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Biomedical subjects

M Grant

Publications and source records attributed to M Grant.

At least 37 records · Page 2Linked to original sources
PubMed2001

Domain swapping and gene shuffling identify sequences required for induction of an Avr-dependent hypersensitive response by the tomato Cf-4 and Cf-9 proteins.

The tomato Cf-4 and Cf-9 genes confer resistance to infection by the biotrophic leaf mold pathogen Cladosporium. Their protein products induce a hypersensitive response (HR) upon recognition of the fungus-encoded Avr4 and Avr9 peptides. Cf-4 and Cf-9 share >91% sequence identity and are distinguished by sequences in their N-terminal domains A and B, their N-terminal leucine-rich repeats (LRRs) in domain C1, and their LRR copy number (25 and 27 LRRs, respectively). Analysis of Cf-4/Cf-9 chimeras, using several different bioassays, has identified sequences in Cf-4 and Cf-9 that are required for the Avr-dependent HR in tobacco and tomato. A 10-amino acid deletion within Cf-4 domain B relative to Cf-9 was required for full Avr4-dependent induction of an HR in most chimeras analyzed. Additional sequences required for Cf-4 function are located in LRRs 11 and 12, a region that contains only eight of the 67 amino acids that distinguish it from Cf-9. One chimera, with 25 LRRs that retained LRR 11 of Cf-4, induced an attenuated Avr4-dependent HR. The substitution of Cf-9 N-terminal LRRs 1 to 9 with the corresponding sequences from Cf-4 resulted in attenuation of the Avr9-induced HR, as did substitution of amino acid A433 in LRR 15. The amino acids L457 and K511 in Cf-9 LRRs 16 and 18 are essential for induction of the Avr9-dependent HR. Therefore, important sequence determinants of Cf-9 function are located in LRRs 10 to 18. This region contains 15 of the 67 amino acids that distinguish it from Cf-4, in addition to two extra LRRs. Our results demonstrate that sequence variation within the central LRRs of domain C1 and variation in LRR copy number in Cf-4 and Cf-9 play a major role in determining recognition specificity in these proteins.

Amino Acid Sequence↗
PubMed2001

Walking ability as a measure of treatment effect in early rheumatoid arthritis.

OBJECTIVE: To assess the clinical usefulness of a prototype walkmat system in patients with early rheumatoid arthritis (RA). SUBJECTS: Twenty-four subjects with early RA and symptomatic forefoot disease requiring therapy with second-line drugs were recruited. DESIGN: Each subject underwent clinical assessment together with gait analysis on the contact sensitive walkmat system and Kistler forceplate before and after six months of treatment with second-line drugs. Two subjects were lost to follow-up. RESULTS: There was the expected improvement in disease activity in response to therapy. Significant differences were also demonstrated in defined gait parameters that indicated improved weight-bearing and enhanced forefoot propulsion. CONCLUSION: Medical therapy improved walking ability in patients with RA and the walkmat system provided a useful adjunct to existing outcome measures in the assessment of lower limb function.

Adult↗
PubMed2001

Low proliferative rate of invasive node-negative breast cancer predicts for a favorable outcome: a prospective evaluation of 669 patients.

This study was designed to compare outcome in terms of disease-free survival (DFS) in women with histologically negative axillary lymph nodes and documented low proliferative rate cancer to other well-defined prognostic factors including type of adjuvant treatment. Between 1988 and 1998, we studied 669 patients with invasive node-negative breast cancer up to 5 cm in size and low proliferative rate measured by flow cytometry to determine S-phase fraction (SPF) or by histochemistry (Ki67/MIB1). At a median follow-up of 53 months, 5-year DFS for the entire group was 94% and did not differ significantly by type of systemic adjuvant treatment: none (133 patients, 95% DFS), tamoxifen (441 patients, 94% DFS), or chemotherapy with doxorubicin and cyclophosphamide (95 patients, 92% DFS). In a multivariate prognostic factor analysis, only tumor size was significant; 5-year DFS was 96% for T1N0 cancer versus 89% for T2N0 cancer (P = 0.01). We have prospectively confirmed that a low rate of proliferation as measured by SPF or MIB1 determination confers an excellent prognosis in invasive node-negative breast cancer up to 5 cm in size, regardless of adjuvant treatment.

Adult↗
PubMed2000

Analysis of pain content in nursing textbooks.

This paper reports on one goal of a project designed to improve end-of-life (EOL) care in nursing education. The goal was to improve the content regarding pain and EOL care included in major nursing textbooks. A descriptive study used content analysis of 50 textbooks selected from a potential of over 700 texts used in nursing education. The 50 texts included 45,683 pages. The text review was conducted using an analysis framework and included content analysis as well as quantification of the content present in the texts. While pain was the most common topic in the texts, the 248 pages of pain content represents only 0.5% of total text content. All nine areas of EOL content (902 pages) comprised only 2% of overall text. Particular weaknesses in the review of pain content were recognized in pharmacologic management of pain. In summary, nursing texts have limited content on pain. Increased attention to this area is essential to prepare nurses to care for patients at the end of life.

