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Biomedical subjects

S P Ho

Publications and source records attributed to S P Ho.

12 recordsLinked to original sources

Interleukin-2 and syngeneic bone marrow transplantation in a murine fibrosarcoma model.

Mice received interleukin-2 (IL-2) either before and after, or just after intravenous inoculation of syngeneic fibrosarcoma cells. Fewer pulmonary tumor colonies were observed in those animals treated with IL-2, and the best results were observed when IL-2 was administered prior to tumor inoculation. When mice were lethally irradiated and reconstituted with tumor-contaminated bone marrow, IL-2 treatment was also associated with fewer tumor lung colonies. IL-2 may prove to be a useful adjuvant therapy, particularly in the setting of autologous bone marrow transplantation when the infused marrow is contaminated with tumor cells.

Animals

The effects of interleukin-2 on bone marrow engraftment in a murine model.

Strategies have been developed to rid bone marrow of microscopic tumor prior to infusion in the autologous bone marrow transplant setting. We have previously demonstrated that recombinant human interleukin-2 (IL-2) is effective in such an experimental setting involving a methylcholanthrene-induced fibrosarcoma in mice. The purpose of the current work was to determine whether IL-2 treatment after, or before and after bone marrow transplantation would influence bone marrow engraftment or degree of hematologic reconstitution. We found that stem cell number (CFU-S) and posttransplant marrow cellularity were comparable in IL-2-treated or saline-treated mice. Furthermore, after engraftment, marrow stem cell and myeloid progenitor cell numbers were greater in the IL-2 treatment group. These results suggest that IL-2 will prove to be safe when administered in bone marrow transplant patients.

Animals

Effect of host age upon interleukin-2-mediated anti-tumor responses in a murine fibrosarcoma model.

The age-associated decline in immune function may be an important factor in both the pathogenesis of neoplastic diseases and the response to immunopharmacological therapies. With the increased efforts to develop immunotherapy with such agents as interferon and interleukin-2 (IL-2), the question of the effect of host age upon response is of practical importance. Phase I and phase II clinical trials of IL-2 have included primarily young patients, and toxicity and efficacy have not been reported with specific reference to host age. In this study, we examined young and old mice with regard to in vitro natural killer and lymphokine-activated killer (LAK) cell functions. We also assessed the effects of exogenously administered recombinant human IL-2 in tumor-bearing mice of various ages. We found that natural killer cell function was demonstrably lower in old mice but that LAK cell function was comparable (young versus old). Furthermore, IL-2 treatment was successful in increasing survival time in old mice, similar to results in young mice. Our observations allow the prediction that immune senescence per se does not preclude successful anti-neoplastic treatment with IL-2.

Aging

Lymphocyte-induced angiogenesis factor is produced by L3T4+ murine T lymphocytes, and its production declines with age.

Lymphocyte-induced angiogenesis factor (LIA) is a product of T lymphocytes which has been shown to stimulate new vessel formation. Because immune senescence most profoundly affects T lymphocyte functions, we suspected that LIA production would decline with age. An assay for angiogenesis stimulated by allogeneic reaction was performed by injecting spleen cells from young or old donor mice into the skin of irradiated allogeneic recipient mice. The spleen cells from young mice induced a significantly greater number of vessels than did cells from older mice. In additional experiments, spleen cells from young and old animals were treated with a monoclonal antibody GK 1.5) directed at the L3T4 antigen on murine T helper lymphocytes. Such treatment significantly reduced the new vessel formation induced by young lymphocytes but had no effect on that induced by lymphocytes from old animals. Studies employing indirect immunofluorescence demonstrated that the proportion of L3T4+ cells in the mononuclear fraction of splenocytes was nearly identical in both young and old mice. From these investigations we can conclude that (1) L3T4+ lymphocytes are responsible for LIA production, and (2) production, like that of other T lymphokines, declines with age.

Age Factors

The design, synthesis, and crystallization of an alpha-helical peptide.

Twelve- and sixteen-residue peptides have been designed to form tetrameric alpha-helical bundles. Both peptides are capable of folding into amphiphilic alpha-helices, with leucyl residues along one face and glutamyl and lysyl residues along the opposite face. Four such amphiphilic alpha-helices are capable of forming a noncovalently bonded tetramer. Neighboring helices run in antiparallel directions in the design, so that the complex has 222 symmetry. In the designed tetramer, the leucyl side chains interdigitate in the center in a hydrophobic interaction, and charged side chains are exposed to the solvent. The designed 12-mer (ALPHA-1) has been synthesized, and it forms helical aggregates in aqueous solution as judged by circular dichroic spectroscopy. It has also been crystallized and characterized by x-ray diffraction. The crystal symmetry is compatible with (but does not prove) the design. The design can be extended to a four-alpha-helical bundle formed from a single polypeptide by adding three peptide linkers.

Amino Acid Sequence

Soft-tissue sarcoma of undetermined histogenesis: an ultrastructural study.

A certain proportion of soft-tissue sarcomas are difficult to classify accurately. In this case report, initial light microscope observations of a soft-tissue tumor suggested a diagnosis of a monophasic synovial sarcoma. However, critical evaluation of the histologic features, results of studies with special stains, and ultrastructural observations indicated that this tumor is best categorized as an undifferentiated soft-tissue sarcoma of "undetermined histogenesis."

Adult