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M Freeman

Publications and source records attributed to M Freeman.

At least 73 records · Page 4Linked to original sources
PubMed1997

Cell determination strategies in the Drosophila eye.

Cells in the Drosophila eye are determined by inductive signalling. Here I describe a new model of eye development that explains how simple intercellular signals could specify the diverse cell types that constitute the ommatidium. This model arises from the recent observation that the Drosophila homologue of the EGF receptor (DER) is used reiteratively to trigger the differentiation of each of the cell types--successive rounds of DER activation recruit first the photoreceptors, then cone and finally pigment cells. It seems that a cell's identity is not determined by the specific signal that induces it, but is instead a function of the state of the cell when it receives the signal. DER signalling is activated by the ligand, Spitz, and inhibited by the secreted protein, Argos. Spitz is initially produced by the central cells in the ommatidium and diffuses over a small distance. Argos has a longer range, allowing it to block more distal cells from being activated by low levels of Spitz; I have termed this interplay between a short-range activator and a long-range inhibitor 'remote inhibition'. Since inductive signalling is common in many organisms and its components have been conserved, it is possible that the logic of signalling may also be conserved.

Animals↗
PubMed1996

Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye.

The Drosophila eye has contributed much to our knowledge of cell differentiation. This understanding has primarily come from the study of the R7 photoreceptor; much less is known about the development of the other classes of photoreceptor or the nonneuronal cone or pigment cells. I have used a dominant-negative form of the Drosophila epidermal growth factor receptor (DER) to show that this receptor tyrosine kinase (RTK) is required for the differentiation of all these cell types, and I have also shown that DER is sufficient to trigger their development. DER is even required in R7, where it can replace Sevenless, another RTK. These results broaden our view of eye development to include the whole ommatidium and suggest that reiterative activation of DER is critical for triggering the differentiation of all cell types.

Animals↗
PubMed1996

Marginal leakage of cast gold crowns luted with zinc phosphate cement: an in vivo study.

Marginal gaps of cast restorations are filled with luting agents that are soluble in intraoral fluids. This study investigated the marginal openings in eight extracted teeth with cast crowns that had been intraoral for 20 years or more. These teeth were extracted either because of periodontal disease or to facilitate insertion of a removable partial denture. Initially, the roots of the teeth were sealed with two coats of fingernail polish within 2 mm of the crown-tooth interface. Next, the teeth were immersed in a 0.05% aqueous solution of basic fuchsin die for 24 hours. Finally, each tooth was sectioned at four locations 1 mm apart. At each of these four sections, cement film thickness between tooth and casting, and microleakage were determined. The results of this study showed a mean cement film thickness of 74 microns on the mesial surface and 57 microns on the distal surface. Mean microleakage values were 432 microns on the mesial surface and 274 microns on the distal surface.

Adult↗
PubMed1996

Bridging the gap between theory and practice: a multimedia tutorial for students of voice therapy.

A computer-based tutorial for speech and language therapy students is described in which a digitized video-recording of a diagnostic interview with a voice-disordered client was dynamically linked to an on-screen transcript window. A student-centered tutorial package, which provided guidance through questions, assessment tasks, and commentary from an experienced speech and language pathologist as well as the lecturer in voice disorder, was constructed. Evaluation of the tutorial as an aid to active learning, including feedback from students and supervising clinicians, is reported and the role of this type of program as a preparation for clinical practice is discussed.

Adult↗
PubMed1996

Laparoscopic management of a rudimentary horn pregnancy.

Rudimentary horn pregnancies are rare, and are associated with a high rate of maternal morbidity and mortality. The standard treatment is laparotomy, as patients usually experience massive abdominal hemorrhage or pregnancies too large to attempt laparoscopic removal. In our patient, early sonographic discovery facilitated laparoscopic management.

Adult↗
PubMed1996

Argos transcription is induced by the Drosophila EGF receptor pathway to form an inhibitory feedback loop.

