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Biomedical subjects

C O'Connell

Publications and source records attributed to C O'Connell.

At least 19 recordsLinked to original sources
PubMed2006

Dilatation of the ascending aorta in paediatric patients with bicuspid aortic valve: frequency, rate of progression and risk factors.

OBJECTIVES: To describe the incidence and rate of dilatation of the ascending aorta in children with bicuspid aortic valve (BAV) and to determine factors that predict rapid aortic dilatation. DESIGN: Retrospective cohort study. SETTING: Regional tertiary care children's hospital. PATIENTS: All children aged 0-18 years seen at the authors' institution between 1990 and 2003 with an "isolated" BAV. All patients had had more than one technically adequate echocardiogram, at least six months apart, with concomitant height and weight data. INTERVENTIONS: Offline echocardiographic measurements of multiple levels of the aortic root were completed for each participant at each serial echocardiogram. These measurements were then compared with expected measurements derived from a normal local control population. MAIN OUTCOME MEASURES: Rate of change of the ascending aorta size over time, where aortic size is expressed as the number of standard deviations above or below the mean size expected for a given body surface area (z score). RESULTS: 279 echocardiograms spanning a period of from 9 months to 13.3 years were analysed for 88 patients with BAV. The ascending aorta in the BAV group was larger than expected for body surface area at diagnosis and continued to increase in relative size at each of the four subsequent follow-up echocardiograms. Ascending aortic z score increased at an average rate of 0.4/year. A faster rate of increase in z score was predicted by both larger initial aortic valve gradient and non-use of beta blockers. CONCLUSIONS: Children with BAV are at risk of having a dilated ascending aorta. This risk increases with longer follow up.

Adolescent↗
PubMed2006

Hose instability and wake generation by an intense electron beam in a self-ionized gas.

The propagation of an intense relativistic electron beam through a gas that is self-ionized by the beam's space charge and wakefields is examined analytically and with 3D particle-in-cell simulations. Instability arises from the coupling between a beam and the offset plasma channel it creates when it is perturbed. The traditional electron hose instability in a preformed plasma is replaced with this slower growth instability depending on the radius of the ionization channel compared to the electron blowout radius. A new regime for hose stable plasma wakefield acceleration is suggested.

Journal Article↗
PubMed2004

Molecular characterization of guinea - pig (Cavia porcellus) CD8alpha and CD8beta cDNA.

CD8 is expressed on cytotoxic T cells (CTL) and functions as a coreceptor for recognition of major histocompatibility complex (MHC) class I peptide complexes by the T-cell receptor (TCR). The CD8 molecule consists of two subunits (alpha and beta) and exists either as a heterodimer (alphabeta) or a homodimer (alphaalpha). We report the cloning of full-length cDNAs of guinea pig CD8alpha and CD8beta. The deduced amino acid sequence of CD8alpha and CD8beta reveals characteristic structural features including a signal peptide, an immunoglobulin (Ig) variable-like region, hinge region, transmembrane, and cytoplasmic domains. In addition to the full-length cDNA, a splice variant of CD8beta cDNA was observed, suggesting splicing events as reported for human CD8beta. The sequence homology of guinea pig CD8 indicates greater homology to human, canine, and feline counterparts than to rodent CD8. As the guinea pig serves as an ideal non-primate animal model to several human infectious diseases, such as syphilis, tuberculosis, and chlamydial genital and ocular infection, the CD8 sequence information provides a necessary molecular tool for studying the cell-mediated immune response.

Alternative Splicing↗
PubMed2003

Plasma wakefield acceleration in self-ionized gas or plasmas.

