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Biomedical subjects

A L Hart

Publications and source records attributed to A L Hart.

At least 19 recordsLinked to original sources
PubMed2005

Gene profiling of a compatible interaction between Phytophthora infestans and Solanum tuberosum suggests a role for carbonic anhydrase.

Late blight of potato, caused by the oomycete pathogen Phytophthora infestans, is a devastating disease that can cause the rapid death of plants. To investigate the molecular basis of this compatible interaction, potato cDNA microarrays were utilized to identify genes that were differentially expressed in the host during a compatible interaction with P. infestans. Of the 7,680 cDNA clones represented on the array, 643 (12.9%) were differentially expressed in infected plants as compared with mock-inoculated control plants. These genes were classified into eight groups using a nonhierarchical clustering method with two clusters (358 genes) generally down-regulated, three clusters (241 genes) generally up-regulated, and three clusters (44 genes) with a significant change in expression at only one timepoint. Three genes derived from two down-regulated clusters were evaluated further, using reverse transcription real-time polymerase chain reaction analysis. For these analyses, both incompatible and compatible interactions were included to determine if suppression of these genes was specific to compatibility. One gene, plastidic carbonic anhydrase (CA), was found to have a very different expression pattern in compatible vs. incompatible interactions. Virus-induced gene silencing was used to suppress expression of this gene in Nicotiana benthamiana. In CA-silenced plants, the pathogen grew more quickly, indicating that suppression of CA increases susceptibility to P. infestans.

Base Sequence↗
PubMed2004

Azathioprine dose escalation in inflammatory bowel disease.

BACKGROUND: Forty per cent of patients with inflammatory bowel disease fail to respond to standard dose azathioprine (2 mg/kg/day). AIMS: To evaluate the efficacy and safety of increasing the azathioprine dose according to a fixed schedule and guided by clinical response and adverse effects. METHODS: We reviewed the records of all patients with inflammatory bowel disease treated by a single clinician over 6 years, unresponsive to at least 3 months treatment with standard dose azathioprine, and whose dose was subsequently increased. RESULTS: Forty patients (27 male; 24 Crohn's, 16 ulcerative colitis) with chronic active disease or recurrent flares despite standard dose azathioprine for a median 8 months (range 3-114) increased their dose from a median 2.02 (1.61-3.19) mg/kg/day to 2.72 (2.37-3.99) mg/kg/day in one to four increments of 0.5 mg/kg/day, and were followed over a median 6 (0.5-54) months. Eleven of the 40 patients (seven Crohn's, four ulcerative colitis) responded or had reduced frequency of flare-ups at the end of follow-up, while 17 of the 40 patients had no benefit. Response was more likely for maximum doses < or =2.5 mg/kg/day (six of 11 patients) than for doses >2.5 mg/kg/day (five of 29 patients) (P = 0.042). Twelve patients (11 of whom received maximum doses >2.5 mg/kg/day) were unable to maintain an increased azathioprine dose because of leukopenia in eight, nausea in three, and raised liver enzymes in one (all transient and reversible). CONCLUSIONS: Increasing the azathioprine dose up to 2.5 mg/kg/day appears beneficial in patients who have not responded to 2 mg/kg/day. Further increase above 2.5 mg/kg/day is less likely to be efficacious, and is associated with a substantial risk of adverse reactions.

Adult↗
PubMed2004

Prospective evaluation of intestinal homing memory T cells in ulcerative colitis.

BACKGROUND: Intestinal homing (beta7+) memory T cells reflect the mucosal environment in which they were primed. We hypothesized that prospective assessment of cytokine production by intestinal homing (beta7+) memory T cells in ulcerative colitis patients followed from remission to early relapse may elucidate shifts in cytokine production relevant to the mucosal environment associated with the early phase of inflammation. METHODS: Twelve patients with frequently relapsing ulcerative colitis (> or = 2 relapses in the previous 12 months) were recruited in remission and followed prospectively until relapse. Antibody labeling of whole blood and flow cytometry were used to identify beta7+ cells and beta7- populations within CD3+CD45RA- leukocytes. Production of cytokines (IFN-gamma, TNF-alpha, IL-2, IL-10, TGF-beta, and IL-4) was determined by intracellular labeling. RESULTS: Early relapse of ulcerative colitis was associated with a shift of T cells from the naive to the memory T cell pool, and further the ratio of beta7+:beta7- memory T cells was significantly reduced at relapse (p < 0.01). A greater proportion of intestinal homing beta7+ memory T cells produced IL-4 (p < 0.02) and TNF-alpha (p < 0.05) at disease relapse compared with remission. Non-intestinal homing beta7- memory T cells also showed a tendency toward an increased production of TH1 and TH2 cytokines. CONCLUSIONS: The earliest phase of intestinal inflammation in ulcerative colitis patients is associated with an increase in both TH1 (TNF-alpha and TH2 (IL-4) cytokines by intestinal homing beta7+ memory T cells. These data support the principles of targeting lymphocyte trafficking as therapies in ulcerative colitis.

