bluuebunny/crossref_metadata_2025_split huggingface dataset:
CYP17 MspA1 Polymorphism and Age at Menarche: A Meta‐Analysis
Authors: Pei Yu-Fang , Zhang Lei , Deng Hong-Wen , Dvornyk Volodymyr 
Published: June 2013

Objective: Literature data on the effects of CYP17 MspA1 polymorphism on age at menarche (AAM) are inconsistent. To reexamine this controversy, we performed a meta‐analysis.Study design: In total 16 studies containing more than 11000 individuals of various ethnicities were selected for the analyses. For 11 case‐control studies, odds ratio (OR) was employed to evaluate the risk of late AAM for each study, using homozygote at the wild‐type allele as a control group. For the 5 studies with continuous outcomes, the effect size was estimated using the Hedges’ adjusted g, which is calculated based on the standardized mean difference between groups of subjects with early and late AAM.Results: We did not find evidence for association of the MspA1 polymorphism with AAM in the combined case‐control sample with mixed ethnic background (OR = 1.03, 95% CI: 0.90–1.18, P = 0.66), in the monoethnic case‐control sample of Caucasian females (OR = 1.09, 95% CI: 0.99–1.20, P = 0.08) and in the combined sample with continuous traits (Hedges’ g = 0.33 and −0.041, 95% CI: −0.14–0.80 and −0.18–0.10, P values 0.17 and 0.56 for the pooled population sample and monoethnic sample of Caucasian females, respectively).Conclusion: Our study showed that CYP17 MspA1 polymorphism was not a significant independent risk factor of AAM. Further studies are needed to clarify the effects of the interaction between this gene and other genetic and/or environment factors on AAM.
Sensitivity and Frequencies of Dystrophin Gene Mutations in Thai DMD/BMD Patients As Detected by Multiplex PCR
Authors: Sura Thanyachai , Eu-ahsunthornwattana Jakris , Pingsuthiwong Sarinee , Busabaratana Manisa 
Published: June 2013

Background: Duchenne muscular dystrophy (DMD), a lethal X‐linked disease affecting 1 in 3500 male births, and its more benign variant, Becker muscular dystrophy (BMD), are caused by mutations in the dystrophin gene. Because of its large size, analysing the whole gene is impractical. Methods have been developed to detect the commonest mutations i.e. the deletions of the exons. Although these tests are highly specific, their sensitivity is inherently limited by the prevalence of deletions, which differs among different populations.Methods: We reviewed our database for the detection of Dystrophin gene mutation by means of 31‐exon multiplex PCR in Thai males, diagnosed clinically and biochemically with DMD or BMD from July 1994 to November 2006. One index patient was chosen from each family for statistical analysis. The overall sensitivity of the test, the number of fragment deleted, and the deletion frequency of each fragment were calculated, along with their 95% confidence intervals (C.I.).Results: We found deletions in 99 out of the 202 index patients (49%; Bayesian 95% C.I. = 42%–56%). 51% of these had deletion in only one of the 31 exons tested, while the patient with the most extensive deletions had 14 exons deleted. The mean number of deleted exons were 2.84 (BCa bootstrap 95% C.I. = 2.37–3.48), or 5.02 (3.81–6.85) if all the untested exons adjacent to the confirmed deleted exons were assumed to be deleted. The region spanning exons 44‐52 was the most frequently deleted. These were similar to those reported in the Japanese.Conclusion: The multiplex PCR detected deletions only in about half of the Thai patients. The diseases therefore should not be excluded solely on the negative result if DMD/BMD is strongly suspected.
Circulating Cell‐Free DNA in Plasma of Locally Advanced Rectal Cancer Patients Undergoing Preoperative Chemoradiation: A Potential Diagnostic Tool for Therapy Monitoring
Authors: Zitt Matthias , Müller Hannes M. , Rochel Marina , Schwendinger Verena , Zitt Marion , Goebel Georg , DeVries Alexander , Margreiter Raimund , Oberwalder Michael , Zeillinger Robert , Öfner Dietmar 
Published: June 2013

