bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of HLA-DQ3.2β Ligands: evidence of multiple registers in class II binding peptides
Authors: Tong Joo Chuan , Zhang Guang Lan , Tan Tin Wee , August J. Thomas , Brusic Vladimir , Ranganathan Shoba 
Published: March 2006

Abstract
Motivation: While processing of MHC class II antigens for presentation to helper T-cells is essential for normal immune response, it is also implicated in the pathogenesis of autoimmune disorders and hypersensitivity reactions. Sequence-based computational techniques for predicting HLA-DQ binding peptides have encountered limited success, with few prediction techniques developed using three-dimensional models.
Methods: We describe a structure-based prediction model for modeling peptide-DQ3.2β complexes. We have developed a rapid and accurate protocol for docking candidate peptides into the DQ3.2β receptor and a scoring function to discriminate binders from the background. The scoring function was rigorously trained, tested and validated using experimentally verified DQ3.2β binding and non-binding peptides obtained from biochemical and functional studies.
Results: Our model predicts DQ3.2β binding peptides with high accuracy [area under the receiver operating characteristic (ROC) curve AROC &gt; 0.90], compared with experimental data. We investigated the binding patterns of DQ3.2β peptides and illustrate that several registers exist within a candidate binding peptide. Further analysis reveals that peptides with multiple registers occur predominantly for high-affinity binders.
Contact: shoba@els.mq.edu.au
Supplementary information: Supplementary data is available at Bioinformatics online.
Family specific rates of protein evolution
Authors: Luz Hannes , Vingron Martin 
Published: March 2006

Abstract
Motivation: Amino acid changing mutations in proteins are contstrained by purifying selection and accumulate at different rates. We estimate evolutionary rates on multiple alignments of eukaryotic protein families in a maximum likelihood framework and spot sets of slow and fast evolving proteins.
Results: We find that the evolution of indispensable proteins is constrained by selection and that protein secretion is coupled to an increased evolutionary rate.
Contact: luz@molgen.mpg.de
Supplementary information:
Techniques for identifying the epidural space: a survey of practice amongst anaesthetists in the UK
Authors: Wantman A. , Hancox N. , Howell P. R. 
Published: February 2006

SummaryA postal survey of all UK members of the Obstetric Anaesthetists' Association was carried out to ascertain their preferred method for identifying the epidural space in obstetric and non‐obstetric patients. Over 1200 questionnaires were returned (79.3% response rate). In obstetric patients, the single most common technique (used by 58% of anaesthetists) was continuous advancement of the epidural needle and loss of resistance with saline, followed by intermittent needle advancement with air (21%). A minority of respondents used other variants, including intermittent advancement with saline (16%) and continuous advancement with air (4%). Consultant anaesthetists showed greater variety in techniques used than did trainees (p < 0.001). Less than 5% of respondents used a paramedian approach, and these were almost exclusively senior staff. Only 48% of anaesthetists said they would try an alternative if they experienced difficulty with their preferred technique. A similar pattern was seen for lumbar epidurals in non‐obstetric surgical patients (89% used the same technique as in obstetrics), although for thoracic epidurals, 23% used a different technique to that which they would use for obstetrics, and the paramedian approach was more popular (21%). When inserting lumbar epidurals to supplement general anaesthesia in surgical patients, 18% of anaesthetists said they usually performed the block with the patient asleep, whereas for thoracic epidurals, this figure fell to 14%.
Volumetric assessment of left heart preload by thermodilution: comparing the PiCCO‐VoLEF® system with transoesophageal echocardiography*
Authors: Hofer C. K. , Ganter M. T. , Matter‐Ensner S. , Furrer L. , Klaghofer R. , Genoni M. , Zollinger A. 
Published: February 2006

SummaryThe new Volumetric Ejection Fraction monitoring system (VoLEF®), when combined with the Pulse Contour Cardiac Output monitoring system (PiCCO®) system, allows measurement of left and right heart end‐diastolic volumes by thermodilution. The aim of this study was to evaluate whether the left heart end‐diastolic volume index determined by the VoLEF system (LHEDI) better reflects left ventricular end‐diastolic area index (LVEDAI) measured by transoesophageal echocardiography than does global end‐diastolic volume index (GEDI) measured by the PiCCO system alone. Following induction of anaesthesia, PiCCO, VoLEF and transoesophageal echocardiography measurements were performed before and after a fluid challenge in 20 patients scheduled for elective cardiac surgery. Both left ventricular end‐diastolic area index and global end‐diastolic volume index, but not left heart end‐diastolic volume index, significantly increased after fluid administration. Mean bias ± 2 SD for ΔLHEDI–ΔLVEDAI was − 2.2 ± 32.0% and for ΔGEDI–ΔLVEDAI − 0.6 ± 16.8%. In contrast to global end‐diastolic volume index, the use of left heart end‐diastolic volume index determined by the VoLEF system cannot be recommended as an estimate of left ventricular preload.
Access to emergency hormonal contraception from community pharmacies and family planning clinics
Authors: Lewington Gaye , Marshall Kay 
Published: March 2006

