Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Biomarker testing”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 1,099 records · Page 61Linked to original sources
PubMed2005

The diagnostic utility of cardiac biomarkers in detecting myocardial infarction.

Cardiac biomarkers, eg, cardiac troponin, have become the standard test in combination with clinical and electrocardiographic findings for physicians to conduct prompt and effective triage of patients presenting with chest pain. Cardiac biomarkers are protein components of cell structures that are released into circulation when myocardial injury occurs. The purpose of this article is multifold. First, to identify specific cardiac biomarkers and review current guidelines based on study findings on the diagnostic utility of cardiac biomarkers in detecting myocardial infarction. Recent guidelines of the European Society of Cardiology, the American College of Cardiology, the American Heart Association, and the National Academy of Clinical Biochemistry were examined, as well as relevant studies relating to the development of these guidelines. Second, to analyze the clinical significance of cardiac biomarker measurements and the challenges with existing cardiac biomarker assays. Third, to discuss our findings regarding our evaluation of the analytical performance of a chemiluminescent microparticle immunoassay for the quantitative determination of cardiac troponin I in human serum and plasma on an automated immunoassay instrument system (ARCHITECT) to aid in the diagnosis of myocardial infarction.

Biomarkers↗
PubMed2005

Early prediction of acute renal injury using urinary proteomics.

AIMS: The lack of early biomarkers for acute renal failure (ARF) has crippled our ability to launch potentially effective therapeutic measures. We tested the hypothesis that urinary proteomics could identify novel early biomarker patterns for ischemic renal injury. METHODS: Sixty patients undergoing cardiopulmonary bypass (CPB) were enrolled. Urine samples obtained at 2 and 6 h post CPB were analyzed by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS). The primary outcome variable was ARF, defined as a 50% or greater increase in serum creatinine. RESULTS: Fifteen patients (25%) developed ARF 2-3 days after CPB. SELDI-TOF-MS analysis of urine from the ARF group at baseline versus at 2 and 6 h post-CPB consistently showed a marked and statistically significant enhancement of protein biomarkers with m/z of 6.4, 28.5, 43 and 66 kDa. The same biomarkers were enhanced when comparing control versus ARF groups at 2 and 6 h post-CPB. The sensitivity and specificity of the 28.5-, 43- and 66-kDa biomarkers for the prediction of ARF at 2 h following CPB was 100%. The receiver operating characteristic curves revealed an area under the curve of 0.98. CONCLUSION: SELDI-TOF-MS is a novel, non-invasive, sensitive, highly predictive, reproducible, rapid method for the prediction of acute renal injury following CPB.

Acute Kidney Injury↗
PubMed2004

Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer.

Early detection remains the most promising approach to improve long-term survival of patients with ovarian cancer. In a five-center case-control study, serum proteomic expressions were analyzed on 153 patients with invasive epithelial ovarian cancer, 42 with other ovarian cancers, 166 with benign pelvic masses, and 142 healthy women. Data from patients with early stage ovarian cancer and healthy women at two centers were analyzed independently and the results cross-validated to discover potential biomarkers. The results were validated using the samples from two of the remaining centers. After protein identification, biomarkers for which an immunoassay was available were tested on samples from the fifth center, which included 41 healthy women, 41 patients with ovarian cancer, and 20 each with breast, colon, and prostate cancers. Three biomarkers were identified as follows: (a) apolipoprotein A1 (down-regulated in cancer); (b) a truncated form of transthyretin (down-regulated); and (c) a cleavage fragment of inter-alpha-trypsin inhibitor heavy chain H4 (up-regulated). In independent validation to detect early stage invasive epithelial ovarian cancer from healthy controls, the sensitivity of a multivariate model combining the three biomarkers and CA125 [74% (95% CI, 52-90%)] was higher than that of CA125 alone [65% (95% CI, 43-84%)] at a matched specificity of 97% (95% CI, 89-100%). When compared at a fixed sensitivity of 83% (95% CI, 61-95%), the specificity of the model [94% (95% CI, 85-98%)] was significantly better than that of CA125 alone [52% (95% CI, 39-65%)]. These biomarkers demonstrated the potential to improve the detection of early stage ovarian cancer.

