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Biomedical subjects

G N Burrow

Publications and source records attributed to G N Burrow.

At least 55 records · Page 3Linked to original sources
PubMed1988

Organic iodine inhibits deoxyribonucleic acid synthesis and growth in FRTL-5 thyroid cells.

FRTL-5 thyroid epithelial cells in culture were used to study the possible inhibitory effects of iodine on thyroid growth. NaI exerted a dose-dependent, thyroid epithelial cell-specific inhibitory effect on [methyl-3H]thymidine incorporation into DNA, reduced the DNA content in the cell layer, and limited the increase in cell number mediated by TSH. The inhibitory effects of sodium iodide applied to growth stimulated by TSH-, cAMP-, and non-cAMP-dependent mechanisms and were prevented by 1-methylimidazole-2-thiol (methimazole) and 2-ethylthioisonicotinamide (ethionamide). The latter findings indicate that the inhibitory effects of NaI are mediated by some iodine-containing organic compound. The inhibitory effects of organic iodine on growth subsided 24-48 h after removal of excess NaI from the culture medium. In contrast, NaI had no effect on normal rat kidney fibroblast or thyroid fibroblast [methyl-3H]thymidine incorporation stimulated by epidermal growth factor or serum. These data demonstrate a specific inhibitory effect of organic iodine on thyroid epithelial cell growth.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

Failure of gonadotropin therapy secondary to chorionic gonadotropin-induced antibodies.

Seventeen years after first receiving treatment with hCG (at age 8 yr), a man with hypogonadotropic hypogonadism no longer responded to gonadotropin therapy. He had received hCG for 6 months when he was 8 yr old, from age 18-21 yr and from age 21-25 yr, when the resistance developed. Anti-hCG antibodies were found in his serum. Three sequential treatment regimens were tried to obviate the effect of these antibodies. 1) hCG treatment (2000 IU, three times per week) concomitant with weekly plasmapheresis (since the patient's response to an hCG challenge test was improved after a reduction of antibody titer by plasmapheresis) resulted in only a temporary increase in testosterone production. 2) Treatment with human (h) LH (400 IU/week) and hFSH (25 IU/week) was used because of the low cross-reaction of the antibodies with hLH and a response to a hLH-challenge test. This treatment maintained serum testosterone levels within the normal range for long periods, but had to be discontinued when the supply of hLH was exhausted. 3) Pulsatile LHRH administration (25 ng/kg, sc, every 2 h) for 2 months did not induce the release of pituitary gonadotropins. These results indicated that 1) conventional hCG treatment was impaired by antibody-induced changes in the kinetics of hCG after its im administration; 2) hLH was an effective substitute for hCG, and the combined hLH-hFSH administration initiated a moderate amount of spermatogenesis; and 3) the patient differs from most individuals with hypogonadotropin hypogonadism in that he did not have normal responses to repetitive LHRH administration.

Antibodies↗
PubMed1988

Hashimoto's disease in Turner's syndrome.

Sera from 52 patients with Turner's syndrome were analyzed for thyroxine and TSH concentrations, resin T3 uptake, and thyroid antibodies. Thyroid antibody titers were compared to those previously obtained in 53 women with long-standing infertility. Thyroid microsomal and/or thyroglobulin antibody titers were elevated to a level diagnostic of Hashimoto's disease (greater than 1:400) in 25 (48%) patients with Turner's syndrome. Microsomal antibody levels only were elevated in five (9%) patients with infertility. The mean microsomal antibody titers in the patients with Turner's syndrome (1:25, 167 +/- 31,531) were significantly higher than in the infertile patients (1:2560 +/- 2149). The incidence of Hashimoto's disease did not differ significantly among the various karyotypes. The entire clinical spectrum of Hashimoto's thyroiditis was present in Turner's syndrome. Three patients had overt hypothyroidism necessitating L-thyroxine, four had compensated hypothyroidism (serum TSH concentration greater than 10 microU/L and normal serum thyroxine concentrations), while the remaining 18 had normal thyroid function. No relationship was demonstrated between Hashimoto's disease or family history of thyroid disease and karyotype.

Adolescent↗
PubMed1988

From bench to bedside--the impact of the transfer of the new biology to clinical medicine.

