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Biomedical subjects

M Bowles

Publications and source records attributed to M Bowles.

8 recordsLinked to original sources
PubMed1988

Large scale production and purification of paraquat and desipramine monoclonal antibodies and their Fab fragments.

We describe the rapid, large scale purification of Fab fragments from mouse monoclonal antibodies. Antibodies against two clinically important and often fatal toxins, paraquat and desipramine, were isolated from mouse ascites fluid by preparative high performance hydroxylapatite (HPHT) or ion exchange (DEAE) high performance liquid chromatography. A competitive inhibition ELISA was used to determine the cross-reactivity of the antibody with analogs of the antigens. Papain digests of the IgGs were subjected to further HPHT followed by Sephadex G-100 chromatography to yield homogeneous Fab fragment preparations. The high purity of these preparations, demonstrated by SDS polyacrylamide gel electrophoresis, has only been achieved previously by affinity chromatography. Intrinsic association constants for the intact IgG and the Fab fragment--antigen interactions, determined by competitive inhibition ELISA, were similar. This indicates that antigen-binding activity was conserved during the production and purification of the Fab fragments.

Animals↗
PubMed1988

Comparison of paraquat-specific murine monoclonal antibodies produced by in vitro and in vivo immunization.

The techniques of in vitro and in vivo immunization have been used to produce murine hybridomas secreting anti-paraquat IgM and IgG antibodies, respectively. The monoclonal antibodies from these IgM-secreting and IgG-secreting cell lines have been purified by HPLC and characterized by ELISA for their affinities to eliciting antigen and cross-reactivity. Both antibody preparations exhibited high selectivity and similar affinities for paraquat. There was only a minor degree of interaction with a range of paraquat analogs that differed in the nature and position of group substituents.

Animals↗
PubMed1987

Repeated hemoperfusion and continuous arteriovenous hemofiltration in a paraquat poisoned patient.

Prompt hemodialysis or hemoperfusion can be of value during the first 24 hours after paraquat ingestion particularly when the patient has developed acute renal failure. However, many cases of paraquat poisoning occur in areas where hemoperfusion facilities are unavailable. In contrast, continuous arteriovenous hemofiltration (CAVH) could be instituted easily. We have measured the removal of paraquat from the body by CAVH in a 46 year old male cane farmer who ingested 70 ml, 20% paraquat and died twelve days later from pulmonary fibrosis. Renal failure developed rapidly. Concentrations of paraquat were measured by an indirect competitive ELISA using a murine paraquat monoclonal IgG antibody. Hemoperfusion was performed daily for five days, beginning 78 hours post-ingestion. By 180 hours, when the patient was in respiratory failure, hemoperfusion was replaced with CAVH which was continued for 46 hours. During this time interval, 1.1 mg paraquat was recovered in the hemofiltrate and 1.56 mg paraquat in the urine. The extraction of paraquat by the hemofilter was close to 100%. The plasma clearance of paraquat across the hemofilter was 6.1 ml/min and the renal clearance was 8.2 ml/min. The mean hemoperfusion clearance of paraquat was 50 ml/min and the total amount of paraquat removed by the 34 hours of hemoperfusion was 9 mg. Because of the relative ease with which CAVH can be performed, its low cost, compared to that of hemoperfusion or hemodialysis, and the continuous nature of the procedure, CAVH may be worth considering in paraquat poisoning. It could be used particularly in those patients who have developed renal failure or while patients are being prepared for hemoperfusion.

Hemofiltration↗
PubMed1981

Long-term antianginal action of verapamil assessed with quantitated serial treadmill stress testing.

The long-term efficacy of verapamil in a dose of 360 mg daily in patients with chronic stable angina pectoris was assessed by quantitated serial treadmill exercise tests. Twenty-eight patients were investigated with a placebo-controlled, double-blind, crossover protocol of 2 weeks each and afterward all patients were put on long-term therapy. Exercise tests were performed at the end of the placebo period and after 2, 4, 8, 16, 24 and 52 weeks of verapamil therapy. All 28 experienced angina during treadmill tests on placebo and the mean (+/- standard error of the mean) exercise time was 6.6 +/- 0.5 minutes. This increased to 9.2 +/- 0.8 minutes at 2 weeks and 50 11.2 +/- 0.8 minutes at 4 weeks. Fifteen and 20 of the 28 patients became angina-free during treadmill exercise at 2 and 4 weeks, respectively. The consumption of nitroglycerin showed a similar improvement. The improvement was maintained at 1 year of follow-up. The on-line computer-analyzed S-T segment changes showed a statistically significant improvement at all follow-up periods. Withdrawal of verapamil produced a return to pretreatment levels. The adverse effects noted were constipation in seven patients and reversible P-R interval prolongation in two. No heart failure occurred in any patient. These findings suggest that verapamil possesses a powerful and sustained antianginal action and, in a dose of 360 mg daily, merits a place as a primary therapeutic agent in the management of chronic stable angina.

Adult↗