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Results for “Biomarker variability”

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PubMed2002

Multivariate analysis of survival, recurrence, progression and development of mestastasis in T1 and T2a transitional cell bladder carcinoma.

BACKGROUND: Determination of prognosis factors associated with survival, recurrence, progression, and development of metastasis in T1 and T2a transitional cell carcinoma (TCC) of the bladder is discussed. METHODS: A study was conducted of a group of 210 patients with primary bladder TCC at classification T1 (n = 175) and T2aN0M0 (n = 35). A total of 177 variables were studied in each patient. The monoclonal antibodies used were the following: DO7 (p53) and MIB-1 (Ki-67). Prognosis was obtained using Kaplan-Meier methodology and Cox proportional hazards model. RESULTS: The average follow-up period was 6.7 years. Cancer-related survival rates at 5 and 10 years were 82.96% and 74.78%, respectively. The independent survival variables were the following: age and expression of p53. Recurrence free survival at 5 and 10 years stood at 51.80% and 42.71%, respectively. The independent recurrence variables were T2a classification, tumor multifocality, tumor size of greater than 3 cm, carcinoma in situ in random biopsy, and expression of Ki-67. Progression free survival rates at 5 and 10 years were 75.31% and 69.16%, respectively. The independent progression variables were age, T2a classification, and expression of p53. Metastasis free survival rates at 5 and 10 years stood at 87.23% and 84.55%, respectively. The expression of p53 was the sole variable to provide an independent prediction of metastasis. CONCLUSIONS: The expression of p53 clearly has an independent effect on the prediction of survival, progression and development of metastasis, showing a dose-response effect. Tumor multifocality and T2a classification are the variables that best predict recurrence.

Aged↗

PubMed2000

Metallothionein expression in epithelial ovarian cancer: effect of chemotherapy and prognostic significance.

BACKGROUND AND PURPOSE: Regimens containing platinum drugs continue to be amongst the most effective therapies for ovarian cancer. However, despite high initial response rates most patients relapse and die of their disease. Elevation of metallothionein has been implicated as a mechanism by which tumour cells become resistant to platinum anticancer drugs, although most of these studies have been carried out in vitro. This study was carried out to determine whether metallothionein expression was associated with response or survival in patients with epithelial ovarian cancer. METHODS: Metallothionein was determined by radioimmune assay using frozen ovarian tumour tissue taken either before or following cytotoxic chemotherapy. RESULTS: An increase in expression of metallothionein was seen in tumour tissue from patients who had undergone cytotoxic chemotherapy, although this did not attain significance. However, a preliminary study using biopsy material from the same patient, taken both before and after chemotherapy, showed a statistically significant increase in metallothionein. An analysis of these data showed that the level of metallothionein expression was not associated with survival or response. CONCLUSION: These data do not support the hypothesis that metallothionein expression is a determinant of response in ovarian cancer. There is some preliminary evidence from the study of paired samples which indicates that cytotoxic chemotherapy may increase metallothionein expression. An increase in metallothionein was also seen in the study using unmatched biopsies although this did not attain statistical significance, due in part to the large inter-patient variability in expression of this protein.

Adult↗

PubMed2006

Quantitative ultrasound variables of the heel in Finnish men aged 18-20 yr: predictors, relationship to bone mineral content, and changes during military service.

INTRODUCTION: Determinants of BUA and SOS and their changes during military service-associated physical training were studied in 196 army recruits and 50 control men, aged 18-20 years. METHODS: Heel ultrasound measurement, DXA, muscle strength test, Cooper's running test and genetic analyses were performed. Lifestyle factors were recorded. Sex steroids and bone turnover markers were determined. Heel ultrasound was repeated after six months. RESULTS: Exercise was the most significant determinant of both BUA (p<0.0001) and SOS (p<0.0001). There were 10% and 1.3% differences in BUA (p=0.006) and SOS (p=0.0001), respectively, between men belonging to the lowest and highest quartiles of exercise index. Weight associated with BUA (p=0.005) and height with SOS (p=0.03). BUA and SOS correlated with BMC and BMD (p<0.0001) but explained only up to 21% of their variance. Over six months SOS increased more in recruits than in control men (p=0.0043), the increase being higher, the lower muscle strength at baseline (r =-0.27, p=0.0028). CONCLUSION: Exercise is the most important determinant of ultrasonographic variables in men, aged 18-20 years. Physical loading during military training increases SOS.

