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Biomedical subjects

J Legg

Publications and source records attributed to J Legg.

7 recordsLinked to original sources
PubMed2004

Epithelial inducible nitric oxide synthase activity is the major determinant of nitric oxide concentration in exhaled breath.

BACKGROUND: The fractional concentration of nitric oxide (NO) in exhaled breath (FeNO) is increased in asthma. There is a general assumption that NO synthase (NOS) 2 in epithelium is the main source of NO in exhaled breath. However, there is no direct evidence to support the assumption and data from animal models suggest that non-inducible NOS systems have important roles in determining airway reactivity, regulating inflammation, and might contribute significantly to NO measured in exhaled breath. METHODS: Bronchial epithelial cells were obtained from healthy, atopic, and asthmatic children by non-bronchoscopic brushing. Exhaled NO (FeNO) was measured directly using a fast response chemiluminescence NO analyser. RNA was extracted from the epithelial cells and real time polymerase chain reaction was used to determine the expression of NOS isoenzymes. NOS2 was examined in macrophages and epithelial cells by immunohistochemistry. RESULTS: NOS1 mRNA was not detectable. NOS3 mRNA was detected in 36 of 43 samples at lower levels than NOS2 mRNA which was detectable in all samples. The median FeNO was 15.5 ppb (95% CI 10 to 18.1). There was a significant correlation between FeNO and NOS2 expression (R = 0.672, p<0.001). All epithelial cells exhibited NOS2 staining, whereas staining in the macrophages was variable and not related to phenotype. CONCLUSIONS: Only NOS2 expression was associated with FeNO in respiratory epithelial cells obtained from children (R = 0.672; p<0.001). This suggests that FeNO variability is largely determined by epithelial NOS2 expression with little contribution from other isoforms.

Adolescent↗
PubMed2001

The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44.

The neurofibromatosis-2 (NF2) gene encodes merlin, an ezrin-radixin-moesin-(ERM)-related protein that functions as a tumor suppressor. We found that merlin mediates contact inhibition of growth through signals from the extracellular matrix. At high cell density, merlin becomes hypo-phosphorylated and inhibits cell growth in response to hyaluronate (HA), a mucopolysaccharide that surrounds cells. Merlin's growth-inhibitory activity depends on specific interaction with the cytoplasmic tail of CD44, a transmembrane HA receptor. At low cell density, merlin is phosphorylated, growth permissive, and exists in a complex with ezrin, moesin, and CD44. These data indicate that merlin and CD44 form a molecular switch that specifies cell growth arrest or proliferation.

3T3 Cells↗
PubMed2000

Asthma--the changing face of drug therapy.

Until the recent introduction of long acting beta 2-agonists and the leukotriene antagonists, the drug treatment of asthma had remained largely unchanged for a quarter century. Recent studies have demonstrated the efficacy of the long acting beta 2-agonists in the management of asthma in children and highlighted their value as an adjunct to inhaled corticosteroids. The leukotriene antagonists are an important new class of drug therapy which target a specific area of asthma pathogenesis. Whilst they have been shown to be effective for asthma, their exact role in the clinical situation remains to be established. Recent guidelines have emphasised the important role of inflammation in persistent asthma and recommended the early institution of anti-inflammatory treatment. Many patients remain uncontrolled despite high doses of anti-inflammatory agents including oral corticosteroids. Recent experience with other immunomodulatory agents such as cyclosporin, methotrexate and intravenous immunoglobulin has highlighed their potential as steroid sparing agents. With improved understanding of asthma pathogenesis the potential for specific targeted therapies has become evident. Monoclonal antibodies to IgE and certain cytokines are being investigated as possible treatments for asthma. Similarly, preliminary studies of selective phosphodiesterase inhibitors in asthmatic individuals have been encouraging. Other potential therapies include platelet-activating factor receptor antagonists, tryptase inhibitors and prostaglandin E analogs. The continued development of such targeted treatments should ensure a greater diversity of therapeutic options for the management of asthma in the new millennium.

Adrenergic beta-Agonists↗
PubMed1998

Discrete domains within the hyaluronan receptor CD44 regulate membrane localization and cell migration.

CD44 is the principle transmembrane receptor for the extracellular matrix glycosaminoglycan, hyaluronan. This receptor: ligand interaction is required for many normal cellular processes including lymphocyte homing into inflammatory sites, assembly of a pericellular matrix during chondrogenesis, wound healing and tissue morphogenesis during development. In order to mediate these diverse events, CD44 expressing cells must be able to regulate, and respond to, interactions with hyaluronan. The mechanisms responsible have been subject to scrutiny over the past few years as it has become clear that their disruption can underlie the progression of both metastatic tumours and chronic inflammatory diseases. Here we describe recent data identifying discrete regions within the transmembrane and cytoplasmic domains of CD44 which regulate this important adhesion receptor.

Animals↗
PubMed1982

Vulnerability of the self: barrier and penetration scores of depressed patients.

Brief Psychiatric Rating Scale measures and percentage of Barrier and Penetration responses on the Holtzman Inkblot Technique were used as indicators of vulnerability of the self during a depressive episode. Sixty-three depressed inpatients grouped according to diagnostic categories and depressive subtypes were evaluated prior to and after three weeks of treatment, and compared with twenty-one normal controls. Patients differed from normals initially and improved on rating measures of severity of illness and depression. Barrier scores did not reflect difference or improvement and, contrary to the predicted vulnerability theory, normals had higher penetration scores than the patients. Results were discussed in terms of vulnerability being a potential sign of emotional responsiveness rather than pathology.

Adolescent↗