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L Jones

Publications and source records attributed to L Jones.

At least 19 recordsLinked to original sources
PubMed2006

The role of skin-homing T cells in extrinsic atopic dermatitis.

BACKGROUND: T cells that express Cutaneous Lymphocyte-Associated antigen (CLA) have the potential of migrating to the skin, and are hypothesized to play a role in cutaneous atopic disease. AIM: To investigate the immune phenotype and cytokine responses to Der p 1 stimulation of CLA+ T cells in extrinsic atopic dermatitis (EAD). DESIGN: In vitro testing, with controls. METHODS: Peripheral blood mononuclear cells (PBMC) were obtained from EAD patients (n=27) and non-atopic healthy individuals (n=22). Phenotypic analysis of naive, CLA+ and non-CLA+ memory/effector CD4+ and CD8+ T cells used markers of cell activation, differentiation, adhesion, apoptosis and chemokine receptor expression. Cytokine responses in these cells were studied following Der p 1 stimulation. RESULTS: CLA+ T cells from EAD patients expressed significantly higher levels of CD25, HLA-DR, CD38, CD71, CXCR1, CXCR2 and lower levels of bcl2, CCR5, CCR7, CXCR3, and CD62L (p<0.05). DISCUSSION: In EAD patients, CLA+ T cells express increased levels of markers associated with activation, adhesion and apoptosis, show differences in the level of expression of differentiation markers and display a distinct chemokine receptor preference, compared with cells from healthy controls. These data suggest a significant role for CLA+ T cells in the pathogenesis of cutaneous atopic disease.

Adult↗
PubMed2006

Inhibition of cardiac voltage-gated sodium channels by grape polyphenols.

BACKGROUND AND PURPOSE: The cardiovascular benefits of red wine consumption are often attributed to the antioxidant effects of its polyphenolic constituents, including quercetin, catechin and resveratrol. Inhibition of cardiac voltage-gated sodium channels (VGSCs) is antiarrhythmic and cardioprotective. As polyphenols may also modulate ion channels, and possess structural similarities to several antiarrhythmic VGSC inhibitors, we hypothesised that VGSC inhibition may contribute to cardioprotection by these polyphenols. EXPERIMENTAL APPROACH: The whole-cell voltage-clamp technique was used to record peak and late VGSC currents (INa) from recombinant human heart NaV1.5 channels expressed in tsA201 cells. Right ventricular myocytes from rat heart were isolated and single myocytes were field-stimulated. Either calcium transients or contractility were measured using the calcium-sensitive dye Calcium-Green 1AM or video edge detection, respectively. KEY RESULTS: The red grape polyphenols quercetin, catechin and resveratrol blocked peak INa with IC50s of 19.4 microM, 76.8 microM and 77.3 microM, respectively. In contrast to lidocaine, resveratrol did not exhibit any frequency-dependence of peak INa block. Late INa induced by the VGSC long QT mutant R1623Q was reduced by resveratrol and quercetin. Resveratrol and quercetin also blocked late INa induced by the toxin, ATX II, with IC50s of 26.1 microM and 24.9 microM, respectively. In field-stimulated myocytes, ATXII-induced increases in diastolic calcium were prevented and reversed by resveratrol. ATXII-induced contractile dysfunction was delayed and reduced by resveratrol. CONCLUSIONS AND IMPLICATIONS: Our results indicate that several red grape polyphenols inhibit cardiac VGSCs and that this effect may contribute to the documented cardioprotective efficacy of red grape products.

Animals↗
PubMed2006

Severe atopic dermatitis is associated with a reduced frequency of IL-10 producing allergen-specific CD4+ T cells.

