bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Assessment in Patients with Hepatic Encephalopathy
Authors: García-Martínez Rita , Simón-Talero Macarena , Córdoba Juan
Published: June 2013

Hepatic encephalopathy (HE) is a common complication of liver failure that is associated with poor prognosis. However, the prognosis is not uniform and depends on the underlying liver disease. Acute liver failure is an uncommon cause of HE that carries bad prognosis but is potentially reversible. There are several prognostic systems that have been specifically developed for selecting patients for liver transplantation. In patients with cirrhosis the prognosis of the episode of HE is usually dictated by the underlying precipitating factor. Acute-on-chronic liver failure is the most severe form of decompensation of cirrhosis, the prognosis depends on the number of associated organ failures. Patients with cirrhosis that have experienced an episode of HE should be considered candidates for liver transplant. The selection depends on the underlying liver function assessed by the Model for End-stage Liver Disease (MELD) index. There is a subgroup that exhibits low MELD and recurrent HE, usually due to the coexistence of large portosystemic shunts. The recurrence of HE is more common in patients that develop progressive deterioration of liver function and hyponatremia. The bouts of HE may cause sequels that have been shown to persist after liver transplant.
Associations of Single Nucleotide Polymorphisms in the Adiponectin Gene with Adiponectin Levels and Cardio-Metabolic Risk Factors in Patients with Cancer
Authors: Al Khaldi Rasha Mazen , Al Mulla Fahd , Al Awadhi Shafika , Kapila Kusum , Mojiminiyi Olusegun A.
Published: June 2013

Objectives: The aims of this study are to (1) study the influence of polymorphisms in adiponectin gene on adiponectin levels and potential associations with breast, prostate and colon cancer; (2) investigate the associations of adiponectin levels with other adipokines and breast, prostate and colon cancers.

Subjects: We measured fasting adiponectin, leptin, insulin, Sex steroids in 132 (66 females, 66 males) cancer patients and 68 age and sex matched apparently healthy subjects. Body Mass Index (BMI) and waist circumference were used as indices of obesity. Insulin Resistance was assessed using Homeostasis Model Assessment (HOMA). Three single nucleotide polymorphisms (SNP rs182052 (G-10066-A), SNP rs1501299 (276G > T), SNP rs224176 (45T > G) in adiponectin gene were studied using Real Time Polymerase Chain Reaction.

Results: GG genotype of SNP rs1501299 was significantly associated with higher levels of adiponectin (OR=1.2, 95%CI(1.03–1.3),p= 0.02); breast (OR=8.6, 95%CI(1.03–71),p= 0.04), colon cancers (OR= 12, 95%CI(1.2–115),p= 0.03). GT genotype was also associated significantly with colon cancer (OR=2.6, 95%CI (1.1–6),p= 0.03). However SNP rs224176 was associated with only breast cancer.

Conclusion: Our results demonstrate that adiponectin gene SNP rs1501299 and SNP rs224176 may be the predisposing factors in some cancers but our results differ from what has been reported in other populations suggesting a complex relationship between genetic variations and phenotypic adiponectin levels.
IL-10 Promoter Genetic Polymorphisms and Risk of Kawasaki Disease in Taiwan
Authors: Hsieh Kai-Sheng , Lai Tsung-Jen , Hwang Yu-Tung , Lin Ming-Wei , Weng Ken-Pen , Chiu Yi-Ten , Ho Tsyr-Yuh , Chen Chi-Shan , Shiue Yow-Ling , Hsiao Michael , Tsai Shih-Feng , Ger Luo-Ping
Published: June 2013

Kawasaki disease (KD) is the most common cause of pediatric acquired heart disease. KD patients have spontaneously high plasma/serum levels of IL-10 during the acute phase. Therefore, two independent studies were carried out to investigate the association between genetic variants in IL-10 promoter (−1082, −819, and −592) and risk of KD. A total of 134 trios were included for the family-based association study. A significantly preferential transmission of the C allele at loci −819 T > C and −592 A > C for KD cases was observed (Ppermutation= 0.029 and Ppermutation= 0.034, respectively). There was a significant increase in the transmission of haplotype CC (p= 0.016) at the above two loci (OR, 1.632; 95% CI, 1.090–2.443; Ppermutation= 0.019). We also carried out a follow-up case-control study that included 146 KD cases and 315 unrelated healthy children. {The haplotype CC (−819, −592) showed an increased risk of KD (but statistically non-significant; OR, 1.332; 95% CI, 0.987–1.797;p= 0.061). In diplotype analysis, a trend was found between number of CC haplotype and risk of KD (but non-significant,p= 0.061). In conclusion, CC genotype and CC/CC diplotype at IL-10-819T > C and −592A > C were significantly associated with risk of KD in case-parent trio study, which were replicated partially in our follow-up case-control study.
Crosstalk between Activated and Inactivated c-Src in Hepatocellular Carcinoma
Authors: Chen Mei-Lin , Chai Chee-Yin , Yeh Kun-Tu , Wang Shen-Nien , Tsai Chia-Jung , Yeh Yao-Tsung , Yang Sheau-Fang
Published: June 2013

