Showing papers by "University of Leicester published in 1992"

Development of a shuttle walking test of disability in patients with chronic airways obstruction.

Abstract: BACKGROUND: The aim was to develop a standardised and externally paced field walking test, incorporating an incremental and progressive structure, to assess functional capacity in patients with chronic airways obstruction METHODS: The usefulness of two different shuttle walking test protocols was examined in two separate groups of patients The initial 10 level protocol (group A, n = 10) and a subsequent, modified, 12 level protocol (group B, n = 10) differed in the number of increments and in the speeds of walking Patients performed three shuttle walking tests one week apart Then the performance of patients (group C, n = 15) in the six minute walking test was compared with that in the second (modified) shuttle walking test protocol Heart rate was recorded during all the exercise tests with a short range telemetry device RESULTS: The 12 level modified protocol provided a measure of functional capacity in patients with a wide range of disability and was reproducible after just one practice walk; the mean difference between trial 2 v 3 was -20 (95% CI -219 to 179) m There was a significant relation between the distance walked in the six minute walking test and the shuttle walking test (rho = 068) but the six minute walking test appeared to overestimate the extent of disability in some patients The shuttle test provoked a graded cardiovascular response not evident in the six minute test Moreover, the maximal heart rates attained were significantly higher for the shuttle walking test than for the six minute test CONCLUSIONS: The shuttle walking test constitutes a standardised incremental field walking test that provokes a symptom limited maximal performance It provides an objective measurement of disability and allows direct comparison of patients' performance

Extra-pair paternity results from female preference for high-quality males in the blue tit.

Abstract: EXTRA-PAIR copulations (EPCs) seem to be one of the most widespread alternative reproductive behaviours by which male birds can increase their fitness1,2. In many species females actively solicit or freely engage in EPCs3–5, which suggests that they benefit from them. Of the eight hypothetical benefits proposed2,6, the most likely are genetic2. Often females engage in EPCs with more dominant males3,7 or with males with more elaborate ornaments8,9. In species in which paternity was assigned, extra-pair young were divided asymmetrically between males10–12. Here, combining detailed behavioural work with DNA-fingerprinting of an entire population, we present evidence that such an asymmetry is indeed caused by female behaviour, and that 'attractive' males do not suffer lost paternity, survive better and recruit more young. Our results support the genetic quality hypothesis.

Accretion power in astrophysics.

Abstract: 1. Accretion as a source of energy 2. Gas dynamics 3. Plasma concepts 4. Accretion in binary systems 5. Accretion discs 6. Accretion on to a compact object 7. Active galactic nuclei 8. Accretion discs in active galactic nuclei 9. Accretion power in active galactic nuclei 10. Thick discs 11. Accretion flows.

A highly conserved repeated DNA element located in the chromosome of Streptococcus pneumoniae.

Abstract: We report the discovery of a group of highly conserved DNA sequences located, in those cases studied, within intergenic regions of the chromosome of the Gram positive Streptococcus pneumoniae. The S. pneumoniae genome contains about 25 of these elements called BOX. From 5' to 3', BOX elements are composed of three subunits (boxA, boxB, and boxC) which are 59, 45 and 50 nucleotides long, respectively. BOX elements containing one, two and four copies of boxB have been observed; boxB alone was also detected in one instance. These elements are unrelated to the two most thoroughly documented families of repetitive DNA sequences present in the genomes of enterobacteria. BOX sequences have the potential to form stable stem-loop structures and one of these, at least, is transcribed. Most of these elements are located in the immediate vicinity of genes whose product has been implicated at some stage in the process of genetic transformation or in virulence of S. pneumoniae. This location raises the intriguing possibility that BOX sequences are regulatory elements shared by several coordinately controlled genes, including competence-specific and virulence-related genes.

Quality-Of-Life Assessment: Can We Keep it Simple?

Abstract: The importance of general statistical principles of study design and analysis to quality-of-life assessment in clinical trials is emphasized. Basic methods are reviewed briefly, with reference to three examples. Careful use of standard tools supplemented with context-specific scales is recommended. Problems of weighting and aggregation are discussed; the use of simple weighting schemes supplemented by sensitivity analysis is suggested. Some technical issues are explored, including factorial question structure, components of variance to distinguish mean treatment and patient-specific treatment effects and informative loss to follow-up

Premature dissolution of the microsporocyte callose wall causes male sterility in transgenic tobacco.

