability study. Such validation studies can detect the various components of variability of a biomarker and indicate needed improvements of the assay, along with possible use in field studies.

Amino Acids↗

PubMed1998

Uncertainty analysis methods for comparing predictive models and biomarkers: A case study of dietary methyl mercury exposure.

Biologically based markers (biomarkers) are currently used to provide information on exposure, health effects, and individual susceptibility to chemical and radiological wastes. However, the development and validation of biomarkers are expensive and time consuming. To determine whether biomarker development and use offer potential improvements to risk models based on predictive relationships or assumed values, we explore the use of uncertainty analysis applied to exposure models for dietary methyl mercury intake. We compare exposure estimates based on self-reported fish intake and measured fish mercury concentrations with biomarker-based exposure estimates (i.e., hair or blood mercury concentrations) using a published data set covering 1 month of exposure. Such a comparison of exposure model predictions allowed estimation of bias and random error associated with each exposure model. From these analyses, both bias and random error were found to be important components of uncertainty regarding biomarker-based exposure estimates, while the diary-based exposure estimate was susceptible to bias. Application of the proposed methods to a simple case study demonstrates their utility in estimating the contribution of population variability and measurement error in specific applications of biomarkers to environmental exposure and risk assessment. Such analyses can guide risk analysts and managers in the appropriate validation, use, and interpretation of exposure biomarker information.

Animals↗

PubMed2002

Non-linear hierarchical models for monitoring compliance.

As biomarkers transformable by specific drug agents increasingly become available, so their usefulness also increases for monitoring compliance in clinical and prevention trials, and for subsequent monitoring in the general population if a treatment is found successful. Marker levels measured over the course of a treatment yield a longitudinal trajectory that is typically non-linear, with varying velocities during the phase-in and steady-state periods of treatment, followed by decays back to normal in the presence of non-compliance. There is often considerable between-individual variability both in the mean parameters of the trajectory and the variability over time. An example is the biomarker mean corpuscular volume (MCV), which increases by 20 per cent from the drug zidovudine (AZT), and has been used to monitor compliance to AZT. Using MCV data from a previous AIDS clinical trial as an example, we describe a non-linear hierarchical growth model suitable for biomarkers that exhibit sigmoidal and/or asymptotic growth behaviour and show how such models can be supplemented with a change-point to identify potential times of non-compliance. We perform a fully Bayesian analysis to obtain a variety of posterior summaries for the behaviour of the longitudinal trajectory and the times of non-compliance, and describe how to obtain predictions of non-compliance for new individuals.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Serum levels of ochratoxin A in healthy adults in Tuscany: correlation with individual characteristics and between repeat measurements.

Ochratoxin A (OTA), a mycotoxin widely contaminating staple foods and beverages, has been classified as a "possible human carcinogen (Group 2B)" by the IARC. Serum levels of OTA were measured in a group of 138 healthy adults (age, 35-65 years) living in the area surrounding Florence (Tuscany, central Italy) and detected in all but four samples (97%). After the exclusion of one subject with a peak value of 57.2 ng/ml, OTA levels ranged between 0.12 and 2.84 ng/ml, with mean and median values of 0.56 and 0.48 ng/ml, respectively. OTA levels were significantly higher in men than in women (0.64 versus 0.50) and correlated positively with height. A strong association was found with the season in which blood samples were obtained, with summer values higher than autumn values. On the other hand, OTA levels tended to be negatively associated with blood pressure, either systolic or diastolic; no association was evident with age, weight, body mass index, and smoking history. The associations with height and season persisted in a multivariate regression analysis. A subgroup of subjects provided a repeat blood sample approximately 1 year later. The Spearman correlation coefficient between 68 pairs of original and repeat measurements was practically null (r = 0.05). Only two subjects (2.9%) had OTA levels of >1 ng/ml on both occasions. These results suggest that OTA contamination is widespread in foods consumed by this population, in agreement with previous reports from Italy and other countries. A strong seasonal variation, which possibly differs from year to year, was observed. OTA serum levels are a short-term biomarker with a high within-subject variability; therefore they have limited use at the individual level but can be used to characterize populations or subgroups of subjects. Additional analyses are needed to explore the dietary determinants of OTA levels in this population.

Adult↗

PubMed2005

Molecular biomarkers and adaptation to environmental stress in moon jelly (Aurelia spp.).

We describe a strategy that identifies molecular biomarkers and links the study of abiotic stress to evolutionary history. By utilizing the moon jellyfish Aurelia spp. as a model, we identified genes differentially regulated in response to the chemical stressor tributyltin by means of complementary DNA subtraction analyses. Expression of 3 out of 25 identified candidate genes, one oxidative stress gene, one heat shock (hsp70) gene, and one GTP-binding gene, was quantified under laboratory conditions and in field tests using semiquantitative reverse transcriptase polymerase chain reaction. Differential expression patterns were found following exposure to tributyltin and temperature treatments. The findings suggest that the identified genes are involved in response to chemical as well as heat- induced stress and may serve as biomarkers for monitoring marine habitats. Gene regulatory patterns combined with phylogenetic inferences of the hsp70 gene support a possible role of ecologically driven divergence within the genus Aurelia. We show that added information on genetic variability can raise the predictive power of molecular biomarkers in studies of individual stress response.

Adaptation, Biological↗

PubMed2001

Hematologic and blood biochemical variables of captive chimpanzees: cross-sectional and longitudinal analyses.

