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Biomedical subjects

S M Dunn

Publications and source records attributed to S M Dunn.

At least 91 records · Page 5Linked to original sources
PubMed1995

The effect of independent film and object rotation on projective geometric standardization of dental radiographs.

Digital alignment of dental X-ray images using projective invariants has been shown to be a feasible method for detecting changes through digital subtraction radiography. Previous research on the validity of the standardization procedure has considered the effects of motion of the X-ray source alone. Here the effects of independent motion of the film and the object on the standardization are investigated. This is accomplished by fitting a wire grid to the X-ray source, which allows for correction of film motion separately. The usefulness of separating the motion corrections is discussed, as well as some possible sources of error in the overall standardization procedure. The results of the standardization were found not to differ significantly whether the motions were corrected for separately or simultaneously.

Algorithms↗
PubMed1994

Requirement for nuclear factor (NF)-kappa B p65 and NF-interleukin-6 binding elements in the tumor necrosis factor response region of the granulocyte colony-stimulating factor promoter.

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor produced by mesenchymal and myeloid cells following activation by inflammatory stimuli. It has previously been shown that a region of the G-CSF promoter, (-200 to -165) containing the decanucleotide CK-1 element and two repeated sequences that resemble nuclear factor (NF)-interleukin-6 (IL-6) binding sites, is required for activation of the G-CSF gene by tumor necrosis factor-alpha (TNF-alpha) and IL-1 beta. We now show that the NF-kappa B p65 protein can bind to and activate this TNF response region. There are several unusual features of this p65 interaction with the TNF response region. First, NF-kappa B p65 but not the related NF-kappa B p50 binds to the CK-1 element and a p50/65 hybrid protein that relies on the p50 rel homology domain for DNA binding does not transactivate the TNF response region. Second, p65 transactivation of this region is cell specific and requires not only its own binding site but also the NF-IL6 consensus sites. NF-IL6 also binds to the TNF response region of the G-CSF promoter. Electrophoretic mobility shift studies show that p65 and NF-IL6 can bind cooperatively to the TNF response region. The ability of this region to respond to TNF-alpha or p65 is correlated with the ability to form the p65/NF-IL6 ternary complex.

Animals↗
PubMed1994

Effects of calcium channel blockers on the kinetics of voltage-dependent changes in synaptosomal calcium concentrations.

Synaptosomal preparations from rat cerebral cortex have been used in stopped-flow fluorescence studies to measure rapid changes in intrasynaptosomal calcium concentrations upon depolarization. Synaptosomes were loaded with the fluorescent calcium chelating dye, Fura-2, by incubation with the membrane permeant acetoxymethyl ester derivative. Depolarization by elevated external K+ concentration resulted in a rapid increase in cytoplasmic Ca2+ as measured by a quench in Fura-2 fluorescence when excited at 390 nm. The fluorescence change could be reasonably fit by a single exponential process with an apparent rate of 10-15 s-1 and the magnitude of the response was voltage-dependent, increasing with increasing external K+ over the range of 5-30 mM. The observed quench was blocked by micromolar concentrations of the inorganic calcium channel blockers, Cd2+, Co2+ and La3+. Nimodipine, a dihydropyridine which blocks L-type calcium channels, inhibited only 10-15% of the flux response while nitrendipine had no consistent effect. omega-Conotoxin GVIA, a blocker of N-type channels in many species, had only a small inhibitory effect at high (1-10 microM) concentrations. The response was, however, inhibited by pre-incubation of the synaptosomes with venom of the funnel web spider. Agelenopsis aperta (0.1-300 micrograms/ml). Inhibition was observed with both a purified polyamine fraction (FTX) from the venom (IC50 = 4 nl/ml) and a purified peptide toxin, omega-AgaIVA (IC50 = 30 nM). These results indicate that voltage-dependent Ca2+ uptake by mammalian nerve terminals is mediated primarily by channels that are insensitive to dihydropyridines and omega-conotoxin GVIA but are sensitive to components of funnel web spider venom.

Animals↗
PubMed1994

Reconstitution of purified GABAA receptors: ligand binding and chloride transporting properties.

