scispace - formally typeset
Search or ask a question

Showing papers by "University of Glasgow published in 1993"


Journal ArticleDOI
29 Apr 1993-Nature
TL;DR: The results show that p53 exerts a significant and dose-dependent effect in the initiation of apoptosis, but only when it is induced by agents that cause DNA-strand breakage.
Abstract: Death by apoptosis is characteristic of cells undergoing deletion during embryonic development, T- and B-cell maturation and endocrine-induced atrophy. Apoptosis can be initiated by various agents and may be a result of expression of the oncosuppressor gene p53 (refs 6-8). Here we study the dependence of apoptosis on p53 expression in cells from the thymus cortex. Short-term thymocyte cultures were prepared from mice constitutively heterozygous or homozygous for a deletion in the p53 gene introduced into the germ line after gene targeting. Wild-type thymocytes readily undergo apoptosis after treatment with ionizing radiation, the glucocorticoid methylprednisolone, or etoposide (an inhibitor of topoisomerase II), or after Ca(2+)-dependent activation by phorbol ester and a calcium ionophore. In contrast, homozygous null p53 thymocytes are resistant to induction of apoptosis by radiation or etoposide, but retain normal sensitivity to glucocorticoid and calcium. The time-dependent apoptosis that occurs in untreated cultures is unaffected by p53 status. Cells heterozygous for p53 deletion are partially resistant to radiation and etoposide. Our results show that p53 exerts a significant and dose-dependent effect in the initiation of apoptosis, but only when it is induced by agents that cause DNA-strand breakage.

2,333 citations


Journal Article
TL;DR: Whatever the specific nature of their physiological roles, the presence of an endogenous selective agonist and antagonist acting at NMDA receptors must continue to present exciting possibilities for understanding the pathological basis of several CNS disorders as well as developing new therapeutic approaches.
Abstract: In a little more than 10 years, the kynurenine metabolites of tryptophan have emerged from their former position as biochemical curiosities, to occupy a prominent position in research on the causes and treatment of several major CNS disorders. The pathway includes two compounds, quinolinic acid and kynurenic acid, which are remarkably specific in their pharmacological profiles: one is a selective agonist at receptors sensitive to NMDA, whereas the other is a selective antagonist at low concentrations at the strychnine-resistant glycine modulatory site associated with the NMDA receptor. It has been argued that these agents cannot be of physiological or pathological relevance because their normal extracellular concentrations, in the nanomolar range, are at least 3 orders of magnitude lower than those required to act at NMDA receptors. This is a facile argument, however, that ignores at least two possibilities. One is that both quinolinate and kynurenate may be present in very high concentrations locally at some sites in the brain that cannot be reflected in mean extracellular levels. Similar considerations apply to many neuroactive agents in the CNS. The fact that both compounds appear to be synthesised in, and thus emerge from, glial cells that are well recognised as enjoying a close physical and chemical relationship with some neurones in which the intercellular space may be severely restricted may support such a view. Certainly the realisation that NMDA receptors may not be fully saturated functionally with glycine would be consistent with the possibility that even quite low concentrations of kynurenate could maintain a partial antagonism at the glycine receptor. A second possibility is that there may be a subpopulation of NMDA receptors (or, indeed, for a quite different amino acid) that possesses a glycine modulatory site with a much lower sensitivity to glycine or higher sensitivity to kynurenate, making it more susceptible to fluctuations of endogenous kynurenine levels. Whatever the specific nature of their physiological roles, the presence of an endogenous selective agonist and antagonist acting at NMDA receptors must continue to present exciting possibilities for understanding the pathological basis of several CNS disorders as well as developing new therapeutic approaches. An imbalance in the production or removal of either of these substances would be expected to have profound implications for brain function, especially if that imbalance were present chronically.(ABSTRACT TRUNCATED AT 400 WORDS)

936 citations


Journal ArticleDOI
TL;DR: The facilitative glucose transporters are specific for the D-enantiomer of glucose and are not coupled to any energy-requiring components, such as ATP hydrolysis or a HI gradient.
Abstract: possess a transport system for glucose of the facilitative diffusion type; these transporters allow the movement of glucose across the plasma membrane down its chemical gradient either into or out of cells. These transporters are specific for the D-enantiomer of glucose and are not coupled to any energy-requiring components, such as ATP hydrolysis or a HI gradient [1]. The facilitative glucose transporters are distinct from the Na+dependent transporters, which actively accumulate glucose [2,3]. The importance of glucose as a cellular metabolite has led to

767 citations


Journal ArticleDOI
TL;DR: Reflecting the new urban entrepreneuralism, city marketing is more than the mere promotion of place, being used in some cities to rebuild and redefine their image, allied to which has been a strate...
Abstract: Reflecting the new urban entrepreneuralism, city marketing is more than the mere promotion of place, being used in some cities to rebuild and redefine their image, allied to which has been a strate...

