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R J Walker

Publications and source records attributed to R J Walker.

At least 37 records · Page 2Linked to original sources
PubMed2000

Galileo magnetometer measurements: a stronger case for a subsurface ocean at Europa.

On 3 January 2000, the Galileo spacecraft passed close to Europa when it was located far south of Jupiter's magnetic equator in a region where the radial component of the magnetospheric magnetic field points inward toward Jupiter. This pass with a previously unexamined orientation of the external forcing field distinguished between an induced and a permanent magnetic dipole moment model of Europa's internal field. The Galileo magnetometer measured changes in the magnetic field predicted if a current-carrying outer shell, such as a planet-scale liquid ocean, is present beneath the icy surface. The evidence that Europa's field varies temporally strengthens the argument that a liquid ocean exists beneath the present-day surface.

Extraterrestrial Environment↗
PubMed2000

Involvement of ryanodine receptors in EPYLRFamide-mediated reduction of acetylcholine-induced inward currents in helix lucorum identified neurones.

The effects of several modulators of ryanodine receptors (RYRs) on the reduction of acetylcholine induced inward current (ACh-current) evoked by EPYLRFamide (5 microM, bath application), the potent N-terminally modified analogue of the endogenous Helix heptapeptide SEPYLRFamide, were investigated. These modulators were applied intracellularly. Inward currents were recorded from identified Helix lucorum LPa2, LPa3, RPa3, RPa2 neurones in ganglia preparations using the two-electrode voltage clamp technique. ACh was applied ionophoretically. BAPTA (0.1 mM), chelator of intracellular Ca(2+), ryanodine (0.1 mM), agonist/antagonist of RYRs and dantrolene (0.1 mM), antagonist of RYRs decrease the effect of EPYLRFamide. Adenosine (1 mM), alpha,beta-methylene ATP (0.1 mM), the nonhydrolisable ATP analogue and cyclic adenosine diphosphate ribose (0.1 mM) (agonists of RYRs) potentiate the modulatory effect of EPYLRFamide. Ruthenium red (1 mM), antagonist of RYRs and caffeine (1 mM), agonist of RYRs do not change the modulatory effect of EPYLRFamide. These data suggest that intracellular Ca(2+) and RYRs are involved in the modulatory effect of EPYLRFamide on ACh-currents. It was concluded that EPYLRFamide decreases ACh-current through elevation of basal intracellular level of a putative endogenous agonist of RYRs which activates RYR-dependent mobilization of Ca(2+) by binding to the adenine nucleotide site of the ryanodine receptor-channel complex and does not bind the site activated by caffeine.

Acetylcholine↗
PubMed2000

The management of alcohol-related seizures: an overview.

Alcohol-withdrawal seizures are one of the common medical emergencies. The seizures are generalized and usually occur abruptly between 6-8 hours after cessation of alcohol use (peak 12-24 hours). These patients are often uncooperative and therefore need careful assessment. Lorazepam is the first-line drug for termination and prophylaxis of alcohol-withdrawal seizures.

Adult↗
PubMed2000

Plasma cholesteryl ester fatty acid composition, insulin sensitivity, the menopause and hormone replacement therapy.

This study was designed to determine the effect of menopause and hormone replacement therapy (HRT) on plasma cholesteryl ester fatty acid (CEFA) composition and insulin sensitivity and the relationships between these variables in perimenopausal women (aged 40-55 years) including 49 who were premenopausal and 32 who were postmenopausal. Plasma cholesteryl ester proportions of dihomo-gamma-linolenic acid (20:3 n-6) were correlated significantly with insulin sensitivity index (r=-0.319, P=0.005), fasting serum insulin levels (r=0.230, P=0.038), body mass index (r=0.242, P=0.03) and per cent body fat (r=0.329, P=0.003) in perimenopausal women (n=81). Similar associations were observed in premenopausal women. Regression analysis suggested the relationships between 20:3 n-6 proportions and indices of insulin action may be partly mediated by levels of adiposity. In postmenopausal women, 6 months of HRT significantly (P=0.008) increased the ratio of arachidonic acid (20:4 n-6) to linoleic acid (18:2 n-6), which is an indicator of activity in the pathway of 20:4 n-6 synthesis, compared with placebo. These findings suggest that the type of fat in the diet indicated by plasma CEFA composition is linked to adiposity and insulin action. They also suggest that in postmenopausal women, HRT may increase the synthesis of 20:4 n-6, which is the precursor for eicosanoids with important cardiovascular functions.

