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Authors: Anders, Mario | Sarbia, Mario | Grotzinger, Carsten | Meining, Alexander | Hofler, Heinz | Wiedenmann, Bertram | Rosch, Thomas
Article Type: Research Article
Abstract: In the current study we aimed to clarify the potential of EpCAM and villin as in vivo biomarkers for both Barrett esophagus (BE)-associated neoplasia and BE versus cardiac mucosa. Immunohistochemical staining in BE with various degrees of intraepithelial neoplasia (IN), Barrett carcinoma (BC) and in normal cardiac mucosa (CM) revealed a lack of EpCam and villin in squamous esophageal epithelium. All specimens of IN and BC showed EpCam with varying staining intensities. In 57% of CM …samples a weak signal was detected; the remainder displayed strong EpCam expression. Villin was found in 97% of BE specimens and in all those with IN; 37% of BC and 75% of CM specimens were~also positive. We conclude that expression of EpCam and villin differs only between squamous epithelium and BE. Determination of these proteins does not allow discrimination between different degrees of neoplasia or between esophageal intestinal metaplasia and cardiac mucosa. Show more
Keywords: Barrett, metaplasia, dysplasia, neoplasia, villin, EpCam, endoscopy, biomarker
Citation: Disease Markers, vol. 24, no. 6, pp. 287-292, 2008
Authors: Baye, Tesfaye M. | Perry, Rodney T. | Wiener, Howard W. | Chen, Zuomin | Harrell, Lindy E. | Go, Rodney C.P.
Article Type: Research Article
Abstract: The objective of this research was to develop a procedure to identify candidate genes under linkage peaks confirmed in a follow-up of candidate regions of interests (CRIs) identified in our original genome scan in the NIMH Alzheimer's diseases (AD) Initiative families (Blacker et al. [1]). There were six CRIs identified that met the threshold of multipoint lod score (MLS) of ⩾ 2.0 from the original scan. The most significant peak (MLS = 7.7) was at 19q13, …which was attributed to APOE. The remaining CRIs with 'suggestive' evidence for linkage were identified at 9q22, 6q27, 14q22, 11q25, and 3p26. We have followed up and narrowed the 9q22 CRI signal using simple tandem repeat (STR) markers (Perry et al. [2]). In this confirmatory project, we have followed up the 6q27, 14q22, 11q25, and 3p26 CRIs with a total of 24 additional flanking STRs, reducing the mean interval marker distance (MID) in each CRI, and substantially increase in the information content (IC). The linkage signals at 6q27, 14q22 and 11q25 remain 'suggestive', indicating that these CRIs are promising and worthy of detailed fine mapping and assessment of candidate genes associated with AD. We have developed a bioinformatics approach for identifying candidate genes in these confirmed regions based on the Gene Ontology terms that are annotated and enriched among the systematic meta-analyzed genes, confirmed by at least three case-control samples, and cataloged in the "AlzGene database" as potential Alzheimer disease susceptibility genes (http://www.alzgene.org). Show more
Keywords: Alzheimer, linkage, QTL, STR, SNP, Genomic scan, Candidate gene, bioinformatics, gene ontology, GO, Alzforum, Alzgene database
Citation: Disease Markers, vol. 24, no. 6, pp. 293-309, 2008
Authors: Piwowar, Agnieszka | Knapik-Kordecka, Maria | Warwas, Maria
Article Type: Research Article
Abstract: Aim: The main goal of the present study was the evaluation of ischemia-modified albumin (IMA) in patients with type 2 diabetes mellitus and estimation of its connection with vascular complications, glycemic control, hypertension, dyslipidemia and obesity. Methods: In 76 diabetic patients and 25 control subjects, a plasma level of IMA by manually performed, spectrophotometric Co(II)-albumin binding assay was determined. Other parameters such as glucose, fructosamine, HbA_{1c} , total cholesterol and its fractions (HDL, …LDL), triglicerydes were estimated by routine methods. Results: Diabetic patients had significantly higher level of IMA in comparison with control subjects. There were not significant differences between groups with various states of vascular complications although the lowest concentration of IMA was observed in patients with microangiopathy. Patients with poor glycemic control had higher IMA level in comparison with these with good glycemic control. Significant correlation was observed between IMA and HbA_{1c} . Among the risk factors, only blood pressure and LDL showed a weak relationship with IMA level. Conclusions: Our results revealed, for the first time, higher level of IMA in diabetic patients which confirms that it may be of non-cardiac origin. We can suggest that the albumin molecule in plasma of diabetic patients is modified in the chronic hypoxia conditions provoked mainly by hyperglycemia and oxidative stress in diabetes. Show more
