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M T Scott

Publications and source records attributed to M T Scott.

At least 37 records · Page 2Linked to original sources

75Se-methionine labelled Trypanosoma cruzi blood trypomastigotes: opsonization by chronic infection serum facilitates killing in spleen and liver.

Blood trypomastigote forms of Trypanosoma cruzi have been labelled with 75Se-methionine. Opsonization by sera from mice chronically infected with T. cruzi promoted their uptake by both liver and spleen. Opsonized parasites within spleens and livers were less infectious when transferred to normal recipients demonstrating in situ parasite killing by these organs.

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Cell surface antigens of Trypanosoma cruzi: use of monoclonal antibodies to identify and isolate an epimastigote specific glycoprotein.

A monoclonal antibody was produced by cell fusion from mice immunized with Trypanosoma cruzi epimastigotes. The antibody was epimastigote specific but not strain specific; the antibody bound to Y, Peru and Tulahuén epimastigotes but did not bind to Y amastigotes or trypomastigotes. The antigen recognised by the monoclonal antibody was a 72 000 molecular weight cell surface glycoprotein which represented only 0.04% of the whole cell protein. Analysis of the glycoprotein purified by antibody affinity chromatography revealed a carbohydrate content of 52% by weight which was composed of glucosamine, mannose, galactose, glucose and three different pentoses: fucose, xylose and ribose. Immunisation with the purified glycoprotein did not protect mice from a lethal infection of T. cruzi.

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The nature of immunity against Trypanosoma cruzi in mice recovered from acute infection.

Protective immunity against a lethal, Y strain, T. cruzi infection could be transferred to normal mice by either serum or spleen cells from mice which had recovered from the acute phase of infection. The ability of spleen cells to transfer immunity was abolished by B lymphocyte removal (anti-Ig column fractionation), but was relatively insensitive to T lymphocyte depletion (anti-Thy 1.2 plus complement) or macrophage removal (Sephadex G-10 fractionation). Immune spleen cells gave an anamnestic antibody response when injected together with T. cruzi antigen into lethally irradiated recipients and these antibodies conferred protection in a passive transfer system. T cell depletion reduced, but did not abolish, this antibody response. These data imply that the protective immunity of T. cruzi-convalescent mice is predominantly B cell-mediated with T cell involvement being restricted to a helper role.

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Delayed hypersensitivity to Trypanosoma cruzi in mice: specific suppressor cells in chronic infection.

In mice chronically infected with Trypanosoma cruzi there are antigen-specific suppressor cells which inhibit the development of delayed hypersensitivity (DTH) to T. cruzi antigen but not to an unrelated antigen, keyhole limpet haemocyanin (KLH). This was shown by comparing the 24 hr footpad reactivity, elicited by injection of soluble T. cruzi antigen, of infected mice with that of mice immunized with killed T. cruzi antigen after pretreatment with cyclophosphamide. In the latter, 24 hr footpad swelling represented a DTH reaction in that the cellular infiltrate was predominantly mononuclear and the reactivity could be transferred to normal recipients by lymphoid cells but not by serum. Chronically-infected mice also developed 24 hr footpad swelling but the fact that this was undiminished from an earlier 3 hr reaction and could not be transferred to normal recipients by either local or systemic injection of cells, as well as the histological features, all implied that it represented a prolonged Arthus reaction. The absence or minimal levels of specific DTH detectable in chronic T. cruzi infected mice was accompanied by the presence in their spleens of cells which specifically suppressed the generation of DTH to T. cruzi in normal mice. Suppressor cell activity was radioresistant (10 Gy/1000 rad) and T-cell mediated as defined by significantly decreased and increased suppression following anti-Thy 1.2 serum treatment and nylon wool fractionation, respectively. The ability of chronic T. cruzi mice to develop DTH to an unrelated antigen KLH was unimpaired.

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Antitumor activity of purified cell walls from Corynebacterium parvum.

Cell walls (CW), containing peptidoglycan and carbohydrate, were prepared from Corynebacterium parvum and tested for lymphoreticular stimulation and antitumor effects in CBA-T6T6 mice. CW did not induce splenomegaly. Peritoneal macrophages became cytostatic to Rl leukemia cells in vitro after ip injection of CW or of peptidoglycan but not of carbohydrate; however, on a dry-weight basis the activity was low (less than 10%) compared with that of C. parvum. Tumor outgrowth was significantly suppressed after sc injection of mixture of M4 fibrosarcoma cells and CW, but again the activity of CW was less than 10% of the of C. parvum. In contrast to injection of C. parvum, intratumor injection of CW failed to retard tumor growth in normal mice, although a suppressive effect was found in mice presensitized to C. parvum. Again, unlike C. parvum, CW did not act as an adjuvant for tumor-specific transplantation antigen, as judged by a lack of enhanced resistance to tumor challenge after injection of mixtures of CW and irradiated M4 cells. The distribution and persistence of 125l-labeled C. parvum and CW after sc or ip injection were similar. CW activity was not restored by attachment to oil droplets or emulsification in Freund's incomplete adjuvant.

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Protection of mice against viral infection by Corynebacterium parvum and Bordetella pertussis.

Mice could be significantly protected against infection with herpes simplex virus (HSV) by i.p. or i.v. injection of killed Corynebacterium parvum 7 days before infection. This protection was seen in inbred strains of mice with a different degree of sensitivity to HSV and after both i.p. and i.v. infection. Resistant mice immunosuppressed by X-irradiation and showing an increased susceptibility to HSV could also be protected by a previous injection of C. parvum. Elevated levels of interferon were demonstrated in the serum of mice injected with C. parvum 5 to 12 days previously. Four different strains of anaerobic coryneforms were compared and only those which were able to induce a systemic activation of the lymphoreticular system (as reflected by splenomegaly) protected against HSV infection. Protection against HSV-infection could also be demonstrated by using killed Bordetella pertussis. C. parvum also protected against Semliki Forest virus infection in two different strains of mice.

