Search PubMed⌕ Search

Biomedical subjects

M N Sheppard

Publications and source records attributed to M N Sheppard.

At least 91 records · Page 5Linked to original sources
PubMed1992

Distribution of the cytoskeletal protein beta-tubulin in normal lung, cryptogenic fibrosing alveolitis and lung tumours.

Tubulin is the major protein of microtubules. The immunocytochemical distribution of tubulin within the human respiratory tract has not been investigated in detail and no analysis of diseased lung or lung tumours has been undertaken. We therefore studied the distribution of beta-tubulin in formalin-fixed normal lung (n = 6), cryptogenic fibrosing alveolitis (n = 10) and lung tumours (n = 66), using a monoclonal antibody to beta-tubulin. In normal lung positive immunostaining was observed in all ciliated epithelium from the trachea down to bronchiolar level; blood vessel endothelium, vascular smooth muscle and nerve bundles were also strongly positive; pneumocytes, cartilage and airway smooth muscle gave weak staining. A similar distribution of beta-tubulin was seen in cryptogenic fibrosing alveolitis, but with strong tubulin immunostaining of fibroblasts in the interstitium and of the cytoplasm of ciliated respiratory epithelial cells. In lung tumours, six of 17 (35%) adenocarcinomas, one of two adenosquamous and one of 17 (5%) squamous cell carcinomas gave strong immunostaining. All six large cell carcinomas gave strong immunostaining for tubulin. In neuroendocrine tumours, two of seven (28%) carcinoids, two of seven (28%) atypical carcinoids and seven of 10 (70%) small cell carcinomas were strongly positive for tubulin. beta-Tubulin is widely distributed in the normal and diseased respiratory tract and is found in many lung tumours, particularly in large cell and small cell carcinomas which are highly aggressive in behaviour.

Humans↗
PubMed1992

Symptomatic cysts in otherwise normal lungs of children and adults.

The clinical and pathological features of 28 lung cysts resected in the period 1980-1989, excluding those from patients with emphysema elsewhere in their lungs, have been reviewed. In 12 children aged 8 days to 17 years, five cysts were congenital adenomatoid malformations, three were bronchogenic cysts, two were intralobar sequestrations, one was a cystic haemangioma and one resembled the cysts excised from 16 adult patients. This latter group ranged in age from 20 to 62 years and included 11 cigarette smokers and five asthmatics. Twelve of these cysts were intralobar and four were attached by a pedicle to the pleural surface of the lung. All these cysts had a fibromuscular wall showing varying degrees of acute and chronic inflammation. The presence of at least a partial lining of epithelial cells in all the cysts was confirmed using an immunocytochemical marker. The surrounding lung did not show any significant pathology. These cysts are labelled as simple fibromuscular pulmonary cysts. In the childhood cases, a congenital cause could be established in the majority. The pathogenesis of the adult cysts remains unclear. The presence of inflammation in the cyst walls does not necessarily suggest a role for infection, as secondary infection of cysts cannot be ruled out. An aetiological role for local damage due to cigarette smoking or asthma must be taken into consideration.

Adolescent↗
PubMed1992

New perspectives on basic mechanisms in lung disease. 1. Lung injury, inflammatory mediators, and fibroblast activation in fibrosing alveolitis.

It is over 25 years since Scadding first defined the term fibrosing alveolitis. It has since been established that complex mechanisms underlie its pathogenesis, including epithelial and endothelial injury, vascular leakage, production of inflammatory cells and their mediators, and fibroblast activation. Only through a detailed knowledge of how these cellular and molecular events are interlinked will we learn how to combat this disease, which is notoriously resistant to present treatments. So far the only therapeutic advances have been refinements in immunosuppression, and even these treatments are frequently disappointing. We believe that future advances in treatment will come from the development of agents that protect endothelial and epithelial cells from further injury and agents that can inhibit release of inflammatory mediators. A better knowledge of the mechanisms of collagen gene activation and the biochemical pathways of collagen production may also allow the identification of vulnerable sites at which new treatments may be directed. A combined approach to modifying appropriate parts of both the inflammatory component and the fibroblast/collagen component should provide a new stimulus to research. Further epidemiological studies are also needed to identify the environmental causes of lung injury that initiate the cascade of events leading to interstitial fibrosis.