GABAA receptors have been solubilized from bovine brain membranes and, following purification by benzodiazepine affinity chromatography, have been reconstituted into phospholipid vesicles. Reconstituted vesicles were about 120 nm in diameter, and, on average, each vesicle contained fewer than one GABAA receptor which was reconstituted in an outside-out orientation. These preparations have been used in parallel studies of radiolabeled ligand binding and chloride flux, the latter being measured by following the fluorescence changes of a chloride-sensitive probe which was trapped within the vesicles at the time of reconstitution. The benzodiazepine [3H]flunitrazepam binds to an apparently homogeneous population of sites in these preparations (Kd of 5 nM) whereas the GABA analogue [3H]muscimol binds to both high- and low-affinity sites (KdS of 10 nM and 0.27 microM). Muscimol stimulated chloride flux with an EC50 of 0.2 microM and, at similar concentrations (EC50 = 0.16 microM), potentiated [3H]flunitrazepam binding, suggesting that occupancy of the low-affinity sites may be important for these effects. Diazepam shifted the dose-response curve for muscimol-stimulated flux to about 4-fold lower concentrations without affecting the maximum response. Diazepam did not, however, alter the equilibrium binding of [3H]muscimol. The purified receptor showed densensitization since flux responses were abolished by prior exposure to muscimol. The competitive antagonist bicuculline and the channel blocker picrotoxin completely inhibited ion flux mediated by 3 microM muscimol with EC50 values of 5.3 and 2.5 microM, respectively. These results are discussed in terms of possible mechanisms for activation, inhibition, and modulation of GABAA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Phorbol ester-induced transcription of an immediate-early response gene by human T cells is inhibited by co-treatment with calcium ionophore.

Human T cells require two discrete signals to initiate their proliferation. In Jurkat T cells the first signal can be provided by the phorbol ester TPA and the second by the calcium ionophore A23187. We have isolated a cDNA from Jurkat T cells representing mRNA induced by TPA but inhibited by simultaneous treatment of the cells with antibody, lectin, or A23187. Sequencing revealed identity of the Jurkat clone to a cDNA, termed ETR101, recently isolated from HL60 promyelocytic leukaemia cells and shown to be an immediate early gene expressed upon TPA stimulation of these cells [Shimizu et al.: J Biol Chem 266:12157, 1991]. The gene is also induced very rapidly upon TPA treatment of Jurkat cells and is superinduced by co-treatment with cycloheximide. The predicted amino acid sequence encoded by ETR101 has weak homology to JunB and JunD, therefore it is of some interest that these three genes share the chromosomal localization, 19p13.2. The divergent effects of TPA treatment upon cell proliferation and differentiation in different circumstances allow some speculation about a possible role for the ETR101 gene product upon cellular differentiation.

Base Sequence↗
PubMed1994

Pattern recognition and interpretation of electromyogram data from cat jaw muscle.

This study investigates the effect of emotional behavior on the masseteric muscle EMG response patterns. Two experimental protocols are utilized: (1) does not elicit emotional behavior (stick chewing) and (2) elicits emotional behavior (hypothalamic stimulation). The Karhunen-Loève transform is used to compute features which exactly represent the correlated patterns of mean-zero observations, with data compression and noise immunity. Using nonparametric tests, it is found that the populations of biting and hissing features are significantly different (p < 0.05), with increased statistical significance as the size of the training set is increased. No statistically significant difference is seen in a test of the two biting populations.

Animals↗
PubMed1994

Patient participation in the cancer consultation: evaluation of a question prompt sheet.

BACKGROUND: Active participation and asking questions are important ways in which patients can ensure they understand what the doctor has said. This study evaluated a question prompt sheet designed to encourage patients to ask questions in the cancer consultation. PATIENTS AND METHODS: Patients (n = 142) were randomised to receive (i) a question prompt sheet or (ii) a general sheet informing patients of services available through the regional Cancer Council. Recall of information was assessed in a structured interview 4-20 days after the consultation. Questionnaires to assess patient satisfaction and adjustment to cancer were sent by mail. RESULTS: The question prompt sheet had a significant effect in one content area: prognosis. Thirty-five percent of patients who received the question handout asked questions about prognosis compared to 16% of those receiving the information handout. The prompt sheet did not increase the mean number of questions asked overall. Age, in/out-patient status, gender and involvement preference were predictive of both number and duration of patient questions. CONCLUSIONS: A question prompt sheet has a limited but important effect on patient question asking behaviour in the cancer consultation.