Abstract: Male sterility in a petunia cytoplasmic male sterile line has been attributed to the early appearance of active callase, a beta-1,3-glucanase, in the anther locule. This leads to premature dissolution of the callose walls surrounding the microsporogenous cells. We have mimicked this aspect of the petunia line in transgenic tobacco by engineering the secretion of a modified pathogenesis-related vacuolar beta-1,3-glucanase from the tapetum prior to the appearance of callase activity in the locule. Plants expressing the modified glucanase from tapetum-specific promoters exhibited reduced male fertility, ranging from complete to partial male sterility. Callose appearance and distribution are normal in the male sterile transgenic plants up to prophase I, whereupon callose is prematurely degraded. Meiosis and cell division occur normally. The resultant microspores have an abnormally thin cell wall that lacks sculpturing. The tapetum shows hypertrophy. Male sterility is probably caused by bursting of the aberrant microspores at a time corresponding to microspore release. These results demonstrate that premature callose degradation is sufficient to cause male sterility and suggest that callose is essential for the formation of a normal microspore cell wall.

Effect of early intravenous heparin on coronary patency, infarct size, and bleeding complications after alteplase thrombolysis: results of a randomised double blind European Cooperative Study Group trial.

Abstract: OBJECTIVE--To determine whether concomitant treatment with intravenous heparin affects coronary patency and outcome in patients treated with alteplase thrombolysis for acute myocardial infarction. DESIGN--Double blind randomised trial. TREATMENT REGIMENS--Alteplase 100 mg (not weight adjusted) plus aspirin (250 mg intravenously followed by 75-125 mg on alternate days) plus heparin (5000 units intravenously followed by 1000 units hourly without dose adjustment) was compared with alteplase plus aspirin plus placebo for heparin. SETTING--19 cardiac centres in six European countries. SUBJECTS--652 patients aged 21-70 years with clinical and electrocardiographic features of infarcting myocardium in whom thrombolytic therapy could be started within six hours of the onset of major symptoms. MAIN OUTCOME MEASURE--Angiographic coronary patency 48-120 hours after randomisation. RESULTS--Coronary patency (TIMI grades 2 or 3) was 83.4% in the heparin group and 74.7% in the group given placebo for heparin. The relative risk of an occluded vessel in the heparin treated group was 0.66 (95% confidence interval 0.47 to 0.93). Mortality was the same in both groups. There were non-significant trends towards a smaller enzymatic infarct size and a higher incidence of bleeding complications in the group treated with heparin. CONCLUSIONS--Concomitant intravenous heparin improves coronary patency in patients with alteplase. Whether this can be translated into improved clinical benefit needs to be to be tested in a larger trial.

The frequency of uniparental disomy in Prader-Willi syndrome. Implications for molecular diagnosis.

Abstract: Background Prader—Willi syndrome is a genetic disorder characterized by infantile hypotonia, obesity, hypogonadism, and mental retardation, but it is difficult to diagnose clinically in infants and young children In about two thirds of patients, a cytogenetically visible deletion can be detected in the paternally derived chromosome 15 (15q11q13) Recently, patients with Prader—Willi syndrome have been described who do not have the cytogenetic deletion but instead have two copies of the 15q11q13 region that are inherited from the mother (with none inherited from the father) This unusual form of inheritance is known as maternal uniparental disomy Using molecular genetic techniques, we sought to determine the frequency of uniparental disomy in Prader—Willi syndrome Methods We performed molecular analyses using DNA markers within 15q11q13 and elsewhere on chromosome 15 in 30 patients with Prader—Willi syndrome who had no cytogenetically visible deletion We also studied their parents Three pat

Synthesis of a functional anti-phytochrome single-chain Fv protein in transgenic tobacco.

Abstract: We have expressed a synthetic gene that encodes an antigen–binding single–chain Fv protein (scFv) in transgenic tobacco plants. The scFv gene was created by polymerase chain reaction (PCR) amplification of the variable domain coding regions from a mouse monoclonal hybridoma cell line. The monoclonal cell line secretes an IgG1 antibody that binds to the plant regulatory photoreceptor protein, phytochrome. The cloned scFv gene was expressed initially in Escherichia coli and shown to produce a 28 kD, phytochrome–binding scFv protein. Transgenic tobacco plants expressing the scFv gene were also found to produce a functional scFv protein, and seeds from transgenic R1 progeny displayed aberrant phytochrome–dependent germination. The scFv from transgenic tobacco could be isolated, to near homogeneity, by a single phytochrome–Sepharose affinity chromatography step.

