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Biomedical subjects

J Ellis

Publications and source records attributed to J Ellis.

At least 163 records · Page 9Linked to original sources

Measuring expectations for participative decision making among graduating nurses.

This paper reports on the initial stage of a research program that examines decisions nurses expect to participate in and the methods by which they expect to participate. This stage of the research focuses on the development of a scale, the Participative Decision Making Scale for Nurses (PDMSN), to measure expectations for participative decision making (PDM) among graduating nurses. It has four subscales that measure expectations for participation in clinical, unit, hospitalwide, and strategic decisions. The PDMSN was administered to two groups of graduating nursing students. Results indicate that the subscales of the PDMSN have high internal consistency; alpha coefficients in Study 1 and Study 2 ranged from .70 to .85 and from .76 to .90, respectively. Patterns of correlations among the subscales and significant correlations with an alternative scale measuring PDM indicate that it is a valid instrument.

Adult↗

A microstructural flow analysis within a bileaflet mechanical heart valve hinge.

BACKGROUND AND AIMS OF THE STUDY: During recent clinical trials, the Medtronic Parallel bileaflet heart valve was found to have an unacceptable thrombosis complication rate. As patient- and material-related factors proved negative causes for this outcome, it was hypothesized that the flow fields within the valve's hinge pocket contributed to the thrombus formation. METHODS: A microstructural flow analysis within the hinge pocket is presented which uses the techniques of flow visualization, computational fluid dynamics (CFD), and laser Doppler velocimetry (LDV). The application of these techniques towards solving this problem has become possible through (i) the ability to manufacture dimensionally correct 1-X transparent heart valve housings, (ii) advances in CFD technology, and (iii) advances in LDV measurement techniques. RESULTS: This analysis showed that a vortex was present at the hinge pocket's inflow channel during forward flow and degenerated to a disturbed three-dimensional structure during reverse flow with zones of turbulent shear stress large enough to cause blood cell damage. In addition, multiple zones of flow stagnation and disturbed flow existed along the leaflet's pivot throughout the entire cardiac cycle. It was felt that these complex fluid structures created conditions which resulted in the formation of thrombus within the hinges of the Medtronic Parallel valve. These findings were supported by limited clinical explant data which illustrated early thrombus formation within the Parallel valve's hinge pocket at sites predicted by the analysis. CONCLUSIONS: This study provides, for the first time, an understanding of the detailed flow structures within the hinges of a mechanical heart valve and demonstrates an analysis technique by which future mechanical heart valve designs may be assessed for the potential of thrombus formation within the valve's hinge regions.

Computer Simulation↗

Transcription of interferon-alpha 2 alleles from virus-induced human leucocytes and lymphoblastoid cells of African origin.

It has been previously shown that the genomic DNA of both the lymphoblastoid cell line (Namalwa) and certain human donors (of African origin) contain sequences corresponding to two allelic variants, b and c, of the interferon-alpha 2 gene (IFNA2). Little is known however about the relative expression of these two alleles in heterozygous cells. We have therefore examined the transcription of allelic variants of the human IFNA2 locus by both normal human leucocytes (from a heterozygous donor) and Namalwa cells. Analysis of cDNA clones identified sequences of both allelic variants, IFNA2b and c, indicating active transcription by both cell types. Analysis of tryptic and peptic peptides derived from purified IFN-alpha 2 also demonstrated both IFN-alpha 2b and IFN-alpha 2c proteins. Populations of virus induced heterozygous cells can therefore effectively transcribe and secrete both forms of IFN-alpha 2 simultaneously, with no apparent restrictions on expression of either allele.

Alleles↗

Kinetic mechanism of chloramphenicol acetyltransferase: the role of ternary complex interconversion in rate determination.

