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Biomedical subjects

M S Martin

Publications and source records attributed to M S Martin.

At least 37 records · Page 2Linked to original sources

Effects of cyclosporin A on progressive and regressive tumors induced by two cancer lines derived from a single colon carcinoma chemically induced in the rat.

The effects of cyclosporin-induced immunosuppression were assessed in a rat model of progressive and regressive colonic tumors. Two cloned cell variants, obtained from the same chemically induced colonic carcinoma, differ in their capacity to grow when injected into the syngeneic rat. PROb cells yield progressive tumors and often metastases; in contrast, REGb cells produce tumors which regress in 3 to 6 weeks. Cyclosporin A (CsA) administered daily, 20 mg/kg subcutaneously (s.c.) for 30 days after tumor cell inoculation, drastically enhanced the local growth of PROb tumors and increased the number of metastases. It increased the local growth and prevented the regression of REGb tumors which persisted even as long as 8 weeks after the termination of CsA administration and occasionally yielded metastases. CsA prevented the accumulation of inflammatory cells with the T lymphocyte phenotype at the periphery of both PROb and REGb tumors but did not alter the tumor infiltration by macrophages and NK cells. CsA did not modify the natural cytotoxicity of peripheral blood mononuclear cells against PROb and REGb target cells. These results suggest that CsA-induced suppression of T lymphocyte activity may enhance tumor progression and suppress tumor regression in this model.

Animals↗

Effects of a single injection of anti-asialo GM1 serum on natural cytotoxicity and the growth of a regressive colonic tumor in syngeneic rats.

The REGb tumor cell line is a cloned variant of the DHD-K12 cell line, established from a colon carcinoma chemically induced in the rat. Unlike the parent DHD-K12 cell line, or other clones, which give progressive tumors when inoculated to the syngeneic rat, REGb cells produce tumors which regress in 3 to 5 weeks and never cause metastasis. In order to explore the role of natural killer (NK) cells in REGb tumor regression, each rat was given one injection of anti-asialoGM1 (anti-asGM1) serum, a known inhibitor of NK activity. This injection was done 24 hr before REGb cell challenge. This injection significantly depressed the in vitro cytotoxicity of peripheral blood lymphocytes on REGb cells for 2 weeks. REGb tumors grew larger and regressed later in the treated animals than those in the controls. Furthermore, a progressive or recurrent tumor was observed in 4 out of 10 treated rats, giving lung and/or lymph-node metastases in 2 cases. Immuno-histological study of the cells infiltrating the REGb tumors in control and treated animals showed a decrease number of asGM1+ and OX8+ lymphocytes, presumably NK cells, after anti-asGM1 treatment. An increase in number of macrophages was demonstrated in the progressive tumors of treated animals. These results suggest that NK cells play an important role in the initial stage of the regression TSb tumors in untreated syngeneic rats.

Animals↗

An immunohistological study of cells infiltrating progressive and regressive tumors induced by two variant subpopulations of a rat colon cancer cell line.

In order to understand the mechanisms leading up to progression or regression, tumors resulting from the s.c. inoculation of progressive or regressive variants of a cell culture established from a chemically-induced rat colonic carcinoma were subjected to sequential histological study. As immunological factors have been previously described in this system of progressive or regressive tumors, special interest was given to inflammatory cells, T and B lymphocytes and macrophages, located inside and outside the tumor. Immunohistological methods using monoclonal or polyclonal antibodies and enzyme histology were performed to identify different populations of infiltrative cells. In both variants of tumors an accumulation of these cells were seen at the periphery of the tumor, surrounding the nodules. In contrast, very few inflammatory cells, macrophages or T lymphocytes were seen inside the clumps of tumor cells where cytolytic cells could have a contact-dependent tumoricidal effect. Only small differences were found between progressive and regressive tumors in the density of the various populations of T helper, T cytotoxic/suppressor, B lymphocytes or macrophages inside or around the tumor nodules. On the other hand, progressive and regressive tumors clearly differ in the relationship between tumor cells and the fibroblastic reaction they induce. Regressive tumors were rapidly encircled by a fibroblastic reaction isolating them from the peripheral tissues. The fibroblastic reaction was less dense around the progressive tumor cells which were able to migrate and invade the periphery. This suggests that immunological factors leading to tumor progression or regression could act indirectly through a control of the fibroblastic reaction, rather than through a direct cytotoxic effect on the tumor cells.