Amino Acid Sequence↗
PubMed2006

Serial testing of B-type natriuretic peptide and NTpro-BNP for monitoring therapy of heart failure: the role of biologic variation in the interpretation of results.

BACKGROUND: B-Type natriuretic peptide (BNP) and NTpro-BNP are widely used for diagnosis and risk stratification of patients with heart failure (HF). Although not currently cleared by the Food and Drug Administration as a test indication, there is interest in using these biomarkers for monitoring the success of HF medications. An assessment of the analytical and biologic variations is necessary to interpret the results of serial testing. METHODS AND RESULTS: The intra-individual biologic variances and analytical assay variances of BNP and NT-proBNP from healthy subjects and those with stable HF were reviewed. The analytical variability of BNP and NT-proBNP assays was reported, as some have suggested that only the analytical variance is important in interpreting the results of tightly regulated hormones. The reference change values (RCV) for serial measurements were derived and used to interpret results of therapeutic studies whereby serial changes in BNP and NT-proBNP concentrations were obtained to evaluate the therapeutic success of short-term (inpatient) and long-term (outpatient) management. The use of RCV may also be important in studies comparing BNP-guided versus physician-guided HF drug therapy. CONCLUSIONS: Relative to the RCV, short-term therapeutic studies of inpatients have largely resulted in a statistically significant decline in BNP and NT-proBNP with clinical evidence of patient improvements. In contrast, many therapeutic studies involving long-term outpatient monitoring have produced changes in BNP/NT-proBNP that do not exceed the biologic variances. The value of BNP for monitoring therapeutic success can be questioned for trials that demonstrate clinical benefit without statistically significant decreases in biomarker levels.

Adult↗
PubMed2000

Metallothioneins in terrestrial invertebrates: structural aspects, biological significance and implications for their use as biomarkers.

During the last few years the subject of metallothioneins (MTs) in terrestrial invertebrates has gained increasing attention. One reason for this may be that terrestrial invertebrates provide new insights into the biological diversity of MTs, with the potential of discovering alternative models of structural and functional relationships. Four groups of terrestrial invertebrates have been studied in detail, namely nematodes, insects, snails and earthworms, with the present article focusing on MTs from the latter two groups. Snails are interesting because they possess distinct MT isoforms involved in different metal-specific tasks. In the Roman snail (Helix pomatia), for example, one isoform is predominantly expressed in the midgut gland, accounting for the accumulation, binding and detoxification of cadmium. The second isoform, which is present in the snail's mantle, is substantially different regarding its primary structure. Furthermore, it binds nearly exclusively copper, and thus is probably involved in the homeostatic regulation of essential trace elements. Earthworm MTs merit our attention because of another peculiarity: they seem to be much more unstable than snail MTs, particularly under conventional conditions of preparation. The cDNA of the brandling worm (Eisenia foetida), for instance, codes for a putative MT, which is about twice the size of the actual protein. The isolated MT peptide binds four Cd2+ ions and represents a one-domain MT entity that is stable and functional in vitro. This strongly suggests that earthworm MTs are either posttranslationally modified, or subjected to enzymatic cleavage during preparation. Both snail and earthworm MTs are inducible by metal exposure, especially by cadmium, thus supporting the idea of using them as potential biomarkers for environmental metal pollution. Whilst snail MTs have already been tested in this respect with some success, the use of earthworm MTs as biomarkers still remains to be evaluated, especially in the light of the unknown significance of their posttranslational instability.

Amino Acid Sequence↗
PubMed2003

Considerations on development, validation, application, and quality control of immuno(metric) biomarker assays in clinical cancer research: an EORTC-NCI working group report.

