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Biomedical subjects

M S Mitchell

Publications and source records attributed to M S Mitchell.

At least 127 records · Page 7Linked to original sources
PubMed1976

A virally induced osteosarcoma in rats. A model for immunological studies of human osteosarcoma.

Inoculation of Moloney sarcoma virus into the medullary canal of the tibia in newborn Wistar-Lewis rats resulted in an initially localized osteosarcoma which usually metastasized to the lung and resulted in the death of the animal within four to five weeks. Tumor cells were grown in tissue culture and used as target cells in the assay of lymphocyte-mediated cytotoxicity using a microcytotoxicity and a radioisotope labeling method. Lymphocyte-mediated cytotoxicity was demonstrated throughout the course of the clinical disease as well as in a small number of animals which showed spontaneous regression of their tumors. Serum factors which could "block" or augment the cellular response were also identified. This model resembles the spontaneous osteosarcoma of humans in many respects and may be useful for studies of the human disease.

Animals↗
PubMed1976

Studies on the immunogical effects of BCG and its components: theoritical and therapeutic implications.

Bacillus Calmette-Guérin (BCG) has had significant antitumor effects in rodents and in man. In mice, BCG is capable of increasing lymphocyte-mediated immunity to allogenic leukemia cells and of creating "pseudoimmune" cytotoxic lymphocytes when administered alone. Lymphocyte-activating factor (LAF) produced by macrophages, a T-lymphocyte mitogenic substance, is increased significantly by the administration of BCG and may play a role in the evocation of cytotoxic cells. BCG acts as a mitogen for splenic and thymic cells "in vitro". Macrophages were important regulators in the response, since a critical concentration (at least 0.25 % to 0.5 %) were required for T-cell stimulation and a high concentration (approximately 5 to 10 %) inhibited splenic lymphocytes. LAF was increased 20-fold above baseline "in vitro" by BCG. Methanol extraction residue (MER) stimulated thymic and splenic cells as well as did whole BCG. A delipidated cell fraction (DMC) stimulated only splenic non-T lymphocytes. BCG has antagonized several sorts of immunosuppression and may be useful clinically in this regard. There is also the possibility of antagonizing the myelosuppressive toxic effects of chemotherapeutic agents through the stimulation of the macrophage-made granulocyte colony stimulating factor. Finally, if BCG can induce cytotoxic lymphocytes (or macrophages) in vitro, it may be possible to use these in clinical adoptive immunotherapy. BCG is a useful prototype of an immunological adjuvant with antitumor activity. Elucidation of its actions on lymphoid cells and its effects in therapeutic situations can serve as a model for future investigations with other substances with similar potential.

Animals↗
PubMed1976

Pulmonary manifestations in Behçet syndrome. Case report and review of the literature.

Behçet syndrome in association with pulmonary abnormalities is rare. We described a patient with Behçet syndrome who had pulmonary involvement. A review of the literature disclosed 12 similar cases. Thrombophlebitis, superior vena cava obstruction, and hemoptysis are characteristic clinical features of patients with Behçet syndrome and pulmonary infiltrates. Once diffuse pulmonary infiltration and massive hemoptysis appear, the prognosis is poor; death from pulmonary exsanguination is likely to occur. Treatment with cyclophosphamide and prednisone, in addition to blood transfusions, may be beneficial.

Adult↗
PubMed1976

Immunological enhancement of leukemia L1210 by Corynebacterium parvum in allogeneic mice.

The effect of Corynebacterium parvum on the immune response of C57BL/6 mice (H-2b) to the allogeneic leukemia L1210 (H-2d) was investigated. Mice were either left untreated or given C. parvum i.v. or i.p. in various dosages. Seven days later they were challenged with 2.5 to 10 X 10(6) live L1210 cells i.p. Control animals almost always rejected the challenge. In contrast, most mice pretreated with either 1.0, 0.5, or 0.25 mg of C. parvum i.v. and 1.0 or 0.5 mg i.p. exhibited enhanced growth of leukemia L1210 as indicated by gross ascites and significantly greater weight gain. This sometimes progressed to the death of the animal, but more often regressed after several days. Spleen cell-mediated cytotoxicity to alloantigens, evaluated in vitro by release of 51Cr from P815Y (H-2d) target cells, was significantly decreased in the mice pretreated with either 1.0 or 0.5 mg of C. parvum i.v. or 0.5 mg of C. parvum i.p. This suppression could not be reversed by reduction of the concentration of macrophages in the spleen cell suspensions. Complement-dependent cytotoxic antibody, measured by release of 51Cr from L1210 cells, was profoundly suppressed in mice pretreated with C. parvum i.v. in dosages ranging from 1.0 to 0.1 mg. These data suggest an immunological basis for the enhanced growth of leukemia L1210 caused by C. parvum at these schedules.

Animals↗
PubMed1976

Cell-mediated immunity and blocking factor in ovarian carcinoma.

