PubMed Health⌕ Search

Biomedical subjects

P A Smith

Publications and source records attributed to P A Smith.

At least 19 recordsLinked to original sources
PubMed1992

Effects of somatostatin on potassium currents in bullfrog sympathetic ganglion neurones: possible role of receptor subtypes.

The effects of whole somatostatin (wSS; somatostatin-28) and cyclic somatostatin (cSS; somatostatin-14) were examined on patch-clamped bullfrog sympathetic ganglion neurones. In the C-cells, where muscarine produces hyperpolarization, wSS was also inhibitory and activated an inwardly-rectifying K+ current; cSS was ineffective. By contrast, in the B-cells, where muscarine produces excitatory effects, cSS was also excitatory and was more effective than wSS in suppressing a voltage-dependent, non-inactivating K(+)-current (IM). These results are consistant with the idea that excitatory and inhibitory effects of somatostatin-derived peptides may be mediated via different receptor subtypes.

Animals↗
PubMed1992

The suppressor of Hairy-wing binding region is required for gypsy mutagenesis.

We undertook a deletional analysis of the gypsy retrotransposon in order to determine which sequences of the element are required for its mutagenic effect. We show that a phenotype indistinguishable from that of y2 flies can be generated by transforming y- flies with a construct containing the yellow gene and a gypsy element located at the same insertion site in yellow as found in y2 flies. When flies are transformed with similar constructs in which increasing amounts of the 5' transcribed untranslated region of gypsy have been removed, either a partial y2 revertant or a completely revertant phenotype is obtained. These results yield direct proof that the region of gypsy to which the su(Hw) protein binds is required for the generation of mutant phenotypes by this retrotransposon.

Amino Acid Sequence↗
PubMed1992

M-currents in frog sympathetic ganglion cells: manipulation of membrane phosphorylation.

1. The inward current and the M-current (IM) suppression produced when muscarine is applied to frog sympathetic ganglion cells was recorded by means of the whole-cell patch-clamp technique. The holding potential was -30 mV and [K+]o was 6 mM. 2. The steady-state IM was maintained for at least 20 min when the patch pipette contained neither adenosine 5'-triphosphate (ATP) nor adenosine 3':5'-cyclic monophosphate (cyclic AMP). Inclusion of these substances or the ATP antagonist, beta,gamma-methyleneadenosine 5'-triphosphate (beta,gamma-MethATP; 1 or 2 nM) (failed to alter the rate of IM 'run down'. By contrast, inclusion of adenosine-5'-O-(3-thiotriphosphate) (ATP-gamma-S, 1 or 2 mM) resulted in a 60% reduction of the current within 18 min. 3. Despite the inability of ATP-gamma-S to maintain steady-state IM, it had no effect on the ability of muscarine (2-100 microM) to suppress a constant fraction of the available current. ATP-gamma-S and beta,gamma-MethATP increased the rise time and duration of the response to muscarine. 4. Inclusion of a phosphatase inhibitor, diphosphoglyceric acid (DPG, 1-2.5 mM) or alkaline phosphatase (100 micrograms ml-1) failed to affect the amplitude of muscarinic responses. 5. These results question the role of the phosphorylation and/or dephosphorylation reactions in the transduction mechanism for muscarine-induced IM suppression but are consistent with the possibility that M-channels are 'directly coupled' via G-protein to the muscarinic receptor.

Animals↗
PubMed1992

Papillary cystic neoplasm of the pancreas: presentation and natural history in two cases.

Two young women, one white and one Chinese, with the rare but increasingly recognised papillary and cystic neoplasm of the pancreas are reported. The initial symptom in both was non-specific abdominal pain which, after investigation, was found to be caused by a pancreatic tumour. One patient did not come to surgery until five years after the initial diagnosis when she developed jaundice. In the five year interval between diagnosis and the development of jaundice computed tomography showed no change in the size (20 cm) of the pancreatic mass. Histology after resection, however, showed signs of lymphatic invasion. Cystic neoplasm of the pancreas can thus be regarded as an indolent, very slow growing tumour with potential for local invasion and hence metastatic spread.

Adolescent↗
PubMed1992

Trophic regulation of action potential in bullfrog sympathetic neurones.

These experiments tested the hypothesis that the normal electrophysiological properties of mature bullfrog sympathetic ganglion (BFSG) neurones are maintained by the retrograde supply of nerve growth factor-like molecules from peripheral target tissues. Maintenance of these cells in explant culture in the absence of nerve growth factor (NGF) for up to 30 days produced electrophysiological changes that resemble those previously shown to accompany axotomy in vivo. These included (i) an increase in action potential (ap) duration (spike width), (ii) a decrease in the amplitude of the afterhyperpolarization (ahp), which follows the ap, and (iii) a rapidly developing decrease in ahp duration. When murine NGF (2.5 s; 50 ng/mL) was included in the culture medium there was less attenuation of ahp amplitude. Inclusion of affinity-isolated sheep IgG antibodies (0.5 micrograms/mL; raised against murine 2.5 s NGF) in the culture medium promoted a greater reduction in ahp amplitude than was seen in the "control" explants that were maintained in the absence of NGF. By contrast, the decrease in ahp duration that occurred in control explants was neither attenuated by exposure to NGF nor was it enhanced by NGF antibodies. Also, the increase in spike width that was seen in control explants was enhanced both by murine NGF and by NGF antibodies. Although some of the data support the hypothesis that factor(s) with some similarity to NGF may be synthesized by BFSG in vitro, loss of the retrograde transport of such factors does not explain all aspects of the electrophysiological response to target deprivation and (or) axotomy.

