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Biomedical subjects

C Edwards

Publications and source records attributed to C Edwards.

At least 91 records · Page 5Linked to original sources
PubMed1998

Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins.

Abeta1-42 is a self-associating peptide whose neurotoxic derivatives are thought to play a role in Alzheimer's pathogenesis. Neurotoxicity of amyloid beta protein (Abeta) has been attributed to its fibrillar forms, but experiments presented here characterize neurotoxins that assemble when fibril formation is inhibited. These neurotoxins comprise small diffusible Abeta oligomers (referred to as ADDLs, for Abeta-derived diffusible ligands), which were found to kill mature neurons in organotypic central nervous system cultures at nanomolar concentrations. At cell surfaces, ADDLs bound to trypsin-sensitive sites and surface-derived tryptic peptides blocked binding and afforded neuroprotection. Germ-line knockout of Fyn, a protein tyrosine kinase linked to apoptosis and elevated in Alzheimer's disease, also was neuroprotective. Remarkably, neurological dysfunction evoked by ADDLs occurred well in advance of cellular degeneration. Without lag, and despite retention of evoked action potentials, ADDLs inhibited hippocampal long-term potentiation, indicating an immediate impact on signal transduction. We hypothesize that impaired synaptic plasticity and associated memory dysfunction during early stage Alzheimer's disease and severe cellular degeneration and dementia during end stage could be caused by the biphasic impact of Abeta-derived diffusible ligands acting upon particular neural signal transduction pathways.

Alzheimer Disease↗
PubMed1998

Development of a bioassay employing the desert locust (Schistocerca gregaria) for the detection of saxitoxin and related compounds in cyanobacteria and shellfish.

Monitoring paralytic shellfish toxins (PST) in shellfish and freshwater cyanobacteria is largely dependent on the mouse bioassay. An alternative assay was devised using the desert locust Schistocerca gregaria. The bioassay successfully identified the optimum extraction procedure for PST from cyanobacterial cells and was also suitable for screening acid extracts of shellfish flesh. These results demonstrate the potential of the locust bioassay for the routine screening of PST in a range of sample matrices.

Animals↗
PubMed1998

The Maudsley Addiction Profile (MAP): a brief instrument for assessing treatment outcome.

AIM: To develop a brief, multi-dimensional instrument for assessing treatment outcome for people with drug and/or alcohol problems. The Maudsley Addiction Profile (MAP) is the first instrument to be developed in the United Kingdom for this purpose. DESIGN: Field testing with quota-recruitment of problem drug users and problem alcohol users in treatment with researcher and clinician-administered test-retest interviews. SETTING: Two community and two inpatient services at the Bethlem Royal and Maudsley Hospital, London. PARTICIPANTS: Subjects (160 drug users and 80 alcohol users) interviewed by eight interviews (four researchers and four clinicians), each of whom interviewed 30 subjects on two occasions. MEASURES: Sixty items across substance use, health risk, physical/psychological health and personal/social functioning domains. FINDINGS: Average completion time of the MAP was 12 minutes. The questionnaire was acceptable to a majority of subjects and performed well with both researcher and clinician interviewers. Internal reliability and feasible concurrent validity assessments of the scales and items were highly satisfactory. Test-retest reliability was good, average intraclass correlation coefficients across eight substances were 0.94 and 0.81 across health risk, health problems, relationship conflict, employment and crime measures. CONCLUSIONS: The MAP can serve as a core research instrument with additional outcome measures added as required. The collection of a set of reliable quantitative measures of problems among drug and alcohol users by research or treatment personnel for outcome evaluation purposes need not be time-consuming.

Adult↗
PubMed1998

An evaluation of lectin-mediated magnetic bead cell sorting for the targeted separation of enteric bacteria.

Lectin-labelled magnetic beads were assessed and compared with antisera as an alternative approach for the targeted separation and isolation of enteric bacteria. Of the 16 lectins tested against a range of bacterial species, concanavalin A (conA) showed the greatest potential. Agglutination of bacterial cells in suspension using conA and methods for effective labelling of the magnetic beads with the lectin were optimized. ConA-labelled magnetic beads were compared with antibody-labelled beads for recovery of bacterial cells from pure or mixed laboratory cultures and from natural populations in river water. Recovered cell populations were free from environmental impurities and a high percentage of the culturable cells was extracted. Specific cell recovery was found to be variable, but the use of lectins offers some promise as an alternative cell discriminator.

