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Biomedical subjects

G J Wilson

Publications and source records attributed to G J Wilson.

At least 19 recordsLinked to original sources
PubMed2001

The role of crosslinking in modification of the immune response elicited against xenogenic vascular acellular matrices.

We have used detergent and enzymatic extraction of natural arteries to produce an acellular matrix vascular prosthesis (AMVP). Implanted as an allograft in a canine model, this AMVP shows excellent handling characteristics, low thromboreactivity, no evidence of aneurysm, and exceptional graft patency in the peripheral vasculature. As a first step in the development of xenograft AMVPs, we processed caprine carotid arteries to AMVP and implanted them as femoral interposition grafts in dogs. Explanted xenografts at 4 weeks showed multifocal mixed inflammatory infiltrates and focal destruction of the medial elastin in the inflammatory foci. To further study the immune response to xenogenic AMVP, we implanted canine-derived AMVPs and fresh canine arteries for 4 weeks in a Lewis rat model. Extraction to AMVP markedly reduced the circulating antibody response to the xenogenic implants; however, histological analysis revealed that both xenograft arteries and AMVPs produced a marked immune response with penetration of mononuclear cells into the media and adventitia. To modify the immune response, we applied three crosslinking techniques to the canine AMVPs: glutaraldehyde, polyglycidyl ether, and carbodiimide. All crosslinkers significantly reduced degradation and cellular infiltration of the prostheses. However, crosslinking neither eliminated the chronic inflammatory response surrounding the implants nor reduced the humoral response to the xenogenic materials.

Animals↗
PubMed2001

Aerobic biodegradation of gasoline oxygenates MTBE and TBA.

MTBE degradation was investigated using a continuously stirred tank reactor (CSTR) with biomass retention (porous pot reactor) operated under aerobic conditions. MTBE was fed to the reactor at an influent concentration of 150 mg/l (1.70 mmol/l). A second identical reactor was operated as a control under the same conditions with the addition of 2.66 g/l of sodium azide, to kill any biological activity. Results from these experiments suggest that biomass retention is critical to the degradation of MTBE. The rate of MTBE removal was shown to be related to the VSS concentration. MTBE removal exceeded 99.99% when the VSS concentration in the reactor was over 600 mg/l. Results obtained from batch experiments conducted on mixed liquor samples from the porous pot reactor indicate that the individual rates of biodegradation of MTBE and TBA were higher for initial concentrations of 15 mg/l than for concentrations of 5 mg/l. The presence of TBA at lower concentrations did not effect the rate of MTBE degradation, however higher concentrations of TBA did reduce the rate of biodegradation of MTBE. Denaturing Gradient Gel Electrophoresis (DGGE) analysis reveals that the culture consisted of a community of bacterial organisms of about 6 species.

Bacteria, Aerobic↗
PubMed2000

Acellular bladder matrix allografts in the regeneration of functional bladders: evaluation of large-segment (> 24 cm) substitution in a porcine model.

OBJECTIVES: To evaluate the use of a large-segment (> 24 cm2) bladder substitution with porcine bladder acellular matrix allograft (BAMA) in a large animal model. Materials and methods Bladders were harvested from pigs at the time of necropsy and subjected to detergent and enzymatic extractions to render them acellular. The BAMA produced had the surgical handling and suture-retaining properties of normal bladder tissue. Six pigs had BAMA segments implanted under general anaesthesia, through a low midline abdominal incision and after partial cystectomy. The defect was repaired with a BAMA patch (mean size 43.88 cm2, range 12-72), with no urinary diversion. Two animals each were then killed at 9, 16 and 30 days and the bladders explanted. The native bladder and BAMA patch were analysed morphometrically to evaluate cellular re-population and matrix re-organization. RESULTS: All animals survived surgery; there were no urinary leaks and no stones detected in any of the bladders. At 9 days there was a diffuse infiltration with acute inflammatory cells, but no areas of necrosis. There were isolated areas of smooth muscle cell (SMC) infiltration of the BAMA. At 16 days the luminal surface was lined with a single layer of urothelium, there was stromal infiltration with disorganized SMC and angiogenesis, with mature vessels in the BAMA patch. At 30 days the urothelium was multilayered with organizing groups of SMCs and angiogenesis. The highest cell density was at the periphery of the repopulated BAMA patch, decreasing towards the centre. CONCLUSIONS: The implantation of large patches of BAMA is technically feasible and may prove to be a viable surgical alternative to bladder augmentation with intestinal segments. The advantages of BAMA include the potential for complete and functional regeneration of a bladder substitute. This model provides a tool with which to obtain a better understanding of the cellular and molecular aspects of matrix re-population.