Education, Nursing↗
PubMed2000

Human immunodeficiency virus type 1 replication, immune activation, and circulating cytotoxic T cells against uninfected CD4+ T cells.

Cytotoxic T lymphocytes (CTL) that kill uninfected activated CD4+ T cells can be induced in vitro by stimulating CD8+ T cells with activated autologous CD4+ T cells. Similar CTL have been detected in circulating T cells from human immunodeficiency virus type I (HIV)-infected individuals. To define the in vivo correlates of this CTL activity, we studied plasma beta-2 microglobulin and HIV RNA levels, T-lymphocyte subset counts, and expression of CD28 on CD8+ T cells concurrently with circulating CTL activity against uninfected CD4+ T cells in 75 HIV-infected individuals at different stages of disease progression. Mean values of each parameter were compared in subsets of this group of 75 segregated on the basis of this CTL activity. The group with CTL against uninfected activated CD4+ T lymphocytes had more CD8+ T cells, a higher percentage of CD28 CD8+ T cells, and higher plasma levels of HIV RNA and beta-2 microglobulin. CTL against uninfected activated CD4+ T cells were predominantly CD28 and in HIV-infected individuals were associated with immunological or virological evidence of progressive disease. In HIV infection, circulating CTL activity against uninfected activated CD4+ T lymphocytes is associated with immune activation, CD8+ T cell expansion, accumulation of CD28 CD8+ T cells, and inadequate suppression of HIV replication.

CD28 Antigens↗
PubMed2000

AtBI-1, a plant homologue of Bax inhibitor-1, suppresses Bax-induced cell death in yeast and is rapidly upregulated during wounding and pathogen challenge.

Extensive searches have so far failed to identify functional plant homologues of the mammalian apoptotic machinery. Here we report the isolation and characterisation of an Arabidopsis thaliana homologue of human Bax Inhibitor-1, AtBI-1, isolated during a differential screen of plants challenged with the phytopathogen Pseudomonas syringae. AtBI is a member of a small gene family in Arabidopsis, members of which display extensive amino acid identity to human BI-1. AtBI-1 is also functionally similar to BI-1 in its ability to suppress the lethal phenotype in yeast conferred by expression of the mammalian proapoptotic protein, Bax. Expression of AtBI-1 is rapidly upregulated in plants during wounding or pathogen challenge, suggesting a role in responses to biotic and abiotic stress. AtBI-1 upregulation appears R gene independent and is not markedly affected by mutations required for specific classes of R genes. However, the accumulation of AtBI-1 message is significantly reduced in coi1, in which defence responses to insects, pathogens and wounding are compromised.

Amino Acid Sequence↗
PubMed2000

The RPM1 plant disease resistance gene facilitates a rapid and sustained increase in cytosolic calcium that is necessary for the oxidative burst and hypersensitive cell death.

Early events occurring during the hypersensitive resistance response (HR) were examined using the avrRpm1/RPM1 gene-for-gene interaction in Arabidopsis challenged by Pseudomonas syringae pv. tomato. Increases in cytosolic Ca2+ were measured in whole leaves using aequorin-mediated bioluminescence. During the HR a sustained increase in Ca2+ was observed which was dependent on the presence of both a functional RPM1 gene product and delivery of the cognate avirulence gene product AvrRpm1. The sequence-unrelated avirulence gene avrB, which also interacts with RPM1, generated a significantly later but similarly prolonged increase in cytosolic Ca2+. Accumulation of H2O2 at reaction sites, as revealed by electron microscopy, occurred within the same time frame as the changes in cytosolic Ca2+. The NADPH oxidase inhibitor diphenylene iodonium chloride did not affect the calcium signature, but did block H2O2 accumulation and the HR. By contrast, the calcium-channel blocker LaCl3 suppressed the increase in cytosolic Ca2+ as well as H2O2 accumulation and the HR, placing calcium elevation upstream of the oxidative burst.

Aequorin↗
PubMed2000

The anti-idiotypic antibody 1F7 selectively inhibits cytotoxic T cells activated in HIV-1 infection.

