Biomedical subjects

T W Ford

Publications and source records attributed to T W Ford.

28 records · Page 2Linked to original sources

PubMed1988

Adrenergic and opioidergic modulation of a spinal reflex in the decerebrated rabbit.

1. In the decerebrated and spinalized rabbit, electrical stimulation of the sural nerve evokes a short-latency reflex in the ipsilateral ankle extensor gastrocnemius medialis (GM) which is tonically suppressed by endogenous opioids. In the present study we have investigated the inhibitory influences affecting this reflex in non-spinalized, decerebrated rabbits. 2. In non-spinalized rabbits, the thresholds and latencies of the sural-GM reflex were significantly higher than in spinalized preparations. The opioid antagonist naloxone and the alpha-adrenoceptor antagonist idazoxan potentiated the reflex in both preparations. Naloxone was significantly more effective in spinalized rabbits whereas idazoxan had a much larger effect in non-spinalized animals. 3. When the spinal cord was sectioned in the presence of naloxone alone, the GM reflex always increased in size. An ipsilateral hemisection of the cord was as effective as total section in this respect. When the section was performed in the presence of idazoxan and naloxone, the response usually decreased in size. 4. The alpha 2-adrenoceptor agonist clonidine depressed the reflex in spinalized rabbits, an action that was reversed by idazoxan but not by naloxone. 5. These data show that in the decerebrated, non-spinalized rabbit, the sural-GM reflex is tonically suppressed by endogenous opioids, presumably acting at the segmental level, and by an ipsilateral descending pathway which involves an alpha-adrenoceptor-mediated synapse. Activity in this descending pathway masks the facilitatory effects of opioid antagonists on spinal reflexes in this preparation.

Adrenergic alpha-Antagonists↗

PubMed1987

A sputtered gold microelectrode in combination with a multibarrelled micropipette: a low impedance extracellular recording electrode with the facility of iontophoresis.

The manufacture of a metal film electrode on a multibarrelled micropipette is described. Gold film is sputtered onto the external surface of a multibarrelled micropipette and subsequently insulated. Gold film exposed at the tip operates as an extracellular recording microelectrode and the micropipettes may be used for iontophoresis of drugs or marker dyes. This method may be used to produce electrodes with increased numbers of iontophoresis channels at the tip without altering the low impedance and good recording characteristics of the metal film (recording) electrode.

Animals↗

PubMed1987

The effect of selective electrical stimulation of non-myelinated vagal fibres on heart rate in the rabbit.

The bradycardia evoked by electrical stimulation of the peripheral cut end of the rabbit vagus nerve is mediated by both myelinated and non-myelinated fibres. The purpose of this study was to assess the effects of non-myelinated fibres on heart rate in the rabbit using selective electrical stimulation techniques. In 8 rabbits selective activation of non-myelinated fibres using reversed polarity triangular shaped pulses (10 Hz, 20 s), resulted in a slowly developing fall in heart rate of 24.1 +/- 1.1 beats/min which outlasted the period of stimulation by 58.4 +/- 4.2 s. In 4 rabbits stimulation of myelinated fibres at 10 Hz for 20 s resulted in a fall in heart rate of 24.5 +/- 2.6 beats/min. On stimulation of both myelinated and non-myelinated fibres heart rate fell by 39.9 +/- 3.2 beats/min. Heart rate returned rapidly to control value following stimulation of myelinated fibres (5.6 +/- 0.5 s) but only slowly after stimulation of both myelinated and non-myelinated fibres (56.7 +/- 4.9 s). Atropine (5 mg/kg, i.v.) abolished all effects of vagal stimulation on heart rate. Hexamethonium (15 mg/kg, i.v.) abolished the effect of myelinated fibres on heart rate but did not affect the fall in heart rate produced by non-myelinated fibres. We suggest that the prolonged effects on stimulation of non-myelinated fibres may reflect the persistent action of a non-cholinergic excitatory transmitter at the cardiac parasympathetic ganglia.

Animals↗

PubMed1987

The contributions of mu-, delta- and kappa-opioid receptors to the actions of endogenous opioids on spinal reflexes in the rabbit.

Spinal reflexes in the rabbit are suppressed tonically by endogenous opioids. The contributions made to this suppression by mu-, delta- and kappa-opioid receptors have been investigated by studying the actions of a range of opioid antagonists and agonists on reflexes evoked by sural nerve stimulation in the ankle extensor gastrocnemius medialis (g.m.), and in the knee flexor semitendinosus (s.t.). When given at a total dose of 88.5 micrograms kg-1 i.v., either of the universal opioid receptor antagonists (-)-naloxone and (-)-quadazocine enhanced the g.m. response to more than 7 times the pre-drug control values, and the s.t. reflex to 1.5 times controls. The effects of quadazocine were stereospecific. The selective delta antagonist ICI 174864 (3.5 mg kg-1 i.v. total) also augmented the g.m. reflex but only to twice pre-drug controls. The mu-agonists fentanyl (100 micrograms kg-1) and morphine (50 mg kg-1) suppressed both g.m. and s.t. reflex responses to less than half control levels by a naloxone-reversible mechanism. The kappa-agonists bremazocine (50 micrograms kg-1 total), tifluadom (100 micrograms kg-1), ethylketocyclazocine (200 micrograms kg-1) and U50488H (1 mg kg-1) potentiated the g.m. reflex and had variable effects on the s.t. response. Naloxone usually added to the facilitatory actions of these drugs. kappa-Opioid receptor agonists also caused a profound, naloxone-reversible depression of arterial blood pressure. It may be concluded that the endogenous opioid-mediated suppression of spinal reflexes in the rabbit is mediated mainly, if not exclusively, through mu-receptors. There are no known endogenous ligands which are specific for the mu-receptor, so in the present case it seems that selectivity is determined by the receptor population rather than by the ligand.

