Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Recipients with In Utero Induction of Tolerance Upregulated MHC Class I in the Engrafted Donor Skin Sun, 20 Jul 2014 12:11:47 +0000 http://www.hindawi.com/journals/dm/2014/531092/ The alterations in MHC class I expression play a crucial step in immune evasion of cancer or virus-infected cells. This study aimed to examine whether tolerized grafts modified MHC class I expression. FVB/N mice were rendered tolerant of C57BL/6 alloantigens by in utero transplantation of C57BL/6 marrows. Postnatally, engrafted donor skins and leukocytes were examined for their MHC expression by quantitative real-time PCR and flow cytometry. Engrafted donor skins upregulated their MHC class I related gene transcripts after short-term (1~2 weeks) or long-term (>1 month) engraftment. This biological phenomenon was simultaneously associated with upregulation of TAP1 gene transcripts, suggesting an important role of TAP1 in the regulation of MHC class I pathway. The surface MHC class I molecules of H-2 in engrafted donor leukocytes consistently showed overexpression. Conclusively, the induction of allograft tolerance involved biological modifications of donor transplants. The overexpression of MHC class I within engrafted transplants of tolerant mice might be used as the tolerance biomarkers for identifying a state of graft tolerance. Jeng-Chang Chen, Liang-Shiou Ou, Hsiu-Yueh Yu, Ming-Ling Kuo, Pei-Yeh Chang, and Hsueh-Ling Chang Copyright © 2014 Jeng-Chang Chen et al. All rights reserved. K-ras Mutational Status in Cytohistological Tissue as a Molecular Marker for the Diagnosis of Pancreatic Cancer: A Systematic Review and Meta-Analysis Wed, 16 Jul 2014 12:14:36 +0000 http://www.hindawi.com/journals/dm/2014/573783/ Background. More clinically meaningful diagnostic tests are needed in pancreatic cancer (PC). K-ras mutations are the most frequently acquired genetic alteration. Methods. Original research articles involving the diagnostic accuracy of K-ras mutation detection in PC were selected. Data were presented as forest plots and summary receiver operating characteristic (SROC) curve analysis was used to summarize the overall test performance. Results. We assessed 19 studies from 16 published articles. The reports were divided into three groups according to the process used to obtain the test material. The summary estimates for detecting K-ras status using an invasive method (fine needle aspiration (FNA), endoscopic retrograde cholangiopancreatography (ERCP), or surgery) were better than cytology: the pooled sensitivity was 77% (95% confidence interval (CI): 74–80%) versus 54% (95% CI: 47–61%); specificity was 88% (95% CI: 85–91%) versus 91% (95% CI: 83–96%); and diagnostic odds ratio (DOR) was 20.26 (11.40–36.03) versus 7.52 (95% CI: 2.80–20.18), respectively. When two procedures were combined, the diagnostic accuracy was markedly improved. Conclusions. The analysis of K-ras mutations in pancreatic tissue has a promising diagnostic significance in PC. Further valuable studies are needed. Jing Yang, Jingjing Li, Rong Zhu, Huawei Zhang, Yuanyuan Zheng, Weiqi Dai, Fan Wang, Miao Shen, Kan Chen, Ping Cheng, Yan Zhang, Chengfen Wang, Junshan Wang, Yujing Xia, Jie Lu, Yingqun Zhou, and Chuanyong Guo Copyright © 2014 Jing Yang et al. All rights reserved. Serum Interleukin 17 Levels in Patients with Crohn’s Disease: Real Life Data Wed, 16 Jul 2014 10:23:17 +0000 http://www.hindawi.com/journals/dm/2014/690853/ The aim of this study was to investigate serum IL17 levels in patients with Crohn’s disease (CD) and to investigate the relationship between serum IL17 levels with disease activity. Methods. Fifty patients with CD and sex- and age-matched 40 healthy controls were included in the study. The serum IL17 levels, complete blood count, blood chemistry, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were measured, and Crohn’s disease activity was calculated using Crohn’s disease activity index (CDAI). Results. The mean serum IL17 level of CD patients did not differ from those of healthy controls (). There was no difference between the mean serum IL levels of active CD patients and of quiescent CD patients (). However, the mean IL17 level of active patients was lower than of control subjects (). Serum IL17 was not correlated with inflammatory markers (ESR, CRP, white blood count, platelet count, and albumin) and CDAI. Conclusions. Peripheral blood serum IL17 levels of CD patients were not higher than of healthy controls, and also, serum IL17 level was not correlated with clinical disease activity. Peripheral IL17 measurement is not a useful tool for detecting and monitoring Crohn’s disease which is understood to have complex etiopathogenesis. Abdurrahman Sahin, Turan Calhan, Mustafa Cengiz, Resul Kahraman, Kubra Aydin, Kamil Ozdil, May Korachi, and H. Mehmet Sokmen Copyright © 2014 Abdurrahman Sahin et al. All rights reserved. Comparison of Different Blood Collection, Sample Matrix, and Immunoassay Methods in a Prenatal Screening Setting Tue, 15 Jul 2014 13:07:04 +0000 http://www.hindawi.com/journals/dm/2014/509821/ We compared how measurements of pregnancy-associated plasma protein A (PAPP-A) and the free beta subunit of human chorionic gonadotropin (fβ-hCG) in maternal blood are influenced by different methods for blood collection, sample matrix, and immunoassay platform. Serum and dried blood spots (DBS) were obtained by venipuncture and by finger prick of 19 pregnant women. PAPP-A and fβ-hCG from serum and from DBS were measured by conventional indirect immunoassay on an AutoDELFIA platform and by antibody microarray. We compared methods based on the recoveries for both markers as well as marker levels correlations across samples. All method comparisons showed high correlations for both marker concentrations. Recovery