Barbara C. Halpern

Urinary excretion levels of unconjugated pterins in cancer patients and normal individuals.

Urinary excretion levels of seven unconjugated pterins in healthy individuals and in cancer patients, most of whom were undergoing chemotherapy, were measured utilizing a newly developed high-pressure liquid chromatographic system. Excretion of pterins in the control group appears to be under strict metabolic control as the values obtained were confined within a small range. When the mean excretion levels in control subjects were compared with those in cancer patients, we found a significant increase in the excretion of xanthopterin, neopterin and pterin and a significant decrease in isoxanthopterin by cancer patients. Biopterin levels, on the other hand, were found only slightly but not significantly increased, whereas pterin-6-carboxylic acid and 6-hydroxymethylpterin were found to be excreted in approximately equal amounts in both groups. Urinary excretion levels of pterins were monitored for a period of nine months in a patient being treated with chemotherapy for metastatic ovarian carcinomatosis. We found that the excretion pattern of pterins appeared to correlate with the clinical status of the patient. These results indicate that a definite imbalance in pterin, and possibly folate metabolism, is associated with the presence of malignant diseases.

N5-methyltetrahydrofolate: homocysteine methyltransferase activity in extracts from normal, malignant and embryonic tissue culture cells.

Abstract Malignant cells (J111, L1210, W-256) and human embryonic cells (FL) are unable to survive and grow when homocystine replaces methionine in tissue culture media containing excess vitamin B12 and folic acid. Extracts of these same cells when grown in media containing methionine and more than adequate vitamin B12 and folic acid have diminished N5-methyltetrahydrofolate: homocysteine methyltransferase activities in the absence of added cyanocobalamin when compared with extracts of normal cells (adult rat thymus and liver fibroblasts). Extracts of human monocytic leukemia (J111) and human amnion cells (FL) have normal enzymatic activity in the presence of added cyanocobalamin whereas the rodent malignant cells (W-256 and L1210) have abnormally low activity in the absence or presence of added vitamin B12.

Nicotinamide: A natural inhibitor of tRNA methylase

Abstract A dialyzable tRNA methylase inhibitor has been isolated from rat liver. By chromatographic and electrophoretic data as well as ultraviolet and mass spectral data, the inhibitor is identified as nicotinamide. Kinetic evidence indicates that nicotinamide is an inhibitor of tRNA methylase.

Quantitative determination of pterins in biological fluids by high-performance liquid chromatography

During our continuing study of pteridine metabolism, the need arose for a more rapid and quantitative determination of pterins in biological fluids. By adopting and modifying previously developed techniques, we have obtained a rapid and sensitive method that allows the simultaneous determination of eight different pterins in human urine and blood. When examined over a 10-day period, the levels of pterins excreted by a normal individual averaged the following values expressed in picomoles per mg of creatinine: biopterin, 9104; neopterin, 6018; xanthopterin, 6561; pterin, 1136; isoxanthopterin, 636; pterin-6-carboxylate, 483; and 6-hydroxymethylpterin, 315. Moreover, 6-hydroxymethylpterin and pterin-6-carboxaldehyde were detected for the first time in the blood of normal individuals.

Transfer RNA methylase inhibitors in neoplastic and normal rat tissue

Abstract With acid precipitation and dialysis, we show the presence of tRNA methylase inhibitors in normal adult rat liver. These inhibitors are virtually absent from the cortex of the highly malignant Walker-256 carcinoma from the rat. The tRNA methylase inhibitors of the rat liver are slowly dialyzable. It is proposed that the differences in the rate of tRNA methylase activity of normal and neoplastic tissues is in large part due to the difference in inhibitor content of each tissue.

Fractionation of mucopolysaccharides by countercurrent distribution in aqueous polymer two-phase systems☆

A new procedure for the fractionation of mucopolysaccharides based upon differences in their partition behavior in aqueous polymer two-phase systems has been devised. Systems containing dextran, poly(ethylene glycol), trimethylamino-poly(ethylene glycol), potassium bromide and sodium phosphate buffer were employed. Countercurrent distributions were performed with a miniature countercurrent distribution device designed especially for use with aqueous polymer two-phase systems. An advantage over the widely used procedures involving precipitation of mucopolysaccharides as their quaternary ammonium detergent complexes is that the countercurrent distribution pattern of a particular mucopolysaccharide is not affected by the simultaneous presence of other mucopolysaccharides. Preliminary distributions of labelled mucopolysaccharides isolated from the cells and culture medium of monolayer cultures of rat tumor cells demonstrate that the procedure is particularly well suited for the fractionation of very minute quantities of mucopolysaccharides.

Effect of methionine replacement by homocystine in cultures containing both malignant rat breast carcinosarcoma (walker-256) cells and normal adult rat liver fibroblasts

SummaryWhen malignant W-256 rat breast carcinosarcoma cells are mixed with an equal number of normal adult rat liver fibroblasts and allowed to grow in a medium containing sufficientl-methionine and an excess of vitamin B12 and of folic acid, the malignant cells outgrow the normal cells, and within 2 weeks the tissue culture flasks contain only neoplastic cells. However, when ampledl-homocystine or homocysteine replaces methionine in the medium containing the same amount of vitamin B12 and folic acid, and seeded with the same type and number of malignant and normal cells, the malignant cells die and the normal cells thrive. Substantiating this concusion are the results of injections into rats of comparable numbers of cells from each group after 3 weeks of growth in tissue culture. Fatal malignancies are produced by the methionine-cultured cells, whereas no malignancies are produced by the homocystein-cultivated cells.

The Relation of the Kidney to Body Growth and to the Utilization of Protein and Urea–Parti. Effects of Subtotal Nephrectomy on the Growth of Rats on Diets with and without Urea Supplementation

Part I. Effects of Subtotal Nephrectomy on the Growth of Rats on Diets with and without Urea Supplementation Subtotally nephrectomized rats, in contrast to normal rats, show impaired