Biomedical subjects
Publications and source records attributed to B Corrin.
A fetus with intrapericardial teratoma had a large pericardial effusion diagnosed by echocardiography. Cardiac tamponade, a common cause of fetal death, was averted by intrauterine pericardiocentesis. Planned obstetric and neonatal management permitted surgical treatment before cardiorespiratory distress developed. The tumor was completely excised and the infant is asymptomatic.
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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.
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.
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The Himalayan villages of Chuchot Shamma and Stok were surveyed because silicosis had been suspected from the radiographs of some of the inhabitants. The villages are agricultural, and Chuchot is exposed to frequent dust storms. Chest radiographs of villagers aged 50-62 were assessed blind by two independent observers using ILO criteria. In Chuchot five of seven men and all of the nine women examined showed varying grades of silicosis, compared with three of 13 men and seven of 11 women in Stok, which lies 300 metres higher and is exposed to fewer dust storms. The difference in prevalence of silicosis between the two villages was significant, as was the differences between men and women. Three patients from the village adjoining Chuchot were later found to have radiological evidence of progressive massive fibrosis. A necropsy on a man in a neighbouring village in the Indus valley showed classical silicosis in a hilar lymph node. Chemical analysis of the inorganic dust in the lung showed that 54.4% was elemental silicon [corrected]. This was similar to the silicon [corrected] content of dust samples collected from houses in Chuchot, which included particles of respirable size. X-ray microanalysis showed that quartz formed 16-21% of the inorganic lung dust. This study suggests that silicosis is common among the older inhabitants of these Himalayan villages. The dust exposure is clearly environmental and not industrial. Further studies are needed to define the extent and severity of silicosis in this community and to examine possible preventive measures.
Most studies of lung histology in systemic sclerosis have been based on autopsy specimens and consequently emphasize end-stage fibrotic disease. Although occasional pathologic descriptions of open-lung biopsies have recognized the presence of inflammatory cells, suggesting a similarity to "lone" cryptogenic fibrosing alveolitis, the two conditions have never been formally compared. In this study we describe the morphologic features of 49 open-lung biopsies from 34 systemic sclerosis patients with interstitial lung disease, many of whom had their lung disease diagnosed at an early stage. None had pulmonary hypertension. Examination of lung tissue by light microscopy showed the earliest changes to include patchy lymphocyte and plasma cell infiltration of the alveolar walls, interstitial fibrosis, and increased macrophages but only occasional polymorphonuclear cells and lymphocytes in the alveolar spaces. Alveolitis was not observed without fibrosis. Comparison of 22 biopsies with a similar number from patients with lone cryptogenic fibrosing alveolitis, matched for age and sex, revealed no qualitative or quantitative differences, other than a higher prevalence of focal lymphoid hyperplasia (follicular bronchiolitis) in the systemic sclerosis patients than in the lone cryptogenic fibrosing alveolitis controls (23 and 5%, respectively). There was an inverse correlation between the extent of interstitial inflammation and patients' age (p less than 0.05), disease duration (p less than 0.05), and age at onset of systemic sclerosis (p less than 0.01). There was also an inverse correlation between DLCO and interstitial fibrosis (p less than 0.01) and loss of lung architecture (p less than 0.05). Ultrastructural studies of eight systemic sclerosis biopsies showed evidence of endothelial and epithelial injury together with interstitial edema and excess collagen deposition. Occasional mast cells were observed, often in close contact with interstitial fibroblasts, but there were no tubuloreticular structures or evidence of immune complexes.(ABSTRACT TRUNCATED AT 250 WORDS)
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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.
Paraffin sections of 66 surgically resected lung tumours were immunostained with antisera to human endothelin-1 and to the C-terminal peptide of big endothelin. With both antisera, strong immunoreactivity was demonstrated in 11 of 15 squamous cell carcinomas and 11 of 16 adenocarcinomas. Focal immunoreactivity was seen in small cell carcinoma (2/12), large cell carcinoma (2/5), and carcinoid tumours (2/11). Four lymphomas and three sarcomas did not show endothelin immunoreactivity. Cryostat sections of 22 of the 66 tumours were hybridized with radiolabelled complementary RNA probes prepared from the 3' non-coding region of endothelin-1 cDNA, and the chromosomal genes encoding endothelin-2 and -3. In situ hybridization demonstrated the presence of endothelin mRNAs in 4 of 7 squamous cell carcinomas and in 5 of 8 adenocarcinomas, in a pattern similar to that shown by immunocytochemistry. No hybridization signals were obtained from the other types of tumours. In lung tissue adjacent to the tumours, endothelin-like immunoreactivity and mRNA were detected in pulmonary endocrine cells and, in some cases, other epithelial cells, and in alveolar capillary endothelial cells. This study demonstrates the expression of endothelin in a number of pulmonary tumours and suggests a possible role for this peptide in the growth and/or differentiation of these tumours.
