bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered β‐Amyloid Precursor Protein Isoforms in Mexican Alzheimer’s Disease Patients
Authors: Sánchez-González V. J. , Ortiz G. G. , Gallegos-Arreola P. , Macías-Islas M. A. , Arias-Merino E. D. , Loera-Castañeda V. , Martínez-Cano E. , Velázquez-Brizuela I. E. , Rosales-Corral S. A. , Curiel-Ortega C. R. , Pacheco-Moisés F. , García J. J. 
Published: June 2013

Objective: To determine the β‐amyloid precursor protein (βAPP) isoforms ratio as a risk factor for Alzheimer’s Disease and to assess its relationship with demographic and genetic variables of the disease.Methods: Blood samples from 26 patients fulfilling NINCDS‐ADRDA diagnostic criteria for AD and 46 healthy control subjects were collected for Western blotting for βAPP. A ratio of βAPP isoforms, in optical densities, between the upper band (130 Kd) and the lower bands (106–110 Kd) was obtained. Odds ratios were obtained to determine risk factor of this component.Results: βAPP ratio on AD subjects was lower than that of control subjects: 0.3662 ± 0.1891 vs. 0.6769 ± 0.1021 (mean ± SD, p<0.05). A low βAPP ratio (<0.6) showed an OR of 4.63 (95% CI 1.45 ± 15.33). When onset of disease was taken into account, a βAPP ratio on EOAD subjects of 0.3965 ± 0.1916 was found vs. 0.3445 ± 0.1965 on LOAD subjects (p>0.05).Conclusions: Altered βAPP isoforms is a high risk factor for Alzheimer’s disease, although it has no influence on the time of onset of the disease.
C242T Polymorphism in CYBA Gene (p22phox) and Risk of Coronary Artery Disease in a Population of Caucasian Italians
Authors: Nasti Sabina , Spallarossa Paolo , Altieri Paola , Garibaldi Silvano , Fabbi Patrizia , Polito Luisa , Bacino Luca , Brunelli Michele , Brunelli Claudio , Barsotti Antonio , Ghigliotti Giorgio 
Published: June 2013

Background: specific polymorphisms of genes regulating intracellular redox balance and oxidative stress are related to atherogenesis. Some studies have identified a relationship between progression of atherosclerosis and C242T mutation in CYBA gene coding for p22phox, a subunit of the NADH/NADPH oxidase system.Design: we investigated whether the C242T nucleotide transition is associated with the presence of coronary artery disease (CAD) in a population of 494 Caucasian Italians undergoing coronary angiography to diagnose the cause of chest pain.Results: the frequency of the T mutant allele that we found in 276 patients with angiographically documented CAD was significantly higher compared to what we observed in 218 subjects with normal coronary arteries (Controls) (respectively: 0.400 and 0.332, p < 0.01). The prevalence of the T allele was even stronger when we compared: 1) early onset (age ≤55) vs late onset (age ≥65) single‐vessel CAD patients (respectively: 0.75 and 0.48, p < 0.05), and 2) the subgroup of CAD patients with at least one ≥98% stenosis in a coronary vessel vs those with no ≥98% stenosis in a coronary vessel (respectively: 0.425 and 0.365, p < 0.05).Conclusions: these results support the increased risk of developing early CAD and of having rapid progression of coronary stenosis in subjects carrying the C242T nucleotide transition among the Italian population.
MGMT Methylation Status: The Advent of Stratified Therapy in Glioblastoma?
Authors: Hau Peter , Stupp Roger , Hegi Monika E. 
Published: June 2013

