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J M Daly

Publications and source records attributed to J M Daly.

At least 19 recordsLinked to original sources
PubMed2006

Antibody and IFN-gamma responses induced by a recombinant canarypox vaccine and challenge infection with equine influenza virus.

In horses, equine influenza virus (EIV) is a leading cause of respiratory disease. Conventional inactivated vaccines induce a short-lived immune response. By comparison, natural infection confers a long-term immunity to re-infection. An aim of new equine influenza vaccines is to more closely mimic natural infection in order to achieve a better quality of immunity. A new live recombinant vaccine derived from the canarypox virus vector and expressing haemagglutinin genes of EIV (subtype H3N8) has been developed. Stimulation of the immune system was studied after immunisation with this canarypox-based vaccine and challenge infection by exposure to a nebulised aerosol of EIV. The humoral immune response was evaluated by measuring serum antibody levels using the single radial haemolysis (SRH) assay. The cellular immune response was assessed by the measurement of interferon gamma (IFN-gamma) synthesis in peripheral blood mononuclear cells (PBMC). Clinical signs of the disease (temperature, coughing, nasal discharge, dyspnoea, depression and anorexia) and virus excretion were monitored after challenge infection. Clinical signs and virus shedding were significantly reduced in vaccinates compared with unvaccinated controls. EIV-specific immunity was stimulated by vaccination with a recombinant vaccine as serological responses were detected after immunisation. This study also provided the first evidence for increased IFN-gamma protein synthesis in vaccinated ponies following challenge infection with EIV compared with control ponies.

Animals↗
PubMed2006

Investigation of equine influenza cases exhibiting neurological disease: coincidence or association?

Equine influenza is usually a transient and self-limiting disease. However, during an outbreak of equine influenza in the UK in 2003 there were reports of unusually severe clinical signs among unvaccinated animals. Two influenza-infected horses developed neurological signs, and one was subjected to euthanasia. Post-mortem examination of the brain revealed viral-type non-suppurative encephalitis, and influenza virus antigen was demonstrated by immunolabelling of sections of nasal mucosa. A syndrome known as influenza-associated encephalopathy has been described in man. Although not proved, the data suggest that similar disease mechanisms may operate in horses, and that equine influenza virus infection can result in encephalitis in the natural host, perhaps due to an aberrant host immune response.

Amino Acid Sequence↗
PubMed2006

Vaccination against equine influenza: quid novi?

Equine influenza virus is a leading cause of respiratory disease in the horse. Equine influenza vaccines containing inactivated virus were first developed in the 1960s. Despite their intensive use, equine influenza outbreaks still continue to occur and therefore new strategies of vaccination are necessary to improve vaccine efficacy. Numerous methods of vaccination have been evaluated and commercialised in the horse, the most recent being the cold-adapted influenza virus and poxvirus-based vaccines. As a large animal model, the horse is also a useful species in which to evaluate the potential of new generations of influenza vaccine such as live-attenuated influenza virus engineered by reverse genetics. This report details the equine immune responses conferring protection against influenza. It then undertakes a selective review of different strategies of vaccination against equine influenza that have been developed over the last two decades and discusses factors that may influence the efficacy of vaccination. Finally it outlines progress in the development of a novel vaccination strategy against equine influenza using reverse genetics.

Age Factors↗
PubMed2006

Description of the outbreak of equine influenza (H3N8) in the United Kingdom in 2003, during which recently vaccinated horses in Newmarket developed respiratory disease.

