Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. The Prognostic Value of Intermedin in Patients with Breast Cancer Wed, 28 Jan 2015 07:47:37 +0000 http://www.hindawi.com/journals/dm/2015/862158/ This study aimed to evaluate the prognostic value of preoperative plasma intermedin levels in breast cancer patients. Plasma intermedin levels of 252 breast cancer women and 100 healthy women were determined using radioimmunoassay kit. Adverse event was defined as first local recurrence, distant metastasis, second primary cancer of another organ, or death from any cause during 5-year follow-up. Disease-free survival was defined as the time between surgery and the date of any adverse event whichever appeared first. Overall survival was defined from surgery to death for any cause. The relationships between plasma intermedin levels and clinical outcomes of breast cancer patients were evaluated using multivariate analysis. The results showed that preoperative plasma intermedin levels were substantially higher in patients than in healthy subjects using t-test. Intermedin was identified as an independent predictor for 5-year mortality, adverse event, disease-free survival, and overall survival using multivariate analysis. Based on receiver operating characteristic curve analysis, preoperative plasma intermedin levels had high predictive value for 5-year mortality and adverse event. In conclusion, preoperative plasma intermedin levels are highly associated with poor patient outcomes and intermedin may be a potential prognostic biomarker for patients with breast cancer. Yi-Min Lu, Jian-Bo Zhong, Hai-Yong Wang, Xiong-Fei Yu, and Zhong-Qi Li Copyright © 2015 Yi-Min Lu et al. All rights reserved. Correlation between Sperm Parameters and Protein Expression of Antioxidative Defense Enzymes in Seminal Plasma: A Pilot Study Tue, 27 Jan 2015 08:34:37 +0000 http://www.hindawi.com/journals/dm/2015/436236/ Background. Semen analysis is the cornerstone in the evaluation of male (in)fertility. However, there are men with normal semen tests but with impaired fertilizing ability, as well as fertile men with poor sperm characteristics. Thus, there is rising interest to find novel parameters that will help to predict and define the functional capacity of spermatozoa. Methods. We examined whether there is a correlation between semen parameters (count, progressive motility, and morphology) and protein expression/activity of antioxidative defense enzymes in seminal plasma from 10 normospermic subjects. Results. Sperm progressive motility was in positive correlation with seminal plasma protein expression of both superoxide dismutase (SOD) isoforms (MnSOD and CuZnSOD) and catalase. Also, positive correlation was observed between sperm count and MnSOD protein expression, as well as between sperm morphology and protein expression of catalase in seminal plasma. In contrast, protein expression of glutathione peroxidase was not in correlation with any sperm parameter, while its activity negatively correlated with sperm morphology and motility. Conclusions. These data suggest that evaluation of protein expression of antioxidative defense enzymes in seminal plasma might be of importance in the evaluation of male fertility status and that could be used as an additional biomarker along with classic semen analysis in assessment of semen quality. Biljana Macanovic, Milica Vucetic, Aleksandra Jankovic, Ana Stancic, Biljana Buzadzic, Eliana Garalejic, Aleksandra Korac, Bato Korac, and Vesna Otasevic Copyright © 2015 Biljana Macanovic et al. All rights reserved. Next Generation Sequencing to Determine the Cystic Fibrosis Mutation Spectrum in Palestinian Population Mon, 26 Jan 2015 08:18:02 +0000 http://www.hindawi.com/journals/dm/2015/458653/ An extensive molecular analysis of the CF transmembrane regulator (CFTR) gene was performed to establish the CFTR mutation spectrum and frequencies in the Palestinian population, which can be considered as an understudied population. We used a targeted Next Generation Sequencing approach to sequence the entire coding region and the adjacent sequences of the CFTR gene combined with MLPA analysis of 60 unrelated CF patients. Eighteen different CF-causing mutations, including one previously undescribed mutation p.(Gly1265Arg), were identified. The overall detection rate is up to 67%, and when we consider only CF patients with sweat chloride concentrations >70 mEq/L, we even have a pickup rate of 92%. Whereas p.(Phe508del) is the most frequent allele (35% of the positive cases), 3 other mutations c.2988+1Kbdel8.6Kb, c.1393-1G>A, and p.(Gly85Glu) showed frequencies higher than 5% and a total of 9 mutations account for 84% of the mutations. This limited spectrum of CF mutations is in agreement with the homozygous ethnic origin of the Palestinian population. The relative large portion of patients without a mutation is most likely due to clinical misdiagnosis. Our results will be important in the development of an adequate molecular diagnostic test for CF in Palestine. O. Essawi, M. Farraj, K. De Leeneer, W. Steyaert, K. De Pauw, A. De Paepe, K. Claes, T. Essawi, and P. J. Coucke Copyright © 2015 O. Essawi et al. All rights reserved. Fatigue in Patients with Multiple Sclerosis: Is It Related to Pro- and Anti-Inflammatory Cytokines? Mon, 19 Jan 2015 07:32:36 +0000 http://www.hindawi.com/journals/dm/2015/758314/ Objective. To investigate the pathophysiological role of pro- and anti-inflammatory cytokines in primary multiple sclerosis-related fatigue. Methods. Fatigued and non-fatigued patients with multiple sclerosis (MS) were recruited and their cytokine profiles compared. Patients with secondary fatigue were excluded. Fatigue was assessed with the self-reported Checklist Individual Strength (CIS20r), subscale fatigue. A CIS20r fatigue cut-off score of 35 was applied to differentiate between non-fatigued (CIS20r fatigue 34) and fatigued (CIS20r fatigue 35) patients with MS. Blood was collected to determine the serum concentrations of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, IL-12p70, IL-17, TNFα, and IFN-γ) and anti-inflammatory cytokines (IL-4, IL-5, IL-10, and IL-13). We controlled for the confounding effect of age, gender, duration of MS, disease severity, type of MS, and use of immunomodulatory drugs. Results. Similar