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Administration of lymphokine-activated killer (LAK) cells in combination with interleukin 2 (IL-2) has been effective in reducing tumor mass in humans, but has been accompanied by significant toxicity. We used a chronic awake sheep model to investigate the cause of the vascular leak syndrome associated with IL-2 administration. Sheep repeatedly infused with human recombinant IL-2 (hrIL-2) developed mild pulmonary hypertension, systemic hypotension, acidemia, hypoxemia, and increased flow of protein rich lung lymph. We hypothesized that LAK cells may damage lung endothelium in vivo and cause increased lung vascular permeability. Sheep peripheral blood and lung lymph lymphocytes incubated in vitro with hrIL-2 generated cytotoxic activity for human K-562 cells and sheep pulmonary microvascular endothelial cells. In addition, cytotoxic effector cells were isolated from the peripheral blood of a sheep which had received hrIL-2. These observations suggest that LAK cells possess the ability to damage endothelial cells and may contribute to an increased pulmonary vascular permeability observed following hrIL-2 infusion in sheep.

Adenosine, an intermediate product in the metabolism of ATP, is thought to produce vasodilation in all vascular beds with the exception of the kidney. Due to its theoretical potential as a pulmonary vasodilator, we studied the hemodynamic effects of adenosine in the pulmonary vasculature of chronically instrumented awake sheep. Adenosine produced significant pulmonary vasoconstriction instead of the expected vasodilatation. Bolus injections of adenosine into the superior vena cava produced a dose-dependent increase in pulmonary artery pressure that was entirely due to an increase in vascular resistance, since cardiac output decreased slightly. This effect is produced via activation of specific cell surface adenosine receptors, since it was blocked by the adenosine-receptor antagonists theophylline and dipropylsulfophenylxanthine. The cell type involved in adenosine-induced pulmonary vasoconstriction appears to be located within the lung, since vasoconstriction was blunted when adenosine was infused into the left atrium, distal to the lung. However, adenosine does not directly vasoconstrict the pulmonary vasculature, because its effect could be completely abolished by cyclooxygenase inhibition with either indomethacin or ibuprofen and by a thromboxane A2/prostaglandin endoperoxide-receptor antagonist (SQ 29,548). Adenosine-induced vasoconstriction was also greatly reduced after inhibition of thromboxane synthesis. Thus, adenosine produced pulmonary vasoconstriction through generation of a thromboxane/endoperoxide product. Whether endogenous adenosine is involved in the generation of pulmonary vasoconstriction seen in pathophysiological states remains to be determined. To our knowledge, this is the first clear evidence for adenosine-induced vasoconstriction outside the kidney and for an interaction between adenosine and eicosanoid mechanisms.

The regulatory subunit (R) of Type I cAMP-dependent protein kinase from rabbit skeletal muscle can serve as a substrate for its catalytic subunit (C). The degree of phosphorylation depends on both the concentration of C and the the time of incubation. Moreover, the phosphorylation can be totally blocked by protein kinase inhibitors. In contrast, cAMP stimulates the phosphorylation of R using the holoenzyme. The purified holoenzyme isolated from rabbit skeletal muscle can be further fractionated into two fractions on DEAE Sephadex column. The first fraction eluted with low salt (50 mM NaCl) contains a much lower concentration of kinases than the second fraction eluted with high salt (100 mM NaCl), but the low salt kinase can be readily phosphorylated in the presence of MgATP. Our data thus implies that only a small fraction of Type I cAMP-dependent protein kinases in the skeletal muscle is present as the phosphorylatable species.

Although health education is a relatively new professional discipline, health educators have actively utilized television for informational and persuasive purposes since its inception as a public mass medium. Informational messages have been developed for classroom and public television, while persuasive messages have been developed for commercial television. With the current health education emphasis on developing and maintaining behaviors conductive to health, the school health educator can blend both informational and persuasive methods to create a more dynamic classroom teaching environment.

In mice affected with equine encephalomyelitis, the first pathological disturbance in infant animals is an inflammatory reaction, which is usually less pronounced in adult animals. A characteristic type of parenchymal damage appears to be independent of the inflammation. In such foci of injury there is initially a vacuolation of intercellular tissue. Neurones in such areas are at first intact, later show cytoplasmic changes, and finally nuclear alterations. Complete disintegration of tissue and all its elements may be the end result.