Younan A. Sidky

Effect of Hibernation on the Hamster Spleen Immune Reaction in vitro

Summary Spleen explants from hamsters kept at room temperature responded strongly when immunized with sheep red blood cells in vitro. Spleens from cold-adapted animals behaved essentially like those obtained from normal animals. In contrast, spleen explants obtained from hibernating animals tended to be less capable or incapable of giving a detectable response to the same antigen under identical conditons of cultivation. Restoration of competence was obtained by cultivation of spleen explants in combination with a number of other tissues.

ONTOGENY OF THYMUS CELL FUNCTION

Primitive thymus stem cells were studied with regard to in vitro maturation, sensitivity to x radiation, sensitivity to corticosteroids, and development of thymocytes from nude embryos. Studies were also conducted on thymus helper cell function. (HLW)

Effect of interferon alpha, interferon beta, and interferon gamma on the in vitro growth of human renal adenocarcinoma cells

Interferon-α, interferon-β, and interferon-γ differ in their antiproliferative effects for several cell lines. Interferons were thus assessed for their activity in inhibiting proliferation of three renal cell carcinoma cell lines. The malignant epithelial phenotype of each of these cell lines was confirmed by electron microscopy, histology, karyotype and tumorigenicity. When compared on an anti-viral unit basis, naturally produced interferon-β was more effective than natural interferon-α for all cell lines and clones. Proliferation of each of the cell lines was inhibited by interferon-γ. In all cases, removal of interferons from culture media resulted in resumption of the rate of cell growth after a variable delay of 6–10 days. If the antiproliferative effects of interferons predominate in mediating tumor regression, clinical response may depend upon the type of interferon to which the tumor is exposed.

Brown Fat: Its Possible Role in Immunosuppression During Hibernation

Summary Brown fat from hibernating ground squirrels can depress the primary immune response of hamster spleen fragments in tissue culture. The immunosuppressive activity is preserved in brown fat homogenates and appears to be associated with the crude lipid layer. We acknowledge the excellent technical assistance of H. Anderson, L. Kubai, and L. Morrissey.

Lyt phenotype analysis of the effector cells responsible for evoking lymphocyte-induced angiogenesis (LIA)

Abstract Lymphocyte-induced angiogenesis (LIA) is a vascular response observed when allogeneic or semiallogeneic immunocompetent lymphocytes are inoculated intradermally into immunosuppressed or irradiated host mice. The reported experiments were carried out to characterize the effector cell population(s) responsible for causing LIA. Lyt 1.2, Lyt 2.2, and monoclonal Thy 1.2 antisera were used for negative selection with complement (C′) to investigate the ability of selected subsets of lymphocytes to evoke angiogenesis. Treatment of C57BL/6 spleen cells with either anti-Lyt 1.2 or anti-Thy 1.2 and C′ resulted in an almost complete abrogation of the LIA reaction. In contrast, depletion of Lyt 2+ cells, under conditions which fully abrogated their ability to generate cell-mediated cytotoxicity in allogeneic mixed leukocyte cultures, resulted only in a partial (45%) reduction in the induced vascular response. Synergistic interaction between cell preparations treated separately with either anti-Lyt 1.2 or anti-Lyt 2.2 serum was not observed. We conclude that (i) Lyt 1 + 2−T lymphocytes can induce a significant LIA reaction; (ii) lymphocytes resistant to negative selection with anti-Lyt-1.2 serum are incapable of inducing such a reaction; and (iii) Lyt 1 + 2+ cells directly or indirectly play an additional role in generating a maximal LIA response.

Response of the Host Vascular System to Immunocompetent Lymphocytes: Effect of Preimmunization of Donor or Host Animals

Summary We have previously shown that immunocompetent lymphocytes can induce angiogenesis following intradermal inoculation into allogeneic or semi-allogeneic host animals. Experiments are described demonstrating that preimmunization of donor animals leads to a specific increase in angiogenesis-inducing capacity of effector spleen cells, while preimmunization of host animals results in a selective, specific reduction in lymphocyte-induced vascular changes. The results are discussed in terms of the increasing evidence that lymphocyte-induced angiogenesis is mediated by soluble factors (lymphokines) released following lymphocyte activation.

Chemoprophylaxis by Interferons or Inducers against Chemical Carcinogenesis

Human malignancies arise commonly after exposure to environmental carcinogens. Bladder cancer is a well-studied and excellent preclinical model for this process. Transitional cell carcinoma (TCC) of the lower urinary tract accounts for approximately 4% of human cancers. Most of the TCC arise in the urinary bladder, with a male:female ratio in the U.S. of about 3:1. Chemical carcinogen-induced mouse and rat tumors in situ and transplantable bladder cancer models, which mimic the pathogenesis of the human disease, have been developed (1–4). Neoplasms can be histologically graded and staged in a manner similar to that for human bladder carcinoma.