cytokine levels were observed between MS patients with and without fatigue . Adjusted multiple regression analyses showed a single significant positive relationship, that of IL-6 with CIS20r fatigue score. The explained variance of the IL-6 model was 21.1%, once adjusted for the confounding effect of age. Conclusion. The pro-inflammatory cytokine interleukin-6 (IL-6) may play a role in the pathophysiology of primary fatigue in patients with MS. Trial Registrations. ISRCTN69520623, ISRCTN58583714, and ISRCTN82353628. Arjan Malekzadeh, Wietske Van de Geer-Peeters, Vincent De Groot, Charlotte Elisabeth Teunissen, Heleen Beckerman, and TREFAMS-ACE Study Group Copyright © 2015 Arjan Malekzadeh et al. All rights reserved. High CD133 Expression in the Nucleus and Cytoplasm Predicts Poor Prognosis in Non-Small Cell Lung Cancer Sun, 18 Jan 2015 11:34:56 +0000 http://www.hindawi.com/journals/dm/2015/986095/ Objective. The aim of this study was to investigate the expression of Prominin-1 (CD133) in cancer cells and its potential value as a prognostic indicator of survival in patients with non-small cell lung cancer (NSCLC). Methods. Cancerous tissues and matched normal tissues adjacent to the carcinoma from 239 NSCLC patients were obtained immediately after surgery. Immunohistochemistry of tissue microarrays was used to characterize the expression of CD133 in NSCLC and adjacent tissues. The correlation of CD133 expression with clinical characteristics and prognosis was determined by statistical analysis. Results. CD133 protein expression levels in both the cytoplasm and nucleus were significantly higher in NSCLC tissues compared with corresponding peritumoral tissue (). CD133 expression in the nucleus of NSCLC cells was related to tumor diameter (), tumor differentiation (), and TNM stage (). Kaplan-Meier survival and Cox regression analyses revealed that high CD133 expression in the nucleus was an independent predictor of poor prognosis of NSCLC, as was high cytoplasmic CD133 expression (). Conclusion. Our findings provide the first evidence that high expression of CD133 in both the nucleus and cytoplasm is associated with poor prognosis in NSCLC. Minjie Huang, Huijun Zhu, Jian Feng, Songshi Ni, and Jianfei Huang Copyright © 2015 Minjie Huang et al. All rights reserved. Nasal Potential Difference in Cystic Fibrosis considering Severe CFTR Mutations Thu, 15 Jan 2015 14:16:23 +0000 http://www.hindawi.com/journals/dm/2015/306825/ The gold standard for diagnosing cystic fibrosis (CF) is a sweat chloride value above 60 mEq/L. However, this historical and important tool has limitations; other techniques should be studied, including the nasal potential difference (NPD) test. CFTR gene sequencing can identify CFTR mutations, but this method is time-consuming and too expensive to be used in all CF centers. The present study compared CF patients with two classes I-III CFTR mutations (10 patients) (G1), CF patients with classes IV-VI CFTR mutations (five patients) (G2), and 21 healthy subjects (G3). The CF patients and healthy subjects also underwent the NPD test. A statistical analysis was performed using the Mann-Whitney, Kruskal-Wallis, χ2, and Fisher’s exact tests, . No differences were observed between the CF patients and healthy controls for the PDMax, Δamiloride, and Δchloride + free + amiloride markers from the NPD test. For the finger value, a difference between G2 and G3 was described. The Wilschanski index values were different between G1 and G3. In conclusion, our data showed that NPD is useful for CF diagnosis when classes I-III CFTR mutations are screened. However, if classes IV-VI are considered, the NPD test showed an overlap in values with healthy subjects. Ronny Tah Yen Ng, Fernando Augusto de Lima Marson, Jose Dirceu Ribeiro, Antonio Fernando Ribeiro, Carmen Silvia Bertuzzo, Maria Angela Gonçalves de Oliveira Ribeiro, Silvana Dalge Severino, and Eulalia Sakano Copyright © 2015 Ronny Tah Yen Ng et al. All rights reserved. Study on the Usefulness of APR Scores from the Viewpoint of Proinflammatory Cytokines Thu, 15 Jan 2015 12:46:11 +0000 http://www.hindawi.com/journals/dm/2015/981981/ Background. Delayed diagnosis and treatment of newborn infection adversely impact outcomes. Clinical laboratory parameters have aimed to obtain the most correct and prompt diagnosis and treatment of this disease. This study simultaneously observed changes over time in APR as well as proinflammatory cytokines and anti-proinflammatory cytokines and aims to clarify usefulness of APR scores. Methods. We evaluated the usefulness of acute phase reactants (APR) in 46 newborns whose serum up to age 7 days had been stored, with comparison of three types (Group I: infection 15, Group F: fetal inflammatory response syndrome 17, and Group C: control 14) of APR-based scores, those of C-reactive protein (CRP), alpha1-acid glycoprotein (AGP), and haptoglobin (Hp), with proinflammatory cytokine levels. APR scores for CRP, AGP, and Hp and the levels of the proinflammatory cytokines IL-1β, IL-6, IL-8, IL-10, and TNFα were determined. Results. The cytokine levels started to increase from age 0 days and then decreased rapidly. The three APR scores, CRP, AG, and Hp, were elevated at age 0 days and then gradually decreased in infection (Group I) and fetal inflammatory response syndrome (Group F). The duration of antibiotic administration according to APR scores was significantly shorter in Group F than in Group I. Conclusion. This study demonstrated APR scores to be more useful for deciding whether antibiotics should be discontinued than proinflammatory cytokine levels. T. Nakamura, D. Hatanaka, T. Yoshioka, S. Yamada, and H. Goto Copyright © 2015 T. Nakamura et al. All rights reserved. Microinflammation Factors in the Common Diseases of the Heart and Kidneys Wed, 14 Jan 2015 11:35:14 +0000 http://www.hindawi.com/journals/dm/2015/470589/ Aim. To determine levels of interleukin-8 (IL-8) and plasminogen activator inhibitor-1 (PAI-1) in different cardiorenal syndrome (CRS) modalities and to compare findings to some already investigated direct and indirect parameters of inflammation and atherosclerosis. Materials and Methods. Testing involved 114 examinees, divided into control and clinical groups suffering from different modalities and were formed according to the basis