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Biomedical subjects

D S Nelson

Publications and source records attributed to D S Nelson.

At least 55 records · Page 3Linked to original sources
PubMed1986

Endothelial cell enhancement of PWM induced immunoglobulin synthesis by peripheral blood mononuclear cells.

The effect of various exogenous cells on the in-vitro PWM stimulation of immunoglobulin synthesis by normal human peripheral blood mononuclear cells was investigated. The accessory cells tested were bovine and human endothelial cells, bovine and human fibroblasts, normal human monocytes, and a monocyte cell line U937. Bovine and human endothelial cells boosted PWM-induced IgG and IgM synthesis, sometimes threefold. The enhancement was maintained over the 7-11 day period of culture and probably required cell to cell contact. It was not seen with the other cell types added and was, therefore, unlikely to be a consequence of an allogeneic or a xenogeneic stimulation, or a nonspecific 'feeder cell' effect.

Animals↗
PubMed1985

Acetylspiramycin and the immune system. I. Effects of acetylspiramycin on phagocytosis by mouse macrophages in vitro and in vivo.

A study was made of the effect of acetylspiramycin (ASPM) on the phagocytic activity of mouse macrophages in vitro and in vivo, using opsonized, 51Cr-labelled sheep red blood cells (SRBC) as test particles. Resident mouse peritoneal macrophages cultured with ASPM (25-100 micrograms/ml for 18 h) showed a 62-92% reduction in phagocytosis. This was due to decreases in both attachment and ingestion of SRBC and was additional to the detachment of some macrophages from the surface of the culture chamber. Morphologically the macrophages were vacuolated, with some nuclear condensation. When the cells were cultured for a further 48 h after removal of ASPM there was almost complete functional and morphological recovery. When mice were treated with ASPM (50-100 mg/kg orally for 7 days) their peritoneal macrophages showed increases of 57-121% in phagocytic activity in vitro. In mice treated with ASPM (200 mg/kg orally for 7-21 days) the clearance of i.v. injected opsonized SRBC was significantly accelerated. Thus, although ASPM is reversibly toxic to macrophages in vitro, it is not toxic in vivo, but actually stimulates the mononuclear phagocyte system. It is possible that metabolites of ASPM, such as neospiramycin, produced in vivo but not in vitro, are responsible for the stimulation.

Adjuvants, Immunologic↗
PubMed1985

Stimulation of proliferation in mixed cultures of mouse tumor cells and nonimmune peritoneal cells. I. Occurrence of stimulation and cyclical variation in tumor cell activity.

Mixtures of mouse tumor cells and resident peritoneal cells (PC) from nonimmune mice frequently incorporated [methyl-3H]thymidine [( 3H]dThd) in culture to a far greater extent than did either cell population alone. With PC-to-tumor cell ratios of 10:1, stimulation indices of up to 21 were recorded. Syngeneic, semisyngeneic, and allogeneic mixtures were active. PC elicited by thioglycollate or proteose-peptone could participate in the reaction. PC from mice injected with Corynebacterium parvum also could do so, provided they were precultured for 48 hours. Normal mouse spleen cells and fibroblasts and human Chang cells were inactive. There was considerable variation between experiments in the extent of stimulation observed, even with the same tumor. When tumors were cloned in vitro, freshly isolated clones differed widely in the extent of stimulation. Individual clones studied over a period of time varied markedly and cyclically in the degree of stimulation they exhibited in mixed cultures. This variation appeared to be unrelated to the density of the cultures from which the clones were obtained, to the base-line incorporation of [3H]dThd by tumor cells alone, or to the frequency of passage in vitro. It is suggested that the cyclical variation may be related to the generation of variant cells, which could be important in tumor progression and metastasis.

Animals↗
PubMed1985

Stimulation of proliferation in mixed cultures of mouse tumor cells and nonimmune peritoneal cells. II. Stimulation of tumor cells by macrophages and of lymphocytes by a tumor cell product.