Circulating cell‐free DNA opens up an interesting field for therapy monitoring, in particular during multimodal therapy protocols. The objective of this proof of principle study was to evaluate whether the amount of circulating plasma DNA has the potential to serve as a marker for therapy monitoring during the treatment course of locally advanced rectal cancer patients. We especially focused on kinetics of circulating DNA to assess whether variances in kinetics have the potential to discriminate between therapy responders and nonresponders.The amount of circulating DNA in plasma of rectal cancer patients undergoing preoperative chemoradiation was determined using real‐time PCR before chemoradiation, after the end of chemoradiation and at the end of treatment. The study population was divided into responders (ypT0‐T2 stage) and nonresponders (ypT3‐T4 stage). Both groups showed comparable median plasma DNA values before and after the end of chemoradiation. At the end of treatment responders showed a further decrease in circulating DNA, whereas in nonresponders the circulating DNA manifestly increased (P = 0.006).This study demonstrates that circulating DNA in plasma of rectal cancer patients undergoing preoperative chemoradiation might serve as a surrogate marker to discriminate between responders and nonresponders. Therefore, we hypothesize that quantification of plasma DNA could be of use as an easily accessible tool for therapy monitoring in these patients.
Polymorphisms of Toll Like Receptors in the Genetics of Severe RSV Associated Diseases
Authors: Mailaparambil Beena , Krueger Marcus , Heinze Jessica , Forster Johannes , Heinzmann Andrea 
Published: June 2013

Toll like receptors (TLRs) are an essential part of the innate immune response. So far, ten different TLRs were identified in humans. They recognize a wide range of microbial and viral pathogens. Infection by respiratory syncytial virus (RSV) is still a major health problem, about 2% of all children are hospitalised due to RSV bronchiolitis during their first 2 years of live. TLR4 has already been described in association with RSV associated diseases by us and others.Thus we were interested whether other TLRs are also involved in the genetics of severe RSV infection. We genotyped 19 polymorphisms in the autosomal TLRs, these are TLR1, 2, 3, 5, 6, 9 and 10. Association analyses by the Armitage′s Trend test revealed weak association of one TLR9 promoter polymorphism with RSV infection (p = 0.013). In addition, association was found with TLR10 haplotypes (p = 0.024).We conclude from our data – that – although we can not rule out a minor involvement of TLR9 polymorphism and TLR10 haplotypes – TLRs other than TLR4 do not play a major role in the genetics of severe RSV associated diseases. Future studies should focus on additional genes of the innate immune response.
Detection of Membrane Fluidity in Submitochondrial Particles of Platelets and Erythrocyte Membranes from Mexican Patients with Alzheimer Disease by Intramolecular Excimer Formation of 1,3 Dipyrenylpropane
Authors: Ortiz G.G. , Pacheco-Moisés F. , El Hafidi M. , Jiménez-Delgado A. , Macías-Islas M. A. , Corral S. A. Rosales , de la Rosa A. Célis , Sánchez-González V. J. , Arias-Merino E. D. , Velázquez-Brizuela I. E. 
Published: June 2013

It has been suggested that mitochondrial dysfunction and defects in membrane structure could be implied in AD pathogenesis. The aim of the present work was the study of membrane fluidity in submitochondrial platelet particles and erythrocyte membranes from Mexican patients. Blood samples were obtained from 30 patients with Alzheimer disease and 30 aged‐matched control subjects. Membrane fluidity determinations were done using a very low concentration of the fluorescent dipyrenylpropane probe incorporated in both types of membranes. This probe is able to give excimer and monomer fluorescence, therefore it can be used to monitor fluidity changes in biological membranes.The data obtained showed that in submitochondrial particles from AD patients, the excimer to monomer fluorescent intensity ratio was lower (0.231 ± 0.008) than aged‐matched control subjects (0.363 ± 0.014). Therefore, membrane fluidity was lower in AD samples. On the other hand, we found similar membrane fluidity in erythrocytes from AD patients and aged‐matched controls: the fluorescent intensity ratios were 0.312 ± 0.03 and 0.305 ± 0.033, respectively. In addition, lipid peroxidation in submitochondrial particles and erythrocyte membranes was higher in AD samples than in aged‐matched controls. These data suggest that submitochondrial platelet particles are more sensitive to oxidative stress than erythrocyte membranes.
Candidate Gene Discovery Procedure after Follow‐Up Confirmatory Analyses of Candidate Regions of Interests for Alzheimer’s Disease in the NIMH Sibling Dataset
Authors: Baye Tesfaye M. , Perry Rodney T. , Wiener Howard W. , Chen Zuomin , Harrell Lindy E. , Go Rodney C. P. 
Published: June 2013

