Disease Markers - Volume 31, issue 6

Authors: Lucchi, Naomi W. | Jain, Vidhan | Wilson, Nana O. | Singh, Neeru | Udhayakumar, Venkatachalam | Stiles, Jonathan K.

Article Type: Research Article

Abstract: Biomarkers have been used to diagnose and prognosticate the progress and outcome of many chronic diseases such as neoplastic and non communicable diseases. However, only recently did the field of malaria research move in the direction of actively identifying biomarkers that can accurately discriminate the severe forms of malaria. Malaria continues to be a deadly disease, killing close to a million people (mostly children) every year. One life-threatening complication of malaria is cerebral malaria (CM). Studies …carried out in Africa have demonstrated that even with the best treatment, as high as 15–30% of CM patients die and about 10–24% of CM survivors suffer short-or long-term neurological impairment. The transition from mild malaria to CM can be sudden and requires immediate intervention. Currently, there is no biological test available to confirm the diagnosis of CM and its complications. It is hoped that development of biomarkers to identify CM patients and potential risk for adverse outcomes would greatly enhance better intervention and clinical management to improve the outcomes. We review here what is currently known regarding biomarkers for CM outcomes. A Pub Med literature search was performed using the following search terms: "malaria," "cerebral malaria," "biomarkers," "mortality" and "neurological sequelae." This search revealed a paucity of usable biomarkers for CM management. We propose three main areas in which researchers can attempt to identify CM biomarkers: 1) early biomarkers, 2) diagnostic biomarkers and 3) prognostic biomarkers. Show more

Keywords: Biomarkers, cerebral malaria, severe malaria, malaria

DOI: 10.3233/DMA-2011-0854

Citation: Disease Markers, vol. 31, no. 6, pp. 327-335, 2011

Authors: Fernandez, Sonia | French, Martyn A. | Price, Patricia

Article Type: Research Article

Abstract: HIV-infected individuals responding to antiretroviral therapy (ART) after severe CD4^{+} T-cell depletion may retain low responses to recall antigens [eg: cytomegalovirus (CMV)] and altered expression of T-cell co-stimulatory molecules consistent with immunosenescence. We investigated the capacity of phenotypically senescent cells to generate cytokines in HIV patients receiving long-term ART (n=18) and in healthy controls (n=10). Memory T-cells were assessed by interferon (IFN)-γ ELISpot assay and flow …cytometrically via IFN-γ or IL-2. Proportions of CD57^{bright} CD28^{null} CD4^{+} T-cells correlated with IFN-γ responses to CMV (p=0.009) and anti-CD3 (p=0.002) in HIV patients only. Proportions of CD57^{bright} CD28^{null} CD8^{+} T-cells and CD8^{+} T-cell IFN-γ responses to CMV peptides correlated in controls but not HIV patients. IL-2 was predominantly produced by CD28^{+} T-cells from all donors, whereas IFN-γ was mostly produced by CD57^{+} T-cells. The findings provide evidence of an accumulation of immunosenescent T-cells able to make IFN-γ. This may influence the pathogenesis of secondary viral infections in HIV patients receiving ART. Show more

Keywords: CD57, HIV, immune activation, immunosenescence

DOI: 10.3233/DMA-2011-0847

Citation: Disease Markers, vol. 31, no. 6, pp. 337-342, 2011

Authors: Becerik, Sema | Afacan, Beral | Öztürk, Veli Özgen | Atmaca, Harika | Emingil, Gülnur

Article Type: Research Article

Abstract: Aim: The aim of the present study was to investigate gingival crevicular fluid (GCF) calprotectin, osteocalcin and cross-linked N-terminal telopeptide (NTx) levels in health along with different periodontal diseases. Material and methods: Twenty chronic periodontitis (CP), 20 generalized aggressive periodontitis (G-AgP), 20 gingivitis and 20 healthy subjects were included. Probing depth, clinical attachment level, plaque index and papillary bleeding index was recorded. GCF calprotectin, osteocalcin and NTx levels were analyzed by enzyme-linked immunosorbent assay (ELISA). …Results: CP, G-AgP and gingivitis groups had higher GCF calprotectin total amount compared to healthy subjects (p< 0.008). CP and G-AgP groups had similar, but higher levels compared to gingivitis groups (p< 0.008). CP and G-AgP groups had lower GCF osteocalcin total amount compared to gingivitis and healthy groups (p< 0.008). CP group had higher GCF NTx but lower osteocalcin total amount and osteocalcin/NTx ratio than the G-AgP group (p< 0.008). Conclusions: Our results suggest that elevated GCF calprotectin levels play a role as a reliable inflammatory marker in the pathogenesis of periodontal disease. Fluctuating GCF levels of osteocalcin and NTx might point out to the abnormal bone turnover in periodontitis. Our data document for the first time the role of NTx in the pathogenesis of different periodontal diseases. Show more