Argos is a secreted molecule with an atypical EGF motif. It was recently shown to function as an inhibitor of the signaling triggered by the Drosophila EGF receptor (DER). In this work, we determine the contribution of Argos to the establishment of cell fates in the embryonic ventral ectoderm. Graded activation of DER is essential for patterning the ventral ectoderm. argos mutant embryos show expansion of ventral cell fates suggesting hyperactivation of the DER pathway. In the embryonic ventral ectoderm, argos is expressed in the ventralmost row of cells. We show that argos expression in the ventral ectoderm is induced by the DER pathway: argos is not expressed in DER mutant embryos, while it is ectopically expressed in the entire ventral ectoderm following ubiquitous activation of the DER pathway. argos expression appears to be triggered directly by the DER pathway, since induction can also be observed in cell culture, following activation of DER by its ligand, Spitz. Argos therefore functions in a sequential manner, to restrict the duration and level of DER signaling. This type of inhibitory feedback loop may represent a general paradigm for signaling pathways inducing diverse cell fates within a population of non-committed cells.

Animals↗
PubMed1996

Expression of the macrophage scavenger receptor, a multifunctional lipoprotein receptor, in microglia associated with senile plaques in Alzheimer's disease.

The macrophage scavenger receptor is a multifunctional receptor whose ligands include oxidized low density lipoprotein (LDL), as well as several other polyanionic macromolecules. Although the capacity of the receptor to bind modified LDL has implicated it in the process of atherosclerosis, its physiological role remains uncertain. We have examined human brain for expression of macrophage scavenger receptor as part of ongoing studies of lipoprotein receptors in the central nervous system. The receptor is expressed on microglia, but not on astrocytes, neurons, or vessel-associated structures. In Alzheimer disease, there is strong expression of the scavenger receptor in association with senile plaques.

Aged↗
PubMed1996

Triaging seniors in health crisis in the emergency department: a three-year summary.

The "geriatric triage" approach for management of the most complex frail older adult population by geriatric nurses in the emergency department setting was a benefit to the patient/family and the health care system. The patients, through assessment and individualized plans of care, received the right care in the right setting. Seniors were assessed and their care planned by health care professionals who had geriatric knowledge, understood the complexity of their problems, and acted as their advocate. Geriatric triaging resulted in benefits across the health care system. Resources were used effectively. Patients received care in the most appropriate and cost-efficient setting. This new and creative approach served as a catalyst for improvement in services and care for the senior population. Health care workers in the hospitals as well as the community increased their knowledge of geriatrics through consultation with this service. The community and hospitals had a formal linkage, which provided an opportunity for collaboration and continuity of care. The hospital system experienced decreased competition for scarce acute care beds due to diverted admissions. The emergency department had consultants to assist with the decision-making for this high-risk population and decreased the number of patients held in emergency department awaiting an inpatient bed. The community system received patients with a comprehensive plan of care that provided creative and innovative care management strategies. Home care adapted its service to respond with immediate services to assist with health crises in addition to what had been traditionally available. The finding of this study supports a new approach to care of the elderly and chronically ill population who present to the emergency department in health crisis. Creative strategies are required to meet the needs of the aging population in these times of fiscal restraint. The nursing geriatric triage service is one strategy that holds merit.

Aged↗
PubMed1995

Inhibition of Drosophila EGF receptor activation by the secreted protein Argos.

The Drosophila homologue of the mammalian epidermal growth factor (EGF) receptor (DER) is a receptor tyrosine kinase involved in many stages of fly development, including photoreceptor determination, and wing-vein formation. Its primary activating ligand is the Spitz protein, which is similar to mammalian TGF-alpha. Argos is a secreted protein that, like Spitz, contains a single EGF motif. It is a repressor of cell determination in the eye, and acts in other tissues, including the wing. Because Argos has the opposite effects to DER in the eye (the former blocks photoreceptor determination, the latter promotes it) we have tested whether it acts by blocking the DER pathway. We show that Argos does indeed repress this pathway in vivo and find that, in vitro, Argos protein can inhibit the activation of DER by Spitz. Thus the determination of cells by the DER pathway is regulated by a balance between extracellular activating and inhibiting signals. This is the first in vivo example of an extracellular inhibitor of a receptor tyrosine kinase.

Animals↗
PubMed1995

The influence of flavor and color on drink identification by children and adults.

