PubMed Health⌕ Search

Biomedical subjects

R Edwards

Publications and source records attributed to R Edwards.

At least 37 records · Page 2Linked to original sources
PubMed1999

Individuals from North America, Australasia, and Africa are infected with four different genotypes of human herpesvirus 8.

To study human herpesvirus 8 (HHV-8) transmission between individuals and in populations, we developed a system for genetic fingerprinting of HHV-8 strains based on variation in the HHV-8 K1, glycoprotein B (gB), and glycoprotein H (gH) genes. Using this system, we sequenced nearly the entire K1 gene (840 bp); two segments of the gB gene (open reading frame 8), totaling 813 bp; and a 702-bp segment of the gH gene (open reading frame 22) from blood and tissue samples obtained from 40 human immunodeficiency virus-infected and noninfected individuals, including those with Kaposi's sarcoma, primary effusion lymphoma, or Castleman's disease. The specimen collection was assembled from individuals living in diverse geographical locations, including the United States, Australia, New Zealand, Uganda, and Zambia. As reported by others, K1 was the most variable gene, with up to 16% variation at the nucleotide sequence level and up to 32% variation at the amino acid sequence level. Despite this extensive sequence variation, the K1 amino acid sequence contained 14 conserved cysteine sites, suggesting a conserved tertiary structure. gB and gH sequences were highly conserved, in most cases differing by <0.6% in pairwise comparisons. K1 was the most useful gene for strain discrimination, but the other genes enabled the discrimination of strains with identical K1 sequences. Individuals from diverse geographic locations were infected with four different HHV-8 genotypes; strains did not strictly segregate by continent of origin. The majority of HHV-8 strains from the United States and Europe were relatively closely related, whereas some strains identified from Uganda and Australia were phylogenetically distant. Genotype I strains were the most common and were found on three continents. Identical sequences were found in specimens obtained from different body sites and at different times from the same individual.

AIDS-Related Opportunistic Infections↗
PubMed1999

Parkinsonian tremor and simplification in network dynamics.

We explore the behavior of richly connected inhibitory neural networks under parameter changes that correspond to weakening of synaptic efficacies between network units, and show that transitions from irregular to periodic dynamics are common in such systems. The weakening of these connections leads to a reduction in the number of units that effectively drive the dynamics and thus to simpler behavior. We hypothesize that the multiple interconnecting loops of the brain's motor circuitry, which involve many inhibitory connections, exhibit such transitions. Normal physiological tremor is irregular while other forms of tremor show more regular oscillations. Tremor in Parkinson's disease, for example, stems from weakened synaptic efficacies of dopaminergic neurons in the nigro-striatal pathway, as in our general model. The multiplicity of structures involved in the production of symptoms in Parkinson's disease and the reversibility of symptoms by pharmacological and surgical manipulation of connection parameters suggest that such a neural network model is appropriate. Furthermore, fixed points that can occur in the network models are suggestive of akinesia in Parkinson's disease. This model is consistent with the view that normal physiological systems can be regulated by robust and richly connected feedback networks with complex dynamics, and that loss of complexity in the feedback structure due to disease leads to more orderly behavior.

Humans↗
PubMed1999

Quantitative analysis of rapid pointing movements in Cree subjects exposed to mercury and in subjects with neurological deficits.

To quantify rapid and precise proximo-distal movements, we have developed a simple system (eurythmokinesimeter or EKM) which requires the subject to touch alternately the center of proximal and distal targets with a stylus. Ninety-six participants, including 30 controls subjects, 36 Cree subjects exposed to mercury, 21 subjects with Parkinson disease, 6 with presumed cerebellar deficit, and 3 with essential tremor, participated in the study. A total of nine measures, including precision, imprecision, contact duration, unsureness, tremor, transit time, irregularity, speed, and Fitts' constant, were calculated. Test-retest reliability was above 0.8 for most measures and above 0.9 for many measures. Correlations between measures and number of outliers with respect to the control group distribution for each measure were used to reduce the set of measures to five (i.e., precision, imprecision, tremor, Fitts' constant, and irregularity). An ANOVA on the three largest groups generated significant results for tremor, Fitts' constant, and irregularity between the Cree and the control subjects and on Fitts' constant and irregularity between the subjects with Parkinson's disease and the control subjects. Three subgroups of the same mean age composed of six subjects each were selected. One was composed of Cree subjects with the highest level of mercury exposure, another with Cree subjects having a low level of mercury exposure, and a third with control subjects. An ANOVA on these three groups revealed a significant difference between both groups of Cree subjects and the control group for Fitts' constant and irregularity. These preliminary results suggest that the EKM system is able to discriminate the performance of different groups of subjects.

