bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glyco‐biomarkers: Potential Determinants of Cellular Physiology and Pathology
Authors: Alavi Azita , Axford John S. 
Published: June 2013

Once dismissed as just the icing on the cake, sugar molecules are emerging as vital components in life’s intricate machinery. Our understanding of their function within the context of the proteins and lipids to which they are attached has matured rapidly, and with it the far reaching clinical implications are becoming understood.Recent advances in high‐throughput glycomic techniques, glyco biomarker profiling, glyco‐bioinformatics and development of increasingly sophisticated glyco‐arrays, combined with our increased understanding of the molecular details of glycosylation have facilitated the linkage between aberrant glycosylation and human diseases, and highlighted the possibility of using glyco‐biomarkers as potential determinants of disease and its progression.The focus of this review is to give an insight into the biological significance of these glycomodifications, highlight some specific examples of glyco‐biomarkers in relation to autoimmunity and in particular rheumatoid arthritis, and to explore the exciting possibility of exploiting these for diagnostic and prognostic strategies.
Metabolic Background Determines the Importance ofNOS3Polymorphisms in Restenosis after Percutaneous Coronary Intervention: A Study in Patients with and without the Metabolic Syndrome
Authors: Pons Douwe , Monraats Pascalle S. , Zwinderman Aeilko H. , de Maat Moniek P. M. , Doevendans Pieter A. F. M. , de Winter Robbert J. , Tio René A. , Waltenberger Johannes , Jukema J. Wouter 
Published: June 2013

Variation in theNOS3gene has been related to the development of restenosis. The Glu298Asp polymorphism has previously been investigated for its effect on NO levels and the development of restenosis. However, the variability of findings gave rise to the hypothesis that the functional significance of this polymorphism may only become manifest under conditions of endothelial dysfunction. Since patients with the metabolic syndrome are known to have endothelial dysfunction, we aimed to investigate if the significance ofNOS3polymorphisms may depend on the presence of the metabolic syndrome.We examined the impact of the -949 A/G, the -716 C/T and the Glu298Asp polymorphisms in theNOS3gene on the risk of clinical restenosis in a previously described subpopulation of the GENDER-study, a multicenter prospective study design that enrolled consecutive patients after successful PCI. This subpopulation consisted of 901 patients of whom sufficient data were available to establish absence or presence of the metabolic syndrome. Of these patients, 448 had the metabolic syndrome. Clinical restenosis, defined as target vessel revascularization (TVR), was the primary endpoint.We demonstrated that the minor -949G, -716T and 298Asp alleles were associated with a significantly increased risk of TVR in patients with the metabolic syndrome (HR: 1.58 [95%CI: 1.04–2.40], HR: 1.95 [95%CI: 1.02–3.70] and HR: 1.67 [95%CI: 1.09–2.54], respectively). In the group without the metabolic syndrome we observed no association between the three polymorphisms and TVR.
Serum Surfactant Protein D during Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Shakoori Tania Ahmed , Sin Don D. , Ghafoor Farkhanda , Bashir Saira , Bokhari S. Nazim Hussain 
Published: June 2013

Background: There is a paucity of lung specific biomarkers to diagnose exacerbations of chronic obstructive pulmonary disease (COPD) and to track their progression. Surfactant protein D (SP-D) is a pulmonary collectin regulating the innate immunity of the lung and its serum expression is perturbed in COPD. However, it is not known whether serum levels change during exacerbations. We sought to determine whether serum SP-D levels are raised in COPD exacerbations.Objectives: To determine whether or not patients with exacerbations have elevated serum SP-D levels compared with asymptomatic controls, stable disease.Study design: case control study.Methods: We measured serum SP-D levels from patients with stable COPD (n= 14), patients experiencing acute exacerbations (n= 13) and in control subjects (n= 54) using a specific immunoassay and compared the levels using analysis of variance.Results: Serum SP-D levels were significantly increased in patients who experienced an acute exacerbation (227 ± 120 ng/mL) compared to patients with stable disease (151 ± 83 ng/mL) or control subjects (128 ± 65 ng/mL;p= 0.003). Serum SP-D levels were also found to be inversely related to various lung function parameters including FEV1/FVC% predicted.Conclusions: Our study suggests that serum SP-D levels are increased in patients during exacerbations and may be a potential diagnostic biomarker for COPD exacerbations.
Natriuretic Peptides~: Prediction of Cardiovascular Disease in the General Population and High Risk Populations
Authors: Hildebrandt Per 
Published: June 2013

