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Biomedical subjects

T E Sadler

Publications and source records attributed to T E Sadler.

At least 19 recordsLinked to original sources
PubMed1979

Effects of intravenous injection of two different strains of Corynebacterium parvum in the mouse.

A strain of C. parvum, CN6134, known to have antitumour activity, caused thrombosis in the sites where the organism is phagocytosed. It bound to macrophages in vitro and activated the alternate pathway of complement. A strain of C. parvum, CN5888, which fails to show antitumour activity, did not show thrombosis. It did not bind to macrophages or activate guinea-pig complement. It did, however, cause marrow infarction which seems to result from a diminished clearance of the organism from the circulation.

Animals↗
PubMed1978

Effects of Corynebacterium parvum and cortisone on the primary Lewis tumour and its metastases.

The effects of Corynebacterium parvum and cortisone acetate (CA) on the primary Lewis lung carcinoma and its pulmonary metastases were investigated. C. parvum given IV either on the same day or 7 days after tumour inoculation, reduced primary tumour growth, while 2.5 mg CA (high-dose) given SC 4 and 11 days after tumour, alone or in combination with C. parvum, administered on day 0, reduced primary tumour growth to the same extent as C. pravum alone. High-dose CA given on days 2 and 6 had no effect on primary tumour growth or the action of C. parvum, administered on day 7, while 0.05 mg CA (low-dose) given on days 4 and 11 did not alter tumour growth or the action of C. parvum given at the same time as tumour. High-dose CA given 4 and 11 days after tumour caused a significant enhancement in metastases. C. parvum given to these mice on the same day as tumour significantly reduced the pulmonary nodules but only to the level found in control, saline-treated mice. In mice given C. parvum alone, metastases were significantly reduced when compared with controls. Similarly, high-dose CA given on days 2 and 6 significantly enhanced metastases, and C. parvum on day 7 reduced their level to that found in control mice. Low-dose CA had no effect on the number of metastases or the antimetastatic action of C. parvum. The relevance of these results to the clinical situation is discussed.

Animals↗
PubMed1978

Effects of amputation and Corynebacterium parvum on tumour metastases in mice.

The effects of operation (lower-limb amputation) on the growth of the Lewis lung tumour and its metastases were studied. The role of C. parvum in counteracting these effects was investigated. Anaesthesia alone or with amputation did not affect primary tumour growth. C. parvum depressed this growth. Anaesthesia did not affect the number of pulmonary metastases, but amputation caused a significant increase. C. parvum inhibited metastases and completely counteracted the effects of operation on them. Large doses of cortisone acetate significantly increased metastases but small doses had no effect. Experiments with adrenalectomized mice suggested the effects of operation were due to non-specific stress.

Adrenalectomy↗
PubMed1977

Effect of Corynebacterium parvum on peripheral blood platelets.

The level of peripheral blood platelets was determined after i.v. injection of Corynebacterium parvum in normal C57BL mice and in those bearing the Lewis lung carcinoma. Twenty minutes after injection of a formalin-killed active strain (CN6134, (CN6134, which inhibited tumour metastases) or a killed inactive strain (CN 5888, which did not inhibit metastases) the number of circulating blood platelets was reduced by 50%. The level of platelets returned to control values by 8 h after the active, and by approximately 3 days after the inactive strain. The active strain alone caused a second and prolonged fall in platelet numbers, from approximately 16 h to 21 days after injection. Heparin given 3 X weekly to these mice restored the platelet count to normal values by 10 days after injection of active-strain C. parvum. The level of platelets in tumour-bearing mice was essentially similar to that in normal mice. Possible causes of the thrombocytopenia and the significance of platelets in metastasis are discussed.

Animals↗
PubMed1977

Radiolabelling of Corynebacterium parvum and its distribution in mice.

Corynebacterium parvum was labelled by growing live bacteria in the presence of [3H]thymidine. The bacteria were killed by formalin, washed thoroughly and resuspended at a concentration of 7 mg dry weight/ml. An activity of 1-6 X 10(5) ct/min/0-1 ml was obtained. The biological properties (inhibition of tumour growth and hepatosplenomegaly) of the labelled C. parvum were compared with those of commercially available vaccine, and were found to be similar. Labelled C. parvum was injected i.v., i.p., or s.c. into normal C57BL mice and the localization of activity determined at 4 h and 1,3,7 and 14 days after injection. After i.v. or i.p. injection, highest counts were recorded in the liver. Moderate activity was found in the spleen, lungs and small gut. After s.c. injection, the majority of radioactive label was detected at the site of injection and little found in other tissues. The distribution of injected C. parvum was also studied in mice bearing Lewis tumour, and was found to be similar to that in normal mice. Moderate amounts of labelled C. parvum were recovered from tumour. There appeared to be no relationship between the antitumour effect of C. parvum given by a particular route of injection and the concentration of C. parvum recovered from the tumour.

Animals↗
PubMed1977

Effects of C. parvum on growth and induction of intracerebral tumours in mice.

An investigation was made into the effect of Corynebacterium parvum therapy on cerebral tumours in mice. I.v. C. parvum caused a slight but significant increase in the survival of BALB/c mice injected intracerebrally (i.c.) with not more than 50 Meth A cells. C. parvum was most effective if given on the same day or 5 days after tumour. If this interval was increased there was no effect. Multiple i.v. injections were no more effective than a single dose. I.v. C. parvum had no influence on the survival of C57BL mice injected i.c. with Lewis tumour cells, and had little effect on the induction of i.c. or s.c. tumours by methylcholanthrene. It was concluded that C. parvum therapy was of little use in the treatment of cerebral tumour in mice. The clinical implications of these findings are discussed.

