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E Dempsey

Publications and source records attributed to E Dempsey.

25 records · Page 2Linked to original sources

Genetic and molecular characterization of a-mrh-Mrh, a new mutable system of Zea mays.

A new allele of the maize A1 gene, a gene required for anthocyanin pigment biosynthesis, was identified in a genetic stock exhibiting a high frequency of chromosome breakage at the second microspore mitosis. This allele, a-mrh, is unstable in both somatic and germinal tissue when an independent locus, Mrh, is present in the genome. a-mrh was molecularly cloned, and a 246 bp DNA insertion with characteristics of a transposable element was identified within the fourth exon of the gene. Southern blot analysis of germinal derivatives of a-mrh suggests that the DNA insert rMrh is excised from the locus when a wild-type phenotype is restored. Genetic crosses with components of other two-element mutable systems of maize failed to induce mutability. We therefore conclude that rMrh is a member of a new, two-element transposon system of maize. The genetic and molecular characteristics of the elements involved are discussed with respect to stress-activated transposition, response of an element to developmental signals, and a possible new role of plant transposons in gene evolution.

Alleles

Exercise-induced myocardial ischemia in a cold environment. Effect of antianginal medications.

The influence of cold on the threshold for myocardial ischemia and the efficacy of antianginal drugs in a cold environment were assessed in 24 patients with stable angina and exercise-induced ST depression. Treadmill exercise tests were done according to a randomized double-blind protocol 90 minutes after administration of placebo, 80 mg propranolol, or 120 mg diltiazem, each at both -8 degrees and 20 degrees C. Eight of the patients were classified by history as cold-sensitive before the study. For the entire group, none of the exercise end points differed significantly between cold and normal temperatures with placebo. However, cold-sensitive patients developed 1 mm ST depression 30% sooner (169 +/- 41 versus 244 +/- 38 seconds, p less than 0.01) at -8 degrees C compared with 20 degrees C. At the onset of ischemia, rate-pressure product was lower in the cold (19.8 +/- 1.0 versus 22.0 +/- 1.6 x 10(-3), p less than 0.05). Both propranolol and diltiazem prolonged time to onset of 1 mm ST depression at both temperatures. The magnitude of improvement at -8 degrees C was equal to that at 20 degrees C, and differences between the two drugs were not statistically significant. Only diltiazem prolonged total exercise duration. Thus, as assessed by exercise testing, cold does not worsen ischemic threshold in most stable angina patients. However, in a subgroup identifiable by history, ischemic threshold is lower in the cold. Propranolol and diltiazem are as effective for exercise-induced ischemia in a cold environment as at normal temperatures.

Angina Pectoris

Safety, tolerability, antiemetic efficacy, and pharmacokinetics of oral dolasetron mesylate in pediatric cancer patients receiving moderately to highly emetogenic chemotherapy.

PURPOSE: The safety, antiemetic efficacy, and pharmacokinetics of single oral doses of dolasetron, a new highly selective 5-HT3 receptor antagonist, were evaluated in children with cancer undergoing treatment with moderately to highly emetogenic chemotherapy. PATIENTS AND METHODS: A total of 32 children, ages 3 to 18 years, were enrolled in a nonrandomized, multicenter, open-label, dose-escalation study. Three oral dose levels (0.6, 1.2, or 1.8 mg/kg) were studied. Safety, efficacy, and pharmacokinetic parameters were assessed over 24 hours at each dosage level. RESULTS: The most effective dose was 1.8 mg/kg; 60% of the patients achieved a complete or major response (< or =2 emetic episodes in 24 hours). A complete response was achieved in 3 of 9 patients (33%) who received 0.6 mg/kg, 4 of 13 (31%) patients who received 1.2 mg/kg, and 5 of 10 (50%) patients who received 1.8 mg/kg of dolasetron. Overall, dolasetron was well tolerated. Adverse events were mild and similar to those reported in adults. Peak plasma concentrations (Cmax) of dolasetron's active reduced metabolite, MDL 74,156, were dose proportional and occurred, on the average, within 1 hour of oral administration. The half-life (t1/2) in plasma was approximately 6 hours for all dose levels, and the mean clearance (CLapp) was unrelated to dose. CONCLUSIONS: Oral dolasetron is safe and effective in reducing chemotherapy-induced nausea and vomiting, particularly at the 1.8-mg/kg dose level. These results support further evaluation of oral dolasetron in larger randomized clinical trials in the pediatric cancer population.

Administration, Oral