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Biomedical subjects

R D Stevens

Publications and source records attributed to R D Stevens.

At least 19 recordsLinked to original sources
PubMed2005

Ontology driven dynamic linking of biology resources.

Biologists were early adopters of the Web and continue to use it as the primary means of delivering data, tools and knowledge to their community. The Web is made by the links between pages, yet these links have many limitations: they are static and maintained by hand; they can only link one lexical item to another single resource; ownership is necessary for the placement of link anchors and the link mechanism is essentially inflexible. Dynamic linking services, supported by ontologies, offer a mechanism to overcome such restrictions. The Conceptual Open Hypermedia Service (COHSE) system enhances web resources through the dynamic addition of hypertext links. These links are derived through the use of an ontology and associated lexicon along with a mapping from concepts to possible link targets. We describe an application of COHSE to Bioinformatics, using the Gene Ontology (GO) as an ontology and associated keyword mappings and GO associations as link targets. The resulting demonstrator (referred to here as GOHSE) provides both glossary functionality and the possibility of building knowledge based hypertext structures linking bioinformatics resources.

Animals↗
PubMed2004

Exploring Williams-Beuren syndrome using myGrid.

MOTIVATION: In silico experiments necessitate the virtual organization of people, data, tools and machines. The scientific process also necessitates an awareness of the experience base, both of personal data as well as the wider context of work. The management of all these data and the co-ordination of resources to manage such virtual organizations and the data surrounding them needs significant computational infra-structure support. RESULTS: In this paper, we show that (my)Grid, middleware for the Semantic Grid, enables biologists to perform and manage in silico experiments, then explore and exploit the results of their experiments. We demonstrate (my)Grid in the context of a series of bioinformatics experiments focused on a 1.5 Mb region on chromosome 7 which is deleted in Williams-Beuren syndrome (WBS). Due to the highly repetitive nature of sequence flanking/in the WBS critical region (WBSCR), sequencing of the region is incomplete leaving documented gaps in the released sequence. (my)Grid was used in a series of experiments to find newly sequenced human genomic DNA clones that extended into these 'gap' regions in order to produce a complete and accurate map of the WBSCR. Once placed in this region, these DNA sequences were analysed with a battery of prediction tools in order to locate putative genes and regulatory elements possibly implicated in the disorder. Finally, any genes discovered were submitted to a range of standard bioinformatics tools for their characterization. We report how (my)Grid has been used to create workflows for these in silico experiments, run those workflows regularly and notify the biologist when new DNA and genes are discovered. The (my)Grid services collect and co-ordinate data inputs and outputs for the experiment, as well as much provenance information about the performance of experiments on WBS. AVAILABILITY: The (my)Grid software is available via http://www.mygrid.org.uk

Algorithms↗
PubMed2003

Investigating semantic similarity measures across the Gene Ontology: the relationship between sequence and annotation.

MOTIVATION: Many bioinformatics data resources not only hold data in the form of sequences, but also as annotation. In the majority of cases, annotation is written as scientific natural language: this is suitable for humans, but not particularly useful for machine processing. Ontologies offer a mechanism by which knowledge can be represented in a form capable of such processing. In this paper we investigate the use of ontological annotation to measure the similarities in knowledge content or 'semantic similarity' between entries in a data resource. These allow a bioinformatician to perform a similarity measure over annotation in an analogous manner to those performed over sequences. A measure of semantic similarity for the knowledge component of bioinformatics resources should afford a biologist a new tool in their repertoire of analyses. RESULTS: We present the results from experiments that investigate the validity of using semantic similarity by comparison with sequence similarity. We show a simple extension that enables a semantic search of the knowledge held within sequence databases. AVAILABILITY: Software available from http://www.russet.org.uk.

Artificial Intelligence↗
PubMed2003

Semantic similarity measures as tools for exploring the gene ontology.

Many bioinformatics resources hold data in the form of sequences. Often this sequence data is associated with a large amount of annotation. In many cases this data has been hard to model, and has been represented as scientific natural language, which is not readily computationally amenable. The development of the Gene Ontology provides us with a more accessible representation of some of this data. However it is not clear how this data can best be searched, or queried. Recently we have adapted information content based measures for use with the Gene Ontology (GO). In this paper we present detailed investigation of the properties of these measures, and examine various properties of GO, which may have implications for its future design.

Classification↗
PubMed2001

Manganese(III) biliverdin IX dimethyl ester: a powerful catalytic scavenger of superoxide employing the Mn(III)/Mn(IV) redox couple.

