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Ectopic dendrite initiation: CNS pathogenesis as a model of CNS development.

The neuronal storage diseases are a rare group of disorders with profound clinical consequences including severe mental retardation and death in early childhood. A subset of these disorders, those with elevated levels of GM2 ganglioside, are further characterized by the reinitiation of primary dendrites on mature cortical neurons. These ectopic dendrites are unusual as primary dendrite initiation is normally confined to a narrow developmental window. Thus, ectopic dendritogenesis appears to be a recapitulation of the normal developmental program temporally displaced. Consequently, understanding ectopic dendritogenesis should offer insights into both the pathogenesis of the neuronal storage diseases as well as mechanisms of normal CNS development. Using a feline model of GM2 gangliosidosis, we compared patterns of gene expression in normal newborn and mature diseased animals (both undergoing active primary dendritogenesis) with normal, mature controls (where primary dendritogenesis has ceased). From this work, we have identified two genes that appear to function in primary dendrite initiation. One, tomoregulin, is an integral membrane protein with both EGF- and follistatin-like motifs in its extracellular domain. The second, Tristanin, is a member of the positive regulatory domain (PRD) family of a zinc-finger transcription factors. Both genes are up regulated in the disease state, and both show a shift in their intracellular location to the nucleus in diseased animals that is not observed in age matched controls. In normal mouse brain, tomoregulin and Tristanin reveal developmental patterns consistent with a role in dendrite initiation and show changes in subcellular localization similar to that observed in the cat.

Animals↗

Rescue of ataxia and preplate splitting by ectopic expression of Reelin in reeler mice.

The gene mutated in reeler (reelin) encodes a protein secreted by neurons in the developing brain that controls laminar positioning of migrating cells in the CNS by an unknown mechanism. To investigate Reelin function, we used the nestin promoter to express Reelin ectopically in the ventricular zone and other brain regions in transgenic mice. In the presence of the endogenous protein, ectopic Reelin did not alter cell migration in the neocortex or the cerebellum. However, in the reeler background, ectopic Reelin induced tyrosine phosphorylation of Dab-1 in the ventricular zone and rescued some, but not all, of the neuroanatomic and behavioral abnormalities characteristic of reeler. These results indicate that Reelin does not function simply as a positional signal. Rather, it appears to participate in multiple events critical for neuronal migration and cell positioning.

Animals↗

Ectopic thymic tissue: a cause of emphysema in infants.

Ectopic thymic tissue can present a diagnostic dilemma when it is located in the posterior mediastinum. The diagnosis can be made by awareness of it and by use of computed tomography (CT) and magnetic resonance imaging (MRI). Rarely, ectopic thymus are reported to cause airway obstruction. In infants ectopic thymic tissue should also be considered in the differential diagnosis of secondary pneumonias and emphysema especially located in the upper lung zones.

Choristoma↗

Loss of the beta-catenin homologue aardvark causes ectopic stalk formation in Dictyostelium.

Aardvark (Aar) is a Dictyostelium beta-catenin homologue with both cytoskeletal and signal transduction roles during development. Here, we show that loss of aar causes a novel phenotype where multiple stalks appear during late development. Ectopic stalks are preceded by misexpression of the stalk marker ST-lacZ in the surrounding tissue. This process does not involve the kinase GSK-3. Mixing experiments show that ectopic ST-lacZ expression and stalk formation are cell non-autonomous. The protein-cellulose matrix surrounding the stalk of aar mutant fruiting bodies is defective, and damage to the stalk of wild-type fruiting bodies leads to ectopic ST-lacZ expression. We postulate that poor synthesis of the stalk tube matrix allows diffusion of a stalk cell-inducing factor into the surrounding tissue.

Animals↗

Ectopic lens induction in fish in response to the murine homeobox gene Six3.

Recent findings show an unexpected conservation of genes involved in vertebrate and insect eye development. The Drosophila homeobox gene sine oculis is crucial for eye development. Its murine homologue, Six3 is expressed in the anterior neural plate, a region which is involved in lens induction in Xenopus. To examine whether Six3 participates in the process of eye formation, mouse Six3 was ectopically expressed in fish embryos. The results show that Six3 is sufficient to promote ectopic lens formation in the area of the otic vesicle and that retinal tissue is not a prerequisite for ectopic lens differentiation. Our findings suggest a conserved function for Six3 in metazoan eye development.

Animals↗

BMP-2 induces ectopic expression of cardiac lineage markers and interferes with somite formation in chicken embryos.

