Showing papers by "University of Leicester published in 1993"

Respiratory viruses and exacerbations of asthma in adults.

Abstract: OBJECTIVE--To study the role of respiratory viruses in exacerbations of asthma in adults. DESIGN--Longitudinal study of 138 adults with asthma. SETTING--Leicestershire Health Authority. SUBJECTS--48 men and 90 women 19-46 years of age with a mean duration of wheeze of 19.6 years. 75% received regular treatment with bronchodilators; 89% gave a history of eczema, hay fever, allergic rhinitis, nasal polyps, or allergies; 38% had been admitted to hospital with asthma. MAIN OUTCOME MEASURES--Symptomatic colds and asthma exacerbations; objective exacerbations of asthma with > or = 50 l/min reduction in mean peak expiratory flow rate when morning and night time readings on days 1-7 after onset of symptoms were compared with rates during an asymptomatic control period; laboratory confirmed respiratory tract infections. RESULTS--Colds were reported in 80% (223/280) of episodes with symptoms of wheeze, chest tightness, or breathlessness, and 89% (223/250) of colds were associated with asthma symptoms. 24% of 115 laboratory confirmed non-bacterial infections were associated with reductions in mean peak expiratory flow rate > or = 50 l/min through days 1-7 and 48% had mean decreases > or = 25 l/min. 44% of episodes with mean decreases in flow rate > or = 50 l/min were associated with laboratory confirmed infections. Infections with rhinoviruses, coronaviruses OC43 and 229E, influenza B, respiratory syncytial virus, parainfluenza virus, and chlamydia were all associated with objective evidence of an exacerbation of asthma. CONCLUSIONS--These findings show that asthma symptoms and reductions in peak flow are often associated with colds and respiratory viruses; respiratory virus infections commonly cause or are associated with exacerbations of asthma in adults.

Phytochrome A null mutants of Arabidopsis display a wild-type phenotype in white light.

Abstract: Phytochrome is a family of photoreceptors that regulates plant photomorphogenesis; the best-characterized member of this family is phytochrome A. Here, we report the identification of novel mutations at three Arabidopsis loci (fhy1, fhy2, and fhy3) that confer an elongated hypocotyl in far-red but not in white light. fhy2 mutants are phytochrome A deficient, have reduced or undetectable levels of PHYA transcripts, and contain structural alterations within the PHYA gene. When grown in white light, fhy2 mutants are morphologically indistinguishable from wild-type plants. Thus, phytochrome A appears to be dispensable in white light-grown Arabidopsis plants. fhy2 alleles confer partially dominant phenotypes in far-red light, suggesting that the relative abundance of phytochrome A can affect the extent of the far-red-mediated hypocotyl growth inhibition response. Plants homozygous for the recessive fhy1 and fhy3 mutations have normal levels of functional phytochrome A. The FHY1 and FHY3 gene products may be responsible for the transduction of the far-red light signal from phytochrome A to downstream processes involved in hypocotyl growth regulation.

On the edge

Abstract: The Origins of Order: Self-Organization and Selection in Evolution. By Stuart A. Kauffman. Oxford University Press: 1993. Pp. 709. $75, £55 (hbk); $29.95, £17.95 (pbk).

X-ray spectra and time variability of active galactic nuclei

Abstract: The history and the present status of X-ray observations of AGN are outlined with reference to Seyfert Is, Seyfert IIs, and quasars. Fe K emission lines, other distortions at E greater tha 6 keV, excess emission below 2 keV, absorption, and ionized material are discussed. The continuum flux variability and line variability in Seyfert Is and the continuum variability in Seyfert IIs are examined. Models and theories of the continuum are reviewed, and the total energy budget of AGN and their similarity to Galactic black holes are also discussed.

Iron uptake mechanisms of pathogenic bacteria

Abstract: Most of the iron in a mammalian body is complexed with various proteins. Moreover, in response to infection, iron availability is reduced in both extracellular and intracellular compartments. Bacteria need iron for growth and successful bacterial pathogens have therefore evolved to compete successfully for iron in the highly iron-stressed environment of the host's tissues and body fluids. Several strategies have been identified among pathogenic bacteria, including reduction of ferric to ferrous iron, occupation of intracellular niches, utilisation of host iron compounds, and production of siderophores. While direct evidence that high affinity mechanisms for iron acquisition function as bacterial virulence determinants has been provided in only a small number of cases, it is likely that many if not all such systems play a central role in the pathogenesis of infection.

