Showing papers by "University of Aberdeen published in 1982"

The binding spectrum of narcotic analgesic drugs with different agonist and antagonist properties

Abstract: Four groups of narcotic analgesic drugs have been assessed for their opiate activities by using three binding assays and three pharmacological bioassays. In the binding assays, their inhibition constants (K I, nM) were determined against the binding of the μ-ligand, [3H]-[d-Ala 2 ,MePhe 4 , Gly-ol5]enkephalin, of the δ-ligand, [3H]-[d-Ala 2 ,d-Leu 5]enkephalin and of the ϰ-ligand, [3H]-(±)-ethylketazocine after suppression of μ- and δ-binding by 100 nM of the unlabelled μ-ligand and 100 nM of the unlabelled δ-ligand. The pharmacological agonist or antagonist activities were assayed on the guinea-pig ileum, mouse vas deferens and rat vas deferens. The first group of compounds were pure agonists in all three pharmacological bioassays. The majority of the compounds showed preference to μ-binding but phenazocine and particularly etorphine had also high affinities to the δ- and ϰ-binding sites. The second group consisted of N-allyl and N-cyclopropylmethyl homologues of the morphine, 3-hydroxymorphinan and normetazocine series which had agonist and antagonist activities in the guinea-pig ileum and mouse vas deferens but were pure antagonists in the rat vas deferens. In the binding assays, μ-binding and ϰ-binding were prominent. The third group was made up by the ketazocine-like compounds which in the guinea-pig ileum and mouse vas deferens were pure agonists and in the rat vas deferens pure antagonists. The binding spectrum showed particularly high binding to the ϰ-binding site. The fourth group was the antagonists which were devoid of agonist activity with the exception of diprenorphine and Mr 2266 which had retained some agonism. The binding spectrum showed considerable variation, naloxone in low concentration being a selective μ-antagonist, Mr 2266 having high affinities to the μ- and ϰ-binding sites and diprenorphine having considerable affinities to the μ-, δ- and ϰ-binding sites. Since each of the four groups of compounds, whether pure agonists, agonist-antagonists, ketazocine-like drugs or pure antagonists, shows independent varittions in the affinities to the μ- and ϰ-binding sites, their different pharmacological behaviour cannot be solely due to difference in the binding spectra.

Dynorphin 1-8 and dynorphin 1-9 are ligands for the κ-subtype of opiate receptor

Abstract: It is generally accepted that there are three subtypes of opiate receptor: µ, δ and κ. The main endogenous ligands for the µ-and δ-sites are Met5-enkephalin, Leu5-enkephalin and β-endorphin, whereas the putative endogenous ligands for the κ-binding site were unknown until recent observations suggested that dynorphin1–13 might be a candidate. The most convincing evidence for this view has been presented by Goldstein and his colleagues who showed that dynorphin1–13 is a specific endogenous ligand for the κ-receptor and has a high potency and long duration of action1–13. We show here that the sequences Leu5-enkephalyl-Arg-Arg-Ile (dynorphin1–8) and, particularly, Leu5-enkephalyl-Arg-Arg-Ile-Arg (dynorphin1–9) are selective ligands for the κ-binding site. Whereas dynorphin1–13 and dynorphin1–17 are relatively resistant to the action of peptidase and have a long duration of action in vitro after wash-out, dynorphin1–8 and dynorphin1–9 are readily degraded by peptidases and their duration of action is much shorter. For this and other reasons, the possibility will have to be considered that dynorphin1–8 or dynorphin1–9 may be transmitters or modulators at the κ-binding site while dynorphin1–13 and dynorphin1–17 may act hormonally, that is, at a distance from the site of release.

Conservation of high efficiency promoter sequences in Saccharomyces cerevisiae.