BACKGROUND: Several studies have investigated levels of T-cell-derived interleukin (IL)-10 in individuals with atopic dermatitis, with conflicting results. AIMS/HYPOTHESIS: In order to address whether stratification of disease severity may help resolve the different findings, the hypothesis was tested that individuals with severe atopic dermatitis have a lower frequency of circulating IL-10-producing, allergen-specific CD4+ T cells than do individuals with mild disease. METHODS: Using peripheral blood mononuclear cells derived from individuals with severe (n=12) and mild atopic dermatitis (n=10) and from nonatopic controls (n=10), we investigated production by CD4+ T cells of tumour necrosis factor (TNF)-alpha, IL-4, IL-5, IL-13 and IL-10 in response to phorbol myristate acetate/ionomycin and Der p1 allergen. RESULTS: It was observed that there were significantly higher frequencies of allergen-specific circulating CD4+ T cells producing TNF-alpha- IL-4-, IL-5- and IL-13, and lower frequencies of these cells producing IL-10 in individuals with severe atopic dermatitis compared with mildly affected individuals and nonatopic controls (P<0.01 for all comparisons). Furthermore, the Der p1-specific CD4+ T cells were enriched within the subset of cells positive for cutaneous lymphocyte-associated antigen. CONCLUSIONS: Analysis of levels of allergen-specific CD4+ T-cell production of IL-10 in relation to disease severity argues in favour of a role for IL-10 in the control of atopic dermatitis.

CD4-Positive T-Lymphocytes↗
PubMed2006

Selective extra-dimensional set shifting deficit in a knock-in mouse model of Huntington's disease.

People with early-stage Huntington's disease have been found to have a specific deficit in performing an extra-dimensional shift. To date no evidence of this deficit has been identified in transgenic or knock-in rodent models of the disease. The aim of the present paper then, was to test whether homozygous knock-in mice derived from the Hdh(CAG(150)) mouse line were impaired in any of five 2-choice discrimination tasks (simple, compound, compound reversal, intra-dimensional shift and extra-dimensional shift), and whether these mice were impaired at recalling these tasks on the following day. On the extra-dimensional shift task the Hdh(CAG(150)) homozygous mice required a greater number of trials to reach criteria than mice and the percentage of correct choices within the trials was also significantly reduced compared with the animals. For the recall tasks, a deficit for recalling the compound reversal test was found in the Hdh(CAG(150)) homozygous mice for both number of trials required to reach criteria and percentage of correct choices within the trials. Recall for the intra-dimensional shift task was also impaired in these animals when measured by the percentage of correct choices. Our results demonstrate a pronounced deficit in the Hdh(CAG(150)) mice not only on extra-dimensional shift performance in agreement with human studies, but also on recall tasks for both the compound reversal and the intra-dimensional shift tasks.

Animals↗
PubMed2006

Development of a disease-specific Quality of Life questionnaire module for patients with gastrointestinal neuroendocrine tumours.

Quality of life (QoL) measurements are increasingly being used as an end point in cancer clinical trials. Standard generic QoL questionnaires may not assess symptoms produced by neuroendocrine tumours. Here we report the development of a disease-specific quality of life score questionnaire for patients with neuroendocrine tumours of the gut to supplement the EORTC core cancer questionnaire, the QLQ-C30. Phases 1-3 of the EORTC quality of life group guidelines for module development were used to design the new questionnaire. Forty-one relevant issues (questions) were generated after an extensive literature search. Following interviews of 15 health care workers and 35 patients, a 35 question provisional questionnaire was constructed. This was translated into seven European languages and pre-tested in 180 patients resulting in a 21-item module that will be validated in an international clinical trial. The EORTC QLQ-NET21 provides a site-specific module to supplement the QLQ-C30 for patients with neuroendocrine tumours.

Adolescent↗
PubMed2006

Potassium titanyl phosphate (KTP) laser treatment for molluscum contagiosum.

We report a case of an immunocompromised 38-year-old Asian patient who developed several hundred atypical lesions of molluscum on her face and neck, resistant to conventional treatment. These lesions were treated successfully by potassium titanyl phosphate (KTP) laser without pigmentary disturbance. KTP laser is a novel treatment for molluscum contagiosum.

Adult↗
PubMed2006

A colorectal cancer patient focus group develops an information package.

