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Biomedical subjects

N Jones

Publications and source records attributed to N Jones.

At least 37 records · Page 2Linked to original sources

Evaluation of antigen-specific responses using in vitro enriched T cells.

Antigen-specific lymphocytes are important in the immune response to viral infection. Peripheral blood mononuclear cells (PBMC) are traditionally used as a source of effector cells in most immunological studies. We described here the use of the bispecific monoclonal antibodies (BSMAB) anti CD3:CD8 (CD3,8) and anti CD3:CD4 (CD3,4B) to expand and selectively enrich CD4+ and CD8+ T cells populations, respectively. The expanded cells demonstrated >90% CD3+CD4+ or CD3+CD8+ by 14 days. We measured HIV- and CMV-specific responses of these subset-enriched T cell and found that sensitivity and specificity is similar or higher when compared to PBMC in various cellular immunology assays (CMI). Vbeta analysis of BSMAB-enriched cells demonstrated comparable repertoire to the parent PBMC. Although both CD45RA(hi) and CD45RO(hi) cell populations were expanded with the BSMAB, selective subset depletion demonstrated that the antigen-specific T cell responses were restricted to the initial CD45RO(hi) memory effector subgroup. In conclusion, BSMAB in vitro enrichment of T cells allows significant expansion of the cell population without loss of specificity. This technique of cell expansion permits studies of T cell subset function in situations where the initial cell source is scarce, and presents an alternative for viable and functional T cells in immunological assays.

Antibodies, Bispecific↗

Impaired sense of smell in patients with nasal surgery.

The aim of the study was to determine the incidence of olfactory disorders before and following nasal and paranasal sinus surgery. It was a prospective observational study. Over a 6-month period, all patients who had been listed for nasal and paranasal sinus surgery underwent preoperative and postoperative evaluation of their sense of smell. A questionnaire and the 'Smell Diskettes Test' were used to assess olfaction. One hundred and eighty-four patients were studied. Preoperatively, 19 patients (10.3%) had an impaired sense of smell (8.1% before septoplasty, 6.1% before rhinoplasty and 17.1% before endoscopic sinus surgery). Only 16 (84%) of these patients were aware of their impaired sense of smell. Following surgery, four patients (2.5%) who were normal preoperatively developed impaired olfaction on questioning, and this was supported by testing it. In the subgroup that had a septoplasty, no patient developed hyposmia compared to one patient (2.6%) after rhinoplasty and one patient (3%) after endoscopic sinus surgery. No patient developed anosmia. Preoperatively, 10.3% of patients had an altered sense of smell, making it desirable that this is documented in order to avoid postoperative claims that this was caused by surgery. It also helps to audit the results of surgery.

Female↗

New technical advances in swivel walkers.

Swivel walkers were commonly prescribed for children with complete thoracic lesion myelomeningocele in the 1970s and 80s, when the incidence of spina bifida in the UK was of the order of 3 per 100,000 live births. The advent of reciprocal walking orthoses provided a more suitable alternative for those with good upper limb and trunk function, and swivel walkers were then used primarily for very young or more severely disabled patients. Pre-natal screening has dramatically reduced the incidence of spina bifida in the UK and subsequently swivel walkers have been used in a wider range of pathology, including spinal muscular atrophy, multiple sclerosis, muscular dystrophy and other neurological conditions that lead to lower limb dysfunction. The detail design of these devices has been adapted to accommodate the specific problems encountered in these conditions. In particular the designs have been updated to: enable very young patients to be more readily fitted at the age of 1 year; allow the walking mechanisms to be conveniently adjusted for easier ambulation when weakness or lack of confidence inhibits performance; permit simple adjustment to a standing frame mode to enhance stability in situations of increased risk; promote manual handling practice that is compatible with the National Health Service (NHS) policy of compliance with relevant regulations. To underpin appropriate prescription and safe supply the NHS Procurement Agency have encouraged the development of a common course for all types of swivel walker.

Adolescent↗

Pyrolysis of composite plastic waste.

