Immunohistochemistry of ultimobranchial thyroid carcinomas in seven slaughtered cows and one bull. (1/14)

Eight thyroid gland epithelial tumors were found in 7 cows and 1 bull in a retrospective study of thyroid gland lesions in slaughtered cattle. All tumors were classified as ultimobranchial thyroid carcinomas based on morphology and immunohistochemistry. All tumors consisted of solid sheets and nests of polygonal to oval epithelial cells, with more sparsely dispersed colloid-filled follicles. Connective tissue separating nests of epithelial cells varied from delicate fibrovascular stroma to dense collagenous stroma. Fusiform epithelial cells with rare neural fibers and ganglion cells were present in 1 tumor. Cells within solid areas of these tumors were immunoreactive for calcitonin, calcitonin gene-related peptide, neuron-specific enolase, and synaptophysin. Colloid and follicle cells were immunoreactive for thyroglobulin. Few follicle cells also were reactive for calcitonin gene-related peptide. Neoplastic cells invaded the fibrous capsules in all 8 cattle. These tumors represented proliferation of a mixed population of undifferentiated cells, C cells, and thyroid follicular epithelial cells, presumably derived from the thyroid ultimobranchial bodies. These ultimobranchial carcinomas in slaughtered cattle are comparable to ultimobranchial tumors described in dairy bulls and the intermediate type of thyroid gland carcinomas (mixed thyroid medullary carcinomas) described in human beings.  (+info)

Calcitonin biosynthesis: evidence for a precursor. (2/14)

Calcitonin biosynthesis has been studied in chicken ultimobranchial glands incubated in vitro in the presence of radioactive amino acids. The results obtained suggest the existence of a biosynthetic precursor of higher molecular weight or procalcitonin. This precursor has been identified by pulse-chase experiments, molecular weight determinations, biological activity measurements and analysis of tryptic peptides. Its molecular weight is about 13000 (calcitonin, about 3500) as determined by polyacrylamide gel electrophoresis. Procalcitonin is present in small amounts in chicken ultimobranchial glands and it is biologically active in rats.  (+info)

Expression and localization of prohormone convertase PC1 in the calcitonin-producing cells of the bullfrog ultimobranchial gland. (3/14)

We examined the expression and localization of the prohormone convertases, PC1 and PC2, in the ultimobranchial gland of the adult bullfrog using immunohistochemical (IHC) and in situ hybridization (ISH) techniques. In the ultimobranchial gland, PC1-immunoreactive cells were columnar, and were present in the follicular epithelium. When serial sections were immunostained with anti-calcitonin, anti-CGRP, anti-PC1, and anti-PC2 sera, PC1 was found only in the calcitonin/CGRP-producing cells. No PC2-immunopositive cells were detected. In the ISH, PC1 mRNA-positive cells were detected in the follicle cells in the ultimobranchial gland. No PC2 mRNA-positive cells were detected. RT-PCR revealed expression of the mRNAs of PC1 and the PC2 in the ultimobranchial gland. However, very little of the PC2 mRNA is probably translated because no PC2 protein was detected either by IHC staining or by Western blotting analysis. We conclude that the main prohormone convertase that is involved in the proteolytic cleavage of procalcitonin in the bullfrog is PC1.  (+info)

Cystic tumor of the atrioventricular node of the heart appears to be the heart equivalent of the solid cell nests (ultimobranchial rests) of the thyroid. (4/14)

We studied a series of 10 solid cell nests (SCNs) of the thyroid and a case of cystic tumor of the atrioventricular node (CTAVN) of the heart and reviewed the literature. The CTAVN and SCNs appeared as cystic and/or solid (squamoid) structures mainly composed of polygonal or oval cells (main cells) admixed with occasional clear cells (neuroendocrine and C cells). Main cells were immunoreactive for simple and stratified epithelial-type cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, carbohydrate antigen 19.9, p63, bcl-2, and galectin-3. Neuroendocrine (and C) cells were positive for simple-type cytokeratins, carcinoembryonic antigen, calcitonin, chromogranin, synaptophysin, and thyroid transcription factor-1. Our data support the hypothesis that the CTAVN of the heart and the SCNs of the thyroid are identical structures that represent the same lesional process. The assumption that CTAVN is a ultimobranchial heterotopia fits with the known role of cardiac neural crest cells in cardiovascular development.  (+info)

Origin of the ultimobranchial body cyst: T/ebp/Nkx2.1 expression is required for development and fusion of the ultimobranchial body to the thyroid. (5/14)