Adult↗
PubMed2000

Physiological and pharmacological studies on nematodes.

Classical transmitters and neuroactive peptides act as transmitters or modulators within the central and peripheral nervous systems of nematodes, for example Ascaris suum and Caenorhabditis elegans. Acetylcholine (ACh) and gamma-aminobutyric acid (GABA) are respectively the excitatory and inhibitory transmitters onto somatic body wall muscle while 5-hydroxytrypamine (5-HT) is the excitatory transmitter onto pharyngeal muscle. 5-HT also reduces ACh-induced contractions of somatic muscle and this action of 5-HT is mediated through activation of adenylate cyclase while that on pharyngeal muscle is mediated through inositol phosphate activation. Glutamate, dopamine and octopamine also have transmitter roles in nematodes. Neuroactive peptides of the RFamide family can excite somatic muscle, for example, AF-1 (KNEFIRFamide), AF-2 (KHEYLRFamide), AF-3 (AVPGVLRFamide) and AF-4 (GDVPGVLRFamide) or inhibit and relax this muscle, for example, PF-1 (SDPNFLRFamide), PF-2 (SADPNFLRFamide) and PF-4 (KPNlRFamide). In addition PF-3 (AF-8) (KSAYMRFamide) has a biphasic action on pharyngeal muscle, excitation followed by inhibition while AF-1 only inhibits this muscle. The peptide effects can be either pre- or postsynaptic or both and are likely to be mediated through second messenger systems. In addition these peptides modulate the action of classical transmitters, particularly ACh.

Acetylcholine↗
PubMed1999

Impaired endothelial function following a meal rich in used cooking fat.

OBJECTIVES: The purpose of this study was to test the hypothesis that intake of used cooking fat is associated with impaired endothelial function. BACKGROUND: Diets containing high levels of lipid oxidation products may accelerate atherogenesis, but the effect on endothelial function is unknown. METHODS: Flow-mediated endothelium-dependent dilation and glyceryl trinitrate-induced endothelium-independent dilation of the brachial artery were investigated in 10 men. Subjects had arterial studies before and 4 h after three test meals: 1) a meal (fat 64.4 g) rich in cooking fat that had been used for deep frying in a fast food restaurant; 2) the same meal (fat 64.4 g) rich in unused cooking fat, and 3) a corresponding low fat meal (fat 18.4 g) without added fat. RESULTS: Endothelium-dependent dilation decreased between fasting and postprandial studies after the used fat meal (5.9 +/- 2.3% vs. 0.8 +/- 2.2%, p = 0.0003), but there was no significant change after the unused fat meal (5.3 +/- 2.1% vs. 6.0 +/- 2.5%) or low fat meal (5.3 +/- 2.3% vs. 5.4 +/- 3.3%). There was no significant difference in endothelium-independent dilation after any of the meals. Plasma free fatty acid concentration did not change significantly during any of the meals. The level of postprandial hypertriglyceridemia was not associated with change in endothelial function. CONCLUSIONS: Ingestion of a meal rich in fat previously used for deep frying in a commercial fast food restaurant resulted in impaired arterial endothelial function. These findings suggest that intake of degradation products of heated fat contribute to endothelial dysfunction.

Adult↗
PubMed1999

Structure-activity relationships of the Helix neuropeptide, SEPYLRFamide, and its N-terminally modified analogues on identified Helix lucorum neurones.

