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L O'Keefe

Publications and source records attributed to L O'Keefe.

11 recordsLinked to original sources
PubMed2000

arrow encodes an LDL-receptor-related protein essential for Wingless signalling.

The Wnt family of secreted molecules functions in cell-fate determination and morphogenesis during development in both vertebrates and invertebrates (reviewed in ref. 1). Drosophila Wingless is a founding member of this family, and many components of its signal transduction cascade have been identified, including the Frizzled class of receptor. But the mechanism by which the Wingless signal is received and transduced across the membrane is not completely understood. Here we describe a gene that is necessary for all Wingless signalling events in Drosophila. We show that arrow gene function is essential in cells receiving Wingless input and that it acts upstream of Dishevelled. arrow encodes a single-pass transmembrane protein, indicating that it may be part of a receptor complex with Frizzled class proteins. Arrow is a low-density lipoprotein (LDL)-receptor-related protein (LRP), strikingly homologous to murine and human LRP5 and LRP6. Thus, our data suggests a new and conserved function for this LRP subfamily in Wingless/Wnt signal reception.

Animals↗
PubMed1999

A putative exchange factor for Rho1 GTPase is required for initiation of cytokinesis in Drosophila.

Cytokinesis ensures the successful completion of the cell cycle and distribution of chromosomes, organelles, and cytoplasm between daughter cells. It is accomplished by formation and constriction of an actomyosin contractile ring that drives the progression of a cleavage furrow. Microinjection experiments and in vitro transfection assays have suggested a requirement for small GTPases of the Rho family in cytokinesis. Yet, the identity of proteins regulating Rho signaling pathways during cytokinesis remains unknown. Here we show that in Drosophila, Pebble (Pbl), a putative exchange factor for Rho GTPases (RhoGEF), is required for the formation of the contractile ring and initiation of cytokinesis. The dynamics of Pbl expression and its distribution during mitosis, as well as structure-function analysis, indicate that it is a key regulatory component of the pathway. pbl interacts genetically with Rho1, but not with Rac1 or Cdc42, and Pbl and Rho1 proteins interact in vivo in yeast. Similar to mutations in pbl, loss of Rho1 or expression of a dominant-negative Rho1 blocks cytokinesis. Our results identify Pbl as a RhoGEF specifically required for cytokinesis and linked through Rho1 activity to the reorganization of the actin cytoskeleton at the cleavage furrow.

Amino Acid Sequence↗
PubMed1997

Spitz and Wingless, emanating from distinct borders, cooperate to establish cell fate across the Engrailed domain in the Drosophila epidermis.

A key step in development is the establishment of cell type diversity across a cellular field. Segmental patterning within the Drosophila embryonic epidermis is one paradigm for this process. At each parasegment boundary, cells expressing the Wnt family member Wingless confront cells expressing the homeoprotein Engrailed. The Engrailed-expressing cells normally differentiate as one of two alternative cell types. In investigating the generation of this cell type diversity among the 2-cell-wide Engrailed stripe, we previously showed that Wingless, expressed just anterior to the Engrailed cells, is essential for the specification of anterior Engrailed cell fate. In a screen for additional mutations affecting Engrailed cell fate, we identified anterior open/yan, a gene encoding an inhibitory ETS-domain transcription factor that is negatively regulated by the Rasl-MAP kinase signaling cascade. We find that Anterior Open must be inactivated for posterior Engrailed cells to adopt their correct fate. This is achieved by the EGF receptor (DER), which is required autonomously in the Engrailed cells to trigger the Ras1-MAP kinase pathway. Localized activation of DER is accomplished by restricted processing of the activating ligand, Spitz. Processing is confined to the cell row posterior to the Engrailed domain by the restricted expression of Rhomboid. These cells also express the inhibitory ligand Argos, which attenuates the activation of DER in cell rows more distant from the ligand source. Thus, distinct signals flank each border of the Engrailed domain, as Wingless is produced anteriorly and Spitz posteriorly. Since we also show that En cells have the capacity to respond to either Wingless or Spitz, these cells must choose their fate depending on the relative level of activation of the two pathways.

Animals↗
PubMed1996

The incidence of bacteria in middle ear effusions.

Otitis media with effusion (OME) is a common condition in paediatric ENT practice. Whilst surgical management is in many cases the mainstay of treatment for resistant OME, the use of antibiotics has been advocated by some authorities. Over one quarter of middle ear effusions analysed in this study contained potentially pathogenic bacteria. Antibiotics may be of value in the treatment of OME in these children.

Anti-Bacterial Agents↗
PubMed1994

Reconstruction of discharging mastoid cavities using the temporalis myofascial flap.

Muscle obliteration of the troublesome mastoid cavity is one method of achieving a permanently dry ear, although long-term results are often disappointing. An operation is described, which is a modification of existing techniques and utilizes a temporalis myofascial flap. This procedure has been used on 46 discharging mastoid cavities and produced encouraging results. It provides a simple, safe and reliable solution to the problem.

