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S M Dunn

Publications and source records attributed to S M Dunn.

At least 163 records · Page 9Linked to original sources
PubMed1982

Activation and desensitization of Torpedo acetylcholine receptor: evidence for separate binding sites.

The acetylcholine receptor from Torpedo californica was labeled by reaction with the fluorescent probe 4-[N-(iodoacetoxy)ethyl-N-methyl]amino-7-nitrobenz-2-oxa-1,3-diazole without apparent effect on its in vitro ligand binding and functional properties. Addition of acetylcholine or carbamoylcholine to the labeled-receptor preparations enhanced the fluorescence of the bound probe, and this effect was specific for agonists and inhibited by prior incubation with excess alpha-bungarotoxin. Equilibrium fluorescence titrations gave apparent dissociation constants of 0.86 +/- 0.14 mM for carbamoylcholine and 79 +/- 11 microM for acetylcholine, in good agreement with the dissociation constants measured for the permeability response of the receptor. Stopped-flow experiments showed that the fluorescence change was a single exponential process whose rate increased with ligand concentration, reaching a saturating value for carbamoylcholine of approximately 400 s-1. The equilibrium binding of carbamoylcholine was not significantly affected by prior incubation of the receptor with d-tubocurarine or histrionicotoxin and the dissociation constant was only slightly increased in the presence of lidocaine. These inhibitory ligands do not, therefore, compete directly with agonists for this low-affinity binding site, suggesting that their mode of action may be indirect.

Acetylcholine↗
PubMed1981

Effects of local anesthetics and histrionicotoxin on the binding of carbamoylcholine to membrane-bound acetylcholine receptor.

The effects of local anesthetics and perhydrohistrionicotoxin on the kinetic mechanism of carbamoylcholine binding to the membrane-bound acetylcholine receptor have been studied by stopped-flow methods. Receptor-enriched membrane fragments from Torpedo californica were reduced and then alkylated by 5-(iodoacetamido)salicylic acid, and the agonist binding kinetics were monitored by the fluorescence changes of this bound probe. The alkylation procedures did not alter the ability of the receptor to mediate agonist-induced cation flux. Preincubation of such modified receptor preparations with saturating concentrations of lidocaine, prilocaine, or dimethisoquin did not significantly affect the equilibrium dissociation constant for carbamoylcholine binding. The multiphasic kinetic signal which accompanies the binding of the agonist was, however, much simplified in the presence of local anesthetics, and the observed kinetics could be described by a mechanism in which a single conformational change follows the formation of the initial complex. Perhydrohistrionicotoxin did not act in the same way as the local anesthetics examined since saturating concentrations did not significantly perturb the agonist binding kinetics.

Amphibian Venoms↗
PubMed1981

Kinetics of substrate, coenzyme, and inhibitor binding to Escherichia coli dihydrofolate reductase.

Reduced nicotinamide adenine dinucleotide phosphate (NADPH), folate, dihydrofolate, and the inhibitors trimethoprim and methotrexate bind rapidly and reversibly to both dihydrofolate reductase isoenzymes isolated from Escherichia coli RT500. The coenzyme and substrates appear to bind to only one of the mixture of two forms of the isoenzyme present at equilibrium, while the inhibitors bind to both forms. The proportions of the two forms are different for the two isoenzymes and are pH dependent in each case. The measured association rate constants for substrates and inhibitors lie in the range (1--2) x 10(-7) M-1 s-1 at 25 degrees C but are unlikely to be diffusion controlled. The rate constant for NADPH binding is 2 x 10(6) M-1 s-1. The formation of binary complexes takes place through a multistep mechanism. A minimum of three steps is required to explain the kinetic results. An equilibrium between two or more forms of the enzyme--ligand complex governs the overall dissociation. The stability of this equilibrium is largely responsible for the tighter binding of inhibitors relative to substrate or coenzyme and also for the different binding strengths of inhibitors to the isoenzymes.

Escherichia coli↗
PubMed1980

Kinetics of carbamylcholine binding to membrane-bound acetylcholine receptor monitored by fluorescence changes of a covalently bound probe.

