bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased IP-10 and Elevated TGFβ1 Levels are Associated with Viral Clearance Following Therapy in Patients with Hepatitis C Virus
Authors: Lee Silvia , Varano Julius , Flexman James P. , Cheng Wendy , Watson Mark W. , Rossi Enrico , Adams Leon A. , Bulsara Max , Price Patricia
Published: June 2013

The role of pro-fibrogenic cytokines in the outcome of infections with hepatitis C virus (HCV) and the response to treatment with pegylated interferon-alpha (pegIFNα) and ribavirin remains unclear. To address this issue, we assessed hepatic fibrosis and plasma markers pertinent to T-cell mediated fibrogenesis and inflammation at the start of treatment. Levels of soluble (s)CD30, interleukin-13 receptor alpha 2 (IL-13Rα2), total and active transforming growth factor-beta 1 (TGFβ1), interleukin-18 (IL-18) and interferon-gamma inducible protein-10 (IP-10, CXCL10) were correlated with the severity of fibrosis and with treatment outcome using multiple logistic regression modelling. The Hepascore algorithm was confirmed as a marker of fibrosis, but was a poor predictor of treatment outcome. Inclusion of all immunological markers improved prediction based on Hepascore alone (p= 0.045), but optimal prediction was achieved with an algorithm (“TIPscore”) based on TGFβ1 (total), IP-10, age, sex and HCV genotype (p= 0.003 relative to Hepascore). Whilst this was only marginally more effective than predictions based on HCV genotype age and sex (p= 0.07), it associates high TGFβ1 and low IP-10 levels with a failure of therapy.
Genetic Variation of Myeloperoxidase Gene Contributes to Aggressive Periodontitis: A Preliminary Association Study in Turkish Population
Authors: Erciyas Kamile , Pehlivan Sacide , Sever Tugce , Orbak Recep
Published: June 2013

Myeloperoxidase (MPO) is a lysosomal enzyme found in the azurophilic granules of polymorphonuclear leukocytes. It is involved in the defense against periodontal bacteria, and is also able to mediate inflammatory tissue destruction in aggressive and chronic periodontitis. The aim of this study was to explore the association between MPO-463G/A gene polymorphism and aggressive periodontitis (AgP) and chronic periodontitis (CP). The study included 147 subjects. Probing depth (PD), clinical attachment loss (CAL), plaque index (PI), and gingival index (GI) were recorded as the clinical parameters. Genomic DNA was obtained from the peripheral blood of 32 subjects with AgP, 25 with CP, and 90 reference controls. We genotyped the MPO-463G/A polymorphism using the PCR-RFLP method. All data were analyzed using SPSS version 13.0 for windows. There were no significant differences between the CP patients and controls regarding MPO-463A/G gene polymorphism either in terms of allele frequency or genotype frequency of MPO-463A/G. However, either in terms of allele frequency or genotype frequency of MPO-463A/G, there were significant differences between the AgP patients and the controls. In conclusion, our data suggest that MPO-463G/A may be associated with increased risk of aggressive periodontitis in Turkish patients.
The Wiskott-Aldrich Syndrome: The Actin Cytoskeleton and Immune Cell Function
Authors: Blundell Michael P. , Worth Austen , Bouma Gerben , Thrasher Adrian J.
Published: June 2013

Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive primary immunodeficiency characterised by immune dysregulation, microthrombocytopaenia, eczema and lymphoid malignancies. Mutations in the WAS gene can lead to distinct syndrome variations which largely, although not exclusively, depend upon the mutation. Premature termination and deletions abrogate Wiskott-Aldrich syndrome protein (WASp) expression and lead to severe disease (WAS). Missense mutations usually result in reduced protein expression and the phenotypically milder X-linked thrombocytopenia (XLT) or attenuated WAS [1-3]. More recently however novel activating mutations have been described that give rise to X-linked neutropenia (XLN), a third syndrome defined by neutropenia with variable myelodysplasia [4-6]. WASP is key in transducing signals from the cell surface to the actin cytoskeleton, and a lack of WASp results in cytoskeletal defects that compromise multiple aspects of normal cellular activity including proliferation, phagocytosis, immune synapse formation, adhesion and directed migration.
GSTT1as a Prognosticator for Recurrence and Progression in Patients with Non-Muscle-Invasive Bladder Cancer
Authors: Ha Yun-Sok , Yan Chunri , Lym Min Su , Jeong Pildu , Kim Won Tae , Kim Yong-June , Yun Seok-Joong , Lee Sang-Cheol , Moon Sung-Kwon , Choi Yung Hyun , Kim Wun-Jae
Published: June 2013

Although polymorphisms in glutathione S-transferase (GST) have been associated with the risk of bladder cancer (BC), few reports provide information about the development of BC. The aim of the present study was to investigate the effect of homozygous glutathione S-transferase-μ (GSTM1) and glutathione S-transferase-&phis; (GSTT1) deletions as prognostic markers in non-muscle-invasive bladder cancer (NMIBC). A total of 241 patients with primary NMIBC were enrolled in this study. GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR) using blood genomic DNA. The results were compared with clinicopathological parameters. The prognostic significance of the GSTs was evaluated by Kaplan-Meier and multivariate Cox regression model. A statistically significant association between genotype and histopathological parameter was not observed. The patients with the GSTT1-positive genotype had significantly reduced recurrence- and progression-free survival than those with the GSTT1-null genotype (log-rank test,p< 0.05, respectively). Recurrenceand progressionfree survival were not related to the GSTM1 genotypes. In multivariate regression analysis, the GSTT1positive genotype was the independent predictor for recurrence [hazard ratio (HR), 1.631;p= 0.043] and progression (HR, 3.418;p= 0.006). These results suggested that the GSTT1 genotype could be a useful prognostic marker for recurrence and progression in NMIBC.
Blood Serum Alpha Fetoprotein Enhancer Binding Protein, a Tumor Suppressor, Decreases in Chronic HBV Hepatitis Patients as Hepatocellular Cancer Appears
Authors: Riggins James N. , Corey William , Fonteh Alfred N. , Harrington Michael G.
Published: June 2013

