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Results for “Biomarker variability”

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PubMed1998

Multivariate analyses of DNA index, p62c-myc, and clinicopathological status of patients with ovarian cancer.

AIM: To determine if either DNA index or p62c-myc is an independent prognostic variable in ovarian cancer. METHODS: Multivariate and univariate analyses of the relation between DNA index, p62c-myc, FIGO stage, histological type, tumour grade, completeness of surgery, and patient survival in ovarian cancer were examined. RESULTS: Multivariate analysis showed significant association of survival only with stage and grade. There was no relation between survival and DNA index. CONCLUSIONS: DNA index is not an independent prognostic variable in ovarian cancer.

Analysis of Variance↗

PubMed2002

Is the hair nicotine level a more accurate biomarker of environmental tobacco smoke exposure than urine cotinine?

STUDY OBJECTIVE: The aim of this study was to compare the two biomarkers of exposure to environmental tobacco smoke (ETS); urine cotinine and hair nicotine, using questionnaires as the standard. DESIGN: A cross sectional study of children consecutively admitted to hospital for lower respiratory illnesses during the period of the study. SETTINGS: Three regional hospitals in the larger Wellington area, New Zealand. PARTICIPANTS: Children aged 3-27 months and admitted to the above hospitals during August 1997 to October 1998. A total of 322 children provided 297 hair samples and 158 urine samples. MAIN RESULTS: Hair nicotine levels were better able to discriminate the groups of children according to their household's smoking habits at home (no smokers, smoke only outside the home, smoke inside the house) than urine cotinine (Kruskall-Wallis; chi(2)=142.14, and chi(2)=49.5, respectively (p<0.0001)). Furthermore, hair nicotine levels were more strongly correlated with number of smokers in the house, and the number of cigarettes smoked by parents and other members of the child's households. Hair nicotine was better related to the questionnaire variables of smoking in a multivariate regression model (r(2)=0.55) than urine cotinine (r(2)=0.31). CONCLUSIONS: In this group of young children, hair nicotine was a more precise biomarker of exposure to ETS than urine cotinine levels, using questionnaire reports as the reference. Both biomarkers indicate that smoking outside the house limits ETS exposure of children but does not eliminate it.

Biomarkers↗

PubMed2003

Evaluation of biochemical methods for estimating the sodium intake of dairy cows.

Samples of blood and urine were taken from 334 dairy cows in 29 herds, and the concentrations of sodium and potassium were measured in the serum and urine. The herds were split into five groups according to the amount of supplementary salt they were given: three groups given 10 to 20, 30 to 50 or 70 to 100 g salt per day, and two groups fed an ad libitum supply, given either in bowls or in the form of salt blocks, which were replaced either regularly or irregularly. The groups which received 70 to 100 g of salt daily or were supplied regularly ad libitum had significantly higher urinary sodium concentrations than the other groups. The group receiving 10 to 20 g a day had a significantly higher ratio of potassium:sodium in their urine than all the other groups, in which the ratio decreased as the level of supplementary salt increased. There were wider differences between the groups in terms of the urinary potassium:sodium ratio than in terms of the urinary sodium concentration but less variability within each group.

Animals↗

PubMed2004

Analysis of chondrocyte functional markers and pericellular matrix components by flow cytometry.

Flow cytometry has been used as a procedure to characterize the phenotype and function of human articular cartilage cells cultured as monolayers or in gelled artificial matrices. Procedures allowing intact cells with their cell-associated matrix, to be obtained have been described. Appropriate monoclonal antibodies have allowed plasma membrane-associated proteins, e.g., growth factors and cytokine receptors, as well as the cell-associated extracellular matrix macromolecules, to be studied. Intracellular compounds have been traced in permeabilized cells after blocking of their intracellular transport and secretion mechanisms. We report the use of fluorescent dye-labeled monoclonal antibodies or specific binding proteins against extracellular matrix compounds such as hyaluronan, aggrecan, types I and II collagen, and fibronectin. The autocrine and paracrine growth factor and cytokine pathways considered include the insulin-like growth factor-1 (IGF-1)/IGF receptor I (IGFRI), and the transforming growth factor-beta1 (TGF-beta1)/TGF-beta receptor II (TGF-betaRII) cascades, as well as the interleukin-1alpha/beta (IL-1alpha/beta)/interleukin-1 receptors I and II (IL-1RI and II) systems. Catabolic enzymes that mediate extracellular matrix turnover, e.g., some matrix metalloproteinases and their natural inhibitors, were also studied. Finally, flow cytometry was used to assess the results of some pharmacological interventions on the aforementioned variables in cultured chondrocytes.

