1,720,967 research outputs found
Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies
No full textAim: The value of immunohistochemical staining in differentiating between malignant mesothelioma and pulmonary adenocarcinoma was re-examined using newly available commercial antibodies, with the aim of increasing the sensitivity and specificity of diagnosis, and simplifying the antibody panel required. Methods: Forty one malignant mesotheliomas and 35 lung adenocarcinomas were studied. Commercial antibodies to calretinin, E-cadherin, N-cadherin, surfactant apoprotein A (SP-A), thyroid transcription factor 1 (TTF-1), thrombomodulin, and cytokeratin 5/6 were applied using the streptavidin–biotin–peroxidase complex procedure on formalin fixed, paraffin wax embedded tissue. Results: E-cadherin was expressed in all adenocarcinomas and in 22% of the mesotheliomas. TTF-1 expression was detected in 69% of the adenocarcinomas and none of the mesotheliomas. Positive staining with polyclonal anticalretinin was detected in 80% of the mesotheliomas and 6% of the adenocarcinomas. N-cadherin was expressed in 78% of mesotheliomas and 26% of adenocarcinomas. Thrombomodulin was expressed in 6% of the adenocarcinomas and in 53% of the mesotheliomas. Cytokeratin 5/6 expression was detected in 6% of the adenocarcinomas and 63% of the mesotheliomas. The results were compared with the standard laboratory panel for mesothelioma diagnosis: anticarcinoembryonic antigen (anti-CEA), LeuM1, BerEP4, and HBME-1. Conclusion: Of the antibodies used in this study, E-cadherin was 100% sensitive for pulmonary adenocarcinoma and TTF-1 was 100% specific for pulmonary adenocarcinoma. The application of these two antibodies alone was adequate for the diagnosis of 69% of adenocarcinomas and 78% of mesotheliomas. Where TTF-1 is negative and E-cadherin is positive, a secondary panel of antibodies, including BerEP4 and LeuM1 (CD15) and antibodies directed against CEA, calretinin, cytokeratin 5/6, thrombomodulin, and N-cadherin, is required for differentiation between malignant mesothelioma and pulmonary adenocarcinoma
Asthma deaths; persistent and preventable mortality
No full textBronchial asthma remains a significant cause of mortality at all ages, despite the increased understanding of its pathogenesis and the range of drugs available for its treatment. Changes in therapeutic management can influence death rates and constant surveillance, combined with high-quality post mortem investigations, is essential. Disease severity, poor disease management and adverse psychosocial circumstances are all risk factors for asthma mortality. Bronchial asthma causes characteristic histological changes in the mucosa of the airways which are present even before the clinical diagnosis of asthma can be made. These include fibrous thickening of the lamina reticularis of the epithelial basement membrane, smooth muscle hypertrophy and hyperplasia, increased mucosal vascularity and an eosinophil-rich inflammatory cell infiltrate. In addition, mucoid plugging of the airway lumen is frequently associated with fatal asthma. The recognition of these changes can allow the diagnosis of asthma to be made for the first time at autopsy, in those cases where asthma goes undiagnosed in life. Acute severe asthma may be accompanied by pneumothorax and surgical emphysema of the mediastinum. Disorders which may mimic asthma include pulmonary embolism, chronic obstructive pulmonary disease and anaphylaxis, but careful post mortem examination and appropriate investigations should reveal the true cause of death
Cadherins, catenins and APC in pleural malignant mesothelioma
No full textMalignant mesothelioma is an aggressive disease of the pleura, and less commonly the peritoneum, with a very poor prognosis. The present study has examined the expression of cell adhesion molecules including cadherins, catenins, and APC in order to determine whether abnormal expression of components of the Wnt signalling pathway contribute to the variable phenotype of malignant mesothelioma. Sixty-three malignant mesotheliomas and nine cases of reactive mesothelial hyperplasia were analysed by immunohistochemistry for E-cadherin, N-cadherin, ?-catenin, ?-catenin, and the C- and N-terminals of APC. In addition, DNA was extracted from formalin-fixed, paraffin wax blocks, and a 226 bp fragment of exon 3 of the -catenin gene was amplified, sequenced, and screened for activating mutations in the glycogen synthase kinase 3? (GSK-3?) phosphorylation targets. E-cadherin expression was detected in 48% of the epithelioid mesotheliomas but was observed in only 7% of sarcomatoid mesotheliomas. N-cadherin, ?-catenin, ?-catenin, and the C- and N-terminals of APC did not show differential expression between the mesothelioma phenotypes. Abnormal nuclear localization of -catenin was demonstrated in 19% of mesotheliomas. Mutations of ?-catenin phosphorylation sites were not detected in any of the 62 mesotheliomas examined. Positive staining for the N-terminal of APC was seen in all of the cases of reactive mesothelial hyperplasia, as well as in all the mesotheliomas. Staining for the C-terminal of APC was negative in 23% mesotheliomas, despite being present in all the cases of reactive hyperplasia. The present study provides the first evidence that ?-catenin accumulates in the nucleus in malignant mesotheliomas. In addition, APC expression was altered in some mesotheliomas, suggesting that a truncated APC gene product may contribute to abnormal Wnt signalling and dysregulation of cell proliferation in malignant mesothelioma
Airway inflammation and atopic asthma: a comparative bronchoscopic investigation
