Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Hemostatic Parameters according to Renal Function and Time after Transplantation in Brazilian Renal Transplanted Patients Wed, 01 Jul 2015 11:52:07 +0000 http://www.hindawi.com/journals/dm/2015/472750/ Kidney transplantation is the key for patients with end-stage renal disease, improving quality of life and longer survival. However, kidney transplant triggers an intense inflammatory response and alters the hemostatic system, but the pathophysiological mechanisms of these changes are not completely understood. The aim of this cross-sectional cohort study was to investigate hemostatic biomarkers in Brazilian renal transplanted patients according to renal function and time after transplantation. A total of 159 renal transplanted patients were enrolled and D-Dimer (D-Di), Thrombomodulin (TM), von Willebrand Factor (VWF), and ADAMTS13 plasma levels were assessed by ELISA. An increase of D-Di was observed in patients with higher levels of creatinine. ADAMTS13 levels were associated with creatinine plasma levels and D-Di levels with Glomerular Filtration Rate. These results suggested that D-Di and ADAMTS13 can be promising markers to estimate renal function. ADAMTS13 should be investigated throughout the posttransplant time to clarify the participation of this enzyme in glomerular filtration and acceptance or rejection of the graft in Brazilian transplanted patients. Ana Paula Lucas Mota, Patrícia Nessralla Alpoim, Roberta Carvalho de Figueiredo, Ana Cristina Simões e Silva, Karina Braga Gomes, and Luci Maria SantAna Dusse Copyright © 2015 Ana Paula Lucas Mota et al. All rights reserved. Radiosynthesis, In Vivo Biological Evaluation, and Imaging of Brain Lesions with [123I]-CLINME, a New SPECT Tracer for the Translocator Protein Thu, 25 Jun 2015 11:10:42 +0000 http://www.hindawi.com/journals/dm/2015/729698/ The high affinity translocator protein (TSPO) ligand 6-chloro-2-(4′-iodophenyl)-3-(N,N-methylethyl)imidazo[1,2-a]pyridine-3-acetamide (CLINME) was radiolabelled with iodine-123 and assessed for its sensitivity for the TSPO in rodents. Moreover neuroinflammatory changes on a unilateral excitotoxic lesion rat model were detected using SPECT imaging. [123I]-CLINME was prepared in 70–80% radiochemical yield. The uptake of [123I]-CLINME was evaluated in rats by biodistribution, competition, and metabolite studies. The unilateral excitotoxic lesion was performed by injection of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid unilaterally into the striatum. The striatum lesion was confirmed and correlated with TSPO expression in astrocytes and activated microglia by immunohistochemistry and autoradiography. In vivo studies with [123I]-CLINME indicated a biodistribution pattern consistent with TPSO distribution and the competition studies with PK11195 and Ro 5-4864 showed that [123I]-CLINME is selective for this site. The metabolite study showed that the extractable radioactivity was unchanged [123I]-CLINME in organs which expresses TSPO. SPECT/CT imaging on the unilateral excitotoxic lesion indicated that the mean ratio uptake in striatum (lesion : nonlesion) was 2.2. Moreover, TSPO changes observed by SPECT imaging were confirmed by immunofluorescence, immunochemistry, and autoradiography. These results indicated that [123I]-CLINME is a promising candidate for the quantification and visualization of TPSO expression in activated astroglia using SPECT. F. Mattner, M. Quinlivan, I. Greguric, T. Pham, X. Liu, T. Jackson, P. Berghofer, C. J. R. Fookes, B. Dikic, M.-C. Gregoire, F. Dolle, and A. Katsifis Copyright © 2015 F. Mattner et al. All rights reserved. Aldehyde Dehydrogenase Polymorphisms and Blood Pressure Elevation in the Japanese: A Cross-Sectional and a Longitudinal Study over 20 Years in the Shimane CoHRE Study Mon, 22 Jun 2015 11:19:35 +0000 http://www.hindawi.com/journals/dm/2015/825435/ Purpose. Effects of a genetic polymorphism in the aldehyde dehydrogenase-2 (ALDH2) on blood pressure (BP) were investigated in a cross-sectional and a longitudinal study over 20 years on Japanese rural residents. Methods. Health examinations were held through 2006 to 2012, and 3,202 participates were recruited for this study. Among these participants, 560 individuals had medical records that were obtained in a health examination 20 years ago. Genomic DNA of participants was extracted from blood and the genotype of a polymorphism in ALDH2 was determined by the TaqMan method. Multivariate regression analyses were performed to examine association between BP and the genetic polymorphism in the ALDH2 gene. Results. Systolic and diastolic BP were higher in the ALDH21/1 than the others (ALDH21/2 or ALDH22/2). Genetic variation of the ALDH2 gene apparently influenced drinking behavior as the number of the drinkers was significantly reduced in the ALDH22/2 after 20 years of the observation period. This polymorphism, however, did not confer a risk for BP increase in the longitudinal observation. Conclusion. The present cross-sectional study confirmed a genetic effect of the ALDH2 gene on BP. In contrast, no significant effects on BP were identified in a longitudinal study, which may require a careful consideration. Minoru Isomura, Tao Wang, Masayuki Yamasaki, Md. Zahid Hasan, Kuninori Shiwaku, and Toru Nabika Copyright © 2015 Minoru Isomura et al. All rights reserved. The Impact of Gene Polymorphisms on the Success of Anticholinergic Treatment in Children with Overactive Bladder Wed, 17 Jun 2015 11:55:50 +0000 http://www.hindawi.com/journals/dm/2015/732686/ Aim. To determine the impact of gene polymorphisms on detrusor contraction-relaxation harmony in children with lower urinary tract symptoms (LUTS). Materials and Methods. Toilet trained children older than 5 years of age with LUTS and normal neurological examination underwent videourodynamic study. The control group was composed of age matched children with no voiding complaints. The study group who filled out the voiding dysfunction symptom score before and after the treatment received standard oxybutynin treatment and was reevaluated 1 year after treatment. Genomic DNA was isolated from all patients and subjected to PCR for amplification. Genotyping of ARGHEF10, ROCK2, ADRB3, and CYP3A4 was carried out with Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results. 