levels of PAPP-A from DBS were 30% lower, while those of fβ-hCG from DBS were 50% higher compared to conventional venipuncture serum. The recoveries were not affected by blood collection or immunoassay method. The high correlation coefficients for both markers indicate that DBS from finger prick can be used reliably in a prenatal screening setting, as a less costly and minimally invasive alternative for venipuncture serum, with great logistical advantages. Additionally, the use of antibody arrays will allow for extending the number of first trimester screening markers on maternal and fetal health. Jeroen L. A. Pennings, Jacqueline E. Siljee, Sandra Imholz, Sylwia Kuc, Annemieke de Vries, Peter C. J. I. Schielen, and Wendy Rodenburg Copyright © 2014 Jeroen L. A. Pennings et al. All rights reserved. Prognostic Value of VEGF in Patients Submitted to Percutaneous Coronary Intervention Mon, 07 Jul 2014 09:00:19 +0000 http://www.hindawi.com/journals/dm/2014/135357/ We examined the longitudinal changes of VEGF levels after percutaneous coronary intervention for predicting major adverse cardiac events (MACE) in coronary artery disease (CAD) patients. VEGF was measured in 94 CAD patients’ serum before revascularization, 1-month and 1-year after. Independently of clinical presentation, patients had lower VEGF concentration than a cohort of healthy subjects (median, IQ: 15.9, 9.0–264 pg/mL versus 419, 212–758 pg/mL; ) at baseline. VEGF increased to 1-month (median, IQ: 276, 167–498 pg/mL; ) and remained steady to 1-year (median, IQ: 320, 173–497 pg/mL; ) approaching control levels. Drug eluting stent apposition and previous medication intake produced a less steep VEGF evolution after intervention (). Baseline VEGF concentration <40.8 pg/mL conveyed increased risk for MACE in a 5-year follow-up. Results reflect a positive role of VEGF in recovery and support its importance in CAD prognosis. Catarina Ramos, Patrícia Napoleão, Mafalda Selas, Cláudia Freixo, Ana Maria Viegas Crespo, Miguel Mota Carmo, Rui Cruz Ferreira, and Teresa Pinheiro Copyright © 2014 Catarina Ramos et al. All rights reserved. Haplotype Map of Sickle Cell Anemia in Tunisia Wed, 02 Jul 2014 11:48:48 +0000 http://www.hindawi.com/journals/dm/2014/938301/ β-Globin haplotypes are important to establish the ethnic origin and predict the clinical development of sickle cell disease patients (SCD). To determine the chromosomal background of Tunisian sickle cell patients, in this first study in Tunisia, we have explored four polymorphic regions of β-globin cluster on chromosome 11. It is the 5′ region of β-LCR-HS2 site, the intervening sequence II (IVSII) region of two fetal ( and ) genes and the 5′ region of β-globin gene. The results reveal a high molecular diversity of a microsatellite configuration describing the sequences haplotypes. The linkage disequilibrium analysis showed various haplotype combinations giving 22 “extended haplotypes”. These results confirm the utility of the β-globin haplotypes for population studies and contribute to knowledge of the Tunisian gene pool, as well as establishing the role of genetic markers in physiopathology of SCD. Imen Moumni, Maha Ben Mustapha, Sarra Sassi, Amine Zorai, Ikbel Ben Mansour, Kais Douzi, Dorra Chouachi, Fethi Mellouli, Mohamed Bejaoui, and Salem Abbes Copyright © 2014 Imen Moumni et al. All rights reserved. The Clinicopathological Significance of miR-133a in Colorectal Cancer Tue, 01 Jul 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/919283/ This study determined the expression of microRNA-133a (MiR-133a) in colorectal cancer (CRC) and adjacent normal mucosa samples and evaluated its clinicopathological role in CRC. The expression of miR-133a in 125 pairs of tissue samples was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and correlated with patient’s clinicopathological data by statistical analysis. Endogenous expression levels of several potential target genes were determined by qRT-PCR and correlated using Pearson’s method. MiR-133a was downregulated in 83.2% of tumors compared to normal mucosal tissue. Higher miR-133a expression in tumor tissues was associated with development of distant metastasis, advanced Dukes and TNM staging, and poor survival. The unfavorable prognosis of higher miR-133a expression was accompanied by dysregulation of potential miR-133a target genes, LIM and SH3 domain protein 1 (LASP1), Caveolin-1 (CAV1), and Fascin-1 (FSCN1). LASP1 was found to possess a negative correlation (), whereas CAV1 exhibited a significant positive correlation (), and a stronger correlation was found in patients who developed distant metastases (). In addition, a negative correlation of FSCN1 was only found in nonmetastatic patients. In conclusion, miR-133a was downregulated in CRC tissues, but its higher expression correlated with adverse clinical characteristics and poor prognosis. Timothy Ming-Hun Wan, Colin Siu-Chi Lam, Lui Ng, Ariel Ka-Man Chow, Sunny Kit-Man Wong, Hung-Sing Li, Johnny Hon-Wai Man, Oswens Siu-Hung Lo, Dominic Foo, Alvin Cheung, Thomas Yau, Jensen Tung-Chung Poon, Ronnie Tung-Ping Poon, Wai-Lun Law, and Roberta Wen-Chi Pang Copyright © 2014 Timothy Ming-Hun Wan et al. All rights reserved. A New Susceptibility Locus for Myocardial Infarction, Hypertension, Type 2 Diabetes Mellitus, and Dyslipidemia on Chromosome 12q24 Thu, 26 Jun 2014 12:10:03 +0000 http://www.hindawi.com/journals/dm/2014/291419/ We examined the role of hepatic nuclear factor-1 alpha (HNF1a) gene polymorphism on coronary artery disease (CAD) traits in 4631 Saudi angiographed individuals (2419 CAD versus 2212 controls) using TaqMan assay on ABI Prism 7900HT sequence detection system. Following adjustment for confounders, the rs2259820_CC (1.19 (1.01–1.42); ), rs2464196_TT (1.19 (1.00–1.40); ), and rs2259816_T (1.13 (1.01–1.26); ) were associated with MI. The rs2259820_T (1.14 (1.03–1.26); ) and rs2464196_C (1.12 (1.02–1.24); ) were associated with type 2 diabetes mellitus (T2DM), while the rs2393791_T (1.14 (1.01–1.28); ), rs7310409_G (1.16 (1.03–1.30); ), and rs2464196_AG+GG (1.25 (1.05–1.49); ) were implicated in hypertension. Hypertriglyceridemia was linked to the rs2393791_T (1.14 (1.02–1.27); ), rs7310409_G (1.12 (1.01–1.25); ), rs1169310_G (1.15 (1.04–1.28); ), and rs1169313_CT+TT (1.24 (1.06–1.45); ) and high low density lipoprotein-cholesterol levels were associated with rs2259820_T (1.23 (1.07–1.41); ), rs2464196_T (1.22 (1.06–1.39); ), and rs2259816_T (1.18 (1.02–1.36); ). A 7-mer haplotype CATATAC (; ), constructed from the studied SNPs, was associated with MI, and CATATA implicated in T2DM (; ). Hypertriglyceridemia was linked to TGCGGG (; ), and obesity to ACGGGT (; ). Our results suggest that the HNF1a is a common susceptibility gene for MI, T2DM, hypertension, and dyslipidemia. Salma M. Wakil, Nzioka P. Muiya, Asma I. Tahir, Mohammed Al-Najai, Batoul Baz, Editha Andres, Nejat Mazhar, Nada Al Tassan, Maie Alshahid, Brian F. Meyer, and Nduna Dzimiri Copyright © 2014 Salma M. Wakil et al. All rights reserved. Urinary N-Acetyl-beta-D-glucosaminidase as an Early Marker for Acute Kidney Injury in Full-Term Newborns with Neonatal Hyperbilirubinemia Tue, 24 Jun 2014 12:12:46 +0000 http://www.hindawi.com/journals/dm/2014/315843/ Purpose. To investigate renal function estimated by markers in full-term newborns with hyperbilirubinemia. Methods. A total of 332 full-term newborns with hyperbilirubinemia and 60 healthy full-term newborns were enrolled. Total serum bilirubin, serum creatinine (Cr), serum blood urea nitrogen (BUN), serum cystatin C (Cys-C), urinary beta-2-microglobulin (β2MG) index, and urinary N-acetyl-beta-D-glucosaminidase (NAG) index were measured before and after treatment. All newborns were divided into three groups according to total serum bilirubin levels: group 1 (221-256), group 2 (256-342), and group 3 (>342). Results. The control group and group 1 did not differ significantly in regard to serum Cr, serum BUN, serum Cys-C, urinary β2MG index, and urinary NAG index. Urinary NAG index in group 2 was significantly higher than that in control group (). Between control group and group 3, serum Cys-C, urinary β2MG index, and urinary NAG index differed significantly. The significant positive correlation between total serum bilirubin and urinary NAG index was found in newborns when total serum bilirubin level was more than 272 μmol/L. Conclusions. High unconjugated bilirubin could result in acute kidney injury in full-term newborns. Urinary NAG might be the suitable marker for predicting acute kidney injury in full-term newborns with hyperbilirubinemia. Bangning Cheng, Yulian Jin, Guanghui Liu, Zhiheng Chen, Hongmei Dai, and Min Liu Copyright © 2014 Bangning Cheng et al. All rights reserved. Serum Levels of Resistin, Adiponectin, and Apelin in Gastroesophageal Cancer Patients Tue, 24 Jun 2014 06:49:28 +0000 http://www.hindawi.com/journals/dm/2014/619649/ The aim of the study was the investigation of relationship between cachexia syndrome and serum resistin, adiponectin, and apelin in patients with gastroesophageal cancer (GEC). Material and Methods. Adipocytokines concentrations were measured in sera of 85 GEC patients and 60 healthy controls. They were also evaluated in tumor tissue and appropriate normal mucosa of 38 operated cancer patients. Results. Resistin and apelin concentrations were significantly higher in GEC patients than in the controls. The highest resistin levels were found in cachectic patients and in patients with distant metastasis. Serum adiponectin significantly decreased in GEC patients with regional and distant metastasis. Serum apelin was significantly higher in cachectic patients than in the controls. Apelin was positively correlated with hsCRP level. Resistin and apelin levels increased significantly in tumor tissues. Weak positive correlations between adipocytokines levels in serum and in tumor tissue were observed. Conclusions. Resistin is associated with cachexia and metastasis processes of GEC. Reduction of serum adiponectin reflects adipose tissue wasting in relation to GEC progression. Correlation of apelin with hsCRP can reflect a presumable role of apelin in systemic inflammatory response in esophageal and gastric cancer. Dorota Diakowska, Krystyna Markocka-Mączka, Piotr Szelachowski, and Krzysztof Grabowski Copyright © 2014 Dorota Diakowska et al. All rights reserved. Immunophenotypes and Immune Markers Associated with Acute Promyelocytic Leukemia Prognosis Thu, 19 Jun 2014 08:29:55 +0000 http://www.hindawi.com/journals/dm/2014/421906/ CD2+, CD34+, and CD56+ immunophenotypes are associated with poor prognoses of acute promyelocytic leukemia (APL). The present study aimed to explore the role of APL immunophenotypes and immune markers as prognostic predictors on clinical outcomes. A total of 132 patients with de novo APL were retrospectively analyzed. Immunophenotypes were determined by flow cytometry. Clinical features, complete remission (CR), relapse, and five-year overall survival (OS) rate were assessed and subjected to multivariate analyses. The CD13+CD33+HLA-DR-CD34− immunophenotype was commonly observed in patients with APL. Positive rates for other APL immune markers including cMPO, CD117, CD64, and CD9 were 68.7%, 26%, 78.4%, and 96.6%, respectively. When compared with patients with CD2− APL, patients with CD2+ APL had a significantly higher incidence of early death (50% versus 15.7%; ), lower CR rate (50% versus 91.1%; ), and lower five-year OS rate (41.7% versus 74.2%; ). White blood cell (WBC) count before treatment was found to be the only independent risk factor of early death, CR