The natriuretic peptides, especially the B-type peptide (BNP) and its inactive split-product N-terminal proBNP (Nt-proBNP) are increasingly used in screening for heart failure, primarily with reduced systolic function, in patients with symptoms suggestive of heart failure, as well in the stable (General Practitioner) setting as in the acute setting.Supporting this use is a very strong prognostic value of the natriuretic peptides. This has been shown in as well heart failure as acute coronary syndromes, but also in the general population and in high-risk groups as patients with diabetes, hypertension and coronary artery disease.This has of course raised interest for the use of the natriuretic peptides as a risk marker and for screening for heart failure with reduced systolic function in these populations. In symptomatic persons and in high risk populations, the natriuretic peptides have demonstrated a high sensitivity for ruling out the disease, if the right decision limits are choosen. Thus the number of normal echocardiographies can be reduced.More recently, the use in screening asymptomatic persons for left ventricular systolic dysfunction has gained more interest. In the unselected population, screening would probably not be cost-effective. In populations with a higher pre-test probability for heart failure, as patients with diabetes, hypertension and stable coronary artery disease, screening would presumably be more cost-effective, but evidence for the use in this setting is still lacking.
HLA Haplotype A33-B58-Cw10 May Modulate Radiographic Development of Bamboo Spine in Taiwanese Patients with Primary Ankylosing Spondylitis
Authors: Lu Ming-Chi , Yang Kuo-Liang , Huang Kuang-Yung , Tung Chien-Hsueh , Liu Su-Qin , Lai Ning-Sheng 
Published: June 2013

Objective: To evaluate the possible relationship between HLA alleles and bony ankylosis of the spine (bamboo spine) in Taiwanese patients with ankylosing spondylitis (AS).Methods: A small cohort of HLA-B27 positive AS patients was conducted to analyze the effects of alleles and haplotypes on the development of bamboo spine. DNA typing of HLA class I and class II genes were performed by SSP method on primary ankylosing spondylitis patients with bamboo spine (n= 84) and spinal enthesopathy controls (n= 228). Odds ratios with 95% confidence intervals andPvalue were estimated. Determination of the most probable HLA haplotypes on all patients were constructed by comparison of the alleles carried by each patient with the HLA haplotype database established in Taiwanese population studies using homozygosity approach [1] and by expectation-maximum algorithm [2].Results: Allele frequencies of HLA A33, B58, Cw10, DR4, DR17 and DQ2 were significantly lower in bamboo patients as compared to non-bamboo controls. In contrast, allele frequencies of A24, B54, Cw15, DR11 and DR14 were significantly higher in bamboo patients. Less remarkably, high frequencies of B39, B51, Cw1 and Cw2 alleles were also noted in bamboo patients. Considering linkage disequilibria of alleles in haplotypes, HLA-A11-B27-Cw12 was the most common haplotype in both bamboo and non-bamboo groups (95.23% vs. 91.22%, respectively,P= 0.238). Haplotypes A33-B58-Cw10, A33-B58-Cw10-DR13 and A33-B58-Cw10-DR17 were significantly lower in bamboo patients as compared to those in controls (P< 0.001,P= 0.001,P= 0.002, respectively).Conclusion: Haplotypes A33-B58-Cw10, A33-B58-Cw10-DR13 and A33-B58-Cw10-DR17 showed a strong association with bamboo spine in Taiwanese AS patients. Detection of such haplotypes might be a great aid in the management of patients with the disease.
Frequency ofP16INK4aandP14ARFGenes Methylation and Its Impact on Bladder Cancer Cases in North Indian Population
Authors: Ali Hosseini Seyed , Sobti Ranbir Chander , Malekzadeh Kianoosh , Singh Shrawan Kumar , Joshi Kusum 
Published: June 2013