Animals↗
PubMed1999

Chloride channel inhibition blocks the protection of ischemic preconditioning and hypo-osmotic stress in rabbit ventricular myocardium.

The objective of this study was to examine the role of chloride (Cl-) channels in the myocardial protection of ischemic preconditioning (IP). Isolated rabbit ventricular myocytes were preconditioned with 10-minute simulated ischemia (SI) and 20-minute simulated reperfusion (SR) or not preconditioned (control). The myocytes then received 180-minute SI or 45-minute SI/120-minute SR. Indanyloxyacetic acid 94 (IAA-94, 10 micromol/L) or 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, 1 micromol/L) was administered before IP or before SI or SI/SR to inhibit Cl- channels. Electrophysiological studies indicate that these drugs, at the concentrations used, selectively abolished Cl- currents activated under hypo-osmotic conditions (215 versus 290 mOsm). IP significantly (P<0.001) reduced the percentage of dead myocytes after 60-minute (30.8+/-1.3%, mean+/-SEM), 90-minute (35.3+/-1.3%), and 120-minute (39.2+/-1.7%) SI compared with controls (44.7+/-1.6%, 54.5+/-1.3%, and 58.9+/-1.8%, respectively) and after 45-minute SI/120-minute SR (36.3+/-0.6%) compared with control (56.6+/-2.2%). Hypo-osmotic stress also produced protection similar to IP. IAA-94 or NPPB abolished the protection of both IP and hypo-osmotic stress. In buffer-perfused rabbit hearts preconditioned with three 5-minute ischemia/10-minute reperfusion cycles given before the 40-minute long ischemia and 60-minute reperfusion, IP significantly (P<0.0001) reduced infarct size (IP+vehicle, 4.7+/-0.9%, versus control+vehicle, 26.6+/-3.3%; mean+/-SEM). Again, IAA-94 or NPPB abolished the protection of IP. Our results implicate Cl- channels in the IP protection of the myocardium against ischemic/reperfusion injury and demonstrate that hypo-osmotic stress is capable of preconditioning cardiomyocytes.

Alkaloids↗
PubMed1999

Longitudinal relaxation times of 129Xe in rat tissue homogenates at 9.4 T.

Longitudinal relaxation times of 129Xe were measured in homogenates of rat brain, kidney, liver, and lung at varying oxygenation levels as a means to assess the feasibility of magnetic resonance (MR) imaging of tissue using laser-polarized (LP) 129Xe as the signal source. The measured relaxation times ranged from 4.4 +/- 0.4 sec in deoxygenated lung homogenate to 22 +/- 2 sec in deoxygenated brain homogenate. When the LP gas is introduced to the subject via inhalation, these relaxation times are long enough to allow accumulation and subsequent MR imaging of LP 129Xe in tissues. Imaging of dissolved LP 129Xe will yield an intrinsic signal-to-noise ratio (SNR) that is approximately 3% of the proton intrinsic SNR. This relatively low intrinsic SNR is expected to be adequate for some tracer applications. T1 of 129Xe was found to depend on the oxygenation level of the tissue, and the effect of oxygenation is likely dependent on the amount of hemoglobin in the tissue homogenate.

Animals↗
PubMed1999

In situ measurements of skeletal muscle power output using new capacitive strain gauge.