34 (45%) and 42 (55%) patients were enrolled in the study and control group, respectively. ARGEF10 GG, ADRB3 TC, and CYP3A4 AG genotype patients displayed insignificant difference between pre- and posttreatment voiding dysfunction symptom score and bladder volumes. Conclusions. The polymorphism of genes in the cholinergic pathway did not significantly differ clinical parameters. On the other hand, polymorphic patients in the adrenergic pathway seemed to suffer from clinical disappointment. For this reason, we think that the neglected adrenergic pathway could be a new therapeutic target for the treatment of anticholinergic resistant LUTS in children. Serhat Gurocak, Ece Konac, Iyimser Ure, Cem Senol, Ilke Hacer Onen, Sinan Sozen, and Adnan Menevse Copyright © 2015 Serhat Gurocak et al. All rights reserved. Retracted: System Accuracy Evaluation of the GlucoRx Nexus Voice TD-4280 Blood Glucose Monitoring System Wed, 17 Jun 2015 08:59:13 +0000 http://www.hindawi.com/journals/dm/2015/496928/ Disease Markers Copyright © 2015 Disease Markers. All rights reserved. Predicting Preterm Labour: Current Status and Future Prospects Mon, 15 Jun 2015 11:59:40 +0000 http://www.hindawi.com/journals/dm/2015/435014/ Preterm labour and birth are a major cause of perinatal morbidity and mortality. Despite modern advances in obstetric and neonatal management, the rate of preterm birth in the developed world is increasing. Yet even though numerous risk factors associated with preterm birth have been identified, the ability to accurately predict when labour will occur remains elusive, whether it is at a term or preterm gestation. In the latter case, this is likely due to the multifactorial aetiology of preterm labour wherein women may display different clinical presentations that lead to preterm birth. The discovery of novel biomarkers that could reliably identify women who will subsequently deliver preterm may allow for timely medical intervention and targeted therapeutic treatments aimed at improving maternal and fetal outcomes. Various body fluids including amniotic fluid, urine, saliva, blood (serum/plasma), and cervicovaginal fluid all provide a rich protein source of putative biochemical markers that may be causative or reflective of the various pathophysiological disorders of pregnancy, including preterm labour. This short review will highlight recent advances in the field of biomarker discovery and the utility of single and multiple biomarkers for the prediction of preterm birth in the absence of intra-amniotic infection. Harry M. Georgiou, Megan K. W. Di Quinzio, Michael Permezel, and Shaun P. Brennecke Copyright © 2015 Harry M. Georgiou et al. All rights reserved. Serum Chemerin Levels in relation to Osteoporosis and Bone Mineral Density: A Case-Control Study Mon, 15 Jun 2015 07:17:07 +0000 http://www.hindawi.com/journals/dm/2015/786708/ Background. To evaluate serum chemerin levels in patients with osteoporosis and healthy controls and to investigate the relationship between serum chemerin levels and bone mineral density (BMD). Methods. An age- and gender-matched case-control study was conducted. Pearson’s correlation test was performed to investigate the relationship between serum chemerin levels and BMD. Results. There were 93 patients included in the osteoporosis group and 93 matched controls. Serum chemerin level was significantly higher in patients with osteoporosis ( ng/mL) than patients in control ( ng/mL) (). There was a negative correlation between femoral bone mineral density and chemerin in both groups (, in osteoporosis group; , in control) and also a negative correlation between lumbar bone mineral density with chemerin in both groups (, in osteoporosis group; , in control). Conclusions. Patients with osteoporosis presented a higher level of serum chemerin, which witnessed an inverse correlation with BMD. Further studies are needed to explore the role of chemerin in the pathophysiology of osteoporosis. Jing He, Ji-Chun Li, Hua Xie, Zhong-Hua Xu, Ya-Wen Sun, and Qiao Shan Copyright © 2015 Jing He et al. All rights reserved. Serum Cystatin C for the Diagnosis of Acute Kidney Injury in Patients Admitted in the Emergency Department Mon, 15 Jun 2015 06:53:07 +0000 http://www.hindawi.com/journals/dm/2015/416059/ Background. Early diagnosis of acute kidney injury (AKI) at emergency department (ED) is a challenging issue. Current diagnostic criteria for AKI poorly recognize early renal dysfunction and may cause delayed diagnosis. We evaluated the use of serum cystatin C (CysC) for the early and accurate diagnosis of AKI in patients hospitalized from the ED. Methods. In a total of 198 patients (105 males and 93 females), serum CysC, serum creatinine (sCr), and estimated glomerular filtration rate (eGFR) were calculated at 0, 6, 12, 24, 48, and 72 hours after presentation to the ED. We compared two groups according to the presence or absence of AKI. Results. Serial assessment of CysC, sCr, and eGFR was not a strong, reliable tool to distinguish AKI from non-AKI. CysC > 1.44 mg/L at admission, both alone (Odds Ratio = 5.04; 95%CI 2.20–11.52; ) and in combination with sCr and eGFR (Odds Ratio = 5.71; 95%CI 1.86–17.55; ), was a strong predictor for the risk of AKI. Conclusions. Serial assessment of CysC is not superior to sCr and eGFR in distinguishing AKI from non-AKI. Admission CysC, both alone and in combination with sCr and eGFR, could be considered a powerful tool for the prediction of AKI in ED patients. Cristina Bongiovanni, Laura Magrini, Gerardo Salerno, Chiara Serena Gori, Patrizia Cardelli, Mina Hur, Marco Buggi, and Salvatore Di Somma