494 citations



Proceedings ArticleDOI
01 Jul 1993
TL;DR: This work proposes an automatic technique for improving theiency of programs, by removing many of these intermediate lists, based on a single, simple, local transformation.
Abstract: Lists are often used as “glue” to connect separate parts of a program together. We propose an automatic technique for improving the efficiency of such programs, by removing many of these intermediate lists, based on a single, simple, local transformation. We have implemented the method in the Glasgow Haskell compiler.

449 citations


Journal ArticleDOI
TL;DR: In this paper, the use of electrochemically polymerized films to immobilize enzymes at electrode surfaces is reviewed, and the interpretation and modelling of the results from these studies are discussed.

432 citations


Journal ArticleDOI
TL;DR: The enzyme activity of J774 cells was not restored after the removal of SNAP by gel filtration, suggesting that NO inhibits NO synthase irreversibly.
Abstract: 1. A murine macrophage cell line, J774, expressed nitric oxide (NO) synthase activity in response to interferon-gamma (IFN-gamma, 10 u ml-1) plus lipopolysaccharide (LPS, 10 ng ml-1). The enzyme activity was first detectable 6 h after incubation, peaked at 12 h and became undetectable after 48 h. 2. The decline in the NO synthase activity was not due to inhibition by stable substances secreted by the cells into the culture supernatant. 3. The decline in the NO synthase activity was significantly slowed down in cells cultured in a low L-arginine medium or with added haemoglobin, suggesting that NO may be involved in a feedback inhibitory mechanism. 4. The addition of NO generators, S-nitroso-acetyl-penicillamine (SNAP) or S-nitroso-glutathione (GSNO) markedly inhibited the NO synthase activity in a dose-dependent manner. The effect of NO on the enzyme was not due to the inhibition of de novo protein synthesis. 5. SNAP directly inhibited the inducible NO synthase extracted from activated J774 cells, as well as the constitutive NO synthase extracted from the rat brain. 6. The enzyme activity of J774 cells was not restored after the removal of SNAP by gel filtration, suggesting that NO inhibits NO synthase irreversibly.

410 citations


Journal ArticleDOI
22 May 1993-BMJ
TL;DR: Currently evaluated cholesterol lowering drugs seem to produce mortality benefits in only a small proportion of patients at very high risk of death from coronary heart disease, and future trials should aim to clarify the level of risk above which treatment is of net benefit.
Abstract: OBJECTIVE--To investigate the level of risk of death from coronary heart disease above which cholesterol lowering treatment produces net benefits. DESIGN--Meta-analysis of results of randomised controlled trials of cholesterol lowering treatments. METHODS--Published and unpublished data from all identified randomised controlled trials of cholesterol lowering treatments with six months or more follow up and with at least one death were included in the meta-analysis. The analyses were stratified by the rate of death from coronary heart disease in the control arms of the trials. MAIN OUTCOME MEASURES--Death from all causes, from coronary heart disease, and from causes other than coronary heart disease. RESULTS--In the pooled analysis, net benefit in terms of total mortality from cholesterol lowering was seen only for trials including patients at very high initial risk of coronary heart disease (odds ratio 0.74; 95% confidence interval 0.60 to 0.92). In a medium risk group no net effect was seen, and in the low risk group there were adverse treatment effects (1.22; 1.06 to 1.42). In a weighted regression analysis a significant (p

405 citations


Journal ArticleDOI
TL;DR: It is demonstrated that juvenile Atlantic salmon, Salmo salar, switch between diurnal and nocturnal foraging solely in response to environmental temperature, and independently of photoperiod and season.
Abstract: The activity patterns of animals, whether diurnal, crepuscular or nocturnal, are usually fixed endogenous rhythms, entrained by environmental Zeitgebers. Here we demonstrate that juvenile Atlantic salmon, Salmo salar, switch between diurnal and nocturnal foraging solely in response to environmental temperature, and independently of photoperiod and season. Above 10 degrees C juvenile Atlantic salmon fed predominantly during daylight, spending the night exposed in the water column but relatively quiescent. As temperature dropped below 10 degrees C they became increasingly nocturnal, hiding in refuges by day but emerging to feed at night. It has previously been shown that parallel physiological changes take place in the retinae of several species of salmonids: the quantity and composition of the visual pigments change so as to make the fish more dark adapted at low temperatures. As the fish were found to be far less aggressive by night than by day at all temperatures, the switch to nocturnal activity was also accompanied by a change in social structure. We suggest that this temperature-dependent strategy maximizes feeding efficiency in summer but reduces predation risk in winter.