Stimulation of [methyl-3H]thymidine incorporation in mixed cultures of mouse peritoneal cells (PC) and tumor cells required a large adherent PC. Flow cytometric analysis, as well as autoradiography, showed that the stimulation involved increased proliferation of tumor cells. The stimulation required contact between tumor and PC; it was partly inhibited by Trasylol (aprotinin) and potentiated by dexamethasone. In addition, there was minor stimulation of PC by a soluble product of tumor cells; this stimulation was not affected by Trasylol or dexamethasone. It is suggested that macrophages can stimulate tumor cell proliferation and that such stimulation may be an important factor in host-tumor relationships.

Animals↗
PubMed1985

Successful tumour immunotherapy: possible role of antibodies to anti-inflammatory factors produced by neoplasms.

Phenol-saline tumour extracts, active in the immunotherapy of bovine ocular squamous cell carcinoma (BOSCC), were used to immunize mice. The immunized mice became resistant to the depression of delayed type hypersensitivity (DTH) reactions by products of BOSCC cells or cultured mouse or rat tumour cells. They also showed partial resistance to the growth of an unrelated tumour. Monoclonal antibodies to a type C retrovirus protein, p15E, also induced resistance to the depression of DTH by products of BOSCC and mouse tumours. It is suggested that successful immunotherapy of BOSCC is associated with the induction of resistance to anti-inflammatory or immunosuppressive tumour cell products, allowing the operation of host defences, and that these products share antigenic determinants with a retrovirus protein.

Animals↗
PubMed1984

Modulation of natural and acquired immunity of rats to tumour isografts.

Syngeneic tumour cell suspensions were injected into the foot or intravenously in normal rats or rats bearing subcutaneous tumours. Resistance was assessed by measuring the swelling of the foot due to the growth of the tumours or by counting lung colonies or metastases. The tumours included two methyl-cholanthrene-induced fibrosarcomas (D7, D8), a metastatic variant of D8 (D8M) and a spontaneous adenocarcinoma (ST-2). D8, D8M and ST-2 induced concomitant immunity to challenge in the foot. D8 and ST-2, but not D8M, induced concomitant immunity in the lung. Concomitant immunity was, in each case tested, non-specific and could be expressed against a tumour which itself failed to induce concomitant immunity. Irradiation significantly enhanced the growth of D7, D8 and ST-2 in the feet of non-immune rats. Irradiation, carrageenan and silica significantly reduced the growth of D8M in the feet of non-immune rats. Irradiation increased the growth of D8 and D8M and carrageenan increased the growth of D8 in the feet of concomitantly immune rats (i.e., depressed resistance). Carrageenan decreased lung colony formation by D8 in normal and concomitantly immune rats and silica decreased colony formation by D8 in concomitantly immune rats (i.e., increased resistance). Thymus-deprived rats allowed greater growth of D8 in the feet but still expressed concomitant immunity. It is concluded that: (1) both natural and acquired tumour immunity may be modulated non-specifically in rats; (2) concomitant immunity, which has a large non-specific component, may contribute to the suppression of metastases but may also have site specificity; (3) the exact nature of the rat host-tumour relationship differs from tumour to tumour.

Adenocarcinoma↗
PubMed1984

Effect of tumour-associated macrophages on the growth of tumours in rats.

Tumours that had grown in syngeneic rats were depleted of macrophages in vitro. A comparison was made with non-depleted tumours of their growth in the feet and spread to the popliteal lymph nodes in untreated, irradiated (500 rads) or carrageenan-treated rats. A non-metastasizing methylcholanthrene-induced fibrosarcoma (D8) grew better in the feet of all three groups after macrophage depletion but metastasized more extensively only in irradiated rats; irradiation increased the growth of non-depleted D8 in the feet. D8M, a metastatic variant of D8, grew less extensively in the feet of normal rats after macrophage depletion. Its metastatic spread was increased by macrophage depletion in carrageenan-treated rats only. Non-depleted D8M grew less well in the feet or irradiated or carrageenan-treated rats than in normal rats. A metastasizing spontaneous adenocarcinoma (ST-2) grew less well in normal rats after macrophage depletion. The non-depleted tumour grew less well in irradiated rats but macrophage depletion had no further effect. Metastasis of ST-2 to the popliteal node of normal rats was abolished by macrophage depletion. The nature of the host macrophage-tumour relationship seems to differ from tumour to tumour.

Adenocarcinoma↗
PubMed1984

Brugia pahangi: serum-dependent cell-mediated reactions to sheathed and exsheathed microfilariae.

