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Biomedical subjects

J Goddard

Publications and source records attributed to J Goddard.

78 records · Page 5Linked to original sources
PubMedDate not supplied

Fire ant venom alkaloid, isosolenopsin A, a potent and selective inhibitor of neuronal nitric oxide synthase.

Massive, multiple fire ant, Solenopsis invicta, stings are often treated aggressively, particularly in the elderly, despite limited evidence of systemic toxicity due to the venom. Over 95% of the S. invicta venom is composed of piperidine alkaloid components, whose toxicity, if any, is unknown. To assess a possible pharmacological basis for systemic toxicity, an alkaloid-rich, protein-free methanol extract of the venom from whole ants was assayed for inhibitory activity on the following nitric oxide synthase (NOS) isoforms, rat cerebellar neuronal (nNOS), bovine recombinant endothelial (eNOS), and murine recombinant immunologic (iNOS). Cytosolic NOS activity was determined by measuring the conversion of [(3)H]arginine to [(3)H]citrulline in vitro. Rat nNOS activity was inhibited significantly and in a concentration-dependent manner by the alkaloid-rich venom extract. For nNOS, enzyme activity was inhibited by approximately 50% with 0.33 +/- 0.06 microg of this venom extract, and over 95% inhibition of the three isoforms, nNOS, eNOS, and iNOS, was found with doses of 60 microg in 60 microl reaction mixture. These results indicate that the alkaloid components of S. invicta venom can produce potent inhibition of all three major NOS isoforms. Isosolenopsin A (cis-2-methyl-6-undecylpiperidine), a naturally occurring fire ant piperidine alkaloid, was synthesized and tested for inhibitory activity against the three NOS isoforms. Enzyme activities for nNOS and eNOS were over 95% inhibited with 1000 microM of isosolenopsin A, whereas the activity of iNOS was inhibited by only about 20% at the same concentration. The IC(50) for each of three NOS isoforms was approximately 18 +/- 3.9 microM for nNOS, 156 +/- 10 microM for eNOS, and >1000 microM for iNOS, respectively. Kinetic studies showed isosolenopsin A inhibition to be noncompetitive with L-arginine (K(i) = 19 +/- 2 microM). The potency of isosolenopsin A as an inhibitor of nNOS compares favorably with the inhibitory potency of widely used nNOS inhibitors. Inhibition of NOS isoforms by isosolenopsin A and structurally similar compounds may have toxicological significance with respect to adverse reactions to fire ant stings.

Alkaloids↗
PubMedDate not supplied

Meeting the needs of handicapped children and their families. The evolution of Honeylands: a family support unit, Exeter.

A support service for families with mental, physical, sensory or environmental handicap has evolved from a paediatric ward of a District Hospital. Expressed parental needs have been the source of evolutionary change. About 200 families use the various services of specific therapy, day or longer term residential relief, playgroups for those with special needs, school for the chronically ill. The location is a remodelled stately home on large grounds close to the centre of a city of 100 000, and serves a district of 300 000. The demand for permanent residential placement in the age group under 11 years in this area appears to have been reduced by 80%.

Child↗
PubMedDate not supplied

Automated sonomammographic-xeromammographic-pathologic correlations in the assessment of carcinoma of the breast.

Automated sonomammography and xeromammography were compared in a group of 293 patients referred for a variety of symptomatic and asymptomatic conditions. Twenty of the 293 patients had mammographic evidence of carcinoma that was confirmed pathologically. Seventeen of these patients had sonomammographic evidence of a solid mass; 11 of these demonstrated signs of malignancy, such as irregular border, and desmoplastic reaction manifested by thickening of Cooper's ligaments, skin retraction, periductal fibrosis or disruption of architecture. Statistical analysis of the results reveals that a high degree of sensitivity and specificity in the diagnosis of malignant breast disease can be accomplished with automated sonomammography.

Adult↗