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V Booth

Publications and source records attributed to V Booth.

28 records · Page 2Linked to original sources
PubMed1997

Compartmental model of vertebrate motoneurons for Ca2+-dependent spiking and plateau potentials under pharmacological treatment.

In contrast to the limited response properties observed under normal experimental conditions, spinal motoneurons generate complex firing patterns, such as Ca2+-dependent regenerative spiking and plateaus, in the presence of certain neurotransmitters and ion-channel blockers. We have developed a quantitative motoneuron model, based on turtle motoneuron data, toinvestigate the roles of specific ionic currents and the effects of their soma and dendritic distribution in generating these complex firing patterns. In addition, the model is used to explore the effects of multiple ion channel blockers and neurotransmitters that are known to modulate motoneuron firing patterns. To represent the distribution of ionic currents across the soma and dendrites, the model contains two compartments. The soma compartment, representing the soma and proximal dendrites, contains Hodgkin-Huxley-like sodium (INa) and delayed rectifier K+ (IK-dr) currents, an N-like Ca2+ current (ICa-N), and a calcium-dependent K+ current [IK(Ca)]. The dendritic compartment, representing the lumped distal dendrites, contains, in addition to ICa-N and IK(Ca) as in the soma, a persistent L-like calcium current (ICa-L). We determined kinetic parameters for INa, IK-dr, ICa-N, and IK(Ca) in order to reproduce normal action-potential firing observed in turtle spinal motoneurons, including fast and slow afterhyperpolarizations (AHPs) and a linear steady-state frequency-current relation. With this parameter set as default, a sequence of pharmacological manipulations were systematically simulated. A small reduction of IK-dr [mimicking the experimental effect of tetraethylammonium (TEA) in low concentration] enhanced the slow AHP and caused calcium spiking (mediated by ICa-N) when INa was blocked. Firing patterns observed experimentally in high TEA [and tetrodotoxin (TTX)], namely calcium spikes riding on a calcium plateau, were reproduced only when both IK-dr and IK(Ca) were reduced. Dendritic plateau potentials, mediated by ICa-L, were reliably unmasked when IK(Ca) was reduced, mimicking the experimental effect of the bee venom apamin. The effect of 5-HT, which experimentally induces the ability to generate calcium-dependent plateau potentials but not calcium spiking, was reproduced in the model by reducing IK(Ca) alone. The plateau threshold current level, however, was reduced substantially if a simultaneous increase in ICa-L was simulated, suggesting that serotonin (5-HT) induces plateau potentials by regulating more than one conductance. The onset of the plateau potential showed significant delays in response to near-threshold, depolarizing current steps. In addition, the delay times were sensitive to the current step amplitude. The delay and its sensitivity were explained by examining the model's behavior near the threshold for plateau onset. This modeling study thus accurately accounts for the basic firing behavior of vertebrate motoneurons as well as a range of complex firing patterns invoked by ion-channel blockers and 5-HT. In addition, our computational results support the hypothesis that the electroresponsiveness of motoneurons depends on a nonuniform distribution of ionic conductances, and they predict modulatory effects of 5-HT and properties of plateau activation that have yet to be tested experimentally.

Action Potentials↗
PubMed1996

Passive immunization with monoclonal antibodies against Porphyromonas gingivalis in patients with periodontitis.

Selective inhibition of recolonization of Porphyromonas gingivalis was investigated by topical application of monoclonal antibody (MAb). To select a MAb to P. gingivalis with the potential for recognizing most strains of P. gingivalis, we examined seven MAbs, one of which (MAb 61BG 1.3) recognized all 22 laboratory strains and serotypes of P. gingivalis tested as well as 105 human clinical isolates. A comparative study of the number of P. gingivalis bacteria identified by conventional culture and immunofluorescence with MAb 61BG 1.3 showed a very significant correlation between the two methods (Spearman r = 0.85, P < 0.001). Fourteen patients with periodontitis, who harbored P. gingivalis in their subgingival plaque, were treated by root planing and with metronidazole to suppress any detectable P. gingivalis. In this double-blind study, the patients were then divided randomly into two groups; one was treated with MAb to P. gingivalis, and the other was treated with saline. Each patient had four subgingival applications of 3 micrograms of MAb (or saline) per tooth at 1, 3, 7, and 10 days after P. gingivalis was suppressed. The number of P. gingivalis bacteria was then monitored, and significantly less recolonization of the sites with the most severe periodontitis was found in the MAb-treated patients than in the control patients (P < 0.01). This was evident at 6 and 9 months after the application of MAb, but by 12 months, P. gingivalis, was also found to recolonize these sites in two of the MAb-treated patients. The effect of MAb was specific to P. gingivalis, since the numbers of spirochetes were not significantly different between the two groups. However, no significant difference in any clinical periodontal indices between the immunized and control patients at 6 and 12 months was observed. This is the first demonstration that a putative periodontal pathogen can be selectively prevented from recolonization for up to 9 months in sites with the most severe periodontitis. This strategy could be used to establish directly in humans whether a microorganism is involved in the pathogenesis of periodontitis, by repeated application of the corresponding MAb at about 6-month intervals and by comparing the clinical indices between the MAb-treated and control patients.

