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Results for “Biomarker variability”

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PubMed2003

A stochastic model for optimizing composite predictors based on gene expression profiles.

PURPOSE: This project was done to develop a mathematical model for optimizing composite predictors based on gene expression profiles from DNA arrays and proteomics. METHODS: The problem was amenable to a formulation and solution analogous to the portfolio optimization problem in mathematical finance: it requires the optimization of a quadratic function subject to linear constraints. The performance of the approach was compared to that of neighborhood analysis using a data set containing cDNA array-derived gene expression profiles from 14 multiple sclerosis patients receiving intramuscular inteferon-beta1a. RESULTS: The Markowitz portfolio model predicts that the covariance between genes can be exploited to construct an efficient composite. The model predicts that a composite is not needed for maximizing the mean value of a treatment effect: only a single gene is needed, but the usefulness of the effect measure may be compromised by high variability. The model optimized the composite to yield the highest mean for a given level of variability or the least variability for a given mean level. The choices that meet this optimization criteria lie on a curve of composite mean vs. composite variability plot referred to as the "efficient frontier." When a composite is constructed using the model, it outperforms the composite constructed using the neighborhood analysis method. CONCLUSIONS: The Markowitz portfolio model may find potential applications in constructing composite biomarkers and in the pharmacogenomic modeling of treatment effects derived from gene expression endpoints.

Adult↗

PubMed2006

An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans.

The frequency of micronuclei (MN) in peripheral blood lymphocytes (PBL) is extensively used as a biomarker of chromosomal damage and genome stability in human populations. Much theoretical evidence has been accumulated supporting the causal role of MN induction in cancer development, although prospective cohort studies are needed to validate MN as a cancer risk biomarker. A total of 6718 subjects from of 10 countries, screened in 20 laboratories for MN frequency between 1980 and 2002 in ad hoc studies or routine cytogenetic surveillance, were selected from the database of the HUman MicroNucleus (HUMN) international collaborative project and followed up for cancer incidence or mortality. To standardize for the inter-laboratory variability subjects were classified according to the percentiles of MN distribution within each laboratory as low, medium or high frequency. A significant increase of all cancers incidence was found for subjects in the groups with medium (RR=1.84; 95% CI: 1.28-2.66) and high MN frequency (RR=1.53; 1.04-2.25). The same groups also showed a decreased cancer-free survival, i.e. P=0.001 and P=0.025, respectively. This association was present in all national cohorts and for all major cancer sites, especially urogenital (RR=2.80; 1.17-6.73) and gastro-intestinal cancers (RR=1.74; 1.01-4.71). The results from the present study provide preliminary evidence that MN frequency in PBL is a predictive biomarker of cancer risk within a population of healthy subjects. The current wide-spread use of the MN assay provides a valuable opportunity to apply this assay in the planning and validation of cancer surveillance and prevention programs.

Biomarkers↗

PubMed2004

Immunogenetic susceptibility of atherosclerotic stroke: implications on current and future treatment of vascular inflammation.

The understanding of the pathophysiology governing atherosclerosis supports a prominent role for inflammation pathways in plaque initiation and progression that result in stroke and myocardial infarction. Elevated levels of inflammatory markers in the blood, such as C-reactive protein and CD40 ligand/CD40, in concert with increased expression of adhesion molecules, chemokines, cytokines, matrix metalloproteinases (MMP), and inflammatory cells in the plaque, characterize the symptomatic atherothrombotic state. Advances in predictive capabilities of vascular events using a number of these biomarkers are beginning to remodel our clinical practice in the use of medications such as statins and angiotensin receptor blockers for stroke prevention. Although the general inflammatory features of atherosclerosis are becoming widely recognized, factors resulting in individual variability in plaque formation and instability remain poorly defined. Emerging literature points toward several acquired and innate susceptibility factors in the immune pathways that may provide insight into why many plaques rapidly evolve from a "stable" to an "unstable" or symptomatic state. First, exposure of plaque memory T-lymphocytes to infectious or endogenous antigens may result in rapid clonal expansion of T-cell variable beta chain subtypes and stimulate macrophages to release MMPs, causing plaque destabilization. The effects of infectious agents can further be influenced by an individual's major histocompatibility complex class II molecule profiles, which can affect susceptibility to specific organisms. Second, functional polymorphisms of genes that regulate the immune pathway can predispose patients to a more robust inflammatory expression after risk factor exposure. Identification of a susceptibility gene profile and immunologic mediators that promote T-cell activation provides a unique opportunity for early identification of stroke risk and targets for future therapy.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2000

