Showing papers by "University of London published in 1989"

Hay fever, hygiene, and household size.

Abstract: Hay fever has been described as a "post industrial revolution epidemic,"' and successive morbidity surveys from British general practice suggest that its prevalence has continued to increase over the past 30 years.) Other evidence suggests a recent increase in the prevalence of asthma2 and childhood eczema.3 This paper suggests a possible explanation for these trends over time.

Autism diagnostic observation schedule: a standardized observation of communicative and social behavior.

Abstract: The Autism Diagnostic Observation Schedule (ADOS), a standardized protocol for observation of social and communicative behavior associated with autism, is described. The instrument consists of a series of structured and semistructured presses for interaction, accompanied by coding of specific target behaviors associated with particular tasks and by general ratings of the quality of behaviors. Interrater reliability for five raters exceeded weighted kappas of .55 for each item and each pair of raters for matched samples of 15 to 40 autistic and nonautistic, mildly mentally handicapped children (M IQ = 59) between the ages of 6 and 18 years. Test-retest reliability was adequate. Further analyses compared these groups to two additional samples of autistic and nonautistic subjects with normal intelligence (M IQ = 95), matched for sex and chronological age. Analyses yielded clear diagnostic differences in general ratings of social behavior, specific aspects of communication, and restricted or stereotypic behaviors and interests. Clinical guidelines for the diagnosis of autism in the draft version of ICD-10 were operationalized in terms of abnormalities on specific ADOS items. An algorithm based on these items was shown to have high reliability and discriminant validity.

The autistic child's theory of mind: a case of specific developmental delay

Abstract: In previous tests of the lowest level of a "theory of mind" (i.e. first-order belief attribution), 80% of autistic children were found to be impaired relative to a non-autistic mentally-handicapped control group. The present study examines the 20% of autistic children who have a theory of mind at the lowest level, and tests their ability to use a theory of mind at higher levels (i.e. second-order belief attribution). This autistic subgroup, in comparison to Down's Syndrome and normal control groups, was found to be severely impaired at the higher level. Autism is discussed as a possible case of specific developmental delay.

Pathways from Childhood to Adult Life

Abstract: Principles and concepts of development are reviewed in relation to life-span issues noting the need to consider: development in its social context; timing of experiences; intrinsic and experiential factors; continuities and discontinuities; parallels and differences s between normal and abnormal development; heterotypic and homotypic continuities; key life transitions; risk and protective factors; indirect chain affects; mediating mechanisms; age as an index of maturational and experiential factors. Developmental findings from childhood to adult longitudinal studies arc reviewed for possible mediating factors. These include: genetic mechanisms; the(non-genetic) biological substrate; shaping of the environment; cognitive and social skills: self-esteem and self-efficacy; habits, cognitive sins and coping styles: links between experiences

Topology via Logic

Abstract: 1. Introduction 2. Affirmative and refutative assertions 3. Frames 4. Frames as algebras 5. Topology: the definitions 6. New topologies for old 7. Point logic 8. Compactness 9. Spectral algebraic locales 10. Domain theory 11. Power domains 12. Spectra of rings Bibliography.

Antibodies to blood stage antigens of Plasmodium falciparum in rural Gambians and their relation to protection against infection.

Abstract: Cross-sectional and longitudinal studies were performed in a rural population living in The Gambia to examine the relationship between several in vitro assays of the host immune response to asexual stages of Plasmodium falciparum and protection from malaria in vivo. Assays included an enzyme-linked immunosorbent assay for antibodies to schizont antigens; an indirect immunofluorescence assay for total antiblood-stage antibodies; an immunofluorescence assay on glutaraldehyde-fixed parasites to detect antibodies to antigen Pf 155; an assay for serum inhibition of red blood cell invasion; a micro-agglutination assay to detect antibodies to neo-antigens on the surface of infected red blood cells; and an assay using polymorphonuclear leucocytes to detect antibodies capable of opsonizing schizont infected red blood cells. There were marked differences in the age-related pattern of response for different assays performed on sera obtained at a cross-sectional survey of 280 individuals. Examination of the correlation between the various immune responses and malariometric indices at the population level and at the individual level provided no evidence that any of the in vitro assays were related to protective immunity. The relationship between in vitro measurements of the anti-malarial immune response and protection from clinical episodes of malaria was examined in a group of 134 children aged 11 years and under who were monitored weekly throughout an entire malaria transmission season. The only immune factor to show a consistent protective effect against clinical malaria was the titre of antibodies to neo-antigens on the infected erythrocyte surface (P = 0.01). The same longitudinal techniques were used to examine the effect of two non-immunological factors, sickle cell trait and mosquito net usage, both of which showed significant protection against clinical episodes and malaria.

