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Biomedical subjects

Stephen Bell

Publications and source records attributed to Stephen Bell.

8 recordsLinked to original sources

Safety and efficacy of epicardial cryoablation in a canine model.

OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of cryoablation in a closed chest canine epicardial ablation model. BACKGROUND: Limitations of radiofrequency energy in the epicardial space warrants investigation of alternative energy sources. METHODS: A linear-tip catheter with a 3-cm freezing element and a 6-mm-tip catheter were used to create epicardial atrial and ventricular cryolesions. Epicardial coronary arteries were targeted to evaluate the effects of cryoablation on epicardial vessels. Cryoablation was performed at -90 degrees C for 4 minutes per lesion. Pathologic examination of the hearts was performed. Lesions were stained with tetrazolium chloride, analyzed grossly, and examined histologically. RESULTS: Ten of 11 linear catheter atrial lesions were transmural (average depth 1.5 +/- 1.3 mm). Only three of 13 6-mm-tip atrial lesions were transmural (average depth 1.1 +/- 1.2 mm). Ventricular lesions were continuous and not transmural (average depth of lesion for the linear and 6-mm-tip catheters: 2.7 +/- 1.3 mm and 1.6 +/- 0.7 mm, respectively). Angiographic stenosis (20-100%) during freezing was detected in 9 of 28 lesions, with TIMI III flow present in all vessels 5 minutes following thaw. Neointimal proliferation was present in 13 vessels, with no evidence of damage in vessels with internal diameters greater than 0.7 mm. Occlusive injury was identified in one small branch vessel. CONCLUSIONS: Creation of transmural lesions was possible in the atria but not in the ventricles. Cryothermal ablation can cause neointimal proliferation, with the probability that damage will be directly proportional to lesion depth and inversely proportional to vessel diameter.

Animals↗

Ab initio study of the barriers to methyl torsion and torsional frequencies of acetyl molecules.

A wide range of ab initio and hybrid density functional methods and basis sets have been employed to calculate the barriers to methyl internal rotation in a range of molecules with the acetyl moiety. Comparison is made of the computed torsional frequency with the experimental torsional frequency, nu(obs), for each molecule. With the MP2/6-311+G(3df,2p) combination of method and basis set, the agreement is better than 4 cm-1 for most of the molecules, where nu(obs) or the V3 barrier is well-determined experimentally.

Acetaldehyde↗

Phytophotodermatitis in grounds operatives.

Occupational dermatoses account for a significant proportion of work-related morbidity. Phytophotodermatitis is an unusual work-related dermatosis, but should be considered in the differential diagnosis of such conditions. An outbreak of 'strimmer rash' is described in three grounds operatives. The identification, aetiology and management of the condition are discussed.

Adult↗

Conjugate addition of organocopper reagents to gamma-alkoxybutenolides and application to the synthesis of non-racemic alkyl cyclopentenones.

Simple organocopper reagents are shown to undergo anti-stereoselective 1,4-addition to menthyloxy-substituted lactone 1 in the presence of BF3.OEt2; the Lewis acid causes partial epimerisation of the acetal centre after conjugate addition. Enolate alkylation of the adducts leads to di- and trisubstituted lactones that are converted, in favourable cases, into di- and trisubstituted cyclopentenones.

Copper↗

Procaspase 3 expression in ovarian carcinoma cells increases survivin transcription which can be countered with a dominant-negative mutant, survivin T34A; a combination gene therapy strategy.

Increased survivin expression is a negative prognostic marker in many tumours, including ovarian cancer. We show here that ovarian carcinoma cells upregulate survivin transcription in response to increased expression of the proapoptotic protein procaspase 3. We have utilized this observation in a combination gene therapy strategy using adenoviral constructs expressing the dominant-negative mutant survivin T34A (Ad Survivin T34A) and procaspase 3 (Ad Caspase 3) in ovarian carcinoma cell lines. Transfection of ovarian carcinoma cells with Ad Survivin T34A induces apoptosis via a caspase 9-mediated pathway that is not affected by cell cycle block prior to G2/M. Ad Survivin T34A-induced apoptosis can be significantly enhanced by cotransfection with Ad Caspase 3, and the combination of Ad Survivin T34A and Ad Caspase 3 leads to a significant increase in survival in a murine intraperitoneal ovarian carcinoma model with some long-term survivors. This suggests that inhibiting endogenous survivin activity while also delivering high levels of procaspase 3 allow proteolytic cleavage and activation of the terminal caspase cascade leading to tumour cell death.

Adenoviridae↗

A resonance Raman, surface-enhanced resonance Raman, IR, and ab initio vibrational spectroscopic study of nickel(II) tetraazaannulene complexes.

The IR and resonance Raman spectra of the nickel(II) complexes of dibenzo[b,i][1,4,8,11]tetraaza[14]annulene (TAA) and 5,7,12,14-tetramethyldibenzo[b,i][1,4,8,11]tetraaza[14]annulene (TMTAA) have been measured and compared with ab initio calculations of the vibrational wavenumbers at the B3-LYP level using the LanL2DZ basis set. An excellent fit is found between the experimental and calculated data, enabling precise vibrational assignments to be made. Surface-enhanced resonance Raman spectra were obtained following adsorption on Ag electrodes, with potentials in the range -0.1 to -1.1 V vs Ag/AgCl. There is evidence for contributions from both the electromagnetic and charge transfer (CT) surface enhancement mechanisms. The data indicate that variations in band intensities with electrode potential can be interpreted in terms of the CT mechanism.

Journal Article↗

Novel integrating adenoviral/retroviral hybrid vector for gene therapy.

A hybrid adenoviral vector system was designed to incorporate an excisable retroviral cassette that can be stably integrated into the host cell genome. The vector contains the terminal sequences of two Moloney murine leukemia virus retroviral long terminal repeats (LTRs), fused to form a junction fragment, and is flanked by two loxP recognition sequences. Cre recombinase-directed excision liberates a circular, double-stranded DNA molecule containing the LTR junction fragment. Despite the natural intermediate for retroviral integrase being a linear DNA molecule, we show that, in the presence of Cre and retroviral Gag and Pol, the excised circle can be integrated into the target cell genome through both specific integrase (Int)-directed mechanisms and by a random integration process. The loxP cassette, carrying in addition a selectable marker gene, was incorporated into the E1-deleted region of an adenoviral vector. Infection of cells expressing Cre, Gag, and Pol generated clones that survived long term in drug selection (>3 months). Int-mediated integration was demonstrated in seven of nine clones by sequencing of the integration sites. In addition, the introduction of the loxP cassette into 293 cells coexpressing Cre and Int alone in the absence of other Gag and Pol proteins was sufficient to catalyze the integration mechanism. These experiments demonstrate that it is possible to generate high-titer adenovirus-mediated delivery of a C-type retroviral provirus that can subsequently undergo retroviral Int-mediated integration into dividing and nondividing cells.

Adenoviruses, Human↗