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J Barrett

Publications and source records attributed to J Barrett.

At least 19 recordsLinked to original sources
PubMed2006

Local gene therapy of solid tumors with GM-CSF and B7-1 eradicates both treated and distal tumors.

Gene therapy-induced expression of immunostimulatory molecules at tumor cell level may evoke antitumor immune mechanisms by recruiting and enhancing viability of antigen-processing cells and specific tumoricidal lymphocytes. The antitumor efficacy of a plasmid, coding for granulocyte-macrophage colony-stimulating factor (GM-CSF) and the B7-1 costimulatory immune molecule, delivered into growing solid tumors by electroporation was investigated. Murine fibrosarcomas (JBS) growing in Balb/C mice (<or=100 mm3) were transfected with GM-CSF/B7-1-expressing plasmid. Complete tumor regression occurred in greater than 60% of treated animals. This response was systemic, durable and tumor specific, with all responding animals resistant to repeat tumor challenge. Using a liver metastatic model, effective cure of distal metastases was achieved following treatment of the primary subcutaneous tumor. This treatment strategy could be applicable in the clinical setting for effective elimination of both primary tumors and associated metastatic disease.

Animals↗
PubMed2006

The effects of birdsfoot trefoil (Lotus corniculatus) and chicory (Cichorium intybus) when compared with perennial ryegrass (Lolium perenne) on ovine gastrointestinal parasite development, survival and migration.

Two experiments were conducted to investigate the effects of birdsfoot trefoil and chicory on parasitic nematode development, survival and migration when compared with perennial ryegrass. In experiment one, sheep faeces, containing 10,385 Cooperia curticei eggs were added to 25 cm diameter pots containing birdsfoot trefoil, chicory or ryegrass, and the pots maintained under optimal conditions for nematode parasite development. Replicate pots of each forage type were destructively sampled on day 8, 16, 20, 28 and 37 to collect the nematode larvae. When forages were compared on a dry matter basis, by day 16 there were 31% and 19% fewer larvae on birdsfoot trefoil and chicory than on ryegrass, respectively (P<0.01). In the second experiment, replicate 1m(2) field plots of birdsfoot trefoil, chicory and ryegrass were sub-sampled on day 14, 21, 35 and 49 for larval counts following the application of sheep faeces containing 585,000 Teladorsagia circumcincta eggs to each plot on day 0. Results showed there were a minimum of 58% and 63% fewer infective stage parasitic larvae on birdsfoot trefoil and chicory, respectively, compared with ryegrass on day 14 and 35 when forages were compared on a forage dry matter, plot area sampled and leaf area basis (P<0.01). Overall, these results indicate that the number of infective stage larvae on birdsfoot trefoil and chicory pasture was reduced by the effect of their sward structure on the development/survival/migration of ovine parasitic nematodes. These effects may be one of the ways in which these forages may affect parasitic infections in grazing livestock.

Analysis of Variance↗
PubMed2006

Population pharmacokinetics of ibandronate in Caucasian and Japanese healthy males and postmenopausal females.