Metabotropic and ionotropic effects evoked by the endogenous Helix heptapeptide, SEPYLRFamide, and four analogues, i.e., where the amino acid sequences at the N-terminal (EPYLRFamide, SEGYLRFamide, SRPYLRFamide and SKPYLRFamide) were modified, were compared on identified Helix lucorum LPa2, LPa3, RPa3, RPa2 neurones using two electrode voltage clamp and current clamp techniques. All peptides (bath application) reduce reversibly the inward current to local ionophoretic application of acetylcholine onto the neurone soma with an order of potency: EPYLRFamide=SEGYLRFamide=SRPYLRFamide>SEPYLRFamide+ ++>SKPYLRFamide. The reductions of the acetylcholine-induced inward current evoked by SEPYLRFamide and its analogues at concentrations of 0.01-10 microM are not accompanied by a change of amplitude of the leak inward current caused by constant negative shift of a holding potential. At concentration of 50 microM all peptides increase reversibly the resting membrane conductance to an equal degree. Local application under pressure of SEPYLRFamide and its analogues onto the soma of neurones evoke hyperpolarizations with similar values. These results indicate that the N-terminal three amino acids of the peptide molecule are not responsible for the degree of ionotropic effect on the neurones studied. In contrast the amino acid sequence at the N-terminal modifies the degree of the modulatory effects of the YLRFamide-related analogues. Changes at the SEPYLRFamide N-terminal (Ser1-Glu2-Pro3) intensify the inhibitory action of the analogues as compared with effect evoked by the endogenous peptide, that is, removal of Ser1 (Glu1-Pro2), replacement of Pro3 with Gly3 (Ser1-Glu2-Gly3), replacement of Glu2 with Arg2 (Ser1-Arg2-Pro3). Replacement of Glu2 with Lys2 (Ser1-Lys2-Pro3) reduces the modulatory potency. It is concluded that ionotropic and metabotropic effects of these YLRFamide-related peptides may occur at different membrane binding sites.

Acetylcholine↗
PubMed1999

Dual action of the benzodiazepine receptor inverse agonist RU34347 on responses to exogenously applied GABA in the rat cerebellar slice.

The benzodiazepine receptor inverse agonist has been shown to produce agonist-like effects at low concentrations. RU34347 has both inverse agonist (attenuation of GABA-responses) and agonist-like (reduction of spontaneous Purkinje cell firing rate) in the cerebellar slice preparation. The benzodiazepine antagonist flumazenil prevented the inverse agonist actions, but only partially reduced the agonist-like effects. Further, brief application of RU34347 to slices mimicked the response to GABA, and pharmacological investigation determined that this action was mediated through increased GABA through action at a site proximal to the parallel fiber-basket cell synapse, at an as yet undetermined receptor.

Animals↗
PubMed1999

The inhibitory action of tamoxifen on the contraction of Ascaris suum somatic muscle in response to acetylcholine.

The somatic muscle of Ascaris suum is principally under the excitatory control of neuromuscular junction transmitter, acetylcholine (ACh). However, it has recently been shown that neuropeptides also play an important role in the motor-nervous system and one of these, AF3 (AVPGVLRFamide), also contracts muscle. The events which trigger contraction to ACh and AF3 would appear to be different, with ACh activating a nicotinic acetylcholine receptor whilst the response to AF3 is most likely to involve a G-protein coupled receptor negatively coupled to adenylate cyclase. In order to further elucidate differences in the cellular signalling pathways through which ACh and AF3 elicit muscle contraction, we investigated the actions of protein kinase C inhibitors, tamoxifen and chelerythrine, on the dorsal somatic muscle strip of A. suum. Contractions in response to 1 microM AF3 were potentiated by 17% in the presence of 10 microM tamoxifen (P < 0.05; n = 8); however, contractions in response to 10 microM ACh were markedly inhibited (tamoxifen IC50 44 +/- 18 microM; n = 6). Tamoxifen also blocked muscle cell depolarizations to 5 microM ACh (IC50 4 +/- 1 microM; n = 6) and 1 microM levamisole (IC50 14 +/- 6 microM; n = 4). This was unlikely to be a non-specific effect on the membrane as hyperpolarizations to 10 microM GABA were unaffected (93% of control with 10 microM tamoxifen; n = 6; P > 0.05). However, another inhibitor of mammalian protein kinase C, chelerythrine, did not affect the response either to ACh or AF3 (n = 6).

Acetylcholine↗
PubMed1999

Actions of nematode FMRFamide-related peptides on the pharyngeal muscle of the parasitic nematode, Ascaris suum.