Adolescent↗

PubMed1988

Cellular and molecular correlates of aging in the nervous system.

Three characteristic features of aging in the nervous system are reviewed: deficits in the regulation of nerve-cell calcium levels, increased leakage of synaptic transmitters and changes in neuronal arborization. In hippocampal cells and motor nerve terminals, the rate of calcium clearance from the immediate vicinity of the membrane decreases with age. There is further evidence of decreased rates of transmembrane Ca2+ flux in synaptosomal preparations from aged animals. Stimulation-evoked transmitter release, which is calcium dependent, appears to increase at some neuromuscular junctions during aging; in contrast, high-K+-induced release in brain tissue appears to decline. A much more consistent age-related increase in "basal" transmitter efflux, under nonstimulated conditions, has been observed in both the peripheral and the central nervous system. This may be related to increased nerve-terminal arborization, which occurs in actively used muscles during aging. Likewise, dendritic branching becomes more extensive with moderate age; at advanced age, though, branching decreases. Furthermore, motor nerve terminal branching also decreases with age in muscles subject to disuse. This variability among morphologic features during aging illustrates the need to standardize ages and preparations when comparing these types of data.

Aging↗

PubMed1995

Prognostic value of combined response markers among human immunodeficiency virus-infected persons: possible aid in the decision to change zidovudine monotherapy.

To clarify useful clinical parameters for determining the need for changes in antiretroviral regimens, 586 persons who were seropositive for the human immunodeficiency virus (HIV) and who had intermediate-stage HIV disease underwent follow-up semiannually for a median of 3.1 years after zidovudine monotherapy was instituted. The strongest predictors of time to the development of AIDS and of survival were an increased CD4 lymphocyte count (> 50/microL), a decreased neopterin level (> 2.4 nmol/L), and no increase in the number of symptoms after 7-12 months of zidovudine therapy. Men who had the best quartile CD4 lymphocyte and neopterin responses and who also had no increase in the number of symptoms were 23 times less likely to die (reflecting a 96% increase in survival) than were men who had the worst responses in these variable categories. After 7-12 months of zidovudine therapy, 5-year survival rates were 63% for men with good responses in all three variable categories, 47%-49% for those with good CD4 lymphocyte responses and good responses in one other variable category, 31% for those with only a good CD4 lymphocyte response, and 0 for those with poor responses in all three variable categories.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Comparison of inert markers [chromic oxide or insoluble ash (Celite)] for determining apparent metabolizable energy of wheat- or barley-based broiler diets with or without enzymes.

A broiler chick bioassay was used to measure the effect of two inert digestibility markers on the determination of dietary AME. Diets contained 80% of either wheat or barley (with or without enzyme) and either chromic oxide at 0.5% or one of three levels of insoluble ash (0.5, 1.0, or 1.5%) as markers. The various cereal and marker diet combinations were consumed ad libitum (0 to 21 d) by two groups of 10 male broilers in each of two trials. The AME of each diet was determined by measuring the respective marker ratios between diet and excreta (collected for 24 h at 7 or 21 d) or ileal digesta collected at 21 d. Growth and feed conversion were measured on each group of birds between 0 and 21 d. There was no effect of marker on growth or feed efficiency. However, determination of AME of wheat- or barley-based diets with or without enzymes were affected by choice of marker and whether markers were measured in excreta (7 or 21 d) or ileal digesta. Chromic oxide was viewed as the least accurate method for determining AME, based on chronic oxide's inability to define AME differences between barley-based diets with and without enzymes, whereas insoluble ash clearly demonstrated improved AME of wheat- and barley-based diets with an enzyme. The optimum levels of insoluble ash for accuracy and repeatability were between 0.5 and 1.0%. The AME of the diets were, on average, 5% lower when determined with 7 vs 21 d excreta and 2.5% lower for ileal digesta than excreta collected at 21 d. It was concluded that identification of components that result in variability in AME levels of diets will be improved if a bioassay uses insoluble ash as a marker.

