Biomedical subjects

Ian Bruce

Publications and source records attributed to Ian Bruce.

8 recordsLinked to original sources

PubMed2006

A spiking neuron model of cortical correlates of sensorineural hearing loss: Spontaneous firing, synchrony, and tinnitus.

Hearing loss due to peripheral damage is associated with cochlear hair cell damage or loss and some retrograde degeneration of auditory nerve fibers. Surviving auditory nerve fibers in the impaired region exhibit elevated and broadened frequency tuning, and the cochleotopic representation of broadband stimuli such as speech is distorted. In impaired cortical regions, increased tuning to frequencies near the edge of the hearing loss coupled with increased spontaneous and synchronous firing is observed. Tinnitus, an auditory percept in the absence of sensory input, may arise under these circumstances as a result of plastic reorganization in the auditory cortex. We present a spiking neuron model of auditory cortex that captures several key features of cortical organization. A key assumption in the model is that in response to reduced afferent excitatory input in the damaged region, a compensatory change in the connection strengths of lateral excitatory and inhibitory connections occurs. These changes allow the model to capture some of the cortical correlates of sensorineural hearing loss, including changes in spontaneous firing and synchrony; these phenomena may explain central tinnitus. This model may also be useful for evaluating procedures designed to segregate synchronous activity underlying tinnitus and for evaluating adaptive hearing devices that compensate for selective hearing loss.

Acoustic Stimulation↗

PubMed2005

Magnetically responsive carboxylated magnetite-polydipyrrole/polydicarbazole nanocomposites of core-shell morphology. Preparation, characterization, and use in DNA hybridization.

Novel bis-heterocyclic mono- and dicarboxylated dipyrrole and dicarbazole monomers have been synthesized in a modular manner. Their oxidative polymerization around magnetite nanosized particles has been investigated and optimized toward new magnetic magnetite-polydipyrrole/polydicarbazole nanocomposites (NCs) of a core-shell morphology. These NCs were thoroughly characterized by FT-IR, TGA (Thermal Gravimetric Analysis), low- and high-resolution TEM/HR-TEM microscopies, and Mössbauer spectroscopy along with magnetization studies. Exploiting the versatile COOH chemistry (activation by water-soluble diimides) introduced by the polymeric shell, DNA hybridization experiments have been conducted onto NC surfaces using an efficient blue-colored HRP-based enzymatic screening biological system. Highly parallel NC-supported DNA hybridization experimentations revealed that these NCs presented an interesting potential for DNA-based diagnostic applications.

Biocompatible Materials↗

PubMed2005

Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: further support that PTPN22 is an autoimmunity gene.

OBJECTIVE: The protein tyrosine phosphatase N22 (PTPN22) gene exhibits regulatory activities for both T cells and B cells. A missense single-nucleotide polymorphism (SNP) within this gene (rs2476601) has recently been associated with 4 autoimmune diseases: rheumatoid arthritis (RA), systemic lupus erythematosus, autoimmune thyroid disease, and type 1 diabetes mellitus, all of which are T cell-mediated and associated with the elaboration of autoantibody. The aim of this study was to investigate associations of the missense SNP of PTPN22 in a number of autoimmune diseases in the UK population, including RA, juvenile idiopathic arthritis (JIA), psoriasis, psoriatic arthritis (PsA), and multiple sclerosis (MS), some of which have not been examined previously. METHODS: The PTPN22 missense SNP was genotyped in 886 RA, 661 JIA, 279 psoriasis, 455 PsA, and 379 MS patients and in 595 healthy controls. Association with the PTPN22 SNP was analyzed by chi-square test as implemented in Stata software. RESULTS: There was a significant association between the PTPN22 SNP and RA (P = 1.8 x 10(-8)) and JIA (P = 0.0005). In contrast, no association with psoriasis, PsA, or MS was detected. CONCLUSION: We replicated the findings of a previous association with RA and identified a novel association with JIA. Together with previous data showing associations with other autoimmune diseases, our findings provide further evidence that the PTPN22 gene plays a role in the pathogenesis of a subgroup of autoimmune diseases.

Adult↗

PubMed2004

Essential role for the p110delta phosphoinositide 3-kinase in the allergic response.

Inflammatory substances released by mast cells induce and maintain the allergic response. Mast cell differentiation and activation are regulated, respectively, by stem cell factor (SCF; also known as Kit ligand) and by allergen in complex with allergen-specific immunoglobulin E (IgE). Activated SCF receptors and high-affinity receptors for IgE (FcvarepsilonRI) engage phosphoinositide 3-kinases (PI(3)Ks) to generate intracellular lipid second messenger signals. Here, we report that genetic or pharmacological inactivation of the p110delta isoform of PI(3)K in mast cells leads to defective SCF-mediated in vitro proliferation, adhesion and migration, and to impaired allergen-IgE-induced degranulation and cytokine release. Inactivation of p110delta protects mice against anaphylactic allergic responses. These results identify p110delta as a new target for therapeutic intervention in allergy and mast-cell-related pathologies.

Anaphylaxis↗

PubMed2004

Long-chain formoterol analogues: an investigation into the effect of increasing amino-substituent chain length on the beta2-adrenoceptor activity.

The synthesis of a series of long-chain formoterol analogues in which the terminal ether residue of the beta-phenethyl-amino-substituent has been extended beyond the methyl ether residue present in the parent compound are described. Evaluation of these analogues as beta(2)-adrenoceptor agonists was used to provide an insight into the factors controlling the magnitude and duration of receptor activation.

Adrenergic beta-2 Receptor Agonists↗

PubMed2004

Rapid access to azepine-fused oxetanols from alkoxy-substituted maleimides.

[reaction: see text] UV irradiation of alkoxy-substituted N-alkenylmaleimides induces a sequence involving a [5 + 2] cycloaddition followed by a Norrish-Yang cyclization. The resulting highly strained alkylidene oxetanol-fused azepines are formed in good yield and with high diastereoselectivities

Journal Article↗

PubMed2004

New magnetically responsive polydicarbazole-magnetite nanoparticles.

Magnetically responsive COOH-polydicarbazole-magnetite nanocomposites have been prepared by chemical oxidation of three COOH-dicarbazole monomers and - in the presence of magnetite nanoparticles. These functionalized nanoparticles have been tested for DNA hybridization experiments.

Journal Article↗

PubMed2003

Therapeutic potential of phosphoinositide 3-kinase inhibitors.

At least one Holy Grail for many academic researchers and pharmaceutical research divisions alike has been to identify therapeutically useful selective PI3K inhibitors. There are several different but closely related PI3Ks which are thought to have distinct biological roles. Until now, however, researchers have been frustrated by poor selectivity of the available pharmacological inhibitors, which are unable to distinguish the different isoforms of PI3K adequately. Fortunately, recently published work gives cause for optimism; there are now several patent specifications published that describe new PI3K inhibitors, including some that are more selective for the delta isoform of PI3K. Given the involvement of PI3Ks in a plethora of biological settings, such isoform-selective inhibitors may have immense potential use for the treatment of patients with inflammatory and autoimmune disorders as well as cancer and cardiovascular diseases.

Autoimmune Diseases↗