Action Potentials↗
PubMed1992

Regulation of the M current: transduction mechanism and role in ganglionic transmission.

Slow excitatory postsynaptic potentials in sympathetic ganglia often involve suppression of a voltage-dependent potassium current termed the M current. This current is suppressed by the muscarinic action of acetylcholine, by peptides such as luteinizing hormone releasing hormone, and sometimes by alpha-adrenoceptor agonists. Activation of beta-adrenoceptors sometimes produces weak potentiation. The voltage dependence of the M current is such that its suppression increases the excitability of ganglionic neurones. Since this sometimes leads to spontaneous discharge, activation of the slow excitatory postsynaptic potential mechanism (or modulation of M current) within a sympathetic ganglion produces effects that manifest in the autonomic outflow to the target organ. In frogs, M currents are present in the neurones of both paravertebral sympathetic ganglia and cardiac parasympathetic ganglia. Since the M current is suppressed by adrenaline in the parasympathetic ganglia and these ganglia often receive adrenergic fibres from sympathetic ganglia, this might reflect an important means of interaction between the two branches of the autonomic system. At the cellular level, M-current suppression is little affected by drugs that interfere with membrane phosphorylation--dephosphorylation processes. This observation is discussed in relationship to the current understanding of the transduction mechanism for agonist-induced M-current suppression.

Animals↗
PubMed1992

Consequences of the change to standards for air-conduction hearing levels. A cautionary note.

The issue of BS 2497 Parts 5 and 6 in 1988 brought British Standards into line with the latest revisions to ISO 389. As a consequence, many audiometers that were previously calibrated using a 9-A coupler will now have to be calibrated with an artificial ear. Whilst this may appear to be a seemless change involving merely alterations to measurement apparatus, this technical note illustrates for two earphone types that it entails a shift in the Hearing Level standard by a maximum of 3 dB at 2 kHz. This has ramifications for longitudinal studies of hearing and for monitoring of hearing threshold levels in persons exposed to noise.

Audiometry↗
PubMed1991

Inhibition of electrical activity in mouse pancreatic beta-cells by the ATP/ADP translocase inhibitor, bongkrekic acid.

Bongkrekic acid causes fatal food poisoning which is associated with hyperglycaemia. Here we demonstrate that bongkrekic acid, a potent inhibitor of the mitochondrial ATP/ADP translocase, inhibits glucose-induced electrical activity in the pancreatic beta-cell through the stimulation of ATP-sensitive potassium channel (K-ATP-channel) activity. By comparison of its effects with those of oligomycin, we suggest that bongkrekic acid acts by the inhibition of glucose metabolism and may induce hyperglycaemia by impairing beta-cell function.

Adenosine Triphosphate↗
PubMed1991

Slow frequency-dependence of action potential afterhyperpolarization in bullfrog sympathetic ganglion neurones.

The after hyperpolarizatin (AHP) which follows the action potential (AP) in bullfrog sympathetic ganglion B-cells involves activation of Ca(2+)-sensitive K+ conductances following Ca2+ influx via Ca2+ channels. The duration of AHPs evoked at 2-s stimulus intervals were 70.05 +/- 3.76% of those evoked at 90-s stimulus intervals (n = 35). Since there was no consistent effect of ryanodine (5 microM), ruthenium red, (300 microM) or dantrolene Na (35 microM) on this frequency dependence, it is unlikely to result from release of Ca2+ from intracellular stores. Ca2+ currents (ICa), studied by means of the whole-cell patch-clamp technique, exhibited a slow frequency dependence as a result of a slow inactivation process which was independent of Ca(2+)-induced ICa inactivation and ICa run-down. There was excellent correlation (r = 0.964) between the estimated changes in Ca2+ influx and the expected activation of the Ca(2+)-sensitive K+ current, IAHP. This result is consistent with the hypothesis that the frequency dependence of the AHP is a consequence of the slow inactivation of ICa.

Action Potentials↗
PubMed1991

Plasma osmolality, iodine concentration and urographic images following high and low osmolar contrast media.

Three contrast media (sodium iothalamate, iopamidol and sodium/methylglucamine ioxaglate) in a dose of 240 mg iodine per kilogram of body weight were compared in clinical urography. The ionic monomer sodium iothalamate was the only medium to significantly elevate the plasma osmolality though it returned to normal values within 4 min. All three media exhibited first order linear kinetics. When corrected for the effects of diuresis, sodium iothalamate was shown to give the highest urinary iodine concentrations. On visual scoring sodium iothalamate produced better nephrograms and overall urograms than either of the low osmolar agents.

