PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Biomarker variability”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,135 records · Page 63Linked to original sources
PubMed1998

Exfoliated oral cell messenger RNA: suitability for biomarker studies.

The efficacy of chemoprevention trials can be improved by the use of biomarkers of carcinogenesis that serve as surrogate end points. The aim of this study was to assess the perspectives of using mRNA isolated from oral exfoliated cells for biomarker research in chemoprevention of upper aerodigestive tract cancer. When using reverse transcription-PCR in combination with Southern blotting and hybridization, it was possible to detect transcripts from only five cells. With the quantitative RNase protection assay, we could only detect highly abundant transcripts. The integrity of the RNA was verified by Northern blotting, which showed a variable degree of degradation, depending on the gene studied. Interestingly, although specific transcripts were found to be intact to a certain extent, the rRNA appeared to be completely degraded, suggesting that a specific protein synthesis shut-off mechanism exists in terminally differentiated oral epithelial cells. Altogether, this differential RNA degradation makes accurate measurement of transcript levels of most genes, as determined in exfoliated oral cells, unreliable. Because this RNA degradation process is likely to start before the cells are shed from the tissue, the results of measurements of transcript levels in biopsies of oral tissue should be interpreted with caution.

Adult↗
PubMed2005

Analysis of clonal immunoglobulin heavy chain rearrangements in ocular lymphoma.

BACKGROUND: The morphologic diagnosis of primary and metastatic intraocular lymphoma (IOL) was made difficult by the paucicellular specimens with fragile populations of lymphocytes retrieved through pars plana vitrectomy (PPV). The analysis of immunoglobulin heavy chain (IgH) gene rearrangements (AIGHR) was used as an adjunct to cytopathology and flow cytometry in systemic lymphoma. In IOL, the sensitivity and specificity of AIGHR are unknown. METHODS: The authors reviewed the clinical records of patients who underwent PPV for suspicion of IOL at the Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary (Boston, MA) between 2000 and 2002. AIGHR was performed as a routine diagnostic test on cell lysates isolated from < 0.5 mL of vitreous fluid. The authors used seminested polymerase chain reaction (PCR) with consensus primers for the VDJ-region of the IgH gene. PCR products were analyzed by polyacrylamide gel electrophoresis. RESULTS: Thirty patients (37 specimens) with chronic vitritis and 17 patients (23 specimens) with IOL were included. The specificity of vitreous fluid cytopathology, flow cytometry, and AIGHR was 1.0, and the sensitivity values were 0.24, 0.36, and 0.64, respectively. AIGHR was negative in two patients for whom cytopathology or flow cytometry revealed the diagnosis of lymphoma. Clonal IGHR was found in four specimens classified as negative for lymphoma based on cytopathology and flow cytometry. CONCLUSIONS: AIGHR supplemented cytopathology and flow cytometry to increase the diagnostic yield in IOL.

Adolescent↗
PubMed2000

Whole-body metabolic rate appears to determine the rate of DNA oxidative damage and glycation involved in aging.

While aging has been found to be a multifactorial process, it seems logical that different aging parameters which reflect the deleterious effects of normal basal metabolism should be directly related. Three such putative aging parameters were therefore measured in adult male Fischer 344 rats on three different long-term diets which have been shown to yield different lifespans. It was found that the daily caloric intake per unit organ weight, a measure of whole-body metabolic rate, was directly proportional to: (1) the level of 8-hydroxydeoxyguanosine in skin dermal cells, used as a measure of the rate of DNA oxidative damage; (2) the proportion of hemoglobin that was glycated, used as a measure of the rate of glycation. This appears to be the first evidence suggesting that whole-body metabolic rate plays a role in determining both the rate of DNA oxidative damage and the rate of glycation involved in aging, because whole-body metabolic rate was the only one of these three variables manipulated in the study. The study also found that there were no significant between-group differences in brain, kidney and liver 8-hydroxydeoxyguanosine, suggesting that DNA oxidative damage in non-mitotic and slow-dividing cells is not a reliable linear biomarker of aging.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

Risk factors for progressive chronic kidney disease.