Aims To evaluate differences in the time taken to access progestogen‐only emergency hormonal contraception (EHC) by young women from family planning (FP) or community pharmacy settings.Methods An observational study of 203 women requesting EHC from FP clinics and community pharmacies in South‐west Kent Primary Care Trust (PCT) from December 2002 to October 2003.Results Access to EHC from community pharmacy was significantly faster than from FP clinics (16 h vs. 41 h, P < 0.001). Older teenagers tended to seek EHC more quickly and were more likely to have had a contraceptive failure rather than have used no contraception at all.Conclusion The results provide further support for pharmacist involvement in the supply of EHC.
Paroxetine: population pharmacokinetic analysis in late‐life depression using sparse concentration sampling
Authors: Feng Yan , Pollock Bruce G. , Ferrell Robert E. , Kimak Mark A. , Iii Charles F. Reynolds , Bies Robert R. 
Published: March 2006

AimTo develop a population pharmacokinetic (PK) model using sparse sampling of long‐term treatment with paroxetine in elderly depressed subjects, incorporating CYP2D6 genotype as well as other covariates.MethodsElderly subjects (age ≥ 70 years) with nonpsychotic, nonbipolar major depressive disorder from the inpatient and outpatient clinic were treated with paroxetine in a 5‐year clinical trial investigating ‘Maintenance Therapies in Late‐Life Depression’ (MTLD‐2). Plasma concentrations were collected during regular visits. CYP2D6 genotype was determined using polymerase chain reaction (PCR) for each individual. A nonlinear mixed‐effects model was developed with NONMEM® for these subjects who received 10–40 mg day−1 of paroxetine during treatment. One‐ and two‐compartment models with linear and nonlinear elimination (Michaelis–Menten) were evaluated. PK parameters as well as interindividual and residual variability were estimated. The effects of age, weight, sex, race and CYP2D6 genotypes on the pharmacokinetics of paroxetine were evaluated.ResultsOne hundred and seventy‐one subjects with a mean age of 77 years (range 69–95) and a mean weight of 72.0 kg (range 32.9–137.0) were enrolled in the MTLD‐2 clinical trial. A total of 1970 paroxetine concentrations were available for population PK analyses. Approximately 10 samples were taken per subject. A two‐compartment nonlinear PK model with additive and proportional error provided the best base model for description of the data. Weight and CYP2D6 polymorphisms were found to have a significant effect on maximal velocity (Vm), whereas sex had an effect on volume of distribution of the central compartment. The Vm estimates in each of the CYP2D6 phenotypic groups were: 125 µg h−1 in poor metabolizer (n = 1), 182 µg h−1 in intermediate metabolizers (n = 28), 454 µg h−1 in extensive metabolizers (n = 36) and 3670 µg h−1 in ultra‐rapid metabolizers (n = 5).ConclusionsThe population PK model adequately described paroxetine data in this elderly depressed population. The data indicate that female and male subjects with different CYP2D6 polymorphisms have different elimination rates and therefore may need to be dosed differently based on metabolizer genotype.
Exposure to thiopurine drugs through breast milk is low based on metabolite concentrations in mother‐infant pairs
Authors: Gardiner Sharon J. , Gearry Richard B. , Roberts Rebecca L. , Zhang Mei , Barclay Murray L. , Begg Evan J. 
Published: March 2006