In Drosophila induction of the homeobox gene tinman and subsequent heart formation are dependent on dpp signaling from overlying ectoderm. In order to define vertebrate heart-inducing signals we screened for dpp-homologues expressed in HH stage 4 chicken embryos. The majority of transcripts were found to be BMP-2 among several other members of the BMP family. From embryonic HH stage 4 onwards cardiogenic mesoderm appeared to be in close contact to BMP-2 expressing cells which initially were present in lateral mesoderm and subsequently after headfold formation in the pharyngeal endoderm. In order to assess the role of BMP-2 for heart formation, gastrulating chick embryos in New culture were implanted with BMP-2 producing cells. BMP-2 implantation resulted in ectopic cardiac mesoderm specification. BMP-2 was able to induce Nkx2-5 expression ectopically within the anterior head domain, while GATA-4 was also induced more caudally. Cardiogenic induction by BMP-2, however remained incomplete, since neither Nkx2-8 nor the cardiac-restricted structural gene VMHC-1 became ectopically induced. BMP-2 expressing cells implanted adjacent to paraxial mesoderm resulted in impaired somite formation and blocked the expression of marker genes, such as paraxis, Pax-3, and the forkhead gene cFKH-1. These results suggest that BMP-2 is part of the complex of cardiogenic signals and is involved in the patterning of early mesoderm similar to the role of dpp in Drosophila.

Animals↗

Ectopic bone formation in nude rats using human osteoblasts seeded poly(3)hydroxybutyrate embroidery and hydroxyapatite-collagen tapes constructs.

PURPOSE: The aim of this study was to evaluate the ectopic bone formation using tissue engineered cell-seeded constructs with two different scaffolds and primary human maxillary osteoblasts in nude rats over an implantation period of up to 96 days. MATERIAL AND METHODS: Collagen I-coated Poly(3)hydroxybutyrate (PHB) embroidery and hydroxyapatite (HAP) collagen tapes were seeded with primary human maxillary osteoblasts (hOB) and implanted into athymic rnu/run rats. A total of 72 implants were placed into the back muscles of 18 rats. 24, 48 and 96 days after implantation, histological and histomorphometric analyses were made. The osteoblastic character of the cells was confirmed by immunocytochemistry and RT-PCR for osteocalcin. RESULTS: Histological analysis demonstrated that all cell-seeded constructs induced ectopic bone formation after 24, 48 and 96 days of implantation. There was more mineralized tissue in PHB constructs than in HAP-collagen tapes (at day 24; p < 0.05). Bone formation decreased with the increasing length of the implantation period. Osteocalcin expression verified the osteoblastic character of the cell-seeded constructs after implantation time. No bone formation and no osteocalcin expression were found in the control groups. CONCLUSIONS: Cell-seeded constructs either with PHB embroidery or HAP-collagen tapes can induce ectopic bone formation. However, the amount of bone formed decreased with increasing length of implantation.

Animals↗

Left-sided congenital diaphragmatic hernia associated with intrathoracic ectopic liver lobule.

A case of intrathoracic ectopia of the left lobe lateral segment of the liver in a patient with left-sided diaphragmatic hernia is described. The ectopic liver part was found in the left hemithorax during excision of the diaphragmatic hernia sac, but it was not the content of the sac. The ectopic liver part has not been described previously in the left hemithorax and is actually the primary abnormality. The diaphragmatic hernia is merely a secondary development through this potential gap on the diaphragm where the pedicle of the ectopic liver lobule passes.

Choristoma↗

Ectopic pregnancy months after laparoscopic supracervical hysterectomy.

Although it is an easy diagnosis to eliminate, pregnancy is rarely considered in a woman with acute abdominopelvic pain and history of hysterectomy. A 37-year-old woman was seen because of acute onset of pelvic pain. Her history was significant for laparoscopic supracervical hysterectomy performed 4 months previously. A urine pregnancy test was positive. At diagnostic laparoscopy, an area in the right tube was consistent with ectopic pregnancy. Bilateral salpingectomy was performed, and pathology confirmed an ectopic pregnancy in the right tube. A diagnosis of ectopic pregnancy should be entertained in any woman with pain and intact ovaries.

Adult↗

Comparison of local injection of methotrexate and linear salpingostomy in the conservative laparoscopic treatment of ectopic pregnancy.