A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells.

A new monoclonal antibody (MUM1p) was used to study the cell/tissue expression of human MUM1/IRF4 protein, the product of the homologous gene involved in the myeloma-associated t(6;14) (p25;q32). MUM1 was expressed in the nuclei and cytoplasm of plasma cells and a small percentage of germinal center (GC) B cells mainly located in the "light zone." Its morphologic spectrum ranged from that of centrocyte to that of a plasmablast/plasma cell, and it displayed a phenotype (MUM1(+)/Bcl-6(-)/Ki67(-)) different from that of most GC B cells (MUM1(-)/Bcl-6(+)/Ki67(+)) and mantle B cells (MUM1(-)/Bcl-6(-)/Ki67(-)). Polymerase chain reaction (PCR) analysis of single MUM1(+ )cells isolated from GCs showed that they contained rearranged Ig heavy chain genes with a varying number of V(H) somatic mutations. These findings suggest that these cells may represent surviving centrocytes and their progeny committed to exit GC and to differentiate into plasma cells. MUM1 was strongly expressed in lymphoplasmacytoid lymphoma, multiple myeloma, and approximately 75% of diffuse large B-cell lymphomas (DLCL-B). Unlike normal GC B cells, in which the expression of MUM1 and Bcl-6 were mutually exclusive, tumor cells in approximately 50% of MUM1(+) DLCL-B coexpressed MUM1 and Bcl-6, suggesting that expression of these proteins may be deregulated. In keeping with their proposed origin from GC B cells, Hodgkin and Reed-Sternberg cells of Hodgkin's disease consistently expressed MUM1. MUM1 was detected in normal and neoplastic activated T cells, and its expression usually paralleled that of CD30. These results suggest that MUM1 is involved in the late stages of B-cell differentiation and in T-cell activation and is deregulated in DLCL-B. (Blood. 2000;95:2084-2092)

Antibodies, Monoclonal↗

PubMed2006

Aberrant neuropeptide Y and macrophage inhibitory cytokine-1 expression are early events in prostate cancer development and are associated with poor prognosis.

Studies to elucidate dysregulated gene expression patterns in premalignant prostate lesions have identified several candidate genes with the potential to be targeted to prevent the development and progression of prostate cancer and act as biomarkers of early disease. Herein, we explored the importance of two proteins, neuropeptide Y (NPY) and macrophage inhibitory cytokine-1 (MIC-1), as biomarkers of preinvasive prostate disease and investigated the relationship of expression to biochemical recurrence following treatment for localized prostate cancer. NPY and MIC-1 protein expression was determined by immunohistochemistry on tissue microarrays containing 1,626 cores of benign, low-grade prostatic intraepithelial neoplasia (PIN), high-grade PIN (HGPIN), and prostate cancer tissue from 243 radical prostatectomy patients. Both NPY and MIC-1 showed higher proportional immunostaining in HGPIN and prostate cancer compared with benign epithelium (P < 0.0001). NPY and MIC-1 immunostaining was higher in low-grade PIN compared with other benign tissues (both P < 0.0001) and was equivalent to immunostaining in HGPIN. NPY immunostaining of prostate cancer was independently associated with relapse, after adjusting for traditional prognostic factors, as a categorical variable in 20% intervals (P = 0.0449-0.0103) and as a continuous variable (P = 0.0017). Low MIC-1 immunostaining (20% categories) was associated with pathologic stage >2C after adjusting for predictors of pathologic stage (P = 0.3894-0.0176). This is the first study to show that altered NPY and MIC-1 expression are significantly associated with prostate cancer progression and suggests that these molecules be developed further as biomarkers in the management of prostate disease.

