Showing papers by "University of Hertfordshire published in 1991"

Investigation into species variants in tachykinin NK1 receptors by use of the non-peptide antagonist, CP-96,345.

Abstract: The affinity of the non-peptide antagonist CP-96,345 for tachykinin NK1 receptors has been estimated in a range of species by use of both radioligand binding and functional assays. CP-96,345 was 30-120 fold less active at NK1 receptors in rat and mouse than in the other species examined, including man. These results demonstrate the existence of species variations in NK1 receptors.

Complementation of snf1, a mutation affecting global regulation of carbon metabolism in yeast, by a plant protein kinase cDNA

Abstract: A cDNA, cRKIN1, encoding a putative homologue of the yeast (Saccharomyces cerevisiae) SNF1-encoded protein-serine/threonine kinase, has been isolated from a library prepared from rye endosperm mRNA. Northern blot analysis demonstrated the presence of cRKIN1-related transcripts in developing endosperms but not in shoots, and Southern blot analysis showed the presence of a small gene family. SNF1 plays a central role in carbon catabolite repression in yeast and expression of the RKIN1 sequence in yeast snf1 mutants restored SNF1 function. This suggests that the RKIN1 protein has a role in the control of carbon metabolism in endosperms of rye.

Gene amplification and insecticide resistance.

Abstract: Recapitulation des travaux portant sur le mecanisme de resistance des insectes face aux substances toxiques, base sur l'amplification des genes de resistance. Evaluation du mecanisme, de cette amplification, de l'origine et de la stabilite des genes impliques

A method for assessing the goodness of computer simulation of soil processes

Abstract: SUMMARY Any satisfactory computer simulation model of a soil process must match actual behaviour in the laboratory or field; a model can be evaluated by how well it does so. This paper describes a method for assessing models using anion diffusion and nitrate leaching as examples. The method partitions the sum of squares of the differences between measurement and simulation into two components, one calculated from the differences between the simulation and the mean of replicate measurements (the ‘lack of fit’), and the other calculated from the variance within each set of replicate measurements (the ‘pure error’). If the former is not significantly larger than the latter than the data present no grounds for rejecting the model. Where a model simulates the change in a process with time the method can also take account of how experimental error in the initial measurements affects the goodness of fit of the simulation of subsequent measurements. The method is particularly valuable where it is difficult or costly to take many replicate measurements, such as often happens in soil science or agriculture; nonetheless, some replicates must be taken.

A 5-HT4-like receptor in human right atrium.

Abstract: The effects of 5-carboxamidotryptamine (5-CT) and the gastrokinetic benzamides renzapride and cisapride on contractile force were investigated using isolated paced right atrial appendages from patients treated with β-adrenoceptor blocking agents who were undergoing open heart surgery. These effects were compared to those of 5-hydroxytryptamine (5-HT). The effects of the drugs on atrial cyclic AMP levels and cyclic AMP-dependent protein kinase ratios were also investigated. The drugs all increased contractile force rank order of potency was 5-HT > renzapride > cisapride > 5-CT. The maximum responses, expressed as a fraction of the response to 200 μmol/l (−)-isoprenaline, were 5-HT 0.6, 5-CT 0.6, renzapride 0.4 and cisapride ≥ 0.2, suggesting that the latter two are partial agonists. 5-HT, 5-CT and renzapride but not cisapride caused significant shortening of time to peak force. The effects of the four drugs were blocked by molar concentrations of ICS 205-930, suggesting an involvement of 5-HT4 receptors. As expected of partial agonists both renzapride and cisapride caused simple competitive antagonism of the positive inotropic effects of 5-HT The estimated equilibrium dissociation constants pK p (−log mol/l K p ) were 6.7 for renzapride and 6.2 for cisapride. 5-CT at concentrations up to 10 μmol/l did not antagonise the effects of 5-HT. In the presence of (±)-propranolol 0.4 μmol/I, 5-HT 10 μmol/l, 5-CT 100 μmol/I, renzapride 10 μmol/l and cisapride 40 μmol/I significantly increased cyclic AMP levels. 5-HT and renzapride also significantly increased cyclic AMP-dependent protein kinase activity, whereas 5-CT caused only marginal stimulation and cisapride was ineffective. The results confirm the existence of a human right atrial 5-HT receptor that is similar in nature to, but not necessarily identical with, the 5-HT4 receptor of mouse embryonic colliculi neurones. The main difference is that in human right atrium the benzamides are less potent and efficacious than 5-HT and that cisapride is less potent and less efficacious than renzapride while in mouse embryonic colliculi these two benzamides are equipotent with and more efficacious agonists than 5-HT We designate the human right atrial 5-HT receptor 5-HT4-like. The human right atrial 5-HT4-like receptor greatly resembles porcine sinoatrial and left atrial 5-HT4-like receptors and also appears to be similar to 5-HT4-like receptors of guinea-pig ileum and rat oesophagus.

