bluuebunny/crossref_metadata_2025_split huggingface dataset:
PIANA: protein interactions and network analysis
Authors: Aragues Ramon , Jaeggi Daniel , Oliva Baldo 
Published: March 2006

Abstract
Summary: We present a software framework and tool called Protein Interactions And Network Analysis (PIANA) that facilitates working with protein interaction networks by (1) integrating data from multiple sources, (2) providing a library that handles graph-related tasks and (3) automating the analysis of protein–protein interaction networks. PIANA can also be used as a stand-alone application to create protein interaction networks and perform tasks such as predicting protein interactions and helping to identify spots in a 2D electrophoresis gel.
Availability: PIANA is under the GNU GPL. Source code, database and detailed documentation may be freely downloaded from .
Contact: ramon.aragues@upf.edu; boliva@imim.es
GALGO: an R package for multivariate variable selection using genetic algorithms
Authors: Trevino Victor , Falciani Francesco 
Published: March 2006

Abstract
Summary: The development of statistical models linking the molecular state of a cell to its physiology is one of the most important tasks in the analysis of Functional Genomics data. Because of the large number of variables measured a comprehensive evaluation of variable subsets cannot be performed with available computational resources. It follows that an efficient variable selection strategy is required. However, although software packages for performing univariate variable selection are available, a comprehensive software environment to develop and evaluate multivariate statistical models using a multivariate variable selection strategy is still needed. In order to address this issue, we developed GALGO, an R package based on a genetic algorithm variable selection strategy, primarily designed to develop statistical models from large-scale datasets.
Availability: GALGO can be downloaded from
Contact: vtrevino@itesm.mx; f.falciani@bham.ac.uk
Supplementary information: Supplementary data are available at
Semi‐purification of the immunoglobulin E‐sweat antigen acting on mast cells and basophils in atopic dermatitis
Authors: Tanaka A. , Tanaka T. , Suzuki H. , Ishii K. , Kameyoshi Y. , Hide M. 
Published: March 2006

Background:  Sweating aggravates the symptoms of atopic dermatitis (AD). We have recently reported positive skin reactions and histamine release from basophils in response to autologous sweat in patients with AD.Objective:  To characterize the biochemical and immunological properties of the substance in sweat that evokes histamine release and to study the usability of the basophil‐histamine release test with the sweat antigen for AD.Methods:  Sweat collected from healthy volunteers was purified using chromatographies. Serum immunoglobulin (Ig)E of four patients with AD were purified using an affinity‐chromatography column with anti‐IgE antibodies. The amount of semi‐purified sweat antigen (138 ng protein/ml) that induced a half‐maximum reaction of basophils of a patient with AD was utilized for the basophil histamine release test. The involvement of specific IgE and high‐affinity IgE receptor (FcɛRI) in the reactions was examined using basophils of healthy volunteers, a human mast cell line (LAD2), and a rat basophilic leukemia cell line transfected with human α‐subunit of FcɛRI (RBL‐48).Results:  The semi‐purified sweat antigen induced histamine release from the basophils of 47 of 61 (74.6%) patients with AD and four of 46 (8.7%) healthy controls. Both basophils and mast cells sensitized with the patient‐derived IgE showed degranulation upon stimulation with the sweat antigen. However, no reaction was observed when cells were sensitized with myeloma IgE or the antigen was treated with proteases.Conclusion:  The semi‐purified standardized sweat antigen consists of a protein that induces degranulation of basophils and mast cells via antigen‐specific IgE and FcɛRI in patients with AD.
Pharmacokinetic modelling of the interaction between St John’s wort and ciclosporin A
Authors: Murakami Yuichi , Tanaka Tomoaki , Murakami Hideyasu , Tsujimoto Masayuki , Ohtani Hisakazu , Sawada Yasufumi 
Published: March 2006

