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Biomedical subjects

M J Burton

Publications and source records attributed to M J Burton.

At least 19 recordsLinked to original sources
PubMed1992

Thrombospondin receptor expression in human neutrophils coincides with the release of a subpopulation of specific granules.

The extracellular matrix (ECM) protein thrombospondin (TSP) binds specifically to polymorphonuclear leucocyte (PMN) surface receptors and promotes cell adhesion and motility. TSP receptor expression increases 30-fold after activation with the synthetic chemotactic peptide, N-formylmethionyl-leucylphenylalanine (FMLP) or the Ca2+ ionophore A23187, in combination with cytochalasin B. The expression of TSP receptors was correlated with the exocytosis of both specific and azurophil granules. Newly expressed TSP receptors are not derived from easily mobilized specific granules since agents that trigger some specific granule release [phorbol myristate acetate (PMA), FMLP or ionophore A23187 alone] do not increase TSP receptor expression. In this study we used the anion-channel blocker, 4,4'-di-isothiocyanatostilbene-2,2'-disulphonic acid (DIDS) to investigate the source of these newly expressed receptors. When PMNs were exposed to cytochalasin B and FMLP or to cytochalasin B and ionophore A23187 in the presence of 30-100 microM-DIDS, TSP receptor expression increased coincidently with vitamin B12-binding protein release from specific granules. Under these same conditions, the release of the azurophil granule component, myeloperoxidase, was significantly inhibited. Using agonists that cause release of specific granules, or both specific granules and azurophil granules, we determined that DIDS blocked the release of PMA-mobilized specific granules and cytochalasin B plus FMLP- or cytochalasin B plus ionophore A23187-mobilized myeloperoxidase-containing azurophil granules but not specific granules mobilized by cytochalasin B plus FMLP or cytochalasin B plus ionophore A23187. These results suggested that PMNs contain at least two subpopulations of specific granules: one that is easily mobilized, lacks TSP receptors and is inhibitable by DIDS, and one that is difficult to mobilize, contains a large pool of TSP receptors and the release of which is enhanced in the presence of DIDS.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Steady-state evoked potentials to amplitude modulated tones in the monkey.

A frequency-specific, objective assessment of hearing thresholds is required for use in subjects unable to perform behavioural audiometry. One such method using steady-state evoked potentials (SSEPs) in response to amplitude-modulated tones was evaluated in an experimental animal, the macaque monkey. An amplitude-modulation frequency of 165 Hz was found to produce optimum response detection in the anaesthetised animal. Auditory thresholds determined by a computerised automatic response detection system accurately reflected behavioural thresholds previously described in this species.

Animals↗
PubMed1991

Human neutrophil adherence to thrombospondin occurs through a CD11/CD18-independent mechanism.

Thrombospondin (TSP), a 450-kDa trimeric glycoprotein secreted by platelets and endothelial cells at sites of tissue injury or inflammation, may play an important role in polymorphonuclear leukocyte (PMN) adherence to blood vessel walls before diapedesis. We have examined the adherence of PMN to TSP and compared it to adherence to other extracellular matrix proteins. PMN adherence to TSP-coated plastic was complete by 60 min with spreading completed by 2 h. The kinetics of adhesion and spreading on TSP were similar to that of vitronectin (VN), laminin (LN), and fibronectin (FN). Activation of PMN with the calcium ionophore A23187 or the chemotactic peptide FMLP increased PMN adherence to LN and FN, but not to TSP or VN, suggesting that PMN activation may differentially regulate expression of TSP and VN receptors as compared to LN and FN receptors. The specificity of PMN adherence to TSP was confirmed by competition with saturating amounts of TSP and inhibition with anti-TSP antibodies. mAb A6.1, which binds to the protease-resistant core of TSP, was the most effective in blocking PMN adherence to TSP. Using TSP proteolytic fragments, we demonstrated that the primary interaction of PMN with TSP was mediated through the 140-kDa COOH-terminal domain. Inasmuch as the 140-kDa fragment of TSP contains an Arg-Gly-Asp sequence similar to the cell recognition site of FN and VN, we determined whether RGDS peptides would inhibit PMN adhesion. RGDS did not significantly inhibit PMN adhesion to TSP, VN, or LN, but reduced PMN adhesion to FN by 50%. To determine if PMN adhesion to TSP was mediated by a beta 2 integrin receptor such as LFA-1, MO-1, or p150,95, we performed adhesion assays using PMN isolated from patients with leukocyte adhesion deficiency that lack beta 2 receptors. Leukocyte adhesion deficiency PMN exhibited normal adherence to TSP. In contrast, adherence to VN, LN, and FN was reduced by 95%. Therefore, adherence to TSP is probably not mediated by a beta 2 integrin receptor. These data contribute to the accumulating evidence that PMN can interact with extracellular matrix proteins through a CD11/CD18-independent process.

