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PubMed2003

Epigenetic assembly of centromeric chromatin at ectopic alpha-satellite sites on human chromosomes.

To investigate the mechanism of chromatin assembly at human centromeres, we isolated cultured human cell lines in which a transfected alpha-satellite (alphoid) YAC was integrated ectopically into the terminal region of host chromosome 16, where it was stably maintained. Centromere activity of the alphoid YAC was suppressed at ectopic locations on the host chromosome, as indicated by the absent or reduced assembly of CENP-A and -C. However, long-term culture in selective medium, or short-term treatment with the histone deacetylase inhibitor Trichostatin A (TSA), promoted the re-assembly of CENPA, -B and -C at the YAC site and the release of minichromosomes containing the YAC integration site. Chromatin immunoprecipitation analyses of the re-formed minichromosome and the alphoid YAC-based stable human artificial chromosome both indicated that CENP-A and CENP-B assembled only on the inserted alphoid array but not on the YAC arms. On the YAC arms at the alphoid YAC integration sites, TSA treatment increased both the acetylation level of histone H3 and the transcriptional level of a marker gene. An increase in the level of transcription was also observed after long-term culture in selective medium. These activities, which are associated with changes in chromatin structure, might reverse the suppressed chromatin state of the YAC at ectopic loci, and thus might be involved in the epigenetic change of silent centromeres on ectopic alphoid loci.

Acetylation↗
PubMed2003

Dual ectopic thyroid: report of a case.

Dual ectopic thyroid is very rare. We report a case of dual ectopic thyroid in the lingual and infrahyoid areas in a 20-year-old female patient with no thyroid gland in its normal anatomical location. On physical examination, there was a 7 x 5 cm anterior midline neck swelling just below the hyoid bone and a 2 x 2 cm mass in the base of the tongue. Triiodothyronine (T(3)), thyroxine (T(4)), and thyroid-stimulating hormone (TSH) levels were normal. A thyroid scan with technetium-99m sodium pertechnate confirmed dual ectopic thyroid with no iodine uptake in the normal anatomical location of the thyroid gland. The infrahyoid ectopic thyroid was surgically removed for cosmetic reasons, and the lingual thyroid, which was symptomatic, was left untouched. The importance of thyroid scanning in the evaluation of anterior midline neck swellings and treatment options are discussed.

Adult↗
PubMed1988

Pediatric upper airway obstruction due to ectopic thyroid: classification and case reports.

Few clinical situations can be as frightening, challenging, and as rewarding as stabilizing the airway of a child. Most causes of pediatric upper airway obstruction are well recognized, often discussed in the literature, and commonly encountered in practice. However, ectopic thyroid (i.e., thyroid tissue found in places other than its normal location) may be an unusual cause of pediatric upper airway obstruction with which the clinician may not be familiar. The resulting airway obstruction may be slow or rapid in onset, total or partial, and the relationship of the thyroid to the airway may be clear or obscure. Two cases of obstructing ectopic thyroid are presented which demonstrate the spectrum within which this form of airway obstruction may occur. One case is the first reported example in the English literature of pediatric intratracheal thyroid. A review of the literature is also presented. Four types of ectopic thyroid (lingual, sublingual, thyroglossal, and intralaryngotracheal) are illustrated and discussed in relation to their effect upon the pediatric upper airway. The authors also review the developmental anatomy of the thyroid and present two major theories regarding the development of intralaryngotracheal thyroid. The possible etiologies of the other ectopic forms are also discussed.

Airway Obstruction↗
PubMed1994

Potassium and magnesium distribution, ECG changes, and ventricular ectopic beats during beta 2-adrenergic stimulation with terbutaline in healthy subjects.