Abstract: The position of the yeast phosphoglycerate kinase (PGK) gene has been mapped on a 2.95kb Hind III fragment. We have determined the nucleotide sequence of the 5' flanking region and compared this sequence with those from 16 other yeast genes. PGK, like all other yeast genes has an adenine residue at position -3. It has two possible TATA boxes at positions -114 and -152 and a CAAT box at -129. In addition we have defined a structure at position -63 to -39 that is common to all yeast genes that encode an abundant RNA. This structure is a CT-rich block followed, about 10 nucleotides later, by the sequence CAAG.

Ecology of Bat Reproduction

Abstract: The ecology of reproduction became firmly established as a discrete area of investigation with the publication of Sadlier’s monograph in 1969, The Ecology of Reproduction in Wild and Domestic Animals. I witnessed the gestation of this book, for Sadlier wrote it in the Wellcome Institute in the London Zoo, where I was working at the time on a doctoral thesis. It stimulated me, as it has stimulated others, to adopt techniques and approaches to the study of wild mammals similar to those long used by students of domestic species.

Spectrum of the μ-, δ- and κ-binding sites in homogenates of rat brain

Abstract: 1 In homogenates of rat brain, the binding characteristics of tritiated opiates and opioid peptides were examined and the relative capacities of mu-, delta- and kappa-binding sites of the opiate receptor determined by saturation analysis.2 In competition experiments, binding of the selective mu-ligand [(3)H]-[D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin at the mu-site was displaced by [D-Ala(2),D-Leu(5)]enkephalin with rather low affinity (K(I) = 12.6 nM) and more readily by the ketazocine-like compounds (-)-ethylketazocine (K(I) = 3.1 nM) and (-)-bremazocine (K(I) = 0.32 nM), which also displaced the binding of [(3)H]-[D-Ala(2),D-Leu(5)]enkephalin from the delta-site. In contrast, the binding to the kappa-site was easily displaced by ethylketazocine (1.0 nM) and bremazocine (0.37 nM) but not by the mu-ligand [D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin (K(I) = 2000-3000 nM) or the delta-ligand [D-Ala(2),D-Leu(5)]enkephalin (K(I) > 20,000 nM).3 The dissociation equilibrium constant (K(D)) and the binding capacity (pmol/g) of the mu-binding site were determined with the selective mu-ligand [(3)H]-[D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin. For the delta-site, [(3)H]-[D-Ala(2),D-Leu(5)]enkephalin was used in the presence of unlabelled [D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin in order to suppress cross-reactivity to the mu-binding site. For the estimation of kappa-binding, [(3)H]-(+/-)-ethylketazocine or [(3)H]-(-)-bremazocine were used in the presence of unlabelled mu- and delta-ligands for the suppression of cross-reactivities to the mu- and delta-binding sites.4 In rat brain the capacity of the mu-binding site was 7.3 pmol/g brain, that of the delta-binding site 6.7 pmol/g brain and that of the kappa-binding site 2.0 pmol/g brain. Thus, the kappa-binding site had the lowest value whereas in the guinea-pig brain the capacity of the mu-binding site was lower than that of the delta- or kappa-binding site.

Ecology of Insects Ectoparasitic on Bats

Abstract: About 6000 species of insects belonging to seven orders are known to be external parasites as adults of warm-blooded vertebrates. Of these, 687 described species of four orders are known to parasitize bats, with members of all the bat families except for three small ones (Craseonycteridae, Mystacinidae, and My-zopodidae) acting as hosts (Tables I and II). The six insect families involved (Fig. 1) are all exclusively associated with bats except for the Cimicidae: of the 89 species of cimicids known, 61 (68%) are parasitic upon bats (including the two species of bedbugs, Cimex hemipterus (F.) and C. lectularius L., commonly associated with man), and the remainder upon birds. Members of five of the six families have piercing-sucking mouthparts and feed on blood, and there is no doubt that they are truly parasitic; however, arixeniids have chewing mouthparts and feed on solid material such as skin detritus and host feces and may in fact be commensals rather than parasites. Three unusual families of Diptera, each containing a single species, have been reported from bat roosts: the Chiropteromyzidae in Finland, Mormotomyiidae in Kenya, and Mystacinobiidae in New Zealand (Holloway, 1976; Maa, personal communication). But in this review I assume these to be commensals and do not consider them further. For a more complete discussion of ectoparasite taxonomy see Marshall (1981a).