The occurrence of chronic kidney disease and subsequent rate of loss of renal function are highly variable among individuals with the same underlying cause of renal injury or degree of functional impairment. Individual variability of risk is typical of complex diseases and reflects the multifactorial nature of the biologic mechanisms that are involved in the underlying disease process. The utility of the risk factor concept in developing CKD prevention and control strategies includes identifying individuals at high risk for the occurrence and progression of CKD, defining at-risk populations, elucidating potential targets for intervention, and generating explanatory hypotheses for the variable risk of CKD noted in different populations. Future application of the risk factor concept in the prevention and control of CKD will entail developing multivariate prediction equations; using spatial and temporal, as well as personal, characteristics, to define at-risk populations; identifying biomarkers for complex risk factors like race; and translating this information into testable interventions. This should include active extension of our current understanding of health care, social, and economic risk factors at both the individual and the community level.

Adolescent↗
PubMed2003

Isolation and characterisation of vascular endothelial growth factor-165 specific scFv fragments by phage display.

Vascular endothelial growth factor (VEGF) is a multifunctional cytokine which plays a major role in angiogenesis. Alternative splicing causes the production of several different isoforms (VEGF-A 121, 145, 165, 189, 206). VEGF is essential for tumor angiogenesis and several studies have correlated elevated VEGF levels with tumor stage, metastases and progression. Antibody phage display was employed to isolate two scFv antibody fragments, D8 and F10, with specificity for the VEGF165 isoform. It was shown by ELISA and competitive immunohistochemistry that each clone bound to VEGF165 but not VEGF121. Immunohistochemistry with D8 and F10 on colorectal carcinoma and adenoma sections revealed positive staining similar to that shown by a polyclonal VEGF antibody. The scFv antibody fragments, D8 and F10, will be useful in specifically detecting circulating VEGF165 in cancer patients as most studies to date have quantified the total level of circulating VEGF (121 and 165). These reagents will allow further elucidation of the role of VEGF in tumor angiogenesis.

Adenoma↗
PubMed2005

Serum hyaluronan levels and radiographic knee and hip osteoarthritis in African Americans and Caucasians in the Johnston County Osteoarthritis Project.

OBJECTIVE: Serum hyaluronan (HA) has been proposed as a potential biomarker of osteoarthritis (OA). We examined associations between serum HA and radiographic OA in an ethnically diverse, population-based sample. METHODS: Participants were selected from the Johnston County Osteoarthritis Project, using stratified simple random sampling to achieve balance according to radiographic knee OA status, ethnic group, sex, and age group. Serum HA was measured by enzyme-linked immunosorbent assay. Radiographic OA variables included knee OA, knee OA laterality, knee OA severity, concomitant knee and hip OA, and total number of OA-affected knee and hip joints. Analysis of covariance was used to assess differences in mean serum levels of natural log-transformed HA (ln serum HA) between groups, adjusting for ethnicity, sex, age, body mass index (BMI), and self-reported comorbidities. RESULTS: Levels of ln serum HA were positively associated with all definitions of radiographic OA (P < 0.0001). Levels of ln serum HA were higher in Caucasians (P = 0.0094) and in men (P = 0.0038) and were moderately correlated with age (r = 0.35, P < 0.0001). The associations with radiographic OA, ethnicity, sex, and age remained statistically significant after adjustment (P < 0.0045). There were no interactions between ethnicity and the other covariates. CONCLUSION: These cross-sectional data support a role for serum HA as a biomarker of radiographic OA. The variations in levels of serum HA attributable to ethnicity, sex, and age were not explained by radiographic OA, BMI, or comorbidities. The lack of strong confounding between serum HA and comorbidities further supports a role for serum HA as a potential biomarker.

Black or African American↗
PubMed2001

Urinary cadmium elimination as a biomarker of exposure for evaluating a cadmium dietary exposure--biokinetics model.