The Construction of the Total Alkali-Silica Chemical Classification of Volcanic Rocks*

Abstract: This paper describes the reasoning that lies behind the construction of the field boundaries in the Total Alkali-Silica diagram (TAS) for the chemical classification of volcanic rocks. It shows that by utilizing nomenclature in common use by petrologists in combination with a large computer database of geochemical analytical information derived from the published literature, it was possible to construct a Total Alkali-Silica diagram for volcanic rocks of only 15 fields, which has straight-line boundaries and necessitates the definition of only 11 points to construct the diagram. One of the principal constraints on the positioning of the boundaries between the various named fields was to minimize the degree of overlap between adjacent fields.

Race and ethnicity in health research.

Abstract: 'Race' and 'ethnicity' are increasingly being used as variables in health research. However, studies have been mainly descriptive and have not been used to develop and evaluate strategies to improve health care. In part this reflects the poor analytical standards. The status of the concepts of 'race' and 'ethnicity' as research tools are rarely considered and there is poor consistency in terminology. This paper gives an overview of the research literature and raises questions about the validity of 'race' and 'ethnicity' as epidemiological variables. The tendency to collect routine ethnic data and include ethnic variables in an ad hoc and uncritical way in the United Kingdom and other countries may help transform minorities into mere statistical categories and produce data and findings which reinforce stereotypes. Multiculturalist ethnic health explanations also tend to displace more material explanations of health outcomes. It is concluded that more thought and care is needed before data are routinely categorized by ethnicity, or race or ethnicity are included as variables in research.

Differential Rates of Psychiatric Disorders in Adults with Down's Syndrome Compared with Other Mentally Handicapped Adults

Abstract: The total number of adults with Down's syndrome living in Leicestershire, ascertained by widespread enquiry, was found to be 378. Of these, 371 were matched with adults with mental handicap due to other pathologies, on the basis of age, sex, and type of residence. Those with Down's syndrome were found to have a different spectrum of mental disorders from those without the syndrome. In particular, Down's syndrome patients were more likely to have been diagnosed as having depression and dementia; the controls were more likely to have been diagnosed as suffering from conduct disorder, personality disorder, or schizophrenia/paranoid state. The same proportion of each group had been given a diagnosis of autism.

Properties of cooling flows in a flux-limited sample of clusters of galaxies

Abstract: An analysis of the mass flow rates of cooling flows in an X-ray flux-limited sample of clusters of galaxies, in which most of the clusters have been observed with both imaging and spectroscopic detectors, is presented. Using high-quality images and constraints from broad-band spectra, it is found that the fraction of clusters with central cooling times less than the Hubble time is high (at least 70 per cent and possibly 90 per cent), indicating that cooling flows are a common and long-lived phenomenon. The fraction is higher than found in previous studies, due to our consideration of the effects of the spatial resolution and the signal-to-noise ratio of the images

Analysis of the actin-binding domain of alpha-actinin by mutagenesis and demonstration that dystrophin contains a functionally homologous domain.

Abstract: To define the actin-binding site within the NH2-terminal domain (residues 1-245) of chick smooth muscle alpha-actinin, we expressed a series of alpha-actinin deletion mutants in monkey Cos cells. Mutant alpha-actinins in which residues 2-19, 217-242, and 196-242 were deleted still retained the ability to target to actin filaments and filament ends, suggesting that the actin-binding site is located within residues 20-195. When a truncated alpha-actinin (residues 1-290) was expressed in Cos cells, the protein localized exclusively to filament ends. This activity was retained by a deletion mutant lacking residues 196-242, confirming that these are not essential for actin binding. The actin-binding site in alpha-actinin was further defined by expressing both wild-type and mutant actin-binding domains as fusion proteins in E. coli. Analysis of the ability of such proteins to bind to F-actin in vitro showed that the binding site was located between residues 108 and 189. Using both in vivo and in vitro assays, we have also shown that the sequence KTFT, which is conserved in several members of the alpha-actinin family of actin-binding proteins (residues 36-39 in the chick smooth muscle protein) is not essential for actin binding. Finally, we have established that the NH2-terminal domain of dystrophin is functionally as well as structurally homologous to that in alpha-actinin. Thus, a chimeric protein containing the NH2-terminal region of dystrophin (residues 1-233) fused to alpha-actinin residues 244-888 localized to actin-containing structures when expressed in Cos cells. Furthermore, an E. coli-expressed fusion protein containing dystrophin residues 1-233 was able to bind to F-actin in vitro.