AimsTo determine infant exposure to 6‐thioguanine and 6‐methylmercaptopurine nucleotides (6‐TGN and 6‐MMPN, respectively) during maternal use of azathioprine in breastfeeding.MethodsMother‐infant pairs provided blood for determination of 6‐TGN and 6‐MMPN concentrations, and TPMT genotype.ResultsFour women taking azathioprine 1.2–2.1 mg kg−1 day−1 and their infants were studied. All had the wild‐type TPMT genotype. Maternal 6‐TGN and 6‐MMPN concentrations ranged from 234 to 291 and 284 to 1178 pmol per 8 × 108 red blood cells, respectively, and were consistent with those associated with improved therapeutic outcomes. Neither 6‐TGN nor 6‐MMPN was detected in any of the infants, despite a sensitive assay.ConclusionsThe data suggest that azathioprine may be ‘safe’ during breastfeeding in patients with the wild‐type TPMT genotype (∼90% of caucasian patients) taking ‘normal’ doses.
A polymorphism of MS4A2 (−109T>C) encoding the β‐chain of the high‐affinity immunoglobulin E receptor (FcɛR1β) is associated with a susceptibility to aspirin‐intolerant asthma
Authors: Kim S. ‐H. , Bae J. ‐S. , Holloway J. W. , Lee J. ‐T. , Suh C. ‐H. , Nahm D. ‐H. , Park H. ‐S. 
Published: March 2006

SummaryBackground and objective
The MS4A2 gene, the β chain of the high‐affinity receptor for immunoglobulin (Ig)E, has previously been linked to atopy and asthma. The β‐chain of FcɛR1 enhances receptor maturation and signal transduction capacity, leading to the release of proinflammatory mediators and cytokines that can exacerbate the symptom of asthma. This study was performed to evaluate whether two genetic polymorphisms of the FcɛR1β gene (FcɛR1β−109T>C and FcɛR1β E237G) are associated with aspirin‐intolerant asthma (AIA).Methods
The MS4A2 gene polymorphisms (FcɛR1β−109T>C and FcɛR1β E237G) were determined by SNP‐IT™ assays in patients with AIA (N=164), aspirin‐tolerant asthma (ATA, N=144) and normal controls (NC, N=264) recruited from a Korean population.Results
The genotype frequencies of FcɛR1β−109T>C and E237G polymorphisms were not significantly associated with the pathogenesis of AIA. However, FcɛR1β−109T>C polymorphism was significantly associated with the presence of specific IgE to Staphylococcal enterotoxin B (SEB); the number of subjects carrying both homozygous TT genotype of FcɛR1β−109T>C and specific IgE to SEB was significantly higher in the AIA group when compared with the other control groups (P=0.01, odds ratio (OR)=7.723, 95% confidence interval (CI)=1.327–39.860 for AIA vs. ATA; P=0.02, OR=6.364, 95% CI=1.149∼35.229 for AIA vs. NC). In addition, luciferase reporter assays also showed that the FcɛR1β−109T allele was associated with higher promoter activity of MS4A2 in both RBL‐2H3 and A549 cell lines.Conclusion
FcɛR1β−109T>C polymorphism may increase expression of MS4A2 by mast cells, leading to enhanced release of proinflammatory mediators in the asthmatic airway, contributing to increased susceptibility to AIA.
Fibrosis in heart disease: understanding the role of transforming growth factor‐β1 in cardiomyopathy, valvular disease and arrhythmia
Authors: Khan Razi , Sheppard Richard 
Published: March 2006

SummaryThe importance of fibrosis in organ pathology and dysfunction appears to be increasingly relevant to a variety of distinct diseases. In particular, a number of different cardiac pathologies seem to be caused by a common fibrotic process. Within the heart, this fibrosis is thought to be partially mediated by transforming growth factor‐β1 (TGF‐β1), a potent stimulator of collagen‐producing cardiac fibroblasts. Previously, TGF‐β1 had been implicated solely as a modulator of the myocardial remodelling seen after infarction. However, recent studies indicate that dilated, ischaemic and hypertrophic cardiomyopathies are all associated with raised levels of TGF‐β1. In fact, the pathogenic effects of TGF‐β1 have now been suggested to play a major role in valvular disease and arrhythmia, particularly atrial fibrillation. Thus far, medical therapy targeting TGF‐β1 has shown promise in a multitude of heart diseases. These therapies provide great hope, not only for treatment of symptoms but also for prevention of cardiac pathology as well. As is stated in the introduction, most reviews have focused on the effects of cytokines in remodelling after myocardial infarction. This article attempts to underline the significance of TGF‐β1 not only in the post‐ischaemic setting, but also in dilated and hypertrophic cardiomyopathies, valvular diseases and arrhythmias (focusing on atrial fibrillation). It also aims to show that TGF‐β1 is an appropriate target for therapy in a variety of cardiovascular diseases.
Oestradiol potentiates the suppressive function of human CD4+ CD25+ regulatory T cells by promoting their proliferation
Authors: Prieto G. Aleph , Rosenstein Yvonne 
Published: March 2006

