Biomedical subjects

T M Ellis

Publications and source records attributed to T M Ellis.

At least 19 recordsLinked to original sources

PubMed2006

Comparison of sensitivity and specificity in three commercial foot-and-mouth disease virus non-structural protein ELISA kits with swine sera in Taiwan.

Three commercialized ELISA kits for the detection of antibodies to the non-structural proteins (NSPs) of FMD virus were compared, using sera from uninfected, vaccinated, challenged and naturally infected pigs. The kinetics of the antibody response to NSPs was compared on sequential serum samples in swine from challenge studies and outbreaks. The results showed that ELISA A (UBI) and ELISA B (CEDI) had better sensitivity than that of the 3ABC recombinant protein-based ELISA C (Chekit). The peak for detection of antibodies to NSPs in ELISA C was significantly delayed in sera from natural infection and challenged swine as compared to the ELISA A and B. The sensitivity of the three ELISAs gradually declined during the 6-month post-infection as antibodies to NSP decline. ELISA kits A and B detected NSP antibody in 50% of challenged pigs by the 9-10th-day and 7-8th-day post-challenge, respectively. ELISA B and C had better specificity than ELISA A on sequential serum samples obtained from swine immunized with a type O FMD vaccine commercially available in Taiwan. Antibody to NSPs before vaccination was not detected in swine not exposed to FMD virus, however, antibody to NSPs was found in sera of some pigs after vaccination. All assays had significantly lower specificity when testing sera from repeatedly vaccinated sows and finishers in 1997 that were tested after the 1997 FMD outbreak. However, when testing sera from repeatedly vaccinated sows or finishers in 2003-2004, the specificity for ELISAs A, B and C were significantly better than those in 1997. This effect was less marked for ELISA A. The ELISA B was the best test in terms of the highest sensitivity and specificity and the lowest reactivity with residual NSP in vaccinates.

Animals↗

PubMed2006

The virtual crossmatch--a screening tool for sensitized pediatric heart transplant recipients.

Heart transplantation in the setting of human leukocyte antigen (HLA) sensitization is challenging, as a time-consuming prospective crossmatch (XM) may be required, severely limiting the number of potential donors. We evaluated a 'virtual XM', defining a positive virtual XM as the presence of recipient pre-formed anti-HLA antibodies to the prospective donor HLA type, and compared the virtual XM to a standard direct XM. Bead-based flow cytometric analysis was used to identify anti-HLA antibody (Ab) present in a child listed for heart transplantation. Using recipient serum, direct-flow cytometric T- and B-cell XM were run for potential donors against whose HLA type the recipient had specific antibodies (group 1, n = 7) and for potential donors with predicted compatible HLA types by virtual XM (group 2, n = 7). Results were expressed as median channel difference (MCD) between the control and recipient serum. A positive T-cell XM was defined as MCD > 50, whereas MCD > 100 constituted a positive B-cell result. The rate of T-cell reactivity was significantly less in group 2 than in group 1 (29% vs. 100%, p = 0.02); similarly, B-cell reactivity was also less for group 2 (14% vs. 100%, p = 0.005). The virtual XM was 100% sensitive in detecting positive flow cytometric XM results for T and B cells. Although only 72% specific in predicting a negative T-cell XM, and 86% specific for negative B-cell XM, the false negatives were weakly positive and would probably have been clinically acceptable. Currently, potentially suitable donor organs are often declined for lack of a prospective XM; these organs may ultimately be allocated to more distant recipients or perhaps not used at all. While further studies are needed, virtual XM has the potential to improve availability of organs for sensitized patients and improve the overall allocation process.

B-Lymphocytes↗

PubMed2006

Use of avian influenza vaccination in Hong Kong.

Outbreaks of H5N1 highly pathogenic avian influenza (HPAI) that occurred in Hong Kong up until February/March 2002 were controlled by stamping out. With endemic presence of the virus in the region and large daily importation of poultry to Hong Kong, the Administration considered that further risk management measures, in addition to improved biosecurity and enhanced surveillance, were necessary to prevent outbreaks. Vaccination using a killed H5N2 vaccine was evaluated over a 12-month period in the district with the last HPAI cases in the early 2002 outbreak. The vaccination trial showed that farmer-administered killed H5N2 vaccine produced suitable flock antibody responses; vaccinated birds were protected against H5N1 HPAI virus challenge and excreted significantly less H5N1 virus; and vaccination was able to control virus excretion in flocks during field outbreaks. Universal vaccination of local chicken farms was introduced in June 2003 and by the end of 2003 all chickens entering the live poultry markets in Hong Kong were vaccinated by killed H5N2 vaccine. In addition to vaccination, an enhanced biosecurity programme on farms and in live poultry markets and a comprehensive surveillance programme in poultry, wild birds, recreation park birds and pet birds were in place. Vaccination use and performance is closely monitored. This programme was successful in protecting local farms and live poultry markets from H5N1 outbreaks during the regional H5N1 outbreaks in 2004.