Experiments are described in which a fatigue index is determined for the latissimus dorsi muscle of sheep in situ, using capacitive strain gauges. Parallel experiments for invasive and non-invasive measurements are conducted, measuring global contraction and relaxation rates and shortening duration for paced muscle. The results show that, above one pulse per burst (5 V, 100 microseconds pulsewidth), contraction rates (62 +/- 11 mm s-1) and relaxation rates (50 +/- 7 mm s-1) are constant for unloaded muscle. For one animal, fatigue testing with a 2.5 kg load at six pulses per burst shows shortening rates increasing to a maximum (80 mm s-1) after 30 s and reducing to 5 mm s-1 after 150 s. The decrease in shortening amplitude is used as a fatigue index, log displacement against time. Power output is load dependent, measuring 4.7 W kg-1 with a 2.5 kg load. There is good agreement between the invasive and non-invasive measurements, thus providing a method for monitoring changes in muscle parameters non-invasively during future pacing transformation.

Animals↗
PubMed1999

A comparison of drop jump training methods: effects on leg extensor strength qualities and jumping performance.

The purpose of this study was to determine the effects of two drop jump (DJ) training methods on the strength qualities of the leg extensors and vertical jumping performance. Thirty-five males were allocated to either a control group or one of two training groups, required to perform 72-90 DJ per week for 6 weeks: DJ for maximum rebound height (DJ-H) or DJ for maximum height and minimum ground contact time (DJ-H/t). The subjects were tested before and after the training on leg extensor function for maximum strength and speed-strength under concentric and stretch-shortening cycle muscular actions, and on vertical jumps from a standing position and a run-up. ANOVA with repeated measures showed that a 20% gain in reactive strength (RS) for the DJ-H/t group was significantly greater (p < 0.05) than the other groups, however, this did not transfer to vertical jumping performance. The DJ-H group did not achieve a significant training effect. It was concluded that DJ-H/t method was effective for the development of RS, but training with DJ-H was not intense and/or specific enough to stimulate gains in strength qualities of the leg extensors or jumping performance.

Adult↗
PubMed1999

Clinical outcomes of acute myocarditis in childhood.

OBJECTIVE: To describe clinical outcomes of a paediatric population with histologically confirmed lymphocytic myocarditis. DESIGN: A retrospective review between November 1984 and February 1998. SETTING: A major paediatric tertiary care hospital. PATIENTS: 36 patients with histologically confirmed lymphocytic myocarditis. MAIN OUTCOME MEASURES: Survival, cardiac transplantation, recovery of ventricular function, and persistence of dysrhythmias. RESULTS: Freedom from death or cardiac transplantation was 86% at one month and 79% after two years. Five deaths occurred within 72 hours of admission, and one late death at 1.9 years. Extracorporeal membrane oxygenation support was used in four patients, and three patients underwent heart replacement. 34 patients were treated with intravenous corticosteroids. In the survivor/non-cardiac transplantation group (n = 29), the median follow up was 19 months (range 1.2-131.6 months), and the median period for recovery of a left ventricular ejection fraction to > 55% was 2.8 months (range 0-28 months). The mean (SD) final left ventricular ejection and shortening fractions were 66 (9)% and 34 (8)%, respectively. Two patients had residual ventricular dysfunction. No patient required antiarrhythmic treatment. All survivors reported no cardiac symptoms or restrictions in physical activity. CONCLUSIONS: Our experience documents good outcomes in paediatric patients presenting with acute heart failure secondary to acute lymphocytic myocarditis treated with immunosuppression. Excellent survival and recovery of ventricular function, with the absence of significant arrhythmias, continued cardiac medications, or restrictions in physical activity were the normal outcomes.

Acute Disease↗
PubMed1999

Preclinical evaluation of a rheolytic catheter for percutaneous coronary artery/saphenous vein graft thrombectomy.

