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J R Gosney

Publications and source records attributed to J R Gosney.

At least 37 records · Page 2Linked to original sources
PubMed1996

Endocrine cells in tumour-bearing lungs.

BACKGROUND: When hormones are detected in the serum of patients with bronchial carcinoma they are generally considered to originate from the tumour, but this may be not the only explanation. Pulmonary endocrine cells proliferate in lungs affected by non-neoplastic disease and their products are often demonstrable in the serum. The aim of this study was to examine the pulmonary endocrine systems of a series of tumour-bearing lungs to see whether any changes in them could possibly account for raised levels of pulmonary peptides in the blood. METHODS: The morphology, number, distribution, and content of pulmonary endocrine cells in 30 pairs of tumour-bearing lungs from patients coming to necropsy with bronchial carcinoma were examined. These features were related to the pathology of the tumour and to other pathological changes present in the lungs, and compared with pulmonary endocrine cells in 10 pairs of control lungs from patients without pulmonary disease. RESULTS: Increased numbers of endocrine cells, often in the form of large abnormal aggregates, were present in 17 pairs of tumour-bearing lungs where they were associated not with the tumour but with non-tumoral pathology, especially inflammation and changes associated with cardiac failure. Appropriate and inappropriate peptides were identified within them. CONCLUSION: The possibility is raised that, in some subjects with bronchial carcinoma who have raised serum hormone levels, the source of these substances might be the endocrine cells in the diseased lung around the tumour.

Aged↗
PubMed1995

Absence of overexpression of p53 protein by intestinal carcinoid tumours.

A recessive gene on chromosome 17 encodes a protein, known as p53, which normally acts to regulate the cell cycle, its mutation and overexpression being amongst the commonest genetic abnormalities in human malignant neoplasms. As detected by immunolabelling using the anti-p53 protein antibody D07, overexpression was absent from a series of 22 intestinal carcinoid tumours (ten ileal, nine appendiceal, and three colorectal), nine overtly malignant, but was readily demonstrable in five of five colorectal adenocarcinomas, five of six cloacogenic carcinomas, and four of five squamous carcinomas of the anal canal used as controls. These observations are in keeping with previous similar studies of pulmonary carcinoid tumours and suggest possible differences in the pathogenesis of such neoplasms in comparison with non-endocrine differentiated tumours arising at equivalent sites.

Carcinoid Tumor↗
PubMed1995

Orthostatic hypotension and vasodilatory peptides in bronchial carcinoma.

AIM: To determine whether inappropriately secreted vasodilatory peptides have a role in the pathogenesis of orthostatic (postural) hypotension, a recognised paraneoplastic effect of bronchial malignancies usually attributed to immune mediated destruction of autonomic ganglia. METHODS: Serum concentrations of three vasodilatory peptides, atrial natriuretic peptide (ANP), vasoactive intestinal polypeptide (VIP) and calcitonin gene related peptide (CGRP), were measured in 111 patients with bronchial carcinoma and 35 controls prospectively screened for orthostatic hypotension (> 20 mmHg drop in systolic blood pressure on repeated occasions on standing from the supine position) and in whom other causes of this condition were excluded. RESULTS: Twenty two (20%) patients with carcinoma and two (6%) controls had orthostatic hypotension according to the criteria used. Serum concentrations of ANP, VIP and CGRP were elevated above normal in, respectively, 25 (23%), 10 (9%) and eight (7%) patients with carcinoma and in six (18%), zero and three (9%) controls. There was no correlation between orthostatic hypotension and concentrations of any of the vasodilatory peptides. CONCLUSION: Elevated serum concentrations of ANP and CGRP were no more frequent in subjects with bronchial carcinoma than in controls and could not be attributed to the tumour, although there was a possible association for VIP. Orthostatic hypotension was more common in patients with carcinoma, but there was no evidence that the peptides measured played a role in its pathogenesis.

Aged↗
PubMed1995

Pulmonary endocrine cells in plexogenic pulmonary arteriopathy associated with cirrhosis.

