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Biomedical subjects

J Millar

Publications and source records attributed to J Millar.

At least 19 recordsLinked to original sources
PubMed1992

Gut protection by cyclophosphamide "priming" in patients receiving high-dose melphalan--effect of drug scheduling.

A "priming" injection of cyclophosphamide (400 mg/m2 given i.v. on day -7) has been shown to reduce intestinal permeability and thus gut toxicity in patients receiving high-dose melphalan. To determine the optimal timing for this injection, patients receiving 200 mg/m2 melphalan with an autologous bone marrow transplant were randomly assigned to receive cyclophosphamide at 5, 7 or 9 days before the melphalan. The median percentage of [51Cr]-ethylenediaminetetraacetic acid excretion was similar (9.1% vs 7.1% vs 7.7%, respectively), with equivalent duration of WHO grade 2-4 mucositis and diarrhoea being recorded for each group. Thus, the timing of the cyclophosphamide prime is not critical, and the priming injection may be given between 5 and 9 days prior to high-dose melphalan.

Bone Marrow Transplantation↗
PubMed1992

Continuous scan cyclic voltammetry (CSCV): a new high-speed electrochemical method for monitoring neuronal dopamine release.

This report describes a new form of fast cyclic voltammetry which samples electrochemical reactions of dopamine at one every 10 ms. We have called this technique 'continuous scan cyclic voltammetry' (CSCV). The technique uses a carbon fibre microelectrode which is connected to a continuously active sine-wave source. The applied voltage is a 100 Hz precision sine wave. Faradaic signals due to cycles of continuous oxidation and reduction of dopamine at the tip of the electrode can be observed superimposed on a fixed charging current. The technique is insensitive to moderate concentrations of ascorbate as a depletion zone for ascorbate is rapidly established around the electrode. In a brain slice preparation the technique can show the time course of dopamine release on a millisecond time scale. It should prove a valuable new tool for the investigation of dopamine transmission in the brain.

Animals↗
PubMed1992

Vitamin C--the primate fertility factor?

The loss of the ability of primates and man to synthesise ascorbic acid (vitamin C) is usually seen as an evolutionary accident, with no benefit to the species. This paper argues that the loss of this biosynthetic ability has allowed vitamin C to act as a 'fertility factor' in primate societies. It is argued that the requirement for vitamin C increases with age, and so in times of food shortages the older members of society suffer higher mortality than the younger. This reduces the median age of the population towards the younger and most fertile members, and so enables the population to regrow rapidly when food resources are restored.

Aging↗
PubMed1992

No increase in relapse in patients with myeloid leukaemias receiving rhGM-CSF after allogeneic bone marrow transplantation.

Twenty patients with leukaemia received recombinant human GM-CSF (rhGM-CSF) after allogeneic bone marrow transplantation (BMT) in a double blind controlled trial, with a significant promotion of granulopoiesis when compared with 20 control patients. The follow-up in survivors is now sufficiently long to assess the potential for promotion of relapse in the patients with myeloid leukaemias. Six patients with myeloid leukaemias are alive 22-38 months after transplantation. Eight other patients with myeloid leukaemias died within 12 weeks of transplantation without active active disease. None of these 14 patients with myeloid leukaemias have relapsed. This study supports the view that rhGM-CSF does not increase the probability of relapse after allogeneic BMT in patients with myeloid leukaemia.

Bone Marrow Transplantation↗
PubMed1991

Monitoring exocytosis from single mast cells by fast voltammetry.

We have used fast differential ramp voltammetry with carbon-fibre electrodes to monitor exocytotic secretion in single rat mast cells. The oxidation peak and other aspects of the electrochemical profile of the substance released were similar to those of 5-hydroxytryptamine (5-HT) and the signals were increased by preloading the secretory granules with exogenous 5-HT. Metabolic blockade inhibited both visible degranulation and the electrochemical signal. For comparison, quinacrine, which is fluorescent and accumulates in secretory vesicles, was used as an alternative means of detecting secretion in single cells. The amplitude of the electrochemical signals observed during degranulation correlated well with the loss of quinacrine fluorescence. Both methods were used to record successive rounds of secretion in single mast cells in response to repeated applications of compound 48/80.

Animals↗
PubMed1991

cdc25 M-phase inducer.

