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Biomedical subjects

T O'Neill

Publications and source records attributed to T O'Neill.

At least 55 records · Page 3Linked to original sources

Modulation of the serological response of specific pathogen-free (EHV-free) foals to EHV-1 by previous infection with EHV-4 or a TK-deletion mutant of EHV-1.

EHV-1 was inoculated into specific pathogen-free (SPF) foals in order to study uncomplicated primary responses. Infection resulted in a strong serological response recognizing EHV-1-specific antigens; this contrasts with a previous publication where a weak response was recorded in SPF animals. Antibodies to EHV-1 were readily detected by four techniques (virus neutralization, complement fixation, Western blots and immune precipitation), yet there was comparatively little cross-reaction to EHV-4 target antigen. Re-inoculation with the same virus strain stimulated antibodies to EHV-1 but no additional antigens were recognized and antibodies cross-reacting with EHV-4 antigens were not enhanced. Having characterized the uncomplicated primary response to EHV-1 in SPF foals, further animals were exposed to either EHV-4 or a thymidine kinase-deficient mutant of EHV-1 prior to challenge with w/t EHV-1 to investigate how these infections might modulate the immune responses to EHV-1 or 4. Primary inoculation with EHV-4 or with a thymidine kinase-deficient mutant of EHV-1 produced productive infections as evidenced by virus shedding and pyrexia. In both these cases, however, in contrast to that with w/t EHV-1, the serological response was very weak. Re-infection of foals primed with either EHV-4 or TK-deficient EHV-1 with w/t EHV-1 resulted in a strong response to EHV-1 antigens detected by all four methods. In addition, in the foals given a primary inoculation with EHV-4, superinfection with EHV-1 resulted in a strong cross-reactive response to EHV-4 target antigens. The relevance of these observations to the interpretation of previously reported serological responses to EHVs in SPF and naturally reared animals is discussed.

Animals↗

Responses of ponies to equid herpesvirus-1 ISCOM vaccination and challenge with virus of the homologous strain.

An experimental (ISCOM) vaccine previously shown to protect hamsters from lethal challenge with equid herpesvirus-1 (EHV-1), was tested in horses. Vaccination with EHV-1 ISCOMs induced serum antibodies to the major virus glycoproteins gp10, 13, 14, 17, 18 and 21/22a, whereas antibody responses to gp2 were weak or absent. High levels of virus neutralising antibody of long duration were induced, but did not prevent challenge infection with virus of the homologous strain. However, in the vaccinated ponies there was a significant reduction in clinical signs, nasal virus excretion and cell associated viraemia compared with age-matched unvaccinated controls. There was a strong correlation between pre-challenge levels of serum virus neutralising antibody and the duration and total amount of virus excreted from the nasopharynx.

Animals↗

The epidemiology of vertebral fractures. European Vertebral Osteoporosis Study Group.

Vertebral fractures are recognised as a hallmark of osteoporosis, yet little is known of their epidemiology. This deficiency limits accurate characterisation of the public health importance of osteoporosis. Assessment of the impact of vertebral fractures has been hampered by the absence of formal criteria for identifying fractures on a thoracolumbar radiograph. Initial methods relying upon subjective radiological assessments have given way to morphometric measurements of vertebral heights, with deformities defined according to various algorithms. These methods have been used in a series of studies performed in Rochester, MN, to determine the incidence, outcome, and time trends of vertebral deformities. The results suggest a prevalence rate of vertebral deformity of 25.3 per 100 Rochester women aged 50 years and over (95% CI, 22.3-28.2), with an estimated incidence of 17.8 per 1,000 person-years. The incidence of clinically diagnosed vertebral fractures among women in the same population was 5.3 per 1,000 person-years, suggesting that around 30% of such deformities in women receive clinical attention. Morphometric measurement on the radiographs of women with clinically diagnosed fractures revealed that 80% had grade 2 ( > 4 SD) deformities. Comparable data on the occurrence and health impact of vertebral deformities throughout Europe are urgently required. The European Vertebral Osteoporosis Study (EVOS) is a multicentre epidemiological study that aims to address this issue. It is designed as a radiographic prevalence study in 34 European centres.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Egg size and reproductive allocation in the pitcherplant mosquito Wyeomyia smithii (Diptera: Culicidae).