A major dilemma associated with immuno(metric) assays for biomarkers is that various kits employing antibodies with differing specificities and binding affinities may generate non-equivalent test results. Also, variation in sample processing and the use of different standards (reference material) may result in discordant test results. Therefore, assays and procedures should be standardized and the quality of biomarker assay results should be monitored by continuous between-laboratory proficiency testing of performance. External quality control requires an established network of expert laboratories in which the investigators interact freely and where technical issues are discussed. Although such networking is more often praised than practiced, we strongly endorse and advocate between-laboratory exchange of experience and information. The present study discusses analytical aspects of immuno(metric) biomarker assays and presents recommendations of the Receptor and Biomarker Group of the EORTC (European Organisation for Research and Treatment of Cancer) how such tests should be validated for first time and day to day use. Moreover, a model for an appropriate quality assurance program is presented.

Biomarkers, Tumor↗
PubMed2000

Plasma alpha-glutathione S-transferase: a sensitive indicator of hepatocellular damage during polymicrobial sepsis.

HYPOTHESIS: Since studies have found the liver enzyme alpha-glutathione S-transferase (alphaGST) to be a marker of hepatic injury after hemorrhagic shock, alphaGST also may serve as a sensitive indicator of hepatocellular damage during the early stage of polymicrobial sepsis. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Male adult rats were subjected to the cecal ligation and puncture (CLP) model of polymicrobial sepsis or sham operation, followed by fluid resuscitation with isotonic sodium chloride solution. Systemic blood samples were taken at 2, 5, 10, or 20 hours after CLP or sham operation. Plasma levels of alphaGST and lactate were determined using an enzyme immunoassay and enzymatic assay, respectively. Additional animals were examined for morphologic alterations in liver ultrastructure of septic animals using electron microscopy. RESULTS: A similar level of alphaGST (mean +/- SEM, 30.5 +/- 3.5 microg/L) was found in the sham group at all measured time points. Although plasma levels of alphaGST did not change at 2 hours after CLP, they were elevated by 249% at 5 hours after the onset of sepsis and continued to increase throughout the septic course. Plasma lactate levels were significantly increased only at 20 hours after CLP (P<.001). Previous studies have shown that liver transaminase levels did not increase at 5 hours, but at 10 and 20 hours after CLP. In addition, electron microscopy revealed structural changes in hepatocyte morphology at 5 and 20 hours after CLP that were indicative of hepatocellular injury. CONCLUSION: Since plasma alphaGST levels increased earlier than plasma lactate and liver transaminase levels, alphaGST may be a more sensitive indicator of early liver injury and should be used in monitoring hepatocellular damage during the progression of sepsis.

Animals↗
PubMedDate not supplied

Lack of carcinogenicity of daminozide, alone or in combination with its contaminant 1,1-dimethylhydrazine, in a medium-term bioassay.

The carcinogenicity of daminozide (succinic acid-2,2-dimethylhydrazide; Alar), a plant growth regulator used primarily in apple orchards, has been the subject of recent investigations by several national and international organizations because of contradictory study results. The aim of the present study was to assess the carcinogenicity of daminozide alone and in combination with 1,1-dimethylhydrazine (UDMH), its major contaminant, in a novel medium-term bioassay in Fischer 344 rats, the DEN-PH model. Rats were given diethylnitrosamine (DEN) at 200 mg/kg body weight intraperitoneally and then 2 weeks later were given daminozide at 20,000 ppm or daminozide plus UDMH at 75, 150, or 300 ppm in the diet for 6 weeks and were then killed; all rats underwent a partial (two-thirds) hepatectomy (PH) at week 3. Hepatocarcinogenic potential was assessed by comparing the number and area of preneoplastic foci positive for the glutathione S-transferase placental form (GST-P+) in the liver of treated rats, with those in controls given DEN alone. Daminozide, UDMH, and the combination were not carcinogenic in this model. This novel medium-term bioassay for carcinogenicity is considered to be practical for the rapid evaluation of both agrochemical formulations and contaminants found in agrochemicals and other compounds.