Circulating CD8+ T lymphocyte numbers rise substantially following infection with HIV-1. This expanded CD8+ T cell population includes HIV-specific CTL and CTL that kill activated uninfected CD4+ lymphocytes. Experimental, epidemiological and clinical evidence supports the possibility that expansion of CD8+ CTL contributes to CD4+ T cell depletion and disease progression in human HIV infection. Therefore, modulation of CD8+ T cell numbers or of certain CD8+ CTL activated in HIV-infected individuals may be beneficial. It was found that 1F7, a mAb against an idiotype common to anti-HIV and anti-simian immunodeficiency virus (SIV) antibodies, selectively inhibited both anti-HIV CTL and CTL against uninfected CD4+ T cells. Alloantigen-specific CTL and NK cells from either HIV-infected individuals or controls were unaffected by 1F7. Prolonged incubation of CD8+ T cells from HIV-infected individuals with 1F7 induces apoptosis, which was shown to be reflected functionally in reduced total CTL activity and in especially reduced CTL activity against uninfected CD4+ lymphocytes. The selective reactivity of 1F7 with certain CD8+ CTL could be applied towards the modulation of CD8+ T cell responses involved in AIDS pathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Symptoms and their impact on nutrition.

OBJECTIVES: To provide assessment guidelines and management strategies for symptoms affecting nutritional status in patients with cancer. DATA SOURCES: Published articles, book chapters, and research reports. CONCLUSIONS: Patients with cancer experience a variety of symptoms that affect their nutritional status. It is possible to reduce the impact of these symptoms on the nutritional status of the patient through effective symptom management strategies, nutritional assessments, and interventions. IMPLICATIONS FOR NURSING PRACTICE: The nutritional status of cancer patients can be supported by anticipating and managing disease- and treatment-related symptoms. Nurses contribute actively to the achievement of positive patient outcomes when they manage symptoms in a manner that enhances nutrition.

Anorexia↗
PubMed2000

EMDR: a new treatment for trauma and chronic pain.

EMDR (eye movement desensitization and reprocessing) is a new psychological treatment for trauma that is capable of facilitating rapid and permanent reduction in distressing thoughts and feelings (Carlson et al. 1998,Wilson et al. 1995). In addition to reduction of psychological distress, the method leads to more adaptive attitudes and functioning. The utility of the method also appears to extend beyond trauma with positive results reported in the treatment of addictions, phobias, and pain (Henry 1996, Goldstein & Feske 1994, Grant 1986). As a treatment for pain EMDR offers a method of facilitating permanent changes in how pain is experienced somatically and emotionally. Knowledge and understanding of the principles underlying EMDR can also provide a guide for more effective interventions by pain specialists.

Adaptation, Psychological↗
PubMed2000

Validation of a blind transpyloric feeding tube placement technique in pediatric intensive care: rapid, simple, and highly successful.

OBJECTIVE: Nasogastric feeding in intensive care is poorly tolerated as a result of gastroparesis. Transpyloric (TP) feeding has been limited by difficulty in tube placement. This study was to independently validate the success rate of a previously published bedside TP feeding tube (FT) placement technique. DESIGN: Prospective interventional study. SETTING: Tertiary pediatric intensive care unit (PICU) in a university hospital. PATIENTS: Children whose intensivist requested TP feeding, and who were without known fundoplication, pharyngeal trauma, or gastric ulceration. INTERVENTIONS: After informed consent, an unweighted polyurethane feeding tube with a flexible wire stylet was inserted using a standard technique with metoclopramide, right lateral position, and air insufflation during advancement until <2 mL air could be aspirated after insufflation of 5-10 mL air. The tubes were inserted by one of the authors, whose training was only to observe one insertion, then perform one insertion with supervision. MEASUREMENTS AND MAIN RESULTS: Patient demographics, procedural data, and success rate based on radiography were prospectively recorded. There were 71 insertions on 38 patients from February 1999 to October 1999. Patients were aged 56 +/- 69.8 months, weighed 17.8 +/- 18 kg, 69% were ventilated, and 56% received procedural sedation. Success rate for TP-FT placement was 63/71 insertions (88.7%) in an average of 7.43 +/- 6.85 mins (median, 5 mins; range, <1-45 mins); of 38 patients, 36 had a successful TP- FT (95%). Insertion was well tolerated. Of the successful TP-FTs, on day 1 (n = 63) the FT was in distal duodenum or jejunum in 51% and by days 3-5 (n = 51), this increased to 75%. CONCLUSIONS: Bedside placement of a TP-FT with this technique is simple, rapid, well tolerated, and highly successful with little training. Immediate radiograph to confirm TP placement may not always be necessary. In our experience, this technique has obviated the need to search for another method to achieve a transpyloric feeding tube.

Journal Article↗
PubMed2000

Phase-field modeling of eutectic growth.

A phase-field model of eutectic growth is proposed in terms of a free energy F, which is a functional of a liquid-solid order parameter psi, and a conserved concentration field c. The model is shown to recover the important features of a eutectic phase diagram and to reduce to the standard sharp-interface formulation of nonequilibrium growth. It is successfully applied to the study of directional solidification when the solid phase is a single or two phase state. The crystallization of a eutectic compound under isothermal conditions is also considered. For that process, the transformed volume fraction and psi-field structure factor, both measured during numerical simulations, closely match theoretical predictions. Three possible growth mechanisms are also identified: diffusion-limited growth, lamellar growth, and spinodal decomposition.

Journal Article↗