Adult longevity and lifetime fecundity, but not fertility, of northern (Maine, USA) Wyeomyia smithii (Coquillet) increase with female pupal weight. Mean egg size does not vary with pupal weight, but the standard deviation in egg size shows a marginally significant increase with pupal weight. Egg sizes are not skewed but are leptokurtic in their distribution; neither skewness nor kurtosis changes with female pupal weight. Mean egg size is not correlated with weight-specific adult longevity or with weight- and longevity-specific lifetime fecundity. Reproductive effort early in adult life does not affect longevity, reproductive effort late in life, or reproductive rate late in life. Finally, there is no significant correlation late in adult life between weight-specific rate of egg production and the size of eggs being produced. Egg size does vary within females but is not a variable entered into the physiological allocation of resources among survivorship, fecundity, or rate of egg production.

Animals↗

Serological responses of specific pathogen-free foals to equine herpesvirus-1: primary and secondary infection, and reactivation.

Serum antibody (virus neutralisation, complement fixation, IgM and IgG) responses to equine herpesvirus-1 (EHV-1) infection were measured in six foals which were initially free from EHV-1 and EHV-4 infection and maternally-derived antibodies. Following primary infection, high titres of virus neutralisation and complement fixation antibodies were detectable against EHV-1, however, corresponding antibody levels against EHV-4 were low or inapparent, although the two viruses share a number of cross-reactive epitopes. In addition, following the primary infection with EHV-1, IgM levels increased before those of IgG, virus neutralisation and complement fixation antibodies, peaked sooner and thereafter declined. Stimulation of IgM levels was observed on secondary infection with EHV-1 given 61 days later. In contrast, IgG, virus neutralisation and complement fixation antibodies following primary infection were more sustained and no increase in their levels was observed on secondary infection. No consistent changes in IgM or IgG levels were seen after administration of dexamethasone to reactivate latent virus.

Animals↗

Integration of cell culture with continuous, on-line sterile downstream processing.

The development of an integrated system for the continuous, automated production of pure cell culture derived proteins is discussed. The system comprises a cell culture subunit for the continuous culture of mammalian cells and a purification subunit linked on-line to the cell culture subunit. The cells are compartmentalized and continuously perfused with culture medium. The cell culture medium leaving the bioreactor is perfused through a sterile immunoaffinity column that instantaneously removes the product from the culture fluid. This results in improved product quality because the product is quickly removed from the cell culture, thus minimizing contact with degradative enzymes. The culture medium, stripped from the secreted product, is recirculated into the bioreactor. The system allows simple, automated, and economical production of purified proteins with higher quality than that possible with current production methods. The integration also allows on-line, real-time process monitoring, thus simplifying process development and allowing more consistent production of biologics.

Animals↗

Maturation of human immunodeficiency virus particles assembled from the gag precursor protein requires in situ processing by gag-pol protease.

The vaccinia virus expression system was used to determine the role of human immunodeficiency virus type 1 (HIV-1) protease in viral morphogenesis and maturation. The unprocessed p55 gag precursor polyprotein alone was assembled to form HIV-1 particles which budded from cells. The particles were spherical and immature, containing an electron-dense shell in the particle submembrane; there was no evidence of core formation. Expression of both gag and pol proteins from a recombinant containing the complete gag-pol coding sequences resulted in intracellular processing of gag-pol proteins and the production of mature particles with electron-dense cores characteristic of wild-type HIV virions. To ascertain the role of protein processing in particle maturation, the pol ORF in the gag-pol recombinant was truncated to limit expression of the pol gene to the protease domain. With this recombinant expressing p55 gag and protease, intracellular processing was observed. Some of the resultant particles were partially mature and contained processed gag protein subunits. In contrast, particle maturation was not observed when the HIV-1 protease and p55 gag were coexpressed from separate recombinants, despite evidence of intracellular gag processing. These findings suggest that HIV-1 protease must be an integral component of the full-length gag-pol precursor for optimal processing and virion maturation.

Fusion Proteins, gag-pol↗

Protection against lethal equine herpes virus type 1 (subtype 1) infection in hamsters by immune stimulating complexes (ISCOMs) containing the major viral glycoproteins.

An experimental ISCOM vaccine has been prepared from gradient purified equine herpes virus type 1 (EHV-1). Radiolabelling studies demonstrated that this vaccine contained all the major viral glycoproteins in relative amounts similar to those found in non-detergent disrupted viral preparations. This EHV-1 ISCOM vaccine generated fully protective responses in hamsters challenged with an otherwise lethal dose of the hamster-adapted EHV-1 strain RACH.