of a valid classification for CRS. Results. C-reactive protein (CRP) was significantly higher in all CRSs in comparison to the control group . PAI-1 in CRSs was statistically higher than in the control group. IL-8 was increased in all CRSs, and especially in CRS-5, where no significance was found. PAI-1 correlated with IL-8 in all CRSs, with significant value in CRS-2 and CRS-5. Correlation for PAI-1 and high-density lipoproteins (HDL) was found in CRS-4, while IL-8 was found to be related to CRP level in all CRSs, with significance only in CRS-1 . Conclusions. C-reactive protein, IL-8, and PAI-1 could be useful for clinical differentiation of chronic modalities of CRSs. Inflammation was the most pronounced in CRS-4. Lipid status parameters could be useful for differentiation of CRSs. Furthermore, HDL in chronic primary kidney diseases and triglycerides and total cholesterol in CRS-5 could be valuable. Danijela Tasic, Sonja Radenkovic, Gordana Kocic, Marina Deljanin Ilic, and Aleksandra Ignjatovic Copyright © 2015 Danijela Tasic et al. All rights reserved. Association between BMP4 rs17563 Polymorphism and NSCL/P Risk: A Meta-Analysis Mon, 12 Jan 2015 06:16:23 +0000 http://www.hindawi.com/journals/dm/2015/763090/ Objective. To investigate the association between bone morphogenetic protein 4 (BMP4) rs17563 polymorphism and nonsyndromic cleft lip with or without palate (NSCL/P) risk. Methods. Four online databases were researched and the related publications were collected. Odds ratio (OR) with 95% confidence interval (CI) was applied to assess the relationship; publication bias, metaregression, and sensitivity analysis were conducted to guarantee the strength of results. Results. Six published case-control studies were collected. Overall, no significant association between BMP4 rs17563 polymorphism and NSCL/P risk was found. It was notable that significant susceptibility on different ethnicity was observed in the stratified analysis. For Chinese population, the BMP4 rs17563 polymorphism was a significantly increased risk for NSCL/P (C versus T: OR = 1.52, 95% CI = 1.28–1.82, , %; CC versus TT: OR = 2.58, 95% CI = 1.74–3.82, , %; TC + CC versus TT: OR = 1.45, 95% CI = 1.14–1.84, , %; CC versus TT + TC: OR=2.46, 95% CI = 1.46–4.14, , %). On the contrary, significantly protective effects were found in Brazilian population (C versus T: OR = 0.69, 95% CI = 0.50–0.96, , %; TC versus TT: OR = 0.52, 95% CI = 0.40–0.68, , %; TC + CC versus TT: OR = 0.52, 95% CI = 0.35–0.78, , %). Conclusion. This meta-analysis indicated that BMP4 rs17563 polymorphism could play a different role during the development of NSCL/P based on ethnicity diversity. Yuan-Yuan Hu, Chuan-Qi Qin, Mo-Hong Deng, Yu-Ming Niu, and Xing Long Copyright © 2015 Yuan-Yuan Hu et al. All rights reserved. Validation of Serum Biomarkers Derived from Proteomic Analysis for the Early Screening of Preeclampsia Mon, 05 Jan 2015 09:30:59 +0000 http://www.hindawi.com/journals/dm/2015/121848/ Aim. To examine the potential value of previously identified biomarkers using proteomics in early screening for preeclampsia (PE). Methods. 24 blood samples from women who subsequently developed PE and 48 from uncomplicated pregnancies were obtained at 11–13 weeks and analysed after delivery. Cystatin-C, sVCAM-1, and Pappalysin-1 were quantified by ELISA. Maternal characteristics and medical history were recorded. Results. Median values of Cystatin-C, sVCAM-1, and Pappalysin-1 in the PE group as compared to controls were 909.1 gEq/mL versus 480.0 gEq/mL, , 832.0 gEq/mL versus 738.8 gEq/mL, , and 234.4 gEq/mL versus 74.9 gEq/mL, , respectively. Areas under the receiver-operating characteristic curves (AUC, standard error (SE)) for predicting PE were Cystatin-C: 0.90 (SE 0.04), VCAM-1: 0.66 (SE 0.074), and Pappalysin-1: 0.63 (SE 0.083). To discriminate between cases at risk for PE and normal controls, cut-off values of 546.8 gEq/mL for Cystatin-C, 1059.5 gEq/mL for sVCAM-1, and 220.8 gEq/mL for Pappalysin-1 were chosen, providing sensitivity of 91%, 41%, and 54% and specificity of 85%, 100%, and 95%, respectively. Conclusions. sVCAM-1 and Pappalysin-1 do not improve early screening for PE. Cystatin-C, however, seems to be associated with subsequent PE development, but larger studies are necessary to validate these findings. Aggeliki Kolialexi, Dimitrios Gourgiotis, George Daskalakis, Antonis Marmarinos, Alexandra Lykoudi, Danai Mavreli, Ariadni Mavrou, and Nikolas Papantoniou Copyright © 2015 Aggeliki Kolialexi et al. All rights reserved. High Frequency of CD8 Positive Lymphocyte Infiltration Correlates with Lack of Lymph Node Involvement in Early Rectal Cancer Tue, 30 Dec 2014 09:47:13 +0000 http://www.hindawi.com/journals/dm/2014/792183/ Aims. A trend towards local excision of early rectal cancers has prompted us to investigate if immunoprofiling might help in predicting lymph node involvement in this subgroup. Methods. A tissue microarray of 126 biopsies of early rectal cancer (T1 and T2) was stained for several immunomarkers of the innate and the adaptive immune response. Patients’ survival and nodal status were analyzed and correlated with infiltration of the different immune cells. Results. Of all tested markers, only CD8 () and TIA-1 () were significantly more frequently detectable in early rectal cancer biopsies of node negative as compared to node positive patients. Although these two immunomarkers did not display prognostic effect “per se,” CD8+ and, marginally, TIA-1 T cell infiltration could predict nodal involvement in univariate logistic regression analysis (OR 0.994; 95% CI 0.992–0.996; and OR 0.988; 95% CI 0.984–0.994; , resp.). An algorithm significantly predicting the nodal status in early rectal cancer based on CD8 together with vascular invasion and tumor border configuration could be calculated (). Conclusion. Our data indicate that in early rectal cancers absence of CD8+ T-cell infiltration helps in predicting patients’ nodal involvement. Silvio Däster, Serenella Eppenberger-Castori, Christian Hirt, Inti Zlobec, Tarik Delko, Christian A. Nebiker, Savas D. Soysal, Francesca Amicarella, Giandomenica Iezzi, Giuseppe Sconocchia, Michael Heberer, Alessandro Lugli, Giulio C. Spagnoli, Christoph Kettelhack, Luigi Terracciano, Daniel Oertli, Urs von Holzen, Luigi Tornillo, and