failure, and five-year mortality rate. Flow cytometric immunophenotype analysis can facilitate prompt APL diagnosis. Multivariate analysis has demonstrated that WBC count before treatment is the only known independent risk factor that predicts prognosis for APL in this study population. Fang Xu, Chang-Xin Yin, Chun-Li Wang, Xue-Jie Jiang, Ling Jiang, Zhi-Xiang Wang, Zheng-Shan Yi, Kai-Kai Huang, and Fan-Yi Meng Copyright © 2014 Fang Xu et al. All rights reserved. Clinical Usefulness of Novel Serum and Imaging Biomarkers in Risk Stratification of Patients with Stable Angina Thu, 19 Jun 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/831364/ Inflammatory mediators appear to be the most intriguing yet confusing subject, regarding the management of patients with acute coronary syndromes (ACS). The current inflammatory concept of atherosclerotic coronary artery disease (CAD) led many investigators to concentrate on systemic markers of inflammation, as well as imaging techniques, which may be helpful in risk stratification and prognosis assessment for cardiovascular events. In this review, we try to depict many of the recently studied markers regarding stable angina (SA), their clinical usefulness, and possible future applications in the field. George Tsaknis, Iraklis Tsangaris, Ignatios Ikonomidis, and Argirios Tsantes Copyright © 2014 George Tsaknis et al. All rights reserved. Comparative Plasma Protein Profiling of Hemoglobin H Disease Sun, 15 Jun 2014 12:36:17 +0000 http://www.hindawi.com/journals/dm/2014/340214/ HbH and HbH-constant spring (HbH-CS) are the most common forms of α-thalassemia detected in the Thai population. The accumulation of excess β globin chains in these diseases results in increased red cell hemolysis, and patients with HbH-CS normally have a more severe clinical presentation than patients with HbH disease. This study aimed to detect alterations in the expression of plasma proteins of HbH and HbH-CS patients as compared to normal plasma. Platelet poor plasma was separated from HbH and HbH-CS and normal subjects and differential plasma proteins were detected using two-dimensional gel electrophoresis and identified using LC/MS/MS. A total of 14 differentially expressed proteins were detected of which 5 proteins were upregulated and 9 were downregulated. Most of the differentially expressed proteins are liver secreted proteins involved in hemolysis, oxidative stress response, and hemoglobin degradation. Seven proteins were found to be differentially expressed between HbH and HbH-CS. Levels of haptoglobin, a hemoglobin scavenging protein, were significantly increased in HbH patients as compared to HbH-CS patients. The identification of differentially expressed proteins may lead to a better understanding of the biological events underlying the clinical presentation of HbH and HbH-CS patients and can have application as hemolytic markers or severity predictors. Kamonlak Leecharoenkiat, Wannapa Sornjai, Kornpat Khungwanmaythawee, Atchara Paemanee, Chartchai Chaichana, Sittiruk Roytrakul, Suthat Fucharoen, Saovaros Svasti, and Duncan R. Smith Copyright © 2014 Kamonlak Leecharoenkiat et al. All rights reserved. Erratum to “Molecular Targeted Approaches for Advanced BRAF V600, N-RAS, c-KIT, and GNAQ Melanoma” Mon, 02 Jun 2014 09:06:01 +0000 http://www.hindawi.com/journals/dm/2014/246751/ Giovanni Ponti, Giovanni Pellacani, Aldo Tomasi, Pietro Loschi, Gabriele Luppi, Fabio Gelsomino, and Caterina Longo Copyright © 2014 Giovanni Ponti et al. All rights reserved. Study of Leptin and Adiponectin as Disease Markers in Subjects with Obstructive Sleep Apnea Thu, 29 May 2014 06:16:29 +0000 http://www.hindawi.com/journals/dm/2014/706314/ Background. Published studies showed conflicting results of the associations between adiponectin and leptin levels and obstructive sleep apnoea (OSA). In obese patients, plasma leptin is elevated and adiponectin is decreased, and we postulate that these adipokines could be potential markers of clinical and metabolic perturbations in patients with OSA. Methods. 147 patients with suspected OSA had polysomnography to determine the Respiratory Disturbance Index (RDI). We measured fasting plasma glucose (FPG), fasting serum insulin, plasma leptin, adiponectin, and full lipid profile. Patients were classified on the basis of the RDI, degree of adiposity, and insulin resistance (IR) (homeostasis model assessment of insulin resistance (HOMAIR)). Results. 28.6% of subjects had normal polysomnography, 34.8% had mild OSA, 19.6% had moderate OSA, and 17% had severe OSA. Obesity was more prevalent in subjects with moderate-severe OSA (47%). Adiponectin decreased significantly with increasing severity of OSA. Though BMI was significantly higher in subjects with severe OSA, paradoxically, leptin was lowest in those subjects independent of gender dimorphism. Conclusions. Adiponectin is an independent marker of disease severity in patients with OSA. The paradoxical decrease in circulating leptin, which suggests impaired secretion, deserves further studies as a potential marker of severe OSA. Sana Al Mutairi, Olusegun A. Mojiminiyi, Alia Al Alawi, Tahani Al Rammah, and Nabila Abdella Copyright © 2014 Sana Al Mutairi et al. All rights reserved. Proteome Changes in the Plasma of Myelodysplastic Syndrome Patients with Refractory Anemia with Excess Blasts Subtype 2 Sun, 25 May 2014 11:03:07 +0000 http://www.hindawi.com/journals/dm/2014/178709/ The goal of this study was to explore the plasma proteome of myelodysplastic syndrome (MDS) patients with refractory anemia with excess blasts subtype 2 (RAEB-2) in comparison to healthy controls. 20 plasma samples were separated with 2D electrophoresis and statistically processed with Progenesis SameSpots software. 