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Biomedical subjects

A Shaw

Publications and source records attributed to A Shaw.

At least 55 records · Page 3Linked to original sources
PubMed1999

Effect of simulated sunlight on atrazine and metolachlor toxicity of surface waters.

Atrazine and metolachlor are the two most widely used herbicides in the United States; through non-point-source runoff both herbicides may cause toxicity to aquatic organisms. Toxicity changes were measured for atrazine and metolachlor in surface waters after exposure to simulated sunlight (0, 20, and 40 kJ/m2) using a Xenon Weather-Ometer. A Microtox toxicity test, using the marine luminescent bacterium Vibrio fischeri, was conducted on deionized, river, and bay water samples mixed with atrazine or metolachlor herbicide (12 mg/liter) after exposure to simulated sunlight. Microtox test (EC50%) results demonstrated that the toxicity decreased with increasing light intensity for both herbicides in river and bay water. These results also indicate that the toxicity of the bay water, with high concentrations of organic and suspended matter, was reduced, for both herbicides, compared with the toxicity of the river water, possibly through photodegradation of pesticides.

Acetamides↗
PubMed1999

Obstacles on the path to a primary-care led National Health Service: complexities of outpatient care.

An interpretive qualitative study was carried out as part of a large cohort study of factors affecting outpatient re-attendance. Individuals from three groups involved in the provision of care across the primary-secondary interface were interviewed: patients, general practitioners and consultants. The aim was to explore understandings concerning referral to and re-attendance at outpatients, and to elicit detailed descriptions of the complexities of the outpatient experience for both providers and recipients of care at the primary/secondary interface, given the policy commitment to a 'primary-care led National Health Service'. Semi-structured interviews were carried out with nine individuals currently attending outpatients, ten general practitioners, and ten consultants. Transcripts were analysed individually and cross-checked between analysts for validity of interpretation, to identify key themes and subthemes. Data were compared across the three groups. Negative case analysis was employed. Seven major issues were identified, some of which could be identified with interests and experience of the three obvious groupings, and some of which were common. The three groupings are not as homogeneous as is often supposed. From the cross-group analysis common themes included: interpersonal communication, knowledge, power relations and anxiety/reassurance. Issues of trust, social status, funding and consumerism/litigation were also highlighted. The analysis has implications for altering the balance of care across the interface, for example in the finding of what could be termed a dissonance in power perceptions, in that consultants perceived general practitioners as relatively powerful and able to influence things', whereas general practitioners often expressed themselves as relatively powerless and unable to be proactive in 'reclaiming' their patients. The analysis highlights the complexity of the outpatient experience, drawing attention to detailed areas of contradiction, irony and conflict in the total context of outpatient care. These areas should be addressed in policy development designed to shift the balance of care further towards the primary sector.

Ambulatory Care↗
PubMed1999

Proposed standard thermal test object for medical ultrasound.

A general design for a thermal test object (TTO) is proposed. A number of novel features make the design particularly suitable for use as a standardised device for assessing the heating capability of diagnostic ultrasound beams. To assess performance, soft-tissue TTOs have been made containing thin-film thermocouples sandwiched between discs of tissue-mimicking gel. Installed in an appropriate measurement system, these TTOs exhibit excellent thermal and spatial resolution, allowing the ultrasound beam to be located rapidly and reproducibly. The measured temperature rise after 3 minutes of heating has been compared with theoretical predictions based on measured pressure distributions, and agreement is within 10%. Other studies have shown that soft-tissue- and bone-mimicking TTOs can be used to evaluate a wide range of ultrasound fields and that different physical tissue models can be simulated. It is concluded that this design would be suitable for providing reference assessments of the thermal hazard posed by diagnostic ultrasound under standardised conditions.

Hot Temperature↗
PubMed1999

Protein engineering of alpha-amylase for low pH performance.