Between March and May 2003, equine influenza virus infection was confirmed as the cause of clinical respiratory disease among both vaccinated and unvaccinated horses of different breeds and types in at least 12 locations in the UK. In the largest outbreak, 21 thoroughbred training yards in Newmarket, with more than 1300 racehorses, were affected, with the horses showing signs of coughing and nasal discharge during a period of nine weeks. Many of the infected horses had been vaccinated during the previous three months with a vaccine that contained representatives from both the European (A/eq/Newmarket/2/93) and American (A/eq/Newmarket/1/93) H3NN8 influenza virus lineages. Antigenic and genetic characterisation of the viruses from Newmarket and elsewhere indicated that they were all closely related to representatives of a sublineage of American viruses, for example, Kentucky/5/02, the first time that this sublineage had been isolated in the uk. In the recently vaccinated racehorses in Newmarket the single radial haemolysis antibody levels in acute sera appeared to be adequate, and there did not appear to be significant antigenic differences between the infecting virus and A/eq/Newmarket/1/93, the representative of the American lineage virus present in the most widely used vaccine, to explain the vaccine failure. However, there was evidence for significantly fewer infections among two-year-old horses than older animals, despite their having similar high levels of antibody, consistent with a qualitative rather than a quantitative difference in the immunity conveyed by the vaccination.

Amino Acid Sequence↗
PubMed2005

Characterisation of CTL and IFN-gamma synthesis in ponies following vaccination with a NYVAC-based construct coding for EHV-1 immediate early gene, followed by challenge infection.

Equine herpesvirus-1 (EHV-1) is a ubiquitous pathogen of horses, which continues to cause respiratory and neurological disease and abortion, despite the widespread use of vaccines. Cell mediated immunity (CMI) is thought to play a major role in protection against infection with EHV-1. The aim of this study was to characterise the virus-specific CMI response in ponies vaccinated with vP1014, a vaccinia-based construct (NYVAC) coding for the immediate early gene (gene 64) of EHV-1. This gene product is a CTL target protein for an equine MHC class I allele expressed on the A3 haplotype. EHV-primed yearling ponies expressing this haplotype were vaccinated once (n = 1), three (n = 1), or four times (n = 2), and one pony was kept as an unvaccinated control. Cytotoxic T lymphocyte (CTL) activity and interferon gamma (IFN-gamma) synthesis were measured before and after vaccination and challenge infection with EHV-1. Multiple immunisations with vP1014 resulted in increased CTL activity and IFN-gamma synthesis specific for EHV-1 compared with unvaccinated or singly vaccinated ponies. The phenotype of EHV-1 specific T-cells synthesising IFN-gamma was also modified by immunisation. In the unvaccinated pony, the predominant population synthesising IFN-gamma after EHV-1 stimulation was CD8alpha+. In contrast, multiply vaccinated ponies demonstrated an increased proportion of CD8alpha- T-cells synthesising IFN-gamma. The results demonstrated that vaccination with a NYVAC-based construct coding for gene 64 stimulated CMI. This immune response alone did not protect against challenge infection. However, the study does illustrate that vaccinia-based vaccines can stimulate CMI in the horse and may therefore contribute to protection against disease caused by EHV-1.

Animals↗
PubMed2005

Equine interferon gamma synthesis in lymphocytes after in vivo infection and in vitro stimulation with EHV-1.

Equine cytotoxic T lymphocyte (CTL) responses to equine herpesvirus-1 (EHV-1) are well characterised but little is known about the cytokine response after infection or vaccination. EHV-1 is common in horses and infects lymphocytes in vivo. This virus was used as a model to measure the synthesis of interferon gamma (IFN-gamma) by equine peripheral blood mononuclear cells (PBMC) after in vivo infection and/or in vitro stimulation with EHV-1. Both flow cytometry and ELISPOT assays were used to quantify equine IFN-gamma using a mouse anti-bovine IFN-gamma monoclonal antibody (clone CC302; shown to cross-react with recombinant equine IFN-gamma) and a rabbit anti-canine IFN-gamma polyclonal antibody. The percentage of PBMC synthesising IFN-gamma after in vitro stimulation with EHV-1 increased with age. In yearlings infected experimentally with EHV-1, PBMC showed two peaks of IFN-gamma synthesis, 11 and 56 days after infection. The IFN-gamma synthesis was principally associated with CD8(+) cells. The patterns of IFN-gamma synthesis detected by intracellular IFN-gamma staining or ELISPOT were compared with CTL data and shown to be similar. These methods were also applied successfully to frozen samples of PBMC. Measurement of equine IFN-gamma using these simple techniques can now be applied to future studies on protective cellular immune responses following virus infection and/or vaccination of horses.

