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Biomedical subjects

C J Evans

Publications and source records attributed to C J Evans.

At least 37 records · Page 2Linked to original sources
PubMed2000

The C. elegans apoptotic nuclease NUC-1 is related in sequence and activity to mammalian DNase II.

The Caenorhabditis elegans nuc-1 gene has previously been implicated in programmed cell death due to the presence of persistent undegraded apoptotic DNA in nuc-1 mutant animals. In this report, we describe the cloning and characterization of nuc-1, which encodes an acidic nuclease with significant sequence similarity to mammalian DNase II. Database searches performed with human DNase II protein sequence revealed a significant similarity with the predicted C. elegans C07B5.5 ORF. Subsequent analysis of crude C. elegans protein extracts revealed that wild-type animals contained a potent endonuclease activity with a cleavage preference similar to DNase II, while nuc-1 mutant worms demonstrated a marked reduction in this nuclease activity. Sequence analysis of C07B5.5 DNA and mRNA also revealed that nuc-1(e1392), but not wild-type animals contained a nonsense mutation within the CO7B5.5 coding region. Furthermore, nuc-1 transgenic lines carrying the wild-type C07B5.5 locus demonstrated a complete complementation of the nuc-1 mutant phenotype. Our results therefore provide compelling evidence that the C07B5.5 gene encodes the NUC-1 apoptotic nuclease and that this nuclease is related in sequence and activity to DNase II.

Amino Acid Sequence↗
PubMed2000

Patterns of reflux and severity of varicose veins in the general population--Edinburgh Vein Study.

OBJECTIVES: several studies have used duplex ultrasound to assess valvular incompetence in symptomatic patients. This cross-sectional survey was performed to determine, for the first time in a general population sample, the relationship between trunk varices and the presence of reflux in lower limb venous segments. MATERIALS AND METHODS: 1238 subjects (554 male, 684 female), aged 18-64 years, were randomly selected. The presence and severity of any trunk varices was assessed and classified into Grades 1-3; hyphenweb and reticular varices were noted. The presence or absence of reflux > or = 0.5 s in five deep and three superficial venous segments in each leg was assessed using duplex ultrasound. RESULTS: the prevalence of reflux increased in both superficial and deep segments with more severe grades of trunk varices (p< or = 0.01), except the upper SFV in women. Fifteen per cent of females showed reflux confined to the superficial system, compared with 9% of males (p< or = 0.001); 22% of males showed deep reflux, compared with 11% of females (p < or = 0.001). 71% of men and 48% of women with Grade 2-3 trunk varices had mixed deep and superficial reflux. Above-knee popliteal segments had a higher prevalence of reflux than lower SFV segments in all groups. There was no consistent relationship between the presence of hyphenweb or reticular varices and deep or superficial reflux. CONCLUSION: segmental venous reflux can be detected in the deep and superficial leg veins of subjects without trunk varices, but superficial and mixed reflux are increasingly found in subjects with more severe varices.

Adolescent↗
PubMed2000

Trends in case-fatality in 117 718 patients admitted with acute myocardial infarction in Scotland.

OBJECTIVES: To analyse short- and long-term case-fatality trends following admission to hospital with a first acute myocardial infarction, in men and women between 1986 and 1995, after adjusting for risk factors known to influence survival. DESIGN: A Scottish-wide retrospective cohort study. SETTING: The Linked Scottish Morbidity Record Database was analysed. This contains accurate data on all hospital admissions since 1981, for the Scottish population of 5.1 million. It is linked to the Registrar General's death certificate data. SUBJECTS: All 117 718 patients admitted to Scottish hospitals with a principal diagnosis of first acute myocardial infarction (ICD-9 code 410) between 1986 and 1995. MAIN OUTCOME MEASURES: The outcome was death, both in and out of hospital, from any cause, at 30 days, 1 year, 5 and 10 years. RESULTS: Overall case-fatality following hospital admission with acute myocardial infarction was 22. 2%, 31.4%, 51.1% and 64.0% at 1 month, 1 year, 5 and 10 years, respectively. Multivariate analyses identified statistically significant independent prognostic factors. Thirty day mortality increased twofold for each decade of increasing age, and increased with any prior admission to hospital. When comparing the most deprived category to that of the most affluent, men had a 10% increased mortality (P<0.01), whilst women had an increased mortality of 4% (not significant). After adjustment for age, sex, deprivation and prior admission to hospital, case-fatality rates fell significantly between 1986 and 1995. Short-term case-fatality fell by 46% in men (27% in women) and long-term by 34% in men (30% in women) (both P<0.001). CONCLUSIONS: Population-based case-fatality rates in Scotland have fallen dramatically since 1986, particularly in men. The increasing survival in patients admitted to hospital suggests that the trial-based efficacy of modern therapies is now translating into population-based effectiveness. However, an individual's life expectancy still halves after a diagnosis of acute myocardial infarction. Of the variables that we could examine, age was the most powerful predictor of prognosis.

