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Biomedical subjects

C Turner

Publications and source records attributed to C Turner.

At least 19 recordsLinked to original sources
PubMed1998

Relocation of the t-SNARE SNAP-23 from lamellipodia-like cell surface projections regulates compound exocytosis in mast cells.

For regulated secretion, mast cells and several other cell types utilize compound exocytosis, a combination of granule-plasma membrane and granule-granule fusions. The molecular machinery that controls this massive export process has not been identified. We report that SNAP-23, a t-SNARE related to SNAP-25, relocates in response to stimulation from plasma membrane lamellipodia-like projections to granule membranes in permeabilized mast cells. While relocation is a prerequisite for secretion, it can occur without membrane fusion and will expedite a subsequent secretory response. After relocation, SNAP-23 is required for exocytosis, implying a crucial role in promoting membrane fusion. Thus, relocation of this SNARE regulates compound exocytosis and links granule-plasma membrane and granule-granule fusions.

Animals↗
PubMed1998

Insect juvenile hormone resistance gene homology with the bHLH-PAS family of transcriptional regulators.

Juvenile hormone analog (JHA) insecticides are relatively nontoxic to vertebrates and offer effective control of certain insect pests. Recent reports of resistance in whiteflies and mosquitoes demonstrate the need to identify and understand genes for resistance to this class of insect growth regulators. Mutants of the Methoprene-tolerant (Met) gene in Drosophila melanogaster show resistance to both JHAs and JH, and previous biochemical studies have demonstrated a mechanism of resistance involving an intracellular JH binding-protein that has reduced ligand affinity in Met flies. We cloned the Met+ gene by transposable P-element tagging and found reduced transcript level in several mutant alleles, showing that underproduction of the normal gene product can lead to insecticide resistance. Transformation of Met flies with a Met+ cDNA resulted in susceptibility to methoprene, indicating that the cDNA encodes a functional Met+ protein. MET shows homology to the basic helix-loop-helix (bHLH)-PAS family of transcriptional regulators, implicating MET in the action of JH at the gene level in insects. This family also includes the vertebrate dioxin receptor, a transcriptional regulator known to bind a variety of environmental toxicants. Because JHAs include a diverse array of chemicals with JH activity, a mechanism whereby they can exert effects in insects through a common pathway is suggested.

Amino Acid Sequence↗
PubMed1998

Central effects of the H1-antihistamine, cetirizine.

BACKGROUND: Effects of the H1-antihistamine, cetirizine, were studied on daytime alertness and performance to establish whether the drug would be suitable for use by air personnel and others involved in skilled activity. METHODS: The investigation was carried out in six healthy volunteers, and the effects of the drug (5, 10, and 15 mg) were studied on sleep latency, subjective sleepiness, digit symbol substitution, tracking and vigilance from 0.5 h to 7.5 h after ingestion. The study was placebo-controlled and double-blind with a six-way cross-over design. Promethazine (10 mg) was used as an active control to establish the sensitivity of the experimental procedures. RESULTS: Promethazine (10 mg) decreased the mean level of vigilance over the day, increased objective and subjective sleepiness from 1.5 to 5.5 h, and impaired tracking 5.5 h after ingestion. Cetirizine (10 and 15 mg) led to shortened sleep latencies over the day, and at 7.5 h sleep latencies were shorter with 10 mg cetirizine than with placebo. Subjective sleepiness with cetirizine was increased compared with placebo after 5 mg at 1.5 h, 10 mg at 7.5 h, and 15 mg at 5.5 h and when meaned over the day. Tracking was impaired with 5 and 15 mg cetirizine 0.5 h after ingestion. CONCLUSION: The study failed to establish dose-response effects of cetirizine, but it is evident that cetirizine is not free of central activity over the therapeutic range, and so its use by air personnel is not recommended.

Administration, Oral↗
PubMed1998

Intensive and sustained air operations: potential use of the stimulant, pemoline.

