Theresa Chiang

Experimental Beryllium-Induced Lung Disease

In previous studies, we found that endotracheal administration of beryllium oxide (BeO) produced cell-mediated immunity and granulomatous lung disease in strain 2 but not strain 13 guinea pigs. This report describes phenotypic and functional studies of bronchial lavage cells from both guinea pig strains after BeO exposure. In BeO-treated strain 2 animals, the percentage of T (ER+)3 lymphocytes was significantly (p less than 0.05) elevated above normal by 2 weeks after BeO exposure, while T lymphocytes were not increased in strain 13. Giant cells containing crystalline material in fused, coalesced phagolysosomes were observed in treated animals of both strains. BeO-exposed strain 2 alveolar macrophages (AM) demonstrated enhanced killing of Listeria monocytogenes and enhanced chemiluminescence, while AM of strain 13 had responses below controls. Findings support the presence of BeO-induced cellular immunologic activity in strain 2 animals and, on the other hand, suggest BeO toxicity to lavage cells in strain 13.

Immunologic studies of experimental beryllium lung disease in the guinea pig.

Abstract An experimental model for chronic, granulomatous beryllium lung disease was produced in Hartley (outbred) and strain 2 guinea pigs by endotracheal injection of beryllium oxide. These animals demonstrated positive skin tests to intradermal injections of beryllium sulfate and their peripheral lymphocytes showed significant blast transformation to beryllium salts in vitro. Treatment with prednisone decreased severity of the lung disease as graded by histologic evaluation. This beneficial effect disappeared within 8 weeks after therapy was discontinued. l -Asparaginase and cytoxan treatments had a similar effect. Guinea pigs made tolerant to beryllium by intravenous or oral administration of beryllium sulfate developed minimal disease when challenged with endotracheal beryllium oxide. In the study of inbred strains 2 and 13, the former consistently developed lung disease whereas the latter did not, although chemical analyses of lung tissue for beryllium content showed equivalent amounts to be deposited in both strains. In strain 2 guinea pigs, the disease as well as delayed skin reactivity could be transferred by spleen cells. These studies support the participation of immune mechanisms in beryllium lung disease.

Combination therapy with a synthetic peptide of C-reactive protein and interleukin 2: augmented survival and eradication of pulmonary metastases

A synthetic peptide (RS-83277) derived from the structure of human C-reactive protein (CRP) was previously shown to have antitumor activity in three different murine tumor models when administered in multilamellar vesicles (MLV). The therapeutic effects were comparable to those seen with MLV-encapsulated native CRP. The present study evaluated the therapeutic and immunomodulatory effects of administering CRP peptide RS-83277 MLV simultaneously with low-dose recombinant interleukin-2 (IL-2) to C57B1/6 mice bearing established pulmonary metastases of fibrosarcoma T241. Results demonstrated that the capacity of RS-83277 MLV to inhibit tumor metastases and prolong survival was significantly augmented by combination with 10 000 U/day IL-2 i.p. Treated animals showed no evidence of toxicity. By immunohistochemistry, increased Thy 1.2+ cells were detectable in lungs of RS-83277 MLV/IL-2-treated animals compared to those receiving RS-83277 MLV alone. Circulating tumor necrosis factor α (TNF) and interferon (IFN) were not detectable in animals receiving RS-83277 MLV alone, but TNF was significantly elevated in animals receiving IL-2. In the presence of combination therapy, however, circulating TNF was not detectable. Results suggest that the combination of synthetic CRP peptide RS-83277 MLV and low-dose IL-2 offers a therapeutic advantage over either agent alone.

Tumor-Enhancing Effects of Cimetidine

The effects of cimetidine were studied in mice bearing a transplantable syngeneic fibrosarcoma. Both tumor size and extent of lung metastasis were enhanced by cimetidine when drug treatment was commen

Specific triiodothyronine binding by tumor cells and spleen cells in a thyroid hormone dependent mouse tumor system.

Abstract We have reported thyroid hormone dependency of syngeneic mouse tumor (fibrosarcoma T241 in C57Bl/6J mice) for growth and spread. To study further the mechanisms of thyroid hormone action we assayed tumor cells and spleen cells for thyroid hormone receptors. Cells were incubated at 37°C for 1 hr with [ 125 I]triiodothyronine with and without unlabeled T3. Competitive inhibition of [ 125 I]T3 bound to spleen cells was demonstrated by increasing the amount of unlabeled T3 and T4. Similar competitive inhibition of binding was minimal for intact tumor cells. Saturable binding sites in muclei were demonstrated in all these cell populations. A Scatchard analysis of nuclei fraction from these cells showed equilibrium dissociation constant (K d ) of 0.56 × 10 −9 for normal spleen cells and tumor cells and 1.4 × 10 −9 M for tumor-bearing mice spleen cells. The estimated maximum binding capacity for nuclei of these cells was 26 fmol/10 × 10 6 cells for normal spleen cells, 46 mol/10 × 10 6 cells for tumor-bearing mice spleen cells and 45 fmol/10 #x0000D7; 10 6 cells for tumor cells. Our results established the presence of T3 receptors in nuclei of tumor cells as well as spleen cells and suggests the direct metabolic effect of thyroid hormone as a possible mechanism for thyroid hormone dependency of this tumor.