Recent advances in cellular and molecular biology have enormous implications for clinical medicine. Of particular interest is the ability to diagnose genetic diseases. Although enormous advances have been made in the diagnosis of monogenic disorders, these diseases account for a relatively small percentage of patients seen in adult medicine. Of more interest in terms of clinical impact are the chronic diseases with a genetic component which occur in about 10% of the population e.g. diabetes mellitus, heart disease, malignancy. If a subgroup of patients with a chronic disease such as diabetes mellitus, who are at particular risk to develop complications, can be identified, the physician will have to convince them to alter their lifestyle. The transfer of basic science to clinical medicine may ultimately lead to a greater emphasis on the art of medicine.

Genetic Diseases, Inborn↗
PubMed1987

Effect of SMS 201-995, a long-acting somatostatin analogue, on the secretion and morphology of a pituitary growth hormone cell adenoma.

The present study reports the effects of SMS 201-995, a long-acting somatostatin analogue, on blood GH levels, glucose tolerance and tumour morphology in a 36-year-old, previously untreated acromegalic woman. Treatment (50 micrograms s.c., 8-hourly) resulted in marked suppression of GH concentration and an improvement in glucose tolerance. After 10 d of treatment, the tumour was removed by transsphenoidal surgery and studied by histology, immunohistochemistry, transmission electron microscopy and morphometry. Histologically, the tumour was an acidophilic adenoma which contained immunoreactive GH in many adenoma cells. By electron microscopy, the tumour was composed of densely granulated somatotrophs containing numerous large secretory granules and many lysosomes showing crinophagy. No cell necrosis or vascular impairment were evident. Using morphometry, the tumour was compared with 10 densely granulated somatotroph adenomas, removed from acromegalic patients not treated with somatostatin. The nuclear and cytoplasmic areas of the adenoma subjected to SMS 201-995 treatment were smaller, and the lysosomes occupied more of the cytoplasmic volume than those of controls. The nuclear/cytoplasmic ratio, cytoplasmic volume densities of endoplasmic reticulum, Golgi apparatus, mitochondria, secretory granules and secretory granule diameters were within the range of control adenomas. In vitro, treated adenoma cells secreted GH and retained responsiveness to both GRH stimulation and somatostatin suppression. The morphologic findings after SMS 201-995 treatment, are consistent with suppression of GH release. There is no evidence that somatostatin has any direct cytotoxic or vasotoxic effects. It appears that SMS 201-995 represents a potent and promising drug in the medical treatment of acromegaly, however, more work is needed to elucidate the mechanism of somatostatin suppression and to provide evidence for adenoma shrinkage.

Acromegaly↗
PubMed1987

Regulation of differentiated thyroid function by iodide: preferential inhibitory effect of excess iodide on thyroid hormone secretion in sheep thyroid cell cultures.

Primary cultures of sheep thyroid cells have been used to study the inhibitory effects of iodide on thyroid function. Under the influence of TSH, iodide was concentrated with a cell to medium ratio of 20. When thyroid hormone secretion was measured from cells cultured without addition of exogenous iodide, preferential T3 secretion was evident. The optimum iodide concentration for T4 and T3 synthesis and secretion was 10(-6) M. Prior exposure to 10(-5) M or more iodide decreased subsequent iodide transport in a concentration-dependent manner compared to that in cells acutely exposed to iodide. Although cell to medium ratios were decreased, intracellular iodide concentrations continued to rise with increasing external iodide concentrations, and iodide available for thyroid hormone synthesis was not in limited supply. Iodide concentrations of 10(-4) M or greater inhibited iodothyronine synthesis and thyroid hormone secretion, assessed by both assay of trichloroacetic acid-insoluble Na125I activity in cells and RIA of T4 and T3 in the medium and cell layer. An intermediate concentration of 10(-5) M iodide had a marked inhibitory effect on T4 and T3 secretion, but iodothyronine formation on thyroglobulin was only slightly affected. Our results suggest a preferential inhibitory effect of elevated iodide concentrations on thyroid hormone secretion. The adaptive advantages of this selective inhibition would allow storage of iodothyronines in times of iodide sufficiency while maintaining euthyroidism.

Animals↗
PubMed1987

Role of non-TSH factors in thyroid cell growth.