Animals↗

PubMed2005

Japanese encephalitis in a racing thoroughbred gelding in Hong Kong.

A horse in Hong Kong that had been vaccinated against Japanese encephalitis suffered a pyrexic episode that culminated in a hyperexcitable state and self-inflicted trauma. Japanese encephalitis was diagnosed on the basis of clinical, pathological and serological observations, and confirmed by the detection of genomic sequences of the virus in spinal cord tissue. Phylogenetic analyses of E gene and NS5-3'UTR sequences revealed divergent clustering of these segments with previously described genotypes, suggesting the possibility that the horse might have been infected with a recombinant between genotype I and genotype II viruses. Horses are considered to be dead-end hosts for the disease, but the occurrence of an infected horse in a population may have implications for the health status of the national herd. The effect that this case had on the horse industry in Hong Kong is discussed with specific reference to the movement of horses and the vaccination programme for Japanese encephalitis.

Animals↗

PubMed2005

Role of domestic ducks in the propagation and biological evolution of highly pathogenic H5N1 influenza viruses in Asia.

Wild waterfowl, including ducks, are natural hosts of influenza A viruses. These viruses rarely caused disease in ducks until 2002, when some H5N1 strains became highly pathogenic. Here we show that these H5N1 viruses are reverting to nonpathogenicity in ducks. Ducks experimentally infected with viruses isolated between 2003 and 2004 shed virus for an extended time (up to 17 days), during which variant viruses with low pathogenicity were selected. These results suggest that the duck has become the "Trojan horse" of Asian H5N1 influenza viruses. The ducks that are unaffected by infection with these viruses continue to circulate these viruses, presenting a pandemic threat.

Animals↗

PubMed2005

Are ducks contributing to the endemicity of highly pathogenic H5N1 influenza virus in Asia?

Wild waterfowl are the natural reservoir of all influenza A viruses, and these viruses are usually nonpathogenic in these birds. However, since late 2002, H5N1 outbreaks in Asia have resulted in mortality among waterfowl in recreational parks, domestic flocks, and wild migratory birds. The evolutionary stasis between influenza virus and its natural host may have been disrupted, prompting us to ask whether waterfowl are resistant to H5N1 influenza virus disease and whether they can still act as a reservoir for these viruses. To better understand the biology of H5N1 viruses in ducks and attempt to answer this question, we inoculated juvenile mallards with 23 different H5N1 influenza viruses isolated in Asia between 2003 and 2004. All virus isolates replicated efficiently in inoculated ducks, and 22 were transmitted to susceptible contacts. Viruses replicated to higher levels in the trachea than in the cloaca of both inoculated and contact birds, suggesting that the digestive tract is not the main site of H5N1 influenza virus replication in ducks and that the fecal-oral route may no longer be the main transmission path. The virus isolates' pathogenicities varied from completely nonpathogenic to highly lethal and were positively correlated with tracheal virus titers. Nevertheless, the eight virus isolates that were nonpathogenic in ducks replicated and transmitted efficiently to naïve contacts, suggesting that highly pathogenic H5N1 viruses causing minimal signs of disease in ducks can propagate silently and efficiently among domestic and wild ducks in Asia and that they represent a serious threat to human and veterinary public health.

Animals↗

PubMed2005

Identification of a novel coronavirus in bats.

Exotic wildlife can act as reservoirs of diseases that are endemic in the area or can be the source of new emerging diseases through interspecies transmission. The recent emergence of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) highlights the importance of virus surveillance in wild animals. Here, we report the identification of a novel bat coronavirus through surveillance of coronaviruses in wildlife. Analyses of the RNA sequence from the ORF1b and S-gene regions indicated that the virus is a group 1 coronavirus. The virus was detected in fecal and respiratory samples from three bat species (Miniopterus spp.). In particular, 63% (12 of 19) of fecal samples from Miniopterus pusillus were positive for the virus. These findings suggest that this virus might be commonly circulating in M. pusillus in Hong Kong.

