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K Wharton

Publications and source records attributed to K Wharton.

6 recordsLinked to original sources
PubMed1996

Molecular lesions associated with alleles of decapentaplegic identify residues necessary for TGF-beta/BMP cell signaling in Drosophila melanogaster.

We have identified the molecular lesions associated with six point mutations in the Drosophila TGF-beta homologue decapentaplegic (dpp). The sites of these mutations define residues within both the pro and ligand regions that are essential for dpp function in vivo. While all of these mutations affect residues that are highly conserved among TGF-beta superfamily members, the phenotypic consequences of the different alleles are quite distinct. Through an analysis of these mutant phenotypes, both in cuticle preparations and with molecular probes, we have assessed the functional significance of specific residues that are conserved among the different members of the superfamily. In addition, we have tested for conditional genetic interactions between the different alleles. We show that two of the alleles are temperature sensitive for the embryonic functions of dpp, such that these alleles are not only embryonic viable as homozygotes but also partially complement other dpp hypomorphs at low temperatures. Our results are discussed with regard to in vitro mutagenesis data on other TGF-beta-like molecules, as well as with regard to the regulation of dpp cell signaling in Drosophila.

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PubMed1995

Genetic screens to identify elements of the decapentaplegic signaling pathway in Drosophila.

Pathways for regulation of signaling by transforming growth factor-beta family members are poorly understood at present. The best genetically characterized member of this family is encoded by the Drosophila gene decapentaplegic (dpp), which is required for multiple events during fly development. We describe here the results of screens for genes required to maximize dpp signaling during embryonic dorsal-ventral patterning. Screens for genetic interactions in the zygote have identified an allele of tolloid, as well as two novel alleles of screw, a gene recently shown to encode another bone morphogenetic protein-like polypeptide. Both genes are required for patterning the dorsalmost tissues of the embryo. Screens for dpp interactions with maternally expressed genes have identified loss of function mutations in Mothers against dpp and Medea. These mutations are homozygous pupal lethal, engendering gut defects and severely reduced imaginal disks, reminiscent of dpp mutant phenotypes arising during other dpp-dependent developmental events. Genetic interaction phenotypes are consistent with reduction of dpp activity in the early embryo and in the imaginal disks. We propose that the novel screw mutations identified here titrate out some component(s) of the dpp signaling pathway. We propose that Mad and Medea encode rate-limiting components integral to dpp pathways throughout development.

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PubMed1988

Radiofrequency catheter ablation of the left and right ventricles: anatomic and electrophysiologic observations.

Certain untoward effects associated with the use of direct-current electrical catheter ablation of the ventricular endomyocardium have been noted. We assessed the efficacy and safety of closed-chest catheter ablation of the left and right ventricles using radiofrequency (RF) energy (750 kHz) in six dogs. Mean RF energies between 93 and 123 joules (J) were randomly delivered to three left ventricular (LV) sites via two distal adjacent electrodes (bipolar configuration) using 6-7F USCI tripolar or quadripolar catheters with an interelectrode distance of 5-10 mm. Another 90-143 J were given to two right ventricular (RV) sites in single or multiple divided applications between a distal electrode and an external patch electrode (unipolar configuration). Ventricular arrhythmias were not observed during application of RF energy. Programmed ventricular stimulation before and after the procedure did not induce ventricular tachycardia (VT) or fibrillation except in one dog who had inducible VT prior to ablation. There were no significant changes in LV and RV effective refractory periods after the procedures. Occasional premature ventricular beats and rare episodes of non-sustained VT (3-12 beats) were observed in ambulatory electrocardiographic recordings (13-24 hrs) done immediately after ablation. Dogs were sacrificed after 4-5 days. Pathology showed well-demarcated round or ovoid lesions of varying sizes. Mural thrombus was found in one dog. Microscopic findings consisted of circumscribed areas of coagulation necrosis with a peripheral zone of cellular infiltration. Transmural necrosis without perforation was occasionally seen in the thin RV wall when higher energies were delivered. In conclusion, discrete areas of desiccation injury in the ventricles can be achieved by transcatheter bipolar or unipolar ablation using RF energy. The complications associated with this method appear to be minimal. Further experiments are needed to evaluate its potential for catheter ablation of ventricular tachycardia.

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