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Biomedical subjects

C Walker

Publications and source records attributed to C Walker.

At least 55 records · Page 3Linked to original sources
PubMed2001

Differential cell counts in sputum in respiratory epidemiology: a pilot study.

BACKGROUND: The aim of this pilot study was to determine whether measuring sputum differential cell counts, particularly eosinophils, could be a useful method of validating self-reported symptoms suggesting asthma in epidemiologic studies. MATERIALS AND METHODS: In this cross-sectional study, we selected four groups of adult subjects by reported symptoms and diagnoses from among those previously randomly identified in a population study. Subjects were selected with no respiratory symptoms ever (normal group), or reporting a diagnosis of asthma (asthma group), or reporting recurrent wheezing not diagnosed as asthma (wheeze group), or reporting exposure to industrial irritants, but not asthma or wheezing (exposed group). Current respiratory symptoms, airway responsiveness to methacholine challenge, and sputum cell counts were determined. The study was completed by 107 subjects aged 20 to 44 years. RESULTS: There were no significant differences in FEV(1) percent predicted, total cell count, and sputum eosinophil count among the four groups. Subjects with reported asthma had greater airway responsiveness as reflected in a lower bronchial reactivity (BR) index. There was a weak correlation between BR index and sputum eosinophils. CONCLUSION: In a community setting, induced sputum eosinophil cell counts in subjects reporting asthma or wheezing were most often within the normal range and not sufficiently often abnormal to be useful in validating a diagnosis of asthma in epidemiologic studies.

Adult↗
PubMed2001

Doxycycline dosing.

Explore the source record for details and available documents.

Anti-Bacterial Agents↗
PubMed2001

cis-Urocanic acid does not induce the expression of immunosuppressive cytokines in murine keratinocytes.

trans-Urocanic acid (UCA) acts as a chromophore for UV radiation in the epidermis and isomerizes to cis-UCA which then initiates some of the changes leading to UV-induced immunosuppression. The mechanism of the immunomodulation by cis-UCA is unknown at present, but one possibility is that the interaction between cis-UCA and keratinocytes causes the release of immunosuppressive cytokines locally. To test this hypothesis, PAM-212 cells, a murine keratinocyte cell line, were incubated with 0.10-100 micrograms/mL trans- and cis-UCA for 6 or 24 h, respectively. The expression of interleukin (IL)-10, transforming growth factor (TGF)-beta and tumor necrosis factor (TNF)-alpha messenger RNA (mRNA) was then measured by reverse transcription-polymerase chain reaction in comparison with the mRNA for the house-keeping gene, beta-actin. No change or significant induction of any of the cytokine messages occurred. However, the expression of IL-10 messenger RNA (mRNA) was induced 24 h after UVB irradiation (300 J/m2) and that of TNF-alpha mRNA occurred 6 h after treatment with phorbol myristate acetate. The expression of IL-10 protein was also examined by immunostaining in both PAM-212 cells and B16-F10 murine melanoma cells between 3 and 48 h after incubation with 10 and 100 micrograms/mL cis- and trans-UCA. No alteration was seen with either isomer at either concentration. In contrast, UVB irradiation of both cell lines resulted in a marked increase in intracellular IL-10 protein at 24 and 48 h. Therefore the upregulation of the immunosuppressive cytokines, IL-10, TNF-alpha and TGF-beta, in keratinocytes is unlikely to be the mechanism by which cis-UCA induces immunosuppression in mice.

Animals↗
PubMed2001

An environmental survey relating to improvised and emulsion/gel explosives.

The detection and identification of traces of inorganic ions and sugars can play a major role in the forensic investigation of an explosives related incident. This survey investigated the background levels of these substances in the general environment. Six sampling locations were selected from around the mainland of the United Kingdom, representing urban and rural sites. Swab and vacuum samples were collected from different locations within each site including motor vehicles, private houses, hotels, the exterior of buildings, road surfaces, and street signs. Sampling was carried out in summer and winter to investigate changes in the levels of the target species due to seasonal factors such as road treatments or weather. The samples were extracted with water and analyzed for a range of inorganic anions, cations, and sugars using ion chromatography. Most of the target anions were found to be common to all locations. Chloride, sulphate, nitrate, and phosphate were found to be the most common and the most abundant. Chlorate was found at a low level in some external samples. Perchlorate and thiocyanate were not detected in any samples. There was a marked increase in the quantity of sodium and chloride detected in samples collected during the winter. Sodium and calcium were detected in most samples. Potassium and magnesium were detected in approximately half of the samples. Ammonium was less common but detected at significant levels in wall samples. Glucose, fructose, and sucrose were detected in the vacuum samples from the interior surfaces of houses, hotels, and cars.

