A Lie algebra attached to a projective variety

Each choice of a K\"ahler class on a compact complex manifold defines an action of the Lie algebra \slt on its total complex cohomology. If a nonempty set of such K\"ahler classes is given, then we prove that the corresponding \slt-copies generate a semisimple Lie algebra. We investigate the formal properties of the resulting representation and we work things out explicitly in the case of complex tori, hyperk\"ahler manifolds and flag varieties. We pay special attention to the cases where this leads to a Jordan algebra structure or a graded Frobenius algebra.Comment: AMSTeX v2.1, 46 page

Localization of interleukin (IL) -4 but not IL-5 to human mast cell secretory granules by immunoelectron microscopy

Background Human mast cells synthesize and secrete many cytokines of relevance to the pathogenesis of allergic diseases such as asthma and rhinitis. In particular, interleukin (IL) ‐4 and IL‐5 are likely to play key roles in the development of the inflammatory response that characterizes these diseases. Immunohistochemical studies on human nasal and bronchial mucosal biopsies suggest that IL‐4 and IL‐5 may be stored preformed in mast cells. Objective To identify whether IL‐4 and IL‐5 are stored within mast cell secretory granules. Methods We used immunogold electron microscopic analysis on bronchial mucosa and lung parenchyma from resected lung specimens, and a nasal mucosal biopsy from a patient with active allergic rhinitis. Samples were fixed in 4% paraformaldehyde plus 0.5% glutaraldehyde and processed into Lowicryl K4M resin by the ‘Progressive Lowering of Temperature’ technique. Ultrathin sections were stained immunohistochemically by an indirect immunogold method. Results Immunoreactivity for IL‐4, but not IL‐5, was localized to the granules of mast cells in all tissue samples. IL‐5 was localized to the matrix of eosinophil granules in these samples, but neither cytokine was detected in T cells. IL‐4 immunoreactivity increased in the granules of mast cells 24 h after immunoglobulin (Ig) E‐dependent activation (mean 17.5 ± 1.4 gold particles per granule) compared with nonactivated mast cells (mean 6.8 ± 0.8 gold particles per granule, P < 0.001), suggesting replenishment of stores by newly generated protein. Immunoreactive IL‐5 remained undetectable in mast cells 24 h after activation, a time point at which they are known to secrete large quantities of this cytokine. Conclusion Human mast cells store IL‐4 within the matrix of their granules. Very few, if any, lung or nasal mast cells store IL‐5. A store of preformed IL‐4 within mast cell granules is likely to have an important influence during the initiation and maintenance of the allergic immunological response

Fetal exposure to intact immunoglobulin E occurs via the gastrointestinal tract

Background Consideration of the evolutionary significance of IgE might provide insight into the immunological interactions occurring in utero and during early post-natal life that regulate later atopic disease.Objective We postulated that the fetal gut is exposed to intact amniotic fluid IgE that might interact with local IgE receptors.Methods IgE levels in matched maternal blood and amniotic fluid (n = 47) or breast milk (n = 15) collected from pregnant women in the UK (Southampton) and Brazil (Sao Paulo) were studied. Expression of IgE receptors, FcRI and FcRII (CD23), in fetal gastrointestinal tract (n = 19) and skin (n = 11) was examined immunohistochemically.Results Human amniotic fluid at 16–18 weeks' gestation contained intact IgE at levels that increased as maternal circulating levels increased (Spearman's ? = 0.897; P < 0.001). Circulating IgE levels from women in Sao Paulo, Brazil, associated positively not only with term (> 37 weeks' gestation) amniotic fluid (? = 0.993; P < 0.001) but also breast milk IgE levels (? = 0.785; P = 0.001). Maternal levels of IgE did not change significantly over pregnancy and fetal circulating levels of IgE were very low (< 0.6 IU/mL). Low-affinity IgE receptors (CD23) were expressed in lymphoid follicles of the fetal gut from 16 weeks of gestation (6/8), but not from 11 to 16 weeks (0/11) or in the skin.Conclusion Amniotic fluid contains intact IgE that might bind to CD23+ cells within the lymphoid follicles of the fetal gastrointestinal tract. The evolutionary significance of these interactions might be to prepare the immune system for helminthic parasite exposure at birth via IgE-mediated antigen focusing, or 'education' of the developing immune system about the prevailing extrauterine environment. However, at present in societies where helminthosis is not a significant health issue, this pathway may still be operational and associated with the development of atopic disease

Inhaled heparin in cystic fibrosis

Cystic fibrosis (CF) is characterised by inspissated airway secretions and chronic endobronchial infection associated with exuberant neutrophilic inflammation. Unfractionated heparin may be mucolytic and has demonstrated a number of anti-inflammatory properties; however, further safety data are needed in these subjects who are at risk of airway bleeding. The current study aimed to assess the medium-term safety and tolerability of moderately high-dose inhaled heparin in CF adults and to explore possible in vivo mucolytic and anti-inflammatory outcomes. A randomised, double-blind, placebo-controlled crossover study of twice daily inhalation of 50,000 IU of heparin for 2 weeks was undertaken in CF adults, with a 1-week washout period. Eighteen subjects were randomised and 14 (mean±SD age 23±7.8 yrs and percentage-predicted forced expiratory volume in one second 52.1±15.56%) completed the study protocol. Heparin neither affected blood coagulation parameters nor resulted in any increase in adverse events. Heparin inhalation had no significant effect upon forced expiratory volume in one second, symptoms of sputum clearance or sputum inflammatory markers. The current pilot study demonstrated no evidence of improved sputum clearance with 50,000 IU of inhaled heparin given twice daily to adult cystic fibrosis subjects. However, inhaled heparin was safe and the future evaluation of larger doses over a longer period may be warranted

