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Biomedical subjects

M Harrison

Publications and source records attributed to M Harrison.

At least 55 records · Page 3Linked to original sources
PubMed2000

Glucoamylase: structure/function relationships, and protein engineering.

Glucoamylases are inverting exo-acting starch hydrolases releasing beta-glucose from the non-reducing ends of starch and related substrates. The majority of glucoamylases are multidomain enzymes consisting of a catalytic domain connected to a starch-binding domain by an O-glycosylated linker region. Three-dimensional structures have been determined of free and inhibitor complexed glucoamylases from Aspergillus awamori var. X100, Aspergillus niger, and Saccharomycopsis fibuligera. The catalytic domain folds as a twisted (alpha/alpha)(6)-barrel with a central funnel-shaped active site, while the starch-binding domain folds as an antiparallel beta-barrel and has two binding sites for starch or beta-cyclodextrin. Certain glucoamylases are widely applied industrially in the manufacture of glucose and fructose syrups. For more than a decade mutational investigations of glucoamylase have addressed fundamental structure/function relationships in the binding and catalytic mechanisms. In parallel, issues of relevance for application have been pursued using protein engineering to improve the industrial properties. The present review focuses on recent findings on the catalytic site, mechanism of action, substrate recognition, the linker region, the multidomain architecture, the engineering of specificity and stability, and roles of individual substrate binding subsites.

Amino Acid Sequence↗
PubMed2000

Repeat general anaesthesia for paediatric dentistry.

AIMS: To investigate patterns of referral, disease and treatment for healthy children who had received two or more dental general anaesthetics (DGA) for exodontia. METHODS: Records from 200 episodes of repeat DGA were studied retrospectively. RESULTS: The mean age of patients at first referral was 5y4m, and the mean interval before repeat was 22 months. Self-referrals rose from 14% at DGA1 to 30% at DGA2. New caries at second referral, where all diagnosed disease had been treated at DGA1, accounted for only 15% of the total. Where a specific request was made in the referral, only 8% of letters matched the charting made in hospital. 30% of all specific requests were honoured, but then required treatment for previously diagnosed caries at DGA2.75% of single-tooth extractions required repeat DGA for caries left at DGA1. CONCLUSIONS: It may be too optimistic to address only the most grossly diseased teeth when a child requires GA exodontia. A more radical treatment-planning approach, combining primary care, secondary care and public health considerations, may be required to avoid the unnecessary use of DGA.

Anesthesia, Dental↗
PubMed2000

Identification of lipid-accessible sites on the nephrops 16-kDa proteolipid incorporated into a hybrid vacuolar H(+)-ATPase: site-directed labeling with N-(1-Pyrenyl)cyclohexylcarbodiimide and fluorescence quenching analysis.

Proton translocation by the vacuolar H(+)-ATPase is mediated by a multicopy transmembrane protein, the 16-kDa proteolipid. It is proposed to assemble in the membrane as a hexameric complex, with each polypeptide comprising four transmembrane helices. The fourth helix of the proteolipid contains an intramembrane acidic residue (Glu140) which is essential for proton translocation and is reactive toward N,N'-dicyclohexylcarbodiimide (DCCD). Current theoretical models of proton translocation by the vacuolar ATPase require that Glu140 should be protonated and in contact with the membrane lipid. In this study we present direct support for this hypothesis. Modification with the fluorescent DCCD analogue N-(1-pyrenyl)cyclohexylcarbodiimide, coupled to fluorescence quenching studies and bilayer depth measurements using the parallax method, was used to probe the position of Glu140 with respect to the bilayer. Glutamate residues were also introduced mutagenically as targets for the fluorescent probe in order to map additional lipid-accessible sites on the 16-kDa proteolipid. These data are consistent with a structural model of the 16-kDa proteolipid oligomer in which the key functional residue Glu140 and discrete faces of the second and third transmembrane helices of the 16-kDa proteolipid are exposed at the lipid-protein interface.

Amino Acid Sequence↗
PubMed2000

Rational treatment of empyema in children.