Steady-state analysis of 3-phase cage motors with rotor-bar and end-ring faults

Abstract: An analysis is developed for 3-phase induction motors with any distribution and number of rotorbar and end-ring failures. The method is verified, using an inverted-geometry cage motor on which careful measurements of rotor-bar currents are made. The analysis is then used to investigate a rotor-bar fault on a 250 hp, 8-pole, 60 Hz motor.

Toxicity of the immune suppressant cyclosporin A in the rat

Abstract: Cyclosporin A (Cy A) administered orally (100 mg/kg/24 hr) to adult Sprague-Dawley rats for 21 days caused a number of functional and structural changes. Behavioural effects, including fits, were also observed during the first week. Two animals (25 per cent.) died on days 6 and 10 respectively; a third was killed on day 7 because of fits. Hair loss was continuous during the experimental period. There were marked decreases in total serum protein, albumin and aspartate aminotransferase, accompanied by rises in alkaline phosphatase and total bilirubin. Examination of the liver revealed moderate centrilobular fatty change and minor dilatation of endoplasmic reticulum. Impaired renal function was also evident from increases in serum urea and creatinine and a striking rise in urinary N-acetyl-β-D-glucos-aminidase activity. Kidneys examined at 21 days showed focal proximal tubular cell (PTC) vacuolation and necrosis, clearly evident on light microscopy. Ultrastructural studies revealed dilatation and vesiculation of the smooth endoplasmic reticulum within PTC, together with increased lysosome production and the formation of myeloid figures. Glomeruli and distal tubular cells were unaffected. Cy A caused marked lymphopenia, with a progressive increase in circulating neutrophils and monocytes. This was accompanied by the appearance of atypical mononuclear cells in the peripheral blood. The cellularity of the bone marrow was significantly reduced. In the thymus, there was very marked depletion of the medullary zones, and histiocytes containing cellular debris appeared throughout. The most striking feature in the spleen was the loss of lymphocytes within the periarteriolar sheaths and marginal zones.

Root contraction in transpiring plants

Abstract: SUMMARY Experimental data published previously (Faiz and Weatherley, 1977) emphasized the existence of considerable hydraulic resistance in the perirhizal soil of rapidly transpiring plants. This was evident when soil water potential (Ψs in the root zone was as high as −2 or −3 bars. In a further paper (Faiz and Weatherley, 1978) the hypothesis was put forward that it is the soil-root interface which presents a high resistance to the flow of water through the soil-plant system. This resistance, it was thought, could increase as a result of contraction of stressed-roots, with the formation of vapour gaps between soil and root. In this paper we demonstrate that the root tissues may contract by as much as 25 % of their turgid volume when the water potential of the leaves (Ψl) falls to around −15 bars. Under such conditions the extensive formation of vapour gaps would be expected and a reduction of water stress should therefore follow if the gaps could be closed mechanically. Such closure was attempted by either squeezing or vibrating the soil mass containing the root system. Both of these treatments led to a temporary reduction in water stress in the plants and the existence of vapour gaps was thus supported.

Water in malignant tissue, measured by cell refractometry and nuclear magnetic resonance.