Chronic hepatitis increases the risk of hepatocellular carcinoma (HCC). To test whether circulating proteins reflect hepatic carcinogenesis, sera from patients and controls were albumin depleted, enriched for glycoproteins, digested with trypsin, and subjected to reverse phase chromatography and tandem mass spectrometry. Alpha-fetoprotein enhancer binding protein (AFPebp), a tumor suppressor, was repeatedly identified in sera from chronic HBV hepatitis patients. We independently identified and quantified AFPebp with a deuterated, phenylisocyanate-labeled synthetic peptide standard. Elevated AFPebp levels in sera from chronic HBV hepatitis patients decreased as cancer developed. These data suggest that rising AFPebp levels in chronic HBV hepatitis may be protective, while falling levels may contribute to HCC development.
Genetic and Epidemiological Risk Factors in the Development of Bronchopulmonary Dysplasia
Authors: Mailaparambil Beena , Krueger Marcus , Heizmann Ulrike , Schlegel Katharina , Heinze Jessica , Heinzmann Andrea
Published: June 2013

Bronchopulmonary dysplasia (BPD) is the chronic lung disease of preterm infants and still represents a major burden of prematurity. Several clinical risk factors for the onset of the disease are already known. In addition, some candidate genes have recently been identified. We set out to determine clinical as well as genetic risk factors for the development of BPD in the German population.

155 infants born with a gestational age ࣘ 28 at the tertiary neonatal Centre, Freiburg, were recruited. Clinical data were recorded from hospital charts. 47 children developed moderate or severe BPD. For genetic analyses, 37 polymorphisms within sixteen genes were genotyped on all children.

The strongest epidemiological risk factor for BPD was birth weight, followed by low gestational age. Genetic association was detected with single polymorphisms within Tumour necrosis factor alpha, Toll like receptor 10 and vascular endothelial growth factor. The former two genes showed also association with BPD in haplotype analyses. In conclusion, association of BPD was far more convincingly found with a few clinical factors than with genetic polymorphisms. This underscores the genetic complexity of the disease. Furthermore, the identification of predisposing genetic polymorphisms might be hampered by the complex interaction between clinical and genetic factors.
Plasma Protein Oxidation and Its Correlation with Antioxidant Potential During Human Aging
Authors: Pandey Kanti Bhooshan , Mehdi Mohd Murtaza , Maurya Pawan Kumar , Rizvi Syed Ibrahim
Published: June 2013

Previous studies have indicated that the main molecular characteristic of aging is the progressive accumulation of oxidative damages in cellular macromolecules. Proteins are one of the main molecular targets of age-related oxidative stress, which have been observed during aging process in cellular systems. Reactive oxygen species (ROS) can lead to oxidation of amino acid side chains, formation of protein-protein cross-linkages, and oxidation of the peptide backbones. In the present study, we report the age-dependent oxidative alterations in biomarkers of plasma protein oxidation: protein carbonyls (PCO), advanced oxidation protein products (AOPPs) and plasma total thiol groups (T-SH) in the Indian population and also correlate these parameters with total plasma antioxidant potential. We show an age dependent decrease in T-SH levels and increase in PCO and AOPPs level. The alterations in the levels of these parameters correlated significantly with the total antioxidant capacity of the plasma. The levels of oxidized proteins in plasma provide an excellent biomarker of oxidative stress due to the relative long half-life of such oxidized proteins.
Absolute Quantitation of DNA Methylation of 28 Candidate Genes in Prostate Cancer Using Pyrosequencing
Authors: Vasiljeviš Nataڑa , Wu Keqiang , Brentnall Adam R. , Kim Dae Cheol , Thorat Mangesh A. , Kudahetti Sakunthala C. , Mao Xueying , Xue Liyan , Yu Yongwei , Shaw Greg L. , Beltran Luis , Lu Yong-Jie , Berney Daniel M. , Cuzick Jack , Lorincz Attila T.
Published: June 2013

Aberrant DNA methylation plays a pivotal role in carcinogenesis and its mapping is likely to provide biomarkers for improved diagnostic and risk assessment in prostate cancer (PCa). We quantified and compared absolute methylation levels among 28 candidate genes in 48 PCa and 29 benign prostate hyperplasia (BPH) samples using the pyrosequencing (PSQ) method to identify genes with diagnostic and prognostic potential.

RARB, HIN1, BCL2, GSTP1, CCND2, EGFR5, APC, RASSF1A, MDR1, NKX2-5, CDH13, DPYS, PTGS2, EDNRB, MAL, PDLIM4, HLAa, ESR1andTIG1were highly methylated in PCa compared to BPH (p < 0.001), whileSERPINB5, CDH1, TWIST1, DAPK1, THRB, MCAM, SLIT2, CDKN2aandSFNwere not. RARB methylation above 21% completely distinguished PCa from BPH. Separation based on methylation level ofSFN, SLIT2andSERPINB5distinguished low and high Gleason score cancers, e.g.SFNandSERPINB5together correctly classified 81% and 77% of high and low Gleason score cancers respectively. Several genes includingCDH1previously reported as methylation markers in PCa were not confirmed in our study. Increasing age was positively associated with gene methylation (p < 0.0001).

