Biomedical subjects

Louise Jones

Publications and source records attributed to Louise Jones.

At least 19 recordsLinked to original sources

PubMed2007

Acceptability of an advance care planning interview schedule: a focus group study.

There is growing recognition that patients should have greater opportunity to plan their future care, a process known as advance care planning. The aims of this phase I qualitative focus group study were (1) to explore the acceptability of an interview schedule, designed to encourage conversations regarding future care; and (2) to explore the suitability of such discussions and inquire about their possible timing, nature and impact. Purposive sampling was used to achieve a balanced sample of 22 palliative care and oncology patients, relatives and user group members. The results showed that, although some patients welcome the opportunity to discuss end-of-life care, others may not feel ready or able to do so. The timing of a discussion is likely to influence its acceptability and effect. A discussion might best be initiated after recurrence of disease. The person initiating discussion should be skilled in responding to the cues of the patient, and should enable the patient to close the topic down at the end of the discussion, in order to avoid dwelling too much on the end of life. Advance care planning should take place over a number of meetings, and be conducted by an appropriately trained professional with sufficient time to talk through the issues raised, and with the knowledge and skills to answer questions, tailor the discussion to the individual, and avoid destroying hope. Advance decisions to refuse treatment should not be the focus of the discussion, but one component of a broader conversation about end-of-life issues. If patients make an advance decision to refuse certain treatments, they should be given the opportunity to change their minds in the future.

Adult↗

PubMed2006

Interleukin-4 promotes human CD8 T cell expression of CCR7.

Despite strong evidence supporting a pathway of human T cell differentiation characterized by changes in the expression of CCR7, CD28, CD27 and CD62L, few studies have addressed the mechanisms of pathway regulation. Cutaneous lymphocyte-associated antigen (CLA)-positive skin-homing CD8(+) T cells expressed significantly elevated levels of activation markers compared with CLA(-) CD8(+) T cells in individuals (n = 27) with cutaneous atopic disease. Despite such an activated phenotype, CLA(+) T cells expressed significantly higher levels of CCR7 than a CLA(-) T cell subset. Interleukin (IL)-4 was found to dramatically promote CCR7 expression by antigen-specific CD8(+) cells. Furthermore, skin-homing CD8(+) T cells from individuals with severe disease produced significantly less IL-10 than those derived from mildly affected atopic subjects. Thus in a T-helper 2 dominated disease, tissue-specific CD8(+) T cells show altered CCR7 expression and cytokine production, which may contribute to continued lymph node homing, antigen presentation and disease. IL-4 promotes expression of CCR7, a marker linked to existing models of CD8(+) T cell differentiation.

CD8-Positive T-Lymphocytes↗

PubMed2006

A novel fluorescent sensitive assay for detection of differential T cell mediated lysis of multiple adherent target cells.

There are few studies that have investigated T cell mediated lysis of adherent cells. We have developed a novel, rapid and sensitive fluorescent dye-swap assay that allows efficient detection of adherent target cell lysis. The assay allows simultaneous use of multiple differentially sensitised targets and facilitates concomitant surface or intracellular effector cell phenotypic analysis.

Cell Adhesion↗

PubMed2006

Virus-induced gene silencing of argonaute genes in Nicotiana benthamiana demonstrates that extensive systemic silencing requires Argonaute1-like and Argonaute4-like genes.

Several distinct pathways of RNA silencing operate in plants with roles including the suppression of virus accumulation, control of endogenous gene expression, and direction of DNA and chromatin modifications. Proteins of the Dicer-Like and Argonaute (AGO) families have key roles within these silencing pathways and have distinct biochemical properties. We are interested in the relationships between different silencing pathways and have used Nicotiana benthamiana as a model system. While not being an amenable plant for traditional genetics, N. benthamiana is extensively used for RNA-silencing studies. Using virus-induced gene silencing technology we demonstrate that both NbAGO1- and NbAGO4-like genes are required for full systemic silencing but not for silencing directed by an inverted repeat transgene. Phenotypic differences between the virus-induced gene silencing plants indicate that NbAGO1 and NbAGO4 like act at different stages of the silencing pathways. Suppression of NbAGO1 expression recapitulated the hypomorphic mutant phenotype of certain Arabidopsis (Arabidopsis thaliana) ago1 alleles, however, suppression of NbAgo4 like resulted in phenotypes differing in some respects from those reported for Arabidopsis ago4. We suggest that the small interfering RNA amplification step required for full systemic silencing is dependent upon a nuclear event requiring the activity of NbAGO4 like.