The presence of thrombus increases the rate of acute complications and restenosis in percutaneous revascularization of native coronary arteries and saphenous vein grafts. Rheolytic thrombectomy uses high velocity saline jets to create a Bernoulli effect for thrombus entrainment, dissociation, and evacuation of debris, providing a novel approach to the treatment of thrombotic lesions. The study objective was to determine the preclinical safety and effectiveness of a 5 French rheolytic thrombectomy catheter designed for use in coronary arteries and saphenous vein grafts. In vitro testing was performed to evaluate catheter effectiveness (clot removal rate) and safety (particle generation and hemolysis). This was followed by acute (n = 6) and chronic (n = 6) canine studies to determine hemodynamic, angiographic, and histopathologic effects of the catheter. The results showed effective clot removal with minimal embolization: 99.4% of the total clot volume was removed with only 0.1% proximal embolization and 0.5% distal embolization. 98.4% of the embolic particles were less than 10 microm. Canine studies revealed no significant angiographic, hemodynamic, histopathologic, or electrocardiographic abnormalities with the exception of transient heart block in one animal. There was transient hemolysis which normalized within 24 hours with no adverse effects. These results demonstrate the effectiveness and safety of coronary rheolytic thrombectomy and provided the basis for clinical trials to further evaluate this promising new approach for coronary thrombectomy.

Animals↗
PubMed1998

EPR and CD spectroscopy of fast myosin light chain conformation during binding of trifluoperazine.

The conformations of isolated rabbit fast myosin light chains (LCs) were modified using trifluoperazine (TFP), the hydrophobic calmodulin inhibitor. CD spectroscopy showed that TFP altered secondary structural content of the LCs, with half-maximal effects at TFP concentrations of approximately 14-50 microM, which is within the range required to alter muscle fiber contraction in both agonistic and antagonistic ways [Kurebayashi, N. & Ogawa, Y. (1988) J. Physiol. 403, 407-424]. EPR spectroscopy provided structural information from paramagnetic probes on C-terminal domain surfaces. In the absence of TFP, tauR (rotational correlation time) was 1.6 ns for both alkali light chains (ALCs) and 1.8 ns for light chain 2 (LC2). This was faster than expected for proteins of this size (approximately 10 ns). TFP progressively recruited the probes into populations with tauR sevenfold to 12-fold slower, with half-maximal effects at a TFP concentration of approximately 370-800 microM. The differences probably indicate that CD spectroscopy detects changes in protein conformation due to 'specific' TFP binding at the LC hydrophobic core, while less specific binding at higher TFP concentrations is required to effect conformational changes on the protein surfaces near the paramagnetic probes. TFP binding was generally not cooperative. Comparative sequence analysis between calmodulin, troponin C, and myosin LCs indicated considerable conservation between residues expected to bind TFP.

Amino Acid Sequence↗
PubMed1998

Preferential regulation of rabbit cardiac L-type Ca2+ current by glycolytic derived ATP via a direct allosteric pathway.

