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Biomedical subjects

P B Medawar

Publications and source records attributed to P B Medawar.

At least 19 recordsLinked to original sources
PubMed1986

T-cell depletion of allogeneic bone marrow prevents acceleration of graft-versus-host disease induced by exogenous interleukin 2.

Highly purified human recombinant interleukin 2 (IL-2) markedly accelerated lethal GVHD in the H-2-identical B10.BR----CBA combination, but had no effect when the donor cells were depleted of mature (Thy-1.2-positive) T lymphocytes, indicating a strong immunopotentiating effect of IL-2 on mature T cells causing GVHD. In the same donor-host combination, IL-2 did not influence the recovery from the post-transplantation bone marrow aplasia. The results suggest that IL-2 could be considered for adjuvant hormonal therapy to enhance immune recovery in recipients of T-cell-depleted allogeneic marrow.

Animals↗
PubMed1985

Influence of dendritic cells on tumor growth.

Dendritic cells (DC) exposed to antigen are potent initiators of immune responses, and the numbers of DC and the dose of antigen control the level of response. The influence of these variables was tested on the growth of mouse sarcoma cells in vivo. When normal syngeneic DC (100,000) were given to mice with palpable tumors, tumor regression or delay in tumor growth was obtained. DC exposed to increasing doses of tumor extract in vitro before administration had progressively less effect. DC exposed to antigen delayed tumor growth significantly only when given on the same day as 500 tumor cells. The studies suggested that low doses of antigen on DC elicit immune responses and that high doses block them. The numbers of antigen-presenting cells and the dose of antigen modulate the degree of immunity to mouse sarcoma in vivo.

Animals↗
PubMed1985

Acquired immunological tolerance of foreign cells is impaired by recombinant interleukin 2 or vitamin A acetate.

The susceptibility of newborn mice to the inception of tolerance after exposure to antigen is associated with their deficiency in the production of endogenous interleukin 2 (IL-2). As further evidence of the complicity of IL-2 in the inception and maintenance of tolerance, it is shown here that a solid and long-lasting state of tolerance induced by the intravenous injection into newborn CBA mice of lymphoid cells from (CBA X C57BL/10ScSn)F1 hybrids can be brought to an end by the administration of exogenous IL-2 or by supplementing an otherwise normal diet with vitamin A acetate, the effect of which is to increase the proportion of the moiety of the T-cell population that produces IL-2. These results indicate that certain nonspecific stimuli can influence whether immunological tolerance is maintained.

Animals↗
PubMed1984

Retinyl acetate-mediated augmentation of resistance to a transplantable 3-methylcholanthrene-induced fibrosarcoma. The dose response and time course.

An otherwise conventional diet supplemented with retinyl acetate (vitamin A acetate; VAA) increased a specific antitumor resistance in vivo in mice, and this appeared to be due to the enhancement of immune functions rather than a direct antitumor activity. A range of VAA doses (up to 0.8 g VAA per kg of diet), fed for more than 6 months, did not induce any obvious signs or symptoms of hypervitaminosis A. The augmentation of resistance to transplanted tumor was linearly dependent on the dose of VAA. There was also a positive linear relationship between the resistance to transplanted tumor and the length of exposure to supplementary VAA relative to tumor inoculation time. The maximum resistance to transplanted tumor was observed in VAA-fed mice when the enrichment of the diet with VAA started three or more weeks before inoculation of tumor, whereas initiation of the VAA diet on the day of tumor administration or later had a negligible effect on the growth of tumor.

Animals↗
PubMed1983

Can fetal antigens be used for prophylactic immunization?

Even if the inoculation of fetal tissue cells were a dependable and uniformly successful method of protecting experimental animals against chemically or virally induced tumours, it would for obvious reasons still not be feasible to use fetal tissues for such a purpose in human beings. Among possible substitutes syngeneic spermatozoa were tested on the grounds that they are the only adult cells that express T-alleles, but neither they nor teratocarcinoma cells protected mice against tumours raised by 3-methylcholanthrene. Testicular and thymic cells and tissue fragments have given effective protection in a number of experiments and it is noteworthy that fetal tissues, testicular cells and thymus cells are cross-reactive in respect of anti-embryo antibodies. Testicular cells probably act like fetal cells and, like fetal cells, are very prone to give rise to 'enhancement'. Thymic cells do not 'enhance' and may act quite differently. The variability of results--a source of grave concern--is attributed to the insensitivity of the test system which is ill-adapted to show up low degrees of protection.

Animals↗
PubMed1983

Host recognition of fetal antigens: do they induce specific antibodies?

