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Biomedical subjects

E G Black

Publications and source records attributed to E G Black.

13 recordsLinked to original sources

Basic fibroblast growth factor: an autocrine mitogen of rat thyroid follicular cells?

Basic fibroblast growth factor (FGF) is a mitogen for the rat thyroid cell line FRTL-5. A possible autocrine role for this growth factor has been investigated in rat thyroid follicular cells both in vitro and in vivo. We report here the synthesis and localisation of basic FGF and one of its high affinity receptors (flg) in FRTL-5 cells, shown by Northern hybridization analysis, Western blotting, and immunohistochemistry. Two major species of basic FGF mRNA of approximately 2.2 and 7.0 kilobases and one major species of flg mRNA of approximately 4.2 kilobases were identified in FRTL-5 cells. The basic FGF immunoreactivity observed histologically was attributed to a heparin-binding protein of approximately 20 kilodaltons mol wt. The physiological relevance of basic FGF to the thyroid is underlined by the demonstration of significant stores of immunoreactive protein, predominantly in the basement membrane of thyroid follicular cells, in paraffin sections of the normal rat thyroid, although basic FGF mRNA was not detected by in situ or Northern hybridization analysis. The mitogenic response of FRTL-5 cells to human recombinant basic FGF has been further characterized, and the factor shown to stimulate with an ED50 of 4 ng/ml. The mitogenic effects of exogenously supplied and endogenously produced basic FGF were shown to be potentiated by heparin. Examination of the mitogenic activity of both exogenous and endogenous basic FGF and its immunoneutralization in vitro suggests that locally produced basic FGF may be an important autocrine regulator of thyroid follicular cell growth.

Animals

Serum thyroglobulin measurements in thyroid cancer: evaluation of 'false' positive results.

OBJECTIVE: Serum thyroglobulin (Tg) should be undetectable in patients successfully treated for thyroid carcinoma. We have examined the course of disease in 19 patients with raised serum Tg (greater than 5 micrograms/l) on initial measurement but no other evidence of residual, recurrent or metastatic cancer. DESIGN: 416 patients from several centres were followed for periods between 1 and 9 years. Serum Tg was measured at 6-12-month intervals. PATIENTS: All had differentiated thyroid cancer, treated by partial or total thyroidectomy and/or 131I ablation, and were receiving suppressive thyroxine therapy. MEASUREMENT: Serum Tg was measured and clinical, X-ray and scan assessment made of presence or absence of residual, recurrent or metastatic cancer. RESULTS: Of 416 patients initially assessed, only 19 had Tg greater than 5 micrograms/l but no clinical or radiological evidence of disease. At follow-up, 11 patients had developed overt signs of malignancy; one had been treated with 131I with a subsequent fall in Tg; five had Tg between 5 and 20 micrograms/l with incompletely suppressed TSH levels; two subjects remained with slightly elevated Tg and undetectable TSH. CONCLUSION: Patients with elevated Tg require careful follow-up even in the apparent absence of disease. Moderate elevation of serum Tg may be due to inadequate thyroxine suppression therapy, assessed by detectable TSH values measured in a sensitive assay.

Biomarkers, Tumor

Serum thyroglobulin concentrations and whole-body radioiodine scan in follow-up of differentiated thyroid cancer after thyroid ablation.

Measurement of serum thyroglobulin (Tg) concentrations and whole-body radioiodine scan were performed simultaneously during follow-up of 32 patients with differentiated thyroid cancer who had undergone thyroid ablation by operation and radioiodine. Almost all patients in whom serum Tg was undetectable had normal scans. Concentrations exceeding 50 ng/ml were invariably associated with residual or metastatic tumour uptake in the scan. Out of 21 observations of detectable values below 50 ng/ml, 14 were in patients whose scans showed subclinical or sub-radiological tumour uptake and seven in patients with normal scans. The sensitivity of serum Tg as a tumour marker compared favourably to that of the whole-body scan. A scan is unnecessary when serum Tg is undetectable, but in patients with detectable serum Tg concentrations, particularly if these are below 50 ng/ml, a scan is important to assess and localise tumour uptake of iodine before advising treatmet with iodine-131.

Adenocarcinoma

Effects of surgical stress and corticotrophin on the peripheral metabolism of thyroid hormones in rabbits.

The effect of surgical stress and ACTH injection on the peripheral monodeiodination of thyroxine (T4) was studied in the rabbit. These stimuli resulted in a switch from the peripheral formation of tri-iodothyronine (T3) to reverse T3 in normal rabbits and in rabbits whose thyroidal secretion was suppressed by administration of T4. This is analogous to the situation in man. These changes were not due to alterations in the serum binding capacity for thyroid hormones.

