Seropositivity for the human heat shock protein (Hsp)60 accompanying seropositivity for Chlamydia trachomatis is less prevalent among tubal ectopic pregnancy cases than individuals with normal reproductive history.

PubMed

Ozyurek, Eser S; Karacan, Tolga; Ozdalgicoglu, Cenk; Yilmaz, Salih; Isik, Salman; San, Mevlide; Kaya, Erdal

2018-04-01

To investigate the role of anti-human heat shock protein 60 (hHsp60) antibody positivity in the pathogenesis of ectopic pregnancy, following Chlamydia trachomatis (CT) infection. In a case-control study, serological tests for anti-hHsp60 were performed in ectopic pregnancies (study group) and parturients with normal reproductive histories (control group). All participants in both groups were CT IgG(+). hHsp60 IgG(+) prevalences were compared between the two groups, by semiquantitative ELISA. Data were evaluated using nonparametric and parametric tests and multivariable regression. After an initial pilot study, two groups were formed: 63 ectopic gestations (study group) and 95 normal parturients (control group), all CT IgG(+). Blood samples from all cases were tested for anti-hHsp60 IgG. Age, gravidity, and practising contraception were higher in the control group, while a history of pelvic infections were more common in the study group. Hsp60 IgG(+) was found to be significantly higher in the control group (63/95, 66.3%) compared to study group (30/63, 47.6%). Regression analysis revealed anti-hHsp60 positivity was an independent factor delineating the two groups. Immunity to hHsp60 is less common in CT IgG(+) ectopic pregnancies than CT IgG(+) fertile subjects without a history of ectopic pregnancies. Hence, our findings suggest that hHsp60 seropositivity may decrease the probability of an ectopic gestation in subjects with previous CT infections. Copyright © 2018 Elsevier B.V. All rights reserved.

Role of MRI in the early diagnosis of tubal ectopic pregnancy.

PubMed

Si, Ming-Jue; Gui, Shuang; Fan, Qin; Han, Hong-Xiu; Zhao, Qian-Qian; Li, Zhi-Xin; Zhao, Jiang-Min

2016-07-01

To determine the role of MRI in the early diagnosis of tubal ectopic pregnancy (EP). Clinical and MRI features of 27 cases of tubal pregnancy were reviewed. A thick-walled gestational sac (GS)-like structure was demonstrated lateral to the uterus in all cases. On T2-weighted images, the thick wall typically exhibited 3 discrete rings in 22 cases (81 %), among which 17 cases (63 %) displayed small vessels and 6 cases (33 %) exhibited small areas of fresh haemorrhage inside the thick wall. The contents demonstrated non-specific liquid in 26 %, papillary solid components in 56 %, and fresh blood or fluid-fluid level in 19 % of the cases. Dilatation of the affected fallopian tube associated with hematosalpinx was demonstrated in 18 cases (67 %) and marked enhancement of the tubal wall was observed in 22 cases (81 %). No correlation was found between the size of the GS and the estimated gestational age (r = 0.056). MRI plays an important role in the early diagnosis and management of tubal pregnancy. The characteristic MRI features include a GS-like structure with a "three rings" appearance on T2-weighted images, presence of solid components in the sac, dilatation of the affected fallopian tube with hematosalpinx, and tubal wall enhancement. • MR imaging has served as a problem-solving procedure in ectopic pregnancy. • MR imaging features can be criteria for early diagnosis of tubal pregnancy. • Detailed assessment of ectopic implantation is necessary for management decision-making.

The NESH/Abi-3-based WAVE2 complex is functionally distinct from the Abi-1-based WAVE2 complex.

PubMed

Sekino, Saki; Kashiwagi, Yuriko; Kanazawa, Hitoshi; Takada, Kazuki; Baba, Takashi; Sato, Seiichi; Inoue, Hiroki; Kojima, Masaki; Tani, Katsuko