OBJECTIVE: To study the effect of intravenous (i.v.) terbutaline on potassium (K) and magnesium (Mg) distribution, ECG changes, and prevalence of ventricular ectopic beats in healthy subjects. DESIGN: Randomized double-blind, placebo-controlled crossover. Subjects received either placebo or terbutaline (bolus, 0.25 mg; maintenance dose, 5 micrograms/min). SETTING: University Department of Clinical Chemistry. PARTICIPANTS: Ten healthy male volunteers. Mean age was 24.1 (range, 20 to 31) years. MAIN OUTCOME MEASURES: Serum potassium and magnesium muscle potassium and magnesium, and muscle sodium-potassium pump number. Urinary excretion of potassium and magnesium. ECG changes (T-wave and QTC interval) and the number of ventricular ectopic beats. MAIN RESULTS: Terbutaline produced an immediate decrease in serum potassium level from 4.17 (4.04 to 4.30) mmol/L to a nadir of 3.32 (3.06 to 3.58) mmol/L (p < 0.001). The urinary excretion of potassium decreased from 0.077 mmol/min (0.052 to 0.102) to 0.038 mmol/min (0.025 to 0.051) (p < 0.01). There was an increase in the number of sodium potassium pumps from 1,104.1 nmol/kg dry weight (1,030.6 to 1,177.5) to 1,273.3 nmol/kg dry weight (1,193.5 to 1,353.2) (p < 0.01), but no measurable change in muscle potassium. The QTC interval increased from 395 (385 to 405)ms to 449 (432 to 466) ms (p < 0.003). There was no change in the number of ventricular ectopic beats. CONCLUSIONS: Short-term i.v. administration of terbutaline produced hypokalemia partly due to an increase in the number of sodium-potassium pumps. Furthermore, terbutaline induced changes in ECG with a highly significant lengthening of the QTc interval but with an unchanged number of ventricular ectopic beats in healthy subjects.

Adult↗
PubMed2003

Pleural space as a site of ectopic gene delivery: transfection of pleural mesothelial cells with systemic distribution of gene product.

STUDY OBJECTIVES: Successful ectopic gene therapy requires the transfection of the cells at the ectopic site, with local and systemic delivery of the gene product. This study aimed to evaluate the pleural mesothelial surface as a potential site for ectopic gene therapy. DESIGN: A secreted placental alkaline phosphatase (PALP) plasmid was injected bilaterally into the pleural spaces of seven rabbits via a chest tube, while an irrelevant reporter plasmid was injected into seven control rabbits. Blood was collected at baseline and at 24, 48, and 72 h after the injections. Pleural fluid was collected by lavage at 24, 48, and 72 h after the injections. The PALP level was measured by chemiluminesence. MEASUREMENTS AND RESULTS: Significant expressions of PALP proteins were observed in the serum of the treatment rabbits, with a threefold increase over baseline at 24 h, a ninefold increase at 48 h, and a twofold increase at 72 h. The serum PALP levels in the control rabbits remained at baseline levels at all time points. The pleural fluid PALP levels peaked at 24 h and decreased over the next 72 h. Mimicking the in vivo pattern, pleural mesothelial cells transfected in vitro demonstrated a similar increase in PALP levels. CONCLUSIONS: The results of the present short-term pilot study suggest that pleural mesothelial cells can be successfully transfected with plasmids, with increases in both the local and systemic levels of the gene product. The pleural space should be further evaluated for ectopic gene therapy.

Alkaline Phosphatase↗
PubMed2006

Synaptic plasticity in CNGA3(-/-) mice: cone bipolar cells react on the missing cone input and form ectopic synapses with rods.

In the mammalian retina, rods and cones connect to distinct sets of bipolar cells. Rods are presynaptic to a single type of rod bipolar cell, whereas cones connect to different types of cone bipolar cells. Synaptic rewiring between cone photoreceptor terminals and rod bipolar cell dendrites has been described as a general result of photoreceptor degeneration. To investigate whether cone bipolar cells also show synaptic plasticity in the absence of cone input, we studied the connectivity of cone bipolar cell dendrites in CNGA3(-/-) mice, a model with specific loss of cone photoreceptor function. Dendritic connections of ON and OFF cone bipolar cells were visualized using specific cell markers or by intracellular injection with fluorescent dyes. The results show that cone bipolar cells in CNGA3(-/-) mice form ectopic synapses with rods. In contrast, cone bipolar cells do not form ectopic synapses with rods in CNGA3(-/-)Rho(-/-) mice, in which both types of photoreceptors are nonfunctional. In analogy with these results, we found that input-deprived rod bipolar cells form ectopic synapses with functional cones in Rho(-/-) mice but not with inoperable cones in the CNGA3(-/-)Rho(-/-) mouse. Our data indicate that the formation of ectopic bipolar cell synapses in the outer plexiform layer requires a functional presynaptic photoreceptor.