Adjuvants, Immunologic↗
PubMed1992

Molecular marker test standardization.

A review of the status of standardization of laboratory tests of particular interest to oncologists is presented. Currently, relatively few of these tests are standardized; as a result, interlaboratory and interinstitutional comparison of data is problematic. In 1992, additional interlaboratory studies of common tumor markers will be initiated by the College of American Pathologists. The National Committee for Clinical Laboratory Standards also has begun to develop standard methods and guidelines for these important tests.

Biomarkers, Tumor↗
PubMedDate not supplied

Mechanistic data and cancer risk assessment: the need for quantitative molecular endpoints.

The cancer risk assessment process as currently proposed by the U.S. Environmental Protection Agency allows for the use of mechanistic data to inform the low-dose tumor response in humans and in laboratory animals. The aim is to reduce the reliance on defaults that introduce a relatively high level of uncertainty to the risk estimates. The types of data required for this purpose are those that help identify key events in tumor formation following exposure to environmental chemicals. Informative biomarkers of tumor responses could then be developed for describing the shape of a dose-response curve at low doses (i.e., a qualitative assessment) and for predicting tumor frequency at these low doses (i.e., a quantitative assessment). A number of recently developed molecular approaches could aid in the development of qualitatively and quantitatively informative biomarkers. An overview of these with examples of their use is presented. These methods include quantitative gene expression array techniques, quantitative proteomic assays, and the assessment of DNA alterations at the single gene level and at the genome level of detection. It is most likely that a combination of approaches at different levels of cellular organization (i.e., DNA, RNA, and protein) will be the most productive for biomarker development. The rapid progress that is being made will make this tool kit even more applicable for the cancer risk assessment process.

Biomarkers, Tumor↗
PubMed2002

Impaired fibrinolysis in the pathogenesis of dengue hemorrhagic fever.

The mechanisms contributing to bleeding complications in dengue hemorrhagic fever were studied by investigating the pattern of activation of the coagulation and fibrinolytic systems in 50 children with severe dengue hemorrhagic fever. Thirteen patients (26%) died, and activation of coagulation was most pronounced in the deceased group. Fibrinolysis was also activated, but this activation was relatively weak compared with that of coagulation as a result of persistently high plasminogen activator inhibitor levels. Plasminogen activator inhibitor also prevented a switch from the procoagulant to the profibrinolytic state in lethal dengue hemorrhagic fever, which was further enhanced by an acquired protein C deficiency. The present study is the first to demonstrate such a mechanism in a viral infection. This imbalance between coagulation and fibrinolysis may be used as a prognostic marker, but it may also be a target for future therapeutic intervention.

Biomarkers↗
PubMed1990

Discriminant analysis for assessing the value of amniotic fluid microvillar enzymes in the prenatal diagnosis of cystic fibrosis.

We have analysed the sensitivity, specificity, and reliability of biochemical diagnosis based on microvillar membrane enzyme assay and using discriminant analysis in amniotic fluid samples obtained from 54 pregnancies at high risk for cystic fibrosis and 125 normal pregnancies. Our results show that amniotic fluid trehalase, alkaline phosphatase, alkaline phosphatase isoenzymes and gamma-glutamyltransferase enzyme activities measured during 16-20 gestational weeks, in spite of their non-specificity for cystic fibrosis, have a very good predictive value for fetal cystic fibrosis or exclude the possibility of the disease. Overall enzyme activity analysis provided over 90 per cent reliability of the method.

Alkaline Phosphatase↗
PubMed2000

Quantitative method for biomarkers of collagen degradation using liquid chromatography tandem mass spectrometry.