Amino Acid Sequence↗

PubMed2006

Persistent high frequencies of varicella-zoster virus ORF4 protein-specific CD4+ T cells after primary infection.

Open reading frame 4 (ORF4) of varicella-zoster virus (VZV) encodes an immediate-early protein that is believed to be important for viral infectivity and establishing latency. Evidence suggests that VZV-specific T cells are crucial in the control of viral replication, but there are no data addressing the existence of potential ORF4 protein-specific CD4+ T cells. We tested the hypothesis that VZV ORF4 protein-specific CD4+ T cells could be identified and characterized within the peripheral blood of healthy immune donors following primary infection. Gamma interferon (IFN-gamma) immunosorbent assays were used to screen peripheral blood mononuclear cells obtained from healthy seropositive donors for responses to overlapping ORF4 peptides, viral lysate, and live vaccine. High frequencies of ORF4 protein-specific T cells were detected ex vivo in individuals up to 52 years after primary infection. Several immunogenic regions of the ORF4 protein were identified, including a commonly recognized epitope which was restricted through HLA-DRB1*07. Total ORF4 protein-specific responses comprised 19.7% and 20.7% of the total lysate and vaccine responses, respectively, and were dominated by CD4+ T cells. Indeed, CD4+ T cells were found to dominate the overall virus-specific IFN-gamma cellular immune response both ex vivo and after expansion in vitro. In summary, we have identified an ORF4 protein as a novel target antigen for persistent VZV-specific CD4+ T cells, with implications for disease pathogenesis and future vaccine development.

Adult↗

PubMed2006

Estimating needs in life threatening illness: a feasibility study to assess the views of patients and doctors.

BACKGROUND: Provision of palliative care for patients with non-cancer conditions is hindered by the difficulty of predicting when people will die and fear of causing distress by raising end-of-life issues. OBJECTIVES: To compare patients' and professionals' (1) estimations of prognosis; (2) perceptions of the seriousness of the illness and needs for supportive care; and (3) acceptability of this sensitive research, in end-stage cancer and non-cancer diseases. DESIGN: Prospective cohort study. SETTING: A teaching hospital and a Marie Curie hospice in London. SUBJECTS: Twenty patients with advanced non-malignant disease (heart failure, chronic obstructive pulmonary disease and renal failure) and 20 patients with advanced cancer, and their physicians in charge. METHOD: A feasibility study using vignettes to aid patients and doctors estimate of prognoses. Main outcome measures were (1) patients' and physicians' estimates of health status, care needs and prognosis; and (2) patient survival. RESULTS: Patients were willing and able to estimate their own life expectancy and cancer patients correctly estimated that they had a poorer prognosis than non-cancer patients. Non-cancer patients perceived that they had similar needs for supportive care as cancer patients. Physicians made little distinction in palliative care needs between patients with and without cancer, but tended to make more pessimistic estimates of prognosis in non-cancer patients. CONCLUSIONS: Patients are able to judge their health status and life expectancy and do not object to questions about end-of-life care. Cancer and non-cancer patients have similar needs for supportive care. We need further evidence on the value of self-rated prognosis and how to provide palliative and supportive care for all patients who are near death.

Attitude of Health Personnel↗

PubMed2005

Measuring spiritual belief: development and standardization of a Beliefs and Values Scale.

BACKGROUND: Higher levels of religious involvement are modestly associated with better health, after taking account of other influences, such as age, sex and social support. However, little account is taken of spiritual beliefs that are not tied to personal or public religious practice. Our objective was to develop a standardized measure of spirituality for use in clinical research. METHOD: We characterized the core components of spirituality using narrative data from a purposive sample of people, some of whom were near the end of their lives. These data were developed into statements in a scale to measure strength of spiritual beliefs and its reliability, validity and factor structure were evaluated in order to reach a final version. RESULTS: Thirty-nine people took part in the qualitative study to define the nature of spirituality in their lives. These data were used to construct a 47-item instrument that was evaluated in 372 people recruited in medical and non-medical settings. Analysis of these statements led to a 24-item version that was evaluated in a further sample of 284 people recruited in similar settings. The final 20-item questionnaire performed with high test-retest and internal reliability and measures spirituality across a broad religious and non-religious perspective. CONCLUSIONS: A measure of spiritual belief that is not limited to religious thought, may contribute to research in psychiatry and medicine.