Animals↗
PubMed1991

Acromegaly due to ectopic growth hormone-releasing hormone secretion by a bronchial carcinoid tumour. Dynamic hormonal responses to various stimuli.

Ectopic GHRH is a relatively uncommon cause of acromegaly, which should be differentiated from pituitary adenoma, in order to avoid damage to the pituitary gland from unnecessary interventions. We report here on a 66-year-old man with acromegaly due to a GHRH-secreting bronchial carcinoid tumour, who recovered completely following removal of the tumour. His hormonal status was studied before and after the operation. Basal GH, GHRH, IGF-I and PRL levels, as well as plasma GH response to glucose load and TRH administration were abnormal before the operation, and became normal thereafter. The somatostatin analogue SMS 201-995 was found to be a potent inhibitor of the ectopic GHRH and the GH secretion (greater than 500 to 42 ng/l and 15.4 micrograms/l to 0.8 microgram/l, respectively). The effect on GHRH proved to be due to direct effect of somatostatin on the tumour cells, as demonstrated in tissue culture studies. A mixed meal was found immediately to suppress GHRH levels without such an effect on GH secretion. We conclude that the neuroendocrine tests usually practised in acromegaly cannot differentiate between ectopic GHRH secretion and pituitary adenoma. High plasma GHRH levels may serve as a diagnostic test for excessive GHRH production, which is almost always ectopic. These high levels are suppressible by somatostatin and a mixed meal.

Acromegaly↗
PubMed1998

Expression of adrenomedullin and adrenomedullin mRNA in ectopic ACTH-secreting tumors.

OBJECTIVE: To study the expression of adrenomedullin, a potent vasodilator peptide originally isolated from a pheochromocytoma, in ectopic ACTH-secreting tumors. METHODS: Tumor tissue concentrations of adrenomedullin, calcitonin gene-related peptide, neuropeptide Y, endothelin-1, corticotropin-releasing hormone and ACTH were measured in three ectopic ACTH-secreting tumors by RIA. The expression of adrenomedullin mRNA was examined by northern blot analysis of tissue from one of the tumors. RESULTS: Immunoreactive adrenomedullin was detected in tumor tissues of three ectopic ACTH-secreting tumors (0.60-18.5 pmol/g wet weight). Calcitonin gene-related peptide, neuropeptide Y, endothelin-1 and corticotropin-releasing hormone were also detected in the tumor tissues. The tumor tissue concentrations of immunoreactive adrenomedullin were comparable to those of these four peptides, but much lower than those of ACTH. Northern blot analysis showed the expression of adrenomedullin mRNA in one tumor from which sufficient tissue was available for such study. The plasma concentration of immunoreactive adrenomedullin was increased in one patient (41.3 pmol/l, control 13.5 +/- 3.6 pmol/l, mean +/- S.D., n = 12). CONCLUSIONS: These results suggest that adrenomedullin is produced by ectopic ACTH-secreting tumors, together with other neuropeptides, and raise the possibility that adrenomedullin is related to the pathophysiology of these tumors.

Adrenocorticotropic Hormone↗
PubMed2001

Cushing's syndrome due to intermittent ectopic ACTH production showing a temporary remission during a pulmonary infection.