The objective of this research was to develop a procedure to identify candidate genes under linkage peaks confirmed in a follow‐up of candidate regions of interests (CRIs) identified in our original genome scan in the NIMH Alzheimer’s diseases (AD) Initiative families (Blacker et al. [1]). There were six CRIs identified that met the threshold of multipoint lod score (MLS) of ≥ 2.0 from the original scan. The most significant peak (MLS = 7.7) was at 19q13, which was attributed to APOE. The remaining CRIs with ‘suggestive’ evidence for linkage were identified at 9q22, 6q27, 14q22, 11q25, and 3p26. We have followed up and narrowed the 9q22 CRI signal using simple tandem repeat (STR) markers (Perry et al. [2]). In this confirmatory project, we have followed up the 6q27, 14q22, 11q25, and 3p26 CRIs with a total of 24 additional flanking STRs, reducing the mean interval marker distance (MID) in each CRI, and substantially increase in the information content (IC). The linkage signals at 6q27, 14q22 and 11q25 remain ‘suggestive’, indicating that these CRIs are promising and worthy of detailed fine mapping and assessment of candidate genes associated with AD.We have developed a bioinformatics approach for identifying candidate genes in these confirmed regions based on the Gene Ontology terms that are annotated and enriched among the systematic meta‐analyzed genes, confirmed by at least three case‐control samples, and cataloged in the “AlzGene database” as potential Alzheimer disease susceptibility genes (http://www.alzgene.org).
Ischemia‐Modified albumin level in type 2 diabetes mellitus—Preliminary report
Authors: Piwowar Agnieszka , Knapik-Kordecka Maria , Warwas Maria 
Published: June 2013

Aim: The main goal of the present study was the evaluation of ischemia‐modified albumin (IMA) in patients with type 2 diabetes mellitus and estimation of its connection with vascular complications, glycemic control, hypertension, dyslipidemia and obesity.Methods: In 76 diabetic patients and 25 control subjects, a plasma level of IMA by manually performed, spectrophotometric Co(II)‐albumin binding assay was determined. Other parameters such as glucose, fructosamine, HbA1c, total cholesterol and its fractions (HDL, LDL), triglicerydes were estimated by routine methods.Results: Diabetic patients had significantly higher level of IMA in comparison with control subjects. There were not significant differences between groups with various states of vascular complications although the lowest concentration of IMA was observed in patients with microangiopathy. Patients with poor glycemic control had higher IMA level in comparison with these with good glycemic control. Significant correlation was observed between IMA and HbA1c. Among the risk factors, only blood pressure and LDL showed a weak relationship with IMA level.Conclusions: Our results revealed, for the first time, higher level of IMA in diabetic patients which confirms that it may be of non‐cardiac origin. We can suggest that the albumin molecule in plasma of diabetic patients is modified in the chronic hypoxia conditions provoked mainly by hyperglycemia and oxidative stress in diabetes.
Homogeneous Assay of rs4343, an ACE I/D Proxy, and an Analysis in the British Women’s Heart and Health Study (BWHHS)
Authors: Abdollahi Mohammad Reza , Huang Shuwen , Rodriguez Santiago , Guthrie Philip Alexander Isles , Smith George Davey , Ebrahim Shah , Lawlor Debbie A. , Day Ian N. M. , Gaunt Tom R. 
Published: June 2013

Current literature suggests that ACE SNP rs4343, ACE 2350A>G in exon 17, T202T, may be the best proxy for the ACE Alu I/D whereas rs4363 and rs4362 may be slightly stronger predictors of ACE levels. Considering reported difficulties in genotyping ACE I/D and stronger associations of rs4343 than ACE I/D with plasma ACE levels in Africans, and suitability of rs4343 for allelic mRNA (cDNA) studies, we developed and validated a liquid phase assay for rs4343, which has advantage on both functional and technical grounds. We confirmed that rs4343, is in near perfect linkage disequilibrium (D’=1, r2 =0.88, n=64) with ACE I/D in Europeans (A and G alleles of rs4343 marking insertion and deletion alleles of ACE I/D respectively).We then studied its association with metabolic and cardiovascular traits in 3253 British women (60–79 years old).Apart from a nominal trend of association with diastolic blood pressure (p anova=0.08; p trend=0.05), no other associations were observed. A post‐hoc vascular and general phenome scan revealed no further associations.We conclude that ACE I/D is not a major determinant of metabolic and cardiovascular traits in this population. Liquid phase genotyping of SNP rs4343 may be preferable to gel based ACE I/D genotyping both for technical and functional reasons.
Matriptase and Survivin Expression Associated with Tumor Progression and Malignant Potential in Breast Cancer of Chinese Women: Tissue Microarray Analysis of Immunostaining Scores with Clinicopathological Parameters
Authors: Tsai Wen-Chiuan , Chu Chi-Hong , Yu Cheng-Pin , Sheu Lai-Fa , Chen Ann , Chiang Hung , Jin Jong-Shiaw 
Published: June 2013