Abstract: It has been known that tumour-bearing tissues often have a significantly higher water content than the normal tissues from which they have been derived. Most of the evidence suggesting this in recent years has been obtained from methods employing nuclear magnetic resonance (NMR), which, although undoubtedly indicative of hydration, cannot at present be precisely quantified. Furthermore it has not been possible by these means to determine whether this overall increase in the water content of the tissue is principally an increase in the extracellular fluid or whether the water content of the tumor cells and the cells immediately adjacent to the tumours increases also. In this investigation, which is the first of its kind, a combination of NMR and immersion refractometry techniques have been used to examine the water content of normal and tumour bearing tissues. NMR measurements were made on pieces of normal and tumour bearing tissue from rat livers: intact living cells were also isolated from these pieces and their refractive indices measured by immersion refractometry from which the water content of their cytoplasm was calculated. It was found that all the cells so measured obtained from hepatomas had more water in their cytoplasm (usually over 5% more water) than any of the cells from normal livers; and that normal-looking liver cells taken from the vicinity of hepatomas also all had more water in them than those of normal liver cells, although the differences in this case were less. These results were closely parallel to those obtained by NMR measurements. It is therefore concluded that an appreciable proportion of the increase in the water content of the tissue as a whole that occurs during carcinogenesis, must, in this tissue, be an increase in intracellular water.

Oil Pollution and Seabird Populations

Abstract: Large numbers of seabirds may be killed from time to time by individual incidents of oil pollution, and throughout the year, especially in winter, dead seabirds, many of them oiled, are washed up on our shores. These dramatic events have given rise to a great deal of public concern about the effect of oil pollution on the wellbeing of seabird populations. It is important to consider this question from the point of view of population dynamics of seabirds so as to determine whether or not the observed mortality is substantial and additional in relation to the natural mortality. Such an approach requires detailed information on the distribution and numbers of seabirds at breeding colonies and at sea in their pre-breeding years, in association with their breeding activities and also in their `wintering' areas. While the data from breeding colonies provide censuses of breeding birds in defined geographical areas, movements and dispersal of breeding birds result in great uncertainty about their distribution and abundance while at sea. Since many oil polluting incidents, and much of the chronic oil pollution, affect birds while they are at sea, it is very difficult to asess the size and the provenance of the populations of various species that are actually at risk. Some evidence about the numbers of birds killed by oil and other causes can be obtained from both the beached bird survey, which are carried out monthly throughout the winter, and also from the recoveries of ringed birds. These sources of evidence give rather different results, but both are subject to difficulties of interpretation. Most seabirds are long-lived, with low mean annual adult mortality rates, and many of them do not breed until they are several years old. An attempt is made to relate the numbers of birds found dead, and the numbers oiled to the numbers that might be expected to die according to the measured rates of annual mortality. Again there are very considerable problems in attempting to relate these two sets of information. However, it seems that in western European waters the numbers killed by oil pollution is in tens of thousands per winter on average, while the number expected to die naturally is in hundreds of thousands per year. It is not known whether or not oil-induced mortality is additional to natural mortality. It is also pointed out that current environmental circumstances seem favourable and that the present resilience of populations may not persist if conditions change. Emphasis is placed on the very large numbers of pre-breeding birds and the need for information on the means by which they are recruited to breeding colonies. Recent monitoring of the numbers of breeding seabirds throughout Britain shows that most populations are increasing.

Changes in body temperature and oxygen consumption rate of conscious mice produced by intrahypothalamic and intracerebroventricular injections of delta 9-tetrahydrocannabinol.

Abstract: delta 9-Tetrahydrocannabinol (delta 9-THC) was injected into the preoptic area of the anterior hypothalamus or into the third or fourth cerebral ventricle of the conscious mouse through a chronically implanted cannula and the effects on body temperature and oxygen consumption rate were measured. At an ambient temperature of 22 degrees C, injections of delta 9-THC into the fourth ventricle (5 and 10 microgram) produced dose-dependent falls in rectal temperature. Hypothermia was also observed after injections of the drug into the hypothalamus (5 and 10 microgram) or into the third ventricle (10 microgram). The hypothermia produced by delta 9-THC was associated with a fall in oxygen consumption rate. Falls in rectal temperature and in oxygen consumption rate were significantly greater after injection of delta 9-THC than after injection of the drug vehicle, Tween 80. The falls in rectal temperature and oxygen consumption rate produced by injection of delta 9-THC into the fourth ventricle were abolished by elevation of the ambient temperature from 22 to 32 degrees C. A pretreatment that consisted of subcutaneous injections of delta 9-THC (20 mg/kg) given once daily for three days produced tolerance to the hypothermic effect of the drug when injected on day 4 either into the fourth ventricle (10 microgram) or into a lateral tail vein (2.0 mg/kg). The results suggest that delta 9-THC acts centrally to alter thermoregulation in mice not only when it is injected directly into the hypothalamus or cerebral ventricles but also when it is given intravenously. After intraventricular or intravenous administration the drug may act at extrahypothalamic as well as at hypothalamic sites. The data also support the hypothesis that in mice, tolerance to the hypothermic effect of A9-THC is pharmacodynamic and does not depend on changes in metabolism or distribution of the drug.