Cytokines↗

PubMed2005

Classic and molecular cytogenetic analyses reveal chromosomal gains and losses correlated with survival in head and neck cancer patients.

PURPOSE: Genetic biomarkers of head and neck tumors could be useful for distinguishing among patients with similar clinical and histopathologic characteristics but having differential probabilities of survival. The purpose of this study was to investigate chromosomal alterations in head and neck carcinomas and to correlate the results with clinical and epidemiologic variables. EXPERIMENTAL DESIGN: Cytogenetic analysis of short-term cultures from 64 primary untreated head and neck squamous cell carcinomas was used to determine the overall pattern of chromosome aberrations. A representative subset of tumors was analyzed in detail by spectral karyotyping and/or confirmatory fluorescence in situ hybridization analysis. RESULTS: Recurrent losses of chromosomes Y (26 cases) and 19 (14 cases), and gains of chromosomes 22 (23 cases), 8 and 20 (11 cases each) were observed. The most frequent structural aberration was del(22)(q13.1) followed by rearrangements involving 6q and 12p. The presence of specific cytogenetic aberrations was found to correlate significantly with an unfavorable outcome. There was a significant association between survival and gains in chromosomes 10 (P = 0.008) and 20 (P = 0.002) and losses of chromosomes 15 (P = 0.005) and 22 (P = 0.021). Univariate analysis indicated that acquisition of monosomy 17 was a significant (P = 0.0012) factor for patients with a previous family history of cancer. CONCLUSIONS: The significant associations found in this study emphasize that alterations of distinct regions of the genome may be genetic biomarkers for a poor prognosis. Losses of chromosomes 17 and 22 can be associated with a family history of cancer.

Adult↗

PubMed1998

High-affinity recombinant phage antibodies to the pan-carcinoma marker epithelial glycoprotein-2 for tumour targeting.

The tumour-associated antigen epithelial glycoprotein-2 (EGP-2) is a promising target for detection and treatment of a variety of human carcinomas. Antibodies to this antigen have been successfully used in patients for imaging of small-cell lung cancer and for adjuvant treatment of minimal residual disease of colon cancer. We describe here the isolation and complete characterization of high-affinity single-chain variable fragments (scFv) to the EGP-2 antigen. First, the binding kinetics of four murine whole antibodies directed to EGP-2 (17-1A, 323/A3, MOC-31 and MOC-161) were determined using surface plasmon resonance (SPR). The MOC-31 antibody has the lowest apparent off-rate, followed by MOC-161 and 323/A3. The V-genes of the two MOC hybridomas were cloned as scFv in a phage display vector and antigen-binding phage were selected by panning on recombinant antigen. The scFvs compete with the original hybridoma antibodies for binding to antigen and specifically bind to human carcinomas in immunohistochemistry. MOC-31 scFv has an off-rate which is better than those of the bivalent 17-1A and 323/A3 whole antibodies, providing it with an essential characteristic for tumour retention in vivo. The availability of these high-affinity anti-EGP-2 antibody fragments and of their encoding V-genes creates a variety of possibilities for their future use as tumour-targeting vehicles.

Animals↗

PubMed2004

Ganoderma lucidum ("Lingzhi"), a Chinese medicinal mushroom: biomarker responses in a controlled human supplementation study.