Accurate quantitative measurement of gene methylation in PCa appears promising and further validation of genes likeRARB, HIN1, BCL2, APC and GSTP1is warranted for diagnostic potential andSFN, SLIT2andSERPINB5for prognostic potential.
Gene Expression Changes in Femoral Head Necrosis of Human Bone Tissue
Authors: Balla Bernadett , Pintér Csaba , Kósa János P. , Podani János , Takács István , Nagy Zsolt , Speer Gábor , Horváth Balázs , Korányi László , Lakatos Péter
Published: June 2013

Osteonecrosis of the femoral head (ONFH) is the result of an interruption of the local circulation and the injury of vascular supply of bone. Multiple factors have been implicated in the development of the disease. However the mechanism of ischemia and necrosis in non-traumatic ONFH is not clear. The aim of our investigation was to identify genes that are differently expressed in ONFH vs. non-ONFH human bone and to describe the relationships between these genes using multivariate data analysis. Six bone tissue samples from ONFH male patients and 8 bone tissue samples from non-ONFH men were examined. The expression differences of selected 117 genes were analyzed by TaqMan probe-based quantitative real-time RT-PCR system. The significance test indicated marked differences in the expression of nine genes between ONFH and non-ONFH individuals. These altered genes code for collagen molecules, an extracellular matrix digesting metalloproteinase, a transcription factor, an adhesion molecule, and a growth factor. Canonical variates analysis demonstrated that ONFH and non-ONFH bone tissues can be distinguished by the multiple expression profile analysis of numerous genes controlled via canonical TGFB pathway as well as genes coding for extracellular matrix composing collagen type molecules. The markedly altered gene expression profile observed in the ONFH of human bone tissue may provide further insight into the pathogenetic process of osteonecrotic degeneration of bone.
Exploratory Investigation on Functional Significance ofETS2andSIM2Genes in Down Syndrome
Authors: Chatterjee Arpita , Dutta Samikshan , Sinha Swagata , Mukhopadhyay Kanchan
Published: June 2013

Trisomy of the 21st chromosome leads to an over dosage of several regulatory genes in Down syndrome (DS). Though allelic and genotypic combinations formed between genes are interesting, till date, this particular area has never been explored in DS. In the present investigation four SNPs in two transcription factors, Single minded 2 (SIM2) and V-ets erythroblastosis virus E26 oncogene homolog2 (ETS2), located in the 21st chromosome were genotyped to understand their role in DS. Genomic DNA of eastern Indian probands with DS (N= 132), their parents (N= 209) and ethnically matched controls (N= 149) was subjected to PCR-based analyses of functionally important SNPs followed by statistical analyses.ETS2rs461155 showed high heterozygosity in DS. Significantly lower frequency ofSIM2C-G haplotype (rs2073601-rs2073416) was noticed in individuals with DS (Pvalue = 0.01669) and their fathers (Pvalue = 0.01185). Significantly lower frequency of the A-C-C-G with higher frequency of A-C-A-G haplotypes was also noticed in subjects with DS (Pvalue = 0.02089 and 0.00588 respectively). Data obtained indicate that the rs2073601 ‘A’ allele, responsible for nonsynonymous substitution of leucine to methionine, may have some role in DS in this population.
No Association ofPTGDR−441C/TPolymorphism with Asthma in a North Indian Population
Authors: Birbian Niti , Singh Jagtar , Jindal Surinder Kumar , Joshi Amit , Batra Navneet
Published: June 2013

Background:Asthma is the most prevalent disease in India according to the national survey conducted by NFHS 2 in 1998–399. Prostaglandin D2 (PGD2) is a bronchoconstriction inducing metabolite of arachidonic acid in the mast cells, which is produced on exposure to allergens and acts as a ligand for the Prostaglandin D2 Receptor (PTGDR). Polymorphisms in thePTGDRgene have been suggested to be involved in the mechanism of asthma.

Objective:This is the first study conducted in India, investigating the role ofPTGDR−441C/Tpromoter polymorphism in asthma pathogenesis.

Methods:A case-control study was performed with a total of 992 subjects, including 410 adult asthmatics and 582 healthy controls from regions of North India. ThePTGDR−441C/Tpolymorphism was genotyped by Tetra-Primer Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra-Primer ARMS PCR).

Results:Statistical analysis of the results between asthma cases and controls for thePTGDR−441C/Tpolymorphism showed Chi2(χ2) = 0.29, OR = 0.95, 95% CI (0.70–1.15) andp= 0.599. Neither the genotypic nor the allelic frequencies observed for thePTGDR−441C/Tpolymorphism, were significantly associated with asthma or asthma phenotypes.

Conclusions:ThePTGDR−441C/Tpolymorphism is not associated with asthma or its phenotypes in the studied North Indian population.
Epigenetic Aspects of Posttraumatic Stress Disorder
Authors: Schmidt Ulrike , Holsboer Florian , Rein Theo
Published: June 2013

Development of psychiatric diseases such as posttraumatic stress disorder (PTSD) invokes, as with most complex diseases, both genetic and environmental factors. The era of genome-wide high throughput technologies has sparked the initiation of genotype screenings in large cohorts of diseased and control individuals, but had limited success in identification of disease causing genetic variants. It has become evident that these efforts at the genomic level need to be complemented with endeavours in elucidating the proteome, transcriptome and epigenetic profiles. Epigenetics is attractive in particular because there is accumulating evidence that the lasting impact of adverse life events is reflected in certain covalent modifications of the chromatin.

