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L Theodore

Publications and source records attributed to L Theodore.

3 recordsLinked to original sources

Recent evolutionary history of the metallothionein gene Mtn in Drosophila.

A new allele of one of the metallothionein genes of D. melanogaster, Mtn.3, sheds light on the recent evolution of this gene. In comparison to the previously studied Mtn1 allele found in Canton S, this new allele, Mtn.3, produces a transcript that is 49 bases longer and 65-70% less abundant. We detected Mtn.3 in several laboratory strains as well as in isofemale lines derived from natural populations. Sequence comparison showed that Mtn.3 differs from Mtn1 in that it has: (a) base-pair substitution and an extra 49 bp-segment in the 3' untranslated region, (b) a substitution in the coding region that replaces the terminal Glu40 in Mtn1 with Lys40, and (c) two base-pair substitutions in the promoter region. The Mtn.3-type was detected in six species of the melanogaster group by restriction analysis, and this result was confirmed by sequencing the D. simulans Mtn gene. Thus Mtn.3, which produces a less abundant transcript, appears to be the oldest of the two alleles. We also found that the duplications previously isolated from natural populations all derived from Mtn1, the more recent allele. Thus, two evolutionary steps: Mtn.3 to Mtn1 and Mtn1 to Dp(Mtn1), are accompanied by an overall 5- to 6-fold increase of RNA accumulation. The two changes seem to have occurred in non-African populations since Mtn.3 but not Mtn1 was detected in our sample from tropical Africa, while Mtn1 and Dp (Mtn1) are prevalent in European and North American samples.

Amino Acid Sequence

The pharmacokinetics and pharmacodynamics of d- and dl-verapamil in rabbits.

The pharmacokinetics and pharmacodynamics of d- and dl-verapamil were studied in conscious rabbits in randomized cross-over fashion. Following a single intravenous dose, there was a biexponential decline in plasma concentration with time. No differences were observed in the pharmacokinetic properties of the compounds. The mean (+/- SD) clearances of d- and dl-verapamil were 0.13 +/- 0.03 and 0.12 +/- 0.05 L/min/kg, respectively. The mean (+/- SD) steady-state volume of distribution was 9.7 +/- 5.2 L/kg for d-verapamil and 8.1 +/- 4.1 L/kg for dl-verapamil. No difference was observed between the compounds in their binding to plasma proteins. The mean (+/- SD) half-life in plasma was 98.7 +/- 63.8 min for d-verapamil and 96.3 +/- 38.0 min for dl-verapamil. In contrast to the lack of stereoselective differences in the pharmacokinetic properties of verapamil, there were marked differences in the pharmacodynamics of d- and dl-verapamil. dl-Verapamil appeared to prolong the PR interval to a greater degree than did d-verapamil, consistent with the more potent calcium channel effects of the l-enantiomer. Similarly, dl-verapamil had more potent hypotensive effects compared with the d-enantiomer, which produced no effects on systemic arterial pressure. Chronotropic effects, judged to be caused by autonomic reflexes in response to the hypotensive effects of the compound, were also statistically greater for dl-verapamil than for d-verapamil. These results demonstrate stereo-selective pharmacodynamic effects in vivo of verapamil.

Animals