Proteasomes: multicatalytic proteinase complexes

Abstract: The multicatalytic proteinase complex (proteasome) is a highmolecular-mass (approximately 700 kDa) intracellular proteinase which has been isolated under a variety of different names from a wide variety of eukaryotic cells and tissues (reviewed, Rivett, 1989a; Orlowski, 1990). The proteinase complex is composed of at least 24 subunits which include many different polypeptides arranged in a cylindrical structure. Other multi-subunit complexes with cylindrical structures include 'prosomes', that are widely distributed 19 S ribonucleoprotein particles which were thought to be involved in the control of translation (Schmid et al., 1984; Martins de Sa et al., 1986), erythrocyte cylindrin (Harris, 1988), and a number of other partially characterized 16-22 S cylindrical particles. 'Prosomes' and certain related particles have been shown to have proteolytic activity and to share antigenic cross-reactivity with the multicatalytic proteinase (Falkenburg et al., 1988) and are therefore believed to be the same. The particles are most often referred to either as multicatalytic proteinase complexes (Dahlmann et al., 1988; Orlowski and Wilk, 1988) or, more recently, as proteasomes (Arrigo et al., 1988) and their properties are broadly similar irrespective of the

A prospective study of nausea and vomiting during pregnancy.

Abstract: The symptoms of nausea and vomiting in pregnancy were described by 363 pregnant women who kept daily symptom diaries. All delivered a single live baby. The majority of information collected was prospective, with the median day from last menstrual period to initial interview by the study midwife being day 57. It was found that 80% of women had symptoms, 28% experienced nausea only, while 52% had nausea and vomiting. The mean number of days from last menstrual period to onset and cessation of symptoms was 39 and 84, respectively, and 40% of women's symptoms ended abruptly. Cessation of symptoms occurred at approximately the same day from the last menstrual period whether they had begun early or later, severely or mildly [corrected]. The median total number of hours of nausea per pregnancy in those 292 women experiencing symptoms was 56, with peak symptoms occurring in the ninth week. Eighty five per cent of women experienced days with two episodes of nausea. Fifty three per cent of episodes of vomiting occurred between 06.00 hours and 12.00 hours. The symptom complex can be defined as episodic daytime pregnancy sickness. Among the study population, 206 women were in paid employment. Seventy three of these women (35%) spent a mean of 62 hours away from their paid work because of symptoms of nausea and vomiting, showing the socioeconomic significance of this condition. The detailed information gathered should help in the investigation of the aetiology of nausea and vomiting during pregnancy.

The 43-kilodalton N-terminal fragment of the DNA gyrase B protein hydrolyzes ATP and binds coumarin drugs

Abstract: We have cloned and overexpressed a gene encoding a 43-kDa protein corresponding to the N-terminal fragment of the DNA gyrase B subunit. We show that this protein hydrolyzes ATP and binds coumarin drugs. The hydrolysis of ATP shows distinctly non-Michaelis-Menten kinetics and is consistent with a scheme in which the active form of the protein is a dimer, a conclusion supported by molecular weight studies. The coumarin drugs bind very tightly to the 43-kDa fragment, with novobiocin binding to the protein monomer and coumermycin A1 apparently inducing the formation of a dimer. The implications of these results with respect to the mechanism of supercoiling by DNA gyrase and the inhibition of gyrase by coumarin drugs are discussed.

Comparison of a Hartree, a Hartree-Fock, and an exact treatment of quantum-dot helium.

Abstract: We compare energies, pair correlation functions, and particle densities of the ground state of quantum-dot helium in a magnetic field obtained by a Hartree, a Hartree-Fock (HF), and an exact treatment. The exact and HF results for the triplet state agree well, which illustrates the importance of the exchange interaction for systems of few electrons. The results for the singlet state differ significantly and we show that this is caused by a lack of correlation between the angular momenta of the electrons in the HF approximation.

