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 397 records · Page 22Linked to original sources
PubMed2002

Calcium bioavailability in relation to bone health.

A well established stable isotope technique exists for measuring calcium absorption from single foods and meals, but the long term effects of calcium on bone health cannot be assessed from acute bioavailability studies. Bone health depends primarily on the degree of mineralization, measured as bone mineral density (BMD), and phenotypic variations depend on genetic and environmental factors including calcium supply. Since almost all retained calcium is used for bone mineralization and remodeling, BMD can be used as a long-term (> six months) marker of dietary calcium bioavailability. However, BMD is a very insensitive marker of calcium bioavailability, so its use in dietary intervention studies is restricted to periods of significant bone growth or loss. Biochemical markers of bone metabolism may be used to predict the overall bioavailability of dietary calcium over a shorter time period (> four weeks), but they have a high coefficient of variation, so may not be appropriate for some dietary intervention studies. A group of European laboratories is currently developing an alternative approach using a long-lived radioisotope (41Ca) to label bone calcium and to directly measure the rate of calcium loss from urinary excretion data. The efficiency of calcium absorption is inversely related to intake; whole body balance of the mineral is dependent on rates of absorption and excretion and limited by calcium-binding substances in the gut. Dietary data and indirect measures of bone health indicate that bioavailability is important when habitual intakes are low, especially during periods of bone growth or loss. Further research is required to quantify the effects of major dietary modulators of calcium balance on bone health and to understand their relationship with genetic and physiological variables.

Biological Availability↗
PubMed1996

First trimester biological markers for the prediction of pregnancy-induced hypertension.

The purpose of this study is to predict pregnancy-induced hypertension (PIH) by standard methods at the first antenatal visit prior to the 12th gestational week (GW). This is a retrospective study of 1189 primipara and 957 multipara who delivered singleton babies having no major malformations after the 32nd GW. Multiple regression analysis for the development of PIH was performed using the mean arterial blood pressure (MBP), body mass index (BMI), hematocrit count at the first visit prior to the 12th GW, a family history of hypertension number of pregnancies, number of deliveries, past history of hypertension and evidence of threatened abortion as explanatory variables in primipara and multipara, respectively. We obtained a significant regression equation in both primipara and multipara. Multiple correlation coefficient for primipara was 0.40223 (p < 0.01) and for multipara was 0.50764 (p < 0.01). When MBP was over 80 mm Hg, BMI was over 23.6, a family history of hypertension was present, or a past history of hypertension was present, these variables were significantly correlated with the development of PIH both in primipara and multipara. By combining these variables, we obtained 32.7% positive predictive value, 93.5% negative predictive value, 31.7% sensitivity, and 93.7% specificity in primipara and 24.6%, 96.7%, 52.6%, and 89.8% in multipara, respectively. As the incidence of PIH was 8.7% in primipara and 5.9% in multipara, we could predict 3.7 and 4.1 times higher than the true incidence. PIH can therefore be predicted by the simple combination of MBP, BMI, a family history of hypertension, and a past history of hypertension prior to the 12th GW. It can also be predicted by the multiple-regression equation with the use of nine explanatory variables.

Adult↗
PubMed2006

Elevated levels of urinary 8-hydroxy-2 -deoxyguanosine, lymphocytic micronuclei, and serum glutathione S-transferase in workers exposed to coke oven emissions.