371 citations


Journal ArticleDOI
25 Jun 1993-Science
TL;DR: By adoptive transfer of cloned T cell lines, direct evidence is provided that both TH1 and TH2 subsets of CD4+ T cells can protect mice against Plasmodium chabaudi chabaud infection.
Abstract: CD4+ T cells play a major role in protective immunity against the blood stage of malaria, but the mechanism of protection is unclear. By adoptive transfer of cloned T cell lines, direct evidence is provided that both TH1 and TH2 subsets of CD4+ T cells can protect mice against Plasmodium chabaudi chabaudi infection. TH1 cells protect by a nitric oxide-dependent mechanism, whereas TH2 cells protect by the enhancement and accelerated production of specific immunoglobulin G1 antibody.

Book ChapterDOI
TL;DR: The role of the immune response to Leishmania, with particular reference to the cutaneous disease caused by L. major, is discussed, and the concept of suppressor T cells is reviewed.
Abstract: Publisher Summary This chapter discusses the role of the immune response to Leishmania, with particular reference to the cutaneous disease caused by L. major. Leishmaniasis is caused by species of the intracellular protozoan parasite belonging to the genus Leishmania. There are three main categories of leishmaniasis: cutaneous leishmaniasis (oriental sore), mucocutaneous leishmaniasis (espundia), and visceral leishmaniasis (kala-azar). In humans, infection with Leishmania results in a spectrum of disease dependent upon the species involved and the efficiency of the host's immune response to the parasite. Diagnosis of active leishmaniasis is based primarily on the demonstration of the parasite in biopsies. A skin test using a killed whole parasite preparation (leishmanin) is used as a presumptive test. Genetic regulation of leishmaniasis is discussed in reference to mouse and humans, and the concept of suppressor T cells is reviewed. The various cytokines in leishmaniasis, including interferon (IFN) γ and interleukin (IL)-4, IL-10, IL-1, and IL-2 are also discussed.


Journal ArticleDOI
01 Jul 1993
TL;DR: In this article, the effect of the number of flux guides/barriers on the saliency ratio of the synchronous reluctance motor is analyzed. But the main originality is the analysis of the effect is not the performance of the motor but rather the parameters on which it depends.
Abstract: Recent interest in the synchronous reluctance motor has increased in the context of possible applications in field oriented AC drives. The absence of rotor slip losses and the apparent simplicity of the control suggest the possibility of performance and cost advantages over the induction motor. With field oriented control, and continuous shaft position feedback, the synchronous reluctance motor does not need a starting cage and can be designed for maximum saliency ratio (L/sub d//L/sub q/ ratio). This ratio is by far the most important parameter for achieving high power factor, torque/ampere, and constant-power speed range. This paper analyses the various known forms of the synchronous reluctance motor, to determine the maximum achievable saliency ratio and identify the parameters on which it depends. The main originality is the analysis of the effect of the number of flux guides/barriers. It is shown that a minimum number is required for the performance to surpass that of the induction motor. The analysis also reveals the optimum ratio of flux guide/flux barrier thicknesses and the effects of the tooth/slot geometry and stator saturation. Test results are included from three motors ranging from 50 W at 2000 r.p.m. to 7.5 kW at 1500 r.p.m., covering both axially laminated and transversely laminated types.< >

Journal ArticleDOI
22 Oct 1993-Cell
TL;DR: It is predicted that normal partition of most circular chromosomes requires the participation of site-specific recombination to convert any multimers (arising by homologous recombination) to monomers.

Journal ArticleDOI
TL;DR: A range of techniques, based on impurity diffusion, dielectric capping and laser annealing, have been developed to enhance the quantum well intermixing (QWI) rate in selected areas of a wafer as discussed by the authors.
Abstract: Intermixing the wells and barriers of quantum well structures generally results in an increase in the band gap and is accompanied by changes in the refractive index. A range of techniques, based on impurity diffusion, dielectric capping and laser annealing has been developed to enhance the quantum well intermixing (QWI) rate in selected areas of a wafer; such processes offer the prospect of a powerful and relatively simple fabrication route for integrating optoelectronic devices and for forming photonic integrated circuits (PICS). Recent progress in QWI techniques is reviewed, concentrating on processes which are compatible with PIC applications, in particular the achievement of low optical propagation losses.