Adult↗

PubMed2005

Expression of thrombospondin-1 in resected colorectal liver metastases predicts poor prognosis.

PURPOSE: The aim of this study was to examine the expression and prognostic relevance of thrombospondin-1 (TSP-1) in tumor biopsies taken from a consecutive series of liver resections done at the University Hospitals of Leicester and the Royal Liverpool Hospital. EXPERIMENTAL DESIGN: Patients having undergone a liver resection for colorectal liver metastases at our institutions between 1993 and 1999 inclusive were eligible. Inclusion criteria were curative intent, sufficient tumor biopsy, and patient follow-up data. One hundred eighty-two patients were considered in this study. Standard immunohistochemical techniques were used to study the expression of TSP-1 in 5-microm tumor sections from paraffin-embedded tissue blocks. TSP-1 was correlated with survival using the Kaplan-Meier method and log-rank test for univariate analysis and the Cox proportional hazard model for multivariate analysis. RESULTS: One hundred eighty-two patients (male, n = 122 and female, n = 60) ages between 25 and 81 years (mean, 61 years) were included. TSP-1 was expressed around blood vessels (n = 45, 25%) or in the stroma (n = 59, 33%). No expression was detected in the remaining tumors. TSP-1 significantly correlated with poor survival on univariate (P = 0.01 for perivascular expression and P = 0.03 for stromal expression) and multivariate analysis (P = 0.01 for perivascular expression). CONCLUSION: TSP-1 is a negatively prognostic factor for survival in resected colorectal liver metastases.

Adult↗

PubMed2005

An RNA-dependent RNA polymerase prevents meristem invasion by potato virus X and is required for the activity but not the production of a systemic silencing signal.

One of the functions of RNA silencing in plants is antiviral defense. A hallmark of RNA silencing is spreading of the silenced state through the plant. Little is known about the nature of the systemic silencing signal and the proteins required for its production, transport, and reception in plant tissues. Here, we show that the RNA-dependent RNA polymerase RDR6 in Nicotiana benthamiana is involved in defense against potato virus X at the level of systemic spreading and in exclusion of the virus from the apical growing point. It has no effect on primary replication and cell-to-cell movement of the virus and does not contribute significantly to the formation of virus-derived small interfering (si) RNA in a fully established potato virus X infection. In grafting experiments, the RDR6 homolog was required for the ability of a cell to respond to, but not to produce or translocate, the systemic silencing signal. Taking these findings together, we suggest a model of virus defense in which RDR6 uses incoming silencing signal to generate double-stranded RNA precursors of secondary siRNA. According to this idea, the secondary siRNAs mediate RNA silencing as an immediate response that slows down the systemic spreading of the virus into the growing point and newly emerging leaves.

Base Sequence↗

PubMed2005

Supportive care: experiences of cancer patients.

The aim of this study was to explore how cancer patients with progressive disease perceived and experienced supportive care at the different stages of their cancer journey and to compare this to the perceptions of health care professionals. It was a single centre study using qualitative data obtained from two focus group interviews in an independent centre for specialist palliative care. Eight patients attending the centre were interviewed in two focus groups to ascertain their views on the supportive care that they had experienced during the course of their illness, focusing on: time of diagnosis, acute treatment phase and palliative care phase. Themes that emerged from the analysis of the interview transcripts using the QSR NUD*IST (version 4) software package included the following: manner in which diagnosis was revealed, information made available to family and friends, patients' acceptance of cancer; service provision such as a named contact person, choices in treatment and care, problems of limited resources; feelings of being unsupported, and ways in which supportive care could be improved.

Adult↗

PubMed2005

The effects of immediate-release morphine on cognitive functioning in patients receiving chronic opioid therapy in palliative care.