A clear association has been described between numbers of pulmonary endocrine cells and the migration and/or proliferation of myofibroblasts which is thought to underlie the vascular changes seen in plexogenic pulmonary arteriopathy due to cardiac shunts and primary pulmonary hypertension. In contrast, the pulmonary endocrine system in a subject with florid pulmonary plexogenic arteriopathy associated with cirrhosis was entirely normal, suggesting possible differences in its pathogenesis.

Adult↗
PubMed1995

Reliability of commercially available immunocytochemical markers for identification of neuroendocrine differentiation in bronchoscopic biopsies of bronchial carcinoma.

BACKGROUND: Although neuroendocrine differentiation occurs quite commonly in non-small cell bronchial malignancies, its biological significance and implications for management remain uncertain. Determining these facts requires its recognition early, ideally at diagnosis, which is usually made on tissue from bronchoscopy, but the best means of its detection in such material is unclear. A prospective comparative study was performed of 10 commercially available antisera to a series of markers of neuroendocrine differentiation, to test their efficacy when applied to fibreoptic bronchoscopy biopsy specimens. METHODS: Expression of chromogranin A, synaptophysin, neurone-specific enolase, protein gene product 9.5, the BB isoenzyme of creatine kinase, gastrin releasing peptide, adrenocorticotrophic hormone, calcitonin, calcitonin gene related peptide, and leucine enkephalin was sought by immunolabelling of bronchoscopic biopsy tissue from 83 primary bronchial carcinomas, 22 of them of small cell type. RESULTS: Only synaptophysin and chromogranin were sensitive and specific enough for neuroendocrine differentiation to discriminate between small cell and non-small cell lesions, whereas protein gene product 9.5 and creatine kinase were neither particularly sensitive nor specific and neurone-specific enolase actually labelled more non-small cell tumours than small cell lesions. Of the five secretory products sought, only gastrin releasing peptide was detectable in just one tumour. Three squamous and two morphologically undifferentiated tumours immunolabelled for synaptophysin and chromogranin, almost certainly indicating neuroendocrine differentiation in the absence of small cell morphology. CONCLUSIONS: Of the markers studied, only synaptophysin and chromogranin were sufficiently specific and sensitive for neuroendocrine differentiation to justify their inclusion in any panel of antibodies used in its detection in tissue obtained at fibreoptic brochoscopy.

Biomarkers, Tumor↗
PubMed1993

Exposure to cigarette smoke and expression of the protein encoded by the p53 gene in bronchial carcinoma.

Mutation of the onco-suppressor gene encoding the protein known as p53 may cause synthesis of a mutant p53 protein which can bind to and inactivate its wild-type equivalent. This protein is detectable in many malignant neoplasms, including bronchial carcinoma, and has been associated with cigarette smoking. Of 59 tissue biopsy specimens of primary bronchial malignancies immunolabeled for p53 by the avidin-biotin technique using the antibodies PAb 1801, CM1, and D07, 13 (22%) expressed the protein. Of these 13 patients, 10 (77%) smoked more than 20 cigarettes a day and their mean total exposure was 53 pack-years. Corresponding figures for those with p53-negative tumors were 21 (46%) smoking more than 20 cigarettes a day with a mean total exposure of 36 pack-years. There was, however, no difference between the groups in total duration of exposure (46 vs. 47 years). Although p53 was expressed more commonly in adenocarcinoma (30% of 10) and squamous carcinoma (28% of 29) than in small cell tumors (10% of 20), this could be accounted for by the smoking history. This study supports a relationship between mutations of the p53-encoding gene associated with overexpression of its protein product and intensity of exposure to cigarette smoke.

Adenocarcinoma↗
PubMed1993

Pulmonary neuroendocrine cells in species at high altitude.

Ever since pulmonary neuroendocrine cells were first described, a chemoreceptor function has been attributed to them. This hypothesis proposes that the innervated clusters of these cells, which are known to degranulate when the oxygen tension around them is reduced, respond to hypoxia to initiate activity in a reflex arc and ultimately adjust some aspect of pulmonary function. If this were true, one might expect to see changes in the pulmonary neuroendocrine system in species exposed to the unremitting hypoxia at natural high altitude. Whilst evidence from some studies suggests that such changes do occur, others have been unable to demonstrate any effect. To some extent this may be attributable to species variability, but might also reflect whether the organism is genetically adapted or merely acclimatized to life in an oxygen-poor environment.