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The distribution and persistence in vivo of Corynebacterium parvum in relation to its antitumor activity.

Killed Corynebacterium parvum was labeled with fluorescein isothiocyanate or 125I, and both preparations were shown to retain lymphoreticular stimulatory and antitumor activity. Large amounts of C. parvum injected i.v. were found in the liver, spleen, and lungs with less in bone marrow and lymph nodes. Apart from a rapid loss from the lungs within 24 hr, the persistence of killed C. parvum was striking, and some intact bacteria were still detectable in the liver and spleen at 15 days. (By contrast, the breakdown of an inactive C. parvum strain in the liver was considerably faster). The blood clearance of 125I-labeled C. parvum injected i.v. into tumor-bearing mice was more rapid than in normal mice, and the absolute, but not the unit, amounts of C. parvum taken up by the spleen and tumor-draining node were increased. 125I-labeled C. parvum was found within the body of established solid tumor, but there was no correlation between the amounts of C. parvum taken up by various mouse solid tumors after i.v. injection and their susceptibility to i.v. C. parvum therapy. The distribution and persistence of C. parvum injected into a tumor lesion was similar to that after s.c. injection. The bulk of the inoculum was retained at the injection site and draining lymph node. Contralateral nodes were unlabeled, and uptake in the liver and spleen was considerably less than after i.v. injection. Although no C. parvum was found in peritoneal cells after i.v. injection, the macrophages in this population became activated and were capable of nonspecifically inhibiting tumor cell growth in vitro.

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Comparison of the potentiation of specific tumor immunity in mice by Corynebacterium parvum or BCG.

Two independent studies have compared killed C. parvum (CP) vaccine with viable BCG (Pasteur) and BCG (Glaxo) vaccines, respectively, for potentiation of antitumor immunity when injected with irradiated tumor cells into B6D2F1 AND CBA-T6T6 mice. Both studies concurred that, for a given number of irradiated tumor cells, larger amounts (dry weight equivalent) of BCG than CP were required to produce similar degrees of tumor immunity. Evidence also showed that stronger and more protracted immunity was mediated by CP than by BCG.

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The accumulated effects of repeated systemic or local injections of low doses of Corynebacterium parvum in mice.

The effects of 14 weekly injections, s.c. or i.v., of "human equivalent" doses (5.25 mg/sq m) of Corynebacterium parvum (CP) in mice have been compared. Both s.c. and i.v. CP caused significant splenomegaly and antibody to CP, but stimulation was considerably greater after i.v. CP. Delayed hypersensitivity levels to CP were similar after s.c. and i.v. injection. T-cell competence, as judged by phytohemagglutinin reactivity and delayed hypersensitivity to sheep cells, was unimpaired after s.c. CP and augmented by i.v. CP. Activated peritoneal macrophages capable of nonspecifically inhibiting tumor growth in vitro were detected only after i.v. CP, and in vivo resistance to tumor cell challenge was greater after CP administered i.v. than s.c.

Adjuvants, Immunologic↗

Effect of the nature and amount of dietary energy on lipid composition of rat bone marrow.

The effect of the nature and amount of dietary calories on the lipid composition of bone marrow of rats was studied. Male weanling rats were fed 3 isocaloric diets, containing high carbohydrate, normal protein, and high protein, and a fourth high fat diet for 49 days. Feeding of the high carbohydrate, high protein, and high fat diets caused a significant increase in the level of total lipids compared to the normal protein diet. This increase of total lipids was due primarily to the increase in the level of triglycerides. There was no significant difference in fatty acid composition of either nonpolar or polar lipids of bone marrow among rats fed high carbohydrate diet and those fed normal protein diet. A comparison of fatty acid compositions between bone marrow lipids of rats fed high protein diet and the other 2 isocaloric diets revealed that the proportion of palmitic acid was higher and the proportion of oleic acid was lower in animals fed high protein diet than in animals fed the other 2 diets. Compared to the 3 isocaloric low fat diets, dietary feeding of high fat diet caused a decrease in the proportion of palmitic and palmitoleic acids and an increase in the proportion of oleic and linoleic acids in total fatty acids of both nonpolar and polar lipids.

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In vivo cortisone sensitivity of nonspecific antitumor activity of Corynebacterium parvum-activated mouse peritoneal macrophages.

The nonspecific antitumor activity of Corynebacterium parvum-activated mouse peritoneal macrophages in vitro was inhibited by their prior treatment with cortisone acetate in vivo. Inhibition was marked (60 percent) 24 hours after cortisone injection and was still significant at 7 days, but antitumor activity was completely recovered by 9 days. This transient inhibition was sufficient to abolish the non-specific protection afforded by C. parvum in an in vivo pretreatment model.

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Potentiation of the tumor-specific immune response by Corynebacterium parvum.

Strong, specific, cell-mediated antitumor immunity resulted from the sc injection into mice of Corynebacterium parvum (CP) mixed with irradiated cells from mastocytoma P815 (MA), whereas injection of irradiated MA alone was without effect. Maximum immunity was achieved with small doses of CP, and the injection sites of CP and irradiated MA did not need to be coincident but required common lymphoid drainage for immunity to result. The process was largely T-cell dependent but not dependent on the development of a specific immune response to CP; it was also demonstrable and effective in a therapy situation. No such immunity was evident after systemic administration of CP and irradiated MA. Simultaneous systemic injection of CP and irradiated MA did, however, nonspecifically reduce the enhancing effect of systemic injection of irradiated MA alone.

Adjuvants, Immunologic↗