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1.  Assignment of EPR Transitions in a Manganese-Containing Lipoxygenase and Prediction of Local Structure 
Applied magnetic resonance  2001;21(3-4):413-424.
A new variant of lipoxygenases, one containing manganese instead of iron, is characterized by electron paramagnetic resonance (EPR) at two frequencies. In the manganous state (Se = 5/2), maganese lipoxygenase (MnLO) yields very broad X-band (9.2 GHz) EPR signals, extending over about 800 mT. In contrast, at W-band (94 GHz), the signal is much simplified, consisting of nested transitions centered near the free electron g-value. Computer simulation has been employed to derive estimates of the zero-field splittings for MnLO, with data from these two EPR frequencies. The general features of both X- and W-band spectra are fit, first, by simulations with Se = 5/2, but no nuclear hyperfine splitting. The simulations are then refined by inclusion of the hyperfine splitting. On the basis of the simulations, the ranges of zero-field splitting parameters are D = +0.07 to +0.10 cm−1, and E/D = 0.13 to 0.23. Comparison of the value of D for MnLO with that of other manganese-containing proteins suggests that MnLO has three N-ligands to the metal center and O-ligands in the remainder of 6 coordination positions. The coordination environment of MnLO is similar to that in iron lipoxygenases.
PMCID: PMC1388185  PMID: 16518455
2.  Exploring Surfaces and Cavities in Lipoxygenase and Other Proteins by Hyperpolarized Xenon-129 NMR 
This paper presents an exploratory study of the binding interactions of xenon with the surface of several different proteins in the solution and solid states using both conventional and hyperpolarized 129Xe NMR. The generation of hyperpolarized 129Xe by spin exchange optical pumping affords an enhancement by 3–4 orders of magnitude of its NMR signal. As a result, it is possible to observe Xe directly bound to the surface of micromolar quantities of lyophilized protein. The highly sensitive nature of the 129Xe line shape and chemical shift are used as indicators for the conditions most likely to yield maximal dipolar contact between 129Xe nuclei and nuclear spins situated on the protein. This is an intermediate step toward achieving the ultimate goal of NMR enhancement of the binding-site nuclei by polarization transfer from hyperpolarized 129Xe. The hyperpolarized 129Xe spectra resulting from exposure of four different proteins in the lyophilized, powdered form have been examined for evidence of binding. Each of the proteins, namely, metmyoglobin, methemoglobin, hen egg white lysozyme, and soybean lipoxygenase, yielded a distinctly different NMR line shape. With the exception of lysozyme, the proteins all possess a paramagnetic iron center which can be expected to rapidly relax the 129Xe and produce a net shift in its resonance position if the noble gas atom occupies specific binding sites near the iron. At temperatures from 223 to 183 K, NMR signals were observed in the 0–40 ppm chemical shift range, relative to Xe in the gas phase. The signals broadened and shifted downfield as the temperature was reduced, indicating that Xe is exchanging between the gas phase and internal or external binding sites of the proteins. Additionally, conventional 129Xe NMR studies of metmyoglobin and lipoxygenase in the solution state are presented. The temperature dependence of the chemical shift and line shape indicate exchange of Xe between adsorption sites on lipoxygenase and Xe in the solvent on the slow to intermediate exchange time scale. The NMR results are compared with N2, Xe, and CH4 gas adsorption isotherms. It is found that lipoxygenase is unique among the proteins studied in possessing a relatively high affinity for gas molecules, and in addition, demonstrating the most clearly resolved adsorbed 129Xe NMR peak in the lyophilized state.
doi:10.1021/ja991443+
PMCID: PMC1317562  PMID: 16429610
3.  Prioritising the cardiac surgery waiting list: the angina patient's perspective. 
Heart  1997;77(4):330-332.
OBJECTIVE: To determine patients' views on how clinical and demographic factors should affect priorities for cardiac revascularisation. DESIGN: A descriptive survey of patients' views conducted immediately after angiography and treatment counselling. SUBJECTS: 136 patients who were awaiting coronary angioplasty in either of the two regional cardiology centres in Northern Ireland. RESULTS: About half the subjects (52%) felt that certain social factors such as having dependent relatives should be taken into account when deciding priority for surgery. A sizeable minority felt that younger subjects and non-smokers (40% and 44%, respectively) should be accorded higher priority, with older subjects and smokers being more likely to hold such views. CONCLUSIONS: While there is little evidence that demographic and lifestyle factors affect the relative efficacy of surgery, the challenge remains to devise a prioritisation guideline that can properly reflect societal values and the evidence base.
