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Biomedical subjects

J R Gosney

Publications and source records attributed to J R Gosney.

52 records · Page 3Linked to original sources

Pulmonary endocrine cells in hypertensive pulmonary vascular disease.

A study was made of the number of pulmonary endocrine cells, immunoreactive for gastrin-releasing peptide (bombesin) or calcitonin, in the terminal bronchioles of 39 cases of pulmonary vascular disease. In 25 of these, the form of vascular disease was plexogenic pulmonary arteriopathy, primary in 12 and secondary in 13, while the remaining 14 subjects had a wide range of other varieties of hypertensive pulmonary vascular disease. We found that pulmonary endocrine cells, especially those containing bombesin, were increased in number in both the primary and secondary forms of plexogenic pulmonary arteriopathy but not in other varieties of pulmonary hypertension. The prominent bombesin-containing cells were found in cases with cellular plexiform lesions but occurred even more prominently at an earlier stage when vascular smooth muscle cells were migrating from the inner media into the intima.

Adult↗

Serum leucine-enkephalin in bronchial carcinoma and its relation to tumour location.

Serum concentrations of the opioid peptide leucine-enkephalin were measured by radioimmunoassay in 30 patients with histologically confirmed bronchial carcinoma and 10 control subjects. This peptide, which is present in greatest amounts in the central and autonomic nervous systems, has previously been found in bronchial neoplasms. The mean serum concentration of leucine-enkephalin was significantly greater in the patients with carcinoma (1035 pg/ml) than in the control subjects (426 pg/ml). In the 23 patients with a tumour in non-apical regions of the lung, however, the mean concentration of the peptide (422 pg/ml) did not differ significantly from that in control subjects; serum concentrations in the seven patients with an apical neoplasm (mean 3050 (range 1259-5820) pg/ml) were significantly greater than values in either the control subjects or the patients with non-apical lung tumours. All seven subjects with an apical tumour had one or more features of Horner's syndrome and the three with all four components of the syndrome had the highest serum concentrations. Serum concentrations of leucine-enkephalin were unrelated to tumour type or presence of metastatic disease. No patient had evidence of metastases in the central nervous system or adrenal glands. Raised serum concentrations of leucine-enkephalin in patients with an apical tumour probably reflect invasion of cervical sympathetic ganglia with release of the peptide into the circulation rather than elaboration of the peptide by the neoplasm.

Carcinoma, Bronchogenic↗

Plasma growth hormone and digital clubbing in carcinoma of the bronchus.

Growth hormone is a secretory product of some primary bronchial neoplasms and has been associated with the development of hypertrophic pulmonary osteoarthropathy and acromegaly in occasional patients with such tumours; it has not, however, generally been considered important in the pathogenesis of digital clubbing. Plasma levels of growth hormone at the time of diagnostic bronchoscopy were measured in 60 patients with histologically proved bronchial carcinoma, divided according to whether clubbing was present (n = 21) or absent (n = 39), and in 13 control subjects undergoing the same procedure but with no neoplasm. The median plasma level of growth hormone ( and interquartile range) was 0.74 (0.5-1.0) mU/l in five control subjects with no pulmonary disease, 0.83 (0.4-1.3) mU/l in eight subjects with non-neoplastic pulmonary disease, 1.1 (0.6-3.3) mU/l in patients with carcinoma but without clubbing, and 3.1 (0.8-9.0) mU/l in 21 patients with carcinoma and clubbing. The highest growth hormone level was seen in a patient with a small cell carcinoma and pronounced clubbing; levels had fallen to normal by the time chemotherapy was completed and clubbing completely resolved. Thus growth hormone or a similar substance might have a role in the pathogenesis of clubbing in patients with bronchial neoplasms.

Bronchoscopy↗

Pulmonary endocrine cells in chronic bronchitis and emphysema.

Pulmonary endocrine cells have been studied according to their immunoreactivity for neuron-specific enolase, gastrin-releasing peptide (GRP), calcitonin, leucine-enkephalin, and serotonin in the lungs of subjects with chronic bronchitis and emphysema. The overall population was significantly greater in comparison with matched controls. The change was most marked in lobes affected by pneumonic consolidation, and did not affect equally the sub-populations of cells as identified by their content of peptide; the difference was much greater for calcitonin-containing cells than for those immunoreactive for GRP. This change may be the basis of the hypercalcitoninaemia and hypercalcitoninuria which have been reported in patients with inflammatory pulmonary disease.

Aged↗

Use of somatostatin in the management of pancreatic haemobilia.