A rapid and convenient assay for counting cells cultured in microwell plates: application for assessment of growth factors

Abstract: There is currently much interest in the role of mediators that regulate cell proliferation. Methods to assay proliferative effects of such mediators usually involve cell counting techniques, which are tedious to perform, or methods based on uptake of radiolabelled thymidine, which may be prone to errors caused by precursor pool artefacts. We describe here an assay for estimating the number of adherent cells present in a microculture and its application to the study of growth factors. The assay depends on the binding of Methylene Blue to the fixed monolayer at pH 8.5 and, after washing the monolayer, release of dye by lowering pH. The use of an elution solvent containing acidified ethanol ensures a linear correlation between absorbance of the dye and cell number, and enables the assay to be carried out in 96-well plates measuring absorbance with an automated vertical light-path microplate photometer. The assay is rapid, highly reproducible and easy to perform, making it ideal for screening large numbers of samples. It was shown to be applicable to a number of foetal and adult cell lines derived from man and experimental animals. It was also demonstrated to be useful for assaying purified growth factors and detecting growth promoting activity in cell and tissue extracts.

Honey--a remedy rediscovered.

Abstract: Honey has had a valued place in traditional medicine for centuries. The prescription for a standard wound salve discovered in the Smith papyrus (an Egyptian text dating from between 2600 and 2200 BC) calls for a mixture of mrht (grease), byt (honey) and ftt (lint/fibre) as transliterated from hieroglyphic symbols 1•2• The ancient Egyptians, Assyrians, Chinese, Greeks and Romans employed honey for wounds and diseases of the gut. Honey was the most popular Egyptian drug being mentioned 500 times in 900 remedies', Whilst Hippocrates (3rd and 4th centuries BC) made little use of drugs in treatment he prescribed a simple diet, favouring honey given as oxymel (vinegar and honey) for pain, hydrornel (water and honey) for 'thirst'3,4, and a mixture of honey, water and various medicinal substances for acute fevers\", During the Biblical era honey received religious endorsement by both Christianity and Islam. When the Children of Israel were in Egypt or were journeying through the desert, the promise was made that their destination was to be 'a land flowing with milk and honey\". The holy Qur'an vividly illustrates the potential therapeutic value of honeyl-\", Thy Lord has inspired the Bees, to build their hives in hills, on trees and in man's habitations, From within their bodies comes a drink of varying colours, wherein is healing for mankind, Verily in this is a Sign, for those who give thought. Although a vast number of papers and articles have been published on the subject, most have concentrated on the biochemical analysis arid food and non-food commercial uses9•1O• In the past, scientific opinions on honey's nutritive and medical uses have differed and clashed with folklore. Controversies within the scientific communityf have re-kindled interest in the therapeutic uses of honey in modern medicine. Recently, scientific support has emerged with a proliferation in publications on the successful therapeutic use of honey in several general medical and surgical conditions. The antibacteriallU\" and antifungal-\" properties of honey have been well documented, with growth of organisms such as Staphylococcus aureus, Enteropathogens and Candida albicans inhibited in undiluted honey. Jeddar et al. l 2 have shown that honey at a concentration of 40% was bactericidal to various gram-negative and gram-positive bacteria. In particular, Salmonella shigella, enteropathogenic Escherichia coli and Vibrio cholera all of which are major causes of morbidity and mortality worldwide. Used at concentrations of between 30% to 50% honey 10 Wood SM, Kraenzlin ME, Adrian TE, Bloom SR. Treatmentofpatientswithpancreatic endocrine tumours using a new long acting somatostatin analogue, symptomatic and peptide responses. Gut 1985;26: 438-44

The development of endomycorrhizal root systems: VII. A detailed study of effects of soil phosphorus on colonization.

