PubMed Health⌕ Search

Biomedical subjects

D Button

Publications and source records attributed to D Button.

8 recordsLinked to original sources
PubMed1991

A phase II clinical and pharmacokinetic study of Lonidamine in patients with advanced breast cancer.

Lonidamine is a substituted indazole carboxylic acid with a unique mechanism of action and early clinical studies have reported anti-tumour activity. In a phase II study 32 patients with previously treated advanced breast cancer were given Lonidamine in a daily divided oral dose of 600 mg. Of 28 patients evaluable for response, three (11%) achieved a partial response (4-24+ months) and three (11%) a minor response. Two patients have stable disease (greater than 3 months) and 20 progressed. Toxicity was very mild. Sixteen (53%) of 31 patients had myalgia which lasted a median of 2 weeks. This was investigated with nuclear magnetic resonance spectroscopy in four patients but the changes were unrelated to the degree of myalgia. No other major side-effect was seen, and no dose reduction was required. Lonidamine pharmacokinetics have been investigated in 17 patients 1 month after the start of therapy. Lonidamine was detected in the plasma of all patients, but there was no clear relationship between Lonidamine levels and clinical response or toxicity. Lonidamine appears to be active against advanced breast cancer and its low toxicity would allow combination studies with chemotherapy.

Adenosine Triphosphate↗
PubMed1991

The pharmacokinetics of oral lonidamine in breast and lung cancer patients.

The plasma levels of lonidamine have been studied in 24 breast or lung cancer patients as part of the Phase II evaluation of the drug. The pharmacokinetic studies were performed when the patients had been on oral lonidamine therapy for 27 to 47 days (mean 32 days) and the studies were conducted over a 24 hour period. Lonidamine was administered in three divided doses of 150 mg (t = 0h), 150 mg (t = 7h), and 150 mg or 300 mg (t = 14h). Plasma levels of lonidamine were determined by high-performance liquid chromatography (HPLC) with fluorescence detection. Lonidamine was detected in the plasma of all patients studied, and the absolute range for the peak plasma levels of the drug following the first and second doses were 4.6-33.8 and 4.8-33.3 micrograms/ml, respectively. The range of times after administration at which the peak occurred was 0.5 to 4.2 hours for the first dose and 0.5 to 4.1 hours for the second. The absolute range for the trough levels observed over the 24-hour study period was 1.0 to 12.6 micrograms/ml and in 19 of the patients it was possible to define the apparent half life of lonidamine that was found to be within the range 2.5 to 11.7 hours. In addition to lonidamine, a number of fluorescent components were detected in the plasma of patients following lonidamine treatment that were not detected in pretreatment plasma samples. One component, a compound that eluted from the HPLC more rapidly than lonidamine, was found in some patients to be sensitive to hydrolysis with beta-glucuronidase. Comparison of the pharmacokinetic data with patient characteristics and clinical biochemistry results failed to establish any clear relationship. Similarly there was no relationship between lonidamine pharmacokinetics and either drug-induced myalgia or testicular pain. Insufficient responses were seen in the patient group studied to allow the relationship between lonidamine pharmacokinetics and response to be evaluated.

Absorption↗
PubMed1988

Simple method for scanning immunoblots.

Scanning laser densitometry was performed on immuno- and dot blots developed on nitrocellulose by treatment of the nitrocellulose with xylene. This method permits the development of simple methods for recording results of immunoblots and of producing semi-quantitative assays from dot blots.

Antigens, Fungal↗
PubMed1987

Regulation of ligand-receptor dynamics by guanine nucleotides. Real-time analysis of interconverting states for the neutrophil formyl peptide receptor.

Intact neutrophils exhibit interconverting active and inactive receptor states with half-times for dissociation of 10 s and 2 min, respectively. We examined the effect of guanine nucleotides on ligand-receptor dynamics at 37 degrees C in neutrophils permeabilized with digitonin using continuous fluorometric measurements. The permeabilized cells exhibit a single class of slowly dissociating receptors with a half-time similar to the inactive state. The slowly dissociating state is lengthened in the presence of 10 mM by Mg2+ about two-fold but is relatively insensitive to substitutions of Na+ or K+. When guanine nucleotide is added the receptors dissociate uniformly with a half-time similar to the active state but are sensitive to the substitution of Na+ or K+ (K+ or K+/Mg2+ approximately 10 s; Na+ or Na+/Mg2+ approximately 4 s). When receptors in permeabilized cells are ADP-ribosylated with pertussis toxin the rapidly dissociating state is detected. In the presence of nonsaturating nucleotide or incomplete ribosylation, complex rates of ligand dissociation intermediate between the active and inactive forms are observed. Micromolar concentrations of Ca2+ block the effect of guanine nucleotide on the receptor. The relationships between ligand-receptor dynamics in intact neutrophils and interconverting states regulated by guanine nucleotides and ions in permeabilized cells are discussed.

Adenosine Diphosphate Ribose↗
PubMed1976

Lipoteichoic acid from Bacillus licheniformis 6346 MH-1. Comparative studies on the lipid portion of the lipoteichoic acid and the membrane glycolipid.

A lipoteichoic acid and a membrane glycolipid were isolated from Bacillus licheniformis 6346 MH-1. The fatty acid composition of the two preparations were similar. Most of the fatty acids were of the branched chain type. The glycolipid was shown to be a diacyl derivative of O-beta-D-glucopyranosyl-(1 leads to 6)-O-beta-D-glucopyranosyl-(1 leads to 3)-glycerol. The lipoteichoic acid contained lipid, polyglycerol phosphate, and glucosamine. The lipid was released by treatment with hydrofluoric acid and by hydrolysis in dilute acid and was shown to have a structure identical with that of the membrane glycolipid.

Bacillus↗
PubMed1976

Teichoic acids and lipids associated with the membrane of a Bacillus licheniformis mutant and the membrane lipids of the parental strain.

Bacillus licheniformis 6346 MH-1 and a phosphoglucomutase-deficient poorly lytic mutant, B. licheniformis 6346 MH-5, both contain cardiolipin, phosphatidyl ethanolamine, and phosphatidyl glycerol but are devoid of phosphoglycolipids. Gentiobiosyl diglyceride is present in the parent organism but glycolipids are absent from the mutant. Lipoteichoic acid was extracted from the whole cells of MH-5 with hot aqueous phenol and contained fatty acids, glucosamine, and 1,3-polyglycerol phosphate. The fatty acids were predominantly of the branched-chain type and were esterified to hydroxyl groups of a terminal glycerol residue. The polyglycerol phosphate chains contained, on average, 32 to 40 glycerol residues, some of which were substituted at the secondary hydroxyl group with alpha-N-acylglucosaminyl residues. Phenol extraction of the supernatant fluid that remained when walls were removed from preparations of disrupted cells of MH-5 yielded membrane teichoic acid, which consisted of substituted polyglycerol phosphate but was devoid of fatty acids.

Bacillus↗