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At least 613 records · Page 34Linked to original sources
PubMed2001

Molecular evolution of duplicated amylase gene regions in Drosophila melanogaster: evidence of positive selection in the coding regions and selective constraints in the cis-regulatory regions.

In this study, we randomly sampled Drosophila melanogaster from Japanese and Kenyan natural populations. We sequenced duplicated (proximal and distal) Amy gene regions to test whether the patterns of polymorphism were consistent with neutral molecular evolution. F(st) between the two geographically distant populations, estimated from Amy gene regions, was 0.084, smaller than reported values for other loci, comparing African and Asian populations. Furthermore, little genetic differentiation was found at a microsatellite locus (DROYANETSB) in these samples (G'st = -0.018). The results of several tests (Tajima's, Fu and Li's, and Wall's tests) were not significantly different from neutrality. However, a significantly higher level of fixed replacement substitutions was detected by a modified McDonald and Kreitman test for both populations. This indicates that positive selection occurred during or immediately after the speciation of D. melanogaster. Sliding-window analysis showed that the proximal region 1, a part of the proximal 5' flanking region, was conserved between D. melanogaster and its sibling species, D. simulans. An HKA test was significant when the proximal region 1 was compared with the 5' flanking region of Alcohol dehydrogenase (Adh), indicating a severe selective constraint on the Amy proximal region 1. These results suggest that natural selection has played an important role in the molecular evolution of Amy gene regions in D. melanogaster.

Alleles↗
PubMed1998

Improvement in gastrointestinal tolerability of the selective cyclooxygenase (COX)-2 inhibitor, meloxicam, compared with piroxicam: results of the Safety and Efficacy Large-scale Evaluation of COX-inhibiting Therapies (SELECT) trial in osteoarthritis.

SELECT is a large-scale, prospective, international, multicentre, double-blind, double-dummy, randomized, parallel-group trial. Patients with exacerbation of osteoarthritis were treated with the recommended dose of meloxicam (7.5 mg) or piroxicam (20 mg) once daily for 28 days; 4320 patients were administered meloxicam and 4336 piroxicam. The incidence of adverse events was significantly lower in the meloxicam group (22.5%) compared with the piroxicam group (27.9%; P < 0.001), mainly due to the significantly lower incidence of gastrointestinal (GI) adverse events in the meloxicam than in the piroxicam group (10.3% vs 15.4%,; P < 0.001), while the efficacy of both drugs was equivalent. Individual GI events occurred significantly less often with meloxicam than piroxicam: dyspepsia (3.4% vs 5.8%; P < 0.001), nausea/vomiting (2.5% vs 3.4%; P < 0.05) and abdominal pain (2.1% vs 3.6%; P < 0.001). There were 16 patients with perforations, ulcerations or bleeding (PUBs) of the upper GI tract in the piroxicam group compared with seven in the meloxicam group (relative risk piroxicam:meloxicam = 1.4). Four PUBs were complicated (perforations or bleedings); none of these occurred in the meloxicam group (relative risk piroxicam:meloxicam = 1.9). The outcome of SELECT is consistent with that of the large-scale clinical trial of similar design and size which compared 7.5 mg meloxicam with 100 mg diclofenac in patients with osteoarthritis, and with a previous global analysis of the safety of meloxicam. It adds further data to the proposed relationship between selective inhibition of cyclooxygenase-2 and improved GI tolerability of non-steroidal anti-inflammatory drugs.

Aged↗
PubMed2004

Effect of non-selective, non-steroidal anti-inflammatory drugs and cyclo-oxygenase-2 selective inhibitors on the PFA-100 closure time.

The place of cyclo-oxygenase (COX)-2 selective non-steroidal anti-inflammatory drugs (NSAIDs) in the peri-operative period remains under discussion. Due to the absence of COX-2 in platelets, the risk of bleeding in patients who use selective NSAIDs is thought to be decreased. We studied the influence of aspirin, diclofenac, lornoxicam and rofecoxib on the in vitro bleeding time using the platelet function analyser (PFA-100). The PFA-100 simulates the process of platelet adhesion and aggregation after vascular injury in vitro. Measurements in 43 volunteers were performed at three time points: before, 3 h, and 12 h after oral ingestion of one of the randomly assigned study medications. Aspirin, diclofenac and lornoxicam had a significant effect on the in vitro closure time, while rofecoxib did not show this effect. This supports the use of COX-2 selective drugs in the peri-operative period to minimise the risk of bleeding.

