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Biomedical subjects

S Waxman

Publications and source records attributed to S Waxman.

At least 163 records · Page 9Linked to original sources

Appearance of C-type virus-like particles after co-cultivation of a human tumor-cell line with rat (XC) cells.

A serially progagated cell line (L104) was established by co-cultivation of alung adenocarcinoma (L-1) from a patient with concurrent chronic lymphocytic leukemia and XC, a non-producer rat line, known to carry the Rous sarcoma virus (RSV) genome. Karyotype of the L104 cultures revealed predominantly rat-like patterns; however, about 5% of the cells reacted with HLA antibodies and demonstrated human isozyme patterns. Electron microscopy of L104 cells revealed the presence of C-type particles budding from the cell membranes and in cytoplasmic vacuoles. Virus was not detected in any of the other normal lung, lung tumor or XC cells examined after co-cultivation with XC cells. The particles isolated from tissue culture fluids had the biochemical and biophysical characteristics common to other known mammalian C-type particles and were serologically related to the woolly monkey virus (WMV)/gibbon ape leukemia virus (GaLV) complex. Cross-hybridization between viral 3H-DNA transcripts and cellular RNAs from virus-infected cells clearly show the presence of sequences in the L104 cellular RNA related to both the GaLV/WMV group of viruses and rat viruses. Hydroxyapatite chromatography reveals however that the primate-related sequences in the viral RNA are indistinguishable from WMV in thermal elution profile. The host range of L104 virus appears to vary greatly from WMV in being xenotropic and, in the cell lines thus far tested appears, to infect only rat cells. The virus gave positive KC but negative XC assays. Inoculation of whole cells or cell-free supernatants into weaning hamster did not result in either solid tumors or leukemia. Co-cultivation of appropriate cell lines may represent an approach to the detection of latent viruses in human neoplasia.

Adenocarcinoma↗

Folate binding proteins.

The physical and physiologic properties of serum, milk and cellular FABP have been presented. Several investigators have shown that FABP with similar characteristics is present throughout the body fluids and tissue. Thus, FABP appears to be established as a protein which can significantly influence folate metabolism.

Cell Membrane↗

Isolation and characterization of a novel vitamin B12-binding protein associated with hepatocellular carcinoma.

High levels of a novel vitamin B12-binding protein (hepatoma B12 BP) have been observed recently in plasma obtained from three adolescent patients with hepatocellular carcinoma. This protein has now been isolated in homogeneous form from the plasma and pleural fluid of two of these patients by the use of affinity chromatography with vitamin B12-Sepharose. The hepatoma B12 BP belongs to the R-type group of B12-binding proteins and is essentially indistinguishable from the recently isolated human milk and saliva R-type proteins in terms of: (a) immunologic properties based on immunodiffusion and immunoprecipitation assays; (b) amino acid composition; (c) molecular weight based on amino acid and carbohydrate content; and (d) absorption spectra. Both hepatoma B12 BPs contain more sialic acid and less fucose than the milk and saliva B12 BPs. All four proteins contain similar amounts of galactose, mannose, galactosamine, and glucosamine. Differences in sialic acid content appear to account for the differences in electrophoretic mobility that were observed among the four proteins. Differences in total carbohydrate content appear to account for the differences in apparent molecular weight that were observed with both gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Tumor tissue from one of the patients contained 10 times as much R-type protein as did normal liver tissue from the same patient. This suggests, although it does not prove, that synthesis by the tumor is the cause of the high levels of R-type protein found in the plasma of certain patients with hepatocellular carcinoma. Plasma survival studies performed with rabbits indicate that the hepatoma B12 BP has a prolonged plasma survival and suggests that his parameter is also of importance.

Aged↗

Interaction of chemotherapeutic agents with methotrexate and 5-fluorouracil and its effect on de novo DNA synthesis.

The transport of methotrexate is known to be affected by corticosteroids and vincristine in L1210 leukemia cells. The deoxyuridine suppression test was used to measure the metabolic consequences of using these drugs with the antimetabolites, methotrexate and 5-fluorouracil, in both L1210 leukemia cells and normal human marrow cells. The deoxyuridine suppression test can be utilized as a sensitive measure of methotrexate and 5-fluorouracil biological activity in producing defective de novo DNA synthesis. The deoxyuridine suppression test was found to detect changes in biological activity equal to 20 ng (0.044 nmole) of methotrexate and 200 ng (1.94 nmoles) of 5-fluorouracil. Hydrocortisone and prednisone, but not dexamethasone or prednisolone, decreased the methotrexate effect to one-half in both L1210 and human cells as measured by the deoxyuridine suppression test. 5-Fluorouracil biological activity was not affected by any steroid studied. Vincristine produced variable results, but on the average it decreased the methotrexate effect in human marrow. Vincristine consistently decreased the methotrexate effect in L1210 systems. Cephalosporin, 75 mug/ml (0.214 mumole), had no effect. In parallel studies, hydrocortisone decreased the uptake of methotrexate, but no folic acid, in human and L1210 cells. The deoxyuridine suppression test warants further investigation as a method of screening drugs for interaction with antagonists of de novo DNA synthesis. This tudy extends earlier evidence of drug interaction with methotrexate in a murine system to human cells and demonstrates that there is a metabolic consequence, reduced potency of methotrexate, as a result of reduced transport produced by certain corticosteroids.

Animals↗