Collagen↗
PubMed1992

Primary leiomyoma of the pulmonary vein.

The first case of a primary leiomyoma in a pulmonary vein in an adult is presented. Although rare, leiomyoma and leiomyosarcoma of the lung and great vessels should be included in the differential diagnosis of intrathoracic space occupying lesions.

Female↗
PubMed1991

Localization of beta 2-adrenoceptor messenger RNA in human and rat lung using in situ hybridization: correlation with receptor autoradiography.

We have used in situ hybridization to study the localization of mRNA encoding the beta 2-adrenoceptor in tissue sections of the human and rat lung and compared this with the distribution of beta 2-receptor binding sites using receptor autoradiography. To localize beta 2-receptor mRNA, a [32P]labeled antisense RNA probe (riboprobe) was generated from human or rat beta 2-receptor cDNA. A similar distribution of beta 2-receptor mRNA was identified in both species. The highest intensity of beta 2-receptor mRNA was detected in smooth muscle of small airways, airway epithelium and pulmonary blood vessels. Lower intensity of beta 2-receptor mRNA was identified in smooth muscle of large airways, and alveolar epithelium (presumably type I and type II pneumocytes). No significant hybridization signal was detected in interstitial tissue. The specificity of the hybridization signal was confirmed with a sense probe (having identical sequence to the mRNA) and preincubation with RNase A, and by Northern blot analysis which revealed a single band of mRNA of 2.2 kb. There was a correspondence between mRNA localization and the distribution of beta 2-receptors visualized by [125I]iodocyanopindolol autoradiographically in the presence of CGP 20712 (a beta 1-selective antagonist). However, alveolar walls that showed a high beta 2-receptor density had relatively low levels of mRNA. This cellular heterogeneity may reflect differences in RNA stability or transcription rate in different lung cells. This approach opens up new options in the investigation of the regulation of pulmonary beta 2-receptor gene expression in health and disease.

Animals↗
PubMed1991

Expression of chromogranin A mRNA in small cell carcinoma of the lung.

Chromogranin A (CgA) is the most specific neuroendocrine marker but in small cell carcinoma of the lung (SCCL) CgA immunoreactivity cannot always be detected, possibly owing to poor granularity. The localization of CgA mRNA could be a more useful indicator of CgA synthesis in SCCL. We have therefore studied the expression of CgA mRNA in SCCL, using in situ hybridization and Northern blot analysis, comparing it with CgA immunoreactivity. The expression of CgA mRNA and immunoreactivity in other types of lung tumours was also investigated. Freshly fixed, surgically resected SCCL (n = 5), adenocarcinoma (n = 10), squamous cell carcinoma (n = 10), large cell carcinoma (n = 5), and primary lymphoma (n = 2) were examined. Weak immunoreactivity to CgA was seen in one SCCL but all five strongly expressed CgA mRNA. The specificity of the in situ hybridization signal and the probe was confirmed by the use of a sense probe and Northern blot analysis. Non-SCCLs were negative for both CgA mRNA and immunoreactivity. This study provides evidence for CgA synthesis in SCCL and confirms the specificity of CgA for neuroendocrine differentiation. In situ hybridization appears to be a very useful tool for investigating the nature of tumour cells, especially in the absence of the end product of the gene transcript.

Blotting, Northern↗
PubMed1991

An unusual presentation of systemic lupus erythematosus.

A case of right hemiparesis in a 22-year-old, caucasian male is presented. Echocardiography and an indirect left ventriculogram revealed a mass in the left ventricle which was eventually removed at surgery. Histology of the ventricular wall revealed thrombus superimposed on a full thickness myocardial infarction with florid intimal proliferation of small arteries. This histological picture suggested a diagnosis of systemic lupus erythematosus. Serum immunology revealed raised antibody titres in keeping with systemic lupus erythematosus. This is an unusual presentation where the only manifestation of disease was hemiparesis secondary to an embolic episode, from thrombus in the left ventricle subsequent to a small localised myocardial infarct.