2015-10-01

Abl interactor (Abi) family proteins play significant roles in actin cytoskeleton organization through participation in the WAVE complex. Mammals possess three Abi proteins: Abi-1, Abi-2, and NESH/Abi-3. Abi-1 and Abi-2 were originally identified as Abl tyrosine kinase-binding proteins. It has been disclosed that Abi-1 acts as a bridge between c-Abl and WAVE2, and c-Abl-mediated WAVE2 phosphorylation promotes actin remodeling. We showed previously that NESH/Abi-3 is present in the WAVE2 complex, but neither binds to c-Abl nor promotes c-Abl-mediated phosphorylation of WAVE2. In this study, we characterized NESH/Abi-3 in more detail, and compared its properties with those of Abi-1 and Abi-2. NESH/Abi-3 was ectopically expressed in NIH3T3 cells, in which Abi-1, but not NESH/Abi-3, is expressed. The expression of NESH/Abi-3 caused degradation of endogenous Abi-1, which led to the formation of a NESH/Abi-3-based WAVE2 complex. When these cells were plated on fibronectin-coated dishes, the translocation of WAVE2 to the plasma membrane was significantly reduced and the formation of peripheral lamellipodial structures was disturbed, suggesting that the NESH/Abi-3-based WAVE2 complex was unable to help produce lamellipodial protrusions. Next, Abi-1, Abi-2, or NESH/Abi-3 was expressed in v-src-transformed NIH3T3 cells. Only in NESH/Abi-3-expressed cells did treatment with an Abl kinase inhibitor, imatinib mesylate, or siRNA-mediated knockdown of c-Abl promote the formation of invadopodia, which are ventral membrane protrusions with extracellular matrix degradation activity. Structural studies showed that a linker region between the proline-rich regions and the Src homology 3 (SH3) domain of Abi-1 is crucial for its interaction with c-Abl and c-Abl-mediated phosphorylation of WAVE2. The NESH/Abi-3-based WAVE2 complex is functionally distinct from the Abi-1-based one, and NESH/Abi-3 may be involved in the formation of ventral protrusions under certain conditions.

Indole-3-Butyric Acid Induces Ectopic Formation of Metaxylem in the Hypocotyl of Arabidopsis thaliana without Conversion into Indole-3-Acetic Acid and with a Positive Interaction with Ethylene.

PubMed

Fattorini, Laura; Della Rovere, Federica; Andreini, Eleonora; Ronzan, Marilena; Falasca, Giuseppina; Altamura, Maria Maddalena

2017-11-21

The role of the auxins indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) and of the auxin-interacting phytohormone ethylene, on the ectopic formation of primary xylem (xylogenesis in planta) is still little known. In particular, auxin/ethylene-target tissue(s), modality of the xylary process (trans-differentiation vs. de novo formation), and the kind of ectopic elements formed (metaxylem vs. protoxylem) are currently unknown. It is also unclear whether IBA may act on the process independently of conversion into IAA. To investigate these topics, histological analyses were carried out in the hypocotyls of Arabidopsis wild type seedlings and ech2ibr10 and ein3eil1 mutants, which are blocked in IBA-to-IAA conversion and ethylene signalling, respectively. The seedlings were grown under darkness with either IAA or IBA, combined or not with the ethylene precursor 1-aminocyclopropane-1-carboxylic acid. Adventitious root formation was also investigated because this process may compete with xylogenesis. Our results show that ectopic formation of protoxylem and metaxylem occurred as an indirect process starting from the pericycle periclinal derivatives of the hypocotyl basal part. IAA favoured protoxylem formation, whereas IBA induced ectopic metaxylem with ethylene cooperation through the EIN3EIL1 network. Ectopic metaxylem differentiation occurred independently of IBA-to-IAA conversion as mediated by ECH2 and IBR10, and in the place of IBA-induced adventitious root formation.

Potential link between excess added sugar intake and ectopic fat: a systematic review of randomized controlled trials

PubMed Central

Ma, Jiantao; Karlsen, Micaela C.; Chung, Mei; Jacques, Paul F.; Saltzman, Edward; Smith, Caren E.; Fox, Caroline S.

2016-01-01

Context: The effect of added sugar intake on ectopic fat accumulation is a subject of debate. Objective: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to examine the potential effect of added sugar intake on ectopic fat depots. Data Sources: MEDLINE, CAB Abstracts, CAB Global Health, and EBM (Evidence-Based Medicine) Reviews – Cochrane Central Register of Controlled Trials databases were searched for studies published from 1973 to September 2014. Data Extraction: RCTs with a minimum of 6 days’ duration of added sugar exposure in the intervention group were selected. The dosage of added sugar intake as a percentage of total energy was extracted or calculated. Means and standard deviations of pre- and post-test measurements or changes in ectopic fat depots were collected. Data Synthesis: Fourteen RCTs were included. Most of the studies had a medium to high risk of bias. Meta-analysis showed that, compared with eucaloric controls, subjects who consumed added sugar under hypercaloric conditions likely increased ectopic fat, particularly in the liver (pooled standardized mean difference = 0.9 [95%CI, 0.6–1.2], n = 6) and muscles (pooled SMD = 0.6 [95%CI, 0.2–1.0], n = 4). No significant difference was observed in liver fat, visceral adipose tissue, or muscle fat when isocaloric intakes of different sources of added sugars were compared. Conclusions: Data from a limited number of RCTs suggest that excess added sugar intake under hypercaloric diet conditions likely increases ectopic fat depots, particularly in the liver and in muscle fat. There are insufficient data to compare the effect of different sources of added sugars on ectopic fat deposition or to compare intake of added sugar with intakes of other macronutrients. Future well-designed RCTs with sufficient power and duration are needed to address the role of sugars on ectopic fat deposition. PMID:26518034

