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Results for “Biomarker variability”

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PubMed2004

Reconstructing population exposures from dose biomarkers: inhalation of trichloroethylene (TCE) as a case study.

Physiologically based pharmacokinetic (PBPK) modeling is a well-established toxicological tool designed to relate exposure to a target tissue dose. The emergence of federal and state programs for environmental health tracking and the availability of exposure monitoring through biomarkers creates the opportunity to apply PBPK models to estimate exposures to environmental contaminants from urine, blood, and tissue samples. However, reconstructing exposures for large populations is complicated by often having too few biomarker samples, large uncertainties about exposures, and large interindividual variability. In this paper, we use an illustrative case study to identify some of these difficulties, and for a process for confronting them by reconstructing population-scale exposures using Bayesian inference. The application consists of interpreting biomarker data from eight adult males with controlled exposures to trichloroethylene (TCE) as if the biomarkers were random samples from a large population with unknown exposure conditions. The TCE concentrations in blood from the individuals fell into two distinctly different groups even though the individuals were simultaneously in a single exposure chamber. We successfully reconstructed the exposure scenarios for both subgroups - although the reconstruction of one subgroup is different than what is believed to be the true experimental conditions. We were however unable to predict with high certainty the concentration of TCE in air.

Adult↗

PubMed2001

Validation of biomarkers as early predictors of disease.

The development and validation of biomarkers that link environmental exposures to the pathogenesis of human disease is a leading priority in the field of environmental research. The validation of biomarkers as early predictors of clinical disease can enhance health risk assessment and contribute to effective new disease prevention policies in environmental and occupational settings. The process of validating biomarkers involves dealing with a range of characteristics that include the intrinsic qualities of the biomarker, its determinants, and the analytic procedure. We discuss here a three phase approach to validation. The final phase, consisting of longitudinal studies, is reached after the biomarker has been determined to be technically reliable and after the effect of external variables on the association with the outcome has been evaluated. We provide some examples of biomarkers reputed to be early predictors of cancer and cardiovascular disease (CVD). We then present original data to support the potential of DNA adducts to predict cancer and show, through re-evaluation of the Italian database on cytogenetic biomarkers, a lack of association between the frequency of chromosomal aberrations in circulating lymphocytes and CVD mortality rates -- a finding that should not be considered conclusive. In general, whenever a biomarker has been determined to be a valid predictor of disease, it should be used in risk assessment and public health policy.

Biomarkers↗

PubMed2006

Patient attitudes towards self-report and biomarker alcohol screening by primary care physicians.

AIMS: One of the many barriers to more frequent alcohol screening by primary care physicians is a reported concern that patients may be offended by questions about drinking. However, evidence suggests that patients do not object to alcohol screening and actually expect physicians to ask about lifestyle factors that influence their health. The aim of this study was to provide more detailed information on patient attitudes toward self-report and biomarker alcohol screening and to explore whether demographic variables were related to these attitudes. METHODS: We administered (i) a survey about attitudes towards alcohol screening, and (ii) the Alcohol Use Disorders Identification Test-C (AUDIT-C) to primary care outpatients at the time of their medical appointments. The survey contained 10 items on patient opinions about being screened for at-risk drinking by physicians. Participants rated their levels of agreement with each statement using a 5-point Likert scale. Participants also provided demographic information. RESULTS: The majority of patients reported that they were supportive of physician screening about alcohol use. Responses on 3 of the 10 statements were related to patient race, age, and/or AUDIT-C results. CONCLUSIONS: In general, results support the fact that patients are in favour of being screened for at-risk drinking by their physicians whether the screening instrument was a self-report measure or an alcohol biomarker laboratory test. In addition, the majority of patients are open to advice from physicians about their alcohol use.

Adult↗

PubMed2006

Phylogenetic and functional biomakers as indicators of bacterial community responses to mixed-waste contamination.

