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A coherent optical system composed of a holographic mask and two Fourier lenses is described for performing an arbitrary linear transform. A set of equations for determining the amplitude-phase distribution of the mask is given. As a specific transform, the Walsh-Hadamard transform for orders 32 and 64 is optically made in 1-D space.

A principal mechanism of action of the clinical antitumor drugs etoposide (1) and teniposide (2) is the inhibition of catalytic activity of type II DNA topoisomerase and concurrent enzyme-mediated production of lethal DNA strand breaks. Substitution of the glycosidic moiety of 1 or 2 by ester and ethers, as well as the esterification and etherification of alpha-peltatin (4) including its glucosidic ethylidene and thenylidene cyclic acetals (25 and 26), has afforded compounds of much less activity than that of 1. The in vitro cytotoxicity (KB) appears to have no correlation with the inhibitory activity of the human DNA topoisomerase II.

The alkaloid derivative 4'-demethylepipodophyllotoxin 9-(4,6-O-ethylidene)-beta-D-glucopyranoside (etoposide, VP-16) is believed to exert cytotoxicity by causing double-stranded DNA breaks through interruption of the breaking-resealing reaction of topoisomerase II (topo II). Thus it was conceivable that cells could become resistant to VP-16 by a decrease in topo II enzyme level, since this would lead to fewer DNA breaks. As well, given the structure of VP-16, it was also possible that a pleiotropic mechanism of resistance could decrease sensitivity to this drug. To study these possibilities, a series of VP-16-resistant human KB cell lines was established by stepwise selection. The concentrations of VP-16 required to inhibit cell proliferation by 50% in the parent line and KB/1c, KB/7d, KB/20a, and KB/40a lines were, respectively, 0.16, 4.7, 24, 31, and 47 microM. These cell lines expressed cross-resistance to 4'-(9-acridinylamino)methanesulfon-m-anisidide, doxorubicin, vincristine, and methotrexate, although the pattern of relative drug sensitivity was quite different from that of pleiotropic resistant cell lines reported elsewhere. The resistance to vincristine and methotrexate did not increase above the level of the KB/1c cells, and resistance to VP-16, doxorubicin, and especially vincristine was unstable in VP-16-resistant cells cultured in the absence of drug. Although the drug resistance marker Mr 180,000 glycoprotein could not be detected in any of our cell lines, cellular accumulation of [3H]VP-16 was reduced 50-75% in the resistant lines compared with parent KB. With increasing VP-16 resistance, the level of topo II protein, detected by antibody staining, decreased at each step of selection, concomitant with a general decrease in topo II unknotting activity. Sensitivity of the topo II unknotting assay to inhibition by VP-16 was the same for the parent and all resistant cell lines. The level of topo I activity and enzyme increased slightly in the resistant cells. Thus, these cell lines are resistant to VP-16 by virtue of at least two mechanisms: (a) reduced levels of topo II, which confers cross-resistance to other compounds which are topo II-dependent cytotoxic agents; and (b) reduced accumulation of drug, which is likely also responsible for vincristine and methotrexate resistance. However, the possible existence of other mechanisms of resistance cannot be ruled out.

Several ring C aromatized analogues of podophyllotoxin were synthesized for testing against human DNA topoisomerase II. The results indicate that aromatization of ring C gave rise to no inhibition of this enzyme at 200 microM. A comparison of the cytotoxicity among these compounds also demonstrates that a free hydroxyl group at C-4 contributes to significant cytotoxicity.

The prevalence of byssinosis was studied in two cotton mills by a standardized questionnaire and pulmonary function measurements (forced expiratory volume in 1 second; FEV1). In mill A, the dust level was high (57-159 mg/m3). Among 90 participants, 80 were interviewed twice at an interval of 4 months, and disagreement on actual presence or absence of byssinosis was 7.5 percent. Twenty out of ninety workers had complaints of Monday symptoms and the prevalence was 22.2 percent. In mill B, the dust control (6.8 mg/m3) was relatively good. Among 173 participants from the carding room, two had complaints of Monday symptoms and the prevalence was 1.2 percent. A significant correlation was found between duration of employment and prevalence of byssinosis in mill A. FEV1 was measured in 9 byssinotics, 29 nonbyssinotics, and 30 controls before and after work on Mondays and Wednesdays. A significant decrease of 177 ml on average (7.8%) was found in byssinotics after work on Monday, whereas in nonbyssinotics, the decrease of FEV1 was nonsignificant. In controls, a slight increase in FEV1 after work was observed.