The immune mechanisms operating on the sheath and the cuticle of the Brugia pahangi microfilariae have been studied in vitro. The intact and exsheathed parasites were used for this purpose with serum from albino rats immunized with sonicated homogenates of the parasites as the source of antibodies. The IgG component of the serum was found to promote adherence of rat leucocytes and death of the sheathed and exsheathed parasites in presence of fresh normal serum. EDTA and EGTA abolished the adherence activity suggesting the involvement of complement components via the classical pathway. Both macrophages and neutrophils participate in this reaction. Eosinophils exhibit marginal activity only on exsheathed parasites. The intensity of adherence and killing by neutrophils in the presence of immune serum was greater with the exsheathed microfilariae than with the sheathed ones.

Animals↗
PubMed1983

Cyclosporin A inhibits lymphokine production but not the responses of macrophages to lymphokines.

Cyclosporin A (Cs A) exerted a dose-related inhibitory effect on antigen (ovalbumin, OVA) and phytohaemagglutinin (PHA)-induced transformation of guinea-pig lymph node cells (LNC). Whereas 0.05 micrograms/ml was sufficient to depress these responses markedly, it required 100-fold this concentration of Cs A to inhibit the production of lymphocyte activating factor (LAF) by lipopolysaccharide (LPS) stimulated peritoneal macrophages. Addition of Cs A together with insoluble concanavalin A (iCon A) to LNC cultures resulted in suppressed lymphokine production, as assessed by measurement of migration inhibition factor (MIF), the generation of macrophage procoagulant activity (MPCA) and the release of lymphocyte-derived-macrophage chemotactic factor (LDCF). Cs A also inhibited MIF and procoagulant production by sensitized peritoneal exudate cells in response to antigen, at the same concentrations which blocked lymphocyte transformation. In contrast, Cs A had no direct effect on the migration of peritoneal cells from capillary tubes, or on the responses of macrophages to preformed MIF, the lymphokine inducing MPCA or LDCF. Overnight incubation of macrophages with Cs A did, however, result in mild inhibition of their basal level of procoagulant activity.

Animals↗
PubMed1983

Chiasmatic gliomas of childhood. A reappraisal of natural history and effectiveness of cranial irradiation.

Disagreement exists concerning the natural history and treatment of chiasmatic gliomas (CG) of childhood. We reviewed our experience in 21 cases of surgically verified CG with a median age of 4 years at time of diagnosis, followed for a median of 5.3 years (range 3-14.8 years). Initial treatment included radiation therapy (RT) in 18 patients, chemotherapy in 2, and observation in 1. Disease recurrence, defined as progressive visual or neurological deterioration, was documented in 10 children (48%), occurring at a median of 6 years after diagnosis. 5-year actuarial survival was 89%, but fell to 60% by 10 years. Visual improvement after RT was uncommon, occurring once. Intellectual deficits were noted in 5 of 17 survivors. We compared our results to that of other patients reported and concluded that: (1) CG may act aggressively independent of their location in the visual pathway at time of diagnosis; (2) the beneficial effects of RT are difficult to document; (3) progressive disease may occur late in the course of illness, and (4) intellectual sequelae are common in long-term survivors.

Astrocytoma↗
PubMed1983

Modification of delayed-type hypersensitivity reactions to ovalbumin in cyclosporin A-treated guinea-pigs.

Cyclosporin A (Cs A) administered daily (25 mg/kg per os) to outbred guinea-pigs for 2 weeks following immunization with ovalbumin (OVA; CsA 0-13) caused profound suppression of 14-day delayed-type hypersensitivity (DTH) skin reactions. Very marked impairment of DTH was also found when Cs A was given for the first time 24 hr before skin testing and at 6 and 24 hr thereafter. In contrast, Cs A given on days 0-4 following OVA immunization (Cs A 0-4) caused dose-related potentiation of 14-day skin responses. These changes in the magnitude and character of DTH in vivo were accompanied by striking alterations in lymphocyte transformation responses and in the extent of macrophage migration inhibition and lymphokine production. Whereas Cs A (0-13) caused almost total suppression of the mitogenic responses of lymph node cells to PHA and antigen, OVA-induced migration inhibition and production of the lymphokine inducing macrophage procoagulant activity (MPCA), Cs A (0-4) augmented these responses to OVA, but did not affect lymphocyte transformation or lymphokine production in response to mitogen. Strain 13 guinea-pigs treated with Cs A (0-4) showed depressed Arthus, but augmented DTH responses to OVA. This significant increase in cell-mediated immunity could be passively transferred using spleen and peritoneal exudate cells, suggesting that under these circumstances Cs A (0-4) may interfere with the generation of a population of suppressor cells which regulate DTH reactions in the guinea-pig.

