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Biomedical subjects

S T Crooke

Publications and source records attributed to S T Crooke.

At least 307 records · Page 17Linked to original sources
PubMed1977

Specificity of antisera produced against bleomycin.

The specificity of antisera produced in a goat or rabbit for use in bleomycin radioimmunoassay has been examined using competitive experiments employing several bleomycin analogs. These studies demonstrate that the antiserum distinguished alterations in both the nucleus and the terminal structure of the molecule. Removal of the terminal structure or addition of an aminosugar moiety in the bleomycin nucleus resulted in a significant decrease in immunoreactivity. Antisera produced in goat and rabbit hosts had different specificity for the terminal structure. The goat antisera demonstrated greater specificity for the terminal side chain than the rabbit antisera although this may not reflect a species-related event.

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

Phase I study of oral mitomycin C.

This study demonstrates that the gastrointestinal absorption of oral mitomycin C is variable and that myelosuppression correlates most closely with the peak serum concentration. The probable maximal-tolerated dose of oral mitomycin C is 45-50 mg/m2.

Administration, Oral↗
PubMed1975

Ultrastructural study of the effect of bleomycin A2 on the nucleolus and its possibly related cytoplasmic constituents in Novikoff hepatoma cells.

Treatment of Novikoff hepatoma ascites cells with bleomycin A2, in vivo as well as in vitro, in varying doses produced marked alterations in nucleolar and cytoplasmic ultrastructural organization. A series of changes occur including formation of fibrillar centers, fragmentation of fibrillar nucleolar elements, appearance of microspherules, and the loss of fibrillar elements from these nucleoli. A bleomycin concentration of 10 mug/ml in vitro produced an increased number of fibrillar centers with well-defined nucleolonemas. At a concentration of 50 mug/ml, there was an increase in number and fragmentation of these fibrillar centers and many microspherules were found throughout the nucleolus. Approximately one-fourth of the cells contained cytoplasmic fibrillar bodies and amorphous fibrous tufts around the nuclear envelope. At a bleomycin concentration of 100 mug/ml, the nucleoli contained more granular elements and numerous microspherules. Almost 90% of the cells contained cytoplasmic fibrillar bodies. The effects of bleomycin in vivo (10 mg/kg) closely resemble those found in vitro with concentrations of 50 and 100 mug/ml.

Animals↗
PubMed1975

Biochemical effects of bleomycin A2 on Novikoff hepatoma ascites cells.

Purified nucleolar DNA was markedly degraded at a concentration of 13 mug/ml by bleomycin A2; bleomycin concentrations 20-30 times greater were required to degrade nucleoplasmic DNA. Whole nuclear DNA was degraded to only a small extent at 13 mug/ml but was markedly degraded at higher bleomycin concentrations. Treatment of the various types of DNA with high concentrations of bleomycin A2 produced low molecular weight (approximately 6S) fragments that were no longer sensitive to degradation by bleomycin A2. Hybridization studies demonstrated a loss of ribosomal DNA sequences from nucleolar DNA treated with bleomycin A2 in vitro. Studies on RNA synthesis in Novikoff hepatoma ascites cells in vitro showed there was a decreased uptake of 32Pi into high molecular weight nuclear RNA in the presence of bleomycin A2. These results indicate that nucleolar function is inhibited by a direct effect of bleomycin A2 on nucleolar DNA.

Ascitic Fluid↗
PubMedDate not supplied

Antileukemia (L1210) activity and toxicity of cis-dichlorodiammineplatinum(II) analogs.

cis-Dichlorodiammineplatinum(II) (cis-platinum) and 40 of its analogs were evaluated for antitumor activity in BDF1 mice implanted ip with 10(6) L1210 leukemia cells. Several of these analogs were also evaluated for their ability to cause elevation in BUN and to produce leukopenia in normal BDF1 mice. In 11 experiments, cis-platinum given on Day 1 or Days 1--9 after implant produced T/C (treated/control) values between 164% and 214% and 157% and 285% respectively. On the basis of single experiments, 13 analogs were judged to be comparable to cis-platinum in that they produced T/C values greater than or equal to 167% after a single dose or greater than or equal to 200% after daily doses for 9 days. These active compounds included various substituted amine derivatives of dichloroplatinum(II), malonatoplatinum(II), aquasulfatoplatinum(II), and chloroacetatoplatinum(II) and derivatives of dihydroxydichloroplatinum(IV). Twelve of these active analogs and cis-platinum were evaluated for toxicity at doses ranging from near the optimal therapeutic dose to greater than or equal to the LD50. Only five of the 12 analogs and cis-platinum caused an increase in BUN to greater than 30 mg/100 ml, while eight of the analogs produced leukopenia comparable in incidence and severity to that produced by cis-platinum.

Animals↗
PubMedDate not supplied

Pharmacokinetics of bleomycin after im administration in man.

The pharmacokinetics of bleomycin were studied after im injection in patients with malignant lymphoma. Mean peak serum concentrations of 0.133, 0.326, and 0.587 milliunits/ml were obtained approximately 1 hour after injection of 2, 5, and 10 units/m2, respectively. The mean half-life was 155 minutes, with a range of 65--235 minutes. Thirty-three percent of the administered dose was recovered in the urine after 4 hours. The urinary excretion of bleomycin was 61% during the 24 hours after injection, with some variability that was not explained by differences in dose or creatinine clearance.

Aged↗