Antibodies, Monoclonal↗

PubMed2006

Influence of chromium-enriched yeast on blood glucose and insulin variables, blood lipids, and markers of oxidative stress in subjects with type 2 diabetes mellitus.

The aim of this study was to determine the effect of chromium (Cr)- enriched yeast on blood glucose and insulin variables, blood lipids, and blood markers of oxidative stress in persons with type 2 diabetes mellitus (median duration: 3.0 yr). Thirty-six subjects (9 men, 27 women; mean age: 61.3 yr; mean body mass index: 34.33 kg/m2) were supplemented with 400 microg Cr/d as Cr-enriched yeast (n = 19) or placebo (n = 17) for 12 wk in a randomized, double-blind study. The most interesting results were obtained by comparison of the change in the placebo group to the change in the Cr group. The Cr group showed a significantly greater increase in serum Cr compared to the placebo group (p < 0.05). Supplementation with Cr-enriched yeast was associated with a significant decrease in fasting serum glucose compared to placebo (p < 0.01). Blood markers of oxidative stress glutathione peroxidase activity and levels of reduced glutathione were essentially unchanged in the Cr group after 12 wk, but decreased significantly in the placebo group (p < 0.05, p < 0.01, respectively). Serum HbA1c and glycated protein (fructosamine) were essentially unchanged in the Cr group, whereas HbA1c tended to increase in the placebo group (from 6.94% to 7.11%). Fasting serum insulin decreased in both groups, with a greater tendency in the Cr group (-16.5% vs -9.5%). These data suggest that supplementation of well-controlled type 2 diabetics with Cr-enriched yeast is safe and can result in improvements in blood glucose variables and oxidative stress.

Aged↗

PubMed2005

Measure of glycosylated hemoglobin.

Glycosylated hemoglobin (HbA1c) is a marker of evaluation of long-term glycemic control in diabetic patients and predicts risks for the development and/or progression of diabetic complications. Glycosylation process depends on the exposure to glucose, so on the half-life of erythrocyte. It was demonstrated, however that metabolic control concerning the last 90-120 days had only a 10% effect on the result of HbAlc; mean blood glucose of the last 30 days contributes for 50% of HbA1c value. Blood glucose value in the afternoon and in the evening better correlate with HbA1c levels if compared with blood glucose values in the morning. It is important to know that there may be, in the evaluation of HbAlc, interference in the dosage, due to a condition of uremia, hyperlipemia, bad conservation and hemolysis of the sample, increase of leucocytes and presence of anomalous hemoglobins. Moreover the use of different methods, the lack of a common calibration concerning the same methods and the variability of instrumentation do not make reproducible results yet, in different laboratories.

Artifacts↗

PubMed2005

Congenital heart defects and maternal biomarkers of oxidative stress.

