This large, sibling-controlled, multisite study of young adult survivors of childhood leukemia, Hodgkin's disease, and non-Hodgkin's lymphoma found that survivors had significant increased risk for reporting symptoms of depression and somatic distress and that intensive chemotherapy added to this risk. However, being a cancer survivor did not compound the effects of gender and SES variables on the 2 outcomes measured. The ability of SES, gender, and treatment-related variables to predict psychological symptoms in this cohort of childhood survivors and sibling controls calls for future research into varied biological and psychosocial pathways by which cancer influences future psychosocial functioning.

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Endotoxic shock is associated with acute vascular endothelial injury resulting in edema. Tumor necrosis factor (TNF) and interleukin 1 (IL-1) are cytokines produced by endotoxin-stimulated mononuclear phagocytes that are potential mediators of endotoxic shock. In this study, we investigated the effects of TNF and IL-1 alpha on vascular endothelial cell permeability in vitro. The movement of radiolabeled macromolecules of different sizes (57Co-vitamin B12, 125I-cytochrome c, and 131I-albumin; 6.5-35A) across bovine aortic endothelial cell monolayers was measured after exposure to these cytokines. TNF induced a time- and dose-dependent increase in endothelial cell monolayer permeability that was enhanced in the presence of serum. The peak increase was noted after 12 h of incubation with less alteration of permeability with longer incubations. IL-1 alpha caused a similar time-dependent increase in endothelial cell monolayer permeability, but the peak effect of IL-1 alpha was seen after 24 h. Therefore the increased permeability seen with TNF cannot be explained by release of endogenous IL-1 alone. Neither TNF nor IL-1 alpha increased release of [14C]adenine, and the only effect on lactate dehydrogenase release was a small, but statistically significant, increase after 24 h of incubation. From these studies, we conclude that TNF and IL-1 alpha directly increase vascular endothelial cell permeability in vitro and speculate that these cytokines may be involved in the acute vascular endothelial injury associated with endotoxic shock.

Phorbol esters bind to and activate a calcium phospholipid-dependent protein kinase (C kinase). Some researchers believe that activation of C kinase is necessary for the induction of phorbol ester biologic effects. Our research indicates that bryostatin, a macrocyclic lactone that binds to the phorbol ester receptor in human polymorphonuclear leukocytes, also binds to this receptor in the human promyelocytic leukemia cell line, HL-60. Bryostatin activates partially purified C kinase from HL-60 cells in vitro, and when applied to HL-60 cells in vivo, it decreases measurable cytoplasmic C kinase activity. Unlike the phorbol esters, bryostatin is unable to induce a macrophage-like differentiation of HL-60 cells; however, bryostatin, in a dose-dependent fashion, blocks phorbol ester-induced differentiation of HL-60 cells and, if applied within 48 hr of phorbol esters, halts further differentiation. These results suggest that activation of the C kinase by some agents is not sufficient for induction of HL-60 cell differentiation and imply that some of the biologic effects of phorbol esters may occur through a more complex mechanism than previously thought.Considerable evidence suggests that the biochemical mechanism of action of tumor-promoting phorbol esters involves the activation of a calcium phospholipid-dependent protein kinase (C kinase) (1). When cell-free preparations were studied, this enzyme was found to copurify with the cellular phorbol ester receptor (2). Further studies have shown that[3H]phorbol 12,13-dibutyrate ([3H]PBt2) binds to homogeneous preparations of C kinase isolated from mouse brain (3-5) and that phorbol esters compete directly with 1,2-diacylglycerols, the natural activators of the C kinase, for binding to this enzyme (6). The addition of phorbol esters to intact cells induces a marked increase in membrane-associated C kinase (7) and in the phosphorylation of specific membrane proteins-e.g., the transferrin and insulin receptors (8, 9). Activation of C kinase by phorbol esters has been implicated in several biologic responses, including platelet and polymorphonuclear leukocyte (PMN) degranulation, Swiss 3T3 cell mitogenesis, and human lymphocyte activation (1,(10)(11)(12)(13)(14) Recently, bryostatin, a macrocyclic lactone with a significantly different structure from phorbol esters (Fig. 1), has been isolated from the marine bryozoan Bugula neritina (25)(26)(27) 1334The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.