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A 74 year old woman presented with a two month history of recurrent small hemoptyses and died after a subsequent massive haemoptysis. At postmortem examination the source of bleeding was found to be a leaking saccular, atheromatous abdominal aortic aneurysm, which had ruptured through the diaphragm into the lower lobe of the right lung.
This review attempts to provide up to date information on structure/function relationships of the pleura and on the pathology of pleural effusions, pneumothorax, pleural repair, pleural infections, pleural involvement in systemic connective tissue disorders, non-malignant asbestos-induced pleural disease, mesothelioma and other pleural tumours.
Ten diffuse pleural mesotheliomas of connective tissue type have been compared with 14 examples of pleural granulation tissue and 7 localized fibrous tumours of the pleura, using immunohistochemistry to identify cytokeratins of low and high molecular weight and vimentin. Low molecular weight cytokeratin and vimentin were both detected in 8 of the 10 mesotheliomas and in 12 of the 14 reactive lesions. High molecular weight cytokeratin was rarely detected in either lesion. The seven localized fibrous tumours of the pleura were all positive for vimentin and negative for both cytokeratins. These findings support an origin of connective tissue type mesotheliomas from multipotential submesothelial spindle cells and of localized fibrous tumours of the pleura from either conventional fibroblasts or resting submesothelial spindle cells. Antibodies to cytokeratin help distinguish these two neoplasms but provide no assistance in the more difficult diagnostic problem of distinguishing mesotheliomas of connective tissue type from pleural reactions characterized by abundant granulation tissue.
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Systemic sclerosis is frequently complicated by fibrosing alveolitis although clinical and radiological abnormalities are not usually apparent until the lung disease is well established. The aim of this study was to investigate pulmonary involvement in systemic sclerosis by thin section CT scan, bronchoalveolar lavage (BAL) and 99mTc-DTPA clearance studies, and assess the value of these tests in defining pulmonary abnormalities in patients with a normal chest radiograph. Patients were divided into those with an abnormal chest radiograph (Group I, n = 14) and those with a normal chest radiograph (Group II, n = 16). CT scans were abnormal in all patients in Group I and 7 of 16 (44%) in Group II. BAL inflammatory cell counts were raised in all 12 (100%) patients studied in Group I and 11 of 15 (73%) in Group II. There was no difference in the type of inflammatory cells observed between the two groups. 99mTc-DTPA clearance was faster than normal controls in ten of 14 patients (71%) in Group I and seven of 15 (47%) in Group II and correlated with carbon monoxide transfer factor (P less than 0.05). Lung biopsies were performed on nine patients in Group I and three in Group II all of whom had abnormal CT scans. Fibrosing alveolitis was confirmed in every case. Group II biopsies could not be distinguished from Group I biopsies; both showed fibrosis as well as inflammation suggesting that pulmonary fibrosis is an early abnormality in systemic sclerosis. Our results indicate that CT scans, BAL and 99mTc-DTPA are frequently abnormal in asymptomatic patients with systemic sclerosis who have normal chest radiographs. When the CT scan is normal abnormalities of BAL and/or 99mTc-DTPA (99mTechnetium diethylenetriamine pentacetate) clearance may indicate lung disease at a still earlier stage. This observation requires further investigation.
Forty-seven thymomas have been examined by DNA flow cytometry and results correlated with histology, stage, associated clinical features and survival. Twenty-five cases were DNA diploid, 14 were aneuploid and no results could be obtained for eight cases. The presence of aneuploidy correlated with more advanced (stage II and III) disease and the presence of myasthenia gravis and was more frequent in epithelial predominant thymomas. Tumour recurrence was more frequent in DNA aneuploid tumours, stage II/III disease and epithelial predominant neoplasms. Multifactorial analysis showed that DNA aneuploidy was predictive of tumour recurrence independent of the effects of stage and histology.