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Biomedical subjects

R Murdoch

Publications and source records attributed to R Murdoch.

At least 19 recordsLinked to original sources
PubMed2003

5-HT moduline: an endogenous inhibitor of 5-HT(1B/1D)-mediated contraction in pulmonary arteries.

(1) 5-HT moduline (5-HTm) is tetrapeptide (Leu-Ser-Ala-Leu) previously shown to act as a specific endogenous antagonist to central 5-HT(1B/1D) receptors. Its effects were investigated in rat and rabbit pulmonary arteries (PAs). (2) In rabbit PAs, contractile responses to the 5-HT(1B/1D) receptor agonist 5-carboxamidotryptamine (5-CT) were inhibited by 1 and 10 micro M 5-HTm in a non-competitive fashion with the maximum contractile response (E(max), per cent of response to 50 mM KCl) being reduced from 65.6+/-7% (n=6) to 39.7+/-6.5% (n=6) and 25.2+/-7.9 (n=4), respectively. The ability of 5-HTm to inhibit responses to 5-CT was increased by the aminopeptidase inhibitor bestatin (10 micro M). (3) In the rabbit PAs, the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methylester (L-NAME) potentiated responses to 5-CT (E(max): 106+/-22.5 (n=4)) and this response was also inhibited by 10 micro M 5-HTm (E(max): 38+/-13% (n=8)). (4) 5-HTm (10 micro M) inhibited responses to 5-CT in rat PAs, the E(max) being reduced from 24.8+/-4.1% (n=7) to 15.5+/-3.7% (n=9). 5-HTm induced relaxation of 5-CT-pre-constricted rat PAs with a pIC(50) of 9.0+/-0.6 (n=9). (5) In PAs from chronic hypoxic, pulmonary hypertensive rats, the maximum response to 5-CT was increased to 80+/-8.5% (n=11). 5-HTm reduced this response to 34.4+/-6.3% (n=12). L-NAME markedly inhibited the ability of 5-HTm to inhibit responses to 5-CT (E(max) before 5-HTm: 100.5+/-16% (n=5), E(max) after 5-HTm: 107+/-11.3% (n=4)). (6) In conclusion we show here for the first time that 5-HTm is a non-competitive inhibitor of 5-HT(1B/1D) receptor-mediated constriction in PAs. In rat PAs, L-NAME can inhibit this effect of 5-HTm.

Animals↗
PubMed2000

A mesoscale phytoplankton bloom in the polar Southern Ocean stimulated by iron fertilization.

Changes in iron supply to oceanic plankton are thought to have a significant effect on concentrations of atmospheric carbon dioxide by altering rates of carbon sequestration, a theory known as the 'iron hypothesis'. For this reason, it is important to understand the response of pelagic biota to increased iron supply. Here we report the results of a mesoscale iron fertilization experiment in the polar Southern Ocean, where the potential to sequester iron-elevated algal carbon is probably greatest. Increased iron supply led to elevated phytoplankton biomass and rates of photosynthesis in surface waters, causing a large drawdown of carbon dioxide and macronutrients, and elevated dimethyl sulphide levels after 13 days. This drawdown was mostly due to the proliferation of diatom stocks. But downward export of biogenic carbon was not increased. Moreover, satellite observations of this massive bloom 30 days later, suggest that a sufficient proportion of the added iron was retained in surface waters. Our findings demonstrate that iron supply controls phytoplankton growth and community composition during summer in these polar Southern Ocean waters, but the fate of algal carbon remains unknown and depends on the interplay between the processes controlling export, remineralisation and timescales of water mass subduction.

Atmosphere↗
PubMed2000

In vitro culture of brushtail possum (Trichosurus vulpecula) epididymal epithelium and induction of epididymal sperm maturation in co-culture.

A medium modified from eutherian systems was used to culture epididymal epithelial cells of the brushtail possum (Trichosurus vulpecula) for more than 2 months. Epididymal tubule fragments from the caput, corpus and cauda epididymides were used to generate cell monolayers. All three epididymal cell culture systems supported maturational changes in marsupial spermatozoa and enabled immature possum spermatozoa to differentiate from a T-shape to a streamlined shape, accompanied by the development of progressive motility after co-culture with 7-day-old cultured epididymal cell monolayers. This epididymal cell and sperm co-culture system for marsupial species may facilitate the identification of specific epithelial factors that affect sperm maturation, particularly in a species in which morphological maturation is readily visible.

Animals↗
PubMed1999

A mass in the buttock of a schizophrenic.

A 70-year-old man with a 10-year history of depot injections with anti-psychotic drugs for schizophrenia developed a diffuse large B-cell lymphoma at the injection site in the buttock. This would appear to be a unique case and lends weight to the suggestion that prolonged local antigenic stimulation may be responsible for the development of extranodal lymphomas.

Aged↗
PubMed1998

Persistent desensitisation of the beta 2 adrenoceptors expressed by cultured equine sweat gland epithelial cells.