47 significantly differing () spots were observed, and 27 different proteins were identified by nano-LC-MS/MS. Mass spectrometry-based relative label-free quantification showed a 2-fold increase of the leucine-rich alpha-2-glycoprotein (LRAG) peptide levels in the RAEB-2 group. Changes in the fragments of the inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) protein were observed. Western blot analysis showed no differences in albumin and ITIH4 levels, while increased expression was observed for LRAG in the RAEB-2 group. Quantification using ELISA showed decreased plasma level of alpha-2-HS glycoprotein in the RAEB-2 group. In conclusion, this is the first time that alpha-2-HS glycoprotein and LRAG were proposed as new biomarkers of RAEB-2 and advanced MDS, respectively. Alpha-2-HS glycoprotein, a protein involved in the bone marrow development and previously proposed as a MDS biomarker candidate, was significantly decreased in RAEB-2. Increased expression and changes in modification(s) were observed for LRAG, a protein involved in granulocytic and neutrophil differentiation, and angiogenesis. Pavel Majek, Zuzana Riedelova-Reicheltova, Jiri Suttnar, Klara Pecankova, Jaroslav Cermak, and Jan E. Dyr Copyright © 2014 Pavel Majek et al. All rights reserved. Gene Expression Profiling of Colorectal Tumors and Normal Mucosa by Microarrays Meta-Analysis Using Prediction Analysis of Microarray, Artificial Neural Network, Classification, and Regression Trees Mon, 19 May 2014 12:12:30 +0000 http://www.hindawi.com/journals/dm/2014/634123/ Background. Microarray technology shows great potential but previous studies were limited by small number of samples in the colorectal cancer (CRC) research. The aims of this study are to investigate gene expression profile of CRCs by pooling cDNA microarrays using PAM, ANN, and decision trees (CART and C5.0). Methods. Pooled 16 datasets contained 88 normal mucosal tissues and 1186 CRCs. PAM was performed to identify significant expressed genes in CRCs and models of PAM, ANN, CART, and C5.0 were constructed for screening candidate genes via ranking gene order of significances. Results. The first screening identified 55 genes. The test accuracy of each model was over 0.97 averagely. Less than eight genes achieve excellent classification accuracy. Combining the results of four models, we found the top eight differential genes in CRCs; suppressor genes, CA7, SPIB, GUCA2B, AQP8, IL6R and CWH43; oncogenes, SPP1 and TCN1. Genes of higher significances showed lower variation in rank ordering by different methods. Conclusion. We adopted a two-tier genetic screen, which not only reduced the number of candidate genes but also yielded good accuracy (nearly 100%). This method can be applied to future studies. Among the top eight genes, CA7, TCN1, and CWH43 have not been reported to be related to CRC. Chi-Ming Chu, Chung-Tay Yao, Yu-Tien Chang, Hsiu-Ling Chou, Yu-Ching Chou, Kang-Hua Chen, Harn-Jing Terng, Chi-Shuan Huang, Chia-Cheng Lee, Sui-Lun Su, Yao-Chi Liu, Fu-Gong Lin, Thomas Wetter, and Chi-Wen Chang Copyright © 2014 Chi-Ming Chu et al. All rights reserved. Biomarkers of Inflammatory Bowel Disease Mon, 19 May 2014 10:51:21 +0000 http://www.hindawi.com/journals/dm/2014/710915/ Inflammatory bowel disease (IBD) is a chronic disease mostly involved with intestine with unknown etiology. Diagnosis, evaluation of severity, and prognosis are still present as challenges for physicians. An ideal biomarker with the characters such as simple, easy to perform, noninvasive or microinvasive, cheap, rapid, and reproducible is helpful for patients and clinicians. Currently biomarkers applied in clinic include CRP, ESR, pANCA, ASCA, and fecal calprotectin. However, they are far from ideal. Lots of studies are focused on seeking for ideal biomarker for IBD. Herein, the paper reviewed recent researches on biomarkers of IBD to get advances of biomarkers in inflammatory bowel disease. Yi Fengming and Wu Jianbing Copyright © 2014 Yi Fengming and Wu Jianbing. All rights reserved. Hypertrophy of Ligamentum Flavum in Lumbar Spine Stenosis Is Associated with Increased miR-155 Level Sun, 18 May 2014 09:38:08 +0000 http://www.hindawi.com/journals/dm/2014/786543/ Hypertrophy of ligamentum flavum (LF) contributes to lumbar spinal stenosis (LSS) and is caused mainly by fibrosis. Recent data indicate that miR-155 plays a crucial role in the pathogenesis of different fibrotic diseases. This study aimed to test the hypothesis that miR-155 exerts effects on LF thickness by regulating collagen expression. We found that LF thickness and the expression of collagen I and, collagen III were higher in LF from LSS patients than in LF from lumbar disc herniation (LDH) patients (). The expression of miR-155 was significantly higher in LF from LSS group than in LF from LDH group (). miR-155 level was positively correlated with LF thickness (, ), type I collagen level (, ), and type III collagen level (, ). miR-155 mimic increased mRNA and protein expression of collagen I and collagen III in fibroblasts isolated from LF, while miR-155 sponge decreased mRNA and protein expression of collagen I and III in fibroblasts. In conclusions, miR-155 is a fibrosis-associated miRNA and may play important role in the pathogenesis of LF hypertrophy. Jianwei Chen, Zude Liu, Guibin Zhong, Lie Qian, Zhanchun Li, Zhiguang Qiao, Bin Chen, and Hantao Wang Copyright © 2014 Jianwei Chen et al. All rights reserved. Beta2-Microglobulin as a Diagnostic Marker in Cerebrospinal Fluid: A Follow-Up Study Thu, 08 May 2014 07:21:49 +0000 http://www.hindawi.com/journals/dm/2014/495402/ Beta2-Microglobulin (β2-m) is a low molecular weight protein occurring in all body fluids. Its concentration increases in various pathologies. Increased values in cerebrospinal fluid (CSF) are ascribed to an activation of immune system. Using immunoturbidimetry, we examined concentrations of beta2-microglobulin in cerebrospinal fluid in a large group of 6274 patients with defined neurological diseases. Cell counts, total protein, albumin, glucose, lactic acid, immunoglobulins concentrations, and isofocusing (IEF) were also evaluated. We found substantial changes of CSF β2-m concentrations in purulent meningitis, leptomeningeal metastasis, viral meningitis/encephalitis, and neuroborreliosis, while in multiple sclerosis these changes were not significant. Intrathecal synthesis and immune activation were present in these clinical entities. A new normative study enables better understanding of beta2-microglobulin behavior in CSF. Jana Svatoňová, Klára Bořecká, Pavel Adam, and Věra Lánská Copyright © 2014 Jana Svatoňová et al. All rights reserved. Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio: Novel Markers for Diagnosis and Prognosis in Patients with Idiopathic Sudden Sensorineural Hearing Loss Wed, 07 May 2014 11:49:25 +0000 http://www.hindawi.com/journals/dm/2014/702807/ Background. We aim to provide useful evidence about the association of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with idiopathic sudden sensorineural hearing loss (ISSNHL) and its possibility of emerging as a cheap, reliable, and independent prognostic marker of ISSNHL. Methods. 348 patients diagnosed with ISSNHL were included in our retrospective data analysis. Blood samples and the hearing assessments of the patients were carried out. Then, the patients were divided into 2 groups as “recovered” and “unrecovered” according to their response to the treatment. Results. Both mean NLR and PLR values of the ISSNHL patients were significantly higher than the control group (both ). The NLR value was in the unrecovered group and in the recovered group (). After adjustment in a binary logistic regression model, only NLR value was associated with the recovery of ISSNHL (). Discussion. We demonstrated for the first time that NLR and PLR values were significantly high in ISSNHL patients. Also the NLR level might be taken into account as a novel potential marker to predict the patients’ prognosis in terms of recovery. Young Joon Seo, Jun hui Jeong, Jae Young Choi, and In Seok Moon Copyright © 2014 Young Joon Seo et al. All rights reserved. Assessment of Urinary Osteopontin in Association with Podocyte for Early Predication of Nephropathy in Diabetic Patients Sun, 04 May 2014 07:06:23 +0000 http://www.hindawi.com/journals/dm/2014/493736/ Objectives. Microalbuminuria has been clinically used for noninvasive evaluation of renal dysfunctions. However, it is a nonspecific marker of diabetic nephropathy (DN). Methods. This study was conducted from March 2012 to April 2013 at Biochemistry Unit, King Fahd Medical Research Center (KFMRC). In this study, urinary osteopontin, podocytes number, and levels of immunoglobulin M (IgM) were determined in 60 patients (diabetic normoalbuminuria, diabetic microalbuminuria, and nephritic syndrome) compared with healthy subjects. Results. It was found that in diabetic microalbuminuria patients have a highly significant increase in urinary IgM, osteopontin, and podocyte levels as compared to other groups. Nephrotic syndrome patients showed a moderate significant elevation of these parameters compared to control subjects. At a given specificity of 97%, podocytes yielded the highest sensitivity of all markers, 95.5%. The sensitivity was considerably higher compared to IgM and osteopontin. Podocyte number was positively correlated with serum IgM and osteopontin ( and 0.56), respectively. Its cutoff corresponding to the 10% coefficient of variation was most appropriate for early diagnosis of DN. Conclusion. Monitoring urinary podocyte may provide a noninvasive tool that is a sensitive, accurate, and specific biomarker of glomerular injury and can be used in combination with osteopontin and IgM to more reliably detect and monitor prognosis. Abdulrahman L. Al-Malki Copyright © 2014 Abdulrahman L. Al-Malki. All rights reserved. Expression of the Microtubule-Associated Protein MAP9/ASAP and Its Partners AURKA and PLK1 in Colorectal and Breast Cancers Wed, 30 Apr 2014 07:02:09 +0000 http://www.hindawi.com/journals/dm/2014/798170/ Background. Colorectal and breast cancers are among the most common cancers worldwide. They result from a conjugated deficiency of gene maintenance and cell cycle control. Objective. We investigate the expression of the microtubule-associated protein MAP9/ASAP and its two partners AURKA and PLK1 in colorectal tumors as well as in ductal breast cancers. Materials and Methods. 26 colorectal cancer samples and adjacent normal tissues and 77 ductal breast cancer samples from grade I to grade III were collected. Real-time quantitative PCR was used to analyse the expression of MAP9, AURKA, and PLK1. Results. Expression of MAP9 is downregulated in colorectal cancer compared to normal tissues (), whereas those of AURKA and PLK1 are upregulated (). In ductal breast cancer, we found a grade-dependent increase of AURKA expression (), while the variations of expression of MAP9 and PLK1 are not significant (). Conclusions. MAP9 downregulation is associated with colorectal malignancy and could be used as a disease marker and a new drug target, while AURKA and PLK1 are upregulated. In ductal breast cancer, AURKA overexpression is strongly associated with the tumor grade and is therefore of prognostic value for the progression of the disease. Sylvie Rouquier, Marie-Jeanne Pillaire, Christophe Cazaux, and Dominique Giorgi Copyright © 2014 Sylvie Rouquier et al. All rights reserved. Haptoglobin 2-2 Genotype Is Associated with TNF-α and IL-6 Levels in Subjects with Obesity Tue, 29 Apr 2014 11:33:31 +0000 http://www.hindawi.com/journals/dm/2014/912756/ Objective. To evaluate the association between