Microbial adjuvant and autoimmunity. II. Production of lesions in mice immunized with syngeneic tissue extracts together with the capsular polysaccharide of Klebsiella pneumoniae.

The target organs of mice immunized with the respective syngeneic tissue extracts together with the capsular polysaccharide of Klebsiella pneumoniae (CPS-K) as a powerful adjuvant were examined for production of lesions. In 15 out of 24 mice injected three times or more with syngeneic eyeball extracts and CPS-K adjuvant at intervals approximately 30 days, severe eyeball lesions developed in which the normal structure was almost completely lost. A large part of the eyeball tissue of these mice was replaced by infiltration with cells such as lymphocytes, plasma cells and other mononuclear cells and by connective tissue. No definite eye lesions developed in mice injected with CPS-K alone, eyeball extracts alone or eyeball extracts emulsified in complete Freund's adjuvant (CFA). In all of mice injected four times with thyroid gland extracts and CPS-K at intervals of approximately 30 days, definite thyroid gland lesions were produced. In three out of five mice of this group, the thyroid lesions were so severe that the normal thyroid follicular structure was almost completely lost, and a large part of the thyroid gland was replaced by infiltration with lymphocytes, plasma cells and other mononuclear cells and in part by connective tissue. In only one out of five mice injected with thyroid gland extracts emulsified in CFA, definite but milder thyroid gland lesions developed. No definite thyroid lesions developed in the remaining four mice of this group and also in any of the mice injected with thyroid gland extracts alone or CPS-K alone. Repeated injections of lymphoid tissue extracts and CPS-K also induced pathological changes in the spleen and lymph nodes, although less marked than those in the cases of the eyes and thyroid gland. The most remarkable change was a decrease in numbers of small lymphocytes at the areas surrounding the central arterioles in the white pulp of the spleen and the post-capillary venules in the cortex of the lymph nodes. From these results it has been concluded that our system can provide new and useful models for autoimmune diseases in man.     

Iodide excess exerts oxidative stress in some target tissues of the thyroid hormones

Environmental iodine deficiency continues to be a significant public health problem worldwide. On the other hand, iodide excess results principally from the use of iodine-containing medicinal preparations or radiographic contrast media. For this reason we intended to explore iodide excess impairment on prooxidant/antioxidant balance of the thyroid gland, hepatic tissue and in blood and the effect of selenium administration on oxidative stress markers under the same circumstances. Experiments were performed for 10 days with white, male, Wistar rats, as follows: group 1: control-normal iodine supply group; 2: high iodine diet, group; 3: high iodine diet and selenium; group 4: high iodine diet and Carbimasole. Oxidative stress markers such as lipid peroxides were determined in thyroid gland, hepatic tissue and in blood. Measuring H+ donor ability of the sera and catalase activity in thyroid gland and in hepatic tissue assessed antioxidant defense. Iodide excess had prooxidant effects, leading to an increased lipid peroxides level and catalase activity in target tissues and in blood and to a decreased H+ donor ability of the sera. Selenium supplementation had opposite effects. Present data allow us to conclude that the alterations due to iodide excess in thyroid gland, hepatic tissue and in blood are mediated through oxidative stress.     

Demonstration of the heterogeneity of the mast cell population on the basis of the mucopolysaccharide content.

From the aspect of its mucopolysaccharide content the mast cell population is not homogeneous. The pulmonary and heart muscle mast cells of the rat are alcian blue positive, the mast cells of the thyroid gland, lymph nodes, subcutaneous connective tissue, mesentery and peripheral nerve are safranin positive, whereas among the mast cells of the peritoneal cavity and the thymus there are both alcian blue and saffranin positive forms. The least acid mucopolysaccharides are in the mast cells of the peritoneal fluid, the mesentery and the lungs, whereas the most acid ones are in the mast cells of the lymph nodes, the subcutaneous connective tissue and the thyroid gland. There is a considerable difference between the two last mentioned organs. The mast cells of the subcutaneous connective tissue are end-product cells without amine or precursor turnover, whereas the mast cells of the thyroid gland incorporate and deliver amines, which may participate in the regulation of the host gland.     

