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At least 1,207 records · Page 67Linked to original sources
PubMed2003

Ectopic germinal center formation in rheumatoid synovitis.

Synovial inflammation in rheumatoid arthritis is closely related to the formation of ectopic lymphoid microstructures. In synovial tissue from some patients, one finds seemingly diffuse infiltrates; in others, T cells and B cells cluster in aggregates with interdigitating dendritic cells (DCs) but no follicular DCs (FDCs). In a third group, T cell/B cell follicles with germinal center (GC) reactions are generated. Within a given patient, aggregates and GCs are mutually exclusive and stable over time. Because antigen storage capacity, lymphoid density, and three-dimensional topography of GCs optimize immune responses, synovial GCs should play a crucial role in the breakdown of self-tolerance. We have identified factors critical for ectopic GCs, thereby transforming the synovial inflammatory process. Tissues with GCs produced 10- to 20-fold higher amounts of the chemokines CXCL13 and CCL21. CXCL13 derived from three sources, endothelial cells, synovial fibroblasts, and FDC networks. The level of CXCL13 transcripts strongly predicted GCs; however, some tissues had high levels of CXCL13 but lacked GCs. Tissue expression of LT-beta emerged as a second key factor. LT-beta protein was detected on follicular center and mantle zone B cells. Multivariate regression analysis identified CXCL13 and LT-beta as the only cytokines predicting GCs. Remarkably, LT-alpha did not contribute independently. The contribution of B cells to ectopic lymphoid organogenesis was not limited to LT-beta production. Rather, synovial tissue B cells were critical in regulating T cell activation. In adoptive transfer experiments in human synovium-SCID mouse chimeras, activation of synovium-derived CD4 T cells was strictly dependent on T cell/B cell follicles. Depletion of synovial tissue B cells abrogated T cell function, and non-B cell antigen-presenting cells could not maintain T cell stimulation. Unexpectedly, GC function in the rheumatoid lesion was also dependent on CD8 T cells. The majority of T cell receptors derived from CD8 T cells were shared between distinct GCs. Depletion of CD8 T cells disrupted synovial GCs, FDC networks disappeared, and transcription of LT-beta, IgG, and Igkappa declined. Follicle-sustaining CD8 T cells were located at the edge of or within the mantle zone. Cell-cell communication in the mantle zone, including CD8 T cells, appears to be critical for ectopic GC formation in rheumatoid synovitis.

Animals↗
PubMed1992

Ectopic activity in demyelinated spinal root axons of the rat.

1. We have provoked ectopic discharges from demyelinated rat spinal roots by applying 1 mM-4-aminopyridine (4-AP), and recorded membrane currents and action potentials extracellularly by spike-triggered averaging. The demyelination was caused by intrathecal injection of diphtheria toxin, 6-9 days previously. 2. Mapping the distribution of membrane currents in the vicinity of an ectopic site showed that in most cases (eight out of twelve recorded) the impulses arose from one end of a continuously conducting internode, and conducted in both directions. In the remaining cases the impulses also arose from a site of demyelination. 3. The 4-AP-induced activity resembled the activity occurring spontaneously in some preparations, and was often highly regular (5-20 Hz). Recordings of membrane potential revealed a pacemaker potential, which was localized to the site of impulse initiation. One ectopic site was tested with applied currents and found to have a linear current-frequency relation for steady currents. 4. The time course of the pacemaker potential resembled that of the small after-hyperpolarization seen in normal fibres, due to a slow K+ conductance (GKs). Tetraethylammonium and barium ions, which block GKs, made spontaneously active fibres fire much more rapidly, or to fire bursts of action potentials. 5. Possible mechanisms for these ectopic discharges are discussed. GKs appears to contribute to the pacing of the activity, but not its generation. The increased excitability of the active fibres could not be attributed directly to the loss of myelin, nor to extracellular K+ accumulation. We suggest that they may have been depolarized by stretch-activated or ligand-gated channels in the demyelinated axon membrane.

4-Aminopyridine↗
PubMedDate not supplied

Ectopic activity in ventricular cells induced by early afterdepolarizations developed in Purkinje cells.