The Lin28/Let-7 System in Early Human Embryonic Tissue and Ectopic Pregnancy

PubMed Central

Steffani, Liliana; Martínez, Sebastián; Monterde, Mercedes; Ferri, Blanca; Núñez, Maria Jose; AinhoaRomero-Espinós; Zamora, Omar; Gurrea, Marta; Sangiao-Alvarellos, Susana; Vega, Olivia; Simón, Carlos; Pellicer, Antonio; Tena-Sempere, Manuel

2014-01-01

Our objective was to determine the expression of the elements of the Lin28/Let-7 system, and related microRNAs (miRNAs), in early stages of human placentation and ectopic pregnancy, as a means to assess the potential role of this molecular hub in the pathogenesis of ectopic gestation. Seventeen patients suffering from tubal ectopic pregnancy (cases) and forty-three women with normal on-going gestation that desired voluntary termination of pregnancy (VTOP; controls) were recruited for the study. Embryonic tissues were subjected to RNA extraction and quantitative PCR analyses for LIN28B, Let-7a, miR-132, miR-145 and mir-323-3p were performed. Our results demonstrate that the expression of LIN28B mRNA was barely detectable in embryonic tissue from early stages of gestation and sharply increased thereafter to plateau between gestational weeks 7–9. In contrast, expression levels of Let-7, mir-132 and mir-145 were high in embryonic tissue from early gestations (≤6-weeks) and abruptly declined thereafter, especially for Let-7. Opposite trends were detected for mir-323-3p. Embryonic expression of LIN28B mRNA was higher in early stages (≤6-weeks) of ectopic pregnancy than in normal gestation. In contrast, Let-7a expression was significantly lower in early ectopic pregnancies, while miR-132 and miR-145 levels were not altered. Expression of mir-323-3p was also suppressed in ectopic embryonic tissue. We are the first to document reciprocal changes in the expression profiles of the gene encoding the RNA-binding protein, LIN28B, and the related miRNAs, Let-7a, mir-132 and mir-145, in early stages of human placentation. This finding suggests the potential involvement of LIN28B/Let-7 (de)regulated pathways in the pathophysiology of ectopic pregnancy in humans. PMID:24498170

Ectopic third molars in the sigmoid notch: etiology, diagnostic imaging and treatment options.

PubMed

Hanisch, Marcel; Fröhlich, Leopold F; Kleinheinz, Johannes

2016-12-06

The etiology of ectopic third molars located in the sigmoid notch of the mandible is unclear. Only a few cases have been reported. The aim of this article is to discuss the etiology as well as treatment options and diagnostic imaging techniques. A PubMed and Medline search of the literature from 1965 to 2015 to ectopic third molars in the mandibular notch was performed. Furthermore, a clinical case provided by the authors is reported. Among the eight reviewed cases, two male and six female patients were affected that ranged from 25 to 62 years of age (mean 48.4). Pain and swelling in the preauricular region or trismus but also the absence of symptoms was reported. Only in two of the summarized articles an extra-oral access for the removal of the tooth was used. The etiology seems to be individually different, however dentigerous cysts and chronic inflammation seem to play an important role in their appearance. While previous diagnostic reports described two-dimensional diagnostic imaging, currently the three-dimensional imaging is common for preoperative surgical planning with respect to removing ectopic molars. Ectopic third molars in the mandible are a rare condition. The etiology seems to be individually different. Nowadays, three-dimensional imaging is common for preoperative surgical planning.

A Low-Cost Simulation Model for R-Wave Synchronized Atrial Pacing in Pediatric Patients with Postoperative Junctional Ectopic Tachycardia

PubMed Central

Michel, Miriam; Egender, Friedemann; Heßling, Vera; Dähnert, Ingo; Gebauer, Roman

2016-01-01

Background Postoperative junctional ectopic tachycardia (JET) occurs frequently after pediatric cardiac surgery. R-wave synchronized atrial (AVT) pacing is used to re-establish atrioventricular synchrony. AVT pacing is complex, with technical pitfalls. We sought to establish and to test a low-cost simulation model suitable for training and analysis in AVT pacing. Methods A simulation model was developed based on a JET simulator, a simulation doll, a cardiac monitor, and a pacemaker. A computer program simulated electrocardiograms. Ten experienced pediatric cardiologists tested the model. Their performance was analyzed using a testing protocol with 10 working steps. Results Four testers found the simulation model realistic; 6 found it very realistic. Nine claimed that the trial had improved their skills. All testers considered the model useful in teaching AVT pacing. The simulation test identified 5 working steps in which major mistakes in performance test may impede safe and effective AVT pacing and thus permitted specific training. The components of the model (exclusive monitor and pacemaker) cost less than $50. Assembly and training-session expenses were trivial. Conclusions A realistic, low-cost simulation model of AVT pacing is described. The model is suitable for teaching and analyzing AVT pacing technique. PMID:26943363

Carcinoma in ectopic breast: a cytological diagnosis.