SCINTIGRAMS OF THE THYROID GLAND—The Diagnosis of Morphologic Abnormalities with I131

Functioning thyroid tissue containing sufficient radioiodine can be visualized by scanning the gland with a directional scintillation counter.⁴ This visual representation of the gland is called a “scintigram.” Scintigrams have been invaluable in the detection and study of both “toxic” and non-functioning nodules, diffuse enlargement in hyperthyroidism and the subsequent reduction in gland size after treatment, carcinoma, and aberrant thyroid tissue.     

Difference between the thyroid gland of normal and hypomyelinated jimpy mice--a light microscopic study

A light microscopic quantitative analysis was performed on normal and jimpy male mice for studying the difference between the structures of the thyroid glands of the two animals. The results of this analysis showed that the thyroid gland of the normal mice consisted of numerous homogenous round follicles with cuboidal follicular cells, separated by thin interlobular and interfollicular connective tissue and a few adipose tissue. The thyroid gland of jimpy mice consisted of a few, small follicles surrounded by columnar follicular cells and intraepithelial capillaries, separated by thick connective tissue and abundant adipose tissue. The number of thyroid follicles are significantly less in the jimpy mice than in the normal mice. Another striking difference is that almost every follicular cell surrounding the follicular lumen of jimpy mice is accompanied by an intraepithelial capillary. In addition, the ratio of the number of intraepithelial capillaries to the number of the thyroid follicular cells are significantly higher in the jimpy mice than in the normal mice. The S-follicles or ultimobranchial cysts of the thyroid gland are well developed in the jimpy mice. The parafollicular cells are normal in appearance. Morphological evidence suggested that the thyroid follicular cells of the jimpy mice are very active in the transport, synthesis and release of thyroglobulin, and secretion of thyroid hormones. But owing to the significantly decreased number of thyroid follicles, the inadequate secretion of the thyroid hormones result in the hypothyroidism and the hypomyelination of the jimpy mice.     

Concentration of selenium in the whole blood and the thyroid tissue of patients with various thyroid diseases

We investigated the possible differences between the concentrations of selenium in the whole blood and thyroid tissue of patients with thyroid disease. The study comprises 41 women with nodular goiter, 19 women and 2 men with thyroid cancer, 18 women with Graves’ disease, and 7 women with thyroiditis. The concentration of selenium was determined by the TRXRF method. The lowest mean selenium level was achieved in the whole blood of women with Graves’ disease and the highest in the whole blood of healthy people. In the thyroid cancer tissue, we found the lowest concentration of selenium and the highest in the thyroid gland of women with nodular goiter and Graves’ disease. The low selenium levles in the thyroid tissue may increase thyroid cancer risk.     

Sex differences in the development of the thyroid gland in human prenatal ontogeny

A comparative study of the thyroid gland development in the human male and female embryos and prefoetuses was carried out. The development of incretory part of the testicles was shown to occur earlier than the differentiation of follicles in the thyroid gland and the appearance of colloid in it. Sexual differences were noted in the appearance of follicles, connective tissue, nerve fibres in the thyroid gland (earlier in the male foetuses). The processes of organ differentiation in the male foetuses were more active than in the female ones during the whole prenatal period of development. A suggestion is put forward that the sexual hormones of embryonic testicles influence the thyroid gland differentiation.     

Neuromedin U-like immunoreactivity in the thyroid gland of the rat

Summary Neuromedin U is a novel neuropeptide found to have a widespread distribution extending throughout the mammalian central nervous system, gastrointestinal tract and the endocrine cells of the pituitary gland. In order to investigate the possibility that neuromedin U-like immunoreactivity is also present in the thyroid gland of the adult rat we have examined its localisation and molecular nature by radioimmunoassay, immunocytochemistry and chromatographic analysis. The neuromedin U content of the whole thyroid gland was found to be 331±67 fmol/gland (mean±SEM), and this value significantly decreased (163±17 fmol/gland) as a result of 14 days of treatment with the anti-thyroid agent methimazole (10 mg/rat/day. Thyrotoxicosis induced by exogenous T4 (10 g/rat/day) failed to alter the thyroid content of this peptide. Immunostaining studies localised neuromedin U to a minor population of parafollicular C-cells in untreated animals. Complementary chromatographic studies revealed a single molecular form of neuromedin U-like immunoreactivity in thyroid tissue extracts which was indistinguishable from synthetic rat neuromedin U standard.     