The development of early afterdepolarizations (EADs) in Purkinje fibers and their propagation to ventricular muscle cells are studied by computer modeling. The Purkinje-ventricular system has been simulated by a two-dimensional model of a Purkinje fiber (PF) connected to a thin sheet of ventricular muscle tissue (VMT). EADs are induced in the PF by enhancing the fast second inward current, iCa,f, and blocking the delayed K+ current, iK, while the VMT is kept under physiological conditions. Different phenomena are observed depending on the EAD conditions applied. For 70% iK blockade and iCa,f enhancement greater than 60%, a single phase 3 EAD developed in the PF propagates to the VMT generating an ectopic beat. For 80% iK blockade and iCa,f enhancement in the range from 0% to 70%, multiple ectopic beats appear in the VMT. However, for iK blockades over 80%, action potentials in PF cells do not repolarize and the ectopic activity in the VMT disappears. In our simulations, the ionic mechanism underlying phase 3 EAD development is the reactivation of the fast sodium current in the PF. Our results demonstrate that there exists a critical range of EAD conditions that favor the development of EADs in the PF and their propagation to the VMT as ectopic activity. This phenomenon could underlie the genesis of some triggered arrhythmias.

Action Potentials↗
PubMed1984

Ectopic integration of chromosomal genes in Streptococcus pneumoniae.

When a DNA fragment containing a marker gene was ligated to random chromosomal fragments of Streptococcus pneumoniae and used to transform a recipient strain lacking that gene, the gene was integrated at various locations in the chromosome. Such ectopic integration was demonstrated for the malM gene, and its molecular basis was analyzed with defined donor molecules consisting of ligated fragments containing the malM and sul genes of S. pneumoniae. In a recipient strain deleted in the mal region of its chromosome, these constructs gave Mal+ transformants in which the malM and sul genes were now linked, with malM located between duplicate sul segments. Ectopic integration was unstable under nonselective conditions; mal(sul) ectopic insertions were lost at a rate of 0.05% per generation. Several possible mechanisms of ectopic integration were examined. The donor molecule is most likely to be a circular form of ligated homologous and nonhomologous fragments that, after entry into the cell, undergoes circular synapsis with the recipient chromosome at the site of homology, followed by repair and additive integration.

Chromosomes, Bacterial↗
PubMed1997

Ectopic gene targeting exhibits a bimodal distribution of integration in murine cells, indicating that both intra- and interchromosomal sites are accessible to the targeting vector.

Ectopic gene targeting is an alternative outcome of the gene targeting process in which the targeting vector acquires sequences from the genomic target but proceeds to integrate elsewhere in the genome. Using two-color fluorescent in situ hybridization analysis, we have determined the integration sites of the gene targeting vector with respect to the target locus in a murine fibroblast line (LTA). We found that for ectopic gene targeting the distribution of integration sites was bimodal, being either within 3 Mb of the target or on chromosomes distinct from the chromosome carrying the target locus. Inter- and intrachromosomal sites appeared to be equally accessible to the targeting vector, with site-specific variations. Interestingly, interphase analysis indicated that vector sequences which had integrated ectopically in chromosomes other than the target colocalized with the target locus at a significant frequency compared to that of colocalization to random unlinked loci. We propose that ectopic gene targeting could be used to determine which chromosomal domains within the genome are accessible to a given genetic locus. Thus, recombination access mapping may present a new paradigm for the analysis of DNA accessibility and interaction within the genome.

Animals↗
PubMed2004

Defined sequence modules and an architectural element cooperate to promote initiation at an ectopic mammalian chromosomal replication origin.

A small DNA fragment containing the high-frequency initiation region (IR) ori-beta from the hamster dihydrofolate reductase locus functions as an independent replicator in ectopic locations in both hamster and human cells. Conversely, a fragment of the human lamin B2 locus containing the previously mapped IR serves as an independent replicator at ectopic chromosomal sites in hamster cells. At least four defined sequence elements are specifically required for full activity of ectopic ori-beta in hamster cells. These include an AT-rich element, a 4-bp sequence located within the mapped IR, a region of intrinsically bent DNA located between these two elements, and a RIP60 protein binding site adjacent to the bent region. The ori-beta AT-rich element is critical for initiation activity in human, as well as hamster, cells and can be functionally substituted for by an AT-rich region from the human lamin B2 IR that differs in nucleotide sequence and length. Taken together, the results demonstrate that two mammalian replicators can be activated at ectopic sites in chromosomes of another mammal and lead us to speculate that they may share functionally related elements.

Animals↗
PubMed1998

Segmental wall motion abnormalities alter vulnerability to ventricular ectopic beats associated with acute increases in aortic pressure in patients with underlying coronary artery disease.