PubMed

Shukla, Shailaja; Sehgal, Shivali; Rai, Preeti; Agarwal, Kiran

2015-01-01

Ectopic breast carcinoma in the axillary region is rare with an incidence ranging from 0.3-6%. We report a case of infiltrating duct carcinoma in an adult female arising in aberrant breast tissue in the axilla diagnosed on fine needle aspiration cytology. There was history of recent increase in size of the lump which was otherwise present for the past 5 years. This case highlights the role fine needle aspiration cytology can play in the early diagnosis of malignant transformation of lumps.

The rectourogenital connection in anorectal malformations is an ectopic anal canal.

PubMed

Rintala, R; Lindahl, H; Sariola, H; Rapola, J; Louhimo, I

1990-06-01

Histological investigation of the rectal blind pouch and rectourogenital or rectoperineal connection was performed in 10 patients with high or intermediate anorectal malformations. Nine of the patients underwent postoperative manometric evaluation. In nine of the 10 patients, transitional epithelium typical of the normal anal canal could be found in the distal rectum or rectal end of the fistulous connection. The zone of transitional epithelium was aganglionic and showed abnormally strong acetylcholinesterase reaction. A positive rectoanal inhibitory reflex was found manometrically in all cases in which the distal rectal pouch was utilized in the reconstruction of the anal canal. The slow pressure wave activity of the reconstructed anal canal was characteristic of a normal anal canal. The manometric evidence strongly suggests that there is a functional internal sphincter in high and intermediate anorectal malformations. The present study shows that in anorectal malformations the distal rectal pouch with the fistulous connection is actually an ectopic anal canal.

Is there still a role for reconstructive microsurgery in tubal infertility?

PubMed

Schippert, Cordula; Garcia-Rocha, Guillermo-José

2011-06-01

To review the current role of tubal reconstructive surgery in the era of assisted reproductive techniques (ARTs). After tubal reconstructive surgery, couples may have unlimited attempts to conceive naturally. Operative risks are low; the risk for ectopic pregnancy after surgery is 4-10%. ART is associated with a number of potential complications: severe ovarian hyperstimulation syndrome (0.25-2%), multiple pregnancies (up to 25%), a higher rate of major malformations and stillbirths, and ectopic pregnancy (1-13%). Birth rates following ART differ between 19 and 35%, depending on different laws governing the fertilization of a limited number of oocytes and the number of embryos transferred. Resterilization is a main indication for microsurgery with resulting pregnancy rates up to 84%. Salpingostomy and dense adhesiolysis have the lowest success rates (term pregnancy rates: 3-65%). Proximal tubal obstructions can be successfully treated by tubocornual anastomosis. Hydrosalpinges should be removed prior to in-vitro fertilization if they cannot be reconstructed. ART is recommended for patients older than 37-38 years, for women with severe tubal pathology, after repeated ectopic pregnancies, and in case of male infertility. Tubal reconstructive surgery still plays a role in infertility treatment. ART has not replaced microsurgery routinely as first-line treatment for tubal infertility.

The role of Sox6 in zebrafish muscle fiber type specification.

PubMed

Jackson, Harriet E; Ono, Yosuke; Wang, Xingang; Elworthy, Stone; Cunliffe, Vincent T; Ingham, Philip W

2015-01-01

The transcription factor Sox6 has been implicated in regulating muscle fiber type-specific gene expression in mammals. In zebrafish, loss of function of the transcription factor Prdm1a results in a slow to fast-twitch fiber type transformation presaged by ectopic expression of sox6 in slow-twitch progenitors. Morpholino-mediated Sox6 knockdown can suppress this transformation but causes ectopic expression of only one of three slow-twitch specific genes assayed. Here, we use gain and loss of function analysis to analyse further the role of Sox6 in zebrafish muscle fiber type specification. The GAL4 binary misexpression system was used to express Sox6 ectopically in zebrafish embryos. Cis-regulatory elements were characterized using transgenic fish. Zinc finger nuclease mediated targeted mutagenesis was used to analyse the effects of loss of Sox6 function in embryonic, larval and adult zebrafish. Zebrafish transgenic for the GCaMP3 Calcium reporter were used to assay Ca2+ transients in wild-type and mutant muscle fibres. Ectopic Sox6 expression is sufficient to downregulate slow-twitch specific gene expression in zebrafish embryos. Cis-regulatory elements upstream of the slow myosin heavy chain 1 (smyhc1) and slow troponin c (tnnc1b) genes contain putative Sox6 binding sites required for repression of the former but not the latter. Embryos homozygous for sox6 null alleles expressed tnnc1b throughout the fast-twitch muscle whereas other slow-specific muscle genes, including smyhc1, were expressed ectopically in only a subset of fast-twitch fibers. Ca2+ transients in sox6 mutant fast-twitch fibers were intermediate in their speed and amplitude between those of wild-type slow- and fast-twitch fibers. sox6 homozygotes survived to adulthood and exhibited continued misexpression of tnnc1b as well as smaller slow-twitch fibers. They also exhibited a striking curvature of the spine. The Sox6 transcription factor is a key regulator of fast-twitch muscle fiber differentiation in the zebrafish, a role similar to that ascribed to its murine ortholog.