INTRODUCTION: Ibandronate is a potent, nitrogen-containing bisphosphonate that is licensed as a once-monthly oral preparation and is currently in clinical development as a novel intermittent intravenous (i.v.) injection in osteoporosis. Ibandronate pharmacokinetic (PK) data were used to develop a PK model that could ultimately be incorporated into a PK pharmacodynamic (PD) model to assist the ibandronate development program through computer-assisted trial design. This manuscript reports the use of non-linear mixed-effects modeling to characterize the PK of ibandronate, to examine the possible influence of ethnicity on the disposition of ibandronate and to develop an appropriate population PK model for ibandronate. METHODS: A retrospective, cross-study population PK analysis was performed using PK data from five phase I studies with i.v. ibandronate (0.125 - 2.0 mg) conducted in Caucasian and Japanese healthy male volunteers, postmenopausal Caucasian women without osteopenia and postmenopausal Japanese women with osteopenia. The following covariates were investigated to establish their influence on the central volume of distribution (V1) and drug clearance (CL): age, body weight, gender, disease status (healthy versus osteopenic), creatinine clearance (CLCR), and ethnicity (Japanese versus Caucasian). Serum concentrations of ibandronate were quantified by GC-MS or ELISA, and data were modeled using non-linear mixed-effects modeling implemented by the software program NONMEM. RESULTS: The PK of ibandronate was adequately described by a linear 3-compartment model. Disease status, body weight, gender and CLCR significantly influenced ibandronate CL (10 34%) and the latter 3 also influenced V1 (20 29%). Ethnicity was not a determinant for ibandronate PK in the final model. Although gender was the most influential covariate, differences in V1 and CL between the sexes were modest (29 and 34%, respectively) and the overall effects on ibandronate exposure (Cmax and AUC) were not clinically relevant. The final model described the observed PK of ibandronate well, and all PK parameters were estimated with an acceptable degree of precision (SE < 13%). CONCLUSION: The PK of i.v. ibandronate was well described by a linear 3-compartment population PK model that included disease status, body weight, gender and CLCR as covariates, but without greatly affecting ibandronate exposure (Cmax and AUC). Ethnicity did not influence ibandronate PK and was not included in the final model.

Adult↗
PubMed2005

Prevention and treatment of urinary incontinence after stroke in adults.

BACKGROUND: Urinary incontinence can affect 40-60% of people admitted to hospital after a stroke, with 25% still having problems on hospital discharge and around 15% remaining incontinent at one year. OBJECTIVES: To determine the optimal methods for prevention and treatment of urinary incontinence after stroke in adults. SEARCH STRATEGY: We searched the Cochrane Incontinence and Stroke Groups specialised registers (searched 15 December 2004 and 26 October 2004, respectively), CINAHL (January 1982 to November 2004), national and international trial databases for unpublished data, and the reference lists of relevant articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials evaluating the effects of interventions designed to promote continence in people after stroke. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment were undertaken by two reviewers working independently. Disagreements were resolved by a third reviewer. MAIN RESULTS: Seven trials with a total of 399 participants were included in the review. Participants were from a mixture of settings, age groups and phases of stroke recovery. No two trials addressed the same comparison. Four trials tested an intervention against usual care, including acupuncture, timed voiding, and two types of specialist professional intervention. One cross-over trial tested an intervention (oestrogen) against placebo. One trial tested a specific intervention (oxybutynin) against another intervention (timed voiding), and one trial tested a combined intervention (sensory-motor biofeedback plus timed voiding) against a single component intervention (timed voiding alone). Reported data were insufficient to evaluate acupuncture or timed voiding versus usual care, oxybutynin versus timed voiding, or sensory motor biofeedback plus timed voiding versus usual care. Evidence from a single small trial suggested that structured assessment and management of care in early rehabilitation may reduce the number of people with incontinence at hospital discharge (1/21 versus 10/13; RR 0.06, 95% CI 0.01 to 0.43), and have other benefits. Evidence from another trial suggested that assessment and management of care by Continence Nurse Practitioners in a community setting may reduce the number of urinary symptoms (48/89 versus 38/54; RR 0.77, 95% CI 0.59 to 0.99), and increase satisfaction with care. AUTHORS' CONCLUSIONS: There was suggestive evidence that specialist professional input through structured assessment and management of care and specialist continence nursing may reduce urinary incontinence after stroke. Data from trials of other physical, behavioural, complementary and anticholinergic drug interventions are insufficient to guide continence care of adults after stroke.

Acupuncture Therapy↗
PubMed2005

Analysing proteomic data.

