Showing papers by "University of Leicester published in 1987"

The closing of Tethys and the tectonics of the Himalaya

Abstract: Recent geological and geophysical data from southern Tibet allow refinement of models for the closing of southern (Neo-) Tethys and formation of the Himalaya. Shelf sediments of the Indian passive continental margin which pass northward into deep-sea Tethyan sediments of the Indus-Tsangpo suture zone were deposited in the Late Cretaceous. An Andean-type margin with a 2,500-km-long Trans-Himalayan (Kohistan-Ladakh-Gangdese) granitoid batholith formed parallel to the southern margin of the Lhasa block, together with extensive andesites, rhyolites, and ignimbrites (Lingzizong Formation). The southern part of the Lhasa block was uplifted, deformed, and eroded between the Cenomanian and the Eocene. In the western Himalaya, the Kohistan island arc became accreted to the northern plate at this time. The northern part of the Lhasa block was affected by Jurassic metamorphism and plutonism associated with the mid-Jurassic closure of the Bangong-Nujiang suture zone to the north. The timing of collision between the two continental plates (ca. 50-40 Ma) marking the closing of Tethys is shown by (1) the change from marine (flysch-like) to continental (molasse-like) sedimentation in the Indus-Tsangpo suture zone, (2) the end of Gangdese I-type granitoid injection, (3) Eocene S-type anatectic granites and migmatites in the Lhasa block, and (4) the start of compressional tectonics in the Tibetan-Tethys and Indus-Tsangpo suture zone (south-facing folds, south-directed thrusts). After the Eocene closure of Tethys, deformation spread southward across the Tibetan-Tethys zone to the High Himalaya. Deep crustal thrusting, Barrovian metamorphism, migmatization, and generation of Oligocene-Miocene leucogranites were accompanied by south-verging recumbent nappes inverting metamorphic isograds and by south-directed intracontinental shear zones associated with the Main Central thrust. Continued convergence in the late Tertiary resulted in large-scale north-directed backthrusting along the Indus-Tsangpo suture zone. More than 500 km shortening is recorded in the foreland thrust zones of the Indian plate, south of the suture, and > 150 km shortening is recorded across the Indian shelf (Zanskar Range) and the Indus suture in Ladakh. There was also large-scale shortening of the Karakoram and Tibetan microplates north of the suture; as much as 1,000 km shortening occurred in Tibet. The more recent deformation, however, involved the spreading of this thickened crust and the lateral motion of the Tibetan block along major approximately east-west–trending strike-slip fault zones.

Cardiovascular and catecholamine responses to laryngoscopy with and without tracheal intubation

Abstract: The catecholamine and cardiovascular responses to laryngoscopy alone have been compared with those following laryngoscopy and intubation in 24 patients allocated randomly to each group. Following induction with fentanyl and thio-pentone, atracurium was administered and artificial ventilation undertaken via a face mask for 2 min with 67% nitrous oxide in oxygen. Following laryngoscopy, the vocal cords were visualized for 10 s. In one group of patients, ventilation was then re-instituted via a face mask, while in the second group the trachea was intubated during the 10-s period and ventilation of the lungs maintained. Arterial pressure, heart rate and plasma noradrenaline and adrenaline concentrations were measured before and after induction and at 1, 3 and 5 min after laryngoscopy. There were significant and similar increases in arterial pressure and circulating catecholamine concentrations following laryngoscopy with or without intubation. Intubation, however, was associated with significant increases in heart rate which did not occur in the laryngoscopy-only group.

Chromosome 5 allele loss in human colorectal carcinomas.

