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Biomedical subjects

L Brent

Publications and source records attributed to L Brent.

At least 19 recordsLinked to original sources
PubMed1992

Is epidermal cell proliferation in psoriatic skin grafts on nude mice driven by T-cell derived cytokines?

Plasminogen activity and DNA synthesis by epidermal cells have been reported to be doubled in psoriatic skin grafts compared with grafts of normal skin 6 weeks after transplantation to nude mice. In our study human lymphocytes disappeared from such grafts within 48 h whilst some DR-positive human dendritic cells were retained in the grafts for up to 4 weeks. However, the grafts were infiltrated by Thy 1.2+ mouse lymphocytes within 6 days and this infiltration persisted at a moderate level throughout the observation period. It consisted of perivascular aggregates, scattered dermal and papillary T cells, and some mouse T cells were also found in the epidermal compartment. Grafts of psoriatic and non-psoriatic control skin were infiltrated to a similar extent, suggesting a low-grade rejection response against the human xenografts. These findings raise the possibility that psoriatic keratinocytes are responding abnormally to inflammatory cytokines released by mouse lymphocytes reacting against the skin grafts.

Animals↗
PubMed1991

Construction of playgrounds for chimpanzees in biomedical research.

An outdoor 9,000 sq. ft. playground connected to the indoor-outdoor runs of the breeding facility at Southwest Foundation for Biomedical Research was constructed to simulate a near natural environment for chimpanzees in biomedical research. It is divided into three 75 X 40 ft. compounds to allow several groups of animals to utilize the area simultaneously. Environmental enrichment devices have been added to improve physical and psychological well-being.

Animals↗
PubMed1991

Evaluation of a chimpanzee enrichment enclosure.

A large, three-part playground for captive chimpanzees was constructed and evaluated in terms of area use and behavior changes. Comparative behavioral samples were obtained on 38 subjects in the existing indoor-outdoor run and in the enclosure. The chimpanzees used the inside run, connective chute, concrete slab, and grass areas most. Activity and environmental manipulation increased in the enclosure while abnormal and self-directed behaviors decreased.

Age Factors↗
PubMed1989

On the feasibility of inducing tolerance in man: a study in the cynomolgus monkey.

Our previous work on the in vitro generation of cytotoxic T lymphocytes from the blood of 15-22-week-old fetuses, and on the induction of immunological tolerane in both radiation chimeras and neonatal mice, using T lymphocyte-depleted allogeneic bone marrow cells, has led us to believe that it should be possible to establish red cell chimerism in human fetuses by the infusion of allogeneic adult bone marrow cells. The essential prerequisite appears to be the removal of immunocompetent T lymphocytes from the bone marrow transplant, for new T cells generated from donor stem cells become tolerant to the histocompatibility antigens of the host's thymus and cannot, therefore, cause graft-versus-host disease (GVHD). Such an approach could be used in the treatment of fetuses diagnosed at an early stage as suffering from life-threatening inherited blood disorders. The experiments described here were designed to test this hypothesis in a sub-human primate species, Macaca fascicularis. Twenty-two cynomolgus monkeys received infusions of haploidentical (paternal) bone marrow between days 51 and 95 of gestation. There was no evidence of chimerism in animals inoculated after day 75 from mating. Eight out of 14 fetuses inoculated before day 70 were late intra-uterine deaths, four were hydropic and in one, histological confirmation of GVHD was obtained, indicating that tolerance can be induced at this time, as GVHD can occur only if donor cells survive. The T cell-depletion technique used here did not appear to prevent GVHD.

Animals↗
PubMed1988

Tolerance to minor histocompatibility antigens.

A neonatal tolerance model employing fully allogeneic lymphoid cells as tolerogen was used in an investigation of tolerance to self and donor minor histocompatibility antigens (miHA). Tolerance was assessed by skin grafting and subsequently by the generation of cytotoxic T lymphocytes. Two strain combinations were investigated. In the first, BALB/c-B10, none of the mice became tolerant to H-2d: all gave responses to BALB/c and B10.D2 antigens comparable to uninjected controls. However, tolerance was secured to BALB miHA in the face of reactivity to the original donor cells (i.e., BALB/c), showing that multiple miHA can induce tolerance independently of major histocompatibility complex (MHC) antigens. In the reverse strain combination, in which tolerance to B10 antigens was successfully established in BALB/c recipients, MHC restriction of tolerance to self miHA could not be demonstrated, as mice tolerant to B10 were unresponsive to BALB.B antigens, too. Again, the induction of tolerance to multiple donor miHA proved to be independent of tolerance to donor MHC antigens, and a great deal easier.

Animals↗
PubMed1988

An immunological approach to the treatment of inherited life-threatening bone marrow defects.

The evidence that the human fetus at 15-22 weeks gestation is still immunoincompetent when judged by the generation of cytotoxic T cell responses is briefly reviewed. It suggests that it might be possible to induce immunological tolerance in the human fetus by the inoculation of allogeneic cells, thus offering a potential treatment for fetuses that have been shown to suffer from life-threatening inherited bone marrow disorders. Adult bone marrow or fetal liver thus transplanted could be expected to establish cellular chimerism and ameliorate the symptoms of the disease. Graft-versus-host disease (GVHD), brought about by mature lymphocytes present in adult bone marrow, poses the main threat. Rodent experiments have shown that GVHD can be avoided if T cell-depleted bone marrow is used in the induction of tolerance. This report summarises experiments in cynomolgus monkeys designed to test this approach rigorously by the inoculation of T-depleted paternal bone marrow cells into fetuses of different ages. Although it has become clear that tolerance can be induced there have been many in utero deaths, at least some of them from GVHD. Those fetuses that went to term were not chimeric. The possible reasons for these disappointing results are discussed.

Animals↗
PubMed1987

The inheritance of a Macaca fascicularis red cell antigen detected by CAMPATH-1 antibody.

CAMPATH-1 monoclonal antibody is reactive with human lymphocytes and monocytes and it has been shown to bind to antigens on the red cells of a number of primate species, including Macaca fascicularis. Our study within a closed colony of breeding M. fascicularis monkeys has confirmed this finding, and shown that the antibody identified a single red cell antigen inherited in Mendelian fashion as a dominant character. We have, further, confirmed that the antigen is present on blood lymphocytes, even in animals whose red cells are negative. This CAMPATH-1 antigen can therefore serve as a useful red cell marker in experiments involving bone marrow transplantation or blood transfusion.

Animals↗
PubMed1987

Activation of lymphocytes isolated from the gastric mucosa of the mouse.

A method for the isolation of lymphocytes and epithelial cells from the murine gastric mucosa has been developed. Gastric lymphocytes were stimulated by T-cell mitogens in vitro. When mice were sensitized systemically with human gammaglobulin (HGG) and given the antigen orally 4 days before cell isolation, both the number of mucosal lymphocytes and their capacity to incorporate [3H]thymidine ([3H]TdR) was enhanced. Gastric epithelial cells added to cultures of syngeneic spleen cells enhanced both phytohaemagglutinin (PHA) responsiveness and mixed lymphocyte reactions (MLR) in low numbers, but significantly suppressed these responses at high concentrations. These findings suggest that gastric lymphocytes, like those of the gut, are involved in the immune response against antigens taken in by mouth, and that there may be in vivo interactions between gastric mucosa lymphocytes and epithelial cells.

Animals↗