The rapid growth of proteomics has been made possible by the development of reproducible 2D gels and biological mass spectrometry. However, despite technical improvements 2D gels are still less than perfectly reproducible and gels have to be aligned so spots for identical proteins appear in the same place. Gels can be warped by a variety of techniques to make them concordant. When gels are manipulated to improve registration, information is lost, so direct methods for gel registration which make use of all available data for spot matching are preferable to indirect ones. In order to identify proteins from gel spots a property or combination of properties that are unique to that protein are required. These can then be used to search databases for possible matches. Molecular mass, pI, amino acid composition and short sequence tags can all be used in database searches. Currently the method of choice for protein identification is mass spectrometry. Proteins are eluted from the gels and cleaved with specific endoproteases to produce a series of peptides of different molecular mass. In peptide mass fingerprinting, the peptide profile of the unknown protein is compared with theoretical peptide libraries generated from sequences in the different databases. Tandem mass spectroscopy (MS/MS) generates short amino acid sequence tags for the individual peptides. These partial sequences combined with the original peptide masses are then used for database searching, greatly improving specificity. Increasingly protein identification from MS/MS data is being fully or partially automated. When working with organisms, which do not have sequenced genomes (the case with most helminths), protein identification by database searching becomes problematical. A number of approaches to cross species protein identification have been suggested, but if the organism being studied is only distantly related to any organism with a sequenced genome then the likelihood of protein identification remains small. The dynamic nature of the proteome means that there really is no such thing as a single representative proteome and a complete set of metadata (data about the data) is going to be required if the full potential of database mining is to be realised in the future.

Animals↗
PubMed2005

Provably secure experimental quantum bit-string generation.

Coin tossing is a cryptographic task in which two parties who do not trust each other aim to generate a common random bit. Using classical communication this is impossible, but nontrivial coin tossing is possible using quantum communication. Here we consider the case when the parties do not want to toss a single coin, but many. This is called bit-string generation. We report the experimental generation of strings of coins which are provably more random than achievable using classical communication. The experiment is based on the "plug and play" scheme developed for quantum cryptography, and therefore well suited for long distance quantum communication.

Journal Article↗
PubMed2005

Ice-active proteins from the Antarctic nematode Panagrolaimus davidi.

The Antarctic nematode Panagrolaimus davidi has an ice-active protein that shows recrystallization inhibition but no thermal hysteresis. It belongs to a class of ice-active proteins found in a variety of freezing-tolerant organisms that display insignificant levels of thermal hysteresis in the context of the environmental temperatures to which they are exposed. The recrystallization inhibition activity of the P. davidi ice-active protein is present at low concentrations, is relatively heat stable, is affected more by acid than by alkaline pH, is not calcium dependant and is not affected by reagents that target carbohydrate residues or sulphydryl linkages. A hexagonal ice crystal growth form also indicates the presence of an ice-active protein. This protein could have important functions in the survival of intracellular freezing by this organism by controlling the stability of ice after its formation.

Acclimatization↗
PubMed2005

Nephrotic syndrome: an under-recognised immune-mediated complication of non-myeloablative allogeneic haematopoietic cell transplantation.

Nephrotic syndrome (NS) is an extremely rare complication of myeloablative allogeneic haematopoietic cell transplantation (HCT) that usually occurs in association with chronic graft-versus-host disease (C-GVHD). We observed an unexpectedly high incidence of NS in a cohort of 163 consecutive patients undergoing non-myeloablative HCT from a related human leucocyte antigen-compatible donor. Seven patients developed NS at a median 318 d post-transplant (range 119-1203 d; cumulative incidence 6.1%). The median age at onset of NS was 46 years (range 33-59 years); three of the seven patients had no evidence of C-GVHD while four had accompanying limited C-GVHD. At diagnosis, median proteinuria was 16.5 g/24 h (range 3-24 g/24 h). Renal biopsy was performed in four cases and revealed membranous nephropathy. NS was not always associated with other symptoms of C-GVHD, and in contrast to previous reports, usually did not improve with the re-initiation of aggressive immunosuppression, resulting in progressive renal failure necessitating dialysis in three of seven cases. Membranous nephropathy resulting in NS is a previously unrecognised and clinically significant complication of non-myeloablative HCT.

Adolescent↗
PubMed2004

Psychosocial and geriatric correlates of functional status after total hip replacement.