BACKGROUND: Women who have had pregnancies that were affected by nonsyndromic congenital heart defects have alterations in the homocysteine-methionine pathway that may indicate increased exposure to oxidative stress or reduced antioxidant defense or both. OBJECTIVE: Our goal was to establish a maternal metabolic risk profile for nonsyndromic congenital heart defects that would enhance current preventive strategies. DESIGN: Using a case-control design, we measured biomarkers of the transsulfuration pathway in a population-based sample of women whose pregnancies were affected by congenital heart defects (331 cases) and in a control group of women (125 controls). Plasma concentrations of reduced and oxidized glutathione, vitamin B-6, homocysteine, cysteine, cysteinylglycine (CysGly), and glutamylcysteine (GluCys) were compared between cases and controls after adjustment for lifestyle and sociodemographic variables. RESULTS: After covariate adjustment, cases had significantly lower mean plasma concentrations of reduced glutathione (P < 0.0001), GluCys (P < 0.0001), and vitamin B-6 (P = 0.0023) and significantly higher mean concentrations of homocysteine (P < 0.0001) and oxidized glutathione (P < 0.0001) than did controls. CONCLUSIONS: Biomarkers of oxidative stress involved in the transsulfuration pathway were significantly higher in women with pregnancies affected by congenital heart defects than in women without such a history. Further analysis of relevant biomarkers of oxidative stress and genetic and environmental factors is required to define the basis for the observed alterations. Identifying the nature and extent of alterations in biomarkers of oxidative stress may suggest primary intervention strategies and provide clues to a greater understanding of the pathogenesis of congenital heart defects.

Adult↗

PubMed1991

Use of laboratory tests for immune biomarkers in environmental health studies concerned with exposure to indoor air pollutants.

The immune system is likely to be involved in some of the health effects caused by certain indoor air exposures, and immune biomarkers can help determine which exposures and health effects have important immune components. However, the lack of standardized laboratory tests for most human immune markers and the many confounding variables that can influence them makes interpretation of results for exposure and disease end points uncertain. This paper presents an overview of the immune system and the considerations involved in using tests for immune markers in clinical epidemiology studies, particularly those concerned with indoor air exposures. Careful study design, well-characterized laboratory methods, and rigorous documentation of exposure status are required to determine the predictive value of such tests. Clinical tests currently available for some immune markers could help identify and characterize both irritative and hypersensitivity reactions to indoor air pollutants. Newer tests developed in research settings might provide more incisive indicators of immune status that could help identify exposure, susceptibility, or preclinical disease states, but their methodologies must be refined and tested in multicenter studies before they can be used reliably in public health applications.

Air Pollutants↗

PubMed2003

A biomarker of n-3 compliance in patients taking fish oil for rheumatoid arthritis.

Dietary fish oil supplements have been shown to have benefits in rheumatoid arthritis (RA), other inflammatory diseases, and in cardiovascular disease. As with any medical advice, variability will exist with regard to adherence and consequent biochemical or pharmacophysiologic effects. The aim was to explore the utility of plasma phospholipid EPA as a measure of n-3 PUFA intake and response to standardized therapeutic advice given in an outpatient or office practice setting, to increase dietary n-3 PUFA, including a fish oil supplement. Patients with early RA were given verbal and written advice to alter their dietary n-3 PUFA intake, including ingestion of 20 mL of bottled fish oil on juice daily. The advice included instructions to increase n-3 PUFA and to avoid foods rich in n-6 PUFA. Every 3 mon, blood samples were obtained for analysis of plasma phospholipid FA. Plasma phospholipid EPA was used as the primary index of n-3 PUFA intake. A diverse response was seen, with about one-third of patients achieving a substantial elevation of plasma phospholipid EPA over the 12-mon study period. A third had little change, with the remainder achieving intermediate levels. Data obtained longitudinally from individual patients indicated that substantial elevations of EPA (> 5% total plasma phospholipid FA) could be maintained for more than 3 yr. Plasma phospholipid EPA is a convenient measure of adherence to advice to take a dietary n-3 PUFA-rich fish oil supplement This measure may prove a useful adjunct to intention to treat analyses in determining the effect of dietary fish oil supplements on long-term outcomes in arthritis and other chronic inflammatory diseases. It may also provide a guide to the effectiveness of therapeutic and preventive messages designed to increase n-3 PUFA intake.

Arachidonic Acid↗

PubMed2004

Flow cytometric detection of intracellular TH1/TH2 cytokines using whole blood: validation of immunologic biomarker for use in epidemiologic studies.

