NCI's cancer information systems--bringing medical knowledge to clinicians.

The National Cancer Institute's computerized information systems have been designed to help physicians cope with the information explosion by translating the medical literature into usable forms. Systems developed by the NCI's International Cancer Information Center provide access to a comprehensive source of bibliographic citations on cancer research (the CANCERLIT database) and to current, peer-reviewed syntheses of state-of-the-art clinical information on cancer (the PDQ database). This article describes how the PDQ databases were developed and are kept up-to-date, and how physicians and other health professionals can access PDQ and other NCI information by computer and fax.

Heparin-induced aggregation of lymphoid cells.

The effects of different carbohydrates on cell-to-cell adhesion were examined in an aggregation assay, which consisted of swirling a suspension of cells and monitoring the loss of single cells with a Coulter Counter. Of the carbohydrates tested, only heparin and dextran sulfate induced cell aggregation. This effect occurred in freshly isolated mouse splenocytes and in cultured cells of lymphoid origin (P388, YAA-CI) but not in cell lines of fibroblastic origins (3T3, SV-3T3, BHK, and PY-BHK). Using the YAA-CI cell line for further study, we found that aggregation could be induced by relatively small amounts of heparin (less than 10 micrograms/ml). Binding experiments with 3H-heparin showed that under normal physiological conditions each YAA-CI cell bound approximately 2 X 10(6) molecules of heparin at saturation with a Kd of 3.5 X 10(-7) M. This binding was blocked by both unlabelled heparin and dextran sulfate but not by other carbohydrates. When the pH of the medium was decreased, the heparin-induced aggregation was inhibited, and the Kd of the 3H-heparin binding was increased. In a similar fashion, when the ionic strength of the medium was increased, heparin-induced aggregation was inhibited and the Kd of the interaction was increased. These results suggest that the aggregation is inversely related to the Kd of the interaction and that the binding of heparin to the cell surface is primarily of an ionic nature.

Characterization and identification of the hyaluronate binding site from membranes of SV-3T3 cells.

Previous research has shown that binding sites for hyaluronate are present on the surfaces of a number of different cell types. To further characterize these binding sites, membranes were prepared from SV-3T3 cells and dissolved in a solution of sodium deoxycholate. Hyaluronate binding activity was detected by mixing the sodium deoxycholate extract with [3H]hyaluronate and then adding an equal volume of saturated (NH4)2SO4, which precipitated the binding protein and any [3H]hyaluronate associated with it, but left free [3H]hyaluronate in solution. Following partial purification by hydroxylapatite chromatography, the binding site was examined by molecular sieve chromatography and by rate-zonal centrifugation, which revealed that it has a Stokes radius of 6.5 nm and a sedimentation coefficient of 4.8 S. From these values, it was possible to calculate that the sodium deoxycholate-solubilized binding site has a frictional coefficient of 1.87 and a molecular weight of 132,000. Since this latter value applies to the complex of both detergent and protein, the binding protein by itself must have a molecular weight lower than 132,000. To determine the molecular weight of the hyaluronate binding site itself, the protein was purified by the sequential application of hydroxylapatite chromatography, molecular sieve chromatography, rate-zonal centrifugation, and finally lectin-affinity chromatography on concanavalin A-agarose. Analysis of the purified material by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed an 85,000 Mr protein which has been identified as the binding site. This protein was also detected on nitrocellulose blots which had been specifically stained for concanavalin A binding material, suggesting that the binding site is a glycoprotein.