Citation: Disease Markers, vol. 24, no. 6, pp. 311-317, 2008
Authors: Santos, Mónica | Yan, Jin | Temudo, Teresa | Oliveira, Guiomar | Vieira, José Pedro | Fen, Jinong | Sommer, Steve | Maciel, Patrícia
Article Type: Research Article
Abstract: In this work we explored the role of the 3'UTR of the MECP2 gene in patients with clinical diagnosis of RTT and mental retardation; focusing on regions of the 3'UTR with almost 100% conservation at the nucleotide level among mouse and human. By mutation scanning (DOVAM-S technique) the MECP2 3'UTR of a total of 66 affected females were studied. Five 3'UTR variants in the MECP2 were found (c.1461+9G>A, c.1461+98insA, c.2595G>A, c.9961C>G and c.9964delC) in …our group of patients. None of the variants found is located in putative protein-binding sites nor predicted to have a pathogenic role. Our data suggest that mutations in this region do not account for a large proportion of the RTT cases without a genetic explanation. Show more
Keywords: Autism, neurodevelopment, 3'untranslated region
Citation: Disease Markers, vol. 24, no. 6, pp. 319-324, 2008
Authors: Sinués, Blanca | Vicente, Jorge | Fanlo, Ana | Mayayo-Sinués, Esteban | González-Andrade, Fabricio | Sánchez-Q, Dora | Martínez-Jarreta, Begoña
Article Type: Research Article
Abstract: Polymorphisms in CYP3A genes, such as CYP3A5} and CYP3A4, as well as in the MDR1 gene, which encodes for P-glycoprotein, have been implicated as genetic markers in several disorders. Differences in the frequency distribution of the allelic variants CYP3A5*3, CYP3A4*1B, and MDR1 3435T have been demonstrated between distinct ethnic groups. In this study we examined the frequency of these allelic variants in 317 healthy Mestizo individuals from Ecuador and made comparisons with …results reported in the literature. The genotypes were determined by PCR-RFLP. Allele and genotype differences were studied by chi-square test. The MDR1 T allele frequency was similar to that of Spaniard or Asian populations, which is consistent with the ethnic origin of Ecuadorian Mestizo individuals (Amerindian and Spaniard Caucasians). By contrast, the CYP3A5*3 allele frequency was significantly lower in Ecuadorians than in Spaniards and other white populations and higher than in Central Americans, Asians and blacks. CYP3A4*1B was more common in Ecuadorians than in Caucasian or Asian populations but less present than in blacks. The differences in the polymorphism found in this work should be considered in allele-disease association studies. Show more
Keywords: CYP3A5*3, CYP3A4*1B, MDR1 C3435T, Ecuadorians, disease markers
Citation: Disease Markers, vol. 24, no. 6, pp. 325-331, 2008
Authors: Koshy, Linda | Easwer, H.V. | Neetha, N.V. | Natarajan, Chandrasekhar | Bhattacharya, R.N. | Banerjee, Moinak
Article Type: Research Article
Abstract: Endothelial nitric oxide synthase (eNOS) gene polymorphisms have been implicated as predisposing genetic factors that can predict aneurysmal subarachnoid hemorrhage (aSAH), but with controversial results from different populations. Using a case-control study design, we tested the hypothesis whether variants in eNOS gene can increase risk of aSAH among South Indian patients, either independently, or by interacting with other risk factors of the disease. We enrolled 122 patients, along with 224 ethnically …matched controls. We screened the intron-4 27-bp VNTR, the promoter T-786C and the exon-7 G894T SNPs in the eNOS gene. We found marked interethnic differences in the genotype distribution of eNOS variants when comparing the South Indian population with the reported frequencies from Caucasian and Japanese populations. Genotype distributions in control and patient populations were found to be in Hardy-Weinberg equilibrium. In patients, the allele, genotype and estimated haplotype frequencies did not differ significantly from the controls. Multiple logistic regression indicated hypertension and smoking as risk factors for the disease, however the risk alleles did not have any interaction with these risk factors. Although the eNOS polymorphisms were not found to be a likely risk factor for aSAH, the role of factors such as ethnicity, gender, smoking and hypertension should be evaluated cautiously to understand the genotype to phenotype conversion. Show more