Adult↗
PubMed1991

Rheumatoid arthritis and cryptogenic organising pneumonitis.

We describe three patients with rheumatoid arthritis who presented with non-specific pulmonary symptoms, a restrictive defect in lung function and bilateral changes on chest radiograph. Lung histology showed characteristic features of cryptogenic organising pneumonitis and treatment with steroids produced significant improvement. The clinical and laboratory features of cryptogenic organising pneumonitis (otherwise known as bronchiolitis obliterans organising pneumonia, 'BOOP') are discussed and compared with those of bronchiolitis obliterans with which the condition should not be confused. Cryptogenic organising pneumonitis should be considered as one of the pulmonary manifestations of rheumatoid arthritis, but lung biopsy is essential to make the diagnosis.

Arthritis, Rheumatoid↗
PubMed1991

Tumours of mesothelial origin in rats following inoculation with biogenic silica fibres.

Pleural implant experiments using Sprague-Dawley rats have shown that those injected with the carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenenthren-17-one (11-methyl-17-ketone) intraperitoneally followed by silica fibres intrapleurally develop mesotheliomas. These tumours were histologically similar to those induced by crocidolite alone. The intraperitoneal injection of 11-methyl-17-ketone also induced leukaemia.

Adenoma↗
PubMed1991

Pathology of the lung in leukaemia and lymphoma: a study of 87 autopsies.

Histopathological findings in the lungs in a series of autopsies on 87 patients suffering from various types of leukaemia or lymphoma who had received no treatment, or various combinations of radiotherapy, chemotherapy and bone marrow transplantation were reviewed. Thirteen untreated patients showed neoplastic infiltration (4), thromboembolism (4), infection (5) or amyloidosis (1). Seventy-two treated cases showed malignant infiltration (14), vascular damage (21), infections (32) and/or diffuse alveolar damage (47). One patient treated with local irradiation for myeloma had acute bronchopneumonia alone and another treated with [32P] for polycythaemia rubra vera had extensive thrombo-embolism of the large pulmonary vessels. Clinical and autopsy evidence of infection correlated very poorly. Non-infective pulmonary disease was a frequent finding. Bacterial, fungal or pneumocystis pneumonia particularly affected the chemotherapy and radiotherapy groups, while cytomegalovirus infection was seen only in the bone marrow transplant group. This study shows that diffuse alveolar damage is a common and important problem in patients treated with radiotherapy and chemotherapy.

Antineoplastic Agents↗
PubMed1990

Expression of gastrin-releasing peptide (human bombesin) gene in large cell undifferentiated carcinoma of the lung.

Production of the growth factor gastrin-releasing peptide (GRP) or human bombesin has been shown to be a feature of neuroendocrine tumours of the lung, particularly small cell carcinoma, and is possibly responsible for the characteristically rapid growth of this tumour. Large cell undifferentiated carcinoma of the lung (LCC) is also characterized by rapid growth and there is increasing evidence that some LCCs exhibit neuroendocrine differentiation. We therefore investigated GRP/bombesin immunoreactivity and the expression of GRP gene in ten LCCs. Histologically, all were composed of large cells with abundant cytoplasm, open nuclei, and prominent nucleoli, and there was no evidence of squamous, glandular, or neuroendocrine differentiation. At the ultrastructural level, most showed squamous or glandular differentiation but none contained neuroendocrine granules. None of the tumours showed immunoreactivity for GRP/bombesin but seven of the ten showed a focal hybridization signal when treated with 32P-labelled GRP cRNA probes, indicating the presence of GRP mRNA. This was confirmed by northern blot analysis. This study shows for the first time that GRP gene is expressed in LCC. The production of GRP may contribute to the aggressive behaviour of LCC.

Bombesin↗