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Biomedical subjects

E Gray

Publications and source records attributed to E Gray.

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

Monoclonal antibodies against platelet membrane glycoproteins IIb/IIIa and Ibalpha inhibit platelet dependent thrombin generation by different mechanisms.

The antithrombotic effect of antiplatelet agents is principally due to their anti-aggregatory action, but these agents may also interfere with coagulation. We have investigated the effect of monoclonal antibodies (MAb) to platelet membrane glycoproteins (GP) IIb/IIIa and Ibalpha on thrombin generation. Antibodies to platelet membrane glycoprotein IIb/IIIa (RFGP56 and c7E3) were shown to inhibit platelet-mediated thrombin generation stimulated by both intrinsic and extrinsic methods. An antibody to GP Ibalpha (RFGP37) also inhibited thrombin generation in these systems. FITC-annexin V was used to determine the effect of these antibodies on the exposure of procoagulant phospholipids on the platelet membrane, and it was found that the anti-IIb/IIIa antibodies reduced this, whereas the anti-Ibalpha antibody caused an increase. We conclude that our monoclonal antibodies against platelet membrane glycoproteins IIb/IIIa and Ibalpha inhibit platelet dependent thrombin generation by different mechanisms.

Animals↗
PubMed2000

A collaborative study to establish the 5th International Standard for Unfractionated Heparin.

Twenty-four laboratories participated in a collaborative study to calibrate a replacement for the 4th International Standard for Unfractionated Heparin (82/502). Both candidate materials A and B, gave excellent intra- and inter-laboratory variations (majority of mean %gcv <10%) when assayed against the 4th International Standard. No major differences of potency estimates were found between methods, although the USP method generally gave lower potencies than the other methods and candidate B gave a greater variation between methods than A. Overall, this study showed that the differences between the candidates are marginal. Based on its narrower molecular weight profile, higher specific activity and slightly lower inter-method variation, candidate A, 97/578, was proposed and accepted in October, 1998, by the Expert Committee on Biological Standardisation of the World Health Organisation to be the 5th International Standard for Unfractionated Heparin with an assigned potency of 2031 IU/ampoule.

Blood Coagulation Tests↗
PubMed2000

Characterization of unfractionated heparin: comparison of materials from the last 50 years.

Physicochemical and anticoagulant characteristics of 27 samples from recent batches of commercially produced unfractionated heparin have been determined as part of the process of establishment of the 5th International Standard Unfractionated Heparin. They have been compared with current heparin standards (European Pharmacopoeia, United States Pharmacopoeia, Chinese), with the 4th International Standard Unfractionated Heparin. and with the three predecessor International Standards. The results indicate that the 4th International Standard Unfractionated Heparin, established in 1982, has significantly lower molecular weight and specific activity than recently produced heparin; this is also true of all preceding International Standard Heparins and of the United States Pharmacopoeial standard. The composition of commercial unfractionated heparin may therefore have changed over time; reasons for this are discussed.

Blood Coagulation Tests↗
PubMed1999

Measuring accumulated health-related benefits of exercise participation for older adults: the Vitality Plus Scale.

BACKGROUND: Existing measures fail to capture the perceived benefits attributed to exercise participation by older adults themselves. Noticeable improvements in sleep, energy level, bodily aches and pains, constipation, and other psychophysical aspects of "feeling good" may represent ongoing sources of motivation for continued participation. The Vitality Plus Scale (VPS) was developed to measure these potential health-related benefits of exercising. METHODS: The 10-item VPS was developed using an inductive approach, in collaboration with regularly exercising older adults and their instructors. Multiple samples of exercises and nonexercisers ranging in age from 40 to 94 were used to examine the reliability and validity of the new scale. RESULTS: The VPS showed good internal consistency and test-retest reliability over one week. Scores were able to discriminate on the basis of various indicators of health status and self-reported level of physical activity, and were related to two measures of functional mobility. Convergence was found with several subscales of the SF-36, whereas low correlations emerged with a measure of episode-specific sensations. Responsiveness to change was found with various types of exercise for individuals with low to moderate scores prior to participation. CONCLUSIONS: Improvements in sleep, energy level, mood, and generally feeling good appear to be the most noticeable benefits of exercising for many adults. These associations are reinforced by sustained exercise participation. Capturing these interrelated psychophysical constructs in a single, short measure will enable exercise researchers and instructors to measure incremental improvements previously reported only anecdotally.

Adult↗
PubMed1999

Screening methods for thyroid hormone disruptors.