Several different composite plastics were pyrolysed in a fixed bed reactor at final temperatures between 350 and 800 degrees C. The composites studied were polyester, phenolic, epoxy, vinylester, polypropylene and PET resins, reinforced with glass and/or carbon fibre. The product yields of oil gas and solid residue were determined together with a detailed composition of the derived gases. There was evidence to suggest that calcium carbonate filler, present in the polyester and phenolic composites, decomposed to form carbon dioxide at 800 degrees C, which was subsequently involved in char gasification reactions. Polyester, phenolic and epoxy composites generated highly aromatic, oxygenated condensable products. There was no noticeable correlation between the composition of these products and the final pyrolysis temperature. The tensile strength of recovered glass fibre was lower than that of virgin fibre and decreased markedly as the final pyrolysis temperature increased from 650 to 800 degrees C.

Conservation of Natural Resources↗

Peer-group risk assessment: a post-traumatic management strategy for hierarchical organizations.

BACKGROUND: Organizations have moral and legal duties to consider the psychological needs of their workforce following exposure to potentially traumatic events related to the workplace. Additionally, it makes economic sense to avoid loss of valuable personnel to the effects of psychological trauma. There have been attempts to provide a range of psychological interventions for staff after exposure to potentially traumatizing events, but recent evidence-based medicine publications have questioned their effectiveness and, indeed, some studies show that single-session psychological debriefings may be harmful. AIM: This paper presents a post-traumatic management strategy based upon peer-group risk assessment which was developed by the British military and is in use with other hierarchical organizations. The presented model keeps employees functioning after traumatic events and provides support and education to those who require it. Additionally, the strategy aims to identify those who are unable to cope after potentially traumatizing events and aims to refer them for early intervention, which has been shown to be of benefit.

Adult↗

Constructing management practice in the new public management: the case of mental health managers.

There has been a growth in managerialism of professionals in the Public Sector. This paper contributes to this debate by examining perceptions of senior managers in mental health services within Health Authorities, NHS Trusts and Local Authorities' Social Services departments in Wales. The paper explores how different professions responded differently to the growth of managerialism. The results suggest important differences and similarities between management in health and social services settings.

Administrative Personnel↗

Malignant astrocytoma arising 10 years after combined treatment of craniopharyngioma.

Craniopharyngioma is the third most common intracranial tumor in childhood. Following surgery, virtually all patients present with hypopituitarism and are at considerable risk of tumor recurrence. Secondary tumors, however, are rare, occurring usually 10 years after diagnosis and associated with poor prognosis. We report on a 5 year-old boy in whom craniopharyngioma was diagnosed due to unilateral visual loss. After surgery he underwent conventional radiation therapy with a total tumor dose of 55 Gy, and had hormonal support with DDAVP, thyroxine, and a variable dose of hydrocortisone. Growth velocity declined slowly in the first 4 years, but improved later on again without GH therapy despite abnormal provocative tests. At the age of 15 years he developed peripheral facial nerve palsy due to a malignant astrocytoma (WHO grade III/IV). Repeated conventional radiation therapy with an additional stereotactic boost and chemotherapy could not prevent the fatal outcome. This observation may temper the use of radiosurgery in benign intracranial tumors.

Astrocytoma↗

Energy metabolism and intracellular pH in boar spermatozoa.

