Showing papers by "University of Leicester published in 1988"

Spontaneous mutation rates to new length alleles at tandem-repetitive hypervariable loci in human DNA.

Abstract: Tandem-repetitive minisatellite regions in vertebrate DNA frequently show substantial allelic variation in the number of repeat units. This variation is thought to arise through processes such as unequal crossover or replication slippage1–12. We show here that the spontaneous mutation rate to new length alleles at extremely variable human minisatellites is sufficiently high to be directly measurable in human pedigrees. The mutation rate at different loci increases with variability in accord with the neutral mutation/random drift hypothesis, and rises to 5% per gamete for the most unstable human minisatellite isolated. Mutations are sporadic, occur with similar frequencies in sperm and oocytes, and can involve the gain or loss of substantial numbers of repeat units, consistent with length changes arising primarily by unequal exchange at meiosis. Germline instability must therefore be taken into account when using hypervariable loci as genetic markers, particularly in pedigree analysis and parenthood testing.

International Nosology of Heritable Disorders of Connective Tissue, Berlin, 1986.

Abstract: The heritable disorders of connective tissue have proven to be very heterogeneous and problems have arisen concerning syndromic boundaries, nomenclature, and classification. In an attempt to resolve these dilemmas, a group of experts participated in a Workshop held during the 7th International Congress of Human Genetics, Berlin, in September, 1986. At the Workshop, overviews were given of the uses and limitations of nosology (McKusick), diagnostic criteria (Pyeritz), and practical issues in biochemical and molecular diagnosis (Hollister). Invited speakers then gave brief comments on the current status of the nosology of specific categories of inherited connective tissue disorders and made recommendations for possible modification. The Workshop was followed by two closed committee meetings at which the participants attempted to reach agreement on syndromic definition and a standardized nomenclature. The final proposals, with brief comment where relevant, form the subject of this communication.

Amplification of human minisatellites by the polymerase chain reaction: towards DNA fingerprinting of single cells

Abstract: Hypervariable minisatellites can be amplified from human DNA by the polymerase chain reaction, using primers from DNA flanking the minisatellite to amplify the entire block of tandem repeat units. Minisatellite alleles up to 5-10 kb long can be faithfully amplified. At least six minisatellite loci can be co-amplified from the same DNA sample and simultaneously detected to provide a reproducible and highly variable DNA fingerprint which can be obtained from nanogram quantities of human DNA. The polymerase chain reaction can also be used to analyse single target minisatellite molecules and single human cells, despite the appearance of spurious PCR products from some hypervariable loci. DNA fingerprinting at the level of one or a few cells therefore appears possible.

The social construction of lesbianism

Abstract: Rhetoric in Research on Lesbianism and Male Homosexuality Social Scientific Accounts Eliciting and Assessing Lesbian Accounts Lesbian Identities Lesbian Politics The Social Construction of Prejudice The Future for Research on Lesbianism

Suramin: a reversible P2-purinoceptor antagonist in the mouse vas deferens.

Abstract: The trypanocide Suramin was tested as a possible antagonist at the P2-purinoceptor of the mouse vas deferens. At a concentration of 100 microM, Suramin antagonized the response to alpha,beta-methylene ATP, while responses to carbachol and noradrenaline were unaffected. These results suggest that Suramin may provide a starting point for the development of specific antagonists for P2-purinoceptors.

Structural rearrangement of the retinoblastoma gene in human breast carcinoma.

Abstract: Structural changes of the human retinoblastoma gene have been demonstrated previously in retinoblastoma and some clinically related tumors including osteosarcoma. Structural aberrations of the retinoblastoma locus (RB1) were observed in 25% of breast tumor cell lines studied and 7% of the primary tumors. These changes include homozygous internal deletions and total deletion of RB1; a duplication of an exon was observed in one of the cell lines. In all cases, structural changes either resulted in the absence or truncation of the RB1 transcript. No obvious defect in RB1 was detected by DNA blot analysis in primary tumors or cell lines from Wilms' tumor, cervical carcinoma, or hepatoma. These results further support the concept that the human RB1 gene has pleiotropic effects on specific types of cancer.

