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G Duncan

Publications and source records attributed to G Duncan.

At least 19 recordsLinked to original sources
PubMed1996

Calcium ionophore induced proteolysis and cataract: inhibition by cell permeable calpain antagonists.

Two dipeptide aldehyde cell permeable calpain inhibitors, cBz-Val-Phe and calpeptin, have been assessed for their ability to prevent cytoskeletal proteolysis and loss of transparency in whole rat lenses. Calcium overload, induced by ionomycin in artificial aqueous humor with 1mM calcium, resulted in lens opacification and degradation of cytoskeletal proteins including spectrin, filensin, and vimentin. No such changes resulted from incubation in ionomycin in the absence of calcium. In calcium overload lenses both inhibitors gave some protection against cytoskeletal protein degradation and loss of transparency. These experiments indicate that calpain has a role in cortical opacification in high calcium lenses and that cell penetrating calpain inhibitors do indeed enter lens cells and reduce both proteolysis and opacification.

Animals↗
PubMed1996

A study of human lens cell growth in vitro. A model for posterior capsule opacification.

PURPOSE: After intraocular lens (IOL) implant surgery for cataract, cell growth on the posterior capsule is responsible for renewed visual impairment in approximately 30% of patients. The authors have, therefore, developed a human lens capsule system to study this growth in vitro. METHODS: Sham cataract surgery, including anterior capsulorhexis, nucleus hydroexpression, and aspiration of lens fibers, was performed on donor eyes. In some cases, a polymethylmethacrylate IOL implant was placed in the capsular bag. The capsular bag was dissected free, pinned flat on a plastic culture dish, covered with Eagle's minimum essential medium supplemented with 10% fetal calf serum and observed by phase-contrast and dark-field microscopy for as long as 100 days. At the end-point, capsules were examined by fluorescence microscopy for actin, vimentin, and chromatin. RESULTS: Within 24 hours, there was evidence of cell growth in the equatorial region. After 2 to 3 days, cells were normally observed growing from the rhexis onto the posterior capsule and across the anterior surface of the IOL, if present. Growth proceeded rapidly so that the posterior capsule, for example, was totally covered by a confluent monolayer of cells at 5.8 +/- 0.6 days and 7.2 +/- 0.7 days for capsules aged < 40 years and > 60 years, respectively. Total cover of the anterior IOL surface generally followed 4 to 5 days behind that of the capsule. Capsular wrinkles became increasingly apparent as time progressed, causing a marked rise in light scatter. An increase in capsular tension also occurred, and the actin filaments became more polarized near the wrinkles. CONCLUSIONS: The model presented here for posterior capsule opacification shows many of the changes seen in vivo, including rapid lens cell growth, wrinkling, tensioning, and light scatter in the posterior capsule. It will be possible to develop strategies for inhibiting cell growth with this system.

Actins↗
PubMed1995

Public education and depth of primary malignant melanoma, Hutt Hospital, 1985-92.

AIMS: To document the depth of primary malignant melanoma treated at the Wellington regional plastic and maxillo-facial surgical unit, Hutt Hospital, from 1985-92. To determine the effects of public education campaigns commenced in 1987, on the presentation of melanoma at Hutt Hospital, and to ascertain whether the Department of Health, Health Goals for 1995 were attained in relation to Hutt Hospital. METHODS: A surgical audit was established in 1985 to record all cases of melanoma treated at the plastic surgical unit, Hutt Hospital. Data relating to the depth (Breslow index) of each primary melanoma was extracted from this audit, and reviewed. Metastatic or recurrent disease was excluded. RESULTS: The number of cases of primary melanoma treated at this unit increased greatly following the Cancer Society initiated Spotcheck programme in 1987. There was a significant increase (p < 0.001) in the number and proportion of thin (less than 0.76mm) invasive melanomas treated, from 30% of the total in 1985, through to 70% in 1992. There was no increase in the actual number of thick (> 0.75mm) invasive melanoma, with the total number of cases being treated remaining relatively constant from 1989 onwards. CONCLUSIONS: Significantly more patients are presenting with thin melanoma. This may be due to the nature of the disease itself, alterations in referral patterns, or due to earlier identification of malignant lesions due to greater public education. The education campaigns appear to be responsible for the observed increase in cases of melanoma presenting to our unit. The Department of Health goals for 1995 have already been achieved with > 60% of primary malignant melanoma being < 0.76 mm in depth at time of presentation.