Journal Article↗
PubMed2001

Kawasaki disease: is it caused by an infectious agent?

Kawasaki disease (KD) is an acute systemic febrile illness of unknown aetiology, predominantly affecting children under five years of age. Initially described in 1967 by Tomisaku Kawasaki, it is now the most common cause of acquired heart disease in children in the developed world. Although normally self-limiting, KD is associated with a range of complications, the most important of which is the development of life-threatening coronary artery abnormalities. Here, we examine the evidence supporting the concept that KD is caused by an infectious agent. Various infectious agents--including bacterial, viral and Rickettsial organisms--have been implicated as potential causes, as have certain immunological agents such as bacterial toxin-mediated superantigens, allergens such as anionic detergents and house-dust mites, and some chemicals (including heavy metals). Following extensive research, however, no links between any of these individual agents and the disease have been established irrefutably. Despite this, most of the epidemiological and immunological evidence currently available indicates that the causative agent is most likely to be infectious in nature; and additional evidence highlights the likelihood that development of KD is multifactorial in nature, requiring certain genetic and immunological factors, and possibly a vector.

Bacterial Infections↗
PubMed2000

Immunization of BALB/c mice with DNA encoding equine herpesvirus 1 (EHV-1) glycoprotein D affords partial protection in a model of EHV-1-induced abortion.

DNA-mediated immunization was assessed in a murine model of equine herpesvirus 1 (EHV-1) abortion. Whilst there are differences between the model and natural infection in the horse, literature suggests that EHV-1 infection of pregnant mice can be used to assess the potential ability of vaccine candidates to protect against abortion. Female BALB/c mice were inoculated twice, 4 weeks apart, with an expression vector encoding EHV-1 glycoprotein D (gD DNA). They were mated 15 days after the second inoculation, challenged at day 15 of pregnancy and killed 3 days later. The gD DNA-inoculated mice had fewer foetuses which were damaged or had died in utero (6% in gD DNA, 21% vector DNA and 28% in nil inoculated groups challenged with EHV-1), a reduction in the stunting effect of EHV-1 infection on foetuses (gD DNA: 0.40g+/-0.06, vector DNA: 0.34g+/-0.10), reduced placental and herpesvirus-specific lung histopathology and a lower titre of virus (TCID(50)+/-SEM/lung) in maternal lung than control groups (gD DNA 4.7+/-0.3, vector 5.3+/-0.2, nil 5.6+/-0.2). Maternal antibody to EHV-1 gD was demonstrated in pups born to a dam inoculated 123 days earlier with gD DNA. Although protection from abortion was incomplete, immunization of mice with gD DNA demonstrated encouragingly the potential of this vaccine strategy.

Abortion, Veterinary↗
PubMed2000

Syk-deficient eosinophils show normal interleukin-5-mediated differentiation, maturation, and survival but no longer respond to FcgammaR activation.

The tyrosine kinase Syk has been proposed to play a critical role in the antiapoptotic effect of interleukin (IL)-5 in human eosinophils. However, little is known about the involvement of Syk in other IL-5-mediated activation events. To further address these questions, the role of Syk in IL-5-induced eosinophil differentiation, activation, and survival was analyzed using cells obtained from Syk-deficient mice. We could demonstrate that Syk-deficient fetal liver cells differentiate into mature eosinophils in response to IL-5 at the same rate as wild-type fetal liver cells and generate the same total number of eosinophils. Moreover, no difference in IL-5-induced survival of mature eosinophils between Syk(-/-) and wild-type eosinophils could be demonstrated, suggesting that the antiapoptotic effect of IL-5 does not require Syk despite the activation of this tyrosine kinase upon IL-5 receptor ligation. In contrast, eosinophils derived from Syk-deficient but not wild-type mice were incapable of generating reactive oxygen intermediates in response to Fcgamma receptor (FcgammaR) engagement. Taken together, these data clearly demonstrate no critical role for Syk in IL-5-mediated eosinophil differentiation or survival but underline the importance of this tyrosine kinase in activation events induced by FcgammaR stimulation.