Amino Acid Sequence↗

PubMed2004

H5N1 influenza: a protean pandemic threat.

Infection with avian influenza A virus of the H5N1 subtype (isolates A/HK/212/03 and A/HK/213/03) was fatal to one of two members of a family in southern China in 2003. This incident was preceded by lethal outbreaks of H5N1 influenza in waterfowl, which are the natural hosts of these viruses and, therefore, normally have asymptomatic infection. The hemagglutinin genes of the A/HK/212/03-like viruses isolated from humans and waterfowl share the lineage of the H5N1 viruses that caused the first known cases of human disease in Hong Kong in 1997, but their internal protein genes originated elsewhere. The hemagglutinin of the recent human isolates has undergone significant antigenic drift. Like the 1997 human H5N1 isolates, the 2003 human H5N1 isolates induced the overproduction of proinflammatory cytokines by primary human macrophages in vitro, whereas the precursor H5N1 viruses and other H5N1 reassortants isolated in 2001 did not. The acquisition by the viruses of characteristics that enhance virulence in humans and waterfowl and their potential for wider distribution by infected migrating birds are causes for renewed pandemic concern.

Animals↗

PubMed2004

Combined effects of Matrigel and growth factors on maintaining undifferentiated murine embryonic stem cells for embryotoxicity testing.

Undifferentiated, murine embryonic stem (mES) cells have shown promise as a substrate for identifying embryotoxic chemicals and for studying mechanisms of early developmental injury. However, long-term maintenance of mES cells in an undifferentiated state is problematic. The present study evaluates the combination of Matrigel matrix and three growth factors for this purpose. Biomarkers of mES cell pluripotency, apoptosis, chromosome number and cardiomyocyte differentiation were monitored over 119 population doublings. D3 mES cells retained undifferentiated characteristics, including sustained expression of alkaline phosphatase and stage specific embryonic antigen-1 (SSEA-1) and continued transcription of Pou5f1 (Oct-4). Cell viability remained at > or=95% and population-doubling times averaged 14.3 h over 10 weeks of observation. Caspase-3 activation, a marker of cellular death by apoptosis, was measured in early- and late-passage mES cells. Early-passage cells showed dose-responsive caspase-3 activation following exposure to sodium arsenite, whereas caspase-3 activation of late-passage cells dropped to background levels at toxicant dosages above 50 ppb. Aneuploidy and impaired differentiation into beating cardiomyocytes were noted for late-passage mES cells. Matrigel, combined with growth factors, may sustain undifferentiated mES cells. However, aneuploidy, reduced caspase-3 activation, and inability to differentiate suggests further modifications to the culture system may be needed for long-term propagation of cells for embryotoxicity endpoints.

Aneuploidy↗

PubMed2004

Immunity to adeno-associated virus serotype 2 delivered transgenes imparted by genetic predisposition to autoimmunity.

Adeno-associated virus (AAV) is widely considered a promising vector for therapeutic gene delivery. This promise is based on previous studies assessing AAVs safety and toxicity, ability to infect nondividing cells, elicit a limited immune response and provide long-term gene expression. However, we now find that earlier studies underappreciated the degree of AAV immunogenicity as well as the extent to which genetic background, through regulation of immune responsiveness, influences the duration of gene expression and thereby the effectiveness of AAV-mediated gene therapy. We evaluated antibody responses in 12 mouse strains to AAV serotype 2 (AAV2) and AAV2-expressed transgene products including green fluorescent protein (GFP), human alpha1-antitrypsin and murine interleukin-10. As expected, all immunocompetent mice administered AAV2 developed serologic evidence of immune responsiveness to the virus. However, a previously unidentified serologic prozone effect was observed suggesting that the concentrations of anti-AAV2 antibodies may have historically been subject to marked underestimation. Furthermore, strains with genetic predisposition to autoimmunity (eg, NOD, NZW, MRL-lpr) specifically imparted a functionally deleterious immune response to AAV-delivered transgene products. These findings suggest that more thorough studies of anti-AAV immunity should be performed, and that genetic predisposition to autoimmunity should be considered when assessing AAV efficacy and safety in humans.

Animals↗

PubMed2004

Recombinant adeno-associated virus-mediated alpha-1 antitrypsin gene therapy prevents type I diabetes in NOD mice.

