PubMed Health⌕ Search

Biomedical subjects

Margaret Patterson

Publications and source records attributed to Margaret Patterson.

5 recordsLinked to original sources
PubMed2005

Anti-allodynic efficacy of the chi-conopeptide, Xen2174, in rats with neuropathic pain.

Xen2174 is a structural analogue of Mr1A, a chi-conopeptide recently isolated from the venom of the marine cone snail, Conus marmoreus. Although both chi-conopeptides are highly selective inhibitors of the norepinephrine transporter (NET), Xen2174 has superior chemical stability relative to Mr1A. It is well-known that tricyclic antidepressants (TCAs) are also potent NET inhibitors, but their poor selectivity relative to other monoamine transporters and various G-protein-coupled receptors, results in dose-limiting side-effects in vivo. As TCAs and the alpha(2)-adrenoceptor agonist, clonidine, have established efficacy for the relief of neuropathic pain, this study examined whether intrathecal (i.t.) Xen2174 alleviated mechanical allodynia in rats with either a chronic constriction injury of the sciatic nerve (CCI-rats) or an L5/L6 spinal-nerve injury. The anti-allodynic responses of i.t. Mr1A and i.t. morphine were also investigated in CCI-rats. Paw withdrawal thresholds were assessed using calibrated von Frey filaments. Bolus doses of i.t. Xen2174 produced dose-dependent relief of mechanical allodynia in CCI-rats and in spinal nerve-ligated rats. Dose-dependent anti-allodynic effects were also produced by i.t. bolus doses of Mr1A and morphine in CCI-rats, but a pronounced 'ceiling' effect was observed for i.t. morphine. The side-effect profiles were mild for both chi-conopeptides with an absence of sedation. Confirming the noradrenergic mechanism of action, i.t. co-administration of yohimbine (100 nmol) with Xen2174 (10 nmol) abolished Xen2174s anti-allodynic actions. Xen2174 appears to be a promising candidate for development as a novel therapeutic for i.t. administration to patients with persistent neuropathic pain.

Analgesics, Opioid↗
PubMed2005

Feedback interactions between MKP3 and ERK MAP kinase control scleraxis expression and the specification of rib progenitors in the developing chick somite.

Cells in the early vertebrate somite receive cues from surrounding tissues, which are important for their specification. A number of signalling pathways involved in somite patterning have been described extensively. By contrast, the interactions between cells from different regions within the somite are less well characterised. Here, we demonstrate that myotomally derived FGFs act through the MAPK signal transduction cascade and in particular, ERK1/2 to activate scleraxis expression in a population of mesenchymal progenitor cells in the dorsal sclerotome. We show that the levels of active, phosphorylated ERK protein in the developing somite are crucial for the expression of scleraxis and Mkp3. MKP3 is a dual specificity phosphatase and a specific antagonist of ERK MAP kinases and we demonstrate that in somites Mkp3 transcription depends on the presence of active ERK. Therefore, MKP3 and ERK MAP kinase constitute a negative feedback loop activated by FGF in sclerotomal progenitor cells. We propose that tight control of ERK signalling strength by MKP3 is important for the appropriate regulation of downstream cellular responses including the activation of scleraxis. We show that increased or decreased levels of phosphorylated ERK result in the loss of scleraxis transcripts and the loss of distal rib development, highlighting the importance of the MKP3-ERK-MAP kinase mediated feedback loop for cell specification and differentiation.

Animals↗
PubMed2004

Dynamic expression of Lef/Tcf family members and beta-catenin during chick gastrulation, neurulation, and early limb development.

Members of the Lef/Tcf family of HMG-box transcription factors mediate the response to Wnt as part of the canonical Wnt signaling cascade. Positive and negative cofactors, including beta-catenin, CtBP, and Smad3, regulate the activity of Lef/Tcf transcription complexes. Interaction of Lef/Tcfs with beta-catenin results in target gene activation or repression, depending on the context. Here, we report the cloning of a novel chick Tcf-1 splice variant and of a partial cDNA for chick Tcf-3. We describe their expression patterns during early development and have compared them with the expression profiles of Lef-1 and beta-catenin. We found restricted patterns during gastrulation, neurulation, somitogenesis, and early limb development. beta-catenin and Lef/Tcf expression did not always coincide, indicating developmental contexts in which Lef/Tcf proteins may interact with other cofactors and conversely, the areas in which beta-catenin may interact with other coregulators, or be involved in regulating adhesive properties of cells.

Animals↗
PubMed2003

Beta-thalassemia in association with a new delta-chain hemoglobin variant [delta116(g18)Arg-->Leu]: implications for carrier screening and prenatal diagnosis.

We describe a complicated genetic counseling and prenatal diagnostic case involving an East Indian couple that had lost two consecutive pregnancies. Hemoglobinopathy screening was conducted to investigate the possibility of Hb Bart's hydrops fetalis or Hb H hydrops fetalis. The initial work-up indicated that alpha-thalassemia was not a contributing factor, with both parents being carriers of single gene deletions (-alpha(3.7)/alphaalpha). However, the Hb electrophoresis results indicated that the couple might be at risk for having children with Hb E/Hb Lepore disease. Subsequent DNA testing demonstrated that the father carried the Hb E mutation, but failed to confirm that the mother carries the Hb Lepore deletion. Sequence analysis revealed that the mother was heterozygous for a common East Indian beta(0)-thalassemia mutation, yet had a normal level of Hb A(2). The mother also carried a previously unreported missense mutation of the delta-globin gene, in cis with the beta(0)-thalassemia mutation, which gave rise to the minor Hb variant originally misidentified as Hb Lepore. This case illustrates the importance of comprehensive molecular analyses for accurate assessment of genetic risks for hemoglobinopathy syndromes.

Abortion, Spontaneous↗