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Overexpression of NGF within the heart of transgenic mice causes hyperinnervation, cardiac enlargement, and hyperplasia of ectopic cells.

Nerve growth factor (NGF) supports the survival of developing sympathetic and a subpopulation of sensory neurons. In the adult it participates in maintenance of the neurotransmitter phenotype of responsive neurons. The amount of NGF synthesized by a given target tissue determines its final innervation density; those developing neurons that fail to receive sufficient NGF undergo apoptosis. In order to examine the ramifications of this principle in the context of a specific target organ, a transgenic mouse model was developed in which NGF expression was increased in developing and adult cardiac tissue by placing a NGF minigene under the transcriptional control of the cardiac-specific alpha-myosin heavy chain promoter. Transgenic mice developed cardiac enlargement secondary to both an increase in myocardial mass and the presence of an abundant ectopic cell population. Immunohistochemical analyses with the neural marker S-100 revealed staining of a subpopulation of ectopic cells, suggesting their derivation from the neural crest. Whereas immunostaining for the neuronal-specific protein neuron-specific enolase demonstrated labeling of another subpopulation of ectopic cells within the heart. Measurements of cardiac tissue catecholamine levels revealed a marked elevation in transgenic mice, consistent with sympathetic hyperinnervation. Analysis of mediastinal sympathetic ganglia revealed increases in both the size and the number of neurons. In this model, increased expression of NGF produced hyperinnervation of the heart, pathological cardiac growth, and the recruitment and/or expansion of an ectopic, neural crest-derived cell type.

Animals↗

Ectopic CNS projections guide peripheral neuron axons along novel pathways in leech embryos.

Previous studies have indicated that the formation of stereotyped segmental nerves in leech embryos depends on the interactions between CNS projections and ingrowing afferents from peripheral neurons. Especially, CNS-ablation experiments have suggested that CNS-derived guidance cues are required for the correct navigation of several groups of peripheral sensory neurons. In order to directly test this hypothesis we have performed transplantations of CNS ganglia into ectopic sites in segments from which the resident ganglia have been removed. We find that the transplanted ganglia extend numerous axons distributed roughly equally in all directions. When these CNS projections reach and make contact with peripheral sensory axons they are used as guides for peripheral neurons to grow toward and into the ectopic ganglia even when this means following novel pathways that cross the midline and/or segmental boundaries. The peripheral sensory axons turn and grow toward the ectopic ganglia only when in physical contact with CNS axons, suggesting that diffusible chemoattractants are not a factor. These results demonstrate that the guidance cues provided by ectopic CNS projections are both necessary and sufficient to steer peripheral sensory neuron axons into the CNS.

Animals↗

Ectopic expression of the Arabidopsis AtMYB23 gene induces differentiation of trichome cells.

The control of epidermal cell fate is a complex molecular process and requires the regulatory activity of different transcription factors. Here, we describe the isolation of a member of the Arabidopsis MYB transcription factor family, AtMYB23, that is involved in trichome development. Expression of the AtMYB23 gene under the control of the viral CaMV 35S promoter causes the development of ectopic trichomes. The formation of ectopic trichomes depends on TRANSPARENT TESTA GLABRA1 but not on GLABRA1. The absence of the negative regulator TRIPTYCHON leads to branching of the ectopic trichomes on cotyledons and the formation of ectopic trichomes in the leaf subepidermal cell layer. The CaMV 35S promoter-controlled expression of AtMYB23 can partially rescue the glabra1 mutant phenotype. Together, the presented data indicate that the AtMYB23 gene has partially overlapping functions with GLABRA1 in controlling the initiation of trichome development.

Arabidopsis↗

Ectopic overexpression of Drosophila lamin C is stage-specific lethal.

