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Biomedical subjects

A Sutherland

Publications and source records attributed to A Sutherland.

At least 19 recordsLinked to original sources

Anaesthetists' attitudes to teamwork and safety.

A questionnaire survey was conducted with 222 anaesthetists from 11 Scottish hospitals to measure their attitudes towards human and organisational factors that can have an impact on effective team performance and consequently on patient safety. A customised version of the Operating Room Management Attitude Questionnaire (ORMAQ) was used. This measures attitudes to leadership, communication, teamwork, stress and fatigue, work values, human error and organisational climate. The respondents generally demonstrated positive attitudes towards the interpersonal aspects of their work, such as team behaviours and they recognised the importance of communication skills, such as assertiveness. However, the results suggest that some anaesthetists do not fully appreciate the debilitating effects of stress and fatigue on performance. Their responses were comparable with (and slightly more favourable than) those reported in previous ORMAQ surveys of anaesthetists and surgeons in other countries.

Anesthesia↗

Trophoblast-specific expression and function of the integrin alpha 7 subunit in the peri-implantation mouse embryo.

For implantation and placentation to occur, mouse embryo trophoblast cells must penetrate the uterine stroma to make contact with maternal blood vessels. A major component of the uterine epithelial basement membrane and underlying stromal matrix with which they interact is the extracellular matrix protein laminin. We have identified integrin alpha 7 beta 1 as a major receptor for trophoblast-laminin interactions during implantation and yolk sac placenta formation. It is first expressed by trophectoderm cells of the late blastocyst and by all trophectoderm descendants in the early postimplantation embryo through E8.5, then disappears except in cells at the interface between the allantois and the ectoplacental plate. Integrin alpha 7 expression is a general characteristic of the early differentiation stages of rodent trophoblast, given that two different cultured trophoblast cell lines also express this integrin. Trophoblast cells interact with at least three different laminin isoforms (laminins 1, 2/4, and 10/11) in the blastocyst and in the uterus at the time of implantation. Outgrowth assays using function-blocking antibodies show that alpha 7 beta 1 is the major trophoblast receptor for laminin 1 and a functional receptor for laminins 2/4 and 10/11. When trophoblast cells are cultured on substrates of these three laminins, they attach and spread on all three, but show decreased proliferation on laminin 1. These results show that the alpha 7 beta 1 integrin is expressed by trophoblast cells and acts as receptor for several isoforms of laminin during implantation. These interactions are not only important for trophoblast adhesion and spreading but may also play a role in regulating trophectoderm proliferation and differentiation.

Alternative Splicing↗

Automated edge-detection technique for measurement of brachial artery reactivity: a comparison of concordance with manual measurements.

Concerns have been raised about the reproducibility of brachial artery reactivity (BAR), because subjective decisions regarding the location of interfaces may influence the measurement of very small changes in lumen diameter. We studied 120 consecutive patients with BAR to address if an automated technique could be applied, and if experience influenced reproducibility between two observers, one experienced and one inexperienced. Digital cineloops were measured automatically, using software that measures the leading edge of the endothelium and tracks this in sequential frames and also manually, where a set of three point-to-point measurements were averaged. There was a high correlation between automated and manual techniques for both observers, although less variability was present with expert readers. The limits of agreement overall for interobserver concordance were 0.13 +/- 0.65 mm for the manual and 0.03 +/- 0.74 mm for the automated measurement. For intraobserver concordance, the limits of agreement were - 0.07 +/- 0.38 mm for observer 1 and - 0.16 +/- 0.55 mm for observer 2. We concluded that BAR measurements were highly concordant between observers, although more concordant using the automated method, and that experience does affect concordance. Care must be taken to ensure that the same segments are measured between observers and serially.

Automation↗

Recent advances in the biosynthetic studies of lovastatin.

The fungal metabolite lovastatin and its derivatives are widely prescribed cholesterol-lowering drugs that act as potent inhibitors of (3S)-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMG-CoA reductase). These drugs and a number of analogs that have been approved for use in humans are manufactured by fermentation in combination with subsequent chemical or microbial modification. This review highlights early work done in the elucidation of lovastatin biosynthesis involving the use of labeled precursors and the incubation of putative intermediates with cell-free extracts from various fungal sources. A series of more contemporary papers are also reviewed, describing the use of gene cloning to identify the various functions of the enzymes involved in the biosynthesis of lovastatin. In particular, overexpression, purification and the subsequent investigation of the various roles of lovastatin nonaketide synthase (LNKS) during lovastatin biosynthesis are discussed.

Animals↗

Syringomyelia in children with primary scoliosis.

The clinical notes of 35 children presenting with scoliosis were reviewed; all 35 had been investigated with MRI. Seven were found to have syringomyelia, and six of these had Chiari malformation. Correction of the syrinx resulted in improvement or stabilisation of the spinal curvature. We recommend that all cases presenting with primary scoliosis should have MRI and should be treated if a syrinx is found.

