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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
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↗
PubMed2000

Predictive performance study of two digoxin assays in subjects with various degrees of renal function.

This prospective study was conducted to compare the predictive performance of fluorescence polarization immunoassay (FPIA, Abbott TDx Digoxin II) and radioimmunoassay (RIA, Kallestad Labs) with combined low-pressure liquid chromatography/RIA (LPLC/RIA) digoxin assay in measuring 15-17 serum digoxin concentrations (SDC) obtained after a single 10 microg/kg intravenous digoxin dose in patients with various degrees of renal function and at different SDC ranges. Eighteen men and women were stratified into 3 age- and gender-matched groups based upon renal function [N = 6 in each, group I (Cl(cr) < 10 mL/min), group II (Cl(cr) = 10-50 mL/min), and group III (Cl(cr) > 50 mL/min)]. Serum digoxin concentrations were measured at time zero; at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, and 12 hours; and at 2, 3, 4, and 5-7 days after the digoxin dose, using the three different digoxin assays. TDx Digoxin II was unbiased [mean error -0.09 (95% CI -0.19, 0.01)] and RIA biased [mean error -0.29 (95% CI -0.36, -0.21)] to over-predict SDC by 14.2%. In group I patients, the analysis revealed a bias to over-predict SDC by 6.0% for TDx Digoxin II [mean error -0.16 (95% CI -0.29, -0.07)] and an unbiased performance by RIA. In groups II and III, both TDx Digoxin II and RIA showed biased performance, the mean magnitude of bias was low (< 20%). For intermediate SDC range (> 0.5 ng/mL and < or = 3.0 ng/mL), TDx Digoxin II was unbiased in predicting SDC, whereas RIA was biased to under-predict SDC [mean error 0.13 (95% CI 0.10, 0.16)] by 9.9%. The magnitude of bias observed in all cases was less than 20%. Both assays, TDx Digoxin II and RIA, imprecisely measured SDC for all samples combined, different groups and SDC ranges. In all time-paired samples, TDx Digoxin II (FPIA) performed better than the RIA. In conclusion, the magnitude of bias observed with either assay at different groups and SDC ranges was not likely to be clinically relevant. Therefore, either assay may be used to measure SDC in clinical practice.

Anti-Arrhythmia Agents↗
PubMed2000

Modern thoughts on fissure sealants.

It has long been known that fissure sealants are an important part of the prevention and control of dental caries in pits and fissures. However, their usage is still sporadic and generally not related to evidence-based guidelines. Caries prevalence has changed since sealants were introduced and this has significant implications for the criteria on which to select patients who would most benefit from their usage. The clinical technique for successful fissure sealant application is very moisture and operator sensitive. However, there is accumulating evidence that use of fissure sealants can be extended, given suitable investigation, to the early carious lesion as a 'preventive resin restoration'.

Adolescent↗
PubMed1999

Can cardiovascular clinical characteristics be identified and outcome models be developed from an in-patient claims database?

The objective of this study was to assess whether administrative (claims) databases can be used to assess clinical variables and predict outcome. Although administrative databases are useful for assessing resource utilization, their utility for assessing clinical information is less certain. Prospectively gathered clinical databases, however, are expensive and not widely available. The UB92 formulation of the hospital bill was used as an administrative source of data and compared with the clinical cardiovascular database at Emory University. The claims database was compared with the clinical database for 11 variables. Outcome models were developed with multivariate methods. A total of 11,883 patients who underwent catheterization (5,255 underwent percutaneous transluminal coronary angioplasty [PTCA] and 3,794 underwent coronary artery bypass surgery [CABG]) between 1991 and 1995 were included. For some variables, the claims database correlated well (diabetes, sensitivity 87%, specificity 99%), whereas for others the claims database was less accurate (peripheral vascular disease, sensitivity 20%, specificity 99%). Uncertain coding in the claims database, which can result in the same code being used for co-morbid states and severity of disease, as well as complications, limited the ability of claims to predict outcome. Clinical databases may also be limited by lack of objectivity and missing data. The utility of claims databases to assess severity of disease and co-morbid states is limited, and outcome modeling and risk assessment from claims databases may be inappropriate and spurious. Developing better data standards and less expensive methods for acquisition of clinical data is necessary for improved outcome assessment.