Epithelial expression and release of FGF-2 from heparan sulphate binding sites in bronchial tissue in asthma

Background: The most characteristic structural change evident in endobronchial biopsies in asthma, even in mild disease, is subepithelial collagen deposition within the lamina reticularis. This has been associated with progressive loss of lung function and the persistence of airway hyperresponsiveness, and has been linked to airway fibroblast proliferation. A potent fibroproliferative factor in bronchoalveolar lavage fluid in asthma is fibroblast growth factor-2 (FGF-2). FGF-2 is a member of a family of heparin binding growth factors that bind to heparan sulphate proteoglycans (HSPG), an important determinant of FGF-2 activity. This study compared the level of expression and distribution of FGF-2 in relation to HSPG in bronchial tissue from normal and asthmatic subjects.Methods: The distribution of FGF-2 and HSPG in intact and cleaved forms in endobronchial biopsies from normal and asthmatic subjects was examined using an immunohistochemical approach. A novel ELISA based method was developed to detect solubilisation of FGF-2 following addition of heparin and heparitinase to bronchial tissue slices.Results: Immunohistochemical analysis showed that FGF-2 was co-localised to HSPG in epithelial and endothelial basement membranes. Epithelial FGF-2, but not HSPG, was significantly more abundant in patients with mild asthma than in normal subjects. In vitro experiments indicated that FGF-2 was released from binding sites in the tissue by heparin and heparitinase I.Conclusions: FGF-2 is bound by HSPG in bronchial tissue. The mast cell, through the release of heparin and endoglycosidase, may make a unique contribution to tissue remodelling in allergic asthma

Perspective conducting HIV prevention research in South Africa.

Preliminary observations of the clinical efficacy of intravenous immunoglobulin in two patients with severe corticosteroid insensitive asthma are reported. In both patients treatment with intravenous immunoglobulin resulted in clinical improvement and enabled a significant reduction in the dose of prednisolone. In one of the patients fibreoptic bronchoscopy with endobronchial biopsies was performed and peripheral blood was analysed by flow cytometry before and after treatment. Immunohistological analysis of the biopsy samples after treatment showed a decrease in the number of all cell types, especially CD3+ T cells, CD4+ T cells, and activated CD25+ T lymphocytes, which was associated with a reduction in peripheral blood T cell activation. Intravenous immunoglobulin may be a valid option for the treatment of corticosteroid insensitive asthma. To elucidate the role and mode of action of intravenous immunoglobulin further studies in larger groups of patients are needed

Altered colonic mucosal availability of n-3 and n-6 polyunsaturated fatty acids in ulcerative colitis and the relationship to disease activity

Background and AimsThe polyunsaturated fatty acids (PUFA) arachidonic acid (AA, n-6) and eicosapentaenoic acid (EPA, n-3) are precursors of eicosanoids and other lipid mediators which have critical roles in inflammation. The mediators formed from the different PUFA have different potencies. We hypothesised that metabolic changes associated with colonic mucosal inflammation would modify the bioavailability of the eicosanoid precursors AA and EPA.MethodsColonic mucosa biopsies were obtained from patients with ulcerative colitis and from matched controls. Inflammation was graded endoscopically and histologically. Esterified and non-esterified fatty acids were determined within the biopsies using gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry, respectively.ResultsBiopsy samples were collected from 69 UC patients (54 providing both inflamed and non-inflamed mucosa) and 69 controls. Inflamed mucosa had higher AA (p < 0.001) and lower EPA (p < 0.010) contents and a higher AA:EPA ratio (p < 0.001). Inflamed mucosa also had higher docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) and lower linoleic acid (LA) and ?-linolenic acid (?-LNA) contents (all p < 0.001), compared to non-inflamed and controls. There were significant correlations between severity of inflammation and contents of AA, DPA and DHA (positive correlations) and of LA, ?-LNA and EPA (negative correlations).ConclusionsHigher AA, AA:EPA ratio, DPA and DHA and lower LA, ?-LNA and EPA are seen in inflamed mucosa in UC and correlate with severity of inflammation. This suggests an alteration in fatty acid metabolism in the inflamed gut mucosa, which may offer novel targets for intervention and should be considered if nutritional strategies are used

Critical analysis of the utility of initial pleural aspiration in the diagnosis and management of suspected malignant pleural effusion

Introduction Current guidelines recommend an initial pleural aspiration in the investigation and management of suspected malignant pleural effusions (MPEs) with the aim of establishing a diagnosis, identifying non-expansile lung (NEL) and, at times, providing a therapeutic procedure. A wealth of research has been published since the guidelines suggesting that results and outcomes from an aspiration may not always provide sufficient information to guide management. It is important to establish the validity of these findings in a 'real world' population. Methods A retrospective analysis was conducted of all patients who underwent pleural fluid (PF) sampling, in a single centre, over 3 years to determine the utility of the initial aspiration. Results A diagnosis of MPE was confirmed in 230/998 (23%) cases, a further 95/998 (9.5%) were presumed to represent MPE. Transudative biochemistry was found in 3% of cases of confirmed MPE. Positive PF cytology was only sufficient to guide management in 45/140 (32%) cases. Evidence of pleural thickening on CT was associated with both negative cytology (χ 2 1df=26.27, p<0.001) and insufficient samples (χ 2 1df=10.39, p=0.001). In NEL 44.4% of patients did not require further procedures after pleurodesis compared with 72.7% of those with expansile lung (χ 2 1df=5.49, p=0.019). In patients who required a combined diagnostic and therapeutic aspiration 106/113 (93.8%) required further pleural procedures. Conclusions An initial pleural aspiration does not achieve either definitive diagnosis or therapy in the majority of patients. A new pathway prioritising symptom management while reducing procedures should be considered.