Hematologic and blood biochemical variables are of great importance in medical and veterinary practice. In addition, these analytes may have significance as potential biomarkers of aging. Previous reports on normative values of these variables in the chimpanzees are based on cross-sectional studies that did not include individuals of advanced age. To address this omission, we performed cross-sectional and longitudinal analyses of hematologic and blood biochemical data collected from chimpanzees over a 9-year period. One-hundred forty-six females and 106 males of ages representing the entire life span of the species were studied. We derived normative cross-sectional values of 14 commonly measured hematologic and 20 blood biochemical variables, which should provide a useful reference for clinical blood studies in chimpanzees. In addition, we found in a cross-sectional regression analysis of our data that most analytes varied significantly between males and females, and that they varied markedly with age. Most variables had year-to-year consistency within the same individuals, as indicated by statistically significant intra-year correlation coefficients. Finally, we performed a longitudinal analysis of the analytes in chimpanzees by calculating the slopes and intercepts of the best-fitting trend line for each individual. The resulting slopes were analyzed by sex and by decade of age of subjects to determine whether trends were consistent. Consistent trends detected in the longitudinal analysis were usually restricted to the first decade of life, and thus represented maturational processes. The overall lack of within-animal trends covering all or most of the period from early adulthood through old age in this 9-year study suggests that a longer period of follow-up than used here may be required to document senescence-related changes.

Aging↗

PubMed2005

An approach to estimate between- and within-group correlation coefficients in multicenter studies: plasma carotenoids as biomarkers of intake of fruits and vegetables.

In a multicenter study, the overall correlation between two variables can be broken down into a within- and a between-group correlation reflecting associations at the individual and aggregate levels, respectively. A random-effects model is used to estimate variance components of nutrition-related variables and the within- and between-group correlation coefficients. Using data from the European Prospective Investigation into Cancer and Nutrition (EPIC), the authors analyzed the association between levels of three plasma carotenoids (alpha-carotene, beta-cryptoxanthin, and lycopene) and dietary intake of three items (total fruits, carrots, and tomatoes), assessed through dietary questionnaire and single 24-hour dietary recall measurements, in a cross-sectional study involving 3,089 subjects from nine European countries. Intraclass correlation coefficients were 0.178 for alpha-carotene, 0.216 for beta-cryptoxanthin, and 0.299 for lycopene. The between-group correlation coefficients were higher than the within-group coefficients for all three carotenoids. For beta-cryptoxanthin and fruit intake, the between-group versus the within-group correlations were 0.78 and 0.26 for the dietary questionnaire and 0.85 and 0.19 for the 24-hour dietary recall. Results indicate that variability of exposure is driven mainly by the individual compared with the aggregate variation and that biomarker levels perform fairly accurately in discriminating population-level consumption of fruits and vegetables.

Adult↗

PubMed2000

Detection of the dipicolinic acid biomarker in Bacillus spores using Curie-point pyrolysis mass spectrometry and Fourier transform infrared spectroscopy.

Thirty-six strains of aerobic endospore-forming bacteria confirmed by polyphasic taxonomic methods to belong to Bacillus amyloliquefaciens, Bacillus cereus, Bacillus licheniformis, Bacillus megaterium, Bacillus subtilis (including Bacillus niger and Bacillus globigii), Bacillus sphaericus, and Brevi laterosporus were grown axenically on nutrient agar, and vegetative and sporulated biomasses were analyzed by Curie-point pyrolysis mass spectrometry (PyMS) and diffuse reflectance-absorbance Fourier-transform infrared spectroscopy (FT-IR). Chemometric methods based on rule induction and genetic programming were used to determine the physiological state (vegetative cells or spores) correctly, and these methods produced mathematical rules which could be simply interpreted in biochemical terms. For PyMS it was found that m/z 105 was characteristic and is a pyridine ketonium ion (C6H3ON+) obtained from the pyrolysis of dipicolinic acid (pyridine-2,6-dicarboxylic acid; DPA), a substance found in spores but not in vegetative cells; this was confirmed using pyrolysis-gas chromatography/mass spectrometry. In addition, a pyridine ring vibration at 1447-1439 cm-1 from DPA was found to be highly characteristic of spores in FT-IR analysis. Thus, although the original data sets recorded hundreds of spectral variables from whole cells simultaneously, a simple biomarker can be used for the rapid and unequivocal detection of spores of these organisms.

Bacillus↗

PubMed1998

Use of urine biomarkers to evaluate menstrual function in healthy premenopausal women.

A total of 403 healthy, premenopausal women, residing near Santa Clara, California, were recruited from a large health care plan in California for a study of menstrual function. After a telephone interview, participants collected daily urine samples and recorded bleeding and other information in diaries. Data were collected during 1990-1991. Urine samples were analyzed for creatinine and for estradiol and progesterone metabolites by enzyme-linked immunoassay. Computer algorithms were developed to derive menstrual segment length, ovulatory status, day of ovulation, and other parameters from the urine and diary data. (We use "segment" rather than "cycle" to avoid implying that normal cycling occurred.) The average length of participation was 141 (standard deviation, 45) days. The mean segment length was 28.8 (standard deviation, 4.4) days; follicular phase length, 16.0 (standard deviation, 4.4) days; and luteal phase length, 12.9 (standard deviation, 1.7) days; 19 (4.7%) women experienced anovulatory episodes. In exploratory multivariate analyses, important associations included the following: age of > or = 35 years with decreased segment and follicular phase lengths; heavier weight (upper quartile) with anovulation and increased follicular phase and decreased luteal phase lengths; Hispanic ethnicity with anovulation and increased segment length; and past difficulty in achieving pregnancy with anovulation and increased length and variability of segments and follicular phases. Urine biomarkers can be used successfully to evaluate menstrual function in epidemiologic studies.

Adult↗