Aquaporin 5 Plays a Role in Estrogen-Induced Ectopic Implantation of Endometrial Stromal Cells in Endometriosis

PubMed Central

Jiang, Xiu Xiu; Fei, Xiang Wei; Zhao, Li; Ye, Xiao Lei; Xin, Liao Bin; Qu, Yang; Xu, Kai Hong; Wu, Rui Jin; Lin, Jun

2015-01-01

Aquaporin 5 (AQP5) participates in the migration of endometrial cells. Elucidation of the molecular mechanisms associated with AQP5-mediated, migration of endometrial cells may contribute to a better understanding of endometriosis. Our objectives included identifying the estrogen-response element (ERE) in the promoter region of the AQP5 gene, and, investigating the effects of AQP5 on ectopic implantation of endometrial cells. Luciferase reporter assays and electrophoretic mobility shift assay (EMSA) identified the ERE-like motif in the promoter region of the AQP5 gene. After blocking and up-regulating estradiol (E2) levels, we analysed the expression of AQP5 in endometrial stromal (ES) cells. After blocking E2 /or phosphatidylinositol 3 kinase(PI3K), we analysed the role of AQP5 in signaling pathways. We constructed an AQP5, shRNA, lentiviral vector to knock out the AQP5 gene in ES cells. After knock-out of the AQP5 gene, we studied the role of AQP5 in cell invasion, proliferation, and the formation of ectopic endometrial implants in female mice. We identified an estrogen-response element in the promoter region of the AQP5 gene. Estradiol (E2) increased AQP5 expression in a dose-dependent fashion, that was blocked by ICI182,780(an estrogen receptor inhibitor). E2 activated PI3K /protein kinase B(AKT) pathway (PI3K/AKT), that, in turn, increased AQP5 expression. LY294002(PI3K inhibitor) attenuated estrogen-enhanced, AQP5 expression. Knock-out of the AQP5 gene with AQP5 shRNA lentiviral vector significantly inhibited E2-enhanced invasion, proliferation of ES cells and formation of ectopic implants. Estrogen induces AQP5 expression by activating ERE in the promoter region of the AQP5gene, activates the PI3K/AKT pathway, and, promotes endometrial cell invasion and proliferation. These results provide new insights into some of the mechanisms that may underpin the development of deposits of ectopic endometrium. PMID:26679484

Ectopic expression of H2AX protein promotes TrkA-induced cell death via modulation of TrkA tyrosine-490 phosphorylation and JNK activity upon DNA damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jung, Eun Joo; Kim, Deok Ryong, E-mail: drkim@gnu.ac.kr

2011-01-21

Research highlights: {yields} We established TrkA-inducible U2OS cells stably expressing GFP-H2AX proteins. {yields} GFP-H2AX was colocalized with TrkA in the cytoplasm. {yields} {gamma}H2AX production was significantly increased upon activation of TrkA and suppressed by TrkA inhibitor or JNK inhibitor. {yields} Ectopic expression of H2AX promoted TrkA-mediated cell death through the modulation of TrkA tyrosine-490 phosphorylation and JNK activity upon DNA damage. -- Abstract: We previously reported that TrkA overexpression causes accumulation of {gamma}H2AX proteins in the cytoplasm, subsequently leading to massive cell death in U2OS cells. To further investigate how cytoplasmic H2AX is associated with TrkA-induced cell death, we establishedmore » TrkA-inducible cells stably expressing GFP-tagged H2AX. We found that TrkA co-localizes with ectopically expressed GFP-H2AX proteins in the cytoplasm, especially at the juxta-nuclear membranes, which supports our previous results about a functional connection between TrkA and {gamma}H2AX in TrkA-induced cell death. {gamma}H2AX production from GFP-H2AX proteins was significantly increased when TrkA was overexpressed. Moreover, ectopic expression of H2AX activated TrkA-mediated signal pathways via up-regulation of TrkA tyrosine-490 phosphorylation. In addition, suppression of TrkA tyrosine-490 phosphorylation under a certain condition was removed by ectopic expression of H2AX, indicating a functional role of H2AX in the maintenance of TrkA activity. Indeed, TrkA-induced cell death was highly elevated by ectopic H2AX expression, and it was further accelerated by DNA damage via JNK activation. These all results suggest that cytoplasmic H2AX could play an important role in TrkA-mediated cell death by modulating TrkA upon DNA damage.« less

MAPK Target Sites of Eyes Absent Are Not Required for Eye Development or Survival in Drosophila

PubMed Central

Jusiak, Barbara; Abulimiti, Abuduaini; Haelterman, Nele; Chen, Rui; Mardon, Graeme

