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Biomedical subjects

David Parker

Publications and source records attributed to David Parker.

At least 19 recordsLinked to original sources
PubMed2006

Modulation of cellular and synaptic variability in the lamprey spinal cord.

Variability is increasingly recognized as a characteristic feature of cellular, synaptic, and network properties. While studies have traditionally focused on mean values, significant effects can result from changes in variance. This study has examined cellular and synaptic variability in the lamprey spinal cord and its modulation by the neuropeptide substance P. Cellular and synaptic variability differed in different types of cell and synapse. Substance P reduced the variability of subthreshold locomotor-related depolarizations and spiking in motor neurons during network activity. These effects were associated with a reduction in the variability of spiking in glutamatergic excitatory network interneurons and with a reduction in the variance of excitatory interneuron-evoked excitatory postsynaptic potentials (EPSPs). Substance P also reduced the variance of postsynpatic potentials (PSPs) from crossing inhibitory and excitatory interneurons, but it increased the variance of inhibitory postsynpatic potentials (IPSPs) from ipsilateral inhibitory interneurons. The effects on the variance of different PSPs could occur with or without changes in the PSP amplitude. The reduction in the variance of excitatory interneuron-evoked EPSPs was protein kinase A, calcium, and N-methyl-d-aspartate (NMDA) dependent. The NMDA dependence suggested that substance P was acting postsynaptically. This was supported by the reduced variability of postsynaptic responses to glutamate by substance P. However, ultrastructural analyses suggested that there may also be a presynaptic component to the modulation, because substance P reduced the variability of synaptic vesicle diameters in putative glutamatergic terminals. These results suggest that cellular and synaptic variability can be targeted for modulation, making it an additional source of spinal cord plasticity.

Action Potentials↗
PubMed2006

Synthesis and characterisation of dimeric eight-coordinate lanthanide(III) complexes of a macrocyclic tribenzylphosphinate ligand.

The macrocyclic ligand 1,4,7,10-tetraazacyclododecane-1,4,7-triyl(methylenebenzyl-phosphinic acid) H3L3, has been prepared and its complexes with Eu, Gd and Tb(III) studied by NMR, relaxometry, luminescence and single crystal X-ray crystallography. In solution and in the crystal, the complexes have eight-coordinate metal centres with bridging phosphinate groups linking the two twisted square antiprismatic coordination polyhedra. A single stereoisomer crystallises from solution with an RRR and SSS configuration at the P centres in each sub-unit. The relaxivity of [GdL3]2 is low (1.9 mM-1 s-1, 298 K, 20 MHz), consistent with the absence of any proximate water molecules. The terbium dimer possesses a relatively long excited state lifetime (2.47 ms, 298 K).

Journal Article↗
PubMed2006

On the role of the counter-ion in defining water structure and dynamics: order, structure and dynamics in hydrophilic and hydrophobic gadolinium salt complexes.

The crystal structures of the hydrated salts of [Gd.DOTAM]3+ and its more hydrophobic derivative [Gd.]3+, bearing 4 alpha-phenylethyl groups, (both Gd and Yb salts) are reported and compared. The nature of the anion determines the degree of ordering in the lattice and the extent of hydration. These effects are correlated with the results of 17O and 1H NMR measurements of water exchange dynamics in solution. With [Gd.DOTAM]3+, structural ordering or the extent of hydration in the hydrated lattice follows the sequence Cl->Br->I- and this order also defines the water exchange rate in solution: 7.3, 19.5, 33.3x10(4) s-1 (298 K), respectively. For [Gd.]3+ salts, the measured relaxivity is determined purely by the outer sphere term and the water exchange rate at 298 K is very similar (typically 1x10(4) s-1) for chloride, bromide, iodide, acetate, triflate and nitrate salts, notwithstanding the different nature and extent of hydration found in the crystalline lattice.

Journal Article↗
PubMed2006

A cationic lanthanide complex binds selectively to phosphorylated tyrosine sites, aiding NMR analysis of the phosphorylated insulin receptor peptide fragment.

The binding of two cationic europium complexes to a differentially phosphorylated insulin receptor peptide has been studied by emission spectroscopy and (31)P NMR and (1)H NMR TOCSY methods. Analysis of the europium emission and NMR spectral data was consistent with the presence of species in slow exchange on the NMR and emission timescales, in agreement with selective binding of the lanthanide ion to the phospho-tyrosine site, allowing such complexes to be considered as prototypical chemoselective paramagnetic derivatising agents.