Age Factors↗
PubMed2004

The effects of strain heterology on the epidemiology of equine influenza in a vaccinated population.

We assess the effects of strain heterology (strains that are immunologically similar but not identical) on equine influenza in a vaccinated population. Using data relating to individual animals, for both homologous and heterologous vaccinees, we estimate distributions for the latent and infectious periods, quantify the risk of becoming infected in terms of the quantity of cross-reactive antibodies to a key surface protein of the virus (haemagglutinin) and estimate the probability of excreting virus (i.e. becoming infectious) given that infection has occurred. The data suggest that the infectious period, the risk of becoming infected (for a given vaccine-induced level of cross-reactive antibodies) and the probability of excreting virus are increased for heterologously vaccinated animals when compared with homologously vaccinated animals. The data are used to parameterize a modified susceptible, exposed, infectious and recovered/resistant (SEIR) model, which shows that these relatively small differences combine to have a large effect at the population level, where populations of heterologous vaccinees face a significantly increased risk of an epidemic occurring.

Animals↗
PubMed2003

Diagnostic methods applied to analysis of an outbreak of equine influenza in a riding school in which vaccine failure occurred.

An outbreak of equine influenza H3N8 in a riding school is described retrospectively with emphasis on diagnosis and putative vaccine failure. In March 1995 an outbreak of equine influenza occurred among 11 horses in a riding school, where most horses had received basic primary immunizations and several booster vaccinations against influenza. Six of the 11 diseased horses had received their last booster vaccination within 5 months of the outbreak. Nevertheless, the influenza infection spread rapidly and clinical manifestations were prominent with frequent, harsh, dry coughing often accompanied by high fever. Nasal swabs were taken from 11 diseased horses. Influenza A virus of the equine H3N8 (equi-2) subtype was isolated from five nasal swab extracts. Stored nasal swab extracts were also retrospectively investigated in two different enzyme immunoassays designed to detect the type-specific conserved nucleoprotein of influenza A viruses, and in a single-tube reverse transcription-PCR (RT-PCR) using a set of primers based on highly conserved regions of the matrix gene of influenza A viruses. Five nasal swab extracts were found positive in a DAS-ELISA and seven in the Directigen((R)) Flu A (DFA) assay, respectively. Two nasal swab extracts from which virus was isolated did not give a positive result in the DAS-ELISA, and one of these also did not give a positive result in the DFA assay. Nine nasal swab extracts were found positive by RT-PCR. Moreover, all virus isolation and/or ELISA positive nasal swab extracts were confirmed by RT-PCR. Three nasal swab extracts were negative by virus isolation, PCR and ELISA. A significant rise in HI titre against influenza A/eq/Miami/63 (H3N8) virus was detected in seven of the nine paired sera available. In acute phase serum samples from 10 horses, SRH antibody levels varied widely. However, some horses with high, or at least putatively clinically protective SRH antibody levels, showed clinical signs and infection was confirmed. Antigenic analysis of two isolates showed that A/eq/Holland/1/95 (H3N8) and A/eq/Holland/2/95 (H3N8) cluster with the UK isolate Osgodsby/92, the Swedish isolate Borlänge/91 and some other European isolates, with H/2/95 identical in reactivity to Borlänge/91 and H/1/95 more similar in reactivity to Osgodsby/92 than H/2/95. Nucleotide and deduced amino-acid sequences showed large differences of both isolates as compared with Miami/63, Fontainebleau/79 and Kentucky/81, the influenza A H3N8 subtype strains incorporated in the vaccines used in this riding school. The role of antigenic drift in vaccine breakdown is discussed in the light of evidence for vaccine breakdown in the UK in 1989, Sweden in 1991 and in the USA since 1991.