Adjuvants, Immunologic↗

An evaluation of an anticoagulant clinic.

Patient comprehension of the risks of anticoagulation, tablet recognition skills and knowledge of complications of warfarin therapy were evaluated in 160 patients attending the anticoagulant clinic in a central Dublin teaching hospital group. Potential complications from over- and under- dosage with warfarin were unknown to 119 (74%) and 97 (60%) patients respectively. 1, 3 and 5 mg tablets could not be identified by 40 (25%), 55 (34%) and 60 (37%) patients respectively. The current prescribed dose could not be recollected by 31 (19%) patients. Haemorrhagic complications occurred in 23 (14%) subjects over one year, four of whom required hospital admission and two blood transfusions. No thromboembolic episodes were noted. This study reveals a widespread lack of understanding of anticoagulation and its potential complications in patients receiving warfarin therapy and has led to a critical reappraisal of patient education, patterns of referral and supervision of such individuals in our clinic.

Female↗

Postnatal depression--aetiological factors.

One hundred and forty-two women at six weeks postpartum were asked to complete Cox's Edinburgh Postnatal Depression Scale. Thirty-eight scored positively for depression and 28 of these were followed up by a psychiatrist. Twenty-eight controls were randomly selected from those who scored negatively. Numerous variables were considered, including the type of labour, whether the mother was breastfeeding or not, and the presence or absence of a psychiatric history. In addition the depressed group completed the Eysenck Personality Inventory. A past psychiatric history was found to be a very significant risk factor and there is a definite association between postnatal depression and delivery by forceps, vacuum or caesarian section. Maternal age and breastfeeding were not found to be of aetiological significance.

Depression↗

Fatal aplastic anaemia following prolonged diclofenac use in an elderly patient.

Aplastic anaemia is recognised to occur following the use of some non-steroidal anti-inflammatory drugs. We report a case of fatal aplastic anaemia following prolonged administration of diclofenac in a 77 year old lady with rheumatoid arthritis. To our knowledge this is the first report of fatal aplastic anaemia associated with diclofenac use in an elderly patient.

Aged↗

Antibody isotype responses in the serum and respiratory tract to primary and secondary infections with equine influenza virus (H3N8).

Serum antibody (IgGab, IgM and IgA) responses to primary and secondary infection with influenza A/equine/Newmarket/79 (H3N8) by nebulised aerosol were compared with local (nasopharyngeal and tracheal) antibody responses in ponies. Circulating IgGab antibody was of long duration after primary infection, whereas IgM responses were short-lived after both primary and secondary infections. The antigenic stimulation of secondary infection with equine influenza was sufficient to induce elevations of serum IgM and IgA in the presence of high levels of circulating IgGab. These results support the potential of virus-specific IgM measurement for the detection of recent exposure to virus in horses which have high levels of circulating IgGab. Unlike serum IgGab, nasal and tracheal wash antibody of this isotype did not show long duration after primary infection, but local antibody memory was demonstrated by anamnestic responses on rechallenge. Nasopharyngeal IgA developed later than IgGab and IgM, and was more durable.

Aerosols↗

Immature cervical teratoma arising in one fetus of a twin pregnancy. Case report and review of the literature.

This is the first recorded case of an immature cervical teratoma arising in one fetus of a twin pregnancy. Although real-time ultrasound detected the presence of an abnormality, its true nature was not established until after histological examination. Extra-amniotic prostaglandin pregnancy termination was performed at 20 weeks' gestation due to the onset of acute hydramnios and the rapid increase in tumor size. Delivery of both fetuses was performed under general anesthesia. Extraction of the abnormal twin was only possible after the tumor was separated off from the fetal neck in utero.

Abortion, Induced↗

Myocardial hypertrophy, fibrosis and infarction following exposure of the heart to radiation for Hodgkin's disease.

A 35 year old man was treated for stage IIA Hodgkin's disease by radiation to the upper thorax, axillae and neck. Three years later he presented with intractable and ultimately fatal congestive heart failure. Autopsy revealed massive biventricular hypertrophy with widespread subendocardial fibrosis and myocardial infarction, but with little coronary artery disease. Such a complex of features has not previously been described after radiation therapy and cannot be adequately explained by other known causes of heart muscle disease. Ventricular hypertrophy with extensive subendocardial fibrosis may be part of the spectrum of radiation heart disease.

Adult↗