Adult↗
PubMed1983

The effect of selective and non-selective beta-adrenoceptor blockade, and of naloxone infusion, on the hormonal mechanisms of recovery from insulin-induced hypoglycaemia in man.

The rise in plasma adenosine-3',5'-monophosphate occurring in response to insulin induced hypoglycaemia in normal human subjects, was abolished by non-selective beta-adrenoceptor blockade but unaffected by selective beta 1-adrenoceptor blockade. This implies that the rise is secondary to beta 2-adrenoceptor stimulation. The abolition of this rise by non-selective beta-adrenoceptor blockade had no pronounced effect on the recovery from hypoglycaemia. Endogenous opiate receptor blockade with naloxone had no significant effect on the recovery from insulin induced hypoglycaemia, or the hormonal mechanisms involved.

Adrenergic beta-Antagonists↗
PubMed1985

Beta 1-selective and non-selective beta-adrenoceptor blockade, anaerobic threshold and respiratory gas exchange during exercise.

The effect of oral doses of the beta 1-selective adrenoceptor antagonist atenolol (50 mg), the non-selective antagonist propranolol (40 mg) and placebo was investigated during exercise in a crossover comparison in six healthy but untrained subjects. Descriptors of ventilation, respiratory gas exchange, and arterialized blood lactate and glucose were obtained during steady state bicycle ergometric exercise at 20% and 60% of the subjects' previously determined maximal oxygen uptake (VO2 max). At these work intensities, the previously reported increase of respiratory exchange ratio (RER) during non-selective beta-adrenoceptor blockade was found to be trivial (placebo = 0.96 +/- 0.03 s.e. mean; propranolol = 0.97 +/- 0.01; atenolol = 0.97 +/- 0.04; 60% VO2 max, 10 min exercise) and only present during the early minutes of effort. Oxygen uptake and carbon dioxide production did not differ between treatments. Both drugs produced highly significant falls in peak expiratory flow (PEF) rates and tidal volume (VT) which were compensated by an increase in respiratory rate. PEF, 60% VO2 max: placebo = 3.8 +/- 0.3 l/s; propranolol 3.6 +/- 0.3 l/s (P less than 0.03); atenolol 3.1 +/- 0.3 l/s (P less than 0.01). VT, 60% VO2 max: placebo 2.0 +/- 0.1 l; propranolol 1.8 +/- 0.21 (P less than 0.05); atenolol 1.7 +/- 0.1 1 (P less than 0.01). Arterialized lactate was significantly elevated during work at 20% and 60% VO2 max, but rose progressively at the 60% VO2 max load. Ventilation, oxygen uptake and ventilatory equivalent for carbon dioxide also rose progressively at this workload. Ventilatory equivalent for oxygen showed no significant rise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1981

Hormonal and substrate responses during recovery from hypoglycaemia in man during beta 1-selective and non-selective beta-adrenergic blockade.

Recovery from acute hypoglycaemia induced by the injection of insulin has been examined in six human subjects under control conditions, under non-selective beta blockade (propranolol) and under selective beta 1 blockade (metoprolol). The normal blood glucose recovery was biphasic with an initial rapid and a slower subsequent phase of recovery. The early recovery mechanism was unaffected by either form of beta blockade, but with propranolol the late phase of recovery was significantly prolonged. Rises in blood lactate and plasma free fatty acids following hypoglycaemia were markedly reduced by propranolol but to a much lesser degree with metoprolol. The counterregulatory hormonal responses of glucagon, cortisol and growth hormone were augmented appropriately for the prolonged hypoglycaemia associated with propranolol. Non-selective beta adrenergic blockade with propranolol is associated with an impairment of the late phase of blood glucose recovery from hypoglycaemia. The possible mechanisms of this impairment are discussed.

Acetoacetates↗
PubMed1976

The selection of students for medical education: select bibliography, 1970-75.