BACKGROUND: Intensive and sustained military operations involve long periods of overnight work and the occasional use of a stimulant to maintain performance may be beneficial. In this context a dose response study was carried out to investigate the effects of pemoline, a dopamimetic agent, on overnight work and to assess potential residual effects on subsequent sleep. METHODS: Six healthy volunteers participated in a placebo-controlled, double-blind, cross-over trial involving a 12-h period of work during which subjective alertness and performance on a range of tasks were assessed at 1.5 h intervals following ingestion at 2000 hours of pemoline (10, 20, 30 and 40 mg) and, on two occasions, placebo. The work period was preceded by a 6-h sleep period with temazepam 20 mg, and followed by a 4-h recovery sleep with no medication. All sleep periods were recorded electroencephalographically. RESULTS: There was no difference between sleep periods preceding the work period. Subjective alertness and performance on all tasks deteriorated significantly during the work period, with the earliest impairments in performance observed at 0200 hours. Pemoline increased subjective alertness and performance on all but two tasks, compared with placebo. The onset of activity was seen 4.5 h after drug ingestion and alerting effects of 30 and 40 mg pemoline persisted beyond the work period, disturbing morning recovery sleep. Doses of 10 and 20 mg pemoline had no effect on recovery sleep. CONCLUSION: The present studies indicate that a 20 mg dose of pemoline may be suitable for maintaining nocturnal performance without having adverse effects on recovery sleep.

Adult↗
PubMed1997

Factors determining more efficient large-scale release of a periplasmic enzyme from E. coli using lysozyme.

Large scale use of lysozyme for periplasmic release has been impeded by the cost of the pure enzyme and its subsequent presence as a contaminant in later downstream processing steps. In this paper, we discuss the use of lysozyme for pilot scale recovery of a periplasmic enzyme from E. coli. The effects of concentration of sucrose, lysozyme and cells on periplasmic enzyme release were examined. Lysozyme concentration can be reduced 5-fold from previous reports and a reduction in sucrose concentration from 20 to 15% (w/v) allows an improvement in centrifugal harvesting by reducing viscosity. High levels of release were still achieved using this technique and further improvements in yield were obtained by optimising other components of the releasing mixture. Results show that some release is still achieved in circumstances where no lysozyme use is possible. Results also indicate that a substantial proportion (up to 70%) of lysozyme remains bound to the cellular debris after its action and is removed with this material.

Escherichia coli↗
PubMed1997

Properties of developing lateral geniculate neurones in the mouse.

This study describes the properties of neurones recorded in vitro from the dorsal lateral geniculate nucleus (dLGN) of the mouse between developmental stages E16 and P36 and represents the first systematic study of the development of rodent thalamic neurones. The results demonstrate that thalamo-cortical neurones in the mouse dLGN undergo a series of important changes as they mature. Prenatally recorded cells had low resting potentials and could not generate action potentials but as they mature, mouse dLGN neurones become more polarised and show an increase in membrane time constant and spike threshold, while action potentials increase in amplitude and decrease in width. The low-threshold spike (LTS) complex appears at the time of birth, but does not show properties typical of adult cells until at least the third postnatal week. Immature action potentials are primarily sodium-dependent but gain a significant calcium component in the second postnatal week, which is associated with a supra-threshold oscillation of the membrane potential. The electrical activity during this critical period is strongly influenced by the interaction of powerful inward and outward rectification with calcium conductances which determines the appearance of voltage responses to intracellular current injection. The membrane potential in recordings from neurones during the first postnatal week was dominated by intense TTX-sensitive depolarising synaptic-like events which attained amplitudes of 60 mV in several neurones at stages P5-P8. These changes are discussed in relationship to the formation of appropriate connections in the developing visual system.

Aging↗
PubMed1997

Why immunise. Care giver understanding of childhood immunisation.