Lingzhi (Ganoderma lucidum) is a woody mushroom highly regarded in traditional medicine and is widely consumed in the belief that it promotes health and longevity, lowers the risk of cancer and heart disease and boosts the immune system. However, objective scientific validation of the putative health benefits of Lingzhi in human subjects is lacking, and issues of possible toxicity must be addressed. The present double-blinded, placebo-controlled, cross-over intervention study investigated the effects of 4 weeks Lingzhi supplementation on a range of biomarkers for antioxidant status, CHD risk, DNA damage, immune status, and inflammation, as well as markers of liver and renal toxicity. It was performed as a follow-up to a study that showed that antioxidant power in plasma increased after Lingzhi ingestion, and that 10 d supplementation was associated with a trend towards an improved CHD biomarker profile. In the present study, fasting blood and urine from healthy, consenting adults (n 18; aged 22-52 years) was collected before and after 4 weeks supplementation with a commercially available encapsulated Lingzhi preparation (1.44 g Lingzhi/d; equivalent to 13.2 g fresh mushroom/d) or placebo. No significant change in any of the variables was found, although a slight trend toward lower lipids was again seen, and antioxidant capacity in urine increased. The results showed no evidence of liver, renal or DNA toxicity with Lingzhi intake, and this is reassuring. The present study of the effects in healthy, well-nourished subjects provides useful, new scientific data that will support controlled intervention trials using at-risk subjects in order to assess the therapeutic effect of Lingzhi in the promotion of healthy ageing.

Adult↗

PubMed2004

Monocyte activation in patients with age-related macular degeneration: a biomarker of risk for choroidal neovascularization?

OBJECTIVE: To evaluate the activation state of macrophage function in patients with age-related macular degeneration (AMD) by quantifying the production of the proinflammatory and angiogenic factor tumor necrosis factor alpha (TNF-alpha) and by correlating its expression with dry and wet AMD. METHODS: Circulating monocytes were obtained from the blood of patients with AMD or age-matched control subjects by gradient centrifugation. The monocytes were then analyzed for either TNF-alpha release from cultured macrophages in response to retinal pigment epithelium-derived blebs and cytokines or TNF-alpha messenger RNA content by reverse transcriptase-polymerase chain reaction. RESULTS: In human monocytes obtained from controls and AMD patients, TNF-alpha was expressed by freshly isolated monocytes and produced by macrophages in culture after stimulation with retinal pigment epithelium-derived blebs. However, wide variability in TNF-alpha expression was observed among different patients. Patients with monocytes that expressed the greatest amount of TNF-alpha demonstrated higher prevalence of choroidal neovascularization. CONCLUSIONS: Both controls and AMD patients vary in the activation state (defined as TNF-alpha expression) of circulating monocytes. Partially active monocytes, defined as high TNF-alpha expression, may be a biomarker to identify patients at risk for formation of choroidal neovascularization. CLINICAL RELEVANCE: Early diagnostic testing may prove useful to detect those patients who will progress to the more severe complications of the disease.

Adult↗

PubMed2003

Oxidative DNA damage estimated by urinary 8-hydroxydeoxyguanosine: influence of taxi driving, smoking and areca chewing.

Nitrogen oxides (NOx) and polycyclic aromatic hydrocarbons are common air pollutants generated from automobile exhaust and cigarette smoke. This study was to investigate urinary 8-hydroxydeoxyguanosine (8-OHdG) as an effective biomarker on DNA damage from traffic exhaust and/or smoking in exposed and non-exposed individuals. With subject consents, the levels of plasma NOx, urinary 1-hydroxypyrene (1-OHP) and 8-OHdG were determined for 95 male taxi drivers and 75 male community residents as the reference group. After adjusting for associate variables, there was a significant correlation between the levels of urinary 8-OHdG and 1-OHP but not NOx. The average level of urinary 8-OHdG was significantly higher in drivers than in community men (13.4+/-4.7 vs. 11.5+/-4.7 microg/g creatinine in mean+/-standard deviation). Compared with non-smoking community men, the multivariate logistic regression showed that the odds ratios (OR) of having elevated levels of urinary 8-OHdG (greater than the overall median value, 12.1 microg/g creatinine) were 6.6 (95% confidence interval (CI)=2.1-20.8) for smoking community men, 5.0 (95% CI=1.7-14.7) for non-smoking taxi drivers and 4.6 (95% CI=1.4-15.0) for smoking taxi drivers. Higher risk was also observed for areca quid chewers compared with non-chewers (OR=1.6; 95% CI=1.1-3.6). In conclusion, taxi driving and smoking may contribute independently to elevated DNA damage using urinary 8-OHdG levels as a sensitive biomarker. This effect is most potent on heavy smokers.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2026