The problems of student selection are constantly in the mind of medical school administrators and medical teachers. When reviewing current policies there is clearly a need to study the recent journal literature, but the term 'student selection' is not a subject heading in Index Medicus; consequently no convenient listing of journal articles on this important topic is readily available. To assist administrators and medical teachers a bibliography has now been prepared. The references are taken from Index Medicus 1970-75 and presented here in a quick-reference alphabetical format. To the list has been added World Health Organization publication EURO 6203 which is considered an important document on the subject. The bibliogrraphy therefore provides a concise reference to the recent literature on student selection for medical education.

Bibliographies as Topic↗
PubMed1994

Comparative conformational analyses of mu-selective dermorphin and delta-selective deltorphin-II in aqueous solution by 1H-NMR spectroscopy.

Two-dimensional 1H-NMR methods have been used to obtain complete proton resonance assignments and possible solution conformations of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) and deltorphin-II (H-Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2), naturally occurring mu- and delta-selective opioids, respectively, in order to examine the conformational characteristics that are closely related to the selectivities towards mu/delta-opioid receptors. With the use of the proton-proton distances derived from ROESY measurements in aqueous solution, 50 possible 3D structures are generated by means of distance geometry calculations. The conformers which satisfy the distance constraints and the torsion angles estimated from JNHC alpha H vicinal coupling constants within the allowable range are then subjected to molecular dynamics simulations for 10 ps after equilibration. Although dermorphin and deltorphin-II are both in equilibrium among many flexible conformers, some conformational differences are observed between these peptides: many conformers of dermorphin show a structure rounded at the N-terminal Tyr-D-Ala-Phe-Gly-Tyr and C-terminal Gly-Tyr-Pro-Ser-NH2 moieties, which are almost at right angles to each other, while those of deltorphin-II are characterized by a 'hook'-shaped backbone structure in which the nearly extended conformation of the Val-Val-Gly-NH2 sequence is located under the folded conformation of the N-terminal Tyr-D-Ala-Phe-Glu sequence. The possible relationship between these conformational characteristics and the mu/delta-opioid receptor selectivities is discussed.

Amino Acid Sequence↗
PubMed2006

Attentional set mixing: Effects on target selection and selective response activation.

Performance is impaired under set mixing conditions that require frequent readjustments of attentional focus over an extended time period. We compared set repetitions within pure blocks (constant focus of attention) to physically identical repetitions within mixed blocks (changing focus of attention). The aim was to investigate how set mixing affects target selection, indexed by the N2pc component, and selective response activation, indexed by the lateralized readiness potential (LRP). We found that set mixing prolonged the evolution of the N2pc while leaving its onset unaffected. Impaired target selection indicated by the N2pc mixing effect also delayed the start of response planning indexed by an onset delay of the stimulus-locked LRP, explaining one part of the behavioral mixing cost. A larger part of mixing cost could be attributed to a prolonged response planning phase, indexed by an earlier onset of the response-locked LRP.

Adult↗
PubMed2004

Selective site pacing: defining and reaching the selected site.

Selective site right ventricular pacing has been suggested as an approach to reduce the incidence of ventricular dysfunction and hopefully influence the morbidity resulting from traditional right ventricular apical pacing. Pacing from the right ventricular apex allows a stable ventricular rate, and together with atrial pacing and sensing, helps maintain atrioventricular synchrony but does not allow physiological activation of the left ventricle. Traditional atrial pacing sites like the right atrial appendage may encourage atrial tachyarrhythmias, whereas lead placement in right atrial septal sites may reduce the frequency of symptomatic atrial tachyarrhythmia episodes, especially when combined with prevention algorithms. Researchers attempting to pace the heart from these selective sites have been hindered by the lack of uniform definitions of where these sites actually lie and the inadequacy of tools to consistently reach these locations and verify correct placement. This lack of definition consensus may have contributed to the apparent conflict of data, particularly in the right ventricle. There is an urgent need for a standardization of terms and identifying measures for selective pacing sites.

Cardiac Pacing, Artificial↗
PubMed2002

Functional selectivity of dopamine receptor agonists. I. Selective activation of postsynaptic dopamine D2 receptors linked to adenylate cyclase.