To gain insight into the function of the developmentally regulated A-type lamins we transformed Drosophila melanogaster with a construct containing the hsp70 promoter followed by the Drosophila lamin C (an analog of vertebrate A-type lamins) cDNA. Lamin C was expressed ectopically after heat shock of embryos and localized to the nucleus. No phenotypic change was observed after lamin C expression in embryos that normally do not contain lamin C. However, ectopic expression of lamin C during most larval (but not pupal) stages stalled growth, inhibited ecdysteroid signaling (in particular during the larval-prepupal transition), resulted in development of melanotic tumors, and finally caused death. During pupation in control animals, when massive apoptosis of larval tissues takes place, lamin C is proteolyzed into a fragment with a size similar to that predicted by caspase cleavage. The ectopically expressed lamin C is identically cleaved, resulting in a large increase of the steady-state level of the lamin C fragment. A null mutation of the dcp-1 gene, one of the two known Drosophila caspase genes, also results in development of melanotic tumors and larval death, suggesting that the ectopically expressed lamin C inhibits apoptosis through competitive inhibition of caspase activity.

Age Factors↗

Interactions between astroglia and ectopic granule cells in the cerebellar cortex of normal adult rats: a morphological and cytochemical study.

The cytology and organization of astroglial cells associated with ectopic granule cells (EGCs) have been studied in the cerebellar cortex of normal adult rats, using Golgi preparations, immunohistochemistry against the glial fibrillary acidic protein (GFAP) and ultrastructural analysis. Elongated perikarya of EGCs scattered in the molecular layer were usually attached to radial Bergmann fibers, which exhibited a normal morphology. A second configuration of EGCs consisted of intrafissural colonies of ectopic neurons. The molecular layer that surrounded these ectopic colonies showed disorientation of both Bergmann fibers and parallel fibers. Within the ectopic tissue, typical velate astrocytes were commonly observed. They formed homologous associations with EGC perikarya and cerebellar glomeruli. However, a restricted astroglial plasticity was detected in the form of heterologous interactions between astrocytes and Purkinje cell dendrites, including their associated synapses with parallel fibers. In spite of this astroglial plasticity, our results suggest that in the physiological systems of granule cell ectopia studied here, the different specific interactions of Bergmann glia and astrocytes with neurons tend to be conserved.

Animals↗

Ectopic granule cell layer in mouse cerebellum after methyl-azoxy-methanol (MAM) treatment.

Previous results from our laboratory (Bejar et al. 1985) indicated that a single injection in mouse pups of the antimitotic/mutagenic agent methylazoxymethanol at postnatal day 5 typically produces hypogranular cerebella with no changes in foliation, in contrast to the severe alterations observed after the more usual injection on the day of birth. Here we report that injection of a higher dose (30 mg/kg) of methylazoxymethanol, always at postnatal day 5, leads to the additional presence of a ectopic cell layer in adult cerebellum. Immunostaining with several antibodies recognizing cell specific proteins ruled out the possibility that these ectopic cells were glial and electron microscopy indicated that they were morphologically mature granule cells. In the molecular layer of other cerebellar areas and apparently unrelated with granule cell ectopia, ectopic Golgi epithelial cells were observed. The reason for the presence of these ectopic cells of different type in the molecular layer was discussed in relation with analogous ectopias obtained by other means.

Animals↗

Redirected perforant and commissural of connections of eutopic and ectopic neurons in the hippocampus of methylazoxymethanol-acetate treated rats.

In an earlier study, it was reported that clusters of ectopic neurons developed postnatally in the hippocampus of rats which were exposed to Methylazoxymethanol acetate (MAMac) during fetal development (Singh, 1977b). This paper describes the perforant tract and commissural connections of hippocampal eutopic and ectopic neurons. These connections were traced with a reduced-silver method (Eager, 1970). Two observations of significance were made: (i) Ectopic neurons misplaced in stratum radiatum received terminals from axons in the perforant tract. The upper boundary for these redirected fibers was stratum pyramidale--approximately 350 mu outside the normal boundary which is situated near the hippocampal fissure. (ii) Ectopic neurons received a dramatically reduced commissural projection, compared with eutopic pyramidal neurons in Ammon's horn. Eutopic neurons in the hippocampus were found to receive afferent perforant tract and commissural fibers in the same way--i.e., density and distribution, as in control rats.

Animals↗

Adenocarcinoma of the cervical oesophagus arising from ectopic gastric mucosa. The histochemical determination of its origin.