Animals↗

Gut-associated lymphoid tissue and 1,2-dimethylhydrazine intestinal tumors in the rat: an histological and immunoenzymatic study.

The association between chemically-induced intestinal carcinoma and gut lymphoid patches was studied in 20 male Sprague-Dawley rats 7 months after the first of 16 weekly injections of 1,2 dimethylhydrazine (DMH). The lymphoid patches of DMH-treated rats and of 14 untreated control animals were systematically studied histologically on sections of "swiss-rolled" whole intestine. It was found that 78% of the small-intestine carcinomas and 73% of the colorectal carcinomas were associated with intestinal lymphoid patches. Furthermore, misplaced and often atypical glandular crypts were often found in the parafollicular or interfollicular areas of lymphoid patches, in treated as well as in control animals. These glands could be the origin of the lymphoid-patch-associated carcinoma. Immunohistological staining with monoclonal antibodies (MAbs) against T-lymphocyte antigens or anti-IgM serum labelling B lymphocytes clearly localized early carcinoma and atypical glands in the T-dependent, interfollicular and parafollicular area of lymphoid follicles. An MAb directed against la-antigen stained some well-differentiated carcinomas and some atypical glands found in control rats. On the other hand, lymphoid patches, when not invaded by a carcinoma, were not modified in their number, size, morphology or cellular composition in DMH-treated rats as compared to control animals.

1,2-Dimethylhydrazine↗

Serial hemodynamic assessment of aortobifemoral bypass.

Clinical, arteriographic, and vascular diagnostic laboratory (VDL) data on 157 patients undergoing aortobifemoral bypass (ABF/BP) more than 5 years previously were compared in terms of the perspective provided by noninvasive testing, particularly when performed in the face of superficial femoral artery (SFA) occlusion. To the traditional outcome criteria (operative mortality rate, 3.2%; amputation rate, 1.4%; early patency rate, 98%; and late patency rate, 86%), VDL data added an initial hemodynamic failure rate of 14% and a late deterioration rate of 8%. Those patients with occluded SFAs fared worse in regard to initial patency (94% vs. 100%), initial hemodynamic failure (29% vs. 2%), late deterioration (8.8% vs. 5.4%), and late failure rates (16% vs. 10%), whereas those patients with open SFAs suffered more distal disease progression (11.5% vs. 1.3%). "Prediction" of postoperative ankle/brachial index (ABI) from preoperative thigh/brachial index (TBI) and ABI was 92% accurate for limbs with open SFAs but only 84% for limbs with occluded SFAs; prediction was made with a formula based on proportional transmission and with TBI measured with a regularly sized cuff (best combination). Neither additive transmission formula nor measurement of TBI with a large cuff allowed accurate prediction when the SFA was occluded. No advantage, in terms of initial hemodynamic result or late outcome, could be demonstrated for limited profundaplasty in the absence of significant profunda femoral stenosis and end-to-end vs. end-to-side proximal anastomosis.

Amputation, Surgical↗

Interaction between two cellular subpopulations of a rat colonic carcinoma when inoculated to the syngeneic host.

From a single, chemically-induced rat colonic carcinoma, two subpopulations of tumor cells have been isolated. When injected into syngeneic rats, TR cells give rise to progressive tumors in most of the animals, whereas TS cells give rise to no tumors or to tumors which regress in less than 30 days. TS cells inhibit the growth of TR tumors, whether they are injected before TR cells or simultaneously, at a different site or mixed with the TR cells. Lymph nodes and spleen lymphocytes from animals having rejected TS tumors also inhibit TR-cell growth. On the other hand, TS cells are able to give rise to progressive tumors when they are injected into rats bearing established TR tumors. Lymph nodes and spleen cells of TR tumor-bearing rats are able to enhance TS cell growth. These results suggest that subpopulations of cancer cells contained in the same tumor interact with each other through their effect on the host immune system. The growth of a whole tumor probably depends not only on the growth potential of each constituent subpopulation, but also on the interaction between the subpopulations themselves.

