Search PubMed⌕ Search

Biomedical subjects

J Fletcher

Publications and source records attributed to J Fletcher.

At least 127 records · Page 7Linked to original sources
PubMed1996

Invasion of tissue culture cells by diarrhoeagenic strains of Escherichia coli which lack the enteroinvasive inv gene.

Invasive Escherichia coli strains of certain serotypes invade by the same mechanism as the Shigella sp. It has been proposed that invasion of epithelial cells by EPEC strains may also occur; this is a previously overlooked property. In the present study E. coli strains isolated from patients with diarrhoea or ulcerative colitis, lacking the inv plasmid mediating classical invasion, but hybridizing with probes for different adhesins, were analyzed for their ability to invade HeLa and Caco-2 cells. The majority of strains invaded Caco-2 cells to a higher extent than HeLa cells. Adhesion to Caco-2 cells was a prerequisite for subsequent invasion of the cells but EAF, eae, EAgg and other known virulence factors were not sufficient to mediate invasion. In 8/9 E. coli strains invasion was enhanced after growth under iron restriction. Growth during anaerobic conditions did not influence subsequent invasion by E. coli strains whereas 6/9 strains had their invasive ability significantly decreased after growth in the presence of 1% glucose. The invasive process was inhibited by mannose but not by lactose, fucose or galactose. Our data indicate that strains of E. coli may invade Caco-2 cells by novel mechanisms which require adhesion to the cells but which differ from those of Salmonella sp., Yersinia sp., Shigella sp. and classical enteroinvasive E. coli.

Adhesins, Bacterial↗
PubMed1996

Hydrogen peroxide generation by polymorphonuclear leukocytes exposed to peritoneal dialysis effluent.

In the presence of peritoneal dialysis effluent (PDE), human polymorphonuclear leukocytes (PMN) showed reduced production of hydrogen peroxide and hypochlorous acid (H2O2 and HOCl, respectively) when at rest and when stimulated with both soluble (formylmethionyl-leucyl-phenylalanine and phorbol myristate acetate) and particulate (Staphylococcus epidermidis) agonists. This effect occurred in a concentration-dependent manner between 0 and 70%. (vol/vol) dialysis effluent. The inhibition of H2O2 and HOCl observed in resting, formy-methionylleucyphenyalanine-stimulated, and S. epidermidis-stimulated PMN was confined to a low-molecular-mass (< 10,000-Da) fraction of PDE, whereas the inhibition of the PMA response was equally dispersed throughout both low (< 10,000-Da)- and high-molecular-mass (> 10,000-Da) fractions. Human serum albumin, a major component of PDE, also inhibited H2O2 and HOCl production by PMN; however, results from cell-free systems suggested that human serum albumin was not wholly responsible for the inhibition of PMN function seen with PDE. The solute(s) responsible did not affect myloperoxidase but very rapidly scavenged H2O2 and HOCl. These data suggest that the factors capable of affecting H2O2 and HOCl production by PMN accumulate in uremia and are removed from the circulation into dialysis effluent.

Ascitic Fluid↗
PubMed1996

Day surgery and community health services work load: a descriptive study.

This prospective descriptive study of primary health care workload in the five days after day surgery is based on a questionnaire to patients who received day surgery in a specialist unit in Oxford. Half of all patients received health care, the mean consultation time was 16 minutes, and half the consultations were within two days of surgery.

Ambulatory Surgical Procedures↗
PubMed1995

The effect of pregnancy on polymorphonuclear leukocyte function.

Pregnancy exerts suppressive effects on a number of chronic inflammatory conditions, particularly rheumatoid arthritis. We isolated peripheral blood polymorphonuclear leukocytes (PMN) from pregnant women at 30 to 34 wk (n = 34) and showed significant reductions in respiratory burst activity compared with nonpregnant controls (n = 34), as determined by lucigenin-enhanced chemiluminescence (LUCL). Responses to FMLP were reduced by 54% (p = 0.0046) and to zymosan-activated serum (ZAS) by 69% (p = 0.0043). Following LUCL responses to these agonists in women throughout the course of their pregnancy (n = 7) revealed significantly reduced responses by the second and third trimesters (p < 0.005). Intracellular H2O2 production in PMN at 30 to 34 wk gestation was significantly reduced (p = 0.0454) in response to FMLP, compared with the nonpregnant controls. Investigation of adhesion molecule expression revealed no differences in CD11b or CD18. However, loss of CD62L from the PMN surface in response to FMLP and ZAS was significantly reduced at 30 to 34 wk, as compared with controls (FMLP, p = 0.049; ZAS, p = 0.01; n = 34). There were no significant differences in cell surface formyl peptide receptor expression, although there were statistical differences in LUCL responses to all concentrations of FMLP used (p < 0.05). Incubating PMN with TNF, IL-8, and granulocyte-macrophage CSF increased formyl peptide receptor expression but revealed no differences between the two groups. Priming of pregnancy PMN with the same cytokines gave significantly reduced LUCL when cells were subsequently stimulated with FMLP (p < 0.05; n = 6). Our results show a reduction in PMN NADPH-oxidase activity during pregnancy and may offer a partial explanation for the remission of symptoms observed in rheumatoid arthritis.