INTRODUCTION: In order to deliver high quality care and empower cancer patients in decision-making, good quality information and communication are essential. We describe the development of an information booklet. PATIENTS AND METHODS: A total of 22 colorectal cancer patients (12 male; median age, 72 years, range, 40-86 years) met on 3 occasions. Patients were asked to define their information needs and score them (1-4) according to importance. The information document was written. The second meeting involved feedback on the booklet. The modified booklet was reviewed/approved by the group before submission for local ethics committee approval prior to its distribution to other patients. RESULTS: All participants felt the project a good idea. Essential information included the surgeon's individual morbidity, mortality, survival, recurrence data and details of adjuvant therapies (score = 4). Also important were type of surgery, complications and postoperative recovery (score = 3). Simple anatomical drawings were also considered important. CONCLUSIONS: The booklet is now used to personalise information for all our patients and serves, in part, as a record of the key issues discussed during the consultation. The booklet has been evaluated in a randomised trial.

Adult↗
PubMed2005

A poor response to proton pump inhibition is not a contraindication for laparoscopic antireflux surgery for gastro esophageal reflux disease.

BACKGROUND: We aimed to determine if a poor response to proton pump inhibitors (PPIs) can predict a poor outcome following laparoscopic antireflux surgery (LARS) in our surgically treated population. METHODS: A total of 324 patients undergoing LARS were included in this study. Following standardized assessment, patients recorded the efficacy of their medication on visual analogue scales. Pre- and postoperative symptom scores were recorded, with outcomes measured by modified Visick scores. RESULTS: There were 233 good responders (>50% relief) and 91 poor responders (<49% relief). Both groups demonstrated a significant decline in postoperative symptom scores. Ninety-four percent of good responders had an excellent or good outcome, compared to 87% of poor responders. Twenty-seven patients reported a fair or poor outcome, despite improved postoperative symptom scores. Fifteen of these patients reported continuing heartburn; five had positive pH tests. CONCLUSION: Our results do not support the assumption that a poor response to PPIs equates to a poor outcome after LARS.

Adult↗
PubMed2005

CandidaDB: a genome database for Candida albicans pathogenomics.

CandidaDB is a database dedicated to the genome of the most prevalent systemic fungal pathogen of humans, Candida albicans. CandidaDB is based on an annotation of the Stanford Genome Technology Center C.albicans genome sequence data by the European Galar Fungail Consortium. CandidaDB Release 2.0 (June 2004) contains information pertaining to Assembly 19 of the genome of C.albicans strain SC5314. The current release contains 6244 annotated entries corresponding to 130 tRNA genes and 5917 protein-coding genes. For these, it provides tentative functional assignments along with numerous pre-run analyses that can assist the researcher in the evaluation of gene function for the purpose of specific or large-scale analysis. CandidaDB is based on GenoList, a generic relational data schema and a World Wide Web interface that has been adapted to the handling of eukaryotic genomes. The interface allows users to browse easily through genome data and retrieve information. CandidaDB also provides more elaborate tools, such as pattern searching, that are tightly connected to the overall browsing system. As the C.albicans genome is diploid and still incompletely assembled, CandidaDB provides tools to browse the genome by individual supercontigs and to examine information about allelic sequences obtained from complementary contigs. CandidaDB is accessible at http://genolist.pasteur.fr/CandidaDB.

Candida albicans↗
PubMed2005

Systematic review of recent evidence for the safety and efficacy of elective endovascular repair in the management of infrarenal abdominal aortic aneurysm.