Adaptation, Psychological↗
PubMed1994

An intrathecal fentanyl dose-response study in lower extremity revascularization procedures.

BACKGROUND: Intrathecal opioids routinely are administered to surgical patients to provide prolonged postoperative analgesia. This study evaluated the dose-response effects of intrathecal fentanyl in an elderly patient population undergoing lower extremity revascularization procedures. METHODS: Surgical anesthesia was induced using a continuous spinal technique. No patient received perioperative antiemetics or opioids. Postoperatively, after complete regression of spinal anesthesia, patients received via the spinal catheter either 0, 5, 10, 20, 40, or 50 micrograms fentanyl. Blood pressure, heart rate, respiratory rate, oxyhemoglobin saturation, and visual analog pain scores were recorded approximately every minute for 15 min after study drug administration. After this initial observation period, blood pressure, heart rate, respiratory rate, oxyhemoglobin saturation were recorded every 15 min for the next 2 h, then every 30 min thereafter. A verbal analog pain score, with 0 equivalent to no pain and 10 the worst pain imaginable, was obtained with each set of vital signs. The study was concluded when the verbal analog pain score was > or = 3, the patient was medicated, and the time was recorded. Any side effects, such as respiratory depression, nausea, vomiting, and pruritus, were recorded. RESULTS: Minimal analgesia was derived from the 0-, 5-, and 10-micrograms doses. Beginning at 20 micrograms, patients experienced the onset of satisfactory analgesia (visual analog pain scores < 3) within 4 min. All patients in the 40- and 50-micrograms groups had excellent analgesia (visual analog pain scores < 1) within 10 min. No patient experienced respiratory depression (respiratory rate < 9 breaths/min), hypoxemia (oxyhemoglobin saturation < 90%), or any hemodynamic alterations (20% change greater or less than baseline heart rate or blood pressure). In the 50-micrograms group, five of ten patients complained of pruritus. CONCLUSIONS: Results indicate that 40 micrograms intrathecal fentanyl provides satisfactory analgesia for approximately 5 h in an elderly patient population, with a low incidence of side effects.

Aged↗
PubMed1994

The take-home message: patients prefer consultation audiotapes to summary letters.

PURPOSE: Despite reports of poor patient understanding and recall after cancer consultations, few doctors provide communication aids. We conducted a randomized trial comparing an audiotape of the consultation versus individualized summary letters to patients after their first consultation with a medical oncologist. METHODS: One hundred eighty-two cancer patients were randomized to receive either (1) the audiotape followed 7 to 10 days later by the letter or (2) the letter followed by the audiotape. Outcome measures included patient recall, anxiety and depression, satisfaction with and use of the communication aids, and patient preferences for six communication options. Demographic and disease variables and information and involvement preferences were documented. RESULTS: Eighty percent of patients wanted all information and 72% wanted to participate in treatment decisions. Patients listened to the tape on average 2.3 times and read the letter 2.8 times over 4 weeks, and 90% showed the tape or letter to a friend, relative, or doctor. Satisfaction with the tape and letter were uniformly high and they did not differentially affect recall, anxiety, or depression. When asked to rank six communication options, 46% of patients gave the highest rank to the tape and 21% to the letter. CONCLUSION: Patients use audiotapes of their cancer consultation and individualized letters to review the information given and communicate information to relatives and friends. They prefer audiotapes to letters. Clinicians should consider installing audiotape-recording facilities that could be used to tape new-patient consultations.

Adult↗
PubMed1994

The use of fentanyl added to morphine-lidocaine-epinephrine spinal solution in patients undergoing cesarean section.

