Paclitaxel is a frontline therapy for ovarian cancer. Our laboratory has shown that paclitaxel induces IL-8, a member of the C-X-C family of chemokines, in subsets of human ovarian cancer cells. However, the critical issue concerns the biological significance of this chemokine in human ovarian cancer. To study the influence of IL-8 on tumor growth, human ovarian cancer cell lines were transfected with an expression vector for human IL-8 and tested for their ability to form tumors in nude mice. IL-8 expression by the transfected cells did not alter their growth properties in vitro. In contrast, tumor growth in vivo was significantly attenuated in animals receiving IL-8-expressing cells when compared with mice injected with control cells. As additional evidence that IL-8 is a crucial factor in tumor growth, it was noted that ovarian cell lines in which constitutive IL-8 expression is elevated did not form tumors. Injection of neutralizing Ab to IL-8 reverted the phenotype and caused tumor growth in vivo. Examination of tissue from the inoculation site revealed a dramatically elevated cellularity, containing neutrophils and macrophages, in mice receiving IL-8-expressing tumor cells. These results suggest that IL-8 production by human ovarian tumor cells can play a role in reducing the rate of tumor growth; this effect may be mediated by the increased targeting of neutrophil and other mononuclear cells to the tumor injection site. These studies indicate a role for IL-8 in ovarian cancer control and suggest that chemotherapy-induced IL-8 may have a positive role in controlling tumor growth.

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Muscle biopsies were obtained from vastus lateralis muscles of four volunteers exercising at increasing work rates on a bicycle ergometer. Samples were taken at rest (t1), after a work load 23% below the blood lactate threshold (t2), 23% above this threshold (t3), and at exhaustion (t4). Individual muscle fibers were typed by their lactate dehydrogenase and adenylokinase levels and assayed for lactate, glucose-6-phosphate, and malate, (which preliminary data indicated to be the most responsive to increased activity) as well as ATP and phosphocreatine. The results in three of the four cases indicated that by the time of the t2 sample, almost all fibers, regardless of type, had been recruited. Additionally, there were no major differences in lactate concentration between type 1 and 2 fibers from muscle samples taken at t1, t2, and t3. It is concluded that in a muscle with fast-twitch glycolytic and slow-twitch oxidative fibers, all fibers share in the contraction to a substantial degree, even at moderate work loads, and that both the type 1 and 2 fibers contribute significantly to the initial rise in blood lactate during a graded exercise task. Metabolite responses in type 2 fibers differed in certain respects among the four participants. This is attributed to differences in their training backgrounds and consequent differences in type 2 fiber oxidative enzyme levels.

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The distribution of choline acetyltransferase (ChAT) within the amygdaloid complex has been studied to evaluate what should primarily represent the terminal field of the cholinergic projection from the basal forebrain. Two currently available methods have been combined for the comparison: immunohistochemistry with a monoclonal antibody against ChAT, by a double peroxidase-antiperoxidase procedure, and quantitative histochemistry involving micro-assay of the ChAT activity of contiguous microdissected samples. Both methods indicate prominent ChAT activity in the basolateral amygdaloid nucleus (especially rostrally), the nucleus of the lateral olfactory tract (especially layer II), and the amygdalohippocampal area. Regions of lower ChAT activity were not accurately represented by the immunohistochemistry, but could be discriminated by the quantitative assays. Lowest activity was found in the medial nucleus of the amygdala. Most other regions had activities at least as high as average brain or neocortex. Gradients of enzyme activity were found within several regions, including the basolateral and lateral amygdaloid nuclei and the nearby posterior piriform cortex. In the piriform cortex, a region of particularly high ChAT activity was found at its medial edge near the nucleus of the lateral olfactory tract. The immunohistochemical method shows a few intensely reactive somata in layer III within this zone. Comparison of the results seen with immunohistochemistry and quantitative histochemistry suggests an advantage in using them together, since their respective strengths and weaknesses tend to complement each other.