[A stress-coping model].
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Biomedical subjects
Publications and source records attributed to D W Scott.
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We have recently described three "immature" B cell lymphomas which are exquisitely sensitive to growth inhibition by anti-Ig reagents and may serve as models for tolerance induction in normal B cells. These cells are inhibited from cell cycle progression into S after receiving a negative signal in early G1. In this paper, we demonstrate that the growth inhibition by anti-Ig can be prevented and reversed by the addition of supernatants from T cell lines. One such line, called Tova, produces factors which restore normal levels of DNA synthesis in the presence of concentrations of anti-Fab or anti-kappa immunoglobulins which cause up to a 90% inhibition of thymidine incorporation in a 2- to 3-day culture period. This factor is at least partially effective when added up to 24 hr after anti-Ig to unsynchronized lymphoma cells and it does not alter the growth of control cultures. Studies using synchronized lymphoma cells indicated that the T cell factor permitted cycle progression into S when added during the early G1 exposure to anti-kappa and was less effective when added late in G1. Preliminary characterization suggests that both B cell growth factor II (interleukin 5) and B cell stimulatory factor 1 (interleukin 4) have additive activity in this system, although another unidentified lymphokine may also be involved. The relevance of T cell reversal of Ig receptor-mediated negative signaling to neonatal B cell tolerance is emphasized.
Cellulitis and subcutaneous abscess formation was diagnosed in a 3-month-old Thoroughbred filly. Clinical signs consisted of a large ulcerated plaque, with satellite pustules on the medial aspect of the right hock and subcutaneous abscesses in the right inguinal and mammary gland areas. Laboratory analysis revealed mature neutrophilia. Rhodococcus equi was isolated from the cellulitis and the subcutaneous abscess. Oral administration of erythromycin and rifampin for 35 days resulted in a clinical cure.
Cutaneous mast cell neoplasia was diagnosed in 14 cats from January 1975 to September 1985. Review of the available medical records and client communication provided information on tumor description, location, and recurrence, and each cat's current status. Twenty-three cutaneous mast cell neoplasms were surgically excised, examined, and graded histologically. In this study, feline cutaneous mast cell tumors did not metastasize to lymph nodes or viscera, did not recur at a previous excision site, and did not cause or contribute to the death of any cat. A histologic grading system described for canine mast cell tumors apparently provided no prognostic information for the cats in this study. There was a predilection for older male cats to develop cutaneous mast cell tumors, especially on the head and neck.
Ketoconazole, an antifungal imidazole derivative, was used successfully to treat Tricophyton mentagrophytes infection in a dog. The drug was administered orally (11 mg/kg of body weight, q 24 h) and continued for 90 days. Though ketoconazole is not licensed currently for veterinary purposes, it has been used successfully to treat dermatophyte infections as well as intermediate and deep fungal diseases in both dogs and cats. In this case, ketoconazole was found to be nontoxic and less expensive than griseofulvin in the treatment of dermatophytosis.
The role of antigen nonspecific cytokines in T- and B-lymphocyte responses is now well established. Interleukin-1 (IL-1) has been shown to augment B-cell maturation and proliferation. While the major source of IL-1 is from monocytes or macrophages, other cell types have been shown to produce IL-1-like cytokines. Epidermal cells produce a cytokine termed "epidermal cell-derived thymocyte-activating factor" (ETAF) which is similar if not identical with monocyte-derived IL-1. In this report we show that ETAF induces polyclonal stimulation of murine B cells. We show that ETAF augments B cell proliferation and differentiation in the absence of any added antigens or mitogens. This activity can be partially inhibited by anti-IL-1 antibodies. ETAF appears to activate B cells directly, although its activity is increased in the presence of T cells. Thus, ETAF may be involved in local polyclonal antibody responses occurring in the skin.
An infectious center viral plaque assay has been utilized to quantitate activated T suppressor (Ts) cells. This assay is based on two observations. Namely, resting T cells do not serve as good replicative hosts for many viruses, including vesicular stomatitis virus (VSV), and that Ts cells can be enriched by their ability to bind to antigen-coated dishes. Our data show that Ts cells specific for either the TNP hapten or for dextran will replicate VSV upon antigenic and/or mitogenic activation, whereas resting Ts and hapten-specific B cells are less efficient in this process. This system will now allow the direct quantitation of Ts cells and their activation properties.