Journal ArticleDOI
13 Nov 1993-BMJ
TL;DR: The design of questionnaires is a craft which has been badly neglected by the medical profession and is capable of coping with all possible responses, satisfactorily coded, piloted, and ethical.
Abstract: The design of questionnaires is a craft which has been badly neglected by the medical profession. A questionnaire should be appropriate, intelligible, unambiguous, unbiased, capable of coping with all possible responses, satisfactorily coded, piloted, and ethical. The key steps in designing a questionnaire are to: decide what data you need, select items for inclusion, design the individual questions, compose the wording, design the layout and presentation, think about coding, prepare the first draft and pretest, pilot, and evaluate the form, and perform the survey. Despite the apparently complicated nature of the task, theoretical knowledge is no substitute for practical experience.

Journal ArticleDOI
TL;DR: The aims of the present studies were to determine whether OS is due to CAD or CHF per se and to determine if a wider range of more specific markers of OS are abnormal in CHF.
Abstract: Chronic heart failure (CHF) due to coronary artery disease (CAD) has been shown to be associated with increased plasma thiobarbituric reactive substances (TBARS) and reduced plasma thiol (PSH) concentrations, suggesting oxidative stress (OS). The aims of the present studies were (a) to determine whether OS is due to CAD or CHF per se and (b) to determine if a wider range of more specific markers of OS are abnormal in CHF. In the first study, two groups of patients (n = 15 each) were compared. Group 1 (11 male, mean age 56 years) had CHF due to CAD and group 2 (12 male, mean age 53 years) had non-CAD CHF. Median plasma TBARS in controls was 7.6 nmol . ml−1 , 10.0 nmol . m−1 in group 1 and 9.3 nmol. ml−1 in group 2 ( P < 0.01 both groups vs control). Median PSH was 505 384 and 364 nmol. ml−1 ( P < 0.05 and P < 0.01 vs control) respectively. Fifty-three patients with CHF were recruited in the second study. Malondialdehyde and PSH were 10.3 and 409 nmol. ml−1 respectively, compared to control values of 7.9 and 560 nmol. ml.1 (both P < 0.001). The median values for the following additional measures of OS in controls and patients were: erythrocyte superoxide dismustase 131 vs 114 U . l−1 ( P = 0.005); caeruloplasmin oxidase 97 vs 197 U. l−1 ( P < 0.01); erythrocyte glutathione 1.56 nmol . ml−1 vs 1.77 nmol . ml−1 ( P < 0.02); plasma conjugated dienes 0.28 vs 0.33 optical density units ( P = ns). Chronic heart failure, regardless of aetiology, is associated with abnormalities of a range of markers of OS.


Journal ArticleDOI
TL;DR: It is demonstrated that endothelin-1 is capable of reducing blood flow to pathologically low levels and provide a new model of controlled focal ischaemia followed by reperfusion.
Abstract: The capacity of endothelin-1 to induce severe reductions in cerebral blood flow and ischaemic neuronal damage was assessed in anaesthetised rats. Endothelin-1 (25 microliters of 10(-7)-10(-4) M) was applied to the adventitial surface of an exposed middle cerebral artery and striatal blood flow assessed by the hydrogen clearance technique. Endothelin-1 induced severe dose-dependent reductions in cerebral blood flow (e.g., minimum CBF at 10(-5) M of 9 +/- 11 ml 100 g-1 min-1 compared to 104 +/- 22 ml 100 g-1 min-1 with vehicle, p < 0.05), which persisted for at least 60 min at each concentration of endothelin-1. Application of endothelin-1 to the middle cerebral artery produced dose-dependent ischaemic brain damage (e.g., volume of damage of 65 +/- 34 mm3 at 10(-5) M compared to 0.22 +/- 0.57 mm3 for vehicle, p < 0.01). These data demonstrate that endothelin-1 is capable of reducing blood flow to pathologically low levels and provide a new model of controlled focal ischaemia followed by reperfusion.

Journal ArticleDOI
TL;DR: In this paper, the authors argue from economic first principles that it is more logical to use some form of residual income definition than one based on a prescribed ratio of housing costs to income.
Abstract: The term 'afford ability' has been gaining currency in housing policy debates, but neither government nor academic researchers have given much consideration to defining it. This paper considers what meanings have been given to the term affordability in practice and suggests a range of analytically more useful definitions. It argues from economic first principles that it is more logical to use some form of residual income definition than one based on a prescribed ratio of housing costs to income. Most researchers have been using a ratio definition. The paper then uses data from a household survey in the Glasgow Travel-to-Work Area in 1988/89 to examine the incidence of 'unaffordability' of housing costs according to a variety of definitions.