The fluorescent probe 5-(iodoacetamido)salicylic acid has been used to alkylate acetylcholine receptor enriched membrane fragments from Torpedo californica following their reduction with low concentrations of dithiothreitol. This modification did not affect the equilibrium binding of carbamylcholine to the receptor. The fluorescence of bound 5-(iodoacetamido)salicyclic acid was enhanced when the labeled membrane fragments were mixed with carbamylcholine. This increase in fluorescence was abolished by preincubation of the membrane fragments with excess alpha-bungarotoxin and was therefore specific for the acetylcholine receptor. Estimates of dissociation constants obtained from centrifugation experiments with radioactive ligand and from fluorescence titration data were in good agreement, showing that the observed fluorescence enhancement was an accurate reflection of receptor-carbamylcholine complex formation. The kinetics of carbamylcholine binding to labeled membrane fragments have been investigated over a wide range of ligand concentrations by using stopped-flow fluorescence techniques. The kinetic signal was complicated, and four distinct exponential phases were observed. A kinetic mechanism has been proposed to account for this behavior.

Acetamides↗
PubMed1980

Kinetics of ternary complex formation between dihydrofolate reductase, coenzyme, and inhibitors.

The kinetics of ligand binding to dihydrofolate reductase from Lactobacillus casei (MTX/R) to form the ternary enzyme-inhibitor-coenzyme complex have been investigated by the stopped-flow fluorescence technique. The fluorescence changes observed when coenzymes or inhibitors bind to the binary complex of the enzyme with the complementary ligand occur in a single fast phase. Under pseudo-first-order conditions the reaction traces could be fitted with precision to a single-exponential decay, and apparent bimolecular rate constants in the range 2 x 10(6) to 3 x 10(7) M-1s-1 have been measured assuming a bimolecular-unimolecular model. The kinetic constants obtained suggest that prior binding of an inhibitor to the enzyme may, to a minor extent, interfere with coenzyme binding but the rates of inhibitor binding seem to be unaffected by the presence of a bound coenzyme. Dissociation rate constants appear to be less than 1 s-1 which suggests that both coenzymes and inhibitors are tightly bound in the ternary complex. An investigation of the effects of pH on the kinetics of ternary complex formation indicated the involvement of ionizable groups in ligand binding, but this shows some ligand dependence. The rates of ligand bindings to form the ternary complex are fairly high, but it is unlikely that these associations are diffusion controlled because their measured activation energies of 7.8-14.5 kcal mol-1 are higher than expected from reactions whose rates are limited by diffusion in aqeous solution.

Hydrogen-Ion Concentration↗
PubMed1979

An outbreak of gastroenteritis in young children caused by adenoviruses.

During October and November, 1978, gastroenteritis developed in 17 of 24 young children aged between eight months and two years from an R.A.F. station in the U.K. The illness, in which diarrhoea was always the predominant symptom, had an incubation period of eight to ten days and lasted about a week. It seemed to be transmitted from child to child, and in all but one instance parents and older siblings remained well. Stool specimens from 14 of the affected children were examined bacteriologically and virologically, and a highly significant association was found between the presence of adenovirus particles in stools, identified by electron microscopy, and the acute stage of the illness. This evidence suggests that an adenovirus was the cause of this outbreak of gastroenteritis.

Adenoviridae Infections↗
PubMed1979

Specific binding of perhydrohistrionicotoxin to Torpedo acetylcholine receptor.

Torpedo californica postsynaptic membrane fragments were treated with base, which resulted in membranes that were depleted of many nonacetylcholine receptor polypeptides and contained acetylcholine receptor subunits of Mr 40,000, 50,000, 60,000, and 65,000 (Raftery, M.A., Vandlen, R.L., Reed, K.L. & Lee T. (1975) Cold Spring Harbor Symp. Quant. Biol. 40, 193-202). A 43,000-Mr polypeptide and some other components were quantitatively extracted. Base-treated membranes retained the capacity to bind [3H]perhydrohistrionicotoxin and the local anesthetics dibucaine and tetracaine. The regulation of this binding by carbamylcholine, as well as the kinetic mechanism of perhydrohistrionicotoxin binding, was unchanged. [3H]Perhydrohistrionicotoxin binding activity was largely reconstituted from 2% sodium cholate extracts of base-treated membranes. Therefore, the perhydrostrionicotoxin binding site appears to be located on one or more of the acetylcholine receptor polypeptides, and the reconstitution of that binding site from detergent extracts does not require the presence of a 43,000-Mr polypeptide.