Animals↗
PubMed1976

The effects of Corynebacterium parvum and surgery on the Lewis lung carcinoma and its metastases.

The effects of Corynebacterium parvum on the mouse primary Lewis lung carcinoma and its metastases were studied. C. parvum was given at the same time as subcutaneous inoculation of tumour or in combination with surgical excision of the primary after 10 days' growth. When intravenous C. parvum was given at the same time as tumour there was a reduction in the primary tumour growth rate. There was a similar reduction in growth if the drug was given intravenously 7 days after tumour inoculation. Intraperitoneal and subcutaneous administration of C. parvum had no effect on the primary tumour. The number of pulmonary metastases were significantly reduced after intravenous or intraperitoneal C. parvum given at the same time as tumour. When C. parvum and surgery were combined and C. parvum was given not more than 2 days before operation there was only a slight reduction in metastases, but when the injection was given intravenously or intraperitoneally 3-4 days before operation the number of metastases was significantly reduced. Subcutaneous administration of C. parvum had little effect on metastases. There was no difference in the number of metastases in C. parvum-treated mice were killed after 21 or 28 days. C. parvum given on the same day as surgery was more effective if tumour excision was performed before day 10 when the metastases were less well established. It was concluded that in well-defined conditions C. parvum is effective against metastases of the Lewis lung carcinoma.

Animals↗
PubMed1976

Trapping and destruction of blood-borne syngeneic leukaemia cells in lung, liver and spleen of normal and leukaemic rats.

Leukaemic cells from rats with a lymphoid (HRL) or myeloid (SAL) leukaemia were labelled with 125IUDR and injected i.v. into either normal or leukaemic syngeneic recipients. The fate of the injected cells was studied in terms of the radioactivity in various tissues at various times up to 24 h later. In normal animals the leukaemia cells were destroyed rapidly in the reticulo-endothelial (RE) system; immediately after injection most recoverable activity was in the lung, with smaller amounts in the blood, spleen and liver but by 24 h only 20-30% of the injected activity could be recovered. In leukaemic recipients with high numbers of blasts in the blood the amount of activity recoverable from the lungs and bone-marrow was markedly reduced, while that in the blood was doubled. Nonetheless, the overall rate at which radioactivity was eliminated was not significantly different from that found in normal rats, in spite of the fact that the RE system was extensively infiltrated by leukaemia cells.

Animals↗
PubMed1975

Accelerated cytodifferentiation of antibody-secreting cells in guinea-pig lymph nodes stimulated by sheep erythrocytes and lymphokines.

Lymphokines, produced in response to structurally unrelated antigens, altered the course of a primary anti-sheep erythrocyte plaque-forming cell response within the regional lymph nodes of normal guinea-pigs. Intralymphatic injection of a small dose of lymphokines (0-5-8 mug) 1 day after antigen priming accelerated the rate of indirect plaque-forming cell cytodifferentiation between the 5th and the 9th days of the response. This effect was not related to changes in the level of antigen trapping by lymph node macrophages, but the lymphocyte mitogenic activity may have been important for the response since there was a significant increase in [3H]thymidine incorporation within the lymphokine-treated nodes on the 3rd day following immunization.

Animals↗
PubMedDate not supplied

Mechanism of action of C. parvum on a solid, subcutaneous mouse tumour.

The effects of i.v. C. parvum on the growth of a.s.c. inoculum of the Lewis lung carcinoma were studied in normal C57 B1 mice, and in those in which separate components of the immune response were impaired. C. parvum given either at the same time as tumour inoculation or when the carcinoma was 1 cm in diameter, and fully vascularised, reduced tumour growth. Macrophages were impaired by silica (Si), cortisone acetate (CA) or trypan blue (TB), and T cells by thymectomy and sublethal irradiation (TXR) or antilymphocyte serum (ALS). TB did not affect tumour size, whereas Si, CA, TXR, or ALS (initiated before tumour inoculation) reduced it. When C. parvum was given in combination with TB, or ALS (initiated after tumour inoculation), its antitumour effects were unchanged. C. parvum given after ALS (before tumour), TXR, Si, or CA had no further effect on tumour growth. We have shown that C. parvum inhibits the growth of inoculated Lewis tumour. However, it has not been possible to clearly define in vivo the immunological mechanisms involved.

Animals↗
PubMedDate not supplied

Distribution of 3H-thymidine-labelled C. parvum in mice.

Little is known of the localisation of injected Corynebacterium parvum. We therefore developed a method of radiolabelling this vaccine and determined its distribution in the mouse. Live C. parvum (Wellcome, strain CN 6134) was grown in the presence of 3H-thymidine and subsequently killed by formalin. A high activity, 1-6 x 10(5) cpm/0.1 ml of a 7 mg dry weight/ml concentrated suspension, was obtained. Its biological properties (hepatosplenomegaly and antitumour effects) were similar to those of commercially available vaccine. After intravenous or intraperitoneal injection into normal mice, high activity was recovered in liver and moderate activity in spleen, lungs and small gut. In contrast, after subcutaneous injection, most activity was recorded at the injection site, and little in other tissues. A similar distribution of labelled C. parvum was found in tumour-bearing mice. Only moderate counts were detected in tumour.

Animals↗