Animals↗
PubMed2003

Hand-assisted laparoscopic splenectomy for giant spleens.

BACKGROUND: Laparoscopic splenectomy for massive splenomegaly is technically difficult, and the morcellated splenic tissue may be inadequate for histologic study. A hand-assisted technique may provide a technical advantage and allow removal of larger pieces of spleen. METHODS: Patients who underwent hand-assisted laparoscopic splenectomy for massive splenomegaly were reviewed. Demographic information, operative data, and outcomes data were tabulated. RESULTS: Sixteen patients met these criteria. Mean age was 56 years (range, 35-78 years). Operating time averaged 240 min (range, 165-360 min), and median blood loss was 425 cc (range, 100-1800 cc). There were no conversions to an open procedure. Mean weight of extracted spleens was 2008 g (range, 543-4090 g). Postoperative length of stay averaged 3.3 days (range, 2-7 days). There was one postoperative complication (6.25%) and no mortality. CONCLUSIONS: Hand-assisted laparoscopic splenectomy for massive splenomegaly is feasible and safe while preserving the recovery benefits of minimal access surgery. It provides an adequate specimen for histologic study.

Adult↗
PubMed2003

Comparison of hamster and pony challenge models for evaluation of effect of antigenic drift on cross protection afforded by equine influenza vaccines.

REASONS FOR PERFORMING STUDY: Vaccination and challenge studies in ponies are the most relevant experimental system for predicting whether strains included in equine influenza vaccines are relevant, but they are difficult to perform. OBJECTIVES: In order to investigate the feasibility of using a small animal model, results of a cross-protection study in hamsters were compared with those from a previous pony challenge experiment. METHODS: Animals were immunised with inactivated vaccines containing one of 4 strains of equine influenza A H3N8 subtype virus isolated over a 26 year period (1963 to 1989), then challenged with a 1989 strain. RESULTS: Although there was no significant difference in titres of excreted virus between groups of vaccinated ponies, hamsters immunised with heterologous strains had significantly higher virus titres in the lung than hamsters vaccinated with the homologous strain. In both ponies and hamsters, the number of animals excreting virus was greater the earlier the isolation date of the vaccine strain, although this was only significant in the hamster study. CONCLUSIONS: Despite differences, the overall conclusion of both the pony and hamster models was that heterologous vaccines may be less effective than homologous vaccines at preventing virus excretion. POTENTIAL RELEVANCE: Further validation is required, but the hamster model shows potential for preliminary assessment of the effects of antigenic drift on vaccine efficacy.

Animals↗
PubMed2001

An essential role for Src kinase in ErbB receptor signaling through the MAPK pathway.

ErbB receptor tyrosine kinases are activated by multiple ligands such as epidermal growth factor (EGF) and neuregulins (NRGs), leading to stimulation of intracellular signaling pathways, including the mitogen-activated protein kinase (MAPK) cascade. We show here that Src kinase is essential for rapid EGF- and NRG-induced MAPK activation when the breast carcinoma cell lines T47D and SKBR3 are stimulated with low concentrations of ligand. In the presence of the pharmacological inhibitor CGP77675, which specifically blocks the activity of Src family kinases, ligand-induced MAPK activation was almost completely blocked at 5 min. Although this block was only transient, inactivation of Src suppressed ligand-induced transcription from a MAPK-responsive promoter. At the molecular level, the initial inhibition of MAPK by Src inactivation correlated with impaired ligand-induced Shc phosphorylation. Surprisingly, Src inhibition affected neither association of Shc with ErbB receptors nor phosphorylation of receptor-bound Shc. Thus, ErbB signaling requires the engagement of a novel Src-dependent route to MAPK, to trigger its rapid activation and subsequent efficient stimulation of transcription.

Adaptor Proteins, Signal Transducing↗
PubMed2001

NS-398 treatment after trauma modifies NF-kappaB activation and improves survival.

