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Biomedical subjects

G Knight

Publications and source records attributed to G Knight.

At least 19 recordsLinked to original sources
PubMed2005

To lead or not to lead? Prospective controlled study of emergency nurses' provision of advanced life support team leadership.

BACKGROUND AND OBJECTIVES: In many emergency departments advanced life support (ALS) trained nurses do not assume a lead role in advanced resuscitation. This study investigated whether emergency nurses with previous ALS training provided good team leadership in a simulated cardiac arrest situation. METHODS: A prospective study was conducted at five emergency departments and one nurses' association meeting. All participants went through the same scenario. Details recorded included baseline blood pressure and pulse rate, time in post, time of ALS training, and subjective stress score (1 = hardly stressed; 10 = extremely stressed). Scoring took into account scenario understanding, rhythm recognition, time to defibrillation, appropriateness of interventions, and theoretical knowledge. RESULTS: Of 57 participants, 20 were ALS trained nurses, 19 were ALS trained emergency senior house officers (SHOs), and 18 were emergency SHOs without formal ALS training. The overall mean score for doctors without ALS training was 69.5%, compared with 72.3% for ALS trained doctors and 73.7% for ALS trained nurses. Nurses found the experience less stressful (subjective stress score 5.78/10) compared with doctors without ALS training (6.5/10). The mean time taken to defibrillate from the appearance of a shockable rhythm on the monitor by the nurses and those SHOs without ALS training was 42 and 40.8 seconds, respectively. CONCLUSION: ALS trained nurses performed as well as ALS trained and non ALS trained emergency SHOs in a simulated cardiac arrest situation and had greater awareness of the potentially reversible causes of cardiac arrest. Thus if a senior or middle grade doctor is not available to lead the resuscitation team, it may be appropriate for experienced nursing staff with ALS training to act as ALS team leaders rather than SHOs.

Advanced Cardiac Life Support↗
PubMed2000

Fyn and Lyn phosphorylate the Fc receptor gamma chain downstream of glycoprotein VI in murine platelets, and Lyn regulates a novel feedback pathway.

Activation of platelets by collagen is mediated by the complex glycoprotein VI (GPVI)/Fc receptor gamma (FcR gamma chain). In the current study, the role of 2 Src family kinases, Fyn and Lyn, in GPVI signaling has been examined using murine platelets deficient in one or both kinases. In the fyn(-/-) platelets, tyrosine phosphorylation of FcR gamma chain, phopholipase C (PLC) activity, aggregation, and secretion are reduced, though the time of onset of response is unchanged. In the lyn(-/-) platelets, there is a delay of up to 30 seconds in the onset of tyrosine phosphorylation and functional responses, followed by recovery of phosphorylation and potentiation of aggregation and alpha-granule secretion. Tyrosine phosphorylation and aggregation in response to stimulation by collagen-related peptide is further attenuated and delayed in fyn(-/-)lyn(-/-) double-mutant platelets, and potentiation is not seen. This study provides the first genetic evidence that Fyn and Lyn mediate FcR immune receptor tyrosine-based activation motif phosphorylation and PLC gamma 2 activation after the ligation of GPVI. Lyn plays an additional role in inhibiting platelet activation through an uncharacterized inhibitory pathway. (Blood. 2000;96:4246-4253)

Animals↗
PubMed1999

Edema volume, not timing, is the key to success in lymphedema treatment.

BACKGROUND: There are currently between 1 and 2 million breast cancer survivors in the United States. Is the advocated, early intervention the key to successful treatment, or are there other, more important factors? METHODS: Responses to combined decongestive therapy (CDT) for 69 women were analyzed with regard to duration of lymphedema, differences in arm circumference, percent differences in arm volumes, volume of edema, reduction of edema volumes, and duration of treatment. RESULTS: Two- and three-dimensional (2D and 3D) analyses showed little correlation between duration and volume of edema or between duration and response and treatment. However, they did show a correlation between initial volumes of fluid in the tissues and responses. Patients with initial volumes of 250 mL or less had a mean reduction of 78% with CDT, whereas those with initial volumes between 250 and 500 mL had a mean reduction of 56%. CONCLUSION: The key to predicting successful lymphedema treatment is the initial volume of edema in the tissues regardless of whether the intervention is early or late.