Oncogene expression in a medullary thyroid carcinoma

We report the expression of Ha-ras, fos, c-myc and N-myc mRNA in a human medullary carcinoma of the thyroid gland, both in primary tumor and lymph node metastasis, as demonstrated by in situ hybridization and Northern blot analysis. A significant difference in the oncogene expression in the primary tumor and the metastasis was not observed. Tumor tissue revealed a significant overexpression of Ha-ras, c-myc and N-myc mRNA as compared to the normal thyroid gland. The amount of fos mRNA expression in non tumorous thyroid gland did not significantly differ from tumor tissue, sis, fms and abl mRNA expression was not detectable in tumor tissue and non tumorous thyroid gland. We conclude, that the (over)expression of the oncogenes Ha-ras, c-myc and N-myc may be associated with initiation and progression of medullary thyroid carcinoma. Similar studies on additional cases of human medullary thyroid carcinoma will be necessary to reveal further information.     

Iodine metabolism in the thyroid gland in chronic uranium poisoning]

The exchange of radioactive and stable iodine was studied for 21 days after the I131 injection in the thyroid gland and the blood of rats against the background of chronic uranium intoxication. The latter was accompanied by a decrease in the number of iodine-transport loci of the gland, as well as of the value of the intrathyroid iodine pool and of the stable iodine concentration in the thyroid tissue. The compensatory reaction of the thyroid gland was expressed in the increase of its mass and the rate of the thyroid metabolism as well.     

Cholinergic nerves in the thyroid gland

Summary The cholinergic innervation of the thyroid gland has been studied in the human. AChE positive nerve fibers are localized in the wall of the thyroid artery, arranged in two plexuses, a superficial (adventitial) and a deep one (medial). The glandular tissue is provided with cholinergic nerve fibers, localized between and around thyroid follicles. The present results suggest that the endocrine activity of the thyroid gland is also under the control of the autonomic nervous system.     

Relationship of biochemical and morphological changes in rat thyroid and proton spin-relaxation of the tissue water.

The effect was studied of biochemical and morphological changes induced by antithyroid substances (PTU, C10(-4)) on proton spin-relaxation properties of rat thyroid gland. It was found that thyroid stimulated by PTU (0.05%) or C10(-4) (1.0%) exhibit marked morphological changes (hyperplasia and epithelial hypertrophy) with alteration of the soluble iodoprotein pattern (content and composition.). Both relaxation times spin-lattice (T1) and spin-spin (T2) were increasing with the lenght of treatment with antithyroid drugs. Reversibility of the process was noted in accordance with biochemical and morphological data. The relaxation rate (formula: see text) for thyroid tissue water was in positive correlation with the suluble protein concentration and particularly with the TG content in the gland. There was no difference in relaxation times between normal thyroid and gland of rats treated chronically with excess iodide. The observed difference in T1 between normal glands and glands of PTU,-C10(-4)--treated rats was comparable with that found in cases of human thyroid cancer. This finding is of importance when the diagnostic potential of NMR in the detection of malignancy is considered. In conclusion, a strong correlation was found between microstructural and biochemical changes of the thyroid gland and proton magnetic relaxation of tissue water. The striking difference between the proton spin-relaxation times in normal and in goiter thyroid glands of rats suggests that pulsed NMR spectroscopy could be a method for evaluation of some disturbances in thyroid gland.     

Structure of the thyroid gland, serum thyroid hormones, and the reproductive cycle of the Atlantic stingray, Dasyatis sabina.

