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Biomedical subjects

S M Dunn

Publications and source records attributed to S M Dunn.

At least 127 records · Page 7Linked to original sources
PubMed1991

Real-time sensing of tooth position for dental digital subtraction radiography.

Dental digital subtraction radiography requires accurate repositioning of the patient and X-ray source in order to facilitate correct diagnostic of bone loss. Present mechanical repositioning systems do not allow radiography of posterior teeth, and are uncomfortable for the patient. A new repositioning system that utilizes a six degrees of freedom position sensor and a robot arm with X-ray source is proposed. A mathematical model for the system is given, and the robot arm solution is obtained based on patient position. An error analysis is performed in order to determine the influence of sensor and robot errors on system accuracy. A series of experiments to determine sensor noise and accuracy are described. These tests showed relatively small errors over the work envelope of the sensor. Further tests showed that there is no adverse effect due to the presence of metal work in the patient's mouth. The high bandwidth of the sensor may allow real time tracking of small movements of the patient's head.

Alveolar Bone Loss↗
PubMed1991

Perceptions of self and short stature: effects of two years of growth hormone treatment.

A cohort study was carried out to determine whether childrens' perception of the problem of short stature changed over 2 years of growth hormone (GH) therapy. A total of 66 children (age range, 5-15 years; mean 10.2 years) were selected on the basis of height below the 3rd centile for chronological age, height velocity below the 25th centile for bone age, prepubertal status, and absence of any organic condition causing growth failure or likely to interfere with GH action. The children were taking part in a 2-year multicentre trial to assess the effect of authentic recombinant GH on short, slowly growing children without GH deficiency (GHD). The childrens' and parents' attitudes and emotional adjustment to shortness were assessed before GH therapy commenced, and at 6 months and 2 years, using a growth-specific psychological instrument, the Attitude to Growth scale (ATG). The children were also assessed using the Piers Harris Childrens Self Concept Scale at 2 years. The mean ATG scores increased from 34.2 (95% confidence interval, 33.2-35.2) at intake to 37.2 (95% confidence interval, 36.2-38.2) at 2 years. Younger subjects had a greater increase (p less than 0.05). No sex differences occurred. Two separate factors were identified in the childrens' attitudes: emotional preoccupation with stature and a concrete focus on practical aspects. No differences were present between childrens' and parents' mean scores, though parents' estimates differed on selected items. The mean Piers Harris score at 2 years was within the normal range, and was positively correlated to the ATG but was unrelated to height. It is concluded that GH treatment may have a beneficial effect on childrens' attitudes to being short, particularly in the younger child.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Dihydrofolate reductase from Escherichia coli: probing the role of aspartate-27 and phenylalanine-137 in enzyme conformation and the binding of NADPH.

In the absence of ligands, dihydrofolate reductase from Escherichia coli exists in at least two interconvertible conformations, only one of which binds NADPH with high affinity. This equilibrium is pH dependent, involving an ionizable group of the enzyme (pK approximately 5.5), and the proportion of the NADPH-binding conformer increases from 42% at pH 5 to 65% at pH 8. The role of specific amino acids in enzyme conformation has been investigated by studying the kinetics of NADPH binding to three dihydrofolate reductase mutants: (i) a mutant in which Asp-27, a residue that is directly involved in the binding of folates and antifolates but not NADPH, has been replaced by a serine, (ii) a mutant in which Phe-137 on the exterior of the molecule and distant from the binding sites has been replaced by a serine, and (iii) a mutant in which both Asp-27 and Phe-137 have been replaced by serines. Mutation of the Asp-27 residue reduces the affinity for NADPH by approximately 7-fold. Kinetic measurements have suggested that this is due mainly to an increase in the rate of dissociation of the initial complex and a slight shift in the enzyme equilibrium to favor the nonbinding conformation. The pH dependence of the conformer equilibrium is also shifted by approximately one pH unit to higher pH (pK approximately 6.5). In addition, the pH profile suggests the involvement of a second ionizable group having a pK of about 8 since, above pH 7, the proportion of the NADPH-binding form decreases.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspartic Acid↗
PubMed1990

Knowledge and attitude change as predictors of metabolic improvement in diabetes education.

