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Biomedical subjects

A W Prestayko

Publications and source records attributed to A W Prestayko.

At least 37 records · Page 2Linked to original sources
PubMed1979

Cisplatin, bleomycin, and vinblastine combination therapy of testicular tumors: an analysis.

A combination regimen consisting of cisplatin, bleomycin, and vinblastine was evaluated in 86 patients with metastatic testicular tumors. Prior therapy included surgical resection of primary tumor (84 patients), radiotheapy (21 patients), chemotherapy (33 patients). Thirteen patients received prior bleomycin and vincristine or vinblastine. Of 80 evaluable patients 51 achieved complete response (CR) and 26 achieved partial response (PR), for an overall response rate 96.5%. There was no significant difference in response rates or survival with respect to prior therapy, sites of metastatic lesions, and tumor histology. The median survival time was not reached in an observation period of 44+ months. Sixty patients were alive 11+--44+ months, and 57 of these were free of disease. Thirty-two of the 60 patients (53%) had a survival time greater than 20 months. Toxicities included nephrotoxicity (18 patients) leukopenia, (69 patients), thrombocytopenia (nine patients), and anemia (56 patients). Bleomycin-induced pulmonary toxicity was fatal in one patient. Other toxicities included nausea and vomiting, stomatitis, fever, alopecia, and neurological effects.

Adolescent↗
PubMed1979

Purification and mechanism of action of macromomycin.

Macromomycin (MCR), a polypeptide antibiotic previously shown to have antitumor activity in experimental tumors, has been purified into an electrophoretically homogeneous component with an approximate molecular weight of 12,500. MCR has alanine as an NH2-terminal amino acid, 4 cysteine residues, and no arginine or methionine residues. With a fluorescence assay and agarose gel electrophoresis, MCR was shown to induce strand breaks in PM2 DNA in vitro. 2-Mercaptoethanol inhibited the DNA cleavage activity of MCR. When incubated with Novikoff hepatoma ascites cells in tissue culture, MCR caused Novikoff hepatoma ascites cell DNA degradation as observed by the slower sedimentation of DNA on alkaline sucrose density gradient centrifugation when compared to untreated cell DNA. DNA synthesis in Novikoff hepatoma ascites cells was inhibited by 80% after a two-hr treatment with MCR (0.03 microgram/ml). RNA and protein syntheses were inhibited by 25 and less than 10%, respectively, at this concentration of drug. At a concentration of MCR (1.0 microgram/ml), syntheses of DNA and RNA in Novikoff hepatoma ascites cells were totally inhibited. The results of this study suggest that MCR may inhibit tumor cell growth by causing DNA breakage with subsequent inhibition of DNA and other macromolecule syntheses.

Animals↗
PubMed1979

Role of single-breath carbon monoxide-diffusing capacity in monitoring the pulmonary effects of bleomycin in germ cell tumor patients.

Serial pulmonary function tests including single-breath carbon monoxide-diffusing capacity (DLCO), forced vital capacity (FVC), and forced expiratory volume in 1 sec were performed in a relatively homogeneous group of male patients with germ cell tumors treated with vinblastine, bleomycin, and cis-diamminedichloroplatinum. Of the pulmonary function tests used, the DLCO was shown to be the most sensitive indicator of subclinical bleomycin pulmonary effects. Decreases in DLCO were both total dose and schedule dependent. Patients receiving their total dose of bleomycin at a rate of 25 +/- 2 (S.D.) units/week developed a linear decrease in DLCO with increasing total doses of bleomycin. Changes in FVC did not correlate with bleomycin total dose. Although both the mean DLCO and FVC decreased after completion of bleomycin therapy, the mean FVC returned to base-line levels rapidly, whereas the decrease in mean DLCO was persistent for several months. When routine volumetric tests (FVC and forced expiratory volume in 1 sec) and DLCO are used in a systematic manner, DLCO is the most sensitive indicator of the subclinical pulmonary effects of bleomycin in germ cell tumor patients treated with vinblastine, bleomycin, and cis-diamminedichloroplatinum.

Adult↗
PubMed1978

The effects of prior exposure to bleomycin on the incidence of pulmonary toxicities in a group of patients with disseminated testicular carcinomas.

The incidence of pulmonary toxicities in 12 patients with prior exposure to bleomycin (BLM) was compared to the incidence of pulmonary toxicities in a matched group of 73 patients with state II or IV testicular carcinomas treated with a regimen containing vinblastine, bleomycin, and cis-diamminedichloroplatinum. The comparison demonstrates that prior exposure to bleomycin constitutes a significant risk factor and that the risk is additive; ie, prior doses should be added to current doses to determine the cumulative dose-related probablity of development of pulmonary toxicities.

Adolescent↗
PubMed1978

Cisplatin pharmacokinetics in a patient with renal dysfunction.