C-Src activity is regulated by tyrosine phosphorylation at two distinct sites, Tyr416 and Tyr527, with opposite effects. However, the clinical roles of these sites in human cancers are not well defined. This study aims to determine whether the alterations and crosstalk of these two sites may contribute to hepatocellular carcinoma (HCC). Specimens from 85 patients who had undergone curative hepatectomy were collected for this study. The patterns of p-Tyr416-Src and p-Tyr527-Src, as well as the non-phosphorylated status for each site, were determined using immunohistochemistry and statistically correlated with clinicopathological characteristics and overall survival rate. The active state of c-Src, p-Tyr416-c-Src, was positively correlated with tumour grade (P= 0.062) but inversely correlated with vascular invasion (P= 0.071). Its non-phosphorylated status, non-p-Tyr416-c-Src, was positively correlated with tumour stage and grade (P= 0.041 and 0.020). The inactive state of c-Src, p-Tyr527-c-Src, was decreased in male patients but increased HCV-infected patients (P= 0.044 and 0.033). The Kaplan-Meier survival curve further showed that increased p-Tyr416-c-Src and decreased non-p-Tyr527-c-Src expression were associated with a poor patient survival rate (P= 0.004 and 0.025). Interestingly, the expression of non-p-Tyr416-c-Src was positively correlated with that of p-Tyr527-c-Src in the HCC lesions (P= 0.040). In addition, the patients with concomitantly low p-Tyr416-c-Src and non-p-Tyr527-c-Src expression had a prolonged overall survival rate (P= 0.030). A multivariable COX regression model showed that p-Tyr416-c-Src expression was an effective predictor for patient survival in HCC [OR = 3.78, 95%CI = 1.46–9.76;P= 0.006]. Our results suggest that the active state of c-Src, p-Tyr416-c-Src, may serve as an independent prognostic marker of patient survival in HCC. Relative levels of other phosphorylated or non-phosphorylated c-Src kinases may also present different statuses during HCC development and require further investigation.
Non-Invasive Diagnostic and Prognostic Evaluation of Liver Cirrhosis and Portal Hypertension
Authors: Berzigotti Annalisa , Ashkenazi Eyal , Reverter Enric , Abraldes Juan G. , Bosch Jaime
Published: June 2013

Cirrhosis is the final stage of most of chronic liver diseases, and is almost invariably complicated by portal hypertension, which is the most important cause of morbidity and mortality in these patients. This review will focus on the non-invasive methods currently used in clinical practice for diagnosing liver cirrhosis and portal hypertension. The first-line techniques include physical examination, laboratory parameters, transient elastography and Doppler-US. More sophisticated imaging methods which are less commonly employed are CT scan and MRI, and new technologies which are currently under evaluation are MR elastography and acoustic radiation force imaging (ARFI). Even if none of them can replace the invasive measurement of hepatic venous pressure gradient and the endoscopic screening of gastroesophageal varices, they notably facilitate the clinical management of patients with cirrhosis and portal hypertension, and provide valuable prognostic information.
Combined Analysis of EPHX1, GSTP1, GSTM1 and GSTT1 Gene Polymorphisms in Relation to Chronic Obstructive Pulmonary Disease Risk and Lung Function Impairment
Authors: Lakhdar Ramzi , Denden Sabri , Knani Jalel , Leban Nadia , Daimi Houria , Hassine Mohsen , Lefranc Gérard , Chibani Jemni Ben , Khelil Amel Haj
Published: June 2013

Smoking is considered as the major causal factor of chronic obstructive pulmonary disease (COPD). Nevertheless, a minority of chronic heavy cigarette smokers develops COPD. This suggests important contribution of other factors such as genetic predisposing. Our objective was to investigate combined role of EPHX1, GSTP1, M1 and T1 gene polymorphisms in COPD risk, its phenotypes and lung function impairment. Prevalence of EPHX1, GSTP1, M1 and T1 gene polymorphisms were assessed in 234 COPD patients and 182 healthy controls from Tunisia. Genotypes of EPHX1 (Tyr113His; His139Arg) and GSTP1 (Ile105Val; Ala114Val) polymorphisms were performed by PCR-RFLP, while the deletion in GSTM1 and GSTT1 genes was determined using multiplex PCR. Analysis of combinations showed a significant association of 113His/His EPHX1/null-GSTM1 (OR = 4.07) and null-GSTM1/105Val/Val GSTP1 (OR = 3.56) genotypes with increased risk of COPD (respectively P=0.0094 and P=0.0153). The null-GSTM1/ null-GSTT1, 105Val/Val GSTP1/null GSTT1, 113His/His EPHX1/null-GSTM1 and null-GSTM1/105Val/Val GSTP1 genotypes were related to emphysema (respectively P = 0.01; P = 0.009; P = 0.008 and P = 0.001). Combination of 113His/His EPHX1/null-GSTM1 genotypes showed a significant association with the decrease of ΔFEV1 in patients (P = 0.028).

In conclusion, our results suggest combined EPHX1, GSTP1, GSTM1 and GSTT1 genetic polymorphisms may play a significant role in the development of COPD, emphysema and decline of the lung function.
Chemokines and Chemokine Receptors in Susceptibility to HIV-1 Infection and Progression to AIDS
Authors: Chatterjee Animesh , Rathore Anurag , Vidyant Sanjukta , Kakkar Kavita , Dhole Tapan N.
Published: June 2013

A multitude of host genetic factors plays a crucial role in susceptibility to HIV-1 infection and progression to AIDS, which is highly variable among individuals and populations. This review focuses on the chemokine-receptor and chemokine genes, which were extensively studied because of their role as HIV co-receptor or co-receptor competitor and influences the susceptibility to HIV-1 infection and progression to AIDS in HIV-1 infected individuals.
Oxidized Low-Density Lipoprotein Cholesterol and the Ratio in the Diagnosis and Evaluation of Therapeutic Effect In Patients with Coronary Artery Disease
Authors: Huang Huiling , Ma R. , Liu Dan , Liu Chen , Ma Yuedong , Mai Weiyi , Dong Yugang
Published: June 2013

Objective: The purpose of the present study was to investigate the value of ox-LDL and oxidation ratio of LDL (ox-LDL/TC, ox-LDL/HDL-C and ox-LDL/LDL-C) in diagnosis and prognosis evaluation in CAD patients. Also, we aimed to observe the effect of statins on reducing level of ox-LDL and oxidation ratio of LDL, and explore whether statins still have similar effect on ox-LDL in a short period of therapy (within 2 weeks).

Methods: Blood ox-LDL, TC, HDL-C, LDL-C, and TG were measured in cases with acute myocardial infarction (AMI,n= 177), unstable angina pectoris (UAP,n= 195), stable angina pectoris (SAP,n= 228), normal control (n= 120), and high risk control (n= 140).