Copyright © 2015 Cristina Bongiovanni et al. All rights reserved. HULC and H19 Played Different Roles in Overall and Disease-Free Survival from Hepatocellular Carcinoma after Curative Hepatectomy: A Preliminary Analysis from Gene Expression Omnibus Sun, 07 Jun 2015 13:59:14 +0000 http://www.hindawi.com/journals/dm/2015/191029/ Objective. This study aimed to evaluate the relationships between long noncoding RNAs (lncRNAs) in tumor tissues and hepatocellular carcinoma (HCC) aggressiveness and survival. Methods. We correlated the lncRNAs in tumor tissues with HCC survival and clinicopathological features based on Gene Expression Omnibus expression profile GSE36376. Results. Eight lncRNAs and 240 HCC patients were included. Cox regression analysis indicated that HULC was a positive factor for HCC overall survival (HR = 0.885, 95% CI = 0.797–0.983, and ) and disease-free survival time (HR = 0.913, 95% CI = 0.835–0.998, and ). H19 and UCA1 were both demonstrated to be risk factors of HCC disease-free survival in multivariate Cox model (HR = 1.071, 95% CI = 1.01–1.137, and and HR = 2.4, 95% CI = 1.092–5.273, and , resp.). But Kaplan-Meier method showed no significant association between UCA1 and HCC disease-free survival (log rank ). Logistic regression demonstrated that H19 was overexpressed in HBV-infected patients (OR = 1.14, 95% CI = 1.008–1.29, and ). HULC had a significant association with vascular invasion (OR = 0.648, 95% CI = 0.523–0.803, and ). H19 and MEG3 were both considered to be risk factors for high AFP level (OR = 1.45, 95% CI = 1.277–1.646, and and OR = 1.613, 95% CI = 1.1–2.365, and , resp.). Conclusions. Contributing to decreased susceptibility to vascular invasion, upregulation of HULC in tumor tissues was positively associated with HCC survival. In contrast, H19 overexpression might be risk factor for HCC aggressiveness and poor outcomes. Zongguo Yang, Yunfei Lu, Qingnian Xu, Bozong Tang, Cheol-Keun Park, and Xiaorong Chen Copyright © 2015 Zongguo Yang et al. All rights reserved. First-Trimester Serum Acylcarnitine Levels to Predict Preeclampsia: A Metabolomics Approach Thu, 04 Jun 2015 08:43:12 +0000 http://www.hindawi.com/journals/dm/2015/857108/ Objective. To expand the search for preeclampsia (PE) metabolomics biomarkers through the analysis of acylcarnitines in first-trimester maternal serum. Methods. This was a nested case-control study using serum from pregnant women, drawn between 8 and 14 weeks of gestational age. Metabolites were measured using an UPLC-MS/MS based method. Concentrations were compared between controls () and early-onset- (EO-) PE () or late-onset- (LO-) PE () women. Metabolites with a false discovery rate <10% for both EO-PE and LO-PE were selected and added to prediction models based on maternal characteristics (MC), mean arterial pressure (MAP), and previously established biomarkers (PAPPA, PLGF, and taurine). Results. Twelve metabolites were significantly different between EO-PE women and controls, with effect levels between −18% and 29%. For LO-PE, 11 metabolites were significantly different with effect sizes between −8% and 24%. Nine metabolites were significantly different for both comparisons. The best prediction model for EO-PE consisted of MC, MAP, PAPPA, PLGF, taurine, and stearoylcarnitine (AUC = 0.784). The best prediction model for LO-PE consisted of MC, MAP, PAPPA, PLGF, and stearoylcarnitine (AUC = 0.700). Conclusion. This study identified stearoylcarnitine as a novel metabolomics biomarker for EO-PE and LO-PE. Nevertheless, metabolomics-based assays for predicting PE are not yet suitable for clinical implementation. Maria P. H. Koster, Rob J. Vreeken, Amy C. Harms, Adrie D. Dane, Sylwia Kuc, Peter C. J. I. Schielen, Thomas Hankemeier, Ruud Berger, Gerard H. A. Visser, and Jeroen L. A. Pennings Copyright © 2015 Maria P. H. Koster et al. All rights reserved. Association of FTO Mutations with Risk and Survival of Breast Cancer in a Chinese Population Thu, 04 Jun 2015 08:37:45 +0000 http://www.hindawi.com/journals/dm/2015/101032/ Recently, several studies have reported associations between fat mass and obesity-associated (FTO) gene mutations and cancer susceptibility. But little is known about their association with risk and survival of breast cancer in Chinese population. The aim of this study is to examine whether cancer-related FTO polymorphisms are associated with risk and survival of breast cancer and BMI levels in controls in a Chinese population. We genotyped six FTO polymorphisms in a case-control study, including 537 breast cancer cases and 537 controls. FTO rs1477196 AA genotype had significant decreased breast cancer risk [odds ratio (OR) = 0.54, 95% confidence interval (CI): 0.34–0.86] compared to GG genotype, and this association was only found in women with BMI < 24 kg/m2 (OR = 0.41, 95% CI: 0.22–0.76); and rs16953002 AA genotype conferred significant increased breast cancer risk (OR = 1.80, 95% CI: 1.23–2.63) compared to GG genotype. Haplotype analysis showed that FTO TAC haplotype (rs9939609-rs1477196-rs1121980) had significant reduced breast cancer risk (OR = 0.76, 95% CI: 0.62–0.93) compared with TGC haplotype. But we failed to find any association between FTO polymorphisms and breast cancer survival. These findings suggest that variants in FTO gene may influence breast cancer susceptibility. Xianxu Zeng, Zhenying Ban, Jing Cao, Wei Zhang, Tianjiao Chu, Dongmei Lei, and Yanmin Du Copyright © 2015 Xianxu Zeng et al. All rights reserved. Comparison of Specificity and Sensitivity of AMH and FSH in Diagnosis of Premature Ovarian Failure Sun, 31 May 2015 09:50:28 +0000 http://www.hindawi.com/journals/dm/2015/585604/ Introduction. Anti-Müllerian hormone represents the primitive follicular number and ovarian age. Low level of AMH is in relation to early menopausal state and decreased ovarian reserve. AMH level changes occur prior to FSH level in representing ovarian failure. The aim of this study is to compare sensitivity and