Reactive forms of antigens or haptens have been shown to induce a state of hyporesponsiveness mediated in part by suppressor T cells. Injection of Balb/c x C57B16 F1 (CB6F1) mice with a reactive form of dextran B1355S (periodate oxidized dextran, dex-P) specifically reduced responses to dextran immunization within 1 day after dex-P treatment. This unresponsiveness lasted at least 23 days and required a reactive form of dextran for its induction since native dextran and oxidized/reduced dextran failed to induce tolerance. Furthermore, hyporesponsiveness could be induced by iv injection of dextran-coupled cells, especially peripheral blood lymphocytes, a result which suggests that in vivo coupling to cellular antigens is involved in dex-P-induced hyporesponsiveness. Suppression of the anti-dextran response could be transferred to normal mice with T-cell-enriched spleen cell populations from dex-P-injected mice. Interestingly, the presence of B cells in the transferred cell preparations interfered with detection of suppression. Both Lyt 1+2- and Lyt 1-2+ cells were involved in the dex-P-induced suppression; indeed, mixtures of these types of T cells led to the most profound degree of suppression. The suppressive activity of spleen cells from dex-P-injected mice could be removed by passage over dextran-coated plates. Moreover, cells eluted from the plates specifically suppressed anti-dextran responses of normal mice, indicating that dex-P injection induces a population of antigen-binding suppressor cells. This system will allow the study of the suppressor-T-cell receptors in a well-defined idiotypic system.
Sterile eosinophilic pustulosis is a rare dermatosis of dogs and humans. The clinicopathologic aspects of the disorder are similar in both species. In both the disease is characterized by a moderately generalized, pruritic, sterile, follicular and nonfollicular papulopustular dermatitis. Blood and tissue eosinophilia are usually present. Response to systemic glucocorticoids is better in dogs, probably because of the larger doses that can be used. The disorder is chronic and recurrent in both species.
Zoonotic dermatoses in dogs and cats are an important cause of skin disease in human beings. In addition, human dermatoses may occasionally be transmitted to dogs and cats. The veterinarian and the physician form a critical "health care team" in the proper management of these disorders.
Infection of a relatively resistant strain of mice (C57BL/6J) with the protozoan parasite Trypanosoma cruzi results in both the induction of parasite-specific T-helper cells and nonspecific suppressor cells. A time course study of the activation of help and suppression revealed that parasite-specific T-helper cell activity increases very early in infection (less than 12 days) at a time when suppression of non-parasite-specific responses and suppressor cell activity is increasing. Between 12 and 14 days of infection, the T-helper cell response to T. cruzi, as measured by the antibody response to hapten-T. cruzi in vitro, is suddenly and dramatically regulated. As reported previously, plastic and G-10 adherent cells appear to be responsible for the regulation of antibody responses to heterologous antigen during T. cruzi infection. These adherent suppressor cells are also responsible for the suppression of antibody responses to hapten-T. cruzi following the first 2 weeks of infection. Suppressor cells continue to regulate the parasite-specific response well into chronic infection even though the response to hapten-T. cruzi appears to return to normal levels. These results are the first to directly implicate nonspecific suppressor cells in the regulation of anti-T. cruzi humoral immune responses.
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Data from five behaviour management (token economy) units were analysed for periods of 10-20 weeks before and after the use of a food substitute (Complan), provided when insufficient tokens had been earned to buy a full- or part-meal. The efficacy of this form of negative punishment to control disturbed and aggressive behaviour was examined. No evidence was found to suggest that the contingent use of a food substitute made any contribution to the therapeutic process.
A poorly circumscribed, subcutaneous mass present on the dorsum of a young mature, male domestic short-haired cat was diagnosed as calcinosis circumscripta. Histologically, the mass was composed of multiple, fragmented loculi with a crystalline, light red center surrounded by dense, amorphous, mineralized material. Loculi were separated by variably-dense bands of a connective tissue stroma. The cat was otherwise healthy, and the mass was excised without recurrence.