This study examines the role of the thyroid gland in the control of reproduction in the viviparous Atlantic stingray, Dasyatis sabina. Thyroid activity in individuals in different reproductive stages was assessed both by microscopic examination of the gland, and by analysis of circulating levels of thyroid hormones from the same individuals. The thyroid gland is a cylindric organ, embedded in a connective tissue capsule, and composed of follicles, i.e., monolayer spheres of thyroid epithelial cells. Stingray follicular cells possess several characteristic features, namely apical cilia and a well-developed endoplasmic reticulum. Cells vary in size and shape, according to the activity of the gland. No structural differences were observed between the thyroid glands of the two sexes. Both thyroid hormones, triiodothyronine, [T(3)], and thyroxine, [T(4)], were detected in the serum of all animals examined. Levels ranged from 1.3-2.6 microg/100 ml for total T(4), and from 1.2-2.6 ng/ml for total T(3). The T(4) levels did not vary significantly in any group. Immature individuals and females undergoing oogenesis had the lowest levels of circulating T(3) and mature females from ovulation throughout gestation had high thyroid gland activity and high levels of circulating T(3). J. Exp. Zool. 284:505-516, 1999.     

Synovial sarcoma of the thyroid. Report of a case with aspiration cytology findings and gene analysis

BACKGROUND: Synovial sarcoma, generally known as a soft tissue tumor, can also occur in the head and neck region, including the thyroid gland. Cytologic findings are important to differentiate the tumor from other types of neoplasms arising in the thyroid gland. CASE: A 60-year-old man complained of hoarseness. A palpable neck tumor was detected, and a computed tomography scan showed a thyroid tumor accompanied by destruction of the thyroid and cricoid cartilage. The results of a preoperative fine needle aspiration biopsy showed numerous spindle cells with pale cytoplasm and oval nuclei with fine, granular chromatin, all of which suggested a medullary carcinoma. The extirpated thyroid tissue weighed approximately 120 g, and a grayish white, elastic, solid tumor (6.8 x 6.5 cm) was present in the left lobe. Histologically, fasciculation of spindle cells that had proliferated solidly and densely was observed. Also, the expression of a chimera gene, SYT-SSX, was detected in the tumor tissue. CONCLUSION: Synovial sarcoma of the thyroid is extremely rare, and its diagnosis by fine needle aspiration biopsy is generally considered very difficult. The detailed cytologic findings observed here might be helpful with the differential diagnosis of thyroid neoplasms.     

Early developmental specification of the thyroid gland depends on han-expressing surrounding tissue and on FGF signals

The thyroid is an endocrine gland in all vertebrates that develops from the ventral floor of the anterior pharyngeal endoderm. Unravelling the molecular mechanisms of thyroid development helps to understand congenital hypothyroidism caused by the absence or reduction of this gland in newborn humans. Severely reduced or absent thyroid-specific developmental genes concomitant with the complete loss of the functional gland in the zebrafish hands off (han, hand2) mutant reveals the han gene as playing a novel, crucial role in thyroid development. han-expressing tissues surround the thyroid primordium throughout development. Fate mapping reveals that, even before the onset of thyroid-specific developmental gene expression, thyroid precursor cells are in close contact with han-expressing cardiac lateral plate mesoderm. Grafting experiments show that han is required in surrounding tissue, and not in a cell-autonomous manner, for thyroid development. Loss of han expression in the branchial arches and arch-associated cells after morpholino knock-down of upstream regulator genes does not impair thyroid development, indicating that other han-expressing structures, most probably cardiac mesoderm, are responsible for the thyroid defects in han mutants. The zebrafish ace (fgf8) mutant has similar thyroid defects as han mutants, and chemical suppression of fibroblast growth factor (FGF) signalling confirms that this pathway is required for thyroid development. FGF-soaked beads can restore thyroid development in han mutants, showing that FGFs act downstream of or in parallel to han. These data suggest that loss of FGF-expressing tissue in han mutants is responsible for the thyroid defects.     

