Disease Markers - Volume 34, issue 3

Authors: Kathariya, Rahul | Jain, Hansa | Gujar, Dnyneshwari | Singh, Archana | Ajwani, Himanshu | Mandhyan, Devendra

Article Type: Research Article

Abstract: Periodontal diseases are characterized by a complex set of biologic interactions between a diverse and dynamic microbial ecosystem and the host's multifaceted and responsive immune and inflammatory machinery. Such interactions between microbial pathogens and various host response systems play a critical role in the development and progression of periodontal disease via the release of inflammatory and immune mediators. Advances in periodontal disease diagnostic are moving toward methods whereby periodontal risk can be …identified and quantified by detecting such inflammatory mediators in its sequential pathophysiology. Pentraxins (PTXs) are classical mediators of inflammation and markers of acute-phase reaction. They are a super family of multifunctional molecules characterized by multimeric structure, divided into "short" PTXs and "long" PTXs. C-reactive protein (CRP) and pentraxin-3 (PTX3) are prototypic molecules of the short and long PTX family, respectively. Evidence suggests that PTXs acts as a non-redundant component of the humoral arm of innate immunity, downstream of, and complementary to, cellular recognition, as well as a tuner of inflammation. CRP is a cheaper biomarker and more readily available in everyday clinical practice compared with other inflammatory markers, on the other hand, PTX3 is believed to be the true independent indicator of disease activity and could have clinical implication in diagnosing the "at site" inflammatory status of the periodontal disease. These pentraxins are sensitive and specific in the diagnosis and prognosis of chronic diseases. Thus the pentraxins could be used as preferred biomarkers in periodontal disease diagnosis. Show more

Keywords: Pentraxins, biomarkers, C-reactive protein, pentraxin-3, periodontal disease

DOI: 10.3233/DMA-130963

Citation: Disease Markers, vol. 34, no. 3, pp. 143-151, 2013

Authors: Yamamoto, Masaaki | Imai, Yasutomo | Sakaguchi, Yoshiko | Haneda, Takashi | Yamanishi, Kiyofumi

Article Type: Research Article

Abstract: To characterize serum biomarkers reflecting the severity of generalized pustular psoriasis (GPP), we measured multiple cytokine/chemokine levels in 39 serum samples from 6 cases with GPP during the course of the disease. Serum levels of IL-4, IL-8, CXCL1 and CCL3 were positively correlated with the severity scores of GPP, white blood cell counts and serum C-reactive protein levels. Serum levels of IL-1β, IL-1ra, IL-6, IL-10, IL-12p70, IL-18, IL-22, IFN-γ and VEGF showed strong positive correlations (r> …0.4, p< 0.01) with all those 3 clinical markers. Of those, IL-10 and IL-22 were significantly decreased after treatment in parallel with the GPP score and therefore those two serum cytokines might be useful to evaluate the efficacy of treatment for GPP. Show more

Keywords: Generalized pustular psoriasis, cytokine, chemokine, serum, biomarker, severity of illness index

DOI: 10.3233/DMA-120958

Citation: Disease Markers, vol. 34, no. 3, pp. 153-161, 2013

Authors: Mar-Aguilar, Fermín | Mendoza-Ramírez, Jorge A. | Malagón-Santiago, Ismael | Espino-Silva, Perla K. | Santuario-Facio, Sandra K. | Ruiz-Flores, Pablo | Rodríguez-Padilla, Cristina | Reséndez-Pérez, Diana

Article Type: Research Article

Abstract: MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that can regulate gene expression, thereby affecting crucial processes in cancer development. miRNAs offer great potential as biomarkers for cancer detection because of their remarkable stability in blood and their characteristic expression in different diseases. We investigated whether quantitative RT-PCR miRNA profiling on serum could discriminate between breast cancer patients and healthy controls. We performed miRNA profiling on serum from breast cancer …patients, followed by construction of ROC (Receiver Operating Characteristic) curves to determine the sensitivity and specificity of the assay. We found that seven miRNAs (miR-10b, miR-21, miR-125b, miR-145, miR-155 miR-191 and miR-382) had different expression patterns in serum of breast cancer patients compared to healthy controls. ROC curve analyses revealed that three serum miRNAs could be valuable biomarkers for distinguishing BC from normal controls. Additionally, a combination of ROC curve analyses of miR-145, miR-155 and miR-382 showed better sensitivity and specificity of our assay. miRNA profiling in serum has potential as a novel method for breast cancer detection in the Mexican population. Show more

