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Biomedical subjects

L Shaw

Publications and source records attributed to L Shaw.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cloning and expression of a membrane-bound CMP-N-acetylneuraminic acid hydroxylase from the starfish Asterias rubens.

The sialic acid N-glycolylneuraminic acid (Neu5Gc) is synthesized by the action of CMP-Neu5Ac hydroxylase. The enzyme from various mammals has been purified, characterized and sequenced by cDNA cloning. Although functional sequence motifs can be postulated from comparisons with several enzymes, no global homologies to any other proteins have been found. The unusual characteristics of this hydroxylase raise questions about its evolution. As echinoderms are phylogenetically the oldest organisms possessing Neu5Gc, they represent a starting point for investigations on the origin of this enzyme. Despite many similarities with its mammalian counterpart, CMP-Neu5Ac hydroxylase from the starfish A. rubens exhibits fundamental differences, most notably its association with a membrane and a requirement for high ionic strength. In order to shed light on the structural basis for these differences, the primary structure of CMP-Neu5Ac hydroxylase from A. rubens has been determined by PCR and cDNA-cloning techniques, using initial sequence information from the mouse enzyme. The complete assembled cDNA contained an ORF coding for a protein of 653 amino acids with a molecular mass of 75 kDa. The deduced amino-acid sequence exhibited a high degree of homology with the mammalian enzyme, although the C-terminus was some 60 residues longer. This extension consists of a terminal hydrophobic region, which may mediate membrane-binding, and a preceding hydrophilic sequence which probably serves as a hinge or linker. The identity of the ORF was confirmed by expression of active CMP-Neu5Ac hydroxylase in E. coli at low temperatures.

Amino Acid Sequence↗
PubMed2001

Vegetarian children and dental erosion.

BACKGROUND: There have been recent changes in teenage lifestyle and diet. The increasing consumption of soft drinks and foods containing significant acidic components may play a role in the development of dental erosion. OBJECTIVE: The aims of this investigation were firstly to assess the prevalence of vegetarian children in a cluster random sample of 14-year-old children in Birmingham, United Kingdom. Secondly, to determine the prevalence of dental erosion in these children, and thirdly, to see if there were any differences between vegetarian and non-vegetarian children in the prevalence of dental erosion and dietary intake. DESIGN: A cluster random sample of 418 14-year-old children (209 males and 209 females) were examined from 12 different schools in Birmingham, United Kingdom; a dietary questionnaire was completed and the levels of tooth wear were recorded using a modification of the (TWI) index. All data were analysed using SPSS with t-test and Chi-square analysis. Significance was accepted at the P < 0.05 level. RESULTS: The results showed that 10% of the children were vegetarian; 52% of them had low dental erosion and 48% moderate dental erosion. Statistically there were no significant differences between vegetarian and non-vegetarian children in the prevalence of erosion; however, there were significant differences in some food and drink consumption. CONCLUSIONS: It was concluded that dental erosion is common in teenage children, but there were no significant differences in prevalence between vegetarian and non-vegetarian children.

Adolescent↗
PubMed2001

Investigation of mineral waters and soft drinks in relation to dental erosion.

A range of still and sparkling mineral waters were assessed for their erosive potential together with comparator soft drinks using in vitro dissolution assays with extracted human teeth and powdered hydroxyapatite. Dissolution levels with all of the mineral waters were very low and for several still waters were undetectable. Sparkling mineral waters showed slightly greater dissolution than still waters, but levels remained low and were of the order of one hundred times less than the comparator soft drinks. De-gassing of a sparkling mineral water reduced its dissolution, but the total levels were still relatively low suggesting that carbonation of drinks may not be an important factor per se in respect of erosive potential. The complex and heterogeneous mineral compositions of mineral waters could influence the dissolution equilibrium of apatite in enamel and controlled addition of several ions to ultrapure deionized water was investigated. Calcium ions led to the greatest reduction in hydroxyapatite dissolution, but their effects were moderated by other ions including magnesium and sulphate. Thus, mineral waters appear to offer a safe alternative to more erosive acidic beverages and their complex mineral ion compositions may positively influence any dissolution processes at the tooth surface.

Apatites↗
PubMed2001

Artificial saliva substitutes and mineral dissolution.

The erosive potentials of a number of commercially available artificial saliva substitutes have been investigated using an in vitro hydroxyapatite powder dissolution assay. Most of the saliva substitutes examined did not show any appreciable erosive potential, although one product resulted in greater mineral dissolution levels. There appeared to be little correlation between pH and mineral dissolution levels for the different saliva substitutes examined. Whilst saliva substitutes may be of assistance in maintaining some physiological function in patients with impaired salivary flow, it is important to choose a product with low erosive potential where the natural dentition is present.