OBJECTIVE: To determine whether psychosocial factors, chronic diseases, and common geriatric problems are associated with poor physical function 3 years after primary total hip replacement (THR). METHODS: We studied a sample of Medicare recipients in Ohio, Pennsylvania, and Colorado (n = 922) who underwent primary THR in 1995 (mean +/- SD age 73.1 +/- 5.6 years, 32% men). Participants completed a questionnaire regarding lifestyle factors, medical history, and quality of life approximately 3 years after the surgery. Physical function was measured using the function subscale of the Western Ontario and McMaster Universities Osteoarthritis Index. We assessed the relationship between functional outcome 3 years postsurgery and 4 predictor domains: pain or complications in the operated hip, other musculoskeletal comorbidity, medical factors (obesity, chronic medical comorbidity, rheumatoid arthritis, and such common geriatric problems as falls, poor balance, or incontinence), and psychosocial factors (mental health, regular alcohol consumption, smoking, provider role, living alone, and education). RESULTS: Ten percent of subjects had poor functional status. In a logistic regression model controlling for sex and age, the following factors were associated with an increased risk for poor functional status (in order of importance): pain in the back or lower extremity, severe pain in the operated hip, poor mental health, more than 1 common geriatric problem, obesity, and less than college education. CONCLUSION: Pain in the operated hip was strongly associated with poor functional status 3 years after THR. However, other factors associated with poor functional status were not related to the hip. Our results suggest that a comprehensive assessment of functional status in elderly THR patients should include assessment of common geriatric problems, mental health status, and weight.

Aged↗
PubMed2004

Women's views regarding participation in a proposed randomized controlled trial of twin delivery.

OBJECTIVE: To determine the views of women regarding participation in a proposed multicentre randomized controlled trial comparing planned vaginal birth to planned Caesarean delivery for twins at 32 or more weeks' gestation, in which the first twin (twin A) is presenting as a vertex. METHODS: Pregnant women with a known twin gestation were recruited from 2 hospital centres. Written information was provided about the proposed Twin Birth Study, and the women were then requested to complete a questionnaire to determine their views regarding participation in the proposed trial. RESULTS: Of the 64 women recruited for the study, 31 (48%) indicated they would be willing to consider participating in the proposed trial (95% CI, 37-60%), 14 (22%) were unsure about trial participation (95% CI, 13-33%), and 19 (30%) indicated they would not be willing to participate in the proposed study (95% CI, 20-42%). The most common reason for agreement to participation was altruism (n = 28). Those who responded "not sure" wished to speak with their partner (n = 5) or their doctor (n = 8) before deciding on participation. Of those who indicated they would not participate in the proposed trial, 12 (63%) indicated they preferred to have a vaginal birth, and 7 (37%) preferred to have a Caesarean section. CONCLUSIONS: Almost half the women in our sample were agreeable to considering their participation in a randomized trial that will compare planned vaginal birth to planned Caesarean section for twins at 32 or more weeks' gestation with twin A presenting as a vertex. Altruism was the most common reason for agreeing to participate, whereas preference for a specific mode of delivery was the most common reason for declining participation.

Adult↗
PubMed2004

The transition from bench to bedside: lessons learned in the creation of a new T-cell product for the clinic.

While the technology of translational research is sometimes considered a poor relation to 'basic science', it has become a central focus of work to turn exciting new concepts into practical therapies. Here we use the example of selective T-cell depletion of allografted lymphocytes to illustrate the problems of scale-up, reproducibility, sterility, safety and regulatory concerns encountered during the bench to bedside process.

Aged↗
PubMed2003

The effect of dietary forage on the development and survival of helminth parasites in ovine faeces.