Tunnel ionizing neutral gas with the self-field of a charged particle beam is explored as a possible way of creating plasma sources for a plasma wakefield accelerator [Bruhwiler et al., Phys. Plasmas (to be published)]. The optimal gas density for maximizing the plasma wakefield without preionized plasma is studied using the PIC simulation code OSIRIS [R. Hemker et al., in Proceeding of the Fifth IEEE Particle Accelerator Conference (IEEE, 1999), pp. 3672-3674]. To obtain wakefields comparable to the optimal preionized case, the gas density needs to be seven times higher than the plasma density in a typical preionized case. A physical explanation is given.

Journal Article↗
PubMed2001

Binding of C4b-binding protein to porin: a molecular mechanism of serum resistance of Neisseria gonorrhoeae.

We screened 29 strains of Neisseria gonorrhoeae and found 16/21 strains that resisted killing by normal human serum and 0/8 serum sensitive strains that bound the complement regulator, C4b-binding protein (C4bp). Microbial surface-bound C4bp demonstrated cofactor activity. We constructed gonococcal strains with hybrid porin (Por) molecules derived from each of the major serogroups (Por1A and Por1B) of N. gonorrhoeae, and showed that the loop 1 of Por1A is required for C4bp binding. Por1B loops 5 and 7 of serum-resistant gonococci together formed a negatively charged C4bp-binding domain. C4bp-Por1B interactions were ionic in nature (inhibited by high salt or by heparin), whereas the C4bp-Por1A bond was hydrophobic. Only recombinant C4bp mutant molecules containing the NH2-terminal alpha-chain short consensus repeat (SCR1) bound to both Por1A and Por1B gonococci, suggesting that SCR1 contained Por binding sites. C4bp alpha-chain monomers did not bind gonococci, indicating that the polymeric form of C4bp was required for binding. Using fAb fragments against C4bp SCR1, C4bp binding to Por1A and Por1B strains was inhibited in a complement-dependent serum bactericidal assay. This resulted in complete killing of these otherwise fully serum resistant strains in only 10% normal serum, underscoring the importance of C4bp in mediating gonococcal serum resistance.

Amino Acid Sequence↗
PubMed2001

C4bp binding to porin mediates stable serum resistance of Neisseria gonorrhoeae.

Screening of 29 strains of Neisseria gonorrhoeae revealed that 16/21 serum resistant strains and 0/8 serum sensitive strains bound C4bp, suggesting that C4bp binding to gonococci could contribute to serum resistance. C4bp bound to gonococci retained cofactor (C4b-degrading) function. Using allelic exchange to construct strains with hybrid Por1A/B molecules, we demonstrate that the N-terminal loop (loop 1) of Por1A is required for C4bp binding. Serum resistant Por1B gonococcal strains also bind C4bp via their Por molecule. Using allelic exchange and site-directed mutagenesis, we have shown that loops 5 and 7 together form a negatively charged C4bp binding domain. C4bp-Por1B interactions are ionic in nature (inhibited by high salt as well as by heparin), while the C4bp-Por1A bond is hydrophobic. mAbs directed against SCR1 of the alpha-chain of C4bp inhibit C4bp binding to both Por1A and Por1B. Furthermore, only recombinant C4bp mutant molecules that contain alpha-chain SCR1 bind both Por1A and Por1B gonococci, confirming that SCR1 contains Por binding sites. C4bp alpha-chain monomers do not bind strains with either Por molecule, suggesting that the polymeric form of C4bp is required for binding to gonococci. Inhibition of C4bp binding to serum resistant Por1A and Por1B strains in a serum bactericidal assay using fAb fragments against C4bp SCR1 results in complete killing at 30 min of otherwise fully serum resistant strains in only 10% normal serum, underscoring the role of C4bp in mediating gonococcal serum resistance.

Amino Acid Sequence↗
PubMed2000

Transient spine density increases in the mid-molecular layer of hippocampal dentate gyrus accompany consolidation of a spatial learning task in the rodent.