Abstract: That the sporadic and inherited forms of a particular cancer could both result from mutations in the same gene was first proposed by Knudson. He further proposed that these mutations act recessively at the cellular level, and that both copies of the gene must be lost for the cancer to develop. In sporadic cases both events occur somatically whereas in dominant familial cases susceptibility is inherited through a germline mutation and the cancer develops after a somatic change in the homologous allele. This model has since been substantiated in the case of retinoblastoma, Wilms tumour, acoustic neuroma and several other tumours, in which loss of heterozygosity was shown in tumour material compared to normal tissue from the same patient. The dominantly inherited disorder, familial adenomatous polyposis (FAP, also called familial polyposis coli), which gives rise to multiple adenomatous polyps in the colon that have a relatively high probability of progressing to a malignant adenocarcinoma, provides a basis for studying recessive genes in the far more common colorectal carcinomas using this approach. Following a clue as to the location of the FAP gene given by a case report of an individual with an interstitial deletion of chromosome 5q, who had FAP and multiple developmental abnormalities, we have examined sporadic colorectal adenocarcinomas for loss of alleles on chromosome 5. Using a highly polymorphic 'minisatellite' probe which maps to chromosome 5q we have shown that at least 20% of this highly heterogeneous set of tumours lose one of the alleles present in matched normal tissue. This parallels the assignment of the FAP gene to chromosome 5 (see accompanying paper) and suggests that becoming recessive for this gene may be a critical step in the progression of a relatively high proportion of colorectal cancers.

Estimation and Inference by Compact Coding

Abstract: SUMMARY The systematic variation within a set of data, as represented by a usual statistical model, may be used to encode the data in a more compact form than would be possible if they were considered to be purely random. The encoded form has two parts. The first states the inferred estimates of the unknown parameters in the model, the second states the data using an optimal code based on the data probability distribution implied by those parameter estimates. Choosing the model and the estimates that give the most compact coding leads to an interesting general inference procedure. In its strict form it has great generality and several nice properties but is computationally infeasible. An approximate form is developed and its relation to other methods is explored.

DNA fingerprinting in birds.

Abstract: Several regions of the human genome are highly variable in populations because the number of repeats in these regions of a short 'minisatellite' sequence varies at high frequency. Different minisatellites have a core sequence1,2 in common, however, and probes made up of tandem repeats of this core sequence detect many highly variable DNA fragments in several species including humans1,3, cats4, dogs4 and mice5. The hypervariable sequences detected in this way are dispersed in the genome and their variability means that they can be used as a DNA 'fingerprint', providing a novel method for the identification of individuals2,6, confirmation of biological relationships7,8 and human genetic analysis9,10. We show here that human minisatellite-derived probes also detect highly variable regions in bird DNAs. Segregation analysis in a house sparrow family confirms that these regions comprise many mostly heterozygous dispersed loci and we conclude that house sparrow DNA fingerprints are analagous to those of humans. Fingerprint analysis identified one nestling, with fingerprint bands not present in the parent pair's fingerprints, which we conclude resulted from an extrapair copulation. Extrabond copulations have been described in many wild bird species11–13, but their success and hence adaptive significance have rarely been quantifiable14–20. DNA fingerprinting will be of great significance to studies of the sociobiology, demography and ecology of wild birds.

Characterization of a panel of highly variable minisatellites cloned from human DNA.

Abstract: Summary Five of the most variable loci detected in human DNA by hybridization with DNA fingerprint probes have been cloned and characterized. Each locus consists of a tandem-repetitive minisatellite, with repeat units ranging in length from 9 to 45 base pairs depending on the locus. All of these cloned minisatellites act as locus-specific hybridization probes, and detect extremely variable Mendelian loci with heterozygosities ranging from 90 to 99%. These five hypervariable loci, together with a previously-isolated minisatellite designated pΛg3, are dispersed over four autosomes (chromosomes 1, 5, 7 and 12). Syntenic pairs on chromosomes 1 and 7 show no detectable pair-wise linkage, and thus these hypervariable loci show no evidence of clustering within the genome and should provide valuable markers for mapping inherited disease. The locus-specific minisatellites act as very sensitive hybridization probes, and can be pooled to detect several hypervariable loci simultaneously. The applications of these probes in individual identification, paternity testing and analysis of cell chimaerism are discussed, and are illustrated by an analysis of forensic specimens from two victims who had been sexually assaulted and murdered. We are very grateful to Professor J. Dausset and Dr H. Cann at the Human Polymorphism Study Centre, Paris. for the generous provision of DNA samples from the panel of CEPH families, to Dr Mary Davis for providing DNA from the JDA hybrids, and also to the following people who kindly allowed us to use their hybrids. Dr Ellen Solomon. Dr Nigel Spurr. Dr P. Goodfellow, Dr Denise Sheer, Dr John Cowell and Dr Ben Carritt. We also thank Anabel Kearney who did the enzyme analysis on the hybrids, and Lynne West who did the karyotyping. We are also grateful to the Leicestershire Constabulary for their permission to cite details of the forensic analysis. A.J.J. is a Lister Institute Research Fellow, and this work was supported by a grant to A.J.J. from the Medical Research Council. The minisatellite probes are the subject of Patent Applications, and commercial enquiries should be addressed to the Lister Institute of Preventive Medicine, Brockley Hill, Stanmore. Middlesex, H A7 4JD, U.K.