To investigate associations among occupational exposure to coke oven emissions (COEs), oxidative stress, cytogenotoxic effects, change in the metabolizing enzyme glutathione S-transferase (GST), and internal levels of polycyclic aromatic hydrocarbons (PAHs) in coke oven workers, we recruited 47 male coke oven workers and 31 male control subjects from a coke oven plant in northern China. We measured the levels of 1-hydroxypyrene (1-OHP) and 8-hydroxy-2 -deoxyguanosine (8-OHdG) in urine, micronucleated binucleated cells (BNMNs) in peripheral blood lymphocyte, and GST in serum. Our results showed that the group exposed to COEs had significantly increased levels of 1-OHP [median 5.7; interquartile range (IQR), 1.4-12.0 micromol/mol creatinine] compared with the control group (3; 0.5-6.4 micromol/mol creatinine). In addition, the median levels (IQR) of 8-OHdG, BNMNs, and GST were markedly increased in the exposed [1.9 (1.4-15.4) micromol/mol creatinine; 6 (2-8) per thousand ; 22.1 (14.9-31.2) U/L, respectively] compared with controls [1.3 (1.0-4.0) micromol/mol creatinine, 2 (0-4) per thousand; and 13.1 (9.5-16.7) U/L, respectively]. These results appeared to be modified by smoking. However, multivariate logistic regression analysis revealed that exposure to COEs had the highest odds ratio among variables analyzed and that smoking was not a significant confounder of the levels of studied biomarkers. Overall, the present findings suggest that COE exposure led to increased internal PAH burden, genetic damage, oxidative stress, and GST activity. The consequences of the changes in these biomarkers, such as risk of cancer, warrant further investigations.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

Accuracy and biological variation of human serum paraoxonase 1 activity and polymorphism (Q192R) by kinetic enzyme assay.

BACKGROUND: Paraoxonase 1 (PON1) phenotype is a better predictor of atherosclerosis risk than are PON1 genetic polymorphisms alone. Larger studies are required to determine the role of PON1 and there is a need for standardized PON1 assays between laboratories. METHODS: We have adapted 5 enzyme kinetic assays for high-throughput automated analysis of PON1 activity. Using different substrates and reaction conditions, we measured PON1 activity and used activity ratios to identify the PON1 Q192R genetic polymorphisms and assessed the accuracy of the genotype assignments in 79 adult study participants by comparing them with genotypes determined by AlwI restriction enzyme digestion of a 176-bp PCR amplification product from genomic DNA. Imprecision was determined using pooled serum and purified enzyme preparations. Biological variability was estimated by analysis of serial samples from 17 individuals. Variability parameters were compared with total cholesterol as a point of reference to a recognized biomarker of coronary heart disease risk. RESULTS: Salt stimulation and inhibition ratios were 97.4% and 94.7% correct in assigning Q192R genotype, respectively. Analytical imprecision (CV) was 1.0%-3.0% for phenylacetate and paraoxon substrate assays and 3.0%-8.0% for the para-nitrophenylacetate substrate assays. Combination of the 2 ratios into a double ratio resulted in 100% correct genotype classification. CONCLUSION: The described methods for measurement of PON1 activity and accurate genotype assignment are rapid and have potential to facilitate the efficient investigation of PON1 status in clinical and epidemiological studies.

Adult↗
PubMed2004

Understanding the clinical biochemistry of N-terminal pro-B-type natriuretic peptide: the prerequisite for its optimal clinical use.

With the introduction of the first rapid, fully automated assay for N-terminal pro-B-type natriuretic peptide (Nt-proBNP) determination, clinical laboratories are now able to transfer a number of preliminary information derived from pilot research experiences to the context of clinical cardiology. Some confounding factors may, however, affect the interpretation of the Nt-proBNP test and its clinical value. The objective of this review is to highlight and discuss these potentially confounding variables.

Age Factors↗
PubMed2003

Use of biomarkers for alcohol use disorders in clinical practice.