Health Education↗
PubMed1995

Histamine and ATP mobilize calcium by activation of H1 and P2u receptors in human lens epithelial cells.

1. Cytoplasmic calcium concentration ([Ca2+]1) of single superfused tissue-cultured human lens epithelial cells (HLEC) was monitored using the fluorescent dye fura-2; the resting values were low and stable for several hours ([Ca2+]i = 96 +/- 20 nM; mean +/- S.D., n = 16). 2. Continuous superfusion with either ATP or histamine (0.1-10 microM) produced regular oscillations in [Ca2+]i that could be maintained for a short time in the absence of external calcium. 3. Short (30 s) pulses of histamine (0.1-100 microM) induced a transient rise in [Ca2+]i, the time course of which was insensitive to the removal of external calcium. The rate of rise and the amplitude of the response were very sensitive to agonist concentration, whereas the rate of recovery was relatively constant. 4. The responses to long pulses of histamine (> 100 s) consisted of an initial transient followed by a maintained [Ca2+]i which returned to baseline on removal of external calcium. 5. The kinetics of the responses to short and long pulses of ATP (0.1-100 microM) were very similar to those of histamine and showed a similar sensitivity to the presence or absence of external calcium. 6. The histamine responses were abolished by triprolidine (1 microM), but unaffected by ranitidine (1 microM), indicating that an Hi receptor subtype is activated by histamine. 7. The ATP responses were reversibly inhibited by suramin and the potency sequence for a range of agonists was ATP = UTP = ATP gamma S > ADP = GTP >> AMP = adenosine, indicating that activation of a P2u receptor subtype was responsible for the increase in [Ca2+]i. 8. Both histamine and ATP responses were abolished by thapsigargin (100 nM), confirming that calcium release from intracellular stores was responsible for the initial peak of the response. Application of either agonist during the plateau phase of the thapsigargin response often led to a marked, but reversible, decline in [Ca2+]i, indicating the presence of a further, normally hidden, calcium regulatory factor associated with the presence of the agonist. 9. Maximal concentrations of either histamine or ATP totally emptied the calcium store as a subsequent application of the other agonist (or thapsigargin), in the absence of external calcium, failed to induce a further increase in the calcium signal.

Adenosine Triphosphate↗
PubMed1995

Stroke units.

Explore the source record for details and available documents.

Cerebrovascular Disorders↗
PubMed1995

Gait speed and activities of daily living function in geriatric patients.

OBJECTIVE: To establish the relationship between gait speed (GS) and functional independence in elderly people. DESIGN: GS is suggested as being a criterion standard in rehabilitation reflecting muscle strength. This study assessed the relationship between gait speed and functional independence in Activities of Daily Living (ADL). GS was measured by portable accelerometer over 2 meters. The mean of 3 attempts was taken. ADL function was measured by an occupational therapist using the modified Barthel ADL Index. The relationship between these measures was assessed by a statistician. SETTING: A geriatric unit in a hospital in Scotland. PATIENTS: One hundred sixty-one inpatients and outpatients were selected at random from the patients of a geriatric unit over a 3-month period. Patients were eligible if they were mobile with or without a walking aid. INTERVENTIONS: GS was measured by portable ultrasonic accelerometer. Patients were reviewed by an occupational therapist, blinded to their GS, who recorded functional capacity. Case sheet review provided diagnostic details and cognitive function. The type of floor surface was recorded. MAIN OUTCOME MEASURES: GS (m/sec), and Barthel score. RESULTS: Patients with GS of < .25m/sec were more likely to be dependent in one or more ADL function, p < .01. Those with a GS between .35 and .55m/sec were more likely to be independent in all ADL functions, p < .001. Patients whose GS was > .55m/sec did not maintain this independence. There was no relationship between GS and floor surface or cognitive function. CONCLUSIONS: GS is a useful indicator of ADL function in geriatric patients.