STUDY OBJECTIVE: To compare local injection of metothrexate (MTX) and linear salpingostomy in the conservative laparoscopic treatment of ectopic pregnancy. DESIGN: Prospective, nonrandomized study, July 1991 to May 1994. SETTING: Department of obstetrics and gynecology in a university hospital. PATIENTS: Fourteen women with unruptured ectopic pregnancies without documented fetal heart motion and size below 50 mm as measured by ultrasound. INTERVENTIONS: All 14 women underwent the laparoscopic treatment by either local injection of MTX or linear salpingostomy (7 patients each). MEASUREMENTS AND MAIN RESULTS: Both treatments were successful in all patients. Mean length of operation was 32 +/- 5 minutes (range 25-35 min) in the MTX group versus 67 +/- 15 minutes (range 50-90 min) in the salpingostomy group. Mean length of hospital stay was 2.7 days (range 1-5 days) and 1.7 days (range 1-3 days), respectively. No intraoperative complications occurred, and the postoperative course was uneventful in all women. Mean disappearance time of serum beta-human chorionic gonadotropin (hCG) levels was similar in both groups, although in the linear salpingostomy group the decrease was immediate. No difference in tubal patency on follow-up hysterosalpingography was observed between the two groups. CONCLUSIONS: Although this is a preliminary report with a small number of patients, both types of treatment were safe and effective. An advantage of linear salpingostomy was the predictable and consistent decline of circulating beta-hCG, and consequently a reduced need for a close follow-up. Local MTX injection was safe, economic, effective, and easy to perform, and in our experience the surgical time was statistically shorter than that for linear salpingostomy. Therefore, in selected patients, local injection of MTX could be the treatment of choice for unruptured ectopic pregnancy, avoiding a longer and potentially more dangerous procedure. Long-term outcomes do not seem to differ between the two types of treatment.

Adult↗

Prophylactic vasopressin during laparoscopic salpingotomy for ectopic pregnancy.

STUDY OBJECTIVE: To evaluate the safety and efficacy of prophylactic mesosalpingeal vasopressin injection for hemostasis during laparoscopic salpingotomy for ectopic pregnancy. DESIGN: Prospective, randomized clinical study. SETTING: Reproductive endocrinology and endoscopic surgery clinic of a tertiary care hospital. PATIENTS: Forty women with ectopic pregnancy. INTERVENTIONS: Laparoscopic linear salpingotomy was attempted, with prophylactic mesosalpingeal dilute vasopressin injection in 20 patients (study group), and without vasopressin in 20 patients (control group). The two groups were similar with regard to age, size of ectopic pregnancy, gestational age, and initial beta-hCG values. A multipuncture operative laparoscopy technique was used in all cases and bipolar electrocoagulation was used for hemostasis. MEASUREMENTS AND MAIN RESULTS: The operating time was significantly shorter and the need for electrocoagulation was significantly less in the study than in the control group (p <0.05). Laparoscopic salpingotomy was performed successfully in 85% of study group patients compared with 70% of controls (p >0.05). Postoperative hysterogram revealed patency of the affected tube in 76.5% of women in the study group compared with 57.1% of controls (p >0.05). Possible complications of vasopressin, such as hypertension, bradycardia, and delayed bleeding, did not occur in any patient. CONCLUSIONS: Vasopressin use reduces both operating time and the need for electrocoagulation for hemostasis, which can have undesirable effects on the tube. Vasopressin was not associated with side effects in this relatively small sample.

Adult↗

Ectopic expression of reg protein: A marker of colorectal mucosa at risk for neoplasia.

Pancreatic regenerating gene (reg I) messenger RNA is overexpressed within the pancreas following injury and resection. Its level of expression corresponds to the level of cellular dedifferentiation. Human reg I has been localized to chromosome 2p12, and ectopic expression of its mRNA has been found within colorectal tumors. We postulated that colorectal production of reg I might either be a marker for the presence of cancer or define mucosa at risk for development of neoplasia. Using a monoclonal antibody to reg I, regenerating gene protein was histochemically mapped in 56 cases of documented colorectal adenocarcinoma. In sections of colon from normal control subjects no reg I protein was noted, whereas 58.9% of the specimens from cancer patients stained positive for reg I. Although a correlation was noted between reg I staining and Dukes' stage, there was no correlation with histologic grade or 5-year patient survival. In 39 of 55 cancer specimens the transition zone (interface) between the neoplasm and normal mucosa was visualized; 100% of the transition zones contained cells that stained strongly positive for reg I. We conclude that reg I protein is ectopically expressed in colorectal mucosa at the transition zone of colorectal cancer, and occasionally within the tumor itself. Although ectopic reg I expression in colorectal epithelia is not a marker for the presence of carcinoma, it may be a sensitive marker for mucosa at risk for development of neoplasia.

Adenocarcinoma↗

Differential effects of PPARalpha activators on induction of ectopic expression of tissue-specific fatty acid binding protein genes in the mouse liver.