Introduction:Amongst the genitourinary cancers, carcinoma of the urinary bladder is one of the leading causes of death in India. Hypermethylation of the CpG islands of gene promoter is one of the earliest and most frequent epigenetic alterations leading to cancer as well as in its development. Several studies have suggested that tumour suppressor genes play a key role in the development of cancer. Methylation in theCDKN2Ahas been associated with various malignant diseases, but information with respect to urinary bladder cancer is lacking in north Indian population.Materials and methods:We analyzed the methylation ofP16INK4aandP14ARFin 80 tissues and matched blood samples of patients suffering from bladder cancer and 80 blood samples of cancer-free individuals by MS-PCR.Results:In tissue and matched blood samples of bladder cancer patients, the incidence ofP14ARFhypermethylation significantly increased (OR = 0.31, 95%CI = 0.12–0.8,P= 0.01) and (OR = 0.0, 95%CI=0.0–0.62,P= 0.006) respectively with an increase in age. Clinicopathological analysis revealed that P14ARF hypermethylation in tissue and blood samples was significantly associated with invasive stage (≥ T2) (OR = 0.21, 95%CI = 0.08–0.51,P= 0.0002) and (OR = 0.09, 95%CI = 0.03–0.37,P= 0.00001) respectively. Muscle invasive tumour stage (≥T2) showed significant association with increased risk of P16INK4α promoter hypermethylation in tissue and blood samples of patients (OR = 0.38, 95%CI = 0.17–0.82,P= 0.01) and (OR = 0.13, 95%CI = 0.05–0.36,P= 0.00005) respectively.Conclusion:These results suggest that the CpG island hypermethylation status of the defined panel of genes may be a useful biomarker in patients suffering from bladder cancer.
Association of Hypoadiponectinemia with Hypoglutathionemia in NAFLD Subjects with and without Type 2 Diabetes
Authors: Sandhya Narasimhan , Gokulakrishnan Kuppan , Ravikumar Radhakrishnan , Mohan Viswanathan , Balasubramanyam Muthuswamy 
Published: June 2013

Objective: The aim of this study is to measure the extent of oxidative stress and to see whether it has any correlation to changes in adiponectin levels in NAFLD subjects with and without Type 2 diabetes.Methods: Subjects recruited from the Chennai Urban Rural Epidemiology Study comprise of 1: Normal Glucose Tolerance (NGT) subjects without NAFLD; 2: NGT with NAFLD; 3: Type 2 Diabetic patients [T2DM] without NAFLD and 4: T2DM with NAFLD. Thiobarbituric acid reactive substances (TBARS), protein carbonyl (PCO), glutathione and adiponectin levels were measured by standard methods. Ultrasound of the liver was used to diagnose NAFLD.Results: T2DM subjects with NAFLD had significantly (p< 0.001) higher levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PCO) but lower (p< 0.001) GSH/GSSG ratio and adiponectin levels compared to other three groups. The association of hypoadiponectinemia withNAFLD/Type 2 diabetes was significant even after adjusting for age, gender and BMI, but lost when adjusted for parameters of oxidative stress. While palmitate significantly reduced GSH/GSSG ratio in hepatocytes, addition of exogenous recombinant adiponectin restored the GSH/GSSG ratio comparable to those of untreated cells.Conclusion: There exists an association of hypoglutathionemia and hypoadiponectinemia in subjects with NAFLD and/or T2DM. In addition to the known beneficial effects, out study also exposes the antioxidant nature of adiponectin.
Platelet Markers Correlate with Glycemic Indices in Diabetic, but Not Diabetic-Myelodysplastic Patients with Normal Platelet Count
Authors: Dalamaga Maria , Karmaniolas Konstantinos , Lekka Antigoni , Antonakos George , Thrasyvoulides Apollon , Papadavid Evangelia , Spanos Nikolaos , Dionyssiou-Asteriou Amalia 
Published: June 2013

Background: Altered thrombocyte morphology and function have been reported in patients with diabetes mellitus (DM) type 2. The aim of the present study was to determine the associations between platelet morphology markers and hemoglobin A1C (HbA1c), fasting glucose (FG), hypertension and coronary heart disease (CHD) in patients with myelodysplastic syndromes (MDS) and DM, in patients with DM and in controls.Methods: This cross-sectional study included 30 cases with primary MDS with normal platelet count and non-insulin dependent diabetes, 30 non-insulin dependent diabetic patients and 30 non-diabetic, non-MDS controls matched on age and gender. Results: After adjusting for body mass index, platelet number, CHD and hypertension, HbA1cand FG were significant predictors of mean platelet volume (MPV) and platelet distribution width (PDW) in diabetic patients. There was no correlation between platelet parameters and HbA1cor FG in diabetic MDS patients. In controls, FG and hypertension predicted significant differences in platelet morphology. Platelet count correlated with platelet morphology in diabetic MDS and control groups, but not in diabetics.Conclusions: MPV and PDW are associated with glycemic indices in diabetic patients but not in diabetic MDS patients with normal platelet counts. Non-diabetic controls also exhibit FG related changes in platelet morphology. This suggests other factors inherent to bone marrow dysplasia, platelet turnover and biochemistry, or vascular environment affect platelet morphology in diabetic MDS patients even with normal platelet count. Platelet morphology in this population may be an early marker for myelodysplasia. These findings also support platelet morphology change as a marker for elevated macrovascular disease risk.
Serum Markers of Liver Fibrosis: Combining the BIPED Classification and the Neo-Epitope Approach in the Development of New Biomarkers
Authors: Veidal Sanne Skovgård , Bay-Jensen Anne-Christine , Tougas Gervais , Karsdal Morten Asser , Vainer Ben 
Published: June 2013

