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Biomedical subjects

S Strober

Publications and source records attributed to S Strober.

At least 163 records · Page 9Linked to original sources

Role of the spleen in the growth of a murine B cell leukemia.

A spontaneous B cell leukemia (BCL1) grew progressively in normal BALB/c mice after injection of tumor cells but did not grow in splenectomized recipients. Despite the absence of progressive tumor growth, residual tumor cells with malignant potential were found in the peripheral blood of the splenectomized animals. Splenectomy performed after injection of tumor cells but before the development of marked leukocytosis also prevented progressive tumor growth and death of the host. Thus the spleen appears to be necessary for progressive proliferation of this lymphocytic leukemia early after passage in vivo.

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Immunosuppression and organ transplantation tolerance using total lymphoid irradiation.

Total lymphoid irradiation (TLI) is a method which delivers irradiation daily in fractionated doses (200 rads) to lymphoid organs while shielding bones, lungs, and the majority of the gastrointestinal tract. TLI is lymphocytopenic in mice, rats, dogs, and humans, and both T cells and B cells are eliminated from the circulation. During the recovery phase in mice, B cells appear before Thy 1.2-bearing T cells, and TL-positive T cells are abundant in the spleen and lymph nodes. These T cells exhibit nonspecific suppressive activity on antibody production and cell-mediated immune responses. TLI permits establishment of specific and long-lasting tolerance to alloantigens. Permanent acceptance of allogeneic bone marrow cells without graft-versus-host disease was achieved in rats and dogs across major histocompatibility barriers. Recipients were tolerant to allografts of skin, hearts, and kidney from animals syngeneic to marrow donors or to organs from the marrow donor. This approach may be suitable for pancreas transplantation in diabetes.

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An in vitro line of the B cell tumor BCL1 can be activated by LPS to secrete IgM1.

An in vitro line of the B cell tumor BCL1 was developed. The cell line carried u-, S-, and A-chains on the cell surface as judged by analysis of surface iodinated proteins but did not secret Ig. ASfter stimulation with LPS, limpid A, or bacterial lipoprotein, 20 to 40% of the tumor cells matured to IgM secretors when detected in a plaque assay. Two other polyclonal B cell activators, namely dextransulphate and PPD, had at most a marginal stimulatory effect. The ability of the cells to become activated to IgM secretion as well as the expression of cell surface IgM and IgD makes the BCL1 unique among murine B cell tumors.

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Reversal of nzb/nzw disease with total lymphoid irradiation.

NZB/NZW mice spontaneously exhibit autoimmune disease similar to that seen in human systemic lupus erythematosus (SLE). We demonstrated that total lymphoid irradiation (TLI) reversed well expressed disease in 6-mo-old NZB/NZW females with a prolongation in survival, decrease in proteinuria, and decrease in anti-DNA antibodies as compared to control animals. Few side effects were observed in the treated group. TLI also prolonged survival in animals with advanced renal disease. These findings suggest that TLI may have application to the treatment of human SLE.

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Cardiac allograft survival in rhesus primates treated with combined total lymphoid irradiation and rabbit antithymocyte globulin.

Eighteen abdominal heterotopic cardiac allografts were performed in outbred rhesus primates. For immunosuppression seven animals received six 100-rad/day total lymphoid irradiation (TLI) doses the week preceding transplant and three 3-mg/kg i.m. rabbit antithymocyte globulin (RATG) doses on postoperative days -1, 0, and +1; five animals were given this RATG dose but no irradiation; three were given TLI alone; and three were given no immunosuppressive therapy. Circulating T lymphocyte counts were monitored in all animals (rosettes). Graft survival in the combined TLI-RATG therapy group (169 +/- 15 days) was significantly greater than in untreated (11 +/- 1 days), RATG alone (22 +/- 12 days), or TLI alone (38 +/- 6 days) treated animals (P less than 0.001, 0.0001, and 0.001, respectively). The animals receiving combined TLI-RATG therapy also achieved significantly greater and more prolonged T lymphopenia than that obtained in the other three groups. Six of seven cardiac allografts placed in animals receiving TLI-RATG therapy were removed electively before cessation of electrical activity; however, in four of these rejection pathology was noted. Thus, it seems that combined TLI-RATG therapy may be of benefit in the management of transplant recipients, but its use will probably not abolish these patients' requirements for immunosuppressive maintenance measures.

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Characterization of the spontaneous murine B cell leukemia (BCL1). III. Evidence for monoclonality by using an anti-idiotype antibody.

We have raised an anti-idiotypic antibody against the cell surface IgM of the murine BCL1 tumor cells. This antiserum reacts exclusively with the IgM expressed on the tumor cells and detects a unique population of cells in the spleen and blood of the tumor-bearing mice. When these cells are stimulated in vitro with LPS, they secrete an IgM bearing the same idiotype as the cell surface Ig. These results are discussed in terms of a model for the immunotherapy of a chronic lymphocytic leukemia-like syndrome in mice.

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