Keywords: Breast cancer, miRNAs, biomarkers, serum, miR-382

DOI: 10.3233/DMA-120957

Citation: Disease Markers, vol. 34, no. 3, pp. 163-169, 2013

Authors: Buxhofer-Ausch, Veronika | Ausch, Christoph | Zeillinger, Robert | Oberkanins, Christian | Dandachi, Nadia | Reiner-Concin, Angelika | Kriegshäuser, Gernot

Article Type: Research Article

Abstract: We report the performance evaluation of a non-quantitative reverse-hybridization assay (KRAS-BRAF StripAssay) designed for the simultaneous detection of 10 mutations in codons 12 and 13 of the KRAS gene and BRAF mutation V600E. Dilution experiments using DNA from tumor cell lines or from formalin-fixed paraffin-embedded (FFPE) colorectal cancer (CRC) tissue were performed to assess assay sensitivity. Using 50 ng of total DNA (mutant and wild-type), the KRAS-BRAF StripAssay demonstrated a detection limit of 1% …mutant sequence in a background of wild-type DNA. With respect to BRAF V600E, the KRAS-BRAF StripAssay was evaluated using 60 FFPE CRC samples previously analyzed by high resolution melting (HRM). Test strip hybridization identified 2/60 (3%) samples to carry the BRAF V600E mutation, and results were in agreement with those obtained by HRM analysis. This work demonstrates the KRAS-BRAF StripAssay to be a robust and sensitive method for the detection of common KRAS/BRAF mutations in genomic DNA isolated from FFPE tissue samples. Show more

Keywords: KRAS, BRAF, mutation detection, reverse-hybridization, high-resolution melting

DOI: 10.3233/DMA-120960

Citation: Disease Markers, vol. 34, no. 3, pp. 171-177, 2013

Authors: Luk, Cathy Choi-Wan | Chow, Kai-Ming | Kwok, Jeffrey Sung-Shing | Kwan, Bonnie Ching-Ha | Chan, Michael Ho-Ming | Lai, Ka-Bik | Lai, Fernand Mac-Moune | Wang, Gang | Li, Philip Kam-Tao | Szeto, Cheuk-Chun

Article Type: Research Article

Abstract: BACKGROUND: There is no reliable clinical test to predict the reversibility of acute-on-chronic renal failure. We study whether urinary biomarkers could be used as a noninvasive prognostic marker in patients with acute-on-chronic renal failure. METHODS: We studied 39 adult patients with pre-existing chronic renal impairment presenting to us with acute-on-chronic renal failure. Urinary neutrophil gelatinase-associated lipocalin (NGAL) level was measured. The mRNA of kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), alpha-1-microglobulin …(α1M), sodium/hydrogen exchanger-3 (NHE3), beta-2 microglobulin (β2M), and N-acetyl-β-D-glucosaminidase (NAG) in urinary sediment were quantified. RESULTS: Urinary NGAL level significantly correlated with the serum creatinine at presentation (r=0.762, p< 0.0001) but not baseline serum creatinine. Urinary sediment β2M expression significantly correlated with baseline glomerular filtration rate (GFR) (r= −0.400, p=0.012). Urinary α1M and NHE3 expressions were significantly higher in ischemic acute tubular necrosis than other causes of acute kidney injury (p< 0.0001 and p=0.006, respectively). Urinary α1M expression significantly correlated with the degree of improvement in renal function (r=0.387, p=0.026), as well as the estimated GFR 6 months later (r=0.386, p=0.027). CONCLUSION: In patients with acute-on-chronic renal failure, urinary NGAL level correlates with the severity of renal failure, while urinary α1M expression correlates with the degree of renal function recovery. Quantification of urinary α1M mRNA may be developed as an non-invasive tool for risk stratification of this group of patients. Show more