Adrenaline, forskolin and ATP all evoked accumulation of cyclic AMP in equine sweat gland epithelial cells, although the response to adrenaline was more transient than that to forskolin and ATP. Cells preincubated in adrenaline (10 micromol l-1, 32 min) showed essentially complete, homologous desensitisation, and this phenomenon reversed slowly (half-time 6.3+/-0.9 h). After 10 min of recovery from preincubation in adrenaline, isobutylmethylxanthine (IBMX, 5 mmol l-1) had no effect upon the desensitisation and the cells showed no loss of sensitivity to ATP and forskolin. After 10 h, however, the persistent desensitisation was partially reversed by IBMX and the cells showed reduced responses to ATP and forskolin. Increased phosphodiesterase activity may thus contribute to the persistent desensitisation. Experiments using forskolin-preincubated (100 micromol l-1, 32 min) cells suggested that increased cytosolic cyclic AMP levels did not underlie the initial loss of sensitivity to adrenaline but that this second messenger may initiate the series of events leading to the generalised loss of sensitivity seen after 10 h.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Activation of apical P2U purine receptors permits inhibition of adrenaline-evoked cyclic AMP accumulation in cultured equine sweat gland epithelial cells.

Experiments were undertaken using cultured equine sweat gland epithelial cells that express purine receptors belonging to the P2U subclass which allow the selective agonist uridine triphosphate (UTP) to increase the concentration of intracellular free Ca2+ ([Ca2+]i). Experiments using pertussis toxin (Ptx), which inactivates certain guanine-nucleotide-binding proteins (G-proteins), showed that this response consisted of Ptx-sensitive and Ptx-resistant components, and immunochemical analyses of the G-protein alpha subunits present in the cells showed that both Ptx-sensitive (alpha i1-3) and Ptx-resistant (alpha q/11) G-proteins were expressed. P2U receptors may, therefore, normally activate both of these G-protein families. Ptx-sensitive, alpha i2/3 subunits permit inhibitory control of adenylate cyclase, and UTP was shown to cause Ptx-sensitive inhibition of adrenaline-evoked cyclic AMP accumulation, suggesting that the receptors activate Gi2/3. Experiments using cells grown on permeable supports suggested that P2U receptors became essentially confined to the apical membrane in post-confluent cultures. Polarised epithelia may, therefore, express apical P2U receptors which influence two centrally important signal transduction pathways. It is highly improbable that these receptors could be activated by nucleotides released from purinergic nerves, but they may be involved in the autocrine regulation of epithelial function.

Adenylate Cyclase Toxin↗
PubMed1995

Granisetron as antiemetic therapy in children with cancer.

The safety and efficacy of the new 5HT-3 antagonist granisetron as an antiemetic in children with cancer was evaluated in 40 children at a single dose of 40 micrograms/kg. No adverse affects attributable to the granisetron were noted. The overall major and complete response rate was 82.5% and this was highest in the younger children. Only 2 patients showed no response. Pharmacokinetic studies showed associations between some pharmacokinetic parameters and age which were no longer apparent after normalisation for body weight. Granisetron is an effective and very well-tolerated antiemetic and appears to be an important addition to the supportive care available for children with cancer.

Adolescent↗
PubMed1995

The effect of levcromakalim (BRL 38227) on bladder function in patients with high spinal cord lesions.

The effects of the potassium channel opener levcromakalim (BRL 38227) 7.5 micrograms kg-1 were examined on urodynamic variables and blood pressure during inflow and voiding cystometry in six high spinal cord lesion patients. Levcromakalim administration significantly increased the duration of bladder contraction (197 +/- 128 s to 267 +/- 167 s, P < 0.05) and also reduced blood pressure (126 +/- 13/67 +/- 9 mm Hg to 104 +/- 25/52 +/- 12 mm Hg) but was without effect on other urodynamic parameters. Because of concerns about hypotensive responses, further studies involving higher doses of levcromakalim should be considered only if the drug was administered intravesically.

Adult↗
PubMed1994

Seasonal occurrence of psychrotrophic Bacillus species in raw milk, and studies on the interactions with mesophilic Bacillus sp.

Mesophilic and psychrotrophic isolates of Bacillus species displayed seasonal incidences in raw and pasteurised milk. The incidence of mesophilic isolates was highest in the winter and lowest in the summer/autumn while pschrotroph incidence was conversely lowest in the winter and highest in the late summer/autumn. Spores of Bacillus sp. were isolated from raw milk taken from farm milk machines and bulk tanks, milk tankers, diary silos and pasteurised milk. A consistent seasonal fluctuation in incidence throughout these samples suggested that spores of Bacillus sp. derived from the farm environment survived as important contaminants right through the milk chain to the pasteurised product. Up to seven mesophilic Bacillus sp. were isolated from a single sample with three species commonly occurring in most samples. The predominant mesophilic species isolated were B. pumilus, B. licheniformis and B. subtilis. The dominant psychrotrophic isolate was B. cereus. Selected mesophilic isolates were examined for possible antagonistic effects on the growth of psychrotropic B. cereus and B. pumilus isolates. Bacillus subtilis and B. licheniformis were found to produce antagonistic factors. It was considered that these factors may influence the incidence and growth of psychrotrophic isolates in the farm environment or in milk but the factors are not yet fully characterised or identified.