The Cadmium Dietary Exposure Model (CDEM) utilizes national survey data on food cadmium concentrations and food consumption patterns to estimate dietary intakes in the U.S. population. The CDEM has been linked to a modification of the cadmium biokinetic model of Kjellström and Nordlberg (KNM) to derive predictions of kidney and urinary cadmium that reflect U.S. dietary cadmium intake and related variability. Variability in dietary cadmium intake was propagated through the KNM using a Monte Carlo approach. The model predicts a mean peak kidney cadmium burden of approximately 3.5 mg and a 5th-95th percentile range of 2.2-5.1 mg in males. The corresponding peak renal cortex cadmium concentration in males is 15 microg/g wet cortex (10-22, 5th-95th percentile). Predicted kidney cadmium levels in females were higher than males: 5.1 (3.3-7.6) mg total kidney, 29 (19-43) microg/g wet cortex. Predicted urinary cadmium in males and females agreed with empirical estimates based on the NHANES III, with females predicted and observed to excrete approximately twice the amount of cadmium in urine than males. An explanation for the higher urinary cadmium excretion in females is proposed that is consistent with the NHANES III data as well as experimental studies in humans and animals. Females may absorb a larger fraction of ingested dietary cadmium than males, and this difference may be the result of lower iron body stores in females compared to males. This would suggest that females may be at greater risk of developing cadmium toxicity than males. The predicted 5th-95th percentile values for peak kidney cadmium burden are approximately 60% of the peak kidney burden (8-11 mg) predicted for a chronic intake at the U.S. Environmental Protection Agency (EPA) chronic reference dose of 1 microg/kg-d.

Adolescent↗
PubMed2005

Estrogen-responsive finger protein as a new potential biomarker for breast cancer.

PURPOSE: Estrogen-responsive finger protein (Efp) is a member of RING finger-B box-Coiled Coil family and is also a downstream target of estrogen receptor alpha. Previously, Efp was shown to mediate estrogen-induced cell growth, which suggests possible involvement in the development of human breast carcinomas. In this study, we examined expression of Efp in breast carcinoma tissues and correlated these findings with various clinicopathologic variables. EXPERIMENTAL DESIGN: Thirty frozen specimens of breast carcinomas were used for immunohistochemistry and laser capture microdissection/real-time PCR of Efp. Immunohistochemistry for Efp was also done in 151 breast carcinoma specimens fixed with formalin and embedded in paraffin wax. RESULTS: Efp immunoreactivity was detected in breast carcinoma cells and was significantly associated with the mRNA level (n = 30). Efp immunoreactivity was positively associated with lymph node status or estrogen receptor alpha status and negatively correlated with histologic grade or 14-3-3sigma immunoreactivity (n = 151). Moreover, Efp immunoreactivity was significantly correlated with poor prognosis of breast cancer patients, and multivariate analyses of disease-free survival and overall survival for 151 breast cancer patients showed that Efp immunoreactivity was the independent marker. CONCLUSIONS: Our data suggest that Efp immunoreactivity is a significant prognostic factor in breast cancer patients. These findings may account for an oncogenic role of Efp in the tumor progression of breast carcinoma.

14-3-3 Proteins↗
PubMed2004

Capillary electrophoresis with laser-induced fluorescence detection as a novel sensitive approach for the analysis of desmosines in real samples.

Among various biomarkers believed to behave as descriptors of the disease process in chronic obstructive pulmonary disease (COPD), urinary desmosines are commonly used for monitoring elastin degradation. Given the low concentrations of urinary desmosines, their quantitative determination in this biological matrix often requires preconcentration steps. To minimize both solute losses and effects of sample matrix, and to decrease data variability related to the above-mentioned manipulation processes, we have developed a capillary electrophoresis approach combined with laser-induced fluorescence (CE-LIF) detection system using urine samples not submitted to any pretreatment procedure other than filtering the sample. Urines were hydrolyzed, derivatized with fluorescein isothiocyanate (FITC) and endogenous desmosines were identified by addition of standard analytes and submitting to mass spectrometry (MS) analysis the material collected from micropreparative runs. The assay showed good linearity, reproducibility and precision, allowing to detect amounts of desmosines as low as 10(-8) M (equivalent to 0.1 fmol on column). We conclude that CE-LIF technique is a highly sensitive method for detecting urinary desmosines.