Few studies have demonstrated changes in community structure along a contaminant plume in terms of phylogenetic, functional, and geochemical changes, and such studies are essential to understand how a microbial ecosystem responds to perturbations. Clonal libraries of multiple genes (SSU rDNA, nirK, nirS, amoA, pmoA, and dsrAB) were analyzed from groundwater samples (n = 6) that varied in contaminant levels, and 107 geochemical parameters were measured. Principal components analyses (PCA) were used to compare the relationships among the sites with respect to the biomarker (n = 785 for all sequences) distributions and the geochemical variables. A major portion of the geochemical variance measured among the samples could be accounted for by tetrachloroethene, 99Tc, No3, SO4, Al, and Th. The PCA based on the distribution of unique biomarkers resulted in different groupings compared to the geochemical analysis, but when the SSU rRNA gene libraries were directly compared (deltaC(xy) values) the sites were clustered in a similar fashion compared to geochemical measures. The PCA based upon functional gene distributions each predicted different relationships among the sites, and comparisons of Euclidean distances based upon diversity indices for all functional genes (n = 432) grouped the sites by extreme or intermediate contaminant levels. The data suggested that the sites with low and high perturbations were functionally more similar than sites with intermediate conditions, and perhaps captured the overall community structure better than a single phylogenetic biomarker. Moreover, even though the background site was phylogenetically and geochemically distinct from the acidic sites, the extreme conditions of the acidic samples might be more analogous to the limiting nutrient conditions of the background site. An understanding of microbial community-level responses within an ecological framework would provide better insight for restoration strategies at contaminated field sites.

Bacteria↗

PubMed2025

Prenatal organophosphate ester exposure and epigenetic changes at birth: a characterization of the methylome in the ECHO cohort.

BACKGROUND: Prenatal exposure to organophosphate esters (OPEs) affects multiple child health domains. Alterations to the DNA methylome are a plausible mechanism through which these changes occur. This study characterized DNA methylation signatures at birth associated with prenatal OPE biomarkers. METHODS: We included 736 mother-infant pairs from 7 sites in the Environmental influences on Child Health Outcomes (ECHO) Cohort. Five OPE biomarkers were quantified in maternal urine samples collected during the second and third trimesters and modeled as log2-transformed continuous variables. Using covariate-adjusted linear regression, we tested associations between OPE biomarkers and locus-specific, regional, and global cord blood DNA methylation changes measured by Illumina 450 K and EPIC arrays, and gestational epigenetic age measured by the Knight gestational age epigenetic clock generated with measures from the 27 K, 450 K, and EPIC arrays. When feasible, we examined relationships by sex. FINDINGS: Global hypomethylation at multiple regions was associated with BDCPP concentrations (p = 0.003 to 0.02, coef = -0.002). Differentially methylated regions annotated to PCDHGB1 and SLC43A2 were associated with BDCPP and DPHP concentrations, respectively (FDR q < 0.05). In sex-specific analyses, global hypomethylation was associated with prenatal BDCPP (p = 0.006 to 0.03, coef = -0.0003 to -0.0002) and DBUP_DIBP (p = 0.01, coef = -0.0007 to -0.0006) concentrations in females; and global hypermethylation was associated with DBUP_DIBP concentrations in males (p < 0.05, coef = 0.0004). BCETP concentrations were significantly associated with decelerated epigenetic aging at birth in females (p < 0.05, coef = -0.05). INTERPRETATION: Prenatal exposure to OPEs impacts child methylation at birth, suggesting a potential mechanism for the association between prenatal OPE exposure and child health outcomes.

Humans↗

PubMed1995

Molecular and pathologic markers in stage I non-small-cell carcinoma of the lung.

PURPOSE: Although standard treatment of stage I non-small-cell lung cancer (NSCLC) consists of surgical resection alone, approximately 50% of clinical stage I and 30% to 40% of pathologic stage I patients have disease recurrence and die following curative resection. A large number of traditional pathologic and newer molecular markers have been identified, which appear to have important prognostic significance in this population. This review attempts to summarize these data comprehensively. METHODS: Criteria for study selection were English-language reports, identified using Medline and Cancerline, through the fall of 1994. Abstracts from the American Society of Clinical Oncology (ASCO) and the International Association for the Study of Lung Cancer (IASLG) were also reviewed. RESULTS: Molecular markers are classified as molecular genetic markers, differentiation markers, proliferation markers, and markers of metastatic propensity. A number of these markers have been reported to be highly predictive of outcome in stage I NSCLC, and several reports conclude that a specific biomarker may be, aside from clinical stage, the most powerful determinant of prognosis in NSCLC. However, little has been done to clarify the relationships between these newer biologic markers, classic clinicopathologic variables, and clinical outcome. CONCLUSION: At present, a firm conclusion regarding which biomarkers are most important in predicting outcome is not possible, and a model that reliably integrates all independent prognostic variables cannot be developed. A prospective trial is mandatory to address this issue, and a study design is suggested that would facilitate the development of a prognostic index, while simultaneously asking a therapeutic question. The development of a prognostic index would facilitate future trials in which only high-risk stage I patients could be targeted for investigation of postresection adjuvant treatment strategies.