HYPOTHESIS: Efficacious and cost-effective treatment of pediatric empyema can be accomplished following a protocol based on its radiographic appearance. Therapeutic modalities include thoracostomy tube drainage (TTD) with or without fibrinolytic therapy (FT) and video-assisted thoracoscopic debridement (VATD). DESIGN: Retrospective case series. SETTING: Tertiary referral center. RESULTS: From 1995 through 1999, 31 children were treated ranging in age from 11 months to 18 years (mean age, 5.1 years). Twenty-seven (87.1%) underwent TTD; of these, 22 (81.5%) received FT with urokinase. The TTD failed in 4 children (14.8%) who required salvage VATD. Primary VATD was performed in another 4 children (12.9%). The mean length of stay was 14.6 days (TTD, 14.1 days; salvage VATD, 20. 0 days; primary VATD, 11.5 days), ranging from 8.0 to 30.0 days. Complications included readmission for fever (2 patients [6.5%]) and gastrointestinal bleeding (1 patient [3.2%]). There were no anaphylactic reactions or bleeding episodes due to urokinase. Two patients (7.4%) treated with TTD and FT developed an air leak that resolved spontaneously. The mean hospital charges were $78,832 (TTD with or without FT, $75,450; salvage VATD, $107,476; primary VATD, $69,634). The procedural charges were highest for salvage VATD. CONCLUSIONS: Most cases of pediatric empyema can be treated by TTD with or without FT. This therapy is safe and effective for children with nascent disease. Primary VATD is preferred in children with advanced disease. Cost-effectiveness could be further improved through better prediction of those patients likely to fail TTD and require salvage VATD. An algorithmic approach based on findings from computed tomography or (better) ultrasonography of the chest may be the best way to make this distinction and rationalize care.

Adolescent↗
PubMed2000

From medical astrology to medical astronomy: sol-lunar and planetary theories of disease in British medicine, c. 1700-1850.

After 1700, astrology lost the respect it once commanded in medical circles. But the belief that the heavens influenced bodily health persisted - even in learned medicine - until well into the nineteenth century. The continuing vitality of these ideas owed much to the new empirical and mechanical outlook of their proponents. Taking their cue from the work of Robert Boyle and Richard Mead, a number of British practitioners amassed statistical evidence which purported to prove the influence of the Moon upon fevers and other diseases. Such ideas flourished in the colonies and in the medical services of the armed forces, but their exponents were not marginal men. Some, like James Lind, were widely respected and drew support for their views from such influential figures as Erasmus Darwin.

Astrology↗
PubMed2000

Modeling flavor release from aqueous sucrose solutions, using mass transfer and partition coefficients.

The penetration theory of interfacial mass transfer was used to model flavor release from aqueous solutions containing different concentrations of sucrose. The mass transfer coefficient and the gas/solution partition coefficient are the main factors of the model influencing the release in time. Parameters governing the isolation by a purge and trap method at mouth conditions (volume, temperature, and artificial saliva) were used in the model description of the flavor release. Viscosities of the different sucrose solutions (0-60 w/v %) at 37 degrees C were estimated, and their influence on the mass transfer coefficients was determined. The gas/solution partition coefficients for ethyl acetate, methyl butanoate, ethyl butanoate, hexanal, and octanal were measured for the different sucrose concentrations at 37 degrees C. At lower sucrose concentrations the partition coefficient primarily controls flavor release during a purge time of 10 min, whereas at higher sucrose concentrations the influence of the mass transfer coefficient is more important.

Acetates↗
PubMed2000

Interactions between methyl ketones and beta-lactoglobulin: sensory analysis, headspace analysis, and mathematical modeling.