Results: Mean value of ox-LDL and oxidation ratio of LDL was significantly higher in the CAD group than in the two control groups. The AUC of ROC curve of ox-LDL, ox-LDL/TC, ox-LDL/HDL-C, ox-LDL/LDL-C and apoA1/apoB were more than 0.50 (P< 0.001). Multivariate logistic regression analysis showed that age and ox-LDL/LDL-C related with short-term, while ox-LDL/LDL-C and ox-LDL/TC related with long-term prognosis (P< 0.05). Furthermore, after treatment with statins for 2 weeks, TC, LDL-C, ox-LDL, ox-LDL/TC, ox-LDL/HDL-C and ox-LDL/LDL-C decreased by 22%, 28%, 38%, 29%, 23% and 25% respectively. And the reduction of ox-LDL by statins is independent of lowering of LDL-C and TC.

Conclusions: Ox-LDL and oxidation ratio of LDL are closely related with AS, and they are better biomarkers for discriminating between patients with coronary artery disease and healthy subjects. In addition, statins can decrease level of ox-LDL significantly, which is independent of lowering of LDL-C and TC.
Association of Progranulin and High Sensitivity CRP Concentrations in Gingival Crevicular Fluid and Serum in Chronic Periodontitis Subjects with and without Obesity
Authors: Pradeep A. R. , Priyanka N. , Prasad M. V. R. , Kalra Nitish , Kumari Minal
Published: June 2013

Background: Obesity is considered as a strong risk factor of inflammatory periodontal tissue destruction. The purpose of this study is to determine presence of progranulin (PGRN) and high sensitivity C reactive protein (hs CRP) levels in serum and gingival crevicular fluid (GCF) in obese subjects with chronic periodontitis and to find an association, if any.

Material and methods: 40 subjects (20 males and 20 females) were selected based on their clinical parameters into four groups (10 subjects in each group): group 1 (healthy non obese), group 2 (healthy obese), group 3 (non obese with chronic periodontitis) and group 4 (obese with chronic periodontitis). Serum and GCF PGRN levels were estimated by enzyme linked immunosorbant assay (ELISA) and hs CRP levels were estimated by immunoturbidimetry method.

Results: The mean PGRN and hs CRP concentration both in serum and GCF were highest for group 4 followed by group 3, group 2 and least in Group 1.

Conclusion: PGRN and hs CRP may be novel biomarkers of the chronic inflammatory response in obesity and chronic periodontitis.
In-VitroCarbofuran Induced Genotoxicity in Human Lymphocytes and Its Mitigation by Vitamins C and E
Authors: Sharma Ratnesh Kumar , Sharma Bechan
Published: June 2013

Various efforts have been made in past in order to predict the underlying mechanism of pesticide-induced toxicity usingin vitroand animal models, however, these predictions may or may not be directly correlated with humans. The present study was designed to investigate the carbofuran induced genotoxicity and its amelioration by vitamins C and E by treating human peripheral blood lymphocytes (PBLs) with different concentrations (0, 0.5, 1.25, 2.5, 3.75 and 5.0 μM) of this compound. The treatment of PBLs with carbofuran displayed significant DNA damage in concentration dependent manner. The carbofuran induced genotoxicity could be ameliorated to considerable extent by pretreatment of PBLs with equimolar (10 μM) concentration of each of the vitamins C and E; the magnitude of protection by vitamin E being higher than by vitamin C. Also, it was found that the level of protection by these vitamins was higher when PBLs were treated with lower concentrations of pesticide. The significant DNA damage as observed by H2O2, a positive control in the present study, and its amelioration by natural antioxidants (vitamins C and E) lend an evidence to suggest that carbofuran would have caused genotoxicity via pesticide induced oxidative stress.
Elevated Asymmetric Dimethylarginine in Young Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Preliminary Report
Authors: Sulicka Joanna , Surdacki Andrzej , Strach Magdalena , Kwater Aleksander , Gryglewska Barbara , Ćwiklińska Magdalena , Balwierz Walentyna , Grodzicki Tomasz K.
Published: June 2013

Background:Adult survivors of childhood malignancy are predisposed to late cardiovascular (CV) complications. Our aim was to estimate plasma levels of the endogenous nitric oxide formation inhibitor asymmetric dimethylarginine (ADMA), in long-term survivors of childhood acute lymphoblastic leukemia (ALL) treated with only chemotherapy.

Methods:ADMA and its isomer symmetric dimethylarginine (SDMA) were measured in 25 former ALL patients (aged 18–28 years) who had survived without recurrent disease ≥ 5 years from completing chemotherapy without cranial irradiation, and in 20 healthy controls (aged 20–31 years).

Results:Characteristics of the both groups were similar, except for lower high-density lipoproteins-cholesterol (HDL-C) in ALL survivors. Compared to controls, the former ALL patients exhibited significant, albeit small, rises in levels of ADMA (0.63 ± 0.09 [SD] vs. 0.57 ± 0.07 μmol/L;p= 0.016), but not SDMA, with a consequently increased ADMA to SDMA ratio (1.08 ± 0.22 vs. 0.91 ± 0.16;p= 0.004). The effect of former ALL on ADMA was attenuated (intergroupp= 0.10 [ANCOVA]) upon adjustment for HDL-C (ADMA vs. HDL-C regression coefficient: −0.065 ± 0.030 [SEM];p= 0.03).

