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Biomedical subjects

C Bray

Publications and source records attributed to C Bray.

At least 19 recordsLinked to original sources
PubMed2006

Acetylcholine causes an increase of intracellular calcium in human sperm.

Sperm nicotinic acetylcholine receptors (nAChRs) can influence motility and the initiation of acrosome reaction (AR). We report that AR initiation by acetylcholine (ACh) in capacitated human sperm requires both Na+ and Ca2+ in the external medium. Pre-incubation with 50 microM 3-quinuclidinyl benzilate (QNB) or 50 nM strychnine failed to inhibit the ACh-initiated AR, demonstrating that muscarinic AChRs and nAChRs containing alpha9 subunits do not mediate this event. Choline (2.5, 5 and 10 mM), a highly specific but low potency agonist of the alpha7 nAChR initiated AR, with its effect blocked by the nAChR antagonist methyllycaconitine (MLA). ACh (50-400 microM) stimulated a small transient rise in the intracellular Ca2+ in sperm populations loaded with FURA-2, with 200 microM ACh being maximal (146 nM +/- 23 SEM). The nAChR antagonists, alpha-bungarotoxin (alpha-BTX) and MLA, reduced the ACh-initiated Ca2+ rise by 75 and 78%, respectively, demonstrating the majority of the rise is mediated through nAChRs containing alpha7 or alpha9 subunits. Single cell imaging studies using FLUO-3 resolved two patterns of ACh-stimulated Ca2+ increase in the sperm head: 94% of responding sperm displayed a rise (59.6% +/- 5.7 SEM increase from resting fluorescence intensity), returning to resting levels over a period of 2-3 min. The remaining sperm (6%) displayed a sharp spike of Ca2+ ( approximately 1 min; 86% +/- 4.3 SEM change in fluorescence intensity), followed by abrupt loss of fluorescence, a pattern suggestive of AR. A Ca2+ influx in the sperm midpiece appeared to accompany the Ca2+ influx seen in the head. These observations confirm an ionotropic role for nAChRs in sperm function.

Acetylcholine↗
PubMed2003

Effects of resolution reduction on data analysis.

BACKGROUND: There is often a need in flow cytometry to display and analyze histograms at resolutions lower than those native to the data. It is common, for example, to analyze DNA histograms at 256-channel resolution, even though the data were acquired at 1,024 channels or more. The most common method for reducing resolution, referred to as the consecutive summation (CS) method, can introduce distortions into the shape of histograms. Peaks that were symmetric in the original data can become skewed in the reduced-resolution histogram. Data analysis can be negatively affected by the distortions produced by reducing the histogram resolution. An alternative technique for reducing histogram resolution, the unbiased summation (US) method, minimizes shape distortion. This paper describes the US method and examines the benefits it provides in the analysis of DNA histograms. METHODS: Reduced chi-square (RCS) was used to measure the response to three experimental variables in the least-squares analysis of simulated DNA histograms. For each variable (the percentage of coefficient of variation [%CV], number of events, and mean position of the G1 distribution), a test data set of 1,000 histograms was generated at 1,024-channel resolution. Histogram resolutions were reduced with each method and then analyzed with ModFit LT cell-cycle analysis software (Verity Software House, Topsham, ME). S-phase error and processor computation time of each method also were evaluated. A Monte Carlo experiment was performed to compare CS and US methods to theoretically correct reductions. RESULTS: CS method analysis results were negatively affected by changes in %CV, number of events, and G1 peak position. The US method produced consistently lower RCS values (more accurate results) within the tested ranges. The US method eliminated bias in S-phase error and had negligible impact on analysis processing speed. It improved RCS values 44.50% on average (P < 0.0002) with actual DNA histograms. Whereas the CS method became less accurate (chi-square test) as the amount of reduction increased, the US method was unaffected, producing consistently better results. CONCLUSIONS: The US method is recommended for reducing histogram resolution in modeling applications such as DNA cell-cycle analysis. It may have implications in other areas of flow cytometric data analysis.

Algorithms↗
PubMed2002

Inhibitors of receptor tyrosine kinases do not suppress progesterone-induced [Ca2+]i signalling in human spermatozoa.

