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Biomedical subjects

A Simpson

Publications and source records attributed to A Simpson.

At least 19 recordsLinked to original sources
PubMed1995

The avian eye lens protein delta-crystallin shows a novel packing arrangement of tetramers in a supramolecular helix.

BACKGROUND: Little is known of the intermolecular organization of crystallins in the protein-packed eye lens. The tetrameric structure of the 200,000 Da avian delta-crystallin, which is closely related to the enzyme argininosuccinate lyase and is characteristic of the accommodating, soft lens of birds, has recently been solved at atomic resolution at acidic pH. To help understand how delta-crystallin remains soluble at the very high concentrations found in the avian lens we have now crystallized turkey delta-crystallin at around neutral pH and examined its intermolecular interactions. RESULTS: Turkey delta-crystallin has been crystallized around neutral pH. The X-ray structure has been solved at 4.5 A resolution in space group C2 with three and a half tetramers in the asymmetric unit. The symmetrical 222 tetramers have a novel packing arrangement consisting of continuous helices, with 7(3)2 non-crystallographic symmetry, in an approximately hexagonal close-packed array. The internal 222 symmetry of the tetramers allows different polymeric chains to be constructed, based on the tetramer-tetramer association observed in the crystalline helix. It is possible to build a model of a tubule of diameter 212 A that is very similar to observed tubules of bovine argininosuccinate lyase. CONCLUSIONS: Elements of helical organization may occur in the concentrated solution of the avian eye lens where delta-crystallin is the prominent protein. The symmetry of the tetramer provides a choice in the direction of growth of a helix at each link so that highly hydrated irregular polymers may be formed rather than large compact regular structures that would not be compatible with a transparent lens.

Amino Acid Sequence↗
PubMed1995

High-performance liquid chromatographic assay of plasma thalidomide: stabilization of specimens and determination of a tentative therapeutic range for chronic graft-versus-host disease.

Thalidomide is now widely used to treat chronic graft-versus-host disease, but its use is associated with non-teratogenic side effects such as peripheral neuropathy. To examine the value of monitoring plasma concentrations of the drug in such patients, we have developed a high-performance liquid chromatographic (HPLC) assay. The method uses 0.5 mL plasma, is linear to 10 mg/L and had a detection limit of 0.2 mg/L. Thalidomide in plasma specimens was unstable at physiological pH but could be stabilized for several weeks by simple acidification. We describe a protocol for monitoring patients treated with thalidomide which permits convenient transportation and storage of specimens and report, provisionally, that plasma concentrations in the range 1-7 mg/L are therapeutically effective in chronic graft-versus-host disease without adverse side effects.

Chromatography, High Pressure Liquid↗
PubMed1995

A framework for identifying and managing risk in the operating theatre.

There is much advice available about the development of risk management strategies within the NHS. There are booklets and magazines and there are many management consultancies willing to give advice on the development of strategies. NATN is also working on the development of advice on risk management within the operating theatre department and a document should be available at Congress this year. It was felt, however, that it may be useful to hear a little about the specific experience of the development of a strategy within one operating theatre area and Andrea Simpson, Directorate Nurse Manager for Clinical Services, West Lothian NHS Trust has recorded the development within the directorate. There has been some additional comment from the Director of Nursing and Quality within the Trust, Libby Campbell, who is responsible for risk management there.

Humans↗
PubMed1994

The structure of avian eye lens delta-crystallin reveals a new fold for a superfamily of oligomeric enzymes.

The crystal structure of turkey delta-crystallin, a principal soluble components of the avian lens, has been determined to a resolution of 2.5 A. It is a tetramer, of 200,000 M(r), with 222 symmetry. The subunit has a new fold composed of three mainly alpha-helical domains. One domain is a bundle of five long helices which forms a 20-helix bundle at the core of the tetramer. delta-crystallin shares approximately 90% sequence identity with the enzyme argininosuccinate lyase (EC 4.3.2.1), indicating that it is an example of a 'hijacked' enzyme. It is also distantly related to the class II fumarases, aspartases, adenylosuccinases and 3-carboxy-cis,cis-muconate lactonising enzyme. The structure reveals a putative active-site cleft which is located on the boundary between three subunits of the tetramer. This is the first three-dimensional structure of a representative of this superfamily of enzymes.

Amino Acid Sequence↗
PubMed1992

Evaluation of a method of simulating reduced frequency selectivity.