Animals↗
PubMed1991

Granisetron, a selective 5-HT3 receptor antagonist, for the prevention of radiation induced emesis during total body irradiation.

The antiemetic efficacy of granisetron was tested in an open trial in patients undergoing highly emetogenic treatment by single fraction total body irradiation. Thirty-two consecutive patients were entered. Results were both patient- and observer-rated. Following a single intravenous dose of granisetron 18 patients (56.3%) experienced total protection and a further 13 (40.6%) had major antiemetic protection with four of these patients experiencing nausea only. One patient experienced an anaphylactic reaction on infusion of monoclonal antibody-treated donor marrow 5 h after administration of the trial drug and vomited on multiple occasions. The reaction was associated with hypotension. A further patient experienced transient hypotension secondary to septicaemia 8 h after receiving granisetron. Three patients required a second dose. Headache was the most frequent side-effect occurring in three patients, but in to of these patients the test drug was not thought to be implicated. In conclusion granisetron is a highly effective agent in controlling radiation induced emesis with a favourable toxicity profile.

Adolescent↗
PubMed1988

Circulating concentrations of histamine, neutrophil chemotactic activity, and catecholamines during the refractory period in exercise-induced asthma.

Circulating mediators and catecholamine concentrations have been measured in eight subjects with asthma who were subjected to two bouts of cycle ergometer exercise separated by 1 hour. The maximum falls in FEV1 were 21.9 +/- 2.3% (mean +/- SEM; n = 8) and 5.5 +/- 1.3% (mean +/- SEM; n = 8) after the first and second exercises, respectively. Serum neutrophil chemotactic activity (NCA) and plasma histamine and catecholamine levels in venous blood were measured with a microchemotaxis and two radioenzymatic techniques, respectively. There was a significant increase in NCA and plasma histamine concentrations after both exercise challenges, and there was no significant difference in the release of these mediators between the two exercise tests. Gel filtration chromatography demonstrated that the NCA detected after the first and second exercise tests had molecular sizes of approximately 600,000 daltons. There was no significant time-dependent increase in plasma norepinephrine and epinephrine concentrations after either exercise task, even though the patients were refractory to exercise-induced asthma after the second exercise. These results suggest that the refractory period in exercise-induced asthma is not caused by mediator depletion, as indicated by NCA and histamine measurements, or by protection of the airways through catecholamine release.

Adult↗
PubMed1988

(Imidazo[1,2-a]pyrimidin-2-yl)phenylmethanones and related compounds as potential nonsedative anxiolytics.

Several series of heterocyclic carboxylic esters were found to be active in the benzodiazepine receptor binding assay, a typical example being ethyl 7-ethyl-5-methoxyimidazo[1,2-a]quinoline-2-carboxylate (4b) with an IC50 of 150 nM. The corresponding phenylmethanone 5d was more potent with an IC50 of 14 nM and was orally active in animal models thought to predict anxiolytic effects. The synthesis of a large number of compounds resulted in the optimization of this activity in a series of (imidazo[1,2-a]pyrimidin-2-yl)phenylmethanones of which compounds 7e, 8b, 8h, 8j, and 8k were equipotent with chlordiazepoxide while exhibiting reduced anticonvulsant activity, little or no muscle relaxation, and negligible sedative effects.

Animals↗
PubMed1987

Plasma level of histamine in aspirin-sensitive urticaria.

Twelve patients with a history of aspirin-induced urticaria and/or angioedema were studied before and after the provocation of symptoms with aspirin. The resting plasma histamine levels in these patients (0.95 +/- 0.25 ng/mL) were significantly higher than in 30 control subjects (0.21 +/- 0.02 ng/mL) (P less than .0005) and nine patients with non-aspirin-sensitive urticaria (0.27 +/- 0.06 ng/mL) (P less than .01). The plasma histamine levels fell significantly at the time of adverse reactions to aspirin (P less than .01). The high resting histamine levels, like the high venous prostaglandin F2 alpha levels that we have previously reported in the same group of patients and the high plasma histamine levels we have found in aspirin-sensitive asthmatics suggest an abnormality of mediator release in aspirin-sensitive patients.

Adult↗
PubMed1979

Polymyositis and complete heart block.

The development of complete heart block is described in a patient with polymyositis. The implantation of a permanent pacemaker has controlled the heart block, but the progression of the underlying disease despite treatment with relatively high dosage of corticosteroids makes the outlook uncertain.

Adult↗