Objective: The aim of this study was to examine the expression of matriptase and survivin in breast carcinoma and correlate with clinicopathological parameters.Methods: Immunohistochemical analysis of matriptase and survivin were performed in tissue microarray slides of 290 cases, including 11 normal breast tissue; 27 fibrocystic disease; 17 fibroadenoma; 6 atypical ductal hyperplasia; 39 ductal carcinoma in situ, low grade (DCIS, low grade); 39 ductal carcinoma in situ, high grade (DCIS, high grade); 27 invasive ductal carcinoma, grade I (IDC, grade I); 78 invasive ductal carcinoma, grade II (IDC, grade II); and 46 invasive ductal carcinoma, grade III (IDC, grade III).Results: The average immunostaining scores of matriptase were 44.1 in normal breast tissue, 52.7 in fibrocystic disease, 76.5 in fibroadenoma, 81.7 in atypical ductal hyperplasia, 133.7 in low‐grade DCIS, and 155.8 in high‐grade DCIS. Among 151 breast IDC cases, the average immunostaining scores of matriptase were 172.7 in grade I, 211.7 in grade II, and 221.2 in grade III. Additionally, the average immunostaining scores of surviving also correlate with tumor grades and stages.Conclusions: Higher expressions of matriptase and survivin correlate significantly with clinicopathological parameters in breast cancer and the malignant potential in premalignant lesions. In addition, higher survivin expression had poorer prognosis of breast IDC cases.
Variability of Thiobarbituric Acid Reacting Substances in Saliva
Authors: Behuliak Michal , Pálffy Roland , Gardlík Roman , Hodosy Július , Halčák Lukáč , Celec Peter 
Published: June 2013

Introduction: Salivary TBARS are a potential marker of oxidative stress in the oral cavity. Previous studies have found increased levels of salivary TBARS in various diseases. The aim of this study was to assess the variability of salivary TBARS in both genders.Subjects & Methods: Saliva samples from thirty-eight healthy volunteers (18F & 20M) were collected every day during 30 day period. TBARS levels were measured spectrophotometrically using a high-throughput 96-well plate method. Time series analysis was performed using standard statistical methods.Results: Repeated measures ANOVA showed a significant variation of salivary TBARS within day and subjects (p< 0.001). The dynamics did not differ between genders. Intraindividual variability was very high in both genders with coefficients of variation of more than 60%. Interindividual variability was higher in men than in women (73% vs. 46%;p< 0.01).Discussion: The relatively high intraindividual variability indicates that the use of salivary TBARS will be limited to research on a population level, although some informative value might be gained by repeated samplings. Factors influencing the biological variability of salivary TBARS should be identified in further studies.
A Systematic Review of Studies Examining Inflammation Associated Cytokines in Human Abdominal Aortic Aneurysm Samples
Authors: Golledge Alexandra L. V. , Walker Philip , Norman Paul E. , Golledge Jonathan 
Published: June 2013

Objectives: Inflammation is critical in abdominal aortic aneurysm (AAA) but there is no current consensus on which inflammation related cytokines are important. The aim of this review was to systemically assess previous studies investigating the relative expression of inflammation associated cytokines within human AAA samples.Methods: The MEDLINE database was searched for studies which simultaneously examined an array of different inflammation associated cytokines in aortic samples in order to identify those associated with AAA. Focused searches were then conducted for further studies assessing relative concentrations of these cytokines in aortic samples in relation to AAA. Appropriate studies were assessed by two reviewers independently.Results: Eighteen studies were included. A number of different cytokines have been consistently found to be upregulated within AAA by comparison to aortic samples removed from patients without cardiovascular disease, however findings relative to samples of aortic athero-thrombosis were less consistent. TNFA and INFG appear to be the most consistently associated with AAA in studies using both normal and atherosclerotic controls. Cautious interpretation of these data is recommended due to a number of methodological problems.Conclusions: This systematic review suggests that TNFA and INFG are the most consistently upregulated cytokines in large AAAs. Further studies utilizing larger populations, new proteomic techniques and better patient matching are required.
Clinical Significance of Inflammatory Markers in Polycystic Ovary Syndrome: Their Relationship to Insulin Resistance and Body Mass Index
Authors: Samy Nervana , Hashim Maha , Sayed Magda , Said Mohamed 
Published: June 2013