OBJECTIVE: To evaluate whether patients with coronary artery disease are susceptible to pressure related ventricular arrhythmias, and if so to identify possible risk factors. DESIGN: Interventional study. METHODS: Metaraminol was given to 43 patients undergoing coronary arteriography for ischaemic heart disease to increase their aortic pressure, provided their systolic blood pressure was < 160 mm Hg and they were in sinus rhythm, without any ventricular ectopic activity (or with fewer than six ventricular ectopic beats a minute) during a five minute control period. RESULTS: During the metaraminol infusion, systolic aortic pressure rose from 131 (15) to 199 (12) mm Hg (mean (SD)). Ventricular ectopy appeared (or ventricular ectopic beats increased by > 100%) in 13/43 patients. Ventricular ectopy was not related to age, sex, presence of hypertension, history of myocardial infarction, use of beta blockers, positive exercise test, number of vessels diseased, or heart rate change during metaraminol infusion. There was a strong relation between the appearance of ventricular arrhythmia and segmental wall motion abnormalities: 1/19 (5.3%, 95% confidence interval 0.1% to 26.0%) without abnormality; 2/12 (16.7%, 2.1% to 48.4%) with hypokinesia; and 10/12 (83.3%, 51.6% to 97.1%) with akinesia or dyskinesia, chi 2 = 22.7, p < 0.001). Ejection fraction was also a significant but not independent risk factor. CONCLUSIONS: Patients with segmental wall motion abnormalities are predisposed to ventricular ectopic beats during an increase in systolic aortic pressure. This could be explained by associated electrophysiological inhomogeneity. The presence of mechanical inhomogeneity, as may occur in postinfarction akinesia or dyskinesia, may affect the aortic pressure above which ventricular arrhythmias appear.

Adult↗
PubMed1980

Atrial ectopic foci in the canine heart: hierarchy of pacemaker automaticity.

The sinoatrial node (SAN) and adjacent tissue of the sulcus terminalis were surgically excised in sequential multiple sections to study the location and intrinsic rate of emerging pacemakers in the acute open-chest dog. Under chloralose anesthesia total of 17 ectopic atrial pacemakers emerged in 12 dogs ranging in location from the anterior interatrial band, midsulcus terminalis, and junction of the inferior vena cava-inferior right atrium. Four AV junctional and one idioventricular pacemakers also emerged in these experiments. Each successively inferior focus had a slower rate than the SAN. The average heart rate of the atrial ectopic pacemakers was 73 +/- 4% of the SAN but that the AV junctional pacemakers was 56 +/- 4% of the SAN (P less than 0.05). The greatest reductions in rate were achieved with total excision of the SAN and entire sulcus terminalis, but in only 50% of the animals did this result in a junctional rhythm. The location and rate of atrial ectopic foci support the notion that the AV junctional region is not the fastest pacemaker in the absence of the classically defined SAN and suggest that atrial ectopic pacemakers are intermediate in the hierarchy of cardiac pacemakers in the dog.

Action Potentials↗
PubMed1975

Spatial limits of epileptogenic cortex: its relationship to ectopic spike generation.

In order to investigate if ectopic spike generation was ubiquitous in and specific generation was ubiquitous in and specific to epileptogenic cortex, a method was devised to determine the limits of such an area based on a well-accepted physiologic characteristic of epileptogenicity. The limits of the penicillin-induced epileptogenic cortex were defined in terms of a retinal activation field; this is a circumscribed area whose stimulation by light evokes a characteristic cortical epileptiform wave. All lateral geniculate nucleus (LGN) neurons manifesting ectopic spike generation during interictal epileptiform waves had receptive fields within the activation field. During organized seizures, ectopic spike generation was observed in neurons with receptive fields outside the activation field. Because of these findings it was concluded that ectopic spike generation is a characteristic and specific feature of epileptogenic cortex and that it is a characteristic of the epeleptogenic process rather than a peripheral event related entirely to the direct effect of penicillin on neurons.

Action Potentials↗
PubMed2002

Ectopic XIST transcripts in human somatic cells show variable expression and localization.

XIST encodes a functional RNA that is expressed exclusively from the inactive X in female mammals and is required for the silencing of most of the genes on the chromosome. XIST transcripts remain in the nucleus, and their specific localization to the inactive X is important for silencing; however, it is not known how these transcripts localize to the inactive X chromosome. Expression of mouse and human XIST from ectopic sites has suggested that localization to the chromosome from which the gene is expressed may be dependent upon either the copy number of the integrated constructs or the level of ectopic XIST expression. To further examine the behavior of XIST transgenes when expressed from ectopic sites, we introduced an XIST-containing PAC into the human male somatic cell line HT-1080. In five different transformant clones, the degree of localization and associated DNA condensation of the surrounding chromatin varied within nuclei of the same clone, as well as among different clones. Comparing the number of integrated transgenes and the levels of XIST expression revealed that neither factor was sufficient for a tight localization of the XIST signal. Therefore, the extent of expression and localization of XIST transcripts from ectopic transgenes is likely dependent upon many interacting factors, including the number of integrated transgenes, the level of XIST expression, and the site of integration.