Animals↗
PubMed2026

A GRADE-assessed systematic review and meta-analysis of randomized controlled trials evaluating the effects of olive leaf or olive pomace supplementation on cardiometabolic and anthropometric health markers.

AIMS: Cardiometabolic diseases (CMDs) are major contributors to global morbidity and mortality, and dietary bioactives such as polyphenols may modulate key risk factors. Olive by-products, particularly olive leaves (OL) and olive pomace (OP), are rich in phenolic compounds with antioxidant, anti-inflammatory, and cardiometabolic effects demonstrated across in vitro, preclinical, and clinical studies. DATA SYNTHESIS: This GRADE-assessed systematic review and meta-analysis included 30 randomized controlled trials (n&#x202f;=&#x202f;1726) evaluating OL or OP supplementation on 21 standardized biomarkers, encompassing inflammatory markers, lipid profile, glycemic control, insulin sensitivity, anthropometric measures, and blood pressure. Meta-analyses were conducted using random-effects models, with effect sizes calculated as mean differences (or standardized mean differences for oxLDL). Between-study heterogeneity was assessed with I2 statistics, and sensitivity and subgroup analyses explored potential sources of variability. Publication bias was evaluated using Begg's test and funnel plots where appropriate. OL supplementation significantly improved lipid parameters (total cholesterol, triglycerides, LDL-C, ApoB, oxLDL) and increased ApoA1, while reducing TNF-&#x3b1;, systolic and diastolic blood pressure, body weight, and BMI. No significant effects were observed on glycemic markers. OP supplementation showed no consistent cardiometabolic benefits and was associated with an increase in IL-8. Certainty of evidence ranged from very low to high, with several outcomes downgraded due to imprecision, heterogeneity, or limited study numbers. CONCLUSION: These findings support the targeted use of OL as an adjunctive strategy for cardiometabolic risk management. Evidence for OP supplementation remains limited, underscoring the need for well-powered, high-quality RCTs to clarify its clinical effects.

Humans↗
PubMed2000

Urinary 1-hydroxypyrene as a biomarker of polycyclic aromatic hydrocarbons exposure of workers on a contaminated site: influence of exposure conditions.

The aim of the study was to determine the exposure levels of workers to polycyclic aromatic hydrocarbons on gasworks sites by the measurement of urinary 1-hydroxypyrene. Start-shift and end-shift urine samples were taken every day during an entire week (Monday to Friday), once in November and a second time in June. Four groups of workers were selected according to their activity. Increased exposure was only found among volunteers involved in the remediation of a site, 0.16 to 2.31 mumol/mol creatinine in non-smokers. The median of the non-smoker referent group was 0.02 mumol/mol creatinine (95% confidence interval, 0.01 to 0.04). Smokers had greater exposure levels than non-smokers in every group. Within and between variability was around 200%. Assessment of the exposure of persons on contaminated soil is possible, with the condition that the exposed subjects come in direct contact with the soil.

Analysis of Variance↗
PubMed2004

DNA strand breaks and adducts determined in feral and caged chub (Leuciscus cephalus) exposed to rivers exhibiting variable water quality around Birmingham, UK.

This study forms part of an investigation into the effects on fish of immersion in three rivers around Birmingham, UK. The rivers Blythe, Cole and Tame exhibit relatively high, intermediate and poor overall water quality, respectively, according to combined levels of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs), as well as heavy metals. Specifically, biomarkers of genotoxicity (DNA strand breaks and adducts) were measured in feral and caged chub (Leuciscus cephalus), complementing another study in which data were presented for a number of other hepatic biomarkers measured in the same animals. In both feral and caged chub, there was a general elevation of DNA strand breaks with a decrease in chemical water quality, with some time points exhibiting significantly higher levels at the most (Tame) compared with least polluted sites (Blythe), particularly in the cage-held animals. Combined-season DNA adduct data suggested a higher degree of toxic insult in the feral compared with caged chub and revealed particularly high levels of adducts in fish caught from the Cole. The pattern of adducts shown was typical of exposure to a complex mixture of PAHs which were relatively high, and similar, in both the Cole and Tame. Overall, these data are consistent with exposure of both feral and caged chub to contaminants which are able to induce specific, moderately genotoxic effects.