Adult↗
PubMed2004

Quantitative and functional characteristics of intestinal-homing memory T cells: analysis of Crohn's disease patients and healthy controls.

Circulating memory T cells can be subdivided on the basis of beta7 integrin expression. The beta7+ population contains cells primed in the intestine capable of homing back to the gut. We hypothesized that cytokine production by beta7+ memory T cells reflects the specialized mucosal compartment in which they were primed. Flow cytometry of whole blood was used to assess numbers of beta7+ (beta7hi and beta7int) and beta7- memory T cells and their production of Th1 and regulatory cytokines in healthy controls and Crohn's disease patients. In controls, beta7+ and beta7- memory T cells displayed a similar qualitative profile of cytokine production but the beta7+ population was enriched for cytokine-producing effector cells. In addition, the beta7hi population contained more cytokine-producing cells than the beta7int population, suggesting a gradient of cytokine production based on beta7 integrin expression. In active Crohn's disease, there was altered expression of beta7 integrin with a decrease in intestinal-homing memory T cells and an increase in systemic memory T cells. Furthermore, there was a selective loss of IL-10 and increase in TGF-beta in both beta7+ and beta7- memory T cell subsets which may contribute to the pathogenesis of the inflammatory process in Crohn's disease.

Adult↗
PubMed2004

Modulation of human dendritic cell phenotype and function by probiotic bacteria.

BACKGROUND: "Probiotic" bacteria are effective in treating some inflammatory bowel diseases. However which bacteria confer benefit and mechanisms of action remain poorly defined. Dendritic cells, which are pivotal in early bacterial recognition, tolerance induction, and shaping of T cell responses, may be central in mediating the effects of these bacteria. AIMS: To assess effects of different probiotic bacteria on dendritic cell function. METHODS: Human intestinal lamina propria mononuclear cells, whole blood, or an enriched blood dendritic cell population were cultured with cell wall components of the eight bacterial strains in the probiotic preparation VSL#3 (four lactobacilli, three bifidobacteria, and one streptococcal strains). Dendritic cells were identified and changes in dendritic cell maturation/costimulatory markers and cytokine production in response to probiotic bacteria were analysed by multicolour flow cytometry, in addition to subsequent effects on T cell polarisation. RESULTS: VSL#3 was a potent inducer of IL-10 by dendritic cells from blood and intestinal tissue, and inhibited generation of Th1 cells. Individual strains within VSL#3 displayed distinct immunomodulatory effects on dendritic cells; the most marked anti-inflammatory effects were produced by bifidobacteria strains which upregulated IL-10 production by dendritic cells, decreased expression of the costimulatory molecule CD80, and decreased interferon-gamma production by T cells. VSL#3 diminished proinflammatory effects of LPS by decreasing LPS induced production of IL-12 while maintaining IL-10 production. CONCLUSIONS: Probiotic bacteria differ in their immunomodulatory activity and influence polarisation of immune responses at the earliest stage of antigen presentation by dendritic cells.

Antigen Presentation↗
PubMed2003

The dendritic cell: its role in intestinal inflammation and relationship with gut bacteria.

Dendritic cells are antigen presenting cells that are likely to be pivotal in the balance between tolerance and active immunity to commensal microorganisms that is fundamental to inflammatory conditions, including Crohn's disease and ulcerative colitis. Interactions between dendritic cells and microbial products are discussed and how they contribute to regulation of immune responses. The concept that interactions between dendritic cells and commensal organisms may be responsible for maintaining intestinal immune homeostasis is also explored.

Bacterial Infections↗
PubMed2002

Convenient and rapid detection of pesticides in extracts of sheep wool.

A relatively simple, rapid extraction technique based on acetonitrile was combined with the use of screen-printed electrodes bearing cholinesterases to detect organo-phosphate pesticides from an otherwise intractable matrix, sheep wool. It proved possible to separate, for convenience, the exposure of the electrodes from measurement of their (inhibited) activity. The electrodes were used once and then discarded. Estimation of the extent of inhibition is dependent on reference to the activity of control electrodes. The presence of pesticides in the extracts could be detected with any of three commonly available cholinesterases but the most sensitive enzyme was butyryl cholinesterase from horse serum.

Acetonitriles↗
PubMed2002

The role of the gut flora in health and disease, and its modification as therapy.

The gut flora is a vast interior ecosystem whose nature is only beginning to be unravelled, due to the emergence of sophisticated molecular tools. Techniques such as 16S ribosomal RNA analysis, polymerase chain reaction amplification and the use of DNA microarrays now facilitate rapid identification and characterization of species resistant to conventional culture and possibly unknown species. Life-long cross-talk between the host and the gut flora determines whether health is maintained or disease intervenes. An understanding of these bacteria-bacteria and bacteria-host immune and epithelial cell interactions is likely to lead to a greater insight into disease pathogenesis. Studies of single organism-epithelial interactions have revealed the large range of metabolic processes that gut bacteria may influence. In inflammatory bowel diseases, bacteria drive the inflammatory process, and genetic predisposition to disease identified to date, such as the recently described NOD2/CARD15 gene variants, may relate to altered bacterial recognition. Extra-intestinal disorders, such as atopy and arthritis, may also have an altered gut milieu as their basis. Clinical evidence is emerging that the modification of this internal environment, using either antibiotics or probiotic bacteria, is beneficial in preventing and treating disease. This natural and apparently safe approach holds great appeal.

