bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical, Molecular and Geographical Features of Hereditary Breast/Ovarian Cancer in Latvia
Authors: Gardovskis Andris , Irmejs Arvids , Miklasevics Edvins , Borosenko Viktors , Bitina Marianna , Melbarde-Gorkusa Inga , Vanags Andrejs , Kurzawski Grzegorz , Suchy Janina , Górski Bohdan , Gardovskis Janis 
Published: March 2010

Abstract

Introduction
The aim of the study is to evaluate the incidence and phenotype-genotype characteristics of hereditary breast and ovarian cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by this syndrome.

Materials and methods
In 2002-2004 in two Latvian oncology hospitals (Liepãja Oncology Hospital and Daugavpils Oncology Hospital) cancer family histories were collected from 287 consecutive patients with breast and ovarian cancer. In all cases, when it was possible to obtain the blood sample, DNA testing for founder mutations in the BRCA1 gene was performed.

Results
Among 287 family cancer histories analysed in 8 (2.8%) cases criteria of hereditary breast cancer (HBC) were fulfilled and in 5 (1.7%) cases hereditary breast and ovarian cancer (HBOC) was diagnosed. In 50 (17.4%) cases we have suspicion of hereditary breast cancer (HBC susp.) and in 8 (2.8%) cases - suspicion of hereditary breast and ovarian cancer (HBOC susp.). We have one (0.3%) case with hereditary ovarian cancer (HOC). DNA testing of founder mutations in the BRCA1 gene (exon 20 (5382 insC) exon 5 (300T/G), exon 11, 17 (4153delA)) for 178/287 (62%) patients was performed. In 9/287 (4.9%) cases we found a mutation in the BRCA1 gene. 4 mutations were detected in exon 11, 17 (4153delA) and 4 mutations in exon 20 (5382 insC) and 1 in exon 5.

Conclusions
Existing pedigree/clinical data suggest that in Latvia the clinical frequency of hereditary breast and ovarian cancer is around 5% of consecutive breast and ovarian cancer patients and suspicion of the syndrome is observed in another 20% of cases. Frequency of BRCA1 founder mutations is 5% of all consecutive breast and ovarian cancers. Considerable geographical differences in the clinical and molecular frequency of hereditary breast ovarian cancer have been observed in Latvia.
Cysteinyl-leukotriene type 1 receptors transduce a critical signal for the up-regulation of eosinophilopoiesis by interleukin-13 and eotaxin in murine bone marrow
Authors: Queto Tulio , Gaspar-Elsas Maria I , Masid-de-Brito Daniela , Vasconcelos Zilton F M , Ferraris Fausto K , Penido Carmen , Cunha Fernando Q , Kanaoka Yoshihide , Lam Bing K , Xavier-Elsas Pedro 
Published: March 2010

Abstract
Novel role of eotaxin and IL-13 in regulating bone-marrow eosinophilopoiesis, and a critical role for CysLT1R receptors in transducing eotaxin/IL-13 signals.
IL-13 and eotaxin play important, inter-related roles in asthma models. In the lungs, CysLT, produced by the 5-LO-LTC4S pathway, mediate some local responses to IL-13 and eotaxin; in bone marrow, CysLT enhance IL-5-dependent eosinophil differentiation. We examined the effects of IL-13 and eotaxin on eosinophil differentiation. Semi-solid or liquid cultures were established from murine bone marrow with GM-CSF or IL-5, respectively, and the effects of IL-13, eotaxin, or CysLT on eosinophil colony formation and on eosinophil differentiation in liquid culture were evaluated, in the absence or presence of: a) the 5-LO inhibitor zileuton, the FLAP inhibitor MK886, or the CysLT1R antagonists, montelukast and MK571; b) mutations that inactivate 5-LO, LTC4S, or CysLT1R; and c) neutralizing mAb against eotaxin and its CCR3 receptor. Both cytokines enhanced GM-CSF-dependent eosinophil colony formation and IL-5-stimulated eosinophil differentiation. Although IL-13 did not induce eotaxin production, its effects were abolished by anti-eotaxin and anti-CCR3 antibodies, suggesting up-regulation by IL-13 of responses to endogenous eotaxin. Anti-CCR3 blocked eotaxin completely. The effects of both cytokines were prevented by zileuton, MK886, montelukast, and MK571, as well as by inactivation of the genes coding for 5-LO, LTC4S, and CysLT1R. In the absence of either cytokine, these treatments or mutations had no effect. These findings provide evidence for: a) a novel role of eotaxin and IL-13 in regulating eosinophilopoiesis; and b) a role for CysLTRs in bone marrow cells in transducing cytokine regulatory signals.
Cadmium Promotes Breast Cancer Cell Proliferation by Potentiating the Interaction between ERα and c-Jun
Authors: Siewit Christina L. , Gengler Bridget , Vegas Esera , Puckett Rachel , Louie Maggie C. 
Published: March 2010

