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Biomedical subjects

H Knight

Publications and source records attributed to H Knight.

At least 19 recordsLinked to original sources
PubMed2006

Centralization of services: standard setting and outcomes.

OBJECTIVE: To test specific standards set in the newly established cleft lip and palate service in three regions of the U.K. The standards relate to record collection and outcomes. DESIGN: Retrospective analysis. PATIENTS: Records of 31 children, 5 years of age, who were born in 1997 with complete unilateral clefts of lip and palate and were treated by surgeons in three regions. MAIN OUTCOME MEASURES: Record collection standards were measured by collecting dental study models. Outcomes were measured with the 5-Year-Old Index. RESULTS: Of the 31 subjects, 52% had excellent and good outcomes. The 31 cases represented 62% of the total records collected. CONCLUSIONS: The three regions examined fell short of the standards set, but the outcomes were improved compared with previous national outcomes. The failings in record collection need to be rectified. This study provides baseline data for further development of cleft services within three regions.

Child, Preschool↗
PubMed2001

Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques: implications for the neuropathogenesis of AIDS.

The macrophage is well established as a target of HIV and simian immunodeficiency virus (SIV) infection and a major contributor to the neuropathogenesis of AIDS. However, the identification of distinct subpopulations of monocyte/macrophages that carry virus to the brain and that sustain infection within the central nervous system (CNS) has not been examined. We demonstrate that the perivascular macrophage and not the parenchymal microglia is the primary cell productively infected by SIV. We further demonstrate that although productive viral infection of the CNS occurs early, thereafter it is not easily detectable until terminal AIDS. The biology of perivascular macrophages, including their rate of turnover and replacement by peripheral blood monocytes, may explain the timing of neuroinvasion, disappearance, and reappearance of virus in the CNS, and questions the ability of the brain to function as a reservoir for productive infection by HIV/SIV.

AIDS Dementia Complex↗
PubMed2001

Abiotic stress signalling pathways: specificity and cross-talk.

Plants exhibit a variety of responses to abiotic stresses that enable them to tolerate and survive adverse conditions. As we learn more about the signalling pathways leading to these responses, it is becoming clear that they constitute a network that is interconnected at many levels. In this article, we discuss the 'cross-talk' between different signalling pathways and question whether there are any truly specific abiotic stress signalling responses.

Abscisic Acid↗
PubMed2000

Characterization of pathology in transgenic mice over-expressing human genomic and cDNA tau transgenes.

To examine the normal cellular function of tau and its role in pathogenesis, we have created transgenic mice that overexpress a tau transgene derived from a human PAC that contains the coding sequence, intronic regions, and regulatory regions of the human gene. All six isoforms of human tau are represented in the transgenic mouse brain at the mRNA and protein level and the human tau is distributed in neurites and at synapses, but is absent from cell bodies. A comparison between the genomic tau mice and mice that overexpress a tau cDNA transgene shows that overall, the distribution of tau is similar in the two lines, but human tau is located in the somatodendritic compartment of many neurons in the cDNA mice. Tau-immunoreactive axonal swellings were found in the spinal cords of the cDNA mice, which correlated with a hind-limb abnormality, whereas neuropathology was essentially normal in the genomic mice up to 8 months of age.

Alzheimer Disease↗
PubMed2000

Calcium signaling during abiotic stress in plants.

Plants experience a wide array of environmental stimuli, not all of which are favorable, and, unlike animals, are unable to move away from stressful environments. They therefore require a mechanism with which to recognize and respond to abiotic stresses of many different types. Frequently this mechanism involves intracellular calcium. Stress-induced changes in the cytosolic concentration of Ca2+ ([Ca2+]cyt) occur as a result of influx of Ca2+ from outside the cell, or release of Ca2+ from intracellular stores. These alterations in [Ca2+]cyt constitute a signal that is transduced via calmodulin, calcium-dependent protein kinases, and other Ca(2+)-controlled proteins to effect a wide array of downstream responses involved in the protection of the plant and adjustment to the new environmental conditions. Ca2+ signaling has been implicated in plant responses to a number of abiotic stresses including low temperature, osmotic stress, heat, oxidative stress, anoxia, and mechanical perturbation, which are reviewed in this article.

Anaerobiosis↗
PubMed2000

Comparison of cation-adjusted Mueller-Hinton broth with Iso-Sensitest broth for the NCCLS broth microdilution method.