Animals↗
PubMed2000

Inhibition of antigen-induced eosinophilia and late phase airway hyperresponsiveness by an IL-5 antisense oligonucleotide in mouse models of asthma.

Chronic airway eosinophilia is associated with allergic asthma and is mediated in part by secretion of IL-5 from allergen-specific Th2 lymphocytes. IL-5 is a known maturation and antiapoptotic factor for eosinophils and stimulates release of nascent eosinophils from bone marrow into the peripheral circulation. An antisense oligonucleotide found to specifically inhibit IL-5 expression in vitro was observed to significantly reduce experimentally induced eosinophilia in vivo, in both the murine OVA lung challenge and allergic peritonitis models. Intravenous administration resulted in sequence-dependent inhibition of eosinophilia coincident with reduction of IL-5 protein levels, supporting an antisense mechanism of action. Potent suppression of lung eosinophilia was observed up to 17 days after cessation of oligonucleotide dosing, indicating achievement of prolonged protection with this strategy. Furthermore, sequence-specific, antisense oligonucleotide-mediated inhibition of Ag-mediated late phase airway hyperresponsiveness was also observed. These data underscore the potential utility of an antisense approach targeting IL-5 for the treatment of asthma and eosinophilic diseases.

Adjuvants, Immunologic↗
PubMed2000

Genomics, molecular genetics and the food industry.

The production of foods for an increasingly informed and selective consumer requires the coordinated activities of the various branches of the food chain in order to provide convenient, wholesome, tasty, safe and affordable foods. Also, the size and complexity of the food sector ensures that no single player can control a single process from seed production, through farming and processing to a final product marketed in a retail outlet. Furthermore, the scientific advances in genome research and their exploitation via biotechnology is leading to a technology driven revolution that will have advantages for the consumer and food industry alike. The segment of food processing aids, namely industrial enzymes which have been enhanced by the use of biotechnology, has proven invaluable in the production of enzymes with greater purity and flexibility while ensuring a sustainable and cheap supply. Such enzymes produced in safe GRAS microorganisms are available today and are being used in the production of foods. A second rapidly evolving segment that is already having an impact on our foods may be found in the new genetically modified crops. While the most notorious examples today were developed by the seed companies for the agro-industry directed at the farming sector for cost saving production of the main agronomical products like soya and maize, its benefits are also being seen in the reduced use of herbicides and pesticides which will have long term benefits for the environment. Technology-driven advances for the food processing industry and the consumer are being developed and may be divided into two separate sectors that will be presented in greater detail: 1. The application of genome research and biotechnology to the breeding and development of improved plants. This may be as an aid for the cataloging of industrially important plant varieties, the rapid identification of key quality traits for enhanced classical breeding programs, or the genetic modification of important plants for improved processing properties or health characteristics. 2. The development of advanced microorganisms for food fermentations with improved flavor production, health or technological characteristics. Both yeasts and bacteria have been developed that fulfill these requirements, but are as yet not used in the production of foods.

Bacteriophages↗
PubMed2000

A prime-boost immunization strategy with DNA and recombinant baculovirus-expressed protein enhances protective immunogenicity of glycoprotein D of equine herpesvirus 1 in naïve and infection-primed mice.

The immunogenicity and protective efficacy afforded by intramuscular inoculation of plasmid DNA encoding equine herpesvirus 1 (EHV-1) glycoprotein D (gD) followed by EHV-1 gD expressed by a recombinant baculovirus was assessed in a murine model of EHV-1 respiratory infection. Compared with mice inoculated with DNA or protein only, mice inoculated with the combination of gD DNA and protein had enhanced ELISA and neutralizing antibody titres to EHV-1 and had accelerated clearance of virus from lungs following challenge infection. The enhanced protective effects of this consecutive immunization were also evident in mice which had a previous infection with EHV-1 and had pre-existing antibodies. The T-helper 1 (Th1) type of immune response induced by EHV-1 gD DNA was maintained after the protein boost, despite the gD protein alone appearing to direct a Th2 response.

Animals↗
PubMed2000

Changes in leptin levels during lactation: implications for lactational hyperphagia and anovulation.