Raoul A. Droeser Copyright © 2014 Silvio Däster et al. All rights reserved. Fluvastatin Upregulates the α1C Subunit of CaV1.2 Channel Expression in Vascular Smooth Muscle Cells via RhoA and ERK/p38 MAPK Pathways Tue, 30 Dec 2014 00:10:17 +0000 http://www.hindawi.com/journals/dm/2014/237067/ Abnormal phenotypic switch of vascular smooth muscle cell (VSMC) is a hallmark of vascular disorders such as atherosclerosis and restenosis. And this process has been related to remodeling of L-type calcium channel (LTCC). We attempted to investigate whether fluvastatin has any effect on VSMC proliferation and LTCC subunit expression as well as the potential mechanisms involved. The VSMCs proliferation was assayed by osteopontin immunofluorescent staining and [3H]-thymidine incorporation. The cell cycle was detected by flow cytometric analysis. The activity of RhoA was determined with pull-down assay. MAPK activity and expression were assessed by western blotting. We demonstrated fluvastatin prevented the VSMCs dedifferentiating into a proliferative phenotype and induced cell cycle arrest in the G0/G1 phase in response to PDGF-BB stimulation. Fluvastatin dose-dependently reversed the downregulation of expression induced by PDGF-BB. Inhibition of ROCK, ERK, or p38 MAPK activation largely enhanced the upregulation effect of fluvastatin . However, blockade of JNK pathway had no effect on expression. We concluded was a VSMC contractile phenotype marker gene. Fluvastatin upregulated expression, at least in part, by inhibiting ROCK, ERK1/2, and p38 MAPK activation. Fluvastatin may be a potential candidate for preventing or treating vascular diseases. Qiu-Fang Ouyang, Ying Han, Zhi-Hong Lin, Hong Xie, Chang-Sheng Xu, and Liang-Di Xie Copyright © 2014 Qiu-Fang Ouyang et al. All rights reserved. Tissue Damage Markers after a Spinal Manipulation in Healthy Subjects: A Preliminary Report of a Randomized Controlled Trial Thu, 25 Dec 2014 13:43:26 +0000 http://www.hindawi.com/journals/dm/2014/815379/ Spinal manipulation (SM) is a manual therapy technique frequently applied to treat musculoskeletal disorders because of its analgesic effects. It is defined by a manual procedure involving a directed impulse to move a joint past its physiologic range of movement (ROM). In this sense, to exceed the physiologic ROM of a joint could trigger tissue damage, which might represent an adverse effect associated with spinal manipulation. The present work tries to explore the presence of tissue damage associated with SM through the damage markers analysis. Thirty healthy subjects recruited at the University of Jaén were submitted to a placebo SM (control group; ), a single lower cervical manipulation (cervical group; ), and a thoracic manipulation . Before the intervention, blood samples were extracted and centrifuged to obtain plasma and serum. The procedure was repeated right after the intervention and two hours after the intervention. Tissue damage markers creatine phosphokinase (CPK), lactate dehydrogenase (LDH), C-reactive protein (CRP), troponin-I, myoglobin, neuron-specific enolase (NSE), and aldolase were determined in samples. Statistical analysis was performed through a mixed-model ANOVA. Neither cervical manipulation nor thoracic manipulation did produce significant changes in the CPK, LDH, CRP, troponin-I, myoglobin, NSE, or aldolase blood levels. Our data suggest that the mechanical strain produced by SM seems to be innocuous to the joints and surrounding tissues in healthy subjects. A. Achalandabaso, G. Plaza-Manzano, R. Lomas-Vega, A. Martínez-Amat, M. V. Camacho, M. Gassó, F. Hita-Contreras, and F. Molina Copyright © 2014 A. Achalandabaso et al. All rights reserved. Stepwise Application of Urine Markers to Detect Tumor Recurrence in Patients Undergoing Surveillance for Non-Muscle-Invasive Bladder Cancer Mon, 22 Dec 2014 08:51:30 +0000 http://www.hindawi.com/journals/dm/2014/973406/ Background. The optimal use of urine markers in the surveillance of non-muscle-invasive bladder cancer (NMIBC) remains unclear. Aim of the present study was to investigate the combined and stepwise use of the four most broadly available urine markers to detect tumor recurrence in patients undergoing surveillance of NMIBC. Patients and Methods. 483 patients with history of NMIBC were included. Cytology, UroVysion, fluorescence in situ hybridization (FISH), immunocytology (uCyt+), and NMP22 ELISA were performed before surveillance cystoscopy. Characteristics of single tests and combinations were assessed by contingency analysis. Results. 128 (26.5%) patients had evidence of tumor recurrence. Sensitivities and negative predictive values (NPVs) of the single tests ranged between 66.4–74.3 and 82.3–88.2%. Two-marker combinations showed sensitivities and NPVs of 80.5–89.8 and 89.5–91.2%. A stepwise application of the two-test combinations with highest accuracy (cytology and FISH; cytology and uCyt+; uCyt+ and FISH) showed NPVs for high-risk recurrences (G3/Cis/pT1) of 98.8, 98.8, and 99.1%, respectively. Conclusions. Combinations of cytology, FISH, immunocytology, and NMP22 show remarkable detection rates for recurrent NMIBC. Stepwise two-test combinations of cytology, FISH, and immunocytology have a low probability of missing a high-risk tumor. The high sensitivities may justify the use of these combinations in prospective studies assessing the use of urine markers to individualize intervals between cystoscopies during follow-up. Tilman Todenhöfer, Jörg Hennenlotter, Michael Esser, Sarah Mohrhardt, Stefan Aufderklamm, Johannes Böttge, Steffen Rausch, Johannes Mischinger, Simone Bier, Georgios Gakis, Ursula Kuehs, Arnulf Stenzl, and Christian Schwentner Copyright © 2014 Tilman Todenhöfer et al. All rights reserved. Association of Polymorphisms of Genes Involved in Lipid Metabolism with Blood Pressure and Lipid Values in Mexican Hypertensive Individuals Sun, 21 Dec 2014 08:51:28 +0000 http://www.hindawi.com/journals/dm/2014/150358/ Hypertension and dyslipidemia exhibit an important clinical relationship because an increase in blood lipids yields an increase in blood pressure (BP). We analyzed the associations of seven polymorphisms of genes involved in lipid metabolism (APOA5 rs3135506, APOB rs1042031, FABP2 rs1799883, LDLR rs5925, LIPC rs1800588, LPL rs328, and MTTP