Animals↗
PubMed2006

CLLU1 expression levels predict time to initiation of therapy and overall survival in chronic lymphocytic leukemia.

OBJECTIVES: Chronic lymphocytic leukemia (CLL) is an incurable disease with a highly variable clinical course. IgV(H) mutational status, chromosomal aberrations, CD38 expression and ZAP-70 expression are prognostic markers in CLL, however, they are not exclusively confined to this disease. We recently identified a novel CLL-specific gene (CLL upregulated gene1, CLLU1) that is exclusively upregulated in CLL cells. Here we describe our evaluation of the prognostic significance of CLLU1 in CLL. METHODS: A cohort of 59 previously untreated CLL patients was studied. We determined the expression levels of two CLLU1 transcripts, cDNA1 and CDS, by quantitative RT-PCR. The relation between CLLU1 expression and time to therapy, overall survival and presence or absence of ZAP-70, CD38, chromosomal aberrations or IgV(H) mutations in the 59 patients was analyzed. RESULTS: Analyzed as a continuous, quantitative parameter CLLU1 levels significantly predicted time from diagnosis to initiation of therapy (P < or = 0.0003) Analyzed as a categorical parameter, by segregation of the patients into groups with cDNA1 or CDS expression above or below the median, the CLLU1 levels significantly predicted time from diagnosis to initiation of therapy (P = 0.001) and predicted overall survival with borderline significance (P < or = 0.05). Patient stratification according to clinical stage, cytogenetics, IgV(H) mutational status, ZAP-70 and CD38, demonstrated significantly increased CLLU1 expression in all investigated CLL poor risk groups. CLLU1 expression levels contributed additional prognostic information to ZAP-70-positive patients. CONCLUSIONS: CLLU1 is the first identified CLL specific gene. The CLLU1 mRNA expression level can predict time to initiation of treatment and survival in CLL patients.

ADP-ribosyl Cyclase 1↗
PubMed2001

Bayesian monitoring of a phase 2 chemoprevention trial in high-risk cohorts for prostate cancer.

The objective of phase 2 cancer chemoprevention trials is to evaluate whether a chemopreventive agent will cause significant modulation of intermediate endpoint biomarkers (IEB) in patients at high risk for the disease. A phase 2 chemoprevention trial of 4-hydroxyphenyl retinamide (4-HPR) versus placebo was conducted in men with a histologic diagnosis of early prostate cancer and scheduled to have radical prostatectomy. A Bayesian monitoring method was used to sequentially monitor this trial for evidence of biological activity or ineffectiveness based on a single IEB variable. Different prior distributions were used and posterior distributions were obtained to calculate the probability that treatment differences are greater than or less than a predetermined clinically significant effect. The interim analysis of transforming growth factor-alpha expression indicated a high probability of insufficient biological activity of 4-HPR on this IEB. This study demonstrates the potential utility of Bayesian methods in the decision-making process in the conduct of phase 2 chemoprevention trials.

Anticarcinogenic Agents↗
PubMed2026

MET expression by immunohistochemistry as a biomarker in pancreatic neuroendocrine tumours.