Alterations to either c-erbB-2(neu) or c-myc proto-oncogenes in breast carcinomas correlate with poor short-term prognosis.

Abstract: We have examined the genomic organisation of c-myc, N-myc, L-myc, neu and N-ras in tissue from 41 breast carcinomas, lymph node metastases from 10 of these carcinomas, one fibrosarcoma, 10 cases of benign fibrocystic breast and six fibroadenomas. We have not observed an alteration in either N-myc or N-ras in any of the samples studied. We have seen a 2-fold amplification of L=myc in DNA from one infiltrating ductal (ID) carcinoma, but otherwise we have seen no alterations to this gene. Amplification of c-myc was seen in 22% of ID breast carcinoma sample. Levels of amplification ranged from 2- to 10-fold. We have found a significant (p less than 0.02) correlation between an altered c-myc gene and a very poor short-term prognosis. Amplification of neu was seen in 19% of ID breast carcinomas, but the levels of amplification were higher than those seen for c-myc. Alterations to neu also correlated well with poor short-term prognosis (p less than 0.0002). Finally, we have observed a low level of amplification of c-myc in DNA from a benign fibrocystic breast lesion. This lesion exhibited some features characteristic of those thought to be associated with an increased risk of developing breast cancer.

Candida Infections: An Overview

Abstract: The range of human infections caused by the yeast Candida albicans and a handful of related species is considerable. They range from relatively trivial conditions such as oral and genital thrush to fatal, systemic superinfections in patients who are already seriously ill with other diseases. Interest in Candida infections, and in C. albicans in particular, has become huge in recent years as fatal infections have become more prevalent and new Candida-based pathologies have been recognized. There is now even a large pseudoscientific cult based on the notion that chronic allergy to Candida can cause all sorts of common illnesses. The medical importance of Candida infections and the scientific value of C. albicans as a model for fungal cellular development have stimulated enormous advances in our understanding of the epidemiology of candidosis, pathogenesis of the disease, and the genetics and biochemistry of C. albicans.

Geochemistry of Cenezoic volcanic rocks, Baja California, Mexico: Implications for the petrogenesis of post-subduction magmas