A manganese(III) complex of biliverdin IX dimethyl ester, (MnIIIBVDME)2, was prepared and characterized by elemental analysis, UV/vis spectroscopy, cyclic voltammetry, chronocoulometry, electrospray mass spectrometry, freezing-point depression, magnetic susceptibility, and catalytic dismuting of superoxide anion (O2.-). In a dimeric conformation each trivalent manganese is bound to four pyrrolic nitrogens of one biliverdin dimethyl ester molecule and to the enolic oxygen of another molecule. This type of coordination stabilizes the +4 metal oxidation state, whereby the +3/+4 redox cycling of the manganese in aqueous medium was found to be at E1/2 = +0.45 V vs NHE. This potential allows the Mn(III)/Mn(IV) couple to efficiently catalyze the dismutation of O2.- with the catalytic rate constant of kcat = 5.0 x 10(7) M-1 s-1 (concentration calculated per manganese) obtained by cytochrome c assay at pH 7.8 and 25 degrees C. The fifth coordination site of the manganese is occupied by an enolic oxygen, which precludes binding of NO., thus enhancing the specificity of the metal center toward O2.-. For the same reason the (MnIIIBVDME)2 is resistant to attack by H2O2. The compound also proved to be an efficient SOD mimic in vivo, facilitating the aerobic growth of SOD-deficient Escherichia coli.

Biliverdine↗
PubMed2001

Aqueous solution speciation of Fe(III) complexes with dihydroxamate siderophores alcaligin and rhodotorulic acid and synthetic analogues using electrospray ionization mass spectrometry.

Aqueous solutions of Fe3+ complexes of cyclic (alcaligin) and linear (rhodotorulic acid) dihydroxamate siderophores and synthetic linear eight-carbon-chain and two-carbon-chain dihydroxamic acids ([CH3N(OH)C=O)]2(CH2)n; H2Ln; n = 2 and 8) were investigated by electrospray ionization mass spectrometry (ESI-MS). Information was obtained relevant to the structure and the speciation of various Fe(III)-dihydroxamate complexes present in aqueous solution by (1) comparing different ionization techniques (ESI and FAB), (2) altering the experimental parameters (Fe3+/ligand ratio, pH, cone voltage), (3) using high-stability hexacoordinated Fe(III) siderophore complex mixtures (ferrioxamine B/ferrioxamine E) as a calibrant to quantify intrinsically neutral (H+ clustered or protonated) and intrinsically charged complexes, and (4) using mixed-metal complexes containing Fe3+, Ga3+, and Al3+. These results illustrate that for all dihydroxamic acid ligands investigated multiple tris- and bis-chelated mono- and di-Fe(III) species are present in relative concentrations that depend on the pH and Fe/L ratio.

Calibration↗
PubMed2001

Neuromuscular disorders and anesthesia.

The neuromuscular disorders are associated with diminished cardiopulmonary reserves, deficient airway protection mechanisms, and atypical responses to drugs used during anesthesia. Many of these conditions are uncommon, and methodologically sound evidence to guide clinical practice is limited. The disorders discussed in the present review are the motor neuron diseases, peripheral neuropathies, myasthenic syndromes, and myopathies, including malignant hyperthermia. Recent data on pathogenesis and medical management are outlined, as are studies relating to anesthesia and the perioperative period.

Journal Article↗
PubMed2000

Lumbar plexus block reduces pain and blood loss associated with total hip arthroplasty.