Reported prevalence of urinary incontinence in women in a general practice

Abstract: To determine the prevalence of urinary incontinence and other urinary symptoms a questionnaire was sent to all women aged 25 and over and to women under 21 taking oral contraceptives registered with a rural practice (n=937); the questionnaire was completed by 833 women (89%). The overall prevalence of urinary incontinence was 41% (343/833); rates were lower in nulliparous and postmenopausal women (30/181 (17%) and 120/344 (35%) respectively) than parous and premenopausal women (313/652 (48%) and 225/479 (47%) respectively). Incontinence was significantly associated with perineal suturing after childbirth, being present in 201 of 376 (53%) women with sutures compared with 113 of 270 (42%) without. Of the 166 women with a history of minor gynaecological surgery, 100 had symptoms of incontinence, compared with 263 of the 657 (37%) without such a history. Incontinence was not related to type of delivery, and postnatal exercises for the pelvic floor were not beneficial. Inappropriate leakage of urine is perceived by many women as common and therefore not serious; thus it is often not reported to the doctor. Nevertheless, the 6% of women who always require protection against leakage could be helped by treatment.

Clustering of hypervariable minisatellites in the proterminal regions of human autosomes

Abstract: Six of the human minisatellites detected by DNA fingerprint probes have been localized by in situ hybridization to human metaphase chromosomes. These hypervariable loci are not dispersed at random in the human genome, but show preferential, though not exclusive, localization to terminal G-bands of human autosomes. Two of the proterminal minisatellites are very closely linked to other variable loci. Sequence analysis of one of these additional minisatellites suggests that the two linked minisatellites arose by independent amplification of different repeat units. The proterminal regions of human autosomes may therefore be rich in minisatellites, analogous to the pseudoautosomal terminal pairing region of human sex chromosomes that is similarly abundant in hypervariable minisatellites.

Effects of RNA secondary structure on alternative splicing of Pre-mRNA: Is folding limited to a region behind the transcribing RNA polymerase?

Abstract: The use in vivo of an alternative 5′ splice site sequestered within a short stem of potential RNA secondary structure is determined by the length of the loop. Above a threshold length of loop, the alternative site is used despite the potential structure. In contrast, the alternative site is used very little or not at all during splicing in vitro with all lengths of loop that we have tested. A model is proposed which suggests that pre-mRNA is free to fold only within a limited period after transcription.

Collision tectonics of the Ladakh-Zanskar Himalaya

Abstract: The collision of the Indian Plate with the Karakoram-Lhasa Blocks and the closing of Neo-Tethys along the Indus Suture Zone (ISZ) is well constrained by sedimentologic, structural and palaeomagnetic data at ca. 50 Ma. Pre-collision high P— low T blueschist facies metamorphism in the ISZ is related to subduction of Tethyan oceanic crust northwards beneath the Jurassic-early Cretaceous Dras island arc. The Spontang ophiolite was obducted south westwards onto the Zanskar shelf before the Eocene closure (Dl). The youngest marine sediments on the Zanskar shelf and along the ISZ are Lower Eocene, after which continental molasse deposition occurred. After ocean closure, thrusting followed a SW-directed piggy-back sequence (D2). This has been modified by late-stage breakback thrusts, overturned thrusts and extensional normal faulting associated with culmination collapse and underplating. The ISZ and northern Zanskar shelf sequence are affected by late Tertiary redirected backthrusting (D3), which also affects the Indus molasse. A 50 km wide ‘pop-up’ zone with divergent thrust vergence was developed across the Zanskar Range. Balanced and restored cross sections indicate a minimum of 150 km of shortening across the Zanskar shelf and ISZ. Post-collision crustal thickening by thrust stacking resulted in widespread Barrovian metamorphism in the High Himalaya that reached a thermal climax during Oligocene-Miocene times. Garnet-biotite-muscovite + tourmaline granites were generated by intracrustal partial melting during the Miocene within the Central Crystalline Complex. Their emplacement on the hangingwall of localized ductile shear zones was associated with SW-directed thrusting along the Main Central Thrust (MCT) zone and concomitant culmination collapse normal faulting along the Zanskar Shear Zone (ZSZ) at the top of the slab. Metamorphic isograds have become inverted by post-metamorphic SW-verging recumbent folding and thrusting along the base of the High Himalayan slab. Along the top of the slab, isograds are the right way up but are structurally and thermally telescoped by normal faulting along the ZSZ. 1