The ultimobranchial body (UBB) is an outpocketing of the fourth pharyngeal pouch that fuses with the thyroid diverticulum, giving rise to calcitonin-producing C-cells. In this study, we demonstrate that the UBB is composed of two types of cells: one expressing T/ebp/Nkx2.1 and the other expressing p63. The former cell type, accounting for a majority of the UBB, requires T/ebp/Nkx2.1 for their survival. In contrast, the p63-positive cells, even in the absence of T/ebp/Nkx2.1 expression, can proliferate and give rise to a vesicular structure that is lined by a monolayer of p63-negative cells, surrounded by a cluster and/or single layer of p63-positive cells, displaying the basal/stem cell phenotype. T/ebp/Nkx2.1 haploinsufficiency causes abnormal fusion of the UBB with the thyroid diverticulum, which stays as a cluster of C-cells around the vesicular structure, similar to the one observed in mice null for T/ebp/Nkx2.1 expression. These results demonstrate that T/ebp/Nkx2.1 plays a role in the survival of UBB cells, their dissemination into the thyroid diverticulum, and the formation of UBB-derived vesicular structure.  (+info)

Mash1 regulates the development of C cells in mouse thyroid glands. (6/14)

In mammals, the ultimobranchial body derived from the fourth pharyngeal pouch gives rise to thyroid C cells. The C cells of newborn mice are immunoreactive for calcitonin, calcitonin gene-related peptide (CGRP), protein gene product (PGP) 9.5 and NeuroD, and transiently exhibit the neuronal markers TuJ1 and somatostatin during fetal development. The basic helix-loop-helix (bHLH) transcription factor Mash1 plays a role in the differentiation of autonomic neurons. We show that in wild-type mouse embryos, Mash1 is expressed in the ultimobranchial body at embryonic day (E) 12.5, when the body is located close to the great arch arteries. It is also expressed in the ultimobanchial body fused with the thyroid lobe at E 13.5. Targeted disruption of Mash1 resulted in the absence of C cells in the mouse thyroid glands, since cells displaying the C-cell markers and expressing NeuroD were not detected during fetal development or at birth. The failure of C-cell formation in the null mutant thyroids was also confirmed by electron microscopy. While the formation and migration of the ultimobranchial body were not affected in the Mash1 null mutants, at E 12.5-E 13.5 both the ultimobranchial body located close to the arteries and the organ populating the thyroid lobe exhibited a marked increase in apoptotic cell numbers. Thus, in the mutant mice, the ultimobranchial body fails to complete its differentiation program and finally dies. These results indicate that Mash1 enhances survival of the C-cell progenitors by inhibiting apoptosis.  (+info)

Development of thyroid gland and ultimobranchial body cyst is independent of p63. (7/14)

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Voltage-gated sodium and potassium currents and their variation in calcitonin-secreting cells of the chick. (8/14)

1. The electrical properties of dissociated ultimobranchial cells from chick embryos (18-20 days after fertilization) were studied using whole-cell patch electrodes. Antibodies for immunohistological identification of calcitonin-secreting cells in the preparation were obtained by immunizing rabbits with a conjugated analogue of eel calcitonin. 2. In a proportion of cells, spike-like action potentials were generated in response to depolarization when cells were immersed in standard saline containing 140 mM-Na+ but no Ca2+. When the membrane potential was shifted from a holding potential (-83 - -103 mV) to a test depolarization (-50 mV or more positive) under voltage-clamp conditions, a transient inward current was produced which was followed by a slowly developing outward current. 3. The inward current was identified as a Na+-carried current, since (1) the kinetics of the current seemed fast and the amplitude consistently depended on the holding potential, (2) replacement of external Na+ with choline ions reversibly abolished the current, and (3) external application of tetrodotoxin (1 microM) abolished the current completely. The cells in which inward currents were detected showed intense to intermediate degrees of staining with anti-calcitonin antibodies. 4. In some other cells, no regenerative potentials were evoked even with intense depolarization, but a delayed decrease in membrane depolarization during the current pulse was observed. Voltage-clamp experiments in these cells revealed the existence of slowly developing outward currents, and the cells showed an intermediate degree of antibody staining. 5. The outward currents in both types of cells were selectively diminished in the presence of K+ channel blockers such as tetraethylammonium (1-10 mM) or 4-aminopyridine (1 mM). When the pipette contained 120 mM-CsCl, none of the dissociated cells exhibited any appreciable outward currents. Thus, the outward currents were most likely to be membrane potential-dependent K+ currents. The potential dependency of activation and inactivation of the currents were consistent with those of delayed K+ rectifier. 6. In the remaining cells, only passive responses of membrane potentials were observed with current injection. No discernible voltage-dependent inward or outward currents were detected under voltage-clamp conditions. Although these cells had a similar appearance to the two types of cells previously mentioned under phase-contrast microscopy, none of them showed significant antibody staining. These cells were presumed to represent non-secretory or supporting cells within the gland.(ABSTRACT TRUNCATED AT 400 WORDS)  (+info)

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