The endogenous nematode peptides known as FMRFamide-related peptides (FaRPs) and various "classical" transmitters have a range of effects on nematodes that result in changes in behavior, particularly locomotion, including paralysis and inhibition of feeding. This study describes the application of an in vitro pharmacological approach to further delineate the action of a number of FaRP neurotransmitters on feeding behavior. Contraction of Ascaris suum pharyngeal muscle was monitored using a modified pressure transducer system that detects changes in intrapharyngeal pressure and therefore contraction of the radial muscle of the pharynx. The pharynx did not contract spontaneously. However, serotonin (5-HT, 100 microM) stimulated rhythmic contractions and relaxations (pumping) at a frequency of 0.5 Hz. The native nematode peptide, KNEFIRFamide (AF1), inhibited the pumping elicited by 5-HT. The duration of inhibition was concentration-dependent (1-1000 nM) with a threshold of 1 nM (n = 7). KSAYMRFamide (AF8/PF3) also inhibited pharyngeal pumping. There was no observable effect of any of the following nematode peptides on pharyngeal pumping behavior (1-1000 nM; n = 8): AF2, AF3, AF4, AF6, AF16, PF1/CF1, PF2/CF2, or PF4. Thus, interruption of pharyngeal processes, such as feeding, regulation of hydrostatic pressure, and secretion, may provide a new site of anthelmintic action.

Amino Acid Sequence↗
PubMed1999

Reduced postprandial serum paraoxonase activity after a meal rich in used cooking fat.

Paraoxonase is an enzyme associated with HDL in human serum that hydrolyzes oxidized phospholipids and inhibits LDL oxidation, which is an important step in atherogenesis. In animals, addition of oxidized lipids to the circulation reduces paraoxonase activity, and diets rich in oxidized fat accelerate the development of atherosclerosis. The current randomized, crossover study was designed to compare the effect of a meal rich in oxidized lipids in the form of fat that had been used for deep-frying in a fast food restaurant and a control meal rich in the corresponding unused fat on postprandial serum paraoxonase (arylesterase) activity and peroxide content of LDL and its susceptibility to copper ion catalyzed oxidation in 12 healthy men. Four hours into the postprandial period, serum paraoxonase activity had decreased significantly after the used fat meal (-17%, P=0.005) and had increased significantly after the meal rich in unused fat (14%, P=0. 005). These changes were significantly (P=0.003) different. A time-course study indicated that serum paraoxonase activity remained lower than baseline for up to 8 hours after the used fat meal. Serum apoA1 concentration tended to decrease after the unused fat meal and tended to increase after the used fat meal. These changes were different at a marginal level of significance (P=0.07). Also, a significantly (P=0.03) greater decrease in apoA1 content of postprandial HDL was recorded after the unused fat meal. The peroxide content of LDL tended to decrease after the used fat meal and tended to increase after the control meal. These changes were significantly (P=0.04) different. Susceptibility of isolated LDL to copper ion oxidation and plasma levels of malondialdehyde were unchanged during the study. These data suggest that in the postprandial period after a meal rich in used cooking fat, the enzymatic protection of LDL against accumulation of peroxides and atherogenic oxidative modification may be reduced, possibly due to factors associated with apoA1, without acutely affecting the intrinsic resistance of LDL to in vitro oxidation.

Adult↗
PubMed1999

Plasma cholesterol esterification and transfer, the menopause, and hormone replacement therapy in women.

With the onset of the menopause, plasma lipids and lipoprotein metabolism changes toward a more atherogenic profile that is improved by HRT. To determine whether cholesterol esterification rate (CER) and transfer of cholesteryl esters from high density lipoproteins to apolipoprotein B-containing lipoproteins are affected by menopause and HRT, plasma newly synthesized cholesteryl ester transfer (NCET) activity, CER and plasma lipids, lipoproteins, and apolipoprotein concentrations were measured in perimenopausal women (age range: 40-55 yr), including 49 premenopausal women and 32 postmenopausal women who were subsequently randomized to receive either placebo or 17-beta estradiol/norethisterone for 6 months. Plasma NCET (P = 0.03) and CER (P = 0.008) were significantly higher in postmenopausal women. Plasma low density lipoprotein cholesterol concentration, high density lipoprotein concentration, and body mass index were independent predictors of plasma NCET in premenopausal women, and plasma triglyceride and apolipoprotein B concentrations were corresponding predictors in postmenopausal women. When data were adjusted for plasma triglyceride, plasma NCET activity was no longer significantly different (P = 0.81) between premenopausal and postmenopausal women. Plasma NCET and CER did not change significantly in postmenopausal women during HRT. These data suggest that the determinants of plasma NCET activity after menopause and increased levels of triglyceride-rich lipoprotein acceptors of cholesteryl esters may lead to increased plasma NCET that is not reduced by HRT in postmenopausal women.

