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Biomedical subjects

L H Rees

Publications and source records attributed to L H Rees.

At least 253 records · Page 14Linked to original sources

Lung tumours and ACTH production.

ACTH levels measured by N- and C-terminal immunoassays and cytochemical bioassay, were measured in fourteen lung tumours not associated with the ectopic ACTH syndrome and in macroscopically normal lung tissue taken from the same patients at thoracotomy. Significant concentrations of immunocative (greater than 3 ng/g wet weight) and bioactive (greater than 0.2 ng/g wet weight) ACTH were found in all the carcinoid and oat cell tumours (n=9), a combined tumour (poorly differentiated adenocarcinoma with large cell carcinoid elements), and a poorly differentiated squamous cell tumour. All the carcinoid tumours contained more C- than N-terminal ACTH immunoactivity. The squamous cell tumours (n=2), anaplastic tumours (n=2) and adenocarcinoma contained insignificant ACTH levels. There was a good correlation between the ACTH levels and the presence of secretory granules in the tumours examined ultrastructually. All the macroscopically normal samples of lung tissue contained immuno and bioactive ACTH-like material, the levels of which correlated well with ACTH levels in the tumour tissue. It is suggested that all lung tumours of carcinoid or oat cell type synthesize ACTH-like materials although clinical evidence of the ectopic ACTH syndrome may be absent. The presence of ACTH-like materials in non-tumorous lung tissue in patients with lung cancer may indicate a low level of ACTH production throughout the lung or sequestration of ACTH containing granules secreted by the tumour.

Adenocarcinoma↗

'Big ACTH' and calcitonin in an ectopic hormone secreting tumour of the liver.

A young man presented with rapidly developing Cushing's syndrome which was due to the ectopic secretion of ACTH and beta-MSH-like material from hepatic tumour deposits, possibly originating from biliary radicals. This association of the ectopic ACTH syndrome has not previously been described. During the 22 month course of the illness the plasma immunoreactive ACTH and 'beta-MSH' concentrations rose by logarithmic progression. The plasma calcitonin concentration was also raised but did not change during the last 12 months. At any stage of the illness the plasma concentration of the ecotopically produced hormones was stable except that after hydrocortisone there were inconstant variations. During the course of the illness the ectopic ACTH became biologically less potent. This ineffectural ACTH was present in the plasma, in the tumour, and in the medium in which the tumour was cultured, in a large molecular weight form. This 'big ACTH' differed from the normal ACTH found in the patient's pituitary and from authentic ACTH in its immunochemical character: the C-terminal antigenic determinant (33-39 region of ACTH) was masked in the large molecular weight form but was uncovered after extraction in neutral buffer and this 'big ACTH' was more readily extracted from the tumour at pH 7.0. The tumour tissue also contained immunoreactive beta-MSH-like material and immunoreactive calcitonin which resembled calcitonin M chromatographically.

Adolescent↗

Cyproterone acetate.

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Adrenocorticotropic Hormone↗

Concepts in ectopic hormone production.

Non-endocrine tumours are capable of production of ectopic hormones, precursor molecules subunits and hormone-related fragments. The measurement of these may provide biochemical markers of malignancy, allowing presymptomatic diagnosis which may lead ultimately to an improved prognosis for the patient. The study of ectopic humoral syndromes may yield new insights into the nature of cellular differentation and the fundamental process of malignant change.

Adrenocorticotropic Hormone↗

Ectopic hormone production by bronchial carcinomas in culture.