Conclusions:ADMA is elevated in adult childhood ALL survivors, which can reflect late detrimental chemotherapy effects, partially related to minor lipid profile changes. Whether these subtle ADMA elevations might herald future CV morbidity, remains to be elucidated.
Gingival Crevicular Fluid and Serum Cystatin C Levels in Periodontal Health and Disease
Authors: Sharma Anuj , Pradeep A. R. , Raghavendra N. M. , Arjun P. , Kathariya Rahul
Published: June 2013

Cystatin C (CSTC) is an inhibitor of cysteine proteinases and could play a protective and regulatory role under inflammatory conditions. The present study was designed to assess the concentration of CSTC in gingival crevicular fluid (GCF) and serum, to find out their association if any, in periodontal health and disease. 30 subjects were selected divided into 3 groups consisting of 10 subjects in each group based on clinical parameters: periodontally healthy group, gingivitis group and chronic periodontitis group, while, chronic periodontitis group after 8 weeks of the treatment (scaling and root planing) constituted after periodontal therapy group. GCF and serum samples were collected from all subjects to estimate the levels of CSTC by ELISA. The mean CSTC concentration in GCF and serum was observed to be the highest in periodontitis group and lowest in periodontally healthy group with intermediate concentration in gingivitis group and after periodontal therapy group. CSTC concentration in GCF and serum increased proportionally with the severity of periodontal disease (from health to periodontitis group) and decreased after treatment. This suggests that CSTC increases with disease progression to prevent further periodontal degeneration and decreases after treatment due to bone metabolic homeostasis. Further, longitudinal prospective studies involving larger population are needed to confirm the findings of present study and to better understand the role of CSTC in the pathogenesis of periodontal diseases.
Concentrations of Connective Tissue Growth Factor in Patients with Nonalcoholic Fatty Liver Disease: Association with Liver Fibrosis
Authors: Colak Yasar , Senates Ebubekir , Coskunpinar Ender , Oltulu Yasemin Musteri , Zemheri Ebru , Ozturk Oguzhan , Doganay Levent , Mesci Banu , Yilmaz Yusuf , Enc Feruze Yilmaz , Kiziltas Safak , Ulasoglu Celal , Tuncer Ilyas
Published: June 2013

Aim:In this study, we aimed to investigate the relationship between the histological fibrosis stage of nonalcoholic fatty liver disease (NAFLD) and serum connective tissue growth factor (CTGF) to determine the usefulness of this relationship in clinical practice.

Methods:Serum samples were collected from 51 patients with biopsy-proven NAFLD and 28 healthy controls, and serum levels of CTGF were assayed by ELISA.

Results:Levels of CTGF were significantly higher in patients with NAFLD compared with controls (P= 0.001). The serum CTGF levels were significantly increased, that correlated with histological fibrosis stage, in patients with NAFLD [in patients with no fibrosis (stage 0) 308.2 ± 142.9, with mild fibrosis (stage 1–2) 519.9±375.2 and with advanced fibrosis (stage 3–4) 1353.2 ± 610 ng/l,P< 0.001]. Also serum level of CTGF was found as an independent predictor of histological fibrosis stage in patients with NAFLD (β= 0.662,t= 5.6,P< 0.001). The area under the ROC curve was estimated 0.931 to separate patients with severe fibrosis from patients with other fibrotic stages.

Conclusion:Serum levels of CTGF may be a clinical utility for distinguishing NAFLD patients with and without advanced fibrosis.
Erythrocyte Sialic Acid Content during Aging in Humans: Correlation with Markers of Oxidative Stress
Authors: Mehdi Mohammad Murtaza , Singh Prabhakar , Rizvi Syed Ibrahim
Published: June 2013

Sialic acids are substituted neuraminic acid derivatives which are typically found at the outermost end of glycan chains on the membrane in all cell types. The role of erythrocyte membrane sialic acids during aging has been established however the relationship between sialic acid and oxidative stress is not fully understood. The present work was undertaken to analyze the relationship between erythrocyte membrane sialic acid with its plasma level, membrane and plasma lipid hydroperoxide levels and plasma total antioxidant capacity. Results show that sialic acid content decreases significantly (P< 0.001) in RBC membrane (r= −0.901) and increases in plasma (r= 0.860) as a function of age in humans. Lipid peroxidation measured in the form of hydroperoxides increases significantly (P< 0.001) in plasma (r= 0.830) and RBC membranes (r= 0.875) with age in humans. The Trolox Equivalent Total Antioxidant Capacity (TETAC) of plasma was found to be significantly decreased (P< 0.001,r= −0.844). We observe significant correlations between decrease of erythrocyte membrane sialic acid and plasma lipid hydroperoxide and TETAC. Based on the observed correlations, we hypothesize that increase in oxidative stress during aging may influence the sialic acid decomposition from membrane thereby altering the membrane configuration affecting many enzymatic and transporter activities. Considering the importance of plasma sialic acid as a diagnostic parameter, it is important to establish age-dependent reference.
Prevalence of MDR1 C3435T and CYP2B6 G516T Polymorphisms among HIV-1 Infected South African Patients
Authors: Masebe Tracy Madimabi , Bessong Pascal Obong , Nwobegahay Julius , Ndip Roland Ndip , Meyer Debra
Published: June 2013

Data on genetic polymorphisms associated with response to anti-HIV drugs has accumulated over the years. Information on how polymorphisms influence drug metabolism and transport to target sites is important in guiding dosage or selection of appropriate alternative therapies. This study determined the frequency of MDR1 C3435T and CYP2B6 G516T polymorphisms associated with the transport and metabolism of efavirenz and nevirapine, in a population of South African HIV infected patients. In addition, association of polymorphisms with immunologic and virologic factors was investigated. A 207bp of MDR1 exon 26 and a 161bp of CYP2B6 exon 4 were obtained from patients by polymerase chain reaction. Analysis of population-based sequences of MDR1 revealed a frequency of 89% and 11% of C and T alleles respectively (n=197; X2= 0.974;p=0.324). Restriction fragment length polymorphism (RFLP) analysis of the CYP2B6 gene revealed a prevalence of 9.5% of GG, 78.4% of GT and 12.1% of TT genotype (n= 199; X2= 65.204; p=0.00). There was no significant difference between immune recovery and decline in viral load (n=53), with genotype after repeated calculations of analysis of variance (ANOVA).
The Role of the FOXP Family of Transcription Factors in ASD
Authors: Bowers J. Michael , Konopka Genevieve
Published: June 2013