AimsSt John’s wort (SJW) decreases the blood concentration of ciclosporin A (CsA), which may result in allograft rejection. In addition, the time course of this interaction is not parallel with the administration of SJW. We aimed to develop a pharmacokinetic model to predict the time profile of blood CsA concentrations during and after the intake of SJW.MethodsWe developed a pharmacokinetic model incorporating turnover of detoxicating proteins, with the assumption that the amount of detoxicating proteins is in inverse proportion to the ratio of trough blood concentration to daily dose (C/D ratio) of CsA. First, we collected time profiles of blood CsA during and after the intake of SJW from the literature. Next, we analysed the relationship between D/C ratio and the daily dose of SJW at steady state. Subsequently, the developed model was simultaneously fitted to the time profiles of C/D ratios by using a nonlinear least‐squares method to obtain model parameters.ResultsThe model analysis revealed that the induction of the detoxicating proteins by SJW was saturable with an elimination rate constant of the detoxicating proteins (ke) of 4.72 month−1. Elimination half‐life of the detoxicating proteins calculated from the ke value was 4.4 days, suggesting that the dose of CsA should be carefully monitored for up to 2 weeks after the cessation of SJW intake.ConclusionsThe present model may provide additional information for use in identifying optimal dosage regimens of CsA during and after the intake of SJW to prevent an adverse drug interaction between CsA and SJW.
Selectivity of NSAIDs for COX‐2 and cardiovascular outcome
Authors: Maxwell S. R. J. , Payne R. A. , Murray G. D. , Webb D. J. 
Published: March 2006

BackgroundNonsteroidal anti‐inflammatory drugs (NSAIDs) with increased selectivity for the cyclooxygenase‐2 (COX‐2) isoform reduce gastrotoxicity but may increase adverse cardiovascular events.MethodsWe searched the literature for studies that reported the odds ratio (OR) for such events following exposure to NSAIDs.ResultsFor studies comparing NSAID use with no use, increased COX‐2 selectivity was significantly related to cardiovascular risk (log OR) amongst observational studies (R = −0.34, P < 0.001) and randomized controlled trials (RCTs) (R = −0.56, P < 0.001). For studies comparing NSAIDs, difference in selectivity was related to risk for observational studies (R = −0.28, P = 0.005) but not for RCTs (R = −0.23, P = 0.15).ConclusionsAlthough increased COX‐2 selectivity may reduce gastrotoxicity, this may be at the cost of increasing cardiovascular risk.
Mucin genes have different expression patterns in healthy and diseased upper airway mucosa
Authors: Martínez‐Antón A. , DeBolós C. , Garrido M. , Roca‐Ferrer J. , Barranco C. , Alobid I. , Xaubet A. , Picado C. , Mullol J. 
Published: March 2006

SummaryBackground
Mucus hyper‐secretion is a feature of several airways diseases such as chronic rhinosinusitis, asthma, and cystic fibrosis (CF). Since mucins are major components of mucus, the knowledge of their distribution and regulation in nasal tissues is likely to improve mucus hyper‐secretion therapy.Objective
The aim of this study was to evaluate and compare mucin gene expression at epithelial and glandular levels, and to identify potential mucin expression patterns for specific upper airways pathologies.Methods
Immunohistochemistry for MUC1, MUC2, and MUC4–MUC8 mucins was performed on healthy nasal mucosa (NM; n=12), bilateral nasal polyps (NP; n=38), NP from CF patients (n=10), and antrochoanal (AC) polyps (n=11). MUC2, MUC4, MUC5AC, and MUC6 mRNA expression were also analysed by in situ hybridization.Results
MUC1, MUC4, and MUC5AC mucins were highly expressed in the epithelium and their expression pattern was similar in all NP types, MUC1 and MUC4 being increased and MUC5AC decreased compared with NM. MUC8 was highly detected at both epithelial and glandular levels with marked variability between groups. MUC5B was mainly detected in glands and the expression in all polyp types was higher than in NM. Moreover, MUC5B expression was higher in NP epithelia from CF patients than in bilateral NP and healthy NM. Although MUC2 expression was low, especially in AC polyps, it was detected in most samples. In NM, MUC6 and MUC7 were scarcely detected and MUC7 expression was restricted to glands.Conclusions
These results suggest that NP have a different pattern of mucin expression than healthy NM and that CF polyps (increased MUC5B) and AC polyps (decreased MUC2) have a different mucin expression pattern than bilateral NP.
Cysteinyl leukotriene receptor 1 promoter polymorphism is associated with aspirin‐intolerant asthma in males
Authors: Kim S.‐H. , Oh J.‐M. , Kim Y.‐S. , Palmer L. J. , Suh C.‐H. , Nahm D.‐H. , Park H.‐S. 
Published: March 2006