01 Mar 1993
TL;DR: An overview of the Glasgow Haskell compiler is given, focusing especially on way in which the compiler has been able to exploit the rich theory of functional languages to give very practical improvements in the compiler.
Abstract: We give an overview of the Glasgow Haskell compiler, focusing especially on way in which we have been able to exploit the rich theory of functional languages to give very practical improvements in the compiler. The compiler is portable, modular, generates good code, and is freely available.

Journal ArticleDOI
I. Abt1, T. Ahmed2, Vladimir Andreev3, B. Andrieu4  +381 moreInstitutions (26)
TL;DR: A measurement of the proton structure function F2 (x, Q2) was presented with about 1000 neutral current deep inelastic scattering events for Bjorken x in the range x ⋍ 10−2 − 10−4 and Q2 > 5 GeV2 as discussed by the authors.

Journal ArticleDOI
M. Derrick1, D. Krakauer1, S. Magill1, B. Musgrave1  +459 moreInstitutions (37)
TL;DR: In this article, neutral current scattering of electrons and protons at square-root s = 296 GeV was observed in the ZEUS detector events with a large rapidity gap in the hadronic final state.

Journal ArticleDOI
M. Derrick1, D. Krakauer1, S. Magill1, B. Musgrave1  +464 moreInstitutions (37)
TL;DR: In this article, the first measurement of the F 2 structure function in neutral-current, deep inelastic scattering using the ZEUS detector at HERA, the ep colliding beam facility at DESY, was presented.

Journal ArticleDOI
TL;DR: A new model is presented to explain the events that occur in the insect gut during toxin action and is able to predict the effect on the insect of the formation of a toxic pore.
Abstract: The crystal δ-endotoxins of Bacillus thuringiensis (Bt) are a family of insecticidal proteins which have been known for some time to kill insects by lysing their gut epithelial cells, but the precise molecular mechanism of toxicity has remained elusive. The recent publication of the crystal structure of a Bt δ-endotoxin has made it possible for us to model the molecular events that occur as the toxin binds to its receptor and inserts into the membrane to form a pore. Using our knowledge of insect gut physiology, we can also predict the effect on the insect of the formation of a toxic pore. We present a new model to explain the events that occur in the insect gut during toxin action.

Journal ArticleDOI
P D MacIntyre1, B Bhargava1, K J Hogg1, J D Gemmill1, W S Hillis1 
TL;DR: Sumatriptan, a SHT, receptor agonist administered by the subcutaneous route, causes a vasopressor response in the systemic and pulmonary arterial circulations and coronary artery vasoconstriction.
Abstract: BACKGROUNDSumatriptan (GR43175) is a selective 5-hydroxytryptamine (5HT1) receptor agonist effective in the acute treatment of migraine. Recent in vitro experiments suggest that it has vasoactive properties in vascular beds distinct from the cerebral circulation. The object of this study was to assess the vasoactive effects of the standard 6-mg subcutaneous dose of sumatriptan used in migraine on the systemic and pulmonary circulations and the coronary artery vasculature.METHODS AND RESULTSTen patients undergoing diagnostic coronary arteriography were studied with digital subtraction angiography and invasive hemodynamic monitoring. After subcutaneous injection of sumatriptan, there was no significant change in heart rate or ECG morphology. There was a significant rise in the systemic (20%, p < 0.05 by ANOVA) and pulmonary artery (40%, p < 0.05 by ANOVA) pressures. There was no change in cardiac output, but there was a significant increase in total systemic (27%, p < 0.05) and total pulmonary vascular resi...

Journal ArticleDOI
TL;DR: Four experiments were carried out to extend knowledge of what determines the incidental detection of the critical item and show that if satisfactory coherence can be established without detailed semantic analysis, through the recruitment of suitable information from a sentence, then processing is indeed shallow.
Abstract: Although the establishment of a coherent mental representation depends on semantic analysis, such analysis is not necessarily complete. This is illustrated by failures to notice the anomaly in questions such as, "When an airplane crashes, where should the survivors be buried?" Four experiments were carried out to extend knowledge of what determines the incidental detection of the critical item. Detection is a function of the goodness of global fit of the item (Experiments 1 and 2) and the extent to which the scenario predicts the item (Experiment 3). Global good fit appears to result in shallow processing of details. In Experiment 4, it is shown that if satisfactory coherence can be established without detailed semantic analysis, through the recruitment of suitable information from a sentence, then processing is indeed shallow. The studies also show that a text is not understood by first producing a local semantic representation and then incorporating this into a global model, and that semantic processing is not strictly incremental.

Journal ArticleDOI
F.J. Rixon1
TL;DR: The complex nature of herpesvirus particles, which comprise icosahedral and membrane-bound elements, makes them interesting models for studies of virion organisation and assembly.