The interaction between coumarin drugs and DNA gyrase.

Abstract: The coumarin group of antibiotics have as their target the bacterial enzyme DNA gyrase. The drugs bind to the B subunit of gyrase and inhibit DNA supercoiling by blocking the ATPase activity. Recent data show that the binding site for the drugs lies within the N-terminal part of the B protein, and individual amino acids involved in coumarin interaction are being identified. The mode of inhibition of the gyrase ATPase reaction by coumarins is unlikely to be simple competitive inhibition, and the drugs may act by stabilizing a conformation of the enzyme with low affinity for ATP.

A single point mutation in the DNA gyrase A protein greatly reduces binding of fluoroquinolones to the gyrase-DNA complex.

Abstract: Binding of the quinolone drug norfloxacin to gyrase and DNA has been investigated. We have detected binding to gyrase-DNA complex but find no significant binding to either gyrase or DNA alone. Enzyme containing gyrase A protein with the mutation Ser-83 to Trp (conferring quinolone resistance) showed greatly reduced drug binding.

Making Sense of Emotion in Stories and Social Life

Abstract: This paper is concerned with some limitations of the vignette methodology used in contemporary appraisal research and their implications for appraisal theory. We focus on two recent studies in which emotional manipulations were achieved using textual materials, and criticise the investigators' apparent implicit assumption that participation in everyday social reality is somehow comparable to reading a story. We take issue with three related aspects of this cognitive analogy between life and its narrative representation, by arguing that emotional reactions in real life are not necessarily mediated by symbolic processes, that people are involved participants of real life rather than neutral observers, and that in real life people's evaluations and emotions are typically part of an ongoing dialogue rather than the expression of a soliloquy. Results from these studies of emotional vignettes therefore tend to overestimate the importance of constructive, abstract, and individualistic processes in the everyday causation of social emotions. In real life, people do not necessarily have to calculate, transform, or internally represent the meaning of the dynamic situation in order to make emotional sense of what is happening to them in the social world.

Subtyping of panic disorder by symptom profile.

Abstract: During Phase II of the Cross-National Panic Study, descriptions of the patient's last severe panic attack were collected for 1168 patients. Statistical analysis indicated that patients could be divided into two groups, characterised by the presence or absence of prominent respiratory symptoms. The two groups did not differ on demographic variables or coexisting diagnoses, but they did differ on psychopathology on entry to the study and treatment outcome. The group with prominent respiratory symptoms suffered more spontaneous panic attacks and responded to imipramine, whereas the group without prominent respiratory symptoms suffered more situational panic attacks and responded more to alprazolam. It is important to distinguish spontaneous and situational panic attacks, to aid choice of treatment.

Rules, Reputation and Macroeconomic Policy Coordination

Abstract: Introduction Part I. General Issues: 1. Macroeconomic policy design and control theory - a failed partnership? 2. International policy coordination - a survey 3. The European road to monetary union Part II. Theory and Methodology: 4. The design of feedback rules in linear stochastic rational expectations models 5. Credibility and time consistency in a stochastic world 6. Should rules be simple? 7. Macroeconomic policy design using large econometric rational expectations models Part III. Fiscal and monetary policy in interdependent economies: 8. Macroeconomic policy design in an interdependent world 9. Does international macroeconomic policy coordination pay and is it sustainable?: a two-country analysis 10. International cooperation and reputation in an empirical two-bloc model 11. Fiscal policy coordination, inflation and reputation in a natural rate world 12. The use of simple rules for international policy coordination 13. Evaluating the extended target zone proposal for the G3 Bibliography Index.