BACKGROUND: Biomedical markers may provide additive objective information in screening and confirmation of acute or recent consumption, intoxication, relapse, heavy drinking, hazardous/harmful use/abuse and dependence and alcohol use related organ dysfunction (alcohol use-related disorders: AUDs). AIMS: To review the use of biomarkers in clinical practice to detect AUDs. FINDINGS: About one-fifth of the patients seen in clinical practice have AUDs, which offer a variety of treatment options if diagnosed. The diagnosis of AUDs relies on clinical and alcohol-related history, physical examination, questionnaires and laboratory values. No clinical available laboratory test [e.g. for acute abuse: alcohol in blood or breath; for chronic alcohol abuse: gamma-glutamyl transferase (GGT), mean corpuscular volume (MCV), carbohydrate-deficient transferrin (CDT)] is reliable enough on its own to support a diagnosis of alcohol dependence, harmful use or abuse. Sensitivities, specificities and the predictive values may vary considerably according to patient and control group characteristics (e.g. gender, age or related comorbidity). In patient groups with limited cooperation markers may be helpful when considering treatment options. CONCLUSIONS: More research is needed to determine the value of markers (single or combined, with questionnaires) in the context of clinical decision-making algorithms in defined settings and with defined dichotomous outcome variables.

Age Factors↗
PubMed1994

Genetics of CYP1A1: coamplification of specific alleles by polymerase chain reaction and association with breast cancer.

CYP1A1 is a gene of the cytochrome P-450 family that has been proposed to be a biomarker of cancer risk. We introduce a polymerase chain reaction-based assay to measure allelic variability in exon 7 of the CYP1A1 gene. This genetic variant is associated with an amino acid change at residue 462 in the aryl hydrocarbon hydroxylase protein product. Previously, measurement of CYP1A1 genotypes at this variant site required two assays, one to detect each allele. By using three primers in a single polymerase chain reaction rather than two primers in each of two polymerase chain reactions, the proposed assay may facilitate population-based study protocols. We estimate the frequency of this polymorphism in a Caucasian population to be 0.03, with an observed heterozygosity of 0.06. We have also confirmed the Mendelian segregation of this polymorphism in four multigeneration Centre d'Etude du Polymorphisme Humain families and have placed this locus in a multilocus linkage map on chromosome 15q. The distribution of this polymorphism was the same in breast cancer cases as in two sets of healthy controls.

Adult↗
PubMed1998

Relationship between organochlorine contaminants and mixed function oxidase activity in skin biopsy specimens of Mediterranean fin whales (Balaenoptera physalus).

The relationship between organochlorine contaminants (PCBs and DDTs) and mixed function oxidase, benzo(a)pyrene monooxigenase activity (BPMO), was investigated in skin biopsy specimens from fin whales (Balaenoptera physalus) of the Mediterranean Sea. Skin biopsy material, sampled by a non invasive technique, is suitable for a wide range of chemical and biomarker analysis. In this study PCBs and DDTs were evaluated in subcutaneous blubber and MFO activity in epidermis. An interesting correlation was found in male specimens between the two variables.

Animals↗
PubMed2006

Lipoprotein lipase mRNA expression in whole blood is a prognostic marker in B cell chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is characterized by high individual variability in clinical course and the need for therapy. Differentiation of prognostic subgroups is based primarily on the mutation status of the genes for the variable region of the immunoglobulin heavy chain (IGHV). The time- and labor-intensive nature of this analysis necessitates the use of easily applicable surrogate markers. METHODS: We developed a quantitative PCR (qPCR) method for determining lipoprotein lipase (LPL) mRNA expression and analyzed samples of lysed whole blood and CD19-selected cells from 50 CLL patients. Associations of LPL and ZAP70 [zeta-chain (TCR) associated protein kinase 70 kDa] expression with IGHV mutation status, overall survival (OS), and treatment-free survival (TFS) were investigated. RESULTS: Lysed samples of whole blood and CD19-selected cells were similar with respect to LPL expression (R = 0.88; P <0.0001). LPL expression was significantly associated with IGHV mutation status [chi(2)(1) = 15.3; P <0.0001] and showed an 89.3% specificity, a 68.2% sensitivity, an 83.3% positive predictive value, and a 78.1% negative predictive value for IGHV mutation status. LPL expression was significantly associated with both OS and TFS in log-rank tests (both P values = 0.002). LPL-positive patients had a significantly shorter median TFS time (23 months) than LPL-negative patients (88 months) (P = 0.002). CONCLUSIONS: LPL mRNA expression is a valuable prognostic marker in CLL. The method does not require cell purification, and its applicability with archived samples facilitates its use in the clinical routine and other studies.