Biomarkers↗

PubMed2004

Comparison of basal gene expression profiles and effects of hepatocarcinogens on gene expression in cultured primary human hepatocytes and HepG2 cells.

Toxicogenomics is a relatively new discipline of toxicology. Microarrays and bioinformatics tools are being used successfully to understand the effects of toxicants on in vivo and in vitro model systems, and to gain a better understanding of the relevance of in vitro models commonly used in toxicological studies. In this study, cDNA filter arrays were used to determine the basal expression patterns of human cultured primary hepatocytes from different male donors; compare the gene expression profile of HepG2 to that of primary hepatocytes; and analyze the effects of three genotoxic hepatocarcinogens; aflatoxin B(1) (AFB(1)), 2-acetylaminofluorene (2AAF), and dimethylnitrosamine (DMN), as well as one non-gentoxic hepatotoxin, acetaminophen (APAP) on gene expression in both in vitro systems. Real-time PCR was used to verify differential gene expression for selected genes. Of the approximately 31,000 genes screened, 3-6% were expressed in primary hepatocytes cultured on matrigel for 16 h. Of these genes, 867 were expressed in cultured hepatocytes from all donors. HepG2 cells expressed about 98% of the genes detectable in cultured primary hepatocytes, however, 31% of the HepG2 transcriptome was unique to the cell line. A number of these genes are expressed in human liver but expression is apparently lost during culture. There was considerable variability in the response to chemical carcinogen exposure in primary hepatocytes from different donors. The transcription factors, E2F1 and ID1 mRNA were increased three-fold and six-fold (P < 0.05, P < 0.01), respectively, in AFB(1) treated primary human hepatocytes but were not altered in HepG2. ID1 expression was also increased by dimethylnitrosamine, acetylaminofluorene and acetaminophen in both primary hepatocytes and HepG2. Identification of genes that are expressed in primary hepatocytes from most donors, as well as those genes with variable expression, will aid in understanding the variability in human reactions to drugs and chemicals. This study suggests that identification of biomarkers of exposure to some chemicals may be possible in the human through microarray analysis, despite the variability in responses.

Carcinogens↗

PubMed2006

Occurrence and daily variation of phthalate metabolites in the urine of an adult population.

Phthalates like di-(2-ethylhexyl) phthalate (DEHP) are commonly used as plasticizers and their metabolites are suspect of especially reproductive toxicity. The aim of our study was to assess phthalate exposure in adults by measuring urinary phthalate metabolite levels and to explore individual temporal variability. Urine samples were collected by 27 women and 23 men aged 14-60 years during 8 consecutive days. We quantified four monoesters, four oxidative DEHP metabolites, and two secondary metabolites of di-isononyl phthalate (DiNP) by a LC/LC-MS/MS method. If we analyzed all 399 available samples independent of classification, the highest median values of primary metabolites in this study were found for mono-n-butyl phthalate (MnBP: 49.6 microg/l), followed by mono-isobutyl phthalate (MiBP: 44.9 microg/l), mono-benzyl phthalate (MBzP: 7.2 microg/l), and mono-2-ethylhexyl phthalate (MEHP: 4.9 microg/l). The median concentrations of the oxidized metabolites of DEHP were 8.3 microg/l for mono-(2-carboxymethylhexyl) phthalate (2cx-MMHP), 19.2 microg/l for mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), 14.7 microg/l for mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), and 26.2 microg/l for mono-(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP). The concentrations of the two DiNP secondary metabolites mono (oxoisononyl) phthalate (oxo-MiNP) and mono(hydroxyisononyl) phthalate (OH-MiNP) ranged from <LOD to 304 microg/l (median: 3.0 microg/l, 2.9 microg/g creatinine) and <LOD to 698 microg/l (median: 5.5 microg/l, 5.2 microg/g creatinine), respectively. Phthalate metabolite levels did not consistently differ by sex or age. There was substantial day-to-day variation of urinary levels with considerable within-subject variability. Intraclass correlation coefficients adjusted for sex and age ranged between 0.21 and 0.48 for unadjusted metabolite levels and between 0.20 and 0.57 for creatinine-adjusted levels. The secondary metabolites of DiNP were detectable in nearly all samples and were therefore sensitive biomarkers of DiNP exposure. Our results of within-subject variability suggest that exposure assessment should not be based on a single urine measurement.