Activities of Daily Living↗
PubMed1995

Calcium localization and ultrastructure of clear and pCMPS-treated rat lenses.

PURPOSE: The sulfhydryl complexing agent p-chloromercuri-phenylsulfonate (pCMPS) has been shown to increase lens membrane permeability, Na+ and Ca2+ content, and light scatter in the rat lens in vitro. This study aimed to investigate the ultrastructural changes accompanying the increase in light scatter. In addition, high-resolution histochemistry was used to study the cellular distribution of Ca2+ in normal and cataractous lenses. METHODS: Rat lenses were incubated for 4 hours in normal (1 mM) and high (5 mM) Ca2+ containing media supplemented with 40 microM pCMPS. Control lenses were incubated in 1 mM Ca2+ containing medium. They were prepared for scanning and transmission electron microscopy and for Ca2+ localization using the oxalate-pyroantimonate procedure. RESULTS: Control lenses incubated for 4 hours had normal morphology and showed no evidence of light scatter. Calcium distribution as observed with the oxalate-pyroantimonate precipitation method was low in superficial fibers, high in the membranes of intermediate fibers, and declined again toward the nucleus. In the deeper cortex, there also were small vacuoles of calcium accumulation. pCMPS treatment (in 1 and 5 mM Ca2+) induced a significant influx of calcium into the lens cytoplasm. Calcium-containing extracellular vacuoles also were seen in the intermediate cortex in both cases. The presence of these vacuoles appeared to correlate with the major areas of light scatter in the lens. In 5 mM Ca2+, intracellular vacuoles were observed throughout the superficial cortex. CONCLUSIONS: Most of the calcium observed by oxalate-pyroantimonate in the normal lens is located at the membrane, and the staining appears strongest in the intermediate cortex. In pCMPS treatment, large extracellular vacuoles are present in this intermediate zone and appear to be the major source of light scatter. This zone may be the initiation site of many different types of cataract, including some described in human lenses.

4-Chloromercuribenzenesulfonate↗
PubMed1995

Acute stroke in South Ayrshire: comparative study of pre and post stroke units.

In September 1993 arrangements for managing acute stroke victims in South Ayrshire changed with the opening of a six bedded Acute Stroke Unit and a fifteen bedded Rehabilitation Stroke Unit. Previously all such patients were managed within general medical wards with a few being managed in geriatric assessment and rehabilitation facilities. This study compares the management and outcome from acute stroke before and after the establishment of these new Units. Fifty-eight patients' medical, nursing and paramedical records were studied for the period of investigation in 1992 and 68 for the same period in 1993. There was no significant difference in the age of the patients admitted or in the degree of neurological or functional impairment at the time of admission. There was a reduction in mortality from 37.9% in 1992 to 22.0% in 1993. This was not accomplished by an increase in the number of survivors requiring long term institutional care and there was no significant difference in the degree neurological or functional impairment at the time of discharge. A variety of specific management issues were also addressed by the study and in all areas there were improvements in the quality of care received by this group of patients in 1993. This study supports the view that management of acute stroke victims in specifically designated Stroke Units has a beneficial effect on outcome and quality of care.

Activities of Daily Living↗
PubMed1994

cAMP regulates morphogenesis in the fungal pathogen Ustilago maydis.

The fungal pathogen Ustilago maydis exhibits a dimorphic switch from budding to filamentous growth in response to mating interactions and environmental conditions. We have found that disruption of the uac1 gene, encoding adenylate cyclase, results in a constitutively filamentous phenotype. Budding is restored to the uac1 mutant upon growth in the presence of cAMP or by extragenic suppression because of a mutation in the ubc1 gene. The ubc1 gene encodes a type II regulatory subunit of cAMP-dependent protein kinase (PKA); defects in this gene attenuate the filamentous growth that normally occurs in response to mating and exposure to air. Growth of wild-type cells in cAMP and mutation of the ubc1 gene also cause defects in the separation of mother and daughter cells (cytokinesis) and alter bud site selection. These results indicate a key role for cAMP and PKA in morphogenesis in U. maydis; this role may be common among dimorphic fungal pathogens.