In this review, we outline the characteristics of PTSD as a stress-related disease and survey recent developments revealing epigenetic aspects of stress-related disorders in general. There is also increasing direct evidence for gene programming and epigenetic components in PTSD. Finally, we discuss treatment options in the light of recent discoveries of epigenetic mechanisms of psychotropic drugs.
Association of Endothelial Dysfunction with Endothelin, Nitric Oxide and eNOS Glu298Asp Gene Polymorphism in Coronary Artery Disease
Authors: Saini Vandana , Bhatnagar M. K. , Bhattacharjee Jayashree
Published: June 2013

The endothelial dysfunction has been implicated as a major event in the pathogenesis of atherosclerosis. Therefore, this study was planned to determine (a) role of endothelium-derived nitric oxide (NO) and endothelin as coronary artery disease (CAD) risk markers and (b) intergenotypic variation of endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism in CAD.The endothelin, NO and eNOS genotypes were determined in 60 patients with documented history of CAD. These were compared with 50 age- and sex- matched healthy controls. The genotype frequencies for eNOS gene polymorphism were determined by PCR and RFLP. The plasma endothelin in CAD patients was significantly higher (p< 0.001) whereas, the NO level in CAD group was significantly lower (p< 0.001) than the control group. The genotype frequencies for Glu298/Asp (Glu/Glu and Glu/Asp) genotypes were 75% and 25% in CAD subjects and 88% and 12% in control subjects, respectively. No Asp/Asp was found in any of the groups. The genotype frequencies differed significantly (p< 0.05) between the controls and cases. In conclusion, endothelin and NO may be used as markers of endothelial dysfunction in CAD. Asp allele might be a risk factor for CAD in the North Indian population.
Clinical Utility of Alpha Fetoprotein and HCCR-1, Alone or in Combination, in Patients with Chronic Hepatitis, Liver Cirrhosis and Hepatocellular Carcinoma
Authors: Jirun Peng , Zhang Guoxin , Kim Hyun Kee , Ha Seon-Ah , Zhongtian Jin , Shishi Qiao , Zhuqingqing Cui , Lei Gong , Yoo Jinah , Kim Sanghee , Park Yong Gyu , Wang Jing , Yang Yang , Xu Zekuan , Huang Zuhu , Lee Yun Kyung , Song Eun Young , Kim Jin Woo
Published: June 2013

Serum alpha fetoprotein (AFP) is the most widely used tumor marker in detecting patients with hepatocellular carcinoma (HCC). However, it has been indicated that HCCR-1 (human cervical cancer oncogene 1) might be supplementary to AFP in the detection. We conducted a prospective study in 120 normal and 524 liver disease patients to evaluate the significance of simultaneous measurement of 2 tumor markers (AFP and HCCR-1) in the diagnosis of HCC through the cohort study in Korea and China. We also performed immunohistochemical studies using 25 normal subjects (N), 32 liver cirrhosis (LC) and 116 HCC tissues. The sensitivities of AFP (20 ng/mL) and HCCR-1 (10 ng/mL) in HCC were 55.8% (164/294) and 44.2% (130/294), respectively. When AFP was combined with HCCR-1, sensitivities increased to 4.2% (N), 12.7% (chronic hepatitis; CH), 50.0% (LC), and 77.2% (HCC), respectively. Although there was no significant difference in the diagnostic rate for HCC between AFP and HCCR-1, many cases for AFP-negative HCC were positive for HCCR-1 and vice versa. Moreover, the combined use of AFP and HCCR-1 improved the diagnostic rate to 70.8% in small HCC (< 2 cm) and 81.6% in large HCC (≥ 2 cm), respectively. AFP and HCCR-1 are independent markers. Our result suggests that the HCCR-1 could be an useful biomarker for HCC while the diagnostic rate could be significantly improved in the combined use of HCCR-1 and AFP.
Circulating Endothelial Cells in Patients with Heart Failure and Left Ventricular Dysfunction
Authors: Martínez-Sales Vicenta , Sánchez-Lázaro Ignacio , Vila Virtudes , Almenar Luis , Contreras Teresa , Reganon Edelmiro
Published: June 2013

Introduction and Aims:Acute and chronic heart failure may manifest different degrees of endothelial damage and angiogenesis. Circulating endothelial cells (CEC) have been identified as marker of vascular damage. The aim of our study was to evaluate the evolution of the CEC at different stages of patients with heart failure. We also investigated a potential correlation between CEC and markers of vascular damage and angiogenesis.

Methods:We studied 32 heart failure patients at hospital admission (acute phase) and at revision after 3 months (stable phase) and 32 controls. Circulating markers of endothelial damage (CEC; von Willebrand factor, vWF and soluble E-selectin, sEsel) and angiogenesis (vascular endothelial growth factor, VEGF and thrombospondin-1) were quantified.

Results:Levels of CEC, vWF, sEsel and VEGF are significantly higher in heart failure patients than in controls. Levels of CEC (36.9 ± 15.3 vs. 21.5 ± 10.0 cells/ml;p< 0.001), vWF (325 ± 101 vs. 231 ± 82%;p< 0.001) and VEGF (26.3 ± 15.2 vs. 21.9 ± 11.9 ng/ml;p< 0.001) are significantly higher in the acute phase than in the stable phase of heart failure. CEC levels correlate with vWF and VEGF. Results show than 100% of patients in acute phase and 37.5% in stable phase have levels of CEC higher than the 99th percentile of the distribution of controls (16 cells/ml). Therefore, increases in CEC represent a relative risk of 9.5 for heart failure patients suffering from acute phase.

Conclusions:CEC, in addition to being elevated in heart failure, correlate with vWF levels, providing further support for CEC as markers of endothelial damage. Levels of CEC are associated with the acute phase of heart failure and could be used as a marker of the worsening in heart failure.
CXCL4 and CXCL10 Predict Risk of Fatal Cerebral Malaria
Authors: Wilson Nana O. , Jain Vidhan , Roberts Christina E. , Lucchi Naomi , Joel Pradeep K. , Singh Mrigendra P. , Nagpal Avinash C. , Dash Aditya P. , Udhayakumar Venkatachalam , Singh Neeru , Stiles Jonathan K.
Published: June 2013

