Purification and biochemical characterization of human lymphocyte mitogenic factor (LMF).

Supernatants of human T lymphocytes stimulated by TT antigen release two factors that induce mitogenesis in autologous and allogeneic B lymphocytes. These factors are precipitated by 60% ammonium sulfate and 50% ethanol, and are both destroyed by heating to 70 degrees C for 5 min. By equilibrium ultracentrifugation there was a peak of mitogenic activity in the fraction with a specific gravity of 1.

Mammary cancer: selective action of the estrogen receptor complex.

Progesterone receptors in the autonomous rat mammary tumor MTW-9B are reduced 80 to 90 percent after ovariectomy, but are not reduced if ovariectomized animals are given estrogen. Tumor growth, however, is independent of estrogen status and insensitive to pharmacological doses of estradiol. This represents an unusual system characterized by a selective action of an inducing agent on the genome.

Sex differences in the concentrations of glucocorticoid receptors in rat liver and thymus.

The effects in rats of adrenalectomy, hypophysectomy, ovariectomy or combinations of these operations on the concentrations of glucocorticoid receptors in the cytosol of liver and thymus were measured. The concentrations of glucocorticoid receptors were lower in cytosols from liver and thymus of female than of male rats. After adrenalectomy, there was a significant increase in the concentrations of receptors measured in the cytoplasm from the liver and thymus of female rats and from the liver of male rats.

Induction of human immunoglobulin synthesis and secretion in somatic cell hybrids of mouse myeloma and human B lymphocytes from patients with agammaglobulinemia.

Somatic cell hybrid clones were isolated from the fusion of RPC 5,4 mouse myeloma cells and B lymphocytes from three patients with agammaglobulinemia. One patient had X-linked agammaglobulinemia; the remaining two patients had common varied agammaglobulinemia. All three patients had B lymphocytes which fail to secrete immunoglobulin.

Bone marrow-derived lymphoid cell lines from patients with agammaglobulinemia.

In vitro infection with Epstein-Barr virus of bone marrow-derived (B) lymphocytes from blood of patients with X-linked or common varied agammaglobulinemia resulted in the establishment of long-term B-lymphoid cell lines (LCL). LCL were established only with B lymphocytes from patients whose B cells failed to respond to in vitro mitogenic stimulation. In contrast, lymphocytes from patients without small B lymphocytes or with B cells that synthesized but failed to secrete Ig failed uniformly to establish LCL.

Comparison of the antitumor activity and toxicity of 2,4-diamino-5-(1-adamantyl)-6-methylpyrimidine and 2,4-diamino-5-(1-adamantyl)-6-ethylpyrimidine.

The effects of two new compounds, 2,4-diamino-5-(1-adamantyl)-6-methylpyrimidine (DAMP) and 2,4-diamino-5-(1-adamantyl)-6-ethylpyrimidine (DAEP), on the growth of Walker carcinoma 256 were studied. In Sprague-Dawley rats, both compounds inhibited the growth of the Walker tumor, which is naturally resistant to methotrexate. Murphy-Sturm lymphosarcoma, which is extremely sensitive to methotrexate, was not inhibited by DAMP.

Restricted classes of immunoglobulin produced by a lymphoid cell line from a patient with agammaglobulinemia.

Restricted expression of immunoglobulin by a long-term B lymphoid cell line derived from a patient with X-linked agammaglobulinemia is reproted. The patient had peripheral blood B lymphocytes with surface IgD and IgM. Culture of the B cells in vitro with mitogens did not stimulate immunoglobulin secretion, although pokeweed mitogen stimulation resulted in the development of cytoplasmic IgD and IgM.

Complete correction of the Wiskott-Aldrich syndrome by allogeneic bone-marrow transplantation.

Two patients with the Wiskott-Aldrich syndrome had complete donor lymphoid and hematopoietic engraftment after successful allogeneic bone-marrow transplantation. One patient had had only a temporary donor T-lymphocyte graft after a previous transplantation, for which he had been prepared with cytarabine and cyclophosphamide; the patient's own T lymphocytes returned six months later. A repeat transplant, for which the patient was prepared with anti-human thymocyte serum, total-body irradiation and procarbazine, resulted in complete donor engraftment.

Nuclear binding of steroid-receptor complex to lymphosarcoma P1798 resistant and sensitive cells and effect of concanavalin A on receptor levels.

Glucocorticoid-resistant P1798 cell lines have been found to contain levels of glucocorticoid receptor comparable to receptor levels in glucocorticoid-sensitive P1798 cells. Previously, most of the P1798 resistant cells examined were found to contain low levels of glucocorticoid receptor, and this was thought to account for the resistance of these cells to glucocorticoid treatment. Resistant cells with high receptor levels exhibited 10 to 50 percent lower levels of nuclear binding than did sensitive cells.

Biosynthesis of the third component of complement (C3) in vitro by monocytes from both normal and homozygous C3-deficient humans.

Human monocytes synthesized the third component of complement (C3) up to 5 wk in vitro. Evidence for net C3 synthesis was based on (a) incorporation of 14C-labeled amino acids into C3 protein, (b) indentity of the allotype of C3 produced in vitro with that of the doner's serum C3, even in the presence of carrier C3 protein of a different allotype; (c) correspondence of electrophoretic mobility, size, and subunit structure of C3 protein produced in vitro with serum C3; (d) inhibition of C3 production with cycloheximide. Monocytes from two unrelated C3-deficient patients were studied under conditions that supported C3 synthesis by normal monocytes.

Glucocorticoid receptors in Morris hepatomas and host liver and the correlation of biological activity with receptor levels.

Glucocorticoid-binding macromolecules were examined in Morris hepatomas 7787, 5123tc, 3683F, 7800, and 3683 and the Reuber hepatoma H-35 with the use of the synthetic glucocorticoid, triamcinolone acetonide. The physical properties of the triamcinolone acetonide-binding macromolecules of the hepatomas indicate that they are specific glucocorticoid receptors. The equilibrium association constants (Ka), sedimentation coefficients, and sensitivity to sulfhydryl-blocking reagents were found to be similar when hepatoma receptors were compared with the known properties of the liver receptor.

The prognostic value of acute phase reactants in patients with neuroblastoma.

As part of a more extensive study of the immune response in children with neuroblastoma, serum immunoglobulin and alpha-glycoprotein levels were measured in 58 patients. Twenty-nine children were studied at diagnosis, 18 at some time during the first 2 years of treatment, and 11 who were apparently cured after treatment had been completed. No correlation was found between the levels of IgG, IgA, and IgM and the clinical status of the patient.

Heterogeneity of nephritic factor and its identification as an immunoglobulin.

Complement C3 nephritic factor (NeF) produces alternative pathway-meciated C3 cleavage by binding to and stabilizing the alternative pathway C3 convertase, C3bBb. Some studies have suggested that NeF is an immunoglobulin, while others conclude that it is a distinct serum protein. The heterogeneity of NeF was evaluated by electrophoresis and isoelectric focusing of NeF-containing serum followed by hemolytic demonstration of NeF activity in agar gel.