Autism spectrum disorders (ASD) is a neurodevelopmental disease with complex genetics; however, the genes that are responsible for this disease still remain mostly unknown. Here, we focus on the FOXP family of transcription factors as there is emerging evidence strongly linking these genes to ASD and other genes implicated in ASD. The FOXP family of genes includes three genes expressed in the central nervous system: FOXP1, FOPX2, and FOXP4. This unique group of transcription factors has known functions in brain development as well as the evolution of language. We will also discuss the other genes including transcriptional targets of FOXP genes that have been found to be associated with language and may be important in the pathophysiology of ASD. Finally, we will review the emerging animal models currently being used to study the function of the FOXP genes within the context of ASD symptomology. The combination of gene expression and animal behavior is critical for elucidating how genes such as the FOXP family members are key players within the framework of the developing brain.
DJ-1Variants in Indian Parkinson’s Disease Patients
Authors: Sadhukhan Tamal , Biswas Arindam , Das Shyamal K , Ray Kunal , Ray Jharna
Published: June 2013

Parkinson’s disease (PD) is a common neurodegenerative movement disorder. Among the candidate genes,DJ-1accounts for about 1% of the cases in different populations. We aim to find the contribution of the gene towards PD among Indians. By screeningDJ-1in 308 PD patients of eastern India and 248 ethnically matched controls, a total of 21 nucleotide variants – including two nonsynonymous changes – were detected. p.Arg98Gln was identified in 6 unrelated patients and 2 controls while p.Val35Ile, a novel change, was found only in 2 unrelated patients. A SNP (rs7517357) was observed to be moderately associated with increased risk of PD (p< 0.05). The deletion allele (g.168–185del) of a known 18 bp del/ins/dup polymorphism was found to be over represented (p< 0.05) among older patients (> 40 years) compared to the controls (> 45 years). Two of the patients, also heterozygotes forPINK1mutation, had more severe disease phenotypes, consistent with the reported interaction betweenPINK1andDJ-1gene products [19]. Our results demonstrate that up to 3.9% (12/308) of PD patients of eastern India harborDJ-1variants that should be explored further for any causal relationship with PD.
HypermethylatedFAM5CandMYLKin Serum as Diagnosis and Pre-Warning Markers for Gastric Cancer
Authors: Chen Lu , Su Liping , Li Jianfang , Zheng Yanan , Yu Beiqin , Yu Yingyan , Yan Min , Gu Qinlong , Zhu Zhenggang , Liu Bingya
Published: June 2013

Most cases of gastric cancer (GC) are not diagnosed at early stage which can be curable, so it is necessary to identify effective biomarkers for its diagnosis and pre-warning. We have used methylated DNA immunoprecipitation (MeDIP) to identify genes that are frequently methylated in gastric cancer cell lines. Promoter regions hypermethylation of candidate genes were tested by methylation-specific polymerase chain reaction (MSP) in serum samples, including GC (n= 58), gastric precancerous lesions (GPL,n= 46), and normal controls (NC,n= 30). Eighty two hypermethylated genes were acquired by array analysis and 5 genes (BCAS4, CHRM2, FAM5C, PRACandMYLK) were selected as the candidate genes. Three genes (CHRM2, FAM5CandMYLK) were further confirmed to show methylation rates increased with progression from NC to GPL, then to GC. There was obvious decrease in detection ofFAM5CandMYLKhypermethylation, but notCHRM2, from preoperative to postoperative evaluation (P< 0.001). Combined detection of FAM5C and MYLK hypermethylation had a higher sensitivity in GC diagnosis (77.6%,45/58) and pre-warning (30.4%,14/46) than one single gene detection and also had a high specificity of 90%. The combined hypermethylated status ofFAM5CandMYLKcorrelated with tumor size (P< 0.001), tumor invasion depth (P= 0.001) and tumor-node-metastasis (TNM) stage (P= 0.003). HypermethylatedFAM5CandMYLKcan be used as potential biomarkers for diagnosis and pre-warning of GC.
Diagnostic Value of Neopterin during Neutropenic Fever and Determination of Disease Activity in Childhood Leukemias
Authors: Belen Fatma Burcu , Kocak Ulker , Albayrak Meryem , Kaya Zuhre , Gursel Turkiz
Published: June 2013

Neopterin, a pteridine group compound that is secreted from macrophages is shown to be increased in adult leukemia; however there are few studies in childhood leukemia. This study aimed to investigate neopterin levels during childhood leukemia treatment and neutropenic fever episodes for the possibility of using as a marker for disease activity and differentiation of infections.

A total of 44 children with acute leukemia, 19 children with infection (control group 1) and 21 healthy children (control group 2) were studied. Median serum neopterin level before induction chemotherapy (day 0) in 25 children (patient group 1) was significantly higher (27.7 nmol/L) than those at the beginning of 30 febrile episodes in 19 children in bone marrow remission (2.2 nmol/L) (patient group 2) and in control group 2 (0.4 nmol/L) (p< 0.05). It was (27.7 nmol/L) also significantly higher in control group 1 than in patient group 2 and control group 2 (p< 0.05). Serum neopterin levels at day 15 (2.1 mmol/L) and day 33 (0.4 mmol/L) of induction were significantly lower than day 0 of ALL subgroup at patient group 1. There were no significant difference in neopterin levels between days 0, 3 and 5 of neutropenic fever as well as between patients with microbiologically and/or clinically documented infections and those with fever of unknown origin in patient group 2 (p> 0.05). Serum neopterin did not show significant correlation with absolute neutrophil count and absolute monocyte count (p> 0.05). In conclusion, elevated neopterin at diagnosis of leukemia with decrement during induction therapy suggest that it might be an indicator of leukemic process; however larger studies for its role in identifying infections are warranted.
Elevated IL-1α and CXCL10 Serum Levels Occur in Patients with Homozygous Sickle Cell Disease and a History of Acute Splenic Sequestration
Authors: Driss Adel , Wilson Nana O. , Mason Karlene , Hyacinth Hyacinth I. , Hibbert Jacqueline M. , Serjeant Graham R. , Stiles Jonathan K.
Published: June 2013