Analysis of Variance↗
PubMed1999

Analysis of rapid alternating movements in Cree subjects exposed to methylmercury and in subjects with neurological deficits.

To quantify rapid alternating movements (RAMs) we used a simple prototype developed in our laboratory that requires the subject to rotate two hand-held foam spheres connected to optical encoders via flexible rods. Ninety-six participants, including 30 control subjects, 36 Cree subjects exposed to methylmercury, 21 subjects with Parkinson's disease, 6 subjects with cerebellar deficits, and 3 subjects with essential tremor, were involved in the study (though data for 5 were later removed). Twelve characteristics were developed and calculated from the raw data. Conditions examined included two hands at natural cadence (NC2), right and left hands separately at fast cadence (FCl), and both hands at fast cadence (FC2). Two ratios (FC2/NC2) and (FC2/FC1) combining these conditions were also examined. Test-retest reliability was >0.80 for most characteristics but was <0.70 for some characteristics, especially in the conditions executed at normal cadence. Correlations between characteristics and numbers of outliers with respect to the control group distribution were used to reduce the set of characteristics from 12 to 7 (i.e., duration, range, maximum slope, similarity in shape, smoothness, sharpness, and coherence). ANOVAs on the three largest groups generated significant results for most characteristics in the three conditions and the two ratios for Cree subjects and subjects with Parkinson's disease. ANOVAs on 3 age-matched groups (n=6) suggest that methylmercury affects the performance of the Cree subjects with the higher exposure, especially in terms of smoothness, sharpness, and coherence. These preliminary results suggest that this test is sufficiently specific and sensitive to characterize the performance of different groups of subjects. Ratios tend to improve discrimination for Cree subjects in a few characteristics but not for patients with Parkinson's disease.

Case-Control Studies↗
PubMed1999

Speed-dependent responses in V5: A replication study.

In a previous paper, we used fMRI to examine motion-sensitive responses in human area V5 as a function of stimulus speed. As predicted by electrophysiological findings, we observed optimal responses at intermediate speeds of around 7 to 30 degrees /s. These results revealed a nonlinear (inverted "U") dependency on speed that was also evident in V3a. In this paper we repeated the experiment using an improved stimulus and a larger range of speeds. We replicated our previous findings and extended our characterization of speed-dependent responses: Optimal responses were seen in V5 at speeds of 4 and 8 degrees /s and in V3a at speeds of 4 to 16 degrees /s. We were also able to show an interaction between speed (fast vs slow) and contrast (color > luminance) in V5. This interaction was anticipated on the basis of the different properties of the geniculate and extrageniculate inputs to V5. Finally, we were also able to demonstrate an interaction between motion (moving vs stationary) and contrast (color > luminance) in V4. This suggests that for V4, color-specific responses are augmented in the context of motion; or equivalently, that color contrast enhances any motion-sensitive responses in V4.

Artifacts↗
PubMed1999

An action plan for tobacco control at regional level.