AbstractCadmium is an environmental contaminant that enters the body through diet or cigarette smoke. It affects multiple cellular processes, including cell proliferation, differentiation, and apoptosis. Recently, cadmium has been shown to function as an endocrine disruptor, to stimulate estrogen receptor α (ERα) activity and promote uterine and mammary gland growth in mice. Although cadmium exposure has been associated with the development of breast cancer, the mechanism of action of cadmium remains unclear. To address this deficit, we examined the effects of cadmium treatment on breast cancer cells. We found that ERα is required for both cadmium-induced cell growth and modulation of gene expression. We also determined that ERα translocates to the nucleus in response to cadmium exposure. Additionally, we provide evidence that cadmium potentiates the interaction between ERα and c-Jun and enhances recruitment of this transcription factor complex to the proximal promoters of cyclin D1 and c-myc, thus increasing their expression. This study provides a mechanistic link between cadmium exposure and ERα and demonstrates that cadmium plays an important role in the promotion of breast cancer.
Research Resource: Expression Profiling Reveals Unexpected Targets and Functions of the Human Steroid Receptor RNA Activator (SRA) Gene
Authors: Foulds Charles E. , Tsimelzon Anna , Long Weiwen , Le Andrew , Tsai Sophia Y. , Tsai Ming-Jer , O'Malley Bert W. 
Published: March 2010

AbstractThe human steroid receptor RNA activator (SRA) gene encodes both noncoding RNAs (ncRNAs) and protein-generating isoforms. In reporter assays, SRA ncRNA enhances nuclear receptor and myogenic differentiation 1 (MyoD)-mediated transcription but also participates in specific corepressor complexes, serving as a distinct scaffold. That SRA RNA levels might affect some biological functions, such as proliferation, apoptosis, steroidogenesis, and myogenesis, has been reported. However, the breadth of endogenous target genes that might be regulated by SRA RNAs remains largely unknown. To address this, we depleted SRA RNA in two human cancer cell lines with small interfering RNAs and then assayed for changes in gene expression by microarray analyses. The majority of significantly changed genes were reduced upon SRA knockdown, implicating SRA RNAs as endogenous coactivators. Unexpectedly, only a small subset of direct estrogen receptor-α target genes was affected in estradiol-treated MCF-7 cells. Eight bona fide SRA downstream target genes were identified (SLC2A3, SLC2A12, CCL20, TGFB2, DIO2, TMEM65, TBL1X, and TMPRSS2), representing entirely novel SRA targets, except for TMPRSS2. These data suggest unanticipated roles for SRA in glucose uptake, cellular signaling, T3 hormone generation, and invasion/metastasis. SRA depletion in MDA-MB-231 cells reduced invasiveness and expression of some genes critical for this process. Consistent with the knockdown data, overexpressed SRA ncRNA coactivates certain target promoters and may enhance the activity of some coregulatory proteins. This study is a valuable resource because it represents the first genome-wide analysis of a mammalian RNA coregulator.
Chemical enhancement of torsinA function in cell and animal models of torsion dystonia
Authors: Cao Songsong , Hewett Jeffrey W. , Yokoi Fumiaki , Lu Jun , Buckley Amber Clark , Burdette Alexander J. , Chen Pan , Nery Flavia C. , Li Yuqing , Breakefield Xandra O. , Caldwell Guy A. , Caldwell Kim A. 
Published: March 2010