Adult↗
PubMedDate not supplied

Mytilus trossulus hsp70 as a biomarker for arsenic exposure in the marine environment: laboratory and real-world results.

The highly conserved heat shock protein 70 (hsp70) is induced by heat and chemical toxins, particularly heavy metals such as arsenic (As). The use of Mytilus trossulus (bay mussel) hsp70 as a 'screening' biomarker for marine heavy metals contamination was assessed. Some studies have found high hsp70 sensitivity to heavy metals, while others have found the opposite. Few studies have realistically used low heavy metals exposures, and fewer have used real-world contamination exposures. Clean sub-tidal mussels from the Puget Sound, Washington State (WA), USA, were acclimatized for 2 weeks and exposed for 24 h to As-spiked seawater (n=9) or to contaminated seawater from an arsenical pesticide plant in Tacoma, WA (n=10) followed by a Western blot for hsp70. Hsp70 inductions were insignificant at 10 microg l(-1) As(III), but were strong at 100 microg l(-1) (p<0.05) and 1000 microg l(-1) (p<0.01), with the induction threshold estimated at 30-50 microg l(-1) As(III). Hsp70 induction roughly correlated with arsenical toxicity, with As(III) > As(V) > (CH(3))(2)As(V). Altogether, the inter-individual variability of hsp70 levels tends to mask inductions at low As concentrations, making it a crude toxicity biomarker. In addressing this problem, the following options could prove promising: (1) pre- or post-stressing specimens for greater hsp70 sensitivity, (2) use of internal protein controls such as actin, (3) use of hsp70-reporter gene constructs, and (4) detection with hsp60, heme oxygenase-1, metallothionein, CYP450, MXR or GPx.

Animals↗
PubMed2026

Assessment of the Potential of Different Anthropometric Indices in Predicting the Risk of Diabetes and Associated Co-morbidities.

Diabetes, a chronic disorder, is showing a rapidly increasing trend globally. India holds the second position in the global diabetes epidemic. The present investigation is an assessment of different anthropometric measurements and their association with type 2 diabetes to determine their diagnostic potential for diabetes as well as its co-morbidities. In this cross-sectional study, we have measured anthropometric parameters and blood biomarkers in subjects with diabetes. We have presented the comparisons of cost- and time-effective anthropometric variable with costly and time-dependent biochemical variables in control and diabetic groups (n = 233/group). Correlations between anthropometric variables and biochemical measurements, as well as the diagnostic utility of anthropometric variables for diabetes, were evaluated. The diagnostic utility of anthropometric variables for diabetes was assessed through receiver operating characteristic (ROC) curves. Neck circumference, sagittal abdominal diameter (SAD), skinfold thickness, and body roundness index (BRI) displayed high specificity and diagnostic utility for diabetes, emphasizing their potential in predicting diabetes and the further development of metabolic syndrome. The study highlights the importance of cost- and time-effective anthropometric assessments in diabetes risk evaluation and calls for further research to elucidate this intricate relationship and develop personalized management strategies.

Humans↗
PubMed2002

CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease.