Cations↗
PubMed2006

Engineering emissive europium and terbium complexes for molecular imaging and sensing.

Emissive f-block coordination complexes constitute an important class of optical probes, with applications ranging from sensing of bioactive species, high throughput assays and screening protocols in vitro, to time-resolved imaging studies in cellulo or in vivo. The key chemistry issues to be addressed in complex design and characterisation are defined, with an emphasis on the use of emissive europium and terbium complexes and their conjugates in molecular imaging. Both luminescent 'tags' useful in energy transfer studies and 'responsive' systems for sensing are discussed.

Chemistry↗
PubMed2006

Azaxanthones and azathioxanthones are effective sensitisers for europium and terbium luminescence.

Several azaxanthone and azathioxanthone sensitising chromophores have been incorporated into macrocyclic ligands and form well-defined Eu and Tb complexes in polar media. Excitation of the heterocyclic chromophore in the range 330 to 382 nm leads to modest amounts of aromatic fluorescence and relatively efficient metal-based luminescence, with absolute metal-based quantum yields of up to 24% in aqueous media.

Journal Article↗
PubMed2006

A europium complex that selectively stains nucleoli of cells.

A europium complex selectively staining the nucleolus of NIH 3T3, HeLa, and HDF cells is reported. This complex possesses not only the advantage of the long lifetime of europium emission (0.3 ms), but also a chromophore that allows excitation at a relatively long wavelength (lambda(max) = 384 nm) and gives rise to an acceptable quantum yield (9%). The complex can be used both in live cell and fixed cell imaging, giving an average intracellular concentration on the order of 0.5 microM. Strong binding to serum albumin has been demonstrated by examination of the analogous gadolinium complex, studying relaxivity changes with increasing protein concentration. The intracellular speciation of the complex has been examined by circularly polarized emission spectroscopy and is consistent with the presence of more than one europium species, possibly protein bound.

Animals↗
PubMed2006

Glycoconjugates of gadolinium complexes for MRI applications.

Examples of C-4 symmetric, medium MW conjugates incorporating 12 glucose or galactose groups linked via four dendritic wedges to a central Gd complex have been characterised; their enhanced relaxivity is interpreted in terms of effective motional coupling and large contributions from second sphere water molecules.

Gadolinium↗
PubMed2006

Complexities and uncertainties of neuronal network function.

The nervous system generates behaviours through the activity in groups of neurons assembled into networks. Understanding these networks is thus essential to our understanding of nervous system function. Understanding a network requires information on its component cells, their interactions and their functional properties. Few networks come close to providing complete information on these aspects. However, even if complete information were available it would still only provide limited insight into network function. This is because the functional and structural properties of a network are not fixed but are plastic and can change over time. The number of interacting network components, their (variable) functional properties, and various plasticity mechanisms endows networks with considerable flexibility, but these features inevitably complicate network analyses. This review will initially discuss the general approaches and problems of network analyses. It will then examine the success of these analyses in a model spinal cord locomotor network in the lamprey, to determine to what extent in this relatively simple vertebrate system it is possible to claim detailed understanding of network function and plasticity.

Animals↗
PubMed2006

Profile of machine safety in small metal fabrication businesses.

BACKGROUND: Metal working has been identified as an industry with one of the highest rates of non-fatal injury in the United States. However, the systematic evaluation of machine-related hazards is lacking. METHODS: The Minnesota Machine Guarding Study evaluates the effectiveness of a peer-based technical and educational intervention designed to reduce exposure to amputation hazards among workers in small machining/metal working businesses. The data presented here provide a profile of machine guarding in small (5-100 employees) metal fabrication businesses in Minnesota. A set of checklists to quantify machine-guarding practices were developed. Up to 25 randomly selected machines were evaluated in each facility. In addition, walk-through surveys were conducted to assess machine-related safety practices and programs (e.g., lock out-tag out). RESULTS: A total of 824 machines were evaluated. Overall, 55% (SD 11%) of items addressing machine guarding were present. No single machine complied with all critical safety requirements. Shops with safety committees tended to have better scores than did shops without safety committees. Thirty-five percent of all businesses had established machine guarding procedures and 17% provided training in machine guarding (e.g., use of machine guards and devices in daily operations) to their employees. CONCLUSIONS: These data indicate that machine guarding and related safety programs in small metal fabrication businesses were inadequate. The data also suggest that safety committees are an important component in improving machine safety and related programs in small businesses.

