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Biomedical subjects

A R Gregory

Publications and source records attributed to A R Gregory.

18 recordsLinked to original sources
PubMed1992

Cancer risk--does anyone really care?

Congress has enacted numerous laws in an attempt to protect people from carcinogens. But neither regulators nor oncologists can hope to accomplish this protection via studies in epidemiology. Nor can they hope to accomplish this using unverified models in carcinogenesis bioassays. The only viable hope is to test and utilize models of carcinogenicity that will tell us what we really need to know; i.e., does this substance pose a reasonable risk of carcinogenesis in man? And if so, what is a quantitative estimate of that risk? There is a substantial number of known human carcinogens. Yet, the most elaborate cancer-testing facility in the world continues to operate without the benefit of validating its results using positive controls (known human carcinogens). Without such controls to gauge the potency of the response in the test animal, Congress can pass 10,000 more laws and still the public will remain unprotected.

Animals↗
PubMed1991

Evaluation of a toxoid for protection of rabbits against enterotoxaemia experimentally induced by trypsin-activated supernatant of Clostridium spiroforme.

Investigations were conducted into an enterotoxaemia caused by Clostridium spiroforme responsible for significant losses in commercial rabbit farms in Western Australia. Two trials using laboratory and farm bred rabbits were performed to evaluate the protective value of a toxoid prepared from the supernatant of C. spiroforme cultures against intraperitoneal challenge with the trypsin-activated toxin of C. spiroforme. The trials showed clearly that a single vaccination at weaning (four weeks) was protective against toxin but more complete and lasting protection was conferred following a second vaccination administered 14 days after the first. Adults likewise showed similar levels of protective antibodies but did not appear to pass on this protection to their kits although ELISA results indicated levels of antibody in kits from unvaccinated mother to be lower than progeny from vaccinated mothers. However antibody levels in kits from vaccinated mothers were very low and did not protect against challenge with toxin.

Animals↗
PubMed1990

Uncertainty in health risk assessments.

Considerable scientific evidence has accumulated in the area of risk assessment. Using physiologically based pharmacokinetic models and biologically based dose-response models, more precise estimates of risk are becoming available. Uncertainty analysis performed at three steps of the process will enhance a clearer understanding of the assumptions being made regarding a public health decision. Recommendations are made on how uncertainty in risk assessments can be addressed and the types of future research that are required to this end.

Animals↗
PubMed1989

Inflammatory cell and immune function in Merino sheep with chronic dermatophilosis.

Components of inflammatory and immunological responses were compared in 17 Merino sheep with chronic dermatophilosis (Group 1) and 15 Merino sheep that had recovered from the disease (Group 2). The functions studied included: (i) total and differential white cell counts; (ii) phagocytic function and intracellular killing by neutrophils; (iii) humoral immune response to T-dependent and T-independent antigens and to Dermatophilus congolensis. (iv) lymphocyte blastogenic responses to phytohaemagglutinin; (v) bovine serum albumen and D. congolensis antigens; (vi) quantification of T-lymphocyte subsets in skin lesions resulting after re-infection with D. congolensis zoospores. After all lesions were treated and the sheep were shorn, both groups of sheep were re-infected with D. congolensis. Both groups had similar infection rate, severity of lesions and rate of resolution after re-infection. The Group 2 sheep had significantly higher primary and secondary antibody responses to killed Brucella abortus cells than Group 1 sheep, but Group 1 sheep had higher levels of specific D. congolensis antibody throughout the trial. Neutrophils from Group 1 sheep showed a higher phagocytic rate for D. congolensis zoospores than Group 2 sheep when the zoospores were opsonised by sera from the Group 1 sheep, but there was no difference in their ability to kill ingested zoospores. Although there were some differences between the groups in the proportion of lymphocytes in lesions that reacted with monoclonal antibodies to T4, T8 and T19-19 lymphocyte markers at various times after re-infection, the sheep in Group 2 consistently had higher levels of lymphocytes reacting to a monoclonal antibody for the T6 lymphocyte antigen in skin biopsies collected 9, 15 and 21 days post-inoculation (p.i.) than did sheep in Group 1. Group 2 sheep also had higher levels of epidermal cells with immunohistochemical properties of Langerhans cells at lesion sites 15 and 21 days p.i.

Actinomycetales Infections↗
PubMed1988

Species comparisons in evaluating carcinogenicity in humans.

Some species and strains of experimental animals have such unique mechanisms of developing cancer that the extrapolation of such bioassay results to the human situation would be fraudulent. This fraudulent extrapolation could occur both qualitatively and quantitatively. Although it will be expensive, species other than the rat, mouse, and hamster should be tested, and tested at wider dose ranges than presently used, before risk assessors will have sufficient data to make legitimate risk estimates. Both species- and strain-unique mechanisms and pharmacokinetic information must be made available to the risk assessors before their estimates can be any better than "guesstimates." As more and more data become available, it will become essential that newer techniques of visualization of the data be used in order to evaluate the weight of evidence that an animal carcinogen is or is not a human carcinogen.

Animals↗
PubMed1987

Serum and skin surface antibody responses in merino sheep given three successive inoculations with Dermatophilus congolensis.

Three antigens prepared from different phases of the life cycle of Dermatophilus congolensis were used in an enzyme-linked immunosorbent assay to measure serum and skin surface antibody responses in sheep after a first, second and third inoculation with D. congolensis. After the first inoculation, a strong antibody response to the flagella, filament and soluble antigens was detected after 7-21 days in the sera from sheep that were regularly biopsied; the antibody response at the skin surface was detected 28-42 days after inoculation, when the lesions were resolving. Strong anamnestic responses were detected in the serum of sheep that were biopsied and some of the nonbiopsied sheep after the second and third inoculations, but the skin surface antibody response at these times was variable.

Actinomycetales↗
PubMed1987

Cellular responses in the skin of merino sheep to repeated inoculation with Dermatophilus congolensis.

The cellular response in the skin of Merino sheep was examined after three successive inoculations with Dermatophilus congolensis. There was a massive neutrophil influx into the infected epidermis and underlying dermis at 4-10 days after the first inoculation. A lymphocyte-macrophage response occurred at 10-12 days, followed by a plasma cell response at 14-38 days. Resolution of skin lesions after the first inoculation corresponded to the time when the plasma cell response in the skin was most intense. A second inoculation with D. congolensis, 70 days after the first, failed to produce skin lesions typical of dermatophilosis. Typical lesions of dermatophilosis did develop after a third inoculation of the same sheep 140 days after the first inoculation, but the lesions resolved in most sheep within 13 days. Dermatophilosis did not develop in some of these sheep at sites inoculated with 100-1000-fold lower infective doses of D. congolensis, whereas control sheep did develop lesions.

Actinomycetales↗