No full textFlexible fibre-optic bronchoscopy under local anaesthesia has been used to investigate the cellular airway events in atopic asthma. The findings have been compared to those from atopic individuals without asthma and non-atopic healthy controls, in an attempt to discern those changes relevant to clinical disease expression. Immunohistochemical and electron-microscopic analyses of airway biopsies identified that an atopic diathesis is associated with tissue eosinophil infiltration and mast cell degranulation. The eosinophilia was greatest in those atopic individuals with asthma. Flow-cytometric analysis of airway lavage revealed significantly enhanced T lymphocyte activation in clinical asthma. These findings are consistent with the hypothesis that T lymphocyte activation, through cytokine release, amplifies the tissue eosinophilia in asthma and that this combination is associated with clinical disease expression
Bronchial mucosal manifestations of atopy: a comparison of markers of inflammation between atopic asthmatics, atopic nonasthmatics and healthy controls
No full textWe studied the role of atopy, as defined by positive skin tests to common inhalant allergens, in allergic bronchial inflammation. Endobronchial biopsies were taken via the fibreoptic bronchoscope in 13 symptomatic atopic asthmatics, 10 atopic nonasthmatics, and 7 normals. The numbers of mast cells, identified in the submucosa by immunohistochemistry using the AA1 monoclonal antibody against tryptase, were no different between the three groups, but electron microscopy showed that mast cell degranulation, although less marked in atopic nonasthmatics, was a feature of atopy in general. The numbers of eosinophils, identified by immunohistochemical staining using the monoclonal anti-eosinophil cationic protein antibody, EG2, were greatest in the asthmatics, low or absent in the normals and intermediate in the atopic nonasthmatics. In both atopic groups eosinophils showed ultrastructural features of degranulation. Measurements of subepithelial basement membrane thickness on electron micrographs showed that the collagen layer was thickest in the asthmatics, intermediate in the atopic nonasthmatics and thinnest in the normals. The results suggest that airways eosinophilia and degranulation of eosinophils and mast cells, as well as increased subepithelial collagen deposition, are a feature of atopy in general and suggest that the degree of change may determine the clinical expression of this immune disorder
Quantitation of mast cells and eosinophils in the bronchial mucosa of symptomatic atopic asthmatics and healthy control subjects using immunohistochemistry
No full textWe have used fiberoptic bronchoscopy to obtain endobronchial biopsies in which mast cells and eosinophils were enumerated using monoclonal antibodies directed against mast cell tryptase (AA1) and the eosinophil cationic protein (EG2). Eleven symptomatic atopic asthmatics treated with beta 2-agonists alone and six normal subjects were studied. Over a period of 2 wk prior to bronchoscopy, patients recorded asthma symptom scores, bronchodilator usage, and twice-daily peak expiratory flow. Five days before bronchoscopy, methacholine responsiveness was assessed. Two biopsies were taken from the subcarinae, one of which was processed into araldite for immunostaining by the streptavidin biotin immunoperoxidase method and the other into Spurr resin for electron microscopy. The number of AA1 staining mast cells present in the bronchial mucosa was not significantly different in the epithelium or submucosa between the asthmatic and the normal subjects. However, in the biopsies from asthmatics, there were significantly greater numbers of EG2-staining eosinophils in the epithelium (median, 1.2/mm versus zero; p less than 0.005) and in the submucosa (median, 50/mm2 versus 1/mm2; p less than 0.001). Electron microscopy showed morphologic features of mast cell and eosinophil degranulation in the asthmatics. No correlation could be established between mast cell or eosinophil numbers and indices of disease activity of PC20 methacholine, which points to the complexity of mechanisms responsible for the symptoms and the airway hyperresponsiveness of asthma
Markers of eosinophilic inflammation and tissue re-modelling in children before clinically diagnosed bronchial asthma
No full textChronic inflammatory changes in the bronchial mucosa have been well documented in patients with established asthma. Much less is known of the changes, which occur in the airways of children early in the evolution of their disease with most of the information based on indirect markers of inflammation only. We evaluated markers of inflammation and tissue re-modelling in bronchial biopsies from children with early respiratory symptoms before a clear clinical diagnosis of bronchial asthma could be made. We examined bronchial biopsies performed in 27 children between the ages of 1.2 and 11.7 yr who were bronchoscoped for a clinical indication because of recurrent or chronic respiratory symptoms. The patients were re-evaluated 22–80 months after the original bronchoscopy to determine whether or not they had subsequently developed bronchial asthma. There were more eosinophils in the bronchial mucosa (129.4 vs. 19.1 cells/mm² of lamina propria, p < 0.001) and the thickness of the subepithelial lamina reticularis was greater (4.65 vs. 3.72 ?m, p = 0.044) in children with bronchial asthma diagnosed at follow-up, compared with the children who did not progress to asthma. Eosinophilic inflammation and airway re-modelling occur early in the natural history of bronchial asthma and are present even before asthma would be diagnosed based on clinical symptoms. Recognition of these changes and their significance for clinical disease should emphasize the need for timely detection and diagnosis of asthma in children to facilitate the early introduction of anti-asthma therapy
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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