Dihydrexidine (DHX), the first high-affinity D(1) dopamine receptor full agonist, is only 10-fold selective for D(1) versus D(2) receptors, having D(2) affinity similar to the prototypical agonist quinpirole. The D(2) functional properties of DHX and its more D(2) selective analog N-n-propyl-dihydrexidine (PrDHX) were explored in rat brain and pituitary. DHX and PrDHX had binding characteristics to D(2) receptors in rat striatum typical of D(2) agonists, binding to both high- and low-affinity sites and being sensitive to guanine-nucleotides. Consistent with these binding data, both DHX and PrDHX inhibited forskolin-stimulated cAMP synthesis in striatum with a potency and intrinsic activity equivalent to that of quinpirole. Unexpectedly, however, DHX and PrDHX had little functional effect at D(2) receptors expressed on dopaminergic neurons that mediate inhibition of cell firing, dopamine release, or dopamine synthesis. Quantitative receptor competition autoradiography demonstrated that DHX bound to D(2) receptors in striatum (predominantly postsynaptic receptor sites) with equal affinity as D(2) sites in the substantia nigra (autoreceptor sites). The data from these experiments, coupled with what is known about the location of specific dopamine receptor isoforms, lead to the hypothesis that DHX, after binding to D(2L) and D(2S) receptors, causes agonist-typical functional changes only at some of these receptors. This phenomenon (herein termed "functional selectivity") suggests that drugs may be targeted not only at specific receptor isoforms but also at separate functions mediated by a single isoform, yielding novel approaches to drug discovery.

Adenylyl Cyclases↗
PubMed1999

Selective recognition of vitamin D receptor conformations mediates promoter selectivity of vitamin D analogs.

The transcription factor VDR is the nuclear receptor for 1alpha, 25-dihydroxyvitamin D3 (VD) and the mediator of all genomic actions of the nuclear hormone and its synthetic analogs. The sharp biological profile of the model VD analog 1(S), 3(R)-dihydroxy-20(R)-(5'-ethyl-5'-hydroxy-hepta-1'(E), 3'(E)-dien-1'-yl)-9,10-secopregna-5(Z),7(E),10(19)-triene (EB1089) (i.e., its high antiproliferative effect combined with low calcemic actions) has been correlated with the selectivity of EB1089 to activate heterodimeric complexes of VDR with its partner retinoid X receptor (RXR) on VD response elements (VDREs). These VDREs are formed by an inverted palindromic arrangement of two hexameric core binding motifs spaced by nine nucleotides (IP9) rather than VDREs that are formed by direct repeats with three intervening nucleotides (DR3). In this report, ligand-dependent gel-shift assays were used for a comparison of the ability of VD and EB1089 to stabilize VDR-RXR heterodimers on these two VDRE types. The gel-shift assays revealed EB1089 to be more sensitive for complexes on IP9-type VDREs than on DR3-type VDREs. In addition, a gel-shift clipping method was established to identify and compare complexes of ligand-stabilized VDR-RXR heterodimers on different VDREs. On each VDRE, two complexes could be discriminated that seemed to contain different functional conformations of the VDR and allowed a more differential view on DNA-complexed VDR-RXR heterodimers. The VDR-RXR conformation (which was more ligand-sensitive) gained through EB1089 a higher affinity (7-fold) for DNA binding and a more sensitive (9-fold) activation of an IP9-type VDRE than of a DR3-type VDRE, whereas with the natural hormone VD, no VDRE-type preference could be observed. This indicates that promoter selectivity of VDR ligands is based on their property to selectively increase affinity for VDREs and very sensitively stabilize VDR conformations in VDR-RXR-VDRE complexes.

Calcitriol↗
PubMed1993

Meta-analysis of randomised controlled trials of selective decontamination of the digestive tract. Selective Decontamination of the Digestive Tract Trialists' Collaborative Group.