Studies in New Zealand and the UK have shown that lambs grazing birdsfoot trefoil (Lotus corniculatus) or chicory (Cichorium intybus) have reduced parasite intensities compared to lambs grazing ryegrass swards. However, data in the literature on the influence of forages on helminth parasites is equivocal and the underlying mechanisms by which different forage diets may affect these parasites have not been fully determined. The aim of the experiments reported here was to investigate the hypothesis that the consumption of these forages does not affect the hatching and development of helminth eggs in the faeces subsequently produced by the host animal. Lambs grazed monoculture swards of birdsfoot trefoil, chicory, Italian ryegrass (Lolium multiflorum)/red clover (Trifolium pratense) or perennial ryegrass (Lolium perenne)/white clover (Trifolium repens) for 5 weeks and faecal samples collected on days 14, 21, 28 and 35 directly from the rectum of each lamb were used to prepare replicate cultures for each forage type on each occasion. The experiment was repeated over two consecutive years but ryegrass/red clover was not included in Year 2. The dry matter of all faeces was made constant and the faeces were cultured at 27 degrees C for 7 days, before larvae were extracted, counted and identified according to genus or, where possible, species. Overall, the results showed that forage diet had no effect on egg hatchability but significantly affected the development/survival of infective helminth larvae in the faeces of the host animal. Furthermore, feeding birdsfoot trefoil to lambs was found to increase the percentage of helminth parasites that reached the infective stage in the subsequent faeces compared to other forages. Further work is needed to assess whether this would increase the number of larvae on birdsfoot trefoil swards overall under field conditions and to understand the implications of these findings in an applied farming system.

Animal Husbandry↗
PubMed2003

Crystallization and preliminary crystallographic analysis of a new class of glutathione transferase from nematodes.

Mouse and Heligmosomoides polygyrus constitute a readily manipulated small-animal laboratory model for investigating host-nematode interactions. Two major forms of glutathione transferase (GST) are expressed in H. polygyrus adult worms following primary infection. One of these forms belongs to a new class of GST which has only been found in the nematode phylum and therefore presents a possible target for nematode control. In this study, crystals were obtained of a recombinant representative of this new GST class from H. polygyrus. These crystals belong to the triclinic space group P1, with unit-cell parameters a = 72.7, b = 74.0, c = 88.6 A, alpha = 79.1, beta = 80.1, gamma = 81.5 degrees, and are likely to contain four homodimers in the asymmetric unit. X-ray diffraction data were collected to 1.8 A resolution on station A1 at the Cornell High-Energy Synchrotron Source (CHESS).

Animals↗
PubMed2003

Association of specific interleukin 1 gene cluster polymorphisms with increased susceptibility for Behcet's disease.

OBJECTIVE: The aim of this study was to investigate if the inheritance of specific polymorphisms of interleukin 1 (IL-1) A, IL-1B and IL-1 receptor antagonist (IL-1RN) genes could affect the susceptibility to Behçet's disease (BD). METHODS: A total of 132 BD patients and 105 healthy controls were genotyped for IL-1A -889, IL-1B -511, -35, +5810, +5887, and IL-1RN +8006, +8061, +9589, +11,100 single nucleotide polymorphisms, and IL-1RN 86-bp variable number of tandem repeat polymorphism. chi 2-analysis was used to compare the allele and genotype frequencies of the cases and controls. IL-1A and IL-1B haplotypes were reconstructed using the Phase program. RESULTS: Inheritance of the C allele of the IL-1A -889 polymorphism was associated with BD (OR=2.0, P=0.01) and inheritance of the IL-1A -889C/IL-1B +5887T haplotype was identified as an increased risk for BD. The IL-1A -889 and IL-1B +5887 CC/TT combined genotype was significantly more observed in BD cases than in controls (57.5 vs 38.1%, OR=2.2, P=0.003). No association with BD was found for other investigated polymorphisms in the IL-1B and IL-1RN genes. CONCLUSION: Susceptibility to BD is increased in individuals carrying both the IL-1A -889C and IL-1B +5887T haplotype. Individuals who are both homozygous CC at IL-1A -889 and TT at IL-1B +5887 appear to have twice the risk of developing BD as individuals having other IL-1A -889/IL-1B +5887 genotypes.

Behcet Syndrome↗
PubMed2003

The effect of birdsfoot trefoil (Lotus corniculatus) and chicory (Cichorium intybus) on parasite intensities and performance of lambs naturally infected with helminth parasites.