Arnold-Chiari Malformation↗

The three-dimensional structure of the ternary complex of Corynebacterium glutamicum diaminopimelate dehydrogenase-NADPH-L-2-amino-6-methylene-pimelate.

The three-dimensional (3D) structure of Corynebacterium glutamicum diaminopimelate D-dehydrogenase in a ternary complex with NADPH and L-2-amino-6-methylene-pimelate has been solved and refined to a resolution of 2.1 A. L-2-Amino-6-methylene-pimelate was recently synthesized and shown to be a potent competitive inhibitor (5 microM) vs. meso-diaminopimelate of the Bacillus sphaericus dehydrogenase (Sutherland et al., 1999). Diaminopimelate dehydrogenase catalyzes the reversible NADP+ -dependent oxidation of the D-amino acid stereocenter of mesodiaminopimelate, and is the only enzyme known to catalyze the oxidative deamination of a D-amino acid. The enzyme is involved in the biosynthesis of meso-diaminopimelate and L-lysine from L-aspartate, a biosynthetic pathway of considerable interest because it is essential for growth of certain bacteria. The dehydrogenase is found in a limited number of species of bacteria, as opposed to the alternative succinylase and acetylase pathways that are widely distributed in bacteria and plants. The structure of the ternary complex reported here provides a structural rationale for the nature and potency of the inhibition exhibited by the unsaturated L-2-amino-6-methylene-pimelate against the dehydrogenase. In particular, we compare the present structure with other structures containing either bound substrate, meso-diaminopimelate, or a conformationally restricted isoxazoline inhibitor. We have identified a significant interaction between the alpha-L-amino group of the unsaturated inhibitor and the indole ring of Trp144 that may account for the tight binding of this inhibitor.

Amino Acid Oxidoreductases↗

Synthesis of probes for the active site of leucine dehydrogenase.

A series of novel 3-substituted 2-oxobutanoic acids were prepared and incubated with leucine dehydrogenase giving in one case both a kinetic resolution at C-3 and reductive amination of the ketone. This is the first example of an amino acid dehydrogenase catalysed kinetic resolution and reductive amination.

Amino Acid Oxidoreductases↗

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Journal Article↗

Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6J and A/J mice.

We have previously demonstrated that the C57BL/6J (B/6J) mouse will develop severe obesity, hyperglycemia, and hyperinsulinemia if weaned onto a high-fat, high-sucrose (HH) diet. In the present study, we compared the effects of fat and sucrose separately and in combination on diabetes- and obesity-prone B/6J and diabetes- and obesity-resistant A/J mice. After 4 months, the feed efficiency ([FE] weight gained divided by calories consumed) did not differ across diets in A/J mice, but B/6J mice showed a significantly increased FE for fat. That is, B/6J mice gained more weight on high-fat diets without consuming more calories than A/J mice. The increase in FE was related to adipocyte hyperplasia in B/6J mice on high-fat diets. Fat-induced obesity in B/6J mice was unrelated to adrenal cortical activity. In the absence of fat, sucrose produced a decreased in FE in both strains. Animals fed a low-fat, high-sucrose (LH) diet were actually leaner than animals fed a high-complex-carbohydrate diet. Fat was also found to be the critical stimulus for hyperglycemia and hyperinsulinemia in B/6J mice. In the absence of fat, sucrose had no effect on plasma glucose or insulin. These data clearly show that across these two strains of mice, genetic differences in the metabolic response to fat are more important in the development of obesity and diabetes than the increased caloric content of a high-fat diet.

Adipose Tissue↗

Discrimination of species in the genus Listeria by Fourier transform infrared spectroscopy and canonical variate analysis.

Infrared spectra of type cultures of the six recognized species of the genus Listeria and of Listeria grayi subsp. murrayi were recorded. By use of a library of 59 spectra, comprising at least six replicates of each type, discrimination by canonical variate analysis of the spectral amplitudes allowed all of the spectra to be correctly classified.

Analysis of Variance↗

Extracellular matrix 5: adhesive interactions in early mammalian embryogenesis, implantation, and placentation.

Normal morphogenesis and differentiation depend heavily on the coordination of cell-cell and cell-extracellular matrix interactions. During early mammalian development, the first cell lineages to be established are extraembryonic (trophoblast and extraembryonic endoderm), which are essential for satisfying the nutritional requirements of the developing embryo. This review emphasizes the importance of the cadherin family of cell-cell adhesion molecules and the integrin family of extracellular matrix receptors in mediating interactions between cells and their environment during early development. The review first discusses the critical role of cell-cell interactions in fertilization and early lineage decisions that occur during pre- and peri-implantation development in the mouse, using the calcium-dependent cell adhesion molecule E-cadherin as the primary example. The remainder of the review discusses the importance of cell-ECM interactions in the further morphogenesis and differentiation of the newly segregated lineages. The critical roles of integrins in differentiation, migration, and invasion of trophoblast in both mouse and human are emphasized.

Animals↗