The U.S. Congress has passed legislation requiring the EPA to implement screening tests for identifying endocrine-disrupting chemicals. A series of workshops was sponsored by the EPA, the Chemical Manufacturers Association, and the World Wildlife Fund; one workshop focused on screens for chemicals that alter thyroid hormone function and homeostasis. Participants at this meeting identified and examined methods to detect alterations in thyroid hormone synthesis, transport, and catabolism. In addition, some methods to detect chemicals that bind to the thyroid hormone receptors acting as either agonists or antagonists were also identified. Screening methods used in mammals as well as other vertebrate classes were examined. There was a general consensus that all known chemicals which interfere with thyroid hormone function and homeostasis act by either inhibiting synthesis, altering serum transport proteins, or by increasing catabolism of thyroid hormones. There are no direct data to support the assertion that certain environmental chemicals bind and activate the thyroid hormone receptors; further research is indicated. In light of this, screening methods should reflect known mechanisms of action. Most methods examined, albeit useful for mechanistic studies, were thought to be too specific and therefore would not be applicable for broad-based screening. Determination of serum thyroid hormone concentrations following chemical exposure in rodents was thought to be a reasonable initial screen. Concurrent histologic evaluation of the thyroid would strengthen this screen. Similar methods in teleosts may be useful as screens, but would require indicators of tissue production of thyroid hormones. The use of tadpole metamorphosis as a screen may also be useful; however, this method requires validation and standardization prior to use as a broad-based screen.

Animals↗
PubMed1999

A collaborative study to establish the 2nd International Standard for Antithrombin Concentrate.

Eighteen laboratories participated in a collaborative study to calibrate a replacement for the 1st International Standard for Antithrombin. Concentrate (88/548). Excellent agreement between laboratories, as indicated by mean % gcv of 3.3 and 5.9 for functional and antigenic assays, was observed when the candidate concentrate (96/520) was assayed against the 1st International Standard for Antithrombin, Concentrate (88/548). The functional potency was found to be 7.9% (p<0.05) lower than the antigenic potency. Based on the results and with the agreement of the participants of this study and the authorisation of the Expert Committee on Biological Standardisation of the World Health Organisation, the antithrombin concentrate, coded 96/520, has been established as the 2nd International Standard for Antithrombin, Concentrate, with labelled potencies for both functional (4.7 IU/ampoule) and antigenic (5.1 IU/ampoule) activities.

Antithrombins↗
PubMed1999

Coping with ill health in a rickshaw puller's household in Chittagong, Bangladesh.

The correlation between poverty and ill-health is undeniably strong. Ill-health reduces the earning capacity, and increases the risk of families with ill members to drift down the social and economic ladder. In this article, we present a simulation model of how a poor rickshaw puller in Bangladesh copes with illness, in particular tuberculosis (TB). We first analyze the various coping mechanisms that are set in motion when he starts to suffer from tuberculosis; the impact on household assets, income and food intake will be studied. The simulation model is then used to analyse the effects on his household of a specific health intervention, namely the Directly Observer Treatment Short Course (DOTS) treatment. It shows that DOTS offers positive improvements of the overall well-being of the household by restoring the working capacity of the rickshaw puller in one treatment course and minimizing lost income. Assets and food consumption would be preserved significantly more in the presence of DOTS, rendering the household both financially and physically less vulnerable. The probability of death of the sick rickshaw puller is also significantly reduced, improving household's welfare over the long run.

Adaptation, Psychological↗
PubMed1998

Structural determination of lipid-bound human blood coagulation factor IX.

Human coagulation factor IX (FIX) is a serine protease which binds to a negatively charged phospholipid surface in the presence of Ca ions (Ca2+). FIX two-dimensional (2-D) crystals were obtained by the lipid layer crystallisation technique under near physiological conditions. The 2-D projection map of the protein was calculated to a resolution of 3 nm using electron crystallographic analysis. The structural organisation of membrane-bound FIX is discussed and compared with the known X-ray crystallographic data.

Binding Sites↗
PubMed1998

UKCCSG's germ cell tumour (GCT) studies: improving outcome for children with malignant extracranial non-gonadal tumours--carboplatin, etoposide, and bleomycin are effective and less toxic than previous regimens. United Kingdom Children's Cancer Study Group.