SummaryCD4+ CD25+ regulatory T (Treg) cells play an important role in the control of the immune system by suppressing the proliferation of effector cells, thereby preventing autoreactive, unnecessary or inconvenient responses. Recently, it has been shown that the number of Treg cells increases during pregnancy, a period with high serum levels of female sex hormones. Oestrogen replacement therapy has been reported to alleviate the symptoms of autoimmune diseases, yet the cellular and molecular mechanisms involved are not fully understood. Here, we show that physiological doses of oestradiol (E2) found during pregnancy, combined with activation through CD3/CD28 engagement, promoted the proliferation of Treg cells without altering their suppressive phenotype. Enhanced suppression was detected when Treg cells were pretreated with the hormone as well as when both cell subpopulations (Treg and T effector) were exposed to E2 throughout the experiment. Together, these data suggest that when combined with an activating stimulus, E2 can modulate the function of human Treg cells by regulating their numbers, and highlight a potential use of E2, or its analogs, to manipulate Treg function.
Failure mechanism of ProTaper Ni–Ti rotary instruments during clinical use: fractographic analysis
Authors: Spanaki‐Voreadi A. P. , Kerezoudis N. P. , Zinelis S. 
Published: February 2006

AbstractAim  To evaluate the failure mechanism of ProTaper Ni–Ti rotary instruments fractured under clinical conditions.Methodology  A total of 46 ProTaper instruments that failed (fractured and/or plastically deformed) during the clinical use were collected from various dental clinics, whereas a new set of ProTaper instruments served as control. After inspection under stereomicroscopy the instruments were classified into three categories: (i) plastically deformed but not fractured, (ii) fractured with plastic deformation and (iii) fractured without plastic deformation. Three instruments from each group were analysed with computerized X‐ray microtomography (micro‐XCT) to detect surface and internal defects, whilst all the fracture surfaces were investigated under SEM.Results  Stereomicroscopic inspection showed that 17.4% of the discarded instruments were only plastically deformed, 8.7% were fractured with plastic deformation and 73.9% were fractured without plastic deformation. Micro‐XCT revealed instruments without any surface or bulk defects along with a few files with crack development below the fracture surface. No defects were identified in the unused instruments. SEM examination of fractured surfaces demonstrated the presence of dimples and cones, a typical pattern of dimple rupture developed because of ductile failure.Conclusions  The results suggest that a single overloading event causing ductile fracture of ProTaper instruments is the most common fracture mechanism encountered under the clinical conditions.
Co‐production of vascular endothelial cadherin and inducible nitric oxide synthase by endothelial cells in periapical granuloma
Authors: Hama S. , Takeichi O. , Hayashi M. , Komiyama K. , Ito K. 
Published: February 2006

AbstractAim  To clarify the mechanisms of inflammatory cell migration in human periapical granulomas by examining vascular endothelial (VE) cadherin and inducible nitric oxide synthase (iNOS)‐producing cells.Methodology  Periapical tissues were obtained from patients during endodontic surgery and were divided into two portions. After fixing the tissues with acetone or 4% paraformaldehyde in phosphate‐buffered saline, 5‐μm‐thick paraffin or cryostat sections were prepared, respectively. The paraffin sections of the inflamed tissues were evaluated histologically with haematoxylin–eosin stains. Cryostat sections of the tissue, diagnosed as periapical granulomas, were then examined by either immunohistochemistry using anti‐human VE‐cadherin or iNOS antibodies (Abs) for the characterization of infiltrating cells. In addition, co‐localization of VE‐cadherin and iNOS production was also analysed by two‐colour immunofluorescence image analysis.Results  Endothelial cells were strongly stained with iNOS Abs. Macrophages, lymphocytes, polymorphonuclear leucocytes and fibroblasts also exhibited iNOS production. These iNOS‐positive cells accumulated around the blood vessels. On the other hand, VE‐cadherin production was exhibited in only endothelial cells. Two‐colour immunofluorescence image analysis using VE‐cadherin and iNOS Abs demonstrated that iNOS‐producing endothelial cells also showed VE‐cadherin production.Conclusions  Vascular endothelial‐cadherin produced by endothelial cells could be regulated by iNOS‐producing cells in periapical granulomas and might play a pivotal role in vascular permeability.
The effect of German chamomile (Marticaria recutita L.) extract and tea tree (Melaleuca alternifolia L.) oil used as irrigants on removal of smear layer: a scanning electron microscopy study
Authors: Sadr Lahijani M. S. , Raoof Kateb H. R. , Heady R. , Yazdani D. 
Published: February 2006