INTRODUCTION: MET (c-MET) is a receptor tyrosine kinase implicated in numerous cancers, including pancreatic neuroendocrine tumours (pNETs), by promoting cell proliferation, survival, invasion and angiogenesis. Recognizing its oncogenic potential, there is significant interest in MET-targeted therapies for malignancies like pNETs, which often develop treatment resistance. Immunohistochemistry (IHC) has become a practical method for detecting MET overexpression in cancers. This study evaluates MET expression in pNETs by IHC and assesses its correlation with prognostic variables and survival outcomes. METHODS AND RESULTS: Tissue microarrays containing well-differentiated neuroendocrine tumours from the gastrointestinal tract were analysed. The study included 125 pNET cores from 112 patients after application of inclusion criteria. MET expression was determined using the H-score system. Different variables were assessed for H-score distribution and cross-tables. Survival analyses were conducted based on progression-free survival and overall survival. Positive MET expression was found in 83.5% of cases. Higher MET H-scores were seen in patients with lymphovascular invasion (LVI), distant metastases and higher tumour grade (P&#x2009;<&#x2009;0.05). When assessing different variables for higher MET H-scores, a significant association emerged at the 150-cut-off-point for LVI, perineural invasion, radiological evidence of progression and overall survival. For survival analysis, at a MET H-score threshold of 200, high MET expression was significantly associated with shorter progression-free survival (mean 8.7 versus 13.4&#x2009;years, P&#x2009;<&#x2009;0.05) and overall survival (mean 3.6 versus 7.7&#x2009;years, P&#x2009;<&#x2009;0.05). CONCLUSION: Elevated MET expression is linked to adverse histopathological features and worse clinical outcomes in pNET. Standardizing MET IHC evaluation is critical as anti-MET therapies develop, and identifying patients likely to benefit from these treatments remains essential.

MET protein↗
PubMed2005

Cholinesterases in aquatic biomonitoring: assay optimization and species-specific characterization for a California native fish.

Cholinesterase (ChE) enzyme activity measurements are widely applied in aquatic organisms for water quality monitoring, especially for pesticide contamination in agricultural watersheds. These biomarkers are amenable to measurement in a variety of species, and are therefore useful for examining effects in model organisms relevant to the ecosystem of interest. However, extensive variation in ChE biochemistry exists among tissues and species. This variation is rarely characterized and may lead to biases in the interpretation of activity determinations. We optimized ChE activity measurement parameters and characterized ChE biochemistry in Sacramento sucker (Catostomus occidentalis), a widely distributed fish native to watersheds of the Central Valley of California. Acetylcholinesterase (AChE) was the predominant ChE present in C. occidentalis brain and muscle, and muscle AChE was most sensitive to diazinon inhibition. Field caging experiments indicated that exposures to ChE-inhibiting pesticides were insufficient to induce neurotoxic effects. However, pesticide usage in the Central Valley is highly variable among years, and long-term monitoring of in-stream effects would be necessary to evaluate trends in pesticide contamination. Recent changes to the State Water Code require agricultural landowners to participate in a regional water quality monitoring plan. As with most regional monitoring plans, measurements of in-stream effects, and effects in resident species, are not scheduled to be included. We suggest that inclusion of biomarker measures would lend important information to the monitoring process, and propose these procedures as a template for adapting ChE activity measurements into region-specific monitoring programs to assess in-stream effects of pesticide contamination on native species.

Acetylcholinesterase↗
PubMed2001

Factors contributing to peak broadening and mass accuracy in the characterization of intact spores using matrix-assisted laser desorption/ionization coupled with time-of-flight mass spectrometry.

Factors contributing to peak broadening, accuracy and precision in mass assignment in the matrix-assisted laser desorption/ionization characterization of a lipopeptide desorbed from intact Bacillus spores were investigated. These spores were studied as an example of a thick, topologically irregular sample, which present a more difficult target than a pure peptide or protein. The type of matrix, matrix:sample ratio, laser fluence, and localized repetitive laser irradiation were all found to affect the full-width at half maximum of the biomarker. Both in-source and post-source phenomena were shown to contribute. Sample thickness had less effect. Precision and accuracy of mass assignment were also affected by matrix:sample ratio and laser fluence. In general, this sample was responsive to the same experimental variables as pure peptides, and the use of an internal standard produced significant improvements in precision and accuracy.

Bacillus thuringiensis↗