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Biomedical subjects

E Sabbadini

Publications and source records attributed to E Sabbadini.

36 records · Page 2Linked to original sources

Cytotoxicity in graft-versus-host reaction. I. Role of donor and host spleen cells.

Under in vitro conditions spleen cells from nonirradiated F(1) hybrids, in which a (graft-vs.-host) (GVH) reaction had been induced with lymphoid cells of parental origin, lysed nonspecifically target cells, i.e., cells syngeneic or allogeneic to the parental genotypes. Furthermore, tumor cells exposed in vitro to spleen cells of F(1) hybrid mice undergoing GVH reaction had markedly decreased ability to grow in syngeneic recipients. Experiments involving inhibition of cytotoxicity with alloantisera indicated that this nonspecific effect was due to host cells. By contrast, spleen cells of lethally irradiated F(1) hybrids undergoing GVH reaction lysed specifically the target cells of the genotype against which the parental (donor) cells had been sensitized; this finding further supports the contribution of host cells to the nonspecific cytotoxic effects in GVH reaction. From these results it was deduced that the cytotoxic effects during GVH reaction involve at least two processes: (a) sensitization of the donor cells to the antigens of the recipient resulting in the activation of their potential to lyse specifically the recipient's cells, and (b) activation of the host's cells into a state of nonspecific cytotoxicity, as a consequence of the immunologically specific attack of the donor cells.

Animals↗

The prognostic significance of circulating tumour cells: a five-year follow-up study of patients with cancer of the breast.

One hundred and sixteen patients with proved cancer of the breast were followed up for five years to detect circulating tumour cells. Such cells were found in 61 patients, but, irrespective of the stage of the disease, the five-year survival rate in these was not significantly different from those in whom no tumour cells were found. The higher incidence of patients without circulating tumour cells in Stage I was not sufficient to influence the survival rate of the whole group. While the validity of the identification of these cells is questionable, the results of this study indicate that the presence or absence of tumour cells in the blood is of no prognostic significance.

Breast Neoplasms↗

The submandibular gland: a key organ in the neuro-immuno-regulatory network?

The evidence for the integration of the submandibular gland (SMG) into the neuroimmunoregulatory network has been reviewed. In laboratory rodents, factors extracted from the SMG were shown to stimulate lymphocyte proliferation, to affect the weight of the thymus, spleen and lymph nodes and to induce immunosuppression in several in vivo animal models. The SMG produces significant quantities of nerve growth factor (NGF), epidermal growth factor (EGF), transforming growth factor-beta and kallikreins, which are secreted into the saliva and affect immune and mucosal tissues and nerve endings in the gastrointestinal tract. These factors play a role in regulating mucosal immuno/inflammatory response and in regeneration and healing. The major salivary glands also produce antimicrobial proteins and secretory IgA antibodies which are essential factors in mucosal host defense. SMG-derived NGF, EGF and glandular kallikrein are delivered into the bloodstream where they may act as important systemic immunoregulators and also have major regulatory influences on the central neuroendocrine system. There is evidence to indicate that EGF is involved in the regulation of gonadal function. Growth hormone, prolactin, androgens, thyroid hormone and corticosteroids regulate protein synthesis in the SMG, whereas secretory activity is regulated by sympathetic (alpha- and beta-adrenergic) parasympathetic (muscarinic) and peptidergic (substance P and vasoactive intestinal peptide) nerve fibers. Fluid and electrolyte secretion is promoted by parasympathetic, whereas protein secretion is stimulated by sympathetic nerve impulses. Steroid hormones and cytokines (interleukin-1 alpha, -beta, tumor necrosis factor, interferon-gamma) have a major regulatory influence on protein secretion, including the secretion of immunoglobulin into the saliva. The SMG interacts with the mucosal and systemic compartments of the immune system, with the central and peripheral nervous systems, with the pituitary gland, and with peripheral endocrine organs. These interactions enable the SMG to exert regulatory influences on immune/inflammatory reactions in the gastrointestinal tract, in the lungs, and possibly elsewhere. It is suggested that these functions make this gland a key regulatory organ in the neuroimmunoregulatory network. Evidence is increasing that the major salivary glands fulfill similar functions in other species, including humans.

Animals↗

Immunoregulatory effects of glandular kallikrein from the salivary submandibular gland of rats.

A protein of 40 kD molecular weight was isolated from the salivary submandibular glands of male rats. The protein catalyzed the hydrolysis of alpha-N-benzoyl-L-arginine ethyl ester. This esterase activity was inhibitable with the protease inhibitor aprotinin. The sequence of the first 25 amino acids of this protein was identical to that of rat glandular kallikrein (rGK). When added to cultures of murine lymph node cells suboptimally stimulated with the T cell mitogen concanavalin A, rGK markedly stimulated the proliferative activity of these cells. When injected into mice, rGK suppressed the contact sensitivity response to picryl chloride, a form of delayed-type hypersensitivity. Similar in vitro and in vivo effects were induced with GK from porcine pancreas (pGK). Moreover, the aforementioned in vitro and in vivo effects were abolished by aprotinin either added to the tissue culture medium or injected into the animals immediately before rGK or pGK. This demonstrates that the enzymatic activity of rGK and pGK is important for the induction of immunoregulatory effects. These results suggest that rGK is a systemic immunoregulatory enzyme with immunosuppressive potential. GK is the first example for systemic immunoregulation by an enzyme, the secretion of which is under neuroendocrine control.

Amino Acid Sequence↗

[Co-operation among T cells in the development of cell-mediated cytotoxicity].

Lethally iradiated F1 hybrid mice were given an intravenous injection of parental strain spleen cells. Six days later, their spleen cells were used as the effector cells to measure the in vitro cell-mediated cytotoxicity (CMC) of the parental cells. The treatment of the parental donors with hydrocortisone resulted in a marked decrease of the capacity of their spleen cells to produce a CMC reaction, while the treatment with anti-thymocyte serum (ATS) resulted in an almost complete loss of such activity. The mixing of spleen cells from hydrocortisone-treated parental donors with the spleen cells from ATS-treated parental donors before injection resulted in a synergistic amplification of the cytotoxic response. These results demonstrated a synergistic interaction between hydrocortisone resistant T cells and ATS-resistant T cells in the generation of cytotoxic lymphocytes.

Animals↗