Substrate-specificity of cytochrome P450-mediated detoxification as an evolutionary strategy for specialization on furanocoumarin-containing hostplants: CYP6AE89 in parsnip webworms.

The parsnip webworm, Depressaria pastinacella, is restricted to two hostplant genera containing six structurally diverse furanocoumarins. Of these, imperatorin is detoxified by a specialized cytochrome P450, CYP6AB3. A previous whole-larva transcriptome analysis confirmed the presence of nine transcripts that belong to the CYP6AE subfamily. Here, by examining midgut-specific gene expression patterns we determined that CYP6AE89 transcripts were highly expressed and furanocoumarin-inducible. Computer docking and energy-minimization of a CYP6AE89 model with all six furanocoumarins showed that 5-methoxylated bergapten and 8-methoxylated xanthotoxin had the smallest distances from the heme to the proton-donor residue in the catalytic I-helix, and that the 5,8-dimethoxylated isopimpinellin and bergapten had the smallest energy-minimized distance from the heme oxygen to the furan ring double bond. To evaluate this prediction, we expressed the CYP6AE89 protein in an Escherichia coli system, and used it to detect high catalytic activity against the two mono-methoxylated linear furanocoumarins - bergapten and xanthotoxin - and weak activity against isopimpinellin. Thus, CYP6AE89, like CYP6AB3, is probably specialized for detoxifying only a subset of hostplant furanocoumarins. A maximum-likelihood tree built with six representative lepidopterans with manually annotated cytochrome P450s shows that CYP6AE89 may have evolved much faster than the other CYP6AE proteins, possibly indicative of host selection pressure.

Use of misoprostol for cervical ripening.

BACKGROUND: Misoprostol, the prostaglandin E1 analog, is increasingly used for cervical ripening and induction of labor. We evaluated our experience with misoprostol in an open-label setting. METHODS: Patients were selected for cervical ripening based on clinical profile. At 3 cm cervical dilation, misoprostol was discontinued and other means of labor augmentation were used. Over 13 months, 470 inductions of labor occurred, and 455 charts were available; 254 patients (56%) received misoprostol for cervical ripening, and 144 (32%) received dinoprostone (prostaglandin E2). RESULTS: With misoprostol, mean time from beginning of contractions until delivery was 7 hours, 30 minutes; vaginal birth occurred in 85% of cases, and spontaneous labor occurred in 38%. Hyperstimulation occurred in 4 cases (1.6%) and precipitate labor in 7 (3%). All infants were discharged in excellent condition; one had a 5-minute Apgar score <7, and 33 (13%) had meconium, none with aspiration. Twenty-three patients who had had a previous cesarean section received misoprostol and delivered vaginally. CONCLUSION: Misoprostol was found to be a safe and effective agent for cervical ripening as part of labor induction.

Analysis of tasks performed by certified ophthalmic medical personnel.

BACKGROUND: Proper delegation of routine tasks to trained personnel might increase cost efficiency by freeing the physician to concentrate on the medical and judgmental aspects of patient care. In ophthalmology, certified ophthalmic medical personnel (OMP) assist the physician by performing many tasks. The Joint Commission on Allied Health Personnel in Ophthalmology (JCAHPO) selected 77 specific tasks performed by OMP and conducted a task analysis survey to determine the importance of these tasks to ophthalmic practice. Individual and practice demographics were surveyed simultaneously to compare the effect of individual and practice differences on task importance. METHODS: Certified OMP and their sponsoring ophthalmologists were surveyed independently. Each group was asked to rate the importance of the 77 selected tasks using a five-point scale of importance. Importance ratings from each survey group were used independently to generate a rank order listing of tasks. RESULTS: Only 3 of the 77 tasks differed significantly in importance between ophthalmologists and OMP. The same five tasks were rated as most important by both groups, whereas the second group of the five most important tasks varied only by +/-4. CONCLUSIONS: The similarity in task importance rankings indicates a common perception between ophthalmologists and OMP concerning the role played by OMP in ophthalmic eye care.

Formation of muscle spindles in regenerated avian muscle grafts.

Pigeon muscles lacking muscle spindles were grafted into sites which normally have a muscle containing spindles. The reciprocal transplantations were also made. After two to eight months, the graft of the donor muscle without spindles had regenerated into a muscle containing muscle spindles. The reciprocal grafts, muscles containing spindles transplanted to a site lacking spindle innervation, had neither muscle spindles nor remnants of the spindles. These experiments demonstrate that 1) the innervation is required for formation of the spindle; 2) the original spindles do not survive transplantation; and 3) parts of the original spindle are not required for spindle regeneration.