Currently in Australia, both the National Health and Medical Research Council (NHMRC) and the Public Health Association have stated that our immunisation uptake levels are not of a high enough percentage within the population to prevent outbreaks of childhood vaccine preventable diseases (1996). While the literature discusses factors that are believed to influence care givers' decisions to vaccinate their children, few Australian studies focus on care giver understanding of childhood diseases and vaccination. The purpose of this descriptive study was to profile care givers who presented their children for vaccination at public health clinics regarding their level of understanding of childhood vaccine preventable diseases. Two hundred and forty eight care givers attending one of six public clinics were asked to respond verbally to a researcher administered questionnaire. Demographic information as well as information related specifically to immunisation was collected from each participant. The major findings of this preliminary study indicate a very low level of knowledge among careers presenting their child for vaccination at the public health clinic. Twenty-three percent of carers had no knowledge regarding the vaccinations that their child was receiving and the disease for which the vaccination was administered. In fact, 18 percent of care givers were unsure of the relationship between vaccination and the likelihood of their child contracting an infectious disease. The personal health record was not found to be useful as an educational resource. Although 99 percent of care givers had the booklet in their possession only 8 percent had referred to it as a source of information. The major sources of information were identified as child health nurses (44%) and hospital midwives (34%). The results of this study highlight the disparity in knowledge levels among care givers with regards to vaccination and the diseases they prevent and the important role of the midwife and child health nurse in disseminating information relating to immunisation.

Adolescent↗
PubMed1997

Body mass index, waist circumference, waist-hip ratio, and glucose intolerance in Chinese and Europid adults in Newcastle, UK.

OBJECTIVE: To compare the prevalence of glucose intolerance (impaired glucose tolerance and diabetes), and its relationship to body mass index (BMI) and waist-hip ratio in Chinese and Europid adults. DESIGN: This was a cross sectional study. SETTING: Newcastle upon Tyne. SUBJECTS: These comprised Chinese and Europid men and women, aged 25-64 years, and resident in Newcastle upon Tyne, UK. MAIN OUTCOME MEASURES: Two hour post load plasma glucose concentration, BMI, waist circumference, and waist-hip ratio. METHODS: Population based samples of Chinese and European adults were recruited. Each subject had a standard WHO oral glucose tolerance test. RESULTS: Complete data were available for 375 Chinese and 610 Europid subjects. The age adjusted prevalences of glucose intolerance in Chinese and Europid men were 13.0% (p = 0.04). Mean BMIs were lower in Chinese men (23.8 v 26.1) and women (23.5 v 26.1) than in the Europids (p values < 0.001), as were waist circumferences (men, 83.3 cm v 90.8, p < 0.001; women, 77.3 cm v 79.2, p < 0.05). Mean waist-hip ratios were lower in Chinese men (0.90 v 0.91, p = 0.02) but higher in Chinese women (0.84 v 0.78, p < 0.001) compared with Europids. In both Chinese and Europid adults, higher BMI, waist circumference, and waist-hip ratio were associated with glucose intolerance. CONCLUSIONS: The prevalence of glucose intolerance in Chinese men and women, despite lower BMIs, is similar to or higher than that in local Europid men and women and intermediate between levels found in China and those in Mauritius. It is suggested that an increase in mean BMI to the levels in the Europid population will be associated with a substantial increase in glucose intolerance in Chinese people.

Adult↗
PubMed1997

Promoting sleep in shiftworkers and intercontinental travelers.

A number of techniques and treatments can be used to alleviate the sleep disturbance associated with both shiftwork and transmeridian travel. Optimization of the sleeping environment and avoidance of substances such as caffeine and alcohol before sleep are the best initial approach. Timing sleep to coincide with some of the normal sleep period where possible will improve sleep quality in shiftworkers. Similarly, following transmeridian flight, restricting sleep to the nocturnal period in the new time zone will assist adaptation. Hypnotic drugs may be of benefit to alleviate sleep disturbance experienced by shiftworkers or transmeridian travelers. Selection of the most appropriate medication must take into account required duration of action and possible residual effects of the drug on alertness. Hypnotics may be useful, particularly in middle-aged individuals who already have disturbed sleep, on those occasions when poor sleep is anticipated, for example following an eastward flight or after the initial change to night duty. Over-the-counter preparations should be avoided whenever possible unless it is known that they are not associated with residual sequelae.

