Anaesthetists and care of the critically ill child.
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Anesthesiology↗
Biomedical subjects
A Tomlinson
Publications and source records attributed to A Tomlinson.
ISABEL: a web-based differential diagnostic aid for paediatrics: results from an initial performance evaluation.
AIMS: To test the clinical accuracy of a web based differential diagnostic tool (ISABEL) for a set of case histories collected during a two stage evaluation. METHODS SETTING: acute paediatric units in two teaching and two district general hospitals in the southeast of England. MATERIALS: sets of summary clinical features from both stages, and the diagnoses expected for these features from stage I (hypothetical cases provided by participating clinicians in August 2000) and final diagnoses for cases in stage II (children presenting to participating acute paediatric units between October and December 2000). MAIN OUTCOME MEASURE: presence of the expected or final diagnosis in the ISABEL output list. RESULTS: A total of 99 hypothetical cases from stage I and 100 real life cases from stage II were included in the study. Cases from stage II covered a range of paediatric specialties (n = 14) and final diagnoses (n = 55). ISABEL displayed the diagnosis expected by the clinician in 90/99 hypothetical cases (91%). In stage II evaluation, ISABEL displayed the final diagnosis in 83/87 real cases (95%). CONCLUSION: ISABEL showed acceptable clinical accuracy in producing the final diagnosis for a variety of real as well as hypothetical case scenarios.
Acute Disease↗
Acanthamoeba keratitis.
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Acanthamoeba Keratitis↗
Anti-Acanthamoeba efficacy in contact lens disinfecting systems.
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Acanthamoeba↗
Nitric oxide synthase inhibitors have opposite effects on acute inflammation depending on their route of administration.
The bulk of published data has shown that NO is proinflammatory. However, there also exists the conflicting notion that NO may be protective during an inflammatory insult. In an attempt to resolve this issue, we have compared the effects on inflammation of a range of NO synthase (NOS) inhibitors given either directly to the site of the inflammatory lesion or systemically. It was found that in the carrageenin-induced pleurisy, a single intrapleural injection of the selective inducible NO inhibitors S-(2-aminoethyl) isothiourea (AE-ITU; 3 and 10 mg/kg) and N-(3-(aminomethyl)-benzyl) acetamidine (1400W; 10 mg/kg) or the selective endothelial cell NOS inhibitor L-N(5)(1-iminoethyl)-ornithine (10 mg/kg) not only exacerbated inflammation at the very early stages of the lesion (1-6 h), but also prevented inflammatory resolution. By contrast, administering NOS inhibitors systemically ameliorated the severity of inflammation throughout the reaction. To elucidate the mechanisms by which inhibition of NO synthesis locally worsened inflammation, we found an increase in histamine, cytokine-induced neutrophil chemoattractant, superoxide, and leukotriene B(4) levels at the inflammatory site. In conclusion, this work shows that the local production of NO is protective by virtue of its ability to regulate the release of typical proinflammatory mediators and, importantly, that NOS inhibitors have differential anti-inflammatory effects depending on their route of administration.
Acute Disease↗
Delta/Notch and Boss/Sevenless signals act combinatorially to specify the Drosophila R7 photoreceptor.
The R7 photoreceptor, a unique cell type within the Drosophila ommatidium, was initially proposed to be specified by two distinct signals from neighboring cells, one from the R8 photoreceptor and another from the R1/6 photoreceptor pair. The R8-to-R7 signal is the transmembrane ligand Bride of Sevenless (Boss), which is received by the receptor tyrosine kinase Sevenless (Sev) and transduced via Ras activation within the presumptive R7 cell. However, the identity of the R1/6-to-R7 signal has remained elusive. Here, we present evidence that the transmembrane ligand Delta (Dl), expressed by the R1/6 pair, activates the receptor Notch (N) in the presumptive R7 cell and constitutes the postulated R1/6-to-R7 signal required in combination with the Boss/Sev signal to specify the R7 fate.
Animals↗
What does the phenol red thread test actually measure?