Chloramphenicol acetyltransferase (CAT) catalyzes the acetyl-CoA-dependent acetylation of chloramphenicol (Cm) by a ternary complex mechanism and with a random order of addition of substrates. A closer examination of the mechanism of the reaction catalyzed by the type III CAT variant (CATIII) has included the measurement of the individual rate constants by stopped-flow fluorimetry at 5 degrees C. Under all conditions employed, product release from the binary complexes in both forward and reverse reactions was found to be too slow to account for the observed overall rate of turnover for the reaction. Additional, faster routes for product release are achieved via the formation of the nonproductive ternary complexes (CAT:3-acetyl-Cm:acetyl-CoA and CAT:CoA:Cm). The release of 3-acetyl-Cm from the binary complex is 5-fold slower than kcat (135 s-1 at 5 degrees C), whereas the dissociation rate constants of 3-acetyl-Cm from the ternary complexes with CoA and acetyl-CoA are 120 and 200 s-1, respectively. Arrhenius plots of dissociation rate constants indicate a slow release of products over a broad temperature range. Computer simulations based on the rate constants of CATIII applied to a ternary complex mechanism, assuming random order of substrate addition and product release, yielded nonlinear initial rates of product formation unless both nonproductive ternary complexes were included in the model. Simulated steady-state kinetic analyses based on the latter assumption yielded kinetic parameters that compared favorably with those determined experimentally.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyl Coenzyme A↗

Structural and mechanistic studies of galactoside acetyltransferase, the Escherichia coli LacA gene product.

Escherichia coli galactoside acetyltransferase (GAT) is a member of a large family of acetyltransferases that O-acetylate dissimilar substrates but share limited sequence homology. Steady-state kinetic analysis of over-expressed GAT demonstrated that it accepted a range of substrates, including glucosides and lactosides which were acetylated at rates comparable to galactosides. GAT was shown to be a trimeric acetyltransferase by cross-linking with dimethyl suberimidate. Fluorometric analysis of coenzyme A binding showed that there is a fluorescence quench associated with acetyl-CoA binding whereas CoA has no effect. This difference was exploited to measure dissociation rates for both CoA and acetyl-CoA by stopped-flow fluorometry. The rate of dissociation of CoA (2500 s-1) is at least 170-fold faster than kcat for any substrate tested. The fluorescence response to acetyl-CoA binding is entirely due to Trp-139 since replacement by phenylalanine completely abolished the fluorescence quench. Treatment of GAT by [14C]iodoacetamide resulted in complete inactivation of the enzyme and the incorporation of label into histidyl and cysteinyl residues to approximately equal extents. Following replacement of His-115 by alanine, label was incorporated solely into cysteinyl residues. Furthermore, the substitution results in an 1800-fold decrease in kcat suggesting that His-115 has an important catalytic role in GAT.

Acetyl Coenzyme A↗

Inpatient general medicine is evidence based. A-Team, Nuffield Department of Clinical Medicine.

For many years clinicians have had to cope with the accusation that only 10-20% of the treatments they provide have any scientific foundation. Their interventions, in other words, are seldom "evidence based". Is the profession guilty as charged? In April, 1995, a general medical team at a university-affiliated district hospital in Oxford, UK, studied the treatments given to all 109 patients managed during that month on whom a diagnosis had been reached. Medical sources (including databases) were then searched for randomised controlled trial (RCT) evidence that the treatments were effective. The 109 primary treatments were then classified: 82% were evidence based (ie, there was RCT support [53%] or unanimity on the team about the existence of convincing non-experimental evidence [29%]). This study, which needs to be repeated in other clinical settings and for other disciplines, suggests that earlier pessimism over the extent to which evidence-based medicine is already practised is misplaced.

Clinical Medicine↗

Tryptophan fluorescence of chloramphenicol acetyltransferase: resolution of individual excited-state lifetimes by site-directed mutagenesis and multifrequency phase fluorometry.