Timing of Cenozoic extensional tectonics in west Turkey

Abstract: The timing of the transition from compressional to extensional tectonics in the late Cenozoic evolution of west Turkey has been constrained by K-Ar geochronology from acidic volcanic rocks and tourmaline leucogranite dykes in the central and east margin respectively of the Gordes basin. Dacites and rhyolites in the centre of the Gordes Neogene sedimentary basin cut both the basement ophiolites of the Izmir-Ankara suture zone and the Neogene sediments. On the basin’s eastern margin the leucogranites cut metamorphic basement along a major NE-SW-trending normal fault that controls the regional structure of the basin. Pebbles of these leucogranites occur in adjacent Neogene turfites and conglomerates. K-Ar dates on biotites from the central volcanic rocks vary from 18.4 ± 0.8 Ma to 16.3 + 0.5 Ma (early Miocene) whilst muscovite from a leucogranite on the eastern margin of the basin provides ages of 24.2 ± 0.8 Ma and 21.1 ± 1.1 Ma (latest Oligocene to early Miocene). Geochronological data and field relationships demonstrate that the earlier compressional regime had been replaced by extensional tectonics by latest Oligocene-early Miocene.

Differentiated Caco-2 cells as a model for enteric invasion by Campylobacter jejuni and C. coli.

Abstract: A collection of 44 Campylobacter isolates (37 C. jejuni and seven C. coli) from children with colitis (21 strains) or watery diarrhoea (23 strains) was analysed for toxin production, association with HeLa cells, and invasion of differentiated Caco-2 cell cultures. There was no obvious association of clinical symptoms with species, biotype or enterotoxin production. All colitis strains and most of the isolates from watery diarrhoea were cytotoxic for Chinese hamster ovary cells. Measurements of bacterial association indices with HeLa cells varied with time, and were considered to be unreliable for discriminating between isolates from the two diagnostic groups. Statistically significant differences were observed between the two groups (all colitis strains and 65% of strains from non-inflammatory diarrhoea) with respect to invasion of both HeLa and Caco-2 cell monolayers. However, among the strains from non-inflammatory diarrhoea that did invade, numbers of internalised bacteria were similar to the range observed for colitis strains. Of the colitis strains, 86% were able to transcytose through polarised Caco-2 monolayers grown on filters, compared with 48% of isolates from non-inflammatory disease. We propose the use of Caco-2 cells as a model for studying invasion of intestinal epithelia by C. jejuni and C. coli.

Clinical features of influenza

Abstract: Influenza, an acute, usually self-limited, febrile illness of global importance, appears virtually every year and infects the respiratory tract either sporadically, as a local outbreak, or as a widespread epidemic. The most severe outbreak known, the 1918 to 1919 influenza A pandemic, was responsible for an estimated 20 million deaths globally. In the United States, the influenza pandemics of 1957 and 1968 were associated with an attack rate of up to 50% and an estimated 100,000 deaths. Interpandemic influenza is responsible for considerable morbidity and mortality, which exceed that associated with the introduction of the pandemic strain. Influenza B infections resemble those due to influenza A, but are associated with fewer deaths. Features of influenza include headache, myalgia, malaise, anorexia, sore throat, nonproductive cough, sneezing, and nasal discharge; these symptoms are not pathognomic for influenza, and asymptomatic infection can occur. The pulmonary complications of influenza include pneumonia (viral and bacterial), croup, asthma, and bronchitis. Myocarditis and pericarditis are occasional cardiac complications. In addition to Reye's syndrome, a range of neurologic complications have been noted, including confusion, convulsions, psychosis, neuritis, Guillain-Barre syndrome, coma, transverse myelitis, and encephalomyelitis. Influenza has also been associated with the toxic shock syndrome, myositis, myoglobinuria, and renal failure. In view of its enormous human and economic toll, influenza remains a major target for improved vaccines and vaccine delivery, and antiviral treatment and prophylaxis.

The effect of a five-month delay on children's and adults' eyewitness memory.

Abstract: Child witnesses must endure a delay of around six months between observing or being the victim of an alleged offence and being required to give evidence in a criminal court. While the legal profession seem to believe that young children's memories are particularly sensitive to the passage of time, developmental psychology can offer little relevant data to support or refute this presumption. In the present study, children aged six and nine years and adults witnessed a staged event and were subsequently interviewed in the days following the event and/or five months later. Results indicate that while all witnesses forgot information over this period, the younger children (six years) recalled slightly less information than the older children and the adults. The total amount of incorrect information recalled did not increase over the same period. Two different interviewing techniques were used--cued recall vs. 'enhanced' recall--the latter incorporating some aspects of the cognitive interview procedure. No differences were found relating to the interview techniques employed. The results underline the importance of recording initial interviews with child witnesses wherever possible.