This study investigated how color and flavor influences drink identification by children and adults. The children ranged in age from 2 to 18 years of age. Each subject tasted four drinks that differed in color and flavor. Each drink had an atypical color-flavor pairing (e.g., brown-pineapple) or a typical pairing (e.g., brown-chocolate). After tasting each drink, the subject chose which of four flavor names identified the drink. For the atypical drinks, the selection of color-associated names (e.g., chocolate for a brown drink) decreased, and the selection of flavor-associated names increased with age from the preschoolers to the adults. For the typical drinks, the selection of the correct name was greater than 80% for all ages. These results suggest that drink identification becomes more influenced by flavor as children get older because of an increase in the ability of children to focus on flavor as their perceptual-attentional skills mature.

Adolescent↗
PubMed1995

Renal filtration and excretion of aluminium in the rat: dose-response relationships and effects of aluminium speciation.

The known toxicity of aluminium, and the toxicity of agents (such as desferrioxamine) used to remove aluminium from the body, has prompted us to investigate whether there may be ways of enhancing aluminium excretion by exploiting the normal renal handling of aluminium. Aluminium (as sulphate or citrate) was administered intravenously to conscious rats at doses ranging from 25 micrograms (0.93 mumol) to 800 micrograms (29.6 mumol) aluminium, and aluminium excretion was monitored over the following 2 h. Measurements of the filterability of aluminium from the rat plasma, and the glomerular filtration rate (inulin clearance), enabled us to calculate the filtered load of aluminium, and hence determine aluminium reabsorption. At all doses of administered aluminium, that administered as sulphate was excreted less effectively than that administered as citrate. This difference was attributable to the much greater filterability of aluminium administered as citrate. However, for any given filtered load, the excretion of aluminium administered as citrate was not significantly different (in either fractional or absolute terms) from the excretion of aluminium administered as sulphate. It seems likely that, following aluminium sulphate administration, the filtered aluminium may be an aluminium citrate form which is then reabsorbed in the same way as aluminium administered as citrate. It is thus apparent that aluminium removal from the body could be further enhanced if it were possible to prevent the tubular reabsorption of the aluminium species which is so effectively filtered following aluminium citrate administration.

Absorption↗
PubMed1995

Renal excretion of aluminium in the rat: effect of citrate infusion.

When aluminium is administered intravenously to rats, the speciation of the aluminium has a major effect on its renal excretion. Aluminium administered as citrate is much more effectively excreted than that administered as chloride or sulphate. This suggests that citrate could be therapeutically useful in patients who have been exposed to aluminium. Accordingly, we have performed two series of experiments in rats, in which a citrate infusion (intravenous), was begun either immediately after, or one hour after, the administration of an intravenous aluminium sulphate bolus. Both protocols led to markedly enhanced aluminium excretion compared to controls in which only 0.7% NaCl was infused. The enhancement of aluminium excretion was 783% if citrate infusion was begun immediately after aluminium administration, and 335% if the citrate infusion began after an hour delay. The increased excretion was due to an increase in the freely filterable fraction of aluminium. In the control experiments, in which aluminium sulphate administration was followed by 0.7% NaCl infusion, aluminium was found to be deposited in the liver. Administration of citrate one hour after the aluminium bolus did not reduce this liver deposition. The results indicate that a fraction of the plasma aluminium is accessible to the citrate infused and can thereby be converted into a filterable form which can be excreted. It appears that, for maximum therapeutic effect, citrate should be infused as rapidly as possible after an aluminium load, to limit aluminium binding to ligands which allow it to enter cells.

Alum Compounds↗
PubMed1995

Role of dipyridamole myocardial scintigraphy in carotid artery surgery.