The effects of insulin, the tumour promotor tetradecanoyl phorbol acetate (TPA), TSH and combinations of these factors on growth and DNA synthesis have been examined in the FRTL-5 cell strain and in sheep thyroid cells. In addition the regulation of the production by sheep thyroid cells of the insulin-like growth factors (IGF) by TSH and their possible autocrine roles have been investigated. We found that insulin and the IGF's stimulated DNA synthesis in both rat FRTL-5 cells and sheep cells. TPA also stimulated growth in both cell types, and its effects were additive to those of insulin. In the FRTL-5 cells, TPA was a less potent stimulator of growth than TSH, but the effects of TPA and TSH were not additive which may imply growth stimulation through a common pathway. In sheep cells TSH was not mitogenic and did not appear to activate protein kinase C, the receptor for TPA. Sheep cells, unlike FRTL-5 cells, were found to produce IGF-I and IGF-II, and their syntheses were regulated by TSH. Sheep cells were also found to produce IGF-binding proteins which may modulate the biologic effects of the IGF's. Sheep thyroid IGF binding proteins were found to copurify with urokinase-like plasminogen activator on immunoaffinity chromatography. The production of this serine protease has also been shown to be regulated by TSH.

Animals↗
PubMed1987

The somatostatin analogue SMS 201-995 in acromegaly: prolonged, preferential suppression of growth hormone but not pancreatic hormones.

The treatment of acromegaly is not optimal at present, since many patients have continued growth hormone hypersecretion. We report the acute effects of a cyclic octapeptide analogue of somatostatin, SMS 201-995 (Sandoz) in 9 nondiabetic, acromegalic patients between the ages of 30 and 74. We report potent and prolonged dose-dependent effects to suppress growth hormone secretion. A single 50 micrograms dose of SMS 201-995 inhibited growth hormone concentration rapidly within 15 minutes, with maximal effect in 75 minutes. Maximal inhibition was of the order of 80%, with absolute concentrations under 2 micrograms/L for about 6 hours in 5 of 7 patients. Growth hormone concentrations remained significantly suppressed below placebo control for up to 24 hours after a single dose of SMS 201-995, but the inhibitory effects on insulin and C-peptide concentrations were limited to 2 hours. The effects on glucagon secretion were minimal, and also evident for only 2 hours. Mild transient postprandial elevations of plasma glucose and FFA were documented. No adverse effects were noted; routine hematology, biochemistry, and vital signs were not altered. Thus SMS 201-995, with preferential effects at the pituitary somatotroph, holds considerable promise as an attractive and viable alternative for treatment of acromegaly.

Acromegaly↗
PubMed1986

Growth and differentiation in cultured human thyroid cells: effects of epidermal growth factor and thyrotropin.

Human thyroid cells were grown and subcultured in vitro to examine their responses to known hormones and growth factors, and to serum. The cells were obtained from surgical specimens and were either neoplastic or nonneoplastic. The effects of culture conditions on cell growth were measured by changes in cell numbers and by stimulation of [3H]thymidine incorporation. The results showed that serum (0.5%) was essential for cell proliferation, and that a mixture of insulin (10 micrograms/ml), transferrin (5 micrograms/ml), hydrocortisone (10 micrograms/ml), somatostatin (10 ng/ml), and glycyl-histidyl-lysine (10 ng/ml) enhanced the effect of serum. Maximum growth of the cells was obtained when epidermal growth factor was present at 10(-9) M. Differentiation was measured by production of thyroglobulin, which was found to be stimulated by thyrotropin. This system provides a means to study the hormonal control of growth and differentiation in human thyroid cells.

Cell Differentiation↗
PubMed1986

Thyrotropin-induced formation of functional follicles in primary cultures of ovine thyroid cells.

In primary cultures of ovine thyroid cells, TSH induced the expression of several differentiated functions including the formation of follicles, and synthesis and storage of iodinated thyroglobulin in the follicular lumen. In the present report, these follicles were shown by transmission (TEM) and scanning electron microscopy (SEM) to be intact, comprised of two or more cells and to possess numerous microvilli on the inner cell membranes facing the follicular lumen. The TSH-induced formation of follicles was reversible and dynamic, with the kinetics of formation preceding that of iodination. The follicles were further demonstrated to be functional in terms of thyroglobulin storage and iodination.

Animals↗
PubMed1986

Disparate uptake of 99mTcO4- and 125I- in thyroid cells in culture.

Pertechnetate (99mTcO4-) is a large anion that is thought to be trapped but not organified by the thyroid. In order to determine its usefulness in discriminating trapping from organification in thyroid cell culture, the uptake of 99mTcO4- has been compared to that of 125I- both in sheep thyroid cells and in FRTL5 cells, a functional rat thyroid cell line. We found that uptake of both isotopes was dependent on TSH or agents that raised intracellular cAMP levels and was displaceable with iodide in both cell types. However in rat cell line 99mTcO4- uptake was up to eight-fold higher than 125I- uptake, and 99mTcO4- but not 125I- uptake was doubled by methimazole treatment. A considerable proportion of 99mTcO4- but not 125I- taken up by the FRTL5 cell but not the sheep cells was precipitable with TCA. This proportion was increased by methimazole treatment. We also found marked differences in sensitivity to ouabain between the two cell types. These results illustrate the differences between species in 125I- and 99mTcO4- transport and support the concerns expressed by Socolow and Ingbar (1967) in using 99mTcO4- as a direct and precise indicator of iodide transport activity.