Randomized trials of formal diabetes education have proven that education in isolation from other aspects of diabetes care has limited impact on metabolic control through the simple transfer of information. Comprehensive programme evaluation requires assessment of the process by which knowledge and attitude change affect subsequent control of diabetes. This study examined the impact of a formal diabetes education programme on diabetes-specific knowledge and attitude, and the relationship between these characteristics and metabolic control of the disease over a 15-month period. Knowledge and attitude were assessed using parallel forms of the DKN and ATT39 scales presented randomly as pre-test and post-test to 309 patients attending a 2-day diabetes education programme. Mean knowledge scores increased by 25% (P less than 0.0001) and standardized ATT scores showed a small but significant positive shift after the programme (P less than 0.01) and remained stable in a subset of 177 patients at 3-month follow-up. ATT scores showed a marked convergence towards normal during the intervention (ANOVA, P less than 0.0001). Glycosylated haemoglobin (HbAlc), a medium-term measure of blood glucose control, was recorded in 209 cases for 6 months preceding the programme, and for 15 months following, at intervals of 3 months. The mean HbAlc improvement, from 11.3 to 9.0% (P less than 0.001), was predicted by stepwise regression from initial diabetes control (57% variance) and psychosocial factors (17% variance) including attitude scores and personality characteristics. Diabetes knowledge did not predict improvement in the control of diabetes.

Adaptation, Psychological↗
PubMed1990

Knowledge improvement and metabolic control in diabetes education: approaching the limits?

Evaluation of diabetes education programs (DEPs) has provided minimal empirical support for a relationship between improved knowledge and better metabolic control. We hypothesized that improved knowledge in specific areas is predictive of changes in specific measures of diabetes control. Patients (n = 558) attending one of five DEPs completed a diabetes knowledge questionnaire at baseline and post-DEP. Glycosylated hemoglobin (GHb) was measured at baseline and at 3 months follow-up. Total diabetes knowledge (DKN) scores increased significantly by 18%, but improvement was uncorrelated with changes in GHb (r = 0.03). Improvement in nine specific content areas failed to predict changes in GHb (all P greater than 0.05) and improvement in knowledge of the causes of hypoglycemia did not predict changes in frequency of hypoglycemia (chi 2 = 1.54; P greater than 0.05). We conclude that neither global nor specific knowledge improvement predicts metabolic control in diabetes and suggest that evaluation of diabetes education should focus more intensively on behavioral and attitudinal outcomes.

Adolescent↗
PubMed1990

Rethinking the models and modes of diabetes education.

Diabetes patient education has emerged as an integral component of comprehensive diabetes care during the past 50 years. The medical model of information transfer is now inadequate to support the variety of effective techniques which have been shown to influence patients' knowledge and health behavior. To cope with rapidly changing patterns of diabetes care, diabetes education must develop new models and modes. This article presents a re-evaluation of the traditional concepts of diabetes education and identifies new challenges and new directions for the 1990s.

Diabetes Mellitus↗
PubMed1990

Identifying priorities of psychosocial need in cancer patients.

Inconsistent findings on the efficacy of psychosocial interventions in cancer may be due to their lack of specificity. The aim of this study was to identify priorities of psychosocial need among cancer patients currently receiving treatment in Western Sydney (NSW) as a prelude to targeted intervention. A sample of 188 patients (129 female, median age 52 years, median time since diagnosis 12 months), with various solid tumours, completed a self-report ranking questionnaire listing eight major areas of psychosocial need based on a literature search of relevant studies. The resulting ranking of priorities was: family (1), dealing with emotional stress (2), getting information (3), money (4), work (5), social life (6), sex life (7), and dealing with hospital staff (8). These priorities were independent of demographic characteristics, including time since diagnosis, suggesting that support in the areas of major need may be just as important during follow-up as it is at diagnosis. Males reported less distress than females, and patients with cancer of the head/neck or breast reported most distress. To be maximally effective, psychosocial intervention for cancer patients should focus on the principal areas of family interaction, effective stress management, and access to information.

Adult↗
PubMed1990

A novel tumor necrosis factor-responsive transcription factor which recognizes a regulatory element in hemopoietic growth factor genes.

A conserved DNA sequence element, termed cytokine 1 (CK-1), is found in the promoter regions of many hemopoietic growth factor (HGF) genes. Mutational analyses and modification interference experiments show that this sequence specifically binds a nuclear transcription factor, NF-GMa, which is a protein with a molecular mass of 43 kilodaltons. It interacts with different affinities with the CK-1-like sequence from a number of HGF genes, including granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte (G)-CSF, interleukin 3 (IL-3), and IL-5. We show here that the level of NF-GMa binding is induced in embryonic fibroblasts by tumor necrosis factor-alpha (TNF-alpha) treatment and that the CK-1 sequence from the G-CSF gene is a TNF-alpha-responsive enhancer in these cells. The NF-GMa protein is distinct from another TNF-alpha-responsive transcription factor, NF-kappa B, by several criteria. Firstly, several NF-kappa B-binding sites, although having sequence similarity with the CK-1 sequence, cannot compete efficiently for NF-GMa binding to CK-1. Secondly, the CK-1 sequence from both G-CSF and GM-CSF does not respond to phorbol ester treatment as would an NF-kappa B-binding element. These results demonstrate that NF-GMa is a novel transcription factor inducible by TNF-alpha and binds to a common element in HGF gene promoters.

