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Biomedical subjects

S T Crooke

Publications and source records attributed to S T Crooke.

At least 37 records · Page 2Linked to original sources

Acute ultrastructural effects of the antitumor antibiotic carminomycin on nucleoli of rat tissues.

Male Sprague-Dawley rats were treated with carminomycin i.v. in doses ranging from 1 to 40 mg/kg. Within 1 hr after the administration of carminomycin, 20 mg/kg, nucleoli of cardiac and skeletal muscle cells were segregated, while nucleoli of liver parenchyma cells were unaffected. Three and one-half hr after drug administration, cardiac muscle nucleoli reverted to normal ultrastructure. However, some skeletal muscle cell nucleoli were still segregated. Following treatment with carminomycin, 10 mg/kg, no significant ultrastructural changes were observed. These results demonstrate that at sufficiently high doses carminomycin induces ultrastructural lesions in nucleoli of both cardiac and muscle cells. The dose of carminomycin required to produce nucleolar segregation in cardiac and skeletal muscle is 6 times greater than the dose of Adriamycin (3.5 mg/kg) required to induce equivalent alterations.

Animals

Use of PM-2 DNA degradation as a pharmacokinetic assay for bleomycin.

The PM-2 DNA fluorescence assay has been shown to be a rapid, sensitive, and reproducible assay for bleomycin biochemical activity. The assay can detect bleomycin in human serum in the nmol range. The method measures DNA degradative activity of bleomycin and could be used to determine activity of bleomycin analogs and metabolites. The usefulness of the assay to perform bleomycin pharmacokinetic studies in cancer patients has been demonstrated. Linear regression analyses of parallel bleomycin assays with the radioimmunoassay gave a coefficient of correlation of 0.98 to 0.78 with trichloroacetic acid-treated serum. These results indicate excellent agreement between the two assays.

Adult

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

A spectroscopic investigation of the metal binding site of bleomycin A2. The Cu(II) and Zn(II) derivatives.

Using a combination of ultraviolet-visible absorption, 1H NMR and ESR techniques we have established that N(1) of the imidazole and N(1) of the pyrimidine residues of bleomycin A2 bind to Cu(II) and Zn(II). The observations coupled with the earlier results that the alpha-amino group of the alpha-amino carboxamide function and the carbamoyl moiety are also Cu(II)-ligating groups makes it possible to reconstruct the detailed geometry and stereochemistry of the metal binding site of bleomycin A2.

Binding Sites

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

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

Comparison of two radioimmunoassays and a microbiologic assay for bleomycin.

Recently two radioimmunoassays have been independently developed for determination of bleomycin levels. In this study these assays are compared with each other and with a standard microbiologic assay for bleomycin. Bleomycin levels were determined in serum and urine samples obtained at varying intervals following intramuscular bleomycin injection. There were systematic differences between the assays. One radioimmunoassay indicated bleomycin levels lower than the levels indicated by the microbiologic assay with serum samples. With urine samples, both radioimmunoassays indicated bleomycin levels greater than the microbiologic assay.

Antibody Specificity

Maytansine.

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Animals

Comparative ultrastructural studies of nucleoli of tumor cells treated with adriamycin and the newer anthracyclines, carminomycin and marcellomycin.

This study was designed to determine the effects of several antitimor anthracyclines, including Adriamycin and its analogs, carminomycin and marcellomycin, on the ultrastructure of nucleoli of Novikoff hepatoma cells. Adriamycin and carminomycin, which are structurally related, induce nucleolar segregation following the formation of conspicuous fibrillar centers. Marcellomycin did not induce formation of nucleolar fibrillar centers. Instead, numerous microspherules formed following treatment with marcellomycin; later complete nucleolar segregation developed. The microspherules were observed to be in various stages of extrusion from the nucleolar body. This microspherule "migration" appeared to be both time and drug concentration dependent. These results show that the rate and extent of nucleolar ultrastructural aberration may be related to structural differences of the various anthracyclines.

Animals