Neuroprotective actions of GR89696, a highly potent and selective κ‐opioid receptor agonist

Abstract: 1. The effect of a novel, highly potent and selective kappa-opioid receptor agonist, GR89696, has been evaluated in two animal models of cerebral ischaemia: transient bilateral carotid artery occlusion in the Mongolian gerbil and permanent, unilateral middle cerebral artery occlusion in the mouse. 2. In the Mongolian gerbil model, administration of GR89696 (3 to 30 micrograms kg-1, s.c.), immediately before and at 4 h after insult, produced a dose-dependent reduction in the hippocampal CA1 neuronal cell loss resulting from a 7-min bilateral carotid occlusion. Similar effects were obtained with two other kappa-agonists, GR86014 (1 mgkg-1, s.c.) and GR91272 (1 mgkg-1, s.c.). The neuroprotective effect of GR89696 was completely blocked by prior administration of the opioid receptor antagonist, naltrexone, at 10 mgkg-1, s.c. Repeated post-treatment with GR89696 (100 micrograms kg-1, s.c.) or GR44821 (10 mgkg-1, s.c.) was also effective in protecting completely the hippocampal CA1 neurones from ischaemia-induced neurodegeneration. 3. In the permanent, unilateral middle cerebral artery occlusion model in the mouse, repeated administration of GR89696 at 300 micrograms kg-1, s.c. produced a 50% reduction in cerebrocortical infarct volume. In these experiments GR89696 was dosed 5 min, 4, 8, 12, 16, 20 and 24 h after occlusion on the first day and then three times daily for the next three days. GR89696 (300 micrograms kg-1) also produced a significant 35% reduction in infarct volume in this model when the initiation of dosing was delayed for 6 h after the insult. 4. The results indicate that the potent kappa-opioid receptor agonist, GR89696, is neuroprotective in both global and focal cerebral ischaemia models and suggest that, with this class of compound, there may be a considerable time window for pharmacological intervention.

New culture medium containing ionic concentrations of nutrients similar to concentrations found in the soil solution.

Abstract: A new growth medium which closely approximates the composition of the soil solution is presented. This soil solution equivalent (SSE) medium contains the following components (millimolar): NO3, 2.5; NH4, 2.5; HPO4, 0.005; Na, 2.5; Ca, 4.0; Mg, 2.0; K, 0.503; Cl, 4.0; SO4, 5.0; ethylenediamine-di(o-hydroxyphenylacetic acid), 0.02; and MES [2-(N-morpholino)ethanesulfonic acid] (to maintain the pH at 6.0), 10, plus 0.1% arabinose. The advantages of the SSE medium are discussed.

Stressors and Strains amongst Social Workers: Demands, Supports, Constraints, and Psychological Health

Abstract: Original article can be found at: http://bjsw.oxfordjournals.org/archive/ . Copyright British Association of Social Workers. [Full text of this article is not available in the UHRA]

Relaxation of sheep cerebral arteries by vasoactive intestinal polypeptide and neurogenic stimulation: inhibition by L-NG-monomethyl arginine in endothelium-denuded vessels.