Keywords: Acute kidney injury, biomarker, proteinuria

DOI: 10.3233/DMA-120959

Citation: Disease Markers, vol. 34, no. 3, pp. 179-185, 2013

Authors: Liu, Chiu-Shong | Huang, Ru-Jiun | Sung, Fung-Chang | Lin, Cheng-Chieh | Yeh, Chih-Ching

Article Type: Research Article

Abstract: BACKGROUND: Previous studies inferring that the NOS3 gene was associated with the pathogenesis of metabolic syndrome (MetS) had inconsistent findings. We investigated the role of three NOS3 polymorphisms (T-786C, intron 4b/a, and G894T) in the risk of MetS using a hospital-based case-control study. METHODS: We recruited 339 MetS cases and 783 non-MetS controls at a central Taiwanese hospital. Information on sociodemographic and lifestyle factors was obtained using a self-administered questionnaire. Genotypes of NOS3 …polymorphisms were compared between cases and controls. Effects of interactions between gene polymorphisms and smoking and between gene polymorphisms and drinking on the risk of MetS were also determined. RESULTS: The T-786C TC+CC genotype was significantly associated with a decreased risk of MetS (odds ratio (OR), 0.63; 95% confidence interval (CI), 0.43–0.91), compared to the T-786C TT genotype, according to a logistic regression analysis. This beneficial effect was much greater for those who had ever smoked cigarettes (OR, 0.47; 95% CI, 0.26–0.87) or those who had not consumed alcohol (OR, 0.45; 95% CI, 0.26–0.77). In addition, the intron 4b/a variant genotype was marginally associated with a reduced risk of MetS (OR, 0.68; 95% CI, 0.47–1.00), compared to the intron 4b/a bb genotype, particularly for never alcohol consumers (OR, 0.56; 95% CI, 0.33–0.95). In the haplotype analysis, there was a 53% decrease in the MetS risk among C4bG haplotype carriers (OR, 0.47; 95% CI, 0.25–0.90), compared to those with the most common T4bG haplotype. CONCLUSIONS: Our results suggest that the NOS3 T-786C and intron 4b/a polymorphisms may contribute to the risk of MetS. Further studies are needed to confirm the findings. Show more

Keywords: Metabolic syndrome, endothelial nitric oxide synthase, polymorphisms, smoking, drinking

DOI: 10.3233/DMA-120961

Citation: Disease Markers, vol. 34, no. 3, pp. 187-197, 2013

Authors: Kleczyński, Paweł | Legutko, Jacek | Rakowski, Tomasz | Dziewierz, Artur | Siudak, Zbigniew | Zdzienicka, Joanna | Brzozowska-Czarnek, Agata | Surdacki, Andrzej | Dubiel, Jacek S. | Dudek, Dariusz

Article Type: Research Article

Abstract: PURPOSE: The aim of the study was to evaluate the utility of N-terminal pro-B-type natriuretic peptide (NT-pro BNP, pg/ml) assessment to predict infarct size and left ventricle function after ST-segment elevation myocardial infarction (STEMI) at long-term follow-up. METHODS: In 45 patients with first STEMI less than 3 hours from symptom onset treated with mechanical reperfusion NT-pro BNP was assessed early (at admission) and at 6 months. Cardiac magnetic resonance (CMR) parameters (delayed enhancement infarct …size (IS, %), left ventricular end-diastolic (LVEDVI, ml/m2) and end-systolic (LVESVI, ml/m2) volume indexes) were assessed at 6 months. RESULTS: No significant correlation was found between baseline NT-pro BNP assessment and IS and left ventricle function after 6 months. There was a significant correlation between 6-month NT-pro BNP and IS (r=0.65, p< 0.001) and left ventricle remodeling at 6 months (LVEDVI, r=0.53, p=0.001; LVESVI, r=0.51, p=0.002). CONCLUSIONS: Assessment of NT-pro BNP level 6 months after STEMI remains a good indicator of infarct size and left ventricle function at long-term follow-up. Show more