BACKGROUND: Absence of cardiac symptoms is not a valid indicator of low cardiac risk in the sedentary patient who is being considered for vascular surgery. Invasive methods of cardiac assessment in such patients are associated with risk and are expensive. This study was carried out to evaluate the utility of pre-operative cardiac risk stratification with dipyridamole myocardial scintigraphy (DMS), in patients to undergo carotid artery surgery. STUDY DESIGN: From 1991 to 1994, 174 of 266 carotid endarterectomy patients underwent preoperative DMS. The ability of clinical factors and DMS to predict postoperative cardiac morbidity was assessed retrospectively in a nonrandomized fashion. RESULTS: Forty-seven adverse cardiac events (deaths = 0, myocardial infarction (MI) = 4, congestive heart failure (CHF) = 9, angina = 7, and new dysrhythmias = 27) occurred in 38 (14.3 percent) of 266 patients. Results of DMS were 73 percent normal, 10.3 percent fixed defect, and 16.7 percent reversible defect examinations. Sensitivity and specificity of DMS was 32 and 74 percent for total cardiac morbidity, and 50 and 74 percent for MI. The positive predictive value of DMS for MI, dysrhythmias, CHF, angina, and all cardiac events was 4, 11, 9, zero, and 23 percent, respectively. Negative predictive values were 98, 91, 98, 95, and 82 percent, respectively. Preoperative histories of MI and chest pain were significant independent predictors of adverse cardiac outcomes (p < 0.05) while age greater than 70 years, smoking, hypertension, diabetes mellitus, preoperative arrhythmias, and DMS were not. CONCLUSIONS: Dipyridamole myocardial scintigraphy is an ineffective predictor of adverse cardiac events in patients being evaluated for carotid artery surgery and its routine use is not justified.

Aged↗
PubMed1994

QT dispersion and sudden unexpected death in chronic heart failure.

Death in chronic heart failure (CHF) can be from progression of disease or sudden and unexpected. We have attempted to identify factors that predict sudden death in CHF. We followed up 44 patients with CHF for 12-50 (mean 36) months. 4 patients died of non-cardiovascular causes and were excluded from analysis. There were 7 sudden deaths (symptoms for less than 1 h in a previously stable patient) and 12 from progressive CHF. Patients who died of progressive CHF had lower left-ventricular ejection fractions and higher concentrations of atrial natriuretic factor than the 21 survivors, but there were no differences in these variables between survivors and those who died suddenly. However, the sudden death group had significantly (p < 0.05) greater inter-lead variability in the QT interval on the electrocardiogram (QT dispersion; 98.6 [95% CI 79.1-118] ms1/2) than survivors (53.1 [41.9-64.3] ms1/2) or the group who died from progressive CHF (66.7 [51.8-81.6] ms1/2). QT dispersion is a marker of myocardial electrical instability. The association of increased QT dispersion with sudden death suggests that patients at high risk of such death could be identified by means of this simple, reproducible test. This group might benefit from more intensive treatment.

Aged↗
PubMed1994

Torsades de pointes ventricular tachycardia following right pneumonectomy: insights into the relation between right cardiac sympathetic nerve damage, QT intervals, and arrhythmias.

Polymorphic ventricular tachycardia in association with prolongation of the QT interval on the surface electrocardiogram (ECG) has long been recognized as an important cause of life threatening arrhythmias that can occur with congenital or acquired abnormalities of cardiac repolarization. One hypothesis of the origin of these arrhythmias states that overactivity of the left-sided sympathetic or under activity of the right-sided sympathetic neural input to the heart leads to prolonged repolarization and ventricular arrhythmias. This hypothesis has led to the application of left cervicothoracic sympathetectomy for control of arrhythmias in congenital long QT syndromes. Although animal models have shown QT prolongation following right stellate ganglionic section or left stellate stimulation, spontaneous ventricular arrhythmias following stellate stimulation or block in man have not been demonstrated. We report the case of a patient with life threatening ventricular arrhythmias following surgical damage to the right cardiothoracic sympathetic nerves.

Electrocardiography↗
PubMed1994

The spitz gene is required for photoreceptor determination in the Drosophila eye where it interacts with the EGF receptor.

Little is known about the mechanisms by which photoreceptors other than R7 are determined during Drosophila eye development. By looking for mutations that modify the phenotype caused by ectopic expression of the rhomboid gene in the eye, I have discovered that the spitz gene is required for photoreceptor determination. Mosaic analysis suggests that spitz, which encodes a TGF alpha homologue, produces a diffusible signal during ommatidial development. Other members of the spitz group and the EGF receptor also interact with sev-rho, in a pattern that suggests a model in which rhomboid can act as a mediator of a ligand-receptor interaction between spitz and Egfr in the developing eye. These data suggest that photoreceptors other than R7 use a Ras1 signalling pathway activated by the spitz/Egfr interaction, in a manner analogous to the Ras1 pathway activated by boss/sevenless in photoreceptor R7.

Alleles↗