rs1800591) with blood pressure and lipid values in Mexican hypertensive (HT) patients. A total of 160 HT patients and 160 normotensive individuals were included. Genotyping was performed through PCR-RFLP, PCR-AIRS, and sequencing. The results showed significant associations in the HT group and HT subgroups classified as normolipemic and hyperlipemic. The alleles FABP2 p.55T, LIPC −514T, and MTTP −493T were associated with elevated systolic BP. Five alleles were associated with lipids. LPL p.474X and FABP2 p.55T were associated with decreased total cholesterol and LDL-C, respectively; APOA5 p.19W with increased HDL-C; APOA5 p.19W and FABP2 p.55T with increased triglycerides; and APOB p.4181K and LDLR c.1959T with decreased triglycerides. The APOB p.E4181K polymorphism increases the risk for HT (OR = 1.85, 95% CI: 1.17–2.93; ) under the dominant model. These findings indicate that polymorphisms of lipid metabolism genes modify systolic BP and lipid levels and may be important in the development of essential hypertension and dyslipidemia in Mexican HT patients. Blanca Estela Ríos-González, Bertha Ibarra-Cortés, Guadalupe Ramírez-López, José Sánchez-Corona, and María Teresa Magaña-Torres Copyright © 2014 Blanca Estela Ríos-González et al. All rights reserved. Proteomic Analysis of Serum and Urine of HIV-Monoinfected and HIV/HCV-Coinfected Patients Undergoing Long Term Treatment with Nevirapine Wed, 17 Dec 2014 00:10:34 +0000 http://www.hindawi.com/journals/dm/2014/315824/ Nevirapine (NVP) is an effective nonnucleoside reverse transcriptase inhibitor (NNRTI) of particular interest as it is often used in resource limited countries. However, one of the main concerns with the use of NVP is hepatotoxicity and elevation of liver enzymes as a consequence of highly active antiretroviral therapy (HAART) containing NVP is more often reported in HIV patients coinfected with hepatitis C virus than in HIV-monoinfected patients. To discover possible markers of NVP induced hepatotoxicity, serum and urine samples from twenty-five HIV or HIV/HCV patients, all of whom had received NVP continuously for at least four months, and healthy controls were subjected to in-solution or in-gel proteomic analysis. A total of 83 differentially regulated proteins consisted of 34 proteins identified in serum by in-solution analysis, 2 proteins identified from serum in a 2D gel electrophoresis analysis, and 47 proteins identified in urine in an in-solution analysis. Three proteins, namely, haptoglobin, Rho-related BTB domain containing protein 3, and death-associated protein kinase 3, were selected for further validation by Western blot analysis and results showed that haptoglobin has potential for further development as an additional marker of NVP induced hepatotoxicity. Jeerang Wongtrakul, Thananya Thongtan, Sittiruk Roytrakul, Benjawan Kumrapich, Kanokwan Janphen, Jutarat Praparattanapan, Khuanchai Supparatpinyo, and Duncan R. Smith Copyright © 2014 Jeerang Wongtrakul et al. All rights reserved. Red Cell Distribution Width Is Associated with Presence, Stage, and Grade in Patients with Renal Cell Carcinoma Tue, 16 Dec 2014 07:16:20 +0000 http://www.hindawi.com/journals/dm/2014/860419/ It has been reported that red blood cell width (RDW) is a marker associated with the presence and adverse outcomes of various diseases. However, no data are available on the correlation of RDW with presence, stage, and grade in patients with renal cell carcinoma (RCC) yet. By retrospectively analyzing clinical and laboratory data at baseline of histologically confirmed RCC cases and controls, the present study demonstrated that the RDW values were significantly higher in patients with RCC than those in controls, and the baseline RDW value was independently associated with the presence of RCC. Besides, the data revealed a positive association between RCC stage and grade and the level of RDW. These findings may have important clinical implications due to future application using a RDW value in predicting RCC. Fang-Ming Wang, Gongjun Xu, Yan Zhang, and Lu-Lin Ma Copyright © 2014 Fang-Ming Wang et al. All rights reserved. Mig-6 Gene Knockout Induces Neointimal Hyperplasia in the Vascular Smooth Muscle Cell Wed, 10 Dec 2014 10:26:46 +0000 http://www.hindawi.com/journals/dm/2014/549054/ Although advances in vascular interventions can reduce the mortality associated with cardiovascular disease, neointimal hyperplasia remains a clinically significant obstacle limiting the success of current interventions. Identification of signaling pathways involved in migration and proliferation of vascular smooth muscle cells (SMCs) is an important approach for the development of modalities to combat this disease. Herein we investigate the role of an immediate early response gene, mitogen-inducible gene-6 (Mig-6), in the development of neointimal hyperplasia using vascular smooth muscle specific Mig-6 knockout mice. We induced endoluminal injury to one side of femoral artery by balloon dilatation in both Mig-6 knockout and control mice. Four weeks following injury, the artery of Mig-6 knockout mice demonstrated a 5.3-fold increase in the neointima/media ratio compared with control mice . In addition, Mig-6 knockout vascular SMCs displayed an increase in both cell migration and proliferation compared with wild-type SMCs. Taken together, our data suggest that Mig-6 plays a critical role in the development of atherosclerosis. This finding provides new insight into the development of more effective ways to treat and prevent neointimal hyperplasia, particularly in-stent restenosis after percutaneous vascular intervention. Ju Hee Lee, Sorim Choung, Ji Min Kim, Jung Uee Lee, Koon Soon Kim, Hyun Jin Kim, Jae-Wook Jeong, and Bon Jeong Ku Copyright © 2014 Ju Hee Lee et al. All rights reserved. Serum Clusterin as a Tumor Marker and Prognostic Factor for Patients with Esophageal Cancer Wed, 10 Dec 2014 06:55:00 +0000 http://www.hindawi.com/journals/dm/2014/168960/ Background. Recent studies have revealed that clusterin is implicated in many physiological and pathological processes, including tumorigenesis. However, the relationship between serum clusterin expression and esophageal squamous cell carcinoma (ESCC) is unclear. Methods. The serum clusterin concentrations of 87 ESCC patients and 136 healthy individuals