Adaptation, Physiological↗
PubMed1993

Neuroendocrine cell populations in postnatal human lungs: minimal variation from childhood to old age.

Although changes in the human pulmonary neuroendocrine system have been described in association with a variety of pulmonary diseases, little is known of how the system changes with age in healthy lungs. As delineated by their immunoreactivity for neuron-specific enolase, protein gene product 9.5 and chromogranin A, the density of the system's component cells in terms of the rest of the pulmonary epithelium varied minimally between 10 groups of subjects divided according to age and ranging from children to nonagenarians, figures for the groups varying only between 2.91 and 4.19 neuroendocrine cells per 10,000 epithelial cells. In only three subjects were neuroendocrine cells found in the parenchyma; the vast majority were located in airways with about 65% in bronchi. Cells were more often arranged in the form of clusters in the younger subjects than in the elderly, in whom clusters were extremely rare, but the significance of this observation is unclear.

Adolescent↗
PubMed1993

Ultrastructural heterogeneity in undifferentiated bronchial carcinoma.

Electron microscopy is often suggested as a useful aid to the classification of light microscopically undifferentiated bronchial malignancies, features such as dense-core vesicles, desmosomes or tonofilaments, and microacini, allowing their designation as endocrine, squamous, or adenocarcinomas respectively. However, there is no reason to suppose that the heterogeneity of malignant bronchial tumours so often apparent by light microscopy or on immunolabelling might not occur at the ultrastructural level too. Extensive sampling of all deposits from eight subjects coming to necropsy with undifferentiated bronchial carcinoma revealed ultrastructural features of glandular and squamous differentiation to be widespread and often to occur together, although dense-core vesicles were not seen in any of the tumours studied. Heterogeneity was present within individual tumour deposits and particularly between different deposits of those tumours which had disseminated, such that any ultrastructural diagnosis would have been significantly influenced by sampling. Such variation should be borne in mind when ultrastructural features are used to classify bronchial malignancies.

Bronchial Neoplasms↗
PubMed1993

Granulation tissue polyposis associated with carcinoid tumours of the small intestine.

We report two patients with ileal carcinoid tumours which were associated with polyps due to mucosal granulation tissue proliferation. In both cases the tumours had extensively infiltrated the small bowel wall and mesentery, and one had hepatic metastases. The mucosal surface of each specimen showed numerous, pale brown, sessile polyps which were restricted to the intestinal segment involved by carcinoid tumour, although not always closely related to neoplastic cells. The polyps were formed by the proliferation of capillaries, smooth muscle cells and myofibroblasts as demonstrated by immunohistochemistry and electronmicroscopy.

Aged↗
PubMed1993

Endocrine cells in diffuse pulmonary fibrosis.

BACKGROUND: There is evidence to suggest, particularly from studies in animals, that the products of pulmonary endocrine cells, especially gastrin releasing peptide, may have a role in the pathogenesis of fibrosis in the lung. This study was carried out to examine the morphology, number, distribution, and content of pulmonary endocrine cells in tissue from 49 patients with diffuse pulmonary fibrosis. METHODS: Twenty patients with interstitial pneumonitis, 17 with early fibrosis, and 12 with frank honeycombing were studied, together with five age matched controls without pulmonary disease. Endocrine cells were immunolabeled by the avidin-biotin complex method for two general markers (protein gene product 9.5 and neuron specific enolase) and a range of normal and aberrant secretory products. RESULTS: In the early stages, characterised by vigorous pneumonitis, endocrine cells were normal in appearance and distribution but very few in number. They contained only those secretory products normally found in such cells in health; inappropriate substances were not seen. By the time of early fibrosis endocrine cells were even fewer. None were identifiable in the lungs affected by honeycombing, despite the fact that all contained intact, well preserved epithelium. CONCLUSIONS: It seems unlikely that the products of pulmonary endocrine cells can have any role in the pathogenesis of diffuse pulmonary fibrosis in man, the diminution in their number with advancing fibrosis probably reflecting their loss simply as a consequence of generalised epithelial damage.

Cell Count↗
PubMed1992

Low levels of ras p21 oncogene expression correlates with clinical outcome in head and neck squamous cell carcinoma.