Adolescent↗

PubMed2005

Increased high sensitivity C-reactive protein and neutrophil count are related to increased standard cardiovascular risk factors in healthy Chinese men.

BACKGROUND: Epidemiologic data regarding the role of inflammation in atherosclerosis have been based mainly on Caucasian populations. Thus, we analyzed the cross-sectional relationships of inflammatory biomarkers to cardiovascular risk factors (CVRF) and related variables in a large group of healthy Chinese men, a population with a markedly lower heart disease mortality rate compared with Western populations. METHODS: The study consisted of 8374 men aged 20-80 who attended a voluntary health examination at a metropolitan university center between 1997 and 2002. The relationships between serum high sensitivity C-reactive protein (hsCRP), total white blood cell (WBC), neutrophil, and monocyte counts to CVRF were analyzed using multivariate linear and logistic regression analyses. Whether a dose-response effect existed between elevated levels of each marker and increasing numbers of CVRF was also evaluated. RESULTS: The distribution of hsCRP was similar to Western studies. Both multivariate regression analyses showed all four markers to have significant correlations with body mass index, triglycerides, and adverse high density lipoprotein/low density lipoprotein ratio. Smoking was associated with increased levels of all four markers. Elevated neutrophil count had the most markedly progressive dose-response effect with increasing numbers of CVRF, whereas elevated monocyte count showed a drop in risk with CVRF of five and above. CONCLUSION: We show in our study that with increasing numbers of standard CVRF, healthy Chinese men have progressive and increasing risks of having elevated levels of hsCRP, total WBC, and neutrophil counts. While the inflammatory markers surveyed were largely correlated with CVRF, the similar values of CRP between populations with divergent mortality rates suggest that a more complex relationship may exist between CRP and disease outcome. The possible utility of neutrophil count as a marker for cardiovascular disease risk in healthy men awaits further evaluation in prospective studies.

Adult↗

PubMed2004

Semen quality and reproductive endocrine function with regard to blood cadmium in Croatian male subjects.

In 123 Croatian men with no occupational exposure to metals, the influence of cadmium on reproductive parameters was examined after adjusting for age, smoking, alcohol, and biomarkers of lead, copper, zinc, and selenium. The following variables were measured: blood cadmium (BCd), blood lead (BPb), activity of delta-aminolevulinic acid dehydratase (ALAD), erythrocyte protoporphyrin, serum copper (SCu), serum zinc (SZn), serum selenium (SSe), activity of glutathione peroxidase (GPx) in blood, testis size, semen quality (including sperm concentration, motility, viability, and morphology), indicators in seminal fluid (the lactate dehydrogenase isoenzyme LDH-C4, fructose, zinc, acid phosphatase, and citric acid), and hormones in serum (follicle-stimulating hormone--FSH, luteinizing hormone, prolactin, testosterone, and estradiol). The median and range BCd values were 2.94 (0.49-11.93) microg/L in 61 smokers and 0.59 (0.20-3.71) microg/L in 62 nonsmokers (p < 0.0001). Smoking habits (cigarettes/day) highly significantly correlated with BCd (p < 0.0001). After adjusting for potential confounding variables by multiple regression, BCd was significantly associated with a decrease in testis size (p < 0.03) and an increase in serum estradiol (p < 0.005), FSH (p < 0.03), and testosterone (p < 0.04). Smoking was significantly associated with a decrease in serum prolactin (p < 0.006) and LDH-C4 in seminal fluid (p < 0.03). Several reproductive parameters were significantly associated with BPb and ALAD, biomarkers of lead, and/or with SCu, SZn, SSe, and GPx. The necessity of controlling for various metals, and other potential confounders when assessing the influence of a particular metal on reproductive function in men, is emphasized.