Because of its slow onset of action, intrathecal morphine may not be the optimal drug for intraoperative analgesia during short cases, such as cesarean sections. It is not known whether adding fentanyl to a morphine-lidocaine spinal solution would provide any benefits to patients undergoing cesarean sections. Sixty-two women scheduled for elective cesarean section received intrathecal 5% lidocaine with dextrose (50-70 mg), epinephrine 200 micrograms, preservative-free morphine 0.2 mg, and either 10 micrograms of fentanyl (study group) or preservative-free normal saline (placebo group) in a 0.2-mL volume. Patients were asked to rate their severity of pain on a visual analog scale (VAS) intraoperatively as the uterus was exteriorized and again when the dermatomal level had receded to L1. Intravenous fentanyl was administered if the patient experienced intraoperative discomfort. The VAS scores were 0.8 +/- 1.5 and 2.3 +/- 1.6 (mean +/- SD) in the placebo group at the time of uterine extrusion and in the post-anesthesia care unit (PACU). The corresponding scores in the fentanyl group were 0.4 +/- 1.1 and 2.7 +/- 2.2. There was a significant difference between the two groups in the VAS scores intraoperatively (P < 0.014) but not in the PACU (P not significant). There was also a significant difference (P < 0.015) in the need for supplementation with intravenous (i.v.) fentanyl. Six patients in the placebo group received i.v. fentanyl as compared with none of the patients in the fentanyl group.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Epidural↗
PubMed1994

Collaboration, consultation, and care: developing an effective donor program.

The worsening shortage of organ and tissue donors in the United States has led to new clinical and legislative initiatives designed to increase the number of organs and tissues available for donation. Inlight of these new initiatives, this article reexamines the relationship between hospitals and organ and tissue procurement agencies who coordinate the donation process.

Family↗
PubMed1993

Cholinergic binding sites on the pentameric acetylcholine receptor of Torpedo californica.

The binding of agonists, antagonists, and the acetylcholinesterase inhibitor, eserine, to the nicotinic acetylcholine receptor from Torpedo californica has been monitored by the fluorescence changes of two extrinsic probes that have been covalently attached to the receptor protein. Although both probes, 5-(iodoacetamido)salicylic acid (IAS) and 4-[N-[(2-iodoacetoxy)ethyl]-N-methylamino]-7-nitrobenz-2-oxa-1,3-diaz ol e (IANBD) react with sulfhydryl groups, they do not react at the same location. The conditions for IAS labeling and competition studies have shown that, following reduction of the receptor, this fluorophore reacts with the same cysteines on each of the two alpha subunits that may be labeled by the alkylating agonist, [3H]bromoacetylcholine. The fluorescence of this probe is sensitive to the binding of agonists and competitive antagonists to two high-affinity sites on the receptor. IANBD does not react with the same cysteines as IAS, and its fluorescence is unchanged by the high-affinity binding of agonists and antagonists. The fluorescence of this probe is, however, specifically and saturably enhanced by the binding of agonists to distinct low-affinity sites. Heterogeneity in the NBD fluorescence changes induced by the bis-quaternary agonist, suberyldicholine, has indicated that the stoichiometry of low-affinity sites is also two per receptor. Stopped-flow studies of agonist binding to receptor preparations that had been doubly labeled by both fluorophores demonstrate that the conformational changes detected by IAS occur on slow time scales of seconds to minutes whereas a much faster conformational change is revealed by changes in NBD fluorescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

A high-affinity site for acetylcholine occurs close to the alpha-gamma subunit interface of Torpedo nicotinic acetylcholine receptor.