Acetylcholine↗
PubMedDate not supplied

Communication styles in the cancer consultation: preferences for a patient-centred approach.

OBJECTIVE: Although doctor-patient communication has been the focus of numerous studies, there is a lack of empirical evidence on which to base a curriculum for teaching effective communication skills for use in an oncology setting. Research within the general practice area identifies patient-centred and doctor-centred behaviours as the most important dimensions of doctor-patient communication. This study examined patients and their relatives/friends' preferences for and satisfaction with patient-centred and doctor-centred consulting styles. It was argued that by determining patient preferences for consulting styles, specific recommendations for improving communication in the oncology setting could be formulated. PARTICIPANTS AND METHODS: One hundred and thirteen women who had been treated for breast cancer and 48 of their relatives or friends watched videotaped scenarios of an oncology consultation, using professional actors. Viewers were randomly allocated to either a good prognosis or poor prognosis video, in which the oncologist discussed the patient's diagnosis, treatment and prognosis. These segments were presented in both styles to allow viewers to directly compare and contrast the patient-centred and doctor-centred approach. Outcomes included style preference and satisfaction. Demographic details, information and involvement preferences, anxiety and depression levels were also obtained. RESULTS: Both patients and their relatives or friends significantly preferred a patient-centred consulting style across all aspects of the consultation (p<0.0001), except within the treatment segment of the good prognosis video where there was no significant difference. One third of the viewers preferred a doctor-centred style for the treatment and prognosis segments. Predictors of a patient-centred style preference in the treatment and prognosis segments included watching a poor prognosis video (OR=2.45, 95% CI 1.04-5.81, p=0.04; OR=3.22, 95% CI 1.22-8.50, p=0.02, respectively), and being employed in a professional occupation (OR=2.38, 95% CI 1.02-5.53, p=0.04 for the treatment segment only). Satisfaction ratings varied within and across videos. CONCLUSION: Despite some methodological limitations, this study provides empirical data indicating that patients and their relatives or friends prefer a patient-centred approach to the consultation, particularly when the patient has a poor prognosis. The fact that a substantial minority of patients preferred a doctor-centred style emphasizes the need to enhance physicians' abilities to recognize different patient needs throughout the consultation.

Adaptation, Psychological↗
PubMedDate not supplied

Coping with metastatic melanoma: the last year of life.

BACKGROUND: Few longitudinal studies have concurrently investigated cognitive appraisal, coping and psychological adjustment in patients with terminal cancer. This study aimed to (i) consider patterns of change in these variables during the last year of life and (ii) consider covariates associated with patients' psychological adjustment. METHODS AND PATIENTS: Questionnaires were sent to a cohort of stage IV melanoma patients seen at the Sydney Melanoma Unit between 1991 and 1996, approximately every 3 months, for up to 2 years. A sub-sample of 110 patients completed at least one questionnaire in the last year of life. Repeated measures linear regression was used to model cognitive appraisal, coping and psychological adjustment. RESULTS: In the last year of life, patients' cognitive appraisal of their disease remained relatively stable, whereas their use of active coping strategies increased (p=0. 04). There was some deterioration in psychological adjustment, particularly in patients' ability to minimize the impact of cancer on daily life (p=0.03), but this effect did not remain significant when patients' level of tiredness was included in the model. Cognitive appraisal, coping style and quality of life indicators were all associated with psychological adjustment. CONCLUSION: These findings suggest that while patients work hard to actively cope with their disease, they experience increasing levels of tiredness, and deterioration in their mood and ability to function in their daily lives.

Activities of Daily Living↗
PubMedDate not supplied

Oncologists' reactions to cancer patients' verbal cues.