Confocal immunofluorescence localization of collagen types I, III, IV, V and VI and their ultrastructural organization in term human fetal membranes

Abstract: The distribution of collagen types I, III, IV, V and VI in term human fetal membranes was examined using conventional and confocal indirect immunofluorescence techniques. Collagens I and III were present in most of the layers of fetal membranes except in the trophoblast layer contrary to what has been previously reported. Although collagen IV is considered to be a basement membrane component our study, using monoclonal and polyclonal antibodies, showed its consistent presence in the spongy and reticular layers in high intensity. This was first report on the distribution of type V collagen in the chorion where it was found in the reticular and in the trophoblast layers. Type VI collagen was present mainly in the amnion and the reticular layer. The ultrastructural examination of the extracellular matrix showed that the main fibrous skeleton of the fetal membranes was formed of large banded fibres (Ultrastructurally identical to collagens types I and III) connected together and to the epithelial basement membranes by networks of unbanded filaments (collagen types V, VI and other components). The extensive and continuous networks formed by these collagens may be a major factor responsible for the mechanical integrity of the fetal membranes.

Adenosine-activated potassium current in smooth muscle cells isolated from the pig coronary artery.

Abstract: 1. The perforated patch technique with nystatin or amphotericin was used to record whole cell currents activated by adenosine in smooth muscle cells isolated enzymatically from pig coronary arteries. 2. Adenosine (5-40 microM) activated an outward current at a holding potential of 0 mV in 5 mM [K+]o and an inward current at -60 mV in 143 mM [K+]o. The dependence of the reversal potential for the adenosine-activated current on [K+]o suggests that it flows through K+ channels, while its current-voltage relation is consistent with the channels showing little voltage dependence. 3. The adenosine-activated current was inhibited by the sulphonylurea glibenclamide (5 microM) and by phencyclidine (5 microM). It was unaffected by charybdotoxin (50 nM) or apamin (100 nM), blockers of large and small conductance Ca(2+)-activated K+ channels respectively. 4. At -60 mV in 143 mM K+ solution, openings of single channels passing a current of just over -2 pA could sometimes be detected in the absence of adenosine. Openings became more frequent after the application of adenosine, with several levels then being detected. Openings of channels with a larger conductance were sometimes also seen in the presence of adenosine. Fluctuation analysis gave somewhat lower estimates of unitary current than did direct measurements. 5. The effect of adenosine could be mimicked by the A1 receptor agonist CCPA (2-chloro-N6-cyclopentyladenosine), while the A2 agonist CGS 21680 (2-p-(2-carboxethyl)phenethylamino-5'-N-ethylcarboxamido adenosine hydrochloride) was without effect. The response to adenosine was inhibited by the A1 antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine), but was unaffected by the A2 antagonist CGS 15943A (5-amino-9-chloro-2-(2-furanyl)-1,2,4- triazolo[1,5-C]quinazoline monomethanesulphonate). 6. Our results suggest that adenosine acts at an A1 receptor to activate K+ channels. We consider it most likely that these are ATP-dependent K+ channels. We discuss the mechanism by which K+ channel activation may lead to hyperpolarization and so vasorelaxation.

Pathways for selection of 5' splice sites by U1 snRNPs and SF2/ASF

Abstract: We have used protection against ribonuclease H to investigate the mechanisms by which U1 small nuclear ribonucleoprotein particles (snRNPs) determine the use of two alternative 5' splice sites. The initial binding of U1 snRNPs to alternative consensus splice sites was indiscriminate, and on a high proportion of pre-mRNA molecules both sites were occupied simultaneously. When the sites were close, this inhibited splicing. We propose that double occupancy leads to the use of the downstream site for splicing and that this is the cause of the proximity effect seen with strong alternative splice sites. This model predicts that splicing to an upstream site of any strength requires a low affinity of U1 snRNPs for the downstream site. This prediction was tested both by cleaving the 5' end of U1 snRNA and by altering the sequence of the downstream site of an adenovirus E1A gene. The enhancement of downstream 5' splice site use by splicing factor SF2/ASF appears to be mediated by an increase in the strength of U1 snRNP binding to all sites indiscriminately.