Abstract: 1. Perivascular nerves of the sheep middle cerebral artery show immunoreactivity for both vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP). 2. Rings of endothelium-denuded sheep middle cerebral artery precontracted with 5-hydroxytryptamine were relaxed by CGRP (maximum relaxation = 87.8 +/- 8.1%, pD2 = 7.81 +/- 0.12, n = 12) and by VIP (maximum relaxation = 55.1 +/- 4.1%, pD2 = 7.65 +/- 0.04, n = 18). Rings of endothelium-denuded cat middle cerebral artery precontracted with U46619 were also relaxed by vasoactive intestinal polypeptide (maximum relaxation = 53.1 +/- 6.1%, pD2 = 7.82 +/- 0.11, n = 6). 3. Haemolysate (1 microliters ml-1) inhibited VIP-induced relaxation in endothelium-denuded sheep and cat middle cerebral artery (n = 6) but had no effect on the CGRP-induced relaxation of the sheep middle cerebral artery (n = 6). 4. The relaxant response to VIP in endothelium-denuded sheep middle cerebral artery was inhibited by methylene blue (10 microM) and augmented by either M&B 22948 (10 microM) or superoxide dismutase (150 units ml-1). Indomethacin (1 microM) had no effect. 5. The addition of L-NG-monomethyl arginine (100 microM) inhibited both neurogenic and VIP-induced relaxation of endothelium-denuded sheep MCA by 56 +/- 6% and 60 +/- 6% (n = 5) respectively. The CGRP-induced relaxation was unaffected. 6. It is concluded that neurally mediated vasodilatation in the sheep middle cerebral artery is mediated largely by VIP through a direct action on smooth muscle through a cyclic-GMP-mediated mechanism that appears to involve synthesis of nitric oxide from L-arginine. Vasodilatation by CGRP, which is also contained in perivascular nerves, does not utilize this pathway.

Receptors mediating tachykinin-induced contractile responses in guinea-pig trachea.

Abstract: 1. The classification of tachykinin receptors in the guinea-pig trachea has been investigated. This was of interest because, from previous studies, it was not clear whether the guinea-pig trachea contains either a mixture of NK1 and NK2 receptors or, alternatively, a single type of novel tachykinin receptor. 2. In the present study, the guinea-pig trachea was contracted by tachykinin agonists selective for NK1 receptors (substance P methylester (SPOMe) and GR73632) or NK2 receptors (GR64349) but not NK3 receptors (senktide). 3. Against SPOMe and GR73632, the NK1 antagonist, GR71251, behaved as a reversible competitive antagonist having apparent affinity (pKB 7.05 vs SPOMe) consistent with action at NK1 receptors. GR71251 (3 microM) did not antagonize responses to GR64349. 4. The NK2 antagonists L-659,877 and Ac-Leu-Asp-Gln-Trp-Phe-Gly-NH2 (R396) antagonized GR64349 although only R396 appeared to behave competitively (pKB 5.73). Neither L-659,877 (30 microM) nor R396 (30 microM) blocked responses to SPOMe. 5. For L-659,877 and R396, comparison was made between activity in guinea-pig trachea and in preparations known to contain tachykinin receptors predominantly of the NK2 type. In the rabbit trachea, both L-659,877 and R396 had effects similar to those in guinea-pig trachea. In contrast, in the rat colon muscularis mucosae, both L-659,877 and R396 appeared to behave competitively with pKB values against GR64349 of 7.83 and 6.90 respectively. 6. It is concluded that in guinea-pig trachea, contractile responses can be induced by activation of both NK1 and NK2 receptors. The present data are discussed with reference to the proposed existence of subtypes of the NK2 receptor.

A method for automatic switching and control of lighting

Abstract: The invention relates to a method for automatic switching and control of lighting to a localized area, the switching of the lighting being dependent on the presence or absence of a person in that localized area and the control of the lighting intensity being dependent on the sensed background level of lighting in that localized area. The invention also relates to a lamp fitting and to an automatic control device for controlling the light output of a light source in a "self managed" and "self controlled" energy saving luminaire.

Effect of pokeweed antiviral protein (PAP) on the infection of plant viruses

Abstract: At a concentration of 0.4-mu-g purified pokeweed antiviral protein (PAP)/ml, the formation of local lesions on tobacco leaves caused by tobacco mosaic virus infection was completely inhibited and at 25 ng PAP/ml, 68% inhibition was still obtained. PAP protected plants from infection by viruses from seven virus groups-five RNA viruses: tobacco mosaic virus, cucumber mosaic virus, alfalfa mosaic virus, potato virus X and potato virus Y; and two DNA viruses: African cassava mosaic virus (ssDNA) and cauliflower mosaic virus (dsDNA). Virus infection was probably blocked by PAP at a very early stage. PAP infiltrated into the intercellular spaces through the lower surfaces of leaves inhibited infection by virus inoculated on the upper leaf surface, and partially prevented PVY transmission by aphids. However, PAP did not show any activity against two bacterial and six fungal pathogens.

Optimal ground-based sampling for remote sensing investigations: estimating the regional mean

Abstract: Remote sensing investigations often involve sampling on the ground to estimate the mean of some property within ground resolution elements. Investigators have used classical statistics to determine the size of sample required to produce a desired precision. However, classical statistics is based on assumptions that do not hold when the target population is spatially dependent. Remotely sensed data and ground cover are usually spatially correlated, and in these circumstances the size of sample required will be less when sampling is done on a regular grid. This is demonstrated for several variables measured at the ground.