In previous studies, we observed a transient increase in dendritic spine frequency in the molecular layer of the dentate gyrus at 6h following passive avoidance training [O'Malley A., O'Connell C. and Regan C. M. (1998) Neuroscience 87, 607-613]. To determine if a similar change is associated with spatial forms of learning, we have estimated time-dependent modulations of spine number in the dentate gyrus of the adult rat following water maze training. All animals exhibited significant reductions in the latency to locate the platform over the five training sessions of the single trial (median and interquartile ranges of 60, 8 versus 8, 3 s for trials 1 and 5, respectively) and this improved performance was retained just prior to killing at the 6h post-training time. The unbiased dissector stereological procedure was used to estimate spine number in serial pairs of ultrathin coronal sections obtained at a point 3.3 mm caudal of Bregma. This analysis revealed a significant learning-associated increase in spine number at the 6h post-training time (1.32+/-0.18 spines/microm(3)) as it was not observed in paired controls exposed to the water maze for a similar swim-time (0.66+/-0.11 spines/microm(3)). The increase was transient as spine number returned to control levels at the 72 h post-training time. These spine frequency changes are proposed to reflect increased synapse turnover rate and concomitant change in connectivity pattern in the processing of information for long-term storage.

Animals↗
PubMed2000

CREB phosphorylation coincides with transient synapse formation in the rat hippocampal dentate gyrus following avoidance learning.

Spine density change in the hippocampal dentate gyrus accompanies memory consolidation and coincides with the increased expression of ribosome-rich, hyperchromatic granule cells. Although this suggests increased protein synthesis to be required for synaptic growth in the 5 to 7 h post-training period, little temporal mapping of the associated molecular mechanisms has been done. Here, we demonstrate a similar frequency of hyperchromatic cells in naïve animals and in those sacrificed 6 h post-training, suggesting a transient repression of protein synthesis in the early post-training period. Immunoblot analysis of CREB phosphorylation in the dentate gyrus supported this view, with downregulation from basal levels observed at 2 to 3 h and at 12 h post-training. Protein synthesis reactivation appears to be specific for de novo spine production as no change in spine frequency accompanies the immediate post-training period of depressed protein synthesis. These findings support the view that CREB-mediated gene transcription is a requirement for long-term memory consolidation and may be directly implicated in the process of synaptic growth.

Animals↗
PubMed1999

A culture of change or a change of culture?

As organizations find themselves having to respond to quick changes in rapid succession, at some point the question of whether or not the pace is too much to sustain comes into play. At Sarasota Memorial Hospital, early cultural assessment led to implementation strategies that helped to overcome some of the barriers of major change.

Attitude of Health Personnel↗
PubMed1999

[Administrative perspectives at Sarasota Memorial Hospital].

Sarasota Memorial's Health VISION project goal is to develop an electronic patient record. This requires total reengineering of health care delivery in Sarasota county to provide optimal exchange of aggregate, educational, cost and patient information to hospitals, clinics, offices and homes.

Computer Terminals↗
PubMed1999

A comparison of phonemic, semantic, and alternating word fluency in Parkinson's disease.

Word fluency in 45 medicated non-demented Parkinson's disease (PD) patients and 45 normal control subjects was studied with a Phonemic Word Fluency (PWF) task using the letters F, A, and S, a Semantic Word Fluency (SWF) task using the categories animals, boys' names, and states, and an Alternating Word Fluency (AWF) task requiring the person to alternate between colors and occupations, animals and states, and words beginning with C and P. The number of words generated did not differ for trials with F, A, S, or states, but PD patients generated significantly fewer animal names and boys' names. PD patients also generated significantly fewer words on each of the three AWF trials. The PD patients scored 21% lower than the normal control group on the total AWF score, but only 10% lower for the PWF and SWF scores. The greater impairment on the AWF task which requires the use of internal attentional control to rapidly shift mental set can be considered a type of executive functioning deficit. This is consistent with the growing literature suggesting frontal systems dysfunction in PD and with the view that dopaminergic treatment only incompletely restores functioning in the frontostriatal system.