Keywords: Calprotectin, osteocalcin and NTx in periodontitis

DOI: 10.3233/DMA-2011-0849

Citation: Disease Markers, vol. 31, no. 6, pp. 343-352, 2011

Authors: Birbian, Niti | Singh, Jagtar | Jindal, Surinder Kumar | Joshi, Amit | Batra, Navneet

Article Type: Research Article

Abstract: Background: Asthma is the most prevalent disease in India according to the national survey conducted by NFHS 2 in 1998–399. Prostaglandin D2 (PGD2) is a bronchoconstriction inducing metabolite of arachidonic acid in the mast cells, which is produced on exposure to allergens and acts as a ligand for the Prostaglandin D2 Receptor (PTGDR). Polymorphisms in the PTGDR gene have been suggested to be involved in the mechanism of asthma. Objective: This is the first study conducted in …India, investigating the role of PTGDR -441C/T} promoter polymorphism in asthma pathogenesis. Methods: A case-control study was performed with a total of 992 subjects, including 410 adult asthmatics and 582 healthy controls from regions of North India. The PTGDR -441C/T polymorphism was genotyped by Tetra-Primer Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra-Primer ARMS PCR). Results: Statistical analysis of the results between asthma cases and controls for the PTGDR -441C/T polymorphism showed Chi^{2} (χ ^{2} )=0.29, OR=0.95, 95% CI (0.70–1.15) and p=0.599. Neither the genotypic nor the allelic frequencies observed for the PTGDR -441C/T polymorphism, were significantly associated with asthma or asthma phenotypes. Conclusions: The PTGDR -441C/T polymorphism is not associated with asthma or its phenotypes in the studied North Indian population. Show more

Keywords: Asthma, Prostaglandin D2 (PGD2), Prostaglandin D2 Receptor (PTGDR), Tetra-Primer Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra-Primer ARMS PCR)

DOI: 10.3233/DMA-2011-0850

Citation: Disease Markers, vol. 31, no. 6, pp. 353-359, 2011

Authors: Gandhi, G. | Buttar, B. Singh | Albert, L. | Hasan, Q. | Aggarwal, R.K.

Article Type: Research Article

Abstract: Psoriasis is a common, chronic, recurrent, inflammatory, hyper proliferative disorder of the skin, which has a relatively high prevalence in the general population (0.6–4.8%). Linkage and association analyses in various populations have revealed a major locus for psoriasis susceptibility, PSORS1, at 6p21.3. Association of the disease with human leukocyte antigen (HLA) Cw6, corneodesmosin (CDSN) and the coiled-coil alpha-helical rod protein-1 (CCHCR1) has also been reported. Though the PSORS1 locus accounts for 30–50% of familial psoriasis in …various global population groups, yet no studies have been published from the North Indian population. Some of the SNPs in HLA-C and CCHCR1 genes have been reported as markers for disease susceptibility. Therefore in the present study, DNA samples from psoriasis patients from North India were genotyped for polymorphisms in CCHCR1 and HLA-C genes. The allele frequencies were calculated for patients and controls, and were compared for odds ratio and confidence interval values. SNPn.7*22222 (rs12208888), SNPn.7*22333 (rs12216025), SNPn.9*24118 (rs10456057), CCHCR1_386 (rs130065), CCHCR1_404 (rs130076) and CCHCR1_1364 (rs130071) were found to be significant in psoriasis patients. Linkage disequilibrium analysis revealed two haplotypes (rs12208888, rs2844608, rs12216025, rs10456057, rs130065, rs130066, rs130068, rs130269, and rs12208888, rs2844608, rs12216025, rs130076, rs130066, rs130068, rs130269, rs130071) as highly susceptible haplotypes for psoriasis in the cohort studied. Preliminary analysis of the data also suggests the possibilities of ethnic group specific disease related polymorphisms, pending validation in future studies. Show more