Regional differences of beta 1- and beta 2-adrenoceptor-mediated functions in feline heart. A beta 2-adrenoceptor-mediated positive inotropic effect possibly unrelated to cyclic AMP.

Abstract: The effects of (−)-adrenaline and (−)-noradrenaline were studied on isolated preparations of kitten heart. To define the contribution of β1-adrenoceptors (β1AR) and β2-adrenoceptors (β2AR) we used as tools the highly β1AR-selective antagonist CGP 20,712 A and non-linear analysis of antagonism. The β2AR-mediated responses to the catecholamines, disclosed by CGP 20,712 A, were verified by blockade with the β2AR-selective ICI 118,551. The relative density and contribution of β1AR and β2AR to (−)-adrenaline- and (−)-noradrenaline-induced adenylyl cyclase stimulation was also estimated in right ventricular membranes.

Method and apparatus for generating representation of an image

Abstract: A method of generating a representation of an image comprises scanning a film (2) carrying an image to which the film has been exposed to obtain signals (4,5,6) representing the colour component content of the recorded image. During exposure of the image its appearance has been modified in accordance with a function characteristic of the film. The signals obtained are modified with a function (11,10,8) constituting the inverse of the film characteristic function to compensate.

Vascular 5-HT1-like receptors that mediate contraction of the dog isolated saphenous vein and carotid arterial vasoconstriction in anaesthetized dogs are not of the 5-HT1A or 5-HT1D subtype.

Abstract: 1. There is controversy about whether 5-HT1A receptors mediate contraction of isolated cerebral blood vessels. We have therefore compared the vascular actions of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propyl-amino)-tetralin (8-OH-DPAT) with those of the 5-HT1-like receptor agonist, sumatriptan, on the dog isolated saphenous vein, which contains a 5-HT1-like receptor similar to those on cerebral blood vessels, and in the carotid circulation of the anaesthetized dog. 2. 5-Hydroxytryptamine (5-HT), sumatriptan and 8-OH-DPAT each caused contraction of dog isolated saphenous vein with a rank order of agonist potency of 5-HT greater than sumatriptan greater than 8-OH-DPAT and EC50 values (95% confidence limits) of 0.06 (0.04-0.08), 0.3 (0.1-0.8) and 3.9 (2.0-7.5) microM respectively. The maximum contractile effect produced by each agonist was similar. 3. The contractile effects of 5-HT, sumatriptan and 8-OH-DPAT in the dog isolated saphenous vein were resistant to antagonism by the 5-HT1A receptor antagonists spiperone, spiroxatrine and pindolol (all 1 microM). The 5-HT1D receptor ligands, metergoline (0.1 microM) rauwolscine (1 microM) and yohimbine (1 microM) had little or no antagonist activity. In contrast, the non-selective 5-HT1-like receptor blocking drug, methiothepin (0.03-0.3 microM) potently antagonized the contractile effects of 5-HT, sumatriptan and 8-OH-DPAT to a similar degree, suggesting that all three agonists act at the same receptor. 4. In ganglion-blocked, anaesthetized dogs, intra-carotid administration of 8-OH-DPAT (0.3-3 pggkg-1) and sumatriptan (0.1l-1 pgkg -), caused dose-dependent carotid arterial vasoconstriction. The two agonists were approximately equipotent in this respect. 5. The carotid arterial vasoconstrictor actions of 8-OH-DPAT and sumatriptan were not modified by spiperone (1 mgkg- , i.v.) but were antagonized to a similar extent by the subsequent administration of methiothepin (1 mgkg- 1, i.v.). 6. These results suggest that 8-OH-DPAT contracts the dog isolated saphenous vein and constricts the carotid arterial circulation of anaesthetized dogs by activation of 5-HT1-like receptors which are not of the 5-HTlA subtype, nor, on the basis of data with metergoline in the dog isolated saphenous vein, of the 5-HTID subtype. The receptor involved in these actions appears to be the same as that mediating the vasoconstrictor effects of sumatriptan. This receptor does not appear to be like any known 5-HT1 ligand binding site; hence the current description, 5-HT1-like, remains the most appropriate.

