Tailoring asthma advice to suit the patient.
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Biomedical subjects
Publications and source records attributed to R Booker.
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Octopod (Octo) is a mutation of the moth Manduca sexta, which transforms the first abdominal segment (A1) in the anterior direction. Mutant animals are characterized by the appearance of homeotic thoracic-like legs on A1. We exploited this mutation to determine what rules might be used in specifying the fates of sensory neurons located on the body surface of larval Manduca. Mechanical stimulation of homeotic leg sensilla did not cause reflexive movements of the homeotic legs, but elicited responses similar to those observed following stimulation of ventral A1 body wall hairs. Intracellular recordings demonstrated that several of the motoneurons in the A1 ganglion received inputs from the homeotic sensory hairs. The responses of these motoneurons to stimulation of homeotic sensilla resembled their responses to stimulation of ventral body wall sensilla. Cobalt fills revealed that the mutation transformed the segmental projection pattern of only the sensory neurons located on the ventral surface of A1, resulting in a greater number with intersegmental projection patterns typical of sensory neurons found on the thoracic body wall. Many of the sensory neurons on the homeotic legs had intersegmental projection patterns typical of abdominal sensory neurons: an anteriorly directed projection terminating in the third thoracic ganglion (T3). Once this projection reached T3, however, it mimicked the projections of the thoracic leg sensory neurons. These results demonstrate that the same rules are not used in the establishment of the intersegmental and leg-specific projection patterns. Segmental identity influences the intersegmental projection pattern of the sensory neurons of Manduca, whereas the leg-specific projections are consistent with a role for positional information in determining their pattern.
Several aspects of leg development in the moth Manduca sexta were examined using the homeotic mutation Octopod (Octo). This mutation causes a transformation of the ventral epidermis of the first abdominal segment (A1) to that of the third thoracic segment (T3), resulting in the presence of thoracic-like legs on A1. The degree of transformation of A1 is variable, ranging from bumps on the cuticle to fully segmented thoracic-like legs. In the normal thoracic legs, clusters of undifferentiated cells known as differentiation centers are located around the coxal-trochanteral, femoral-tibial, and tibial-tarsal joints. The adult thoracic legs develop from the differentiation centers at metamorphosis. The homeotic legs of the Octopod larvae also have differentiation centers at comparable positions in the homeotic leg. As a result, the number of leg segments in a mutant adult is correlated with the number of segments and differentiation centers that animal had in its larval homeotic leg. Our data suggest that the differentiation center located at the coxal-trochanteral joint forms the adult coxa and trochanter, the center at the larval femoral-tibial joint the adult femur and tibia, and the differentiation center at the larval tibial-tarsal joint the adult tarsus. Homeotic larval legs which include at least a femur have supernumerary muscles, while adult homeotic legs rarely show discrete muscle. The homeotic larval muscles appear to have thoracic identities, based on their attachment points and the timing of their degeneration at the larval-pupal transition. They are innervated by a motoneuron that is normally present in A1 where it innervates the ventral lateral external muscle (VLE). In mutant animals, the same motoneuron innervates all of the homeotic muscles and the VLE. We consider possible mechanisms underlying the development of homeotic muscles and their innervation. At the larval-pupal transition, the VLE in mutant animals degenerates at its normal time, which is 3 days after the degeneration of the homeotic muscles. Thus, despite their common innervation, the two muscle types degenerate according to their own schedules, indicating that the developmental fates of the muscles are not dictated by their innervating neuron but are intrinsic to the muscles themselves.
Using sequence homology to the Drosophila Antennapedia gene, we isolated a homeobox-containing gene from the lepidopteran, Manduca sexta. Sequence analysis and in situ hybridizations to tissue sections suggest that the Manduca gene encodes a lepidopteran homologue of the Drosophila Bithorax complex gene abdominal-A. The predicted amino acid sequence of a 76 amino acid region that includes the homeobox and the regions immediately flanking it are identical between the Manduca and Drosophila genes. Northern blots reveal that the manduca abd-A gene is expressed first in the early embryo and continues to be expressed throughout later embryonic and larval stages. In situ hybridizations show that the posterior half of the first abdominal segment marks the anterior border of the Manduca abd-A expression. This expression pattern demonstrates the conservation of parasegments as domains of gene activity in the lepidopteran embryo. The Manduca abd-A expression extends from the posterior half of the first abdominal segment through the tenth abdominal segment, a domain that is greater than that of the Drosophila abd-A expression, and reflects the difference in visible segment number between the two insects.
Octopod (Octo) is a mutation of the moth Manduca sexta, which results in the homeotic transformation of the ventral surface of the first (A1) and less often the second (A2) abdominal segments in the anterior direction. The extent of the transformation ranges from a slight deformation of the ventral cuticle, up to the formation of miniature thoracic legs on A1. The extent of the transformation is always less within A2 as compared to A1. A genetic analysis revealed that Octo is an autosomal mutation which shows incomplete dominance. The effect of this mutation on the central nervous system (CNS) was assessed by examining the distribution and fate of the postembryonic neuroblasts in the segmental ganglia of Octo larvae. In each of the thoracic ganglia of wild-type larvae, there is a set of 45-47 neuroblasts; a reduced but homologous array of 24 and 10 neuroblasts are found in A1 and A2, respectively. Ganglion A1 of Octo larvae had 1 to 6 supernumerary neuroblasts, and 20% of the A2 ganglia showed a single ectopic neuroblast. The supernumerary neuroblasts corresponded to identifiable neuroblasts normally found in more anterior ganglia. The Octo mutation also influenced the mitotic activity of stem cells normally present in A1. In this case, the neuroblasts generated a lineage of cells that were typical of a thoracic location rather than A1. These data demonstrate that homeotic mutations can influence the fate of identifiable pattern elements within the CNS of an insect.