Abstract: Late Cenozoic volcanism in Baja California records the effects of cessation of subduction at a previously convergent, plate margin. Prior to 12.5 m.y., when subduction along the margin of Baja ceased, the predominant volcanic activity had a calc-alkaline signature, ranging in composition from basalt to rhyolite. Acidic pyroclastic activity was common, and possibly represented the westermost, distal edge of the Sierra Madre Occidental province. After 12.5 m.y., however, the style and composition of the magmatic products changed dramatically. The dominant rock type within the Jaraguay and San Borja volcanic fields is a magnesian andesite, with up to 8% MgO at 57% SiO2, low Fe/Mg ratios, and high Na/K ratios. These rocks have unusual trace-element characteristics, with high abundances of Sr (up to 3000 ppm), low contents of Rb; K/Rb ratios are very high (usually over 1000, and up to 2500), and Rb/Sr ratios are low (less than 0.01). Furthermore, Lan/Ybn ratios are high, consistent with derivation from a mantle source with fractionated REE patterns. 87Sr/86Sr ratios are less than 0.7048, and usually less than 0.7040, whereas the pre-12.5 m.y. lavas have 87Sr/86Sr ratios between 0.7038 and 0.7063. We have previously termed these rocks bajaites, in order to distinguish them from other magnesian andesites. Bajaites also occur in southernmost Chile and the Aleutian Islands, areas which also have histories of attempted or successful ridge subduction. It is proposed that the bajaite series is produced during the unusual physico-chemical conditions operating during the subduction of young oceanic lithosphere, or subduction of a spreading centre. During normal subduction, the oceanic crust dehydrates, releasing volatiles (water, Rb and other large-ion lithophile elements) into the overlying wedge. Subduction of younger crust will result in a progressive decrease, and eventual cessation of the transfer of volatiles when subduction stops. Thermal rebound of the mantle may cause the slab to melt, perhaps under eclogitestable conditions. The resulting melt will be heavy-REE-depleted, perhaps dacitic, but will otherwise inherit MORB-like Rb/Sr and K/Rb ratios. The ascending melt will react with the mantle to form the source of the bajaitic rocks. Furthermore, any amphibole in the mantle, stabilised during the higher PH2O conditions of earlier subduction, will break down and contribute a high-K/Rb ratio component. The implications of this study are that firstly, the subducted slab does not contribute a highly fractionated REE component in most modern arcs (i.e. the slab does not melt); secondly, Rb has a very short residence time in the mantle, and its abundance in arc rocks is a direct reflection of the input from the dehydrating slab; and thirdly, bajaitelike rocks may provide recognition of attempted or successful ridge subduction in the geologic past.

Mouse DNA "fingerprints" : analysis of chromosome localization and germ-line stability of hypervariable loci in recombinant inbred strains

Abstract: Human minisatellite probes cross-hybridize to mouse DNA and detect multiple variable loci. The resulting DNA "fingerprints" vary substantially between inbred strains but relatively little within an inbred strain. By studying the segregation of variable DNA fragments in BXD recombinant inbred strains of mice, at least 13 hypervariable loci were defined, 8 of which could be regionally assigned to mouse chromosomes. The assigned loci are autosomal, dispersed and not preferentially associated with centromeres or telomeres. One of these minisatellites is complex, with alleles 90 kb or more long and with internal restriction endonuclease cleavage sites which produce a minisatellite "haplotype" of multiple cosegregating fragments. In addition, one locus shows extreme germ-line instability and should provide a useful system for studying more directly the rates and processes of allelic variation of minisatellites.

Histochemical localization of IGF-I and -II mRNA in the developing rat embryo.

Abstract: We describe the histological localization of embryonic and fetal tissues whose cells express the genes coding for insulin-like growth factors I and II (IGF-I and IGF-II) in the developing rat Our studies span the period between early somite stages and full term We have used oligodeoxyribonucleotide probes and obtained results which are both topographically precise and highly reproducible The gene coding for IGF-II is predominant throughout development It is strongly expressed in the liver and yolk sac A variety of other tissues also expresses the IGF-II gene, especially many mesodermally derived structures in the process of differentiation Many tissues do not express IGF genes Thus no IGF mRNA was demonstrable in ectodermally derived structures, including the central and peripheral nervous systems as well as the skin and its derivatives

Highly variable minisatellites and DNA fingerprints.

Abstract: The 23rd Colworth Medal Lecture, delivered on 25 September 1986 at Trinity College, Dublin. This is a licensed copy kindly supplied by the Biochemical Society.

Highly variable minisatellites and DNA fingerprints.

Abstract: The 23rd Colworth Medal Lecture, delivered on 25 September 1986 at Trinity College, Dublin. This is a licensed copy kindly supplied by the Biochemical Society.

The yeast MYO1 gene encoding a myosin-like protein required for cell division.