specificity of AMH with FSH in diagnosis of POF. Material and Methods. This descriptive study is done on 96 patients referred to Dr. Rasekh Clinic. Serum level of AMH and FSH was measured at Day 3 (3rd day of menstrual cycle) and data were analyzed through SPSS 21 software. Results. Results of AMH and FSH serum level indicate that AMH has more sensitivity (80% versus 28.57%) and almost equal specificity (78.89% versus 78.65%) compared with FSH. Also negative predictive value of AMH (98.61%) and FSH (87.5%) is different. But positive predictive value is the same (17.39%). Diagnostic accuracy of AMH is more than FSH and has significant differences. Conclusion. According to the results of this study, AMH serum level is more sensitive than FSH serum level. Also AMH has more negative predictive value. Besides, this hormone can be measured at any time of menstrual cycle, against FSH. AMH seems to be more useful in early diagnosis of POF. Farzaneh Alipour, Athar Rasekhjahromi, Mehrnoosh Maalhagh, Saeid Sobhanian, and Masoumeh Hosseinpoor Copyright © 2015 Farzaneh Alipour et al. All rights reserved. Serum Levels of Progranulin Are Closely Associated with Microvascular Complication in Type 2 Diabetes Thu, 28 May 2015 10:50:06 +0000 http://www.hindawi.com/journals/dm/2015/357279/ Objective. Progranulin (PGRN) was recently introduced as a novel marker of chronic inflammatory response in obesity and type 2 diabetes capable of directly affecting the insulin signaling pathway. This study aimed to investigate the correlation between PGRN and type 2 diabetics with microvascular complications. Methods. PGRN serum levels and glucose metabolism related substance were measured in 84 type 2 diabetic patients with or without microangiopathies and 12 health persons. Further analyses of serum PGRN in different stages of diabetic microangiopathies were conducted. Results. Serum levels of PGRN were markedly higher in type 2 diabetic patients with microangiopathies. PGRN serum levels increased with the progress of diabetic microangiopathies with significantly highest values detectable in clinical diabetic nephropathy (CDN) and proliferative diabetic retinopathy (PDR) groups. Serum PGRN concentrations in all individuals positively and markedly correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), triglyceride (TG), urinary albumin excretion rate (UAER), blood urea nitrogen (BUN), creatinine (CRE), white blood cell (WBC), disease duration, IL-6, and TNF-α, while correlating negatively and significantly with eGFR. Multiple linear regression analysis showed that only UAER and CRE were independently associated with serum PGRN. Conclusion. PGRN might be considered as a marker for diabetic microangiopathy and its severity. Lin Xu, Bo Zhou, Huixia Li, Jiali Liu, Junhui Du, Weijin Zang, Shufang Wu, and Hongzhi Sun Copyright © 2015 Lin Xu et al. All rights reserved. Uric Acid as a Marker of Kidney Disease: Review of the Current Literature Wed, 27 May 2015 13:41:59 +0000 http://www.hindawi.com/journals/dm/2015/382918/ Uric acid has been implicated in the pathophysiology of renal disease; however renal clearance makes a causal relationship difficult to prove. We examine the current literature to support a potential role of uric acid in the development of kidney disease and to determine the potential to use uric acid as a marker for future renal decline. After review, we conclude that uric acid is definitively linked to the development of chronic kidney disease and can be a poor prognostic factor for the development of acute renal failure, as well. However, further human research is needed before predictive models utilizing uric acid can be developed and used in the clinical setting. Christin Giordano, Olga Karasik, Kelli King-Morris, and Abdo Asmar Copyright © 2015 Christin Giordano et al. All rights reserved. Hyperoxia-Induced Protein Alterations in Renal Rat Tissue: A Quantitative Proteomic Approach to Identify Hyperoxia-Induced Effects in Cellular Signaling Pathways Wed, 27 May 2015 12:31:22 +0000 http://www.hindawi.com/journals/dm/2015/964263/ Introduction. In renal tissue as well as in other organs, supranormal oxygen pressure may lead to deleterious consequences on a cellular level. Additionally, hyperoxia-induced effect in cells and related free radicals may potentially contribute to renal failure. The aim of this study was to analyze time-dependent alterations of rat kidney protein expression after short-term normobaric hyperoxia using proteomics and bioinformatic approaches. Material and Methods. Wistar rats were randomized into six different groups: three groups with normobaric hyperoxia (exposure to 100% oxygen for 3 h) and three groups with normobaric normoxia (NN; room air). After hyperoxia exposure, kidneys were removed immediately, after 3 days and after 7 days. Kidney lysates were analyzed by two-dimensional gel electrophoresis followed by peptide mass fingerprinting using tandem mass spectrometry. Statistical analysis was performed with DeCyder 2D software (). Biological functions of differential regulated proteins were studied using functional network analysis (Ingenuity Pathways Analysis and PathwayStudio). Results. Expression of 14 proteins was significantly altered : eight proteins (MEP1A_RAT, RSSA_RAT, F16P1_RAT, STML2_RAT, BPNT1_RAT, LGMN_RAT, ATPA_RAT, and VDAC1_RAT) were downregulated and six proteins (MTUS1_RAT, F16P1_RAT, ACTG_RAT, ACTB_RAT, 2ABA_RAT, and RAB1A_RAT) were upregulated. Bioinformatic analyses revealed an association of regulated proteins with inflammation. Conclusions. Significant alterations in renal protein expression could be demonstrated for up to 7 days even after short-term hyperoxia. The identified proteins indicate an association with inflammation signaling cascades. MEP1A and VDAC1 could be promising candidates to identify hyperoxic injury in kidney cells. Jochen Hinkelbein, Lennert Böhm, Oliver Spelten, David Sander, Stefan Soltész, and Stefan Braunecker Copyright © 2015 