PURPOSE: This study attempts to resolve whether the phenol red thread test (PRT) is a test of tear volume or tear production through comparisons with other techniques. METHODS: Twenty asymptomatic subjects (10 men and 10 women; average age 30.6 +/- 10.8 years) had PRT (Zone Quick, Menicon) results compared with tear turnover rate (by fluorophotometry; Fluorotron Master, OcuMetrics) and tear volumes (from tear meniscus height and back extrapolation from fluorometric data). RESULTS: PRT wetting was not correlated with either tear turnover or volume (by fluorophotometry or tear meniscus height) on a Pearson product moment correlation test (p > 0.05). CONCLUSIONS: No clear experimental evidence in favor of the PRT being a measure of tear production or volume was found. It is probable that the PRT measures uptake of a (small) amount of fluid residing in the eye, stimulates a low degree of reflex tearing, and reflects the absorption characteristics of the thread dependent on the biophysics or composition of tears.
Adolescent↗
Symbiogenesis in learning classifier systems.
Symbiosis is the phenomenon in which organisms of different species live together in close association, resulting in a raised level of fitness for one or more of the organisms. Symbiogenesis is the name given to the process by which symbiotic partners combine and unify, that is, become genetically linked, giving rise to new morphologies and physiologies evolutionarily more advanced than their constituents. The importance of this process in the evolution of complexity is now well established. Learning classifier systems are a machine learning technique that uses both evolutionary computing techniques and reinforcement learning to develop a population of cooperative rules to solve a given task. In this article we examine the use of symbiogenesis within the classifier system rule base to improve their performance. Results show that incorporating simple rule linkage does not give any benefits. The concept of (temporal) encapsulation is then added to the symbiotic rules and shown to improve performance in ambiguous/non-Markov environments.
Algorithms↗
Transducing properties of Drosophila Frizzled proteins.
In Drosophila, two closely related serpentine receptors, Frizzled (Fz) and D-Frizzled2 (Fz2) are able to act as receptors for the secreted Wnt peptide, Wingless (Wg). In addition to transducing the Wg signal, Fz (but not Fz2) is able to transduce a second, unidentified signal that mediates planar polarity. Much attention has been focused on the structure of the N-termini of the Fz-class receptors and their role in ligand binding. Experiments using techniques of high-level expression have suggested a role for the C-termini in specifying which of the two second messenger systems the receptors are able to activate (M. Boutros, J. Mihaly, T. Bouwmeeste and M. Mlodzik (2000). Science 288, 1825-1828). We argue here that experiments involving high level expression of the receptors cannot be adequately interpreted and we have tested the ability of the receptors and chimeric forms when driven at moderate levels to rescue loss of function of the fz and fz2 genes. Under these conditions we find that all receptors tested will function as Wg receptors, but only a subset show the ability to rescue the polarity pathway. The presence of this subset implies that the N terminus is necessary but not sufficient and suggests that the ability to transduce the polarity signal is widely distributed throughout the protein.
Animals↗
Effect of oral contraceptives on tear physiology.
Variations in sex hormones due to the menstrual cycle (and oral contraceptives) were evaluated for their effect on tear physiology. Subjects were 18 females taking oral contraceptives or their age matched controls (no medication), aged 21-33 years. Symptoms of ocular discomfort (visual analog scale), tear film structure (TearScope), non-invasive tear thinning time (HirCal grid), evaporation rate (ServoMed evaporimeter), osmolality (Nanolitre Osmometer), tear turnover rate, tear volume (Fluorotron Master), and tear protein levels (HPLC) were measured around day 2 (D2), actually day 1-4 and day 19 (D19) actually day 18-21 of the cycle. No significant differences were found for any tear parameters between D2 and D19 for either pill users or controls alone, or in the comparison of pill users with controls. No effect on tear physiology was found for serum hormone changes induced by oral contraceptive use or by normal cyclic variations in healthy young females.
Adult↗
arrow encodes an LDL-receptor-related protein essential for Wingless signalling.
