The transformed monocyte͞macrophage cell line J774.2 undergoes apoptosis when treated for 48 h with competitive inhibitors of cyclooxygenase (COX) isoenzymes 1 and 2. Many of these nonsteroid antiinf lammatory drugs (NSAIDs), but in particular diclofenac, induce during this time period a COX activity that coincides with a robust induction of COX-2 protein. Induction of this activity requires high, apoptosis-inducing concentrations of diclofenac (>100 M). Prolonged treatment of J774.2 cells with lower doses of diclofenac inhibits COX activity, indicating that diclofenac is a time-dependent, pseudoirreversible inhibitor of COX-2. It is difficult to wash out the inhibition. However, the activity evoked by high concentrations of diclofenac has a profoundly distinct COX active site that allows diclofenac, its inducer, to be washed readily from its active site. The diclofenac-induced activity also has the unusual property of being more sensitive to inhibition by acetaminophen (IC 50 ‫؍‬ 0.1-1.0 mM) than COX-2 induced with bacterial lipopolysaccharide. Moreover, relative to COX-1 or COX-2, diclofenac-induced enzyme activity shows significantly reduced sensitivity to inhibition by diclofenac or other competitively acting nonsteroid antiinf lammatory drugs (NSAIDs) and the enzyme activity is insensitive to aspirin. If the robust induction of COX-2 observed is responsible for diclofenac-induced COX enzyme activity, it is clear that COX-2 can, therefore, exist in two catalytically active states. A luciferase reporter-construct that contains part of the COX-2 structure and binds into the membrane showed that chronic diclofenac treatment of fibroblasts results in marked mobilization of the fusion protein. Such a mobilization could result in enzymatically distinct COX-2 populations in response to chronic diclofenac treatment.The cloning of cyclooxygenase-2 (COX-2) in 1991 (1-3) explained many long-standing anomalies relating to the previous assumption of a single COX enzyme. However, not all of the problems have been solved by the characterization of two COX enzymes originating from different genes. One such problem is the effect of acetaminophen, which, unlike nonsteroid antiinflammatory drugs (NSAIDs), produces analgesia and antipyresis but has little effect on inflammation. The existence of additional COX enzymes was therefore postulated (4).Acetaminophen is a weak inhibitor of COX-1 and COX-2, which displays some selectivity toward COX enzymes from different organs. Thus, it is a more potent inhibitor of COX from dog and rabbit brain than that of dog spleen (4). The activity of acetaminophen in vitro also depends on the addition of cofactors. In the presence of glutathione and hydroquinone, acetaminophen inhibited COX activity of bull seminal vesicle microsomes but, in the absence of these cofactors, stimulated that of bovine and ram seminal vesicle microsomes (5). After the recognition of COX-1 and COX-2, by using cultured whole cells, acetaminophen demonstrated a low inhibitory potency for COX enzymes. Only IC 3...

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This article exlpores what happens when a documentary film form developed within a specific social, ideological, institutoinal, and aesthetic context—namely, the so-called British Documentary Movement, under the aegis of John Grierson—is deployed in several layers of argument involved, but I will pursue only one of them in the space available here. At a kind of metatheoretical level, it is arguable that Indigenous and Asian cultures are inimical to core values of the Western documentary project: in particular, to the belief in, and rhetorical power of, the material, historical word. In these societies, what might be called 'spiritual' or 'other' worlds have as much everyday reality as Griersonian 'actuality'.