Few biological markers of immune function have been thoroughly validated for use in epidemiologic studies that involve delayed sample processing and analysis. Here, we report our validation results for flow cytometric detection of intracellular T-helper 1/T-helper 2 (Th1/Th2) cytokines using 500 microL of whole blood obtained from children and adults. The detection of Th1/Th2 cytokine profiles by flow cytometry is a practical and mechanistically relevant assay because dysregulated cytokine production has been observed in many immune-mediated disorders, including cancer. We evaluated the intraassay and intraindividual and interindividual variability and the effects of a 24- to 72-hour delayed analysis on Th1 and Th2 end points. We compared the distributions of %CD4 lymphocytes, %Th1, and %Th2 in young children (age 1 year, n = 50) and adults (age 25-52 years, n = 16). Subjects sampled monthly for up to 1 year showed minimal variation in CD4, Th1, and Th2 end points. Delayed analysis of samples (up to 24 hours) resulted in no significant differences in the expression of CD4, Th1, and Th2; however, at 48 and 72 hours, all end points differed significantly from baseline (P < 0.01). A random effects model confirmed that interindividual variability was much greater than intraindividual variability for CD4 and Th1. Compared with adults, children had marginally higher %CD4, similar %Th2, but significantly lower %Th1 (P < 0.01). These results show that flow cytometric detection of CD4, Th1, and Th2 markers using whole blood is reproducible and that these biomarkers can be effectively used in human population studies that involve transported samples, delayed processing and analysis, and limited blood volumes.

Adult↗

PubMed2000

[The public health significance of the measurement of cytokines in serum].

As variable functions of cytokines have been proved in recent years, cytokine levels in biological fluids such as serum, plasma, and synovial fluid of patients with every kind of disease have been enthusiastically measured. As a result, many studies have shown an increase or decrease in the production of cytokines or abnormal cytokine levels in biological fluids. However, the relationship between the abnormal levels of cytokines and the intensity of the clinical symptoms or the prognosis remains unclear. The significance for the measurement of cytokines depends on whether it should be valid for detecting a preclinical status such as AST or ALT used for health checks or for disease screening such as some tumor markers. The purpose of this study is to know whether or not some cytokine levels in serum could be biomarkers for preventive purposes. Serum cytokine levels (IL-4, 6, 8, 12, and IFN-gamma) were measured in three different types of cohorts (nursery school infants, manufacturing workers and middle and old aged women) with chemiluminescence ELISA. The results showed no differences with atopic status in infants, pulmonary fibrosis in workers or with the decrease in bone stiffness, these results are mainly due to a great inter-individual variability of serum cytokine levels. This study concludes that serum cytokine levels are inappropriate as biomarkers for preventive purposes. However, a further detailed evaluation in healthy people with high serum cytokine levels may be necessary.

Adolescent↗

PubMed2006

Clinical implications of ZAP-70 expressionin chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a disease with an extremely heterogeneous prognosis. Because of this and because of the lack of a truly effective therapy, treatment of CLL must be adapted to the individual risk of each patient. Over the last quarter of century, prognosis of patients with CLL has been based on clinical features. In the last few years a number of biological prognostic parameters have been identified. Among them, the expression of ZAP-70 in neoplastic B lymphocytes is increasingly being recognized as of paramount importance to predict outcome. Patients with a low percentage (<20%) of ZAP-70 positive neoplastic B lymphocytes have a much better prognosis that those with a higher proportion (>20%) of ZAP-70 positive neoplastic B lymphocytes.

Biomarkers, Tumor↗

PubMed2005

Signature of B-CLL with different prognosis by Shrunken centroids of surface antigen expression profiling.