Aerospace Medicine↗
PubMed1997

Research into smoking or nicotine and human cognitive performance: does the source of funding make a difference?

AIMS: To establish whether there is a relationship between tobacco industry support of basic research and the conclusions drawn by the authors of that research. DESIGN: A sample of 91 papers investigating the effects of tobacco or nicotine use upon cognitive performance was analyzed to see if the pattern of conclusions drawn by researchers acknowledging tobacco industry support differed from the pattern of conclusions drawn by researchers not acknowledging tobacco industry support. FINDINGS: Scientists acknowledging tobacco industry support reported typically that nicotine or smoking improved cognitive performance while researchers not reporting the financial support of the tobacco industry were more nearly split on their conclusions. CONCLUSIONS: While it is only possible to speculate on the possible reasons, the existence of a possible bias in the published literature according to funding source must be given serious consideration.

Cognition Disorders↗
PubMed1996

Heme-oxygenase-1 induction in glia throughout rat brain following experimental subarachnoid hemorrhage.

The heme released following subarachnoid hemorrhage is metabolized by heme-oxygenase (HO) to biliverdin and carbon monoxide (CO) with the release of iron. The HO reaction is important since heme may contribute to vasospasm and increase oxidative stress in cells. HO is comprised of at least two isozymes, HO-2 and HO-1. HO-1, also known as heat shock protein HSP32, is inducible by many factors including heme and heat shock. HO-2 does not respond to these stresses. To begin to examine HO activity following subarachnoid hemorrhage (SAH), the expression of HO-1 and HO-2 was investigated after experimental SAH in adult rats. Immunocytochemistry for HO-1, HO-2 and HSP70 proteins was performed at 1, 2, 3 and 4 days after injections of lysed blood, whole blood, oxyhemoglobin and saline into the cisterna magna. A large increase in HO-1 immunoreactivity was seen in cells throughout brain following injections of lysed blood, whole blood, and oxyhemoglobin but not saline. Lysed blood, whole blood and oxyhemoglobin induced HO-1 in all of the cortex, hippocampus, striatum, thalamus, forebrain white matter and in cerebellar cortex. HO-1 immunoreactivity was greatest in those regions adjacent to the basal subarachnoid cisterns where blood and oxyhemoglobin concentrations were likely highest. Double immunofluorescence studies showed the HO-1 positive cells to be predominately microglia, though HO-1 was induced in some astrocytes. HO-1 expression resolved by 48 h. HO-2 immunoreactivity was abundant but did not change following injections of blood. A generalized induction of HSP70 heat shock protein was not observed following injections of lysed blood, whole blood, oxyhemoglobin, or saline. These results suggest that HO-1 is induced in microglia throughout rat brain as a general, parenchymal response to the presence of oxyhemoglobin in the subarachnoid space and not as a stress response. This microglial HO-1 response could be protective against the lipid peroxidation and vasospasm induced by hemoglobin, by increasing heme clearance and iron sequestration, and enhancing the production of the antioxidant bilirubin.

Animals↗
PubMed1996

Effects of recombinant human growth hormone on renal function in children with renal transplants.