Agglutination Tests↗
PubMed1998

Substance use, health and social problems of service users at 54 drug treatment agencies. Intake data from the National Treatment Outcome Research Study.

BACKGROUND: The National Treatment Outcome Research Study (NTORS) is the first large-scale, prospective, multi-site treatment outcome study of drug users in the UK. METHOD: Substance use, health and social problems of 1075 service users were assessed at intake to 54 agencies chosen to be representative of the main national drug treatment modalities. RESULTS: Heroin dependence was the most frequently reported problem often with poly-drug and alcohol problems. Most service users injected drugs and a quarter of the injectors shared injecting equipment. Poly-drug use and heavy drinking were more common among service users admitted to residential treatments. High criminality rates were reported. Psychological and physical health problems were common and many service users had prior contact with psychiatric and medical services. CONCLUSIONS: The range and severity of problems adversely affect individual users, their families, and present a challenge to addiction treatment services. These problems create costs for the health care, social service and criminal justice system responses.

Adolescent↗
PubMed1997

Sleep electroencephalographic abnormalities in adolescent depressives: effects of scopolamine.

In contrast to sleep studies of adult depressives that have consistently demonstrated abnormalities of sleep continuity, slow-wave sleep, and REM sleep, existing studies of depressed children and adolescents have been conflicting. Furthermore, only one study has explored the cholinergic regulation of sleep in early-onset depressives. In the present study, the electroencephalographic sleep of 20 adolescent outpatients with major depressive episodes and 13 normal control adolescents was obtained on two separate 2-night sessions, 1 night incorporating challenge with scopolamine. Depressed adolescents showed increased baseline phasic REM sleep measures, increased arousals, a trend toward reduced slow-wave sleep, and a greater difference in the change of first REM period density on the scopolamine night versus placebo night compared to controls. These findings support the continuity of some sleep abnormalities of depression into adolescence, and suggest that adolescent depression may be associated with alterations of cholinergic neurotransmission in some patients.

Adolescent↗
PubMed1997

Differential response of rapid eye movement sleep to cholinergic blockade by scopolamine in currently depressed, remitted, and normal control subjects.

The degree of cholinergic dysregulation of sleep in adult depression was evaluated using scopolamine. On separate sessions, placebo and scopolamine (4.5 micrograms/kg, IM) were administered to 14 patients with unipolar major depression, 16 recovered/remitted patients, and 18 normal controls. Scopolamine increased rapid eye movement (REM) latency (RL), reduced REM activity (RA), REM density (RD), and REM duration, and increased the percentage of stage 4 sleep in all groups. There was a differential effect of scopolamine on RL, RA, and REM duration for the first REM period, and on percentage of stage 4 sleep. Whereas a primary cholinergic hyperactivity could account for the RA and RD responses, the response profile for RL was more compatible with reduced aminergic tone as the proximal cause of the cholinergic hyperactivity. Whether the sleep abnormalities observed in remitted patients reflect an underlying vulnerability for development or recurrence of depression, and/or a scar, remains to be determined.

Adult↗
PubMed1997

Preeclampsia, labor duration and mode of delivery.

OBJECTIVE: To determine if there is a difference in the length of labor, and method of delivery between preeclamptic and normotensive patients. METHODS: A retrospective case control study was performed using a perinatal database. Study subjects included nulliparous patients diagnosed with preeclampsia, and were compared with normotensive nulliparous patients. RESULTS: There were 1454 controls and 727 subjects identified. There was no difference between groups with regard to duration of total labor. There was a statistically but not clinically significant increase in the duration of the second stage in preeclamptics (35 vs. 27 min, P = 0.003). Preeclamptics had a consistently higher risk of cesarean delivery, even when controlled for confounding variables. CONCLUSION: The clinical belief that preeclamptic patients have more rapid labors is not supported. Preeclamptics do seem to have a higher risk of cesarean delivery.

Case-Control Studies↗
PubMed1997

Dimethyldioxirane converts benzene oxide/oxepin into (Z,Z)-muconaldehyde and sym-oxepin oxide: modeling the metabolism of benzene and its photooxidative degradation.