Adenylyl Cyclases↗
PubMed1994

A correlated study of metabolic cell communication and gap junction distribution in the adult frog lens.

By using low molecular weight dye injection and laser scanning confocal microscopy it has been possible to assess the degree of dye communication in several regions (intraepithelial, epithelium-fibre cell, fibre-epithelium and fibre-fibre) of the adult frog lens. These same areas of the lens have also been examined by freeze fracture electron microscopy for the presence and organisation of gap junctions. Epithelial cell lateral membranes have numerous gap junctions which efficiently transmitted dye to their neighbours though none was detectable in the underlying fibre cells. This was correlated with an apparent absence of gap junctions at the epithelium/fibre cell interface. Dye spread between cortical fibre cells was only observed in a subset of fibres in the bow region of the lens. Neither mature cortical fibres nor immature bow fibres appeared to be dye-coupled and we detected no dye passed from fibre cells to adjacent epithelial cells at their anterior ends. This pattern of dye communication was also correlated with the apparent absence of recognisable gap junctions on the lateral membranes of either the recently differentiated bow fibres or the mature cortical fibres. Classical gap junctions were only found on the membranes of fibres between five and ten cells in from the lens bow, i.e. the subset of fibres which were dye-coupled. No gap junctions were found between deeper cortical fibres or nuclear fibres, although they were characterised by a number of square arrays. Though electrically well coupled the adult frog lens may be relatively poorly dye coupled and this could depend on the age and differentiation stage of the cells concerned. The model of a freely communicating lens clearly requires re-examination by correlated physiological and morphological studies.

Animals↗
PubMed1994

The influence of exercise on the energy requirements of adult males in the UK.

Energy expenditure was measured over 10 d using the doubly-labelled water (DLW) and activity diary methods in summer and winter in subjects with 'light' occupations but leisure activities which ranged from 'non-active' to 'very active'. The basal metabolic rate (BMR) and the energy cost of activities were determined by indirect calorimetry. The Department of Health (1991) predicted BMR for the group (6.89 (SD 0.30) MJ/d; n 18) was not significantly different from the measured value (7.17 (SD 0.70) MJ/d; n 18). The range of DLW-derived expenditure values within the group was BMR x 1.41 to 2.41. The largest seasonal change within individuals was BMR x 0.5. The energy expenditure of the group as a whole was lower in winter (BMR x 1.88; SD 0.33; n 9) than summer (BMR x 2.01; SD 0.30; n 9) though the difference was not statistically significant. The average summer and winter DLW-derived expenditure was BMR x 1.96 (SD 0.31; n 17). The activity diary estimate of expenditure was BMR x 1.79 (SD 0.32; n 17). In a subset of the group who were representative of the most active 26% of all adult males in the UK, the DLW-derived expenditure was BMR x 2.08 (SD 0.24; n 11). This is higher than the highest Department of Health (1991) estimate of BMR x 1.6 for individuals in light occupations. The measured energy costs of low-intensity activities were similar to those presented in the Department of Health (1991) report but the value determined for running (BMR x 13.08; SD 2.4; n 6) was higher than the highest value in the report (BMR x 6 to 8). The results indicate that the recent Department of Health (1991) reference values for energy may underestimate the expenditure of a significant proportion of the UK population largely because the energy costs of activity used in the report to calculate expenditure do not accurately reflect those achieved during active leisure in individuals who take regular exercise.

Adult↗
PubMed1994

Living wills: would sick people change their minds?