SUMMARYMovement disorders represent a significant societal burden for which therapeutic options are limited and focused on treating disease symptomality. Early-onset torsion dystonia (EOTD) is one such disorder characterized by sustained and involuntary muscle contractions that frequently cause repetitive movements or abnormal postures. Transmitted in an autosomal dominant manner with reduced penetrance, EOTD is caused in most cases by the deletion of a glutamic acid (ΔE) in the DYT1 (also known as TOR1A) gene product, torsinA. Although some patients respond well to anticholingerics, therapy is primarily limited to either neurosurgery or chemodenervation. As mutant torsinA (ΔE) expression results in decreased torsinA function, therapeutic strategies directed toward enhancement of wild-type (WT) torsinA activity in patients who are heterozygous for mutant DYT1 may restore normal cellular functionality. Here, we report results from the first-ever screen for candidate small molecule therapeutics for EOTD, using multiple activity-based readouts for torsinA function in Caenorhabditis elegans, subsequent validation in human DYT1 patient fibroblasts, and behavioral rescue in a mouse model of DYT1 dystonia. We exploited the nematode to rapidly discern chemical effectors of torsinA and identified two classes of antibiotics, quinolones and aminopenicillins, which enhance WT torsinA activity in two separate in vivo assays. Representative molecules were assayed in EOTD patient fibroblasts for improvements in torsinA-dependent secretory function, which was improved significantly by ampicillin. Furthermore, a behavioral defect associated with an EOTD mouse knock-in model was also rescued following administration of ampicillin. These combined data indicate that specific small molecules that enhance torsinA activity represent a promising new approach toward therapeutic development for EOTD, and potentially for other diseases involving the processing of mutant proteins.
Long-Term Aspirin and Clopidogrel Response Evaluated by Light Transmission Aggregometry, VerifyNow, and Thrombelastography in Patients Undergoing Percutaneous Coronary Intervention
Authors: Madsen Esben Hjorth , Saw Jacqueline , Kristensen Søren Risom , Schmidt Erik Berg , Pittendreigh Cheryl , Maurer-Spurej Elisabeth 
Published: March 2010

Abstract
Background: A reduced response to aspirin and clopidogrel predicts ischemic events, but reliable tests are needed to identify low responders. We compared 3 platelet-function tests during long-term dual treatment with aspirin and clopidogrel.
Methods: Patients who underwent a percutaneous coronary intervention and were receiving a combination of 325 mg/day aspirin and 75 mg/day clopidogrel were followed for 1 year. Blood was sampled 5 times during this period for 3 tests: light transmission aggregometry (LTA) assay, with 5.0 μmol/L ADP or 1.0 mmol/L arachidonic acid (AA) used as an agonist; VerifyNow™ assay, with the P2Y12 or aspirin cartridge (Accumetrics); and thrombelastography (TEG), stimulated by 2.0 μmol/L ADP or 1.0 mmol/L AA.
Results: Twenty-six of 33 patients completed all scheduled visits. A low response to clopidogrel was found in a few patients at variable frequencies and at different visits, depending on the method and criteria used. We found a moderate correlation between the LTA (ADP) and VerifyNow (P2Y12 cartridge) results, but the TEG (ADP) results correlated poorly with the LTA and VerifyNow results. A low response to aspirin was found with the VerifyNow (aspirin cartridge) and TEG (AA) methods on 6 and 2 occasions, respectively, but not with the LTA (AA) method, except for 1 occasion caused by probable noncompliance.
Conclusions: Detecting a low response to clopidogrel depends largely on the method used. Which method best predicts ischemic events remains uncertain. A low response to aspirin is rare with AA-dependent methods used at the chosen cutoffs. In some patients, the response to clopidogrel or aspirin may be classified differently at different times, even with the same method.
Aneuploidy Detection in Mixed DNA Samples by Methylation-Sensitive Amplification and Microarray Analysis
Authors: Brown Lucia , Brown Gregory , Vacek Pamela , Brown Stephen 
Published: March 2010