OBJECTIVE: To determine the clinical benefits of selective decontamination of the digestive tract in patients treated in intensive care units. DESIGN: Meta-analysis of 22 randomised trials that compared different combinations of oral non-absorbable antibiotics, with or without a systemic component, with no treatment in controls. SUBJECTS: 4142 patients seen in general and specialised intensive care units around the world. 2047 received some form of antibiotic treatment, the remainder no prophylaxis. DATA ANALYSIS: Each trial was reviewed through direct contact with study investigators. Data collected were: the randomisation procedure, number of patients, number excluded from the analysis, and numbers of respiratory tract infections and deaths. Data were combined according to an intention to treat analysis with the Mantel-Haenszel-Peto method. MAIN OUTCOME MEASURES: Respiratory tract infections and total mortality. RESULTS: Selective decontamination of the digestive tract significantly reduced respiratory tract infections (odds ratio 0.37; 95% confidence interval 0.31 to 0.43). The value of the common odds ratio for total mortality (0.90; 0.79 to 1.04) suggested at best a moderate treatment effect, reaching statistical significance only when the subgroup of trials of topical and systemic treatment combined was considered separately (odds ratio 0.80; 0.67 to 0.97). No firm conclusions could be drawn owing to large variations in patient mix and severity within and between trials. CONCLUSIONS: The findings strongly indicate that selective decontamination significantly reduces infection related morbidity in patients receiving intensive care. They also highlight why definite conclusions about the effect of prophylaxis on mortality cannot be drawn despite the large number of trials available. Based on the most favourable results obtained by pooling data from trials in which combined topical and systemic treatment was used it may be estimated that 6 (range 5-9) and 23 (13-139) patients would need to be treated to prevent one respiratory tract infection and one death respectively.

Administration, Oral↗
PubMed2001

Enforced expression of Bcl-2 selectively perturbs negative selection of dual reactive antibodies.

We investigated the role of apoptosis in the development of B cell memory by analyzing the (p-azophenylarsonate) Ars response in a line of A strain mice in which expression of human Bcl-2 was enforced in the B cell compartment. Previous studies of the Ars immune response in these A. Bcl-2 mice, demonstrated that a large percentage of the antibodies expressed by the Ars induced memory B cell compartment had accumulated point mutations via somatic hypermutation that increased their affinity for both Ars and the autoantigen DNA ("dual reactive" antibodies). This was in sharp contrast to normal A strain mice which displayed no dual reactive B cells in their Ars induced memory B cell compartment. These data suggested that interference with apoptotic pathways regulated by Bcl-2 allows developing memory B cells that have acquired autoreactivity to bypass a peripheral tolerance checkpoint. Further studies of these mice, reported here, demonstrate that enforced expression of Bcl-2 does not alter serum antibody affinity maturation nor positive selection of B cells expressing somatically mutated antibody with an increased affinity for Ars. Moreover, the somatic hypermutation process was unaffected in A. Bcl-2 mice. Thus, enforced expression of Bcl-2 in A. Bcl-2 mice appears to selectively alter a negative selection process that operates during memory B cell differentiation.

Animals↗
PubMed2004

Selectively advantageous mutations and hitchhikers in neoplasms: p16 lesions are selected in Barrett's esophagus.

Neoplastic progression is an evolutionary process characterized by genomic instability and waves of clonal expansions carrying genetic and epigenetic lesions to fixation (100% of the cell population). However, an evolutionarily neutral lesion may also reach fixation if it spreads as a hitchhiker on a selective sweep. We sought to distinguish advantageous lesions from hitchhikers in the premalignant condition Barrett's esophagus. Patients (211) had biopsies taken at 2-cm intervals in their Barrett's segments. Purified epithelial cells were assayed for loss of heterozygosity and microsatellite shifts on chromosomes 9 and 17, sequence mutations in CDKN2A/MTS1/INK4a (p16) and TP53 (p53), and methylation of the p16 promoter. We measured the expanse of a lesion in a Barrett's segment as the proportion of proliferating cells that carried a lesion in that locus. We then selected the lesion having expanses >90% in the greatest number of patients as our first putative advantageous lesion. We filtered out hitchhikers by removing all expanses of other lesions that did not occur independent of the advantageous lesion. The entire process was repeated on the remaining expanses to identify additional advantageous lesions. p16 loss of heterozygosity, promoter methylation, and sequence mutations have strong, independent, advantageous effects on Barrett's cells early in progression. Second lesions in p16 and p53 are associated with later selective sweeps. Virtually all of the other lesion expansions, including microsatellite shifts, could be explained as hitchhikers on p16 lesion clonal expansions. These techniques can be applied to any neoplasm.

Barrett Esophagus↗
PubMed1994

Teaching multiplication facts to students with learning disabilities: teacher-selected versus student-selected material prompts within the delay procedure.