Lymphocyte-mediated cytotoxicity (cell-mediated immunity) to ovarian carcinoma cells and serum blocking factor were measured in 37 patients. Short-term cultures of tumor cells and a low ratio of effector to target cells were used throughout the study, minimizing nonspecific cytotoxicity. Sixteen patients were followed for long periods of time, and correlation with the course of the disease and with therapy could be obtained. Although the level of cell-mediated immunity did not always correspond to the clinical status of the patient, the presence of blocking factor was associated with clinical relapse in 14 of 16 patients. Chemotherapy with single alkylating agents or combinations of drugs caused no significant or permanent depression of cell-mediated immunity as measured in this way. In addition, blocking factor disappeared in 2 patients during remission. It appears that the chemotherapy for ovarian carcinoma may not be significantly immunosuppressive against established levels of cell-mediated immunity and may in certain instances have effects potentially beneficial to the host as evaluated by lymphocyte-mediated cytotoxicity and blocking factor studies.

Antibodies, Neoplasm↗
PubMed1975

A laboratory model for the study of the immunobiology of osteosarcoma.

Inoculation of Moloney sarcoma virus into the marrow cavity of the tibia of newborn Wistar-Lewis rats resulted in the appearance of an initially localized osteosarcoma in 97.7% of these animals. At least 77.9% of the rats developed lung metastases and died, usually within 6 weeks of inoculation. The remaining 22.1% showed regression of disease after initial growth of the tumor. Tumor cells were maintained in tissue culture and used as target cells for a visual and isotopic (3H-thymidine or 125IUdR) microcytotoxicity assay. Cell-mediated immunity could be measured by these methods throughout the course of the illness in animals with progressive disease as well as in those whose tumors eventually regressed. The presence of serum factors capable of modifying the level of CMI was documented. This Moloney-sarcoma-virus-induced rat osteosarcoma and human osteosarcoma thus appear to have several basic pathologic and immunologic similarities. The model may be useful for studying the effects of a variety of treatment protocols upon the clinical course and immune response to osteosarcoma.

Animals↗
PubMed1975

Stimulation of lymphoid cells by components of BCG.

BCG was fractionated into a delipidated mycobacterial cell fraction (DMC) and lipid by exhaustive chloroform-methanol extraction. The effects of these fractions were tested on mouse spleen cells, nonadherent spleen cells (lymphocytes), thymus cells, and adherent spleen cells (macrophages) in vitro and were compared with effects of the whole bacilli and a methanol-extraction residue (MER). Tritiated thymidine incorporation into spleen cells, purified spleen lymphocytes, and thymus cells was measured as an indicator of activity on these cells; lymphocyte-activating factor (LAF) production was used to measure activation of macrophages. DMC and MER were at least equivalent to, and often exceeded, whole BCG in their stimulation of spleen cells and spleen lymphocytes. DMC was a poor thymic mitogen in contrast to MER, which was as strong as BCG in this regard. Lipid was far less effective a mitogen for all cells tested, and failed to augment the effectiveness of DMC on thymus cells when both were present in the incubation mixture. LAF production was significantly increased by whole BCG (18-fold above controls), whereas each fraction increased production threefold to sixfold. These in vitro results seemed to reflect the known in vivo activity of BCG and its components and suggest further antitumor applications.

Animals↗
PubMed1975

Analysis and reversal of the inhibition of cytophilic antibody receptors produced by antibody.

Administration of hyperimmune antibody to leukemia L1210 to allogeneic mice inhibited the development of macrophage-mediated immunity to L1210 in those hosts. In contrast to immunized mice, animals pretreated with antibody showed rapid activation of their peritoneal macrophages, followed by their disappearance and the inability of the residual peritoneal monocytic cells to attach L1210 cells even in the presence of proved cytophilic antibody to L1210. The inhibitory activity of the antibody, which resided entirely in its IgG2 fraction, was manifested only when the specific antigen (L1210 cells) was also injected within 2 days. Pretreatment with antibody to a different leukemia, EL4, failed to inhibit the monocytic uptake of L1210, but it did inhibit uptake of EL4 by monocytes if injected with its homologous antigen. Restoration of the functional capacity of macrophages was accomplished by injecting 1 X 10-7 bone marrow cells i.v. into "suppressed" mice, but 1.5 X 10-7 thymocytes failed to correct the defect. Significantly, thymocytes antagonized the restorative capability of bone marrow cells when they were injected concomitantly. These results indicate that specific inhibition of cytophilic antibody receptors on monocytes could be accomplished through a direct mechanism involving activation and exhaustion of macrophages and an indirect mechanism, perhaps mediated through "suppressor" thymus-derived cells. Although enhancement of the growth of leukemia cells did not occur, several parallels exist in mice with enhanced growth of different tumors. This inhibiotry phenomenon may thus represent another instance of "blocking" in tumor immunity, where the target of suppressive antibody-antigen is the macrophage as well as the lymphocyte.

Animals↗