Abstract: Leek plants (Allium porrum L.) were grown in a controlled environment on a mixture (2: 1 w/w) γ-irradiated (1.0 Mrad) sandy loam and sand, at six concentrations of bicarbonate-soluble phosphorus (P) ranging from 22 to 344 mg P kg-1 (soil basis). Inoculum of the vesicular-arbuscular (VA) mycorrhizal fungus Glomus mosseae (Nicolson & Gerdemann) Gerdemann and Trappe was placed (M) or not (NM) in a layer 3 cm below the soil surface. At intervals of 10 d, lengths of main axes of roots and their lateral branches, and of the segments of infection within them, were measured. From these data we calculated the mean (harvest interval method} rates of linear extension of root tips and of infection fronts for each member of root, averaged over the whole root system. The mean delay, d, between a root encountering the layer of inoculum and the subsequent formation of internal infection, was also derived. Addition of P to soil did not affect rates of extension of roots, but increased the initiation of main axes and laterals. Infection segments extended twice as fast in laterals as in main axes. At low rates of addition, P did not affect fungal behaviour but increased the length of root available for colonization. When bicarbonate-soluble P exceeded 140 mg kg-1 , the rates of extension of infection fronts in both main axes and laterals were approximately halved, and d was considerably increased. The density (the area ratio of fungal to host tissue in a longitudinal squash) of the hyphae and arbuscules respectively, and the number of entry points per unit length of root, were greatly reduced by added P. However, the ratios of numbers of entry points/hyphal density and of arbuscule density/hyphal density were unaltered, and the morphology of the fungus was not noticeably affected. It is probable that formation of entry points was the rate-limiting step for colonization, and that this rate was reduced by added P.

Characterization of factor XIIIa positive dermal dendritic cells in normal and inflamed skin.

Abstract: SUMMARY The immunocytochemical identificatio n and characterization of indigenous dermal dendritic cells (dermal dendrocytes) using a rabbit polyclonal antibody to clotting enzyme factor XIII subunit A (FXIIIa) was carried out on normal and inflamed human cutaneous tissue. The immunophenotype of FXIIIa positive dendritic cells was analysed with a panel of r8 monoclonal antibodies using immunoperoxidase and double immunofluorescence staining techniques. The antibody against FXIIIa detected highly dendritic dermal cells located particularly in the upper reticular and papillary dermis. Double fluorescence microscopy showed that FXIIIa positive cells were bone marrow derived (HLe-i ^) and co-expressed monocyte, macrophage or antigen presenting cell markers (HLA-DR "^, LFA-I', HLA-DQ ', OKM5 *, Mo 1 ^ , Mono1 ^, Leu M3^). No labelling was obtained with cell markers for Langerhans cells (CDi), T lymphocytes (CD2), granulocytes (LeuMi) fibroblasts (Te7), intercellular adhesion moleculeI (ICAM-i) or endothelial cells (Factor VIII related antigen). Gamma interferon induced increased expression of HLA-DR and co-expression of ICAM-i on FXIIIa^ dermal dendritic cells in normal skin in organ culture. Moreover, in benign inflammatory dermatoses such as atopic eczema and psoriasis there was an increased number of FXIIIa ^,DR + , ICAM-I + cells in the upper dermis and foci of FXIIIa^ cells in the epidermis closely associated with lymphocytes. FXIIIa positive cells in human skin represent a specific population of bone-marrow dermal dendritic cells, distinct from Langerhans cells, that share some features common to mononuclear phagocytes (monocyte/macrophages). In addition, the detection of HLA-DQ on 48"n of FXIIIa" cells and the lack of OKMi in combination with high OKM5 expression suggests an antigen-presenting cell phenotype.

Networks of sexual contacts: implications for the pattern of spread of HIV.