Haptoglobin (HP) gene polymorphisms with inflammatory status in obese subjects. Materials and Methods. A cross-sectional study was carried out. A total of 276 apparently healthy men and nonpregnant obese women were enrolled and allocated according to the HP genotype into the HP1/HP1, HP2/HP1, and HP2/HP2 groups. Distribution of HP genotypes was 49, 87, and 140 for the HP1/HP1, HP2/HP1, and HP2/HP2, respectively. The HP genotype was determined using the polymerase chain reaction method. A multiple linear regression analysis adjusted by age, sex, waist circumference, and total body fat was used to determine the association between HP genotypes with TNF-α, IL-6, and high-sensitivity C-reactive protein (hsCRP) levels. Results. A multiple linear regression analysis adjusted by sex, waist circumference, and total body fat was performed showing a significant association between the HP2/HP2 genotype and TNF-α (β = 0.180; 95% CI 14.41–159.64, P = 0.01) and IL-6 (β = 0.188; 95% CI 1.53–12.72, P = 0.01) levels, but not with hsCRP (β = −0.008; 95% CI −1.64–1.47, P = 0.914) levels, whereas the HP2/HP1 genotype showed no association compared with the HP1/HP1 genotype (control group). Conclusion. Results of our study show that the HP2/HP2 genotype is associated with elevated TNF-α and IL-6, but not with hsCRP, levels in obese subjects. Brissia Lazalde, Héctor M. Huerta-Guerrero, Luis E. Simental-Mendía, Martha Rodríguez-Morán, and Fernando Guerrero-Romero Copyright © 2014 Brissia Lazalde et al. All rights reserved. FT-IR Analysis of Urinary Stones: A Helpful Tool for Clinician Comparison with the Chemical Spot Test Sun, 27 Apr 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/176165/ Background. Kidney stones are a common illness with multifactorial etiopathogenesis. The determination of crystalline and molecular composition and the quantification of all stone components are important to establish the etiology of stones disease but it is often laborious to obtain using the chemical method. The aim of this paper is to compare chemical spot test with FT-IR spectroscopy, for a possible introduction in our laboratory. Methods. We analyzed 48 calculi using Urinary Calculi Analysis kit in accordance with the manufacturer’s instructions. The same samples were analyzed by FT-IR using the Perkin Elmer Spectrum One FT-IR Spectrometer. All FT-IR spectra of kidney stones were then computer matched against a library of spectra to generate a report on the various components. Results. On the basis of FT-IR analysis, the 48 calculi were divided into three groups: pure stone, mixed stone, and pure stone with substances in trace. Results of each group were compared with those obtained with chemical spot test. A general disagreement between methods was observed. Conclusions. According to our data, the introduction of the FT-IR technique in clinical chemistry laboratory may be more responsive to clinician expectations. Aniello Primiano, Silvia Persichilli, Giovanni Gambaro, Pietro Manuel Ferraro, Alessandro D’Addessi, Andrea Cocci, Arcangelo Schiattarella, Cecilia Zuppi, and Jacopo Gervasoni Copyright © 2014 Aniello Primiano et al. All rights reserved. The Clinical Significance of PR, ER, NF-κB, and TNF-α in Breast Cancer Wed, 23 Apr 2014 08:10:49 +0000 http://www.hindawi.com/journals/dm/2014/494581/ Objectives. To investigate the expression of estrogen (ER), progesterone receptors (PR), nuclear factor-κB (NF-κB), and tumor necrosis factor-α (TNF-α) in human breast cancer (BC), and the correlation of these four parameters with clinicopathological features of BC. Methods and Results. We performed an immunohistochemical SABC method for the identification of ER, PR, NF-κB, and TNF-α expression in 112 patients with primary BC. The total positive expression rate of ER, PR, NF-κB, and TNF-α was 67%, 76%, 84%, and 94%, respectively. The expressions of ER and PR were correlated with tumor grade, TNM stage, and lymph node metastasis (, resp.), but not with age, tumor size, histological subtype, age at menarche, menopause status, number of pregnancies, number of deliveries, and family history of cancer. Expressions of ER and PR were both correlated with NF-κB and TNF-α expression (, resp.). Moreover, there was significant correlation between ER and PR as well as between NF-κB and TNF-α expression . Conclusion. PR and ER are highly expressed, with significant correlation with NF-κB and TNF-α expression in breast cancer. The important roles of ER and PR in invasion and metastasis of breast cancer are probably associated with NF-κB and TNF-α expression. Xian-Long Zhou, Wei Fan, Gui Yang, and Ming-Xia Yu Copyright © 2014 Xian-Long Zhou et al. All rights reserved. TRIM29 as a Novel Biomarker in Pancreatic Adenocarcinoma Tue, 22 Apr 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/317817/ Background and Aim. Tripartite motif-containing 29 (TRIM29) is structurally a member of the tripartite motif family of proteins and is involved in diverse human cancers. However, its role in pancreatic cancer remains unclear. Methods. The expression pattern of TRIM29 in pancreatic ductal adenocarcinoma was assessed by immunocytochemistry. Multivariate logistic regression analysis was used to investigate the association between TRIM29 and clinical characteristics. In vitro analyses by scratch wound healing assay and invasion assays were performed using the pancreatic cancer cell lines. Results. Immunohistochemical analysis showed TRIM29 expression in pancreatic cancer tissues was significantly higher   than that in matched adjacent nontumor tissues. TRIM29 protein expression was significantly correlated with lymph node metastasis . Patients with positive TRIM29 expression showed both shorter overall survival and shorter recurrence-free survival than those with negative TRIM29 expression. Multivariate