Although the presence or absence of somatic mutations in the immunoglobulin variable region (IgV(H)) genes in chronic lymphocytic leukemia (B-CLL) identifies subtypes with very different prognoses, the assay is technically complex and unavailable to most laboratories. CD38 expression has been suggested as a surrogate marker for the 2 subtypes. IgV(H) mutations and CD38 expression in 145 patients with B-CLL with a long follow-up were compared. The 2 assays gave discordant results in 41 patients (28.3%). Multivariate analysis demonstrated that Binet stage, IgV(H) mutations and CD38 were independent prognostic indicators. Median survival time in patients whose cells had unmutated IgV(H) genes and expressed CD38 was 8 years; in those with mutated IgV(H) genes not expressing CD38, it was 26 years. For those with discordant results, median survival time was 15 years. Thus, although CD38 expression does not identify the same 2 subsets as IgV(H) mutations in CLL, it is an independent risk factor that can be used with IgV(H) mutations and clinical stage to select patients with B-CLL with the worst prognoses. Using cryopreserved cells taken at intervals during the course of the disease, however, changes of CD38 expression over time were demonstrated in 10 of 41 patients. Causes of the variation of CD38 expression require further study. Additional prospective studies are required for comparing CD38 expression with other prognostic factors and for taking sequential measurements during the course of the disease.

ADP-ribosyl Cyclase↗
PubMed2006

Urinary excretion of acrylamide and metabolites in Fischer 344 rats and B6C3F(1) mice administered a single dose of acrylamide.

Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic, mutagenic to somatic and germ cells, and carcinogenic in mice and rats. AA is also formed during cooking in many commonly consumed starchy foods. Our previous toxicokinetic investigations of AA and its genotoxic metabolite, glycidamide (GA), in rodents showed that AA is highly bioavailable from oral routes of administration, is widely distributed to tissues, and that the dietary route, in particular, favors metabolism to GA. Formation and accumulation of mutagenic GA-DNA adducts in many tissues support the hypothesis that AA is carcinogenic in rodent bioassays through metabolism to GA. The current investigation describes the quantification of 24 h urinary metabolites, including free AA and GA and their mercapturic acid conjugates (AAMA and GAMA, respectively), using LC/MS/MS in F344 rats and B6C3F(1) mice following a dose of 0.1 mg/kg bw given by intravenous, gavage, and dietary routes of administration. Similar groups of rodents were used previously for serum/tissue toxicokinetic and adduct determinations (DNA and hemoglobin). The goal was to investigate relationships between urinary and circulating biomarkers of exposure, toxicokinetic parameters for AA and GA, and tissue GA-DNA adducts in rodents from single doses of AA. Significant linear correlations were observed between urinary levels of AA with AAMA and GA with GAMA in the current data sets for rats and mice. Concentrations of AA and AAMA correlated significantly with average AUC values determined previously for AA in groups of rats and mice similarly dosed with AA. Urinary GA and GAMA concentrations showed significant correlations with average AUC values for GA and liver GA-DNA adducts determined previously in rats and mice similarly dosed with AA. Despite statistical significance, considerable inter-animal variability was observed in all urinary measurements, which limited the degree of correlation with either average toxicokinetic or biomarker data collected from different groups of animals. These results suggest that urinary measurements of AA and its metabolites may be useful for prediction of internal exposures to AA and GA.

Acetylcysteine↗
PubMed2003

Surface antigen expression and correlation with variable heavy-chain gene mutation status in chronic lymphocytic leukemia.

