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Biomedical subjects

B Weintraub

Publications and source records attributed to B Weintraub.

7 recordsLinked to original sources
PubMed1992

Modulation of the physical state of cellular cholesteryl esters by 4,4'-(isopropylidenedithio)bis(2,6-di-t-butylphenol) (probucol).

The effect of 4,4'-(isopropylidenedithio)bis(2,6-di-t-butylphenol) (probucol) on cholesteryl ester physical state was examined in dry mixtures, phospholipid-containing dispersions, and cells. Probucol has little effect on the solid to isotropic transition of cholesteryl oleate, but broadens and decreases the enthalpy of the liquid-crystalline transitions at concentrations as low as 1-2 mol %. A probucol transition is only observed at concentrations greater than 20 mol %. The mesomorphic phases of the cholesteryl oleate/probucol mixtures were identified by visual inspection and polarized light microscopy. Mixtures are liquid at probucol concentrations in excess of 5 mol % at 37 degrees C. Probucol also dramatically reduces the enthalpy of the liquid-crystalline transitions of the cholesteryl oleate core of dispersions of the ester with phospholipids at a concentration of 10 mol %, reducing the enthalpy by greater than 80% and the transition temperatures by approximately 2 degrees C. The phase state of cholesteryl esters in Fu5AH rat hepatoma cells was examined after incubation with cholesterol/phospholipid dispersions that caused the accumulation of anisotropic cholesteryl ester droplets. Differential scanning calorimetry scans of cells incubated with cholesterol-rich phospholipid dispersions indicated a phase transition near 48 degrees C, which was abolished when the cells were co-incubated with 50-100 micrograms/ml of probucol in the loading medium. Subsequent to the formation of isotropic cholesteryl ester droplets in the presence of probucol, the rate of efflux of cholesterol from the cells to phosphatidylcholine-containing acceptors in the medium was increased. These data show that probucol is relatively soluble in cholesteryl esters and that probucol changes the phase state of cholesteryl ester droplets in cells to a more fluid phase in which the cholesteryl esters are more readily mobilized.

Animals↗
PubMed1992

Development of thyroid disease during therapy of chronic viral hepatitis with interferon alfa.

Six of 237 (2.5%) patients with chronic viral hepatitis who were treated with recombinant interferon alfa developed thyroid disease while on treatment. Three patients developed hyperthyroidism, two of whom developed detectable levels of thyroid-stimulating immunoglobulin; three patients developed hypothyroidism in association with high titers of antithyroglobulin and/or antimicrosomal antibodies. The thyroid disease did not remit when interferon therapy was stopped, and all six patients required definitive therapy for the thyroid disease. These findings suggest that a small proportion of patients treated with interferon alfa develop autoimmune reactions and can develop autoimmune thyroid disease.

Adult↗
PubMed1991

Relationship between glutathione levels and drug or radiation sensitivities in human gastric cancer cell lines in vitro.

Permanent cell lines and clones established from an untreated patient (AGS cells) with gastric carcinoma, and from a similar patient who had been treated with Adriamycin, 5FU and cytoxan (SII cells) were used in a study that compared their drug and radiation survival sensitivities to their glutathidine (GSH) values. The SII parental cell line was more resistant than the AGS cells in vitro to chlorambucil, ACT D, Adria, Bleo, and X-rays. This greater resistance was positively correlated with GSH values that were 1.77 times higher than in the AGS parental cell line. By contrast the SII parental cells were more sensitive than the AGS cells to MeCCNU and Melphalan. The drug and radiation sensitivities expressed among the clones of the two cell lines were heterogeneous and did not correlate with their GSH values.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Changes in glutathione content and resistance to anticancer agents in human stomach cancer cells induced by treatments with melphalan in vitro.

A clone of a human gastric carcinoma cell line was used to determine whether cells which had survived a treatment with Melphalan would express altered survival responses when treated again with this agent 1 week or more later. Cells were treated for 1 h each week with 2 micrograms/ml (99% lethal dose). After the first Melphalan treatment, the cells exhibited a 10-fold reduction in sensitivity to Melphalan. This was preceded by a 2-fold increase in intracellular glutathione content. By the end of 10 weekly treatments, the cells were 50 times more resistant than controls (based on changes in survival fractions). They also demonstrated collateral resistance to Actinomycin D, 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea, galactitol, and X-rays, but showed no change in sensitivity to 5-fluorouracil, bleomycin, and Adriamycin. The resistance to Melphalan was not reversible when treatment was withheld for 4 weeks on two different occasions. The results suggest that treatment with a high dose of Melphalan either selects an existing population of cells with a high GSH content or induces mutations leading to increased GSH content or both, and this results in the expression of greater Melphalan resistance at the time of other treatments. Furthermore, Melphalan treatment stimulates a 50% increase in GSH content in resistant cells in just 6 h, an 85% increase in 36 h, and a 150% increase in 72 h. L-Buthionine sulfoximine partially reversed the expression of resistance to Melphalan by inducing a 60% reduction in intracellular glutathione content.

Buthionine Sulfoximine↗
PubMed1978

Ectopic secretion of chorionic gonadotropin by a lung carcinoma. Pituitary gonadotropin and subunit secretion and prolonged chemotherapeutic remission.

The ability of tumor markers to improve cancer therapy is not established. We studied a man with a human chorionic gonadotropin (HCG)-secreting large cell carcinoma of the lung and gynecomastia. Preoperatively, levels of HCG (109 ng/ml), its alpha and beta subunits (3.2 and 21 ng/ml, respectively) and plasma estradiol were elevated. Despite apparently complete tumor resection and total resolution of gynecomastia, HCG titers remained elevated (3.3 ng/ml), heralding tumor recurrence three weeks later. Because the pathophysiologic consequences of the ectopic secretion of HCG on pituitary function are not established, we administered 100 microgram of gonadotropin-releasing hormone (LHRH) and observed a markedly delayed increase in pituitary gonadotropins. Early chemotherapy, guided by persistence of HCG, reduced HCG to undetectable levels, restored to normal the response to LHRH and resulted in a distinctly unusual 30-month complete remission. Use of HCG as a tumor marker levels is more sensitive than the symptom of gynecomastia and may permit detection of small, potentially curable tumor foci.

Carcinoma, Small Cell↗
PubMed1975

Computer aided nystagmus analysis.

The electronystagmogram (ENG) is analyzed with the assistance of a PDP-8 minicomputer for calculating the instantaneous slope, average slope, lead frequency, lag frequency and cycle frequency of both the fast and slow wave components of the ENG. The ENG data is first digitized and displayed on a storage scope in order to permit the operator to select an epoch of data. The results are then displayed on the scope, and the mean and variance of the important parameters are outputted on the teletype. The programs include a system for storing a large library of records.

Computers↗