Contrast Media↗
PubMed1991

The effects of muscarine and adrenaline on patch-clamped frog cardiac parasympathetic neurones.

1. The whole-cell patch-clamp technique was used to record membrane currents from neurones which were acutely dissociated from the intra-atrial parasympathetic ganglia of Rana pipiens. The effects of muscarine and adrenaline were observed at a holding potential of -30 mV. Extracellular potassium concentration ([K+]o) was 2, 6 or 20 mM. 2. Muscarine (10 microM) produced inward current in thirteen cells, outward current in eighteen cells and seven cells were unaffected. Inward currents were observed in six out of ten neurones in which the intracellular solution contained adenosine triphosphate (ATP; 100 microM) and outward currents were seen in eleven out of fourteen neurones which contained adenosine 3',5'-cyclic monophosphate (cyclic AMP; 100 microM). 3. In five out of nine cells tested, the inward current produced by muscarine was attributable to a 30% depression of a voltage-dependent current which resembled the M-current (IM). Muscarine-induced inward current in the other four cells involved a steady-state conductance increase that reached a null potential at -10 mV. Modest IM suppression also contributed to the response in three of these four cells. 4. Adrenaline (10 or 100 microM) produced inward currents in twelve cells, outward current in ten cells and three cells were unaffected. Outward currents were only seen in cells which contained ATP or cyclic AMP (ten out of sixteen cells) whereas inward currents were seen in eight out of nine cells which did not contain adenosine nucleotides. These inward currents were always attributable to IM suppression. 5. The outward currents induced by muscarine and adrenaline resulted from an increase in a potassium conductance (GK) that exhibited inward rectification.

Adenosine Triphosphate↗
PubMed1991

Comparative study of four noise spectra as potential tinnitus maskers.

Ten experienced tinnitus-masker uses compared four widely different noise bands as potential maskers in a laboratory environment. No reliable individual preferences could be found, and most of the noises were acceptable to most of the subjects. A wide-band noise was marginally most frequently preferred. In this sample, there was no indication that individual tailoring of the frequency spectra of tinnitus maskers is required to achieve acceptable masking. Subjects also underwent tests of hearing, tinnitus matching and tinnitus masking. Most subjects chose noise levels for therapeutic masking that only partially masked their tinnitus. This suggests prescription or trial of tinnitus maskers even for patients who have high minimal masking levels.

Audiometry↗
PubMed1990

Spectroscopic and physicochemical studies on the interactions of reversible H+/K(+)-ATPase inhibitors with phospholipid bilayers.

Three complementary techniques, differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy, have been used to characterise the interactions between dimyristoylphosphatidylcholine (DMPC) model biological membranes and two non-covalent inhibitors of the gastric (H+, K+)-ATPase. DSC, FT-IR and deuterium NMR studies of side-chain perdeuterated DMPC (DMPC-d54) support the prediction, based on physical property measurements, that SK&F 96079 partitions readily into phospholipid bilayers, resulting in a slight but measurable disordering of the lipid hydrocarbon side-chain motion and a concomitant reduction in the co-operativity and onset temperature of the gel to liquid crystalline phase transition. However, FT-IR and deuterium NMR studies show that the bilayer structure remains intact even at high (1:4) compound to lipid molar ratios. Proton (1H) NMR nuclear Overhauser effect determinations in sonicated codispersions reveal details of the membrane bound conformations of SK&F 96079. The structurally related analogue SK&F 96464, also studied by 1H-NMR, can be shown, by interpreting the effects of nitroxide-labelled fatty acid relaxation probes, to adopt a well-defined orientation relative to the bilayer, in contrast to SK&F 96079. This orientation directs the proton at the 5-position of the quinoline ring towards the hydrophobic centre of the bilayer, and the quinoline 8-methoxy group towards the surface and hence the aqueous phase. Molecular modelling has been used to rationalise this orientation in terms of hydrogen bonds between the amino NH group of SK&F 96464 and the sn-1 carbonyl group of DMPC, and between the NH group of the protonated quinoline ring of SK&F 96464 and the DMPC phosphodiester group.

Adenosine Triphosphatases↗
PubMed1990

Neuropeptide Y activates inwardly-rectifying K(+)-channels in C-cells of amphibian sympathetic ganglia.

Neuropeptide Y (NPY) is found in the C-cells yet is absent from the B-cells of amphibian sympathetic ganglia. The effects of this peptide on both cell types were studied using the whole-cell patch-clamp recording technique. Although NPY had little effect on the B-cells, it opened inwardly-rectifying K(+)-channels in C-cells. This effect of the peptide on C-cell K(+)-channels was similar to that produced by muscarine and adrenaline and may be related to autoreceptor function.

Animals↗