Background:Fibrosis is a central histological feature of chronic liver diseases and is characterized by the accumulation and reorganization of the extracellular matrix. The gold standard for assessment of fibrosis is histological evaluation of a percutaneous liver biopsy. Albeit a considerable effort have been invested in finding alternative non-invasive approaches, these have not been sufficiently succesfull to replace biopsy assessment.Aim:To identify the extracellular matrix proteins of interest, that as protein degradation fragments produced during extracellular matrix metabolism neo-epitopes, may be targeted for novel biochemical marker development in fibrosis. We used the recently proposed BIPED system (Burden of disease,Investigative,Prognostic,Efficacy andDiagnostic) to characterise present serological markers.Methods:Pubmed was search for keywords; Liver fibrosis, neo-epitopes, biomarkers, clinical trail, extra cellular matrix, protease, degradation, fragment.Results and Conclusion:Implementation of BIPED categorization in the development and validation of fibrosis biomarkers to simplify and standardize the use of existing and future biomarkers seems advantageous. In addition, a systematic use of the neo-epitope approach, i.e. the quantification of peptide epitopes generated from enzymatic cleavage of proteins during extracellular remodeling, may prove productive in the quest to find new markers of liver fibrosis.
Correlation between Eicosanoids in Bronchoalveolar Lavage Fluid and in Exhaled Breath Condensate
Authors: Antczak Adam , Piotrowski Wojciech , Marczak Jerzy , Ciebiada Maciej , Gorski Pawel , Barnes Peter J. 
Published: June 2013

Exhaled breath condensate (EBC) has been increasingly used as a new and non-invasive method to study airway inflammation. In this study we have compared the concentrations of lipid mediators in EBCwith concentrations in bronchoalveolar lavage fluid (BALF).We included 37 patients undergoing bronchoscopy (12 sarcoidosis, 12 COPD, 6 lung cancer, 5 chronic cough, 1 Wegener’s granulomatosis, 1 sclerodermia). Patients were not allowed to have exacerbation or any change in concomitant medication for at least 4 weeks prior to the study. In all patients, EBC was collected immediately prior to the bronchoscopy.The levels of cys-LTs, LTB4, 8-isoprostane were significantly higher in BALF compared to EBC (p < 0.0001, p < 0.001, p < 0.0001 for cys-LTs, LTB4, 8-isoprostane respectively). Moreover, there was a strong positive correlation between both leukotriene B4and 8-isoprostane in BALF and EBC (r= 0.53 andr= 0.79, p < 0.01, respectively) in patients with sarcoidosis and COPD but there was no correlation between eicosanoids BALF and EBC in patients with chronic cough and lung cancer.This is the first study to compare EBC and BALF in different lung diseases which demonstrated significant correlations between the levels of eicosanoids in BALF and EBCin patientswith COPD and sarcoidosis. EBC may be useful inmeasuring inflammation in several inflammatory lung diseases.
Association of PPARγ2(Pro12Ala) and Neuropeptide Y (Leu7Pro) Gene Polymorphisms with Obstructive Sleep Apnea in Obese Asian Indians
Authors: Bhushan Bharat , Guleria Randeep , Misra Anoop , Luthra Kalpana , Kumar Guresh 
Published: June 2013