Prostaglandin E(2) (PGE(2)) production after trauma contributes to immune alterations that increase susceptibility to infections. We hypothesize that blocking PGE(2) with NS-398, a selective COX-2 inhibitor, will modulate this response and improve outcome. This study evaluated the effect of NS-398 given over 7 days on proinflammatory cytokines, intracellular signaling, and survival after a septic challenge. Balb/C mice (n = 8/group) were given 10 mg/kg NS-398 intraperitoneally over 7 days, starting after anesthesia or trauma (femur fracture + 40% hemorrhage). Four groups, anesthesia + vehicle (C), anesthesia + NS-398 (CN), trauma + vehicle (T), or trauma + NS-398 (TN), were studied. On Day 7 after trauma, mice were sacrificed, serum was collected, and splenic macrophages were evaluated for PGE(2), LTB(4), IL-6, TNF-alpha, and NO production. Additionally, macrophage COX-2 mRNA, IkappaB-alpha, and NF-kappaB were evaluated. In a separate study, mice (n = 10-11/group) were traumatized and given NS-398 over 7 days, and then cecal ligation and puncture (CLP) were performed. Mice were then followed for survival over 10 days (via log-rank test). NS-398 treatment of injured mice decreased PGE(2) production compared to T (3.9 +/- 0.3 vs 3.1 +/- 0.4 pg/microg protein), and significantly decreased IL-6, NO, and TNF-alpha production. NS-398 treatment also attenuated COX-2 mRNA levels and NF-kappaB activation. These cellular events correlate with a significant survival advantage in TN versus T mice after CLP. These data suggest that a specific COX-2 inhibitor not only suppresses PGE(2), but normalizes proinflammatory cytokines after trauma through changes that may partly be mediated via transcriptional events. This correlates with significantly increased survival in TN mice given a septic challenge and suggests that COX-2 inhibitors contribute to modulating the inflammatory response and improving survival after trauma.

Animals↗
PubMed2001

Overlapping CRE and E-box promoter elements can independently regulate COX-2 gene transcription in macrophages.

Macrophage cyclooxygenase-2 (COX-2) transcription is mediated through the collaboration of different promoter elements. Here, the role of an overlapping cyclic AMP responsive element (CRE)/E-box was investigated. Nuclear proteins bound both the CRE and E-box, which synergized with other promoter elements to induce COX-2 transcription. Endotoxin induced binding of nuclear proteins to the CRE and E-box and each element independently induced higher COX-2 transcription levels than the overlapping CRE/E-box. Transcription factors associated with the CRE binding complex included c-Jun and CRE binding protein and with the E-box binding complex USF-1; their overexpression significantly induced COX-2 transcription. Therefore, both CRE and E-box promoter elements regulate COX-2 transcription in macrophages.

Animals↗
PubMed2001

Macrophage effector mechanisms in melanoma in an experimental study.

BACKGROUND: The tumor-bearing state is known to induce immune dysfunction that contributes to increased infectious complications and tumor progression. However, the mechanisms underlying this immunosuppression remain unclear. HYPOTHESIS: Macrophage (MO) dysfunction may play a role in tumor-induced immunosuppression. DESIGN AND MAIN OUTCOME MEASURES: Using a murine model, this study investigated the effects of melanoma growth on peritoneal macrophage effector molecule and prostaglandin production, MO-mediated cytotoxicity, and candidacidal mechanisms. Female C57BL/6 mice were inoculated with 106 B16 melanoma cells or a salt solution subcutaneously. Mice were euthanized 3 weeks later and peritoneal MOs were harvested and assayed for nitric oxide, superoxide anion, tumor necrosis factor alpha, and prostaglandin E(2)production. Macrophage-mediated cytotoxicity against B16 melanoma targets and MO candidacidal mechanisms were also measured. RESULTS: Macrophage production of nitric oxide, superoxide anion, and tumor necrosis factor alpha were significantly decreased, while prostaglandin E(2)production was increased in MOs from melanoma-bearing mice. Concomitantly, MO-mediated cytotoxicity and candidacidal mechanisms were significantly impaired. CONCLUSIONS: Melanoma growth leads to decreased MO effector molecule production, increased prostaglandin E(2)production, and impaired MO cytotoxic and candidacidal mechanisms. These results may help explain the observed increased infectious complications in the tumor-bearing host. Strategies aimed at restoring MO function may have therapeutic potential.