The Effects of Cold on the Performance of Serial Choice Reaction Time and Various Discrete Tasks

Abstract: Two experiments are reported in which subjects performed a number of tasks before, during, and following exposure to cold. The main performance task, involving serial choice reaction times, yielded...

The Transfer Matrix Method for the Vibration of Compressed Helical Springs

Abstract: The partial differential equations of motion are obtained for a helical spring subject to a static axial force, the typical element of the spring having six degrees of freedom. The wire cross-section can be any doubly symmetrical shape. The overall transfer matrix is calculated and its application is discussed for obtaining the response to forced sinusoidal vibration. Natural frequencies are found from the transfer matrix by iteration. Comparisons are made with published experiments on the natural frequencies of helical springs, made from round wire, with and without a static axial force. Comparison is also made with published theory for the static buckling of helical springs. Information is given on the effect on the natural frequencies of the static axial force, helix angle, number of active turns, ratio of helix to wire diameter, Poisson's ratio, shear coefficient, and the end conditions. The calculation of the normal modes is discussed.

Familial antithrombin III deficiency.

Abstract: SUMMARY Antithrombin III is the major physiological inhibitor of the coagulation mechanism and a deficiency of this protein results in a marked predisposition to venous thromboembolic disease. Three Scottish families with a deficiency of this protein are described and other reported families are reviewed. The properties, functions and methods of assay of antithrombin III are outlined; the molecular abnormalities, inheritance, clinical and laboratory characteristics of antithrombin IIIdeficiency are described, and the use of antithrombotic drugs and human antithrombin III concentrates in this deficiency is discus

Plasma protein concentrations in interstitial fluid from human aortas.

Abstract: The concentration of plasma proteins was examined in interstitial fluid collected from human aortas, obtained at autopsy, from patients from whom a blood sample had been taken for routine analysis shortly before death. The interstitial fluid was absorbed onto small, preweighed pieces of filter paper which were inserted into natural strip planes in the tunica intima and inner tunica media. After equilibration the papers were removed and weighed to measure the amount of interstitial fluid collected, then analysed by quantitative immunoelectrophoresis for three plasma proteins covering a range of molecular masses ( M r ): low density lipoprotein (LDL) with molecular mass 2.4 x 10 6 , α 2 -macroglobulin ( M r 720 000) and serum albumin ( M r 68 000). In interstitial fluid obtained from normal intima of 20 men and women, the mean levels of the proteins were LDL 215%, α 2 -macroglobulin 115% and albumin 54% of the concentration in the patient’s own plasma. Concentrations were not influenced by depth within the intima, or by distance down the aorta. The patients covered the age range 31-96 years; relative concentrations of LDL, α 2 -macroglobulin and albumin increased in parallel by about 10% per decade. Large samples (up to 7 μl) of interstitial fluid were collected from inner media but they contained no measurable LDL; the levels of α 2 -macroglobulin and albumin were respectively 11 and 18% of plasma concentration. Analysis of interstitial fluid from one sample of normal intima obtained at vascular surgery, and from two freshly killed pigs, suggested that results were not invalidated by the use of autopsy material. Direct comparison of whole intimal tissue and interstitial fluid provided no evidence of preferential binding of LDL in tissue. There was no evidence of preferential adsorbtion of LDL by the filter paper. Interstitial fluid of six samples of normal intima from four patients was compared with normal plasma by two-dimensional immunoelectrophoresis. The peaks produced in the antiserum to LDL were identical in mobility, shape and staining properties. Thus the concentration of LDL found in interstitial fluid from normal aortic intima was more than twice the plasma concentration, and the relation between concentration and molecular mass was the inverse of that reported for peripheral interstitial fluid and lymph. Endothelium appears to trap LDL in the intima instead of keeping it out, and this raises fundamental questions about the function of arterial endothelium.