Comparison of MIC results obtained in different parts of the world is currently difficult because of variations in methods. In this study, cation-adjusted Mueller-Hinton broth, the NCCLS-recommended medium, was compared with Iso-Sensitest broth, which is widely used in Europe. Microbroth dilution testing, using the NCCLS procedure, was performed on 124 Gram-positive (staphylococci and enterococci) and Gram-negative (Enterobacteriaceae and Pseudomonas aeruginosa) isolates from the CDC reference set, with the only variable being the medium used. Twelve antimicrobial agents were tested: amoxycillin-clavulanic acid, ampicillin, ciprofloxacin, erythromycin, gentamicin, imipenem, levofloxacin, oxacillin, gemifloxacin, trimethoprim- sulphamethoxazole, tetracycline and vancomycin. Vancomycin, erythromycin and oxacillin were only evaluated for the Gram-positive organisms. Trimethoprim-sulphamethoxazole was only evaluated for a subset of Gram-negative organisms because of off-scale results. The 124 isolates were tested in one American and one UK laboratory with two batches of cation-adjusted Mueller-Hinton broth and two of Iso-Sensitest broth. A statistical evaluation of the data used a 24 fully specified factorial analysis to determine if there were significant differences in results owing to Gram reaction, site of testing and type and/or batch of broth. In addition, the cumulative results for each antimicrobial agent in each broth were plotted against the range of MIC dilutions tested. MICs of ciprofloxacin, levofloxacin, gemifloxacin, gentamicin and tetracycline were slightly higher (half a doubling dilution) with Iso-Sensitest broth than with Mueller-Hinton broth. MIC results for the other antimicrobial agents were equivalent. Essential and category agreement rates were comparable for all agents (88.4-100% and 88.2-99.0%, respectively).

Anti-Bacterial Agents↗
PubMed2000

Imaging spatial and cellular characteristics of low temperature calcium signature after cold acclimation in Arabidopsis.

Cooling-induced 'calcium signatures' were imaged in aequorin-expressing Arabidopsis plants after cold acclimation or growth at ambient temperature. In all tissues, signatures were altered after acclimation. Characterization of the components generating this response indicates that cold acclimation increases cold-induced vacuolar Ca(2+) release, but does not affect the influx of extracellular calcium.

Adaptation, Physiological↗
PubMed1999

Induced hypothermia as salvage treatment for refractory cardiac failure following paediatric cardiac surgery.

OBJECTIVE: Following corrective cardiac surgery in infants and children for congenital heart disease, a persistent low cardiac output refractory to conventional modes of treatment is associated with a mortality approaching 100%. We advocate the use of whole body hypothermia to reduce tissue oxygen demand and provide a degree of cellular protection against ischaemia allowing time for recovery. We describe our experience. METHODS: Between July 1986 and December 1995, 1885 infants and children underwent surgery (operative mortality, 6%), 1302 requiring cardiopulmonary bypass. Fifty-seven patients had a persistent low cardiac output, impaired respiratory function, decreased urine output and acidosis despite maximal intensive care treatment. Cooling to 32-33 degrees C was therefore started using a thermostatically controlled water filled cooling blanket. RESULTS: Following cooling, there was a fall in heart rate (P<0.001), a rise in mean arterial pressure (P<0.001) and a fall in mean atrial pressure (P<0.001). Significant (P<0.001) increases in pH and urine output were also recorded. Thirty-one (54%) of the 57 patients treated with cooling survived to leave hospital. No long-term sequelae have been noted in these patients. CONCLUSION: Induced hypothermia is a useful salvage treatment, in children following corrective cardiac surgery when all conventional treatment has been tried and failed.

Cardiac Output, Low↗
PubMed1999

Dissection of the ozone-induced calcium signature.

The cellular responses of plants to numerous extracellular stimuli are mediated by transient elevations in the concentration of cytosolic free calcium ([Ca2+]cyt). We have addressed the question of how cells can use this apparently ubiquitous system to initiate so many specific and appropriate end responses. We show that the pollutant gas ozone elicits a biphasic Ca2+ response in intact Arabidopsis plants and a subsequent increase in expression of the gene encoding the antioxidant defence enzyme glutathione-S-transferase (GST). The second of the two [Ca2+]cyt peaks, but not the first, could be eliminated either by pre-treatment of plants with lanthanum chloride, or by reducing the duration of ozone fumigation. Under these conditions, ozone-induced GST expression was abolished. These data provide a functional dissection of the ozone Ca2+ signalling pathway and indicate that the second ozone-induced [Ca2+]cyt peak provides the necessary information to direct expression of GST.

Arabidopsis↗
PubMed1999

Temperature sensing by plants: the primary characteristics of signal perception and calcium response.

Cold elicits an immediate rise in the cytosolic free calcium concentration ([Ca2+]c) of plant cells. We have studied the concerted action of the three underlying mechanisms, namely sensing, sensitisation and desensitisation, which become important when plants in the field are subjected to changes in temperature. We applied different regimes of temperature changes with well-defined cooling rates to intact roots of Arabidopsis thaliana expressing the calcium-indicator, aequorin. Our results indicate that temperature sensing is mainly dependent on the cooling rate, dT/dt, whereas the absolute temperature T is of less importance. Arabidopsis roots were found to be sensitive to cooling rates of less than dT/dt = 0.01 degrees C/s. However, at cooling rates below 0.003 degrees C/s (i.e. cooling 10 degrees C in 1 h) there is no detectable [Ca2+]c response at all. At low temperature, the sensitivity of the plant cold-detection system is increased. This in turn produces greater cooling-induced [Ca2+]c elevations. Prolonged or repeated cold treatment attenuates the [Ca2+]c responses to subsequent episodes of cooling.