Keywords: eNOS, SNP, aneurysm, subarachnoid hemorrhage, India
Citation: Disease Markers, vol. 24, no. 6, pp. 333-339, 2008
Authors: Huang, Huiling | Mai, Weiyi | Liu, Dan | Hao, Yuantao | Tao, Jun | Dong, Yugang
Article Type: Research Article
Abstract: Objective: Oxidized LDL cholesterol (ox-LDL-C) is considered to be a key factor of initiating and accelerating atherosclerosis (AS). The purpose of this study is to elucidate the sensitivity and specificity of ox-LDL and oxidation ratio of LDL in the diagnosis of coronary artery disease (CAD). For the first time, we investigated the ratio of ox-LDL to ALB(ox-LDL/ALB). Methods and results: Blood ox-LDL, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol …(LDL-C), triglyceride (TG) and albumin (ALB) were measured in patients with acute myocardial infarction (AMI, n = 80), unstable angina pectoris (UAP, n = 80), stable angina pectoris (SAP, n = 80), normal control (n = 60), and dyslipidemia control (n = 60). Ox-LDL was measured by competitive ELISA. The level of ox-LDL and oxidation ratio of LDL(ox-LDL/TC, ox-LDL/HDL-C, ox-LDL/ LDL-C and ox-LDL/ALB) were significantly higher in each diseased group than controls (P < 0.001). In CAD group, ox-LDL and oxidation ratio of LDL in subjects complicated with hypertension (HT) and/or diabetes mellitus (DM) increased further (P < 0.001). Ox-LDL/ALB in the AMI group was 7 times higher than normal control group (0.068 ± 0.017 vs 0.009 ± 0.007, P < 0.001). The area under the curve (AUC) of receiver operating characteristic curve (ROC curve) is a criterium to evaluate the accuracy of diagnosing a disease. The AUC of ROC curve of ox-LDL/TC, ox-LDL/HDL-C, ox-LDL, ox-LDL/ALB and ox-LDL/ LDL-C for diagnosing CAD were 0.975, 0.975, 0.966, 0.966, 0.957 respectively (P < 0.001). When ox-LDL/TC = 0.175, the sensitivity and specificity of diagnosing CAD were 0.917 and 0.925, which were almost equal to each other, indicating that the rates of missed diagnosis and misdiagnosis for CAD were the lowest. Conclusions: The level of ox-LDL and the ratio of ox-LDL/TC, ox-LDL/LDL-C, ox-LDL/HDL-C and ox-LDL/ALB are better biomarkers than TC, TG, HDL-C and LDL-C for discriminating between patients with coronary artery disease and healthy subjects. And patients who have a high ratio of ox-LDL /TC may have a higher risk for CAD. Show more
Keywords: Coronary artery disease, atherosclerosis, oxidized low density lipoprotein, cholesterol
Citation: Disease Markers, vol. 24, no. 6, pp. 341-349, 2008
Authors: Zhang, Xianglan | Shu, Xiao-Ou | Signorello, Lisa B. | Hargreaves, Margaret K. | Cai, Qiuyin | Linton, MacRae F. | Fazio, Sergio | Zheng, Wei | Blot, William J.
Article Type: Research Article
Abstract: Individuals from low socioeconomic backgrounds are disproportionately affected by the burden of cardiovascular disease (CVD), yet data regarding risk factors in this population are lacking, particularly regarding emerging biomarkers of CVD such as C-reactive protein (CRP). We measured high-sensitivity CRP and examined its association with demographic and lifestyle factors in a sample of 792 participants aged 40–79 years from the Southern Community Cohort Study, which has an over-representation of socioeconomically disadvantaged individuals …(over 60% with a total annual household income <$15,000). We found that within this population the prevalence of elevated CRP (>3 mg/L) varied significantly by sex, race, smoking status, and body mass index (BMI). The multivariable-adjusted prevalence odds ratios (ORs) (95% CIs) for having elevated CRP were 1.6 (1.1–2.3) for women vs. men, 1.4 (0.9–2.0) for African Americans vs. whites, 2.3 (1.4–3.8) for African American women vs. white men, 1.8 (1.2–2.7) for current smokers vs. non-smokers, and 4.2 (2.7–6.6) for obese (BMI 30.0–44.9 kg/m^{2} ) vs. healthy-weight (BMI 18.3–24.9 kg/m^{2} ) participants. Further stratified analyses revealed that the association between BMI and elevated CRP was stronger among African Americans than whites and women than men, with prevalence ORs (95% CI) comparing obese vs. healthy-weight categories reaching 22.8 (7.1–73.8) for African American women. In conclusion, in this socioeconomically disadvantaged population, sex, race, smoking, and BMI were associated with elevated CRP. Moreover, inflammatory response to obesity differed by race and sex, which may contribute to CVD disparities. Show more
Keywords: C-reactive protein, obesity, race, sex
Citation: Disease Markers, vol. 24, no. 6, pp. 351-359, 2008
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