Smoking is the single biggest preventable cause of death in the UK; killing over 120 000 people each year, contributing to inequalities in health, exacerbating and causing poverty. Smoking has increased steadily among children since 1988 and more recently, among young adults. The current context in the UK is highly favourable for introducing comprehensive tobacco control measures. This paper summarises a regional action plan for tobacco control. Actions at district and regional levels are outlined to establish a comprehensive local tobacco control framework and complement national tobacco control measures. Measures include: a 'SWOT' analysis of current activity; systematic monitoring of smoking prevalence, attitudes to smoking, and the impact of tobacco control interventions; provision of effective smoking cessation support to a minimum standard throughout the health service; increased coverage of smoke-free public places and workplaces; enforcement of legislation on illegal sales to children and against smuggling and selling illegally imported tobacco; paid and unpaid mass media campaigns; and systematic lobbying for fiscal and legislative measures. One of the key components of the plan is the introduction of evidence-based tobacco control strategies at district levels. These should include a performance framework with clear organisational and managerial accountability and employ a co-ordinated, multiagency, partnership approach. Priority groups should be identified. Strategies should seek to engage the public to build support for tobacco control measures. Sufficient time, staff, resources and training must be allocated to tobacco control work and progress towards objectives monitored.

Adolescent↗
PubMed1999

Higher plant tyrosine-specific protein phosphatases (PTPs) contain novel amino-terminal domains: expression during embryogenesis.

Sequences encoding proteins with homology to protein tyrosine phosphatases have been identified in Arabidopsis, soybean and pea. Each contains a predicted catalytic domain containing sequence motifs characteristic of tyrosine-specific protein phosphatases (PTPs) which play an important role in signal transduction in other eukaryotes and are distinct from dual-specificity, cdc25 or low-molecular-weight protein tyrosine phosphatases. Their identity as PTPs was confirmed by characterising the soybean PTP expressed as a recombinant His-tagged fusion protein. The enzyme had phosphatase activity towards p-nitrophenolphosphate (pNPP) and phosphotyrosine, but did not hydrolyse phosphoserine or phosphothreonine at a measureable rate. Phosphotyrosine containing peptides also served as substrates, with Km values in the micromolar range. Activity was abolished by inhibitors specific for tyrosine phosphatases (vanadate, dephostatin) but was unaffected by inhibitors of serine/threonine protein phosphatases (fluoride, cantharidin, metal-chelating agents). Gel filtration chromatography showed that the recombinant enzyme was a monomer. The Arabidopsis PTP sequence was isolated both as a genomic clone and as a partial EST, whereas the pea and soybean sequences were isolated as cDNAs. Southern analysis suggested a single gene in Arabidopsis and a small gene family in pea and soybean. In pea, PTP transcripts were present in embryos, and decreased in level with development; transcripts were also detectable in other tissues. The plant PTPs all contain a similar N-terminal domain which shows no similarity to any known protein sequence. This domain may be involved in PTP functions unique to plants.

Amino Acid Sequence↗
PubMed1999

Dimerisation of maize glutathione transferases in recombinant bacteria.

Two cDNAs encoding novel type III maize (Zea mays) GST subunits, ZmGST VI and ZmGST VII, have been cloned in addition to the previously described ZmGST V. Together with the type I GSTs ZmGST I and ZmGST III, these subunits were expressed in Escherichia coli, both individually and in tandem combinations using a customised pET vector. The GST dimers formed were then characterised. When type I GSTs were co-expressed only the respective homodimers were formed rather than the ZmGST I-III heterodimer. The failure to form this heterodimer, together with the negligible herbicide-detoxifying activity associated with recombinant ZmGST III-III, suggests that the identity of herbicide-detoxifying isoenzymes described in maize as being composed of ZmGST III subunits requires re-evaluation. In contrast, co-expression of the type III GSTs ZmGST V and ZmGST VI resulted in the formation of ZmGST V-V, ZmGST VI-VI and ZmGST V-VI dimers in the ratio 1:1:2 as predicted for random subunit association. ZmGST V-VI had kinetic characteristics intermediate between those of the two homodimers, indicating that the subunits were catalytically independent of one another. Co-expression of ZmGST V and ZmGST VII resulted in the formation of ZmGST V-VII and this isoenzyme was subsequently identified in maize plants. Attempts to dimerise type I GST subunits with type III GST subunits proved unsuccessful. These results demonstrate the utility of co-expressing recombinant GSTs to explore the potential of subunit-subunit associations and to help unravel the complexity of homodimeric and heterodimeric GSTs in plants.