Industrial-scale starch liquefaction is currently constrained to operating at pH 6.0 and above, as the enzyme used in the process, Bacillus licheniformis alpha-amylase, is unstable at lower pH under the conditions used. There is a need to develop an enzyme that can operate at lower pH. Recent progress has been made in engineering the B. licheniformis enzyme for improved industrial performance. The availability of crystal structures and subsequent analysis of improved variants, in a structural context, is revealing common factors and a rationale to make further improvements.

Amino Acid Substitution↗
PubMed1999

Anaesthetic assessment and management of cardiac patients for non-cardiac surgery. Part I: Assessment.

Cardiac disease is known to increase the risk of non-cardiac surgery to patients who suffer from it. Clinical and investigation data may be used to identify those at increased risk. Attempts have been made to integrate these risk factors into systems that can quantify risk in terms of increased morbidity and mortality. In this article we discuss the various aspects of cardiac illness that are known to increase risk for patients and then look at the different scoring systems that have been produced. We consider the type and urgency of surgery and finish by providing an approach to risk assessment for non-cardiac surgery.

Anesthesia↗
PubMed1998

ATP-Citrate lyase as a target for hypolipidemic intervention. 2. Synthesis and evaluation of (3R,5S)-omega-substituted-3-carboxy-3, 5-dihydroxyalkanoic acids and their gamma-lactone prodrugs as inhibitors of the enzyme in vitro and in vivo.

A series of (3R,5S)-omega-substituted-3-carboxy-3, 5-dihydroxyalkanoic acids have been synthesized and evaluated as inhibitors of the recombinant human form of ATP-citrate lyase. The best of these have Ki's in the 200-1000 nM range. As the corresponding thermodynamically favored gamma-lactone prodrugs, a number of compounds are able to inhibit cholesterol and fatty acid synthesis in HepG2 cells and reduce plasma triglyceride levels in vivo. The best of these, compound 77, is able to induce clear hypocholesterolemic and hypotriglyceridaemic responses when administered orally to rat and dog. These results provide evidence to support the hypothesis that compounds which inhibit ATP-citrate lyase have the potential to be a novel class of hypolipidemic agent, which possess combined hypocholesterolemic and hypotriglyceridemic activities.

ATP Citrate (pro-S)-Lyase↗
PubMed1998

The role of ATP citrate-lyase in the metabolic regulation of plasma lipids. Hypolipidaemic effects of SB-204990, a lactone prodrug of the potent ATP citrate-lyase inhibitor SB-201076.

ATP citrate (pro-S)-lyase (EC 4.1.3.8), a cytosolic enzyme that generates acetyl-CoA for cholesterol and fatty acid synthesis de novo, is a potential target for hypolipidaemic intervention. Here we describe the biological effects of the inhibition of ATP citrate-lyase on lipid metabolism in Hep G2 cells, and plasma lipids in rats and dogs, by using SB-204990, the cell-penetrant gamma-lactone prodrug of the potent ATP citrate-lyase inhibitor SB-201076 (Ki=1 microM). Consistent with an important role of ATP citrate-lyase in the supply of acetyl-CoA units for lipid synthesis de novo, SB-204990 inhibited cholesterol synthesis and fatty acid synthesis in Hep G2 cells (dose-related inhibition of up to 91% and 82% respectively) and rats (76% and 39% respectively). SB-204990, when administered orally to rats, was absorbed into the systemic circulation; pharmacologically relevant concentrations of SB-201076 were recovered in the liver. When administered in the diet (0.05-0. 25%, w/w) for 1 week, SB-204990 caused a dose-related decrease in plasma cholesterol (by up to 46%) and triglyceride levels (by up to 80%) in rats. This hypolipidaemic effect could be explained, at least in part, by a decrease (up to 48%) in hepatic very-low-density lipoprotein (VLDL) production as measured by the accumulation of VLDL in plasma after injection of Triton WR-1339. SB-204990 (25 mg/kg per day) also decreased plasma cholesterol levels (by up to 23%) and triglyceride levels (by up to 38%) in the dog, preferentially decreasing low-density lipoprotein compared with high-density lipoprotein cholesterol levels. Overall these results are consistent with the concept that ATP citrate-lyase is an important enzyme in controlling substrate supply for lipid synthesis de novo and a potential enzyme target for hypolipidaemic intervention.