Base Sequence↗
PubMed1989

Characterization of a novel membrane glycoprotein involved in platelet activation.

When platelets bind certain specific ligands they are induced to secrete the contents of their cytoplasmic granules and to aggregate. Studies of the molecular events accompanying this vital physiological response have led to a greater understanding of cell activation in general since the pathways involved are common to a number of cell types. By contrast most of the information about the cell surface molecules that initiate signal transduction has emerged from work on T lymphocyte activation, a process essential to the initiation of the immune response. We have described an activation antigen on T lymphocytes that is involved in the differentiation of these cells. In the present report it is demonstrated that the antigen is expressed on the platelet membrane with about 1,200 copies/platelet. A monoclonal antibody detecting this antigen stimulates platelet secretion and aggregation with a half-maximal response at approximately 10(-8) M. Characterization of the antigen, termed PTA1, reveals a glycoprotein of Mr 67,000 showing extensive N-linked carbohydrate, much of which appears to be heavily sialated. The amino-terminal sequence of PTA1, EEVLWHTSVPFAEXMSLEXVYPSM, indicates that the protein has not previously been characterized. Preliminary investigation of the mechanism by which PTA1 mediates platelet activation suggests involvement of protein kinase C and the 47-kDa protein of platelets is rapidly phosphorylated upon antibody-mediated activation. During this process PTA1 is also phosphorylated, as it is following platelet activation by the other agonists, collagen, thrombin, and 12-O-tetradecanoylphorbol 13-acetate. These results provide the first example of a cell surface glycoprotein that is directly involved in both platelet and T lymphocyte activation.

Amino Acid Sequence↗
PubMed1989

Voltage-dependent calcium channels in skeletal muscle transverse tubules. Measurements of calcium efflux in membrane vesicles.

Transverse tubule membranes isolated from rabbit skeletal muscle consist mainly of sealed vesicles that are oriented primarily inside out. These membranes contain a high density of binding sites for 1,4-dihydropyridine calcium channel antagonists. The presence of functional voltage-dependent calcium channels in these membranes has been demonstrated by their ability to mediate 45Ca2+ efflux in response to changes in membrane potential. Fluorescence changes of the voltage-sensitive dye, 3,3'-dipropyl-2,2'-thiadicarbocyanine, have shown that transverse tubule vesicles may generate and maintain membrane potentials in response to establishing potassium gradients across the membrane in the presence of valinomycin. A two-step procedure has been developed to measure voltage-dependent calcium fluxes. Vesicles loaded with 45Ca2+ are first diluted into a buffer designed to generate a membrane potential mimicking the resting state of the cell and to reduce the extravesicular Ca2+ to sub-micromolar levels. 45Ca2+ efflux is then measured upon subsequent depolarization. Flux responses are modulated with appropriate pharmacological specificity by 1,4-dihydropyridines and are inhibited by other calcium channel antagonists such as lanthanum and verapamil.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Kinetics of [3H]muscimol binding to the GABAA receptor in bovine brain membranes.

The binding of the GABA receptor agonist [3H]muscimol to membrane preparations from bovine cerebral cortex has been investigated in equilibrium and kinetic experiments. Equilibrium binding curves are biphasic and suggest that [3H]muscimol binds to both high-affinity (Kd approximately 10 nM) and low-affinity (Kd approximately 0.5 microM) sites. Binding to each class of sites is inhibited by GABA and by the specific GABAA receptor antagonist bicuculline. The kinetics of [3H]muscimol binding have been measured by using both manual filtration assays and an automated rapid filtration technique which permits the measurement of ligand dissociation on subsecond time scales. Association and dissociation curves are biphasic at all concentrations of [3H]muscimol studied, even under conditions of low receptor saturation when no significant occupancy of the low-affinity sites would be expected. These results cannot be simply explained by the presence of two populations of binding sites in the membrane preparations but suggest the existence of two forms of the monoliganded receptor. Dissociation constants for these two forms have been estimated to be 16 and 82 nM at 23 degrees C. At higher ligand concentrations, kinetic measurements have suggested that the binding of [3H]muscimol to low-affinity sites is accompanied by a slow conformational change of the receptor-ligand complex.

Animals↗
PubMed1989

Regulation of expression of a human intercellular adhesion molecule (ICAM-1) during lymphohematopoietic differentiation.