BACKGROUND: We report the efficacy and late effects of carboplatin, etoposide, and bleomycin (JEB) for extracranial non-gonadal tumours (GCII, 1989-95) compared with the 5 previous regimens (GCI, 1979-1988) consisting of 3 vincristine, actinomycin, and cyclophosphamide (VAC) and 2 platinum-based protocols. METHODS AND RESULTS: Median follow-up for 52 patients in the GCI study and 46 in GCII was 105 and 48 months, respectively. For GCI, 5- and 10-year actuarial survival was 63% (95% Confidence interval 50 to 75%) or 72% (57 to 83%) if 6 cases given low-dose VAC were excluded. For GCII, 5-year survival was significantly greater at 95% (83 to 99%), p = 0.01. Event-free survival was 46% at 5 years for GCI (33 to 59%) or 52% excluding the low-dose VAC cases (38 to 66%), while for GCII it was 87% (74 to 94%), p = 0.002. Five-year event-free survival of 21 children given cisplatin, etoposide, and bleomycin (BEP) in GCI was 57% (37 to 76%) compared with 87% (74 to 94%) for 46 given JEB in GCII, P = 0.02. Late effects in 30 evaluable survivors of GCI and 43 GCII included renal impairment in 6 in GCI and 0 in GCII and deafness in 11 and 4, respectively. Among 17 survivors of sacrococcygeal tumours treated in GCI, 4 have neuropathic bladder/bowel and another shortening of a leg. In GCII, 4 of 26 have neuropathic bladder/bowel with lower limb weakness in one. CONCLUSIONS: We found JEB to be more effective and less toxic than our previous regimens. Some survivors of sacrococcygeal tumours have neurological late effects.

Adolescent↗
PubMed1998

Confirmation of FWT1 as a Wilms' tumour susceptibility gene and phenotypic characteristics of Wilms' tumour attributable to FWT1.

A susceptibility gene for Wilms' tumour (WT), designated FWT1, was previously mapped to chromosome 17q12-q21 by linkage analysis of a single family. We now confirm the existence of this gene by analysis of additional cases in the original family (3-point LOD score=5.69), and by detecting strong evidence of linkage to this region in an unrelated pedigree with seven cases of WT (3-point LOD score=2.56). Analysis of 11 smaller WT families confirms that there is genetic heterogeneity in familial WT, as three families exhibit strong evidence against linkage to FWT1. One of these was subsequently found to have a predisposing WT1 mutation. However, the other two families show evidence against both FWT1 and WT1, suggesting that at least one further familial WT gene exists. Analysis of the phenotype of 16 WT cases from the families linked to FWT1 demonstrates that they present at a significantly older age and a significantly later stage than both sporadic WT and the six cases from two families unlinked to either FWT1 or WT1. The results confirm the role of FWT1 in susceptibility to WT, provide strong evidence for genetic heterogeneity in familial WT and suggest there are phenotypic differences between familial WT due to FWT1, familial WT due to other genes and non-familial WT.

Chromosomes, Human, Pair 17↗
PubMed1998

Tachycardia alone fails to change the myocardial pharmacokinetics and dynamics of lidocaine, thiopental, and verapamil after intravenous bolus administration in sheep.

Previous reports have suggested that tachycardia alone can increase the rate of myocardial uptake of some drugs. As part of a systematic study of the determinants of the myocardial uptake and effects of drugs in critical illness, the effect of tachycardia induced by intracardiac pacing on the myocardial disposition and effects of lidocaine, verapamil, and thiopental were studied in chronically instrumented sheep. For each drug, seven sheep received either 100 mg of lidocaine, 10 mg of verapamil, or 750 mg of thiopental over 2 min in unpaced and paced (140 beats/min) states on separate occasions and in random order. Arterial and coronary sinus (effluent from the heart) blood samples were taken at regular intervals for 30 min, and the maximum rate of change of left ventricular pressure (LV dP/dtmax) was measured as an index of myocardial contractility. There were no differences between unpaced and paced studies in the time courses of arterial and coronary sinus concentrations, or the time-courses of myocardial contractility and blood flow, after bolus iv injections of these drugs. Tachycardia alone does not appear to influence the myocardial kinetics or dynamics of lipophilic drugs that can rapidly diffuse into the heart.

Animals↗
PubMed1998

Antithrombotic activity of a fucosylated chondroitin sulphate from echinoderm: sulphated fucose branches on the polysaccharide account for its antithrombotic action.

The antithrombotic activity of a fucosylated, chondroitin-sulphate-like polysaccharide extracted from the body wall of sea cucumber, and of chemically modified derivatives of the same polysaccharide, have been assessed using a stasis thrombosis model in rabbits. Intravenous administration of the native polysaccharide reduced thrombosis in a dose-dependent manner and, at a dose of 1.5 mg/kg (60 IU/kg) body weight, completely prevented thrombosis after 10 min stasis. Removal of the sulphated fucose branches of the polysaccharide abolished antithrombotic effectiveness. After intravenous injection of an antithrombotic dose of radioactively labelled polysaccharide, a correlation was observed between removal of radioactivity from the plasma and decrease in ex vivo APTT values, demonstrating that antithrombotic effectiveness depends on the level of circulating polysaccharide rather than on an indirect effect of the polysaccharide on the vascular endothelium. Reduction of the glucuronic acid carboxyl groups in the polysaccharide did not affect its in vitro and in vivo activities. Both partial defucosylation and desulphation of the polysaccharide abolished all its anticoagulant or antithrombotic action.