An elderly man, not previously known to have chronic pancreatitis, presented with haematemesis and melaena which was endoscopically diagnosed as haemobilia. Retrograde cholangiopancreatography showed blood clot in both the common bile duct and the pancreatic duct and the computed tomographic scan appearances were those of gross calcific chronic pancreatitis. Despite active bleeding, it was not possible to demonstrate its source at angiography, thus precluding therapeutic embolization. Thirty six hours after commencing an infusion of somatostatin, repeat endoscopy showed no evidence of active or recent bleeding. The infusion was continued for 5 days during which time he had no further bleeding.

Aged↗

Neuroendocrine cell populations in normal human lungs: a quantitative study.

Pulmonary neuroendocrine cells, identified by their positive immunochemical reaction for neurone specific enolase, were readily demonstrable and uniformly distributed in 15 pairs of normal adult human lungs. About 65% contained gastrin releasing peptide and nearly all the rest contained calcitonin. Leucine-enkephalin was not found. Serotonin containing cells were few, and cells immunoreactive for adrenocorticotrophin and antidiuretic hormone were absent. About one in 10 cells was argyrophilic, and costorage of peptides was not seen.

Aged↗

Atrophy of Leydig cells in the testes of men with longstanding chronic bronchitis and emphysema.

The total volume of Leydig cells in the testes of men coming to necropsy with a history of chronic bronchitis and emphysema of at least 15 years' duration, and with morphological evidence at necropsy of the cardiopulmonary effects of hypoxia, was significantly less than the volume in matched controls (0.98 (SD 0.39) and 0.93 (0.42) ml v 1.66 (0.54) and 1.72 (0.52) ml for left and right testes respectively; p less than 0.005). This atrophy may be a consequence of hypoxic inhibition of pituitary synthesis or release of luteinising hormone.

Aged↗

Morphological changes in the pituitary and thyroid of the rat in hypobaric hypoxia.

When a group of adult male Wistar rats was exposed to a barometric pressure of 380 mmHg for 28 days in an hypobaric chamber, profound changes occurred in their hypothalamic-pituitary-thyroidal axes in comparison with normobaric controls. The thyroid glands of the hypoxic animals had an inactive appearance, comprising large colloid-filled follicles lined by low epithelium. The thyrotrophs of the pars distalis of the pituitary glands were markedly decreased in number. They occupied only 0.41% of the total cell population in contrast with 1.34% in the controls (P less than 0.001); a total population which is itself decreased in the hypoxic animals. Classical 'thyroidectomy cells' were not seen. These observations support previous studies which indicate suppression of thyroid function in an hypoxic environment, and tend to suggest that this is a consequence of a direct effect of hypoxia on the hypothalamus or pituitary gland, rather than on the thyroid itself.

Animals↗

Adrenal corticomedullary hyperplasia in hypobaric hypoxia.

Continuous exposure of adult male Wistar albino rats to a barometric pressure of 380 mm Hg (equivalent to an altitude of 5500 m) for 28 days causes a marked increase in adrenal gland weight due to hyperplasia of both adrenal cortex and medulla. The size of the cortical and medullary components of the gland relative to each other is unaffected; in both hypoxic and control animals the cortex occupies approximately 85 per cent of the overall volume of the gland. Cortical hyperplasia is consistent with the elevated levels of ACTH which have previously been shown to occur during hypoxia. Medullary hyperplasia under such conditions presumably reflects a continuing increased requirement for catecholamines in an hypoxic environment. The morphology of these adrenal medullae bears a striking structural resemblance to some phaeochromocytomata. Adrenal medullary hyperplasia does not appear to have been described previously under such conditions and may be an important effect of prolonged severe hypoxia.

Adrenal Cortex↗

Pulmonary endocrine cells immunoreactive for calcitonin in the lungs of fetal and neonatal rats.

Previous studies have shown that the size of the population of bronchopulmonary endocrine (Feyrter) cells appears to be greatest in fetal and neonatal life. This has led to the logical assumption that these cells are important during this period and undergo a subsequent decline in number thereafter. In this study endocrine cells containing calcitonin or a closely related cross reacting peptide have been demonstrated in the lungs of fetal and neonatal rats by immunoenzyme histochemistry. They appear first about three days before birth and their number, expressed as immunoreactive cells per cm2 of histological section, remains relatively constant for up to three weeks after birth. It has been shown previously in this department that endocrine cells immunoreactive for calcitonin are present in the lungs of the normal adult rat. Their number in these adult animals is closely similar to the numbers of cells in the lungs of the developing animals of the present study. It is suggested that, at least in the rat, bronchopulmonary endocrine cells immunoreactive for calcitonin have a role that is not confined merely to the period of transition from fetal to neonatal life.

APUD Cells↗

Quantitative study of endocrine cells immunoreactive for calcitonin in the normal adult human lung.