The effect of a potent peroxisome proliferator-activated receptor (PPAR) alpha activator Wy14,643 on tissue-specific expression of fatty acid binding (FABP) genes was studied. Wy14,643 immediately induced liver-, intestine- and FABP but not PPARgamma-regulated adipose-FABP (or aP2) mRNAs in respective mouse tissues. Moreover, it gradually induced ectopic expression of heart- and adipose-FABP mRNAs to significant levels in the liver. However, ectopic expression was not induced in the liver of PPARalpha-null mouse, indicating an obligatory role of the receptor in the modulated expression. Among the four PPARalpha activators examined, only Wy14,643 induced ectopical expression of heart-FABP in the liver. Thus, tissue-specificity of the FABP gene expression is not absolute and, with a potent activator, can be distorted by PPARalpha.

Adipose Tissue↗

Ectopic pancreatic tissue presenting as an umbilcal mass in a newborn: a case report.

The case of an ectopic pancreatic mass at the umbilicus in an 8-day-old male neonate is reported, the youngest patient with this condition ever reported in an English-language journal. The patient was healthy except for a protruding mass with intermittent mucous discharge at the base of the umbilical stump. Surgical intervention was performed under the impression of the umbilical mass. Pathology diagnosed an ectopic pancreas with acute hemorrhage. To the best of our knowledge, only one case of ectopic pancreas presenting as an umbilical mass with intermittent mucous discharge has previously been reported.

Choristoma↗

Antiangiogenic agent (TNP-470) inhibition of ectopic bone formation induced by bone morphogenetic protein-2.

Bone morphogenetic protein (BMP) is a potent inducer of ectopic bone formation, and TNP-470, a synthetic analog of fumagillin, is an antiangiogenic agent that strongly inhibits neovascular formation in vivo. We investigated the effects of TNP-470 on BMP-induced ectopic bone formation to clarify the role of angiogenesis in bone formation. Collagen pellets containing recombinant human BMP-2 (rhBMP-2) were implanted beneath the fasciae of dorsal muscles in mice. By daily subcutaneous administration of TNP-470, ectopic new bone formation was inhibited in a dose-dependent manner. Histological examination revealed that TNP-470 prevented proliferation of mesenchymal cells and chondrogenesis at the initial step of endochondral bone formation. Immunohistochemical staining with a specific antibody against bone morphogenetic protein type IA receptor showed that TNP-470 reduced the number of receptor-positive cells surrounding the BMP pellets. The inhibitory effect of TNP-470 on bone formation continued during the period of its administration, and discontinuation of treatment was followed by the resumption of the whole process of endochondral bone formation. This study showed that TNP-470 reversibly inhibits the biological activity of rhBMP-2 in the early stage of bone induction, suggesting that angiogenesis may play an essential role in the recruitment of BMP-receptor-positive cells that can respond to rhBMP-2 and differentiate into chondrocytes and/or osteoblasts.

Animals↗

Ectopic bilharziasis.

Ectopic Bilharziasis is discussed and two cases of ectopic pharyngeal affections are reported. The five theories advocated to explain how ectopic lesions can develop outside the portol-caval system are discussed. The clinical picture, age, diagnosis and follow-up of such lesions are mentioned.

Adolescent↗

Ectopic splenic nodules in the olive baboon (Papio cynocephalus anubis).

Post-mortem evaluation of a female sub-adult olive baboon (Papio cynocephalus anubis) revealed a case of ectopic spleen anomaly. Three spherical masses characterized the spleen anomaly. The splenic nodules were located on the left upper quadrant of the stomach, at the distal end of the pancreas. The anterior nodule measures 1.2 cm, the middle nodule 1.9 cm and the posterior nodule 1.3 cm in diameter. Normal spleen was not observed in this case. All the three ectopic splenic nodules showed normal histological architecture. A case of ectopic splenic nodules in baboon is important in that the spleen malformation can readily be mistaken for a pathological process.

Animals↗

Homeotic transformation of the occipital bones of the skull by ectopic expression of a homeobox gene.

Murine Hox genes have been postulated to play a role in patterning of the embryonic body plan. Gene disruption studies have suggested that for a given Hox complex, patterning of cell identity along the antero-posterior axis is directed by the more 'posterior' (having a more posterior rostral boundary of expression) Hox proteins expressed in a given cell. This supports the 'posterior prevalence' model, which also predicts that ectopic expression of a given Hox gene would result in altered structure only in regions anterior to its normal domain of expression. To test this model further, we have expressed the Hox-4.2 gene more rostrally than its normal mesoderm anterior boundary of expression, which is at the level of the first cervical somites. This ectopic expression results in a homeotic transformation of the occipital bones towards a more posterior phenotype into structures that resemble cervical vertebrae, whereas it has no effect in regions that normally express Hox-4.2. These results are similar to the homeotic posteriorization phenomenon generated in Drosophila by ectopic expression of genes of the homeotic complex HOM-C (refs 7-10; reviewed in ref. 3).

Animals↗