Abstract: A yeast gene MYO1 that contains regions of substantial sequence homology with the nematode muscle myosin gene (unc54) has been isolated and sequenced. Although the disruption of MYO1 is not lethal, it leads to aberrant nuclear migration and cytokinesis. The 200-kd myosin heavy chain-like protein, the product of MYO1, cross-reacts with anti-nematode myosin heavy chain IgG and is present in wild-type strains but not in strains carrying the disrupted gene. Instead, a truncated polypeptide with a molecular mass of 120 kd can be detected in some myo1 mutants.

Discovery of an unusual hard X-ray source in the region of supernova 1987A

Abstract: We have discovered a new hard X-ray source near supernova 1987 A, in the Large Magellanic Cloud, from the X-ray astronomy satellite Ginga. The present error box of 0.2° × 0.3° includes the supernova. The energy spectrum is very hard above 10 keV and unusual for any of the known classes of X-ray source. The flux in the range 10–30 keV as of 2–3 September is ˜5×10–11ergcm–2 s–1. The source intensity increased steadily throughout July, August and early September, but an observation in late September revealed no further increase. The positional agreement, a steady brightening and an unusual hard spectrum support the identification of the source as SN1987A.

Conformation of protein secreted across bacterial outer membranes: a study of enterotoxin translocation from Vibrio cholerae

Abstract: The secretion of enterotoxin by Vibrio cholerae is punctuated by the transient entry of the toxin subunits into the periplasm. In this paper, we show that the subunits oligomerize into an assembled holotoxin within the periplasm prior to their secretion across the outer membrane. The rate of toxin assembly was studied by pulse-labeling cells with [35S]-methionine and then monitoring the turnover of radiolabeled subunits as they assembled within the periplasm. The subunits entered the periplasm as monomers and assembled into oligomers with a half-time of approximately 1 min. Since assembly was a rapid event compared to the rate of toxin efflux from the periplasm, which had a half-time of approximately 13 min, we conclude that all of the subunits that pass through the periplasm assemble before they traverse the outer membrane. The average concentration of subunit monomers and assembled holotoxin within the periplasm was calculated to be approximately 20 and approximately 260 micrograms/ml, respectively. This indicates that the periplasm is a suitably concentrated milieu where spontaneous toxin assembly can occur. Our findings suggest that protein movement across bacterial outer membranes, in apparent contrast to export across other biological membranes, involves translocation of polypeptides that have already folded into tertiary and even quaternary conformations.

Low-frequency divergent X-ray variability in the Seyfert galaxy NGC4051

Abstract: The X-ray emission from NGC4051, a nearby low luminosity Type 1 Seyfert galaxy, exhibits variations that are both rapid and apparently quasi-periodic1,2. Many Seyfert galaxies are variable3 but our knowledge of the form of variability has not advanced substantially since early well-resolved observations4 and attempts at statistical description5. Here we report an uninterrupted 62-h observation of NGC4051 with the EXOSAT observatory, giving an order of magnitude improvement in the quality of the time series, allowing comparison with X-ray binaries. The observed power spectral density is roughly proportional to 1/f, similar to Cyg X-l, and characteristic of turbulent processes. No preferred timescale or luminosity gradient has been seen so far. If this behaviour holds generally for active galactic nuclei, quantities derived from short samples will be subject to selection effects. Some naive interpretaions of variability are clearly invalid. Similar conclusions have recently been arrived at by McHardy et al. (see accompanying paper6).

Fractal X-ray time variability and spectral invariance of the Seyfert galaxy NGC5506

Abstract: Rapid X-ray variability has long been sought after in active galactic nuclei (AGN) as an indicator of such parameters as the mass-to-energy conversion efficiency and black hole mass. Although some interesting variability information has been gained from early observations (for example see ref. 1 for a review) the faintness of AGN, combined with the short times devoted to their observation, has resulted in a very sparsely sampled and consequently partially misunderstood picture of AGN variability. The launch of EXOSAT2 in May 1983 provided us with the first opportunity to study seriously AGN X-ray variability and significant variations have been detected in a number of short observations3,4. Here we report the results of a long (3-day) observation of NGC5506 in which continuous rapid variation was detected. Power spectral analysis and fractal analysis both demonstrate that the variability is self-similar, that is, scale invariant, over nearly three decades of frequency, a range similar to that covered by pre-EXOSAT observations of bright galactic sources. If this behaviour is typical of all AGN then the concept of a 'two-folding' timescale is meaningless unless the fractal dimension of the general variability, as well as the specific time interval over which a specific change in flux occurs, are all noted. There is no evidence for any variation in the X-ray spectrum as a function of intensity and we show how this places strong constraints on the emission mechanism, favouring non-thermal models involving shocks.