Adult↗
PubMed1999

Supplementation with tomato juice increases plasma lycopene but does not alter susceptibility to oxidation of low-density lipoproteins from renal transplant recipients.

AIM: Oxidative stress and susceptibility of low-density lipoproteins (LDL) to oxidation are increased in renal transplant recipients. The aim of this study was to determine the effect of dietary supplementation with tomato juice on plasma levels of the antioxidant lycopene, serum indices of lipid peroxidation (fluorescent lipid oxidation products (FLOP) and thiobarbituric acid-reacting substances (TBARS)) and the resistance of isolated low-density lipoprotein (LDL) to oxidation (lag time) in patients with a kidney graft. SUBJECTS AND METHODS: Fifteen patients were randomized to daily consumption of either tomato juice or synthetic orange drink for 4 weeks in a crossover study. Plasma lycopene levels were significantly higher (1.57 micromol/l versus 0.91 micromol/l, p = 0.015) while serum FLOP and TBARS and resistance of LDL to oxidation were not significantly different during supplementation with tomato juice compared with orange drink. At baseline, serum levels of lycopene and FLOP were abnormally high and serum FLOP was correlated significantly with plasma cyclosporine levels (r = 0.646, p = 0.016). CONCLUSION: In conclusion, these data suggest that increased oxidative stress and susceptibility of LDL to oxidation may not be reduced by increasing plasma lycopene levels with regular consumption of tomato juice in renal transplant recipients.

Adult↗
PubMed1999

The actions of FxRFamide related neuropeptides on identified neurones from the snail, Helix aspersa.

Intracellular recordings were made from identified neurones in the suboesophageal ganglia of the snail, Helix aspersa. The actions of the eight FxRFamide analogues were investigated on these neurones. These peptides included ones isolated from arthropods and nematodes. All the peptides excited certain neurones while inhibiting others, though their relative potencies varied. Overall on neurones inhibited by these peptides the potency order was: DNFLRFamide > FMRFamide > PDVDHVFLRFamide = KNEFIRFamide > FLRFamide >> SDRNFLRFamide = SDPNFLRFamide > KHEYLRFamide. However, if the responses are compared on individual cell types, then the picture becomes more complex. For example, on cell F-2, KNEFIRFamide proved to be potent with an EC-50 value of 0.54 microM. On neurones F-13/16 and E-16, PDVDHVFLRFamide was inhibitory while FMRFamide, FLRFamide, SDRNFLRFamide and SDPNFLRFamide were excitatory. In terms of overall excitatory actions, the data are less complete but an approximate order of potency is: FMRFamide > DNFLRFamide >> SDPNFLRFamide > PDVDHVFLRFamide >> KNEFIRFamide = KHEYLRFamide = SDRNFLRFamide. However this again varies between specific neurones. These results demonstrate that peptides from insects, crustacea and nematodes are active on Helix neurones and may activate specific receptor subtypes, indicating the possible presence of endogenous analogues of these non-molluscan peptides in the Helix nervous system.

Amides↗
PubMed1998

Induced magnetic fields as evidence for subsurface oceans in Europa and Callisto.

The Galileo spacecraft has been orbiting Jupiter since 7 December 1995, and encounters one of the four galilean satellites-Io, Europa, Ganymede and Callisto-on each orbit. Initial results from the spacecraft's magnetometer have indicated that neither Europa nor Callisto have an appreciable internal magnetic field, in contrast to Ganymede and possibly Io. Here we report perturbations of the external magnetic fields (associated with Jupiter's inner magnetosphere) in the vicinity of both Europa and Callisto. We interpret these perturbations as arising from induced magnetic fields, generated by the moons in response to the periodically varying plasma environment. Electromagnetic induction requires eddy currents to flow within the moons, and our calculations show that the most probable explanation is that there are layers of significant electrical conductivity just beneath the surfaces of both moons. We argue that these conducting layers may best be explained by the presence of salty liquid-water oceans, for which there is already indirect geological evidence in the case of Europa.

Extraterrestrial Environment↗