Interaction of flavor compounds with proteins is known to have an influence on the release of flavor from food. Hydrophobic interactions were found between beta-lactoglobulin and methyl ketones; the affinity constant increases by increasing the hydrophobic chain. Addition of beta-lactoglobulin (0.5 and 1%) to aroma solutions (12.5, 50, and 100 microL L(-)(1)) of three methyl ketones induces a significant decrease in odor intensity. The chosen methyl ketones were 2-heptanone (K(b) = 330), 2-octanone (K(b) = 950), and 2-nonanone (K(b) = 2440). The release of these flavor compounds (50 microL L(-)(1)) was studied by static headspace in water solution (50 mM NaCl, pH 3) with different concentrations of beta-lactoglobulin (0, 0.5, 1, 2, 3, and 4%). Increasing the concentration of protein increases the retention of volatiles, and this effect is greatest for 2-nonanone, the compound with the highest affinity constant, and lowest for 2-heptanone. A mathematical model previously developed to describe flavor release from aqueous solutions containing flavor-binding polymers (Harrison, M.; Hills, B. P. J. Agric. Food Chem. 1997, 45, 1883-1890) was used to interpret the data. The model assumes that the polymer-flavor interaction is reversible and the rate-limiting step for release is the transfer of volatiles across the macroscopic gas-liquid interface. This model was used to predict the equilibrium partitioning properties and the rate of release of the three methyl ketones. Increasing the affinity constant leads to decreased release rates and a lower final headspace aroma concentration.

Ketones↗
PubMed2000

Balloon tracheal occlusion for congenital diaphragmatic hernia: experimental studies.

PURPOSE: Temporary tracheal occlusion is an effective strategy to enlarge fetal lungs, but the optimal technique to accomplish occlusion is unknown. External clips are effective when applied fetoscopically (Fetendo clip), but require a difficult fetal neck dissection. This study was undertaken to assess the feasibility of intratracheal balloon occlusion, revisiting the internal occlusion strategy. METHODS: (1) The internal diameter (ID) of human fetal trachea (53 fetuses; 14 to 41 weeks' gestation) was compared using a computer-assisted image analyzer and sonography, ex vivo. (2) Volume to diameter relationship of the balloon (balloon configuration curve) was defined using an image analyzing computer. (3) Using the trachea of fetal sheep, pressures that break balloon tracheal seal (seal pressure) were investigated. RESULTS: (1) Between 16 and 41 weeks' gestation, tracheal ID (range, 0.7 to 5.4 mm) correlates significantly with gestational age. (2) Balloon volume required to achieve tracheal seal could be determined based on the tracheal growth curve and the balloon configuration curve. (3) Tracheal seal breaking points varied depending on the tracheal specimen tested. CONCLUSION: Internal tracheal occlusion using a balloon is feasible with minimal tracheal damage if the balloon volume is adjusted to fetal tracheal growth.

Balloon Occlusion↗
PubMed2000

Combined treatment with losartan and an ACE inhibitor in mild to moderate heart failure: results of a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Although the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in patients with heart failure are well recognized, there are theoretical advantages in combining ACE inhibition with angiotensin (AT)1 receptor antagonism. METHODS: Twenty patients with mild to moderate heart failure and maximally treated with an ACE inhibitor were randomly assigned to losartan or placebo. Patients underwent repeated assessment of exercise tolerance, quality of life, central and regional hemodynamics, and neurohumoral and biochemical parameters over a period of 12 weeks. RESULTS: Losartan treatment was well tolerated in terms of adverse events, heart rate, and blood pressure response, and there were no significant changes in serum creatinine or potassium. After 12 weeks of treatment, no significant differences were observed between the losartan and placebo groups in exercise tolerance, quality of life, central and regional hemodynamics, or neurohumoral parameters. CONCLUSIONS: In patients with mild to moderate heart failure already maximally treated with an ACE inhibitor, additional treatment with losartan is well tolerated, but we have not observed any significant improvement in exercise capacity, quality of life, central and regional hemodynamics, or neurohormones. Our data suggest that the combination of losartan with an ACE inhibitor does not offer any substantial advantages over treatment with an ACE inhibitor alone in these patients.

Aged↗
PubMed2000

The impact of the Citibank, NA, health management program on changes in employee health risks over time.

This study estimated the impact of the Citibank Health Management Program on changes in health risks among Citibank employees. McNemar chi-squared tests compared the probability of being at high risk for poor health when the first and last health-risk appraisal surveys were taken. Logistic regression controlled for baseline differences in subsequent analyses when those who participated in more intensive program features were compared with those who participated in less intensive features. Declines in risk were noted for 8 of 10 risk categories. Most changes were small, except those related to exercise habits, seatbelt use, and stress levels. For nine health risk categories, those who participated in more intensive program services were significantly more likely than others to reduce their health risks. Thus, the Citibank Health Management Program was associated with significant reductions in health risk.

Adolescent↗