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Biomedical subjects

T J Alexander

Publications and source records attributed to T J Alexander.

At least 19 recordsLinked to original sources

An approach to the control of disease transmission in pig-to-human xenotransplantation.

Although several major immunologic hurdles need to be overcome, the pig is currently considered the most likely source animal of cells, tissues and organs for transplantation into humans. Concerns have been raised with regard to the potential for the transfer of infectious agents with the transplanted organ to the human recipient. This risk is perceived to be increased as it is likely that the patient will be iatrogenically immunocompromised and the organ-source pig may be genetically engineered in such a way to render its organs particularly susceptible to infection with human viruses. Furthermore, the risk may not be restricted to the recipient, but may have consequences for the health of others in the community. The identification of porcine endogenous retroviruses and of hitherto unknown viruses have given rise to the most concern. We document here the agents we believe should be excluded from the organ-source pigs. We discuss the likelihood of achieving this aim and outline the potential means by which it may best be achieved.

Animals↗

Protective effect of sera raised against different fractions of Streptococcus suis type 2.

Five bands of 44, 54, 78, 86 and 94 kD were identified by Western blot analysis of Streptococcus suis type 2 by the use of sera that were from immune or non-immune pigs and were positive or negative in bactericidal tests in vitro. These bands were cut from the gels and used as antigens to produce antisera in rabbits. Rabbit sera against the 78 and 94 kD bands were positive in bactericidal tests, and the serum against the 94 kD band also protected mice against challenge with a live pathogenic strain of S. suis type 2. The serum raised against the 78 kD band was not protective in mice and appeared to inhibit the protective effect of the 94 kD band antiserum. Rabbit sera raised against the 44, 54 and 86 kD bands were negative in bactericidal tests and failed to protect mice against challenge.

Animals↗

Immunisation of pigs with killed cultures of Streptococcus suis type 2.

Ten intravenous inoculations of 10(10) formalin-killed pathogenic Streptococcus suis type 2 stimulated detectable levels of opsonic antibody and a strong protective response against intravenous challenge with 10(9) viable S suis type 2 of the same strain. Heat-killed organisms did not stimulate a protective response, even though the type-specific antigen was intact and opsonic antibodies were induced. When the number of formalin-killed organisms in the inoculum was increased 10-fold, one inoculation was insufficient to stimulate a protective response, but two inoculations protected pigs against intravenous challenge with live, pathogenic organisms. Four-hour and overnight cultures were equally immunogenic, and the response was not enhanced by either Freund's incomplete adjuvant or aluminium hydroxide gel adjuvant.

Animals↗

Studies of the protective effect of different fractions of sera from pigs immune to Streptococcus suis type 2 infection.

Inoculation of mice with high doses of Streptococcus suis type 2 caused depression, anorexia, lethargy and sometimes death. This was prevented by prior inoculation of whole immune pig serum, the IgM and IgG fractions of immune pig serum and serum enriched with antibody to surface antigens. Clinical signs were not prevented by prior inoculation of pre-immune serum or serum depleted of antibody to surface antigens. Serum fractions that were protective in vivo were also opsonic in vitro. Western blot analysis identified two antigens of 44 and 78 kd that were recognized strongly by protective sera and a further four of 86, 94, 130 and 136 kd that were recognized less intensely.

Animals↗

Detection of heterotopic gastric mucosa in the upper esophagus with 99mTc-pertechnetate scintigraphy.

Five patients with patches of gastric fundal type columnar epithelium in the proximal esophagus at the level of the upper esophageal sphincter diagnosed by upper endoscopy underwent 99mTc-pertechnetate scintigraphy (TcO4-). In all instances, the patches contained both chief cells and mucus-secreting cells. One patient had dysphagia localized to the area of columnar epithelium. Two cases of heterotopic gastric mucosa in the upper esophagus (HGM-UE) were demonstrated by TcO4-. In both, thyroid uptake was absent due to complete suppression of thyroid function by thyroid hormone supplements. TcO4- accumulated in thyroid glands of the other three patients, causing overlapping activity between the thyroid gland and HGM-UE. TcO4- scintigraphy is suitable for the detection of HGM-UE only in those patients who have had a total thyroidectomy or are on suppressive thyroid therapy.

Adolescent↗

Immunisation of pigs with live cultures of Streptococcus suis type 2.

Repeated intravenous injections of pigs with live virulent cultures of Streptococcus suis type 2 stimulated a strong protective response against subsequent challenge. This protection was transferred passively to susceptible pigs by the inoculation of sera from protected pigs. A strong protective response was also stimulated by repeated inoculations of live cultures of non-pathogenic isolates. The protective response did not eliminate S suis type 2 organisms already established in the tonsils or joints, nor prevent the establishment of subclinical infection in the tonsils.

Animals↗

A murine model of Streptococcus suis type 2 meningitis in the pig.

When young or adult mice were infected experimentally with isolates of Streptococcus suis type 2 of known pathogenicity for pigs, the organisms produced disease, young mice being more susceptible than adults. An isolate of S suis type 2 less pathogenic for pigs also appeared less pathogenic in mice. The organism could be reisolated from infected mice for up to 42 days. Inoculum size was one factor influencing the likelihood of an individual mouse developing meningitis following intravenous inoculation. Transmission of the organism from inoculated to in-contact mice occurred in young mice after intravenous or oral administration. These studies indicate that the behaviour of S suis type 2 in mice resembles its behaviour in pigs.

Animals↗

Monitoring herds for Streptococcus suis type 2 by sampling tonsils of slaughter pigs.