Animals↗
PubMed1998

Pathologists dislike sound? Evaluation of a computerised training microscope.

AIM: To evaluate the use of multimedia enhancements, using a computerised microscope, in the training of microscope skills. METHODS: The HOME microscope provides facilities to highlight features of interest in conjunction with either text display or aural presentation. A pilot study was carried out with 10 individuals, eight of whom were at different stages of pathology training. A tutorial was implemented employing sound or text, and each individual tested each version. Both the subjective impressions of users and objective measurement of their patterns of use were recorded. RESULTS: Although both versions improved learning, users took longer to work through the aural than the text version; 90% of users preferred the text only version, including all eight individuals involved in pathology training. CONCLUSIONS: Pathologists appear to prefer visual rather than aural input when using teaching systems such as the HOME microscope and sound does not give added value to the training experience.

Attitude of Health Personnel↗
PubMed1997

Does expert psychological testimony inform or influence juror decision making? A social cognitive analysis.

The authors examined whether expert testimony serves an educational or a persuasive function. Participants watched a simulated sexual abuse trial in which the child witness had been prepared for her testimony (i.e., she was calm, composed, and confident) or unprepared (i.e., emotional, confused, and uncertain). The trial contained different levels of expert testimony: none, standard (i.e., a summary of the research), repetitive (i.e., standard testimony plus a 2nd summary of the research), or concrete (i.e., standard testimony plus a hypothetical scenario linking the research to the case facts) testimony. Repetitive testimony bolstered the child's testimony, whereas concrete and standard testimony did not. Concrete testimony sensitized jurors to behavioral correlates of sexual victimization; standard and repetitive testimony desensitized jurors to these correlates. Implications for the use of procedural innovations in sexual abuse trials are discussed.

Adolescent↗
PubMed1997

Molecular characterization of hpuAB, the haemoglobin-haptoglobin-utilization operon of Neisseria meningitidis.

We previously identified HpuB, an 85 kDa Fe-repressible protein required for utilization of Fe from, and binding to, haemoglobin and the haemoglobin-haptoglobin complex. The gene for hpuB was cloned from Neisseria meningitidis strain DNM2 and the predicted amino acid sequence indicates that HpuB is an outer membrane receptor belonging to the TonB family of high-affinity transport proteins. A second open reading frame, predicted to encode a 34.8 kDa lipoprotein, was discovered 5' to hpuB, and was designated hpuA. HpuA was identified in a total-membrane-protein preparation by construction of a mutant lacking HpuA. Acylation of HpuA was confirmed by [3H]-palmitic acid labelling of meningococci. Consensus promoter sequences were not apparent 5' to hpuB. The hpuA insertion mutation exerted a polar effect, abolishing expression of hpuB, suggesting that hpuA and hpuB are co-transcribed. The 3.5 kb polycistronic hpuAB mRNA was identified and shown to be transcriptionally repressed by iron. The transcriptional start site was identified 33 nucleotides 5' to the hpuA translational start site, appropriately positioned around consensus promoter and ferric uptake regulator (Fur)-box sequences. The structure of this operon suggests that HpuA-HpuB is a two-component receptor analogous to the bipartite transferrin receptor TbpB-TbpA.

Amino Acid Sequence↗
PubMed1997

Molecular weight measurements of low molecular weight heparins by gel permeation chromatography.

The molecular weight profiles of low molecular weight heparin samples have been measured by high-performance gel permeation chromatography using as calibrant the heparinase-degraded material (90/686) now established as the 1st International Reference Preparation (IRP) Low Molecular Weight Heparin for Molecular Weight Calibration Use of the calibrant as a broad molecular weight standard is described and a calibration table provided based on data collected over several years in one laboratory. In order to confirm the assignment of degree of polymerisation to resolved oligosaccharide peaks in the calibrant, molecular weights of oligosaccharides fractionated from the 1st IRP were independently determined by fast atom bombardment mass spectrometry (FAB MS). The molecular weight distributions of commercial low molecular weight heparins have been characterized. Measurements of molecular weight parameters of heparin molecular weight standards from several sources provide comparisons between the molecular weight scales of this and other studies.

Calibration↗