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Biomedical subjects

E D Williams

Publications and source records attributed to E D Williams.

At least 127 records · Page 7Linked to original sources
PubMed1990

Immunocytochemically detectable TGF-beta associated with malignancy in thyroid epithelial neoplasia.

The possible role of changes in TGF-beta expression in the multistage development of thyroid cancer was assessed. The presence of TGF-beta 1 in thyroid epithelial cells was analyzed in sections of normal and tumor tissue using an immunoperoxidase technique employing an antibody directed against the amino-terminal 30 amino acids of mature TGF-beta 1. Specific immunostaining was clearly detected in epithelial cells in 58% of malignant thyroid tumours (including follicular, papillary, and anaplastic variants). However, no positive cells were seen in any of 7 benign tumors nor in any normal thyroid epithelium. Within the cancer group as a whole, there was no significant correlation with pathological grade or clinical stage of tumor but in one subgroup--follicular carcinomas--a significant association was noted between TGF-beta immunostaining and the presence of a specific mutation of the H-ras oncogene (codon 61, gln----arg). We conclude that a major alteration in expression of TGF-beta occurs specifically in the malignant stage of tumor development in thyroid follicular epithelium and speculate on its possible role in this process.

Adenocarcinoma↗
PubMed1990

The pathology of granulomatous diseases of the thyroid gland.

In the present review we comment on granulomatous diseases of the thyroid gland based mainly on combined clinico-pathological criteria. Emphasis is given to diseases restricted to the thyroid (i.e., de Quervain's, palpation and interstitial giant cell thyroiditis), and those that may manifest as primary in the thyroid though they may be part of a generalized process (i.e., sarcoidal, tuberculous, fungal and syphilitic thyroiditis). Other disorders with minor variable granulomatous or pseudogranulomatous components affecting the thyroid are briefly described, and differential diagnoses analysed for granulomatous lesions both specific and non-specific to the thyroid.

Granuloma↗
PubMed1989

Rapid, high-sensitivity reversed-phase liquid chromatographic assay for 9-chloro-2-(2-furyl) [1,2,4]triazolo[1,5-c]quinazolin-5-imine and its oxo metabolite in plasma using fluorescence detection.

A rapid, sensitive and specific assay for 9-chloro-2-(2-furyl) [1,2,4]triazolo[1,5-c]quinazolin-5-imine (I) and its oxo metabolite (II) in plasma was developed and validated employing reversed-phase high-performance liquid chromatography with fluorescence detection. Sample preparation was achieved by a simple ethyl acetate extraction from plasma buffered at pH 10 (0.1 M boric acid-0.1 M potassium chloride). Chromatographic analyses were performed isocratically on a C18 column, with a mobile phase consisting of methanol-0.2 M sodium acetate buffer, pH 5.0 (67:33, v/v). Chromatographic run time was less than 8 min. The assay was linear (r greater than 0.9998) over the concentration range 1.50-10,000 ng/ml for both I and II; for individual studies, curves covering a range of two orders of magnitude were generally employed. Limits of detection for I and II were 0.5 and 1.0 ng/ml, respectively. A preliminary investigation of the plasma concentrations of I and II in the rat following a single 30 mg/kg oral dose demonstrated the applicability of the method for pharmacokinetic studies.

Animals↗
PubMed1989

The ultimobranchial gland and congenital thyroid abnormalities in man.

This study was carried out to investigate the fate of the ultimobranchial contribution to the thyroid in man when the thyroid lobe is not fully descended. Thyroid abnormalities were recorded in 41 of 29,000 autopsies at the London Hospital--a prevalence of 1.41/1000. The 18 major abnormalities included four cases of lingual thyroid, in two of which cystic structures were noted in the neck in the region of the upper parathyroid. Three further cases of lingual thyroid with upper parathyroid cysts were collected from other sources. The multilobulated cystic structures were up to 1.5 cm in diameter and showed a variety of histologic features. In four cases there were glandular nodules of up to 1 mm across lying in the intercystic connective tissue. These nodules showed solid areas of irregularly distributed cells that stained positively for calcitonin and calcitonin gene-related peptide, intermingled with, and sometimes apposed to, follicular structures that showed follicular cells and colloid that stained for thyroglobulin. This study has provided conclusive evidence that the ultimobranchial body contributes both C cells and follicular cells to the thyroid in man, has documented the prevalence of congenital defects of thyroid development, and has described the human ultimobranchial gland as showing a wide developmental potential which may have implications in the histogenesis of thyroid neoplasia.

Animals↗
PubMed1989

The fate of miniplates in facial trauma and orthognathic surgery: a retrospective study.

The fate of 279 Champy miniplates used routinely as permanent implants over a 5-year-period in the management of maxillofacial trauma and orthognathic surgery has been analysed retrospectively. Trauma patients (62) and orthognathic patients (47) were analysed separately; in each group those patients who had plates removed were compared to the patients with retained plates. This study indicates that the morbidity of retaining plates is within acceptable limits and that the routine removal of plates at 3 months may be unnecessary.

Adolescent↗
PubMed1989

Evidence for autocrine production of IGF-1 in human thyroid adenomas.

We have recently shown that epithelial cells from a high proportion of benign human thyroid tumours (follicular adenomas) have escaped from the requirement of the normal cell for an exogenous source of insulin-like growth factor 1 (IGF-1), suggesting either autocrine production or intracellular generation of an IGF-1-induced growth signal. We show here that conditioned medium from these adenoma cells can confer IGF-1 independence on normal thyroid epithelial cells and that this activity is abolished by immunoadsorption with an anti-IGF-1 antibody. In addition, tumour but not normal cells contain immunoreactive IGF-1. Our data provide the first evidence for autocrine production of IGF-1 (or a related factor) in a benign epithelial tumour and suggest that this may be a key early step in thyroid tumorigenesis.