Plasmodium falciparumin a subset of patients can lead to a diffuse encephalopathy known as cerebral malaria (CM). Despite treatment, mortality caused by CM can be as high as 30% while 10% of survivors of the disease may experience short- and long-term neurological complications. The pathogenesis of CM involves alterations in cytokine and chemokine expression, local inflammation, vascular injury and repair processes. These diverse factors have limited the rate of discovery of prognostic predictors of fatal CM. Identification of reliable early predictors of CM severity will enable clinicians to adjust this risk with appropriate management of CM. Recent studies revealed that elevated levels of CXCL10 expression in cerebrospinal fluid and peripheral blood plasma independently predicted severe and fatal CM. CXCR3, a promiscuous receptor of CXCL10, plays an important role in pathogenesis of mouse model of CM. In this study the role of corresponding CXCR3 ligands (CXCL11, CXCL10, CXCL9 & CXCL4) in fatal or severe CM was evaluated by comparing their levels in 16 healthy control (HC), 26 mild malaria (MM), 26 cerebral malaria survivors (CMS) and 12 non-survivors (CMNS) using enzyme linked immunosorbent assay (ELISA). Levels of CXCL4 and CXCL10 were significantly elevated in CMNS patients (p< 0.05) when compared with HC, MM and CMS. Elevated plasma levels of CXCL10 and CXCL4 were tightly associated with CM mortality. Receiver Operating Characteristic (ROC) curve analysis revealed that CXCL4 and CXCL10 can discriminate CMNS from MM (p< 0.0001) and CMS (p< 0.0001) with an area under the curve (AUC) = 1. These results suggest that CXCL4 and CXCL10 play a prominent role in pathogenesis of CM associated death and may be used as functional or surrogate biomarkers for predicting CM severity.
Fucose and Sialic Acid Expressions in Human Seminal Fibronectin andα1-Acid Glycoprotein Associated with Leukocytospermia of Infertile Men
Authors: Kratz Ewa M. , Faundez Ricardo , Kątnik-Prastowska Iwona
Published: June 2013

Introduction: The aim of this study was to compare fucose and sialic acid residue expression on fibronectin andα1-acid glycoprotein in the seminal plasma of men suspected of infertility and suffering from leukocytospermia.

Subjects and methods: Seminal ejaculates were collected from 27 leukocytospermic and 18 healthy, normozoospermic men. The relative degree of fucosylation and sialylation of fibronectin andα1-acid glycoprotein was estimated by ELISA using fucose and sialic acid specific lectins fromAleuria aurantia, Lotus tetragonolobus, andUlex europaeusas well asMaackia amurensisandSambucus nigra, respectively.

Results: Leukocytospermic seminal fibronectin, in comparison with fibronectin of normal fertile group, showed lower relative reactivity with AAL, LTA and UEA, and higher reactivity with MAA and SNA, while the AGP of the leukocytospermic group was less reactive with AAL, and the relative reactivity with LTA and MAA was significantly higher. Fibronectin andα1-acid glycoprotein reactivity with UEA and MAA showed high positive correlations.

Discussion: Leukocytospermia was associated with the alterations of terminal monosaccharide expression in human seminal fibronectin andα1-acid glycoprotein. The increase of sialyl-Lewisxantigen inα1-acid glycoprotein can be used as a marker of genital tract inflammation manifested by leukocytospermia.
Corticotrophin-Releasing Hormone Type 1 Receptor Gene (CRHR1) Variants Predict Posttraumatic Stress Disorder Onset and Course in Pediatric Injury Patients
Authors: Amstadter Ananda B. , Nugent Nicole R. , Yang Bao-Zhu , Miller Alisa , Siburian Richie , Moorjani Priya , Haddad Stephen , Basu Aditi , Fagerness Jesen , Saxe Glenn , Smoller Jordan W. , Koenen Karestan C.
Published: June 2013

Posttraumatic stress disorder (PTSD) is a common and disabling anxiety disorder that may occur in the aftermath of exposure to potentially traumatic life events. PTSD is moderately heritable, but few specific molecular variants accounting for this heritability have been identified. Genes regulating the hypothalamic-pituitary-adrenal (HPA) axis, such as corticotrophin-releasing hormone type 1 receptor gene (CRHR1), have been implicated in traumatic-stress related phenotypes but have yet to be studied in relation to PTSD. The present study sought to examine the relation between 9 single nucleotide polymorphisms (SNPs) in theCRHR1gene and posttraumatic stress symptoms in a prospective study of pediatric injury patients (n= 103) who were first assessed in the acute aftermath of their injury at the hospital. Results indicated that multiple SNPs were associated with acute symptoms at a univariate level, and after correction for multiple testing, rs12944712 was significantly related to acute PTSD symptoms. Longitudinal latent growth curve analyses suggest that rs12944712 is also related to both acute symptom level and trajectory of symptoms over time. The present study adds support for the role ofCRHR1in the stress response following potentially traumatic event exposure in youth. It should be noted that the sample size in this study was small, and therefore statistical power was low; following, results from this study should be considered preliminary. Although results are not definitive, the findings from this study warrant future replication studies on how variation in this gene relates to response to traumatic event exposure in youth.
Asymmetric Dimethylarginine (ADMA) Levels Display a Morning Peak in Patients with Acute Myocardial Infarction
Authors: Bergheanu Sandrin C. , van der Laarse Arnoud , van der Bom Johanna G. , van der Hoeven Bas L. , le Cessie Saskia , de Jong Margreet G. , Liem Su-San , Schalij Martin J. , Jukema J. Wouter
Published: June 2013

High Asymmetric Dimethylarginine (ADMA) levels are associated with increased platelet activity, elevated blood pressure, vasoconstriction and impaired vascular relaxation. We hypothesized that the myocardial infarction morning peak of occurrence is closely related to a morning peak of ADMA levels. We performed a cross-sectional study among patients with documented myocardial infarction who had been enrolled in the prospective MISSION! Intervention Study. In total, serum ADMA levels were measured in their acute setting of myocardial infarction in 120 patients. The frequency of myocardial infarction onset of symptoms and emergency coronary catheterization and the ADMA levels displayed a similar daily pattern with a morning peak between 06:00–11:59 h. The absolute ADMA levels peak was between 06:00–07:59 h with a median (interquartile range) peak value of 1.01 (0.84–1.21) μmol/L for then= 9 patients vs. 0.75 (0.61–0.89) μmol/L for the remaining 111 patients admitted throughout the rest of the 24-hour interval (p= 0.003 for between groups comparison). The amplitude (95% confidence interval) of the circadian variation of ADMA levels was 0.08 μmol/L (0.004–0.16) withp= 0.042 for statistic model significance.