Affinity labeling techniques have been used to investigate the location of high-affinity binding sites for cholinergic agonists on the Torpedo acetylcholine receptor and the extent of overlap of these sites with those for long alpha-neurotoxins. Following reduction of the receptor by dithiothreitol, reaction with [3H]bromoacetylcholine leads to covalent incorporation into each of the two alpha subunits. At high concentrations of [3H]bromoacetylcholine (240 microM) and with prolonged incubation times (1-2 h), this labeling was not inhibited by either alpha-bungarotoxin or alpha-najatoxin. Following maximum labeling by [3H]bromoacetylcholine, no residual high binding sites for [125I]-alpha-bungarotoxin could be detected in the membrane-bound receptor, but 50% of the original sites were recovered by receptor solubilization. Since it has previously been reported that one of the two sites for alpha-bungarotoxin in the membrane-bound receptor is readily reversible but is converted to a high-affinity state by solubilization [Conti-Tronconi, B. M., Tang, F., Walgrave, S., & Gallagher, W. (1990) Biochemistry 29, 1046-1054], these results demonstrate that the covalently bound agonist inhibits the binding of alpha-bungarotoxin only to its higher affinity site in the membrane. When [3H]bromoacetylcholine labeling was carried out after reduction of the receptor by sodium borohydride rather than dithiothreitol, both alpha and gamma subunits of the receptor were labeled. Labeling of both subunits was completely inhibited if the receptor was first reduced with dithiothreitol and the alpha subunit sites were previously covalently labeled by unlabeled bromoacetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

Benzodiazepine binding to GABAA receptors: differential effects of sulfhydryl modification.

The effects of sulfhydryl modification on benzodiazepine binding to gamma-aminobutyric acid type A (GABAA) receptors have been studied in membrane preparations from bovine cerebral cortex. After reduction of membranes with increasing concentrations of dithiothreitol, the binding of the partial inverse agonist [3H]Ro15-4513 (2.5 nM) was inhibited with an IC50 of 4.6 mM, while the binding of the classical agonist [3H]flunitrazepam was affected only at much higher concentrations (> 30 mM). Prior desensitization of the GABAA receptor by incubation with 10 microM muscimol had no effect on dithiothreitol inhibition of [3H]Ro15-4513 binding. In equilibrium assays, 10 mM dithiothreitol increased the KD for [3H]Ro15-4513 binding by more than three-fold and reduced the density of binding sites by more than one-third. The binding sites for [3H]Ro15-4513 were protected from the effects of dithiothreitol by carrying out the reduction step in the presence of 10 microM Ro15-4513 or 10 microM flunitrazepam. Alkylation of brain membranes by N-ethylmaleimide inhibited the binding of both [3H]Ro15-4513 and [3H]flunitrazepam with a similar concentration dependence. Equilibrium binding assays in the presence of 10 mM N-ethylmaleimide showed that both the affinity and number of binding sites for [3H]Ro15-4513 were reduced, whereas only the KD for [3H]flunitrazepam binding was affected. These results demonstrate that sulfhydryl modification of GABAA receptors has different effects on the binding of a classical benzodiazepine agonist and a partial inverse agonist, suggesting differences in the modes of binding of the two ligands.

Animals↗
PubMed1993

An evaluation of an asthma quality of life questionnaire as a measure of change in adults with asthma.

In assessing the effectiveness of management strategies for patients with asthma, it is important to measure outcomes which are relevant to the concerns of patients. Quality of life is one such outcome which may not be adequately reflected in lung function measurements. We have developed an asthma quality of life questionnaire (the AQLQ) for this purpose. The aim of this study was to test the validity and responsiveness of the AQLQ as a measure of change. Forty four adults with asthma were assessed on two occasions 4 months apart. On each occasion subjects completed the AQLQ and the Sickness Impact Profile (SIP). Lung function and the degree of bronchial hyperresponsiveness (BHR) were measured and diary cards were used to derive a symptom score and mean daily peak flow variability. The relation of change in AQLQ scores to change in the other outcomes was assessed. Questionnaire responsiveness was assessed by comparing the change in AQLQ scores between 19 improved and 20 stable subjects. Improvement was assessed on lung function and BHR criteria. As expected, change in AQLQ score was correlated with change in symptom score (r = 0.37, 95% CI -0.04 to 0.64) and change in BHR (r = 0.38, 95% CI 0.06 to 0.64). The associations with change in peak flow variability (r = 0.12, 95% CI -0.26 to 0.47) and change in SIP score (r = 0.18, 95% CI -0.12 to 0.45) were in the expected direction but weaker than expected. The AQLQ was capable of detecting differences between improved and stable subjects (p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