BACKGROUND: Conventional management of abdominal aortic aneurysm (AAA) is by open repair and is associated with a mortality rate of 2-6 per cent. Endovascular aneurysm repair (EVAR) is an alternative technique first introduced in 1991. A systematic review was undertaken of the evidence for the safety and efficacy of elective EVAR in the management of asymptomatic infrarenal AAA. METHODS: Thirteen electronic bibliographical databases were searched, covering biomedical, health-related, science and social science literature. Outcomes were assessed with respect to efficacy (successful deployment, technical success, conversion rates and secondary intervention rates) and safety (30-day mortality rate, procedure morbidity rates and technical issues-endoleaks, graft thrombosis, stenosis and migration). RESULTS: Of 606 reports identified, 61 met the inclusion criteria (three randomized and 15 non-randomized controlled trials, and 43 uncontrolled studies). There were 29 059 participants in total; 19,804 underwent EVAR. Deployment was successful in 97.6 per cent of cases. Technical success (complete aneurysm exclusion) was 81.9 per cent at discharge and 88.8 per cent at 30 days. Secondary intervention to treat endoleak or maintain graft patency was required in 16.2 per cent of patients. Mean stay in the intensive care unit and mean hospital stay were significantly shorter following EVAR. The 30-day mortality rate for EVAR was 1.6 per cent (randomized controlled trials) and 2.0 per cent in nonrandomized trials and case series. Technical complications comprised stent migration (4.0 per cent), graft limb thrombosis (3.9 per cent), endoleak (type I, 6.8 per cent; type II, 10.3 per cent; type III, 4.2 per cent) and access artery injury (4.8 per cent). DISCUSSION: EVAR is technically effective and safe, with lower short-term morbidity and mortality rates than open surgery. However, there is a need for extended follow-up as the long-term success of EVAR in preventing aneurysm-related deaths is not yet known.

Angioplasty↗
PubMed2005

Stage 2 of the Wellcome Trust UK-Irish bipolar affective disorder sibling-pair genome screen: evidence for linkage on chromosomes 6q16-q21, 4q12-q21, 9p21, 10p14-p12 and 18q22.

Bipolar affective disorder (BPAD) is a common psychiatric disorder with complex genetic aetiology. We have undertaken a genome-wide scan in one of the largest samples of bipolar affected sibling pairs (ASPs) using a two-stage approach combining sample splitting and marker grid tightening. In this second stage analysis, we have examined 17 regions that achieved a nominally significant maximum likelihood LOD score (MLS) threshold of 0.74 (or 1.18 for the X-chromosome) in stage one. The second stage has added 135 ASP families to bring the total stage 2 sample to 395 ASPs. In total, 494 microsatellite markers have been used to screen the human genome at a density of 10 cM in the first stage sample (260 ASPs) and 5 cM in the second stage. Under the broad diagnostic model, two markers gave LOD scores exceeding 3 with two-point analysis: D4S392 (LOD=3.30) and D10S197 (LOD=3.18). Multipoint analysis demonstrated suggestive evidence of linkage between BPAD and chromosomal regions 6q16-q21 (MLS=2.61) and 4q12-q21 (MLS=2.38). 6q16-q21 is of particular interest because our data, together with those from two recent genome scans, make this the best supported linkage region in BPAD. Further, our data show evidence of a gender effect at this locus with increased sharing predominantly within the male-male pairs. Our scan also provides support for linkage (MLS> or =1.5) at several other regions that have been implicated in meta-analyses of bipolar disorder and/or schizophrenia including 9p21, 10p14-p12 and 18q22.

Bipolar Disorder↗
PubMed2005

p53-specific CD8+ T-cell responses in individuals with cutaneous squamous cell carcinoma.

BACKGROUND: Systemic immunosuppression is a significant risk factor for cutaneous squamous cell carcinoma (SCC). p53 is mutated and overexpressed in up to 90% of cutaneous SCC lesions. Despite considerable evidence that the immune response is important in the control of cutaneous SCC, there are no studies documenting potential tumour-associated antigens. OBJECTIVES: We tested the hypothesis that individuals with cutaneous SCC have functional circulating CD8+ T cells specific for p53. METHODS: Interferon-gamma immunosorbent assays were used to screen peripheral blood mononuclear cells for reactivity to six p53-derived HLA-A*0201-restricted epitopes from HLA-A*0201-positive patients and controls. RESULTS: We observed significantly elevated frequencies of p53-specific CD8+ T cells in seven of 26 individuals with cutaneous SCC and in one of 10 controls. The degree of lymphocytic infiltrate significantly correlated with the frequency of CD8+ T cells specific for p53 epitopes, but not with control epitopes. CONCLUSIONS: Overall, these data suggest that p53 may represent a target for CD8+ T cells in a proportion of individuals with cutaneous SCC.