were examined. An independent-samples Mann-Whitney test was used to compare serum clusterin concentrations of ESCC patients to those of healthy controls. Univariate analysis was conducted using the log-rank test and multivariate analyses were performed using the Cox proportional hazards model. Results. In healthy controls, the mean clusterin concentration was  μg/mL, while in the ESCC patients, the mean clusterin concentration was higher at  μg/mL (). The 1-, 2-, and 4-year survival rates for the 87 ESCC patients were 89.70%, 80.00%, and 54.50%. Serum clusterin had an optimal diagnostic cut-off point (serum clusterin concentration = 335.5 μg/mL) for esophageal squamous cell carcinoma with sensitivity of 71.26% and specificity of 77.94%. And higher serum clusterin concentration (>500 μg/mL) indicated better prognosis (). Conclusions. Clusterin may play a key role during tumorigenesis and tumor progression of ESCC and it could be applied in clinical work as a tumor marker and prognostic factor. Wei Guo, Xiao Ma, Christine Xue, Jianfeng Luo, Xiaoli Zhu, Jiaqing Xiang, Bo Lu, and Hecheng Li Copyright © 2014 Wei Guo et al. All rights reserved. Methylation of DLEC1 Promoter Is a Predictor for Recurrence in Chinese Patients with Gastric Cancer Tue, 09 Dec 2014 11:57:32 +0000 http://www.hindawi.com/journals/dm/2014/804023/ Purpose. To investigate promoter methylation in the deleted in lung and esophageal cancer 1 (DLEC1) gene in Chinese patients with gastric cancer. Methods. A total of 227 patients with gastric cancer were enrolled. The methylations of the promoter regions of DLEC1 and ACTB were determined using quantitative methylation-specific PCR. The DLEC1 methylation was compared to the clinicopathological variables of gastric cancer. Results. DLEC1 methylation was not associated with the clinicopathological variables of gastric cancer. Patients with DLEC1-hypermethylated gastric cancer had significantly higher recurrence rate than those with DLEC1-hypomethylated gastric cancer (; ). Conclusions. Methylation of DELC1 promoter may be a valuable predictor for recurrence in Chinese patients with gastric cancer. Xiaobing Ye, Gang Feng, Nanlin Jiao, Chun Pu, Guohai Zhao, and Guoping Sun Copyright © 2014 Xiaobing Ye et al. All rights reserved. Peroxisome Proliferator-Activated Receptors Family Is Involved in the Response to Treatment and Mild Clinical Course in Patients with Ulcerative Colitis Mon, 08 Dec 2014 07:16:13 +0000 http://www.hindawi.com/journals/dm/2014/932530/ Background. PPARs play an important role in the regulation of intestinal inflammation. Methods. We included a total of 46 UC patients and 31 controls. The gene expression of PPARs was measured by RT-PCR and protein expression by immunohistochemistry. Results. PPARα gene expression was significantly decreased in patients with active UC compared with remission UC group and controls . We found that low gene expression of PPARα in mucosa confers a higher risk of UC activity (, OR = 22.6). We observed an increase of PPARα expression in patients with UC who were treated with 5-aminosalicylates compared with those who received any other combined therapy (, OR = 0.08). PPARγ gene expression was decreased in the active UC group compared with UC in remission and control group . An increased expression of PPARγ gene was associated with mild clinical course of the disease (, OR = 0.05). No gene expression of PPARβ/δ was found in the colonic mucosa from UC patients and controls. Conclusion. Our results suggest that patients with high gene expression of PPARs have a better response to medical treatment and a mild clinical course of the disease. J. K. Yamamoto-Furusho, M. Jacintez-Cazares, J. Furuzawa-Carballeda, and G. Fonseca-Camarillo Copyright © 2014 J. K. Yamamoto-Furusho et al. All rights reserved. RNA-Seq Data Mining: Downregulation of NeuroD6 Serves as a Possible Biomarker for Alzheimer’s Disease Brains Mon, 08 Dec 2014 00:10:22 +0000 http://www.hindawi.com/journals/dm/2014/123165/ Alzheimer’s disease (AD) is the most common cause of dementia worldwide with no curative therapies currently available. Previously, global transcriptome analysis of AD brains by microarray failed to identify the set of consistently deregulated genes for biomarker development of AD. Therefore, the molecular pathogenesis of AD remains largely unknown. Whole RNA sequencing (RNA-Seq) is an innovative technology for the comprehensive transcriptome profiling on a genome-wide scale that overcomes several drawbacks of the microarray-based approach. To identify biomarker genes for AD, we analyzed a RNA-Seq dataset composed of the comprehensive transcriptome of autopsized AD brains derived from two independent cohorts. We identified the core set of 522 genes deregulated in AD brains shared between both, compared with normal control subjects. They included downregulation of neuronal differentiation 6 (NeuroD6), a basic helix-loop-helix (bHLH) transcription factor involved in neuronal development, differentiation, and survival in AD brains of both cohorts. We verified the results of RNA-Seq by analyzing three microarray datasets of AD brains different in brain regions, ethnicities, and microarray platforms. Thus, both RNA-Seq and microarray data analysis indicated consistent downregulation of NeuroD6 in AD brains. These results suggested that downregulation of NeuroD6 serves as a possible biomarker for AD brains. Jun-ichi Satoh, Yoji Yamamoto, Naohiro Asahina, Shouta Kitano, and Yoshihiro Kino Copyright © 2014 Jun-ichi Satoh et al. All rights reserved. CLCA2 as a Novel Immunohistochemical Marker for Differential Diagnosis of Squamous Cell Carcinoma from Adenocarcinoma of the Lung Sun, 07 Dec 2014 07:28:34 +0000 http://www.hindawi.com/journals/dm/2014/619273/ Recent progress in targeted therapy for lung cancer has revealed that accurate differential diagnosis between squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the lung is essential. To identify a novel immunohistochemical marker useful for differential diagnosis between the two subtypes of lung cancer, we first selected 24 SCC-specific genes and 6 ADC-specific genes using data (case number, 980) from the Cancer Genome Atlas (TCGA) database. Among the genes, we chose the CLCA2 gene, which is involved in chloride conductance and whose protein