analysis revealed that TRIM29 was an independent factor for pancreatic cancer over survival (, 95% CI: 1.324–4.198, ). In vitro, TRIM29 knockdown resulted in inhibition of pancreatic cancer cell proliferation, migration, and invasion. Conclusions. Our results indicate that TRIM29 promotes tumor progression and may be a novel prognostic marker for pancreatic ductal adenocarcinoma. Hongli Sun, Xianwei Dai, and Bing Han Copyright © 2014 Hongli Sun et al. All rights reserved. Longitudinal Relationship between Plasma Reactive Oxygen Metabolites and Periodontal Condition in the Maintenance Phase of Periodontal Treatment Wed, 16 Apr 2014 14:06:48 +0000 http://www.hindawi.com/journals/dm/2014/489292/ Aim. The present cohort study describes the longitudinal relationship between plasma oxidative status and periodontitis progression during the maintenance phase of treatment. Materials and Methods. Forty-five patients (mean age 58.8 years) were monitored from 2008 to 2013. Periodontal conditions, including probing pocket depth (PPD) and clinical attachment level (CAL), were recorded. Measurements of plasma reactive oxygen metabolites (ROM) and biologic antioxidant potential (BAP) were performed to evaluate plasma oxidative status. The patients were assigned into 2 groups as low and high plasma ROM level using a cut-off value which was median of plasma ROM level at baseline. Results. In the subjects with low plasma ROM level at baseline, changes in mean CAL were positively correlated with changes in plasma ROM levels, bleeding on probing, and plaque control record, but not with PPD. In the subjects with high plasma ROM at baseline, changes in CAL were significantly associated with only PPD at baseline. On the other hands there were no significant associations between changes in CAL and those in plasma BAP levels. Conclusions. When plasma ROM level in periodontitis patients was low, increases in plasma ROM level were associated with those in CAL during the maintenance phase of treatment. Tatsuya Machida, Takaaki Tomofuji, Daisuke Ekuni, Mayu Yamane, Toshiki Yoneda, Yuya Kawabata, Kota Kataoka, Naofumi Tamaki, and Manabu Morita Copyright © 2014 Tatsuya Machida et al. All rights reserved. The Role of TPA I/D and PAI-1 4G/5G Polymorphisms in Multiple Sclerosis Wed, 16 Apr 2014 11:58:26 +0000 http://www.hindawi.com/journals/dm/2014/362708/ Background. Previous studies have shown impaired fibrinolysis in multiple sclerosis (MS) and implicated extracellular proteolytic enzymes as important factors in demyelinating neuroinflammatory disorders. Tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1) are key molecules in both fibrinolysis and extracellular proteolysis. In the present study, an association of the TPA Alu I/D and PAI-1 4G/5G polymorphisms with MS was analyzed within the Genomic Network for Multiple Sclerosis (GENoMS). Methods. The GENoMS includes four populations (Croatian, Slovenian, Serbian, and Bosnian and Herzegovinian) sharing the same geographic location and a similar ethnic background. A total of 885 patients and 656 ethnically matched healthy blood donors with no history of MS in their families were genotyped using PCR-RFLP. Results. TPA DD homozygosity was protective (OR = 0.79, 95% CI 0.63–0.99, ) and PAI 5G5G was a risk factor for MS (OR = 1.30, 95% CI 1.01–1.66, ). A significant effect of the genotype/carrier combination was detected in 5G5G/I carriers (OR = 1.39 95% CI 1.06–1.82, ). Conclusions. We found a significantly harmful effect of the combination of the PAI-1 5G/5G genotype and TPA I allele on MS susceptibility, which indicates the importance of gene-gene interactions in complex diseases such as MS. Maja Živković, Nada Starčević Čizmarević, Luca Lovrečić, Inge Klupka-Sarić, Aleksandra Stanković, Iva Gašparović, Polona Lavtar, Evica Dinčić, Ljiljana Stojković, Gorazd Rudolf, Saša Šega Jazbec, Olivio Perković, Osman Sinanović, Juraj Sepčić, Miljenko Kapović, Borut Peterlin, and Smiljana Ristić Copyright © 2014 Maja Živković et al. All rights reserved. Accurate, Fast and Cost-Effective Diagnostic Test for Monosomy 1p36 Using Real-Time Quantitative PCR Tue, 15 Apr 2014 14:14:29 +0000 http://www.hindawi.com/journals/dm/2014/836082/ Monosomy 1p36 is considered the most common subtelomeric deletion syndrome in humans and it accounts for 0.5–0.7% of all the cases of idiopathic intellectual disability. The molecular diagnosis is often made by microarray-based comparative genomic hybridization (aCGH), which has the drawback of being a high-cost technique. However, patients with classic monosomy 1p36 share some typical clinical characteristics that, together with its common prevalence, justify the development of a less expensive, targeted diagnostic method. In this study, we developed a simple, rapid, and inexpensive real-time quantitative PCR (qPCR) assay for targeted diagnosis of monosomy 1p36, easily accessible for low-budget laboratories in developing countries. For this, we have chosen two target genes which are deleted in the majority of patients with monosomy 1p36: PRKCZ and SKI. In total, 39 patients previously diagnosed with monosomy 1p36 by aCGH, fluorescent in situ hybridization (FISH), and/or multiplex ligation-dependent probe amplification (MLPA) all tested positive on our qPCR assay. By simultaneously using these two genes we have been able to detect 1p36 deletions with 100% sensitivity and 100% specificity. We conclude that qPCR of PRKCZ and SKI is a fast and accurate diagnostic test for monosomy 1p36, costing less than 10 US dollars in reagent costs. Pricila da Silva Cunha, Heloisa B. Pena, Carla Sustek D’Angelo, Celia P. Koiffmann, Jill A. Rosenfeld, Lisa G. Shaffer, Martin Stofanko, Higgor Gonçalves-Dornelas, and Sérgio Danilo Junho Pena Copyright © 2014 Pricila da Silva Cunha et al. All rights reserved.