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Biomedical subjects

E Leung

Publications and source records attributed to E Leung.

104 records · Page 6Linked to original sources
PubMed1982

The interaction of pancuronium with cardiac and ileal muscarinic receptors.

The activity of pancuronium as a muscarinic antagonist was compared in atria from several species and in guinea-pig ileal longitudinal muscle. Pancuronium had a 20-fold greater affinity for muscarinic receptors mediating the negative inotropic response to carbachol (CCh) in the guinea-pig left atrium (pKB = 6.96) than for muscarinic receptors in guinea-pig ileal longitudinal muscle (pKB = 5.65). The greater affinity of pancuronium in the atria was not due to an interaction with noradrenergic neurones as pretreatment of atria with propranolol (3 microM) or of guinea-pigs with 6-hydroxydopamine (400 mg/kg total dose) failed to modify the degree of inhibition exhibited in atria. The affinities of pancuronium for muscarinic receptors mediating negative inotropic responses in the kitten left atrium or negative chronotropic responses in guinea-pig or rabbit right atria were not significantly different from that in the guinea-pig left atrium (P greater than 0.05) but the affinity of pancuronium for muscarinic receptors in ileal longitudinal muscle was significantly different (P less than 0.05) from all values obtained in the cardiac preparations suggesting differences in the binding of the antagonist in smooth and cardiac muscle. The A-S plot for pancuronium (0.27 microM-0.20 mM) as an antagonist of negative inotropic responses to CCH was non-linear, showing a flattening at the higher concentrations of pancuronium. This was not apparent in the A-S plot for the inhibition of tonic responses to CCh in ileal longitudinal muscle.

Animals↗
PubMed1982

Modification by hexamethonium of the muscarinic receptors blocking activity of pancuronium and homatropine in isolated tissues of the guinea-pig.

In the guinea-pig left atrium, hexamethonium (C6) (0.1-3 mM) caused a parallel rightward shift of concentration-response curves for the negative inotropic response to carbachol (CCh) and oxotremorine (Oxo), the dose ratios obtained with the latter agonist being significantly greater than those for CCh at all concentrations of C6 investigated. In the presence of C6, the muscarinic receptor blocking activity of homatropine (20 microM) or of pancuronium (0.3-2.7 microM) appears to be reduced but if the effect of hexamethonium on concentration-response curves to the agonists is taken into consideration, the dose ratios produced by the combination of C6 with either homatropine or pancuronium were essentially as predicted for the combination of 2 competitive antagonists. The difference in the affinity of pancuronium for cardiac muscarinic receptors and ileal muscarinic receptors was also reduced in the presence of hexamethonium (0.3 mM).

Animals↗
PubMed1976

Cytological evidence supporting the inclusion of poplar mosaic virus in the carlavirus group of plant viruses.

The filamentous particles of poplar mosaic virus (PopMV) were detected in palisade, mesophyll and parenchyma cells of systemically infected leaves of Nicotiana clevelandii and N. megalosiphon. The particles were sometimes found scattered throughout the cytoplasm, but more often they occurred loosely associated within ovoid aggregates (up to 3.5 x 1.5 mum) adjacent to chloroplasts and/or mitochondria. PopMV did not induce the formation of 'pinwheel' inclusions, nor other conspicuous ultrastructural or cytopathic effects in infected cells. These observations provide additional evidence that PopMV is a Carlavirus and not a Potyvirus nor a mite-borne virus. PopMV particles were also detected occasionally within plasmodesmata.

Chloroplasts↗
PubMedDate not supplied

(R) and (S) RS 56532: mixed 5-HT3 and 5-HT4 receptor ligands with opposing enantiomeric selectivity.