Glioblastomas are the most malignant gliomas with median survival times of only 15 months despite modern therapies. All standard treatments are palliative. Pathogenetic factors are diverse, hence, stratified treatment plans are warranted considering the molecular heterogeneity among these tumors. However, most patients are treated with "one fits all" standard therapies, many of them with minor response and major toxicities. The integration of clinical and molecular information, now becoming available using new tools such as gene arrays, proteomics, and molecular imaging, will take us to an era where more targeted and effective treatments may be implemented.A first step towards the design of such therapies is the identification of relevant molecular mechanisms driving the aggressive biological behavior of glioblastoma. The accumulation of diverse aberrations in regulatory processes enables tumor cells to bypass the effects of most classical therapies available. Molecular alterations underlying such mechanisms comprise aberrations on the genetic level, such as point mutations of distinct genes, or amplifications and deletions, while others result from epigenetic modifications such as aberrant methylation of CpG islands in the regulatory sequence of genes. Epigenetic silencing of the MGMT gene encoding a DNA repair enzyme was recently found to be of predictive value in a randomized clinical trial for newly diagnosed glioblastoma testing the addition of the alkylating agent temozolomide to standard radiotherapy. Determination of the methylation status of the MGMT promoter may become the first molecular diagnostic tool to identify patients most likely to respond that will allow individually tailored therapy in glioblastoma.To date, the test for the MGMT‐methylation status is the only tool available that may direct the choice for alkylating agents in glioblastoma patients, but many others may hopefully become part of an arsenal to stratify patients to respective targeted therapies within the next years.
DNA Methylation in Colorectal cancer—Impact on Screening and Therapy Monitoring Modalities?
Authors: Zitt Marion , Zitt Matthias , Müller Hannes M. 
Published: June 2013

Colorectal cancer (CRC) is a common malignancy. It arises from benign neoplasms and evolves into adenocarcinomas through a stepwise histological progression sequence, proceeding from either adenomas or hyperplastic polyps/serrated adenomas. Genetic alterations have been associated with specific steps in this adenoma‐carcinoma sequence and are believed to drive the histological progression of CRC. Recently, epigenetic alterations (especially DNA methylation) have been shown to occur in colon polyps and CRC. The aberrant methylation of genes appears to act together with genetic alterations to drive the initiation and progression of colon polyps to CRC.DNA methylation changes have been recognized as one of the most common molecular alterations in human tumors, including CRC. Because of the ubiquity of DNA methylation changes and the ability to detect methylated DNA in several body fluids (blood, stool), this specifically altered DNA may serve, on the one hand, as a possible new screening marker for CRC and, on the other hand, as a tool for therapy monitoring in patients having had neoplastic disease of the colorectum.As many CRC patients present with advanced disease, early detection seems to be one of the most important approaches to reduce mortality. Therefore, an effective screening test would have substantial clinical benefits. Furthermore, early detection of progression of disease in patients having had CRC permits immediate commencement of specific treatment regimens (e.g. curative resection of liver and lung metastases) and probably longer survival and better quality of life.
Dickkopf‐3 As a New Potential Marker for Neoangiogenesis in Colorectal Cancer: Expression in Cancer Tissue and Adjacent Non‐Cancerous Tissue
Authors: Zitt Matthias , Untergasser Gerold , Amberger Albert , Moser Patrizia , Stadlmann Sylvia , Zitt Marion , Müller Hannes M. , Mühlmann Gilbert , Perathoner Alexander , Margreiter Raimund , Gunsilius Eberhard , Öfner Dietmar 
Published: June 2013

Gene expression of Dickkopf‐3 (Dkk‐3) has been shown to be upregulated in tumor endothelium of colorectal cancer (CRC). For the first time, we analyzed Dkk‐3 protein expression in CRC and its potential as a marker for neoangiogenesis. We used tissue microarrays (TMAs) to investigate Dkk‐3 in microvessels of 403 CRC samples, 318 appropriate adjacent non‐cancerous samples and 127 normal colorectal samples. Of cancer samples with CD31‐positive microvessels, 67.7% were positive for Dkk‐3. Dkk‐3 staining was demonstrated in endothelial cells of all microvessels in nearly all cases. Dkk‐3‐positive samples showed a higher mean microvessel count than did Dkk‐3‐negative samples (P=0.001). Dkk‐3 expression increased with rising numbers of microvessels per sample (P<0.0001). In adjacent samples with CD31‐positive microvessels, 56% were Dkk‐3‐positive in all microvessels. Similar to cancer samples, Dkk‐3‐positive adjacent samples had a higher mean microvessel count than did Dkk‐3‐negative samples (P<0.0001), and Dkk‐3 expression also increased with rising numbers of microvessels (P<0.0001). All microvessels in normal mucosa samples were negative for Dkk‐3.Dkk‐3 can be considered a putative pro‐angiogenic protein in neovascularization and may possibly be a marker for neoangiogenesis in CRC. Further investigations will elucidate whether Dkk‐3 is a target structure for novel therapies.
Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment
Authors: Millán Mónica , Sobrino Tomás , Arenillas Juan Francisco , Rodríguez-Yáñez Manuel , García María , Nombela Florentino , Castellanos Mar , de la Ossa Natalia Pérez , Cuadras Patricia , Serena Joaquín , Castillo José , Dávalos Antoni 
Published: June 2013

Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels‐related damage in acute stroke patients treated with i.v. t‐PA.Methods: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin‐6, matrix metalloproteinase‐9 and cellular fibronectin were determined in 134 patients treated with i.v. t‐PA within 3 hours from stroke onset in blood samples obtained before t‐PA treatment, at 24 and 72 hours.Results: Serum ferritin levels before t‐PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin‐6 (r = 0.55,
p <0.001) levels at baseline, and with glutamate (r = 0.57,p <0.001), interleukin‐6 (r = 0.49,p <0.001), metalloproteinase‐9
(r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415,
p < 0.001), interleukin‐6 (r = 0.359, p < 0.001) and metalloproteinase‐9 (r = 0.261, p = 0.004) at 72 hours. The association
between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models.Conclusions: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research.
Mitochondrial Transcription Factors TFA, TFB1 and TFB2: A Search for DNA Variants/Haplotypes and the Risk of Cardiac Hypertrophy
Authors: Alonso-Montes Cristina , Castro Mónica G. , Reguero Julián R. , Perrot Andreas , Özcelik Cemil , Geier Christian , Posch Maximilian G. , Morís César , Alvarez Victoria , Ruiz-Ortega Marta , Coto Eliecer 
Published: June 2013

Mitochondrial transcription factors mtTFA, mtTFB1 and mtTFB2 are required for the replication of mitochondrial DNA (mtDNA), regulating the number of mtDNA copies. Mice with a mtTFA deletion showed a reduced number of mtDNA copies, a reduction in respiratory chain activity, and a characteristic dilated cardiomyopathy. DNA variants in these genes could be involved in the risk for cardiac hypertrophy (HCM).We determined the variation in the TFAM, TFB1M, and TFB2M genes (using SSCA, DHPLC, and direct sequencing) in a total of 200 HCM‐patients from Spain and Germany, and in 250 healthy controls. We found several common polymorphisms that defined haplotype blocks in these genes, with frequencies that did not differ between patients and controls. We also found four novel variants in patients which were absent in the controls: ‐91 C > A (5′‐UTR) and Ala105 > Thr in TFAM, and Thr211 > Ala and Arg256 > Lys in TFB1M. The three missense changes were in highly conserved amino acids, and could be involved in HCM‐risk.In conclusion, common variants in the mitochondrial transcription factors were not associated with the risk for HCM. However, rare DNA variants (putative mutations) could be involved in the pathogenesis of HCM in a reduced number of cases.
Investigating Population Risk Factors of Pancreatic Cancer by Evaluation of Optical Markers in the Duodenal Mucosa
Authors: Turzhitsky Vladimir , Liu Yang , Hasabou Nahla , Goldberg Michael , Roy Hemant K. , Backman Vadim , Brand Randall 
Published: June 2013

Pancreatic cancer screening has been hampered by the high rate of complications associated with interrogating the pancreas. The closest non‐invasively accessible mucosa available for pancreatic cancer screening is the periampullary duodenal tissue. Our earlier report has shown the potential of using optical markers to interrogate this tissue for the presence of pancreatic cancer. In this study, we report a larger data set of low‐coherence enhanced backscattering (LEBS) and elastic light scattering fingerprinting (ELF) optical markers from the periampullary duodenal mucosa. Optical measurements from biopsy samples were acquired from a total of 203 patients with varying clinical classification including healthy controls, a family history of pancreatic cancer, pancreatitis, mucinous cystic precursor lesions, pancreatic cancer, and other pancreatic malignancies. Evaluation of the performance of an independent testing set for discriminating healthy control patients from pancreatic cancer patients showed a 95% sensitivity, 71% specificity, and 85% area under the receiver operator characteristic (AUROC) curve. Importantly, this performance was uncompromised for detecting potentially curable stages of the disease. Additionally, optical markers in higher risk populations such as family history and pancreatitis had values between those of healthy control and pancreatic cancer patients, thus allowing for future investigations of screening from these high risk groups.Erratum to “Investigating Population Risk Factors of Pancreatic Cancer by Evaluation of Optical Markers in the Duodenal Mucosa”dx.doi.org/10.3233/DMA-2009-0686
Genetic Association of DLG5 R30Q with Familial and Sporadic Inflammatory Bowel Disease in Men
Authors: Lin Z. , Poritz L. , Franke A. , Li T.Y. , Ruether A. , Byrnes K.A. , Wang Y. , Gebhard A.W. , MacNeill C. , Thomas N.J. , Wu R. , Schreiber S. , Koltun W.A. 
Published: June 2013