Patients admitted acutely to a geriatric medical unit were interviewed on admission about their opinions on cardiopulmonary resuscitation (CPR). They underwent a general examination and their mental health was documented by completing the geriatric depression scale. Those who did not wish CPR in the event of a cardiac arrest were questioned again on recovery. Of 216 patients admitted, only three objected to answering the questions and after the other exclusion criteria were applied, 100 patients were included in the study. A total of 92% of patients wished CPR in the event of a cardiac arrest. The 8% who did not wish CPR contained more people scoring high on the geriatric depression scale. After recovery, three of that eight had changed their minds and wished CPR if required. Patients who are acutely unwell may make decisions that are influenced by their condition at this point in time and it is important to recognize that these decisions may not be maintained. In this study, consultant geriatricians did not reflect their patients' desires in making decisions about who should receive CPR if required.

Acute Disease↗
PubMed1994

Validation of the doubly labeled water method in growing pigs.

The CO2 production (rCO2) of eight growing pigs was determined by continuous collection of CO2 over 21 days and simultaneously estimated using the doubly labeled water (DLW) method. The aim was to assess the accuracy of the method before and after correction for known sources of error and to test for any residual discrepancy arising from as yet unidentified sources of error. Mass spectrometer accuracy was verified by analyzing serial dilutions of the dose material in the form of an artificial decay curve; no significant bias was detected. The physiological errors were linearly dependent on weight gain. DLW-derived rCO2 (corrected only for fractionated water loss) underestimated the true value by 0.270 l CO2/g wt gain or -8% in the restricted (group R) and -16% in the ad libitum-fed (group AL) groups. Known sources of error accounted for -0.006 (methane), -0.032 (fecal 2H losses), -0.108 (fat synthesis), and -0.146 (changing pool size) l CO2/g wt gain. After correction for these sources of error the DLW-derived rCO2 differed from the true value by -2 +/- 3% in group R and 0 +/- 3% in group AL. Thus there was no significant bias in the DLW method after correction for known sources of error, even during rapid weight gain or at weight stability with or without correction. The precision estimates include both dose and background errors and uncertainty in the correction factors used. Strategies for optimizing precision are presented.

Animals↗
PubMed1994

Calmodulin antagonists induce changes in lens permeability and transparency.

Calmodulin has been shown to perform several important functions in the lens including regulation of the plasma membrane Ca(2+)-ATPase. This study investigated the effects of a variety of different CaM antagonists on rat lens membrane potential, membrane resistance, intracellular Na+ and Ca2+ content and transparency, in order to examine the role of CaM in control of lens membrane permeability. W7, calmidazolium and trifluoperazine caused biphasic changes in lens membrane electrical characteristics. Phase 1 consisted of a depolarization of the membrane potential and an increase in resistance, indicating that K+ channels were being blocked. This was confirmed by application of the K+ channel antagonist, quinine, which inhibited Phase 1 changes. Phase 2 was a further depolarization coupled with a decrease in resistance, indicating the activation of a cation conductance. Application of W7 in low Na+ medium slowed the Phase 2 depolarization and decrease in resistance indicating that Na+ is the main charge carrier through the activated conductance. The CaM inhibitors also led to a large increase in the Na+ and Ca2+ contents of the lens. W5, a less potent analogue of W7, caused a depolarization and increase in membrane resistance, but no Phase 2 changes were observed. Na+ and Ca2+ contents were similar to control lenses after 4 hours incubation in 200 microM W5. In addition, exposure to W7, TFP and calmidazolium resulted in a loss of transparency, while W5 treated lenses remained clear. It appears, therefore, that CaM is involved in control of lens membrane permeability. Loss of control of these channels leads to catastrophic changes in the intracellular ionic environment and hence opacification of the lens.

Animals↗
PubMed1993

Patterns of palliative radiotherapy in Canada.