Cardiovascular Diseases↗
PubMed1999

Dental erosion--the problem and some practical solutions.

There has been a clinical impression among dental practitioners, particularly those working with children, that the problem of dental erosion is increasing. Is this really the case or are we more aware of the problem? What is causing this increase, if it really exists? Perhaps more importantly, what can we do about it? This article looks at the prevalence, and aetiology of dental erosion, particularly in children, and makes some practical suggestions for possible control.

Adolescent↗
PubMed1999

Effect of exogenous FSH on ovulation rate in homozygous carriers or noncarriers of the Booroola FecB gene after hypothalamic-pituitary disconnection or after treatment with a GnRH agonist.

We have tested the hypothesis "that the ovulation rate in homozygous carriers (BB) and noncarriers (+2) of the Booroola FecB gene would not be different if the plasma concentrations of follicle-stimulating hormone (FSH) in the two genotypes were similar." For this purpose we used two experimental animal models: 1) the hypothalamic-pituitary disconnected (HPD) ovary-intact ewe; and 2) and GnRH agonist (i.e., Deslorelin)-treated ewe. Following HPD or Deslorelin treatment, the animals had low plasma concentrations of gonadotropins and were anovulatory. In both animal models, BB and +2 ewes were treated with exogenous pregnant mares serum gonadotropin (PMSG) and varying doses of FSH to induce preovulatory follicular growth, and human chorionic gonadotropin (hCG) to induce ovulation. HPD or Deslorelin-treated animals administered with pregnant mares serum gonadotropin without FSH followed by human chorionic gonadotropin failed to ovulate. However for both animal models, the proportion of BB and +2 ewes ovulating to various doses of FSH differed such that significantly greater proportions of +2 animals ovulated relative to the BB genotype (P < 0.05). When HPD or Deslorelin-treated BB and +2 ewes were administered identical doses of FSH, the mean ovulation rate and plasma concentrations of FSH in those animals which ovulated was the same in both genotypes. These findings confirm, at least in part, the aforementioned hypothesis. The results also demonstrated that higher ovulation rates were obtained in both genotypes as the FSH dose was increased. Collectively, these findings infer that the higher mean ovulation rate in normal intact BB ewes compared to the +2 genotype is attributable to effects of the FecB gene at the level of ovarian follicular development as well as at the level of pituitary FSH release.

Animals↗
PubMed1999

The presence of N-acetylneuraminic acid in Malpighian tubules of larvae of the cicada Philaenus spumarius.

Sialic acid-containing glycoconjugates are generally considered to be unique to the deuterostomes, a lineage of the animal kingdom which includes animals from the echinoderms up to the vertebrates. There are, however, two isolated reports of sialic acid occurring in the insect species Drosophila melanogaster and Galleria mellonella. Since insects are classified as protostomes, these findings call previous assumption on the phylogenetic distribution and thus on the evolution of sialic acids into question. Here, we report the occurrence of N-acetylneuraminic acid (Neu5Ac) in larvae of the cicada Philaenus spumarius. Cytochemical analysis of larval sections with lectins from Sambucus nigra and Limax flavus suggested the presence of sialic acids in the concrement vacuoles of the Malpighian tubules. The monoclonal antibody MAb 735, which is specific for polysialic acid, labelled the same structures. A chemical analysis performed by HPLC of fluorescent derivatives of sialic acids and by GLC-MS provided sound evidence for the presence of Neu5Ac in the Philaenus spumarius larvae. These data suggest that in this cicada Neu5Ac occurs in alpha2,8-linked polysialic acid structures and in alpha2,6-linkages. The results provide further evidence for the existence of sialic acids in insects and in linkages known to occur in glycoconjugates of deuterostomate origin.

Animals↗
PubMed1999

A comparison of sampling and analytical methods for assessing occupational exposure to diesel exhaust in a railroad work environment.