Background: The association of DLG5 R30Q with IBD has been replicated in several populations, but is not statistically significant in others. We studied the incidence of DLG5 alleles in a population of IBD patients from Pennsylvania.Methods: DLG5 R30Q (rs1248696) and G1066G (rs1248634) were analyzed with PCR-based RFLP methods in a total of 521 subjects, that included 105 individuals with IBD and 139 without IBD from a familial IBD registry, 107 with sporadic IBD, and 170 unrelated healthy controls. R30Q was further analyzed with SNPlex™ Genotyping System in 473 samples.Results: RFLP genotyping data showed that, DLG5 R30Q was significantly associated with IBD overall (p=0.006), and separately with CD (p=0.009) and UC (p=0.024). The association of R30Q with IBD was entirely due to a male-associated effect (male vs femalep=0.015 vs 0.241 (IBD),p=0.024 vs 0.190 (CD), andp=0.019 vs 0.575 (UC)). The frequency of the A allele carriage was elevated in both affected and unaffected members in the familial IBD cohort compared to healthy controls (p=0.037). In the family pedigrees, we observed differences in the expression of IBD in individuals carrying the A allele between families.Conclusions: In the studied population, DLG5 R30Q was associated with all forms of IBD. An elevated presence of the R30Q variant was observed in all members of a familial IBD registry. This association of the R30Q variant with IBD was male-specific.
Molecular Profiling of Glatiramer Acetate Early Treatment Effects in Multiple Sclerosis
Authors: Achiron Anat , Feldman Anna , Gurevich Michael 
Published: June 2013

Background: Glatiramer acetate (GA, Copaxone®) has beneficial effects on the clinical course of relapsing-remitting multiple sclerosis (RRMS). However, the exact molecular mechanisms of GA effects are only partially understood.Objective: To characterized GA molecular effects in RRMS patients within 3 months of treatment by microarray profiling of peripheral blood mononuclear cells (PBMC).Methods: Gene-expression profiles were determined in RRMS patients before and at 3 months after initiation of GA treatment using Affimetrix (U133A-2) microarrays containing 14,500 well-characterized human genes. Most informative genes (MIGs) of GA-induced biological convergent pathways operating in RRMS were constructed using gene functional annotation, enrichment analysis and pathway reconstruction bioinformatic softwares. Verification at the mRNA and protein level was performed by qRT-PCR and FACS.Results: GA induced a specific gene expression molecular signature that included altered expression of 480 genes within 3 months of treatment; 262 genes were up-regulated, and 218 genes were down-regulated. The main convergent mechanisms of GA effects were related to antigen-activated apoptosis, inflammation, adhesion, and MHC class-I antigen presentation.Conclusions: Our findings demonstrate that GA treatment induces alternations of immunomodulatory gene expression patterns that are important for suppression of disease activity already at three months of treatment and can be used as molecular markers of GA activity.
Could High Levels of Tissue Polypeptide Specific Antigen, a Marker of Apoptosis Detected in Nonalcoholic Steatohepatitis, Improve after Weight Loss?
Authors: Tarantino Giovanni , Mazzarella Claudia , Tarantino Marianna , Di Minno Matteo Nicola Dario , Conca Paolo 
Published: June 2013