BACKGROUND: The usefulness of peripheral nerve blockade in the anesthetic management of hip surgery has not been clearly established. Because sensory afferents from the hip include several branches of the lumbar plexus, the authors hypothesized that a lumbar plexus block could reduce pain from a major hip procedure. METHODS: In a double-blind prospective trial, 60 patients undergoing total hip arthroplasty were randomized to receive general anesthesia with (plexus group, n = 30) or without (control group, n = 30) a posterior lumbar plexus block. The block was performed after induction using a nerve stimulator, and 0.4 ml/kg bupivacaine, 0.5%, with epinephrine was injected. General anesthesia was standardized, and supplemental fentanyl was administered per hemodynamic guidelines. Postoperative pain and patient-controlled intravenous morphine use were serially assessed for 48 h. RESULTS: The proportion of patients receiving supplemental fentanyl intraoperatively was more than 3 times greater in the control group (20 of 30 vs. 6 of 29, P = 0.001). In the postanesthesia care unit, a greater than fourfold reduction in pain scores was observed in the plexus group (visual analogue scale [VAS] pain score at arrival 1.3 +/- 2 vs. 5.6 +/- 3, P < 0.001), and "rescue" morphine boluses (administered if VAS > 3) were administered 10 times less frequently (in 2 of 28 vs. in 22 of 29 patients, P < 0.0001). Pain scores and morphine consumption remained significantly lower in the plexus group until 6 h after randomization (VAS at 6 h, 1.4 +/- 1.3 vs. 2.4 +/- 1.4, P = 0.007; cumulative morphine at 6 h, 5.6 +/- 4.7 vs. 12.6 +/- 7.5 mg, P < 0.0001). Operative and postoperative (48 h) blood loss was modestly decreased in the treated group. Epidural-like distribution of anesthesia occurred in 3 of 28 plexus group patients, but no other side-effects were noted. CONCLUSIONS: Posterior lumbar plexus block provides effective analgesia for total hip arthroplasty, reducing intra- and postoperative opioid requirements. Moreover, blood loss during and after the procedure is diminished. Epidural anesthetic distribution should be anticipated in a minority of cases.

Analgesia, Patient-Controlled↗
PubMed1999

Effects of S-nitrosation on oxygen binding by normal and sickle cell hemoglobin.

S-Nitrosated hemoglobin (SNO-Hb) is of interest because of the allosteric control of NO delivery from SNO-Hb made possible by the conformational differences between the R- and T-states of Hb. To better understand SNO-Hb, the oxygen binding properties of S-nitrosated forms of normal and sickle cell Hb were investigated. Spectral assays and electrospray ionization mass spectrometry were used to quantify the degree of S-nitrosation. Hb A(0) and unpolymerized Hb S exhibit similar shifts toward their R-state conformations in response to S-nitrosation, with increased oxygen affinity and decreased cooperativity. Responses to 2, 3-diphosphoglycerate were unaltered, indicating regional changes in the deoxy structure of SNO-Hb that accommodate NO adduction. A cycle of deoxygenation/reoxygenation does not cause loss of NO or appreciable heme oxidation. There is, however, appreciable loss of NO and heme oxidation when oxygen-binding experiments are carried out in the presence of glutathione. These results indicate that the in vivo stability of SNO-Hb and its associated vasoactivity depend on the abundance of thiols and other factors that influence transnitrosation reactions. The increased oxygen affinity and R-state character that result from S-nitrosation of Hb S would be expected to decrease its polymerization and thereby lessen the associated symptoms of sickle cell disease.

Allosteric Regulation↗
PubMed1999

Nursing the terminally ill. Being with people in difficult times.

There are many impediments to being present and actively listening to people in difficult times. The authors discuss numerous suggestions nurses can use to "be" with patients experiencing a life-threatening or terminal illness. Methods such as eliminating external intrusions, using meditative practices, and ways to create a therapeutic milieu are presented to help the nurse understand how to listen to and be with patients.

Adaptation, Psychological↗
PubMed1998

Protonation of the neutral repeats of the RNA polymerase II CTD.

The CTD (carboxy-terminal repeat domain) of the largest subunit of RNA Polymerase II in most eukaryotes consists of from 26 to 52 seven amino acid repeats, the consensus sequence of which is YSPTSPS. Even though this consensus repeat does not contain residues that are normally protonated under the conditions used for positive ion electrospray mass spectrometry, we find that the CTD acquires about one proton per repeat when analyzed by this procedure. We have termed this phenomenon superprotonation. Superprotonation is apparently a property of the consensus sequence as the repeat peptide, (YSPTSPS)4, is superprotonated whereas other proteins and the repeat peptides (YSPTSPK)4, (YSPTSPR)4 and (YSPTAPR)4 are not. The highly conserved nature of the contiguous consensus repeats in organisms ranging from yeast to mammals implies that the functionally significant behavior of the domain is easily perturbed. We propose that CTD superprotonation is a manifestation of a unique biophysical property that will influence and could be the basis for consensus repeat function in vivo.

Amino Acid Sequence↗
PubMed1998

Surface structure of human mucin using X-ray photoelectron spectroscopy.