A case of adenocarcinoma of the cervical oesophagus was examined by employing a battery of histochemical techniques and was demonstrated to arise from ectopic gastric mucosa. The patient was a 66-year-old Japanese male. Endoscopy revealed an ulcerated tumour on the right anterior wall of the cervical oesophagus, approximately 16 cm from the incisor teeth. Pathological examination of surgically removed specimens showed well-differentiated tubular adenocarcinoma. Ectopic gastric mucosa was found in the oesophageal mucosa adjoining the carcinoma. Histochemical stains for characterizing mucosubstances and immunostains for various antigens were used. In addition to this carcinoma, ectopic gastric mucosa in the oesophagus and normal oesophageal, cardiac, tracheal and bronchial mucosa were also examined. The results showed that the carcinoma contained mucins, which showed reactivities characteristic of the gastric surface mucous cell (galactose oxidase-cold thionin Schiff reactive) and gland mucous cell (paradoxical concanavalin A staining reactive). Ectopic gastric mucosa consistently contained these mucins, but other tissue sites lacked them.

Adenocarcinoma↗

Ectopic expression of beta-lactoglobulin/human serum albumin fusion genes in transgenic mice: hormonal regulation and in situ localization.

We produced transgenic mice carrying the native sheep beta-lactoglobulin (BLG) or fusion genes composed of the BLG promoter and human serum albumin (HSA) minigenes. BLG was expressed exclusively in the mammary glands of the virgin and lactating transgenic mice evaluated. In contrast, transgenic females carrying the BLG/HSA fusion constructs also expressed the HSA RNA ectopically in skeletal muscle, kidney, brain, spleen, salivary gland and skin. Ectopic expression of HSA RNA was detected only in strains that express the transgene in the mammary gland. There was no obvious correlation between the level of the HSA RNA expressed in the mammary gland and that found ectopically. In three transgenic strains analysed, the expression of HSA RNA in kidney and skeletal muscle increased during pregnancy and lactation, whereas in the brain HSA expression decreased during lactation in one of the strains. HSA protein was synthesized in skeletal muscle and skin of strain #23 and its level was higher in lactating mice compared with virgin mice. Expression of HSA was also analysed in males and was found to be more stringently controlled than in females of the same strains. In situ hybridization analyses localized the expressed transgene in the skin, kidney, brain and salivary glands of various transgenic strains. Distinct strain-specific and cell-type specific HSA expression patterns were observed in the skin. This is in contrast to the exclusive expression of the HSA transgene in epithelial cells surrounding the alveoli of the mammary gland. Taken together, these results suggest that the absence of sufficient mammary-specific regulatory elements in the BLG promoter sequences and/or the juxtaposition of the BLG promoter with the HSA coding sequences leads to novel tissue- and cell-specific expression in ectopic tissues of transgenic mice.

Animals↗

Ectopic salivary gland tissue in submucosa of rectum.

A case of ectopic salivary gland tissue in the submucosa of the rectum adjacent to a hyperplastic polyp is described. The two previously reported cases of ectopic salivary gland tissue in the rectum were different in that ectopic gastric mucosa was also present. The 16 cases of ectopic tissue in the rectum noted in the world medical literature are reviewed.

Choristoma↗

Ectopic Breast Caner: Two Case Reports and Review of the Japanese Literature.

Two cases of carcinoma involving ectopic breast tissue are reported, along with a review of the Japanese literature. A total of 65 cases of ectopic breast cancer have been reported; 59 of which occurred in the axilla. Total mastectomy with axillary dissection was performed in 29 cases, and tumor excision with or without nodal dissection was done in 30 cases. Outcome was known in 33 cases, and 5 cases had recurred at the time of this writing. Although the prognosis of ectopic breast cancer was difficult to establish with the limited follow-up data, all the 5 cases in our series with recurrence had axillary lymph node metastases at the time of surgery. Therefore, the complete excision of ectopic breast tissue with nodal dissection, and subsequent chemoendocrine therapy, especially in node-positive patients, is recommended as the treatment of choice.

Journal Article↗

Ectopic accumulation of 99mTc-HMDP in primary lung cancer in comparison with CT findings.