Observer variation in the assessment of dysplasia in ulcerative colitis

Abstract: Six histopathologists allocated 100 sections from patients with long-standing ulcerative colitis into four diagnostic categories, regular hyperplasia, reactive atypia, low-grade and high-grade dysplasia. Their allocations were analysed using kappa statistics, including Fleiss's multiple kappa for groups of observers, and agreement on specific diagnoses was explored by constructing a conditional probability matrix. The nature of their disagreements was investigated using coefficients for systematic and haphazard errors. Over the four diagnostic categories there was a wide range of pairwise agreement from a low of 49% up to 72% and kappa values were only ‘fair’ or ‘moderate’. As expected, agreement over the two categories ‘dysplasia’vs‘no dysplasia’ was better, ranging from 68% to 84%, and for ‘atypia present’ (reactive atypia, low- and high-grade dysplasia) vs‘no atypia’ two pairings achieved over 90% and 11 pairings over 80% agreement. In view of its clinical importance, conditional agreement on high-grade dysplasia was examined. Given that a first observer allocates a case as high-grade dysplasia, pairwise agreement on this diagnosis ranged from 100% down to as low as 33%. However, most of these disagreements fell into the low-grade dysplasia category so that closer follow-up and further biopsies would still have been indicated. It is a truism that the basis for safe management is careful co-operation between clinicians and pathologists who have all the relevant facts and who know and trust one another's judgement. Thus, several aspects of the ideal diagnostic process cannot be evaluated in inter-observer studies and the element of artificiality should be borne in mind when applying the findings to diagnostic practice. Nevertheless, the low level of agreement on the diagnosis of high-grade dysplasia achieved by certain pairings of specialist pathologists is a disturbing outcome of this study. Inaccuracies should be minimized by a concensus approach and we therefore recommend referral of putative cases of dysplasia to interested pathologists for further opinions. We would also advocate that pathologists faced with appearances which are indefinite between reactive atypia and dysplasia, would do better to describe them in terms of ‘atypia, significance uncertain’, so that closer surveillance is undertaken, rather than force them into more precise diagnostic categories which may be incorrect.

Method and apparatus for the perception of computer-generated imagery

Abstract: The invention relates to a 3-dimensional computer graphics system in which an operator can effectively interact with a virtual model generated and displayed by a computer In one embodiment the operator wears a helmet fitted with means which enable both the location of his head and its coordinates relative to the virtual model to be monitored and the information sent to computer The helmet carries miniature VDUs which direct separate images to his individual eyes so that the image is perceived stereoscopically The movement of the operator's eyes is also monitored by means mounted within housings of the helmet and data representing the operator's direction of vision sent to the computer The data transmitted to the computer is used to modify the image of the model as perceived by the operator to enhance its realism

Client perceptions of significant events in prescriptive and exploratory periods of individual therapy.

Abstract: This study compared the impact of helpful and hindering events, as perceived by 40 clients, in two forms of psychotherapy: an exploratory, relationship-oriented therapy, and a prescriptive, cognitive/behavioural therapy. All clients received eight sessions of each type of treatment in a crossover design. Events were obtained by self-report both during and at the end of each period, and content analysed for type of therapeutic impact by three trained raters. Results showed that during treatment the most commonly occurring helpful impacts across both types of treatments were ‘problem solution’, ‘awareness’ and ‘reassurance’, while the most commonly occurring hindering impact was ‘unwanted thoughts’. Similar impacts were reported at the end of each period, with the addition of ‘personal contact’. In addition, it was found that ‘problem solution’ and ‘reassurance’ impacts were more commonly reported in prescriptive treatment, whereas ‘awareness’ and ‘personal contact’ impacts were more prevalent in exploratory treatment. Only the prevalence of ‘unwanted thoughts’ was correlated (negatively) with outcome. Some possible reasons for the lack of correlation between reported impacts and outcome are suggested.