Bacteria↗
PubMed2001

Enhanced T-lineage acute lymphoblastic leukaemia cell survival on bone marrow stroma requires involvement of LFA-1 and ICAM-1.

The bone marrow (BM) microenvironment supports leukaemia cell survival and proliferation. The roles played by adhesive receptor interactions in the survival of T-lineage acute lymphoblastic leukaemia (T-ALL) cells on BM stromal cells are not well understood. Recently, we have developed an assay that partially recapitulates the BM microenvironment using HS-5 BM stromal cells. In this assay, the magnitude of ex vivo T-ALL lymphoblast survival predicts patient outcome. We examined the molecular basis for cell-cell adhesive events leading to T-ALL lymphoblast survival on HS-5 and on donor-derived BM stroma. Lympho cyte function-associated antigen-1 (LFA-1) on T-ALL cell lines bound intercellular adhesion molecule-1 (ICAM-1) on HS-5 monolayers, and survival was inhibited 85-98% with monoclonal antibodies directed against LFA-1 or ICAM-1. We compared these results with patient-derived T-ALL lymphoblasts co-cultured on either HS-5 BM or normal BM monolayers and found that LFA-1 and ICAM-1 were required, but not alone sufficient for ex vivo leukaemic cell survival. On normal BM stroma, but not HS-5 monolayers, two additional adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, were highly expressed and contributed to T-ALL cell survival. This is the first report to demonstrate the importance of LFA-1/ICAM-1-mediated adhesion as a critical event in a cascade of cell surface receptor-ligand interactions that regulate T-ALL survival in the BM microenvironment.

Apoptosis↗
PubMed1996

Measurement of soluble L-lactate in dairy products using screen-printed sensors in batch mode.

Amperometric sensors based on lactate oxidase and platinized carbon were constructed entirely by screen-printing. They were used to estimate the lactate concentration in diluted samples of yoghurt and buttermilk. Estimates made in untreated (apart from dilution) solutions were subject to bias, relative to values obtained from spectrophotometric assays. Removal of cations improved the accuracy of the estimates. Calcium may have made a small contribution to the bias but the nature of the inhibition is otherwise unknown. With untreated samples, determinations of any accuracy require sufficient dilution to avoid such bias, although the smaller signals resulting from dilution place more demands on calibration and manufacturing standards. The relative standard deviations of estimates, based on variation among sensors, of the most dilute samples were generally too high for practical use. The errors of estimates at lower dilutions approached those of screen-printed sensors made under industrial conditions.

Biosensing Techniques↗
PubMed1994

Organizational leadership: meeting the challenge.

Leadership can be learned. Knowledge of leadership theories can serve as basis for developing skills and techniques. Style, trait, and transformational leadership can be applied in both health care institutions and professional associations. Organizational leadership is challenging, but those challenges can help individual nurses grow in the leadership skills that will continue to be demanded in the ever changing healthcare arena.

Humans↗
PubMed1990

Nursing students' perceptions of anxiety-producing situations in the clinical setting.

Aspects of nursing students' clinical experiences are anxiety provoking. High anxiety may contribute to decreased learning. The purpose of this study was to identify potentially anxiety-producing clinical experiences for student nurses. Thirty-nine junior and 53 senior nursing students from a BS degree program completed the "Clinical Experience Assessment Form," a 16-item Likert scale. The items included communication and procedural aspects of patient care, interpersonal relationships with healthcare providers, and interactions with faculty. An open-ended question asked students to identify the most anxiety-producing aspects of their clinical practice. The students expressed the highest anxiety for the initial clinical experience on a unit and the fear of making mistakes. Faculty evaluation and observation were also anxiety-producing. The results of the student t-test indicated that juniors were significantly higher in their expression of anxiety was that students's anxiety was increased in the clinical setting by their perceptions of nonsupportive faculty.

Adult↗
PubMedDate not supplied

School of nursing closure: an example of congruence with Sutton's model of organizational death.

Literature concerning the closing of nursing schools is scarce. When faced with the task of closure, educational administrators are without guides because most nurses have had no experiences in implementing what can be termed "organizational death." The purpose of this article is to describe Sutton's Process Model of Organizational Death and its congruence with the closure of one nursing school. Process model knowledge and application may assist administrators, faculty, and all those connected with a nursing program in positively working through a school closure.

Adaptation, Psychological↗
PubMedDate not supplied

Valuing our staff nurses.

Explore the source record for details and available documents.

American Nurses' Association↗