Acute splenic sequestration (ASS) and chronic hypersplenism are common features of homozygous sickle cell (SS) disease in the first 5 years of life affecting one-third of subjects in the Jamaican Cohort Study. The risk factors are largely unknown and the current study explores a possible role of genetic factors. We have explored these in subjects who received splenectomy in the management of ASS (n=8) or chronic hypersplenism (n=9) along with age, gender, and genotype matched controls using Luminex Technology to assess 42 human cytokines/chemokines, including IL-1α and CXCL10 (IP-10). Levels of IL-1α (p=0.008) and CXCL10 (p=0.009) were significantly elevated in patients treated by splenectomy compared with the control group. Levels of IL-1α were significantly higher in those with a history of ASS compared with matched normal controls (p=0.028) but not in those treated for hypersplenism (p=0.093). Furthermore, several significant differences were found in the median ratios of some cytokine biomarkers between the splenectomized group and the normal controls. These observations are consistent with acute splenic sequestration having a distinct phenotype which may be helpful in predicting those at risk of this complication and suggest that the mechanism of these differences merit further study.
IGF2RGenetic Variants, Circulating IGF2 Concentrations and Colon Cancer Risk in African Americans and Whites
Authors: Hoyo Cathrine , Murphy Susan K. , Schildkraut Joellen M. , Vidal Adriana C. , Skaar David , Millikan Robert C. , Galanko Joseph , Sandler Robert S. , Jirtle Randy , Keku Temitope
Published: June 2013

TheMannose 6 Phosphate/Insulin-like Growth Factor Receptor-2 (IGF2R)encodes a type-1 membrane protein that modulates availability of the potent mitogen, IGF2. We evaluated the associations betweenIGF2Rnon-synonymous genetic variants (c.5002G>A, Gly1619Arg(rs629849), and c.901C>G, Leu252Val(rs8191754)), circulating IGF2 levels, and colon cancer (CC) risk among African American and White participants enrolled in the North Carolina Colon Cancer Study (NCCCS). Generalized linear models were used to compare circulating levels of IGF2 among 298 African American and 518 White controls. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association ofIGF2Rgenetic variants and CC risk. Women homozygous for theIGF2Rc.5002 G>A allele, had higher mean levels of circulating IGF2, 828 (SD=321) ng/ml compared to non-carriers, 595 (SD=217) ng/ml (p-value=0.01). This pattern was not apparent in individuals homozygous for theIGF2Rc.901 C>G variant. Whites homozygous for theIGF2Rc.901 C>G variant trended towards a higher risk of CC, OR=2.2 [95% CI(0.9–5.4)], whereas carrying theIGF2Rc.5002 G>A variant was not associated with CC risk. Our findings support the hypothesis that being homozygous for theIGF2Rc.5002 G>A modulates IGF2 circulating levels in a sex-specific manner, and while carrying theIGF2Rc.901 C>G may increase cancer risk, the mechanism may not involve modulation of circulating IGF2.
Serum Surfactant Protein D: Biomarker of Chronic Obstructive Pulmonary Disease
Authors: Ju Chun-Rong , Liu Wei , Chen Rong-Chang
Published: June 2013

Background: Surfactant protein D (SP-D) is a lung-specific protein proposed to predict clinical outcomes in patients with chronic obstructive pulmonary disease (COPD). However, the changes in serum SP-D during acute exacerbation (AECOPD) episodes and the relationship of serum SP-D with the overall severity of the disease in stable COPD (SCOPD) remain unclear.

Methods: Serum SP-D levels were analyzed in three groups, including AECOPD (n=40), SCOPD (n=71), and controls (n=60). In AECOPD group, serum SP-D levels were determined at 1, 5, 14, and 30 days post-exacerbation. In SCOPD group, BODE (body mass index, airflow obstruction, dyspnea, exercise capacity) index was evaluated for severity assessment.

Results: Serum SP-D levels were sequentially elevated from the controls to the SCOPD, and then to the AECOPD (p< 0.001). During an AECOPD episode, the raised serum SP-D levels subsided at day 5 (p> 0.05), fell markedly at day 14 (p< 0.001), and continued to decline at day 30 (p< 0.001). Among patients with SCOPD, serum SP-D levels correlated positively with the BODE index (p< 0.01).

Conclusions: The longitudinal changes in serum SP-D levels during an AECOPD episode suggest that SP-D may be a potential systemic biomarker for COPD exacerbation. The correlation of serum SP-D levels with the BODE index suggests that circulating SP-Ds can reflect the overall severity of SCOPD.
Evaluation of Reference Genes and Normalization Strategy for Quantitative Real-Time PCR in Human Pancreatic Carcinoma
Authors: Mohelnikova-Duchonova Beatrice , Oliverius Martin , Honsova Eva , Soucek Pavel
Published: June 2013

Histologically verified pairs (n= 10) of pancreatic tumors and non-neoplastic tissues were used for quantitative real-time PCR and the stability of 24 reference genes was analyzed with geNorm and NormFinder software. Raw Cqvalues correlated with the degree of RNA degradation. This correlation was abolished by normalization to Cqof 18S endogenous control gene. Both geNorm and NormFinder programs suggested EIF2B1, ELF1, MRPL19, and POP4 as the same most stable genes. We have thus identified suitable reference genes for future expression studies in pancreatic carcinoma. Normalization method reducing the effects of RNA degradation on the quality of results was also developed.
Molecular Alterations in Epidermal Growth Factor Receptors as Potential Predictors of Invasion in Complete Hydatidiform Moles (CHM)
Authors: Jacob Jemima , Balaram Prabha
Published: June 2013