Abstract: This paper examines the influence of sexual contact patterns (mixing matrices) on the pattern of the AIDS epidemic in a male homosexual community via numerical studies of a mathematical model of the transmission dynamics of HIV. A discussion is presented of the range of possible structures of networks of sexual contacts with extremes of assortative (within sexual activity groups) and disassortative (between sexual activity groups) mixing. The assortative mixing extreme is shown to generate the most rapid growth in the incidence of infection in the early stages of the epidemic while the disassortative extreme is shown to generate the epidemic of the largest magnitude over a long period. High within-group mixing (assortative) may generate multi-peak epidemics. The results are discussed in the context of both the interpretation of observed patterns of the spread of HIV and the acquisition of data on sexual contact patterns.

Cytosine methylation and the fate of CpG dinucleotides in vertebrate genomes.

Abstract: The dinucleotide CpG is a “hotspot” for mutation in the human genome as a result of (1) the modification of the 5′ cytosine by cellular DNA methyltransferases and (2) the consequent high frequency of spontaneous deamination of 5-methyl cytosine (5mC) to thymidine. DNA methylation thus contributes significantly, albeit indirectly, to the incidence of human genetic disease. We have attempted to estimate for the first time the in vivo rate of deamination of 5mC from the measured rate of 5mC deamination in vitro and the known error frequency of the cellular G/T mismatch-repair system. The accuracy and utility of this estimate (m d ) was then assessed by comparison with clinical data, and an improved estimate of m d (1.66x10-16 s-1) was derived. Comparison of the CpG mutation rates exibited by globin gene and pseudogene sequences from human, chimpanzee and macaque provided further estimates of m d , all of which were consistent with the first. Use of this value in a mathematical model then permitted the estimation of the length of time required to produce the level of “CpG suppression” currently found in the “bulk DNA” of vertebrate genomes. This time span, approximately 450 million years, corresponds closely to the estimated time since the emergence and adaptive radiation of the vertebrates and thus coincides with the probable advent of heavily methylated genomes. An accurate estimate of the 5mC deamination rate is important not only for clinical medicine but also for studies of gene evolution. Our data suggest both that patterns of vertebrate gene methylation may be comparatively stable over relatively long periods of evolutionary time, and that the rate of CpG deamination can, under certain limited conditions, serve as a “molecular clock”.

The BCG Story: Lessons from the Past and Implications for the Future

Abstract: BCG (bacille Calmette-Guerin) vaccines are at once among the least satisfactory and yet the most widely used of all vaccines today Their variable efficacy against tuberculosis and leprosy is still not understood and points to a fundamental unsolved problem in vaccine immunology The extensive use of BCG vaccines means that there are few BCG-free populations in the world that would be suitable for trials of future antimycobacterial vaccines These facts have implications with regard to strategies for the development and testing of new vaccines against mycobacterial diseases

Mitochondrial myopathies: Clinical and biochemical features of 30 patients with major deletions of muscle mitochondrial DNA

Abstract: Analysis of mitochondrial DNA (mtDNA) in muscle and blood from 72 patients with mitochondrial myopathy showed that 30 had major deletions of a variable proportion of muscle mtDNA. All of these 30 patients presented with progressive external ophthalmoplegia and limb weakness, and 8 had the additional features of the Kearns-Sayre syndrome. Of the 42 patients without detectable muscle mtDNA deletions, 10 had progressive external ophthalmoplegia and limb weakness, 2 had the Kearns-Sayre syndrome, 11 had limb weakness without extraocular involvement, and 19 had multisystem disorders predominantly affecting the central nervous system. Only 2 patients with mtDNA deletions had clinically affected relatives, compared with 10 of those without deletions. In the 4 patients with polarographic defects exclusively involving complex I (NADH coenzyme Q reductase), the deleted protein-coding genes were confined to those for complex I subunits. Thirteen other patients with apparently identical deletions had variable clinical and biochemical features. Immunoblots of complex I polypeptides from patients with deletions were either indistinguishable from controls or showed only a mild generalized decrease in all identifiable subunits.

Carnosine, homocarnosine and anserine: could they act as antioxidants in vivo?