Journal Article↗
PubMed1998

Differential response of cortical plate and ventricular zone cells to GABA as a migration stimulus.

A microdissection technique was used to separate differentiated cortical plate (cp) cells from immature ventricular zone cells (vz) in the rat embryonic cortex. The cp population contained >85% neurons (TUJ1(+)), whereas the vz population contained approximately 60% precursors (nestin+ only). The chemotropic response of each population was analyzed in vitro, using an established microchemotaxis assay. Micromolar GABA (1-5 microM) stimulated the motility of cp neurons expressing glutamic acid decarboxylase (GAD), the rate-limiting enzyme in GABA synthesis. In contrast, femtomolar GABA (500 fM) directed a subset of GAD- vz neurons to migrate. Thus, the two GABA concentrations evoked the motility of phenotypically distinct populations derived from different anatomical regions. Pertussis toxin (PTX) blocked GABA-induced migration, indicating that chemotropic signals involve G-protein activation. Depolarization by micromolar muscimol, elevated [K+]o, or micromolar glutamate arrested migration to GABA or GABA mimetics, indicating that migration is inhibited in the presence of excitatory stimuli. These results suggest that GABA, a single ligand, can promote motility via G-protein activation and arrest attractant-induced migration via GABAA receptor-mediated depolarization.

Animals↗
PubMed1998

Studies on the teratogen pharmacophore of valproic acid analogues: evidence of interactions at a hydrophobic centre.

Propyl-4-yn-valproic acid (2-propyl-4-pentynoic acid), an analogue of valproic acid with a triple bond in one alkyl side chain, potently induces exencephaly in mice. Given that propyl-4-yn-valproic acid is a branched chain carboxylic acid, we synthesized a series of analogues with n-alkyl side chains of increasing length and correlated their potential to induce neural tube defects and to inhibit proliferation and induce differentiation in cells of neural origin, the latter being crucial to the orderly structuring of the embryo. All analogues significantly increased the incidence of neural tube defects in the embryos of dams exposed to a single dose of 1.25 mmol/kg on day 8 of gestation. This effect occurred in a dose-dependent manner and the rate of exencephaly increased with the progressive increase in n-alkyl side chain length. Moreover, increasing chain length resulted in a dose-dependent inhibition of C6 glioma proliferation rate over a concentration range of 0-3 mM and this was independent of the cell type employed and mode of estimating proliferative rate. The antiproliferative action of these analogues was associated with profound shape change in neuro-2A neuroblastoma involving extensive neuritogenesis and an associated increase in neural cell adhesion molecule (NCAM) prevalence at points of cell-cell contact, the latter exhibiting a dose-dependent increase when the n-alkyl chain was extended to five carbon units. These results suggest an interaction with a specific site in which the n-alkyl side is proposed to serve as an 'anchor' within a hydrophobic pocket to facilitate the ionic and/or H-bonding of the carboxylic acid and high electron density of the carbon-carbon triple bond.

Animals↗
PubMed1998

Ultrastructural analysis reveals avoidance conditioning to induce a transient increase in hippocampal dentate spine density in the 6 hour post-training period of consolidation.

Concepts underlying memory consolidation invoke change in synapse structure and function. Such concepts relate to change in connectivity pattern enabled by increased synapse number, change in synaptic configuration resulting from overproduction and selective pruning, or structural change in synapse transmission zones. This study undertook the unbiased estimation of learning associated change in dendritic spine number on granule cells in the hippocampal dentate gyrus. Rats were trained to acquire a passive avoidance response after which spine number in the mid-molecular layer of the dorsal dentate gyrus were estimated at increasing post-training times. This showed there to be an increase in spine density with time after training which was initiated at 3 h, and maximal at 6 h. The increase at this latter time was not detected in passive control animals. At 72 h post-training spine density was seen to return to basal levels. These results are consistent with the various models for synapse connectivity change in memory formation whether they relate to altered number or connectivity pattern.

Animals↗