Prognostic effect of serum glial fibrillary acidic protein and neurofilament light chain for predicting progression independent of relapse activity in multiple sclerosis: A systematic review.

BACKGROUND: Progression independent of relapse activity (PIRA) is increasingly appreciated as one of the important factors contributing to disability accumulation in MS. sGFAP and sNfL could represent markers reflecting two separate biological processes related to relapse-independent progression in MS. OBJECTIVE: To perform a systematic review of the literature on blood GFAP and/or NfL measured in relation to PIRA or other similar relapse-independent progression endpoints in people with MS. METHODS: PubMed, Scopus, and Web of Science databases were searched from inception to 1 June 2026. The eligible studies were original human studies measuring blood GFAP and/or NfL concentrations in serum, plasma, or any other type of blood-derived material and assessing PIRA, PIRMA, CDP/CDW without relapses, relapse-free EDSS progression, non-inflammatory progression, or comparable relapse-independent disability worsening outcomes. Methodological quality was assessed according to the Newcastle-Ottawa scale and the QUIPS instrument for bias detection in the body of evidence on prognostic factors. Due to heterogeneity of outcomes, biomarker measurements and effect estimates, results were synthesized qualitatively rather than quantitatively. RESULTS: After removing duplicates, 1206 records were screened, followed by full-text review of 120 reports. A total of 18 reports were included. Overall, sGFAP was associated more frequently with PIRA or PIRA-like disability progression, particularly in cohorts with suppressed or limited overt inflammatory activity. Evidence for sNfL was more variable and context-dependent: several studies reported associations with PIRA-like or relapse-independent disability worsening when acute inflammatory activity was absent, suppressed, or analytically separated, whereas other studies reported negative or inconclusive findings. Negative or inconclusive results were reported by several articles, particularly when broad outcomes were evaluated or the study population was small. CONCLUSION: Blood GFAP and NfL give complementary but non-interchangeable information concerning PIRA in MS patients. The existing evidence base does not allow us to perform meta-analysis because of heterogeneity in terms of outcomes, standardization of biomarkers, and treatment context. Further prospective investigations with uniform criteria will be necessary for their use as biomarkers of PIRA in clinical settings.

Humans↗

PubMed1992

Flow cytometry, morphometry and histopathology as biomarkers of benzo[a]pyrene exposure in brown bullheads (Ameiurus nebulosus).

Brown bullheads were given a single intraperitoneal dose of 0, 5, 25 or 125 mg kg-1 benzo[a]pyrene (BaP), a carcinogenic polycyclic aromatic hydrocarbon, and evaluated over 18 months. Flow cytometric analyses of hepatocyte DNA content indicated an increase in DNA synthesis in BaP-exposed fish prior to day 14 post-exposure. Thereafter, all flow cytometric variables returned to initial levels. Histopathological evaluation of livers from fish sampled at 18 months revealed significant differences among treatments in the amount of hepatic macrophage ceroid pigmentation and basophilic staining intensity. No neoplasms or changes in blood cell DNA content were detected. Significant morphometric variations existed among fish, but differences between sexes overshadowed differences attributable to dose. Flow cytometry yielded no evidence of long-term DNA alterations from a single exposure to BaP; however, the differences detected by DNA analysis shortly after the toxic event suggest that flow cytometric cell cycle analysis may be useful for documenting continuing exposures.

Animals↗

PubMed1999

Measurement error in epidemiology: the design of validation studies II: bivariate situation.