OBJECTIVE: To provide accurate measurement of renal function during treatment with recombinant human growth hormone (rhGH). METHODS: We measured glomerular filtration rate and effective renal plasma flow by clearance of inulin and para-aminohippuric acid before rhGH therapy, after 1 week, and then at 6-month intervals for up to 2 years of treatment in 16 children (mean (SD) age = 13.1 (2.2) years; glomerular filtration rate = 52 (27) ml/min per 1.73 m2). The mean (SD) time from transplantation was 6.5 (3.6) years. RESULTS: Linear growth velocity during rhGH therapy increased from 4.0 (1.8) to 8.8 (2.6) cm/yr (p < 0.0001). One child was withdrawn after 9 months because of abnormal glucose tolerance, and another child received a second renal transplant after 18 months. Glomerular filtration rate increased to 57 (29) ml/min per 1.73 m2 at 1 week (p = 0.004), remained improved at 6 months (63 (30); p = 0.013), but was not significantly better at 1 year (59 (33)). Effective renal plasma flow on day 1 was 237 (127) ml/min per 1.73 m2 and was unchanged on day 8 (244 (123)), at 6 months (271 (149)), and after 1 year (269 (157)). During the study there was no significant change in filtration fraction, blood pressure, or kidney volume, and excretion of microalbumin and N-acetylglucosaminidase was unaltered. There was one rejection episode per 14.8 patient-months in the year before treatment, 1 per 18.9 patient-months during the first year of treatment, and 1 per 13 patient-months during the second year of rhGH therapy. CONCLUSION: Treatment with rhGH improves growth in children with renal transplants. Glomerular filtration rate was increased after 1 week and 6 months of rhGH therapy but returned to baseline values thereafter. The data indicate the need for long-term follow-up of children with renal transplants who are receiving rhGH.

Adolescent↗
PubMed1996

Unusual metaphyseal disturbance in two kittens.

This report describes the presenting features, radiographic changes, biochemical alterations and clinical progress of two kittens, from separate litters, which were found to have a growth plate disturbance initially diagnosed and treated as vitamin D3-dependent rickets, but subsequently suspected to be a metaphyseal chondrodysplasia.

Animals↗
PubMed1996

Focal hyperexpression of hemeoxygenase-1 protein and messenger RNA in rat brain caused by cellular stress following subarachnoid injections of lysed blood.

Induction of the hemeoxygenase-1 (ho-1) stress gene is of importance for rapid heme metabolism and protection against oxidative injury in vitro and in vivo. Although ho-1 expression is observed in glia following exposure to whole blood and oxyhemoglobin, expression is mild, and other stress genes are not induced simultaneously in this setting. Hemeoxygenase-1 can be induced by several other physiological stresses in addition to heme. In the brain, ho-1 induction has been observed in the penumbra following focal cerebral ischemia. Because lysed blood is a spasmogen, the authors studied focal hyperexpression of the ho-1 gene after injection of lysed blood, whole blood, or saline into the cisterna magna of adult rats. Immunocytochemical analysis of HO-1 was performed at 1, 2, 3, and 4 days after the injections. Because the 70-kD inducible heat shock protein (HSP70) is induced by cellular stress, alternate sections were immunostained for HSP70 to assess whether focal hyperexpression was a stress phenomenon. An oligonucleotide probe was also used for in situ hybridization to demonstrate that ho-1 messenger (m)RNA was present. Focal HO-1 immunostained areas were observed after lysed blood injection only and were located mainly in the basal cortex and cerebellar hemisphere, although focal hyperexpression was also found in many other regions. The intensity of staining and the number of regions were maximum at 1 day. Double-labeled immunofluorescence revealed that many HO-1-immunoreactive cells were microglia. The HSP70 immunostaining of adjacent sections from the same animals demonstrated focal regions of immunoreactivity whose topography corresponded exactly with the topography of the HO-1-immunostained areas. Conventional histology in regions of HO-1 hyperexpression was often normal. In situ hybridization using the same oligonucleotide demonstrated that ho-1 mRNA was induced in focal areas of forebrain and in large regions of cerebellum within 6 hours of injection. These results demonstrate that focal hyperexpression of the ho-1 stress gene occurs after lysed blood injection and appears to be an indicator of cellular stress and injury in regions in which infarction does not occur. These results also suggest that cellular injury that occurs after injection of lysed blood may go undetected using conventional histology. Although direct heme metabolism was not investigated, our results indicate that rapid metabolism of heme, both intracellular and extracellular, may prove to be beneficial after subarachnoid hemorrhage.

Animals↗