The intercellular adhesion molecule (ICAM-1) is a cell-surface molecule which binds to leukocyte function antigen-1 (LFA-1) and regulates both leukocyte adhesion to endothelial cells and immune functions requiring cell-cell contact. Membrane expression of ICAM-1 is highly regulated on all hematopoietic lineages. Cell membrane antigen is significantly expressed on a small subset of bone marrow (BM) progenitors but is weak or absent on all cell lineages once they enter the circulation. However, strong expression on tissue macrophages and germinal center B cells suggested that activated cells may show upregulated expression. When B cells, T cells, macrophages, or granulocytes were activated in vitro by suitable mitogens, ICAM-1 expression was induced in all cases. Parallel studies of hematopoietic tumors demonstrated a heterogeneity of expression which correlated with expression on their normal cellular counterparts. In particular, a striking correlation between expression on B-cell tumors and corresponding stages of B-cell differentiation was noted. The widely varying expression of ICAM-1 contrasts with LFA-1 which, while variable, is nevertheless significantly positive at all stages of differentiation. This suggests that the major regulation of homotypic adhesion mediated by the LFA-1/ICAM-1 linkage occurs through control of ICAM-1 expression. In keeping with this notion, ICAM-1 expression was also correlated with the "adhesiveness" of B-lymphoid tumors. Large solitary lymphoma masses showed intense expression of ICAM-1. Conversely, chronic lymphocytic leukemia (CLL) cells and lymphoma cells from tumors exhibiting diffuse, widespread lymph node disease showed weak expression. These observations are discussed in relation to the role of ICAM-1 in regulation of lymphoid recirculation and the biology of lymphoid tumors.

Animals↗
PubMed1989

Functional reconstitution of the bovine brain GABAA receptor from solubilized components.

The GABAA/benzodiazepine receptor has been solubilized from membrane preparations of bovine cerebral cortex and has been reconstituted, in a functionally active form, into phospholipid vesicles. In preliminary experiments, the receptor was labeled with the photoactive benzodiazepine [3H]flunitrazepam prior to solubilization. A peptide of apparent molecular weight 53,500 was specifically labeled by this method, and this was used as a marker for the receptor during the reconstitution procedures. The labeled protein was solubilized with approximately 40% efficiency by 1% beta-octyl glucoside. Reconstitution was achieved by mixing the solubilized proteins with a 4:1 mixture of soybean asolectin and bovine brain phospholipids, followed by chromatography on Sephadex G-50-80 to remove detergent. The incorporation of the GABAA receptor into membrane vesicles has been verified by sucrose gradient centrifugation in which the [3H]-flunitrazepam-labeled peptide comigrated with [14C]phosphatidylcholine used as a lipid marker. Vesicles prepared without labeled markers retained the ability to bind both [3H]flunitrazepam and the GABA analogue [3H]muscimol. Furthermore, the binding parameters were very similar to those measured using native membrane preparations. A novel fluorescence technique has been used to measure chloride transport mediated by the GABAA receptor in reconstituted vesicles. Chloride influx was rapidly stimulated in the presence of micromolar concentrations of muscimol and was blocked by preincubation of the membranes with muscimol (desensitization). Flux was also blocked by pretreatment with the competitive GABAA receptor blocker bicuculline or with the noncompetitive GABAA receptor antagonist picrotoxin.

Animals↗
PubMed1989

Fluorescence measurements of anion transport by the GABAA receptor in reconstituted membrane preparations.

A fluorescence assay for measuring the functional properties of the GABAA receptor in reconstituted membrane vesicles is described. This assay is based on a method previously described to measure monovalent cation transport mediated by the nicotinic acetylcholine receptor in membranes from Torpedo electric organ [Moore, H.-P.H., & Raftery, M. A. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 4509-4513]. The GABAA receptor has been solubilized from bovine brain membranes and reconstituted into phospholipid vesicles. Influx of chloride or iodide into the vesicles has been measured in stopped-flow experiments by monitoring the fluorescence quench of an anion-sensitive fluorophore trapped within the vesicles. Muscimol, a GABAA receptor agonist, stimulated a rapid uptake of either chloride or iodide. Stimulation of chloride influx was dependent on the concentration of muscimol, and the midpoint of the dose-response curve occurred at approximately 0.3 microM. Agonist-stimulated uptake was enhanced by diazepam and blocked by desensitization and by the antagonists bicuculline and picrotoxin. These receptor-mediated effects are shown to be qualitatively similar to measurements of 36Cl- and 125I- efflux using synaptoneurosomes prepared from rat cerebral cortex. The advantages of the fluorescence method in terms of its improved time resolution, sensitivity, and suitability for quantitating GABAA receptor function are discussed.

Animals↗