Aerosols↗
PubMed2001

Pulse rate over pressure evaluation (ROPE) is useful in the assessment of compensated haemorrhagic shock.

OBJECTIVE: To evaluate a calculation of pulse rate over pulse pressure as a method of predicting decompensation in patients with compensated haemorrhagic shock. METHODS: A retrospective cohort study was undertaken enrolling 184 adult victims of major road trauma who were not shocked on presentation to the emergency department. A pulse rate over pressure evaluation was calculated at presentation and vital signs were observed during the first 2 h of emergency department management. RESULTS: Thirty-one patients became shocked during their first 2 h. A ROPE value of greater than 3.0 had a positive predictive value of 53% and a value less than 3.0 had a negative predictive value of 86% for the development of decompensated shock. CONCLUSIONS: ROPE is an easily applied and useful clinical tool with a ROPE of less than 3.0 being predictive of a patient remaining well and a ROPE of above 3.0 being predictive of the patient developing decompensated shock.

Adolescent↗
PubMed2001

Distribution and localization of CMP-N-acetylneuraminic acid hydroxylase and N-glycolylneuraminic acid-containing glycoconjugates in porcine lymph node and peripheral blood lymphocytes.

An immunohistochemical analysis was performed on paraplast-embedded sections of porcine lymph node with antibodies specific for CMP-N-acetylneuraminic acid hydroxylase (h-3 antibody) and glycoconjugate-bound N-glycolylneuraminic acid (Neu5Gc), which appears as a result of the hydroxylase reaction (a-Gc antibody). The observed localization of the enzyme in cells of the perifollicular zone, including lymphocytes, was reflected in a similar distribution of glycoconjugate-bound Neu5Gc. This result confirms previous biochemical investigations on the role of the hydroxylase in regulating Neu5Gc biosynthesis in vitro on a histological level. An analysis of lymphocytes isolated from porcine thymus, spleen, lymph node and peripheral blood revealed differences in the amount of Neu5Gc in the various lymphocytes that correlated well with the activity of the hydroxylase determined in these cells. The largest amount of Neu5Gc and highest activity of the enzyme were detected in the peripheral blood lymphocytes (PBL). Immunohistochemical studies with a-Gc and h-3 antibodies on sections of paraplast-embedded PBL showed that these antigens were located at the cell surface and in the cytosol, respectively. Ultrastructural immunocytochemistry with the h-3 antibody and immunogold labelling was used to investigate the subcellular localization of the hydroxylase. The enzyme was detected in the cytosol in the vicinity of the nuclear membrane and the outer membrane of mitochondria, in particular those close to the nucleus. The antigen was also detected on cytoplasmic tubular structures. In addition, a weak labelling of the Golgi apparatus was also observed occasionally. The possibility that this localization may be related to the availability of the substrate CMP-Neu5Ac and the redox partner cytochrome b5 is discussed.

Animals↗
PubMed2001

A time for change and a time for equality--infertility services and the NHS.

The provision of infertility services has always provoked controversy. On the one hand, patients' groups and clinicians involved with infertile couples have long campaigned against the 'postcode lottery'. On the other hand, commissioners have been reluctant to commit resources to what they see as a low priority in health care. The issue has been brought back into the news with the government's decision to ask the National Institute of Clinical Excellence to review the inequalities in provision of fertility services. This article sets out the evidence for viewing infertility as an illness that deserves public funding, and argues that assisted conception should be viewed in the same light as other chronic non-life-threatening conditions that are currently funded by the NHS.

Female↗
PubMed2001

Safety of a new conjugate meningococcal C vaccine in infants.

BACKGROUND: Group C conjugate meningococcal vaccines (Men C) were introduced into the UK primary immunisation schedule in November 1999. There has been extensive professional and public interest in their efficacy and safety. AIM: To determine the occurrence of at least one uncommon adverse event in infants related to the administration of the Chiron Men C vaccine. METHODS: A total of 2796 infants aged approximately 2 months were recruited into the study from areas in and around Sheffield and from Scotland. They were vaccinated with the Chiron Men C vaccine at 2, 3, and 4 months along with routine immunisations. Data on adverse events occurring one month after each dose were collected actively and prospectively and reviewed for possible relation to the vaccine. RESULTS: There were no deaths. There were no serious adverse events considered definitely or probably caused by the vaccine. Four infants developed serious adverse events (hypotonia, screaming syndrome, maculopapular rash, and agitation, respectively) that were considered possibly related to the vaccine. All recovered completely. Adverse events were seen in 1804 children but were considered possibly related to the vaccine in only 49 (1.8%). On subsequent immunisation there were no recurrences of adverse events considered to be possibly related to the vaccine.

Female↗
PubMed2001

Dens evaginatus on the labial surface of a central incisor: a case report.