Phosphatization of soft-tissue in experiments and fossils

Abstract: Soft-tissues phosphatized in laboratory experiments closely resemble fossil phosphatized soft-tissues, indicating that similar processes were involved. The smaller the aggregations of calcium phosphate particles precipitated the greater the fidelity of morphological preservation. The highest fidelity occurs where the bacteria themselves are not replicated even though precipitation is bacterially induced. While extensive phosphatization of larger carcasses, however, may necessitate the build-up of concentrations in the sediment beforehand, this is not the case for phosphatization of small quantities of soft-tissue. Mineralization of soft-tissue in the laboratory is not ‘instant’ but may take several weeks, or even months if decay is inhibited. The precipitation of associated calcium carbonate is controlled by shifts in pH in response to the decay process.

The Impact of Acquired Hearing Impairment on Intimate Relationships: Implications for Rehabilitation

Abstract: Hearing disabilities, due to their interactive nature, strongly affect intimate relationships. This paper reviews the literature on this dimension of the experience of hearing impairment. The effects of progressive hearing loss and of the coping process within the couple are examined borrowing concepts from symbolic interaction theory. A summary of the interactive dimensions of the effects of hearing impairment on the couple is drawn from the relevant studies. Specific needs have been identified for each partner in terms of information, support and communication facilitation. Implications are drawn for the audiological rehabilitation of hearing-impaired adults.

Algorithm and implementation uncertainty in viewshed analysis

Abstract: In most documentation of geographical information systems (GIS) it is very rare to find details of the algorithms used in the software, but alternative formulations of the same process may derive different results. In this research several alternatives in the design of viewshed algorithms are explored. Three major features of viewshed algorithms are examined: how elevations in the digital elevation model are inferred, how viewpoint and target are represented, and the mathematical formulation of the comparison. It is found that the second of these produces the greatest variability in the viewable area (up to 50 per cent over the mean viewable area), while the last gives the least. The same test data are run in a number of different GIS implementations of the viewshed operation, and smaller, but still considerable, variability in the viewable area is observed. The study highlights three issues: the need for standards and/or empirical benchmark datasets for GIS functions; the desirability of publica...

Differential gene expression in nematode‐induced feeding structures of transgenic plants harbouring promoter—gusA fusion constructs

Abstract: Sedentary plant-parasitic nematodes are able to induce specialized feeding structures in the root system of their host plants by triggering a series of dramatic cellular responses. These changes presumably are accompanied by a reprogramming of gene expression. To monitor such changes, a variety of promoter-gusA fusion constructs were introduced into Arabidopsis and tobacco. Transgenic plants were analysed histochemically for GUS activity in the nematode feeding structures after infection with either Heterodera schachtii or Meloidogyne incognita. Promoters of the Cauliflower Mosaic Virus 35S gene, the bacterial nopaline synthase, rooting loci (rol) and T-cyt genes and the plant-derived phenylalanine ammonia-lyase I gene, which are highly active in non-infected roots, were all downregulated in the feeding structures as indicated by the strong decrease of GUS activity inside these structures. Less stringent downregulation was observed with chimeric gusA fusion constructs harbouring truncated rolB and rolC promoter sequences. Similar observations were made with transgenic Arabidopsis lines that carried randomly integrated promoterless gusA constructs to identify regulatory sequences in the plant genome. Most of the lines that were selected for expression in the root vascular cylinder demonstrated local downregulation in feeding structures after infection with H. schachtii. The reverse pattern of GUS activity, a blue feeding structure amidst unstained root cells, was also found in several lines. However, GUS activity that was entirely specific for the feeding structures was not observed. Our data show that the expression of a large number of genes is influenced during the development of the nematode feeding structures.

Mouse minisatellite mutations induced by ionizing radiation

Abstract: The detection of changes in germline mutation rate in human populations remains extremely difficult. Estimating the genetic hazards of radiation and other mutagens in humans therefore depends on extrapolation from experimental systems. Because of the very low frequency of spontaneous mutation at most loci, enormous samples are required to detect increases of mutation rate. A very high rate of spontaneous germline mutation altering the length of minisatellite loci has been found in human populations and therefore this system might be useful for detecting induced mutations in relatively small samples. Here we present evidence that minisatellite mutation rate in mice is increased by low doses of ionizing radiation.

Secretion of a functional single-chain Fv protein in transgenic tobacco plants and cell suspension cultures.