The pharmacological properties of the (R) and (S) enantiomers of RS 56532 have been studied in vitro and in vivo. In radioligand binding studies at 5-HT4 receptors in guinea-pig striatum, (S) RS 56532 exhibited a higher affinity than (R) RS 56532 (-log Ki = 7.6 and 6.5, respectively). (S) RS 56532 acted as a potent agonist at 5-HT4 receptors mediating relaxation of rat oesophageal muscularis mucosae (-log EC50 = 7.9) while (R) RS 56532 acted as a weaker agonist at this receptor (-log EC50 < 6.0). These data suggest that at 5-HT4 receptors, the enantiomeric selectivity of RS 56532 was (S) > (R). In binding studies at 5-HT3 receptors in rat cortex, (R) RS 56532, conversely, exhibited a higher affinity than (R) RS 56532 (-log Ki = 9.1 and 8.0, respectively). At 5-HT3 receptors in guinea-pig isolated ileum, (R) RS 56532 exhibited an affinity (-log KB) of 7.9, whereas (S) RS 56532 (1 nM-1 microM) was inactive. No agonism was observed at ileal 5-HT3 receptors with either enantiomers. These data suggest that at 5-HT3 receptors in rat and guinea-pig, both enantiomers acted as antagonists, with (R) > (S) RS 56532. At the non-5-HT3, high affinity '(R) zacopride' site, (R) RS 56532 exhibited a higher affinity than (S) RS 56532 (-log Ki = 6.1 and 4.9). This site was insensitive to potent 5-HT3 antagonists such as (R) YM 060 or ondansetron. However, it was recognized with relatively high affinity (-log Ki = 7.5) by the (R), but not (S) enantiomer, of RS 42358 (-log Ki = 4.7). Since (S) RS 42358 is a high affinity 5-HT3 receptor antagonist, these data further highlight the dissimilarity between the 5-HT3 receptor and the '(R) zacopride' site. The '(R) zacopride' site also appeared to be pharmacologically distinct from the 5-HT4 receptor, since 5-HT4 ligands such as renzapride, SDZ 205,557 or RS 23597-190 exhibited low affinities. The enantiomeric selectivity of (R) and (S) RS 56532 in vivo was consistent with findings in vitro. At 5-HT4 receptors mediating tachycardia in the pig, 5-HT induced a dose-dependent tachycardia (ED50 = 3 micrograms kg-1, i.v.; maximum response = 90-100 beats min-1). (S) RS 56532 increased heart rate by 88 min-1 with a potency of (ED50) of 3 micrograms kg-1, i.v.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Ultrastructure of cholinergic neurons in the laterodorsal tegmental nucleus of the rat: interaction with catecholamine fibers.

The ultrastructure of choline acetyltransferase (ChAT)-immunoreactive neurons in the laterodorsal tegmental nucleus (TLD) of the rat was investigated by immunohistochemical techniques. The immunoreactive neurons were medium to large in size, with a few elongated dendrites, contained well-developed cytoplasm, and a nucleus with deep infoldings. They received many nonimmunoreactive, mostly asymmetric synaptic inputs on their soma and dendrites. ChAT-immunoreactive, usually myelinated, axons were occasionally seen in TLD. Only one immunoreactive axon terminal was observed within TLD, and it made synaptic contact with a nonimmunoreactive neuronal perikaryon. The synaptic interactions between ChAT-immunoreactive neurons and tyrosine hydroxylase (TH)-immunoreactive fibers in the TLD were investigated with a double immunohistochemical staining method. ChAT-immunoreactivity detected with a beta-galactosidase method was light blue-green in the light microscope and formed dot-like electron dense particles at the electron microscopic level. TH-immunoreactivity, visualized with a nickel-enhanced immunoperoxidase method, was dark blue-black in the light microscope and diffusely opaque in the electron microscope. Therefore, the difference between these two kinds of immunoreactivity could be quite easily distinguished at both light and electron microscopic levels. In the light microscope, TH-positive fibers were often closely apposed to ChAT-immunoreactive cell bodies and dendrites in TLD. In the electron microscope, the cell soma and proximal dendrites of ChAT-immunoreactive neurons received synaptic contacts from TH-immunoreactive axon terminals. These results provide a morphological basis for catecholaminergic regulation of the cholinergic reticular system.