Multifrequency phase fluorometry, in conjunction with site-directed mutagenesis, has allowed the determination of the fluorescence lifetimes of each of the three tryptophan residues of the type III variant of chloramphenicol acetyltransferase (CATIII). The mutant proteins retaining a single tryptophan yield lifetimes of 1.36, 2.00, and 1.17 ns for Trp-16, -86, and -152, respectively. Binding of chloramphenicol shortens the fluorescence lifetimes of all three tryptophans to some extent, in particular those of Trp-86 and Trp-152 (decreases of 51% and 39%, respectively). The mechanism of fluorescence quenching is believed to be radiationless energy transfer. Estimates of Trp-chloramphenicol distances by energy-transfer calculations are in good agreement with those determined from the crystal structure of CATIII. Despite binding at the same site in wild-type CATIII, CoA and ethyl-S-CoA produce different responses in global lifetime measurements--increases of 8% and 31%, respectively. Examination of each of the one-Trp CATIII variants, generated by site-directed mutagenesis, yields a variety of responses. Trp-152, located within the CoA binding site, responds to both CoA and its thioalkyl derivative with a 27-30% increase in fluorescence lifetime. Trp-16, distant from the CoA site, does not differentiate between the two ligands (7% increase in lifetime). However, Trp-86 shows a striking difference in binding responses, only a 4% decrease with CoA but a 14% reduction with ethyl-S-CoA. Each of the two-Trp CAT variants shows little change in global fluorescence lifetime on association with CoA.(ABSTRACT TRUNCATED AT 250 WORDS)

Chloramphenicol O-Acetyltransferase↗

Could a nearby supernova explosion have caused a mass extinction?

We examine the possibility that a nearby supernova explosion could have caused one or more of the mass extinctions identified by paleontologists. We discuss the possible rate of such events in the light of the recent suggested identification of Geminga as a supernova remnant less than 100 parsec (pc) away and the discovery of a millisecond pulsar about 150 pc away and observations of SN 1987A. The fluxes of gamma-radiation and charged cosmic rays on the Earth are estimated, and their effects on the Earth's ozone layer are discussed. A supernova explosion of the order of 10 pc away could be expected as often as every few hundred million years and could destroy the ozone layer for hundreds of years, letting in potentially lethal solar ultraviolet radiation. In addition to effects on land ecology, this could entail mass destruction of plankton and reef communities, with disastrous consequences for marine life as well. A supernova extinction should be distinguishable from a meteorite impact such as the one that presumably killed the dinosaurs at the "KT boundary." The recent argument that the KT event was exceedingly large and thus quite rare supports the need for other catastrophic events.

Journal Article↗

Comparison of the patterns of codon usage and bias between Brugia, Echinococcus, Onchocerca and Schistosoma species.

Patterns of codon usage and bias were compared among taxa of the genera Brugia, Echinococcus, Onchocerca and Schistosoma by metric multidimensional scaling and three commonly used indices of bias: Nc, GC3S and B. The overall codon usage for each taxon was compared, as was the codon usage for each individual gene within the taxa. Differences in the patterns of codon usage observed between taxa were dependent on the overall base composition of the genes analysed. The codon usage of Echinococcus was distinct from that of the other taxa. Furthermore, the pattern of codon usage detected by the average codon usage summed across all genes for each taxon was not shown by all genes from that taxon.

Animals↗

Effects of sequence alignment on the phylogeny of Sarcocystis deduced from 18S rDNA sequences.

The family Sarcocystidae contains a wide variety of parasitic protozoa, some of which are important pathogens of livestock and humans. The taxonomic relationships between two of the genera in this family (Toxoplasma and Sarcocystis) have been debated for a number of years and remain controversial. Recent studies, from comparisons of 18S rDNA-sequence data, have suggested that Sarcocystis is paraphyletic, although a hypothesis supporting monophyly of Sarcocystis could not be rejected. The present study shows that the phylogenetically informative nucleotide positions within the 18S rDNA are primarily located in the regions that make up the helices in the secondary structure of the 18S rRNA. A phylogenetic analysis of 18S rDNA-sequence data aligned by secondary structure constraints, or a subset of the data corresponding to all nucleotides found in the helices, provide unambiguous evidence supporting monophyly of Sarcocystis.

Animals↗

Embryo brain kinase: a novel gene of the eph/elk receptor tyrosine kinase family.