Adult↗
PubMed1999

Electron-immunocytochemical studies of perivascular nerves of mesenteric and renal arteries of golden hamsters during and after arousal from hibernation.

Electron immunocytochemistry was used to examine perivascular nerves of hamster mesenteric and renal arteries during hibernation and 2 h after arousal from hibernation. Vessels from cold-exposed but nonhibernating, and normothermic control hamsters were also examined. During hibernation the percentage of axon profiles in mesenteric and renal arteries that were immunopositive for markers of sympathetic nerves, tyrosine hydroxylase (TH) and neuropeptide Y (NPY), were increased 2-3 fold compared with normothermic and cold control animals. This increase was reduced markedly only 2 h after arousal from hibernation. The small percentage of nitric oxide synthase-1-positive axon profiles found in mesenteric (but not renal) arteries was also increased during hibernation and returned towards control values after arousal. In contrast, the percentage of perivascular axons immunostaining for vasoactive intestinal polypeptide (VIP), a marker for parasympathetic nerves, was reduced in mesenteric arteries during hibernation. There was no labelling of perivascular nerves for substance P in either mesenteric or renal arteries. It is suggested that the increase in percentage of TH- and NPY-immunostained perivascular nerves may account for the increased vasoconstriction associated with high vascular resistance that is known to occur during hibernation. The reduction in the percentage of axons positive for VIP in hibernating animals would contribute to this mechanism since this neuropeptide is a vasodilator.

Animals↗
PubMed1999

Children's behaviour and the design of school furniture.

Children spend a large part of their school days in the classroom, and yet the effect of the design of school furniture on their behaviour and health has received comparatively little attention in the UK. An experimental study is reported that compares the effects on children's behaviour and sitting position of traditional classroom furniture with a recently designed chair known as 'Chair 2000' and associated tables. It was found that children showed a modest but significant improvement in on-task behaviour and a marked change in sitting positions following the introduction of the newly-designed furniture. However, these benefits need to be considered in the light of polarized opinion for and against the new furniture, and a high level of reported incidence of back pain significantly related to the frequency of non-standard sitting. In the absence of radically redesigned furniture, it is suggested that children should be given more choice in their seating, and better guidance should be given to individuals involved in education in order to inform their decision-making about classroom furniture and the postural, anthropometric and orthopaedic aspects of sitting and related activities.

Analysis of Variance↗
PubMed1999

Ultrastructural localization of nitric oxide synthase and endothelin in the renal and mesenteric arteries of the golden hamster: differences during and after arousal from hibernation.

This is a study of the electron-immunocytochemical localization of nitric oxide synthase (type III) and endothelin in renal and mesenteric artery endothelial cells of normal (active) and hibernating hamsters, as well as hamsters exposed to the cold but not hibernating, and hamsters aroused for 2h following hibernation. In the renal artery of hibernating hamsters and cold-exposed hamsters, a subpopulation of nitric oxide synthase-positive endothelial cells displayed immunoprecipitate predominantly in the vicinity of the Golgi complex indicating intracellular translocation from the cytoplasm to the Golgi complex. In hibernating animals, the percentages of both nitric oxide synthase-positive and endothelin-positive endothelial cells were notably lower than those observed either in active, cold-exposed or aroused animals. These changes may reflect a reduced endothelial contribution to the maintenance of vascular tone in these vessels during hibernation and an upregulation of expression of nitric oxide synthase and endothelin in the endothelium early on during arousal from hibernation.

Animals↗
PubMed1998

Enhanced vasoconstrictor responses in renal and femoral arteries of the golden hamster during hibernation.