Animals↗
PubMedDate not supplied

Immunohistochemical localization of peptidylarginine deiminase in the rat brain.

The enzyme peptidylarginine deiminase is responsible for the post-translational modification of certain proteins by catalysing the deimination of arginine residues to citrullines. Recently, peptidylarginine deiminase has been purified from rat skeletal muscle and its primary structure determined by molecular cloning. We have used antibodies raised against this enzyme to examine its distribution in the rat central nervous system. A few discrete neuronal cell groups in the telencephalon were selectively stained. These were the septofimbrial nucleus, the anterior commissural nucleus of the hypothalamus, and the anterodorsal thalamic nucleus. The subcommissural organ was intensely stained; but other circumventricular organs were not. In addition, peptidylarginine deiminase-immunoreactivity was found in a large population of small cells throughout the grey and white matter of the rat brain. Some of these cells contained glial fibrillary acidic protein and could thus be identified as astrocytes. However, in many regions these peptidylarginine deiminase-positive cells appeared distinct from the glial fibrillary acidic protein-positive astrocytes. Light and electron microscopic examination indicated that these cells had the morphology of microglia, however they were not stained by a lectin marker for microglia. These cells often surrounded cerebral capillaries, and sent ramifying processes into the neuropil. Peptidylarginine deiminase has been suggested to be involved in the synthesis of the endothelium-derived relaxing factor nitric oxide from arginine-containing molecules. Thus the distinct peptidylarginine deiminase-positive glial cells surrounding cerebral blood vessels may be in a position to regulate local blood flow in response to neuronal activity.

Animals↗
PubMedDate not supplied

[3H]RS 57639, a high affinity, selective 5-HT4 receptor partial agonist, specifically labels guinea-pig striatal and rat cloned (5-HT4S and 5-HT4L) receptors.

RS 57639, by being a partial agonist in rat esophagus but a competitive antagonist in guinea-pig ileum, is one of several ligands which operationally discriminate among 5-HT4 receptors in different tissues. The discovery of splice variants of the 5-HT4 receptor, 5-HT4S and 5-HT4L, raises the possibility that this functional heterogeneity among 5-HT4 receptors may be due to differences in the interaction of ligands with different isoforms of the receptor. To test this idea, the functional and binding interactions of RS 57639 with rat 5-HT4S and 5-HT4L receptors were characterized. RS 57639 stimulated adenylate cyclase in cells expressing 5-HT4S or 5-HT4L receptors with similar potency (pEC50 = 7.9 +/- 0.1 and 7.6 +/- 0.1) and efficacy (71 +/- 3 and 59 +/- 4% of 5-HT). [3H]RS 57639 also bound to 5-HT4S and 5-HT4L receptors with similar affinity (Kd = 0.09 +/- 0.01 and 0.11 +/- 0.01 nM) and specificity (SB204070 > GR113808 > SDZ 205557 > cisapride > renzapride > alpha me-5-HT > 5-CT). Therefore, the operational differences among 5-HT4 receptors, detected with RS 57639, are not explained by differences in the interaction of the ligand with 5-HT4S and 5-HT4L receptors. [3H]RS 57639 binding to guinea-pig striatal membranes was also characterized. [3H]RS 57639 bound with high affinity (Kd = 0.25 +/- 0.07 nM) and a specificity similar to that of the 5-HT4 receptor antagonist, [3H]GR113808. Therefore, while the mechanism by which RS 57639 operationally distinguishes among 5-HT4 receptors was not determined, [3H]RS 57639 was shown to specifically label native and cloned 5-HT4 receptors. As the first selective agonist radioligand to be described for this receptor, [3H]RS 57639 may prove useful in further studies of receptor coupling and ligand interactions.

