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Biomedical subjects

S Denham

Publications and source records attributed to S Denham.

36 records · Page 2Linked to original sources

Immunity to a syngeneic sarcoma induced in rats by dendritic lymph cells exposed to the tumour either in vivo or in vitro.

Rats were prepared surgically so that peripheral intestinal lymph could be collected from them while a syngeneic tumour (the HSN sarcoma) was growing in each major Peyer's patch of the small intestine. Dendritic lymph cells were isolated from the lymph and injected i.p. into naive, syngeneic rats. Each of the 16 recipients received just under 10(6) such cells and was challenged 10 days later with a subcutaneous dose of 10(4) viable HSN cells. Six weeks after this challenge only 7 of the recipients had a tumour and these were small (mean weight 1.8 g), while 17 controls (which had each been treated with 10(6) thoracic duct lymphocytes from the same donors, and given the same challenge) all had large tumours (mean weight 8.8 g). The remaining 9 test rats were still free of tumours when they were killed and autopsied 4 months after challenge. Dendritic lymph cells from normal rats were 'sensitised' by incubating them overnight on a monolayer of HSN cells. They were then transferred to 5 naive recipients which received the usual challenge. Six weeks later they all had tumours (mean weight 1.3 g) but these were much smaller than those in the 5 controls (mean weight 9.3 g).

Animals↗

A receptor for monomeric IgG2b on rat macrophages.

The binding to rat splenic and peritoneal macrophages of affinity-purified monoclonal rat IgGs, representing all IgG subclasses, was measured by the direct binding of 125I-labelled proteins using an assay that did not require the removal of unbound Ig by washing. Only rat monomeric IgGs of the subclass IgG2b bound specifically and in large amounts to rat macrophages. The binding was temperature dependent and more IgG2b bound to the cells at 4 degrees than at 37 degrees. Spleen macrophages bound approximately 10 times more IgG2b than the same number of peritoneal macrophages, although the association constants (Kas) for the binding were similar for both types of macrophage. The calculated values for the Kas, which varied slightly with each experiment and increased with decrease in temperature, fell within the range 1.3-5.3 X 10(8) M-1; the number of binding sites was estimated as about 10(5)/splenic macrophage and 10(4)/peritoneal macrophage. The binding of 125I-IgG2b to splenic macrophages was inhibited only by unlabelled proteins of the IgG2b isotype and not by IgG1, IgG2a and IgG2c proteins. Soluble IgG2b-antigen complexes also bound to the FcR for monomer but a soluble IgG2a-antigen complex did not inhibit the binding of monomeric IgG2b.

Animals↗

The effect of limited courses of cyclosporine on survival and immunocompetence of allogeneic bone marrow chimeras.

Isolator-maintained CBH/Ola (Rtlc) rats were lethally irradiated and reconstituted with spleen and bone marrow cells from fully allogeneic WAG or Wistar (Rtlu) donors. Hematopoietically reconstituted rats were treated with cyclosporine (CsA)4 as prophylaxis for graft-versus-host disease (GVHD) for periods ranging from 6 to 26 weeks. Following the termination of CsA treatment GVH reactivity developed in all recipients of allogeneic cells regardless of the duration of immunosuppression. Approximately a third of the reconstituted rats survived the post-CsA period of GVH activity; these rats carried peripheral lymphocytes and spleen cells of donor strain origin and were specifically unresponsive to donor strain skin grafts. Surviving chimeras remained healthy for long periods (up to 18 months) after transplantation, although morbidity increased slightly for rats moved to normal animal house conditions. However, all chimeras had some degree of lymphopenia and showed diminished immunological responses to extraneous antigens and third-party skin grafts. Experiments to elucidate the mechanisms by which specific tolerance was maintained in chimeras indicated that neither the deletion of host-reactive lymphocytes from the graft nor an absence of host bone-marrow-derived "stimulator" cells was responsible. It was shown that the potential GVH reactivity of normal donor strain cells was specifically suppressed in vivo (in the chimera) and that this suppression could be transferred to secondary irradiated recipients by transferring chimeric spleen cells. Attempts to demonstrate a role for suppressor cells in the maintenance of the chimeric state yielded inconclusive results.

Animals↗

IgA antibodies in the bile of rats. IV. Synthesis of secretory antibodies in irradiated rats reconstituted with spleen cells: influence of microenvironment on the regulation of IgA production.

Inbred rats were given sub-lethal doses of irradiation so that they were unable to make antibodies unless they were reconstituted with syngeneic lymphoid cells. The ability of the reconstituted rats to make antibodies of the IgA class was measured in terms of the titres of specific antibodies that appeared in their bile. After syngeneic spleen cells, together with antigen, were injected into the spleens of irradiated rats, the titres of specific antibodies that appeared in the bile were low. After the same dose of spleen cells and antigen had been injected into the GALT of irradiated rats, the titres of biliary antibodies were substantial. These results, together with those of appropriate control experiments, suggest that radio-resistant influences in the microenvironment of the GALT may be important in inducing lymphoid cells to produce antibodies of the IgA class in response to local antigen.