1. The present study assessed local regulation of vascular tone of euthermic (control), cold control and hibernating golden hamsters. Sympathetic neurotransmission in the renal artery, the long term effects of hibernation on perivascular nerve activity, and the responsiveness of femoral artery to a number of neurotransmitters and hormones with both constrictor and dilator actions during hibernation are described. 2. The contractile responses of the renal arterial rings to transmural nerve stimulation (80 V, 0.1 ms, 4-64 Hz, for 1 s) were negligible in controls, significantly increased at higher frequencies of stimulation in cold controls and markedly enhanced in the hibernating group at all frequencies tested. The contractile responses to exogenous noradrenaline (NA; 0.1-100 microM) were significantly increased in the renal arteries of hibernating hamsters compared with controls, but not compared with cold controls. Responses to exogenous ATP (1-3000 microM) and KCl (120 mM) were similar among all experimental groups. 3. The maximal contractile responses of femoral arterial rings to the sympathetic co-transmitter ATP and 5-hydroxytryptamine were increased by approximately 124% and 99%, respectively, in hibernating compared with cold control preparations without a change in the concentration of agonist that produces half-maximal response. However, the responses to NA were not altered during hibernation. 4. Vasoconstriction of femoral arterial rings in response to arginine vasopressin was significantly enhanced in both cold controls and hibernating groups, while vasoconstriction in response to endothelin-1 and KCl was unaltered. 5. The dilator responses of femoral arterial rings to acetylcholine, sodium nitroprusside and adenosine were not different among the groups. 6. It is suggested that the marked augmentation of sympathetic neurotransmission, selective supersensitivity of the vascular smooth muscle to sympathetic contractile agents and unaltered vasodilatory mechanisms may provide a means for maintenance of vascular tone and peripheral resistance during hibernation.

Adenosine Triphosphate↗
PubMed1998

Effects of hibernation and arousal from hibernation on mesenteric arterial responses of the golden hamster.

The aim of our study was to investigate the changes that occur in functional responses of the golden hamster mesenteric arterial bed after: 1) 8 wk of hibernation and 2) 2 hr after arousal from hibernation. Age-matched and cold-exposed hamsters were used as controls. At 8 wk after hibernation there was an increase in sensitivity of vasoconstrictor responses to sympathetic nerve stimulation but no significant difference in constrictor responses to norepinephrine, alpha,beta-methylene ATP, uridine 5'-triphosphate or KCl (studied in unconstricted preparations), or in endothelium-dependent vasodilatation to acetylcholine and uridine 5'-triphosphate (in methoxamine-preconstricted preparations) compared with the control groups. In contrast, in the arousal from hibernation group, sympathetic vasoconstriction was similar to that in the control groups, and the maximal response to exogenous norepinephrine, and responses to alpha,beta-methylene ATP were augmented. These results suggest that there is an augmentation of sympathetic neurotransmission of golden hamster mesenteric arteries at 8 wk after hibernation, which appears to be due to pre- rather than postjunctional changes. This is reversed with arousal from hibernation, when the sensitivity of sympathetic contractile responses is not different from that of the controls. However, an increase in maximal constrictor responses to norepinephrine suggests that postjunctional changes may occur in sympathetic neurotransmission during arousal.

Acetylcholine↗
PubMed1997

Validation of a high-performance liquid chromatographic assay method for pharmacokinetic evaluation of busulfan.