X-ray photoelectron spectroscopy (XPS) is a surface sensitive analytical technique that measures the binding energy of electrons in atoms and molecules on the surface of a material. XPS was used to determine the distribution of the oligosaccharide side chains in the glycoprotein, MUC1 mucin. Low-resolution XPS spectra provided elemental composition of MUC1 mucin (fully glycosylated), mucin polypeptide (nonglycosylated), and carbohydrates found in mucin. The nitrogen content of MUC1 mucin was determined to be intermediate between the mucin polypeptide and the carbohydrates. Assuming a uniform distribution of carbohydrate on MUC1 mucin, the average thickness of the carbohydrate layer was calculated to be 4.9 nm using the low-resolution N 1s signals. High-resolution XPS spectra give detailed information about the chemical bonding of the surface molecules. Calculations based on the high-resolution O 1s spectra showed a carbohydrate thickness of 6.6 nm. These experimentally determined values agree reasonably well with an estimated 5 nm of carbohydrate thickness from a simple model which assume that the core protein is a rodlike molecule approximately 5 nm in diameter. Although the carbohydrate coating on the MUC1 mucin appears to be thick enough to cover the core protein entirely, fully glycosylated breast milk MUC1 mucin is susceptible to proteolytic digestion without removal of any oligosaccharide side chain, suggesting areas of exposed core protein. A possible explanation is that the oligosaccharide side chains may form patches of carbohydrate along the core protein with regions of exposed core protein.

Amino Acid Sequence↗
PubMed1997

Treatment of dairy cows at parturition with prostaglandin F2 alpha or oxytocin for prevention of retained fetal membranes.

OBJECTIVE: To evaluate the effects of treatment at parturition with dinoprost tromethamine, fenprostalene, or oxytocin on postpartum disease and reproductive performance during the subsequent breeding season in dairy cows. DESIGN: Prospective study. ANIMALS: 1,400 Holstein cows from 5 commercial dairies. PROCEDURE: Cows were assigned within 2 hours after calving to serve as untreated control cows or to be treated with 1 mg of fenprostalene, SC; 25 mg of dinoprost tromethamine, IM; or 20 IU of oxytocin, IM. Cows were confined to treatment pens and monitored daily until fetal membranes were expelled. Cows with retained fetal membranes (RFM) were treated according to existing treatment protocols for the dairy, with the provision that intrauterine infusions were not allowed. All other disease conditions were recorded, and appropriate treatment was administered. Postpartum reproductive examinations were performed 28 to 56 days after parturition Breeding records were maintained for all cows until pregnancy was confirmed or the cow was removed from the herd. RESULTS: Fetal membranes were retained in 12.1% of all cows, and this outcome was unaffected by treatment. Compared with cows without RFM, cows with RFM had longer intervals to first insemination (76.4 vs 82.0 days), reduced first insemination conception rates (46.8 vs 28.0%), and increased number of days not pregnant (103.2 vs 127.4 days). Farm, as a variable, significantly affected development of RFM and postpartum disease conditions as well as reproductive performance during the subsequent breeding season. Fetal membranes were retained in 12.4, 15.2, 8.7, 6.3, and 16.9% of cows on farms 1, 2, 3, 4, and 5, respectively. Mean days to first insemination varied from 64.5 days (farm 3) to 91.5 days (farm 1). Mean number of days not pregnant varied from 94.8 days (farm 3) to 15.9 days (farm 4). CLINICAL IMPLICATIONS: Administration of prostaglandins or oxytocin at the time of calving does not reduce the incidence of RFM or improve reproductive performance. Farm management practices have the greatest impact on dairy cow performance.

Abortifacient Agents, Nonsteroidal↗
PubMed1997

Evidence for a novel O-linked sialylated trisaccharide on Ser-248 of human plasminogen 2.

Human plasminogen, the inactive precursor of plasmin, exists in two major glycoforms. Plasminogen 1 contains an N-linked oligosaccharide at Asn-289 and an O-linked oligosaccharide at Thr-345. Plasminogen 2 is known to contain only an O-linked oligosaccharide at Thr-345. However, plasminogen 2 displays a further well documented microheterogeneity dependent on the N-acetylneuraminic acid content, which has functional consequences with regard to activation of plasminogen. The proposed structure and number of known oligosaccharide linkages in plasminogen 2 is insufficient to account for this microheterogeneity. In the present study, a combination of trypsin digestion, lectin affinity chromatography, Edman degradation amino acid sequence analysis, carbohydrate composition analysis, and mass spectrometry revealed the existence of a novel site for O-linked glycosylation on plasminogen 2 at Ser-248. Direct evidence for the structure of the carbohydrate was obtained from a combination of lectin affinity chromatography, desialylation experiments, and mass spectrometry analysis. These findings provide a structural basis for some of the observed microheterogeneity, and have implications with regard to the known functional consequences of the extent of sialylation of plasminogen.