Background: Tissue Polypeptide Specific antigen has recently been proposed as diagnostic marker of apoptosis in NonAlcoholic SteatoHepatitis.The aim of this study was to validate in patients suffering from NonAlcoholic SteatoHepatitis the clinical utility of this marker after different programs of weight reduction.Methods: Overweight/obese patients with visceral adiposity and liver histology compatible were assigned to a Calorically-Restricted diet (n= 22), a Calorically-Restricted diet plus EXercise (n= 19) or No Healthy Life Style (control group,n= 21) for six months. The presence of Body-Weight loss was assessed by a Body Mass Index decrease of at least three points. Serum ALanine aminoTransferase, HOmeostasis Model Assessment method value and Tissue Polypeptide Specific antigen concentrations were determined at time 0, after 3 and 6 months in both the Intervention groups and in the controls’ one.Results: In NonAlcoholic SteatoHepatitis patients who obtained Body-Weight reduction, a significant decrease of the serum Tissue Polypeptide Specific antigen values was showed with a clear linear trend across time,P= 0.0001.Decrement of Tissue Polypeptide Specific antigen concentrations best differentiated the Body-Weight loss from the body-weight maintenance in respect to Tissue Polypeptide Specific antigen and HOmeostasis Model Assessment method values.Conclusion: This study support the clinical utility of serum Tissue Polypeptide Specific antigen antigen levels in the follow-up of overweight/obese patients with NonAlcoholic SteatoHepatitis on weight reduction programs.
High Serum Levels of Pro-Brain Natriuretic Peptide (pro BNP) Identify Cardioembolic Origin in Undetermined Stroke
Authors: Rodríguez-Yáñez Manuel , Sobrino Tomás , Blanco Miguel , de la Ossa Natalia Pérez , Brea David , Rodríguez-González Raquel , Leira Rogelio , Dávalos Antonio , Castillo José 
Published: June 2013

Background: Stroke subtype diagnosis leads to specific therapies to reduce recurrences. Because nearly one third of patients remain with unknown etiology after a complete screening workup, we aim to investigate whether molecular markers of myocardial damage were associated with cardioembolic stroke and if they were useful to reclassify strokes of undetermined etiology.Methods: We included 262 patients with first ischemic stroke within the first 12 hours. Stroke subtype was evaluated by TOAST criteria. Stroke of undetermined origin were reclassified into likely atherothrombotic or likely cardioembolic according to a predefined non-validated algorithm. Blood samples were obtained on admission to determine serum levels of molecular markers (pro-BNP, pro-ANP and CK-MB) of myocardial damage.Results: Patients with cardioembolic infarct showed higher levels of pro-BNP, pro-ANP and CK-MB. Pro-BNP > 360 pg/mL was independently associated with cardioembolic stroke (OR: 28.51, CI95%: 5.90–136.75,p< 0.0001). Stroke etiology was undetermined in 82 patients (31%); 34 were reclassified as likely cardioembolic, 22 as likely atherothrombotic, and 26 remained as undetermined. Pro-BNP > 360 pg/mL was the only factor independently associated with likely cardioembolic stroke.Conclusions: Pro-BNP levels higher than 360 pg/mL are associated with cardioembolic stroke and may be useful to reclassify undetermined strokes as of cardioembolic origin.
Methylene Tetrahydrofolate Reductase and Angiotensin Converting Enzyme Gene Polymorphisms Related to Overweight/Obesity among Saudi Subjects from Qassim Region
Authors: Settin Ahmad A. , Algasham Abdullah , Dowaidar Moataz , Ismail Hisham 
Published: June 2013

Background: This work was planned to check for the association of polymorphisms related to methylenetetrahydrofolate reductase (MTHFR) and angiotensin converting enzyme (ACE) genes with overweight/obesity among Saudi subjects from Qassim region.Methods: This work included 130 subjects having overweight or obesity and 111 normal controls. Their age mean ± SD was 27 ± 9.8 and 24 ± 8.8 years respectively. Their DNA was analyzed for polymorphisms of MTHFR; 677C/T and 1298 A/C and ACE; I/D genes using real-time PCR.Results: Genotype and allele frequencies of studied polymorphisms in cases of overweight/obesity showed no significant statistical difference compared to that of controls. However, on analysis of body mass index (BMI), cases showed slightly higher but statistically nonsignificant mean ± SD values among those carrying the mutant MTHFR 677 T allele (CT + TT vs. CC, 30.7 ± 4.5 vs. 29.9 ± 4.9), 1298 C allele (AC + CC vs. AA, 29.9 ± 4.1 vs. 29.7 ± 5.5) and ACE D allele (ID + DD vs. II, 30.0 ± 5.1 vs. 29.1 ± 2.8). In addition controls having the DD and ID genotypes showed higher statistically significant values of BMI than those of the II genotype (22.0 ± 1.9, 21.7 ± 2.6 and 19.5 ± 2.3 respectively,p< 0.05).Conclusion: There is no solid association of polymorphisms related to MTHFR and ACE genes with non-complicated overweight or obesity among Saudi subjects from Qassim Region.