Survival of Halobacteria Within Fluid Inclusions in Salt Crystals

Abstract: SUMMARY: When sodium chloride crystallizes in an evaporitic environment, living halobacteria are entrapped within the fluid inclusions which form as the crystals develop. Trapped cells have been observed in natural salts from a marine saltern and from Lake Magadi. Entrapment occurs under both neutral and alkaline conditions. Salt crystals have been grown under controlled conditions from solutions containing pure culture suspensions of halobacteria at densities comparable to those reported from natural evaporitic habitats. Crystals formed in solutions heavily loaded with bacterial cells contained more and larger inclusions than crystals formed from sterile solutions, and thus bacterial entrapment may affect the physical characteristics of the product. Representative strains of each major grouping within the Halobacteriaceae except the genus Halococcus exhibited entrapment and survival within salt crystals. Continued motility has been demonstrated for up to three weeks after entrapment. All strains tested to date retained viability for a minimum of six months. Non-motile and non-viable cells were also entrapped.

Tetrachromatic colour vision in the duck ( Anas platyrhynchos L.):microspectrophotometry of visual pigments and oil droplets

Abstract: Microspectrophotometric examination of the visual receptors of the duck,Anas platyrhynchos, revealed four types of single cone containing visual pigments absorbing maximally at about 420 nm, 452 nm, 502 nm and 570 nm. A single population of double cones contained the P570 in both members. Rods absorbed maximally at 505 nm.

The localization of laminin mRNA and protein in the postimplantation embryo and placenta of the mouse: an in situ hybridization and immunocytochemical study.

Abstract: In situ hybridization (ISH) and immunocytochemistry were used to localize sites of synthesis and deposition of the basement membrane glycoprotein laminin during development in the postimplantation mouse embryo and extraembryonic membranes. In addition, similar studies were performed on postnatal viscera during the first 20 days after birth. Up to 10 days post coitum, embryonic laminin synthesis was confined to parietal endoderm. In maternal tissue, intense laminin mRNA expression was detected in decidual cells in the mesometrial and antimesometrial endometrium at 5-7 days. At 10 days, uniform expression was still seen within the mesometrial endometrium, with higher levels around migrating trophoblast, but in the antimesometrial aspect expression was restricted to the basal zone. High levels of mRNA expression persisted in parietal endoderm throughout gestation but much lower levels were detected in visceral yolk sac. In the mature placenta, laminin mRNA expression was also found associated with fetal vessels in the labyrinth and giant cells at the fetal/maternal boundary. In the embryo, the external limiting membrane of the cerebral vesicles and spinal cord stained for laminin protein and detectable mRNA was found in the pia mater. Growing peripheral nerves and dorsal and ventral root fibres expressed laminin mRNA and stained for laminin protein. Laminin mRNA expression was found in ureteric buds and nephrogenic vesicles (but not in metanephric blastema) during early prenatal kidney development, and in glomeruli, Bowman's capsule, loops of Henle and collecting duct cells at later stages of development, and after birth. All these structures possessed laminin-rich basement membrane (BM). Laminin mRNA expression fell to below detectable levels in the kidney around weaning. In the gut, laminin expression and protein staining was confined to the muscularis externa and the lamina propria during embryogenesis. After birth, the muscularis externa, muscularis mucosa and lamina propria cells corresponding to fibroblasts had detectable laminin mRNA, but in adult gut no laminin mRNA could be demonstrated in any cell type. In liver, low levels of laminin mRNA were seen in the capsule and in periportal connective tissue. After birth, laminin mRNA was associated with intrahepatic bile channels; no laminin mRNA was detected in the parenchyma and protein deposition was restricted to blood sinus BM. In the adult liver, no laminin mRNA was detected in any cell type. The developing heart showed uniform expression of laminin mRNA from 12 days to before birth. Postnatally, labelling was restricted to connective tissue cells.