Antigens, CD↗
PubMed1991

Long-term results of submandibular duct transposition for drooling.

This study examines the long-term results and morbidity of submandibular duct transposition in drooling children. Twenty-two patients, aged 3 to 18 years, with neurological dysfunction and excessive drooling underwent submandibular duct transposition between 1984 and 1987. In January 1990, 20 patients were reviewed. Their degree of drooling pre-operatively, immediately post-operatively and currently was assessed. The rate of improvement and the occurrence of complications were noted. Drooling was 'much better' in the early post-operative period in 17 of the 20 patients, and this improvement was invariably noted within three weeks. In the three other patients drooling was 'better'. Deterioration occurred in only three patients over the entire follow-up period. Complications all occurred in the first 18 months following surgery; they consisted of salivary retention cysts in four and transient submandibular gland swelling in a fifth patient.

Adolescent↗
PubMed1991

The surgical management of drooling.

As with all branches of surgery, selection of the appropriate operative procedure for a particular patient involves careful weighing of all the alternatives and full discussion with the patient and carers. Each of the procedures described has its devotees and detractors. For an individual patient, however, the risks of each, the likely postoperative course and the results of the surgery--both in terms of the expected chance of improvement in drooling and the presence or otherwise of residual scarring or taste--must be balanced to determine the optimum plan for treatment. The long-term results of submandibular duct transposition for drooling in the author's own institution have recently been reported. An initial improvement in the drooling of all patients was maintained for at least two years in 17 of 20 patients. Only two patients experienced complications requiring further surgery (ranulas in each case). It is suggested that these very satisfactory results, achieved without external scarring and without compromising the sense of taste, support the contention that submandibular duct transposition is the surgical treatment of choice for children and young people with cerebral palsy who drool excessively.

Child↗
PubMed1990

Pharyngeal pouch carcinoma: two unusual cases.

Two patients with carcinomata arising in pharyngeal pouches are reported. In one, the tumour was detected preoperatively by a contrast radiographic study. In the second the lesion was a carcinoma in situ. The English literature is reviewed with reference to these two unusual features.

Aged↗
PubMed1989

Middle-latency responses. I. Electrical and acoustic excitation.

The electrically evoked auditory brain-stem response has been used in the past to assess auditory system function with regard to cochlear prosthesis application. The brief latency of the response makes it susceptible to electrical artifact contamination, and waveform identification is often difficult. As a possible alternative for a noninvasive measure of system excitability, the middle-latency response (MLR), elicited by electrical stimulation, was investigated. Middle-latency responses were recorded in response to acoustic and round-window electrical stimulation in albino guinea pigs. Acoustic and electrically evoked MLR waveforms were similar, as were their respective latency/intensity functions. Amplitude/intensity functions for the electric MLR showed greater variability than acoustically evoked MLR functions. The electric MLR is readily evoked and relatively insensitive to electrical artifact in the guinea pig. It is potentially a useful tool in assessing the integrity of auditory pathways and consequently in the development of diagnostic tests for cochlear implant candidates.

Acoustic Stimulation↗
PubMed1989

Middle-latency responses. II. Variation among stimulation sites.

We investigated the relationship between thresholds of the electrically evoked auditory brain-stem response (EABR) and the electrically evoked middle-latency response (EMLR), and the variation in EMLR thresholds and dynamic ranges with site of stimulation. The EABRs and EMLRs were recorded in albino guinea pigs in response to electrical stimulation at the round window, promontory, scala tympani, and modiolus. The EABR and EMLR thresholds were similar. There was no significant difference between thresholds for round-window and scala tympani stimulation. Amplitude/intensity functions for the EMLR differed with site of stimulation. The EMLR seems to be comparable with the EABR for assessing the electrical excitability of the auditory pathway with less electrical artifact contamination. In this respect, round-window and scala tympani stimulation sites are equally efficacious.