Preclinical efficacy testing commonly involves studies that require considerable resources and time. One valuable tool in this endeavor is the characterization of relevant biomarkers. A method has been developed for the simultaneous determination of collagen biomarker candidates as an instrument in screening compounds for efficacy. Two potential candidates, the 3-hydroxypyridinium crosslinks pyridinoline and deoxypyridinoline, were selected for analysis in collagen degradation models. Tissue or urine samples were collected, prepared, and quantitated for the biomarkers using spiked calibration curves and liquid chromatography tandem mass spectrometry. The development of a quick and simple assay method would allow us to increase the chances for success in efficacy screening by eliminating compounds with poor biomarker profiles. The method proposed here appears to be more selective, convenient, precise (generally <10% RSD), accurate (generally <10% RE), and sensitive relative to previously established methodology.

Amino Acids↗
PubMed2002

Expression of activation markers on alveolar macrophages in allergic asthmatics after endobronchial or whole-lung allergen challenge.

We examined the effect of endobronchial (EB) or whole-lung (WL) challenge with ragweed or Timothy grass extract on alveolar macrophage (AM) activation. Expression of 17 constitutive activation markers on AM was examined by flow cytometry. Late-phase bronchial obstruction was greater after WL challenge, while changes in bronchoalveolar lavage cytology (eosinophil accumulation) were greater after EB challenge. After EB challenge, levels of 10 of 17 markers (CD11a, CD11b, CD14, CD18, CD23, CD32, CD63, CD64, HLA-class I, and HLA-DR) were significantly increased (by 33-234%, P < 0.05). Six markers (CD16, CD29, CD33, CD35, CD44, CD71, and HLA-DQ) remained unchanged. Levels of seven markers following EB challenge (CD14, CD16, CD18, CD29, CD32, HLA-class I, and HLA DQ) correlated with airway sensitivity to methacholine. WL challenge only increased expression of HLA-class I. The different results obtained with the two challenge methods probably depend on higher local concentrations of allergen in the EB challenge. We suggest that activation of AM occurs following EB challenge with antigen in asthmatics.

Adult↗
PubMed2004

Diagnostic molecular markers in thyroid cancer.

The use of molecular assays to analyze clinical tissues in the diagnosis and management of thyroid cancer, similar to other tumors, will likely allow for more accurate characterization of the aggressiveness of individual tumors and may allow for the early diagnosis of recurrence. The application of these methods to thyroid nodules and nodal metastases is less encumbered by difficulties arising from amplification of transcripts in non-thyroid cells. For these tissues, these assays are likely to be used clinically in the near-future. New data arising from cDNA arrays identifying novel markers of malignancy or tumor aggressiveness make this a growing area of interest. The use of molecular assays in diagnosing distant metastases is more problematic due to issues with ectopic expression of either full length or splice variants of genes thought to be thyroid-specific. Assay quantitation is a complex problem owing to variability in the level of expression of "housekeeping" genes and the variety of phlebotomy and RT-PCR methods reported. Additional research in this area is clearly required before a recommendation can be given regarding clinically applicability of these tests.

Biomarkers, Tumor↗
PubMed1999

Analytical biochemistry and clinical significance of N-acetyl-beta-D-glucosaminidase and related enzymes.

Human N-acetyl-beta-D-glucosaminidase, N-acetyl-alpha-D-glucosaminidase, endo-beta-N-acetylglucosaminidase, hexosaminidase, beta-N-acetylgalactosaminidase and glucocerebrosidase have not been so widely studied as the beta-N-acetylhexosaminidases in bacteria, fungi and arthropods. Their biochemical role has been elucidated, however, and their urinary and plasma determination is being adopted for the early detection of diseases before clinical manifestation, in particular for hypertension, renal injuries and disorders, depression and lysosomal storage diseases. The spectrophotometric determinations of N-acetyl-beta-D-glucosaminidase, most often done with 3-cresolsulphone phthaleinyl N-acetyl-beta-D-glucosaminide, have been recently simplified and adapted to automatic instruments.

Acetylglucosaminidase↗