The conservative treatment of acromioclavicular dislocation. Review after five years

Abstract: The treatment of acromioclavicular injuries is controversial; few studies document the late results. We have reviewed 53 patients about five years after conservative management, in nine for subluxation and 44 for dislocation. Subjective and objective results were satisfactory in all cases except for one with painful subluxation, who was the only patient to change her occupation because of the injury. At review, joint stability was demonstrated by improvement in position and by the very small increase in the coracoclavicular gap on stress radiographs.

Process for the production of a polypeptide

Abstract: A process for the production of a polypeptide in which host cells transformed with DNA coding for a fusion protein comprising the polypeptide and a further peptide comprising a C-terminal secretion sequence are cultured to express and secrete the fusion protein. The C-terminal secretion sequence is, for example, the haemolysin C-terminal secretion sequence.

A review of studies of anaesthetic risk, morbidity and mortality

Abstract: In the past two to three decades, advancing knowledge in the areas of physiology, pharmacology and scientific technology have allowed diversification from the purely technical aspects of administration of anaesthesia towards more accurate assessment of outcome for the individual in terms of both anaesthetic-induced morbidity and mortality. In addition, elucidation of the aetiology of the morbidity and mortality produced by anaesthesia, as opposed to that from surgery or concomitant medical or surgical disease processes, is assuming increased importance as a result of the expansion in medical litigation, where anaesthetists find themselves amongst the higher risk specialties in medicine. The morbidity produced by anaesthesia is relatively easy to define for specific populations, but the prediction of risk in an isolated individual remains elusive. For example, there are many studies indicating the incidence of postoperative myocardial infarction following surgical procedures in defined groups; but for the individual patient, more sophisticated risk assessments have so far failed to predict more accurately than the well-established ASA grading system. Nonetheless, it is expected that in future, studies in this area will permit increased precision in the assessment of risk, thereby permitting better consideration by both surgeon and patient of the options available regarding surgical and non-surgical therapy. Increasing emphasis on the safer administration of anaesthesia has been greatly aided by the use of the critical incident technique. By assessing near-misses in addition to existing morbidity and mortality, the technique increases the size and extent of the database, and by removal of the reticence inherent in an anaesthetist's confession of his mistakes, it increases the reporting of potential mishaps. Amongst the useful findings to have emerged from such studies is the previously unforeseen and unsuspected observation that the most dangerous period of anaesthesia is not during induction and recovery, but during the maintenance period. However, perhaps one of the more valuable aspects of this type of methodology is its potential use in quality control and audit within departments. There are undoubted problems and universally acknowledged difficulties in epidemiological research into anaesthetic mortality. Comparison of data between studies is rendered difficult owing to variations in procedure, including its prospective or retrospective nature, the definition of death, the perioperative time period studied, and the patient and hospital populations encompassed.(ABSTRACT TRUNCATED AT 400 WORDS)

The Location Choice of Offices of International Companies

Abstract: There has been a structural shift of employment in developed countries towards the tertiary sector, and an increase in the proportion of economic activity being conducted by international firms. This paper is an examination of the factors that influence location choice of international offices, by means of survey data that facilitate a sectoral analysis of location choice. Analysis of the motives that lead to direct foreign operations is based on the ownership–location–internalisation paradigm, which suggests that international firms tend to be most active in those sectors in which their ownership advantages are most pronounced, and in which these advantages are best exploited internally to the firm. A branch–regional classification is used to distinguish cases in which office-location choice is dominated by external market forces (branch offices) and those in which location is determined by internal organisational forces.The primary influences on location choice are market size and the need for personal ...