A new gene belonging to the Eph/Eck/Elk receptor tyrosine kinase family has been cloned from mouse brain. The gene maps to mouse chromosome 4. In the adult brain it is expressed exclusively and abundantly in the hippocampus. We propose to name it Ebk (embryo brain kinase), as in situ hybridisation shows expression in many parts of the developing mouse brain. The most abundant expression is in the subcommissural organ, and the earliest expression is in the forebrain neural folds, in rhombomeres 2-6, and in somites and heart. Other regions positive at various stages include the cochlear duct, trigeminal ganglion, lung, first branchial arch, and tooth primordia. Also positive are areas of mesenchyme underlying various epithelia during morphogenesis, especially in the mouth and nose, as well as in the eyelids and toes. We compare these patterns with the available data on the 12 other known members of this gene family. Most of them, like Ebk, are expressed in brain (especially adult hippocampus and embryonic rhombomeres) and in organs rich in epithelia (especially lung), although the spatial and temporal patterns differ. We suggest that combinatorial patterns of these receptors act as labels for the regional identity of neurons and epithelia, and could mediate fine control of neurite pathfinding and epithelial morphogenesis.

Aging↗

The effect of a self-management training package on the transfer of aggression control procedures in the absence of supervision.

An aggression replacement and self-management training package reduced the frequency of aggressive behavior among four junior high adolescents identified as seriously emotionally disturbed (SED). During baseline sessions, the students were covertly filmed as they stood unsupervised in front of the school cafeteria. The four subjects engaged in aggressive behavior during 50% of the filmed intervals. These episodes involved provocation by other students, self-initiated provocation, or continuing interaction between students once an aggressive episode had begun. Treatment procedures included instruction, modeling, and role playing of aggression replacement skills. Self-management training included self-assessment, self-recording, and self-reinforcement. Following an 8-week period, subjects demonstrated substantial improvement in prosocial skills without supervision. During reversal-to-baseline conditions, aggressive behavior increased; however, reinstating treatment conditions brought a return to prosocial behavior. Outcomes suggest that aggressive replacement skills may transfer and sustain more adequately using self-management.

Adolescent↗

Immunoblastic transformation of a Sezary syndrome in a black Caribbean patient without evidence of HTLV-I.

We describe an unusual case of Sezary syndrome which transformed into a large T-cell non Hodgkin's lymphoma (immunoblastic) in a black man of Caribbean descent with negative HTLV-I serology and no evidence of HTLV-I infection by DNA analysis using sensitive techniques. The disease presented as a small-cell Sezary syndrome and transformed in an inguinal lymph node one year from diagnosis. Immunological markers in the small and large cells showed a mature T-cell phenotype CD4+, CD8- with expression of T-cell activation markers and a high proliferative rate. Ultrastructural analysis confirmed small Sezary cells with serpentine nucleus in the peripheral blood and immunoblasts in the lymph node. Cytogenetics demonstrated complex clonal chromosome abnormalities with involvement of 7q35, the locus for the beta chain of the T-cell receptor (TCR). Southern-blot analysis showed the same rearrangement of the TCR beta, gamma, delta chain genes in lymph node and peripheral blood cells. Antibodies to HTLV-I were not detected in the serum by ELISA and particle agglutination (PA) nor HTLV-I specific sequences were demonstrated by nested polymerase chain reaction with primers to the envelope proteins, LTR and tax/rex of HTLV-I in both tissues, blood and lymph node. The disease had an aggressive course and was refractory to therapy; the patient died of progressive disease 28 months from presentation. Two unusual features characterised this patient's illness: immunoblastic transformation of a Sezary syndrome in a patient of Afro-Caribbean origin without evidence of HTLV-I DNA sequences and negative HTLV-I serology and the atypical lymph node histology resembling ATLL.

Base Sequence↗

Serum gentamicin levels: a comparison between the Syva Solaris and the Syva QST analysers.

Enzyme-multiplied immunoassay techniques (EMIT) are now widely used as an effective method for monitoring gentamicin concentrations to ensure adequate serum levels. The current EMIT system was to be superseded by an improved version and both were run in parallel over a nine-month period and the results compared. During this time the systems were evaluated for ease of use, and reproducibility of results. The newer, EMIT produced more consistent calibration results with less kit-to-kit variation, which in turn gave more reproducible results both with patients' sera and the monthly NEQAS quality controls. The newer system was put into routine use at the end of the trial.

Enzyme Multiplied Immunoassay Technique↗