Aging↗

PubMed2003

Adenocarcinoma of the thymus: report of two cases, including a previously undescribed mucinous subtype.

We report two cases of primary thymic adenocarcinoma, a very uncommon neoplasm with limited information in the literature. Both patients were men (age 15 and 39 years). The first case was a mucinous carcinoma, a subtype of adenocarcinoma not previously recognized in the thymus. It comprised islands and strips of mucin-rich tumor cells floating in large pools of extracellular mucin. There was transition of carcinomatous epithelium to the attenuated epithelium of a thymic cyst. Immunostaining for high molecular weight cytokeratin furthermore highlighted in one area negatively stained tumor islands wrapped by positively stained residual thymic medullary epithelium, suggesting in situ origin of the carcinoma from the thymic epithelium. The second case was a papillary carcinoma with high nuclear grade and many psammoma bodies. It showed strong immunoreactivity for CD5 and did not stain for CA-125 as well as thyroid, pulmonary, and mesothelial markers. The findings in this study therefore broaden the morphologic spectrum of thymic adenocarcinomas to include a mucinous subtype. Review of the literature indicates that thymic adenocarcinomas usually arise from thymic cyst or type A thymoma, and the clinical outcome is variable.

Adenocarcinoma, Mucinous↗

PubMed2003

Bayesian multiple testing for two-sample multivariate endpoints.

In clinical studies involving multiple variables, simultaneous tests are often considered where both the outcomes and hypotheses are correlated. This article proposes a multivariate mixture prior on treatment effects, that allows positive probability of zero effect for each hypothesis, correlations among effect sizes, correlations among binary outcomes of zero versus nonzero effect, and correlations among the observed test statistics (conditional on the effects). We develop a Bayesian multiple testing procedure, for the multivariate two-sample situation with unknown covariance structure, and obtain the posterior probabilities of no difference between treatment regimens for specific variables. Prior selection methods and robustness issues are discussed in the context of a clinical example.

Bayes Theorem↗

PubMed2006

Overexpression of SOCS3 is associated with decreased survival in a cohort of patients with de novo follicular lymphoma.

The prognostic significance of SOCS3 protein expression was determined in de novo follicular lymphomas (FL) with t(14;18) and bcl-2 overexpression. Presentation lymph nodes from 82 FL patients for whom clinical information was available were immunohistochemically segregated into SOCS3-positive (n = 42) or -negative (n = 40) cohorts, and overall survival (OS) was analysed. SOCS3-positive FL patients had a median OS of 10 years compared with 22 years in SOCS3-negative patients (P = 0.001, log rank test). After adjusting for Follicular Lymphoma International Prognostic Index subgroups, SOCS3 overexpression remained an independent predictor of decreased OS (P < 0.001). These findings suggest that overexpression of SOCS3 may be an independent poor prognostic variable in patients with de novo FL.

Adult↗

PubMed2006

Predictive validity of ventilatory and lactate thresholds for cycling time trial performance.