The diagnosis and treatment of cancer cause considerable psychological distress and morbidity. Consequently, cancer patients have high needs for informational and emotional support and doctors vary in their ability to recognise and address these needs. This study investigated patients' attempts to gain informational and emotional support through the use of verbal cues. The sample consisted of 298 patients with heterogeneous cancers, seeing one of five medical and four radiation oncologists for the first time. Sociodemographic variables and patient anxiety and satisfaction ratings were obtained. Transcripts of the audiotaped consultations were analysed and question-asking, use of indirect cues, cue type (informational or emotional), content categories in which questions and cues occurred and doctor response (responded to or not responded to), were recorded. Patients asked a median of 11 questions and gave two cues per consultation, usually during treatment discussions. Patients gave, and doctors responded to, more informational than emotional cues. Patients gave significantly more informational cues during longer consultations. Younger and female patients gave more cues for emotional support and asked questions. No demographic variables were associated with the doctors' response to emotional and informational cues; however, consultations in which more informational cues were responded to were shorter, even when controlling for the number of cues given. Satisfaction with the consultation and patient anxiety were unaffected by doctors' responses to cues. Overall, results showed that doctors effectively identify and respond to the majority of informational cues; however, they are less observant of and able to address cues for emotional support. Cues can be addressed without lengthening the consultation or increasing patient anxiety.

Adaptation, Psychological↗
PubMedDate not supplied

Localized spatial discrimination of epicardial conduction paths after linear transformation of variant information.

We present a method for the localized statistical discrimination of class populations based on the Karhunen-Loève and Fukunaga-Koontz transforms. These transforms provide features that model the variance of a sample distribution. The spatial series of a 196 channel epicardial electrogram recording from an arrythmogenic postinfarct canine were analyzed. For each type of rhythm studied, Karhunen-Loève and Fukunaga-Koontz expansions were computed from five training sets of spatial data, corresponding to five locations across the surface of the heart. Nonparametric statistical tests were then used for discriminant analysis to compare properties representative of the distribution from each proposed class. In a comparison of properties from sinus rhythm to those of two ventricular tachycardias, several spatial regions exhibited statistically significantly different propagation characteristics. These areas were observed by visual inspection of electrogram activation maps to be characterized by conductive gradients, which differed in magnitude and direction from one rhythm to another. The regions in which the propagation characteristics are of greatest difference in each tachycardia were centered upon sites of conduction block, manifested by reentrant circuit rhythms. Therefore, the importance of the technique for the localization of specific electrophysiologic events is demonstrated. This study extends previous work of our group on biosignal pattern recognition to encompass localized spatial data.

Analysis of Variance↗
PubMedDate not supplied

Integrating emergency medicine residents into a well-established helicopter program.

INTRODUCTION: The institution of an emergency medicine residency in a university-affiliated Level 1 trauma center in July 1993 provided a challenge to develop a curriculum and on-line learning experience for emergency medicine residents in a well-established helicopter program. The purpose of this study was to survey flight crew members, emergency medicine at tending physicians, and emergency medicine residents on the anticipated roles and educational experience of integrating the emergency medicine residents from a new emergency medicine residency into the flight crew of a well-established helicopter program. METHODS: A survey consisting of multiple choice, Likert scale, and open-ended questions was distributed to flight crew members (RN, RT, pilots, communication specialists, EM attendings, and EM residents [n=72]). RESULTS: 92% of surveys were returned. These surveys identified specific issues of concern and those areas believed to be of academic importance for the emergency medicine residents. CONCLUSIONS: The results of this study allowed for the creation and implementation of a progressive flight experience for EM residents that incorporates increasing responsibility on the flight crew as experience is gained.

Air Ambulances↗
PubMedDate not supplied

The measurement of mandibular cortical bone height in osteoporotic vs. non-osteoporotic postmenopausal women.

The asymptomatic progression of osteoporosis, in conjunction with the possibility of catastrophic disability, makes this disorder a major public health priority. Various body sites, including the mandible, have shown susceptibility to decreasing bone density. In 1986, Benson et al. proposed a radiomorphometric technique called the Panoramic Mandibular Index (PMI) as an inexpensive noninvasive dental technique for osteoporosis screening, although no osteoporotic subjects were included in their study. The purpose of our study was to determine whether osteoporotic postmenopausal women would show a decrease in mandibular cortical bone height, as measured by the PMI index, when compared with nonosteoporotic postmenopausal women. Seventy-two Caucasian females (33 cases/39 controls), aged 54-71 years old, were selected through records and screening via a dual-energy x-ray absorptiometry scan (LUNAR-DEXA). ANOVA analysis indicated no differences in the mean PMI between case and control groups (0.37 +/- 0.15 and 0.38 +/- 0.13, respectively; p = 0.69). Other techniques, such as computer digitized radiography should be explored to test the validity of the PMI.

Absorptiometry, Photon↗