Animals↗
PubMed1985

Epidermal growth factor inhibits thyrotropin-mediated synthesis of tissue-specific proteins in cultured ovine thyroid cells.

Primary cultures of ovine thyroid cells were induced to differentiate by addition of thyrotropin (TSH). This was demonstrated as an accumulation of 2 thyroid-specific proteins, thyroglobulin and thyroid peroxidase, using immunofluorescent staining methods and immunoprecipitation of biosynthetically labeled cultures. As an additional measure of differentiation, cells exhibited a morphological response to TSH and regained the ability to incorporate radioactive iodide. Epidermal growth factor (EGF) markedly inhibited differentiation when added together with TSH. Thyroglobulin synthesis was reduced to low levels and peroxidase synthesis was reduced to levels that were undetectable by the methods used. Morphological changes in response to TSH were also diminished by EGF. The antagonistic interaction between TSH and EGF in regulating differentiation in cultured thyroid cells may reflect the type of control that exists in vivo.

Animals↗
PubMed1985

Phorbol esters stimulate growth and inhibit differentiation in cultured thyroid cells.

The potent tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) has biological effects on cell growth and differentiation similar to the effects of epidermal growth factor (EGF) on a variety of cells. Since EGF has been shown recently to stimulate thyroid cell proliferation and inhibit iodine metabolism, we examined the effects of phorbol esters on primary ovine thyroid cultures. TPA stimulated cell growth in a manner similar to EGF. The growth effects of EGF and TPA in combination were not additive. In contrast, TPA (1.6 X 10(-7) M) was a more potent inhibitor of iodine uptake and incorporation than EGF (10(-9) M) at their maximally effective concentrations. The inhibitory effects of TPA were also more rapid and less reversible than those of EGF. TPA and EGF in combination inhibited iodine metabolism more than either agent alone at its maximally effective concentration. Both TPA and EGF reduced the accumulation of cAMP in TSH-stimulated cells, but (Bu)2cAMP and stimulators of adenylate cyclase failed to overcome TPA's inhibition of iodine metabolism. TPA interacted with EGF by reducing the affinity of membrane receptors for [125I]iodo-EGF. Although the alteration in EGF-receptor interaction induced by TPA may play a role in mediating TPA's biological effects, the additive effects of TPA and EGF on iodine metabolism suggest that TPA does not act solely through the EGF receptor-effector system. Agents other than TSH, including phorbol esters and EGF, are potent modulators of thyroid growth and differentiated function. Despite several similarities in biological activity, TPA and EGF do not modulate differentiated function in an identical manner. Both factors act at least partially through a non-cAMP-dependent pathway, providing indirect evidence of another second messenger(s) in the control of thyroid function.

Animals↗
PubMed1985

Cardiovascular surgery in the hypothyroid patient.

The management of hypothyroid patients requiring major cardiovascular surgery is difficult and often controversial. We prospectively studied 500 patients requiring cardiac surgery with cardiopulmonary bypass and found ten with previously undiagnosed mild to moderate hypothyroidism. All ten tolerated surgery well without preoperative thyroid hormone replacement. Our experience with these patients plus an additional five seen in our clinical practice suggests that major cardiovascular surgery can be performed safely in most patients with mild to moderate hypothyroidism. We conclude that untreated hypothyroidism in patients with ischemic heart disease should not be an absolute contraindication to coronary artery bypass surgery.

Adult↗
PubMed1984

Thyrotropin regulation of plasminogen activator activity in primary cultures of ovine thyroid cells.

In primary cultures of ovine thyroid cells, a high level of plasminogen activator (PA) activity was detected in the culture media. This level is much higher than in primary cultures of Sertoli cells, granulosa cells, and pituitary cells. PA activity increased with time in culture and was regulated by TSH and insulin. Activity gel analysis of the culture media revealed a major band of 43,000 daltons and a minor one of 70,000 daltons, suggesting the presence of both of the urokinase-type and the tissue-type PA in the media.

Animals↗