Oxidation of 7-oxabicyclo[4.1.0]hepta-2,4-diene (benzene oxide)/oxepin with dimethyldioxirane (DMDO) gave mainly (Z,Z)-muconaldehyde, with complete diastereoselectivity. Similarly, 2-methyl-7-oxabicyclo[4.1.0]hepta-2,4-diene (toluene 1,2-epoxide)/2-methyloxepin gave (Z,Z)-1,6-dioxohepta-2,4-diene, while 2,6-dimethyl-7-oxabicyclo[4.1.0]hepta-2,4-diene (1,2-dimethylbenzene 1,2-epoxide)/2,7-dimethyloxepin gave (Z,Z)-2,7-dioxo-3,5-octadiene. By monitoring the DMDO oxidation of benzene oxide/oxepin by 1H NMR spectroscopy, a significant byproduct was identified as 4,8-dioxabicyclo[5.1.0]octa-2,5-diene (sym-oxepin oxide). This observation supports the hypothesis that the route to (Z,Z)-muconaldehyde proceeds from oxepin via 6,8-dioxabicyclo[5.1.0]octa-2,4-diene (oxepin 2,3-oxide), with a minor pathway leading to sym-oxepin oxide. The DMDO oxidations described provide model systems for the cytochrome P450-dependent metabolism of benzene and for the atmospheric photooxidation of benzenoid hydrocarbons.

Aldehydes↗
PubMed1997

Anti-cytokeratin 5/6: a positive marker for epithelioid mesothelioma.

AIMS: Previous studies using frozen material have suggested that cytokeratin 5 is expressed by pleural mesothelioma but not by adenocarcinoma. In the present study, reactions for cytokeratins 5 and 6 were investigated in 33 pleural mesotheliomas and 27 secondary adenocarcinomas of the pleura using formalin-fixed, paraffin-embedded material and a commercially available antibody (anti-cytokeratin 5/6). METHODS AND RESULTS: All of the adenocarcinomas originated in the peripheral lung. The epithelioid component of the mesotheliomas gave a strongly positive reaction: the reaction in sarcomatoid or desmoplastic areas was absent or weak. Twenty-two of the adenocarcinomas were negative, in four there was a weak, equivocal reaction, and in one there was patchy positivity. CONCLUSIONS: We conclude that this antibody is potentially a useful positive marker for the identification of the epithelioid variant of mesothelioma in formalin-fixed and paraffin-embedded material.

Antibodies, Neoplasm↗
PubMed1997

Detection, distribution and probable fate of Escherichia coli O157 from asymptomatic cattle on a dairy farm.

The use of commercial anti-Escherichia coli O157-labelled magnetic beads was investigated to improve detection of E. coli O157 by immunomagnetic separation (IMS) from a range of environments on a dairy farm. Immunomagnetic separation proved effective for separation of target cells from laboratory mixtures and during stress in sterile and non-sterile pond water. The IMS procedure was possible with a range of samples (water, faeces, slurry, grass and soil). Non-specific binding of non-target bacterial cells proved problematic in a number of sample types. However, indigenous E. coli O157 cells were detected from samples with a high faecal load, and only with use of IMS. Data on the probable survival and spread of the organism around the farm environment are also discussed.

Animals↗
PubMed1997

Isolation and growth physiology of novel thermoactinomycetes.

A total of 34 thermophilic isolates identified as members of the genus Thermoactinomyces by a range of chemotaxonomic, microscopic and determinative biochemical tests, were isolated from two acid soils. Growth studies in shake flask and fermenter identified the isolates to be moderately acidophilic with growth occurring between pH 4.5 and 6.0 with optima at pH 5.0. The isolates differed considerably from known Thermoactinomyces cultures in their pH profile, colony morphology and in several biochemical tests. Extracellular enzyme activities are identified and partially characterized in terms of their thermostability, pH and temperature profiles from crude supernatant fluid samples. Optimal protease, amylase and pullulanase activity was observed at pH 5.0-5.5 and 75-80 degrees C with each showing T(50) values of 10, 30 and 30 min, respectively. A highly thermotolerant extracellular esterase was also identified which retained 50% activity after 8 h at 90 degrees C. This is the first report of an acidophilic member of the genus Thermoactinomyces.

Actinomycetales↗
PubMed1997

Efficiency of the polymerase chain reaction amplification of the uid gene for detection of Escherichia coli in contaminated water.

Direct detection of Escherichia coli from polluted river water was achieved using polymerase chain reaction (PCR) amplification of the uid gene. Amplification using DNA from environmental samples resulted in non-specific DNA fragments. Specific amplification was achieved through use of the touch-down PCR procedure. Targeting the uidA structural region of the gene gave reproducibly better amplification than targeting the uidR regulatory region. The data demonstrate conditions for optimal specific detection.

Bacteriological Techniques↗