expression in lung cancer is yet to be characterized, and evaluated its protein expression status in 396 cases of primary lung cancer at Hamamatsu University Hospital. Immunohistochemical analysis revealed a significantly higher CLCA2 expression level in the SCCs than in the ADCs and also a significantly higher frequency of CLCA2 protein expression in the SCCs (104/161, 64.6%) as compared with that in the ADCs (2/235, 0.9%) ; sensitivity 64.6%, specificity 99.1%). The CLCA2 protein expression status was associated with the histological tumor grade in the SCCs. These results suggest that CLCA2 might be a novel excellent immunohistochemical marker for differentiating between primary SCC and primary ADC of the lung. Kazuya Shinmura, Hisaki Igarashi, Hisami Kato, Yuichi Kawanishi, Yusuke Inoue, Satoki Nakamura, Hiroshi Ogawa, Takashi Yamashita, Akikazu Kawase, Kazuhito Funai, and Haruhiko Sugimura Copyright © 2014 Kazuya Shinmura et al. All rights reserved. Transporter TAP1-637G and Immunoproteasome PSMB9-60H Variants Influence the Risk of Developing Vitiligo in the Saudi Population Sun, 07 Dec 2014 00:10:47 +0000 http://www.hindawi.com/journals/dm/2014/260732/ We evaluated whether TAP1-rs1135216 (p.637D>G) and PSMB9-rs17587 (p.60R>H) were significantly associated with the risk and severity of vitiligo among Saudi patients. One hundred seventy-two subjects were genotyped for the TAP1-rs1135216 and PSMB9-rs17587 variants using endonuclease digestions of amplified genomic DNA. The TAP1-rs1135216 and PSMB9-rs17587 mutant alleles were strongly associated with vitiligo, with odds ratios showing five fold and two fold risks ( and , resp.). In TAP1-rs1135216, the 637G mutant allele was more frequent in cases (74%) than in healthy controls. In cases, the 60H mutant allele PSMB9-rs17587 was less frequent (42%) than the wild-type 60R allele (58%). Vitiligo vulgaris was the most common type of disease, associated with the DG (55%) and GG (46%) genotypes for rs1135216 and with the RH genotype (59%) for rs17587. The heterozygous 637DG and 60RH genotypes were each linked with active phenotypes in 64% of cases. In conclusion, the TAP1-rs1135216 and PSMB9-rs17587 variants are significantly associated with vitiligo, and even one copy of these mutant alleles can influence the risk among Saudis. Vitiligo vulgaris is associated with genotypes containing the mutant G and H alleles. Nasser Attia Elhawary, Neda Bogari, Essam Hussien Jiffri, Mona Rashad, Abdulhamid Fatani, and Mohammed Tayeb Copyright © 2014 Nasser Attia Elhawary et al. All rights reserved. Genetic Polymorphisms Involved in Folate Metabolism and Maternal Risk for Down Syndrome: A Meta-Analysis Thu, 04 Dec 2014 00:10:13 +0000 http://www.hindawi.com/journals/dm/2014/517504/ Inconclusive results of the association between genetic polymorphisms involved in folate metabolism and maternal risk for Down syndrome (DS) have been reported. Therefore, this meta-analysis was conducted. We searched electronic databases through May, 2014, for eligible studies. Pooled odds ratios with 95% confidence intervals were used to assess the strength of the association, which was estimated by fixed or random effects models. Heterogeneity among studies was evaluated using Q-test and I2 statistic. Subgroup and sensitivity analyses were also conducted. Publication bias was estimated using Begg’s and Egger’s tests. A total of 17 case-controls studies were included. There was evidence for an association between the MTRR c.66A>G (rs1801394) polymorphism and maternal risk for DS. In the subgroup analysis, increased maternal risk for DS was found in Caucasians. Additionally, the polymorphic heterozygote MTHFD1 1958GA genotype was associated significantly with maternal risk for DS, when we limit the analysis by studies conformed to Hardy-Weinberg equilibrium. Finally, considering MTR c.2756A>G (rs1805087), TC2 c.776C>G (rs1801198), and CBS c.844ins68, no significant associations have been found, neither in the overall analyses nor in the stratified analyses by ethnicity. In conclusion, our meta-analysis suggested that the MTRR c.66A>G (rs1801394) polymorphism and MTHFD1 c.1958G>A (rs2236225) were associated with increased maternal risk for DS. Daniella Balduino Victorino, Moacir Fernandes de Godoy, Eny Maria Goloni-Bertollo, and Érika Cristina Pavarino Copyright © 2014 Daniella Balduino Victorino et al. All rights reserved. ZEB1 Expression in Endometrial Biopsy Predicts Lymph Node Metastases in Patient with Endometrial Cancer Wed, 03 Dec 2014 00:10:18 +0000 http://www.hindawi.com/journals/dm/2014/680361/ Purpose. The purpose of this study was to analyze the expression of zinc-finger E-box-binding homeobox 1 (ZEB1) in endometrial biopsy and its correlation with preoperative characteristics, including lymph node metastases in patient with endometrial cancer. Methods. Using quantitative RT-PCR, ZEB1 expressions in endometrial biopsy from 452 patients were measured. The relationship between ZEB1 expression and preoperative characteristics was analyzed. Results. ZEB1 expressions were significantly associated with subtype, grade, myometrial invasion, and lymph node metastases. Lymph node metastases could be identified with a sensitivity of 57.8% at specificity of 74.1% by ZEB1 expression in endometrial biopsy. Based on combination of preoperative characteristics and ZEB1 expression, lymph node metastases could be identified with a sensitivity of 62.1% at specificity of 96.2% prior to hysterectomy. Conclusion. ZEB1 expression in endometrial biopsy could help physicians to better predict the lymph node metastasis in patients with endometrial cancer prior to hysterectomy. Gang Feng, Xiangming Wang, Xiaozhi Cao, Lijuan Shen, and Jiansheng Zhu Copyright © 2014 Gang Feng et al. All rights reserved. Haptoglobin Duplicon, Hemoglobin, and Vitamin C: Analyses in the British Women’s Heart and Health Study and Caerphilly Prospective Study Sun, 30 Nov 2014 00:10:24 +0000 http://www.hindawi.com/journals/dm/2014/529456/ Background. Haptoglobin acts as an antioxidant by limiting peroxidative tissue damage by free hemoglobin. The haptoglobin gene allele Hp2 comprises a 1.7 kb partial duplication. Relative to allele Hp1, Hp2 carriers form protein multimers, suboptimal for hemoglobin scavenging. Objective. To examine the association of