Keywords: Psoriasis, SNP Polymorphism, North-Indian, CCHCR1 gene, HLA-C gene

DOI: 10.3233/DMA-2011-0851

Citation: Disease Markers, vol. 31, no. 6, pp. 361-370, 2011

Authors: Bhatt, Surya Prakash | Nigam, Priyanka | Misra, Anoop | Guleria, Randeep | Luthra, Kalpana | Vaidya, M. | Jain, S.K. | Pasha, M.A. Qadar

Article Type: Research Article

Abstract: Background: Genetics of non-alcoholic fatty liver (NAFLD) in Asian Indians has been inadequately investigated. This study aims to determine the association of the 1784G>C polymorphism in the SREBP-2 gene with NAFLD in Asian Indians in north India. Methods: In this study, (n=335); 162 obese with NAFLD, 91 obese without NAFLD and 82 non-obese without NAFLD subjects were recruited. Abdominal ultrasound, clinical profile, anthropometry, metabolic profile, serum levels of alanine aminotransferase, aspartate aminotransferase, fasting insulin …and high sensitivity C-reactive protein (hs-CRP) were analysed. Polymerase chain reaction and restriction fragment length polymorphism were used to identify individual genotypes, and the association of this polymorphism with clinical and biochemical parameters was assessed. Results: The observed frequency of G allele was 0.73 and C allele was 0.27. Frequency of C/C genotype was higher in NAFLD as compared to obese and non-obese subjects (p=0.003). In NAFLD subjects 57.4% were G/G homozygous, 31.5% G/C heterozygous and 11.1% were C/C homozygous. The SREBP-2 genotype frequencies deviated from the Hardy Weinberg Equilibrium (X^{2} =6.39, p =0.0114). Mean values of TG (p = 0.002), TC (p =0.002), ALT (p =0.04) and AST (p =0.03) levels were significantly higher in NAFLD subjects with G/C genotype as compared to G/G genotypes in obese and non-obese groups. Fasting insulin (p =0.03), HOMA (p =0.009) and hs-CRP levels were significantly higher in NAFLD subjects with G/C genotype as compared to obese and non obese subjects with G/G genotypes. Conclusion: In this study, conducted for the first time in Asian Indians, SREBP-2 1784 G>C genotype was associated with NAFLD. Show more

Keywords: Sterol regulatory element binding protein-2, Non-alcoholic fatty liver disease, Asian Indians, Alanine transaminase

DOI: 10.3233/DMA-2011-0852

Citation: Disease Markers, vol. 31, no. 6, pp. 371-377, 2011

Authors: Tomar, Anil Kumar | Sooch, Balwinder Singh | Raj, Isha | Singh, Sarman | Singh, Tej P. | Yadav, Savita

Article Type: Research Article

Abstract: Human seminal plasma contains a large array of proteins of clinical importance which are essentially needed to maintain the reproductive physiology of spermatozoa and for successful fertilization. Thus, isolation and identification of seminal plasma proteins is of paramount significance for their biophysical characterization and functional analysis in reproductive physiological processes. In this study, we have isolated Concanavalin-A binding glycoproteins from human seminal plasma and subsequently identified them by MALDI-TOF/MS analysis. The major …proteins, as identified in this study, are Aminopeptidase N, lactoferrin, prostatic acid phosphatase, zinc-alpha-2-glycoprotein, prostate specific antigen, progestagen-associated endometrial protein, Izumo sperm-egg fusion protein and prolactin inducible protein. This paper also reports preliminary studies to identify altered expression of these proteins in oligospermia and azoospermia in comparison to normospermia. In oligospermia, five proteins were found to be downregulated while in azoospermia, four proteins were downregulated and two proteins were upregulated. Thus, this study is of immense biomedical interest towards identification of potential male infertility marker proteins in seminal plasma. Show more

Keywords: Azoospermia, glycoproteins, lectin affinity chromatography, male infertility, oligospermia

DOI: 10.3233/DMA-2011-0853

Citation: Disease Markers, vol. 31, no. 6, pp. 379-386, 2011

Article Type: Other

Citation: Disease Markers, vol. 31, no. 6, pp. 387-391, 2011