Adult↗

PubMed2002

Assessment of histologic features and expression of biomarkers in predicting pathologic response to anthracycline-based neoadjuvant chemotherapy in patients with breast carcinoma.

BACKGROUND: There is significant variability in the response of tumors to neoadjuvant chemotherapy, and the underlying mechanism for this variability is unknown. In this study, the authors investigated the roles of tumor nuclear grade, mitotic activity, and biomarker expression profiles in predicting the pathologic response of breast tumors to preoperative chemotherapy. METHODS: Eighty-two patients with breast carcinoma participated in two clinical trials and were treated with neoadjuvant chemotherapy, which consisted of either a conventional dose of fluorouracil, doxorubicin, and cyclophosphamide (FAC) or dose-escalated FAC. The mean age of the patients was 46 years (range, 24-69 years). Nuclear grade, mitotic activity, and biomarker profile (Her2-neu and mitosin expression patterns) in pretreatment tumors were correlated with the postchemotherapy pathologic response. RESULTS: Twelve patients (15%) had a complete pathologic response (CPR), 23 patients (28%) had a near complete response (NCR), and 47 patients (57%) had significant residual disease present either at the primary site or in the axillary lymph nodes. The authors found that the nuclear grade and mitotic activity of pretreatment tumors were correlated significantly with CPR and NCR (P = 0.002 and P = 0.004). Mitosin also was correlated significantly with CPR and NCR (P = 0.028). A higher percentage of patients with Her2-neu-positive tumors had a CPR or an NCR (P = 0.152). CPR and NCR were not correlated significantly with disease stage (P = 0.186) or lymph node positivity (P = 0.498). CONCLUSIONS: The current results indicate that tumor nuclear grade and tumor proliferative activity (mitotic activity and mitosin immunostaining) of pretreatment tumors in patients with breast carcinoma may serve as important indicators for the pathologic responsiveness of tumors to neoadjuvant, anthracycline-based chemotherapy.

Adult↗

PubMed2026

Organoids in translation: a bench-to-bedside framework for pancreatic cancer precision medicine.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with a 5-year survival rate of < 13%. Standard treatments such as FOLFIRINOX or gemcitabine/nab-paclitaxel yield modest response rates, underscoring the urgent need for precision oncology approaches. Patient-derived organoids (PDOs) preserve the genomic, phenotypic, and histopathological features of the source tumor and offer a promising platform for drug screening, biomarker development, and personalized therapy. However, a systematic evaluation of their translational capacities is lacking. METHODS: A systematic review was conducted according to the PRISMA 2020 guidelines (PROSPERO registration pending) using PubMed, EMBASE, and Cochrane CENTRAL (December 10, 2024) to identify English-language PDAC PDO studies that incorporated therapeutic testing. Ninety-five studies met the inclusion criteria. Data extraction captured >75 variables per study, including spanning culture methodology, therapeutic profiling, biomarker integration, and clinical correlation. A 13-domain weighted Translatability Scoring Framework adapted from Wehling et al. assessed predictive validity, biomarker strength, pharmacogenetics, and clinical trial alignment. Scores ranged from 0 to 5 and were categorized as good (>4.0), moderate (3.0-4.0), or low (<3.0) translational potential. RESULTS: Of the 95 studies, 70.5% have been published since 2021, reflecting the rapid growth in this field. The mean PDO generation success rate was 89.7%, with the primary tumor tissue being the predominant source (48.4%). Only 24.8% were directly linked to clinical trials and 5.3% incorporated multi-omic profiling. The median translatability score was 3.13 (range, 1.72-4.59): 45.3% of the studies had low translatability, 50.5% moderate, and only 4.2% had good translational potential. High-scoring studies consistently combine multi-omic biomarker platforms, in vivo validation, clinical outcome correlation, and prospective trial integration. Conversely, the weakest domains were pharmacogenetics, endpoint strategies, and biomarker validation, limiting their overall clinical relevance. CONCLUSIONS: PDOs have demonstrated strong feasibility and in vitro clinical correlation in PDAC; however, their clinical translation remains constrained by limited multi-omic integration, absence of pharmacogenomic modeling, and sparse clinical trial embedding. Standardization of protocols, adoption of harmonized and clinically relevant endpoints, and systematic incorporation of biomarker-driven co-clinical trial frameworks are urgently needed to transition PDOs from promising experimental surrogates to validating precision oncology tools capable of informing therapeutic decision-making in PDAC.