2012-01-01

Eyes absent (Eya) is a highly conserved transcription cofactor and protein phosphatase that plays an essential role in eye development and survival in Drosophila. Ectopic eye induction assays using cDNA transgenes have suggested that mitogen activated protein kinase (MAPK) activates Eya by phosphorylating it on two consensus target sites, S402 and S407, and that this activation potentiates the ability of Eya to drive eye formation. However, this mechanism has never been tested in normal eye development. In the current study, we generated a series of genomic rescue transgenes to investigate how loss- and gain-of-function mutations at these two MAPK target sites within Eya affect Drosophila survival and normal eye formation: eya+GR, the wild-type control; eyaSAGR, which lacks phosphorylation at the two target residues; and eyaSDEGR, which contains phosphomimetic amino acids at the same two residues. Contrary to the previous studies in ectopic eye development, all eya genomic transgenes tested rescue both eye formation and survival equally effectively. We conclude that, in contrast to ectopic eye formation, MAPK-mediated phosphorylation of Eya on S402 and S407 does not play a role in normal development. This is the first study in Drosophila to evaluate the difference in outcomes between genomic rescue and ectopic cDNA-based overexpression of the same gene. These findings indicate similar genomic rescue strategies may prove useful for re-evaluating other long-standing Drosophila developmental models. PMID:23251383

A cardiomyocyte-specific Wdr1 knockout demonstrates essential functional roles for actin disassembly during myocardial growth and maintenance in mice.

PubMed

Yuan, Baiyin; Wan, Ping; Chu, Dandan; Nie, Junwei; Cao, Yunshan; Luo, Wen; Lu, Shuangshuang; Chen, Jiong; Yang, Zhongzhou

2014-07-01

Actin dynamics are critical for muscle development and function, and mutations leading to deregulation of actin dynamics cause various forms of heritable muscle diseases. AIP1 is a major cofactor of the actin depolymerizing factor/cofilin in eukaryotes, promoting actin depolymerizing factor/cofilin-mediated actin disassembly. Its function in vertebrate muscle has been unknown. To investigate functional roles of AIP1 in myocardium, we generated conditional knockout (cKO) mice with cardiomyocyte-specific deletion of Wdr1, the mammalian homolog of yeast AIP1. Wdr1 cKO mice began to die at postnatal day 13 (P13), and none survived past P24. At P12, cKO mice exhibited cardiac hypertrophy and impaired contraction of the left ventricle. Electrocardiography revealed reduced heart rate, abnormal P wave, and abnormal T wave at P10 and prolonged QT interval at P12. Actin filament (F-actin) accumulations began at P10 and became prominent at P12 in the myocardium of cKO mice. Within regions of F-actin accumulation in myofibrils, the sarcomeric components α-actinin and tropomodulin-1 exhibited disrupted patterns, indicating that F-actin accumulations caused by Wdr1 deletion result in disruption of sarcomeric structure. Ectopic cofilin colocalized with F-actin aggregates. In adult mice, Wdr1 deletion resulted in similar but much milder phenotypes of heart hypertrophy, F-actin accumulations within myofibrils, and lethality. Taken together, these results demonstrate that AIP1-regulated actin dynamics play essential roles in heart function in mice. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Potential link between excess added sugar intake and ectopic fat: a systematic review of randomized controlled trials.

PubMed

Ma, Jiantao; Karlsen, Micaela C; Chung, Mei; Jacques, Paul F; Saltzman, Edward; Smith, Caren E; Fox, Caroline S; McKeown, Nicola M

2016-01-01

The effect of added sugar intake on ectopic fat accumulation is a subject of debate. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to examine the potential effect of added sugar intake on ectopic fat depots. MEDLINE, CAB Abstracts, CAB Global Health, and EBM (Evidence-Based Medicine) Reviews - Cochrane Central Register of Controlled Trials databases were searched for studies published from 1973 to September 2014. RCTs with a minimum of 6 days' duration of added sugar exposure in the intervention group were selected. The dosage of added sugar intake as a percentage of total energy was extracted or calculated. Means and standard deviations of pre- and post-test measurements or changes in ectopic fat depots were collected. Fourteen RCTs were included. Most of the studies had a medium to high risk of bias. Meta-analysis showed that, compared with eucaloric controls, subjects who consumed added sugar under hypercaloric conditions likely increased ectopic fat, particularly in the liver (pooled standardized mean difference = 0.9 [95%CI, 0.6-1.2], n = 6) and muscles (pooled SMD = 0.6 [95%CI, 0.2-1.0], n = 4). No significant difference was observed in liver fat, visceral adipose tissue, or muscle fat when isocaloric intakes of different sources of added sugars were compared. Data from a limited number of RCTs suggest that excess added sugar intake under hypercaloric diet conditions likely increases ectopic fat depots, particularly in the liver and in muscle fat. There are insufficient data to compare the effect of different sources of added sugars on ectopic fat deposition or to compare intake of added sugar with intakes of other macronutrients. Future well-designed RCTs with sufficient power and duration are needed to address the role of sugars on ectopic fat deposition. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[Expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in human and nude mouse ectopic endometrium and the effect of estrogen and progestin on their expression].