The bias in relative risk estimates caused by errors in measurement of the relevant exposure is being increasingly recognized in epidemiology. Estimation of the necessary correction factor to remove this bias for univariate exposure has been considered in an earlier paper. We consider here the multivariate situation in which non-differential errors in measurement can lead to incorrect identification of the variable most closely associated with disease. Estimation of the necessary correction factor when the true exposure is unobservable necessarily requires assumptions. We explore the robustness of the estimation to departures from a range of assumptions. The value of good biomarkers is demonstrated. We present a bivariate example in which failure to take account of measurement error leads to the incorrect exposure being identified as the important determinant of disease risk.

Adult↗

PubMed1993

Is there a valid association between skin tags and colonic polyps: insights from a quantitative and methodologic analysis of the literature.

OBJECTIVE: To assess the reported association between skin tags and colonic polyps and to evaluate the methodologic rigor of the studies. DESIGN AND DATA IDENTIFICATION: English-language literature search using MEDLINE, Index Medicus, and bibliographic reviews of texts and all pertinent articles to perform a quantitative and methodologic analysis of all studies from 1983 (the original publication) assessing the association under study. Eligible studies were independently assessed using explicit methodologic guidelines for validity and generalizability of observational research. Two appraisers independently performed tests for heterogeneity and used meta-analytic methods in an attempt to provide summary estimates of the overall strength of association. MEASUREMENTS AND MAIN RESULTS: Significant statistical heterogeneity across studies indicated sharp differences in the direction and magnitude of the odds ratios for the association between skin tags and colonic polyps (chi-square test of homogeneity = 37.42, 9 degrees of freedom; p < 0.005). This marked disparity prevented meaningful pooling of the individual data. The degree of statistical heterogeneity was not significantly reduced after an analysis of specific subgroups of studies. Limitations potentially responsible for the varying outcomes included lack of blinded ascertainment of clinical information, noncomparability of subjects, differing diagnostic evaluations of the colon, and uncontrolled confounding. In addition, all but one study were performed in a tertiary care setting, seriously limiting the results to the "average" subject seen in primary care settings. CONCLUSION: Methodologic limitations and inconsistencies in study outcomes preclude the aggregation of data necessary to compute a valid and meaningful summary estimate of association. Sufficient variability prevents any consensus regarding the association between skin tags and colonic polyps. In addition, the applicability of the results is limited primarily to subjects seen in tertiary care centers, limiting the overall clinical usefulness of skin tags as "biomarkers" of colonic polyps. Recommendations for further research are provided.

Adult↗

PubMed2006

Diagnosing diabetic nephropathy by 1H NMR metabonomics of serum.

OBJECT: The most severe complication of type 1 diabetes (T1DM) is diabetic nephropathy. It is associated with a high risk of cardiovascular complications and premature death and requires early detection to be efficiently treated. The clinical practice to diagnose diabetic nephropathy is also a non-optimal and tedious set up based on albumin excretion rate in multiple overnight or 24h urine samples. Conversely, in this study, these independent diagnostic data are used to provide a realistic testing case for applying (1)H NMR metabonomics of serum in a diagnostic fashion. MATERIALS AND METHODS: 182 T1DM and 21 non-diabetic (non-T1DM) individuals were studied. The (1)H NMR of serum at 500 MHz was targeted at two molecular windows: lipoprotein lipids and low-molecular-weight metabolites. RESULTS: T1DM and non-T1DM individuals were exclusively separated by (1)H NMR. For diabetic nephropathy diagnosis in the T1DM patients, (1)H NMR data (and clinical biochemistry data) gave a sensitivity of 87.1% (83.9%) and a specificity of 87.7% (95.9%). The predictive values of positive and negative tests were 89.0% (95.5%) and 83.6% (79.2%), respectively. CONCLUSIONS: (1)H NMR metabonomics clearly distinguishes metabolic characteristics of T1DM and appears approximately as good a means to diagnose diabetic nephropathy from serum as an advanced set of biochemical variables.

