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Biomedical subjects

D S Nelson

Publications and source records attributed to D S Nelson.

At least 19 recordsLinked to original sources
PubMed1979

Mechanism of resistance of mice to syngeneic methylcholanthrene induced fibrosarcomas.

Mice become resistant to challenge with certain fibrosarcomas when bearing a tumor graft (concomitant immunity) or after injection of a low, non-tumorigenic dose of cells (sinecomitant immunity). Resistance to footpad challenge was depressed or abolished by treatment with carrageenan, niridazole or reserpine, or by sublethal irradiation, all of which also depressed delayed-type hypersensitivity (DTH) reactions. Immune lymphocytes initiating tumor-suppressive reactions in the feet of non-immune mice were Thy-1+, Ly-1+, Ly-2- and Ly-3-. Injection of tumor cells into the peritoneal cavities of immune mice specifically elicited an influx of macrophages. There was evidence of macrophage stimulation in tumor-immune mice. In vitro, anti-tumor effector cells lacking individual tumor specificity could be detected among the resident peritoneal cells of tumor-immune mice and among peritoneal exudate cells of non-immune mice. The expression of acquired resistance to some tumors may involve reactions akin to DTH in which a specific reaction triggers an accumulation of nonspecific effectors.

Animals↗
PubMed1979

Activity of mouse macrophages purified by adherence to, and removal from, a plastic surface.

Mouse peritoneal exudate macrophages were allowed to adhere to plastic Petri dishes and, after washing, were removed by means of EDTA. Cells with the morphology of macrophages were recovered in a fair degree of purity (90-98%) but in low yield (31-34%). The macrophages recovered were fully active in the following ways: re-adherence to glass; pinocytosis of colloidal gold; phagocytosis of opsonized sheep erythrocytes; binding cytophilic antibody; production of lymphocyte activating factor; cytotoxic and cytostatic effects on tumour cells.

Animals↗
PubMed1979

Effect of treatment with azathioprine on the responses of rat lymphocytes to phytohaemagglutinin.

The proliferative responses of rat peripheral blood lymphocytes (PBL) and spleen cells to phytohaemagglutinin (PHA) were studied after single or multiple (daily for 4 days) injections of azathioprine (AZ). Lymphopenia developed within 4 h of a single dose (78 mg/kg) of AZ and persisted for at least 72 h. There was no lymphopenia 24 h after the last of 4 daily injections. In vitro, PBL were more sensitive than spleen cells to the inhibitory effect of AZ. Likewise, the responses of PBL were relatively more depressed than those of spleen cells after single or multiple injections of AZ. The degree of depression was less than was expected from the effect of AZ in vitro. Multiple small doses were more depressive than multiple large doses. Serum from treated rats, used at 20% concentration, was more depressive than normal. Thus, rat lymphocytes are quite sensitive to AZ in vitro, but appear to be relatively resistant in vivo, this resistance resembling the resistance of the primary antibody response to AZ treatment.

Animals↗
PubMed1979

Macrophage heterogeneity.

Macrophages are a mobile, functionally diverse group of cells which may be recruited and stimulated to a high degree of metabolic activity. Heterogeneity may be detected from one site to another and result from local influences, e.g. lung v. peritoneal cells, or occur within a population and arise dur to different stages of differentiation, maturation or activation or possibly from distinct cell lines. Recruitment and turnover are important determinants of the diversity of cells at any one site. In addition, anti-tumour, anti-microbial and secretory capacities of macrophages are greatly influenced by the degree and nature of stimulation possibly affecting only a subpopulation of the cells. Accessory cell activity is also a function of a minor population of macrophages which have distinct surface antigens. The sources of the heterogeneity and the interrelationship between the macrophages subpopulations remain to be determined.

Animals↗
PubMed1979

Human tumour immunology.

Many human cancer cells appear to differ from their normal counterparts in ways that are recognisable by the immune system of the host or patient. The specificities of these differences, however, and the nature, extent and significance of the most responses to them are often not very clear. Disturbances of the immune system generally contribute little to the occurrence, progression and clinical features of common malignant diseases. The present value of immunological monitoring of cancer patients is rather limited. Immunotherapy remains an experimental mode of treatment, the results of which are often disappointing. Current studies of the host-tumour relationship in experimental animals and man suggest, however, that a wholly pessimistic view is not justified.

