Disease Markers - Volume 32, issue 3

Authors: Chatterjee, Animesh | Rathore, Anurag | Vidyant, Sanjukta | Kakkar, Kavita | Dhole, Tapan N.

Article Type: Research Article

Abstract: A multitude of host genetic factors plays a crucial role in susceptibility to HIV-1 infection and progression to AIDS, which is highly variable among individuals and populations. This review focuses on the chemokine-receptor and chemokine genes, which were extensively studied because of their role as HIV co-receptor or co-receptor competitor and influences the susceptibility to HIV-1 infection and progression to AIDS in HIV-1 infected individuals.

Keywords: HIV-1 infection, Polymorphism, Chemokine receptor, Chemokines

DOI: 10.3233/DMA-2011-0874

Citation: Disease Markers, vol. 32, no. 3, pp. 143-151, 2012

Authors: Sharma, Ratnesh Kumar | Sharma, Bechan

Article Type: Research Article

Abstract: Various efforts have been made in past in order to predict the underlying mechanism of pesticide-induced toxicity using in vitro and animal models, however, these predictions may or may not be directly correlated with humans. The present study was designed to investigate the carbofuran induced genotoxicity and its amelioration by vitamins C and E by treating human peripheral blood lymphocytes (PBLs) with different concentrations (0, 0.5, 1.25, 2.5, 3.75 and 5.0 μM) of this compound. The …treatment of PBLs with carbofuran displayed significant DNA damage in concentration dependent manner. The carbofuran induced genotoxicity could be ameliorated to considerable extent by pretreatment of PBLs with equimolar (10 μM) concentration of each of the vitamins C and E; the magnitude of protection by vitamin E being higher than by vitamin C. Also, it was found that the level of protection by these vitamins was higher when PBLs were treated with lower concentrations of pesticide. The significant DNA damage as observed by H_{2} O_{2} , a positive control in the present study, and its amelioration by natural antioxidants (vitamins C and E) lend an evidence to suggest that carbofuran would have caused genotoxicity via pesticide induced oxidative stress. Show more

Keywords: Carbofuran, genotoxicity, comet assay, vitamin C, vitamin E, human lymphocytes

DOI: 10.3233/DMA-2011-0870

Citation: Disease Markers, vol. 32, no. 3, pp. 153-163, 2012

Authors: Sezer, Ufuk | Çiçek, Yasin | Çanakçi, Cenk Fatih

Article Type: Research Article

Abstract: Background: 8-hydroxydeoxyguanosine (8-OHdG) is commonly used as a marker to evaluate oxidative DNA damage in disorders including chronic inflammatory diseases such as inflammatory periodontal pathologies. In the current study we hypothesized that the level of 8-OHdG in saliva increases by the periodontal destruction severity determined by clinical parameters as clinical attachment level (CAL). Materials and methods: A cross-sectional study was conducted on a sum of 60 age gender balanced; chronic periodontitis …(CP) (n=20), chronic gingivitis (CG) (n=20) and healthy (H) (n=20) individuals. Clinical periodontal parameters and salivary 8-OHdG levels were evaluated. Results: The mean 8-OHdG level in the saliva of the CP group was significantly higher than H and CG groups (p< 0.001). Statistically significant correlation was only observed between the salivary levels of 8-OHdG and age (p< 0.05), probing depth (PD) and CAL (p< 0.001) in CP group. However, when CP patients were classified according to their CAL levels (CAL⩾ 3 mm (n=11) and CAL<3 mm (n=9)) statistically significant correlation was only observed between the salivary levels of 8-OHdG and CAL ⩾ 3 mm patients (p< 0.001). Conclusion: We suggest that elevated salivary levels of 8-OHdG may be a marker for disease activity and it may reflect indirectly disease severity parameters such as CAL. Show more

Keywords: Periodontitis, saliva, 8-hydroxydeoxyguanosine, clinical attachment level, disease activity, oxidative DNA damage