Adolescent↗
PubMed1995

Farnesyltransferase inhibitors block the neurofibromatosis type I (NF1) malignant phenotype.

Neurofibromatosis type I (NF1) is a hereditary tumor and developmental disorder whose defective gene was cloned previously. The protein product of the NF1 gene, neurofibromin, contains a domain that shows significant sequence homology to the known catalytic domains of mammalian Ras GTPase-activating proteins (GAP) and the yeast IRA1 and IRA2 proteins. This homologous region of neurofibromin has been shown to exhibit GAP activity toward Ras proteins. Malignant schwannoma cell lines from NF1 patients contain normal levels of GAP and nonmutated Ras proteins but barely detectable levels of neurofibromin, based on genetic mutations in the NF1 gene. Because these cells contain constitutively activated Ras.GTP, it has been proposed that neurofibromin may be the sole negative regulator of Ras in these cells. Overall, these results have implied an important role of the Ras signaling pathway in NF1 malignant schwannomas. Recently, several laboratories have developed small molecule inhibitors of Ras function that inhibit the enzyme farnesyltransferase (FT). FT-mediated post-translational farnesylation of Ras proteins is absolutely necessary for Ras function since this modification is required for the anchoring of Ras proteins to the plasma cell membrane. Although previous studies have shown that FT inhibitors can block the growth of tumor cells carrying mutant Ras proteins, it remained unclear how this class of inhibitors would affect tumor cells such as in NF1, whose malignant growth appears to be mediated by up-regulation of wild-type Ras activity. Thus, in the current study, we investigated whether BMS-186511, a bisubstrate analogue inhibitor of FT, would inhibit the malignant growth properties of a cell line established from malignant schwannoma of an NF1 patient. Our results indicate that the malignant growth properties of ST88-14 cells, the most malignant cell line among several well-characterized NF1 cells, are inhibited by BMS-186511 in a concentration-dependent manner. Following treatment with BMS-186511, ST88-14 cells became flat, nonrefractile, were contact-inhibited, and lost their ability to grow in soft agar. In the drug-exposed cells, Ras proteins were prevented from FT-mediated membrane association. BMS-186511 was found to specifically inhibit FT, but not geranylgeranyltransferase I, a closely related enzyme. Thus, it is conceivable that FT inhibitors may ultimately become the first generation of drugs against the malignant phenotype in NF1 based on rational insights into the mechanism of action of neurofibromin.

Alkyl and Aryl Transferases↗
PubMed1995

Using decision analysis to compare policies for antenatal screening for Down's syndrome.

OBJECTIVE: To compare different screening policies for Down's syndrome across a broad range of outcomes, using decision analysis, with particular reference to the role of maternal serum testing. DESIGN: A decision tree was used to combine data from local sources and the medical literature to predict the likely frequency of several outcomes. Sensitivity analyses were used to test the robustness of the conclusions drawn. SETTING: Oxfordshire Health Authority. MAIN OUTCOME MEASURES: Live births with and without Down's syndrome; miscarriages with Down's syndrome; cases of Down's syndrome detected antenatally; amniocenteses performed (and associated miscarriages); direct NHS screening costs; number of women offered screening. RESULTS: Screening policies for Down's syndrome that include serum testing can produce better population outcomes than programmes that do not. Each option for screening for Down's syndrome that we considered had significant drawbacks. In Oxfordshire, offering serum testing to women of all ages would prevent the birth of approximately one more baby with Down's syndrome per year than would a policy of screening for women aged 30 years or more. The cost of preventing this one extra Down's birth would be one or two normal babies lost after amniocentesis, 4500 blood tests for young women (with the associated anxiety and counselling), approximately 200 false positive serum test results and amniocenteses (with the associated anxiety and distress), and 90,000 pounds for the extra tests, counselling, and amniocenteses. Opinions are divided as to which policy is the better option for the population. CONCLUSIONS: Decision analysis is a useful tool for determining the likely consequences of different policy options across a broad range of outcomes. This focuses debate and decision making on outcomes of care, which in turn makes it clear that the choice of screening programme for Down's syndrome depends on the relative importance ascribed to the different outcomes. If individuals' values vary widely it may be impossible to find one screening policy that meets the needs of all pregnant women.

Adult↗
PubMed1995

Agency registered nurse use of medical equipment: an Australian perspective.

This cross-sectional survey explored how and what 142 registered nurses working for a nursing agency in a large South Australian city initially learn about the medical devices they use in direct patient care, as well as the consequences of device use both for patients and staff. The most frequently identified method of initial learning was reading the user/instruction manual. Furthermore, 87.1% of respondents indicated they had received instruction from another staff member on their units, typically another registered nurse. At least 90% of participants indicated they initially learned the purpose of the device and how to operate it. Medical device use caused 39.4% of registered nurses to feel stress. Only 10% indicated that they had used a medical device that had harmed a patient.

Adult↗
PubMed1995

Medical device education among Australian registered nurses. A comparison of agency and hospital nurses.