The accuracy of a method of simulating reduced frequency selectivity by the spectral smearing of complex stimuli has been evaluated. First an excitation pattern that would be evoked by a given nonsmeared stimulus in an impaired ear with broad auditory filters was estimated. Then the spectral smearing of the stimulus that would be necessary to create the same excitation pattern in a normal ear was calculated. The smearing was based on the shapes of simulated broad auditory filters; both symmetric and asymmetric broad filters were simulated. The method was used to process notched noise, and tones in notched noise, and the processed stimuli were used in a series of experiments with normally hearing subjects measuring the threshold for the tone in notched noise. The resulting data were used to derive auditory filter shapes. The derived filter shapes were generally similar to the expected shapes (based on the type of spectral smearing used), but there were some systematic discrepancies and some individual differences. The discrepancies do not seem to be due to the use of information derived from phase locking, since they were observed both at 1 kHz (where phase locking occurs) and at 6 kHz (where phase locking probably does not occurs). The discrepancies also do not seem to be due to the transmission characteristics of the outer/middle ear, since they occurred both when these characteristics were taken into account in the fitting procedure, and when the stimuli were preshaped to compensate for these characteristics. The influence of the subjects' own auditory filters probably can explain some of the discrepancies; the excitation pattern evoked by the spectrally smeared stimuli can be significantly influenced by the subjects' own filters when those filters are not much sharper than the simulated filters used to produce the smeared stimuli. Finally, some of the discrepancies can probably be explained by subjects combining information across auditory filters, rather than just using the single 'best' filter in each condition; this represents a limitation of the fitting procedure rather than of the simulation itself. Overall, the simulation worked reasonably well, especially when the smearing was based on symmetric filters.

Attention↗
PubMed1992

Support for AuD.

Explore the source record for details and available documents.

Audiology↗
PubMed1990

A comparison of four culture methods for diagnosing infection in continuous ambulatory peritoneal dialysis.

Dialysate effluent from 41 patients presenting with 54 episodes of CAPD peritonitis was examined by four culture techniques, three employing methods for the lysis of peritoneal leucocytes. The most efficient method employed a distilled water lysis-centrifugation technique (81% of episodes culture-positive). Filtration (without leucocyte lysis) was less effective (74% culture-positive). The results of a mechanical leucocyte lysis technique were less satisfactory still, the culture positive rate of 74% being compromised by the recovery of the infecting organism in low numbers, and by an association with a high incidence of plate contamination. The results of a bile-salt lysis technique were the least satisfactory (67% culture-positive).

Bacteria↗
PubMed1990

The effect of anti-Rho(D) and non-specific immunoglobulins on monocyte Fc receptor function: the role of high molecular weight IgG polymers and IgG subclasses.

Anti-Rho(D) immunoglobulin (anti-D) contained more high molecular weight (HMW) IgG polymers than intravenous non-specific immunoglobulin (i.v. Ig). The low-dose anti-D and high-dose i.v. Ig regimens used to treat idiopathic thrombocytopenic purpura (ITP) therefore contained similar total amounts of HMW IgG. In vitro, the HMW IgG polymers were more effective competitive inhibitors of monocyte phagocyte Fc receptors than monomeric IgG. The IgG subclass composition of anti-D and i.v. Ig were both similar to normal human plasma. We conclude that the HMW IgG content but not the IgG subclass composition of anti-D may explain its low-dose therapeutic efficacy in ITP.

Biopolymers↗
PubMed1990

Hepatic drug metabolism is increased in poorly controlled insulin-dependent diabetes mellitus.

In addition to increased glycosylation of hemoglobin, abnormalities of other heme proteins such as cytochrome P-450 might also occur in patients with insulin-dependent diabetes mellitus. Antipyrine is a useful marker drug for cytochrome P-450 dependent hepatic drug metabolism. Antipyrine kinetics and urinary excretion of antipyrine metabolites were measured in 14 patients with insulin-dependent diabetes mellitus in poor metabolic control. Improvement in diabetic control in 9 patients, as measured by more normal HbA1 values, led to normalization of plasma antipyrine half-time (t1/2) and metabolism: the mean antipyrine t1/2 slowed from 4.7 +/- 0.2 (SEM) initially to 7.8 +/- 0.3 h in these 9 patients and was thus nearly identical to that of normal subjects 8.6 +/- 1.0. Antipyrine plasma clearance improved in the 9 diabetic patients whose diabetic control improved. The apparent volume of distribution was normal on both occasions in the diabetic patients. These findings provide a new argument for tight metabolic control in patients with insulin-dependent diabetes mellitus.

Adolescent↗
PubMed1989

Expression of the vitronectin receptor during embryonic development; an immunohistological study of the ontogeny of the osteoclast in the rabbit.