The effect of energy metabolism on intracellular pH was studied in boar spermatozoa using nuclear magnetic resonance (NMR) spectroscopy and confocal microscopy with the pH-sensitive dye seminaphthorhodafluor (SNARF-1). Freshly ejaculated spermatozoa had a high adenylate energy charge (AEC=0.8), which decreased to 0.6 under aerobic conditions and to 0.2 under anaerobic conditions. Correspondingly, no ATP resonances but high AMP resonance were visible in (31)P-NMR-spectra of the spermatozoa. When an artificial oxygen buffer (Fluosol) and a purpose-built air supply system were used during (31)P-NMR data acquisition, ATP resonances reappeared whereas the AMP resonance disappeared. Boar spermatozoa kept under aerobic conditions have intracellular compartments that differ markedly in pH, as demonstrated by both (31)P-NMR spectroscopy and confocal microscopy. Using confocal microscopy, the midpiece of the flagellum in which all mitochondria are located was identified as an acidic compartment (pH(i-mp) 6.7). The intracellular pH of both the head (pH(i-h)) and the long principal piece of the flagellum (pH(i-pp)) were 7.2 and, thus, only slightly below the extracellular pH (pH(e) 7.3). Storage of spermatozoa in a glucose-free medium at 15 degrees C when they are immotile slowly shifted the pH(i-mp) from 6.7 to 6.9 within 20 h, whereas pH(i-h) and pH(i-pp) remained unchanged (pH 7.1-7.2). When glucose was present in the medium, all visible compartments of the spermatozoa as well as the medium were acidified to pH 6.2 within 20 h. Under these conditions a resonance at 4.8 mg kg(-1) appeared representing glycerol 3-phosphate.

Adenosine Diphosphate↗

Deposition and fate of arsenic in iron- and arsenic-enriched reservoir sediments.

Deposition of arsenic to the sediments of Haiwee Reservoir (Olancha, CA) has dramatically increased since March 1996 as a result of an interim strategy for arsenic management in the Los Angeles Aqueduct (LAA) water supply. Ferric chloride and cationic polymer are introduced into the Aqueduct at the Cottonwood treatment plant, 27 km north of the Haiwee Reservoir. This treatment decreases the average arsenic concentration from 25 microg/L above Cottonwood to 8.3 microg/L below Haiwee. Iron- and arsenic-rich flocculated solids are removed by deposition to the reservoir sediments. Analysis of sediments shows a pronounced signature of this deposition with elevated sediment concentrations of iron, arsenic, and manganese relative to a control site. Sediment concentrations of these elements remain elevated throughout the core length sampled (ca. 4% iron and 600 and 200 microg/g of manganese and arsenic, respectively, on a dry weight basis). A pore water profile revealed a strong redox gradient in the sediment. Manganese in the pore waters increased below 5 cm; iron and arsenic increased below 10 cm and were strongly correlated, consistent with reductive dissolution of iron oxyhydroxides and concurrent release of associated arsenic to solution. X-ray absorption near-edge spectroscopy revealed inorganic As(V) present only in the uppermost sediment (0-2.5 cm) in addition to inorganic As(III). In the deeper sediments (to 44 cm), only oxygen-coordinated As(III) was detected. Analysis of the extended X-ray absorption fine structure spectrum indicates that the As(III) at depth remains associated with iron oxyhydroxide. We hypothesize that this phase persists in the recently deposited sediment despite reducing conditions due to slow dissolution kinetics.

Absorptiometry, Photon↗

Evaluation of safety and reliability in an infant reciprocal walking orthosis.

In response to new demands for infant walking orthoses consideration was given to the development of a device for this category of patient. A specially developed hip joint with the required structural properties (Woollam et al., 2001) provided an opportunity for this development. Earlier structural assessment, and limited cyclic load testing of key elements of the orthosis (primarily the body brace), confirmed that a safe device for evaluation with patients could, theoretically, be produced. A provisional prototype was therefore designed and manufactured for initial structural testing of the complete infant orthosis (Stallard et al., 2001). Efficiency of walking is strongly influenced by the lateral rigidity of the orthosis. Monitoring the structural performance of the provisional infant design indicated it would equal or improve on the stiffness of that achieved in the adult specification. Additionally, relative strength was comparable with the adult version, which has proven to be safe and reliable in many years of routine prescription. This, together with the limited cyclic testing of the complete orthosis (Stallard et al., 2001), gave confidence that it was safe to proceed with controlled field evaluation of the infant design when supplied as a rehabilitation engineering device within the provisions of an ISO9001 and EN46001 QA System. This additional study of controlled patient use, and further representative cyclic load testing in parallel with the field evaluation, had established the long-term structural safety of the orthosis. Wider application is now to be introduced through completion of the EC (European Community) Medical Devices Directive formalities.