Type I diabetes results from an autoimmune destruction of the insulin-producing pancreatic beta cells. Although the exact immunologic processes underlying this disease are unclear, increasing evidence suggests that immunosuppressive, immunoregulatory and anti-inflammatory agents can interrupt the progression of the disease. Alpha 1 antitrypsin (AAT) is a multifunctional serine proteinase inhibitor (serpin) that also displays a wide range of anti-inflammatory properties. To test the ability of AAT to modulate the development of type I diabetes, we performed a series of investigations involving recombinant adeno-associated virus vector (rAAV)-mediated gene delivery of human alpha-1 antitrypsin (hAAT) to nonobese diabetic (NOD) mice. Recombinant AAV-expressing hAAT (rAAV2-CB-AT) was administered intramuscularly to 4-week-old female NOD mice (1 x 10(10) i.u./mouse). A single injection of this vector reduced the intensity of insulitis, the levels of insulin autoantibodies, and the frequency of overt type I diabetes (30% (3/10) at 32 weeks of age versus 70% (7/10) in controls). Transgene expression at the injection sites was confirmed by immunostaining. Interestingly, antibodies against hAAT were present in a majority of the vector-injected mice and circulating hAAT was undetectable when assessed 10 weeks postinjection. This study suggests a potential therapeutic role for AAT in preventing type I diabetes as well as the ability of AAV gene therapy-based approaches to ameliorate disease effectively.

Animals↗

PubMed2003

An update on avian influenza in Hong Kong 2002.

An outbreak of highly pathogenic avian influenza caused by multiple genotypes of H5N1 virus occurred in Hong Kong, commencing in January 2002. Infection in local chicken farms was preceded by the detection of virus in multiple retail markets and the main poultry wholesale market. The first case of this disease on a local farm was detected on February 1, 2002. By February 9, 2002, 15 farms were infected, and by late March a total of 22 infected farms had been identified. Three main clusters of infected farms were seen, suggesting multiple incursions of virus, and subsequent limited lateral spread to neighboring firms. Control of this disease has been effected through a combination of quarantine, tightening of biosecurity measures, and depopulation of infected and contact farms. About 950,000 birds have been destroyed. Vaccination using a killed H5 vaccine was introduced in April 2002 to farms in one zone where infection has persisted. None of the viruses isolated contained the internal genes found in the 1997 H5N1 virus.

Animals↗

PubMed2003

Avian influenza in Hong Kong 1997-2002.

In 1997, a high-pathogenicity H5N1 avian influenza virus caused serious disease in both man and poultry in Hong Kong, China. Eighteen human cases of disease were recorded, six of which were fatal. This unique virus was eliminated through total depopulation of all poultry markets and chicken farms in December 1997. Other outbreaks of high-pathogenicity avian influenza (HPAI) caused by H5N1 viruses occurred in poultry in 2001 and 2002. These H5N1 viruses isolated had different internal gene constellations to those isolated in 1997. No new cases of infection or disease in man due to these or other H5N1 viruses have been reported. This paper provides an overview and chronology of the events in Hong Kong relating to avian influenza, covering the period from March 1997 to March 2002.

Animals↗

PubMed2003

Reassortants of H5N1 influenza viruses recently isolated from aquatic poultry in Hong Kong SAR.

The H5N1 virus (H5N1/97) that caused the bird flu incident in Hong Kong in 1997 has not been isolated since the poultry slaughter in late 1997. But the donor of its H5 hemagglutinin gene, Goose/Guangdong/1/96-like (Gs/Gd/96-like) virus, established a distinct lineage and continued to circulate in geese in the area. In 2000, a virus from the Goose/Guangdong/1/96 lineage was isolated for the first time from domestic ducks. Subsequently, it has undergone reassortment, and these novel reassortants now appear to have replaced Gs/Gd/96-like viruses from its reservoir in geese and from ducks. The internal gene constellation is also different from H5N1/97, but these variants have the potential for further reassortment events that may allow the interspecies transmission of the virus.

Animals↗

PubMed2002

Emergence of multiple genotypes of H5N1 avian influenza viruses in Hong Kong SAR.