Concentrations of Vacuolar Inorganic Ions in Individual Cells of Intact Wheat Leaf Epidermis

Abstract: A method is described for quantitative determination of the major inorganic constituents of individual cells of higher plants. The approach utilizes a modified pressure probe to extract samples of undiluted vacuolar sap from single cells. Subsamples of constant volume are taken from these sap samples and are freeze-dried on to thin films along with similarly-sized droplets of standards. The films are placed in a scanning electron microscope and elemental content of the freeze-dried material is determined by X-ray microanalysis. The method has been used to compare levels of a range of ions in two distinct types of epidermal cell from a young wheat leaf and, in association with nanolitre osmometry, was used to assess the relative importance of the inorganic ions in the generation of turgor pressure in these cells. It was found that the concentrations of the major inorganic ions within the vacuole was constant both within and between two anatomically distinct groups of epidermal cells on a leaf.

Presynaptic regulation of electrically evoked dopamine overflow in nucleus accumbens: a pharmacological study using fast cyclic voltammetry in vitro

Abstract: Fast cyclic voltammetry has been used to measure electrically evoked dopamine overflow from slices of rat nucleus accumbens in vitro. The substance detected was shown voltammetrically and biochemically to be dopamine of neuronal origin. Enough dopamine was released by a single electrical pulse to be easily detectable, and under these conditions there was no auto-inhibition by the endogenous transmitter (as demonstrated by the failure of dopamine antagonists to increase the amount released). There was no significant inhibition, or enhancement, of release by agonists at the following receptor types: dopamine D1, 5-hydroxytryptamine, cholinoceptors, alpha 1-, alpha 2-, beta-adrenoceptors, cholecystokinin or neurotensin receptors. However, the dopamine D2 receptor agonist, quinpirole, was capable of totally inhibiting the release; this effect was concentration-dependently antagonized by the D2 antagonists haloperidol, sulpiride, metoclopramide and clozapine, with potencies which corresponded to their affinities for D2 receptors in striatal tissue. The results show that the presynaptic receptors on dopaminergic nerve terminals are of the D2 type and apparently identical to those in the corpus striatum.

Characterization of the 5-HT receptor mediating endothelium-dependent relaxation in porcine vena cava.

Abstract: 1. 5-Hydroxytryptamine (5-HT) relaxes rings of neonatal porcine isolated vena cava by both an endothelium-dependent and an endothelium-independent mechanism. The receptor mediating the latter response has been shown to be a 5-HT1-like receptor (positively coupled to adenylyl cyclase) located on the vascular smooth muscle. The features of the endothelium-dependent response to 5-HT in this preparation are now described. 2. In ring preparations contracted with the stable thromboxane-A2-mimetic, U-46619 (10 nM), and in the presence of the 5-HT2 receptor antagonist ketanserin (1 microM), low concentrations of 5-HT (1-100 nM) evoked an endothelium-dependent, rapid, 'spike-like' relaxation. Higher concentrations of 5-HT (0.1-10 microM) elicited a more sustained, but endothelium-independent relaxation. 3. Relaxation induced by low concentrations (1-100 nM) of 5-HT was abolished by endothelium removal, and was markedly (but not totally) inhibited by the guanylate cyclase inhibitor, methylene blue (10 microM) or by the inhibitor of endothelium-derived nitric oxide (NO) synthesis, L-NG-monomethylarginine (L-NMMA; 100-500 microM). 4. The endothelium-dependent response to 5-HT was mimicked by alpha-methyl-5-HT, 5-methoxytryptamine, tryptamine and 2-methyl-5-HT, but not by sumatriptan or 8-hydroxy-di-n-propylaminotetralin (8-OH-DPAT) at concentrations up to 10 microM. In contrast, relaxation evoked by 5-carboxamidotryptamine (5-CT) was endothelium-independent. 5. The endothelium-dependent relaxation induced by 5-HT or alpha-methyl-5-HT was antagonized by methysergide, methiothepin, cyproheptadine and metergoline, but not by ketanserin, spiperone, ondansetron, verapamil, cyanopindolol, mesulergine, ICS 205-930, or indomethacin. 6. These results suggest that the endothelium-dependent relaxation of porcine vena cava induced by 5-HT is largely mediated by the release of NO (although other endothelium-derived relaxing factors may also be involved) and that 5-HT is acting at a receptor which is not '5-HT1-like', 5-HT2, 5-HT3 or 5-HT4 and is not comparable to recognised 5-HT receptor ligand binding sites. The characteristics of this receptor are discussed in relation to the endothelial 5-HT receptor types in other blood vessels.