Functional Effects of Short-Term Treatment with Amiodarone on Thyroid Tissues of the Rabbit

The effect of short-term treatment with Amiodarone on thyroid gland tissue was studied in a group of 26 New Zealand albino rabbits. Ten rabbits were left untreated and served as controls; the remaining animals were treated with 10 mg/kg/day Amiodarone. The serum levels of serum triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) levels were measured at days 0 (baseline), 7, 30, and 45. The serum selenium levels were also measured, but only on days 0 and 45 of the experiment. At the end of the experiment the animals were sacrificed and the levels of selenium, T3, T4, and iodine were determined in thyroid tissue. After 30 days treatment the values of T3 were significantly lower than those of the untreated controls or the baseline levels (p < 0.001). The T4 level was significantly lower and the TSH value was significantly higher after 45 days of Amiodarone (p < 0.001). In thyroid tissue the T3, T4, and iodine levels were significantly higher in the treated group when compared to untreated controls (p < 0.05). These results show that Amiodarone induces changes in the hormone levels in both serum and thyroid tissues, as well as in the amount of iodine taken up by the thyroid gland in rabbits.     

Sex steroid and thyroid hormone receptor expressions in the thyroid of the American alligator (Alligator mississippiensis) during different life stages

The expression of estrogen receptors, ESR1 (ERα) and ESR2 (ERβ), and androgen receptors (AR) in the thyroid gland has been reported in few vertebrate species other than a few mammals. This study reports the presence of sex steroid hormone receptors and thyroid receptors (ERα, ERβ, AR, TRα, and TRβ) in the thyroid gland of the American alligator at several life stages. It provides a semiquantification and distribution of ERα in the thyroid follicle cells using an immunohistochemical approach as well as reports quantitative differences in mRNA expression of ERα, ERβ, TRα, TRβ, and AR in the same tissue using quantitative real time‐PCR (Q‐PCR) with primers designed specifically for alligators. The thyroid tissue of the American alligator expresses ERα, ERβ, and AR at all of the life stages examined here although no statistically significant differences were observed between male and female in thyroid mRNA expression for any of the genes analyzed. No sexual dimorphism was observed in ERα immunostaining. No statistical analysis across life stages were performed due to confounding factor of season. J. Morphol. 2011. © 2011 Wiley‐Liss, Inc.     

Structure of lymphatic vessels in the rat thyroid gland

The lymphatic bed of the thyroid gland has been studied in 24 intact rats. Three techniques facilitating to reveal lymphatic vessels in the organ have been used: preparation of semithin sections, injection of the blood bed with methyl methacrylate with a successive chemical extraction of the preparations, injection of the blood bed with liquid solution of methyl methacrylate with a consecutive study of the preparations in the scanning electron microscope. Methods of electron histochemistry (revealing horseradish peroxidase) and kryofractography have been applied. Construction of the thyroid lymphatic bed, structure of the wall are described, fibroblastic membrane (F-membrane) is revealed and the signs are presented, that allow to differentiate F-membrane from endothelium of the lymphatic capillaries. The pathways of lymph outflow in the rat thyroid gland consist of the following links: interstitial space in the interlobular spaces of the gland, into them the tissue liquor (lymph) is filtered ; plates of the F-membrane regulating direction of excessive albumin-containing liquor in the lymphatic capillaries, surrounding groups of 5-11 follicles, embracing the microlobule of the gland and situating in the interlobular spaces, deferent lymphatic vessels.     

Arteries define the position of the thyroid gland during its developmental relocalisation

During vertebrate development, the thyroid gland undergoes a unique relocalisation from its site of induction to a distant species-specific position in the cervical mesenchyme. We have analysed thyroid morphogenesis in wild-type and mutant zebrafish and mice, and find that localisation of growing thyroid tissue along the anteroposterior axis in zebrafish is linked to the development of the ventral aorta. In grafting experiments, ectopic vascular cells influence the localisation of thyroid tissue cell non-autonomously, showing that vessels provide guidance cues in zebrafish thyroid morphogenesis. In mouse thyroid development, the midline primordium bifurcates and two lobes relocalise cranially along the bilateral pair of carotid arteries. In hedgehog-deficient mice, thyroid tissue always develops along the ectopically and asymmetrically positioned carotid arteries, suggesting that, in mice (as in zebrafish), co-developing major arteries define the position of the thyroid. The similarity between zebrafish and mouse mutant phenotypes further indicates that thyroid relocalisation involves two morphogenetic phases, and that variation in the second phase accounts for species-specific differences in thyroid morphology. Moreover, the involvement of vessels in thyroid relocalisation sheds new light on the interpretation of congenital thyroid defects in humans.