Although A/Hong Kong/156/97 (H5N1/97)-like viruses associated with the "bird flu" incident in Hong Kong SAR have not been detected since the slaughter of poultry in 1997, its putative precursors continue to persist in the region. One of these, Goose/Guangdong/1/96 (H5N1 Gs/Gd)-like viruses, reassorted with other avian viruses to generate multiple genotypes of H5N1 viruses that crossed to chickens and other terrestrial poultry from its reservoir in geese. Whereas none of these recent reassortants had acquired the gene constellation of H5N1/97, these events provide insight into how such a virus may have been generated. The recent H5N1 reassortants readily infect and kill chicken and quail after experimental infection, and some were associated with significant mortality of chickens within the poultry retail markets in Hong Kong. Some genotypes are lethal for mice after intra-nasal inoculation and spread to the brain. On this occasion, the early detection of H5N1 viruses in the retail, live poultry markets led to preemptive intervention before the occurrence of human disease, but these newly emerging, highly pathogenic H5N1 viruses provide cause for pandemic concern.

Animals↗

PubMed2002

H5N1 influenza viruses isolated from geese in Southeastern China: evidence for genetic reassortment and interspecies transmission to ducks.

The H5N1 viruses (H5N1/97) associated with the "bird-flu" incident in the Hong Kong SAR have not been isolated since the slaughter of poultry in December 1997 brought that outbreak to an end. Recent evidence points to this virus as having arisen through a reassortment of a number of precursor avian viruses and a virus related to Goose/Guangdong/1/96 (H5N1) (Gs/Gd/96) was the likely donor of the H5 hemagglutinin. We characterize the Goose/Guangdong/1/96-like viruses isolated from geese and ducks imported into Hong Kong in the year 2000. Antigenically and genetically, these recent H5N1 viruses fall into two groups, one mainly associated with geese, and the other, recently transmitted to ducks. Further, viruses isolated from a goose and a duck in December 2000 have acquired NS, PA, M, and PB2 genes from the aquatic avian influenza gene pool through reassortment. For pandemic preparedness, it is important to monitor whether these reassortant viruses have the capacity for interspecies transmission to terrestrial poultry or mammals.

Animals↗

PubMed2002

Effect of the interval between shearing and dipping on the spread of Corynebacterium pseudotuberculosis infection in sheep.

OBJECTIVE: To determine whether the spread of Corynebacterium pseudotuberculosis infection to sheep in dips could be controlled by increasing the time between shearing and dipping. DESIGN: A controlled treatment trial where only the time between shearing and dipping was varied. ANIMALS AND PROCEDURE: One hundred and ninety-five sheep were found to be negative for C. pseudotuberculosis exposure by assay of CLA toxin antibody, were divided into four treatment groups. Each was shorn at either 0, 2, 4 or 8 weeks before dipping in a solution containing C. pseudotuberculosis. Blood samples were taken 6 weeks after dipping and sheep were slaughtered 12 weeks after dipping. A fifth smaller group of 14 sheep shorn 26 weeks before dipping, was also exposed to C. pseudotuberculosis and was slaughtered with the other sheep. RESULTS: The occurrence of caseous lymphadenitis abscesses did not differ between groups or with sheep shorn 26 weeks before dipping. The proportion of sheep that seroconverted to the C. pseudotuberculosis toxin and cell wall ELISA was larger in sheep dipped immediately after shearing than in sheep in the other groups. CONCLUSIONS: Delaying dipping until 8 weeks after shearing did not decrease the C. pseudotuberculosis infection rate due to dipping. Sheep dipped immediately after shearing developed higher concentrations of antibody to C. pseudotuberculosis than sheep when dipping occurred between 2 and 8 weeks and later after shearing.

Animal Husbandry↗

PubMed2001

T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer.

Manipulations capable of breaking host tolerance to induce tissue-specific T cell-mediated inflammation are of central importance to tumor immunotherapy and our understanding of autoimmunity. We demonstrate that androgen ablative therapy induces profuse T cell infiltration of benign glands and tumors in human prostates. T cell infiltration is readily apparent after 7-28 days of therapy and is comprised predominantly of a response by CD4+ T cells and comparatively fewer CD8+ T cells. Also, T cells within the treated prostate exhibit restricted TCR Vbeta gene usage, consistent with a local oligoclonal response. Recruitment/activation of antigen-presenting cells in treated prostate tissues may contribute to local T cell activation. The induction of T cell infiltration in prostate tissues treated with androgen ablation may have implications for the immunotherapeutic treatment of prostate cancer as well as other hormone-sensitive malignancies, including breast carcinoma.

Androgen Antagonists↗