PURPOSE: To determine which laboratory measurement best predicts 40 km cycling time-trial (TT) performance. METHODS: Fifteen male cyclists performed lactate-threshold (LT), ventilatory-threshold (VT), 5 km and 40 km TT. Key variables of interest were Watts at thresholds. For VT determination we used: breakpoint of ventilatory equivalent of oxygen (VE/VO2); breakpoint of ventilatory equivalent of carbon dioxide (VE/VCO2); V-slope; respiratory exchange ratio (RER)=1 and 0.95. For LT we used Stegmann's individual anaerobic threshold; the stage preceding the second 0.5 mmol L(-1) increase (Baldari); 4 mmol L(-1); 1 mmol L(-1) increase in 3 min; the stage preceding the first 1 mmol L(-1) increase as criterion methods (<1 mmol). Analyses also included peak power during the incremental threshold tests (MaxVT(watts), MaxLT(watts)) and 5 km performance (5K(avgwatts)). RESULTS: Regression analyses between VT variables and 40K(avgwatts) were significant for V-slope (r2=0.63), VE/VO2 (r2=0.64), RER(0.95) (r2=0.53), RER1 (r2=0.57), and MaxVT(watts) (r2=0.65). Regressions between LT variables and 40K(avgwatts) were significant for Baldari (r2=0.52), 4 mmol L(-1) (r2=0.36), <1 mmol (r2=0.35), Keul (r2=0.34), and MaxLT(watts) (r2=0.51). Regressions between 5K variables and 40K(avgwatts) were significant for 5K(avgwatts) (r2=0.58). Paired t-tests between these variables and the 40K(avgwatts) indicated that absolute power outputs at VE/VO2 (P=0.33), RER(0.95) (P=0.93), and 4 mmol L(-1) (P=0.39) were not significantly different from 40K(avgwatts). CONCLUSION: We conclude that VT-based variables are generally superior to LT variables relative to predicting 40K(avgwatts), the simplest of several valid measures appears to be VE/VO2.

Adult↗

PubMed1995

An isolated cardiac conduction disease maps to chromosome 19q.

Isolated cardiac conduction disease is an autosomal dominant defect that includes various combinations of bundle branch or fascicular blocks. These defects can cause sudden death due to a complete heart block. We used a genome-wide screening approach with polymorphic (CA)n repeat markers to determine the chromosomal position of the gene defect implicated in this disorder. The analyses were carried out on a large Lebanese kindred, which included individuals with either a complete or incomplete right bundle branch block (RBBB) with a vertical-axis deviation (< or = -30 or > or = +100). Linkage to the disease locus was detected with the polymorphic marker D19S604 on the q arm of chromosome 19 (19q13.3) with a multipoint lod score of 7.18. Additionally, we were able to exclude the flanking loci D19S606 and D19S571, which are 13 cM apart because of recombination events in three affected individuals. The histidine-rich calcium-binding protein gene is found in this region and is an attractive candidate gene on the basis of its physiological properties and a tight linkage. There is no expansion in two exon 1 regions known for a variable number of triplet repeats.

Base Sequence↗

PubMed1993

Characterization of a marker of differentiation for tracheal ciliated cells independent of ciliation.

Although morphologic features have been used to follow cell lineage and differentiation, an objective assessment of differentiation can be best established by characterizing the expression of specific proteins that form the phenotypic profile of differentiated cells. Thus, specific markers or probes are required to unequivocally identify the various types of cells resulting from differentiation in a cell lineage. We report characterization of an IgM monoclonal antibody (5B4/H3), which recognized a surface antigen of approximately 130 kD unique to ciliated cells. The antibody reacted with the lumenal surface of the ciliated cells in transmission electron micrographs, in immunohistochemical staining of tracheal sections, and in cultured monolayers of tracheal epithelial cells. Flow cytometry, performed on enzymatically dispersed tracheal epithelial cells tagged with 5B4/H3 and fluorescent-labeled goat anti-mouse IgA/IgG/IgM, produced a population of fluorescent ciliated cells and a mixed nonfluorescent, nonciliated cell population. Ciliated cells were followed in vitro by time-lapse video microscopy for 48 to 72 h. Some of the ciliated cells lost their cilia under these culture conditions, but these cells were still found to react with the 5B4/H3 antibody. The antigen detected by this antibody remained on the surface of the cells after they lost their cilia. These results indicate that 5B4/H3 recognized a cell surface antigen that is specific to the ciliated cells and is independent of cell morphology. This marker will be useful in tissue culture studies of airway epithelial lineage, or differentiation, in which cell morphology is variable and cannot be used as a reliable marker of differentiation.

Animals↗

PubMed1992

Effects of intravenous streptokinase and CLS 2210 (calcium dobesilate) on the biochemical markers of early acute myocardial infarction: a historic comparison with both studies.