Animals↗
PubMed1979

Effect of hydrocortisone, cyclophosphamide, azathioprine and methotrexate on cutaneous delayed and arthus hypersensitivity in the rat.

The effect of 4 immunosuppressive agents--hydrocortisone (HC), cyclophosphamide (CY), azathioprine (AZ) and methotrexate (MTX)--, on cutaneous delayed-type hypersensitivity (DTH) and Arthus reactions to the intradermal injection of ovalbumin (OA) in rats sensitized to OA in Freund's complete adjuvant (FCA) was studied. Multiple doses (daily for 4 days) were given either early, beginning on the day of sensitization, or late, beginning 9 days after sensitization. Single doses were given on the day of challenge with OA. All late multiple doses of drugs except HC depressed the DTH at 24 h in the following order of decreasing magnitude: MTX, CY, AZ. The DTH at 24 h was depressed by early multiple doses of MTX at all doses, by CY at all but the lowest dose, and by AZ at the intermediate dose; HC had no effect. When the drugs were given as single late doses, only CY at the lowest dose and MTX at the higher doses effectively depressed the DTH at 24 h. Increased Arthus reactions occurred after early and late multiple doses of HC and after a late single dose of CY at the highest dose. After late multiple doses the Arthus reaction was unaffected by either CY or MTX but was depressed by all doses of AZ. HC administered as 3 injections around the time of challenge markedly depressed the delayed and Arthus reactions. These results show that each of the 4 immunosuppressive drugs could depress DTH and Arthus reaction to OA, but the degree of depression varied with the time of drug administration relative to sensitization and challenge, and the dose of drug used. Histologic examination of skin test sites showed that an apparently negative reaction did not necessarily imply total absence of a cellular inflammatory response.

Animals↗
PubMed1979

In vivo anti-nuclear antibodies in epithelial biopsies in SLE and other connective tissue diseases.

In vivo anti-nuclear antibody (ANA) was observed by direct immunofluorescence microscopy in epithelial cell nuclei in forty-four biopsies from thirty-three patients. The tissue containing the ANA was macroscopically normal in twenty-seven patients. The thirty-three patients with in vivo biopsy ANA included twenty-three with SLE, three with mixed connective tissue disease, two each with multi-system Sjögren's syndrome, dermatomyositis, and progressive systemic sclerosis, and one with rheumatoid arthritis. Features of sicca syndrome were noted in seventeen patients. The patterns of the in vivo biopsy ANA in the thirty-three patients were speckled (21), homogeneous (6), nodular (2), and both speckled and homogeneous (4). Complement was not detected in the epithelial cell nuclei. Immunoglobulin(s) and/or complement were deposited along the dermoepidermal junction in thirty-two of the forty-four biopsies, and in dermal blood vessels in twenty-two biopsies. Each patient had serum ANA against rat liver substrate; twenty-seven had high titre ANA (1 in 1000 or greater). Elevated levels of DNA-binding were found in twenty patients (61%), but the level of DNA-binding did not correlate with the intensity of in vitro biopsy ANA staining. Serum antibody to ribonucleoprotein (RNP) was present in eight of the twenty-three patients tested (35%), all eight patients having clinical features of sicca syndrome. Hypocomplementaemia was found in thirteen patients (40%), all of whom had active SLE. In vivo biopsy ANA appears to be a real phenomenon of unknown aetiology, and not an artifact, which is found in some patients with active multisystem autoimmune disease, especially SLE.

Adult↗
PubMed1979

IgA synthesis by peripheral blood mononuclear cells from normal and selectively IgA deficient subjects.

IgA secretion and intracellular IgA synthesis by PWM-stimulated peripheral blood lymphocytes from normal and IgA deficient subjects were measured by radioimmunoassay. Cultured lymphocytes from eleven out of twelve IgA deficient subjects had impaired or undetectable IgA production. Measurement of intracellular IgA showed that the defect was more basic than simply defective secretion by IgA plasma cells. Co-culture of lymphocytes from IgA deficient and normal subjects revealed defects in both the B and T cell populations of IgA deficient subjects. In one subject the defect was in the T cells, in another the B cells, and in two others both T and B cells were defective.