In this paper, we have described the critical experiments leading to the discovery and analysis of the cdc25 M-phase inducer. We have shown that timing of mitosis is sensitive to the level of cdc25+ expression and that the cellular concentration of p80cdc25 increases as cells approach mitosis. From these observations we conclude that, in S. pombe, rate of accumulation of p80cdc25 plays an important role in determining the timing of mitosis. We postulate that under a given set of conditions, a critical level of p80cdc25 activity is required to undergo mitosis. The actual level that is required can vary depending on ploidy, growth rate, nutritional status of the cell, and perhaps other parameters. These signals may be monitored through the weel pathway leading to tyrosyl phosphorylation of p34cdc2. We have shown that p80cdc25 encodes a phosphate that acts by directly dephosphorylating the Tyr-15 residue of p34cdc2. Our studies strongly indicate that this aspect of the mitotic control network is generally conserved among eukaryotes. It is conceivable, however, that the mode of regulation of cdc25 activity may vary from species to species. Clearly, in S. cerevisiae the cdc25+ homolog, MIH1, in contrast to cdc25+, is not rate-limiting for M-phase onset. It will be important to determine whether the level of cdc25+ homologs in other organisms also oscillates during the cell cycle, or whether their activity is controlled by localization or posttranslational mechanisms, such as phosphorylation. Furthermore, our finding of more than one cdc25+ homolog in a single species suggests an additional level of complexity to the control of M-phase onset by cdc25 in higher eukaryotes that will require further investigation.

Amino Acid Sequence↗
PubMed1991

Differential effects of dopamine agonists upon stimulated limbic and striatal dopamine release: in vivo voltammetric data.

1. Fast cyclic voltammetry at carbon fibre microelectrodes was used in rats anaesthetized with chloral hydrate to monitor dopamine release in the caudate and nucleus accumbens evoked by electrical stimulation of the median forebrain bundle. Stimulation trains (50 Hz sinusoidal current, 100 +/- 10 microA r.m.s., 2s duration) were repeated every 5 min throughout the experiment. 2. The actions of the dopamine agonists quinpirole, pergolide, SKF 38393, bromocriptine, (+)-3-(3-hydroxyphenyl)-N-n-propylpiperidine ((+)-3PPP) and (-)-3PPP were compared in the two nuclei. 3. Bromocriptine (10 mg kg-1, i.p.) did not affect release in either nucleus while SKF 38393 caused a fleeting decrease in limbic but not striatal dopamine release at a high dose (20 mg kg-1, i.p.). 4. Quinpirole and pergolide (both 1 mg kg-1, i.p.) decreased stimulated dopamine release in the nucleus accumbens while in the caudate the drugs each caused a transient, though not quite significant, elevation of stimulated dopamine release followed by decrease in release of the same magnitude as that seen in the nucleus accumbens. 5. The (-)-enantiomer of 3PPP (20 mg kg-1, i.p.), a partial agonist at the dopamine autoreceptor, increased stimulated dopamine release in both nuclei although the action in the caudate was larger and more prolonged. (+)-3PPP (20 mg kg-1, i.p.), a full agonist, decreased release in the nucleus accumbens. A small, transient and not significant increase in the caudate was followed by decreased release. 6. The results are interpreted as being evidence for differences in the dopamine autoreceptor in the two nuclei, possibly in the affinity state of the receptor in each nucleus.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Human recombinant GM-CSF in allogeneic bone marrow transplantation for leukaemia: double-blind placebo controlled trial.

A double-blind randomised trial compared 20 patients with leukaemia receiving human recombinant granulocyte macrophage colony stimulating factor (GM CSF), with 20 patients receiving placebo for 14 days after allogeneic matched sibling bone marrow transplantation. The median neutrophil count at 14 days was significantly higher in the GM CSF group (1.90 vs. 0.46 x 10(9)/l). The duration of hospital stay, the number of antibiotic days, and the number of fever days was the same for both patient groups. The lymphocyte count was significantly higher in the GM-CSF group than in the placebo group between days 10 and 15 after transplantation. The GM-CSF group had lower haemoglobin concentrations and platelets counts, and higher plasma urea creatinine and bilirubin, than the placebo group. There was no evidence that GM CSF was associated with a greater incidence of leukaemic relapse.