Monolayer tissue culture has been used as a system in which to study aspects of ectopic hormone secretion. Of a series of twenty-four human bronchial carcinomas, nineteen were successfully established in culture and the supernatant medium from each tested for peptide hormones by radioimmunoassay. Six tumours were found to produce adrenocorticotrophin (ACTH), four to release calcitonin (CT) and one to release both of these hormones. No growth hormone or insulin was detected throughout the series. Net in vitro synthesis of both ACTH and CT was demonstrated by recovery of more hormone during culture than was originally contained in the explanted tumour tissue. The production of hormone by four out of six proliferative cultures established, and its persistence through many subculture passages, confirms ectopic hormone production as a stable heritable characteristic of some lung tumours. The ability of hormone-producing bronchial tumour cells to respond to factors known to influence hormone output from normal endocrine cells was tested. ACTH release was stimulated in one tumour by Pitressin and CT in another by gastrin. In addition, the release of CT from the same tumour cell line was shown to be inhibited by the accumulation of high external concentrations of CT as has been reported for normal C-cells.

Adenocarcinoma↗

Chemical characterization of ectopic ACTH purified from a malignant thymic carcinoid tumor.

ACTH was purified from thymic tumor associated with ectopic ACTH production by gel filtration and ion exchange chromatography. Amino acid composition and C- and N-terminal analyses indicated that this tumor ACTH was comprised of the 2-38 sequence of authentic pituitary ACTH. The observations suggest that the mode of cleavage of this tumor ACTH from its precursor is different from that of pituitary ACTH.

Adrenocorticotropic Hormone↗

Radioimmunoassay and chromatographic similarity of circulating endogenous gonadotropin releasing hormone and hypothalamic extracts in man.

A highly sensitive radioimmunoassay for the gonadotropin releasing hormone has been developed in order to study its physiological importance in man. In view of the expected low concentrations in peripheral blood, large volumes of human plasma were extracted by two different methods and characteristics of the radioimmunoassayable material compared with those of synthetic decapeptide and extracts of human hypothalami. The results indicate that radioimmunoassayable gonadotropin releasing hormone is present in some human plasmas but the plasma concentration are less than 2.5 pg/ml. Peripheral levels were more consistently measurable in women at midcycle and after the menopause. The hormone was undetectable in the plasma of normel men, human cerebrospinal fluid, and fetal cerebral tissue, but was present in fetal hypothalami.

Chromatography, Gel↗

Comparison of circulating glycoprotein hormones and their subunits in patients with oat cell carcinoma of the lung and uraemic patients on chronic dialysis.

It has recently been suggested that the measurement of the glycoprotein hormones and their subunits in human serum may serve as biochemical markers of non-endocrine tumours. Using radioimmunoassays for LH, FSH, HCGbeta-, LHbeta- and the common alpha-subunit, significant differences in the levels of these substances could not be detected between patients with oat cell lung tumours and patients with chronic renal failure. However, compared to normal subjects the alpha-subunit levels in serum were elevated in 12% of the male and 30% of the female patients with oat cell carcinoma of the lund and in 80 and 50% of the male and female patients, respectively, with chronic renal failure. The LHbeta-subunit concentration was normal in all tumour patients and none of these patients had detectable (less than 4 ng/ml) levels of HCGbeta-subunit. While such measurements may be of value in relationship to particular neoplasms, it appears that raised levels of glycoproteins and their subunits may be found in other disease states.

Adult↗

Comparison of the redox bioassay with other assays for luteinizing hormone.

The cytochemical (redox) bioassay for LH has been compared with established LH assays. Measurements made by redox bioassays were considerably lower than those made by radioimmunoassay in human female plasma samples obtained at mid-cycle. There was no apparent relationship between measurements on incubation media from cultures of sheep pituitary glands made by redox bioassay and the ovarian ascorbic acid depletion (OAAD) assay. After polyacrylamide gel electrophoresis of a crude extract of a human pituitary gland, redox LH measurements were lower than those of the OAAD assay and radioimmunoassay in the cathodal segments of the gel. By contrast, there was reasonable agreement between LH measurements made by radioimmunoassay and redox assay in cathodal fractions from gel electrophroesis of a purified pituitary LH preparation. Follicle-stimulating hormone, and the alpha- and beta-subunits of LH depressed the response of intact LH in the redox assay; this might explain the relatively low levels of LH measured by redox assay in some of the experiments described. Which type of assay best reflects the biological activity of LH in man remains to be determined.

Animals↗