Recent studies have demonstrated that B-cell chronic lymphocytic leukemia (CLL) consists of two clinical entities with either somatically hypermutated (M-CLL) or unmutated (UM-CLL) immunoglobulin variable heavy-chain (VH) regions. In view of the fact that the cellular biology of these two subsets of disease is currently unexplored, we performed an extensive analysis of the surface antigen expression and correlated this with the VH gene mutation status in a cohort of 32 CLL patients. Using polymerase chain reaction amplification and nucleotide sequencing, the VH genes were shown to be mutated in 10 cases (31%) and unmutated in 22 (69%). The expression of 27 surface membrane antigens in peripheral blood leukemic cells was analyzed by flow cytometry, measuring both the percentage of positive cells as well as the geometric mean fluorescence intensity (GMF). Most of the surface membrane antigens (CD5, CD11c, CD19, CD20, CD21, CD22, CD23, CD25, CD40, CD45, VD79b, CD80, CD95, CD122, CD124, CD126, CD130, CD154, IgM, and IgD) showed a similar expression pattern in both UM-CLL and M-CLL patients. The similarity of M-CLL and UM-CLL, as demonstrated here for the first time with many protein markers, indicates a considerably homogeneous phenotype in both subsets. Furthermore, CD27 was strongly expressed in all cases, which may suggest a memory cell phenotype for both M-CLL and UM-CLL. More positive cells in the UM-CLL group were observed regarding CD38, but CD38 was not a good predictor of VH gene mutation status. Seventy percent of the M-CLL cases, but only 36% of UM-CLL cases, were Ig-lambda+. The most striking differential expression, however, was observed in the two slicing variants of the common leukocyte antigen CD45, namely CD45RO and CD45RA. CD45RO expression was significantly associated with M-CLL, whereas the GMF intensity of CD45RA tended to be associated with UM-CLL. The role of these CD45 splicing variants in the pathogenesis of CLL deserves further investigation.

Antigens, Surface↗
PubMed1997

Projection of molecular epidemiology in medicine.

Molecular epidemiology is a term to describe the incorporation of molecular and other types of biomarkers into epidemiology. Molecular epidemiology uses the same paradigm as traditional epidemiology but the former represents the opportunity to use the enhances resolving power of molecular biology and contemporary biochemical science to assess exposure disease relationships. There are three types of biomarkers that can be used in this regard: They include markers of exposure, effect and susceptibility. These markers can be used as dependent and independent variables in most epidemiologic study designs. Critical in their use is that they are validated and field tested. This requires extensive collaboration between laboratory and public health scientist. Special attention also needs or be paid to the interpretation and communication of biomarker data and the ethical issues attendant to their use.

Biomarkers↗
PubMedDate not supplied

Cerebrospinal fluid biomarkers in primary headache disorders.

OBJECTIVE: The object of this review is to examine the published literature for cerebrospinal fluid laboratory measures of primary headache disorders to identify biomarkers and provide recommendations for future biomarker discovery. BACKGROUND: Biomarkers may distinguish deviation from a normal state, provide insight into mechanisms of pathophysiology, quantify the degree of change, discriminate what may be clinically overlapping disorders, and allow monitoring and/or selection of specific treatment. High-throughput, discovery technologies fuel the ability to reveal more biomarkers than past hypothesis-driven studies. DESIGN OR METHODS: Publications were identified in PubMed, ISI web of knowledge (both Web of Science and BIOSYS), and SciFinder, using the key words for cerebrospinal fluid (CSF) and migraine, headache, or biomarkers. Additional references were sought from the papers identified in these searches. Data were assessed relating to all primary headache types for clinical and scientific methods and results. RESULTS: Fifty-five out of 82 biomarkers were found from 55 publications, though none have been validated for clinical utility. Data for site (ventricular, cervical, lumbar) and timing of CSF collection, headache state, and diagnostic description were patchy, and controls were often poorly defined. Most routinely performed CSF measurements were within normal limits. Most levels of pain-related molecules were reduced, and concentrations of most neurotransmitters, neuropeptides, proteins, and small molecules were increased. Though few studies assessed the specificity of biomarkers for primary headaches, it is clear that there are differences in CSF biomarkers between migraine, cluster headache, tension-type headache, and trigeminal neuralgia. CONCLUSIONS: The high proportion (67%) of biomarkers identified from laboratory measures tested thus far predicts that many more biomarkers will be identified for primary headaches when more candidates are evaluated. In order to discover and evaluate more biomarkers, especially those that may have clinical application for headache management, 3 recommendations are encouraged: prospective design of care-independent studies; evaluation of more clinical variables; and evaluation of substantially more candidates by using discovery-based research methods. Outlines of approaches to pursue these aims are proposed.

Biomarkers↗