A questionnaire study was performed to determine patterns of radiotherapy practice across Canada and the relationship of age, work-load, resources, intent and aims of therapy on departmental policy; 99 returns were analysed. Three case scenarios were given: Brain metastases were treated typically without a simulation as a parallel pair with palliative intent to 2000 cGy in 5 fractions; for locally advanced lung cancer most patients were simulated, but 40% we deemed 'radical' and there was a bimodal pattern of dose fractionation (the age of the radiation oncologist appeared to influence this and geographical differences were also notable); bony metastases from breast cancer were typically simulated as a single field using 2000-2500 cGy in 5 fractions and always considered palliative. Work-load and resources are likely to influence patterns of care. For example, over 20% felt that treatment choice was suboptimal, largely due to lack of radiation technologists and megavoltage equipment. The implications of these determinants on palliative care are discussed. Objective criteria and definitions are required to allow satisfactory workload measurements and comparisons to be made.

Bone Neoplasms↗
PubMed1993

Calcium regulation in tissue-cultured human and bovine lens epithelial cells.

PURPOSE: To study calcium regulatory mechanisms in lens cells with particular reference to the relative contributions from the calcium adenosine triphosphatase of plasma and endoplasmic reticulum membranes, respectively. METHODS: The calcium-sensitive fluorescent dye, Fura 2, was incorporated into tissue-cultured human and bovine epithelial cells and internal calcium was calibrated using the ionomycin (1 microM) method. The dynamics of calcium release from the endoplasmic reticulum were also studied in digitonin-permeabilized bovine cells. RESULTS: Tissue-cultured bovine and human lens cells have very similar resting calcium levels (235 +/- 22 nM and 216 +/- 12 nM, respectively). Thapsigargin caused an increase in cytoplasmic calcium both in the presence and absence of external calcium, but the calmodulin antagonist W7 only initiated an increase in the presence of external Ca2+. The effects of thapsigargin and W7 were additive. Exposing lens cells to Na(+)-free perfusing solutions caused a transient increase in internal Ca2+. Bovine lens cells permeabilized by digitonin-released Ca2+ when exposed to inositol (1,4,5) triphosphate and the effect was maximal at 1 microM. CONCLUSIONS: Lens cytoplasmic calcium is controlled by calcium adenosine triphosphatases at the plasma and endoplasmic reticulum membranes. The former is inhibited by W7 and insensitive to thapsigargin whereas the latter is inhibited by thapsigargin, but insensitive to W7. The lens endoplasmic reticulum store is also controlled by an inositol (1,4,5) trisphosphate calcium-release mechanism. Na+/Ca2+ exchange plays a relatively minor role in calcium regulation, at least at resting calcium levels.

Aged↗
PubMed1993

pCMPS-induced changes in lens membrane permeability and transparency.

PURPOSE: To investigate the role of externally facing membrane protein sulfhydryl groups in controlling lens permeability and transparency using the impermeant sulfhydryl complexing agent p-chloromercuriphenyl sulfonate (pCMPS). METHODS: Membrane permeability changes were studied by measuring lens voltage and resistance. Ion movements were monitored by measuring 22Na+ and 45Ca2+ fluxes, and internal free calcium was monitored by ion-selective microelectrodes. Opacification was quantified by photographing and analyzing back-scattered light. RESULTS: pCMPS, at concentrations above 1 microM, produced a depolarization of membrane potential and decrease in membrane resistance. These changes were accompanied by a marked stimulation in 22Na+ and 45Ca2+ influxes into the lens. There was a concomitant loss of lens transparency, mainly in the bow region. The pCMPS-induced electrical changes could be prevented by substituting N-methyl-D-glucamine for Na+ in the external medium. Na(+)-free solution alone increased 45Ca2+ influx, and the addition of pCMPS further stimulated the influx. Quinine (300 microM) was found to reduce the pCMPS-induced stimulation of 22Na+ and 45Ca2+ influxes and also to reduce opacification. CONCLUSIONS: pCMPS at low concentrations induces many of the cation permeability changes previously found to occur with age and cataract in the lens. The fact that quinine can ameliorate pCMPS-induced changes in ion movements and opacification suggests a novel approach for membrane-based anticataract strategies.

4-Chloromercuribenzenesulfonate↗