Amino Acid Sequence↗
PubMed1999

A role for glutathione transferases functioning as glutathione peroxidases in resistance to multiple herbicides in black-grass.

Black-grass (Alopecurus myosuroides) is a major weed of wheat in Europe, with several populations having acquired resistance to multiple herbicides of differing modes of action. As compared with herbicide-susceptible black-grass, populations showing herbicide cross-resistance contained greatly elevated levels of a specific type I glutathione transferase (GST), termed AmGST2, but similar levels of a type III GST termed AmGST1. Following cloning and expression of the respective cDNAs, AmGST2 differed from AmGST1 in showing limited activity in detoxifying herbicides but high activities as a glutathione peroxidase (GPOX) capable of reducing organic hydroperoxides. In contrast to AmGST2, other GPOXs were not enhanced in the herbicide-resistant populations. Treatment with a range of herbicides used to control grass weeds in wheat resulted in increased levels of hydroperoxides in herbicide-susceptible populations but not in herbicide-resistant plants, consistent with AmGST2 functioning to prevent oxidative injury caused as a primary or secondary effect of herbicide action. Increased AmGST2 expression in black-grass was associated with partial tolerance to the peroxidizing herbicide paraquat. The selective enhancement of AmGST2 expression resulted from a constitutively high expression of the respective gene, which was activated in herbicide-susceptible black-grass in response to herbicide safeners, dehydration and chemical treatments imposing oxidative stress. Our results provide strong evidence that GSTs can contribute to resistance to multiple herbicides by playing a role in oxidative stress tolerance in addition to detoxifying herbicides by catalysing their conjugation with glutathione.

Amino Acid Sequence↗
PubMed1999

Moclobemide in the treatment of major depressive disorder (DSM-3) following traumatic brain injury.

Major depression (MDD) following traumatic brain injury (TBI) is a common phenomenon. There are no adequate studies in the literature defining optimum treatments for this condition following TBI. The opportunity arose to analyse a group of patients who were included in a larger study of an antidepressant (moclobemide). As the treatment, but not the delivery, was known, this has the status of an open study. Twenty-six patients with major depression of late onset (mean 4.67 years post-TBI) were identified (18 male, 8 female), with a mean age at injury 28.49 years. The group was moderately depressed with Hamilton Depression score (HAM-D) of 23.385 and moderately anxious with Hamilton Anxiety score (HAM-A) of 21.231. Mean HAM-D reduction was 81% and HAM-A reduction 81%. Of the 26 subjects 23 were defined as responders. Onset of action was rapid, with 17 responding by day 3. Irritability scores showed a mean reduction of 57% and pain scores a reduction of 39%. It is concluded that moclobemide may be an effective treatment for MDD following TBI, but properly controlled studies must be carried out to confirm this.

Adolescent↗
PubMed1999

Risk: a media perspective.

The joumalist's quest for stories and the media's business needs pose problems for those who work in radiation protection. Accidents are news; routine operations are not. Relations with journalists have been damaged by dishonesty about radiation. Secrecy, a legacy of the atomic bomb, still persists throughout the nuclear industry and distorts public debate. Examples are given. There is also scientific uncertainty about the effects of low-level radiation because of the discoveries being made in Harwell, Dublin and Harvard about genomic instability. The key to how people perceive risks is the degree of control they exert over them. People are not in control of the risks they encounter from radiation. Hence they dislike additions of artificial radioactivity from bomb tests, Chernobyl and Sellafield. This is a sensible response that should be dealt with honestly.

Humans↗
PubMed1999

Thyroid nodules, thyroid function and dietary iodine in the Marshall islands.