Plasma and urine platinum concentrations were measured by atomic absorption spectrophotometry during a three-day course of cisdiamminedichloroplatinum (DDP, cis-platinum, cisplatin) therapy in a patient with acute renal failure who was being treated with hemodialysis. Twenty-four hour urine collections, obtained during the oliguric phase, accounted for only 0.36--0.56 percent of the daily DDP dose. The plasma t1/2beta of platinum was approximately 240 hours after the last DDP dose. Platinum could be measured in the dialysate only during the first two hours after DDP administration. Although the data show that the t1/2beta of DDP is prolonged three fold in a patient with profound renal failure, the clinical implications of these findings await further studies.

Acute Kidney Injury↗
PubMed1977

Comparison of nuclear nonhistone phosphoproteins of rat liver and Novikoff hepatoma.

As part of a continuing comparison of nuclear proteins of tumors and other tissues, 32P-labeled nuclear proteins were extracted successively with 0.15 and 0.35 m NaC1 from the nuclei of normal, regenerating, and thioacetamide-treated rat liver as well as Novikoff hepatoma 3 hr after injection of 32Pi into rats. Separation of proteins of these fractions with aqueous phenol was carried out before two-dimensional electrophoresis on polyacrylamide gels. By autoradiography many common spots were found, but four 32P-labeled protein spots, CU', C13p, C21p, and CMp, were found in the Novikoff hepatoma and not in the various liver samples studied. Two spots, B6 and B10, were found in the liver patterns and not in the tumor. Sot B33 was very dense in regenerating liver but was only a faint spot in thioacetamide-treated liver. The greater density of Spots CU', C13p, C21p, and CMp in the tumor patterns is consistent with the increased density reported earlier for spots of the C-region of a variety of tumors.

Animals↗
PubMed1977

Effects of variations in renal function on the clinical pharmacology of bleomycin administered as an iv bolus.

The clinical pharmacology of bleomycin administered as an iv bolus has been studied in a homogeneous group of patients receiving a single regimen containing bleomycin, vinblastine, and cis-dichlorodiammineplatinum (II). These studies demonstrated that in patients with creatinine clearances greater than or equal to 35 ml/minute, the serum (or plasma) terminal elimination half-life of bleomycin was approximately 115 minutes. In patients with creatinine clearances less than 25-35 ml/minute, the terminal elimination half-life increased exponentially as the creatinine clearance decreased. The volume of distribution was approximately 20 liters, and was unaffected by changes in the creatinine clearance. The microbiologic assay and radioimmunoassay employed gave equivalent results.

Adolescent↗
PubMed1976

Phosphorylation and DNA binding of nuclear rat liver proteins soluble at low ionic strength.

Proteins were extracted from isolated rat liver nuclei with 0.15 M NaCl and 0.35 M NaCl at pH 8.0. The number of phosphoproteins in these extracts was determined by labeling with 32P and autoradiography after two-dimensional gel electrophoresis. Two proteins, B22p and B24p, contained small amounts of 32P and sedimented with the 30S nuclear informofer particle. With the exception of two phosphoproteins, CB and CN', all of the phosphoproteins found in the 0.35 M NaCl extract. Approximately 20% of the 0.15 M NaCl soluble proteins bound to rat liver DNA in 0.05 M KCl-0.05 M Tris-HCl (pH 8). Of these proteins, 1-2% bound to DNA in 0.15 M KCl and were eluted with 2 M KCl. This DNA bound fraction which contained both phosphorylated and nonphosphorylated proteins was similar in both the 0.15 and 0.35 M NaCl extracts. However, two major proteins (C13 and C14) and three minor proteins (C15, C25, Cg') were present only in the 0.15 M NaCl extract. The results of the present study show that there are marked similarities in the two-dimensional gel electrophoretic, phosphorylation, and DNA binding properties of rat liver nuclear proteins soluble in either 0.15 or 0.35 M NaCl.

Animals↗
PubMed1975

Isolation and characterization of protein A24, a "histone-like" non-histone chromosomal protein.

In earlier studies, the nucleolar levels of protein A24 were found to be markedly decreased in the nucleolar hypertrophy induced by thioacetamide or during liver regeneration (Ballal, N.R., Goldknopf, I.L., Goldberg, D.A., and Busch, H. (1974) Life Sci. 14, 1835-1845; Ballal, N.R., Kang, Y.-J., Olson, M.O.-J., and Busch, H.J. Biol. Chem. 250, 5921-5925). To determine the role of protein A24, methods were developed for its isolation in highly purified form. Milligram quantities of highly purified protein A24 were isolated from the 0.4 N H2SO4-soluble proteins of calf thymus chromatin by exclusion chromatography on Sephadex G-100, followed by preparative polyacrylamide gel electrophoresis. Protein A24 was highly purified as shown by its migration as a single spot on two-dimensional polyacrylamide gel electrophoresis, its single NH2-terminal amino acid, methionine, and the production of approximately 50 peptides by tryptic digestion. Like histones 2A, 2B, 3, and 4. A24 was extractable from chromatin with 0.4 N H2SO4 or 3 M NaCl/7 M urea, but unlike most non-histone proteins or histone 1, protein A24 was not extracted with 0.35 M NaCl, 0.5 M HClO4, or 0.6 M NaCl. Protein A24 was present in only 1.9% of the total amount of histones 2A, 2B, 3 and 4; its molecular weight is 27,000.

Amino Acids↗