PMCID: PMC484726  PMID: 9155611
4.  RNA synthesis using a universal, base-stable allyl linker. 
Nucleic Acids Research  1997;25(20):3980-3983.
The application of a universal allyl linker, 9-O-(4,4'-dimethoxytrityl)-10-undecenoic acid, to the solid phase synthesis of RNA molecules is described. Use of this linker simplifies significantly the isolation and purification steps in RNA synthesis. The linker is universal in that it does not contain a nucleoside. The 3'terminal nucleoside is instead attached to the support in the first coupling step. The resultant RNA fragment is then obtained as the 3'-phosphate. The linker is base-stable, and thus all reagents used during deprotection can simply be washed away, leaving the RNA attached. Further, tritylated short fragments resulting from chain cleavage for any reason are also washed away before separation from the support. This linker is compatible with any current synthetic methodology and any amino functionalized support. Of course, silica supports would not be compatible with fluoride reagents. It could also be used to advantage for other applications. Because it is cleaved under conditions orthogonal to those used during many common reactions, the range of post-synthetic manipulations that can be carried out without cleavage from the support is extended significantly.
PMCID: PMC147002  PMID: 9321646
5.  Risks and benefits of coronary angioplasty: the patients perspective: a preliminary study. 
Quality in Health Care  1997;6(3):131-139.
OBJECTIVES: To describe what cardiac patients in Northern Ireland understand to be the benefits of coronary angioplasty and assess the extent to which they have been able to make informed choices about their treatment. DESIGN: An interview based questionnaire survey completed after the patients had undergone coronary angiography, within hours of treatment counselling. SUBJECTS: 150 patients consecutively recruited from two regional cardiology centres in Belfast, Northern Ireland. MAIN OUTCOME MEASURES: The perceived complication rate and the perceived gain in life expectancy from coronary angioplasty. RESULTS: Although most subjects had asked the consultant questions, 70% (n = 104) thought that they contributed negligibly or not at all to the treatment decision. Although 75% (n = 112) recalled discussing the complication rate from the procedure, only 27% accurately estimated this rate (as between 0.5 and 1.5%). Eighty eight per cent (n = 131) thought that their mortality risks would be substantially or greatly reduced by having the procedure. The patients anticipated a gain in life expectancy of some 10 years (median) and this was significantly in excess of the potential gain in life expectancy which dietary prudence to lower blood cholesterol, not smoking, and taking more exercise might produce (median 5 years respectively; P < 0.0001, Wilcoxon matched pairs signed rank test). CONCLUSIONS: Patients vastly overrate the capacity of angioplasty to control their disease: angioplasty is seen as more effective than risk factor modification.
PMCID: PMC1055474  PMID: 10173770
6.  Predictors for waiting time for coronary angioplasty in a high risk population. 
Quality in Health Care  1995;4(4):244-249.
Objective--To describe the clinical and non-clinical factors which influence the waiting time from initial angiography to angioplasty. Design--Follow up of a random sample of 106 patients undergoing their first coronary angiography for whom a decision to revascularise by percutaneous transluminal angioplasty was made in 1991. The period between the date of angiography and the date of angioplasty and various clinical characteristics of patients were retrieved from medical notes in mid 1993. Patients were sampled from those investigated in the two Northern Ireland catheterisation laboratories in Belfast, which provide services for the whole of the province (population 1.5 million). Main measures--The dependent variable was the period between initial angiography and angioplasty, and the independent variables included age, sex, distance from cardiac catheterisation centre, referral source, characteristics of the clinical history, severity of angina, and anatomical extent of disease. Cox's proportional hazards analysis was used to derive a relative hazard, expressing the relative chances of revascularisation occurring at any time during follow up. Results--Of the 106 patients studied, 93 had had percutaneous transluminal angioplasty at follow up. The most important predictors of waiting time were the presence of severe angina (relative hazards 3.1(95 % confidence interval (95% CI) 1.4-6.8) and 2.7(1.2-6.2) for Canadian Cardiovascular grades III and IV v angina grade I angina), a recent history of myocardial infarction (relative hazard, 2.5(1.3-4.8), and whether or not the patient was economically active (relative hazard 0.6(0.4-1.0) for economically inactive v active patients). Although there was also an association with the relative deprivation of the area of residence of the patient it had no clear linear trend. Conclusions--Although waiting time for percutaneous transluminal angioplasty was predictably related to the patient's clinical presentation, demographic factors may also be important in determining access to intervention. These factors clearly merit further study; ultimately, the evaluation of equity in a waiting time distribution may more properly be a societal rather than a clinical judgment.