The purpose of this study was to ascertain whether the protection afforded to adult mice against the induction and growth of 3-methylcholanthrene-induced tumours by prior exposure to syngeneic fetal cells has an immunological basis. Adult CBA mice were inoculated with fetal cells according to a variety of protocols and the sera were tested for their ability to bind to fetal and adult tissue cells, using a staphylococcal protein A binding assay. All 10 sera tested showed some degree of binding though this varied from strong to weak, and there was some cross-reactivity with adult thymic cells but relatively little with adult spleen cells. Absorption studies were carried out with one of these sera and with two others raised against testicular and thymic cells, respectively. The absorption patterns obtained so far suggest that fetal cells possess at least three, and possibly up to five, distinct antigens. Although none of the anti-fetal sera were produced with a sensitizing protocol identical with that used in in vivo protection, some of them were so close as to suggest that protection is associated with, and perhaps causally related to, these IgG antibodies. The in vitro evidence presented here, together with the in vivo data of P. B. Medawar & R. Hunt, shows that antigens are shared between fetal cells and adult thymic and testicular cells. It therefore lends support to the notion that the production of a vaccine against anaplastic neoplasms, using immunogens derived from adult tissues, is within the realms of possibility.

Animals↗
PubMed1983

Enhancement of specific antitumor immunity in mice fed a diet enriched in vitamin A acetate.

Age-matched male CBA mice on a conventional or a vitamin A acetate (VAOAc)-rich diet were immunized with irradiated cloned 3-methylcholanthrene- or Harvey sarcoma virus-induced (McSa-1 or HT3-2.1) sarcoma cells and then challenged with viable corresponding or unrelated (non-crossreacting) syngeneic sarcoma cells. The survival of the specifically immunized mice on the VAOAc diet was significantly prolonged in comparison with all control groups of mice as assessed by using logrank tests. Moreover, the specific immunization markedly decreased the incidence of tumors after the McSa-1 (but not HT3-2.1) challenge in a group of mice on the VAOAc diet (5% tumor incidence) compared with the equivalent group on the control diet (50% tumor incidence). Neither the VAOAc diet nor in vivo immunization alone or combined influenced natural killer cell activity. Specific T-cell-mediated cytotoxicity after in vivo priming and in vitro boosting with sarcoma cells was increased in VAOAc-fed mice. However, the marginal increase in cytotoxicity does not in itself explain the strikingly increased resistance to tumor transplants in preimmunized mice on the VAOAc diet in comparison with preimmunized mice on the control diet. The results indicate that a diet enriched in VAOAc can modify the ability of the immune system of a mouse to respond effectively to tumor antigens and can influence whether a tumor grows or regresses.

Animals↗
PubMed1982

Double-blind controlled trial of immunosuppression in the treatment of multiple sclerosis: final report.

In a double-blind controlled trial 43 patients with relapsing-remitting multiple sclerosis were treated either with anti-lymphocyte globulin, prednisolone, and azathioprine, or with placebo preparations. Treatment began with a combination of the three medicaments but after 1 month was continued for another 14 months with azathioprine (3 mg/kg dialy) only. There was a marginally beneficial effect of immunosuppression on the overall relapse rate and clinical progression. However, there were significant effects on in-vitro lymphocyte function and in the visual evoked potentials in favour of the group receiving suppressive treatment. Placebo-treated patients of the HLA A3 tissue type had significantly more relapses than placebo-treated patients who were not of type HLA A3. Nevertheless, HLA-A3-positive patients treated with immunosuppression had significantly fewer relapses than A3-positive placebo-treated patients.

Adolescent↗
PubMed1981

Supposed lamarckian inheritance of immunological tolerance.

The notion that an adaptation acquired during an organism's lifetime can somehow be imprinted on the genome and so become heritable has been faulted by every critical test to which it has hitherto been exposed, but many naturalists have lost their faith in what seems to them to be the all-encompassing explanatory glibness of neo-darwinism. Although this criticism is unfair it is entirely proper that neo-darwinism should be under constant critical scrutiny. Interest was therefore aroused by the claim of Gorczynski and Steele that tolerance of A strain antigens induced in CBA mice by injecting into them (CBA x A/J)F1 spleen and bone marrow cells could be transmitted down the male line. Such a claim is of particular interest because spermatozoa, unlike oocytes, are produced throughout life and might thus conceivably have participated in the mechanism envisaged by Steele as that responsible for the supposed transfer of genetic information from soma to germ plasm. It was claimed that as many as 60% of the progeny of tolerant fathers mated with normal CBA females were unresponsive or hyporesponsive in an in vitro assay in which their spleen cells were tested for reactivity against A/J strain histocompatibility antigens in the cell-mediated lympholysis assay (CML). We describe here our failure to confirm these findings and our inability to extend them by testing the progeny for their reactivity against skin allografts from the tolerance-conferring strain.

Adaptation, Physiological↗
PubMed1981

Anti-cancer action of retinoids.

The anti-cancer action of retinyl acetate (Vitamin-A acetate, VAA), chosen as a representative retinoid substance, is attributed to its power to exercise immunopotentiation, though other possibilities are considered. The reasons for forming this opinion were: (1) chronic administration of VAA brought about enlargement of the thymus and peripheral lymph nodes; (2) the administration of VAA curtailed the life of skin allografts though (3) its action could be reversed by the concomitant administration of immunosuppressive agents.

Animals↗
PubMed1977

Fear and DNA.

Explore the source record for details and available documents.

Attitude↗