Jochen Hinkelbein et al. All rights reserved. Epstein-Barr Virus Specific Antibody Response in Multiple Sclerosis Patients during 21 Months of Natalizumab Treatment Tue, 26 May 2015 06:59:18 +0000 http://www.hindawi.com/journals/dm/2015/901312/ Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. Natalizumab, a humanized anti-α4 integrin monoclonal antibody, is a highly effective treatment approved for MS. An association between MS and an exposure to Epstein-Barr Virus (EBV) sustained by the levels of antiviral capsid antigen (VCA) and anti-Epstein-Barr nuclear antigen-1 (EBNA-1) IgG has been described. Our goal was to verify the utility of EBV-specific IgG as a marker in Natalizumab treated MS. Twenty patients (17 female and 3 male) in treatment with Natalizumab were enrolled. Serum levels of anti-VCA and anti-EBNA-1 IgG were determined and expressed as arbitrary units (AU) before treatment and every three months for 21 months of therapy. Anti-VCA IgG levels were increased at the 15th month (235410 ± 196712 AU) comparing with the 3rd (98146 ± 47145 AU) and the 6th (109866 ± 52270 AU) months of therapy . No significant differences were found for serum anti-EBNA-1 IgG levels. Our data indicate that a transient, self-limited, EBV reactivation can occur in MS during Natalizumab therapy but our results do not support the use of serum EBV-specific antibody levels as biomarkers for monitoring therapeutic response to Natalizumab in the course of MS. Massimiliano Castellazzi, Serena Delbue, Francesca Elia, Matteo Gastaldi, Diego Franciotta, Roberta Rizzo, Tiziana Bellini, Roberto Bergamaschi, Enrico Granieri, and Enrico Fainardi Copyright © 2015 Massimiliano Castellazzi et al. All rights reserved. Association of PRPS1 Mutations with Disease Phenotypes Sun, 24 May 2015 06:37:24 +0000 http://www.hindawi.com/journals/dm/2015/127013/ Phosphoribosylpyrophosphate synthetase 1 (PRPS1) codes for PRS-I enzyme that catalyzes the first step of nucleotide synthesis. PRPS1 gene mutations have been implicated in a number of human diseases. Recently, new mutations in PRPS1 have been identified that have been associated with novel phenotypes like diabetes insipidus expanding the spectrum of PRPS1-related diseases. The purpose of this review is to evaluate current literature on PRPS1-related syndromes and summarize potential therapies. The overexpression of PRPS1 results in PRS-I superactivity resulting in purine overproduction. Patients with PRS-I superactivity demonstrate uric acid overproduction, hypotonia, ataxia, neurodevelopment abnormalities, and postlingual hearing impairment. On the other hand, decreased activity leads to X-linked nonsyndromic sensorineural deafness (DFNX-2), Charcot-Marie-Tooth disease-5 (CMTX5), and Arts syndrome depending on the residual activity of PRS-I. Mild PRS-I deficiency (DFNX-2) results in non-syndromic progressive hearing loss whereas moderate PRS-I deficiency (CMTX5) and severe PRS-I deficiency (Arts syndrome) present with peripheral or optic neuropathy, prelingual progressive sensorineural hearing loss, and central nervous system impairment. Currently, purine replacement via S-adenosylmethionine (SAM) supplementation in patients with Arts syndrome appears to improve their condition. This suggests that SAM supplementation can alleviate symptoms of PRPS1 deficient patients and open new avenues of therapeutic intervention. Rahul Mittal, Kunal Patel, Jeenu Mittal, Brandon Chan, Denise Yan, M’hamed Grati, and Xue Zhong Liu Copyright © 2015 Rahul Mittal et al. All rights reserved. Monitoring of Serial Presurgical and Postsurgical Changes in the Serum Proteome in a Series of Patients with Calcific Aortic Stenosis Wed, 20 May 2015 16:40:33 +0000 http://www.hindawi.com/journals/dm/2015/694120/ Background. Comprehensive analysis of proteome differentially expressed in response to surgery or drug treatment is useful to understand biological responses to dispensed interventions. Here we investigated expression changes in sera of patients who suffered from calcific aortic stenosis (CAS), before and after surgery for aortic valve replacement. Materials and Methods. Sera obtained before and after surgery with depletion of highly abundant proteins were analyzed with iTRAQ labeling followed by nanoLC-MALDI-TOF/TOF-MS/MS. Results. Fifty-one proteins shared in five patients were identified with differential levels in postsurgical and presurgical sera. Finally, 16 proteins that show statistically significant levels in patients’ sera compared with those in control sera () were identified. Most of the identified proteins were positive acute-phase proteins. Among three proteins other than acute-phase proteins, we confirmed increased levels of antithrombin-III and zinc-α-2-glycoprotein in postsurgical sera by Western blot analysis using other CAS patients’ sera. Furthermore, antithrombin-III and zinc-α-2-glycoprotein were not found among proteins with differential levels in postsurgical and presurgical sera of patients with aortic aneurysms that we identified in a previous study. Conclusions. The results indicated that antithrombin-III and zinc-α-2-glycoprotein would become unique monitoring proteins for evaluating pathophysiological and biochemical processes occurring before and after surgery for CAS. Kazumi Satoh, Kazuo Yamada, Tomoko Maniwa, Teiji Oda, and Ken-ichi Matsumoto Copyright © 2015 Kazumi Satoh et al. All rights reserved. Stability Assessment of Candidate Reference Genes in Urine Sediment of Prostate Cancer Patients for miRNA Applications Wed, 20 May 2015 12:26:45 +0000 http://www.hindawi.com/journals/dm/2015/973597/ We aimed at assessing the stability of candidate reference genes in urine sediments of men subjected to digital rectal examination for suspected prostate cancer (PCa). Two microRNAs (miR-191 and miR-25) and 1 small nucleolar RNA (SNORD48) were assayed in 35 post-DRE urine sediments of men with PCa and in 26 subjects with histologically confirmed benign prostatic hyperplasia (BPH). The stability of candidate reference genes was assessed through BestKeeper algorithm and equivalence test. miR-200b and miR-452 were used to test for the effect of normalization on target genes. Our results proved miR-191 to be the most stable gene, showing the lowest degree of variation and the highest stability value. miR-25 and SNORD48 values fell beyond the cutoff of acceptability. In conclusion, we recommend the use of miR-191 for normalization purposes in post-DRE urine sediments. Maria Giulia Egidi, Giovanni Cochetti, Gabriella Guelfi, Danilo Zampini, Silvana Diverio, Giulia Poli, and Ettore Mearini Copyright © 2015 Maria Giulia Egidi et al. All rights reserved. Serum MicroRNA Profiles Serve as Novel Biomarkers for the Diagnosis of Alzheimer’s Disease Wed, 20 May 2015 09:46:59 +0000 http://www.hindawi.com/journals/dm/2015/625659/ Alzheimer’s disease (AD) is the most common type of dementia, and promptly diagnosis of AD is crucial for delaying the development of disease and improving patient quality of life. However, AD detection, particularly in the early stages, remains a substantial challenge due to the lack of specific biomarkers. The present study was undertaken to identify and validate the potential of circulating miRNAs as novel biomarkers for AD. Solexa sequencing was employed to screen the expression profile of serum miRNAs in AD and controls. RT-qPCR was used to confirm the altered miRNAs at the individual level. Moreover, candidate miRNAs were examined in the serum samples of patients with mild cognitive impairment (MCI) and vascular dementia (VD). The results showed that four miRNAs (miR-31, miR-93, miR-143, and miR-146a) were markedly decreased in AD patients’ serum compared with controls. Receiver operating characteristic curve analysis demonstrated that this panel of four miRNAs could be used as potential biomarker for AD. Furthermore, miR-93, and miR-146a were significantly elevated in MCI compared with controls, and the panel of miR-31, miR-93 and miR-146a can be used to discriminate AD from VD. We established a panel of four serum miRNAs as a novel noninvasive biomarker for AD diagnosis. Hui Dong, Jialu Li, Lei Huang, Xi Chen, Donghai Li, Tao Wang, Caiyou Hu, Jun Xu, Chunni Zhang, Ke Zen, Shifu Xiao, Qiao Yan, Cheng Wang, and Chen-Yu Zhang Copyright © 2015 Hui Dong et al. All rights reserved. OGG1 Mutations and Risk of Female Breast Cancer: Meta-Analysis and Experimental Data Tue, 19 May 2015 13:41:49 +0000 http://www.hindawi.com/journals/dm/2015/690878/ In first part of this study association between OGG1 polymorphisms and breast cancer susceptibility was explored by meta-analysis. Second part of the study involved 925 subjects, used for mutational analysis of OGG1 gene using PCR-SSCP and sequencing. Fifteen mutations were observed, which included five intronic mutations, four splice site mutations, two 3′UTR mutations, three missense mutations, and a nonsense mutation. Significantly () increased (~29 fold) breast cancer risk was associated with a splice site variant g.9800972T>G and 3′UTR variant g.9798848G>A. Among intronic mutations, highest (~15 fold) increase in breast cancer risk was associated with g.9793680G>A (). Similarly ~14-fold increased risk was associated with Val159Gly (), ~17-fold with Gly221Arg (), and ~18-fold with Ser326Cys () in breast cancer patients compared with controls, whereas analysis of nonsense mutation showed that ~13-fold () increased breast cancer risk was associated with Trp375STOP in patients compared to controls. In conclusion, a significant association was observed between OGG1 germ line mutations and breast cancer risk. These findings provide evidence that OGG1 may prove to be a good candidate of better diagnosis, treatment, and prevention of breast cancer. Kashif Ali, Ishrat Mahjabeen, Maimoona Sabir, Humera Mehmood, and Mahmood Akhtar Kayani Copyright © 2015 Kashif Ali et al. All rights reserved. Increased Serum Interleukin-9 Levels in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Pathogenic Role or Just an Epiphenomenon? Tue, 19 May 2015 07:19:43 +0000 http://www.hindawi.com/journals/dm/2015/519638/ The purpose of this paper was to evaluate the levels of IL-9 in patients with SLE and RA compared with controls and the association of IL-9 levels with clinical and laboratory parameters. IL-9 levels were assessed in 117 SLE patients, 67 RA patients, and 24 healthy controls by ELISA. Clinical and laboratory parameters were recorded. The IL-9 serum levels were significantly higher in RA patients (4,77 ± 3,618 pg/mL) and in SLE patients (12,26 ± 25,235 pg/mL) than in healthy individuals (1,22 ± 0,706 pg/mL) . In SLE patients, there were no statistically significant associations or correlations between the levels of IL-9 and SLEDAI or other clinical and laboratorial parameters, with the exception of disease time, which showed a statistically significant negative correlation with IL-9 levels . In RA patients, no association or statistically significant correlation was observed with disease duration, DAS28, HAQ, rheumatoid factor positivity, or erosions on radiography. These data demonstrated increased serum levels of IL-9 in SLE and RA patients, but further studies are needed to clarify the precise role of this cytokine and its potential use as therapeutic target. Andréa Tavares Dantas, Claudia Diniz Lopes Marques, Laurindo Ferreira da Rocha Junior, Mariana Brayner Cavalcanti, Sayonara Maria Calado Gonçalves, Pablo Ramon Gualberto Cardoso, Henrique de Ataide Mariz, Moacyr Jesus Barreto de Melo Rego, Angela Luzia Branco Pinto Duarte, Ivan da Rocha Pitta, and Maira Galdino da Rocha Pitta Copyright © 2015 Andréa Tavares Dantas et al. All rights reserved. Response to: Comment on “Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio: Novel Markers for Diagnosis and Prognosis in Patients with Idiopathic Sudden Sensorineural Hearing Loss” Mon, 18 May 2015 07:26:46 +0000 http://www.hindawi.com/journals/dm/2015/583738/ Young Joon