Gene Expression↗
PubMed2004

Fibrocystic disease of vulvar ectopic breast tissue. Case report and review of the literature.

INTRODUCTION: Mammary glands located in the vulvar region have been named as ectopic breast tissue or anogenital mammary glands by different authors. Literature on pathologies of ectopic breast tissue located in the vulvar region is rare. Most of the reports are about the malignancies arising from this ectopic tissue. CASE REPORT: We report a case of fibrocystic disease of the mammary glands in the vulva in a 25-year-old pregnant woman. Her disease was exaggerated during pregnancy. CONCLUSION: Ectopic breast tissue in the vulva is a rare entity and fibrocystic disease of this tissue has rarely been reported in the English literature.

Adult↗
PubMed2005

Lower urinary tract reconstruction in ectopic ureteroceles.

OBJECTIVES: The management of ectopic ureteroceles is a challenging entity in pediatric urology. In our study, we aimed to determine the outcome after lower urinary tract reconstruction in ectopic ureteroceles. MATERIALS AND METHODS: A total of 18 (12 girls, 6 boys) children with ectopic ureteroceles, treated between 1993 and 2003 by complete reconstruction, were enrolled in the study and their records were retrospectively reviewed. RESULTS: Ureterocele was found to be unilateral in 16 and bilateral in 2 children. Four patients had been previously managed by endoscopic interventions and 1 patient underwent partial nephrectomy. Ureterocelectomy was performed on 20 renal units, and of these 20 renal units, 9 underwent heminephroureterectomy, 1 ureterectomy, and 3 (with single system ureteroceles) nephroureterectomy. Seven (35%) renal units with adequate function underwent ureteral reimplantations. After a mean follow-up of 5.4 years (range 4 months to 9.5 years), no patient required a second procedure. Contralateral reflux that developed in 2 children after surgical treatment resolved spontaneously after 1 year of follow-up. CONCLUSION: In the management of ectopic ureterocele, lower urinary tract reconstruction is an effective treatment alternative. According to the functional status of the renal parenchyma involved, the surgical procedure was limited to the lower urinary tract in 35% of the cases.

Adolescent↗
PubMed2006

Ectopic pancreas in the ampulla of vater with obstructive jaundice. A case report and review of literature.

Ectopic pancreas is an uncommon condition and is usually found in the gastrointestinal tract, such as stomach, duodenum and jejunum. However, ectopic pancreas in the ampulla of Vater is rare and its clinical presentations may be similar to periampullary cancer. It is difficult to diagnose preoperatively. We present such a case where the diagnosis was proven postoperatively. Our patient, a 51-year-old man, presented with epigastric pain, jaundice, weight loss and abnormal laboratory data. Imaging study, including abdominal sonography, abdominal computerized tomography with contrast and endoscopic retrograde cholangiopancreatography, showed a mass protruding into the ampulla of Vater. The mass was resected and histological examination revealed an ectopic pancreas. The patient presented with symptoms of periampullary tumor but the imaging study did not reveal an obvious lesion for us consider the possibility of ectopic pancreas. Surgical excision is indicated for symptomatic cases.

Ampulla of Vater↗
PubMed1986

Ectopic Purkinje cells in the cerebellar white matter of normal adult rodents: a Golgi study.

In Golgi/Río-Hortega preparations of rat and rabbit cerebellar vermis we have occasionally found isolated ectopic Purkinje cells in the white matter. They were located beneath the bases of the folia and their dendritic branches extended within the confines of the white matter without penetrating into the overlying cortical layers. The general morphology of these ectopic cells was variable, particularly in the extension and shape of the dendritic trees, but all of them exhibited a lower density of dendritic branches than normal Purkinje cells. The less-developed ectopic neurons had multipolar dendritic trees with nonplanar branches irregularly studded with spines. The well-developed ones displayed a more extensive arborization of their processes and they usually preserved some morphological features of normal cortical Purkinje cells: distal dendritic branches studded with numerous spines, a pear-shaped soma, clearly defined morphological polarity and a tendency to display planar arrangement of the dendritic arbors. In semithin sections these neurons also showed cytological features of normal Purkinje cells, such as the Nissl substance forming a nuclear cap oriented toward the dendritic pole. We suggest that the abnormal location of the neurons results from a disorder of Purkinje cell migration which occurs naturally during the prenatal development of the cerebellum. The possible morphogenetic mechanisms involved in the migration and differentiation of these ectopic neurons are also discussed.

Animals↗
PubMed1992

Salpingitis isthmica nodosa in infertility and ectopic pregnancy.