CD8-Positive T-Lymphocytes↗
PubMed2005

Interleukin-4 induced down-regulation of skin homing receptor expression by human viral-specific CD8 T cells may contribute to atopic risk of cutaneous infection.

Factors controlling the expression of cutaneous lymphocyte-associated antigen (CLA) by T cells are poorly understood, but data from murine and human CD4(+) T cell systems have suggested that cytokines play an important role. However, there are no data examining the influence of cytokines on the expression of CLA by human antigen-specific CD8(+) T cells. Peripheral blood mononuclear cells (PBMC) were isolated from 10 HLA-A*0201-positive healthy individuals. Using HLA-peptide tetrameric complexes refolded with immunodominant peptides from Epstein-Barr virus (EBV), cytomegalovirus (CMV) and influenza A virus, we investigated the temporal associations of CLA expression by viral-specific CD8(+) T cells following stimulation with antigen. Ex vivo influenza matrix-specific CD8(+) T cells expressed significantly (P < 0.05) greater levels of CLA than EBV BMLF1 and CMV pp65-specific CD8(+) T cells (mean 9.7% influenza matrix versus 1.4% BMLF1 versus 1.1% pp65) and these differences were sustained on culture. However, regardless of viral specificity, interleukin (IL)-12 and IL-4 induced significant (P < 0.05) dose-dependent up-regulation and down-regulation of CLA expression, respectively, with IL-4 showing a dominant negative effect. In many cases, IL-4 resulted in complete abrogation of detectable CLA expression by the viral-specific CD8(+) T cells. Overall these data demonstrate that CLA expression by human viral-specific CD8(+) T cells is highly dynamic and that IL-4 causes significant down-regulation. Disorders associated with a type 2 cytokine shift may reduce the efficiency of skin homing by viral-specific CD8(+) T cells. Furthermore, the ability to modify the local and systemic microenvironment may offer novel therapeutic strategies that influence tissue-specific T cell homing.

Antigens, Differentiation, T-Lymphocyte↗
PubMed2005

Distribution of Ixodes ricinus in the British Isles: investigation of historical records.

Ixodes ricinus Linnaeus (Acari: Ixodidae) is the most abundant and widely distributed tick in the British Isles, and is a vector for a number of bacterial, viral and protozoal pathogens of both medical and veterinary importance. This report provides an update to the historical distribution data of I. ricinus, published by the Biological Records Centre (BRC), Monks Wood in The Provisional Atlas of the Ticks (Ixodidae) of the British Isles by K. P. Martyn (1988), and is supplemented with additional BRC records since 1988, additional data from published scientific literature and unpublished field studies, and enhanced with spatial and temporal information on tick stages collected and their host associations. Records have been mapped at 10 km resolution and enhanced to 5 km, 1 km and 0.1 km. Differentiation between records representing one-off collections from those representing populations of I. ricinus has been achieved through the classification of the records into either reported or established populations. Detailed seasonality and host associations of records are investigated, highlighting the value in obtaining additional detailed contemporary data to aid risk assessments and research within this field.

Animals↗
PubMed2005

Behavioural profiles of inbred mouse strains used as transgenic backgrounds. II: cognitive tests.