Humans↗

PubMed2006

Sub-speciating Campylobacter jejuni by proteomic analysis of its protein biomarkers and their post-translational modifications.

We have identified several protein biomarkers of three Campylobacter jejuni strains (RM1221, RM1859, and RM3782) by proteomic techniques. The protein biomarkers identified are prominently observed in the time-of-flight mass spectra (TOF MS) of bacterial cell lysate supernatants ionized by matrix-assisted laser desorption/ionization (MALDI). The protein biomarkers identified were: DNA-binding protein HU, translation initiation factor IF-1, cytochrome c553, a transthyretin-like periplasmic protein, chaperonin GroES, thioredoxin Trx, and ribosomal proteins: L7/L12 (50S), L24 (50S), S16 (30S), L29 (50S), and S15 (30S), and conserved proteins similar to strain NCTC 11168 proteins Cj1164 and Cj1225. The protein biomarkers identified appear to represent high copy, intact proteins. The significant findings are as follows: (1) Biomarker mass shifts between these strains were due to amino acid substitutions of the primary polypeptide sequence and not due to changes in post-translational modifications (PTMs). (2) If present, a PTM of a protein biomarker appeared consistently for all three strains, which supported that the biomarker mass shifts observed between strains were not due to PTM variability. (3) The PTMs observed included N-terminal methionine (N-Met) cleavage as well as a number of other PTMs. (4) It was discovered that protein biomarkers of C. jejuni (as well as other thermophilic Campylobacters) appear to violate the N-Met cleavage rule of bacterial proteins, which predicts N-Met cleavage if the penultimate residue is threonine. Two protein biomarkers (HU and 30S ribosomal protein S16) that have a penultimate threonine residue do not show N-Met cleavage. In all other cases, the rule correctly predicted N-Met cleavage among the biomarkers analyzed. This exception to the N-Met cleavage rule has implications for the development of bioinformatics algorithms for protein/pathogen identification. (5) There were fewer biomarker mass shifts between strains RM1221 and RM1859 compared to strain RM3782. As the mass shifts were due to the frequency of amino acid substitutions (and thus underlying genetic variations), this suggested that strains RM1221 and RM1859 were phylogenetically closer to one another than to strain RM3782 (in addition, a protein biomarker prominent in the spectra of RM1221 and RM1859 was absent from the RM3782 spectrum due to a nonsense mutation in the gene of the biomarker). These observations were confirmed by a nitrate reduction test, which showed that RM1221 and RM1859 were C. jejuni subsp. jejuni whereas RM3782 was C. jejuni subsp. doylei. This result suggests that detection/identification of protein biomarkers by pattern recognition and/or bioinformatics algorithms may easily subspeciate bacterial microorganisms. (6) Finally, the number and variation of PTMs detected in this relatively small number of protein biomarkers suggest that bioinformatics algorithms for pathogen identification may need to incorporate many more possible PTMs than suggested previously in the literature.

Amino Acid Sequence↗

PubMed2004

Some aspects of interrelations between fungi and other biota in forest soil.

Interrelations of fungal mycelium with other soil biota are of paramount importance in forestry and soil ecology. Here we present the results of statistical analysis of a comprehensive data set collected in the first (and the only) British fungus sanctuary over a period of four months. The variables studied included a number of soil properties, bacteria, protozoan flagellates, ciliates and amoebae, microbial and plant feeding nematodes, various microarthropods, and two fungal biomarkers--glomalin and ergosterol. One way ANOVA showed that the dynamics of the microbiota studied was influenced by seasonal changes. Superimposed on these changes, however, was variability due to biological interactions and habitat characteristics. Two fungal biomarkers, ergosterol and glomalin, were differently influenced by other biota and abiotic variables. The results indicate that the dynamics of soil fungi is influenced not only by soil microarthropods, but also by those found in forest litter. The overall outcome, therefore, is likely to be very complex and will depend upon specific conditions of any particular ecosystem.

Animals↗

PubMed2005

Laboratory markers for COPD in "susceptible" smokers.