Previous studies have implicated receptor tyrosine kinases in progesterone-induced [Ca2+]i signalling, and consequent induction of the acrosome reaction, in human spermatozoa. We have investigated the effects of tyrosine kinase inhibition on [Ca2+]i responses in large numbers of individual human spermatozoa. Genistein (5, 50 and 250 micromol/l), an inhibitor of receptor-linked tyrosine kinases, significantly inhibited the progesterone-induced acrosome reaction (P < 0.05). However, we could detect no effect of genistein on progesterone-induced [Ca2+]i signalling. In control experiments, application of progesterone induced a significant transient [Ca2+]i response in approximately 77% of cells and a sustained [Ca2+]i ramp/plateau in approximately 48% of cells (n = 26; 5411 cells). In preparations pretreated with genistein (50 micromol/l), significant transient and sustained responses were detected in 69.5 and 39.1% of cells respectively (n = 5; 1109 cells). The amplitudes of both transient and sustained [Ca2+]i responses were similar in control and genistein-pretreated preparations. Tyrphostin A47 (100 micromol/l), another receptor tyrosine kinase inhibitor, also failed to inhibit either the transient or sustained [Ca2+]i response (n = 3; 468 cells). Assessment of tyrosine phosphorylation of two sperm proteins (p105/81) showed greatly increased levels of phosphotyrosine in response to capacitation but a negligible increase in response to progesterone stimulation. Pretreatment with genistein (50 and 250 micromol/l) decreased capacitation-induced tyrosine phosphorylation and resulted in a loss of phosphorylation in response to progesterone treatment. We conclude that neither the transient nor sustained phases of the progesterone-induced [Ca2+]i response require receptor tyrosine kinase signalling. Previous reports of modulation of the progesterone-induced [Ca2+]i signal by tyrosine kinase inhibition probably reflect inhibition of the acrosome reaction.

Acrosome↗
PubMed2001

Bullying nurses at work: theorizing a gendered experience.

This paper is about bullying among nurses at work. It presents the psychoanalytically based theory that workplace bullies, impaired during infancy by primary caregivers who were less than loving, project their own hostile personalities onto others and then relate to others without empathy or understanding, in demeaning ways. When these hostile people are employed in a masculine workplace, they protest against the gendered imperatives imposed upon them, hysterically. Because of the masculinization of the workplace, hysterical bullying varies according to gender, with women bullying in a hostile connected way, and men bullying in a hostile separated way. Research data gathered in Canada in the 1990s is utilised in presenting the theories. Suggestions about anti-bullying practices that arise from this theoretical analysis conclude the work.

Female↗
PubMed2000

Biphasic elevation of [Ca(2+)](i) in individual human spermatozoa exposed to progesterone.

Fluorimetric studies on progesterone-induced [Ca(2+)](i) signalling in mammalian spermatozoa show both the well-characterised [Ca(2+)](i) transient and a subsequent sustained phase. However, the sustained phase is thought to reflect release of the fluorochrome during the acrosome reaction and has not been subject to critical investigation. We have used single-cell imaging of [Ca(2+)](i) to analyse the progesterone-induced [Ca(2+)](i) response in large numbers (>2000) of capacitated, human spermatozoa. In 70% of cells, treatment with progesterone induced a transient increase, which typically peaked within 1 min and decayed with a similar time course. Upon rapid application of progesterone this response peaked within 5-20 s. In 35% of progesterone-treated spermatozoa a sustained elevation of [Ca(2+)](i) occurred, which became discernible during the falling phase of the transient response and persisted for at least 20 min. Both [Ca(2+)](i) responses were localised to the postacrosomal region. Averaging of large numbers of single cell responses generated traces similar to those seen in fluorimetric studies. Although the sustained response was strongly associated with the initial, transient response, a few spermatozoa generated sustained responses that were not preceded by a significant transient response (5% of cells). It is concluded that a genuine biphasic [Ca(2+)](i) signal is activated by progesterone and that the sustained response is a discrete signalling event with biological significance.

Acrosome Reaction↗
PubMed1995

Divergent views--patient, career and staff perceptions of diagnosis and reasons for psychiatric admission to a district general hospital.