Keywords: ST-elevation myocardial infarction, infarct size, percutaneous coronary intervention, NT-pro BNP, cardiac magnetic resonance

DOI: 10.3233/DMA-120955

Citation: Disease Markers, vol. 34, no. 3, pp. 199-204, 2013

Authors: Lakpour, Niknam | Mirfeizollahi, Azadeh | Farivar, Shirin | Akhondi, Mohammad mehdi | Hashemi, S. Behnam | Amirjannati, Naser | Heidari-Vala, Hamed | Sadeghi, Mohammad Reza

Article Type: Research Article

Abstract: In this study we aimed to examine the effects of genetic variants of GSTM1 and GSTP1 (Ile105Val and Ala114Val) on GST activity, seminal oxidative stress and sperm chromatin status in infertile men with oligoasthenoteratozoospermia (OAT). The study population (n=121) consisted of 95 infertile men with OAT and 26 controls with normozoospermia. Multiplex polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods were utilized to detect the aforesaid genetic …variants. We measured GST activity and total antioxidant capacity (TAC) of seminal plasma by spectrophotometry. Sperm chromatin integrity and maturity were assessed using toluidine blue and chromomycin A_3 (CMA_3 -positive sperm) staining, respectively. The analysis showed that subgroups of GSTM1 null and GSTP1 C/T+T/T genotypes in comparison with GSTM1 present and GSTP1 wild type (C/C) genotypes did not have statistically significant differences in both OAT or normozoospermic men considering sperm concentration and motility, percentage of CMA_3 -positive sperm, seminal plasma TAC, sperm chromatin integrity and GST activity. Thus, the findings of our study suggest that there are no significant associations between GSTM1 and GSTP1 polymorphisms and sperm parameters at conventional or at molecular levels including OS status, sperm chromatin integrity or maturity in Iranian infertile men with OAT and normozoospermia. However, these polymorphisms could be related to the fertility status of the studied population but not evaluated in this study. Show more

Keywords: GSTM1, GSTP1, normozoospermia, polymorphism, oligoasthenoteratozoospermia, sperm

DOI: 10.3233/DMA-120954

Citation: Disease Markers, vol. 34, no. 3, pp. 205-210, 2013

Authors: Kim, Seong Eun | Kim, Uh Jin | Jang, Mi Ok | Kang, Seung Ji | Jang, Hee Chang | Jung, Sook In | Lee, Shin Seok | Park, Kyung Hwa

Article Type: Research Article

Abstract: INTRODUCTION: In this study, we determined whether serum ferritin levels could be used to differentiate between fever of unknown origin (FUO) caused by infectious and noninfectious diseases. METHODS: FUO patients were hospitalized at Chonnam National University Hospital between January, 2005 and December, 2011. According to the final diagnoses, five causes were identified, including infectious diseases, hematologic diseases, noninfectious inflammatory diseases, miscellaneous and undiagnosed. RESULTS: Of the 77 patients, 11 were caused by …infectious diseases, 13 by hematologic diseases, 20 by noninfectious inflammatory diseases, 8 by miscellaneous diseases, and 25 were undiagnosed. The median serum ferritin levels in infectious diseases was lower than those in hematologic diseases and (median (interquartile range) of 282.4 (149.0–951.8) ng/mL for the infectious disease group, 1818.2 (485.4–4789.5) ng/mL for the hematologic disease group, and 563.7 (399.6–1927.2) ng/mL for the noninfectious inflammatory disease group, p=0.048, Kruskal–Wallis test). By comparison using the Mann–Whitney test, statistically significant differences were found only between the infectious disease and hematologic disease groups (p=0.049) and between the infectious disease and groups (p=0.04). CONCLUSION: An optimal cutoff value of serum ferritin levels to predict FUO caused by a noninfectious disease (hematologic diseases, noninfectious inflammatory diseases) was established as 561 ng/mL. Show more

Keywords: Fever of unknown origin, ferritin

DOI: 10.3233/DMA-130962

Citation: Disease Markers, vol. 34, no. 3, pp. 211-218, 2013