Adult↗
PubMed1996

Characterization of an adherence and antigenic determinant of the ArgI protease of Porphyromonas gingivalis which is present on multiple gene products.

This study was performed to characterize the antigen(s) recognized by a panel of monoclonal antibodies (MAbs) produced to be specific for Porphyromonas gingivalis whole cells which we had previously shown to bind to epitopes recognized by sera from periodontitis patients. Preliminary data had suggested that the arginine-specific proteases of P. gingivalis (ArgI, ArgIA, and ArgIB) contained the antigenic determinants of four of these antibodies (MAbs 1A1, 2B/H9, 7D5, and 3B1). The location of the binding sites was examined with purified P. gingivalis enzymes and recombinant regions of the ArgI polyprotein expressed by subclones of the prpR1 gene in Escherichia coli XL-1 Blue cells. All four antibodies were reactive with protein determinants within the beta subunit, a hemagglutinin and/or adhesin component, of the ArgI dimer. MAb 1A1 strongly inhibited the agglutination of human erythrocytes by P. gingivalis W50 culture supernatant, suggesting that the binding site for this antibody contains residues which are critical for the interaction with the erythrocyte surface. The determinant for MAb 1A1 was examined further by construction of a set of truncated forms of the beta component expressed as fusion proteins with glutathione S-transferase at the N terminus. Analysis of these constructs mapped the binding site for MAb 1A1 to PrpRI residues G-907 to T-931, GVSPKVCKDV TVEGSNEFAP VQNLT. Western blot (immunoblot) analysis of P. gingivalis whole-cell proteins demonstrated that MAb 1A1 reacts with several proteins in the Mr range of 20,000 to 120,000. Furthermore, an oligonucleotide probe corresponding to the coding sequence for the region of the ArgI beta component containing the MAb 1A1 binding site hybridized to multiple bands on genomic digests of P. gingivalis DNA. These data indicate that the MAb 1A1 epitope may be a component of a binding domain common to multiple gene products of this organism and may thus represent a functionally important target of the host's specific immune response to P. gingivalis in periodontal disease.

Adhesins, Bacterial↗
PubMed1995

A minimal, compartmental model for a dendritic origin of bistability of motoneuron firing patterns.

Various nonlinear regenerative responses, including plateau potentials and bistable repetitive firing modes, have been observed in motoneurons under certain conditions. Our simulation results support the hypothesis that these responses are due to plateau-generating currents in the dendrites, consistent with a major role for a noninactivating calcium L-type current as suggested by experiments. Bistability as observed in the soma of low- and higher-frequency spiking or, under TTX, of near resting and depolarized plateau potentials, occurs because the dendrites can be in a near resting or depolarized stable steady state. We formulate and study a two-compartment minimal model of a motoneuron that segregates currents for fast spiking into a soma-like compartment and currents responsible for plateau potentials into a dendrite-like compartment. Current flows between compartments through a coupling conductance, mimicking electrotonic spread. We use bifurcation techniques to illuminate how the coupling strength affects somatic behavior. We look closely at the case of weak coupling strength to gain insight into the development of bistable patterns. Robust somatic bistability depends on the electrical separation since it occurs only for weak to moderate coupling conductance. We also illustrate that hysteresis of the two spiking states is a natural consequence of the plateau behavior in the dendrite compartment.

Animals↗
PubMed1994

Preliminary characterisation of antigens recognised by monoclonal antibodies raised to Porphyromonas gingivalis and by sera from patients with periodontitis.