One of the characteristic manifestations of several neurodegenerative diseases is the progressive decline in cognitive ability. In order to determine the suitability of six mouse strains (129S2/Sv, BALB/c, C3H/He, C57BL/6j, CBA/Ca and DBA/2) as transgenic background strains, we investigated the performance on a variety of tasks designed to identify subtle changes in cognition. In addition, a test of exploratory behaviour was used to probe the level of underlying anxiety in these mouse strains, as anxiety can be a confounding factor on behavioural performance generally. The C3H/He mice exhibited the least anxiogenic behavioural profile spending most time on the open arms of the maze, in contrast to the 129S2/Sv mice which spent the least amount of time in this location and were the quickest to move into a closed arm. The C3H/He mouse strain failed to acquire a visual discrimination task and failed to demonstrate learning on a water maze spatial learning task, in contrast to the CBA/Ca, DBA/2 and C57BL/6j strains which demonstrated a degree of learning in both tasks. No significant strain differences were identified on the object recognition task. These data, taken together, suggest that care must be taken when choosing cognitive tasks to be used with particular mouse strains and that task sensitivity must be considered as a critical element to research protocols with regard to these mouse strains.

Analysis of Variance↗
PubMed2004

Spinal injuries centres (SICs) for acute traumatic spinal cord injury.

BACKGROUND: The majority of complications in traumatic spinal cord injury (SCI) can occur in the first 24 hours and it has been suggested that spinal injury centres (SICs) may influence the pre-transfer care of people with SCI. The specialist SIC concept has been adopted in a number of high-income countries. However, even in such countries, a potentially significant number of people with SCI do not have the opportunity to access this system and are managed in a non-specialist environment. OBJECTIVES: To answer the question: does immediate referral to an SIC result in a better outcome than delayed referral? SEARCH STRATEGY: The following databases were searched: AMED, CCTR, CINAHL, DARE, EMBASE, HEED, HMIC, MEDLINE, NRR, NHS EED, and PsycLIT. Searches were updated in May 2003 and included the Cochrane Injuries Group Specialist Register. The reference lists of retrieved articles were checked. SELECTION CRITERIA: Randomised controlled trials and controlled trials that compared immediate referral to an SIC with delayed referral in patients with a traumatic SCI. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected studies. One reviewer was to have assessed the quality of the studies and extracted data. MAIN RESULTS: No randomised controlled trials or controlled trials were identified that compared immediate referral to an SIC with delayed referral in patients with a traumatic SCI. All of the studies identified were retrospective observational studies and of poor quality. REVIEWERS' CONCLUSIONS: The current evidence does not enable conclusions to be drawn about the benefits or disadvantages of immediate referral versus late referral to SICs. Well-designed, prospective experimental studies with appropriately matched controls are needed.

Hospitals, Special↗
PubMed2004

Laparoscopy and laparoscopic ultrasound in the evaluation of pancreatic and periampullary tumours.

BACKGROUND AND AIMS: The pre-operative determination of resectability of pancreatic and peri-ampullary neoplasia assists the selection of patients for surgical or non-surgical treatment. This study investigated whether the addition of laparoscopy with laparoscopic ultrasound to dual-phase helical CT could improve the accuracy of assessment of resectability. PATIENTS AND METHODS: Prospective study of 305 patients referred to a single unit for consideration of pancreatic resection who underwent dual-phase helical CT scanning +/- laparoscopy with laparoscopic ultrasound. Data were collected on patient demographics, CT findings, assessment of operability, laparoscopic assessment (LA), surgical procedures and histology. RESULTS: LA was undertaken in 239/305 patients, 190 of whom were considered CT resectable, and 49 CT unresectable. Of the 190 CT resectable patients, LA correctly identified unresectability in 28 (15%: metastases in 15; vascular encasement in 6; anaesthesia for laparoscopy found 7 unfit for major resection) and incorrectly in 2 (vascular encasement), but did not identify unresectability in 33; LA correctly confirmed resectability in the remainder (prediction improved, chi(2) = 9.73, p < 0.01). Of the 49 CT unresectable patients, LA correctly identified resectability in 4, and incorrectly in 12, and correctly identified unresectability in the remaining 33. Sixty-six of the 305 patients did not undergo LA, of whom 23 underwent resection. CONCLUSION: When added to dual-phase helical CT, laparoscopy with laparoscopic ultrasound provides valuable information that significantly improves the selection of patients for surgical or non-surgical treatment.

Adult↗