There was no significant variation in the numbers of bronchopulmonary endocrine cells immunoreactive for calcitonin in five pairs of adult human lungs either from case to case or between groups of anatomically equivalent lobes. This was the case whether their numbers were expressed in relation to epithelial length or to the total number of epithelial cells. The mean (SD) values for the frequency of occurrence of these cells in all 25 lobes studied were 4.3 (1.9) per 10 cm of epithelial length or 1.70 (0.78) per 10 000 epithelial cells. Most immunoreactive cells were single and situated in the airways; only three neuroepithelial bodies were observed, and no cells were present in the parenchyma examined. This study provides further evidence that the functional character of these cells may not be confined to early life.

APUD Cells↗

Widespread distribution of bronchopulmonary endocrine cells immunoreactive for calcitonin in the lung of the normal adult rat.

The nature and distribution of bronchopulmonary endocrine cells immunoreactive for calcitonin was studied in normal adult Wistar albino rats by immunoenzyme histochemistry with the peroxidase-antiperoxidase technique. A widespread distribution of both solitary endocrine cells and neuroepithelial bodies immunoreactive for calcitonin was found. Many, but not all, were also immunoreactive for neurone specific enolase. Although both classes of cells were present in airways and parenchyma, most of the solitary cells were found in alveolar ducts and alveoli whereas most of the neuroepithelial bodies were located in bronchi and bronchioles. Bronchopulmonary endocrine cells are generally regarded as being sparse in the adult rat. It is suggested that this may be a consequence of the use of inadequate methods in attempting to identify them. So far as is known, this is the first time that calcitonin has been demonstrated by immunohistochemical methods in the lungs of rats.

Animals↗

The effects of hypobaric hypoxia on the corticotroph population of the adenohypophysis of the male rat.

The effect of hypobaric hypoxia on the corticotroph population of the adenohypophysis has been studied in male rats. After 28 days exposure to a barometric pressure of 380 mm Hg, equivalent to an altitude of 5500 m, there was an increase in their number relative to the total cell population. This may reflect a requirement for a sustained increase in the level of adrenocortical secretion in an hypoxic environment. Alternatively, higher levels of ACTH may be required to maintain normal levels of adrenocortical hormone secretion under these conditions.

Adrenocorticotropic Hormone↗

Effects of hypobaric hypoxia on the Leydig cell population of the testis of the rat.

A group of ten young adult male Wistar albino rats was exposed to hypobaric hypoxia at a barometric pressure of 380 mmHg for 28 days. After this period their testes were of smaller weight (and volume) in comparison with matched controls (1.220 vs 1.553 g; P less than 0.005). Histological examination revealed degeneration and sloughing of spermatogenic cells in occasional tubules. Quantitative methods also revealed a marked difference in the volume of the testis occupied by Leydig cells. These were of a significantly smaller total volume in the hypoxic animals (0.046 vs 0.083 ml; P less than 0.001) and this could not be accounted for merely by the smaller overall testicular volume.

Animals↗

C-erbB-2 expression in squamous cell carcinoma of the head and neck.

Seventy-five squamous cell carcinomas of the head and neck were analysed for c-erbB-2 expression using immunohistochemical techniques with four different c-erbB-2 antibodies. No membrane staining was seen in any of the squamous cell carcinomas studied with any of the antibodies; however, c-erbB-2 cytoplasmic staining was seen in 60 per cent of the tumours. The significance of cytoplasmic staining is discussed and that it may possibly represent elevated c-erbB-2 expression in squamous cell carcinomas. C-erbB-2 cytoplasmic staining was also observed in 10 of 23 normal specimens obtained from the resection margin of the tumours. No correlations were found between positive c-erbB-2 cytoplasmic staining and any of the clinicopathological parameters or survival.

Biomarkers, Tumor↗

c-myc oncoprotein in bronchial carcinoma: expression in all major morphological types.

We have studied the prevalence of a 62 kd protein product of the c-myc oncogene in tissue biopsies from 79 primary bronchial carcinomata using the monoclonal antibody Myc 1-9E10 and the avidin-biotin complex (ABC) technique. This oncoprotein was strongly expressed in 43% of 37 squamous lesions, 29% of 14 adenocarcinomata, 42% of 7 non-small cell lesions not further classifiable and 19% of 21 small cell neoplasms, all of classical morphology. There was no statistical difference between groups in the prevalence of its expression, nor was it related to survival. This oncoprotein is commonly expressed in non-small cell as well as small cell bronchial carcinomata and, in the latter, is not confined to those variant tumours which possess a "large cell" morphology and carry a poor prognosis.

Adenocarcinoma↗