Amino Acid Sequence↗
PubMed1997

Discriminative microcirculatory screening of patients with refractory limb ischaemia for dorsal column stimulation.

OBJECTIVES: (1) To determine the proportion of patients with critical limb ischaemia refractory to invasive treatment that can be successfully treated by dorsal column stimulation (DCS), and (2) to identify potential responders to DCS by a simple test that is sufficiently predictive to limit the need for a prolonged trial stimulation period. PATIENTS AND METHODS: Twenty patients with chronic limb-threatening ischaemia were assessed by a battery of macro- and microcirculatory tests and a DCS trial of 1 week. Favourable response during the trial determined selection for long-term stimulation. RESULTS: During a mean observation period of 14 months, limb salvage rate (LSR) was 63% overall and 83% among patients selected after a favourable trial. Of the tests performed preoperatively, digital subtraction angiography, Doppler assessment, oscillometry, capillaroscopy, foot temperature, and transcutaneous partial pressure of oxygen (tcpO2) in the supine or sitting position did not adequately predict DCS response. The supine-sitting tcpO2 gradient (delta tcpO2) was a good predictor of DCS outcome, with an 88% LSR when delta tcpO2 > 15 Torr, dropping to 12% when delta tcpO2 < or = 15 Torr. CONCLUSIONS: DCS is a rewarding therapeutic option in selected patients with critical limb ischaemia. delta tcpO2 appears to reliably predict response to DCS and may obviate trial stimulation in most cases.

Adult↗
PubMed1996

Oxytetracycline residues in milk after intrauterine treatment of cows with retained fetal membranes.

OBJECTIVE: To establish the maximum concentration and duration of oxytetracycline residues in milk from cows with retained fetal membranes given the antimicrobial via intrauterine infusion, and to investigate whether the number of infusions or the presence of fever (> 39.7 C) affected the duration of residues. DESIGN: Prospective study. ANIMALS: 54 Holstein cows with retained fetal membranes on a single 1,400-cow commercial dairy. PROCEDURE: Cows were treated once a day with 5 g of oxytetracycline (50 ml of 100 mg/ml solution in a povidone base) by intrauterine infusion for at least 2 days, or until the membranes were expelled. Cows that became febrile (rectal temperature > or = 39.7 C) were also given 20,000 IU of procaine penicillin G/kg of body weight, i.m., for 2 to 4 days. Milk samples were collected at 24-hour intervals during treatment. and at 12-hour intervals after the last treatment. All samples were frozen and submitted every 2 weeks for high performance liquid chromatography analysis for oxytetracycline. RESULTS: Oxytetracycline was detected in milk of all cows during treatment, at a maximum concentration ranging from 47.2 to 1,804.6 micrograms/kg (mean, 316.9 micrograms/kg). Duration of oxytetracycline residues after the last infusion ranged from 0 to 144 hours (mean, 52.3 hours). Neither the number of infusions received, nor development of rectal temperature > 39.7 C, affected the maximum concentration or the duration of oxytetracycline residues in milk. CLINICAL IMPLICATIONS: Milk obtained from cows that had been treated for retained fetal membranes by intrauterine infusion of oxytetracycline should be discarded to avoid illegal residues.

Animals↗
PubMed1996

High-level misincorporation of lysine for arginine at AGA codons in a fusion protein expressed in Escherichia coli.

The expression of eukaryotic genes in Escherichia coli is one of the most frequently used tools of modern science. The arginine codon AGA is a common codon in eukaryotic genes but is particularly rare in E. coli. We report here 36 to 42% misincorporation of lysine at three AGA codons in a well-expressed protein. This misincorporation yields a protein whose electrospray mass spectrum (ESMS) shows peaks at the expected mass (M), M-28, M-56 and M-84 with intensities representing 34.5(+/-0.7), 37.5(+/-1.1), 21.2(+/-1.7) and 6.6(+/-0.5) % of the total intensity, respectively. Replacement of either all three AGA codons or the two closest to the 3' end of the gene by the more common CGC arginine codon gave a protein with a single ESMS peak. Misincorporation could also be eliminated by the co-expression of the tRNA(UCL)Arg gene, argU. These studies demonstrate that misincorporation of amino acids at rare codons of recombinant proteins can be far higher than previously thought.

Amino Acid Sequence↗