Abstract
Background: Cell-free fetal nucleic acid, believed to be derived from the placenta/trophoblast, is present in the plasma of pregnant women; however, its use for predictive genetic testing has been severely limited because the circulating fetal DNA is present in a small quantity and mixed with a much larger quantity of maternal DNA. Methods for detecting fetal aneuploidy from the cell-free fetal DNA in plasma are highly sought after, but proposed methods must take into account the small quantity and highly contaminated nature of the available fetal DNA.
Methods: We developed a method for methylation-sensitive amplification of DNA suitable for use with small (approximately 1 ng) samples. We used this method in conjunction with 2-color microarray analysis with a custom-made array to investigate whether relative amplification, and hence relative methylation, could be evaluated for a large number of genomic loci.
Results: Microarray assessment of genomic methylation accurately predicted the degree of methylation measured with bisulfite-conversion PCR and confirmed that DNA from first-trimester trophoblast was generally hypomethylated compared with whole-blood DNA. With a series of 3 samples in which 1 ng of DNA from a trisomic first trimester placenta was mixed with 9 ng of chromosomally normal peripheral blood DNA, we observed that the microarray signal associated with the trisomic chromosome was significantly different from that of the other chromosomes (P &lt; 0.001).
Conclusions: This method has potential to be used for noninvasive detection of fetal aneuploidy.
Genetic polymorphisms of CYP1A2, CYP3A4, CYP3A5, pregnane/steroid X receptor and constitutive androstane receptor in 207 healthy Spanish volunteers
Authors: Oliver Paloma , Lubomirov Rubin , Carcas Antonio 
Published: March 2010

AbstractBackground:Variability of cytochrome P450 (CYP) in humans is largely related to the pharmacological and toxicological effects of drugs and chemicals. Identification of single nucleotide polymorphisms (SNPs) could be important for knowing their involvement in many drugs metabolism. The goal of this study was to analyze the genotype frequency of 10 SNPs related to mirtazapine metabolism [CYP3A4*17, CYP3A4*18, CYP3A5*3A, CYP1A2*1F, pregnane/steroid X receptor (PXR) (rs3814055, rs38114057, rs3814058) and constitutive androstane receptor (CAR) (rs4073054, rs2307424, rs2502815)].Methods:The study was carried out in 207 healthy Spanish volunteers that had participated in phase I clinical trials. Other studies were performed: Hardy-Weinberg equilibrium, haplotype estimation and linkage disequilibrium.Results:No mutation related to CYP3A4*17 and CYP3A4*18 was found. Therefore, we analyzed data for the other eight SNPs. Allele frequencies were in equilibrium with the Hardy-Weinberg equation. Six haplotypes were determined for three PXR SNPs, and four for CAR SNPs. Tests for linkage disequilibrium showed a high association between PXR (rs38114057) and PXR (rs3814058) (p= 0.001), and between the three CAR SNPs (p=0.001), which could be useful for identification of tag SNPs.Conclusions:In the present study, the genotype frequencies of some SNPs related to mirtazapine metabolism in Spaniards were analyzed and showed that our study population is representative of HapMap European population. The results obtained could be analyzed with pharmacokinetic parameters of mirtazapine to elucidate the genotype-phenotype relationship, the involvement of these SNPs in metabolic reactions, drug interactions, and prediction of treatment response.Clin Chem Lab Med 2010;48:635–9.
Development of a low-cost real-time reverse transcriptase-polymerase chain reaction technique for the detection and quantification of hepatitis C viral load
Authors: Shahzamani Kiana , Merat Shahin , Rezvan Houri , Mirab-Samiee Siamak , Khademi Hooman , Malekzadeh Reza , Sabahi Farzaneh 
Published: March 2010

