Interferon effects on microfilament organization cellular fibronectin distribution, and cell motility in human fibroblasts

We have shown previously (Pfeffer et al., 1979, Exp. Cell Res. 121:111-120) that treatment of human fibroblasts, planted at a density of 2x10(3) cells/cm(2), with purified human fibroblasts interferon (640 U/ml) for 3 d at 37 degrees C decreases the overall rate of cell proliferation to 35-40 percent of the control value. In the present experiments we have characterized the phenotype of interferon-inhibited fibroblasts. The mean volume of trypsinized, interferon-treated cells was increased 31 percent abover that of control cells. The interferon-treated population was much more heterogeneous than the control population with respect to volume, and there was a considerable overlap in the volume distributions of the two populations. The cell surface area was, on the average, increased 65 percent after interferon treatment. More than 80 percent of the treated cells had enlarged nuclei, many of which were lobed, and the fraction of binucleated cells was increased fivefold. After interferon treatment, over 40 percent of the cells showed large actin-containing fibers in the form of multiple parallel arrays. Fewer than 5 percent of the control cells contained such large actin fibers. The number of actin fibers of all sizes was tripled in the treated fibroblasts on a per cell basis and, calculated per unit surface area of the cells, the number was increased 82 percent. In contrast, 10-nm filaments and microtubules did not appear to be increased in number per unit surface area of the cells. The increases per cell in the abundance of these structures were directly related to increased cell size. After interferon treatment, fibronection was distributed in arrays of long filaments covering most portions of the cell surface. Interferon treatment markedly decreased the rate of cell locomotion as well as membrane ruffling and saltatory movements of intracellular granules.     

Cerebral gas embolism absorption during hyperbaric therapy: theory.

Cerebral gas embolism is a serious consequence of diving. It is associated with decompression sickness and is assumed to cause severe neurological dysfunction. A mathematical model previously developed to calculate embolism absorption time based on in vivo bubble geometry is used in which various conditions of hyperbaric therapy are considered. Effects of varying external pressure and inert gas concentrations in the breathing mixtures, according to US Navy and Royal Navy diving treatment tables, are predicted. Recompression alone is calculated to reduce absorption times of a 50-nl bubble by up to 98% over the untreated case. Lowering the inhaled inert gas concentration from 67.5% to 50% reduces absorption time by 37% at a given pressure. Bubbles formed after diving and decompression with He are calculated to absorb up to 73% faster than bubbles created after diving and decompression with air, regardless of the recompression gas breathed. This model is a useful alternative to impractical clinical trials in assessing which initial step in hyperbaric therapy is most effective in eliminating cerebral gas embolisms should they occur.     

Phase II protocol for the evaluation of new treatments in patients with advanced gastric carcinoma: results of ECOG 5282

The study was a Phase II randomized study to evaluate the efficacy of new agents for the treatment of advanced gastric carcinoma. Patients were randomized to receive single agent chemotherapy with mitoxantrone, etoposide, aclacinomycin-A or spirogermanium. The patients were stratified by prior use of chemotherapy, prior doxorubicin use and ECOG performance status. Patients with a history of cardiac disease or prior doxorubicin exceeding a dose of 400 mg/m² were restrictively randomized to sopirogermanium or etoposide only. One hundred and fourteen patients were registered for the study. Among 98 evaluable patients there were only two partial responses (both in the etoposide arm), and one complete response in the mitoxantrone arm. The median survival on the study was 3.3 months. One hundred and six patients were analyzable for toxicity. There were four treatment-related deaths and four life-threatening toxicities. Because of low response rates and relatively high toxicities the studied compounds were not deemed worth further investigation for advanced gastric cancer.