Complementary and dual energy finite element principles in magnetostatics

Abstract: A method of providing bounded solutions to a wide range of magnetostatic field problems is outlined. The method extends complementary and dual energy variational principles to encompass the T-Ω formulation of electromagnetic field problems and shows how this leads to efficient finite element implementation of the technique. Examples are given that show clearly the bounded nature of the procedure, and indicate how it may be used to reduce the computational requirements necessary for a specific accuracy of solution.

Shape effects in aeolian grain transport

Abstract: Wind tunnel experiments are reported, the results of which show that grain transport rate is responsive to characteristic grain shape. It is relatively less sensitive to changes of sorting unless these involve the fraction smaller than 50μm. A cubic relationship between transport rate and velocity gradient appears to be valid only for well worked natural grains having high sphericity.

On growth of the octopus Eledone cirrhosa

Abstract: The growth of the octopus Eledone cirrhosa has been studied in a population from the North Sea off Aberdeen. Data are presented for the growth of individuals isolated in aquarium conditions; the growth of size classes in thefieldpopulation; and preliminary information on the growth relationships of gonad, somatic, cardiac and brain components of the body.At 15 °C Eledone cirrhosa is capable of growing from 10 to 1000 g in 270 days. From octopuses which feed readily in captivity, weight specific growth rates of up to about 3–5 % day-1 for animals of 100 g body weight are recorded, falling to a maximum of about 1–5 % day-1 at body sizes above 500 g. Females stop growing when sexually mature, but in the sample captured they were consistently larger than males, a feature which may account for the 7:1 bias towards the incidence of females. On a wet-weight basis, the mean food incorporation into growth is 37 % of the food ingested, which is 49% of the gross weight of crabs killed. Field data for 1978/79 suggest that animals recruited to the population at the beginning of the year grew steadily until December, overwintered without growing, then grew rapidly for several months in the subsequent year before disappearing from the samples. The estimated average age of those animals and by implication, the life span, is 20 months.

Synapse-to-neuron ratios in the visual cortex of adult rats undernourished from about birth until 100 days of age.

Abstract: Male rats undernourished from the 18th day of gestation until 100 days of age were nutritionally rehabilitated until 200 days of age. Six control and six experimental rats at each of 100 and 200 days of age were killed by perfusion with buffered 2.5% glutaraldehyde. Pieces of visual cortex from each rat were postfixed in osmium tetroxide and embedded in resin. Stereological procedures at the light and electron microscopy levels were used to estimate the synapse-to-neuron ratios in cortical layers II to IV. Rats undernourished until 100 days of age had a mean +/- S.E. of 10,350 +/- 470 synapses associated with each neuron. This represented a 13% deficit (P less than 0.05) when compared to the control value of 11,950 +/- 530. Following nutritional rehabilitation till 200 days of age it was found that the previously undernourished rats had about 23% more (P less than 0.05) synapses-per-neuron than their age-matched controls. This was due almost entirely to a substantial increase in the ratio in the previously undernourished animals; the value of controls did not alter significantly between the two age groups. It appears that the deficit in the synapse-to-neuron ratio seen after a lengthy period of undernutrition is not permanent, at least in rats subsequently allowed nutritional rehabilitation. In fact, such animals seem to be capable of not only "catching-up" but "overshooting" the values found in age-matched controls.