Adult↗
PubMed1993

Localized tracheopathia osteoplastica of the subglottis.

Tracheopathia osteoplastica is a benign dysplasia of the tracheobronchial tree which rarely presents clinical problems especially when localized. We present a case which caused an unexpected difficulty in intubation and was subsequently removed endoscopically using the CO2 laser.

Bronchoscopy↗
PubMed1993

Informed consent: using a structured interview changes patients' attitudes towards informed consent.

Patients want to know more about their condition and its proposed treatment. Gaining patients' confidence before treatment reduces the changes of their seeking legal redress for an unexpected outcome. As part of a prospective study of informed consent for surgery we have assessed the attitudes of patients towards informed consent when different types of consent interview are used. We found that most patients are happy to do as their doctor advises but think the informal consent interview is important because it gives them information; they also want to know about most, but not all, complications of the procedure. One quarter worried about the anaesthetic, about one eighth worried about 'not waking up' and similar proportions worried about complications and other things such as pain and nausea. Most patients think that the consent form is a legal document. In addition patients who had an informal interview felt obliged to sign the consent form and thought it had medicolegal implications. In contrast those who had a structured interview felt less obliged to sign the consent form and more involved in the decision to operate.

Adult↗
PubMed1993

Does the type of middle ear aspirate have any prognostic significance in otitis media with effusion in children?

Two hundred and twenty-two children with chronic, bilateral middle ear effusions were assessed during a 2 year follow-up period. At initial myringotomy the middle ear aspirate was found to be serous in 44 children and mucoid in 178 children. Evaluation at 1 and 2 years post-operatively showed no difference in otoscopic fluid clearance or mean hearing threshold at either follow-up time in relation to either type of fluid. There was no greater need for ventilation tube reinsertion in either group during the overall follow-up period. There was found to be no significant difference between the children with serous or mucoid effusions in relation to a range of pre-operative and operative variables. The study suggests that outcome in terms of fluid clearance and hearing thresholds is independent of the fluid type and there appears no greater need for revision ventilation tube insertion in relation to the findings at myringotomy. The type of effusion found on aspiration prior to ventilation tube insertion has no prognostic value. Children with serous fluid should be managed in an identical manner to those in which the fluid is thicker and mucoid in character.

Audiometry, Pure-Tone↗
PubMed1992

Informed consent: the assessment of two structured interview approaches compared to the current approach.

We prospectively studied 190 patients undergoing tonsillectomy or nasal surgery to assess the value of two structured interview techniques. There were four groups: Group A did not have a consent interview during the study period. Group B had an informal interview. Group C had a structured interview and Group D had a structured interview and were given an information sheet. Anxiety assessments were made and patients' recall of the operation name, details of the operation and its complications was assessed. Patients had higher than normal anxiety levels when admitted, but several hours after the interview anxiety was normal for Groups B, C and D. Group A maintained a higher anxiety level. Only 37 per cent correctly recalled the operation name, where as 87 per cent of all groups recalled the explanation of the operation. However, Groups C and D recalled a higher mean number of complications per patient. A structured interview when obtaining informed consent increases the number of complications recalled without increasing pre-operative anxiety.

Adult↗
PubMed1988

Sensitization to cocaine in the nigrostriatal dopamine system.

Behavioral sensitization involving the nigrostriatal dopaminergic tract is manifested after treatment with only a single dose of cocaine and is augmented following repeated treatment. One neurochemical change observed that is consistent with behavioral sensitization is the increase in amphetamine-induced 3H-DA release from striatal slices seen after one injection of cocaine. One day after repeated administration of cocaine, however, the increase is no longer evident. It is possible that transient compensatory changes, such as increased D-2 autoreceptor inhibition, may obscure this effect when it is measured at relatively short times after the repeated administration has been terminated. One day after cessation of repeated cocaine administration, D-2 autoreceptors in both striatum and substantia nigra compacta were upregulated consistent with a compensatory mechanism and the development of behavioral tolerance rather than sensitization. In contrast, DA content, neuronal DA uptake, and postsynaptic D-2 DA receptors in striatum were not regulated by this treatment. Likewise, D-1 DA receptors in striatum and substantia nigra were unaffected. In the mesolimbic system, both the pre- and postsynaptic receptor changes are consistent with sensitization. Amphetamine-stimulated release from nucleus accumbens has not yet been measured in cocaine-sensitized animals. It is possible that changes similar to those seen in striatum may occur in this area. It is interesting that, in general, presynaptic parameters associated with the DA neuron, with the notable exception of the uptake pump, appear to be more sensitive to regulation by cocaine administration than do postsynaptic parameters. The long-lasting effects of a single moderate dose of cocaine are also surprising. It will be important to determine the molecular mechanisms underlying this regulation and whether or not similar changes are induced in mesolimbic dopaminergic systems by single and repeated administration of cocaine.

Animals↗