Seo, Junhui Jeong, Jae Young Choi, and In Seok Moon Copyright © 2015 Young Joon Seo et al. All rights reserved. Th1, Th2, and Th17 Cytokine Involvement in Thyroid Associated Ophthalmopathy Mon, 18 May 2015 07:03:01 +0000 http://www.hindawi.com/journals/dm/2015/609593/ To determine serum cytokine profiles in Graves’ disease (GD) patients with or without active and inactive thyroid associated ophthalmopathy (TAO), we recruited 65 subjects: 10 GD only (without TAO), 25 GD + active TAO, 20 GD + TAO, and 10 healthy controls. Liquid chip assay was used to measure serum Th1/Th2/Th17 cytokines including IFN-γ (interferon-gamma), TNF-α (tumor necrosis factor-alpha), IL-1α (interleukin-1 alpha), IL-1Ra (IL-1 receptor antagonist), IL-2, IL-4, IL-6, and IL-17 and two chemokines: RANTES (regulated upon activation, normal T cell expressed and secreted) and IP-10 (IFN-γ-induced protein 10). Serum levels of TSH (thyroid stimulating hormone) receptor autoantibodies (TRAb) were measured using an enzyme linked immunosorbent assay. Compared with healthy controls, TAO patients showed significantly elevated serum levels of IFN-γ, TNF-α, IL-1α, IL-4, IL-6, IL-17, and IP-10. Comparing active and inactive TAO, serum Th1 cytokines IFN-γ and TNF-α were elevated in active TAO, while serum Th2 cytokine IL-4 was elevated in inactive TAO. Serum Th17 cytokine IL-17 was elevated in GD but reduced in both active and inactive TAO. A positive correlation was found between TRAb and IFN-γ, TNF-α, IL-1α, IL-2, IL-4, and IL-6. Taken together, serum Th1/Th2/Th17 cytokines and chemokines reflect TAO disease activity and may be implicated in TAO pathogenesis. Jie Shen, Zhangfang Li, Wenting Li, Ying Ge, Min Xie, Meng Lv, Yanfei Fan, Zhi Chen, Defu Zhao, and Yajuan Han Copyright © 2015 Jie Shen et al. All rights reserved. Genome-Wide Scan for Methylation Profiles in Keloids Thu, 14 May 2015 13:38:06 +0000 http://www.hindawi.com/journals/dm/2015/943176/ Keloids are benign fibroproliferative tumors of the skin which commonly occur after injury mainly in darker skinned patients. Medical treatment is fraught with high recurrence rates mainly because of an incomplete understanding of the biological mechanisms that lead to keloids. The purpose of this project was to examine keloid pathogenesis from the epigenome perspective of DNA methylation. Genome-wide profiling used the Infinium HumanMethylation450 BeadChip to interrogate DNA from 6 fresh keloid and 6 normal skin samples from 12 anonymous donors. A 3-tiered approach was used to call out genes most differentially methylated between keloid and normal. When compared to normal, of the 685 differentially methylated CpGs at Tier 3, 510 were hypomethylated and 175 were hypermethylated with 190 CpGs in promoter and 495 in nonpromoter regions. The 190 promoter region CpGs corresponded to 152 genes: 96 (63%) were hypomethylated and 56 (37%) hypermethylated. This exploratory genome-wide scan of the keloid methylome highlights a predominance of hypomethylated genomic landscapes, favoring nonpromoter regions. DNA methylation, as an additional mechanism for gene regulation in keloid pathogenesis, holds potential for novel treatments that reverse deleterious epigenetic changes. As an alternative mechanism for regulating genes, epigenetics may explain why gene mutations alone do not provide definitive mechanisms for keloid formation. Lamont R. Jones, William Young, George Divine, Indrani Datta, Kang Mei Chen, David Ozog, and Maria J. Worsham Copyright © 2015 Lamont R. Jones et al. All rights reserved. The Expression of Notch/Notch Ligand, IL-35, IL-17, and Th17/Treg in Preeclampsia Thu, 14 May 2015 12:36:20 +0000 http://www.hindawi.com/journals/dm/2015/316182/ The aim of this study was to examine the interaction of Notch/Notch ligand with Th17/Treg, cytokines IL-35 and IL-17 in cases of preeclampsia (PE). Methods. Peripheral blood was obtained from 42 PE patients and 22 health pregnant women. The mRNA expressions of Notch/Notch ligand, Treg transcription factor FoxP3 and Th17 transcription factor RORγt, EBI3 and P35 (IL-35 two subunits), and IL-17 were determined by qPCR. The serum levels of IL-17 and IL-35 were measured by ELISA. Results. It was observed that the expressions of Foxp3, EBI3, and P35 in PE patients were lower compared with normal pregnancy, whereas the RORγt expression was significantly increased. The results also demonstrated that PE patients exhibited decreased levels of Treg-related cytokine IL-35, whereas IL-17 was significantly increased. PE patients expressed higher levels of Notch receptor (1–4) and Notch ligand of DLL4, whereas Notch ligand of Jagged-1, -2 was much lower. Furthermore, the levels of FoxP3 T cells correlated positively with Jagged-2. In addition, there were positive correlations between the mRNA level of IL-17 and DLL4. Conclusion. Our results indicated that maternal immunological changes may reverse maternal tolerance in PE, and this phenomenon may due to the Th17/Treg imbalance affected by Notch/Notch ligand. Weiping Cao, Xinzhi Wang, Tinmei Chen, Huaying Zhu, Wenlin Xu, Songlan Zhao, Xiaoqing Cheng, and Liangping Xia Copyright © 2015 Weiping Cao et al. All rights reserved. Clinical Implications and Prognostic Values of Prostate Cancer Susceptibility Candidate Methylation in Primary Nonmuscle Invasive Bladder Cancer Wed, 13 May 2015 06:04:22 +0000 http://www.hindawi.com/journals/dm/2015/402963/ DNA methylation is the most common and well-characterized epigenetic change in human cancer. Recently, an association between prostate cancer susceptibility candidate (PRAC) methylation and genitourinary cancer was proposed. The aim of the present study was to evaluate the association between PRAC methylation status and clinicopathological parameters and prognosis in long-term follow-up primary nonmuscle invasive bladder cancer (NMIBC). The clinical relevance of PRAC methylation was determined in 136 human bladder specimens (eight normal controls [NCs] and 128 primary