Morphine and other potent opioids are frequently used in palliative care and pain management. When sustained-release (SR) opioids do not provide adequate background analgesia, additional immediate-release (IR) opioid (e.g. short-acting morphine) may be required to alleviate breakthrough or episodic pain. Despite the frequent use of IR morphine on top of SR opioids, little is known about the effects of such treatment on patients' everyday cognitive functioning. This study therefore used a double-blind, placebo-controlled, cross-over design to assess cognitive functioning in 14 patients receiving palliative care. All patients were taking SR opioid preparations and required <or=2 doses of IR morphine/day. Performance on cognitive measures (as well as subjective measures of pain and mood) after a dose of IR morphine was compared with placebo. Patients experienced significantly more pain-reduction following IR morphine (P=0.03), while other measures of subjective drug effects (e.g. sedation) were largely unaffected. Patients displayed anterograde memory impairment after IR morphine relative to placebo (P=0.003). Intriguingly, patients also had significant 'retrograde' memory impairment: delayed recall of verbal information presented before IR morphine also declined (P=0.024). In addition, IR morphine reduced performance on a complex tracking task (Reitan's trails B; P=0.03) whilst enhancing it on a simpler tracking task (Reitan's trails A; P=0.03). In conclusion, this study suggests that IR morphine, when taken on top of a SR opioid, produces transient anterograde and retrograde memory impairments and a decrement in two-target tracking. These impairments may impact negatively on patients' everyday functioning.

Affect↗

PubMed2004

A conserved functional role of pectic polymers in stomatal guard cells from a range of plant species.

Guard cell walls combine exceptional strength and flexibility in order to accommodate the turgor pressure-driven changes in size and shape that underlie the opening and closing of stomatal pores. To investigate the molecular basis of these exceptional qualities, we have used a combination of compositional and functional analyses in three different plant species. We show that comparisons of FTIR spectra from stomatal guard cells and those of other epidermal cells indicate a number of clear differences in cell-wall composition. The most obvious characteristics are that stomatal guard cells are enriched in phenolic esters of pectins. This enrichment is apparent in guard cells from Vicia faba (possessing a type I cell wall) and Commelina communis and Zea mays (having a type II wall). We further show that these common defining elements of guard cell walls have conserved functional roles. As previously reported in C. communis, we show that enzymatic modification of the pectin network in guard cell walls in both V. faba and Z. mays has profound effects on stomatal function. In all three species, incubation of epidermal strips with a combination of pectin methyl esterase and endopolygalacturonase (EPG) caused an increase in stomatal aperture on opening. This effect was not seen when strips were incubated with EPG alone indicating that the methyl-esterified fraction of homogalacturonan is key to this effect. In contrast, arabinanase treatment, and incubation with feruloyl esterase both impeded stomatal opening. It therefore appears that pectins and phenolic esters have a conserved functional role in guard cell walls even in grass species with type II walls, which characteristically are composed of low levels of pectins.

Commelina↗

PubMed2004

CD4(-)CD8alphaalpha subset of CD1d-restricted NKT cells controls T cell expansion.

Valpha24 invariant (Valpha24i) CD1d-restricted NKT cells are widely regarded to have immune regulatory properties. They are known to have a role in preventing autoimmune diseases and are involved in optimally mounted immune responses to pathogens and tumor cells. We were interested in understanding how these cells provide protection in autoimmune diseases. We first observed, using EBV/MHC I tetrameric complexes, that expansion of Ag-specific cells in human PBMCs was reduced when CD1d-restricted NKT cells were concomitantly activated. This was accompanied by an increase in a CD4(-)CD8alphaalpha(+) subset of Valpha24i NKT cells. To delineate if a specific subset of NKT cells was responsible for this effect, we generated different subsets of human CD4(-) and CD4(+) Valpha24i NKT clones and demonstrate that a CD4(-)CD8alphaalpha(+) subset with highly efficient cytolytic ability was unique among the clones in being able to suppress the proliferation and expansion of activated T cells in vitro. Activated clones were able to kill CD1d-bearing dendritic or target cells. We suggest that one mechanism by which CD1d-restricted NKT cells can exert a regulatory role is by containing the proliferation of activated T cells, possibly through timely lysis of APCs or activated T cells bearing CD1d.

Antigens, CD1↗

PubMed2004

TLR2 is expressed on activated T cells as a costimulatory receptor.