The development and validation of a high-performance liquid chromatographic (HPLC) assay for determination of busulfan concentrations in human plasma for pharmacokinetic studies is described. Plasma samples containing busulfan and 1,6-bis(methanesulfonyloxy)hexane, and internal standard, were prepared by derivatization with sodium diethyldithiocarbamate (DDTC) followed by addition of methanol and extraction with ethyl acetate. The extract was dried under nitrogen and the samples reconstituted with 100 microl of methanol prior to HPLC determination. Chromatography was accomplished using a Waters NovaPak octadecylsilyl (ODS) (150 x 3.9 mm I.D.) analytical column, NovaPak ODS guard column, and mobile phase of methanol-water (80:20, v/v) at a flow-rate of 0.8 ml/min with UV detection at 251 nm. The limit of detection was 0.0200 microg/ml (signal-to-noise ratio of 6) with a limit of quantitation (LOQ) of 0.0600 microg/ml for busulfan in plasma. Calibration curves were linear from 0.0600 to 3.00 microg/ml in plasma (500 microl) using a 1/y weighting scheme. Precision of the assay, as represented by C.V. of the observed peak area ratio values, ranged from 4.41 to 13.5% (13.5% at LOQ). No day-to-day variability was observed in predicted concentration values and the bias was low for all concentrations evaluated (bias: 0 to 4.76%; LOQ: 2.91%). The mean derivatization and extraction yield observed for busulfan in plasma at 0.200, 1.20 and 2.00 microg/ml was 98.5% (range 93.4 to 107%). Plasma samples containing potential busulfan metabolites and co-administered drugs, which may be present in clinical samples, provided no response indicating this assay procedure is selective for busulfan. This method was used to analyze plasma concentrations following administration of a 1 mg/kg oral busulfan dose.

Busulfan↗
PubMed1997

Neurochemical coding in the myenteric plexus of the upper gastrointestinal tract of hibernating hamsters.

As part of our investigation of the plasticity of autonomic nerves in physiological and pathological conditions, we have examined the effect of hibernation on the neurochemical content of myenteric nerves and nerve cell bodies of the upper gastrointestinal tract of the non-seasonal hibernator, the golden hamster. Age matched hamsters kept at room temperature and those kept at 5 degrees C but which failed to hibernate, were used as controls. Possible changes in nerve fibres and nerve cell bodies containing the general neuronal marker, protein gene product 9.5, the peptides, vasoactive intestinal polypeptide, substance P (SP) and calcitonin gene-related peptide (CGRP), the catecholamine synthesizing enzyme tyrosine hydroxylase and the enzyme responsible for synthesizing nitric oxide, nitric oxide synthase, were examined in the oesophagus, proventriculus and proximal and distal stomach of the golden hamsters using immunohistochemical techniques. The results of the present study revealed a significant increase in the number of nerve cell bodies and density of nerve fibres containing SP-immunoreactivity and increased number of CGRP-immunoreactive cell bodies but not the other markers examined in the proximal stomach and proventriculus. In contrast, there was no change in the distribution of any of the neuroactive substances examined in the myenteric plexus of the oesophagus and distal stomach. It is suggested that the change in the environment of the hibernating hamsters perturbs the normal digestive physiology in the proximal stomach and proventriculus that is reflected by the selective changes in SP- and CGRP-containing enteric nerves; these changes may be part of protective reflex mechanisms to the environmental changes resulting from hibernation, where upgrading of nerve cell bodies expressing CGRP and SP has occurred.

Animals↗
PubMed1997

Effects of hibernation on neural and endothelial control of mesenteric arteries of the golden hamster.

The effects of hibernation on mesenteric arterial innervation and function were examined using pharmacological and immunohistochemical techniques in age-matched controls, cold-exposed controls, and 4-wk-hibernated golden hamsters. Electrical field stimulation of the isolated mesenteric arterial bed elicited frequency-dependent vasoconstriction. The sensitivity of responses was significantly increased in tissues from hibernating animals compared with cold-exposed controls. Vasoconstrictor responses to exogenous norepinephrine were also increased in hibernation. However, there was a significant decrease in sensitivity of vasoconstriction to ATP in hibernated and cold-exposed tissue compared with age-matched controls. In preparations preconstricted with methoxamine, endothelium-dependent vasodilator responses to acetylcholine and ATP were similar among the groups. Immunohistochemical investigation of mesenteric arteries revealed no differences among the groups in density of innervation by nerves immunoreactive for tyrosine hydroxylase, neuropeptide Y, and calcitonin gene-related peptide. Postjunctional changes appear to occur in hibernation, leading to augmentation of sympathetic vasoconstriction, which is consistent with the increase in peripheral vascular resistance in hibernation. Endothelium-dependent vasodilatation is not significantly changed in hibernation in the hamster mesenteric arterial bed.