Biomarkers↗

PubMed2006

Effect of chromium(VI) on the status of plasma lipid peroxidation and erythrocyte antioxidant enzymes in chromium plating workers.

OBJECTIVES: The present study was carried out to determine the effect of chromium(VI) on the status of plasma lipid peroxidation and erythrocyte antioxidant enzymes in workers exposed to chromium during chromium plating process. METHODS: Fifty subjects working in chromium plating process formed the study group. An equal number of age-sex matched subjects working in administrative units formed the control group. The control subjects were residing in the same city but away from the work place of study group subjects. Urinary chromium levels were determined by using a graphite furnace atomic absorption spectrophotometer. The plasma lipid peroxidation and erythrocyte antioxidant enzymes were determined by using spectrophotmetric methods. RESULTS: A significant increase of plasma lipid peroxidation and a significant decrease of superoxide dismutase and glutathione peroxidase levels were noted in the study group as compared with the controls. The level of plasma lipid peroxidation was positively and erythrocyte antioxidant enzymes were negatively and significantly correlated with chromium levels in urine. Multiple regression analysis was assessed the oxidative stress associated with chromium and life style confounding factors such as BMI, coffee, tea, alcohol and smoking. The multiple regression analysis showed that the urine chromium levels >10 micro g/g of creatinine, smoking, consumption of green vegetables and BMI variables were significantly associated with the levels of oxidative stress. CONCLUSION: The results show that the increased plasma lipid peroxidation and decreased antioxidant enzymes (superoxide dismutase and glutathione peroxidase) observed in chromium-exposed workers could be used as biomarkers of oxidative stress.

Adult↗

PubMed2006

Plasma cysteine and glutathione are independent markers of postmethionine load endothelial dysfunction.

OBJECTIVES: Oxidative stress caused by acute hyperhomocysteinemia impairs endothelial function in human arteries. We sought to identify markers of endothelial dysfunction during methionine-induced hyperhomocysteinemia. DESIGN AND METHODS: 35 subjects underwent flow-mediated dilation (FMD) of the brachial artery by high-resolution ultrasonography and fasting blood samples before and 3 h postmethionine load (PML). Clinical, conventional biochemical, and redox status (plasma total and reduced homocysteine, glutathione, cysteine, cysteinylglycine, ascorbic acid, alpha-tocopherol, free malondialdehyde, blood glutathione) data were sequentially entered into an univariate and multivariate stepwise linear regression analysis to evaluate their relation with the dependent variable FMD. RESULTS: Median [interquartile range] FMD decreased from 4.1% [2.8-6.3] to 3.2% [0.7-4.3] PML (P=0.02). At the multivariate analysis PML total cysteine (beta=-0.008, P=0.002) and glutathione (beta=0.21, P=0.005) were the only independent variables associated with FMD after methionine, adjusted for baseline FMD. CONCLUSIONS: Elevated plasma total cysteine and decreased plasma total glutathione levels were associated with abnormal FMD PML. Cysteine and glutathione are stronger markers of endothelial dysfunction than clinical and all other biochemical variables explored.

Adult↗

PubMed1999

A marker for differentiation of capabilities for processing of musical harmonies as detected by magnetoencephalography in musicians.

This investigation was designed to study the characteristics of a marker for harmonic processing and to test whether it could be used for differentiating harmonic processing capabilities. The first three chords of an ordinary musical cadenca were presented to the left ear to establish a harmonic context followed by a harmonic or non-harmonic target tone. Cadencas were presented rapidly and randomly in different keys to render the task difficult. Results showed a specific P3m (magnetic P300) effect to the non-harmonic targets which was only visible in subjects with low target recognition errors. Low resolution electro-magnetic tomography current density maps showed P3m sources in the right temporoparietal, left temporoparietal and frontocentral brain areas with right temporoparietal sources being strongest and most reliable. The results offer new possibilities to selectively study harmonic variables in music processing.

Adult↗