Abstract

Background: It is necessary to develop a highly specific and sensitive assay to quantify the exact amount of hepatitis C virus (HCV) RNA in blood of patients with hepatitis C. For this reason, a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay for quantification of HCV RNA in human plasma was developed.

Methods: A pair of primers as well as hybridization probes were selected. A real-time RT-PCR was set up and optimized. To establish the sensitivity of the assay, a serial dilution of HCV standards and reference sera, including the six major HCV genotypes, was used. The performance of the assay was evaluated with 191 known HCV-RNA positive and 100 negative samples.

Results: The real-time assay had a sensitivity of 50 IU/mL, with a dynamic range of detection between 103 and 106 IU/mL. The coefficients of variation of threshold cycle values in intra- and inter-day-runs were <1.77% and 3.40%, respectively. Measurement of HCV-RNA positive samples yielded reproducible data with 100% specificity.

Conclusions: The high sensitivity, simplicity, reproducibility, wide dynamic range, and low cost of this real-time HCV RNA quantification makes this method especially suitable for monitoring viral load during therapy and tailoring of treatment schedules accordingly.
Clin Chem Lab Med 2010;48:777–84.
Automated genomic DNA extraction from saliva using the QIAxtractor
Authors: Keijzer Henry , Endenburg Silvia C. , Smits Marcel G. , Koopmann Miriam 
Published: March 2010

Abstract

Background: Venipuncture is an invasive procedure to obtain whole blood in order to obtain high quality and sufficient amounts of genomic DNA. Obtaining DNA from non-invasive sources is preferred by patients, medical doctors and researchers. Saliva collected with cotton swabs (Salivette®) is increasingly being used to study chemical compounds, and it can also be a source of DNA. However, extracting DNA from Salivettes is very laborious and time consuming. Therefore, we developed a protocol for automated genomic DNA extraction from saliva collected in Salivette® using the QIAxtractor.

Methods: Saliva (0.1–2.0 mL) was collected by chewing on a Salivette® for 1–2 min. A total of 70 samples, collected from healthy volunteers, were extracted with the QIAxtractor robot and a Qiagen DX reagent pack. Quantity and quality was assessed using UV spectrometry and real-time polymerase chain reaction (PCR) (substitution at position –729 in the CYP1A2 gene).

Results: The average DNA concentration from the saliva samples was 6.0 μg/mL (95% CI 5.4–6.6 μg/mL). In 100% of the saliva samples, PCR products were detected with an average cycle threshold of 23.1 (95% CI 22.6–23.6).

Conclusions: DNA can be extracted in sufficient amounts from Salivette® with a fully automated system with a short turnaround time. Real-time PCR can be performed with these samples.
Clin Chem Lab Med 2010;48:641–3.
From jeering to giggling: Spain's dramatic break from a satirical to an avant-garde humor
Authors: Bauer Samuel M. 
Published: March 2010

AbstractA significant philosophical and aesthetic shift occurred in Spanish humor after WWI. The shift was inspired by Ramón Gómez de la Serna's idea that the traditional, caustic “custombrist-festive humor was fundamentally unwholesome together with his serendipitous role as one of the main proponents of the avant-garde in Spain. The New Humor, also called “Pure Humor,” was championed by his disciples “
Advances in Electrochemical Techniques for Corrosion Monitoring and Measurement
Authors: Papavinasam Sankara , Berke Neal S. , Brossia Sean 
Published: March 2010