Toll is the founder of a group of pattern recognition receptors that play a critical role in the innate immunity in Drosophila. At least 10 distinct Toll-like receptors (TLRs), recognizing pathogen-associated molecular patterns, have now been identified in humans. Most investigations on TLRs have focused on cells of the innate system. We report here that naïve human T cells expressed high levels of cell-surface TLR2 after activation by anti-T cell receptor antibody and IFN-alpha. Activated cells produced elevated levels of cytokines in response to the TLR2 ligand, bacterial lipopeptide. Furthermore, CD4(+)CD45RO(+) memory T cells from peripheral blood constitutively expressed TLR2 and produced IFN-gamma in response to bacterial lipopeptide, which also markedly enhanced the proliferation and IFN-gamma production by CD45RO(+) T cells in the presence of IL-2 or IL-15. Thus, TLR2 serves as a costimulatory receptor for antigen-specific T cell development and participates in the maintenance of T cell memory. This suggests that pathogens, via their pathogen-associated molecular patterns, may contribute directly to the perpetuation and activation of long-term T cell memory in both antigen-dependent and independent manner.

Animals↗

PubMed2004

A role for expansins in dehydration and rehydration of the resurrection plant Craterostigma plantagineum.

Craterostigma plantagineum is one of the few higher plants capable of surviving desiccation throughout its vegetative tissues. Water loss results in cell shrinkage and a commensurate folding of the cell wall indicating an unusual degree of wall flexibility. We show that wall extensibility undergoes a marked increase during dehydration and rehydration. Similar increases were observed in the activity of expansins in cell walls during these processes suggesting a role for these proteins in increasing wall flexibility. Three alpha-expansin cDNAs were cloned from dehydrating leaves and transcript levels for one correlated closely with the observed changes in expansin activity during the dehydration and rehydration of leaves.

Adaptation, Physiological↗

PubMed2004

Longitudinal analysis of CD8+ T cells specific for structural and nonstructural hepatitis B virus proteins in patients with chronic hepatitis B: implications for immunotherapy.

The cytotoxic T-cell response in chronic hepatitis B virus (HBV) infection has been described as weak and mono- or oligospecific in comparison to the more robust virus-specific T-cell response present in resolved infection. However, chronic hepatitis B is a heterogeneous disease with markedly variable levels of virus replication and liver disease activity. Here we analyzed (both directly ex vivo and after in vitro stimulation) the HBV-specific CD8 T-cell responses against structural and nonstructural HBV proteins longitudinally in patients with different patterns of chronic infections. We found that the profiles of virus-specific CD8(+)-T-cell responses during chronic infections are highly heterogeneous and influenced more by the level of HBV replication than by the activity of liver disease. An HBV DNA load of <10(7) copies/ml appears to be the threshold below which circulating multispecific HBV-specific CD8(+) T cells are consistently detected. Furthermore, CD8(+) T cells with different specificities are differentially regulated during chronic infections. HBV core-specific CD8(+) T cells are associated with viral control, while CD8(+) T cells specific for envelope and polymerase epitopes can occasionally be found in the setting of high levels (>10(7) copies) of HBV replication. These findings have implications for the design of immunotherapy for chronic HBV infections.

Adult↗

PubMed2003

Cell wall arabinan is essential for guard cell function.

Stomatal guard cells play a key role in the ability of plants to survive on dry land, because their movements regulate the exchange of gases and water vapor between the external environment and the interior of the plant. The walls of these cells are exceptionally strong and must undergo large and reversible deformation during stomatal opening and closing. The molecular basis of the unique strength and flexibility of guard cell walls is unknown. We show that degradation of cell wall arabinan prevents either stomatal opening or closing. This locking of guard cell wall movements can be reversed if homogalacturonan is subsequently removed from the wall. We suggest that arabinans maintain flexibility in the cell wall by preventing homogalacturonan polymers from forming tight associations.

Cell Wall↗

PubMed2003

Expansins and cell growth.

Expansins are now generally accepted to be key regulators of wall extension during growth. Several alternative roles for expansins have emerged in which the emphasis of their action is on wall breakdown or softening in processes such as fruit ripening, pollination, germination and abscission. Expansins are commonly encoded by substantial gene families and have classically been divided into two subfamilies, referred to as alpha- and beta-expansins. Two further subfamilies have now been identified: gamma-expansins, which were first described in Arabidopsis, and delta-expansins, which were identified in rice and are absent from Arabidopsis. Both are truncated versions of alpha- and beta-expansins, with gamma-expansins representing the amino-terminal half of a mature expansin and delta-expansins the carboxy-terminal half of a beta-expansin. Functional roles for gamma- and delta-expansins have yet to be defined, although recent data indicate a signalling role for gamma-expansins.

Amino Acid Sequence↗