A 7-year-old girl in the mixed dentition phase presented with abnormal morphology of the upper right central incisor. The diagnosis was a dens evaginatus, an anomaly of odontogenesis of unknown aetiology. This article describes the management of this anomaly and discusses the importance of maintaining space in the developing dentition. The aetiology and natural history of dens evaginatus are also considered.

Child↗
PubMed2001

Localized scleroderma in a 12-year-old girl presenting as gingival recession. A case report and literature review.

Scleroderma is a connective tissue disorder that displays considerable clinical heterogeneity. This case describes a 12-year-old girl who presented with a localized form of the disease. The consequences were a severe and progressive localized gingival recession affecting two maxillary incisors, a localized lip defect and scarring of the forehead. The case illustrates the difficulties in diagnosis and management of young patients with localized scleroderma.

Child↗
PubMed2000

Clinical characteristics and long-term outcomes of patients with heart failure and preserved systolic function.

Although the syndrome of heart failure with preserved systolic function may occur in up to 40% of all heart failure patients, the clinical, angiographic characteristics, and long-term outcomes of these patients are poorly understood. We prospectively evaluated 2,498 consecutive patients with New York Heart Association class II to IV symptoms and ejection fractions of >40%, who underwent cardiac catheterization between January 1984 and December 1996 at Duke University Medical Center. The median age for the entire cohort was 63 years; 25% of the population was >71 years old. In addition, 55% of the patients were women, 65% had ischemic heart disease, 28% had a history of diabetes, and 62% had a history of hypertension. The median ejection fraction was 58%. One third of the patients had multivessel disease by coronary angiography. The overall 5-year mortality of the total population was 28%. The independent predictors of mortality (p <0.05) using a multivariable Cox proportional hazard model were age, class IV symptoms, ejection fraction, coronary artery disease index, diabetes, peripheral vascular disease, and minority ethnic group. Heart failure with preserved systolic function is characterized by unique clinical and angiographic characteristics associated with a 5-year mortality rate of 28%. Furthermore, several clinical and angiographic characteristics are predictive of long-term survival.

Aged↗
PubMed2000

Development and characterization of human and mouse specific antibodies to CuZn-superoxide dismutase (SOD1).

Mutations in the copper/zinc superoxide dismutase (SOD1) gene are associated with 15-20% of the familial forms of motor neuron disease. Mice where a transgene has been incorporated that encodes for the human SOD1 mutation develop a form of motor neurone disease that closely resembles human forms of this disease. We have produced and characterized species-specific antibodies to epitopes in the SOD1 protein, amino acids 25-37, a region that distinguishes between the human and the mouse species of SOD1. The antisera generated were unable to immunoprecipitate the mouse or the human forms of SOD1 from tissue extracts unless the homodimeric complex of SOD1 was denatured. As SOD1 exists as a homodimeric complex in the cytoplasm of cells, this suggests that amino acids in position, 25-37 are close to the dimeric interface of SOD1.

Animals↗
PubMed2000

RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion.

Focal adhesions and actin cytoskeleton are involved in cell growth, shape and movement and in tumor invasion. Mitogen-induced changes in actin cytoskeleton are accompanied by changes in the tyrosine phosphorylation of several focal adhesion proteins. In this study, we have investigated the role of RAFTK, a cytoplasmic tyrosine kinase related to focal adhesion kinase (FAK), in heregulin-mediated signal transduction in breast cancer cells. Stimulation of T47D cells with heregulin (HRG) induced the tyrosine phosphorylation of RAFTK and the formation of a multiprotein complex. Analyses of the members of the HRG-stimulated complex revealed that RAFTK is associated with p190 RhoGAP (p190), RasGAP and ErbB-2, and plays an essential role in mediating the tyrosine phosphorylation of p190 by Src. Mutation of the Src binding site within RAFTK (402) abolished the phosphorylation of p190. In addition, upon HRG stimulation of T47D cells, association of ErbB-2 with RAFTK was observed and found to be indirect and mediated by Src. Expression of wild-type RAFTK (WT) significantly increased MDA-MB-435 and MCF-7 breast cancer cell invasion, while expression of the kinase-mutated RAFTK-R457 (KM) or the Src binding site mutant RAFTK (402) did not affect this cell invasion. Furthermore, HRG leads to the activation of MAP kinase which is mediated by RAFTK. These findings indicate that RAFTK serves as a mediator and an integration point between the GAP proteins and HRG-mediated signaling in breast cancer cells, and implicate RAFTK involvement in the MAP kinase pathway and in breast cancer cell invasion.

Breast Neoplasms↗
PubMed2000

Development and evaluation of a stand-alone web-based CAL program. A case study.