Acetylcholine↗
PubMed1996

Biochemical characterization of human collagenase-3.

The cDNA of a novel matrix metalloproteinase, collagenase-3 (MMP-13) has been isolated from a breast tumor library (Freije, J. M. P., Dicz-Itza, I., Balbin, M., Sanchez, L. M., Blasco, R., Tolivia, J., and López-Otin, C. (1994) J. Biol. Chem. 269, 16766-16773), and a potential role in tumor progression has been proposed for this enzyme. In order to establish the possible role of collagenase-3 in connective tissue turnover, we have expressed and purified recombinant human procollagenase-3 and characterized the enzyme biochemically. The purified procollagenase-3 was shown to be glycosylated and displayed a M(r) of 60,000, the N-terminal sequence being LPLPSGGD, which is consistent with the cDNA-predicted sequence. The proenzyme was activated by p-aminophenylmercuric acetate or stromelysin, yielding an intermediate form of M(r) 50,000, which displayed the N-terminal sequence L58EVTGK. Further processing resulted in cleavage of the Glu84-Tyr85 peptide bond to the final active enzyme (M(r) 48,000). Trypsin activation of procollagenase-3 also generated a Tyr85 N terminus, but it was evident that the C-terminal domain was rapidly lost, and hence the collagenolytic activity diminished. Analysis of the substrate specificity of collagenase-3 revealed that soluble type II collagen was preferentially hydrolyzed, while the enzyme was 5 or 6 times less efficient at cleaving type I or III collagen. Fibrillar type I collagen was cleaved with comparable efficiency to the fibroblast and neutrophil collagenases (MMP-1 and MMP-8), respectively. Unlike these collagenases, gelatin and the peptide substrates Mea-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 and Mca-Pro-Cha-Gly-Nva-His-Ala-Dpa-NH2 were efficiently hydrolyzed as well, as would be predicted from the similarities between the active site sequence of collagenase-3 (MMP-13) and the gelatinases A and B. Active collagenase-3 was inhibited in a 1:1 stoichiometric fashion by the tissue inhibitors of metalloproteinases, TIMP-1, TIMP-2, and TIMP-3. These results suggest that in vivo collagenase-3 could play a significant role in the turnover of connective tissue matrix constituents.

Amino Acid Sequence↗
PubMed1996

The molecular chaperone alpha-crystallin inhibits UV-induced protein aggregation.

Solutions of gamma-crystallin, and various enzymes, at neutral pH and 24-26 degrees C, became turbid upon exposure to UV radiation at 295 or 308 nm. SDS-PAGE analysis revealed interchain cross-linking and aggregate formation compared to dark control solutions as reported previously. When alpha-crystallin was added to the protein solutions in stoichiometric amounts, UV irradiation resulted in significantly less turbidity than in the absence of alpha-crystallin. For example, addition of 0.5 mg of alpha-crystallin to 0.5 mg of gamma-crystallin in 1.0 ml solution yielded only 25% of the turbidity seen in the absence of alpha-crystallin. Addition of 2.0 mg of alpha-crystallin resulted in 20% of the turbidity. Given the molecular weights of alpha- and gamma-crystallin (about 800 kDa and 20 kDa, respectively), a gamma/alpha 1:1 weight ratio corresponds to a 40:1 molar ratio, and a gamma/alpha 1:4 weight ratio corresponds to a 10:1 molar ratio. Hence, the molar ratio of alpha-crystallin needed to effectively protect gamma-crystallin from photochemical opacification was gamma/alpha = n:1, where n was in the range 10-40. In terms of subunits, this ratio is gamma/alpha = 1:m, where m = 1-4. Thus, each gamma-crystallin molecule needs 1-4 alpha subunits for protection. Similar stoichiometries were observed for protection of the other proteins studied. The protection stems in part from screening of UV radiation by alpha-crystallin but more importantly from a chaperone effect analogous to that seen in thermal aggregation experiments.

Animals↗