PMCID: PMC1055334  PMID: 10156393
7.  Are the economically active more deserving? 
British Heart Journal  1995;73(4):385-389.
OBJECTIVE--To investigate the possibility of an association between the duration of medical treatment before coronary angiography and demographic and non-clinical factors. DESIGN--A systematic review of a random sample of 500 patients undergoing their first angiographic assessment. SUBJECTS--500 cases were selected randomly from patients investigated in 1991 at the two catheterisation centres in Northern Ireland. MAIN OUTCOME MEASURES--The duration of medical management before angiography. RESULTS--346 had elective and 154 urgent catheterisation. The duration of medical management was adjusted for both case mix (age at onset, body mass index, angina grade, history of myocardial infarction, history of hypertension, diabetes or hyperlipidaemia, treatment intensity) and other demographic variables (sex, smoking status, an indicator of "deprivation", and distance of the patient's area of residence from the hospital). After this adjustment the mean duration of medical management before angiography was twice as long for economically inactive patients as for those who were economically active. In a multiple regression, the relevant beta coefficient was 0.44 (95% confidence interval 0.33 to 0.58, P < 0.0001). CONCLUSIONS--These results suggest that, in making discretionary decisions about when to refer patients with angina for revascularisation assessment, doctors may be influenced by non-clinical factors unrelated to disease severity.
PMCID: PMC483836  PMID: 7756076
8.  Expanding access to coronary artery bypass surgery: who stands to gain? 
British Heart Journal  1995;73(2):129-133.
OBJECTIVE--To determine the perceptions of general practitioners (GPs) about the benefits of coronary artery bypass surgery, in terms of gains in life expectancy, for different groups of patients. DESIGN--A questionnaire survey of all GPs in Northern Ireland. SETTING--A survey conducted collaboratively by the departments of public health medicine in each of the four health boards in the province, serving a total population of 1.5 million. MAIN OUTCOME MEASURES--The median and mean gain in life expectancy perceived by groups of doctors for smoking and non-smoking male and female 55 year old patients. The percentage of 50 year old and 70 year old non-smoking patients considered likely to have their lives extended with bypass surgery. Differences were assessed using the Mann-Whitney U test for unpaired samples and the Wilcoxon signed rank tests for paired. RESULTS--541 GPs replied (response rate 56%). The median (and mean) perceived gain in life expectancy after cardiac surgery for non-smoking 55 year old subjects was 120 (104) months for men and 120 (112) months for women (z = 6.42; P < 0.0001; Wilcoxon signed rank test). For male and female smokers of the same age, the perceived gains were 48 (47) and 60 (52) months respectively (z = 6.72; P < 0.0001; Wilcoxon signed ranks test), both figures being significantly different than for non-smokers. The median (and mean) percentage of patients that the doctors considered would have their lives extended by bypass surgery was 70 (64) of every 100 "young" patients and 40 (42) of every 100 "old" patients, (z = 16.2; P < 0.0001). CONCLUSIONS--These results point to a significant overestimation of the benefits of coronary artery bypass surgery by GPs in Northern Ireland and to a need to develop guidelines for referral.
PMCID: PMC483778  PMID: 7696021
9.  Is choice of general practitioner important for patients having coronary artery investigations? 
Quality in Health Care  1994;3(1):17-22.
OBJECTIVE--To determine whether particular sociodemographic characteristics of patients with stable angina affected their general practitioners' (GPs') decisions to refer them for revascularisation assessment. DESIGN--Postal questionnaire survey. SETTING--Collaborative survey by the departments of public health medicine in each of the four health boards in Northern Ireland, serving a total population of 1.5 million. SUBJECTS--All (962) GPs. MAIN MEASURES--The relation between GPs' referral decisions and patients' age, sex, employment status, home circumstances, smoking habits, and obesity. RESULTS--541 GPs replied (response rate 56%). Most were "neutral" towards a patient's sex (428, 79%), weight (331, 61%), smoking habit (302, 56%), employment status (431, 80%), and home circumstances (408, 75%) in making decisions about referral. In assigning priority for surgery most were neutral towards the patient's sex (459, 85%), employment status (378, 70%), and home circumstances (295, 55%). However, most GPs (518, 95%) said that younger patients were more likely to be referred, and a significant minority were less likely to refer patients who smoked (202, 37%) and obese patients (175, 32%) and more likely to refer employed patients (97, 18%) and those with dependents (117, 22%) (compared with patients with otherwise comparable clinical characteristics); these views paralleled the priority which GPs assigned these groups. The stated likelihood of referral of young patients was independent of the GPs' belief in ability to benefit from revascularisation, but propensity to refer and perception of benefit were significantly associated for all other patient characteristics. CONCLUSION--GPs' weighting of certain characteristics in reaching decisions about referral for angiography is not uniform and may contribute to unequal access to revascularisation services for certain patient groups.