Aequorin↗
PubMed1999

The sfr6 mutation in Arabidopsis suppresses low-temperature induction of genes dependent on the CRT/DRE sequence motif.

The sfr mutations, which result in sensitivity to freezing after cold acclimation, define genes that are required for freezing tolerance. We tested plants homozygous for mutations sfr2 to sfr7 for cold-induced gene expression and found that sfr 6 plants were deficient in cold-inducible expression of the genes KIN1, COR15a, and LTI78, which all contain the C repeat/dehydration-responsive element (CRT/DRE) motif in their promoters. Similarly, sfr 6 plants failed to induce KIN1 normally in response to either osmotic stress or the application of abscisic acid. In contrast, cold-inducible expression of genes CBF1, CBF2, CBF3, and ATP5CS1, which lack the CRT/DRE motif, was not affected. The freezing-sensitive phenotype that defines sfr 6 also was found to be tightly linked to the gene expression phenotype. To determine whether the failure of cold induction of CRT/DRE-containing genes in sfr 6 was due to altered low-temperature calcium signaling, cold-induced cytosolic-free calcium ([Ca2+]cyt) elevations were investigated in the sfr 6 mutant, but these were found to be indistinguishable from those of the wild type. We discuss the possibilities that CRT/DRE binding proteins (such as CBF1) require activation to play a role in transcription and that the SFR6 protein is a vital component of their activation.

1-Pyrroline-5-Carboxylate Dehydrogenase↗
PubMed1998

Induced hypothermia in the postoperative management of refractory cardiac failure following paediatric cardiac surgery.

Postoperative low cardiac output states are a major cause of postoperative mortality in infants and children following corrective cardiac surgery for congenital heart defects. In this unit, whole body hypothermia has been used since 1979 in the management of these low output states when they are refractory to conventional modes of therapy. Twenty cases treated in this way between July 1986 and June 1990 were reviewed in 1992. The current report reviews the 50 further cases treated with moderate hypothermia between July 1990 and December 1995. The median (range) age of patients was 8 months (0 days-16 years) with a median weight of 4.1 kg (2.5-33 kg). Following cooling, there was a decrease in heart rate (p < 0.001), an increase in mean arterial pressure (p < 0.001) and a decrease in mean atrial pressure (p < 0.001). Significant increases in pH and urine output were also noticed, the increase in urine output being greater in the surviving group (p = 0.02). A decrease in platelet count occurred (p < 0.001) but white blood cell count remained unchanged (p = 0.18). Twenty-five of the 50 patients survived to leave hospital. Induced hypothermia does not appear to be associated with any complications and after the failure of all conventional treatment, it seems likely that the technique may have been beneficial to outcome in some patients.

Adolescent↗
PubMed1998

A history of stress alters drought calcium signalling pathways in Arabidopsis.

Environmental stresses commonly encountered by plants lead to rapid transient elevations in cytosolic free calcium concentration ([Ca2+]cyt) (Bush, 1995; Knight et al., 1991). These cellular calcium (Ca2+) signals lead ultimately to the increased expression of stress-responsive genes, including those encoding proteins of protective function (Knight et al., 1996; Knight et al., 1997). The kinetics and magnitude of the Ca2+ signal, or 'calcium signature', differ between different stimuli and are thought to contribute to the specificity of the end response (Dolmetsch et al., 1997; McAinsh and Hetherington, 1998). We measured [Ca2+]cyt changes during treatment with mannitol (to mimic drought stress) in whole intact seedlings of Arabidopsis thaliana. The responses of plants which were previously exposed to osmotic and oxidative stresses were compared to those of control plants. We show here that osmotic stress-induced Ca2+ responses can be markedly altered by previous encounters with either osmotic or oxidative stress. The nature of the alterations in Ca2+ response depends on the identity and severity of the previous stress: oxidative stress pre-treatment reduced the mannitol-induced [Ca2+]cyt response whereas osmotic stress pretreatment increased the [Ca2+]cyt response. Therefore, our data show that different combinations of environmental stress can produce novel Ca2+ signal outputs. These alterations are accompanied by corresponding changes in the patterns of osmotic stress-induced gene expression and, in the case of osmotic stress pre-treatment, the acquisition of stress-tolerance. This suggests that altered Ca2+ responses encode a 'memory' of previous stress encounters and thus may perhaps be involved in acclimation to environmental stresses.