PubMed

Lou, Yan-hui; Guo, Xin-hua; Jiang, Hua; Xia, Yu-fang

2010-04-01

To explore the roles of matrix metalloproteinase-1(MMP-1) and tissue inhibitor of metalloproteinase-1(TIMP-1) in the pathogenesis of endometriosis and the effects of estrogen and progestin on their expression. Immunohistochemistry and RT-PCR were employed to detect the expression of MMP-1 and TIMP-1 in the ectopic tissues of 35 patients with endometriosis, 22 eutopic endometrium tissues from women with endometriosis and 28 normal controls. Fifty-nine nude mice were injected with human late secretory endometrial chippings and randomized into estrogen group, progestin group, estrogen-progestin group and control group with corresponding treatments. The implantation rates and graft morphology were observed and MMP-1 and TIMP-1 expressions in the grafts detected by immunohistochemistry. Typical endometrial glands and stroma were observed in all the groups with comparable implantation rates. The administration of progestin was associated with multiple peritoneal implantation sites and significantly larger implants. The transplanted endometria showed proliferative or secretory changes with estrogen or progestin administration. MMP-1 expression significantly increased and TIMP-1 expression decreased with increased MMP-1/TIMP-1 ratio in human and nude mouse ectopic endometria in comparison with those in normal endometria (P<0.05, P<0.01). MMP-1 expression was higher in estrogen and estrogen-progestin groups than in the control group, and was lower in the 3 sexual hormone-treated groups than in the control group. MMP-1 mRNA expression in the eutopic endometrium was significantly higher than that in the normal endometria. Progestrin can not inhibit MMP-1 expression or the effect of estrogen on ectopic endometrium known as progestin resistance. The high expression of MMP-1 and low expression of TIMP-1 in endometriotic tissues confer strong invasiveness of ectopic endometrial tissue, especially in eutopic endometrial tissue, and may play an important role in the pathogenesis of endometriosis.

Ovum transmigration after salpingectomy for ectopic pregnancy.

PubMed

Ross, Jackie A; Davison, Amelia Z; Sana, Yasmin; Appiah, Adjoa; Johns, Jemma; Lee, Christopher T

2013-04-01

What proportion of pregnancies are a result of ovum transmigration after salpingectomy for ectopic pregnancy? Approximately one-third of spontaneously conceived pregnancies are a result of pick-up of the ovum from the ovary contralateral to the remaining tube in women with a history of salpingectomy. The corpus luteum has been found contralateral to tubal ectopic pregnancies in 32% of reported cases. The rate of contralateral ovum pick-up in intrauterine pregnancies is not known. We conducted a retrospective cohort study of clinical and ultrasound records collected over a 12-year period 1999-2010. Ten per cent of cases identified were excluded from the final analysis due to incomplete data or bilateral corpora lutea. Included were 842 pregnancies in 707 women with a history of unilateral salpingectomy for ectopic pregnancy and subsequent spontaneous pregnancy. The study was set in the Early Pregnancy Unit of a large UK inner city teaching hospital. The outcome measure was the side of the corpus luteum in relation to the side of the remaining tube. The corpus luteum was located in the ovary contralateral to the remaining tube in 266/842 pregnancies (31.6%; 95% CI 28.5-34.8%). There was no significant difference in this proportion between intrauterine and ectopic pregnancies [246/769 (32.0%) versus 21/73 (28.8%), P = 0.60]. This was a retrospective study and so did not address the conception rate according to the laterality of ovulation. Our findings were very similar to the frequency of ectopic pregnancies found contralateral to the corpus luteum described in previous studies. Ovum pick-up from the cul-de-sac probably occurs reasonably frequently and is unlikely to have a causative role in the pathogenesis of ectopic pregnancy. It is not known how often this phenomenon occurs in women with intact Fallopian tubes. No specific funding was obtained. The authors have no conflicts of interest to declare.

STAT, Wingless, and Nurf-38 determine the accuracy of regeneration after radiation damage in Drosophila.

PubMed

Verghese, Shilpi; Su, Tin Tin

2017-10-01

We report here a study of regeneration in Drosophila larval wing imaginal discs after damage by ionizing radiation. We detected faithful regeneration that restored a wing disc and abnormal regeneration that produced an extra wing disc. We describe a sequence of changes in cell number, location and fate that occur to produce an ectopic disc. We identified a group of cells that not only participate in ectopic disc formation but also recruit others to do so. STAT92E (Drosophila STAT3/5) and Nurf-38, which encodes a member of the Nucleosome Remodeling Factor complex, oppose each other in these cells to modulate the frequency of ectopic disc growth. The picture that emerges is one in which activities like STAT increase after radiation damage and fulfill essential roles in rebuilding the tissue. But such activities must be kept in check so that one and only one wing disc is regenerated.