Animals↗

PubMed1986

The effects of electrical stimulation of myelinated and non-myelinated vagal fibres on heart rate in the rabbit.

The bradycardia evoked by electrical stimulation of the peripheral end of the rabbit vagus nerve is mediated by both myelinated and non-myelinated fibres. Stimulation of myelinated fibres at 5 Hz for 20 s resulted in a fall in heart rate from a control value of 204 +/- 1.3 to 182 +/- 1.2 beats min-1 (means + S.E. of means). On stimulation of both myelinated and non-myelinated fibres, heart rate fell to 169 +/- 2.1 beats min-1. Heart rate returned rapidly to control value following stimulation of myelinated fibres but only slowly after stimulation of both myelinated and non-myelinated fibres. Thus recruitment of non-myelinated fibres increased both the magnitude and duration of the bradycardia. Atropine abolished all effects of vagal stimulation on heart rate. Hexamethonium abolished the effect of myelinated fibres on heart rate; however, recruitment of non-myelinated fibres still produced a bradycardia. It is suggested that the prolonged effect following stimulation of non-myelinated fibres may reflect the persistent action of a non-cholinergic excitatory transmitter at the ganglion.

Action Potentials↗

PubMed1979

Ribulose 1,5-bisphosphate carboxylase from the thermophilic, acidophilic alga, Cyanidium caldarium (Geitler). Purification, characterisation and thermostability of the enzyme.

An an initial stage in the study of proteins from thermophilic algae, the enzyme ribulose 1,5-bisphosphate carboxylase 2-phospho-D-glycerate carboxylyase (dimerizing, EC 4.1.1.39) was purified 11-fold from the thermophilic alga Cyandium caldarium, with a 24% recovery. This purified enzyme appeared homogeneous on polyacrylamide gels and could be dissociated into two subunit types of molecular weights 55,000 and 14,900. The optimal assay temperature was 42.5 degrees C, whilst enzyme purified from Chlorella spp. showed maximum activity at 35 degrees C. The thermostability of Cyanidium ribulose 1,5-bisphosphate carboxylase was considerably greater than that of the Chlorella enzyme, and the presence of Mg2+ and HCO-3 further enhanced this heat stability. A break in the Arrhenius plot occured at 20 degrees C for Chlorella ribulose 1,5-bisphosphate carboxylase and 36 degrees C for the enzyme from Cyanidium. It is suggested that the thermostability of Cyanidium ribulose 1,5-bisphosphate carboxylase is a result of an inherent stability of the enzyme molecule which permits efficient CO2 fixation at high temperatures but results in low activity in the mesophilic temperature range.

Carboxy-Lyases↗

PubMed1978

Separation of erythropoietin responsive cells in fetal mouse liver.

The erythropoietin responsive cells (ERC) in suspension cultures (ERCSC) of fetal mouse liver and the cells producing erythroid colonies in 2-day plasma clot cultures (CFU-E) sediment at similar rates. However, the sedimented fractions containing the majority of nucleated cells show minimal sensivitity to erythropoietin (Ep) and these cells sediment at a slower rate than the ERCSC. The studies suggest that in short-term suspension cultures of fetal mouse liver, Ep acts on morphologically unrecognizable cells to increase the number of hemoglobin-synthesizing cells rather than by increasing the quantity of hemoglobin synthesized per cell. This effect is similar to the principal in vivo action of Ep.

Animals↗

PubMed1977

Pathophysiological changes in serum erythropoiesis stimulating activity.

The mouse fetal liver cell bioassay has been used to study serum levels of erythropoiesis stimulating activity (ESA) in patients with a variety of haematological disturbances. The results indicate that this assay system provides a quantitative measurement of ESA, the concentration of which varies predictably in a manner which is consistent with it having a function as an in vivo regulator of erythropoiesis. Dose-response curves for serum ESA show highly significant parallelism with those obtained from sheep plasma erythropoietin and the International Reference Preparation of human urinary erythropoietin.

Anemia↗

PubMed1977

Oxymetholone and erythropoiesis: failure to detect an effect in fetal mouse liver cell cultures.

Oxymetholone, a steroid of proven clinical value in the treatment of refractory anemia, was without effect on endogenous or erythropoietin-mediated heme synthesis in fetal mouse liver cell cultures. This conclusion applied both when the cells were exposed to oxymetholone prior to culturing with erythropoietin and when the steroid was present in the cultures simultaneously with erythropoietin. Unlike those steroids having a direct effect on erythroid cells, oxymetholone also failed to increase the proportion of erythropoietin responsive cells in DNA synthesis. The relevance of these observations to the therapeutic benefit of oxymetholone is discussed. While the possibility that oxymetholone has to be metabolized to an active form cannot be excluded, the results suggest that oxymetholone does not seem to be erythropoietically active by a direct effect on erythroid cells. The fact that it is a successful therapeutic agent in some patients with aplastic anemia may be due to its proven ability to increase endogenous erythropoietin levels or to reduce ineffective erythropoiesis.

Animals↗

PubMed1977

The influence of alpha thioglycerol on erythropoiesis in fetal mouse liver cell cultures.

alpha-Thioglycerol has been shown to increase hemoglobin synthesis in suspension cultures of fetal mouse liver cells. The mechanism of this effect is unknown but appears to be directly on S-phase cells increasing their sensitivity to erythropoietin. alpha-Thioglycerol inhibits heme synthesis when S-phase cells have been removed by prior treatment with hydroxyurea. The stimulatory or inhibitory effects of thiols depending on the proportion of cells in S-phase suggests that extreme caution should be used when interpreting cell kinetic studies of cultured cells if thiols are present in the cultures.

Animals↗