Adrenocorticotropic Hormone

The inter-relationship of thyroid hormones, vitamin A and their binding proteins following acute stress.

The effects of surgical stress on the metabolism of the retinol-binding-protein-thyroxine-binding-prealbumin complex were investigated. The immediate postsurgical period was characterized by a rapid decline in the serum concentration of retinol, retinol binding protein and triiodothyronine and an increase in the 24 h urinary excretion of retinol, retinol-binding-protein and thyroxine. Similar, but less pronounced, changes were seen in other subjects suffering acute myocardial infarction but were not observed in normal healthy euthyroid males or in pre-operative euthyroid patients. The preparation of specific anti-retinol binding protein anti-serum and the use of this in 'monorocket' immunoelectrophoresis are also described.

Antibodies

Effects of chronic renal disease on thyroid hormone metabolism.

Serum concentrations of total and free thyroxine and triiodothyronine together with urine losses of unconjugated thyroid hormones have been measured in normal subjects and in patients with renal disease. Serum total hormone values in the hypothyroid range were common the renal group and correlated inversely with the degree of renal impairment but not with renal loss of hormone which in the case of thyroxine exceeded the average normal daily loss ten-fold. The euthyroid state of patients with renal disease was best reflected by serum free thyroxine concentration which in every case was within the normal range. Poor correlation was apparent between the respective urine concentrations of albumin and thyroxine, and the reasons for this are discussed.

Adolescent

Measurement of thyroid hormone in experimental thyroid tumours in rats.

Rats treated with 131I and propylthiouracil were shown to develop thyroid tumours 7--9 months after treatment. In this group, the levels of total thyroxine and tri-iodothyronine, and free thyroxine and tri-iodothyronine in the serum were low, and that of TSH was raised. In a group of rats treated with 131I and then propylthiouracil and thyroxine, thyroid tumours were found despite normal concentrations of total and free thyroxine and tri-iodothyronine in the serum. The level of TSH in the serum was significantly raised in this group. Thyroid tumours were not found in the various control groups of rats.

Animals

Effect of a single dose of dexamethasone on serum concentrations of thyroid hormones.

In ten euthyroid subjects, in whom endogenous thyroid-stimulating hormone (T.S.H.) production was suppressed by oral thyroxine (T4), a single dose of dexamethasone resulted in reduced serum-3,3'5-triidothyronine (T3) concentration and raised serum-3,3',5'-triiodothyronine (reverse T3 or rT3) concentration after 24 h. These changes were not related to changes in free hormones or binding proteins. Adrenal glucocorticoids may have a pathophysiological role in modulating the peripheral metabolism of thyroid hormones in stress.

Adult

Measurement of serum 3,3',5'-(reverse) T3, with comments on its derivation.

A radioimmunoassay for the measurement of l-3,3',5'-triiodothyronine (reverse TO, rT3) has been developed for use with unextracted serum. The highly specific antiserum showed no cross-reactivity with l-3,3'5-triiodothyronine (T3) or tetradiodothyroacetic acid (T4A) and cross-reaction with L-thyroxine (T4) was low enough to be discounted for routine assay purposes. If a normal amount of rT3 was added to serum T4 cross-reactivity decreased considerably. Serial dilutions of hyperthyroid sera gave dose-response curves which were parallel to the rT3 standard curve. Serum concentrations of rT3 (mean+/- SEM) were 0-68 +/- 0-02 nmo1/1 in sixty-seven normal subjects, 0-19 +/- 0-02 nmo1/1 in twelve hypothyroid patients and 1-18 +/- 0-12 nmo1/1 in seventeen hyperthyroid patients. In sixteen patients with TO-toxicosis rTO was 0-42 +/- 0-04 nmo1/1 and eighteen patients with high circulating TBG had a mean rT3 of 0-54 +/- 0-03 nmo1/1.

Antibody Specificity

Altered patterns of thyroid hormones in serum and urine in pregnancy and during oral contraceptive therapy.

Serum total, percentage free fraction and absolute serum free hormone concentration of thyroxine and triiodothyronine were measured in control, pregnant and oral contraceptive users, together with the daily urinary losses of unconjugated thyroid hormones. Increased urinary losses of both hormones, in particular thyroxine, were apparent in pregnancy and these could not be explained in terms either of an increased filtered load of hormone or the presence of proteinuria. The possible existence of filterable small-molecular weight hormone-binding substances in the urine of pregnant patients is discussed. It is concluded that assay of urinary thyroid hormones during pregnancy is of limited diagnostic value because of overlap with thyrotoxic values.

Adult