1. The activity of Ca2+ channels is regulated by a number of mechanisms including direct allosteric modulation by intracellular ATP. Since ATP derived from glycolysis is preferentially used for membrane function, we hypothesized that glycolytic ATP also preferentially regulates cardiac L-type Ca2+ channels. 2. To test this hypothesis, peak L-type Ca2+ currents (ICa) were measured in voltage-clamped rabbit cardiomyocytes during glycolytic inhibition (2-deoxyglucose + pyruvate), oxidative inhibition (cyanide + glucose) or both (full metabolic inhibition; FMI). 3. A 10 min period of FMI resulted in a 40.0 % decrease in peak ICa at +10 mV (-5.1 +/- 0.6 versus -3.1 +/- 0.4 pA pF-1; n = 5, P < 0.01). Similar decreases in peak ICa were observed during glycolytic inhibition using 2-deoxyglucose (-6.2 +/- 0.2 versus -3.7 +/- 0.2 pA pF-1; n = 5, P < 0.01) or iodoacetamide (-6.7 +/- 0.3 versus -3.7 +/- 0.2 pA pF-1; n = 7, P < 0.01), but not following oxidative inhibition (-6.2 +/- 0.4 versus -6.4 +/- 0.3 pA pF-1; n = 5, n.s.). The reduction in ICa following glycolytic inhibition was not mediated by phosphate sequestration by 2-deoxyglucose or changes in intracellular pH. 4. Reductions in ICa were still observed when inorganic phosphate and creatine were included in the pipette, confirming a critical role for glycolysis in ICa regulation. 5. With 5 mM MgATP in the pipette during FMI, peak ICa decreased by only 18.4 % (-6.8 +/- 0.6 versus -5.5 +/- 0.3 pA pF-1; n = 4, P < 0.05), while inclusion of 5 mM MgAMP-PCP (beta,gamma-methyleneadenosine 5'-triphosphate, Mg2+ salt) completely prevented the decrease in peak ICa (-6.9 +/- 0.3 versus -6.5 +/- 0.3 pA pF-1; n = 5, n.s.). 6. Together, these results suggest that ICa is regulated by intracellular ATP derived from glycolysis and does not require hydrolysis of ATP. This regulation is expected to be energy conserving during periods of metabolic stress and myocardial ischaemia.

Adenosine Triphosphate↗
PubMed1998

Eliminating arterial pulsatile strain by external banding induces medial but not neointimal atrophy and apoptosis in the rabbit.

We have examined the role of vessel pulsation and wall tension on remodeling and intimal proliferation in the rabbit infrarenal abdominal aorta. A rigid perivascular polyethylene cuff was used to reduce vessel systolic diameter by 25%, producing a region of reduced circumferential strain. At 6 weeks postoperatively, reduced circumferential strain caused medial atrophy, with 45% reduction of medial area and 30% loss of medial smooth muscle cells. Apoptotic cell death was indicated by DNA fragmentation, propidium iodide staining, and cell morphology. Cuffing the aorta after balloon denudation produced medial atrophy but did not inhibit neointimal growth. At 1 week postoperatively, intimal thickness was slightly decreased in regions with reduced strain; however, intimal thickening in regions of reduced strain was not different from control segments at 3 weeks postoperatively (intimal area was 0.37 +/- 0.05 mm2 with reduced strain and 0.50 +/- 0.08 for controls, mean +/- SEM). We conclude that circumferential strain is a major factor controlling medial structure and cell number, whereas growth of the neointima after injury is not significantly affected by either reduced strain or extensive medial cell death. Vessel cuffing represents a new model of blood vessel remodeling in vivo that involves extensive smooth muscle cell apoptosis.

Animals↗
PubMed1998

Brain damage and myocardial dysfunction: protective effects of magnesium in the newborn pig.

BACKGROUND: Brain damage is associated with myocardial dysfunction resulting from excessive release of endogenous catecholamines and Ca2+ overload. Magnesium ion, a natural Ca2+ blocker, has recently been recognized as a myoprotective agent. METHODS: Myocardial function was assessed in 3- to 7-day-old piglets from pressure-volume data (obtained by the conductance catheter/micromanometer technique) before and for 4 hours after ligation of the aortic arch vessels and was correlated with ultrastructural changes. Group a (n = 6) received MgSO4 immediately after induction of brain damage for 4 hours, whereas group b (n = 6) did not receive MgSO4 and served as control. RESULTS: In both groups after induction of brain damage, there was a significant (p < 0.05) increase in end-systolic elastance and preload-recruitable stroke work that persisted for 1 hour. However, after 2 and 4 hours, there was a significant (p < 0.05) reduction in both variables in group b (end-systolic elastance, 74% +/- 5% and 59% +/- 6%, respectively, and preload-recruitable stroke work, 77% +/- 4% and 64% +/- 3%, respectively, compared with baseline), and in group a, the values returned to baseline. The chamber stiffness index rose significantly (p < 0.05) in group b 15 minutes after induction of brain damage and remained significantly (p < 0.05) higher for 4 hours versus no significant change in group a. Plasma levels of epinephrine and norepinephrine were similar in the groups before and after brain damage. Electron microscopic study showed severe ultrastructural changes in group b and significantly milder changes in group a. CONCLUSIONS: We conclude that MgSO4 may protect the neonatal myocardium when administered immediately after brain damage.