The Wnt family of secreted molecules functions in cell-fate determination and morphogenesis during development in both vertebrates and invertebrates (reviewed in ref. 1). Drosophila Wingless is a founding member of this family, and many components of its signal transduction cascade have been identified, including the Frizzled class of receptor. But the mechanism by which the Wingless signal is received and transduced across the membrane is not completely understood. Here we describe a gene that is necessary for all Wingless signalling events in Drosophila. We show that arrow gene function is essential in cells receiving Wingless input and that it acts upstream of Dishevelled. arrow encodes a single-pass transmembrane protein, indicating that it may be part of a receptor complex with Frizzled class proteins. Arrow is a low-density lipoprotein (LDL)-receptor-related protein (LRP), strikingly homologous to murine and human LRP5 and LRP6. Thus, our data suggests a new and conserved function for this LRP subfamily in Wingless/Wnt signal reception.
Animals↗
Salicylate inhibition of Acanthamoeba attachment to contact lenses: a model to reduce risk of infection.
PURPOSE: Acanthamoeba attachment (adsorption) to hydrogel contact lenses is enhanced by Pseudomonas aeruginosa biofilm. The effect of sodium salicylate on Acanthamoeba attachment to biofilm-coated and uncoated hydrogel lenses was investigated. DESIGN: Experimental study. PARTICIPANTS AND CONTROLS: A minimum of 16 replicates were used for each test condition; a control condition using clean lenses without biofilm was included. METHODS: Four groups of hydrogel contact lenses (etafilcon A) were pretreated with P. aeruginosa to form a biofilm. In addition, two more groups remained untreated. Quartered lenses of all six groups were then incubated in a suspension of A. castellanii trophozoites. Two batches of lenses had either 3 or 30 mM sodium salicylate added to the bacterial suspension (stage 1 intervention). Two other batches of lenses had salicylate added to the amoebal suspension (stage 2 intervention). One of the batches, which had a stage 1 intervention, had salicylate added at the second stage as well. The remaining batches received no salicylate exposure and included lenses with and without biofilm coating. MAIN OUTCOME MEASURE: The outcome measure in this study was the number of Acanthamoeba trophozoites attached, per square centimeter, to the hydrogel surfaces. RESULTS: Biofilm coating from P. aeruginosa gave a significantly increased attachment of A. castellanii trophozoites to the contact lens. When introduced at a first (biofilm) stage, second (trophozoite attachment) stage, or with intervention at both stages, 30 mM sodium salicylate reduced amoebal attachment to the hydrogel lens. When applied to both stages and when applied at stage 2 to the biofilm coated contact lenses, 3 mM sodium salicylate reduced amoebal attachment. The 3 mM concentration was not effective for the lower level of amoebae attachment to uncoated (nonbiofilm) lenses. CONCLUSIONS: Sodium salicylate successfully reduced amoebal trophozoite attachment to hydrogel lenses. This was the result of one of the following possibilities or a combination thereof: inhibition of biofilm formation; a direct effect on the amoebae; an alteration in the biofilm-amoebal attachment and resulting modification of the hydrogel lens surface. The results of this study suggest the major action is at stage 2 (on amoebal attachment to lenses) and favors alteration of the biofilm-amoebal attachment mechanism. This study demonstrates salicylate's potential benefit as a component of contact lens care solutions, designed to reduce microbial attachment and the risk of infection.
Acanthamoeba↗
The role of tear physiology in ocular surface temperature.
PURPOSE: To determine whether the more rapid cooling of the tear film in dry eyes is related to other tear film parameters, a battery of tear physiology tests was performed on dry eye patients and control subjects. METHODS: Tear evaporation rate was measured with a modified Servomed (vapour pressure) evaporimeter and ocular temperature with an NEC San-ei 6T62 Thermo Tracer in 9 patients diagnosed as having dry eye and in 13 healthy control subjects. Variability in temperature across the ocular surface was described by the temperature variation factor (TVF). Lipid layer structure and tear film stability were assessed with the Keeler Tearscope and tear osmolality was measured by freezing point depression nanolitre osmometry. RESULTS: The data were explored by principal component analysis. The subjects with and without dry eye could be separated into two distinct groups entirely on the basis of their tear physiology. Dry eye patients exhibited higher tear evaporation rates, osmolalities and TVF, lower tear film stabilities and poorer-quality lipid layers than the control subjects. A significant linear relationship was found to exist between tear evaporation rate and TVF for all subjects (R2 = 0.242, p = 0.024). CONCLUSIONS: Rapid cooling of the tear film in dry eyes appears to be related to the reduced stability of the tears and the increased rate of evaporation. The higher latent heat of vaporisation, associated with the increased evaporation in dry eyes, may account for the increased rate of cooling of the tear film in this condition.