The tobacco hornworm Manduca sexta exhibits dramatic changes in its body morphology and behavior as it is transformed from a larva into an adult during metamorphosis. Accompanying these changes is an extensive reorganization of this moth's central nervous system (CNS), which involves both the death and remodeling of subsets of larval neurons. We report here that the segmental ganglia of the larvae also contain a stereotyped array of identifiable neuronal stem cells (neuroblasts) that contribute over 2,000 cells to each thoracic ganglion and about 40-80 cells to each abdominal ganglion. The distribution of these neuroblasts varies in a segment specific manner. Dormant neuroblasts are found adjacent to the neuropil in late embryos and early first instar larvae. After the molt to the second instar, these cells enlarge and begin to divide. Through a series of asymmetrical divisions, each neuroblast generates a discrete nest of 10-90 progeny by the end of larval life. These progeny (the imaginal nest cells) are developmentally arrested at an early stage of differentiation and remain so until metamorphosis. At the onset of metamorphosis, a wave of cell death sweeps through the nests, the extent of the death being much greater within the abdominal nests than in the thoracic nests. The surviving imaginal nest cells then differentiate to become functional neurons that are incorporated into the adult CNS.
The nervous system of an adult moth is comprised of retained larval neurons that are remodeled during metamorphosis and a set of new adult specific neurons. The new neurons arise from a stereotyped array of stem cells (neuroblasts) that divide during larval life to generate nests of up to 100 arrested postmitotic immature neurons, the imaginal nest (IN) cells. At the onset of metamorphosis, some of the IN cells die while the remainder differentiate into mature functional neurons. Metamorphosis in insects is regulated by 2 classes of hormones, the ecdysteroids and the juvenile hormones. The transition from larva to pupa requires the disappearance of juvenile hormones followed by 2 releases of ecdysteroids: a small "commitment peak" and a larger "prepupal peak." Through a series of endocrine manipulations, we demonstrate that the death and differentiation observed among the abdominal IN cells at metamorphosis are both influenced by these hormonal cues. If the abdomen was isolated from the hormonal sources in the anterior half of the larva before the onset of metamorphosis, death and differentiation of the IN cells were prevented. Infusion of ecdysteroids into such abdomens, to mimic the prepupal peak, resulted in the IN cells showing the same fate as seen in control animals during the early phases of metamorphosis. The response of the IN cells to the small commitment peak of ecdysteroids was heterogeneous. Exposure to this small peak of steroids caused some cells to become committed to resume their development, making them resistant to juvenile hormone application.(ABSTRACT TRUNCATED AT 250 WORDS)
The segmental ganglia of adults of the moth, Manduca sexta, are constructed both from remodeled larval neurons and from adult-specific cells. The latter are produced by identified stem cells (neuroblasts) during larval life and then differentiate to form functional neurons during metamorphosis. The mitotic activity of the larval neuroblasts could be irreversibly blocked by the DNA-synthesis inhibitor hydroxyurea (HU). Treatment on day 1 of the third larval stage resulted in 80-90% of the neuroblasts being blocked before they produced any progeny while leaving the functional larval neurons unaffected. Treated larvae finished growth, underwent metamorphosis, and produced an adult CNS that contained the normal set of remodeled larval neurons but lacked most of the new adult-specific cells. When HU treatment was delayed until the start of the fourth or fifth larval stage, the neuroblasts produced the early portions of their respective lineages before they were blocked. The immature neurons that were generated prior to treatment survived to contribute adult-specific neurons to the moth CNS, but the remainder of each lineage was missing. This technique therefore enables one to produce adult nervous systems containing the basic set of remodeled larval cells plus defined sets of adult-specific neurons.
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Individual Drosophila melanogaster, with or without heads, can be trained to lift their legs to avoid electric shock. This behavior is similar to the operant conditioning previously demonstrated in intact and headless cockroaches. More than 90% of headless wild-type flies learned to our criterion. In contrast, three mutants (dunce, cabbage, and turnip), originally selected for failure to learn in an olfactory discrimination paradigm, tended to perform poorly in this new learning situation. The difference in learning behavior between normal and mutant flies is distinguishable in individuals and may be useful for mosaic analysis.
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Although there have been reports of the results of treating trichomoniasis with metronidazole 2 g in a single dose, no randomised double-blind comparison of this treatment with a multiple-dose regimen has been reported. In such a comparison, 96 women were treated with metronidazole 2 g in a single dose and 96 women with metronidazole 400 mg twice daily for five days. Forty-eight of 52 women followed for 14 days after the single dose were cured, as were 61 of 66 women followed for 14 days after the start of the five-day regimen. These results compare favourably with previous reports. Side effects were trivial, and we recommend the single 2-g dose, for it is effective, economical, and can be given under supervision in the clinic.
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