Adenoma↗
PubMed1989

Thyroid epithelial cell transformation by a retroviral vector expressing SV40 large T.

A recombinant murine retroviral vector encoding the SV40 virus large T antigen was used to infect stably an immortal line of differentiated rat thyroid epithelial cells, FRTL-5. Expression of SV40 T transformed these cells to anchorage independence and tumorigenicity but did not alter morphology or abolish tissue-specific functions and growth factor requirements. The resulting phenotype provides a model of well-differentiated human thyroid cancer.

Animals↗
PubMed1989

Structure and expression of nuclear oncogenes in multi-stage thyroid tumorigenesis.

We have investigated the possibility that structural alterations of the 'nuclear' oncogene family (c-myc, N-myc, L-myc, fos, myb and p53) leading to aberrant expression might, as in several other tumour types, play a role in the multi-stage development of tumorigenesis in the human thyroid follicular cell. Direct analysis of expression by slot and Northern blot RNA hybridisation showed that normal thyroid expresses surprisingly high levels of fos, and to a lesser extent c-myc, c-myc expression was markedly increased in all tumours, both benign and malignant, but no increase was seen in any other nuclear oncogene. fos expression was reduced specifically in one type of malignant tumour-follicular carcinoma-in inverse correlation with differentiation. Southern blot analysis showed no evidence of rearrangement or amplification of c-myc, or of any other 'nuclear' oncogene in any thyroid tumour. We conclude that there is no evidence that a primary abnormality of these genes plays a role in thyroid follicular cell tumorigenesis and suggest that the observed changes in expression can be adequately explained as secondary consequences of the tumour phenotype.

Adenoma↗
PubMed1989

A postal survey of quality assurance in nuclear medicine imaging in the UK during 1988.

A questionnaire was sent to all the estimated 200 hospital departments providing nuclear medicine imaging services in the UK. Replies were received from 162 (81%). The questionnaire was brief, but covered a wide range of aspects of a nuclear medicine service. While all responses showed departments to have some quality control procedures in operation, they were often not used correctly. In most departments there appears to be scope for improvement so that departmental managers can monitor more closely the quality of service provided.

Hospital Departments↗
PubMed1989

Hyalinizing trabecular adenoma of the thyroid. A report of three cases with immunohistochemical and ultrastructural studies.

We have studied three examples of benign thyroid tumours which conform to the lesion recently described as hyalinizing trabecular adenoma. The prominent feature of this trabecular epithelial lesion is the extracellular deposition of an eosinophilic material that does not show the features of amyloid; the epithelial cells may be elongated, sometimes radially arranged around the eosinophilic material. All three tumours showed positive immunocytochemical staining for thyroglobulin, keratin, chromogranin and neuron-specific enolase. One tumour showed isolated cells with immunoreactivity for somatostatin, argyrophil cytoplasmic granularity with the Grimelius technique, and ultrastructurally demonstrable cytoplasmic electron-dense endocrine granules. The hyaline extracellular material in all three tumours showed strong immunoreactivity for both type IV collagen and laminin. Previous radiation may be important in the causation of this tumour, and it shows a frequent association with severe thyroiditis. We conclude that the main histological feature of this lesion, the hyaline material, is due to the overproduction of a basement membrane-like material by the neoplastic follicular cells. The presence in one tumour of evidence of endocrine differentiation may reflect the potential for follicular cells to show biphasic differentiation, a feature which may be more frequent than has been previously recognized. Several of the other features of this tumour--for example the frequent intranuclear cytoplasmic inclusions--may lead to diagnostic problems, and the entity deserves wider recognition.

Adenoma↗
PubMed1989

Multiple hormone storage by cells of the human pituitary.

While immunostaining serial semi-thin sections of acrylic resin-embedded normal human pituitary using antisera to human pituitary hormones, it became clear that several cells were stained by more than one antiserum. The tissue had been surgically excised from a patient with a prolactinoma. The tumor, which was immunoreactive only with antiprolactin antiserum, was distinctly different from the pieces of tissue under study which had normal pituitary architecture and demonstrated immunoreactivity with antisera against all six of the common pituitary hormones. A major immunoelectron microscopic investigation, using immunocolloidal gold and immunoperoxidase methods, revealed cells in which follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) were co-localized to the same electron-dense granules. Some similar cells also possessed electron-lucent granules immunoreactive only for anti-PRL antiserum. Adrenocorticotrophic hormone (ACTH) and PRL were also found in the same cell but were very largely localized to separate, morphologically different populations of electron-dense and -lucent storage granules. By employing double immunolabeling, a few granules in the ACTH/PRL cells were shown to be immunoreactive to both anti-ACTH and anti-PRL antisera. The possibility that the multipotential stem cells is discussed.

Adult↗
PubMed1989

High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis.

Using polymerase chain reaction amplification and oligonucleotide probing, the activation of ras oncogenes in 24 benign and 20 malignant human thyroid neoplasms was examined. The frequency of ras oncogene activation was similar at all stages of tumorigenesis in this system, being found in 33% of adenomas overall (50% of microfollicular tumours), 53% of differentiated follicular carcinomas and 60% of undifferentiated carcinomas. This supports the contention that mutation of these oncogenes occurs at an early step in tumorigenesis. The predominant amino acid substitution in the differentiated tumours was glutamine to arginine at position 61 of Ha-ras or N-ras, but this mutation was not found in any of the undifferentiated tumours. It was noted that while transition mutations predominated in differentiated tumours (both benign and malignant), transversions were more common in the undifferentiated tumours.

Adenoma↗