Aequorin↗
PubMed1997

Calcium signalling in Arabidopsis thaliana responding to drought and salinity.

Changes in cytosolic free calcium concentration ([Ca2+]cyt) in response to mannitol (drought) and salt treatments were detected in vivo in intact whole Arabidopsis seedlings. Transient elevations of [Ca2+]cyt to around 1.5 microM were observed, and these were substantially inhibited by pretreatment with the calcium-channel blocker lanthanum and to a lesser extent, the calcium-chelator EGTA. The expression of three genes, p5cs, which encodes delta(1)-pyrroline-5-carboxylate synthetase (P5CS), the first enzyme of the proline biosynthesis pathway, rab18 and Iti78 which both encode proteins of unknown function, was induced by mannitol and salt treatments. The induction of all three genes by mannitol was inhibited by pretreatment with lanthanum. Salt-induced p5cs, but not rab18 and Iti78, expression was also inhibited by lanthanum. Induction of p5cs by mannitol was also inhibited by the calcium channel-blockers gadolinium and verapamil and the calcium chelator EGTA, further suggesting the involvement of calcium signalling in this response. Mannitol induced greater levels of p5cs gene expression than an isoosmolar concentration of salt, at both relatively high and low concentrations. However, calcium transients were of a similar magnitude and duration in response to both mannitol and isoosmolar concentrations of salt, suggesting that a factor other than calcium is involved in the discrimination between drought and salinity signals in Arabidopsis. In order to gauge the involvement of the vacuole as an intracellular calcium store in the response of Arabidopsis to mannitol, [Ca2+]cyt was measured at the microdomain adjacent to the vacuolar membrane. The results obtained were consistent with a significant calcium release from the vacuole contributing to the overall mannitol-induced [Ca2+]cyt response. Data obtained by using inhibitors of inositol signalling suggested that this release was occurring through IP3-dependent calcium channels.

1-Pyrroline-5-Carboxylate Dehydrogenase↗
PubMed1996

Reading Rock Festival: a nursing perspective.

Working in the Accident and Emergency (A & E) department at the Royal Berkshire Hospital, Reading, is in itself fairly unremarkable - the unit functions in much the same way as any other Trust Hospital department. It does, however, provide a rather unique opportunity - the option to participate in the running of an on-site medical facility, at the internationally acclaimed Reading Rock Festival. This article explores the impact of the festival on the local A & E department, and highlights the experience of a staff nurse working at the Festival site.

Emergency Service, Hospital↗
PubMed1996

Delay of gratification: mothers' predictions about four attentional techniques.

Mothers' predictions about the ability of their own children to delay gratification using different techniques were investigated. Fifty-one mothers of children 4 to 6 years old were asked to evaluate distraction, thinking about the incentive, tasting the incentive, and a control. These conditions were derived from the research of Mischel and his associates (1974), who demonstrated the effectiveness of distraction in aiding children's delay behavior. Parents were predicted to expect delay to be enhanced by the distraction technique and hampered by the thinking about the incentive and tasting the incentive techniques, with the latter being the least effective. Contrary to our predictions, mothers failed to predict effectiveness of distraction compared with the two incentive-focused techniques. Reasons are advanced for more research on parents' knowledge and valuing of metacognitive strategies appropriate for their children.

Attention↗
PubMed1996

Cold calcium signaling in Arabidopsis involves two cellular pools and a change in calcium signature after acclimation.

Cold shock elicits an immediate rise in cytosolic free calcium concentration ([Ca2+]cyt) in both chilling-resistant Arabidopsis and chilling-sensitive tobacco (Nicotiana plumbaginifolia). In Arabidopsis, lanthanum or EGTA caused a partial inhibition of both cold shock [Ca2+]cyt elevation and cold-dependent kin1 gene expression. This suggested that calcium influx plays a major role in the cold shock [Ca2+]cyt response and that an intracellular calcium source also might be involved. To investigate whether the vacuole (the major intracellular calcium store in plants) is involved, we targeted the calcium-dependent photoprotein aequorin to the cytosolic face of the vacuolar membrane. Cold shock calcium kinetics in this microdomain were consistent with a cold-induced vacuolar release of calcium. Treatment with neomycin or lithium, which interferes with phosphoinositide cycling, resulted in cold shock [Ca2+]cyt kinetics consistent with the involvement of inositol trisphosphate and inositide phosphate signaling in this response. We also investigated the effects of repeated and prolonged low temperature on cold shock [Ca2+]cyt. Differences were observed between the responses of Arabidopsis and N. plum-baginifolia to repeated cold stimulation. Acclimation of Arabidopsis by pretreatment with cold or hydrogen peroxide caused a modified calcium signature to subsequent cold shock. This suggests that acclimation involves modification of plant calcium signaling to provide a "cold memory."

Acclimatization↗