Common organization of gene clusters for production of different capsular polysaccharides (K antigens) in Escherichia coli.

Abstract: Southern blot analysis of cloned K5- and K7-antigen genes, using DNA fragments from cloned K1 genes as radiolabeled probes, demonstrated that each K-antigen gene cluster is organized in a manner similar to that shown for the K1 antigen. That is, a central DNA segment unique for a given antigen type is flanked by DNA sequences that encode common functions for the management of intracellular polymer. This has been confirmed by transposon and deletion mutagenesis of plasmids carrying the K5 and K7 genes. We also describe a series of complementation experiments in which transport or postpolymerizational modification functions for one K antigen are used to complement mutations in the corresponding regions of a different K-antigen gene cluster. Thus, postpolymerizational modification of polysaccharide and transport of mature polysaccharide from the periplasmic space are common mechanisms and are independent of polysaccharide structure.

Late Ordovician–early Silurian destruction of the Iapetus Ocean: Newfoundland, British Isles and Scandinavia—a discussion

Abstract: The available data from Newfoundland, the British Isles and Scandinavia suggest that by late Ordovician–early Silurian times the ocean separating Laurentia from Eastern Avalonia and Baltica had partly closed with the consumption of intervening oceanic crust. Marine seaways, however, persisted until the middle or late Silurian. Phases of crustal transtension and transpression, predominantly under a major sinistral shear couple, occurred throughout the Silurian and early Devonian until the remnant Iapetus Ocean was completely destroyed. The most appropriate Recent plate tectonic models for Silurian sedimentation between Eastern Avalonia and Laurentia are probably the deep-marine foreland basins between Timor and the northern Australian margin, or between Taiwan and mainland China.

Surface X-ray scattering during crystal growth: Ge on Ge(111)

Abstract: The growth of Ge on Ge(111) has been monitored by in situ x-ray reflectivity and diffraction. For suitably chosen geometries, the scattered x-ray intensity is extremely sensitive to atomic-scale surface morphology; dramatic intensity changes occur upon deposition of a fraction of a monolayer. For substrate temperatures up to 200°C oscillations are observed in the scattered intensity, indicating growth by two-dimensional nucleation. Reflectivity curves reveal the detailed surface atomic geometry. All observations can be quantitatively understood by use of kinematical diffraction theory.

Where and why

Abstract: Comparative Plant Ecology: A Functional Approach to Common British Species. By J. P. Grime, J. G. Hodgson and R. Hunt Unwin Hyman:1988. Pp.742. £85, $150.

Geochemical evidence for plume—mantle interactions beneath Kerguelen and Heard Islands, Indian Ocean

Abstract: Within-plate ocean island basalts probably originate by the partial melting of upwelling plumes coming from deep within the Earth's mantle1. Part of the observed heterogeneity in Sr, Nd and Pb isotopic ratios in oceanic basalts may result from the interaction of plumes with the lithosphere 2–4. and asthenosphere2, 5. Kerguelen and Heard Islands, in the southern Indian Ocean, are the latest products of a large and long-lived plume system6, comparable to the Hawaiian–Emperor chain in the Pacific. Kerguelen Island began forming ∼40 Myr ago on the Antarctic plate, near to the embryonic Southeast Indian Ridge (SEIR), and represents the continuation of the hotspot activity preserved on the Indian plate as the Ninety east Ridge7 (Fig. 1). With continuing sea-floor spreading, younger volcanism on Kerguelen has occurred further away from the influence of the SEIR. Here we show that the isotopic compositions of Kerguelen basalts vary in sympathy with this changing tectonic environment, and suggest not only that depleted asthenosphere, but also that Cretaceous oceanic plateau litho-sphere, may have contributed significantly to the earlier magmatic history of the island.