SummaryBackground
Cysteinyl leukotrienes (CysLTs) play important roles in the pathogenesis of eosinophilic airway inflammation characterized by bronchoconstriction, mucus secretion and airway hyper‐responsiveness via cysteinyl leukotriene receptor 1 (CysLTR1)‐mediated mechanism. CysLTR1‐selective antagonists have anti‐bronchoconstrictive and anti‐inflammatory effects in asthma, particularly aspirin‐intolerant asthma (AIA).Methods
To investigate the association of CysLTR1 with AIA development, we identified three single nucleotide polymorphisms (SNPs), −634C>T, −475A>C, −336A>G, in the 5′ upstream region of CysLTR1 gene using a direct sequencing method in 105 AIA patients, 110 ASA‐tolerant asthma (ATA) patients and 125 normal healthy controls (NC).Results
Significant differences were observed in allele frequencies of the three SNPs within male subjects; Male AIA patients had higher frequencies of the minor alleles of these three SNPs than male control groups (P=0.03 for AIA vs. NC; P=0.02 for AIA vs. ATA). Moreover, three‐SNP haplotype, ht2 [T–C–G], was associated with increased disease risk (odds ratio (OR)=2.71, P=0.03 for AIA vs. NC; OR=2.89, P=0.02 for AIA vs. ATA) in males. CysLTR1 haplotypes were also associated with altered gene expression; luciferase activity was significantly enhanced with the ht2 [T–C–G] construct in comparison with the ht1 [C–A–A] construct in human Jurkat cells (P=0.04).Conclusion
These results suggest that genetic variants of CysLTR1 are associated with AIA in a Korean population, and may modulate CysLTR1 expression.
Short-term simvastatin treatment has no effect on plasma cytokine response in a human in vivo model of low-grade inflammation
Authors: Erikstrup C , Ullum H , Pedersen B K 
Published: March 2006

Summary
Statins reduce plasma cholesterol, but clinical trials and in vitro studies indicate that they might also possess anti-inflammatory properties. The effect of simvastatin on circulating cytokines and leucocytes was evaluated in a human in vivo model of low-grade inflammation. Thirty young healthy male participants received an injection of the bacterial cell wall product endotoxin (0·06 ng/kg) to induce systemic inflammation. Participants were then randomized into a control and a simvastatin group. The simvastatin group received simvastatin 20 mg daily for 14 days. All participants returned after 14 days to receive a second endotoxin injection. Plasma concentrations of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1 receptor antagonist were measured by enzyme-linked immunosorbent assay (ELISA) before and hourly for 6 hours after endotoxin administration. Plasma cytokines as well as total leucocyte counts increased in all participants upon endotoxin challenge but were not affected by simvastatin treatment. Tolerance to endotoxin was observed in both groups after 14 days. Short-term treatment with simvastatin (20 mg/day) did not influence circulating cytokine levels during endotoxaemia in this human in vivo study.
Interferon-γ independent formation of pulmonary granuloma in mice by injections with trehalose dimycolate (cord factor), lipoarabinomannan and phosphatidylinositol mannosides isolated fromMycobacterium tuberculosis
Authors: Takimoto H , Maruyama H , Shimada K-I , Yakabe R , Yano I , Kumazawa Y 
Published: March 2006

SummaryThe mechanisms by which pulmonary granuloma formation is caused by administration of mycobacterial glycolipids such as trehalose dimycolate (TDM), lipoarabinomannan (LAM) and phosphatidylinositol mannosides (PIM) were investigated. When peritoneal and alveolar macrophages were stimulated with TDM, LAM and PIM in vitro, TDM exhibited the strongest tumour necrosis factor (TNF)-inducing activity. Responsiveness of macrophages from mice defected Toll-like receptor 4 (TLR4) was much higher than that of the wild-type mice. Although PIM and LAM also had a significant activity, LAM rather than PIM stimulated higher TNF-α production by alveolar macrophage. When mycobacterial glycolipids were injected as water-in-oil-in-water emulsion into mice via the tail vein, development of pulmonary granuloma in response to glycolipids were related closely to their TNF-inducing activity and TDM exhibited the strongest activity. Granuloma formation was observed not only in mice lacking interleukin (IL)-12 signalling but also interferon (IFN)-γ knock-out mice. Granuloma formation caused by glycolipids correlated with TNF-α levels in lungs. Administration of anti-TNF-α monoclonal antibody into TDM-injected IFN-γ knock-out mice decreased in granuloma formation, suggesting that development of pulmonary granuloma by mycobacterial glycolipids such as TDM is due to IFN-γ-independent and TNF-α-dependent pathway.
Development of an immunocapture method for measuring IgA antibodies to tissue transglutaminase in the sera of patients with coeliac disease
Authors: El Alaoui S , Gresti C 
Published: March 2006