ATP Citrate (pro-S)-Lyase↗
PubMed1998

The crystal structure of NADPH:ferredoxin reductase from Azotobacter vinelandii.

NADPH:ferredoxin reductase (AvFPR) is involved in the response to oxidative stress in Azotobacter vinelandii. The crystal structure of AvFPR has been determined at 2.0 A resolution. The polypeptide fold is homologous with six other oxidoreductases whose structures have been solved including Escherichia coli flavodoxin reductase (EcFldR) and spinach, and Anabaena ferredoxin:NADP+ reductases (FNR). AvFPR is overall most homologous to EcFldR. The structure is comprised of a N-terminal six-stranded antiparallel beta-barrel domain, which binds FAD, and a C-terminal five-stranded parallel beta-sheet domain, which binds NADPH/NADP+ and has a classical nucleotide binding fold. The two domains associate to form a deep cleft where the NADPH and FAD binding sites are juxtaposed. The structure displays sequence conserved motifs in the region surrounding the two dinucleotide binding sites, which are characteristic of the homologous enzymes. The folded over conformation of FAD in AvFPR is similar to that in EcFldR due to stacking of Phe255 on the adenine ring of FAD, but it differs from that in the FNR enzymes, which lack a homologous aromatic residue. The structure of AvFPR displays three unique features in the environment of the bound FAD. Two features may affect the rate of reduction of FAD: the absence of an aromatic residue stacked on the isoalloxazine ring in the NADPH binding site; and the interaction of a carbonyl group with N10 of the flavin. Both of these features are due to the substitution of a conserved C-terminal tyrosine residue with alanine (Ala254) in AvFPR. An additional unique feature may affect the interaction of AvFPR with its redox partner ferredoxin I (FdI). This is the extension of the C-terminus by three residues relative to EcFldR and by four residues relative to FNR. The C-terminal residue, Lys258, interacts with the AMP phosphate of FAD. Consequently, both phosphate groups are paired with a basic group due to the simultaneous interaction of the FMN phosphate with Arg51 in a conserved FAD binding motif. The fourth feature, common to homologous oxidoreductases, is a concentration of 10 basic residues on the face of the protein surrounding the active site, in addition to Arg51 and Lys258.

Azotobacter vinelandii↗
PubMed1998

A constitutively activated mutant of galphaq down-regulates EP-cadherin expression and decreases adhesion between ectodermal cells at gastrulation.

We have examined the expression and function of the heterotrimeric GTP-binding protein Gq during early Xenopus embryogenesis. Abundant XGalphaq transcripts were detected in oocytes and early embryos by Northern blot analysis. In situ hybridization revealed that these transcripts are confined to the animal hemisphere of the mature oocyte and to the presumptive ectoderm of cleaving embryos. Microinjection at the two-cell stage of alphaq and Q209Lalphaq, a constitutively activated mutant, causes a disruption in ectodermal cell adhesion at late gastrulation. Dissociation/reaggregation experiments performed on animal cap explants clearly demonstrate that the Q209Lalphaq-induced phenotype occurs after reaggregation of the explants with a time-course similar to that observed in whole embryos. RT-PCR experiments performed on the explants from Q209Lalphaq-injected embryos revealed a selective decrease in the amount of EP-cadherin mRNA. Co-injection of EP-cadherin RNA, but also E-cadherin RNA, rescued the disaggregated phenotype. These data emphasize the functional link between Gq protein-coupled signalling pathways and cadherin molecules in the ectodermal layer during the morphogenetic movements of gastrulation.

Animals↗