Agglutination Tests↗

Effect of cyclosporin A on the anti-leukaemia action associated with graft-versus-host disease.

Graft-versus-host disease (GVHD) was induced in Hooded (Rt1c) strain rats by means of high dose total body irradiation (TBI) and subsequent reconstitution with allogeneic bone marrow and spleen cells from WAG (Rt1u) strain donors. Untreated recipients of allogeneic cells died within 20 days of engraftment, whereas those treated daily with Cyclosporin A (CyA), given either from the day receipt of the graft (Day 0) or from Day 4, survived until the end of the experiment (Day 50). If delayed until Day 7, CyA prophylaxis was totally ineffective. Hooded rats bearing a syngeneic leukaemia were irradiated and reconstituted with allogeneic bone marrow. During the course of the ensuing graft-versus-host response (GVHR) leukaemia cells were eradicated from the spleens of the host animals. However, as a consequence of CyA prophylaxis, whether started on Day 0 or delayed until Day 4, the anti-leukaemia potential of the bone marrow allograft was completely abrogated. Anti-tumour activity after engraftment was detectable first at Day 7, i.e. the time at which the GVHR became intractable to the effects of CyA. The results indicate (1) that CyA suppresses the initial events but not the effector phase of the GVHR, and (2) that the anti-host and anti-tumour action of the GVHR may be temporally inseparable.

Animals↗

Mechanism by which antibodies to non-AgB antigens mediate rejection of rat leukaemia cells.

The August and Hooded rat strains are compatible at the major histocompatibility locus (both are AgB5 or Rtlc). Antisera against the minor histocompatibility antigens of Hooded rats were raised by immunizing August rats with grafts of tumours or normal tissue. Such antisera, if transferred to normal unimmunized August rats, cause them to reject i.v. administered Hooded rat leukemia (HRL) cells within a few hours, and X-irradiated August rats, for whom a graft of HRL is lethal, can survive indefinitely if pretreated with the antiserum. The distribution of 125I-labelled HRL cells in the tissues of August rats was followed at times after their injection, and it was found that, in the presence of antiserum, i.v. administered leukaemic cells are rapidly destroyed in the liver and spleen. The active component of the antiserum is IgG antibody, and its action is independent of the lytic elements of complement. Antibody-mediated splenic and hepatic clearance of the leukaemia cells is unaffected by total-body X-irradiation but reduced by treating the rats with colloidal carbon. The data are consistent with the hypothesis that the rejection of HRL across the histocompatibility barrier studied is, in the presence of antibody, effected by immunophagocytosis.

Acute Disease↗

Reversible suppression of allo-antibody production by cyclosporin A.

Treatment of rats with 25 mg/kg/day of cyclosporin A suppressed their immune response to skin allografts. Withdrawal of cyclosporin A treatment led to complete recovery of specific immune responsiveness and the time taken for recovery was independent of the duration of treatment. Titration of the dose of cyclosporin A administered in vivo indicated that doses of 12 mg/kg/day or less were not fully immunosuppressive.

Animals↗

Evidence of cytotoxic T and B immunoblasts in the thoracic duct of rats bearing tumour grafts.

Wistar rats were immunised with allogeneic or xenogeneic tumour before collection of their thoracic duct lymph. Specifically cytotoxic effector cells were found in the lymph between 3 and 8 days after immunisation, and their occurrence coincided with an increased number of immunoblasts in the lymphocyte population. The immune response in lymph to allogeneic cells appeared to be affected solely by radiosensitive thymus-dependent lymphocytes; no complement-dependent killing was evident and cytotoxic cells failed to appear when immunised animals were deprived of thymus-dependent lymphocytes. In contrast, the response to immunisation with xenogeneic cells elicited both complement-dependent and complement-independent cytotoxicity, but only the former could be detected in animals deprived of thymus-dependent lymphocytes. In normal animals and in animals deprived of thymus-dependent cells, the cytotoxic cells in the thoracic duct lymph appeared to be large lymphocytes or immunoblasts.

Absorption↗

Confronting the monster of family violence.

Family violence has been a harrowing manifestation stalking the lives of families, resulting in physical, emotional, and sexual abuse predominately among women and children. This article identifies beliefs that disregards domestic violence, outlines characteristics of abused persons, and describes primary and secondary prevention strategies. The author outlines the role of nurses to provide preventive education, do case finding, and assist their community to confront family violence through professionally, socially, and personally responsible actions.

Domestic Violence↗