Equipment Safety↗
PubMed2006

Contralateral suppression of otoacoustic emissions in children with specific language impairment.

OBJECTIVE: The purpose of the investigation was to determine whether a group of children with specific language impairments (SLI) have reduced peripheral auditory processes thought to be associated with speech-in-noise intelligibility. DESIGN: Transient evoked otoacoustic emissions (TEOAE) and their suppression by the efferent activity of the medial olivocochlear system (MOCS) in response to contralateral acoustic stimulation were used to compare these processes in 18 children with SLI and 21 controls. RESULTS: The results revealed no group difference in TEOAE suppression effect or left/right asymmetry of TEOAE suppression effect. CONCLUSIONS: These results suggest that children with SLI do not have auditory processing problems at this peripheral level casting doubt on a hypothesized relationship between strength of MOCS activity and language impairment.

Auditory Perceptual Disorders↗
PubMed2006

Functional analysis of Ca3.2 T-type calcium channel mutations linked to childhood absence epilepsy.

PURPOSE: Childhood absence epilepsy (CAE) is an idiopathic form of seizure disorder that is believed to have a genetic basis. METHODS: We examined the biophysical consequences of seven mutations in the Ca(v)3.2 T-type calcium channel gene linked to CAE. RESULTS: Of the channel variants examined, one of the mutants, a replacement of glycine 848 in the domain II-S2 region with serine, resulted in significant slowing of the time courses of both activation and inactivation across a wide range of membrane potentials. These changes are consistent with increased channel activity in response to prolonged membrane depolarizations. CONCLUSIONS: Taken together, these findings suggest that such little changes in channel gating may contribute to the etiology of CAE.

Animals↗
PubMed2005

Synthesis and characterisation of highly emissive and kinetically stable lanthanide complexes suitable for usage "in cellulo".

The synthesis and photophysical characterisation are reported of a series of cationic, neutral and anionic europium and terbium complexes based on structurally related, nonadentate ligands based on the cyclen macrocycle. Each complex incorporates a tetraazatriphenylene moiety and overall absolute emission quantum yields are in the range 15-40% in aerated aqueous media. Dynamic quenching of the lanthanide excited state occurs with electron-rich donors, e.g. iodide, ascorbate and urate, and a mechanistic interpretation is put forward involving an electron transfer process. The cationic lanthanide complexes are taken up by NlH/3T3 cells and tend to localise inside the cell nucleus.

Animals↗
PubMed2005

Machine safety evaluation in small metal working facilities: an evaluation of inter-rater reliability in the quantification of machine-related hazards.

BACKGROUND: Each year there are an estimated 4.2-6.7 amputations per 10,000 workers in the metal fabrication trades in the United States. The Minnesota Machine Guarding Study evaluates the effectiveness of a peer-based technical and educational intervention designed to reduce exposure to amputation hazards among workers in small machining/metal working shops. The study reported here involved the development and evaluation of methods for measuring machine safety, which will be used in the intervention study. METHODS: Using OSHA regulations, ANSI standards, and industry best practices, we developed 23 machine-safety scorecards. The safety scores were dependent on the presence or absence of guards, other safety devices and implements, and the presence or absence of acceptable administrative programs. Inter-rater reliability was assessed for the evaluation of eight types of commonly used metal fabrication machines. RESULTS: Of the 23 most common types of machines, there were a sufficient number of machines to evaluate inter-rater reliability for eight types. Three raters in four shops assessed fifty-nine machines. Overall, the kappa statistic ranged from 0.57 to 0.84, indicating good to very good concordance between raters. In general, machines did not fare well with regard to compliance with current standards. DISCUSSION: The ability to assess machine-related hazards is important in industries where it is difficult to identify and count injuries in a timely fashion. Machinists and safety professionals may use this scoring system as a means of reproducible assessment of machine safety.

Accidents, Occupational↗