The development of the osteoclast during embryogenesis was studied in the rabbit by immunohistological techniques. Two monoclonal antibodies, 13C2 and 23C6, which react with the alpha-chain of the vitronectin receptor were used to define mono and multi-nucleate osteoclasts; being unreactive with other haemopoietic cells these antibodies could discriminate between osteoclasts and cells of the mononuclear phagocyte system. Staged rabbit embryos, from 14 to 28 days of age, were analysed and compared with findings from newborn and adult rabbits. No 13C2/23C6 immunoreactivity was seen in any of the tissues studied prior to day 17. 13C2/23C6-positive, mononuclear cells--presumptive osteoclast precursors--were first observed in the outer perichondrium of long-bones adjacent to the zone of hypertrophic cartilage in day 17 embryos. From day 17 onwards mono and multi-nucleate cells accumulated progressively in the perichondrium/periosteum, and by day 22 within the developing bone marrow cavity attached to bone spicules. No cells expressing the vitronectin receptor were seen at sites of embryonic or foetal haemopoiesis in yolk sac or foetal liver, that is, prior to the formation of the marrow cavity. Macrophages, defined by cross-reactivity with an antibody to human HLA-DR, first appeared in developing marrow spaces 11 days after the first osteoclast precursor appeared, suggesting that osteoclasts and definitive macrophages might develop from separate cell lineages, or that they diverge at an early stage of differentiation of haemopoietic stem cells.

Animals↗
PubMed1989

Asthma and chronic airflow limitation in the highlands of Papua New Guinea: low prevalence of asthma in the Asaro Valley.

The prevalence of asthma in the South Fore region of Papua New Guinea was found to be 7.3%, which is thought exceptionally high for highland areas in this country. To investigate the prevalence of asthma and of chronic airflow limitation in a different highland region with similar living conditions, adults and children from 7 villages in the Asaro Valley were interviewed. Questions were asked about smoking history and about past and present symptoms of cough, of shortness of breath, of chest tightness and of asthma. Of 743 adults interviewed, 206 underwent a clinical study with measurements of lung function, bronchial responsiveness and skin prick tests. Dust was collected from the floors and blankets of 36 houses for counts of house dust mites. We did not find any children with symptoms of asthma. Only 2 adults (0.3%) had symptoms consistent with asthma, and a further 6.2% had symptoms and/or lung function consistent with chronic airflow limitation. Most bronchial hyperresponsiveness was associated with asthma or with chronic airflow limitation. The prevalence of atopy was similar in the Asaro and South Fore populations, but the South Fore had higher house dust mite counts in blanket dust. The low prevalence of asthma in the Asaro Valley is unexplained in terms of factors normally associated with asthma. Because asthma in this area does not appear in childhood and only develops in a small proportion of adults, it may be of different aetiology to asthma in Caucasian populations.

Adult↗
PubMed1988

Mammographic screening for breast cancer: prospects for New Zealand.

The Cancer Society and the Department of Health invited a working group to make recommendations on screening by mammography. Mammography offers the best opportunity for preventing deaths from breast cancer. Randomised trials suggest that mortality can be reduced by about 30% in women over 50; the value of routine mammography in younger women is still uncertain. Apart from financial costs, the main drawback of mammography is that many women receive unnecessary investigation because of false-positive results. Careful design and monitoring of programmes is essential to ensure that the benefits of screening outweigh the disadvantages. In New Zealand there is a shortage of radiologists, pathologists, and clinicians who are skilled in the specialised techniques required for the screening of asymptomatic women. Decisions about routine screening should be delayed until pilot programmes have been established, with assessment of their effectiveness, economic efficiency, and social acceptability. Recommendations for the design of such programmes are made.

Adult↗
PubMed1988

Isolation of a DNA fragment which complements glutamine synthetase deficient strains of S. pombe.

From a gene bank of S. pombe DNA, a 5.6 kb clone was isolated which complemented mutants defective in glutamine synthetase (GS) activity. Sub-cloning fragments of this 5.6 kb clone showed that the complementing activity was localised in a 1.6 kb HindIII-AvaI fragment and a partial DNA sequence revealed an open reading frame preceded by TATA sequences and a TGACTA sequence. Plasmid constructs carrying up to 3.4 kb of DNA used to transform gln- strains gave transformants which showed a wide range of GS activity, in some cases 100 times the wild-type level. These constructs identify DNA sequences lying downstream from the putative coding sequence which have effects on the total amount of enzyme activity, but do not affect the control imposed by the nitrogen source on which the cells are grown.

Amino Acid Sequence↗