In these studies we investigated the time course of changes in circulating leptin levels in lactating rats and the dependence of these changes on the energetic cost of lactation and evaluated the contribution of changes in leptin levels to lactational hyperphagia and infertility. In the first experiment, plasma leptin levels were measured on Days 5, 10, 15, 20, and 25 postpartum in freefeeding lactating rats and age-matched virgin females. Retroperitoneal and parametrial fat pads weights were obtained from the same females. In the second experiment the same measures, together with plasma insulin and prolactin levels, were taken on Days 15 and 20 postpartum from galactophore-cut and sham-operated females. In Experiments 3 and 4, the effects of exogenous leptin administration, either subcutaneously (sc) or intracerebroventricularly (icv), on lactational anovulation, maternal food intake, and dam and litter weights were examined. Circulating leptin levels decreased in lactating rats. Leptin levels were highly positively correlated with fat pad weight. Eliminating the energetic costs of lactation by preventing milk delivery induced dramatic increases in plasma leptin and insulin levels and also increased adiposity. Exogenous leptin administration did not affect length of lactational anovulation but reduced food intake, maternal body weight, and litter weight gain when given centrally and maternal body weight when given systemically. Together, these data show that the energetic costs of lactation are associated with a fall in circulating leptin levels but that these do not make a major contribution to the suppression of reproduction in lactating rats; however, they may be permissive to the hyperphagia of lactation.

Animals↗
PubMed2000

Cortical bone distribution in the femoral neck of strepsirhine primates.

The thickness of the inferior and superior cortices of the femoral neck was measured on X-rays of 181 strepsirhine primate femora representing 24 species. Neck length, neck depth and neck-shaft angle were also measured. The strength of the femoral neck in frontal bending was estimated by modeling the neck as a hollow cylinder, with neck depth as the outer diameter and cortical thickness representing the superior and inferior shell dimensions. Results indicate that the inferior cortex is always thicker than the superior cortex. The ratio of superior to inferior cortical thickness is highly variable but distinguishes two of the three locomotor groups in the sample. Vertical clingers and leapers have higher ratios (i.e., a more even distribution of cortical bone) than quadrupeds. The slow climbers tend to have the lowest ratios, although they do not differ significantly from the leapers and quadrupeds. These results do not confirm prior theoretical expectations and reported data for anthropoid primates that link greater asymmetry of the cortical shell to more stereotypical hip excursions. The ratio of superior to inferior cortical thickness is unrelated to body mass, femoral neck length, and neck-shaft angle, calling into question whether the short neck of strepsirhine primates acts as a cantilever beam in bending. On the other hand, the estimated section moduli are highly correlated with body mass and neck length, a correlation that is driven primarily by body mass. In conclusion, we believe that an alternative interpretation to the cantilever beam model is needed to explain the asymmetry in bone distribution in the femoral neck, at least in strepsirhine primates (e.g., a thicker inferior cortex is required to reinforce the strongly curved inferior surface). As in prior studies of cross-sectional geometry of long bones, we found slightly positive allometry of cortical dimensions with body mass.

Animals↗
PubMed2000

Characterisation of IE and UL5 gene products of equine herpesvirus 1 using DNA inoculation of mice.

The equine herpesvirus 1 (EHV-1) strain HVS25A regulatory genes IE and UL5, encoding homologues of herpes simplex virus 1 (HSV-1) ICP4 and ICP27 respectively, were cloned into a eukaryotic expression vector and the DNA injected intramuscularly into mice. Antibodies produced in this way detected the IE or UL5 gene products as diffuse material in nuclei of RK13 cells transfected with the individual genes but as discrete punctate or large aggregates in RK13 cells infected with EHV-1. Western blotting on EHV-1 infected RK13 cells showed multiple IE products of 120-200 kDa and a UL5 product of 52 kDa. Inoculation with plasmids expressing EHV-1 IE or UL5 provided limited protection against EHV-1 challenge in mice as determined by increased virus clearance from lungs on day 2 post-challenge and a reduction in severity of lung histopathology. However, this protection was relatively weak compared with that provided by inoculation of DNA encoding EHV-1 glycoprotein D (gD), possibly reflecting the importance of neutralising antibody in this model.

Animals↗
PubMed2000

EHV-1 glycoprotein D (EHV-1 gD) is required for virus entry and cell-cell fusion, and an EHV-1 gD deletion mutant induces a protective immune response in mice.