Age Distribution↗
PubMed2000

The relationship between lower limb symptoms and superficial and deep venous reflux on duplex ultrasonography: The Edinburgh Vein Study.

BACKGROUND: Previous work from this group has demonstrated the relationships between lower limb symptoms and the presence and severity of trunk varicose veins as seen on clinical examination to be generally weak, symptom specific, and gender dependent. OBJECTIVE: This study was undertaken to investigate the relationships in the general population between lower limb symptoms and the presence of superficial or deep venous reflux. METHODS: A cross-sectional study was made of an age-stratified random sample of 1566 subjects (699 men and 867 women) aged 18 to 64 selected from 12 general practices in Edinburgh, Scotland. Subjects completed a self-administered questionnaire regarding symptoms (heaviness/tension, a feeling of swelling, aching, restless legs, cramps, itching, tingling) and underwent duplex ultrasound examination of the superficial and deep venous systems of both legs. Reflux of 0.5 seconds or greater was considered pathologic. Deep venous reflux was defined as reflux in at least the popliteal vein. RESULTS: There was a significant positive relationship between isolated superficial reflux and the presence of heaviness/tension (P <.025, both legs) and itching (P =.002, left leg) in women. Isolated superficial reflux in men was not significantly positively associated with any symptom. Isolated deep venous reflux was not significantly related to any symptom in either leg in either sex. Combined reflux was related to a feeling of swelling (P =.018, right leg; P =.0022, left leg), cramps (P =.0049, left leg) and itching (P =.0043, left leg) in men, and aching (P =.03, right leg) and cramps (P =.026, left leg) in women. CONCLUSION: In the general population, only certain lower limb symptoms were related to the presence of reflux on duplex ultrasound scanning. The strongest relationships were observed in the left legs of men with combined superficial and deep reflux.

Adolescent↗
PubMed2000

Use of Monte Carlo computation in benchmarking radiotherapy treatment planning system algorithms.

Radiotherapy treatments are becoming more complex, often requiring the dose to be calculated in three dimensions and sometimes involving the application of non-coplanar beams. The ability of treatment planning systems to accurately calculate dose under a range of these and other irradiation conditions requires evaluation. Practical assessment of such arrangements can be problematical, especially when a heterogeneous medium is used. This work describes the use of Monte Carlo computation as a benchmarking tool to assess the dose distribution of external photon beam plans obtained in a simple heterogeneous phantom by several commercially available 3D and 2D treatment planning system algorithms. For comparison, practical measurements were undertaken using film dosimetry. The dose distributions were calculated for a variety of irradiation conditions designed to show the effects of surface obliquity, inhomogeneities and missing tissue above tangential beams. The results show maximum dose differences of 47% between some planning algorithms and film at a point 1 mm below a tangentially irradiated surface. Overall, the dose distribution obtained from film was most faithfully reproduced by the Monte Carlo N-Particle results illustrating the potential of Monte Carlo computation in evaluating treatment planning system algorithms.

Algorithms↗
PubMed2000

Assessment of background hydrogen by the Monte Carlo computer code MCNP-4A during measurements of total body nitrogen.

The use of a hydrogen internal standard to enable the estimation of absolute mass during measurement of total body nitrogen by in vivo neutron activation is an established technique. Central to the technique is a determination of the H prompt gamma ray counts arising from the subject. In practice, interference counts from other sources--e.g., neutron shielding--are included. This study reports use of the Monte Carlo computer code, MCNP-4A, to investigate the interference counts arising from shielding both with and without a phantom containing a urea solution. Over a range of phantom size (depth 5 to 30 cm, width 20 to 40 cm), the counts arising from shielding increased by between 4% and 32% compared with the counts without a phantom. For any given depth, the counts increased approximately linearly with width. For any given width, there was little increase for depths exceeding 15 centimeters. The shielding counts comprised between 15% and 26% of those arising from the urea phantom. These results, although specific to the Swansea apparatus, suggest that extraneous hydrogen counts can be considerable and depend strongly on the subject's size.