OBJECTIVES: In about 15-20% of patients with ACTH-dependent Cushing's syndrome the source of ACTH is outside the pituitary gland. Pulmonary tumours are the most frequent, yet not unique, source of ectopic ACTH. In some instances the localisation of an ACTH-secreting tumour may be problematic. Occult ectopic ACTH secretion indicates the occurrence of ACTH-dependent hypercortisolism with an unknown origin. Another peculiarity of Cushing's syndrome may reside in the episodic cortisol hypersecretion, which can determine a pattern characterised by hypercortisolism together with periods of remission (cyclic Cushing's syndrome). We describe a very challenging case of Cushing's syndrome due to ectopic ACTH hypersecretion, showing virtually all of the most unusual features of the disease. DESIGN: A 55-year-old woman affected by Cushing's syndrome, presenting with biochemical features of ectopic ACTH secretion, has been followed for 7 years. METHODS: Thorough basal and dynamic hormonal assessment through the past 7 years is reported. In addition, the results of extensive imaging studies are presented. RESULTS: The source of ACTH secretion has not been identified so far, and hypercortisolism has been controlled by octreotide treatment. In addition, the patient showed a cyclic pattern of hypercortisolism with a long-term remission period. A unique feature of this case is represented by the fact that we observed a temporary, yet dramatic, short-lasting remission of ACTH and cortisol hypersecretion during a pulmonary infection, which occurred while the patient was hospitalised for a periodic hormonal assessment. CONCLUSIONS: This case well represents the wide spectrum of clinical variability of Cushing's syndrome. Most interestingly, to our knowledge, this is the first report of a case of Cushing's syndrome showing a remission during an acute infection.

Adrenocorticotropic Hormone↗
PubMed2004

Ectopic Agouti protein overexpression increases stimulated corticosterone production without effect on adenylate cyclase activity in mouse adrenal cells.

OBJECTIVE: The antagonism of Agouti protein (AP) and Agouti-related protein on melanocortin receptors suggests an inhibitory role in the regulation of steroidogenesis. However, we have previously demonstrated that ectopic AP overexpression increased restraint-induced corticosterone release and adrenal reactivity to ACTH in mice. A high steroidogenic response to ACTH may be a consequence of a stimulatory AP action on the adenylate cyclase (AC) and/or intracellular steroidogenic enzymes. The aim of the present study was to estimate the effect of ectopic AP overexpression on the activity of AC and steroidogenic intracellular enzymes. METHODS: ACTH and forskolin were used for AC stimulation, and dibutyryl cAMP and progesterone were used for stimulation of intracellular steroidogenic enzymes in isolated adrenal cells in male C57Bl/6J mice of two Agouti genotypes: A(y)/a (ectopic AP overexpression) and a/a (absence of AP in all tissues). RESULTS: ACTH and forskolin increased cAMP accumulation to the same extent in both A(y)/a and a/a mouse adrenal cells (P<0.001; ANOVA), but resulted in higher corticosterone production in A(y)/a mice (P<0.001 for ACTH and P<0.01 for forskolin; ANOVA). Dibutyryl cAMP- and progesterone-induced corticosterone production was higher in A(y)/a mice than in a/a mice (P<0.001 for dibutyryl cAMP and P<0.01 for progesterone; ANOVA). CONCLUSIONS: Ectopic AP overexpression increased stimulated corticosterone production and intracellular steroidogenic enzyme reactivity to cAMP without an effect on AC activity.

Adenylyl Cyclases↗
PubMed1988

Suprainguinal ectopic scrota of TS inbred rats.

A new rat line (TS inbred rats) showing uni- or bilateral ectopic scrota in about 70% of the males was established. Ectopic scrota were elongated pouches of the thin muscle layer under the suprainguinal body skin, in which hypoplastic testes and epididymides were seen. Genetic analysis revealed that the ectopic scrotum was controlled by multiple genes. Groups of 5 normal, uni- and bilaterally affected rats were killed at 25 weeks of age. Histologically, ectopic testes of uni- and bilaterally affected rats showed arrest of spermatogenesis at the primary spermatocyte stage. Contralateral testes of unilaterally affected rats were normally descended and showed normal spermatogenesis. No abnormality was seen in the urinary system. Plasma concentrations of FSH were significantly elevated in bilaterally affected rats but plasma concentrations of testosterone and LH were unchanged in uni- and bilaterally affected rats. Pituitary contents of LH and FSH were significantly elevated in bilaterally affected rats. The endocrinological status of TS inbred rats was therefore similar to that of experimentally induced cryptorchid rats.