Bone Marrow Transplantation↗
PubMed1991

Growth of primary human acute leukemia in severe combined immunodeficient mice.

Seven populations of human leukaemic cells were implanted i.v. into sublethally irradiated severe combined immunodeficient (scid) mice. Growth of leukaemia was monitored by labelling murine peripheral blood (PB) cells with an anti-HLA monoclonal antibody and flow cytometric analysis. Two of the populations transplanted were fresh acute lymphoblastic leukaemia (ALL) bone marrow (BM) cells which both caused sustained proliferative growth in scid mice. Human cells accounted for up to a mean of 87% of the total nucleated cells (TNC) in the PB of these mice between weeks 12-15. One of these populations was passaged into fresh mice and frank leukaemia was again established. Three populations of cryopreserved acute myeloblastic leukaemia (AML) cells (2 obtained from PB and 1 from BM) and one population of cryopreserved biphenotypic acute leukaemia BM cells, only grew to a maximum of 4% within the 15 week period of the experiment. A cell population from an AML cell line (HL60), however, did engraft and proliferate resulting in a rapid deterioration of these mice between weeks 3-6 when the proportion of human cells accounted for 9% of the TNC in the PB.

Acute Disease↗
PubMed1990

Human recombinant GM-CSF in allogeneic bone-marrow transplantation for leukaemia: double-blind, placebo-controlled trial.

In a randomised, double-blind trial 20 patients with leukaemia received human recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) and 20 received placebo, for 14 days after allogeneic, matched sibling, bone-marrow transplantation. The neutrophil count recovered to 0.5 x 10(9)/l 3 days earlier in the GM-CSF group than in the placebo group (not significant), and the median neutrophil count at 14 days was significantly higher in the GM-CSF group (1.90 vs 0.46 x 10(9)/l). The lymphocyte count was significantly higher in the GM-CSF than in the placebo group between days 10 and 15 after transplantation, but this difference was not associated with a higher incidence of graft-versus-host disease. There was no evidence that GM-CSF was associated with a greater incidence of leukaemic relapse. The GM-CSF group had lower haemoglobin concentrations and platelet counts and higher plasma urea, creatinine, and bilirubin than the placebo group. The duration of hospital stay was the same for both patient groups. Further studies are now indicated to assess the overall effect of GM-CSF on outcome after allogeneic bone-marrow transplantation.

Adolescent↗
PubMed1990

No mediolateral differences in striatal autoreceptor-mediated modulation of dopamine release: in vivo voltammetric data.

Medial and lateral neostriatum differ qualitatively in their sources of dopamine (DA) innervation and in their behavioural functions. The present study sought to ascertain whether these differences were reflected in their response to DA autoreceptor drugs. Fast cyclic voltammetry was used to measure stimulated DA release at medial and lateral carbon fibre microelectrodes. Metoclopramide and (+)-3-PPP were used as autoreceptor antagonist and agonist respectively. No differences were observed in the level of DA release evoked by stimulation or in the agonist and antagonist responses at medial or lateral sites. We therefore conclude that differences between medial and lateral striatal DA function are not evident at the autoreceptor level.

Animals↗
PubMed1979

The effect of bilateral ventral noradrenaline bundle lesions on lever pressing for food in rats.

Food reward has been associated with activation of noradrenergic mechanisms in the brain. Using rats trained to press a lever for food reward, we have investigated the effects of 6-hydroxydopamine lesions, which severly depleted hypothalamic noradrenaline, on the willingness of the rats to press the lever for food reward. We found that performance in the food-rewarded task was significantly impaired following such lesions, and that this was especially marked when the task was made more difficult. From our results we suggest that ventral noradrenaline bundle lesions can decrease the rewarding nature of food, thus making the animals less willing to work for food reward.

Animals↗
PubMed1979

Carbon fibre microelectrodes.

A technique for making recording microelectrodes containing an ultrafine carbon fibre is described. This technique can be used for single- and multi-barrel microelectrodes. These microelectrodes not only have a very low signal-to-noise ratio comparable with that found in tungsten microelectrodes but are simpler to make. When used in a multi-barrel array for iontophoretic application of drugs the carbon fibre microelectrode has many advantages over a fluid electrolyte-filled recording barrel, including very high signal-to-noise ratio and relative immunity to spike distortion during application of iontophoretic current.

Animals↗