Adult↗
Acanthamoeba keratitis occurring with daily disposable contact lens wear.
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Acanthamoeba Keratitis↗
Transcriptional regulation of the Hedgehog effector CI by the zinc-finger gene combgap.
Members of the Hedgehog (HH) family of secreted signaling molecules specify cell fate during animal development by controlling the activity of members of the Gli family of zinc-finger transcription factors in responding cells. In Drosophila the Gli homolog, cubitus interruptus (CI), is expressed only in the anterior compartment where it represses targets such as the signaling molecule genes decapentaplegic (dpp) and wingless (wg). HH is expressed in the posterior and diffuses into the anterior where it antagonizes CI repression resulting in dpp and wg expression immediately anterior to the compartment border. Reducing CI levels results in misexpression of wg and dpp, while CI misexpression in the posterior disrupts differentiation. Thus, normal disc patterning requires high levels of CI in the anterior and the absence of CI in the posterior. Here we show that mutations in combgap (cg) result in deregulation of CI expression, which is now expressed at much lower levels and ubiquitously, i.e., also in the posterior. Consequently, cg mutants phenocopy ci loss-of-function mutants in the anterior and ci gain-of-function mutants in the posterior. cg encodes a putative DNA-binding protein that regulates both transcriptional activation and repression of the ci gene.
Alleles↗
Spatial location studies on the chemical composition of human tear ferns.
Tear ferns are the patterns formed when tears are allowed to dry on a clean smooth surface. The patterns have been categorised according to confluence of pattern, with less confluent ferns indicative of tear film abnormalities. Little is known about the mechanism that gives rise to this phenomenon. Previous work has concentrated on correlation of alterations in tear film composition on the ferning phenomenon. The present study takes a new approach by analysing the locations of chemical elements in the fern to understand how the ferns form. By means of SEM coupled with EDXA, Na, K and Cl were detected within the fern. Sulphur, indicative of the presence of macromolecules such as mucins and proteins, was only found at the very periphery of the dry tear drop. The results suggest that macromolecules do not play a direct role in the formation of the ferns. A model is put forward to explain the observation whereby proteins and mucins are precipitated selectively by increasing salt concentration at the drop margin.
Adult↗
Transducing the Dpp morphogen gradient in the wing of Drosophila: regulation of Dpp targets by brinker.
Dpp, a TGFbeta, organizes pattern in the Drosophila wing by acting as a graded morphogen, activating different targets above distinct threshold concentrations. Like other TGFbetas, Dpp appears to induce transcription directly via activation of a SMAD, Mad. However, here we demonstrate that Dpp can also control gene expression indirectly by downregulating the expression of the brinker gene, which encodes a putative transcription factor that functions to repress Dpp targets. The medial-to-lateral Dpp gradient along the anterior-posterior axis is complemented by a lateral-to-medial gradient of Brinker, and the presence of these two opposing gradients may function to allow cells to detect small differences in Dpp concentration and respond by activating different target genes.
Amino Acid Sequence↗
A LIM-homeodomain combinatorial code for motor-neuron pathway selection.
Different classes of vertebrate motor neuron that innervate distinct muscle targets express unique combinations of LIM-homeodomain transcription factors, suggesting that a combinatorial code of LIM-homeodomain proteins may underlie the control of motor-neuron pathway selection. Studies of LIM-homeodomain genes in mouse, Drosophila melanogaster and Caenorhabditis elegans have revealed functions of these genes in neuronal survival, axon guidance, neurotransmitter expression and neuronal function, but, to our knowledge, none of these studies have addressed the issue of a functional code. Here we study two members of this gene family in Drosophila, namely lim3, the homologue of the vertebrate Lhx3 and Lhx4 genes, and islet, the homologue of the vertebrate Isl1 and Is12 genes. We show that Drosophila lim3 is expressed by a specific subset of islet-expressing motor neurons and that mutating or misexpressing lim3 switches motor-neuron projections predictably. Our results provide evidence that lim3 and islet constitute a combinatorial code that generates distinct motor-neuron identities.
Amino Acid Sequence↗