Adenocarcinoma↗

Role of macrophage in the defense against intestinal cancers.

The capability of activated macrophages to kill tumor cells in vitro is now well documented. The tumoricidal activation of macrophages against intestinal tumor cells by different agents is described and the main hypothesis on the mechanisms of tumor cell killing in vitro are discussed. These in vitro results suggest that the macrophage can constitute an efficient effector cell in the defense against intestinal tumors. The distribution and ratio of macrophages in normal intestine and intestinal tumors is described. At the moment, potent activators of macrophages studied in vivo on experimental and human intestinal tumors give poor results or even enhance the growth of tumors. Macrophages may also interfere with the specific immune response in two directions by enhancing the immune response or decreasing it by elaboration of mediators such as prostaglandins.

Animals↗

Effect of indomethacin on the growth of colon cancer cells in syngeneic rats.

A cell culture line has been established from a colonic tumor induced in a rat by dimethylhydrazine. Indomethacin had no effect on the growth of tumors induced in syngeneic rats by s.c. injection of this cell line. Neither indomethacin, nor prostaglandin E2 modify the growth of this established cell line in vitro or alter its destruction by endotoxin-activated macrophages. Indomethacin has been reported to suppress the growth of colonic tumors induced in rats by various carcinogenic drugs. The difference between these results obtained by others on chemically-induced colon cancer and the data we have obtained with a cell line derived from a similar cancer suggests that cancer cells in established culture may loose their sensitivity to prostaglandins, prostaglandin inhibitors or prostaglandin-dependent effector host cells.

Animals↗

Registry of experimental digestive tract tumours in europe.

A survey was carried out throughout Europe to establish a Registry of Experimental Digestive Tumours, including cancers of the oesophagus, stomach, colon, rectum and pancreas, transplantable tumour lines in animal models, and human digestive tumours grafted into nude mice or immunosuppressed animals. Cell lines from human and animal digestive tract cancers are also included. This registry is to provide information and facilitate communication between interested research workers.

Animals↗

Effects of chronic exposure to insulin on lipid synthesis in 3T3-L1 fatty fibroblasts.

The acute effects of insulin on 3H incorporation into lipid from glucose was measured in 3T3-L1 fatty fibroblasts cultured with and without insulin at 10 microgram/ml for 7 days. Basal lipid synthesis did not differ between control cells and cells treated chronically with insulin. There was no insulin stimulation in treated cells while 3H incorporation into lipid in control cells increased from a basal level of 1.39 to 3.85 nmol/dish/90 min with a maximally-stimulating concentration of insulin. This is the first study of 3T3-L1 fatty fibroblasts which describes a lack of acute insulin responsiveness in cells exposed chronically to insulin as compared to control cells.

Animals↗

Studies of Venezuelan encephalitis in migrating birds in relation to possible transport of virus from South to Central America.

All of 13 species of northward migrating shorebirds and 7 species of songbirds captured on the Pacific coast of Guatemala during April and May of 1974--1976 were susceptible to infection with small doses of either an epizootic or an enzootic strain of Venezuelan encephalitis (VE) virus. They produce moderate to high levels of viremia for 2--4 days post-inoculation; levels high enough to infect both epizootic and enzootic vector mosquitoes. Viremias were often sufficient even on the 3rd day after inoculation, a time that might represent the end of a migratory flight, assuming that the physiological state of the birds after capture reflected that during migratory flight. Birds of many taxa react similarly to infection with strains of VE virus, and have the potential for being moderately to highly effective amplifying hosts. However, whether northward migrating birds could have been the agents for the introduction of the epizootic Ecuadorian strain that initiated the middle-American epizootic of 1969--1971 is less clear. Data are not available for the extent, rates or routes of migration between the region of Ecuador and Central America, but the best information on the real speed of migration from elsewhere indicates that even warblers that fly more slowly than shorebirds could make the flight in 72 hours or less. Still, that there are geographically segregated subtypes of VE virus suggests that avian transport has been of minimal importance over long time spans. The role of inactivated vaccines in the middle-American epizootic remains an open question.

Animals↗