Abstract: A synthetic gene encoding an anti-phytochrome single-chain Fv (scFv) antibody bearing an N-terminal signal peptide has been used to transform tobacco plants. Immunoblot analysis showed that transformed plants accumulate high levels of scFv protein, accounting for up to 0.5% of the total soluble protein fraction, which could be extracted by simple infiltration and centrifugation of leaf tissue. A substantial proportion of the scFv protein extracted in this way was found to possess antigen-binding activity. Callus cell suspension cultures derived from transformed plants secrete functional scFv protein into the surrounding medium. Compared with the levels of scFv protein observed in plants expressing the native scFv gene, the incorporation of an N-terminal signal peptide, to target the scFv to the apoplast, results in elevated accumulation of the protein.

Proterozoic anorogenic magmatism and its orogenic connections

Abstract: There is a major belt of Proterozoic, so-called anorogenic, igneous rocks that extends from the Baltic Shield through southern Greenland and eastern Canada to southern USA. All rocks are situated within a zone of 1.9-1.6 Ga arc-accretionary orogens that consist of juvenile mantle-derived material especially accretionary prism sediments that provided the fertile source for abundant granitic crustal melts. There were two main periods of formation of the anorogenic rocks. 1.76-1.55 Ga rocks are mainly rapakivi granites and rhyolites that formed about 60-200 Ma after the last compressional events in the Svecofennian, Ketilidian and Penokean orogens, the time-lag being caused by the slow thermal relaxation of thickened lower crust that had commonly been depleted by the extraction of earlier granitic crustal melts. 1.45-1.4 Ga anorogenic rocks are mainly rhyolites and peraluminous granites in central/southern USA and anorthosites in eastern Canada that formed in the continental margin of the Grenvillian ocean, the subduction of which led to the Grenville orogen. These anorogenic igneous rocks formed in extensional regimes during the formation and breakup of a 1.5 Ga supercontinent.

Intra-articular fractures of the calcaneum treated operatively or conservatively. A prospective study

Abstract: We report a prospective trial of 66 patients with intraarticular fractures of the calcaneum. All fractures were assessed by CT. Patients with displaced fractures were randomised to receive either conservative (n = 31) or operative treatment (n = 25). Undisplaced fractures (n = 10) were treated conservatively. Operation involved open reduction of the posterior subtalar joint, and fixation with Kirschner wires. All 66 patients were reviewed at a minimum of one year (mean 23 months). After conservative treatment the undisplaced fractures had slightly better results than the displaced fractures. There was no significant difference in outcome between the operatively and the conservatively treated displaced fractures. We have also documented prospectively the natural history of the injury, which is of use in assessing prognosis for both clinical and medicolegal purposes.

The binaural auditory pathway: excitatory amino acid receptors mediate dual timecourse excitatory postsynaptic currents in the rat medial nucleus of the trapezoid body.

Abstract: We show here that synaptic transmission to the medial nucleus of the trapezoid body (MNTB) is mediated principally by excitatory amino acid receptors and has two components. A fast excitatory postsynaptic current (EPSC) is mediated by non-NMDA receptors and a slow EPSC is mediated by NMDA receptors. Each neuron receives a large synaptic input (calyx of Held) which produces an EPSC with a mean peak conductance of 37 nS. The somatic location of this synapse gives good resolution of the EPSC timecourse with the fast EPSC decaying with a time constant of 1.1 ms (at 25 degrees C). The slow EPSC exhibits a double exponential decay with time constants of 41 ms and 106 ms and is voltage dependent in the presence of extracellular magnesium. Other smaller EPSCS mediated by NMDA and non-NMDA receptors, and a strychnine-sensitive synaptic current, are also present. Although the intrinsic membrane properties of MNTB neurons (Forsythe & Barnes-Davies (Proc. R. Soc. Lond. B 251, 143 (1993)), preceding paper) promote high-fidelity transmission, we show that voltage-dependent modulation of synaptic transmission can occur. Given the specialization of the calyx of Held, it seems that the NMDA-receptor ion channel complex is not primarily serving to potentiate a subthreshold input, but may be involved in the development and maintenance of this exuberant somatic synapse.