Animals↗
PubMed2006

An ectopic expression screen reveals the protective and toxic effects of Drosophila seminal fluid proteins.

In Drosophila melanogaster, seminal fluid regulates the reproductive and immune responses of mated females. Some seminal fluid proteins may provide protective functions to mated females, such as antimicrobial activity and/or stimulation of antimicrobial gene expression levels, while others appear to have negative effects, contributing to a "cost of mating." To identify seminal proteins that could participate in these phenomena, we used a systemic ectopic expression screen to test the effects on unmated females of proteins normally produced by the male accessory gland (Acps). Of the 21 ectopically expressed Acps that we tested for ability to assist in the clearance of a bacterial infection with Serratia marcescens, 3 Acps significantly reduced the bacterial counts of infected females, suggesting a protective role. Of the 23 Acps that we tested for toxicity, 3 were toxic, including one that has been implicated in the cost of mating in another study. We also tested ectopic expression females for other Acp-induced effects, but found no additional Acps that affected egg laying or receptivity upon ectopic expression.

Animals↗
PubMed2006

Contribution of matrix vesicles and alkaline phosphatase to ectopic bone formation.

Endochondral calcification involves the participation of matrix vesicles (MVs), but it remains unclear whether calcification ectopically induced by implants of demineralized bone matrix also proceeds via MVs. Ectopic bone formation was induced by implanting rat demineralized diaphyseal bone matrix into the dorsal subcutaneous tissue of Wistar rats and was examined histologically and biochemically. Budding of MVs from chondrocytes was observed to serve as nucleation sites for mineralization during induced ectopic osteogenesis, presenting a diameter with Gaussian distribution with a median of 306 +/- 103 nm. While the role of tissue-nonspecific alkaline phosphatase (TNAP) during mineralization involves hydrolysis of inorganic pyrophosphate (PPi), it is unclear how the microenvironment of MV may affect the ability of TNAP to hydrolyze the variety of substrates present at sites of mineralization. We show that the implants contain high levels of TNAP capable of hydrolyzing p-nitrophenylphosphate (pNPP), ATP and PPi. The catalytic properties of glycosyl phosphatidylinositol-anchored, polidocanol-solubilized and phosphatidylinositol-specific phospholipase C-released TNAP were compared using pNPP, ATP and PPi as substrates. While the enzymatic efficiency (k cat/Km) remained comparable between polidocanol-solubilized and membrane-bound TNAP for all three substrates, the k cat/Km for the phosphatidylinositol-specific phospholipase C-solubilized enzyme increased approximately 108-, 56-, and 556-fold for pNPP, ATP and PPi, respectively, compared to the membrane-bound enzyme. Our data are consistent with the involvement of MVs during ectopic calcification and also suggest that the location of TNAP on the membrane of MVs may play a role in determining substrate selectivity in this micro-compartment.

Alkaline Phosphatase↗
PubMed1984

Refluxing urethral ectopic ureters: recognition by the cyclic voiding cystourethrogram.

Reflux into an ectopic ureter that opens into a girl's urethra has been difficult to demonstrate and has been thought to occur in only about a third of the patients with this anomaly. In an attempt to more reliably demonstrate this reflux, 12 girls aged 1 day to 6 years, who were suspected of having an ectopic ureter, were studied using a method of cyclic filling and voiding during the cystourethrogram. Reflux into their urethral ectopic ureter was shown in 11 (92%). The technique of cyclic voiding cystourethrography should be used in all girls in whom an ectopic ureter is suspected, either because of signs or symptoms or because of a dilated upper pole of a duplex collecting system seen on an excretory urogram or a sonogram. It should also be used when a conventional voiding cystourethrogram has shown no or only minimal reflux.

Child↗
PubMed1995

Ectopic gastric mucosa in the upper esophagus: prevalence and radiologic findings.