Background:Obstructive sleep apnea (OSA) is prevalent in 7.5% in urban Asian Indians.Peroxisome proliferator activated receptor gamma2 (PPARγ2)has been implicated in adipocyte differentiation.Neuropeptide Y (NPY)is also considered as a candidate gene for excess body fat accumulation. The association ofPPARγ2 (Pro12Ala)andNPY (Leu7Pro)gene polymorphisms with OSA has not been studied in Asian Indians.Objective:To study the distribution ofPPARγ2 (Pro12Ala)andNPY (Leu7Pro)polymorphism in Asian Indians with and without OSA.Methods and results:This study was carried out in 252 obese subjects [(body mass index (BMI > 25 kg/m2)]; 142 with OSA and 110 without OSA. Measurements included anthropometric and biochemical parameters (fasting blood glucose, lipid profile, various circumferences and skin-fold thicknesses).PPARγ2 (Pro12Ala) and NPY (Leu7Pro) genepolymorphisms were studied in all subjects. The frequency of the variantallele (Ala12) of PPARγ2 genewas significantly higher in subjects with OSA (14.4%) when compared with subjects without OSA (5.5%; χ2= 9.7;p= 0.001). The distribution of the variantallele (Pro7)ofNPY genewas comparable in subjects with OSA (3.5%) and without OSA (3.6%; χ2= 0.001,p= 0.94).Conclusion:This study reveals a significantly higher frequency ofPPARγ2 (Ala12) allelein obese Asian Indians with OSA when compared to obese Asian Indians without OSA.
Gingival Crevicular Fluid Calprotectin, Osteocalcin and Cross-Linked N-Terminal Telopeptid Levels in Health and Different Periodontal Diseases
Authors: Becerik Sema , Afacan Beral , Öztürk Veli Özgen , Atmaca Harika , Emingil Gülnur 
Published: June 2013

Aim:The aim of the present study was to investigate gingival crevicular fluid (GCF) calprotectin, osteocalcin and cross-linked N-terminal telopeptide (NTx) levels in health along with different periodontal diseases.Material and methods:Twenty chronic periodontitis (CP), 20 generalized aggressive periodontitis (G-AgP), 20 gingivitis and 20 healthy subjects were included. Probing depth, clinical attachment level, plaque index and papillary bleeding index was recorded. GCF calprotectin, osteocalcin and NTx levels were analyzed by enzyme-linked immunosorbent assay (ELISA).Results:CP, G-AgP and gingivitis groups had higher GCF calprotectin total amount compared to healthy subjects (p< 0.008). CP and G-AgP groups had similar, but higher levels compared to gingivitis groups (p< 0.008). CP and G-AgP groups had lower GCF osteocalcin total amount compared to gingivitis and healthy groups (p< 0.008). CP group had higher GCF NTx but lower osteocalcin total amount and osteocalcin/NTx ratio than the G-AgP group (p< 0.008)Conclusions:Our results suggest that elevated GCF calprotectin levels play a role as a reliable inflammatory marker in the pathogenesis of periodontal disease. Fluctuating GCF levels of osteocalcin and NTx might point out to the abnormal bone turnover in periodontitis. Our data document for the first time the role of NTx in the pathogenesis of different periodontal diseases.
Association of CD28 IVS3 +17T/C Polymorphism with Soluble CD28 in Rheumatoid Arthritis
Authors: Ledezma-Lozano I. Y. , Padilla-Martínez J. J. , Leyva-Torres S. D. , Parra-Rojas I. , Ramírez-Dueñas M. G. , Pereira-Suárez Ana Laura , Rangel-Villalobos H. , Ruiz-Quezada S. L. , Sánchez-Hernández P. E. , Muñoz-Valle J. F. 
Published: June 2013

Objective:Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology in which inflammatory pathology involves T cell activation and the CD28 costimulatory molecule involved in T cell presentation. The gene includes the CD28 IVS3 +17T/C polymorphism that could be associated with susceptibility to RA whereas the soluble concentrations of CD28 (sCD28) could be related to clinical activity.Methods:We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients.Methods:We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients.Results:RA patients had significantly higher frequencies of the CD28 T allele compared to HS (p= 0.032 OR = 1.59, C.I. 1.02–2.49). In addition, the IVS3 +17 T/T genotype frequency was also increased in RA vs. HS (p= 0.026). The RA patients showed higher sCD28 serum levels than HS (p= 0.001). Carriers of the T/T genotype in RA patients showed higher sCD28 levels than C/C carriers (p= 0.047). In addition, a correlation between sCD28 and Spanish HAQ-DI (correlation, 0.272;p= 0.016), was found.Conclusion:The T allele in CD28 IVS3 +17T/C polymorphism is associated with a susceptibility to RA in Western Mexico. In addition, increased sCD28 levels are related to T/T genotype in RA patients.