With the aim of identifying the immunophenotypic profile of B-cell chronic lymphocytic leukemia (B-CLL) subsets with different prognosis, we investigated by flow cytometry the expression of 36 surface antigens in 123 cases, all with survivals. By analyzing results with unsupervised (hierarchical and K-means clustering) algorithms, three distinct immunophenotypic groups (I, II, and III) were identified, group I (51/123) with longer survivals, as compared to the group II (36/123) and III (36/123). The immunophenotypic signatures of these groups, as determined by applying the nearest Shrunken centroids method as class predictor, were characterized by the coordinated and differential expression of 12 surface markers, that is, group I: above-average expression of CD62L, CD54, CD49c, and CD25, below-average expression of CD38; group II: above-average expression of CD38, CD49d, CD29, and CD49e; and group III: below-average expression of the above markers, overexpression of CD23, CD20, SmIg, and CD79b. As opposed to groups II-III, group I B-CLLs lacked expression of ZAP-70 and activation-induced cytidine deaminase in the majority of cases, while more frequently had mutated IgV(H) genes and IgV(H) mutations consistent with antigen-driven selection. Our findings contribute to improve the immunophenotypical identification of disease subsets with different prognosis and suggest a set of surface antigens to be employed as prognosticators in routine diagnostic/prognostic procedures.

Adult↗

PubMed2004

Combining longitudinal studies of PSA.

Prostate-specific antigen (PSA) is a biomarker commonly used to screen for prostate cancer. Several studies have examined PSA growth rates prior to prostate cancer diagnosis. However, the resulting estimates are highly variable. In this article we propose a non-linear Bayesian hierarchical model to combine longitudinal data on PSA growth from three different studies. Our model enables novel investigations into patterns of PSA growth that were previously impossible due to sample size limitations. The goals of our analysis are twofold: first, to characterize growth rates of PSA accounting for differences when combining data from different studies; second, to investigate the impact of clinical covariates such as advanced disease and unfavorable histology on PSA growth rates.

Adult↗

PubMed1999

Molecular and clinical remissions in multiple myeloma: role of autologous and allogeneic transplantation of hematopoietic cells.

PURPOSE: To describe molecular monitoring of minimal residual disease in patients with myeloma who have achieved complete remission (CR) after autologous or allogeneic transplantation of hematopoietic cells. MATERIALS AND METHODS: Clonal markers based upon the rearrangement of immunoglobulin heavy-chain genes were generated for each patient and used for polymerase chain reaction (PCR) detection of residual myeloma cells. Fifty-one patients entered the program and 36 achieved CR. After transplantation, molecular monitoring was performed on 29 patients (15 autologous and 14 allogeneic transplants) who had molecular markers. RESULTS: Our data show that molecular remissions are rarely achieved (7%) with high-dose chemotherapy followed by single or double autografting. In addition, virtually all peripheral blood progenitor cell and bone marrow samples contained residual myeloma cells, even when sample collection was scheduled after repeated courses of high-dose chemotherapy. All patients autografted with PCR-positive cells remain positive, and eight of 15 have relapsed. Two patients were autografted with PCR-negative cells: one is in clinical and molecular remission, and one relapsed 25 months after the transplant. In the allografting setting, a higher proportion of patients (50%) achieved molecular remission; there were two relapses, one in the PCR-positive group and one in the PCR-negative group. CONCLUSION: This is the first large study of molecular remissions in myeloma patients to use a PCR-based approach utilizing patient-specific tumor markers. The sizeable fraction of patients who achieved molecular remission after allografting with peripheral blood progenitor cells represents a promising finding in an incurable disease.

Adult↗

PubMed2001

Species-crossreactive scFv against the tumor stroma marker "fibroblast activation protein" selected by phage display from an immunized FAP-/- knock-out mouse.