Methods of assessing occupational exposure to diesel exhaust were evaluated in a railroad work environment. The American Conference of Governmental Industrial Hygienists (ACGIH)-recommended elemental carbon and respirable combustible dust methods of sampling and analysis for assessing diesel exhaust were included in the study. A total of 215 personal and area samples were collected using both size-selective (nylon cyclone and Marple) and non-size-selective samplers. The results demonstrate that the elemental carbon method is suitable for the railroad environment and the respirable combustible dust method is not. All elemental carbon concentrations measured were below the proposed ACGIH Threshold Limit Value (TLV) of 0.15 mg/m3. The concentrations of oxides of nitrogen (nitric oxide and nitrogen dioxide) were also found to be below their respective TLVs. There is no correlation between elemental carbon or respirable combustible dust and the oxides of nitrogen. The elemental carbon as fraction of total carbon is about 13 percent, except for onboard locomotives where it is about 24 percent. Comparison of elemental carbon and respirable combustible dust measurements showed consistent relationships for most sampling locations, with respirable combustible dust concentrations 12 to 53 times higher than the elemental carbon levels.

Data Interpretation, Statistical↗
PubMed1999

Laboratory confirmation of scopolamine co-intoxication in patients using tainted heroin.

BACKGROUND: First described in 1995, at least 325 patients with a history of heroin use have since required emergency medical evaluation in several eastern US cities, because of an anticholinergic toxidrome following use of heroin. This co-intoxication has been alleged to result from an atropine-like compound. We report the clinical findings and laboratory analysis of one of several individuals who presented to our Emergency Department during this epidemic. CASE REPORT: A 23-year-old male was one of 3 patients brought to the Emergency Department due to agitated behavior after insufflating heroin. Following physical and chemical restraint, vital signs were pulse 134 bpm, BP 160/90 mm Hg, RR 24/min, and T 37.3 degrees C. Physical examination was remarkable for dilated pupils 8-9 mm without nystagmus, along with dry mouth, decreased bowel sounds, and flushed dry skin. A bladder catheter was placed and 500 mL of urine was obtained. Electrocardiogram revealed sinus tachycardia only. Additional sedation was required for 12 hours until normal mental status returned. A small sample of the "heroin" used was obtained and analyzed. Scopolamine was confirmed by gas chromatography-mass spectrometry. Further evidence of scopolamine intoxication was supported by identifying scopolamine in the urine of this patient. CONCLUSION: Gas chromatography-mass spectrometry revealed scopolamine to be the cause of anticholinergic findings in a patient following use of tainted heroin. It is unclear whether scopolamine is an adulterant or contaminant in this heroin. Patients with anticholinergic findings following use of heroin may be co-intoxicated with scopolamine.

Adult↗
PubMed1999

Predictive properties of a qualitative urine acetaminophen screen in patients with self-poisoning.

OBJECTIVE: Screening for acetaminophen toxicity is recommended in almost all cases of self poisoning. We compared a qualitative urine acetaminophen screen to the quantitative serum acetaminophen to test the hypothesis that a negative urine acetaminophen screen would be predictive of a negative serum acetaminophen level. METHODS: All adults with intentional ingestions evaluated in our Emergency Department during 1995 were retrospectively identified based on Emergency Department International Classification of Disease--9th edition codes. Laboratory data from each patient including serum and urine toxicologic assays were examined. Predictive properties of urine acetaminophen screens for serum acetaminophen were evaluated. RESULTS: A total of 88 patients were identified who had both a serum acetaminophen and a urine acetaminophen performed. The sensitivity of the urine acetaminophen screen was 100% (95% CI 72-100%) and the specificity was 87% (95% CI 80-95%). All patients with negative urine acetaminophen screens had negative serum acetaminophen levels (negative predictive value 100%; 95% CI 96-100%). Accuracy of the urine acetaminophen screen was 89%. CONCLUSION: A negative urine acetaminophen screen was highly predictive of negative serum acetaminophen levels. It is possible that negative urine acetaminophen screens may obviate the need for 4-hour quantitative serum levels. Further validation in a prospective study is needed.

Acetaminophen↗