Insertional mutagenesis was used to construct an equine herpesvirus 1 (EHV-1) mutant in which the open reading frame for glycoprotein D was replaced by a lacZ cassette. This gD deletion mutant (delta gD EHV-1) was unable to infect normally permissive RK cells in culture, but could be propagated in an EHV-1 gD-expressing cell line (RK/gD). Phenotypically complemented delta gD EHV-1 was able to infect RK cells, but did not spread to form syncytial plaques as seen with wild type EHV-1 or with delta gD EHV-1 infection of RK/gD cell cultures. Therefore EHV-1 gD is required for virus entry and for cell-cell fusion. The phenotypically complemented delta gD EHV-1 had very low pathogenicity in a mouse model of EHV-1 respiratory disease, compared to a fully replication-competent EHV-1 reporter virus (lacZ62/63 EHV-1). Intranasal or intramuscular inoculation of mice with delta gD EHV-1 induced protective immune responses that were similar to those elicited in mice inoculated with lacZ62/63 EHV-1 and greater than those following inoculation with UV-inactivated virus.

Animals↗
PubMed2000

Knee joint kinematics in gait and other functional activities measured using flexible electrogoniometry: how much knee motion is sufficient for normal daily life?

The knee joint kinematics of a group (n=20) of elderly normal subjects (mean age=67 years) were investigated using flexible electrogoniometry. The flexion-extension angle of the knee was recorded during a range of functional activities performed as part of a circuit in and around the hospital. The functions analysed including gait, walking on slopes, stair negotiation, the use of standard and low chairs and a bath. The data were used to produce the pattern of joint angulation against the percentage of the cycle for each individual conducting each activity. Further the maximum and minimum knee joint angles and the excursion of the joint during the cycle were identified. The results indicate gait and slopes require less than 90 degrees of knee flexion, stairs and chairs 90-120 degrees of flexion and a bath approximately 135 degrees of flexion. The data suggests that 110 degrees of flexion would seem a suitable goal for the rehabilitation of motion in the knee. It is concluded that flexible electrogoniometry is a suitable and practical method for evaluating knee motion during a range of functional activities.

Activities of Daily Living↗
PubMed2000

Differing expression of bax and bcl-3 may influence the different cure rates in mouth and orophayrngeal cancer

AIM: To determine the reason for the differing cure rates of cancers between the mouth and oropharynx. MATERIALS AND METHODS: To achieve our aim we carried out immunohistochemistry on paraffin-embedded tissue from 31 oral and 38 oropharyngeal squamous carcinomas using the streptavidin-biotin/HRP method. RESULTS: The results from this study revealed the mean percentage of bax and bcl-2 expression was higher in the oropharyngeal samples (56.34% and 97.36%, respectively) than in the oral samples (6.6% and 82.38%, respectively). In the oral carcinomas bcl-2 was expressed in a higher percentage of cells than bax, and a high proportion of cases were bcl-2 positive in the absence of significant bax expression. In contrast the oropharyngeal cases showed a high percentage of cells expresssing both bcl-2 and bax. CONCLUSION: The predominance of anti-apoptotic bcl-2 over the pro-apoptotic bax may result in a survival advantage of the cells of oral carcinomas over the cells of the oropharynx. Tumours of the oral cavity have been found to be clinically more radioresistant than those of the oropharynx. These findings may have implications for radiotherapy treatment since the cells of oral carcinomas may already have a survival advantage and the carcinomas may be less likely to respond to treatment.

Journal Article↗
PubMed2000

Molecular genetic analysis of archival gliomas using diagnostic smears.

Investigation of the clinical significance of genetic alterations in gliomas requires molecular genetic analysis using samples from retrospective or prospective clinical studies. However, diagnostic tissue is often severely limited and because of fixation, paraffin-embedded tissues (PET) contain degraded DNA. Intra-operative cytological preparations (smears) archived after diagnosis may represent an additional source of clinical material for genetic analysis. In this study, tissue samples were obtained by precision microdissection of archived diagnostic smears from 20 cases (1961-1999). All samples produced polymerase chain reaction (PCR) products for the beta globin gene, but the most recent samples amplified best and gave longer amplimers. For six cases, direct comparison was made between samples microdissected from smears and the corresponding PET. Samples from smears showed improved PCR performance and similar alleles on microsatellite marker analysis. One case, with smears of uninvolved cortex and tumour tissue available for microdissection, showed allelic imbalance at 10q23 on the basis of the smear results alone. PCR products from smears were shown to be suitable for direct sequence analysis (p53 gene). A PTEN mutation, found previously in an anaplastic astrocytoma by analysis of PET, was detected in the corresponding diagnostic smear. The results of this study indicate that tissue samples microdissected from diagnostic intra-operative cytological preparations may be suitable for molecular genetic analysis of gliomas.

Archives↗