SummaryOne of the most reliable sero-diagnostic tests for coeliac disease (CD) is the measurement, by ELISA, of serum IgA antibodies to tissue transglutaminase (tTG) adsorbed to the wells of microtitre plates. In spite of its reliability, however, some discrepancies exist with the results obtained by the antiendomysium histological assay (EMA) and by biopsy the accepted gold standard. Among the reasons for these differences in titres between the ELISA and the last 2 mentioned assays are the conformational changes that proteins undergo on adsorption and the importance of conformational epitopes on tTG for diagnosing CD. To address this problem, a novel procedure was developed using guinea-pig tTG (gptTG) free in solution to interact with IgA antibodies in the sera of CD patients. Any immune complexes so formed are then captured by anti-tTG antibodies preadsorbed to the wells of microtitre plates. This immunocapture method was optimized for the amount of soluble gptTG needed to interact with all the IgA’s anti-tTG present in fixed dilutions of serum samples, the amount of rabbit IgG anti-gptTG used to coat the wells of microtitre plates and the order of addition of the reaction components. Comparison of the IgA titres obtained by immunocapture with those by EMA and ELISA (adsorbed tTG) on 9 highly positive and 6 weakly positive sera from clinically characterized CD patients and 5 negative sera from non-CD control subjects revealed that the IgA titres by the immunocapture procedure were well correlated with those obtained by EMA, whereas the titres on ELISA showed discrepancies with both immunocapture and EMA.
Interleukin 18 and human immunodeficiency virus type I infection in adolescents and adults
Authors: Song W , Wilson C M , Allen S , Wang C , Li Y , Kaslow R A , Tang J 
Published: March 2006

SummaryInterleukin (IL)-18, a proinflammatory cytokine, has been recognized recently as an important factor in both treated and untreated patients with human immunodeficiency virus type 1 (HIV-1) infection. Consistent with all earlier reports, our quantification of serum IL-18 concentrations in 88 HIV-1 seropositive, North American adolescents (14–18 years old) revealed a positive correlation with cell-free HIV-1 viral load at two separate visits (Spearman’s r = 0·31 and 0·50, respectively, P &lt; 0·01 for both), along with a negative correlation with CD4+ T cell counts (r = –0·31 and −0·35, P &lt; 0·01 for both). In additional analyses of 66 adults (21–58 years old) from Zambia, HIV-1 seroconversion was associated uniformly with elevated IL-18 production (P &lt; 0·0001). These epidemiological relationships were independent of other population-related characteristics, including age, gender and ethnicity. In neither study population could serum IL-18 concentrations be associated with the IL-18 gene (IL18) promoter genotypes defined by five major single nucleotide polymorphisms. Collectively, these findings suggest that circulating IL-18 rather than the IL18 genotype may provide a useful biomarker for HIV-1-related events or outcomes.
Prostaglandin E2 production and viability of cells cultured in contact with freshly mixed endodontic materials
Authors: Melegari K. K. , Botero T. M. , Holland G. R. 
Published: March 2006

AbstractAim  To determine whether commonly used endodontic sealers could either induce or increase the release of prostaglandin E2 (PGE2) when in contact with cell types found in the periapical tissues.Methodology  Freshly mixed samples of Roth 801 sealer, Sealapex® and ProRoot® mineral trioxide aggregate (MTA) were placed in contact with cultured macrophages and fibroblasts for 24 h. The supernatant from the cultures was assayed for PGE2 using enzyme‐linked immunosorbent assay. Cell viability counts were made. As a positive control, similar cultures were also exposed to lipopolysaccharide and the supernatant analysed for PGE2. Data were compared by anova.Results  The three materials examined in these experiments did not stimulate increased PGE2 release from either of the cell lines. In control cultures, lipolysaccharide increased PGE2 release from macrophages but not from fibroblasts. Viability counts revealed that, whilst Roth 801 sealer caused some cell death in both fibroblasts and macrophages, Sealapex® led to cell death only in the macrophage cultures. ProRoot® MTA did not lead to statistically significant cell death in either culture.Conclusions  Under 24‐h culture conditions, the three freshly mixed test materials did not increase directly either production or release of PGE2 from either macrophages or gingival fibroblasts. Roth 801 decreased cell viability counts for both fibroblasts and macrophages. Sealapex® decreases macrophage viability. ProRoot® MTA did not affect viability in either cell line.
Healing response of apicomarginal defects to two guided tissue regeneration techniques in periradicular surgery: a double‐blind, randomized‐clinical trial
Authors: Marín‐Botero M. L. , Domínguez‐Mejía J. S. , Arismendi‐Echavarría J. A. , Mesa‐Jaramillo A. L. , Flórez‐Moreno G. A. , Tobón‐Arroyave S. I. 
Published: March 2006