Conventionally, farmers rely upon the routine use of anthelmintics to control helminth parasites and their use has proved highly cost-effective. However, several factors, including the emergence of helminths resistant to pharmaceutical anthelmintics, are forcing farmers to seek alternative approaches to parasite control. Studies in New Zealand have shown that some alternative forages may reduce parasitic infestation in sheep. In the current study, it was found that under UK environmental conditions lambs with naturally acquired helminth infections grazing chicory (Cichorium intybus) and birdsfoot trefoil (Lotus corniculatus) had fewer helminth parasites than sheep grazing ryegrass/white clover (Lolium perenne/Trifolium repens). Twelve pure-bred Lleyn male lambs grazed replicated 0.5ha plots of birdsfoot trefoil, chicory or ryegrass/white clover for 5 weeks. Liveweight and faecal egg counts (FECs) were determined weekly and eight lambs per forage were slaughtered at the end of the trial to determine total helminth intensities. Lambs grazing birdsfoot trefoil had a lower FEC on day 7 (P<0.05) and fewer total adult helminths than those grazing the other forages on day 35 (P<0.01). Lambs grazing chicory did not have significantly lower FEC than lambs grazing other forages but these lambs were found to have fewer total adult abomasal helminths than lambs grazing ryegrass/white clover (P<0.001). As the performance of grazing lambs is inversely correlated with the intensity of helminth parasites, these alternative forages could be used to improve the liveweight gain of lambs produced in the UK. Overall, the results support the contention that alternative forages could have a positive role in the control of helminth parasites in sheep, subject to successful agronomic development and integration of these forages into whole farm systems.

Abomasum↗
PubMed2003

Phylogenetic relationships of Echinostoma Rudolphi, 1809 (Digenea: Echinostomatidae) and related genera re-assessed via DNA and morphological analyses.

In order to investigate the relationships within the Echinostomatidae two data sets of gene sequences were analysed. The first consisted of all previously published ND1 sequences (20) together with 17 new sequences. The latter represented six species from the cosmopolitan genera Echinostoma, Echinoparyphium, Hypoderaeum and Isthmiophora. The second data-set of ITS sequences again included all previously published sequences (12) and three new sequences from species of Echinostoma, Echinoparyphium and Isthmiophora. All new isolates, as well as voucher material from five previously sequenced isolates, were identified on the basis of morphological characters. The phylogenetic trees inferred from the ND1 data set helped to clarify the generic affiliation of all isolates and confirmed the morphological identifications. The only exception was Echinoparyphium aconiatum, whose current position in the genus Echinoparyphium was not supported by the sequence data. Although the ITS data provided insufficient resolution for an unequivocal solution to the relationships within the genus Echinostoma, it supported the identification of Echinoparyphium ellisi and the distinct species status of three isolates of Echinostoma revolutum as predicted from the ND1 data.

Animals↗
PubMed2002

Adoptive transfer of Ag-specific T cells to prevent CMV disease after allogeneic stem-cell transplantation.

BACKGROUND: Cytomegalovirus is a major cause of infectious morbidity and mortality after allogeneic stem-cell transplantation (allo-SCT). Farmacotherapy to prevent or treat CMV reaction and infection is only partially effective, and has considerable toxicity. Adoptive transfer of ex vivo generated CMV specific T cells is a new approach to the management of CMV post-allo-SCT. METHODS: A comprehensive review of the published literature describing 1) the recovery of CMV immunity post-allo-SCT and 2) new strategies for the production of CMV specific T cells for adoptive immunotherapy. RESULTS: CMV specific T cells can be generated using a variety of systems comprising different antigen presenting cells and antigens. DISCUSSION: The ability to raise CMV specific T cells on a clinical scale will have a major impact on the management of CMV post-allo-SCT, but will have to be compared to current pharmacological approaches. Further, the raising of CMV specific T cells may serve as a model, to generate other antigen specific T cells including other anti-viral and anti-tumor T cells.

Adoptive Transfer↗