This study evaluated the effectiveness of the constant time delay procedure, while comparing the efficiency of using teacher-selected and student-selected material prompts, in teaching multiplication facts to 4 male students with learning disabilities ranging in age from 9 years 6 months to 13 years 10 months. The two prompting strategies were compared in the context of a multiple-probe design across groups of multiplication facts, in which the sequence of strategies was counterbalanced across students. Results indicated that although the constant time delay procedure used with material prompts was effective, instruction was more efficient when students were allowed to select the material prompt.

Adolescent↗
PubMed2006

Selection of optimal recording sites for limited lead body surface potential mapping: a sequential selection based approach.

BACKGROUND: In this study we propose the development of a new algorithm for selecting optimal recording sites for limited lead body surface potential mapping. The proposed algorithm differs from previously reported methods in that it is based upon a simple and intuitive data driven technique that does not make any presumptions about deterministic characteristics of the data. It uses a forward selection based search technique to find the best combination of electrocardiographic leads. METHODS: The study was conducted using a dataset consisting of body surface potential maps (BSPM) recorded from 116 subjects which included 59 normals and 57 subjects exhibiting evidence of old Myocardial Infarction (MI). The performance of the algorithm was evaluated using spatial RMS voltage error and correlation coefficient to compare original and reconstructed map frames. RESULTS: In all, three configurations of the algorithm were evaluated and it was concluded that there was little difference in the performance of the various configurations. In addition to observing the performance of the selection algorithm, several lead subsets of 32 electrodes as chosen by the various configurations of the algorithm were evaluated. The rationale for choosing this number of recording sites was to allow comparison with a previous study that used a different algorithm, where 32 leads were deemed to provide an acceptable level of reconstruction performance. CONCLUSION: It was observed that although the lead configurations suggested in this study were not identical to that suggested in the previous work, the systems did bear similar characteristics in that recording sites were chosen with greatest density in the precordial region.

Algorithms↗
PubMed2002

In the polymorphic ciliate Tetrahymena vorax, the non-selective phagocytosis seen in microstomes changes to a highly selective process in macrostomes.

Ciliates use phagocytosis to acquire edible particles. The polymorphic ciliate Tetrahymena vorax appears in two forms ('microstomes' and 'macrostomes'). Transformation of microstomes into macrostomes takes place in the presence of the ciliate Tetrahymena thermophila and enables the macrostome to phagocytose the latter species. The non-specific, constitutive phagocytosis in microstomes thereby changes into a specific inducible process in macrostomes. The purpose of this study was to determine whether the phagocytotic process in macrostomes is specifically aimed at catching T. thermophila. The two forms of phagocytosis represent an interesting model system for studying the mechanism whereby phagosomes are formed. The macrostomal form capture deciliated and ciliated Tetrahymena thermophila, latex beads with diameters of 20.3 and 30.0 microm and small microstomal cells. However, the macrostomes select T. thermophila as a prey when they have the opportunity to choose between deciliated T. thermophila and latex beads and between T. thermophila and microstomes. The non-selective formation of phagosomes seen in microstomes changes to a highly selective process during the transformation to macrostomes. Unlike microstomes, macrostomes do not form a closed vacuole after capturing a latex bead, indicating that mechanical stimulation by the prey does not in itself trigger phagocytosis in the macrostomal form of T. vorax. Although macrostomes captured T. thermophila in preference to microstomes, phagocytosis of microstomes started immediately following capture, indicating that the substance/molecule that triggers the formation of the phagosome is not specific for T. thermophila cells. After capturing a T. thermophila cell, the macrostomal cell, which normally swims in a forward direction, reverses direction and swims backwards for a short time before starting to rotate. Macrostomal cells did not change their swimming pattern after capturing a latex bead. We believe, therefore, that backward swimming is more likely to be related to signals resulting from phagocytosis than from mechanical stimulation of the pouch. Cytochalasin B (10 microg ml(-1)) inhibits phagocytosis in both microstomes and macrostomes, indicating that actin filaments play an active role in phagocytosis in both cell types. The antitubulin drug nocodazole (0.3-30 micromol l(-1)) inhibits the formation of more than one phagosome in the macrostome, indicating that membrane transport to the oral apparatus in macrostomes is guided by microtubules. Nocodazole has no effect on the process of phagocytosis in microstomes.

Actins↗