AbstractAim  To compare healing responses to periosteal sliding grafts and polyglactin 910 periodontal mesh used as guided tissue regeneration (GTR) materials/techniques when both periapical and periradicular bone loss are present.Methodology  Thirty patients with suppurative chronic apical periodontitis with apicomarginal communication were selected and allocated randomly into two groups according to the barrier technique to be used during periradicular surgery: periosteal graft group (n = 15) and bioabsorbable membrane group (n = 15). Clinical and radiological evaluations were completed prior to surgery, a week later and every 3 months after surgery up to 12 months to measure the periodontal pocket depth (PD), clinical attachment level (CAL), gingival margin position (GMP), size of periapical lesion, percentage reduction of the periapical rarefaction, and periapical healing.Results  Both groups showed highly significant (P < 0.001) reductions in periodontal PD, CAL and size of periapical lesion at 12 months whilst GMP was unaltered. No significant difference between the experimental groups was evident for these parameters, or for the percentage reduction of size of the periapical lesion and clinical‐radiographic healing.Conclusion  Guided tissue regeneration applied to apicomarginal defects using sliding periosteal grafts and use of bioabsorbable membranes led to similar enhancements of the clinical outcome of periradicular surgery in terms of periapical healing, gain of periodontal support, PD reduction and minimal recession of the gingival margin.
Reducing fear of pain associated with endodontic therapy
Authors: Van Wijk A. J. , Hoogstraten J. 
Published: March 2006

AbstractAim  To provide subjects with positive information about endodontic treatment (ET) to reduce fear of pain associated with ET.Methodology  A large sample (n = 437) was randomly allocated to read one of five informative paragraphs and afterwards asked to complete two questionnaires (dental anxiety and fear of dental pain). The paragraphs consisted of dental information obtained from patient brochures. One (experimental) paragraph consisted of positive information about pain during ET. Analysis of variance followed by post hoc analysis was used to detect differences in mean score.Results  Subjects who were given the positive information regarding ET indicated they were less fearful of pain associated with ET.Conclusions  The clinical implication of this experiment is that patients should be accurately informed about pain associated with ET. In this way, the patient may be more at ease before and during treatment, decrease avoidance behaviour and make decisions regarding treatment choice, based on common sense rather than fearful expectations.
Evaluation of the effect of EDTA, EDTAC and citric acid on the microhardness of root dentine
Authors: De‐Deus G. , Paciornik S. , Mauricio M. H. P. 
Published: March 2006

AbstractAim  To evaluate the effect of citric acid, ethylenediaminetetraacetic acid (EDTA) and ethylenediaminetetraacetic acid plus Cetavlon (EDTAC) solutions on the microhardness of human root canal dentine.Methodology  Sixteen maxillary human canines were sectioned transversely at the cemento‐enamel junction and the crowns were discarded. Subsequently, each root was embedded in an epoxy resin cylinder and their middle third sectioned horizontally into 4 mm thick slices. The samples were randomly divided into three groups according to the chelating agent employed, as follows (n = 6): group 1: EDTA 17%, group 2: EDTAC 17% and group 3: citric acid 10%. Dentine microhardness was then measured with a load of 50 g for 15 s. At the beginning of the experiment, reference microhardness values were obtained for samples without any etching (t = 0 min). The same samples were then exposed to 50 μL of the chelator solution for 1, 3 and 5 min. The Student's t‐test (P < 0.05) was used to compare results for different times for each chelator and different chelators for each time.Results  Microhardness decreased with increasing time of application of chelating solutions. There were no significant (P > 0.05) differences between initial microhardness for the three groups as well as after 1 min of application of the substances. After 3 min, EDTA produced a significantly greater reduction in microhardness. However, there was no significant difference between EDTA and EDTAC after 5 min. Citric acid caused significantly less reduction in microhardness.Conclusions  Overall, citric acid was least effective in reducing dentine hardness whilst EDTA had the strongest effect.