Aminobenzoates↗
PubMedDate not supplied

A comparison between the adenosine receptors mediating adenylate cyclase inhibition and cardiac depression in the guinea pig heart.

Stable analogues of adenosine were used to investigate the specificity of the receptors mediating its negative chronotropic and inotropic responses in isolated guinea-pig atria. The order of potencies for both responses was NECA = L-PIA = CHA = 2-chloroadenosine much greater than D-PIA. These analogues also inhibited adenylate cyclase in atrial and ventricular membranes, the order of potency being L-PIA = CHA = NECA much greater than D-PIA. The methylxanthines 8-phenyltheophylline, 1,3-diethyl-8-phenylxanthine and isobutylmethylxanthine antagonized both the pharmacologic responses of these agonists and their effect on adenylate cyclase. Antagonism produced by the methylxanthines was competitive as indicated by linear Schild plots for all three antagonists. The affinity constants obtained for the chronotropic and inotropic responses were similar to those obtained for adenylate cyclase inhibition. These results suggest that the negative inotropic and chronotropic effects of adenosine are mediated by RI adenosine receptors coupled to inhibition of adenylate cyclase.

1-Methyl-3-isobutylxanthine↗
PubMedDate not supplied

Demonstration of specific receptors for adenosine in guinea-pig myocardium.

Adenosine analogues N6-phenylisopropyladenosine and 5'-N-ethylcarboxamidoadenosine inhibit cardiac adenylate cyclase in a concentration dependent manner. Inhibition of adenylate cyclase required the presence of guanosine-triphosphate and Mg2+ ion. The concentration of Na+ ion was critically important: maximal inhibition was observed at 50 mmol/l Na+. 8-Phenyltheophylline and isobutylmethylxanthine antagonized the inhibition of adenylate cyclase mediated by adenosine analogues. Adenosine receptors of the inhibitory type (R1 or A1) are present in guinea-pig myocardium and may mediate some actions of adenosine.

Adenosine↗
PubMedDate not supplied

Muscarinic receptor inhibition and other effects of pancuronium in the rabbit ear artery preparation.

The effect of pancuronium in the rabbit ear artery was investigated in order to measure the inhibition it produces at the prejunctional muscarinic receptor on sympathetic nerve endings in this tissue. Pancuronium (0.1-0.2 mmol/l) produced an enhancement of responses to transmural electrical stimulation but this effect was absent in experiments conducted in the presence of cocaine (10 mumol/l) suggesting that an inhibition of the uptake1 mechanism occurs with pancuronium in this tissue. Pancuronium (10 mumol/l) in the presence of cocaine (10 mumol/l) and yohimbine (1 mumol/l) caused a small transient increase in resting output of tritium from arteries preincubated with 3H-noradrenaline but did not affect stimulated output of tritium nor the perfusion pressure in perfused preparations. Pancuronium in the presence of cocaine or cocaine plus yohimbine caused a parallel shift of the concentration-response curve for the inhibitory effect of carbachol (CCh) on the increase in perfusion pressure induced by nervous stimulation. An Arunlakshana-Schild plot of the data was linear but the slopes of 0.92 and 0.95 respectively, were significantly different from unity (P less than 0.05). The calculated pKB value suggests that pancuronium has a different affinity for prejunctional muscarinic receptors on sympathetic nerve endings in this tissue compared to that previously reported in cardiac or ileal smooth muscle.

Animals↗
PubMedDate not supplied

Computers in case management. Advancing health care delivery through technology.

Fast efficient access to patient information is an essential management tool in the current healthcare environment. The clinical case management computer module at Stanford Health Services provides and integrates essential patient data elements to facilitate clinical case coordination and assist the nurse case managers with documentation of clinical data for discharge planning and utilization review. Information systems such as this one are critical to the provision of comprehensive, cost-effective patient care management.

Case Management↗