In a previous double-blind, randomized study, CLS 2210 (a new formulation of calcium dobesilate) or placebo was administered by intravenous infusion to 41 patients having their first acute myocardial infarction. In the present study 19 comparable patients were treated intravenously with streptokinase under identical conditions and the results compared with those from the previous study. In all patients administration was begun within three hours of onset of symptoms and continued over seventy-two hours. Blood samples were taken for the measurement of serum activity of creatine kinase and its isoenzyme MB, and the serum and urinary concentrations of myoglobin and glycosaminoglycans were also measured. The purpose of this study was to determine the effects of CLS 2210, placebo, and streptokinase on these biochemical markers of acute myocardial infarction, thereby assessing their actions in limiting myocardial necrosis. In the CLS 2210-treated patients, the levels of serum creatine kinase and serum and urinary myoglobin were significantly lower than in the placebo patients throughout the seventy-two hours (p = 0.01, 0.005, 0.004 respectively). The levels of creatine kinase MB and serum glycosaminoglycan in the CLS 2210 patients were initially higher than in the placebo patients but fell below placebo levels between the fortieth and fifty-fifth hours, respectively (p = 0.89, 0.02). Only the glycosaminoglycan urinary concentrations were higher in the CLS 2210 group than in the placebo group throughout (p = 0.0005). The values for the six variables investigated showed no statistically significant difference between placebo and streptokinase.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzenesulfonates↗

PubMedDate not supplied

Homocysteine and vascular access thrombosis in end-stage renal disease patients: a retrospective study.

BACKGROUND: Though pathology in end-stage renal disease (ESRD) patients with high total homocysteine (tHcy) can be established, the research findings with vascular access thrombosis (VAT) and tHcy are equivocal. Investigators have found significantly higher homocysteine levels in patients with recurrent VAT compared with one or less episodes of thrombosis. Initial prospective evidence supports an independent association between tHcy levels and access thrombosis. METHODS: One hundred and four patients undergoing dialysis were selected. The experimental group participants were identified as those having one or more vascular access thromboses (VAT) during the previous 14-month period (November 2000 to January 2002) and the control group participants were those with no VAT during the same period. Additional sub-group analyses included the following: a) hypertensive vs. normotensive; b) diabetes mellitus, Type I, Type II, and none; c) gender; d) age. RESULTS: The Mann-Whitney U test for variance revealed no significant difference in tHcy values between VAT groups (U = 1580.5, p = 0.075), no significant differences in VAT and hypertension (U = 1009.0, p = 0.70), and no significant differences in VAT and Diabetes Mellitus (U = 1254.5, p = 0.67). A two-sample t-Test revealed no significant differences in tHcy and age (F-ratio = 1.26, p = 0.47). A Kolmogorov Smirnov test for normality revealed insufficient evidence that the tHcy distribution is not normal. Spearman Rank Correlations were calculated revealing low to moderate associations among variables. CONCLUSIONS: While some studies have demonstrated a relationship between tHcy and VAT, this study found chronically high homocysteine levels in patients with ESRD were not associated with incidence of VAT. There were no significant differences in the number of VAT's across additional variables of age, gender, and previous morbidity. No significant interactions were discovered.

Adult↗

PubMed2004

Associations between reproductive and menstrual factors and postmenopausal sex hormone concentrations.

Reproductive and menstrual characteristics, as well as high circulating estrogen concentrations, are associated with risk of hormone-related cancers in postmenopausal women. To explore possible etiologic relationships between menstrual/reproductive characteristics and risk of hormone-related cancers, we examined associations between menstrual/reproductive factors and serum concentrations of free estradiol, total estradiol, estrone, sex hormone binding globulin (SHBG), and follicle stimulating hormone (FSH). This study was conducted in 173 postmenopausal women using data from the prerandomization visit of an exercise clinical trial. Participants were sedentary, overweight/obese, and not on hormone therapy. Women > or =20 years past menopause had 23% lower total estradiol and 30% lower free estradiol concentrations than women within 4 years of menopause (P for trend = 0.04 and 0.02, respectively). Nulliparous women had 19% higher FSH concentrations than parous women (P = 0.02). Among parous women, parity was positively associated with SHBG and negatively associated with free estradiol concentrations. Women with > or =4 children had 20% lower free estradiol and 38% higher SHBG concentrations compared with women with one birth (P for trend = 0.02 and 0.01, respectively). Total number of months spent breast-feeding was modestly and inversely associated with serum FSH concentrations (P for trend = 0.07). Our results suggest that menstrual/reproductive characteristics may be associated with postmenopausal hormone concentrations; verification of these results in other studies may elucidate how these variables influence risk of hormone-related cancers.