NMIBCs) using quantitative pyrosequencing analysis. PRAC methylation was significantly higher in NMIBC patients than in NCs and was significantly associated with higher grade and more advanced stage of cancer. Kaplan-Meier estimates revealed significant difference in tumor recurrence and progression according to PRAC methylation status (both p < 0.05). Multivariate Cox regression analysis revealed that the PRAC methylation status was a strong predictor of recurrence (hazard ratio [HR], 2.652; p = 0.012) and progression (HR, 9.531; p = 0.035) of NMIBC. Enhanced methylation status of PRAC was positively associated with a high rate of recurrence and progression in NMIBC patients, suggesting that PRAC methylation may be a promising prognostic marker of NMIBC. Young-Won Kim, Hyung-Yoon Yoon, Sung Pil Seo, Sang Keun Lee, Ho Won Kang, Won Tae Kim, Heui Je Bang, Dong Hee Ryu, Seok-Joong Yun, Sang-Cheol Lee, Wun-Jae Kim, and Yong-June Kim Copyright © 2015 Young-Won Kim et al. All rights reserved. Predictive Levels of CD24 in Peripheral Blood Leukocytes for the Early Detection of Colorectal Adenomas and Adenocarcinomas Mon, 11 May 2015 09:48:12 +0000 http://www.hindawi.com/journals/dm/2015/916098/ CD24 is expressed in 90% of colorectal adenomas and adenocarcinomas. Colorectal cancer (CRC) can be mostly prevented but average risk population screening by stool testing or colonoscopy faces many hurdles. Blood testing is clinically needed. We aimed to evaluate the utility of CD24 expression in peripheral blood leukocytes (PBLs). Two independent case studies were conducted in eligible individuals undergoing colonoscopy. Protein extracted from PBLs was subjected to immunoblotting using anti-CD24 monoclonal antibodies. CD24 sensitivity and specificity were determined using receiver operating characteristic (ROC) analysis. Initially, 150 subjects were examined: 63 had CRC, 19 had adenomas, and 68 had normal colonoscopies. The sensitivity and specificity of CD24 for distinguishing CRC from normal subjects were 70.5% (95% CI, 54.8–83.2%) and 83.8% (95% CI, 74.6–92.7%) and for adenomas 84.2% (95% CI, 60.4–96.4%) and 73.5% (95% CI, 61.4–83.5%), respectively. In the second trial (n = 149), a similar specificity but higher sensitivity was achieved: 80.0% (95% CI, 63.1–91.6%) for CRC and 89.2% (95% CI, 74.6–97%) for adenomas. A simple noninvasive blood test evaluating CD24 levels has high sensitivity and specificity for detecting colorectal adenomas and cancer in patients undergoing colonoscopy at an urban medical center. Larger multicenter studies are warranted to establish the potential of this promising test. Sarah Kraus, Shiran Shapira, Dina Kazanov, Inna Naumov, Menachem Moshkowitz, Erwin Santo, Lior Galazan, Ravit Geva, Einat Shmueli, Aharon Hallack, and Nadir Arber Copyright © 2015 Sarah Kraus et al. All rights reserved. Vitamin D Is a Good Marker for Disease Activity of Rheumatoid Arthritis Disease Sun, 10 May 2015 06:44:37 +0000 http://www.hindawi.com/journals/dm/2015/260725/ Aim. This study was conducted to find out the optimal vitamin D cutoff point in predicting activity of RA disease. Materials and Methods. One hundred and two rheumatoid arthritis Saudi patients of both genders were recruited in this study. Vitamin D as 25-hydroxy-vitamin D [25(OH)D] was measured and serum level less than 20 ng/mL defined as deficient patient. Disease activity was measured based on the disease activity score index of a 28-joint count (DAS28) using serum erythrocyte sedimentation rate levels. Receiver operating characteristic (ROC) curves were used to determine the optimal vitamin D cutoff points for identifying disease activity. Results. It has been observed that vitamin D levels were lower (P < 0.05) in patients with high disease activity. A significant inverse correlation between serum 25(OH)D levels and DAS28 (r = −0.277, P = 0.014) was shown. ROC curves results showed that vitamin D less than 12.3 ng/mL predicted high disease activity, and vitamin D more than 17.9 ng/mL predicted low disease activity, with good sensitivity and accuracy results regarding vitamin D. Conclusion. Study results concluded that vitamin D is a good predictor of RA disease activity in Saudi patients. Firas Sultan Azzeh and Osama Adnan Kensara Copyright © 2015 Firas Sultan Azzeh and Osama Adnan Kensara. All rights reserved. Prognostic Value of MicroRNA-182 in Cancers: A Meta-Analysis Thu, 07 May 2015 10:53:16 +0000 http://www.hindawi.com/journals/dm/2015/482146/ Objective. MicroRNA-182 (miR-182) exhibits altered expression in various cancers. The aim of this study was to investigate the predictive value of miR-182 expression for cancer patient survival. Methods. Eligible studies were identified through multiple search strategies, and the hazard ratios (HRs) for patient outcomes were extracted and estimated. A meta-analysis was performed to evaluate the prognostic value of miR-182. Results. In total, 14 studies were included. A high miR-182 expression level predicted a worse outcome with a pooled HR of 2.18 (95% CI: 1.53–3.11) in ten studies related to overall survival (OS), especially in Chinese populations. The results of seven studies evaluating disease-free survival/relapse-free survival/recurrence-free interval/disease-specific survival (DFS/RFS/RFI/DSS) produced a pooled HR of 1.77 (95% CI: 0.91–3.43), which was not statistically significant; however, the trend was positive. When disregarding the DSS from one study, the expression of miR-182 was significantly correlated with DFS/RFS/RFI (pooled HR = 2.52, 95% CI: 1.67–3.79). Conclusions. High miR-182 expression is associated with poor OS and DFS/RFS/RFI in some types of cancers, and miR-182 may be a useful prognostic biomarker for predicting cancer prognosis. However, given the current insufficient relevant data, further clinical studies are needed. Fei Wang, Shanliang Zhong, Haijun Zhang, Wei Zhang, Hongming Zhang, Xue Wu, and Baoan Chen Copyright © 2015 Fei Wang et al. All rights reserved.