Animals↗
PubMed2001

The influence of restricted calorie intake on peritoneal macrophage function.

Malnutrition leads to immune dysfunction with greatly increased morbidity. However, restrictive dietary regimens are also known to preserve immune function in autoimmune-susceptible mice. The macrophage (Mø) is central to both immune effector and autoregulatory functions and is critical to host-defense mechanisms. The aim of this study was to investigate the effect of calorie restriction on Mø functions in mice. Female, 6- to 8-wk-old, Swiss Webster mice were randomized to ad libitum feeding for 7 or 21 d (n = 10 mice/group), restricted feeding (13.5 to 14.0 g/cage/d; n = 10) for 7 d, or restricted feeding (16.5 to 17.0 g/cage/d; n = 10) for 21 d. These restrictions were equivalent to a decrease in calorie intake of 21.9% and 5.1%, respectively, over 7 and 21 d. All mice were allowed free access to water. On days 8 and 22, respectively, the mice were killed, and peritoneal Møs were isolated by lavage and adhered to 96-well polystyrene tissue-culture-treated plates. After stimulation with lipopolysaccharide, supernatant prostaglandin E2 and interleukin-6 levels were measured by enzyme-linked immunosorbent assay. Supernatant NO2- in response to stimulation with lipopolysaccharide and interferon-gamma was determined by the Greiss reaction. Prostaglandin E2 production was significantly elevated in peritoneal Møs from the calorie-restricted mice compared with the ad-libitum-fed mice after 7 d. After 21 d, production of both prostaglandin E2 and nitric oxide was significantly increased (P < 0.05) in peritoneal Møs from the restricted mice compared with the ad-libitum-fed mice. These results indicate that calorie restriction influences immune function by altering prostaglandin E2 and nitric oxide generation by Møs.

Animals↗
PubMed2001

Behavioral and electrophysiological responses of Arhopalus tristis to burnt pine and other stimuli.

The exotic longhorn beetle Arhopalus tristis is a pest of pines, particularly those damaged by fire, and a major export quarantine issue in New Zealand. Actinograph recordings of caged individuals showed that males and females were most active from dusk to midnight. Olfactometer experiments indicated that females moved upwind toward odors from burnt pine (80%, N = 75), compared to unburnt pine (20%). Oviposition choice tests showed that eggs were predominantly laid on burnt logs (79%, N = 20), compared to unburnt logs. Beetles were trapped by funnel traps baited with burnt (mean catch per trap 7.8) and unburnt (mean catch 4.1 per trap) pine bark from inside a screen cage (4 x 3 m), while unbaited traps had a mean catch 0.1 beetles (N = 8 replicates). The treatment of burnt pine bark with a 1:1:2 mixture of green leaf volatiles (E)-2-hexen-1-ol and (E)-2-hexenal) in mineral oil as a repellent reduced trap catch by fivefold in a similar experiment (mean catches of 1.2 beetles per trap to burnt pine bark plus repellent treatment and 6.2 beetles per trap to burnt pine bark alone). The treatment of burnt pine bark with this solution also reduced oviposition by 98.5% (mean eggs per log of 11.1 on burnt pine and 0.3 on burnt pine plus repellent), indicating that oviposition cues have the potential to be significantly disrupted. The electrophysiological responses of adult beetles were recorded to a range of odorants. Normalized responses to monoterpenes known to occur in Pinus radiata ranged from about 20 to about 150, with alpha-terpineol giving the greatest responses in both sexes. Green leaf volatiles also gave high responses. The potential exists to improve the management of this insect using chemical cues in various ways.

Animals↗