Abstract: Carnosine, homocarnosine and anserine have been proposed to act as antioxidants in vivo. Our studies show that all three compounds are good scavengers of the hydroxyl radical (.OH) but that none of them can react with superoxide radical, hydrogen peroxide or hypochlorous acid at biologically significant rates. None of them can bind iron ions in ways that interfere with 'site-specific' iron-dependent radical damage to the sugar deoxyribose, nor can they restrict the availability of Cu2+ to phenanthroline. Homocarnosine has no effect on iron ion-dependent lipid peroxidation; carnosine and anserine have weak inhibitory effects when used at high concentrations in some (but not all) assay systems. However, the ability of these compounds to interfere with a commonly used version of the thiobarbituric acid (TBA) test may have led to an overestimate of their ability to inhibit lipid peroxidation in some previous studies. By contrast, histidine stimulated iron ion-dependent lipid peroxidation. It is concluded that, because of the high concentrations present in vivo, carnosine and anserine could conceivably act as physiological antioxidants by scavenging .OH, but that they do not have a broad spectrum of antioxidant activity, and their ability to inhibit lipid peroxidation is not well established. It may be that they have a function other than antioxidant protection (e.g. buffering), but that they are safer to accumulate than histidine, which has a marked pro-oxidant action upon iron ion-dependent lipid peroxidation. The inability of homocarnosine to react with HOCl, interfere with the TBA test or affect lipid peroxidation systems in the same way as carnosine is surprising in view of the apparent structural similarity between these two molecules.

Are autistic children "behaviorists"? An examination of their mental-physical and appearance-reality distinctions.

Abstract: This paper continues our earlier investigation of autistic children's deficit in attributing beliefs to others—in their “theory of mind.” Three experiments are reported. The first tests the prediction that autistic children will fail to distinguish mental and physical entities. The second tests the prediction that they will also be unaware of the mental function of the brain. The third tests the prediction that they will be unable to take into account their own mental states. This latter prediction was tested using Appearance-Reality (A-R) tasks. All three predictions were supported. Deficits in these areas were not found among mentally handicapped or normal children of the same or lower mental and chronological age, suggesting that they may be autism-specific and independent of general developmental delay. It is argued that autistic children's failure to make A-R distinctions is consistent with Leslie's (1987) metarepresentation theory of autism.

Risk factors for ovarian cancer: a case-control study.

Abstract: A hospital-based case-control study of ovarian cancer was conducted in London and Oxford between October 1978 and February 1983. Menstrual characteristics, reproductive and contraceptive history and history of exposure to various environmental factors were compared between 235 women with histologically diagnosed epithelial ovarian cancer and 451 controls. High gravidity, hysterectomy, female sterilisation and oral contraceptive use were associated with a reduced risk of ovarian cancer. Infertility and late age at menopause were associated with an increase in risk. While these factors were related, they were each found to be independently associated with ovarian cancer risk after adjusting for the effect of the other factors.

Severity of withdrawal symptoms as a predictor of outcome of an attempt to quit smoking

Abstract: In 227 smokers' clinic clients who managed at least one week of abstinence, ratings of withdrawal symptoms were used to predict subsequent return to smoking. Depression, time spent with urges to smoke, and difficulty not smoking during the first week of abstinence were significantly associated with lapse back to smoking during the second week. Depression and difficulty not smoking during the second week significantly predicted smoking status during the third week. No withdrawal symptoms during the third week were associated with a return to smoking during the fourth week. The predictive power of withdrawal symptoms was over and above that of smoke intake and dependence. The findings provide some support for the view that reduction of withdrawal symptoms may be a worthwhile target in programmes for helping smokers to quit.

Estimating maternal mortality: the sisterhood method.

Abstract: This paper describes a new indirect technique for deriving population-based estimates of maternal mortality. The technique, called the "sisterhood method," is relevant to developing countries where the alternative data sources and approaches to estimation are often inadequate and inappropriate. The sisterhood method uses the proportions of adult sisters dying during pregnancy, childbirth, or the puerperium reported by adults during a census or survey, to derive a variety of indicators of maternal mortality. The first field trial of the method was carried out in the North Bank Division of The Gambia, West Africa, in 1987. The results indicate a lifetime risk of maternal mortality of 0.0584, or 1 in 17, approximating a maternal mortality ratio of 1,005 per 100,000 live births, which is consistent with previous estimates for this region.