B cell lymphomas which can be growth inhibited by crosslinking their surface IgM receptors by anti-Ig reagents provide models for normal B cell regulation and tolerance. WEHI-231 and CH31 are two independently derived lines that are exquisitely sensitive to negative signalling by antibodies specific for mu or kappa chains, but are unaffected by antibodies against MHC class 1 or 2 antigens. In order to determine the mechanism of this growth inhibition as a model for tolerance, we have examined the roles played by protein kinase C activation and calcium mobilization/influx during negative signalling in these cells. We found that growth inhibition caused by anti-mu crosslinking was reversed in the presence of either phorbol myristate acetate (PMA) or by lipopolysaccharide (LPS) from E. coli. The effect of PMA on negative signalling was a true reversal since phorbol esters could be added after anti-mu treatment, thus allowing nearly normal cellular progression into the S phase of the cell cycle. In contrast, pretreatment with PMA did not provide protection against the growth inhibition from anti-mu. Indeed, a "desensitization" protocol demonstrated that PMA pretreatment actually decreased reversal by both PMA and LPS of the effects of anti-mu on B lymphoma growth. These studies suggest that both LPS and PMA act via at least one common intermediate, which is assumed to involve activation and translocation of protein kinase C. Analysis of changes in calcium ion concentration after treatment with anti-Ig reagents showed both mobilization from internal stores and influx via calcium channels in WEHI-231, as has been reported for normal B cells. However, these changes did not correlate with negative signalling for the several reasons. Firstly, anti-mu inhibition of the growth of WEHI-231 could be induced in the relative absence of extracellular Ca++ or in quin-2 loaded (buffered) cells. Secondly, pretreatment with high concentrations of PMA ablated calcium mobilization, yet failed to modulate growth inhibition in WEHI-231 cells. Moreover, LPS provided protection from the effects of anti-mu yet did not alter cellular [Cai++]. In addition, PMA posttreatment (under conditions causing a reversal of the effects of anti-mu) can be applied as long as four hours after the initial exposure to anti-mu and the rapid measurable changes in calcium flux. Indeed, such changes in intracellular free calcium occurred in elutriated WEHI-231 lymphoma cells at all phases of the cell cycle, although we have previously identified early G1 as the only critical period in which negative signalling can be delivered.(ABSTRACT TRUNCATED AT 400 WORDS)
Sera from 14 dogs with active pemphigus foliaceus were tested for the presence of circulating antiepithelial antibodies. These antibodies could not be detected in the dogs with indirect immunofluorescent staining or in vitro complement-staining methods.
Functional studies of both polyclonal and antigen-specific responses have suggested that murine B cells differ in the expression of an antigen recognized by a rat anti-mouse monoclonal antibody, called J11d. Using both positive and negative selection, we now demonstrate that the J11d marker is differentially displayed on B lymphocytes responding to LPS vs anti-mu, as well as on unprimed vs specific antigen-primed B cells. Thus, cytotoxic elimination of cells expressing high levels of J11d (J11d-hi) reduced LPS-driven B cell proliferation by 60 to 80% but had no effect on anti-mu stimulated B cell growth. Interestingly, equal numbers of positively selected J11d-hi B cells responded similarly to LPS and anti-mu plus B cell growth factors, a result that suggests that the response to anti-mu of the J11d-lo B cells is normally masked by the majority J11-d-hi cells. In further studies, the primary PFC response of normal murine spleen cells to fluorescein (FL)-coupled TI antigens or to LPS in vitro was reduced dramatically by cytotoxic J11d antibody treatment. In contrast, the anti-FL PFC response of spleen cells from mice primed 1 wk previously with FL-Ficoll was not affected by J11d antibody treatment, whereas the response of these FL-primed B cells to TNP (to which the mice were not primed) was greatly reduced by J11d + complement treatment. Our data indicate that antigen-experienced (activated) B cells are primarily found in the J11d-lo B cell subset and that unprimed (resting) B cells are found in the J11d-hi population, although both populations of murine B cells can respond to anti-mu. These studies also provide further evidence for B cell heterogeneity.