Age Distribution↗

PubMed1990

Tumor markers of head and neck carcinoma.

Evaluation of the various tumor markers that have been studied in patients with SCC of the head and neck reveals no single marker or battery of markers that is sufficiently specific or sensitive to provide useful clinical data in the treatment of patients with these cancers. This finding reinforces previous investigative and clinical impressions that would suggest that carcinoma of the head and neck is a heterogeneous entity. These tumor marker studies provide additional support for the hypothesis that although various carcinomas of the head and neck may appear identical microscopically, their behavior both clinically and biochemically is nevertheless heterogeneous. Due to the wide variability of the behavior of these tumors, the search for the perfect tumor marker continues. The development of additional multiple-marker batteries may provide the closest approximation to a perfect marker that is feasible. Additional studies into the nature and function of oncogenes may provide additional clues to the variability of these tumors and the resultant heterogenicity of their marker expression.

Antibodies, Viral↗

PubMed2006

Data processing and classification analysis of proteomic changes: a case study of oil pollution in the mussel, Mytilus edulis.

BACKGROUND: Proteomics may help to detect subtle pollution-related changes, such as responses to mixture pollution at low concentrations, where clear signs of toxicity are absent. The challenges associated with the analysis of large-scale multivariate proteomic datasets have been widely discussed in medical research and biomarker discovery. This concept has been introduced to ecotoxicology only recently, so data processing and classification analysis need to be refined before they can be readily applied in biomarker discovery and monitoring studies. RESULTS: Data sets obtained from a case study of oil pollution in the Blue mussel were investigated for differential protein expression by retentate chromatography-mass spectrometry and decision tree classification. Different tissues and different settings were used to evaluate classifiers towards their discriminatory power. It was found that, due the intrinsic variability of the data sets, reliable classification of unknown samples could only be achieved on a broad statistical basis (n > 60) with the observed expression changes comprising high statistical significance and sufficient amplitude. The application of stringent criteria to guard against overfitting of the models eventually allowed satisfactory classification for only one of the investigated data sets and settings. CONCLUSION: Machine learning techniques provide a promising approach to process and extract informative expression signatures from high-dimensional mass-spectrometry data. Even though characterisation of the proteins forming the expression signatures would be ideal, knowledge of the specific proteins is not mandatory for effective class discrimination. This may constitute a new biomarker approach in ecotoxicology, where working with organisms, which do not have sequenced genomes render protein identification by database searching problematic. However, data processing has to be critically evaluated and statistical constraints have to be considered before supervised classification algorithms are employed.

Journal Article↗

PubMed2005

A signature-based method to distinguish time-of-flight secondary-ion mass spectra from biological samples.

Time-Of-Flight Mass Spectrometry (TOF-SIMS) was used to determine elemental and biomolecular ions from isolated protein samples. We identified a set of 23 mass-to-charge ratio (m/z) peaks that represent signatures for distinguishing biological samples. The 23 peaks were identified by Singular Value Decomposition (SVD) and Canonical Analysis (CA) to find the underlying structure in the complex mass-spectra data sets. From this modified data, SVD was used to identify sets of m/z peaks, and we used these patterns from the TOF-SIMS data to predict the biological source from which individual mass spectra were generated. The signatures were validated using an additional data set different from the initial training set used to identify the signatures. We present a simple method to identify multiple variables required for sample classification based on mass spectra that avoids overfit. This is important in a variety of studies using mass spectrometry, including the ability to identify proteins in complex mixtures and for the identification of new biomarkers.

Biological Products↗