BACKGROUND: Thyroid nodules have been found to be common in the population of the Marshall Islands. This has been attributed to potential exposure of radioiodines from the nuclear weapons tests on Bikini and Eniwetok between 1946 and 1958. METHODS: In order to get a full picture of thyroid pathology in the Marshallese population potentially exposed to radioactive fallout we performed a large thyroid screening programme using palpation, high resolution ultrasound and fine needle biopsies of palpable nodules. In addition, various parameters of thyroid function (free T3, free T4, thyroid stimulating hormone [TSH]) and anti-thyroid antibodies were examined in large proportions of the total population at risk. Since dietary iodine deficiency is an established risk factor for thyroid nodules, iodine concentration in urine samples of 362 adults and 119 children was measured as well as the iodine content of selected staple food products. RESULTS: The expected high prevalence of thyroid nodules was confirmed. There was no indication of an increased rate of impaired thyroid function in the Marshallese population. A moderate degree of iodine deficiency was found which may be responsible for some of the increased prevalence of thyroid nodules in the Marshallese population. CONCLUSIONS: Studies on the relationship between exposure to radioiodines and thyroid nodules need to take dietary iodine deficiency into account in the interpretation of findings.

Adult↗
PubMed1999

Teaching public health to medical students in the United Kingdom--are the General Medical Council's recommendations being implemented?

BACKGROUND: Despite frequent calls to improve undergraduate medical public health teaching, little is known about whether curricula have changed. We report a survey of undergraduate public health teaching in UK medical schools in 1996. The survey aimed to assess whether the General Medical Council's 1993 recommendations to strengthen undergraduate medical education in public health have been implemented. METHODS: We asked heads of academic departments of public health at all 26 UK medical schools to complete a questionnaire and provide supporting documentation for each undergraduate public health course or module. We compared results from the 1996 survey with those from a similar survey in 1992. RESULTS: Twenty-one out of 26 (81 per cent) medical schools responded. All responding medical schools included public health teaching within their curriculum. The median number of public health courses per medical school was unchanged since 1992. A wide variety of topics were taught. Core public health subjects were taught at most schools, though over a quarter of medical schools did not cover some core topics. Between 1992 and 1996 the proportion of time devoted to teaching by lectures decreased, whereas the following all increased: teaching by small group methods; the proportion of courses using methods of assessment encouraging active learning; and the contribution of public health courses to the final degree assessment. CONCLUSION: The findings suggest that many of the General Medical Council's recommendations for improving the delivery of undergraduate education are being addressed by public health teaching in UK medical schools. However, addressing the gaps in undergraduate public health teaching revealed in this survey is a continuing challenge for academic public health departments. Medical schools should review the content of their undergraduate public health teaching to ensure that tomorrow's doctors are adequately equipped with public health knowledge and skills.

Cross-Sectional Studies↗
PubMed1999

Using frequency domain characteristics to discriminate physiologic and parkinsonian tremors.

The manner in which characteristics of time series in the frequency domain can enhance discrimination between physiologic and parkinsonian tremor when tremor amplitude is low was examined. Rest tremor and postural tremor with and without visual feedback were recorded twice in the two hands of a group of patients with Parkinson's disease (PD) (n = 21) and a group of healthy control subjects (n = 30) using displacement laser systems. Recordings were analyzed quantitatively using amplitude and seven frequency domain characteristics. Postural tremor with no visual feedback allowed the most efficient discrimination between the two groups of subjects especially in velocity and acceleration (derived from displacement) and allowed identification of more patients with PD as separate from the range observed in the control group. Moreover, the frequency domain characteristics that were investigated identified the majority of the patients even when amplitude did not. After eliminating redundant (correlated) characteristics, it was found that the frequency composition of tremor in PD can be described adequately with four characteristics, which are the most reliable, independent, and discriminative elements for detecting early or subtle modifications in tremor. Also, a series of finger flexions was found to enhance physiologic tremor but not tremor in PD. Discrimination of low-amplitude tremor in PD from normal physiologic tremor is enhanced by examining the median frequency of oscillations, the concentration of power in the power spectrum, and the distribution of power in particular ranges. Tremor measurement should not be limited to acceleration data as some information is more visible in velocity time series.

Acceleration↗