A panel of 15 monoclonal antibodies (MAbs) was raised to Porphyromonas gingivalis and used to characterise the antigens which they recognise by ELISA, immunofluorescence (IF), Western blotting and patient serum inhibition studies. All the MAbs were specific for P. gingivalis and did not recognise 24 other species. Eight MAbs gave bright ring-like staining patterns against the majority of serotypes of P. gingivalis tested by IF. The antibodies could be grouped into 5 different antigen recognition profiles on Western blotting, and ELISA indicated that 8 of them bound to a capsular extract. Five antibodies bound to antigenic determinants recognised by sera from patients with periodonitis and 4 of these (1A1, 2B/H9, 3B1, 7D5) bound to a P. gingivalis 47kDa protease preparation on Western blotting. These antibodies are potentially useful for the purification and characterisation of biologically active components of P. gingivalis that are recognised by sera from patients with periodontitis.

Adult↗
PubMed1992

Effectiveness, efficiency, excellence: can they coexist in health care?

The conference certainly provided a great deal of food-for-thought for participants. From the imperatives of funding restraint, presented by Dr Scully and Professor Manga, to the public attitudes and opinions research presented by Allan Gregg and the anticipated public policy initiatives presented by Senator Kirby, the audience was challenged to take a new look at health care. Chief Ovide Mercredi presented a very earnest plea on behalf of the aboriginal people of Canada for restoration of their dignity and self-determination, as a key to better mental and physical health. The message to health care leaders was that quality improvement not only works, but also leads to more efficient use of resources. Dr Donald Berwick blew away the myths that often prevent organizations from establishing quality improvement programs and presented a blueprint for success. Other speakers gave examples of successful QI programs they were personally involved in. One of the most interesting presentations was Dr Naylor's able exposition of the role of research in assuring quality. This must have opened many eyes to how resources can be used without real benefit to patients, when proper outcome measurement is not used. Indeed, outcome measures may be an important key to dealing with some of the problems facing health care.

Canada↗
PubMed1989

The oral health of a group of 15-17 year old British school children of different ethnic origin.

The influence of ethnic origin on the oral health of a group of 472 British schoolchildren aged 15-17 years attending two adjacent schools was investigated. Ethnic origin was assessed as European (E; n = 197), Afro-Caribbean (AC; n = 97) and Asian (As; n = 140) leaving 38 subjects of other or mixed origin. Plaque, bleeding on probing and subgingival retentive factors, together with probing depths and attachment loss were recorded at the four approximal sites of teeth 16, 11, 26, 36, 31, 46. DMFT scores were collected for the whole mouth. Socio-economic status was assessed using a Classification of Residential Neighbourhoods (ACORN). Multiple regression analysis indicated that ethnic origin had a significant influence on plaque, subgingival calculus, gingivitis, pockets and DMFT scores. The overall prevalence of periodontitis was 11.2 per cent; European, Afro-Caribbean and Asian groups had prevalences of 3, 21 and 14 per cent respectively.

Adolescent↗
PubMedDate not supplied

A temporal mechanism for generating the phase precession of hippocampal place cells.

The phase relationship between the activity of hippocampal place cells and the hippocampal theta rhythm systematically processes as the animal runs through the region in an environment called the place field of the cell. We present a minimal biophysical model of the phase precession of place cells in region CA3 of the hippocampus. The model describes the dynamics of two coupled point neurons--namely, a pyramidal cell and an interneuron, the latter of which is driven by a pacemaker input. Outside of the place field, the network displays a stable, background firing pattern that is locked to the theta rhythm. The pacemaker input drives the interneuron, which in turn activates the pyramidal cell. A single stimulus to the pyramidal cell from the dentate gyrus, simulating entrance into the place field, reorganizes the functional roles of the cells in the network for a number of cycles of the theta rhythm. In the reorganized network, the pyramidal cell drives the interneuron at a higher frequency than the theta frequency, thus causing a systematic precession relative to the theta input. The frequency of the pyramidal cell can vary to account for changes in the animal's running speed. The transient dynamics end after up to 360 degrees of phase precession when the pacemaker input to the interneuron occurs at a phase to return the network to the stable background firing pattern, thus signaling the end of the place field. Our model, in contrast to others, reports that phase precession is a temporally, and not spatially, controlled process. We also predict that like pyramidal cells, interneurons phase precess. Our model provides a mechanism for shutting off place cell firing after the animal has crossed the place field, and it explains the observed nearly 360 degrees of phase precession. We also describe how this model is consistent with a proposed autoassociative memory role of the CA3 region.

Action Potentials↗