Heads were removed soon after slaughter from the dressed carcases of 155 pigs belonging to 12 herds with a history of streptococcal meningitis and from 180 pigs from four herds believed to be free from this disease. Deep scrapings from both tonsils were sown on two selective media. Streptococcus suis type 2 was detected in a proportion of pigs from the 12 herds with a history of the disease, including three herds in which no cases were noted during the year this study was made. Pigs in six of these herds had received therapeutic levels of certain antibiotics in their feed as growers. The confirmed detectable tonsillar carrier rates varied between these 12 herds from 20 to 90 per cent and between batches of heads from one herd from 0 to 100 per cent. Carrier rates could not be correlated with disease levels, herd size or husbandry system. S suis type 2 was also detected in pigs from two herds thought to be free of the disease, at rates of 20 and 1.5 per cent.

Animal Husbandry↗

Further studies on the subclinical carrier state of Streptococcus suis type 2 in pigs.

Tonsil swabs were taken from 626 pigs of all ages in four infected herds. Streptococcus suis type 2 was isolated from 106 pigs aged between three weeks and 18 months. Detectable carrier rates in different groups of pigs varied between 0 and 80 per cent and were highest in weaned pigs aged between four and 10 weeks. Deep scrape cultures carried out post mortem suggested that the actual carrier rate was higher than that detected by tonsil swabs before death. Detection was improved by using two selective media. S suis type 2 persisted in the tonsils in the presence of circulating opsonic and binding antibodies and in pigs receiving penicillin-medicated feed. It was detected in the tonsils of individuals for up to 521 days. It was rarely detected in the nose. Some carriers appeared to eliminate the infection. Weaned detectable tonsil carriers transmitted the infection to previously uninfected pigs with which they were mixed. Titres of serum binding antibodies assessed by a micro enzyme-linked immunosorbent assay were relatively low and results from infected and non-infected pigs were not always distinguishable.

Animals↗

The influence of the stage of the estrous cycle and novel cows upon mounting activity of dairy cattle.

The objectives of this study were to determine directly if mounting activity in dairy cattle varied as a function of stage of the estrous cycle and to determine if mounting by cows could be stimulated when novel estrous cows were introduced. Detector cows were normally cycling. Estrous cows were ovariectomized and injected with estradiol cyprionate and progesterone to induce standing estrous behavior. Familiar estrous cows (prior exposure to detector cows) and novel estrous cows (no prior exposure to detector cows) encountered each detector cow (n = 19) in a one-on-one manner for a 10-min period. Mounting activity by detector cows was determined by observation on d 5, 10, 15, day of estrus and d 5 of the subsequent cycle (52). The first d 5 was considered an acclimation day and was deleted from the data because all estrous cows (n = 4) used were novel. These novel estrous cows then became familiar estrous cows on the subsequent days (10, 15, estrus, 52). On these days, familiar (n = 4) and novel (n = 2) estrous cows encountered individually each detector cow in a prearranged sequence. Stage of the estrous cycle influenced (P less than .001) the frequency of mounting by detector cows. Mounting activity of detector cows was inversely related (r = -.64, P less than .001) to concentrations of plasma progesterone. The introduction of novel estrous cows tended to stimulate (P = .07) mounting when all days were considered. In addition, the introduction of novel estrous cows stimulated (P less than .001) mounting on d 15 and 52. A second experiment was conducted to determine if the introduction of novel estrous cows stimulated mounting in the detector cows on the day of estrus if a longer encounter time (30 min) was used. A total of eight detector cows and eight estrous cows (four familiar and four novel) were used. When the detector cow was in standing estrus, she encountered one-on-one each of two familiar estrous cows and each of two novel estrous cows in a prearranged sequence for 30-min. The introduction of novel estrous cows stimulated (P = .001) mounting by the detector cows on the day of estrus (6.50 +/- .48 vs. 4.37 +/- .48 mounts for N and F cows, respectively). We conclude that mounting activity is reduced during midcycle and that the introduction of novel cows stimulated mounting activity on d 15, day of estrus and on d 5 of the estrous cycle.

Animals↗

Medicated early weaning to obtain pigs free from pathogens endemic in the herd of origin.

A field trial was conducted to assess the value of medicated early weaning for obtaining pigs free from some of the pathogens endemic in their herd of origin. The trial comprised 51 sows from a closed herd, which were farrowed in an isolated farrowing house in seven separate groups. The sows in each group were bred at the same time and induced to farrow on the same day. Their thriftiest piglets were weaned at five days of age and moved to an isolated early-weaning unit. At about six weeks of age they were moved to one of three isolated grow-out units where they were held to slaughter weight. Sows in five of the groups were dosed with high levels of tiamulin and trimethoprim-sulphonamide preparations from their entry into the farrowing house until their biggest piglets were weaned. Their piglets were dosed with similar drugs from birth until 10 days of age. The first and seventh groups of sows and their litters were not medicated. Tests were carried out on pigs aged five to 11 weeks, on slaughter pigs, and on pigs which died or were killed at different ages, for Mycoplasma hyopneumoniae, Bordetella bronchiseptica and colonic treponemes, which were readily detectable in the herd of origin. No evidence could be found of mycoplasma or bordetella. Colonic treponemes were recovered from some of the pigs at slaughter, but not from younger pigs. Thirty-seven boars and gilts from the medicated groups were introduced into 11 herds thought to be free of enzootic pneumonia and 13 were introduced into three herds which had enzootic pneumonia. No subsequent signs of enzootic pneumonia were noted in 10 of the enzootic pneumonia-free herds.

Administration, Oral↗