Body Composition↗
PubMed2000

Cloned delta-opioid receptors in GH(3) cells inhibit spontaneous Ca(2+) oscillations and prolactin release through K(IR) channel activation.

Opioid receptors can couple to K(+) and Ca(2+) channels, adenylyl cyclase, and phosphatidyl inositol turnover. Any of these actions may be important in the regulation of neurotransmitter and hormone release from excitable cells. GH(3) cells exhibit spontaneous oscillations of intracellular Ca(2+) concentration ([Ca(2+)](i)) and prolactin release. Activation of cloned delta-opioid receptors stably expressed in GH(3) cells inhibits both spontaneous Ca(2+) signaling and basal prolactin release. The objective of this study was to examine a possible role for K(+) channels in these processes using the patch-clamp technique, fluorescence imaging, and a sensitive ELISA for prolactin. The selective delta receptor agonist [D-Pen(2), D-Pen(2)]enkephalin (DPDPE) inhibited [Ca(2+)](i) oscillations in GH(3) cells expressing both mu and delta receptors (GH(3)MORDOR cells) but had no effect on control GH(3) cells or cells expressing mu receptors alone (GH(3)MOR cells). The inhibition of [Ca(2+)](i) oscillations by DPDPE was unaffected by thapsigargin pretreatment, suggesting that this effect is independent of inositol 1,4,5-triphosphate-sensitive Ca(2+) stores. DPDPE caused a concentration-dependent inhibition of prolactin release from GH(3)MORDOR cells with an IC(50) of 4 nM. DPDPE increased inward K(+) current recorded from GH(3)MORDOR cells but had no significant effect on K(+) currents recorded from control GH(3) cells or GH(3)MOR cells. The mu receptor agonist morphine also had no effect on currents recorded from control cells but activated inward K(+) currents recorded from GH(3)MOR and GH(3)MORDOR cells. Somatostatin activated inward currents recorded from all three cell lines. The DPDPE-sensitive K(+) current was inwardly rectifying and was inhibited by Ba(2+) but not TEA. DPDPE had no effect on delayed rectifier-, Ca(2+)-, and voltage-activated or A-type K(+) currents, recorded from GH(3)MORDOR cells. Ba(2+) attenuated the inhibition of [Ca(2+)](i) and prolactin release by DPDPE, whereas TEA had no effect, consistent with an involvement of K(IR) channels in these actions of the opioid.

Adenylate Cyclase Toxin↗
PubMed2000

Accurate measurement of exposure rate from a 60Co teletherapy source: deviations from the inverse-square law.

A cylindrical gamma-ray 60Co source of activity alpha is predicted to produce an exposure rate X at a distance d in vacuum, given by X = gamma(T)(alpha/d2), where gamma(T) is the specific gamma-ray constant. It has been documented that this formula may be used to approximate X with an accuracy of 1% from a source of length l, provided that d/l > or = 5. It is shown that the formula is accurate to 0.1% under these conditions, provided that the distance is measured from the centre of the source. When absorption in the source and scattering in the collimator are considered, the position of the origin d = 0 can shift by a distance of the order of centimetres. Absorption in air between the source and the ionization chamber adds an exponential factor to the formula. It is shown that even when these modifications are included the discrepancy in the results, although generally less than 1%, is still large compared with the measurement errors. Some suggestions are made for the origin of this discrepancy.

Cobalt Radioisotopes↗
PubMed2000

Neurotrophin dependence domain: a domain required for the mediation of apoptosis by the p75 neurotrophin receptor.

The mechanisms underlying neurotrophin dependence, and cellular dependent states in general, are unknown. We show that a 29 amino acid region in the intracellular domain of the common neurotrophin receptor, p75NTR, is required for the mediation of apoptosis by p75NTR. Furthermore, contrary to results obtained with Fas, monomeric p75NTR is required for apoptosis induction, whereas multimerization inhibits the pro-apoptotic effect. Within the 29-residue domain required for apoptosis induction by p75NTR, a 14-residue region is sufficient as a peptide inducer of apoptosis. This 14-residue peptide requires the positively charged carboxyterminal residues for its effect on cell death, and these same residues are required by the full-length p75NTR. These studies define a novel type of domain that mediates neurotrophin dependence, and suggest that other cellular dependent states may be mediated by proteins displaying similar domains.

Amino Acid Sequence↗
PubMed2000

Ligand-induced changes in surface mu-opioid receptor number: relationship to G protein activation?