Animals↗
PubMed1987

Rapid loss of stimulus-specific satiety after consumption of a second food.

'Meals' consisting of several differently flavoured 'courses' result in greater consumption than meals consisting of identical courses. Experiment 1 confirmed that this effect is found in rats during the dark phase of a LD 12:12 cycle. Two subsequent experiments demonstrated that meals consisting of three or four courses in which only two flavours were alternated produced as great an enhancement of consumption as meals in which each course was differently flavoured. The implications of this result are discussed for the nature of the processes underlying the generation and reversal of this stimulus-specific aspect of satiety.

Animals↗
PubMed1987

Myometrial activity during natural and dexamethasone-induced parturition in the cow.

Myometrial activity was monitored during natural and dexamethasone-induced parturition in 8 Holstein dairy cattle, using strain gauge transducers. Four gauges were attached to the serosal surface of the gravid uterine horn, dividing it into thirds. Parturition was induced in 2 of 4 heifers and 2 of 4 cows (group 1); the remaining animals were allowed to calve spontaneously (group 2). Chains of low-amplitude contractions (repeated small deviations from base line) were detected before parturition was induced, and these were more common at distended parts of the uterus. Uncharacteristically sharp peaks followed by small rhythmic contractions, during preinduction recording, indicated that the myometrium was responsive to fetal movement even several days before parturition. By 18 hours before parturition, discrete single contractions appeared independently of contraction chains, and the first tubocervical peristaltic contraction waves were detected. The mean area under recorded contraction curves (uterine work) increased quadratically and the frequency of contractions decreased linearly from 12 hours before parturition to 2 hours after parturition. There was also an increase in the proportion of tubocervical waves over this period, and contraction chains were no longer present. During the second stage of labor, distended and undistended parts of the uterus were equally active, and forceful maternal straining was associated with larger sustained contractions. Fetal membrane rupture was accompanied by a doubling in the rate of passage of contraction waves along the length of the uterus. After the calf was expelled, contractions became extremely regular, and the majority progressed in a tubocervical direction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Pharmacological investigations of the mechanisms underlying the effects of peripheral 5-HT on flavour consumption and preference.

Systemic administration of serotonin (5-hydroxytryptamine, 5-HT) to non-deprived rats increased saline (0.9%) consumption (5-HT hyperdipsia), without altering saline preference in two-bottle test. When sodium saccharin (0.1%) was the test solution 5-HT suppressed both consumption and preference. 5-HT saline hyperdipsia was blocked by pretreatment with an angiotensin I converting enzyme inhibitor (MK421) and mimicked by isoprenaline-induced stimulation of renin production; saccharin consumption and preference were unaffected by either drug. However, methysergide (a 5-HT antagonist) attenuated the effects of 5-HT on saccharin consumption and preference, thus confirming that these effects are mediated via peripheral 5-HT receptors. It is suggested that the effects of 5-HT on saline consumption are mediated via stimulation of the renin-angiotensin system, but its effects on saccharin consumption and preference are mediated by a separate mechanism at some point subsequent to peripheral 5-HT receptors.

Animals↗
PubMed1986

Dissociation of the anorectic actions of 5-HTP and fenfluramine.

The possible peripheral anorectic actions of 5-hydroxytryptophan (5-HTP) and fenfluramine were examined in food-deprived rats. In a 1-h feeding test the peripherally acting 5-HT antagonist, xylamidine, attenuated the reductions in food intake induced by 5-HT and 5-HTP but not fenfluramine. Thus, the anorectic action of 5-HTP appears to be mediated in part by peripheral 5-HT receptors. Microstructural analyses showed that 5-HTP and fenfluramine induced decreases in eating rate and bout size. Xylamidine reversed the effect of 5-HTP on eating rate, and induced a slight increase in bout size in its own right. Therefore, the peripheral effect of 5-HTP appears to be a slowing of eating rate. No effects of xylamidine on fenfluramine induced changes in feeding were observed. The results indicate a dissociation of the anorectic effects of 5-HTP and fenfluramine based on a peripheral action of 5-HTP. The peripheral action of 5-HTP differs from the previously reported reductions in bout size and bout duration induced by 5-HT. Possible mechanisms for this difference in the peripheral actions of 5-HT and 5-HTP are discussed.