BACKGROUND: Fibroblast activation protein (FAP) is a type II membrane protein expressed on tumor stroma fibroblasts in more than 90% of all carcinomas. FAP serves as a diagnostic marker and is potential therapeutic target for treatment of a wide variety of FAP+ carcinomas. Murine tumor stroma models and FAP-specific antibodies are required to investigate the functional role of FAP in tumor biology and its usefulness for drug targeting. We here describe the development of antibodies with crossreactivity for human (hFAP) and murine FAP (mFAP), which share 89% amino acid identity. MATERIAL AND METHODS: An FAP-/- mouse was sequentially immunized with recombinant murine and human FAP-CD8 fusion proteins. Immunoglobulin cDNA derived from hyperimmune spleen cells was used for the construction of a combinatorial single chain Fv (scFv) library. Phage display selection of FAP-specific scFv was performed on immobilized hFAP followed by selection on cells expressing murine FAP. RESULTS: High-affinity, species-crossreactive, FAP-specific scFv were isolated upon sequential phage display selection. A bivalent derivative (minibody M036) constructed thereof was applied for immunohistochemical analyses and allowed detection of FAP expression on stroma cells of different human carcinomas as well as on murine host stroma in a tumor xenograft model. CONCLUSIONS: MB M036, derived from phage display selected species crossreactive scFv, is suitable for tumor stroma targeting and will be a valuable tool in the analyses of the functional role of FAP in tumor biology as well as in the evaluation of the suitability of FAP for drug targeting.

Amino Acid Sequence↗

PubMed2005

Endocrine biomarkers in ductal lavage samples from women at high risk for breast cancer.

BACKGROUND: Ductal lavage is a method of minimal epithelial sampling of the breast, with potential utility for repeat sampling and biomarker analysis in chemoprevention studies. We report here the baseline findings from a study designed to assess the utility of ductal lavage in this setting. METHODS: Tamoxifen-eligible, high-risk women underwent ductal lavage; epithelial cell number (ECN) and morphology were assessed on Papanicolaou-stained slides. Additional slides were immunostained for estrogen receptor (ER) alpha, Ki-67, and cyclooxygenase-2, and the labeling index (LI) was established by counting negative and positive cells. The ductal lavage supernatant (DLS) was assayed for estradiol, several of its precursors, progesterone, cathepsin D, interleukin-6, and epidermal growth factor (EGF). RESULTS: One hundred sixty-eight women have entered the study (mean age, 51 years; mean 5-year Gail score, 2.8). Ductal lavage was accomplished in 145 (86.3%) women. Data were analyzed by duct and by woman (averaging data across all ducts). Mild atypia was seen in 43 of 145 (29.6%), whereas severe atypia was seen in 2 (1.4%) of women. We observed significant positive correlations between ECN and cytologic atypia, ER LI, cyclooxygenase-2 LI, and Ki-67 LI. EGF levels in supernatant were significantly associated with estrogenic precursors, ER LI and ECN. A factor representing the DLS hormone and protein variables explained 36% of the variance; total ECN was highest when factor score and ER LI were high and was lowest when both were low (P for interaction = 0.001). CONCLUSIONS: Biomarker analyses in epithelial cells and DLS are feasible. The significant associations of EGF with other markers suggest a possible role in increasing epithelial cell mass.

Biomarkers, Tumor↗

PubMed2002

Biomarkers for male reproductive health hazards: are they available?

This review aims to give an overview of some of the biomarkers that have been used for the monitoring of human exposure to xenobiotics as well as to provide a summary of some of the recent epidemiological studies on male reproductive health of exposure to environmental and occupational toxicants. Possible molecular mechanisms on seminal quality change are also suggested. Studies using various biomarkers have no doubt enabled us to better characterize the effect of environmental pollutants on the male reproductive system. However, the sensitivity and specificity of these biomarkers have not been comprehensively validated. Furthermore, many epidemiological findings are difficult to replicate owing to the inherited methodological problems of male reproductive health investigations, such as the small number of study subjects, low compliance rate, substantial intra-individual variability in semen parameters, measurement techniques and misclassifications based on single assay. Oxidative damage, in particular DNA-damage caused by free radicals, generated either by xenobiotics, or endogenously, is now thought to be a key molecular mechanism associated with semen quality and sperm function. Laboratory studies and epidemiological findings have suggested that the male reproductive system is susceptible to reactive oxygen species (ROS). On the other hand, there is so far no single all-encompassing biomarker of reproductive capacity in men. A panel of biomarkers with specific goals should be considered. Collaborative multidisciplinary studies are also needed to overcome some of the issues mentioned here.

Biomarkers↗