In this study, we explored the relationship between regulation of surface mu-opioid receptor number, ligand-induced G protein activation (measured by [(35)]S]guanosine-5'-O-(3-thio)triphosphate (GTPgammaS) binding) and second messenger signaling (measured by the inhibition of cAMP accumulation). Etorphine and two isomers of cis-beta-hydroxy-3-methylfentanyl (RTI-1a and RTI-1b), which were full agonists for G protein activation and signaling, caused approximately a 50% loss of surface receptors after 1 h of treatment. Fentanyl and morphine were full agonists for inhibiting cAMP accumulation and partial agonists for stimulating [(35)S]GTPgammaS binding and internalization. Although both agonists were approximately 80% as efficacious as etorphine in stimulating [(35)S]GTPgammaS binding, fentanyl induced a 35% loss of surface receptors, whereas morphine only caused a 10% loss. Additionally, both long- and short-term treatment with the opioid antagonist naloxone caused increases in surface receptors. Unexpectedly, the weak partial agonists buprenorphine and one isomer of cis-beta-hydroxy-3-methylfentanyl (RTI-1d) also were found to cause an increase in surface receptors. Treatment with pertussis toxin (PTX) diminished agonist-induced loss of surface receptors. Furthermore, the abilities of morphine and fentanyl to cause internalization were more impaired after PTX treatment than that of etorphine. PTX treatment also significantly enhanced the increase in surface receptor number caused by 18-h treatment with naloxone and buprenorphine. The results of this study suggest that disruption of G protein coupling by PTX treatment affects ligand-regulated mu-receptor trafficking and that partial agonists for signaling can vary greatly in the ability to regulate the number of surface mu-opioid receptors.

Animals↗
PubMed2000

Measuring the value of healthcare business assets.

Healthcare organizations obtain valuations of business assets for many reasons, including to support decisions regarding potential mergers, sale of business components, or financing; for tax assessments; and for defense against law-suits. If compliance with regulations may be an issue, such as when a not-for-profit organization is involved in a transaction, healthcare organizations should seek an independent appraisal to ensure that applicable legal standards are met. Whether or not regulatory issues are involved, however, an accurate and useful valuation of business assets depends on many factors. Financial managers must understand the purpose and function of the valuation, choice of appropriate valuation techniques, proper assessment of intangible value, use of realistic growth rates, appropriate emphasis on key focus areas of the valuation (e.g., risk and future income streams), and an accounting of physician compensation.

Capital Financing↗
PubMed2000

Investigation and management of sporadic gastrointestinal infections with potentially Vero cytotoxin producing Escherichia coli in Scotland.

Recognition of the potential of Escherichia coli O157 and other Vero cytotoxin producing E. coli (VTEC) organisms to cause serious disease led to the recommendation that all diarrhoeal stool specimens be examined for E. coli O157. National guidelines exist for the testing and exclusion of cases and contacts of VTEC infection. A survey was conducted to discover the extent to which these recommendations are followed in Scotland by asking about current practices for public health management of identified cases and laboratory investigation of E. coli infection. About two thirds of Scottish health boards followed national guidelines for testing and exclusion of cases and contacts of VTEC O157 infection. Most laboratories tested all diarrhoeal stools for E. coli O157 but detection methods varied and a minority tested selected stools for non-O157 E. coli serogroups. Standardisation of policies for laboratory testing of VTEC infection would improve national surveillance. Adherence to evidence based guidelines would standardise public health management of VTEC infections in Scotland.

Aged↗
PubMed1999

L-type Ca2+ channels and K+ channels specifically modulate the frequency and amplitude of spontaneous Ca2+ oscillations and have distinct roles in prolactin release in GH3 cells.

GH3 cells showed spontaneous rhythmic oscillations in intracellular calcium concentration ([Ca2+]i) and spontaneous prolactin release. The L-type Ca2+ channel inhibitor nimodipine reduced the frequency of Ca2+ oscillations at lower concentrations (100nM-1 microM), whereas at higher concentrations (10 microM), it completely abolished them. Ca2+ oscillations persisted following exposure to thapsigargin, indicating that inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ stores were not required for spontaneous activity. The K+ channel inhibitors Ba2+, Cs+, and tetraethylammonium (TEA) had distinct effects on different K+ currents, as well as on Ca2+ oscillations and prolactin release. Cs+ inhibited the inward rectifier K+ current (KIR) and increased the frequency of Ca2+ oscillations. TEA inhibited outward K+ currents activated at voltages above -40 mV (grouped within the category of Ca2+ and voltage-activated currents, KCa,V) and increased the amplitude of Ca2+ oscillations. Ba2+ inhibited both KIR and KCa,V and increased both the amplitude and the frequency of Ca2+ oscillations. Prolactin release was increased by Ba2+ and Cs+ but not by TEA. These results indicate that L-type Ca2+ channels and KIR channels modulate the frequency of Ca2+ oscillations and prolactin release, whereas TEA-sensitive KCa,V channels modulate the amplitude of Ca2+ oscillations without altering prolactin release. Differential regulation of these channels can produce frequency or amplitude modulation of calcium signaling that stimulates specific pituitary cell functions.