The use of web browser technology allows the construction of computer-aided learning programs which will have a familiar interface to dentists. This paper reports on the evaluation of a web-based CAL program which covered the topic of tooth wear with an emphasis on the rôle of erosion in its aetiology. Evaluation of the software was made by 50 dentists contacted by an electronic mailing list. They completed a questionnaire which evaluated aspects of the functionality of the program educational objectives. The average age of the dentists was 39 years (range 24-70) and 82% were male. The average time of use was 1 h 10 min (range 15 min to 3 h). A significant change in their knowledge of tooth wear before and after using the program was recorded. Both the use of patient cases and leaflets scored highly with other aspects such as treatment planning and patient advice receiving high marks. All dentists commented that they had gained greater knowledge with particular reference to treatment and advice of tooth wear problems. 34 dentists (68%) found the web interface easy to use. Negative comments were mainly attributed to the quality of the pictures (4/50) which were corrected in the final release version. Respondents were asked to compare the program to other educational media on the same subject. 80% rated this CAL program as better than video, and 14% claimed it was as good as video. 84% rated it better than books, and 14% said it was as good as books. 98% preferred it to audio tapes and 86% preferred it to journals. The average amount that they would pay for a CAL package such as "tooth wear" would be 42 ECU. It is concluded that web browser software is a suitable medium for the use of a CAL program and this is reflected in its ease of use by dentists.

Adult↗
PubMed2000

Mechanisms of 17 beta-oestradiol induced vasodilatation in isolated pressurized rat small arteries.

1. The influence of 17 beta-oestradiol on pressurized isolated rat mesenteric and coronary small arteries was investigated. 2. 17 beta-oestradiol caused rapid (t1.0 < 5 mins) concentration-dependent relaxations of pre-contracted pressurized (50 mmHg) isolated rat mesenteric and coronary arteries. Similar responses were observed in both vessel types. Significant relaxations were only observed at concentrations exceeding 3 microM. 3. The vasodilatory responses in both types of artery were unaffected by 10 microM L-nitro arginine (L-NNA) alone or in the presence of 10 microM indomethacin, inhibitors of nitric oxide and prostaglandin synthesis respectively. They were also unaffected by the pre-contracting agent used i.e. high K+ or U46619 (a thromboxane analogue). 4. Neither the oestrogen receptor antagonist ICI 182,780 (10 microM) nor the protein synthesis inhibitor cycloheximide (100 microM) had any effect on the responses of mesenteric arteries to 17 beta-oestradiol. 5. 17 alpha-oestradiol had only a minor effect on mesenteric arterial diameter over a concentration range similar to the effective vasodilatory range for 17 beta-oestradiol. 6. Membrane impermeant 17 beta-oestradiol conjugated to bovine serum albumin (beta-oestradiol-17-hemisuccinate-BSA) (E-H-BSA) resulted in a vasodilatation of pressurized arteries. 7. Wortmannin, an inhibitor of myosin light chain kinase, near maximally relaxed pressurized mesenteric arteries although the time course for the response was significantly slower than that for 17 beta-oestradiol. 8. These results taken together suggest that the acute effects of 17 beta-oestradiol on isolated pressurized arterial tone may be due to effects directly on the vascular smooth muscle via non-genomic mechanisms that involve a stereospecific interaction at the plasma membrane.

Androstadienes↗
PubMed2000

Prediction of myocardial perfusion abnormalities by quantitative regional function using a radionuclide angiography database: a comparison with wall motion analysis.

PURPOSE: Myocardial perfusion and functional information during the same study is now feasible. A new assessment of regional ejection fraction at rest and peak exercise by first-pass radionuclide angiography using a "normal" database file has been developed. OBJECTIVE: This study was performed to assess the relation between this new method of quantitative regional ejection fraction and myocardial perfusion abnormalities and to compare this new technique with visual analysis of regional wall motion. METHODS: Consecutive patients (n = 126) with simultaneous first-pass radionuclide angiography and perfusion SPECT imaging were studied at rest and peak exercise using a same-day protocol. The area under the receiver-operator characteristic curve (C index) was used to assess the concordance probability between perfusion and functional measurements, and logistic regression models were used to examine the ability of functional variables to predict perfusion results. RESULTS: A high concordance was found between the visual analysis of wall motion and perfusion abnormalities (C index = 0.796), and also between regional ejection fraction and perfusion defects (C index = 0.784). The maximal predictive power of functional variables was obtained by combining wall motion analysis and regional ejection fraction (C index = 0.859). Regional ejection fraction contributed, with 20% more information than provided by wall motion analysis alone (chi2 = 9.2, P = 0.0025). CONCLUSIONS: Quantitative regional ejection fraction using a normal database file has a strong relation to perfusion abnormalities and provides incremental information to regional wall motion analysis for predicting perfusion abnormalities. This new technique should be regarded as a potential adjunct to functional studies to evaluate patients with ischemic heart disease.

Cardiac Catheterization↗