OBJECTIVE: Ectopic gastric mucosa of the upper esophagus is an asymptomatic benign lesion that may simulate a more serious lesion on radiographs. We studied the radiographic findings and prevalence of this abnormality. SUBJECTS AND METHODS: During a 1-year period, 1142 consecutive patients (817 men, 325 women) who had an upper gastrointestinal series as part of an annual health checkup were prospectively studied. Routine examination of the esophagus consisted only of fluoroscopy. Radiographs were obtained if any localized irregularities were found in the upper esophageal wall at fluoroscopy. The findings were subsequently confirmed by endoscopy and biopsy. RESULTS: Ectopic gastric mucosa in the upper esophagus was seen in 27 (25 men, two women) of the 1142 patients. Forty-three localized ectopic gastric mucosal patches varying in size from 5 mm to 32 mm were detected at the level of the thoracic inlet in the 27 patients. The most common radiographic finding was a pair of small indentations on the wall of the esophagus (18 patches). Other findings included a rimlike shadow (three patches), a pair of somewhat large indentations with a shallowly depressed area between them (two patches), one indentation (five patches), a small flat elevation (one patch), a serrated irregular outline (five radiologic lesions consisted of 11 patches), other various irregular outlines (two patches), and a polypoid area (one patch). CONCLUSION: Prevalence of radiographic evidence of ectopic gastric mucosa in the upper esophagus is 2.4%. The lesion was found more commonly in men (3.1%) than in women (0.6%). Radiographic findings include a pair of indentations along the lateral margin of the esophagus and a rimlike shadow on the anterior or posterior wall. Recognition of the characteristic radiographic features of this abnormality makes endoscopy and follow-up unnecessary.

Adult↗
PubMed1995

Sonographic demonstration of a normal thyroid gland excludes ectopic thyroid in patients with thyroglossal duct cyst.

OBJECTIVE: Preoperative thyroid scintigraphy has been performed in patients with presumed thyroglossal duct cyst to document a normal thyroid and to exclude the possibility of an ectopic thyroid mimicking a thyroglossal duct cyst. Often, an ectopic thyroid is the patient's only functioning thyroid tissue, and its removal will result in hypothyroidism. The purpose of this study was to determine whether demonstration of a normal thyroid gland by sonography in children with thyroglossal duct cyst can exclude ectopic thyroid and thereby obviate routine preoperative thyroid scintigraphy. MATERIALS AND METHODS: We studied 30 patients with pathologically proved thyroglossal duct cysts who had neck sonograms. The sonograms were evaluated for the presence or absence of a normal thyroid gland. The medical records of these children were also reviewed. Three children had normal preoperative radionuclide thyroid scans. All the children were clinically euthyroid preoperatively. Follow-up was available in 15 of the 30 patients, and all of these patients were clinically euthyroid postoperatively. RESULTS: A sonographically normal thyroid gland was detected in all patients. CONCLUSION: Preoperative sonographic identification of a normal thyroid gland in patients with thyroglossal duct cyst confirms a source of thyroid hormone separate from the thyroglossal duct cyst and thus excludes ectopic thyroid. Routine thyroid scintigraphy is not necessary.

Child↗
PubMed1992

Papillary carcinoma arising in ectopic thyroid tissue within a branchial cyst.

The first case of a papillary carcinoma arising in ectopic thyroid tissue within a branchial cyst in a 34 yr old woman is presented. This also adds to the existing list of unusual sites where ectopic thyroid tissue has been described. All histological types of carcinoma have been reported in ectopic thyroid tissue, papillary carcinoma being the most common histological type, accounting for 85% of these tumors. The criteria for establishing this diagnosis of carcinoma arising in ectopic thyroid tissue within branchial cyst is discussed.

Adult↗
PubMed1984

Ectopic bone after hip replacement. Excision and free fat transplants in four cases.

In four patients ectopic bone formed after total hip replacement was replaced with free fat transplants. One year later the patients were free from pain, and hip flexion had increased by 60 degrees on average. Ectopic bone was completely absent in one patient, and markedly reduced in the remaining three patients. Bone scintigraphy was found to be a sensitive technique to reveal early ectopic bone formation. Fat transplantation seems to be a satisfactory complement in the treatment of ectopic bone.

Adipose Tissue↗