The purpose of this study was to evaluate the frequency and the extent of extraosseous 99mTc-HMDP accumulation in 412 patients with primary lung cancer. CT scanning was also performed and we compared the extraosseous uptake by lung cancer with the internal structure of the tumor on CT scans. The extent of ectopic 99mTc-HMDP accumulation was classified as low, moderate or high. CT scans were used to evaluate the size and internal structure of the tumor, including calcification and necrosis. Ectopic 99mTc-HMDP accumulation in primary lung cancer was found in 32 patients (7.7%), and included 2 cases (0.5%) of high uptake, 8 cases (1.9%) of moderate uptake, and 22 cases (5%) of low uptake. No difference in uptake was observed among the histological types, but a relationship between tumor size and 99mTc-HMDP extraosseous accumulation was observed. CT scans of the 32 tumors exhibiting ectopic 99mTc-HMDP accumulation revealed 5 cases of calcification in the tumor and 18 cases of tumor necrosis. The factors promoting ectopic 99mTc-HMDP accumulation were considered to be tumor size and calcification or necrotic change. In patients with neither calcification nor necrosis, other factors such as increased calcium metabolism and altered vascular permeability may be involved.

Adenocarcinoma↗

Ectopic aldosteronoma associated to another adrenocortical adenoma in the adrenal gland of the same side.

The occurrence of tumors originating from aberrant adrenocortical tissue in ectopic site is very rare. Up to now only two cases of ectopic aldosterone-producing adenoma have been described. We have observed another case of ectopic aldosteronoma, located in the retrocaval region, laterally to the body of the 12th thoracic vertebra. This ectopic tumor was associated to another adrenocortical adenoma, in the adrenal gland of the same side. The diagnostic implications of this observation are discussed.

Adenoma↗

Mitigation of ectopic calcification in osteopontin-deficient mice by exogenous osteopontin.

Ectopic calcification is a major cause of bioprosthetic heart valve failure. New therapeutic opportunities are offered by the growing understanding that ectopic calcification is an actively regulated process involving several key gene products. One of these products, osteopontin (OPN), is a glycosylated phosphoprotein previously shown to inhibit apatite crystal formation, induce carbonic anhydrase II, and promote mineral resorption. In this study, OPN-deficient mice (OPN-/-) were utilized as an in vivo model to stimulate the ectopic calcification of glutaraldehyde-fixed bovine pericardium (GFBP) tissue and to examine OPN delivery and structure-function relationships with respect to its anti-calcific activity. Significant calcification of GFBP tissue was obtained within 7 days of subcutaneous implantation in OPN-/- mice. Direct rescue of the calcification phenotype was achieved by the administration of exogenous recombinant rat, histidine-fused OPN (rat His-OPN) to the implant site via soluble injection (up to 72% mitigation achieved) or adsorption onto the implant materials (up to 91% mitigation achieved). Effects were specific, since neither fibronectin nor polyhistidine alone could mitigate calcification of GFBP. The maximum anti-calcific effect was achieved only when rat His-OPN was adequately phosphorylated and contained a functional arginine-glycine-aspartate (RGD) cell adhesive domain. Furthermore, CAII levels in host cells surrounding GFBP were greatest when phosphorylated, RGD-containing rat His-OPN was adsorbed. These data suggest that both physical inhibition, mediated by phosphorylation sites in OPN, as well as the induction of CAII and mineral regression, mediated by the RGD domain, contribute to the unique ability of OPN to mitigate ectopic calcification of bioprosthetic valve tissue.

Animals↗

Ultrasonographic assessment of the ectopic thyroid tissue in children with congenital hypothyroidism.

BACKGROUND: Ectopic thyroid tissue as a result of thyroid developmental abnormalities is the most frequent cause of congenital hypothyroidism (CH). It is diagnosed by using radionuclide thyroid scanning. OBJECTIVE. To evaluate the sensitivity of US in the detection of such ectopias and to describe their US pattern before and during treatment. MATERIALS AND METHODS: Forty-two neonates (group A; aged 11.3+/-4.0 days) and 33 older children (group B; aged 11.1+/-3.9 years) with a biochemical diagnosis of CH and thyroid ectopia detected by radionuclide scanning were evaluated before (group A) and after (group B) treatment. Thyroid US included a survey of the pathway of the thyroglossal tract and an evaluation of the location, size, echogenicity and vascularity of any tissue along this pathway suggestive of thyroid ectopia. RESULTS: Thyroid ectopia was detected using US in 18 patients (24%) with a similar rate during the neonatal period and thereafter on therapy. Three patients demonstrated double ectopia. These 21 sites of ectopic thyroid tissue were located at the suprahyoid level (n=12), at the level of the hyoid (n=1), and at the infrahyoid level (n=8). The maximum diameter of the ectopic tissue ranged from 4 to 14 mm. In group A (9 patients), the 11 ectopias were all hypervascular. These were hyperechoic in all but one neonate. In group B (9 patients), the ten ectopias were not vascular, and were hyper (n=3) or hypoechoic (n=7). CONCLUSIONS: US allows for detection of ectopic thyroid tissue, but with a lower detection rate than radionuclide scanning. However, it does provide a more detailed description of such ectopias.