Excised tubal segments from 94 infertile women with tubal obstruction, with a mean infertility duration of 5.3 years, and 40 women with ectopic tubal pregnancy were studied histopathologically to evaluate the association with salpingitis isthmica nodosa (SIN). The mean age of the 94 infertile women with tubal obstruction was 24.5 years. Hysterosalpingographies and laparoscopy were performed on all of them. Only the women with ectopic pregnancies we performed salpingectomy on were included in the present study. The incidence of SIN in women with tubal obstruction was 7.4%, in women with ectopic tubal pregnancy 10%, and in the control group the incidence was 0.2%. In 60% of the cases, SIN was present in both of the tubes. Based on this study, we conclude that SIN is significantly associated with infertility and ectopic tubal pregnancy.

Adult↗
PubMed1976

The single ectopic ureter.

32 cases of single ectopic ureter have been reviewed. The more remote the ectopic orifice opens from its normal position the more severe were the associated renal anomalies. In the great majority of cases, the corresponding kidney was dysplastic and radiographically functionless. An embryological explanation is proposed to account for the association of single ectopic ureter with a dysplastic kidney. Clinical symptomatology was dribbling incontinence in most female cases and various urogenital complaints in male. An accurate preoperative diagnosis is usually reached with a pyelogram and micturating cystogram. In some female cases a vaginogram or direct puncture and opacification of a vaginal cystic mass may be contributive. In the male, a radiological non-functioning kidney on one side of the urogram associated with a cystic mass palpated above the prostate is pathognomonic of an ectopic ureter opening in the seminal tract. Deferentography may confirm this diagnosis. Treatment of the condition is surgical. In the great majority of cases nephroureterectomy is required. In the male, the abnormal seminal tract involved in this complex malformation should also be removed.

Cell Differentiation↗
PubMed2000

Pulmonary vein morphology in patients with paroxysmal atrial fibrillation initiated by ectopic beats originating from the pulmonary veins: implications for catheter ablation.

BACKGROUND: Successful ablation of ectopic beats originating from the pulmonary veins (PV) could eliminate paroxysmal atrial fibrillation (PAF). However, information about the structure of the PV in patients with PAF that is initiated by PV ectopic beats has not been reported. METHODS AND RESULTS: We studied the morphology of the PVs and measured their diameters in 3 groups of patients. Group I included 52 patients (aged 66+/-14 years; 44 men) with focal atrial fibrillation (AF) from the PVs. Group II included 8 patients (aged 50+/-10 years; 3 men) with focal AF from the superior vena cava or cristal terminalis. Group III included 23 control patients (aged 55+/-16 years; 17 men). Of the control patients, 11 had AV node and 12 had AV reentrant tachycardia. After an atrial transseptal procedure, selective PV angiography using a biplane system with a right anterior oblique view of 30 degrees, a left anterior oblique view of 60 degrees, and a cranial angle of 20 degrees was performed. The ostial and proximal portions of the right and left superior PVs (RSPV and LSPV) were significantly dilated in group I patients compared with those in groups II and III. Furthermore, the ostia of the RSPV and LSPV were significantly dilated in group II compared with group III patients. However, the mean diameters of the inferior PVs were similar between the 3 groups. Comparisons of the individual PV diameters among the 3 subgroups of group I (which was divided according to where the ectopic focus was located) showed nonselective dilatation of the PV. CONCLUSIONS: Nonspecific dilatation of the ostia and proximal portion of superior PVs were found in patients with PAF initiated by ectopic beats from the superior PVs.

Adult↗
PubMed1975

P waves during ectopic atrial rhythms in man: a study utilizing atrial pacing with fixed electrodes.

Threshold bipolar pacing was performed from one of 12 selected atrial sites with temporary implanted electrodes in 69 patients following open-heart surgery in order to study P wave polarity and morphology and the P-R interval during paced ectopic atrial rhythms. A negative P wave was recorded in lead I only with pacing the left atrium and only when pacing near the left pulmonary veins. A positive bifid P wave in V1 was recorded only with left atrial pacing and only when pacing was near the inferior pulmonary veins and coronary sinus. P wave polarity and morphology were otherwise of no use in localization of the origin of the impulse in these studies. The pacing stimulus to P wave interval was found to vary between 10 and 54 msec, making the duration of the P-R interval an unreliable indicator of the site of origin of the paced impulse. Although the relation of these paced rhythms to spontaneously occurring ectopic rhythms is unclear, the previously published criteria for localizing ectopic atrial rhythms are again demonstrated to be unreliable. P wave polarity and morphology and the P-R interval are of limited value in ascertaining the origin of ectopic atrial rhythms in man.

Adult↗