Animals↗
PubMed1978

Failure of immunogenic tumors to elicit cytolytic T cells in syngeneic hosts.

Immunogenic, methylcholanthrene-induced sarcomas failed to elicit the production of rapidly cytolytic T lymphocytes in syngeneic mice, although they did elicit the production of more slowly cytotoxic cells. They were, however, susceptible to attack by cytolytic T cells from allo-immune mice and, if infected with ectromelia virus, to attack by similar cells from virus-immune, H-2 compatible mice. It is suggested that the failure to elicit cytolytic T cell production may be due to the lack of an appropriate association between tumour-specific antigens and elements of the major histocompatibility complex.

Animals↗
PubMed1978

Effect of hydrocortisone on the response of rat lymphocytes to phytohaemagglutinin.

The proliferative response of rat peripheral blood lymphocytes and spleen cells to phytohaemagglutinin (PHA) was studied following treatment with single or multiple doses of hydrocortisone. A transient lymphopaenia with a rapid recovery at 24 h occurred with both dose schedules. Hydrocortisone in vitro caused a dose-dependent depression of blood lymphocyte response to PHA but enhanced the response of spleen cells when the steroid was added after the mitogen. An inverse relationship between blood and splenic lymphocyte responses to PHA occurred after a single dose of hydrocortisone. Blood lymphocytes from multiple dose hydrocortisone-treated rats had an enhanced response to PHA. Serum collected within 5 min of injection from single dose-treated rats depressed normal rat blood lymphocyte responses. After multiple doses of hydrocortisone serum enhanced blood lymphocyte responses to PHA. The primary antibody response to sheep erythrocytes was only affected by near toxic doses of hydrocortisone.

Animals↗
PubMed1978

Immune reactions in human filariasis.

Sera from cases of elephantiasis due to Wuchereria bancrofti infection promoted an intense adhesion of peripheral blood leukocytes to W. bancrofti microfilariae in vitro. A similar adhesion was also seen using sera from some normal persons living for several years in areas where filariasis is endemic. No such adhesion was evident with sera from microfilaria carriers or from normal subjects from nonendemic areas. The adhesion was complement independent and was associated with the immunoglobulin G fraction of serum. 51Cr release studies suggested the occurrence of cell-mediated cytotoxicity to W. bancrofti microfilariae in the presence of elephantiasis serum. Microfilariae of Litomosoides carinii could be isolated free of blood cells, from the blood of infected rats. In the presence of serum, or its immunoglobulin G fraction, from patients with elephantiasis, L. carinii microfilariae adhered to human peripheral blood leukocytes or rat spleen cells.

Animals↗
PubMed1978

Macrophages and resistance to tumours: influence of agents affecting macrophages and delayed-type hypersensitivity on resistance to tumours inducing concomitant immunity.

Early, specific concomitant immunity to each of four tumours was inhibited by treatment with silica or carrageenan. Late, non-specific concomitant immunity was, with one exception, not inhibited by these agents. Treatment of non-immune mice with silica at certain critical periods before challenge promoted the growth of four of six syngeneic methylcholanthrene-induced tumours in their feet. Treatment with carrageenan was much less effective. Early and late concomitant immunity were inhibited by one or more agents inhibiting delayed-type hypersensitivity: irradiation, niridazole and reserpine. Irradiation of non-immune mice did not effect the growth of tumours in their feet. Treatment of non-immune mice with niridazole or reserpine actually inhibited the growth of some tumours. It is suggested that (a) mice offer some natural resistance to tumour growth, macrophages perhaps being effectors; (b) some tumour isografts may survive only if an inflammatory reaction occurs; (c) mechanisms akin to those of delayed-type hypersensitivity operate in the expression of concomitant immunity; (d) macrophages are important in early, specific concomitant immunity, but perhaps less so in the late non-specific phase.

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