In conclusion, ADMA levels display a 24-hour variation with a significant morning peak in patients with acute myocardial infarction. These findings may relate ADMA levels to the acute onset of thrombotic cardiovascular events.
Evaluation of the Expression of C-kit (CD117) in Ependymomas and Oligodendrogliomas
Authors: Zavalhia Lisiane Silveira , Romitti Mirian , Netto Gabriel Corteze , dos Santos Giovana Tavares , Meurer Rosalva Thereza , Hilbig Arlete , Michalowski Mariana Bohns , Ribeiro Marlise de Castro
Published: June 2013

C-kitis a proto-oncogene located on the long arm of chromosome 4. Its product, CD117, is a specific immunohistochemical (IHQ) marker that is associated with response to a potent tyrosine kinase inhibitor therapy with STI-571 (Gleevec®) in chronic myelogenous leukemia and GISTs. In our study, we aimed to evaluate the expression of CD117 in glial tumors as this finding may guide therapeutic approaches for these brain tumors. Ependymomas and oligodendrogliomas, in formalin fixed and paraffin embedded blocks were assayed for CD117 immunoreactivity using anti-c-kit (CD117, DAKO). GISTs were used as positive control. We observed immunoreactivity of CD117 protein in 25.5% of tumors in both histological types. In oligodendrogliomas, there was an association between older age at diagnosis and positivity for CD117 (P= 0.039). In addition, we observed an association between higher tumor grade (grade III) and positivity for CD117 (P= 0.007). No clinical association was observed in ependymomas (P> 0.05). This study encourages further investigations, considering that CD117 may be a possible oncogenic factor in some glial tumors. In this case, tumors that express this marker may eventually benefit from a therapy with selective inhibitors of receptor kinases.
Assessment of Sialic Acid Diversity in Cancer- and Non-Cancer Related CA125 Antigen Using Sialic Acid-Binding Ig-Like Lectins (Siglecs)
Authors: Mitic N. , Milutinovic B. , Jankovic M.
Published: June 2013

This study was aimed at obtaining insight into the diversity of sialic acids in cancer- and non-cancer-related CA125 antigen, tumour marker of serous ovarian cancer. Starting from available data suggesting the possible relevance of sialic acids for discriminating CA125 antigens of different origin, we have employed a new experimental approach based on the use of human sialic acid-binding Ig-like lectins, Siglecs, as tools for the investigation of sialylation.

Siglec−2, belonging to the group of evolutionarily conserved Siglecs, and Siglec−3, −6, −7, −9 and −10, which are CD33-like Siglecs, were probed in solid-phase binding assays with cancer-related CA125 antigens from pleural fluid of patients with ovarian carcinoma (pfCA125), the OVCAR-3 ovarian carcinoma cell line (clCA125) and a non-cancer-related CA125 antigen, i.e. pregnancy-associated pCA125 antigen.

All Siglecs used showed detectable binding to pCA125 antigen. Siglec−3, Siglec−7 and Siglec−2 exhibited moderately stronger binding to pCA125 antigen than the others. In contrast to this, Siglec−2 and Siglec−3 preferentially recognized pfCA125 with greater total binding than for pCA125, whereas Siglec−9 and Siglec−10 were highly selective for clCA125.

Siglecs promise to be powerful tools for discriminating CA125 of different origin and could propagate further research on other molecular markers of biomedical and diagnostic importance.
MTHFR C677T, MTHFR A1298C, and OPG A163G Polymorphisms in Mexican Patients with Rheumatoid Arthritis and Osteoporosis
Authors: Brambila-Tapia Aniel Jessica Leticia , Durán-González Jorge , Sandoval-Ramírez Lucila , Mena Juan Pablo , Salazar-Páramo Mario , Gámez-Nava Jorge Iván , González-López Laura , Lazalde-Medina B Brissia , Dávalos Nory Omayra , Peralta-Leal Valeria , del Mercado Mónica Vázquez , Beltrán-Miranda Claudia Patricia , Dávalos Ingrid Patricia
Published: June 2013

MTHFR polymorphisms C677T and A1298C are associated with reduced MTHFR enzyme activity and hyperhomocysteinemia, which has been associated with osteoporosis. The A163G polymorphism inosteoprotegerin(OPG) has been studied in osteoporosis with controversial results. The objective of the present study was to investigate the association(s) among MTHFR C677T, MTHFR A1298C, and OPG A163G polymorphisms in Mexican patients with rheumatoid arthritis and osteoporosis. The femoral neck and lumbar spine bone mineral densities (BMDs) were measured in 71 RA patients, and genotyping for the three polymorphisms was performed via restriction fragment length polymorphism analysis. Patients with osteoporosis/osteopenia exhibited statistically significant differences in the genotype frequencies of MTHFR C677T as well as an association with femoral neck BMD; TT homozygotes had lower BMDs than patients with the CT genotype, and both of these groups had lower BMDs than patients with the CC genotype. The associations of the MTHFR C677T polymorphism with osteoporosis/osteopenia and femoral neck BMD suggest that these polymorphisms confer a risk of developing osteoporosis in patients with rheumatoid arthritis, a risk that may be reduced with folate and B complex supplementation.
Human Neutrophil Peptides 1–3 as Gastric Cancer Tissue Markers Measured by MALDI-Imaging Mass Spectrometry: Implications for Infiltrated Neutrophils as a Tumor Target
Authors: Cheng Chun-Chia , Chang Jungshan , Chen Ling-Yun , Ho Ai-Sheng , Huang Ker-Jer , Lee Shui-Cheng , Mai Fu-Der , Chang Chun-Chao
Published: June 2013

Objective: Human neutrophil peptides (HNPs) -1, -2 and -3 are significantly upregulated and were reported as biomarkers in gastric cancer (GC). However, the tissue location and function of HNPs 1-3 are still unclear in GC, and the spatial distribution of the triad needs to be disclosed. The aims of this study were to investigate the distribution and relationships among HNPs-1, -2 and -3, and assess whether infiltrated neutrophils accumulate in gastric tumor.