Choristoma↗

Incontinence due to an infrasphincteric ectopic ureter: why the delay in diagnosis and what the radiologist can do about it.

PURPOSE: To determine (1) the reasons for the frequently long delay in the diagnosis of an infrasphincteric ectopic ureter in girls, and (2) what role the radiologist can play in decreasing the delay. MATERIALS AND METHODS: Twelve girls were referred to our hospital from June 1994 until April 1997 for evaluation of constant urinary dribbling and/or vaginal discharge. Available imaging studies, radiology reports, and clinic notes were reviewed. RESULTS: Mean age at the time of diagnosis was 6 years 7 months (range 2 years 10 months to 11 years 11 months). Mean delay until diagnosis after presentation was 2 years 5 months. Excluding the one girl whose ectopic ureter was diagnosed while she was still in diapers, mean age at the time of the first parental "complaint" was 4 years 9 months. The significance of the classic history of constant urinary dribbling was not recognized by physicians in 7 girls for 4 months to 7 years 10 months after presentation. Physical exam was not meticulously performed, as the ectopic orifice was visible in 8 of 12 girls. Imaging studies were ineffectively utilized: no imaging was done (for 2 years in 2 girls), inappropriate studies were done (ultrasound and voiding cystourethrography) and were misleading, studies were called normal when they were not (ultrasound and excretory urography), or perinatal imaging led to the incorrect assumption of a congenitally absent kidney in one girl and a multicystic dysplastic kidney in another. Excretory urography (EU) was diagnostic in all 10 girls with a duplex kidney, and computed tomography (CT) was supportive in 2 with a dysplastic kidney. CT was an adjunct in 3 girls; a Tc-99m-dimercaptosuccinic acid (DMSA) scan was needed in 2. CONCLUSION: The classic history of constant urinary dribbling in a successfully toilet-trained girl should immediately lead to an imaging search for the portion of kidney (or entire kidney) drained by an infrasphincteric ectopic ureter. EU should usually be the first imaging performed and is often the only imaging study needed.

Child↗

[Ectopic hamartomatous thymoma. Case report with special reference to differential diagnosis].

We report the case of an ectopic hamartomatous thymoma in a 56-year-old male patient. The lesion arose subcutaneously in the supraclavicular region. Histologically, the well-circumscribed but unencapsulated tumour was composed of uniform fusiform tumour cells. In addition, mature fatty tissue, scattered T-lymphocytes, and an epithelial and a myoepithelial tumour cell component were found. The epithelial differentiation of the spindle cell tumour component was confirmed immunohistochemically and by electron microscopy. Ectopic hamartomatous thymoma has to be distinguished from ectopic cervical thymoma, thymolipoma, ectopic salivary tissue, teratoma, peripheral nerve sheath tumours, malignant epithelial tumours with thymus-like differentiation, biphasic synovial sarcoma, and skin adnexal tumours.

Biomarkers, Tumor↗

Anterior abdominal wall--an unusual site for ectopic testis.

Testicular descent can be described in two phases, the transabdominal and the inguinoscrotal. During the inguinoscrotal phase, the testis may deviate from the normal path of descent and "migrate" to an abnormal location; this is called ectopic testis and is a relatively uncommon condition. The common sites for ectopic testes include the superficial inguinal pouch, the perineum, the opposite side of the scrotum, the femoral canal, and the pubopenile region. In addition to these well-recognized sites, preperitoneal and extracorporeal ectopic testes, which are extremely rare, have been reported. We report yet another rare site for ectopic testis, the anterior abdominal wall, probably the first of its nature to be reported in the English literature.

Abdominal Wall↗