A cross-sectional survey was used to compare the medical device education of 142 agency- and 443 hospital-employed Australian registered nurses. The two groups differed significantly on descriptive characteristics and on what they had learned about medical devices. Potential negative aspects of device use were nurse stress and patient harm, with a significantly larger proportion of hospital nurses indicating their use of any medical device had made them feel stress. Fear of harming the patient and being unsure of how to use the device caused stress in the majority of nurses. The incidence of patient harm was approximately 10% for each group.

Adult↗
PubMed1995

Progression from Goodpasture's disease to membranous glomerulonephritis.

An unusual case of a patient with Goodpasture's disease presenting with hemoptysis, severe iron deficiency anemia and microscopic hematuria and proteinuria is described. Both circulating and tissue anti-glomerular basement membrane (GBM) antibodies were present, and renal function remained normal throughout. Immunosuppressive therapy was given for subclinical pulmonary hemorrhage with successful resolution of anemia and disappearance of the circulating anti-GBM antibody. Nine months after presentation he developed nephrotic range proteinuria and a repeat renal biopsy revealed membranous glomerulonephritis with no evidence of his original disease. Both the Goodpasture's associated HLA-DR2 and the membranous associated HLA-DR3 class II antigens were present. The association of antibody mediated and immune complex glomerulonephritis is discussed. The simultaneous presence of HLA-DR2 and HLA-DR3 may predispose to this association.

Adult↗
PubMed1995

Aniridia-associated cytogenetic rearrangements suggest that a position effect may cause the mutant phenotype.

Current evidence suggests that aniridia (absence of iris) is caused by loss of function of one copy of the PAX6 gene, which maps to 11p13. We present the further characterisation of two aniridia pedigrees in which the disease segregates with chromosomal rearrangements which involve 11p13 but do not disrupt the PAX6 gene. We have isolated three human YAC clones which encompass the PAX6 locus and we have used these to show that in both cases the chromosomal breakpoint is at least 85 kb distal of the 3' end of PAX6. In addition, the open reading frame of PAX6 is apparently free of mutations. We propose that the PAX6 gene on the rearranged chromosome 11 is in an inappropriate chromatin environment for normal expression and therefore that a 'position effect' is the underlying mechanism of disease in these families.

Aniridia↗
PubMed1995

Molecular defect of a phosphoglycerate kinase variant associated with haemolytic anaemia and neurological disorders in a large kindred.

The X-chromosome-linked phosphoglycerate kinase (PGK) deficiency associated with severe chronic and acute haemolytic anaemia and mental disorders was first described in a large Chinese kindred in 1969. The molecular abnormality of this original variant remained to be identified. The red cell PGK activity was only about 5%, but the activity of the patients' lymphoblastoid cells was about 15% of normal. The PGK mRNA content of the patients' lymphoblastoid cells were normal. Analysis of the patients' mRNA showed the existence of a nucleotide transversion A-->T at position 491 (counting from adenine of the initiation codon). The mutation should cause an amino acid substitution Asp-->Val at position 163 of the enzyme. The replacement of the acidic aspartic acid by a hydrophobic valine is expected to induce drastic structural instability resulting in severe enzyme deficiency in the patients' tissues. The genotypes of two affected males, their mothers and 22 females of the family were identified by the PCR-mediated method using their genomic DNA samples. 13/24 females examined were found to be variant heterozygous. In this large family, affected males over three generations have died at a pre-adult age. Post- and pre-natal genotyping of the family members may prevent future problems.

Anemia, Hemolytic, Congenital↗
PubMed1995

Snakes and ladders: the immediate future of nurse education?

This paper considers the recent increase in proposals to merge colleges of nursing and midwifery with higher education institutions. It reviews the differing natures of proposed mergers. It considers some major challenges posed by such mergers: the academic, the cultural, the professional, personal and identity, and the epistomological. It reflects on some ways in which these challenges might be met by the application of management theory, and enlightened practice. It concludes by suggesting that the opportunities afforded colleges by individual mergers are so divergent as to risk fragmenting nurse education within the higher education sector, rather than uniting it into a coherent whole, and compromising the development of nursing, midwifery and health visiting as learned practice professions.

Education, Nursing, Baccalaureate↗
PubMed1995

Excavating health care policy: are league tables likely to dig out the truth about hospital performance or dig it in?

This paper considers the extent to which the publication of performance data on aspects of activity within the health service illuminates, or inhibits, judgments as to its effectiveness. In order to set the question of league tables into a wider perspective their use in relation to schools, and the impact of that initiative, is considered first. Research is shown to be sceptical as to the degree to which performance data can act as a proxy for institutional effectiveness. Misgivings centre around the criteria that determine, and the adequacy of the definition of, effectiveness together with concerns that the debate is at heart a political, not a professional one. In considering the question of the publication of performance data in the health service the same three issues, concerning the criteria determining, the definition of, and the politics of, effectiveness are applied. It is concluded that a case exists for the publication of data concerning institutions funded by the taxpayer, provided the information published does concentrate on institutional effectiveness, rather than serving as an attack on professional groups or as a distraction from concern about levels of expenditure.

Education↗