Methods: In this study, paired samples (n=33) of the GC tissues and adjacent normal tissues from the same patients were obtained from surgery. Expression of HNPs 1-3 were detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The distributions of the HNPs 1-3 in GC tissues were investigated. After verification of HNPs-1 by immunohistochemistry, infiltrated neutrophils were also detected. Then, an in vitro assay was used to observe the binding capacity and measure the cytotoxic effect of HNPs-1 against AGS cells.

Results: Comparing to neighboring normal tissue, expressional level of HNPs 1-3 were significantly higher and their distributions overlapped in cancerous tissues of GC patients with high abundance in the lamina propria, whereas HNPs-1 was identified as the highest major peak. Moreover, HNPs-1, -2 and -3 correlated with each other. Besides, we also observed that increased infiltrated neutrophils accumulating in GC tissues, indicating that a strong positive correlation between HNPs 1-3 and infiltrated neutrophils. In addition, the further investigated demonstrated that the major peptide, HNPs-1, was statistically increased with the advance of tumor development from the early to advanced stage of GC (p < 0.05). Moreover, we also noticed that HNPs-1 with a great binding capacity to GC AGS cells in vitro can inhibit tumor cell growth.

Conclusions: Our results suggest that neutrophil secreted peptides, HNPs 1-3, increased in the GC tissues and could be used as potential biomarkers detected using MALDI-TOF MS, implying that elevated neutrophils may be used as a tumor target for tumor treatment. The binding capacity of HNPs-1 with GC cells implies that tracking molecules conjugated with HNPs-1 could be applied as a specific probe for GC diagnoses.
piRNAs Warrant Investigation in Rett Syndrome: An Omics Perspective
Authors: Saxena Alka , Tang Dave , Carninci Piero
Published: June 2013

Mutations in the MECP2 gene are found in a large proportion of girls with Rett Syndrome. Despite extensive research, the principal role of MeCP2 protein remains elusive. Is MeCP2 a regulator of genes, acting in concert with co-activators and co-repressors, predominantly as an activator of target genes or is it a methyl CpG binding protein acting globally to change the chromatin state and to supress transcription from repeat elements? If MeCP2 has no specific targets in the genome, what causes the differential expression of specific genes in the Mecp2 knockout mouse brain? We discuss the discrepancies in current data and propose a hypothesis to reconcile some differences in the two viewpoints. Since transcripts from repeat elements contribute to piRNA biogenesis, we propose that piRNA levels may be higher in the absence of MeCP2 and that increased piRNA levels may contribute to the mis-regulation of some genes seen in the Mecp2 knockout mouse brain. We provide preliminary data showing an increase in piRNAs in the Mecp2 knockout mouse cerebellum. Our investigation suggests that global piRNA levels may be elevated in the Mecp2 knockout mouse cerebellum and strongly supports further investigation of piRNAs in Rett syndrome.
Plasma C-Reactive Protein Is Not Related to Sinus Non-Conversion by Maze Procedure Adjunct to Mitral Valve Surgery
Authors: Chen Chien-Jen , Liu Wen-Hao , Chang Jen-Ping , Ho Wan-Chun , Chen Yung-Lung , Fang Chih-Yuan , Chen Mien-Cheng
Published: June 2013

In Framingham cohort study, C-reactive protein was not associated with incident atrial fibrillation (AF) after adjustment for left atrial size. This study examined whether levels of plasma inflammatory markers would be significant risk factors for failed maze procedure for AF. This study enrolled 88 patients with mitral valve disease undergoing valve surgery (n= 32, sinus control group) or concomitant maze procedure for persistent atrial fibrillation (AF) (n= 56, AF group). The mean follow-up in the AF group was 55.0 ± 17.5 months. The AF and sinus control groups did not differ in preoperative levels of C-reactive protein (p= 0.636). In the AF group receiving maze procedure, the sinus conversion (n= 37) and non-conversion (n= 19) groups did not significantly differ in preoperative levels of interleukin-6 (p= 0.607) and tumor necrosis factor-α(p= 0.379). In multivariate analysis after adjustment for preoperative plasma inflammatory markers, independent factors associated with sinus conversion were AF duration (p=0.003), and left atrial area (p= 0.014). In conclusion, plasma inflammatory markers are not associated with sinus non-conversion by radiofrequency maze procedure.
Polymorphisms of Glutathione S-Transferase Mu 1 (GSTM1), Theta 1 (GSTT1), and Pi 1 (GSTP1) Genes and Epithelial Ovarian Cancer Risk
Authors: Oliveira Cristiane , Lourenço Gustavo Jacob , Sagarra Regina Aparecida Martinho , Derchain Sophie Françoise Mauricette , Segalla José Getulio , Lima Carmen Silvia Passos
Published: June 2013

Background: Exposure of ovarian cells to estrogen, which is detoxified by glutathione S-transferases (GSTs), has been associated with epithelial ovarian cancer (EOC) development.

Objectives: We tested in this study whether theGSTM1,GSTT1andGSTP1Ile105Val polymorphisms alter the risk of EOC.

Materials and methods: Genomic DNA from 132 EOC patients and 132 controls was analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. The differences between groups were analyzed byχ2or Fisher’s exact test.