We have previously demonstrated that the Ha-ras and the Ki-ras oncogenes are overexpressed in squamous cell carcinoma of the head and neck. In this study we have used the Y13-259 monoclonal antibody to p21 ras to determine if expression of the ras oncoprotein correlates with any of the clinico-pathological parameters or with survival in 69 patients with squamous cell carcinoma of the head and neck. Forty-four specimens were from patients with previously untreated tumours and 25 from patients with previously treated disease. We have found a correlation between low levels of ras expression and the disease-free survival period in patients with previously untreated tumours. Three per cent of the patients with ras negative staining were alive 60 months after diagnosis, whereas 54 per cent of the patients with positive staining were still alive after the same time period (P less than 0.05).

Animals↗
PubMed1991

Elevated P53 expression correlates with a history of heavy smoking in squamous cell carcinoma of the head and neck.

Expression of the tumour suppressor gene p53 was examined in squamous cell carcinoma of the head and neck using two p53 antibodies, PAb 421 and PAb 1801. Elevated p53 expression was found in 67% of the 73 patients investigated. P53 expression was not found to correlate with whether the patient had been previously treated or not, nor any of the clinico-pathological parameters. However a correlation was found between the patients smoking history and positive p53 staining. Six out of seven non-smokers did not express p53 whereas 29 of 37 heavy smokers were found to have elevated p53 expression (P less than 0.005). Also, of a group of ten patients who had given up smoking more than 5 years ago, nine had elevated expression. Epidemiological studies have shown a correlation between heavy smoking and head and neck cancer. The present study indicate a genetic link for this correlation.

Carcinoma, Squamous Cell↗
PubMed1990

Basal cell carcinoma with hepatic metastases.

A case of metastatic basal cell carcinoma is presented which illustrates precisely the type of lesion most likely to metastasise to distant sites. The primary growth had been present for over 20 years at presentation, was in the middle third of the face, was widely invasive locally extending to involve bone, and was subject to repeated partially successful attempts at eradication. Histologically it was of the metatypical subtype. All are risk factors for metastasis of basal cell carcinoma which, in this case, eventually developed to the liver.

Aged↗
PubMed1990

Pulmonary endocrine cells in native Peruvian guinea-pigs at low and high altitude.

The role of pulmonary endocrine cells is unclear, but those which are aggregated into innervated clusters are probably chemoreceptors, responding to hypoxia in the airways, whereas solitary endocrine cells are probably quite different in their function. There were significantly more clusters of endocrine cells in the lungs of a group of 10 indigenous Peruvian guinea-pigs considered to be adapted to high altitude, in comparison with controls from sea-level, whereas there was no difference in the number of solitary cells. It is concluded that, whereas the clusters are indeed responding to and affected by hypoxia, the solitary cells are not, and play a distinct and possibly trophic role in the lung.

Altitude↗
PubMed1990

The histopathology of 36 cases of plexogenic pulmonary arteriopathy.

A detailed histopathological study was made of the lungs of 36 cases of plexogenic pulmonary arteriopathy coming to combined heart-lung transplantation. It revealed two dissimilar processes involved in the pathogenesis of this disease. One comprised histological appearances consistent with constriction of muscular pulmonary arteries, a condition that would be likely to be reversed by pulmonary vasodilators. The other was the proliferation of myofibroblasts in the intima and lumen of pulmonary arteries, a disorder of growth unlikely to be influenced by this type of therapy. In previous ultrastructural studies we have shown that the source of these cells of muscular pedigree is muscle cells from the inner half of the media which migrate into the intima through gaps in the inner elastic lamina. In the present study we found a similar proliferation of myofibroblasts in the intima, not only of pulmonary arteries, but also of pulmonary veins, in plexogenic pulmonary arteriopathy. Arterial thrombi found were considered to be a complication rather than a cause of plexogenic pulmonary arteriopathy. Siderophages, cholesterol granulomas and focal fibrosis in the lung were considered to be a consequence of intrapulmonary haemorrhage early in the course of the disease. It is concluded that, while plexogenic pulmonary arteriopathy has an important vasoconstrictive element, it is also based on a disorder of growth of cells of muscular pedigree. This view has clear implications for the therapy of primary plexogenic pulmonary arteriopathy.

Adolescent↗