Smoking is the major risk factor for the development of chronic obstructive pulmonary disease. Apart from the important preventive steps of smoking cessation, there are no other specific treatments for COPD that are as effective in reversing the condition. However, only a relatively small proportion of smokers-about 15%-will develop clinically relevant COPD. Allergy, airway hyper-responsiveness (AHR) to methacholine, and gender differences have been proposed to identify individuals susceptible to the development of COPD. However, variable response to cigarette smoke clearly suggests genetic susceptibility. Among the COPD candidate genes are those (a) that effect the production of proteases and antiproteases, (b) modulate the metabolism of toxic substances in cigarette smoke, (c) are involved with mucocilliary clearance, and (d) that influence inflammatory mediators. Recently, sputum cells from smokers with and without COPD were tested for Microsatellite DNA Instability (MSI) with positive results. This finding suggests that MSI can be a useful marker of genetic susceptibility and thereby indicate destabilization of the genome in the "susceptible" smoker. Nevertheless, COPD lacks established viable biomarkers to predict and monitor disease progression and outcome variables. Such monitoring tools may be induced sputum, exhaled air condensate, peripheral blood, urine, bronchial biopsies, and bronchoalveolar lavage fluid (BALF). This review summarizes recent research on potential laboratory markers in smokers and subsequent COPD development.

Biomarkers↗

PubMed2001

Recent approaches in standardization of cardiac markers.

The development of commercial assays for the determination of new cardiac proteins has been one of the most important innovations in the field of cardiovascular diagnostics in the last decade. This significant and sudden advancement has however led to some analytical and interpretative problems. There are problems in test standardization, imprecision, interference and preanalytical variability. We also need to standardize utilization of biomarkers in diagnosis and management of acute cardiac syndromes and clearly define decision thresholds. Powerful tests, such as cardiac markers, on which critical decisions will rest, need highly reliable methods. The feeling is that some assays are inadequately appraised prior to their introduction in clinical use. More studies are needed to implement new devices in the laboratory routine, and only well documented assays should be used in hospital-based laboratories. The technology to address many analytic problems is at hand, but commitment on the part of manufacturers and their customers in the laboratory community is essential.

Animals↗

PubMed2026

Efforts towards a precision medicine approach in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the commonest group of childhood arthritides. Despite the availability of advanced therapeutics, many children and young people (CYP) with JIA experience disease flares, and in some, chronic joint damage. Tailoring treatment based on unique biological profiles would benefit CYP with JIA given their variable clinical presentation and disease course. To date, biomarkers to predict treatment response are lacking. With advances in single cell technologies, we are now able to profile the genes and proteins of target tissues at unprecedented resolution to define the biological basis of disease and guide novel treatment approaches. The complex analyses and combination of biological and clinical outcome data from large datasets across disease phenotypes have become possible with the development of computational and machine learning methods. Here, we summarize the strategies to integrate data through multimodal based approaches to maximize precision medicine and research priorities for CYP with JIA.

Humans↗

PubMed2006

Association between human fetuin-A and the metabolic syndrome: data from the Heart and Soul Study.

BACKGROUND: Fetuin-A is a multifunctional hepatic secretory protein that inhibits the action of insulin in experimental animals. We evaluated the association between human serum fetuin-A and the metabolic syndrome (MetS) in a cohort of persons with coronary artery disease. METHODS AND RESULTS: We defined MetS by the National Cholesterol Education Program criteria among 711 nondiabetic outpatients with coronary artery disease. The mean age was 67 years, and 82% were male. We divided participants into quartiles by serum fetuin-A concentrations. A total of 45% of participants (80 of 177) in the highest quartile of fetuin-A had MetS compared with 24% of participants (42 of 177) in the lowest quartile (odds ratio, 2.7; 95% confidence interval, 1.7 to 4.2; P<0.001). This association persisted after adjustment for potential confounding variables, including hypertension, body mass index, and inflammatory biomarkers (adjusted odds ratio, 2.0; 95% confidence interval, 1.1 to 3.5; P=0.02). Higher fetuin-A quartiles were also strongly and independently associated with higher low-density lipoprotein, non-high-density lipoprotein (HDL), and triglyceride concentrations and lower HDL concentrations (all P<0.01). CONCLUSIONS: Higher human fetuin-A concentrations are strongly associated with MetS and an atherogenic lipid profile. Future studies should evaluate whether fetuin-A predicts coronary artery disease risk.

Aged↗