Humans↗

Further evidence for the predictive validity of the unstable elevated exposed plus-maze, a behavioural model of extreme anxiety in rats: differential effects of fluoxetine and chlordiazepoxide.

The unstable elevated exposed plus-maze (UEEPM) is a novel model of extreme anxiety which elicits unconditioned flight/escape behaviour in rats. The current studies aimed to investigate further the predictive validity of the paradigm, by examining the effects on UEEPM behaviour of both clinically effective (chronic fluoxetine) and ineffective (acute fluoxetine and chlordiazepoxide) treatments for panic disorder. In the first experiment, male Brown Norway rats received a single injection of fluoxetine (1.0-10.0 mg/kg p.o.) or chlordiazepoxide (CDP, 1.0-10.0 mg/kg i.p.) 30 min prior to UEEPM exposure. In the second experiment, in order to assess the effects of chronic dosing or handling on baseline UEEPM behaviour, subjects received either 21 days vehicle injection (p.o.) or handling, before being exposed to the test. Finally, rats received 21 days fluoxetine (1.0-10.0 mg/kg) in their food, before being tested in the UEEPM. Acute CDP and fluoxetine had no effect on UEEPM behaviour. Chronic handling and vehicle administration (p.o.) significantly reduced escape in the UEEPM, hence preventing the effects of chronic fluoxetine administration from being investigated by p.o. dosing. Chronic fluoxetine in subjects' food (10.0 mg/kg) significantly attenuated animals' propensity to escape from the UEEPM. The results further support the pharmacological similarity between symptoms of panic in humans and escape in the UEEPM and suggest that the UEEPM may represent a paradigm to facilitate investigation into the neurochemical basis of extreme anxiety disorders.

Animals↗

Effects of daily variation in outdoor particulates and ambient acid species in normal and asthmatic children.

BACKGROUND: Evidence suggests that the respiratory health of children may be adversely affected by daily variation in outdoor pollutants, particularly ozone and particulates. However, data from the UK are sparse and the contribution of different particulate fractions and acid species, together with the identification of those individuals most at risk, are not clear. METHODS: One hundred and sixty two 9 year old children were enrolled from two inner city locations and recorded daily symptoms and twice daily peak expiratory flow (PEF) over 8 week periods in the winter and summer. Their results were analysed with daily pollutant levels at appropriate lags using regression models which corrected for trends, weather, pollen, and autocorrelation. RESULTS: Pollutant levels were generally low, especially in the summer. Multiple statistically significant associations were noted between health outcomes and pollutant concentrations, but no consistent patterns in identified effects were apparent between pollutants, lags, direction of observed effect, or location. There was no evidence to suggest that subgroups with atopy or pre-existing wheeze are more sensitive to pollutant effects. CONCLUSION: These data do not suggest that adverse health outcomes are associated with daily variations in pollutants [corrected]. No evidence was found to indicate that particulates or individual acid and anion species are more closely related to adverse health outcomes than other pollutants.

Acids↗

The influence of polymer type, print donor and age on the quality of fingerprints developed on plastic substrates using vacuum metal deposition.

This study investigated fingerprint development on five different polymer substrates using vacuum metal deposition (VMD). The conditions required for optimum development are shown to depend on a number of factors. No one set of conditions will result in good development in all situations. Polymer type has been confirmed as a major factor in determining the types of development that will occur and the optimum VMD conditions required. For more consistently successful VMD development, polymer type should be determined before selecting conditions. While polymer type is a key factor in determining optimum development conditions, there may be variation of the optimum conditions within a polymer type, most likely due to the presence of additives in the plastic. The heaviness of a latent print, i.e. amount of residue that constitutes the print, also affects the VMD conditions required. The donor, manner of deposition, and age of a print affect the heaviness of the deposit. The heavier the print, the higher the gold count necessary for successful VMD development. The occurrence of 'empty prints' (i.e. zinc deposition on the general background but not on or between the print ridges) was found to be related to polymer type and print heaviness. Heavy prints on PVC and PET are the most likely to be 'empty' after VMD treatment. The development of empty prints may be due to the diffusion of print residue into the print valleys. Pre-treatment with cyanoacrylate fuming was also found to affect VMD development. In particular, it was shown that cyanoacrylate pre-treatment was beneficial for print development on PET and PVC. The results of this study were used to formulate guidelines for use as an aid by laboratories using VMD in casework.