This study explores the differing perceptions of patients, carers, and professional staff in relation to psychiatric admission. There is poor to moderate agreement between lay people and professional beliefs about diagnosis or purpose of admission, although good agreement about the necessity of admission. The chronicity of symptoms in admitted patients and a rural-urban divide in rates of admissions are also noted.

Adolescent↗
PubMed1986

Changes in salbutamol concentration in the reservoir solution of a jet nebulizer.

An increase in concentration of salt in the reservoir solution of jet nebulizers driven by dry compressed gas has been observed but changes in salbutamol concentration have not been investigated; therefore: Concentration changes were observed following 10 minutes nebulization for two driving sources and starting volumes. Using an electric compressor, the time courses of changes in drug concentration and output were observed for a 5 mg dose of salbutamol in 2 and 4 ml starting volumes. Changes in drug concentration were smaller for a 4 ml starting volume and for compressor driven nebulizers. Salbutamol concentration increased with the length of nebulization and the rate of increase was inversely related to starting volume. There was poor agreement between fluid and drug output for the 2 ml starting volume and drug output did not increase significantly when nebulization exceeded 4 minutes. For the 4 ml fill there was closer agreement between fluid and drug output and drug output exceeded that for the 2 ml fill after 10 minutes. In conclusion, fluid output alone is an inadequate measure of drug output and changes in drug concentration cannot be overlooked when assessing nebulizers for nebulizer therapy.

Aerosols↗
PubMed1985

Comparison of oxyfedrine and atenolol in angina pectoris--a double-blind study.

We have compared oxyfedrine 24 mg four times daily with atenolol 100 mg once daily in the relief of angina pectoris in a double-blind cross-over study; assessments were by diary cards and treadmill testing. Both oxyfedrine and atenolol reduced the frequency of angina by similar amounts and both produced similar improvements in treadmill performance. Side effects were infrequent and minor with both drugs. The model of action of oxyfedrine appears to be different from atenolol. Oxyfedrine allows the double product of systolic blood pressure X heart rate at peak exercise to be maintained at levels similar to those with placebo; the double product at peak exercise is significantly less with atenolol.

Adult↗
PubMed1983

Reduction in infarct size, arrhythmias and chest pain by early intravenous beta blockade in suspected acute myocardial infarction.

Four hundred seventy-seven patients suspected of having had acute myocardial infarction within less than 12 hours were randomized to receive i.v. atenolol followed by oral treatment for 10 days or to a control group. In patients with ECG changes indicative of infarction at entry, i.v. atenolol significantly reduced enzyme release by one-third and enhanced R-wave preservation. In patients without such ECG changes, treatment significantly prevented the development of infarction in a proportion of patients. There was also a significant reduction in R-on-T ectopics, repetitive ventricular arrhythmias and supraventricular arrhythmias. Treated patients had significantly greater pain relief and required fewer opiate analgesics. Significantly fewer atenolol-treated patients died by 10 days (the treatment period), had nonfatal cardiac arrests, developed heart failure, or suffered reinfarction.

Administration, Oral↗
PubMed1980

Early intravenous atenolol treatment in suspected acute myocardial infarction. Preliminary report of a randomised trial.

214 patients were studied in a randomised trial to determine whether administraiton of intravenous atenolol within 12 hours of chest pain reduced eventual infarct size, as estimated by cumulative enzyme release and by ECG changes. 135 patients already had ECG evidence of infarction at entry; 72 received atenolol which significantly decreased subsequent enzyme release (atenolol and control means = 121 IU, SE +/- 10 and 177 IU, SE +/- 17; 2p < 0.005) and enhanced R-wave preservation (atenolol and control means = 46% +/- 3 and 36% +/- 3; 2p < 0.02). 79 patients had no evidence of infarction at entry; 44 did not receive atenolol and 27 of these subsequently developed infarction, whereas only 11 of 35 treated patients infarcted during their hospital stay (2p < 0.01). In hospital, fewer atenolol patients died (4 vs 9), had non-fatal cardiac arrests (2 vs 6), or required therapy for heart-failure (36 vs 47). Unlike many previous trials which had negative results, in this trial we gave the drug intravenously and promptly (median of 4 hours from onset of pain to injecton), thereby achieving early beta-blockade.

Acute Disease↗