Results: The frequencies ofGSTP1Ile/Ile (57.6% versus 45.5%,P= 0.03),GSTM1null plusGSTP1Ile/Ile (43.5% versus 25.8%;P= 0.03) andGSTM1null plusGSTT1null plusGSTP1Ile/Ile (30.3% versus 7.7%;P= 0.007) genotypes were higher in patients than in controls. Individuals with the respective genotypes had a 1.80 (95% CI: 1.06–3.06), 2.38 (95% CI: 1.08–5.24) and 11.28 (95%CI: 1.95–65.30)-fold increased risks of EOC than those with the remaining genotypes.

Conclusions: Our data present preliminary evidence thatGSTM1,GSTT1andGSTP1polymorphisms, particularly in combination, constitute important inherited EOC determinants in individuals from Southeastern Brazil.
Relation between MicroRNA Expression in Peritoneal Dialysis Effluent and Peritoneal Transport Characteristics
Authors: Chen Jin , Kam-Tao Philip , Kwan Bonnie Ching-Ha , Chow Kai-Ming , Lai Ka-Bik , Luk Cathy Choi-Wan , Szeto Cheuk-Chun
Published: June 2013

Background:The role of microRNAs (miRNAs) in peritoneal transport is uncertain.

Methods:We studied 82 new peritoneal dialysis (PD) patients, 22 prevalent patients without ultrafiltration problem, and 6 patients with documented ultrafiltration problem. Peritoneal transport was determined by standard peritoneal equilibration test (PET). RNA was extracted from the PD effluent after PET, and intra-peritoneal expression of miRNA targets were quantified.

Results:There were significant difference in the PDE expressions of miR-15a and miR-21. There were modest inverse correlations between ultrafiltration volume and PDE expression of miR-17 (r= −0.198,p= 0.041) and miR-377 (r= −0.201,p= 0.041). There was an inverse correlations between dialysate-to-plasma creatinine concentration at 4 hours and PDE expression of miR-192 (r= −0.199,p= 0.040); while mass transfer area coefficient of creatinine correlated with PDE expression of miR-192 (r= −0.191,p= 0.049) and miR-377 (r= 0.201,p= 0.041). Amongst 7 randomly selected patients who had repeat PET after one year, there was a significant correlation between baseline PDE expression of miR-377 and change in ultrafiltration volume (r= −0.852,p= 0.015).

Conclusion:The miRNA expression in PDE, including miR-15a, miR-17, miR-21, miR-30, miR-192, and miR-377, correlated with peritoneal transport characteristics. Our result suggests that miRNA may play a role in the regulation of peritoneal membrane function.
Iron Overload andHFEGene Mutations in Czech Patients with Chronic Liver Diseases
Authors: Dostalikova-Cimburova Marketa , Kratka Karolina , Stransky Jaroslav , Putova Ivana , Cieslarova Blanka , Horak Jiri
Published: June 2013

The aim of the study was to identify the prevalence ofHFEgene mutations in Czech patients with chronic liver diseases and the influence of the mutations on iron status. The presence ofHFEgene mutations (C282Y, H63D, and S65C) analyzed by the PCR-RFLP method, presence of cirrhosis, and serum iron indices were compared among 454 patients with different chronic liver diseases (51 with chronic hepatitis B, 122 with chronic hepatitis C, 218 with alcoholic liver disease, and 63 patients with hemochromatosis). Chronic liver diseases patients other than hemochromatics did not have an increased frequency ofHFEgene mutations compared to controls. Although 33.3% of patients with hepatitis B, 43% of patients with hepatitis C, and 73.2% of patients with alcoholic liver disease had elevated transferrin saturation or serum ferritin levels, the presence ofHFEgene mutations was not significantly associated with iron overload in these patients. Additionally, patients with cirrhosis did not have frequencies ofHFEmutations different from those without cirrhosis. This study emphasizes the importance, not only of C282Y, but also of the H63D homozygous genetic constellation in Czech hemochromatosis patients. Our findings show that increased iron indices are common in chronic liver diseases butHFEmutations do not play an important role in the pathogenesis of chronic hepatitis B, chronic hepatitis C, and alcoholic liver disease.
Micro-RNA Expression in the Urinary Sediment of Patients with Chronic Kidney Diseases
Authors: Szeto Cheuk-Chun , Ching-Ha Kwan Bonnie , Ka-Bik Lai , Mac-Moune Lai Fernand , Cheung-Lung Choi Paul , Gang Wang , Kai-Ming Chow , Kam-Tao Li Philip
Published: June 2013

Background: Evidence indicates that microRNAs (miRNA) play a role in the pathogenesis of chronic kidney diseases (CKD). We explored the possibility of using urinary miRNA as non-invasive biomarkers for CKD.

Methods: We quantified miRNA expression in urinary sediment of 56 CKD patients who underwent kidney biopsy. Patients were followed for 16.2 ± 15.5 months.

Results: Patients with diabetic glomerulosclerosis had lower urinary miR-15 expression, while those with IgA nephropathy had higher urinary miR-17 expression, than other diagnosis groups. Baseline proteinuria had significant inverse correlation with urinary expression of miR-15, miR-192, and miR-216a; baseline renal function correlated with urinary expression of miR-15, miR-17, miR-192, and miR-217. The rate of renal function decline correlated with urinary expression of miR-21 (r= 0.301,p= 0.026) and miR-216a (r= 0.515, p < 0.0001). Patients with a high urinary expression of miR-21 and miR-216a had better dialysis-free survival than those with low expression (log rank test,p= 0.005 andp= 0.003, respectively).

Conclusions: Urinary miR-21 and miR-216a expression correlated with the rate of renal function decline and risk of progression to dialysis-dependent renal failure. Our results suggest that urinary miRNA profiling has the potential of further development as biomarkers of CKD.