DOI: 10.3233/DMA-2011-0876

Citation: Disease Markers, vol. 32, no. 3, pp. 165-172, 2012

Authors: Moura, Karla Cristina Vasconcelos | Junior, Mário Campos | de Rosso, Ana Lúcia Zuma | Nicaretta, Denise Hack | Pereira, João Santos | José Silva, Delson | Santos-Rebouças, Cíntia Barros | Pimentel, Márcia Mattos Gonçalves

Article Type: Research Article

Abstract: Parkinson's disease is one of the most common neurodegenerative disorders associated with aging, reaching ∼ 2% of individuals over 65 years. Knowledge achieved in the last decade about the genetic basis of Parkinson's disease clearly shows that genetic factors play an important role in the etiology of this disorder. Exon dosage variations account for a high proportion of Parkinson's disease mutations, mainly for PARKIN gene. In the present study, we screened genomic rearrangements in SNCA, PARKIN, …PINK1 and DJ-1 genes in 102 Brazilian Parkinson's disease patients with early onset (age of onset ⩽ 50 years), using the multiplex ligation-dependent probe amplification method. Family history was reported by 24 patients, while 78 were sporadic cases. Screening of exon dosage revealed PARKIN and PINK1 copy number variations, but no dosage alteration was found in SNCA and DJ-1 genes. Most of the carriers harbor heterozygous deletions or duplications in the PARKIN gene and only one patient was found to have a deletion in PINK1 exon 1. Data about dosage changes are scarce in the Brazilian population, which stresses the importance of including exon dosage analysis in Parkinson's disease genetic studies. Show more

Keywords: Copy number variation, early-onset, MLPA, Deletion, Duplication

DOI: 10.3233/DMA-2011-0873

Citation: Disease Markers, vol. 32, no. 3, pp. 173-178, 2012

Authors: Mehdi, Mohammad Murtaza | Singh, Prabhakar | Rizvi, Syed Ibrahim

Article Type: Research Article

Abstract: Sialic acids are substituted neuraminic acid derivatives which are typically found at the outermost end of glycan chains on the membrane in all cell types. The role of erythrocyte membrane sialic acids during aging has been established however the relationship between sialic acid and oxidative stress is not fully understood. The present work was undertaken to analyze the relationship between erythrocyte membrane sialic acid with its plasma level, membrane and plasma lipid hydroperoxide levels and plasma …total antioxidant capacity. Results show that sialic acid content decreases significantly (P< 0.001) in RBC membrane (r= −0.901) and increases in plasma (r=0.860) as a function of age in humans. Lipid peroxidation measured in the form of hydroperoxides increases significantly (P<0.001) in plasma (r=0.830) and RBC membranes (r=0.875) with age in humans. The Trolox Equivalent Total Antioxidant Capacity (TETAC) of plasma was found to be significantly decreased (P< 0.001, r=−0.844). We observe significant correlations between decrease of erythrocyte membrane sialic acid and plasma lipid hydroperoxide and TETAC. Based on the observed correlations, we hypothesize that increase in oxidative stress during aging may influence the sialic acid decomposition from membrane thereby altering the membrane configuration affecting many enzymatic and transporter activities. Considering the importance of plasma sialic acid as a diagnostic parameter, it is important to establish age-dependent reference. Show more

Keywords: Erythrocyte, aging, sialic acid, oxidative stress

DOI: 10.3233/DMA-2011-0871

Citation: Disease Markers, vol. 32, no. 3, pp. 179-186, 2012

Authors: Mitic, N. | Milutinovic, B. | Jankovic, M.