Dermatoglyphics↗

Cyclin-mediated export of human Orc1.

Viral cyclin/cdk6 complexes interact with and phosphorylate human Orc1, a component of the origin recognition complex (ORC) that functions in DNA replication. Here we assess the effect that viral cyclin has on the intracellular location of human Orc1, which is present in both nuclear and cytoplasmic pools. Overexpression of K cyclin or cyclin A results in Crm1-dependent export of Orc1 to the cytoplasm, and this process is dependent on the phosphorylation status of several cdk target sites in Orc1. These findings support a model where S phase promoting cyclin activity drives the export of a component of replication complexes.

Amino Acid Sequence↗

Vacuum metal deposition: developing latent fingerprints on polyethylene substrates after the deposition of excess gold.

A previously identified difficulty with the development of latent fingerprints on low-density polyethylene (LDPE) by vacuum metal deposition (VMD) is that excess gold deposition prevents effective zinc deposition and so inhibits latent print development [1]. The investigation of a means to correct for excess gold deposition was the basis for this study. Exposure to zinc and the readmission of air into the vacuum chamber followed by VMD development results in the deactivation of the initial gold clusters due to the formation of zinc oxide and the adsorption of air and water molecules. As a result, the majority of the gold deposited during the second treatment creates new gold clusters rather than adding to the gold clusters previously formed. After excess gold deposition on LDPE, the deposition of 1.5 times the optimum gold amount will result in good-quality normal development. The results also indicate that, on all surfaces, at least twice the initial gold count should be used for re-treatment when further development is required after air has been readmitted to the chamber.

Dermatoglyphics↗

Dok-R plays a pivotal role in angiopoietin-1-dependent cell migration through recruitment and activation of Pak.

Tek/Tie-2 is an endothelial cell (EC)-specific receptor tyrosine kinase that plays a critical role in angiogenesis via its regulation by the angiopoietin family of growth factor ligands. Angiopoietin-1 (Ang1) can promote EC migration; however, the signaling mechanisms underlying this process remain elusive. Here we demonstrate that Dok-R/Dok-2 can associate with Tek in ECs following Ang1 stimulation, resulting in tyrosine phosphorylation of Dok-R and the subsequent recruitment of Nck and the p21-activating kinase (Pak/Pak1) to the activated receptor. Ang1-mediated migration is increased upon Dok-R overexpression and this requires a functional Nck binding site on Dok-R. Localization of this Dok-R-Nck-Pak complex to the activated Tek receptor at the cellular membrane is coincident with activation of Pak kinase. The ability of Dok-R to bind Nck is required for maximal activation of Pak and overexpression of Pak results in increased Ang1-mediated cell motility. Our study outlines a novel signaling pathway underlying Ang1-driven cell migration that involves Dok-R and its recruitment of Nck and the subsequent activation of Pak.

Adaptor Proteins, Signal Transducing↗

The nose and paranasal sinuses physiology and anatomy.

The paranasal sinuses and nose are much more than two cavities behind a projection on the centre of the face. They humidify, filter, warm, and sense what we breathe. The anatomy and physiology interact forming a dynamic system. The anatomy, airflow, nasal resistance, its turbulence, the nasal cycle - a process by which the turbinates or cushions lining the nose alternatively swell and congest from side to side, can all potentially influence the nasal delivery of drugs. Along with these factors mucus rheology and mucociliary clearance influence the removal of substances delivered to the nose. The health of the nose and its immunological response to what is inhaled, be it pollutants, allergens, drugs or vaccines, all need to be considered. It is a fascinating sensor for the body, not only detecting the potentially harmful substances such as smoke, but its psychosexual aspects have far reaching implications and the olfactory pathway has potential as a pathway for the delivery of drugs.

Animals↗