Adjuvants, Immunologic↗
PubMed1983

Lymphokine-like products of cultured tumour cells.

Supernatants from cultures of rat and guinea-pig tumour cells, guinea-pig fibroblasts and kidney cells, but not rat fibroblasts, inhibited the migration of peritoneal exudate macrophages in vitro. The inhibitory activity in tumour-cell supernatants differed from that of lymphokine in being heat stable (60 degrees, 3 hr) and dialysable, not inhibited by fucose and, in the case of guinea-pig line 1 tumour, not absorbed by an anti-lymphokine immunoabsorbent. Rat lymphokine and supernatants from four cultured rat tumours and, to a lesser extent, fibroblasts induced procoagulant activity in rat peritoneal exudate macrophages. The tumour procoagulant-inducing activity was heat stable and non-dialysable. Direct procoagulant activity was also found in rat lymphokine, fibroblast and tumour culture supernatants. This activity was partly or completely heat-labile but was non-dialysable.

Animals↗
PubMed1983

Suppression of delayed-type hypersensitivity reactions and lymphokine production by cyclosporin A in the mouse.

Two consecutive daily i.m. injections of cyclosporin A (Cs A) (greater than 50 mg/kg) inhibited delayed type hypersensitivity (DTH) responses in mice immunized with SRBC. Maximal suppression was observed when Cs A was administered 24 and 48 h after sensitization. Culture of spleen cells from these animals with antigen, insoluble concanavalin A (iCon A) or PHA revealed inhibition of the production of two lymphokines: that inducing macrophage procoagulant activity (MPCA) and macrophage chemotactic factor (LDCF). The inhibitory effect on lymphokine production was not due to depletion of T cells. In vitro, 25 ng/ml Cs A suppressed T cell proliferative responses to antigen and mitogen but much higher doses were required to impair the response to LPS. Similar doses of Cs A also suppressed lymphokine production, but the responses of macrophages to these lymphokines was unaffected, even at doses which totally inhibited lymphokine production. Production of interleukin 1 by LPS stimulated macrophages was inhibited by Cs A only at concentrations much greater than those required to suppress lymphokine production.

Animals↗
PubMed1982

Two anti-tumour cytotoxic cells in the peritoneal cavity of rats: natural occurrence, augmentation and partial characterization.

Mononuclear cells cytotoxic to methylcholanthrene-induced fibrosarcoma cells were detected in the peritoneal cavities of normal rats by means of 16 h 51Cr release and 48 h 125IUdR release assays. Carriage of a tumour which induces concomitant immunity, or intraperitoneal injections of Corynebacterium parvum or proteose-peptone, led to increases in mononuclear cell numbers. Injections of C. parvum and proteose-peptone led to increases in cytotoxicity in 51Cr release assays. Carriage of an immunogenic tumour led to an increase in cytotoxicity to homologous tumour cells in the 125IUdR release assay. Cells were separated by sedimentation velocity, metrizamide density gradients and adherence to glass or plastic. Small cells were more active than large cells in 51Cr release assays. Larger cells tended to be more active in 125IUdR release assays. Generally, low density cells were more active in both assays, except that high density cells induced by C. parvum were most active in 125IUdR release. Adherent cells from C. parvum-injected rats were more active than non-adherent cells in both assays. On the basis of differential stimulation and separation by sedimentation velocity it is suggested that two cell types, possibly NK cells and macrophages, are operative. 125IUdR-labelled fibrosarcoma cells were lysed after intraperitoneal injection into normal and concomitantly immune rats, more rapidly extensively in the latter case. These cytotoxic cells may be important in both natural and acquired resistance of rats to tumour growth.

Animals↗