AbstractAim  To compare the cleaning effectiveness of chamomile hydroalcoholic extract and tea tree oil to 2.5% sodium hypochlorite (NaOCl) solution as an intracanal irrigant for the removal of the smear layer.Methodology  Forty extracted, single‐rooted, mature, permanent, human teeth were allocated at random into one of three experimental groups of ten teeth and two control groups of five teeth. For each tooth, the pulp chamber was accessed and the canal prepared using K‐type files and Gates‐Glidden burs, using a step‐back technique; the apical stop was prepared to a size 30. Each canal was subsequently irrigated with one of the following solutions: distilled water (as a negative control), 2.5% NaOCl + 17% ethylenediamine tetraacetic acid (EDTA) (as a positive control), chamomile or tea tree oil or 2.5% NaOCl. Each tooth was split longitudinally and prepared for examination by scanning electron microscopy (SEM). The quantity of smear layer remaining on the three levels of each canal (coronal, middle and apical) was examined using magnifications of 2000 and 5000×. The data were analysed using nonparametric Kruskal–Wallis and Mann–Whitney U‐tests.Results  The most effective removal of smear layer occurred with the use of NaOCl with a final rinse of 17% EDTA (negative control) followed by the use of a chamomile extract. Chamomile extract was found to be significantly more effective than distilled water and tea tree oil (P < 0.008).The use of a 2.5% NaOCl solution alone, without EDTA and that of tea tree oil, was found to have only minor effects. There was no statistical difference between distilled water, 2.5% NaOCl and tea tree oil.Conclusions  The efficacy of chamomile to remove smear layer was superior to NaOCl alone but less than NaOCl combined with EDTA.
Comparative study on the shaping ability and cleaning efficiency of rotary Mtwo instruments. Part 1. Shaping ability in simulated curved canals
Authors: Schäfer E. , Erler M. , Dammaschke T. 
Published: February 2006

AbstractAim  To compare the shaping ability of Mtwo instruments with K3 and RaCe instruments. Part 1 of this two‐part report describes the efficacy of these nickel–titanium instruments in simulated curved root canals.Methodology  Simulated canals with 28° and 35° curves in resin blocks were prepared with Mtwo instruments using a single length technique and with K3 and RaCe instruments using a crowndown preparation technique (n = 20 canals in each case). Pre‐ and post‐instrumentation images were recorded and assessment of canal shape was completed with a computer image analysis program. Material removal was measured at 20 measuring points, beginning 1 mm from the endpoint of preparation. Incidence of canal aberrations, preparation time, changes of working length and instrument failures were also recorded. The data were analysed statistically using anova and Student–Newman–Keuls test.Results  On an average, canals prepared with Mtwo instruments remained better centred compared with those enlarged with K3 or RaCe instruments. Six RaCe instruments, four K3 files and none of the Mtwo instruments fractured during preparation (P > 0.05). In both of the canal types, Mtwo was significantly faster (P < 0.001). It was possible with all types of instruments to control working length as well.Conclusions  Mtwo instruments prepared curved canals rapidly, respected original canal curvature well and were safe to use.
X‐ray diffraction analysis of mineral trioxide aggregate and Portland cement
Authors: Islam I. , Chng H. K. , Yap A. U. J. 
Published: February 2006

AbstractAim  To compare the major constituents present in ProRoot mineral trioxide aggregate (MTA), ProRoot MTA (tooth coloured formula), ordinary Portland cement and white Portland cement using powder X‐ray diffractometery.Methodology  X‐ray diffractometery of the four materials was carried out with the divergence and scatter slits set at 1° and the receiving slit at 0.10 mm. The scan range was set at 5–70° and continuous scans for the θ–2θ range were run with a scan speed of 2° min−1. The patterns obtained were then compared with the Powder Diffraction Files (PDF) found in the International Centre for Diffraction Data database. The three strongest peaks were used for the identification of the constituents. The relative intensities were plotted against the angle 2θ and compared with the plots in the PDF.Results  The main constituents were found to be tricalcium silicate, tricalcium aluminate, calcium silicate, and tetracalcium aluminoferrite in all the four cements with the additional presence of Bi2O3 in ProRoot MTA and ProRoot MTA (tooth coloured formula).Conclusions  The four cements had similar major constituents. Data on Portland cement may be used for the further development or modification of ProRoot MTA in order to improve its physical characteristics and expand its scope of clinical applications.