Background: Women with polycystic ovary syndrome (PCOS) have an increased prevalence of insulin resistance (IR) and related disorders. Elevated serum levels of high sensitivity CRP (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factorα(TNF-α) reflect low-grade chronic inflammation and have been associated with several insulin-resistant states; they are useful cardiovascular risk markers. The objective of this study was to investigate whether soluble inflammatory markers are altered in PCOS focusing on its relationship with obesity and indexes of insulin resistance.Patients and methods: One hundred and eight women with PCOS and 75 healthy women were recruited. Patients were divided according to body mass index (BMI) into two groups; group I (BMI < 27 kg/m2) and group II (BMI ≥ 27 Kg/m2). Serum levels of hs-CRP, IL-6, and TNF-α, lipid and hormone profiles were measured.Results: PCOS patients had increased levels of testosterone, luteinizing hormone (LH), androstendione, insulin level and HOMA index compared to healthy BMI matched controls. High-density lipoprotein (HDL) concentrations were significantly reduced in both patient groups compared to their controls, while triglyceride levels were significantly increased in obese group compared to controls. There were no significant difference in serum inflammatory markers hs-CRP, IL-6 and TNF-αbetween group I and their matched controls. On the other hand, there were significant increase in these markers between group II and their matched controls. There were highly significant positive correlation between hs-CRP and IL-6 (r= 0.702,P< 0.001) and between hs-CRP and TNF-α(r= 0.621,P<0.001), also between IL-6 and TNF-α(r= 0.543,P< 0.001). These inflammatory markers correlated significantly with BMI and HOMA index. Multiple regression analysis revealed that BMI and HOMA were predictors of IL-6 levels (b= 11.173,P< 0.001,b= 13.564,P< 0.001 respectively) and BMI was the only predictor of hs-CRP levels (b= 12.578,P< 0.001) and TNF-αlevels (b= 0.134,P< 0.001).Conclusion: PCOS and obesity induce an increase in serum inflammatory cardiovascular risk markers. The precise mechanisms underlying these associations require additional studies to clarify the state of the cardiovascular system in women with PCOS compared with controls in large numbers of patients to determine the relative contribution of different factors including insulin resistance, androgen status and BMI.
TPMT and DPD Polymorphisms: Efficient Screening Method for Indian Patients Considering Taking Thiopurine and 5-FU Drugs
Authors: Ashavaid T. F. , Raghavan Rani , Shah Swarup , Kapadia Asha , Almel Sachin , Desai Devendra 
Published: June 2013

Introduction: Development of DNA-based tests for TPMT/DPD polymorphisms can help clinicians and patients to make important decisions about cancer treatment. Also, due to lack of Indian data, we aimed at the development and validation of these tests in Indian patients.Materials and Methods: Molecular assays were used for identifying TPMT/DPD variations; validated by DNA sequencing.Results: Molecular assays have been used for screening TPMT∗2,∗3A,∗3B,∗3C alleles and IVS14+1(G→A) in DPD gene. A patient, exhibiting neutropenia on 6-MP was observed to be G460A-homozygote, while, two Acute Lymphoblastic Leukemia (ALL) patients with side-effects exhibited wild-type alleles. Two patients showing 6-MP side-effects and responding well to the same drug at later stage also carried wild-type alleles.Discussion: G460A homozygosity in a patient allowed clinicians to stop 6-MP treatment, improving patient's health status. Two ALL patients showing side-effects were wild-type, indicating presence of unidentified rare variations. Two patients with wild-type allele showed side-effects during 6-MP treatment, but responded well to same drug at later stage, suggesting side-effects to be attributable to multiple biological and environmental processes. Absence of IVS14+1(G→A) in DPD gene will not exclude possibility of another mutation.Conclusion: Molecular assays for determining common TPMT/DPD variations, can provide accurate diagnosis and efficient therapies in future clinical studies.