Crystal structure of a streptococcal protein G domain bound to an Fab fragment.

Abstract: Protein G is a cell-surface protein from Streptococcus which binds to IgG molecules from a wide range of species with an affinity comparable to that of antigen. The high affinity of protein G for the Fab portion of IgG poses a particular challenge in molecular recognition, given the variability of heavy chain subclass, light chain type and complementarity-determining regions. Here we report the crystal structure of a complex between a protein G domain and an immunoglobulin Fab fragment. An outer beta-strand in the protein G domain forms an antiparallel interaction with the last beta-strand in the constant heavy chain domain of the immunoglobulin, thus extending the beta-sheet into the protein G. The interaction between secondary structural elements in Fab and protein G provides an ingenious solution to the problem of maintaining a high affinity for many different IgG molecules. The structure also contrasts with Fab-antigen complexes, in which all contacts with antigen are mediated by the variable regions of the antibody, and to our knowledge provides the first details of interaction of the constant regions of Fab with another protein.

Hyperplane design techniques for discrete-time variable structure control systems

Abstract: The design of variable structure control schemes for uncertain discrete-time systems is considered. Previous work in this area which parallels the discrete-time sliding mode philosophy with that for the continuous-time case is reviewed. Theoretical results are presented which indicate that such a parallel approach is not necessarily desirable. A novel design methodology for discrete-time variable structure control systems is then formulated. A numerical example is given to illustrate the results described.

Quantitative analysis of the geometry of submarine channels: Implications for the classification of submarine fans

Abstract: Certain attributes of submarine channels measured from GLORIA sidescan sonar data from 16 different submarine fans indicate similarities with fluviatile systems. Channel width, depth, meander radius and wavelength, sinuosity, and gradient were measured. This approach makes it possible to identify high- sinuosity, low-gradient (e.g., Indus Fan channels) and low-sinuosity, high- gradient (e.g., Porcupine Seabight channels) channel systems as end members. Current classifications of submarine fans relate fan shape to grain size or sediment caliber and therefore are inadequate, principally because the shape of the fan is strongly controlled by the shape of the receiving basin, which in turn is dependent upon parameters such as tectonics and diapirism. Overall fan shape is almost invariably independent of the physics of sediment transport. Rather than fan shape, the geometry and other characteristics of submarine channels and canyons provide a more promising means of differentiating deep- marine turbidite systems.

A Latitudinal Cline in a Drosophila Clock Gene

Abstract: The clock gene period determines biological rhythmicity in Drosophila melanogaster and encodes a protein characterized by an alternating series of threonine-glycine pairs The minisatellite region encoding the threonine-glycine repeat is polymorphic in length in natural Drosophila melanogaster populations In this paper we report the geographical analysis of this polymorphism within Europe and North Africa A robust clinal pattern is observed along a north-south axis We suggest the possibility that the length polymorphism could be maintained by thermal selection because the threonine-glycine region has been shown to provide thermostability to the circadian phenotype

Effect of electron-electron interactions on the magnetization of quantum dots.

Abstract: The low-temperature magnetization of parabolic quantum dots is calculated and is shown to be a sensitive probe of interaction effects. The interaction causes the ground state to occur at certain magic values of the total angular momentum, the strength of the magnetic field determining which of them is selected. Increasing the mangetic field causes the ground-state angular momentum to jump from one magic value to another and this causes the discontinuities in the magnetization. The effects of spin lead to extra discontinuities at low magnetic field. The magic angular momenta for the spin-polarized case are derived by a simple physical argument.

The isolation and characterisation of the tapetum-specific Arabidopsis thaliana A9 gene.

Abstract: The Brassica napus cDNA clone A9 and the corresponding Arabidopsis thaliana gene have been sequenced. The B. napus cDNA and the A. thaliana gene encode proteins that are 73% identical and are predicted to be 10.3 kDa and 11.6 kDa in size respectively. Fusions of an RNase gene and the reporter gene β-glucuronidase to the A. thaliana A9 promoter demonstrated that in tobacco the A9 promoter is active solely in tapetal cells. Promoter activity is first detectable in anthers prior to sporogenous cell meiosis and ceases during microspore premitotic interphase. The deduced A9 protein sequence has a pattern of cysteine residues that is present in a superfamily of seed plant proteins which contains seed storage proteins and several protease and α-amylase inhibitors.