Amidines↗
PubMed1986

Effects of peripheral 5-HT on consumption of flavoured solutions.

Non-deprived rats, injected SC with serotonin (5-hydroxytryptamine; 5-HT), showed flavour-dependent alterations in fluid consumption during 2-h tests. The consumption of water, quinine, citric acid or saline was increased by 5-HT, whereas the consumption of sucrose, saccharin or milk was decreased. There were dose-dependent decreases in saccharin and milk consumption with maximal suppression of intake at 2 mg/kg. Two-bottle preference tests (flavour versus water) revealed that 5-HT increased saline consumption without changing saline preference and reduced consumption of, and preference for, both saccharin and sucrose. These results are discussed in terms of the characteristics which identify substances as being "food-like" rather than "water-like", and it is suggested that peripheral 5-HT plays a role in the control of both water and food intake. This latter function may be fulfilled through an alteration in the incentive value of food-related stimuli.

Animals↗
PubMed1986

Behavioural and pharmacological investigations of 5-HT hypophagia and hyperdipsia.

Treatment with 5-hydroxytryptamine (5-HT) reliably induced hypophagia in non-deprived rats and in rats tested following a period of food-deprivation, regardless of the presence or absence of water during testing. The hyperdipsic effect of 5-HT, however, was sensitive to changes in the length of food-deprivation, suggesting a possible interaction between 5-HT hyperdipsia and prandial drinking. Both 5-HT hypophagia and hyperdipsia were attenuated by methysergide pretreatment, thus confirming the involvement of peripheral post-synaptic 5-HT receptors in both effects. Pretreatment with propranolol blocked 5-HT hyperdipsia, but did not alter 5-HT hypophagia, thus suggesting that 5-HT hypophagia and hyperdipsia are mediated by different mechanisms at some point subsequent to the stimulation of peripheral 5-HT receptors. These results are consistent with other evidence that 5-HT hyperdipsia is mediated by stimulation of the renin-angiotensin system. It is tentatively suggested that 5-HT hypophagia could result from 5-HT-induced inhibition of cephalic phase insulin secretion.

Animals↗
PubMed1986

A behavioural and pharmacological examination of phenylethylamine-induced anorexia and hyperactivity--comparisons with amphetamine.

The discovery that trace amine beta-phenylethylamine (PEA) has a number of properties in common with amphetamine (AMPH) has led to the suggestion that PEA may be a neuromodulator of catecholamine release or an "endogenous amphetamine." The present study compared PEA-induced behavioural changes (anorexia and hyperactivity) with AMPH-induced changes in feeding and motor activity. The first experiment examined the effects of PEA (0-35 mg/kg) on the temporal profile of feeding. The results from this experiment revealed important differences between the effects of PEA as compared with AMPH, in particular PEA failed to increase the rate of eating that is characteristic of AMPH-induced anorexia. The second experiment concurrently measured food intake and motor activity following equi-anorectic doses of PEA and AMPH and pretreatment with the neuroleptic pimozide. Pimozide attenuated PEA-induced hyperactivity, AMPH-induced hyperactivity and AMPH-induced anorexia, but failed to attenuate PEA-induced anorexia. These findings are discussed in relation to the possible mechanisms of action of PEA and AMPH.

Animals↗
PubMed1986

Microstructural analysis of the anorectic action of peripherally administered 5-HT.

The anorectic action of systemically administered 5-HT (1, 2 and 4 mg/kg SC) was investigated in food deprived rats using the technique of microstructural analysis; small food pellets were delivered to a food hopper, and the time and occurrence of each pellet removal was recorded. Log-survivor analysis of inter-pellet intervals was used to define feeding bouts, and this was then used to compute measures of bout frequency, bout size, bout duration and eating rate. The 5-HT reduced food intake by selectively decreasing bout size and bout duration. No effects of 5-HT were observed on any of the other parameters measured. These effects of 5-HT are robust over a range of bout criteria, and replicable. Methysergide (3 mg/kg IP) attenuated the anorectic action of 5-HT by a significant increase in bout frequency and an attenuation of the effects of 5-HT on bout size, and bout duration. The results are discussed in terms of a possible role for peripheral 5-HT in the control of satiety, and implications for the mode of action of serotonergic anorectic agents such as fenfluramine.

Animals↗