Description
Fourteen peer-reviewed papers present the latest advances in electrochemical techniques for corrosion monitoring, measurement, modeling, and life prediction in the laboratory and in the field.
Five sections cover:
Keynote papers—electrochemical techniques in corrosion and electrochemical standards for corrosion testing
New experimental set up—application of coupled multielectrode array (MEA) technique in practical systems and an approach to estimate field performance based on laboratory measurements
New methods of analysis—role of localized electrochemical impedance spectroscopy (LEIS) for the study of the corrosion processes
New techniques—comparison of the Cyclic Potentiodynamic Polarization (CPP) technique and the Tsujikawa-Hisamatsu-Electrochemical (THE) method to evaluate the crevice corrosion of Alloy 22; and more
Advances in Field Applications—comparison of five commercial instruments to monitor the corrosion of steel reinforcement in concrete; corrosion behavior of novel phosphoric irons; and corrosion potentials of the internal surface of high pressure pipelines
Effect of acute and prolonged mineralocorticoid receptor blockade on spontaneous and stimulated hypothalamic–pituitary–adrenal axis in humans
Authors: Berardelli Rita , Karamouzis Ioannis , Marinazzo Elisa , Prats Elisa , Picu Andreea , Giordano Roberta , Ghigo Ezio , Arvat Emanuela 
Published: March 2010

ContextMineralocorticoid receptors (MRs) in the hippocampus display an important role in the control of the hypothalamic–pituitary–adrenal (HPA) axis, mediating the proactive feedback of glucocorticoids, which maintains the basal HPA activity. The systemic administration of MR antagonists enhances spontaneous and CRH-stimulated ACTH, cortisol, and DHEA secretion, while the effects of chronic treatment with MR antagonists are scanty. Our study was performed in order to clarify this point.DesignACTH, cortisol, and DHEA levels were studied during the infusion of placebo, canrenoate, a MR antagonist (CAN, 200 mg i.v. bolus at 1600 h followed by 200 mg infused over 4 h), and human CRH (hCRH; 2.0 μg/kg i.v. bolus at 1800 h) before and during the last week of 28-day treatment with CAN (200 mg/day p.o.) in eight young women.ResultsPre-treatment sessions: CAN and hCRH administration increased ACTH, cortisol, and DHEA levels versus placebo (P<0.05). Post-treatment sessions: during placebo infusion, cortisol and DHEA were significantly amplified versus pre-treatment session (P<0.05), while ACTH levels were not modified; CAN infusion, differently from pre-treatment session, was not able to significantly increase ACTH, cortisol, and DHEA levels; ACTH, cortisol, and DHEA responses to hCRH were amplified with respect to pre-treatment session, although statistical significance was obtained for cortisol and DHEA only.ConclusionsMR blockade by acute CAN administration significantly enhances the HPA activity in the afternoon, during the quiescent phase of the circadian rhythm. At the same period, prolonged treatment with CAN amplifies both spontaneous and CRH-stimulated activities of the HPA axis, while it blunts the HPA responsiveness to a further MR-mediated stimulation.
Flowback Performance in Intensely Naturally Fractured Shale Gas Reservoirs
Authors: W. Crafton James 
Published: March 2010

Abstract
In an attempt to quantify post-stimulation flowback strategies, especially for high value wells with multi-stage stimulations, this study compares observed flowback production histories with multi-phase numerical simulation of flow in multiple fractures of various conductivities. A "fit for purpose" finite difference simulator is able to treat the numerical problem of extremely high transmissibility contrast ratios in the fracture patterns with multi-phase flow in the fractures. After simulation of several systems, it became apparent that the greatest behavioral contrast was between gas and liquid-filled fracture systems, regardless of the fracture intensity. The results from this study offer insight into the effect of high versus low rate or drawdown flowbacks in the two systems. It suggests potential stimulation strategies for the maximization of long-term productivity, especially in multi-stage stimulation scenarios.