Adrenergic Agonists↗
PubMed1998

Hypersensitivity myocarditis caused by an allergic reaction to cefaclor.

An adolescent girl was seen with acute heart failure 6 days after the onset of a viral illness and otitis media treated with cefaclor. An endomyocardial biopsy specimen revealed active myocarditis with an eosinophilic infiltrate typical of hypersensitivity myocarditis. The patient showed dramatic improvement within 48 hours after withdrawal of the drug and administration of corticosteroids and immunoglobulin.

Biopsy↗
PubMed1998

Stretch-shorten cycle compared with isometric preload: contributions to enhanced muscular performance.

To isolate any difference muscular contraction history may have on concentric work output, 40 trained male subjects performed three separate isokinetic concentric squats that involved differing contraction histories, 1) a concentric-only (CO) squat, 2) a concentric squat preceded by an isometric preload (IS), and 3) a stretch-shorten cycle (SSC) squat. Over the first 300 ms of the concentric movement, work output for both the SSC and IS conditions was significantly greater (154.8 +/- 39.8 and 147.9 +/- 34.7 J, respectively; P < 0.001) compared with the CO squat (129.7 +/- 34.4 J). In addition, work output after the SSC test over the first 300 ms was also significantly larger than that for the corresponding period after the IS protocol (P < 0.05). There was no difference in normalized, integrated electromyogram among any of the conditions. It was concluded that concentric performance enhancement derived from a preceding stretch of the muscle-tendon complex was largely due to the attainment of a higher active muscle state before the start of the concentric movement. However, it was also hypothesized that contractile element potentiation was a significant contributor to stretch-induced muscular performance under these conditions.

Adult↗
PubMed1998

Absorption, distribution, metabolism, and excretion of atevirdine in the rat.

Atevirdine mesylate (U-87201E) is a highly specific nonnucleoside inhibitor of human immunodeficiency virus type 1 reverse transcriptase. The absorption, metabolism, and excretion of atevirdine were investigated in male and female Sprague-Dawley rats after oral administration of nonradiolabeled atevirdine mesylate at doses of 20 mg/kg/day or 200 mg/kg/day for 8 days, with [14C]atevirdine mesylate single doses of 10 mg/kg or 100 mg/kg on study days 1 and 10. The distribution of [14C]atevirdine mesylate was also evaluated by whole-body autoradiography in male and female Sprague-Dawley, pregnant Sprague-Dawley, and male Long-Evans rats after a single 10 mg/kg oral dose. Plasma levels of atevirdine and its N-desethyl and O-desmethyl metabolites were determined by high-performance liquid chromatography (HPLC) with ultraviolet detection, urine and feces were profiled for atevirdine and metabolites by HPLC with radiochemical detection, major metabolites in urine were isolated and identified by nuclear magnetic resonance and mass spectrometry, and minor urinary metabolites were identified by liquid chromatography/mass spectrometry. Atevirdine was rapidly absorbed. The pharmacokinetics of atevirdine were nonlinear. Gender differences in the pharmacokinetics and metabolism of atevirdine were observed, consistent with the involvement of cytochrome P450 3A. Atevirdine effectively crossed the blood-brain barrier and had a high rate of maternal-fetal transfer. At the low doses, <2% of the dose was excreted as unchanged parent drug, while atevirdine constituted 9%-25% of the dose at the high doses. The metabolism of atevirdine was extensive in the rat and involved N-deethylation, O-demethylation, hydroxylation at the C-6 position of the indole ring, and hydroxylation of the pyridine ring.

Animals↗