PMCID: PMC1055177  PMID: 10136255
10.  Childhood accidental deaths on farms in Northern Ireland. 
The Ulster Medical Journal  1993;62(2):137-140.
Deaths to children on farms in Northern Ireland over a five year period are reviewed. There were seventeen such deaths, the majority of which involved farm machinery. The circumstances of the accidents are described in order to highlight the preventable aspects of these accidents.
PMCID: PMC2449046  PMID: 8303796
11.  Access to coronary catheterisation: fair shares for all? 
BMJ : British Medical Journal  1993;307(6915):1305-1307.
OBJECTIVE--To determine the effects of patient's sex and area's material deprivation on utilisation rates of coronary catheterisation and angiography in the investigation of ischaemic heart disease. DESIGN--Retrospective analysis of routinely collected hospital statistics. SETTING--Acute hospitals throughout Northern Ireland. SUBJECTS--24,179 episodes of patients discharged from hospital with a primary diagnosis of ischaemic heart disease and 1270 episodes relating to patients with an underlying diagnosis of ischaemic heart disease who had either coronary catheterisation or angiography. MAIN OUTCOME MEASURES--Age standardised admission rates for heart disease and age standardised utilisation rates for catheterisation or angiography, or both, for 566 electoral wards ranked by Townsend "deprivation" scores. RESULTS--Catheterisation-angiography rates in men were over fivefold those of women, ranging from 85.5/100,000 v 16/100,000 in patients from "well off" areas to 123/100,000 v 22/100,000 for patients from deprived areas. After admission rates for heart disease were controlled for, the overall rate ratio for women was 0.48 (95% confidence interval 0.38 to 0.60). After differential admission rates for heart disease and other potential clinical confounders were controlled for, the investigation rates of patients from the least and most "deprived" areas were not significantly different (rate ratio 1.04 (0.87 to 1.25)). CONCLUSION--Although investigation rates were significantly lower in women than in men, further clinical data would be required before labelling this underutilisation as evidence of bias. There was no significant difference in invasive investigation rates for heart disease in areas of varying deprivation or affluence.
PMCID: PMC1679460  PMID: 8257883
12.  The influence of the purine 2-amino group on DNA conformation and stability. Synthesis and conformational analysis of d[T(2-aminoA)]3. 
Nucleic Acids Research  1982;10(14):4351-4361.
A self-complementary hexanucleotide consisting of thymidine and 2-amino-deoxyadenosine, d(TA')3, has been synthesized by a solid phase phosphotriester method. Melting studies show that the additional hydrogen bond afforded by the 2-amino group substantially stabilizes the duplex. Moreover, conformational analysis using circular dichroism shows that a salt-induced conformational transition occurs, similar to the B leads to Z transition observed for d(CG)n oligonucleotides.
PMCID: PMC320804  PMID: 7122239
13.  Characterization by 1H NMR of glycosidic conformations in the tetramolecular complex formed by d(GGTTTTTGG). 
Nucleic Acids Research  1991;19(17):4619-4622.
We have conducted two dimensional NOESY studies on the molecule d(G2T5G2) to characterize the structure of the tetramolecular complex previously identified by calorimetric and spectroscopic studies (1). Analysis of the NOE and exchange cross peaks observed in the NOESY spectra establishes the formation of structured conformations at low temperature (5 degrees C). Significantly, within each strand of these structured conformations, the G1 and G8 residues adopt syn glycosidic torsion angles, while the G2 and G9 residues adopt anti glycosidic torsion angles. Consequently, any structure proposed for the tetramolecular complex of d(G2T5G2) must have alternating G(syn) and G(anti) glycosidic torsion angles within each strand. The implications of this observation for potential structures of the tetramolecular complex of d(G2T5G2) are discussed.
PMCID: PMC328700  PMID: 1891352
14.  Methylation of thymine residues during oligonucleotide synthesis. 
Nucleic Acids Research  1985;13(2):573-584.
Thymine residues in an oligodeoxyribonucleotide are subject to methylation at N3 by the internucleotide methyl phosphotriester linkages. This alkylation occurs most rapidly in the presence of a strong base such as DBU, but also takes place, at a much slower rate, during oligonucleotide synthesis.
PMCID: PMC341015  PMID: 4000926

Results 1-14 (14)