Molecular alterations in Epidermal growth factor receptor (EGFR) were investigated for the first time in molar placenta using protein expression, activation status, differential amplification status and mutational analysis. Invasive lesions showed upregulation of internal domain and downregulation of external domain with concomitantly high gene amplification and phosphorylation. Mutations distributed across different exons in non-invasive cases in contrast to single mutations restricted to exons 4 and 6 in invasive cases displayed a strong correlation to overexpression and phosphorylation status suggesting that higher copies of EGFR gene and mutations in exon 4&6 influence the invasive capacity of trophoblasts and can be used as a biomarker of invasion.
Association of theHindIIIand S447X Polymorphisms inLPLGene with Hypertension and Type 2 Diabetes in Mexican Families
Authors: Muñoz-Barrios Salvador , Guzmán-Guzmán Iris Paola , Muñoz-Valle José Francisco , Salgado-Bernabé Aralia Berenice , Salgado-Goytia Lorenzo , Parra-Rojas Isela
Published: June 2013

Lipoprotein lipase (LPL) is a key enzyme in lipid metabolismand is associatedwith obesity, dyslipidemias, hypertension (HTN) and type 2 diabetes mellitus (T2DM).LPLgene polymorphisms can be related with the development of cardiovascular risk factors. The present study was conducted to analyze the relationship of theHindIIIand S447X polymorphisms inLPLgene with cardiovascular risk factors in Mexican families. The study population comprised ninety members of 30 Mexican families, in which an index case had obesity, were included in the study. We evaluated the body composition by bioelectrical impedance. Peripheral blood samples were collected to determine biochemical parameters. Screening for both polymorphisms was made by PCR-RFLPs. In the parents, both polymorphisms were in Hardy-Weinberg’s equilibrium. We found that the genotype T/T ofHindIIIwas associated with diastolic blood pressure ≧ 85 mmHg (OR = 1.1;p= 0.011), whereas the genotype C/C of S447X was associated with systolic blood pressure ≧ 130 mmHg (OR = 1.2;p< 0.001), diastolic blood pressure ≧ 85 mmHg (OR = 1.3;p< 0.001), T2DM (OR = 1.3;p< 0.001) and with increase of total cholesterol (β = 23.6 mg/mL;p= 0.03). These data suggest that theHindIIIand S447XLPLgene polymorphisms can confer susceptibility for the development of hypertension and T2DM in Mexican families.
Maternal Risk for Down Syndrome Is Modulated by Genes Involved in Folate Metabolism
Authors: Zampieri Bruna Lancia , Biselli Joice Matos , Goloni-Bertollo Eny Maria , Vannucchi Hélio , Carvalho Valdemir Melechco , Cordeiro José Antônio , Pavarino Érika Cristina
Published: June 2013

Studies have shown that the maternal risk for Down syndrome (DS) may be modulated by alterations in folate metabolism. The aim of this study was to evaluate the influence of 12 genetic polymorphisms involved in folate metabolism on maternal risk for DS. In addition, we evaluated the impact of these polymorphisms on serum folate and plasma methylmalonic acid (MMA, an indicator of vitamin B12status) concentrations. The polymorphismstranscobalamin II (TCN2)c.776C>G,betaine-homocysteine S-methyltransferase (BHMT)c.742A>G,methylenetetrahydrofolate reductase (NAD(P)H) (MTHFR)c.677 C>T and theMTHFR677C-1298A-1317T haplotype modulate DS risk. The polymorphismsMTHFRc.677C>T and solute carrier family19 (folate transporter), member 1 (SLC19A1)c.80 A>G modulate folate concentrations, whereas the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) c.66A>G polymorphism affects the MMA concentration. These results are consistent with the modulation of the maternal risk for DS by these polymorphisms.
Caveolin-1 Expression in Thyroid Neoplasia Spectrum: Comparison of Two Commercial Antibodies
Authors: Janković Jelena , Paskaš Svetlana , Marečko Ilona , Božić Vesna , Cvejić Dubravka , Savin Svetlana
Published: June 2013

We evaluated caveolin-1 expression in the human thyroid neoplasia spectrum with the aim of examining differences in expression as detected by two anti-caveolin-1 antibodies, and secondly, to investigate the association of caveolin-1 expression levels with aggressive papillary thyroid carcinoma (PTC). Immunohistochemical staining using sc894 or AV09019 antibodies revealed that caveolin-1 was generally overexpressed in the PTC group as a whole (classical and follicular variant) when compared to peritumoral tissue (PT), while it was not detected in about half of follicular thyroid carcinoma (FTC) and majority of follicular adenomas (FTA). Caveolin-1 expression decreased in the following order: clPTC, fvPTC, FTC, PT and FTA. The diagnostic accuracy of AV09019 was better than that of sc894 for discriminating: FTA from FTC, FTA or FTC from the follicular variant of PTC, total PTC from nonmalignant tissue, and malignant tumors from nonmalignant tissue. Spearman's analysis revealed positive correlations of caveolin-1 expression and extrathyroidal invasion (p < 0.05) in PTC for both antibodies. Additionally, AV09019 antibody correlated caveolin-1 upregulation with pathological T status.

To conclude, as an immunohistochemical marker AV09019 antibody performed better than sc894 in distinguishing certain histotypes of thyroid tumors. In addition, increased expression of caveolin-1 may be considered as an indicator of papillary carcinoma progression.
SP-D Polymorphisms and the Risk of COPD
Authors: Shakoori Tania A. , Sin Don D. , Bokhari S. Nazim Hussain , Ghafoor Farkhanda , Shakoori A. R.
Published: June 2013

Introduction: There are limited data linking serum levels of surfactant protein D, its genetic polymorphisms to the risk of Chronic Obstructive Pulmonary Disease (COPD).Objectives: We sought to investigate these relationships using a case control study design.