haptoglobin genotype with a range of phenotypes, with emphasis on vitamin C and hemoglobin levels. Methods. We applied a quantitative PCR assay for the duplication junction to two population cohorts including 2747 British women and 1198 British men. We examined the association of haptoglobin duplicon copy number with hemoglobin and vitamin C and used the copy number to complete a phenome scan. Results. Hemoglobin concentrations were greater in those with Hp2,2 genotype, in women only (Hp1,1 13.45 g/dL, Hp1,2 13.49 g/dL, Hp2,2 13.61 g/dL; ), though statistically there was no evidence of a difference between the sexes ( value = 1.2, ). Haptoglobin genotype was not associated with vitamin C or any other phenotype in either cohort. Conclusions. Our results do not support association of haptoglobin genotype with vitamin C or with other phenotypes measured in two population cohorts. The apparent association between haptoglobin genotype and hemoglobin in the women’s cohort merits further investigation. Philip A. I. Guthrie, Mohammad R. Abdollahi, Tom Gaunt, Debbie A. Lawlor, Yoav Ben-Shlomo, John Gallacher, George Davey Smith, Ian N. M. Day, and Santiago Rodriguez Copyright © 2014 Philip A. I. Guthrie et al. All rights reserved. High SHIP2 Expression Indicates Poor Survival in Colorectal Cancer Mon, 24 Nov 2014 10:11:22 +0000 http://www.hindawi.com/journals/dm/2014/218968/ SH2-containing inositol 5′-phosphatase 2 (SHIP2), which generally regulates insulin signaling, cytoskeleton remodeling, and receptor endocytosis, has been suggested to play a significant role in tumor development and progression. However, the associations between SHIP2 expression and the clinical features to evaluate its clinicopathologic significance in colorectal cancer (CRC) have not been determined yet. In the present study, one-step quantitative real-time polymerase chain reaction (qPCR) test and immunohistochemistry (IHC) analysis with CRC tissue microarrays (TMA) were employed to evaluate the mRNA and protein expression of SHIP2 in CRC. The results showed that SHIP2 expression in the mRNA and protein levels was significantly higher in CRC tissues than that in corresponding noncancerous tissues (both ). The expression of SHIP2 protein in CRC was related to lymph node metastasis , distant metastasis , and overall survival . Kaplan-Meier method and Cox multifactor analysis suggested that high SHIP2 protein level and positive distant metastasis were critically associated with the unfavorable survival of CRC patients. The findings suggested that SHIP2 may be identified as a useful prognostic marker in CRC and targeting CRC may provide novel strategy for CRC treatment. Ju Yang, Maoying Fu, Yaoguang Ding, Yajing Weng, Weifei Fan, Xiaolin Pu, Zhijun Ge, Feng Zhan, Huihui Ni, Wei Zhang, Feng Jin, Ning Xu, Jiang Li, Liang Qiu, Jun Wang, and Xuefeng Gu Copyright © 2014 Ju Yang et al. All rights reserved. The Use of Humoral Responses as a Marker of CMV Burden in HIV Patients on ART Requires Consideration of T-Cell Recovery and Persistent B-Cell Activation Sun, 23 Nov 2014 11:38:11 +0000 http://www.hindawi.com/journals/dm/2014/947432/ Objectives. Elevated humoral responses to cytomegalovirus (CMV) associate with increased risk of cardiovascular disease (CVD) in HIV patients on antiretroviral therapy (ART). To better understand the persistence of CMV humoral responses in relation to CVD, we determined trends in CMV antibody levels over the first 10 years on ART. Design. We describe longitudinal analyses of plasma from 13 HIV patients commencing ART with <210 CD4 T-cells/µL and 27 controls. Antibodies reactive with CMV (fibroblast lysate, gB and IE-1 antigens), EBV-VCA, and HIVgp41 were quantitated. B-cell activation was assessed via total IgG and sBAFF. Inflammation was assessed via sTNF-RI and sCD14. Results. Amongst CMV seropositive HIV patients, levels of antibody reactive with CMV and EBV-VCA peaked after 1 year on ART. Levels of total IgG, sCD14, and sTNF-RI declined to approximate those in controls after 10 years, but sBAFF , EBV-VCA , and CMV antibodies remained elevated. A strong correlation between sBAFF and CMVgB antibody was seen at 10 years and verified in a second cohort. Conclusions. CMV antibody titres peak on ART and remain high. A correlation between CMV antibody and sBAFF suggests a role for HIV-induced B-cell pathology that may affect its use as a marker of CMV burden. Samantha J. Brunt, Silvia Lee, Lloyd D’Orsogna, Christine Bundell, Sally Burrows, and Patricia Price Copyright © 2014 Samantha J. Brunt et al. All rights reserved. Pleural Fluid Mesothelin as an Adjunct to the Diagnosis of Pleural Malignant Mesothelioma Sun, 23 Nov 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/413946/ Rationale. The diagnosis of pleural malignant mesothelioma (MM) by effusion cytology may be difficult and is currently controversial. Effusion mesothelin levels are increased in patients with MM but the clinical role of this test is uncertain. Objectives. To determine the clinical value of measuring mesothelin levels in pleural effusion supernatant to aid diagnosis of MM. Methods and Measurements. Pleural effusion samples were collected prospectively from 1331 consecutive patients. Mesothelin levels were determined by commercial ELISA in effusions and their relationship to concurrent pathology reporting and final clinical diagnosis was determined. Results. 2156 pleural effusion samples from 1331 individuals were analysed. The final clinical diagnosis was 183 MM, 436 non-MM malignancy, and 712 nonmalignant effusions. Effusion mesothelin had a sensitivity of 67% for MM at 95% specificity. Mesothelin was elevated in over 47% of MM cases in effusions obtained before definitive diagnosis of MM was established. In the setting of inconclusive effusion cytology, effusion mesothelin had a positive predictive value of 79% for MM and 94% for malignancy. Conclusions. A mesothelin-positive pleural effusion, irrespective of the identification of malignant cells, indicates the likely presence of malignancy and adds weight to the clinical rationale for further investigation to establish a malignant diagnosis. Jenette Creaney, Amanda Segal, Nola Olsen, Ian M. Dick, A. W(Bill) Musk, Steven J. Skates, and Bruce W. Robinson Copyright © 2014 Jenette Creaney et al. All rights reserved.