Calcium↗
PubMed1999

An MCNP-based model of a linear accelerator x-ray beam.

The Monte Carlo N-Particle radiation transport computer code (MCNP) has been employed on a personal computer to develop a simple model simulating the major components within the beam path of a linear accelerator radiation head, namely the electron target, primary conical collimator, beam flattening filter, wedge filter and the secondary collimators. The model was initially used to calculate the energy spectra and angular distributions of the x-ray beam for the Philips SL 75/5 linear accelerator, in a plane immediately beneath the flattening filter. These data were subsequently used as a 'source' of x-rays at the target position, to assess the emergent beam from the secondary collimators. The depth dose distributions and dose profiles at constant depth for various field sizes have been calculated for a nominal operating potential of 4 MV and found to be within acceptable limits. It is concluded that the technique may be used to calculate the energy spectra of any linear accelerator upon specification of the component dimensions, materials and nominal accelerating potential. It is anticipated that this work will serve as the basis of a quality control tool for linear accelerators and treatment planning systems.

Biophysical Phenomena↗
PubMed1999

Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein Study.

STUDY OBJECTIVE: To determine the prevalence of varicose veins and chronic venous insufficiency (CVI) in the general population. DESIGN: Cross sectional survey. SETTING: City of Edinburgh. PARTICIPANTS: Men and women aged 18-64 years selected randomly from age-sex registers of 12 general practices. MAIN RESULTS: In 1566 subjects examined, the age adjusted prevalence of trunk varices was 40% in men and 32% in women (p < or = 0.01). This sex difference was mostly a result of higher prevalence of mild trunk varices in men. More than 80% of all subjects had mild hyphenweb and reticular varices. The age adjusted prevalence of CVI was 9% in men and 7% in women (p < or = 0.05). The prevalence of all categories of varices and of CVI increased with age (p < or = 0.001). No relation was found with social class. CONCLUSIONS: Approximately one third of men and women aged 18-64 years had trunk varices. In contrast with the findings in most previous studies, mainly conducted in the 1960s and 1970s, chronic venous insufficiency and mild varicose veins were more common in men than women. No evidence of bias in the study was found to account for this sex difference. Changes in lifestyle or other factors might be contributing to an alteration in the epidemiology of venous disease.

Adolescent↗
PubMed1998

ORL-1 and mu opioid receptor antisera label different fibers in areas involved in pain processing.

Mu opioid receptors (MOR) mediate the analgesic effects of opioid drugs such as morphine. The opioid receptor-like (ORL-1) receptor is structurally related to opioid receptors and the ORL-1 receptor agonist, orphanin FQ/nociceptin, induces analgesia at the spinal level, but appears to recruit different circuitry than that used by mu opioids. When administered intracerebroventricularly, orphanin FQ/nociceptin produces hyperalgesia and/or reverses opioid analgesia. The functionally distinct actions elicited by MOR and ORL-1 receptors, which activate similar intracellular signaling systems and show similar regional distributions, could be explained by their differential cellular localization. By using double label immunohistochemistry and confocal microscopy, the present study investigates the distribution of MOR and ORL-1 receptors in regions of the rat nervous system that are involved with nociceptive processing. In general co-localization of MOR and ORL-1 receptor immunoreactivity was not observed in either perikarya or neuropil in the dorsal root ganglia, nor in the Lissauer's tract and superficial laminae of the spinal cord. Likewise, there was no evidence for co-localization of these receptors within the periaqueductal gray, the nucleus raphe magnus, the gigantocellular reticular nucleus, and the nucleus of the solitary tract. These observations indicate that MOR and ORL-1 receptors are expressed predominantly on different fiber systems in these regions. This differential distribution is consistent with the distinct pharmacology of ORL-1 and MOR receptor agonists and suggests that the antisera to MOR and ORL-1 receptors may provide useful markers for further investigations of analgesic and counteranalgesic pathways modulating pain perception.

Amino Acid Sequence↗