Methods: Post bronchodilator values of FEV1/FVC <0.7 were used to diagnose COPD patients (n= 115). Controls were healthy subjects with normal spirometry (n= 106) Single nucleotide polymorphisms (rs721917, rs2243639, rs3088308) were genotyped using polymerase chain reaction (PCR) and restriction analysis. Serum SP-D levels were measured using a specific immunoassay.

Results:Allele ‘A’ at rs3088308 (p< 0.00,B= −0.41) and ‘C’ allele at rs721917 (p= 0.03; B = −0.30) were associated with reduced serum SP-D levels. Genotype ‘T/T’ at rs721917 was significantly associated with risk of COPD (p= 0.01). Patients with repeat exacerbations had significantly higher serum SP-D even after adjusting for genetic factors.

Conclusions:We report for the first time that rs3088308 is an important factor influencing systemic SP-D levels and confirm the previous association of rs721917 to the risk of COPD and serum SP-D levels.
Two Potential Biomarkers Identified in Mesenchymal Stem Cells and Leukocytes of Patients with Sporadic Amyotrophic lateral Sclerosis
Authors: Nachmany Henny , Wald Shane , Abekasis Michal , Bulvik Shlomo , Weil Miguel
Published: June 2013

Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disorder caused by degeneration of motor neurons. The cause for most cases of ALS is multi-factorial,this enhances the need to characterize and isolate specific biomarkers found in biological samples from ALS patients. To this end we use human mesenchymal stem cells (hMSC) derived from the bone marrow of six ALS patients (ALS hMSC) and identified two genes, Cytoplasmic FMR Interacting Protein 2 (CyFIP2) and Retinoblastoma (Rb) Binding Protein 9 (RbBP9) with a significant decrease in post transcriptional A to I RNA editing compared to hMSC of healthy individuals. At the transcriptional level we show abnormal expression of these two genes in ALS hMSC by quantitative real time-PCR (qRT-PCR) and Western blot suggesting a problem in the regulation of these genes in ALS. To strengthen this view we tested by qRT-PCR the expression of these genes in peripheral blood leukocytes (PBL) isolated from blood samples of 17 ALS patients and found that CyFIP2 and RbBP9 levels of expression were significantly different compared to the levels of expression of these two genes in 19 normal PBL samples. Altogether we found two novel ALS potential biomarkers in non-neural tissues from ALS patients that may have direct diagnostic and therapeutic implications to the disease.
Subphenotype-Dependent Disease Markers for Diagnosis and Personalized Treatment of Autism Spectrum Disorders
Authors: Hu Valerie W.
Published: June 2013

Autism spectrum disorders (ASD) are a collection of neurodevelopmental disorders that are currently diagnosed solely on the basis of abnormal reciprocal language and social development as well as stereotyped behaviors. Without genetic or molecular markers for screening, individuals with ASD are typically not diagnosed before the age of 2, with milder cases diagnosed much later. Because early diagnosis is tantamount to early behavioral intervention which has been shown to improve individual outcomes, an objective biomarker test that can diagnose at-risk children perinatally is a medical imperative. The rapidly increasing prevalence of ASD in the United States (now estimated at 1 in 88 individuals) also makes early diagnosis and intervention a public health imperative. This article reviews recent genome-wide (genomic) approaches to the identification of disease markers that may be used not only for diagnosis of ASD, but also for the informed development of novel drugs that target specific core symptoms of ASD. Because of the heterogeneity of clinical manifestations associated with the ASD population, this review also addresses the importance of dividing individuals with ASD into clinically relevant subphenotypes in the quest to identify appropriate biomarkers.
Impact of Renin-Angiotensin-Aldosterone System Gene Polymorphisms on Left Ventricular Dysfunction in Coronary Artery Disease Patients
Authors: Mishra Avshesh , Srivastava Anshika , Mittal T. , Garg N. , Mittal B.
Published: June 2013

Background: Left ventricular dysfunction (LVD), followed by fall in cardiac output is one of the major complications in some coronary artery disease (CAD) patients. The decreased cardiac output over time leads to activation of the renin-angiotensin-aldosterone system which results in vasoconstriction by influencing salt-water homeostasis. Therefore, the purpose of the present study was to explore the association of single nucleotide polymorphisms (SNPs) in angiotensin I converting enzyme;ACE(rs4340), angiotensin II type1 receptor; AT1 (rs5186) and aldosterone synthase;CYP11B2(rs1799998) with LVD.

Methods and results: The present study was carried out in two cohorts. The primary cohort included 308 consecutive patients with angiographically confirmed CAD and 234 healthy controls. Among CAD, 94 with compromised left ventricle ejection fraction (LVEF ≤ 45) were categorized as LVD. The ACE I/D, AT1 A1166C andCYP11B2T-344C polymorphisms were determined by PCR. Our results showed that ACE I/D was significantly associated with CAD but not with LVD. However, AT1 1166C variant was significantly associated with LVD (LVEF ≤ 45) (p value=0.013; OR=3.69), butCYP11B2(rs1799998) was not associated with either CAD or LVD. To validate our results, we performed a replication study in additional 200 cases with similar clinical characteristics and results again confirmed consistent findings (p value=0.020; OR=5.20).

Conclusion: AT1 A1166C plays important role in conferring susceptibility of LVD.
Mutant Mouse Models of Autism Spectrum Disorders
Authors: Provenzano Giovanni , Zunino Giulia , Genovesi Sacha , Sgadó Paola , Bozzi Yuri
Published: June 2013

Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental diseases characterized by a triad of specific behavioral traits: abnormal social interactions, communication deficits and stereotyped or repetitive behaviors. Several recent studies showed that ASDs have a strong genetic basis, contributing to the discovery of a number of ASD-associated genes. Due to the genetic complexity of these disorders, mouse strains with targeted deletion of ASD genes have become an essential tool to investigate the molecular and neurodevelopmental mechanisms underlying ASD. Here we will review the most relevant genetic mouse models developed by targeted inactivation of ASD-associated genes, and discuss their importance for the development of novel pharmacological therapies of these disorders.