Article Type: Research Article

Abstract: This study was aimed at obtaining insight into the diversity of sialic acids in cancer- and non-cancer-related CA125 antigen, tumour marker of serous ovarian cancer. Starting from available data suggesting the possible relevance of sialic acids for discriminating CA125 antigens of different origin, we have employed a new experimental approach based on the use of human sialic acid-binding Ig-like lectins, Siglecs, as tools for the investigation of sialylation. Siglec-2, belonging to the group of …evolutionarily conserved Siglecs, and Siglec-3, −6, −7, −9 and −10, which are CD33-like Siglecs, were probed in solid-phase binding assays with cancer-related CA125 antigens from pleural fluid of patients with ovarian carcinoma (pfCA125), the OVCAR-3 ovarian carcinoma cell line (clCA125) and a non-cancer-related CA125 antigen, i.e. pregnancy-associated pCA125 antigen. All Siglecs used showed detectable binding to pCA125 antigen. Siglec-3, Siglec-7 and Siglec-2 exhibited moderately stronger binding to pCA125 antigen than the others. In contrast to this, Siglec-2 and Siglec-3 preferentially recognized pfCA125 with greater total binding than for pCA125, whereas Siglec-9 and Siglec-10 were highly selective for clCA125. Siglecs promise to be powerful tools for discriminating CA125 of different origin and could propagate further research on other molecular markers of biomedical and diagnostic importance. Show more

Keywords: CA125 antigen, glycans, sialic acid, Siglec

DOI: 10.3233/DMA-2011-0872

Citation: Disease Markers, vol. 32, no. 3, pp. 187-194, 2012

Authors: Chen, Lu | Su, Liping | Li, Jianfang | Zheng, Yanan | Yu, Beiqin | Yu, Yingyan | Yan, Min | Gu, Qinlong | Zhu, Zhenggang | Liu, Bingya

Article Type: Research Article

Abstract: Most cases of gastric cancer (GC) are not diagnosed at early stage which can be curable, so it is necessary to identify effective biomarkers for its diagnosis and pre-warning. We have used methylated DNA immunoprecipitation (MeDIP) to identify genes that are frequently methylated in gastric cancer cell lines. Promoter regions hypermethylation of candidate genes were tested by methylation-specific polymerase chain reaction (MSP) in serum samples, including GC (n=58), gastric precancerous lesions (GPL, n=46), and normal …controls (NC, n=30). Eighty two hypermethylated genes were acquired by array analysis and 5 genes (BCAS4, CHRM2, FAM5C, PRAC and MYLK) were selected as the candidate genes. Three genes (CHRM2, FAM5C and MYLK) were further confirmed to show methylation rates increased with progression from NC to GPL, then to GC. There was obvious decrease in detection of FAM5C and MYLK hypermethylation, but not CHRM2, from preoperative to postoperative evaluation (P< 0.001). Combined detection of FAM5C and MYLK hypermethylation had a higher sensitivity in GC diagnosis (77.6%,45/58) and pre-warning (30.4%,14/46) than one single gene detection and also had a high specificity of 90%. The combined hypermethylated status of FAM5C and MYLK correlated with tumor size (P<0.001), tumor invasion depth (P=0.001) and tumor-node-metastasis (TNM) stage (P=0.003). Hypermethylated FAM5C and MYLK can be used as potential biomarkers for diagnosis and pre-warning of GC. Show more

Keywords: Gastric cancer, hypermethylated DNA, biomarker, diagnosis, pre-warning, FAM5C and MYLK

DOI: 10.3233/DMA-2011-0877

Citation: Disease Markers, vol. 32, no. 3, pp. 195-202, 2012

Authors: Mohelnikova-Duchonova, Beatrice | Oliverius, Martin | Honsova, Eva | Soucek, Pavel

Article Type: Research Article

Abstract: Histologically verified pairs (n=10) of pancreatic tumors and non-neoplastic tissues were used for quantitative real-time PCR and the stability of 24 reference genes was analyzed with geNorm and NormFinder software. Raw C_{q} values correlated with the degree of RNA degradation. This correlation was abolished by normalization to C_{q} of 18S endogenous control gene. Both geNorm and NormFinder programs suggested EIF2B1, ELF1, MRPL19, and POP4 as the same most …stable genes. We have thus identified suitable reference genes for future expression studies in pancreatic carcinoma. Normalization method reducing the effects of RNA degradation on the quality of results was also developed. Show more

Keywords: Pancreas, carcinoma, transcript, quantification, reference gene, normalization

DOI: 10.3233/DMA-2011-0875

Citation: Disease Markers, vol. 32, no. 3, pp. 203-210, 2012