The bHLH Repressor Deadpan Regulates the Self-renewal and Specification of Drosophila Larval Neural Stem Cells Independently of Notch

PubMed Central

Younger, Susan; Huang, Yaling; Lee, Tzumin

2012-01-01

Neural stem cells (NSCs) are able to self-renew while giving rise to neurons and glia that comprise a functional nervous system. However, how NSC self-renewal is maintained is not well understood. Using the Drosophila larval NSCs called neuroblasts (NBs) as a model, we demonstrate that the Hairy and Enhancer-of-Split (Hes) family protein Deadpan (Dpn) plays important roles in NB self-renewal and specification. The loss of Dpn leads to the premature loss of NBs and truncated NB lineages, a process likely mediated by the homeobox protein Prospero (Pros). Conversely, ectopic/over-expression of Dpn promotes ectopic self-renewing divisions and maintains NB self-renewal into adulthood. In type II NBs, which generate transit amplifying intermediate neural progenitors (INPs) like mammalian NSCs, the loss of Dpn results in ectopic expression of type I NB markers Asense (Ase) and Pros before these type II NBs are lost at early larval stages. Our results also show that knockdown of Notch leads to ectopic Ase expression in type II NBs and the premature loss of type II NBs. Significantly, dpn expression is unchanged in these transformed NBs. Furthermore, the loss of Dpn does not inhibit the over-proliferation of type II NBs and immature INPs caused by over-expression of activated Notch. Our data suggest that Dpn plays important roles in maintaining NB self-renewal and specification of type II NBs in larval brains and that Dpn and Notch function independently in regulating type II NB proliferation and specification. PMID:23056424

Ectopic Kidney

MedlinePlus

... Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Ectopic Kidney What is an ectopic kidney? An ectopic kidney is a birth defect in ... has an ectopic kidney. 1 What are the kidneys and what do they do? The kidneys are ...

Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation.

PubMed

Chu, Audrey Y; Deng, Xuan; Fisher, Virginia A; Drong, Alexander; Zhang, Yang; Feitosa, Mary F; Liu, Ching-Ti; Weeks, Olivia; Choh, Audrey C; Duan, Qing; Dyer, Thomas D; Eicher, John D; Guo, Xiuqing; Heard-Costa, Nancy L; Kacprowski, Tim; Kent, Jack W; Lange, Leslie A; Liu, Xinggang; Lohman, Kurt; Lu, Lingyi; Mahajan, Anubha; O'Connell, Jeffrey R; Parihar, Ankita; Peralta, Juan M; Smith, Albert V; Zhang, Yi; Homuth, Georg; Kissebah, Ahmed H; Kullberg, Joel; Laqua, René; Launer, Lenore J; Nauck, Matthias; Olivier, Michael; Peyser, Patricia A; Terry, James G; Wojczynski, Mary K; Yao, Jie; Bielak, Lawrence F; Blangero, John; Borecki, Ingrid B; Bowden, Donald W; Carr, John Jeffrey; Czerwinski, Stefan A; Ding, Jingzhong; Friedrich, Nele; Gudnason, Vilmunder; Harris, Tamara B; Ingelsson, Erik; Johnson, Andrew D; Kardia, Sharon L R; Langefeld, Carl D; Lind, Lars; Liu, Yongmei; Mitchell, Braxton D; Morris, Andrew P; Mosley, Thomas H; Rotter, Jerome I; Shuldiner, Alan R; Towne, Bradford; Völzke, Henry; Wallaschofski, Henri; Wilson, James G; Allison, Matthew; Lindgren, Cecilia M; Goessling, Wolfram; Cupples, L Adrienne; Steinhauser, Matthew L; Fox, Caroline S

2017-01-01

Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P < 5 × 10 -8 ; false discovery rate < 1%). Functional analysis of these genes showed that loss of function of either Atxn1 or Ube2e2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting physiological roles for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes affect adipocyte biology and how their perturbations contribute to systemic metabolic disease.

Percutaneous nephrolithotomy in ectopically located kidneys and in patients with musculoskeletal deformities.

PubMed

Srivastava, A; Gupta, P; Chaturvedi, S; Singh, P; Kapoor, R; Dubey, D; Kumar, A

2010-01-01

To assess the feasibility, safety and results of percutaneous nephrolithotomy (PNL) in ectopically located kidneys and in patients with musculoskeletal deformities. Thirteen such patients underwent PNL between June 2005 and May 2008. Mean stone size was 27.4 mm (16-37 mm). Six patients had severe kyphoscoliosis, 2 patients each had achondroplasia, cross-fused ectopia and pelvic ectopic kidney, and 1 patient had thoracic kidney. All had a preoperative CT scan of the abdomen. Preoperative ultrasound- or CT-guided percutaneous nephrostomy (PCN) was done in 10 patients. Three patients underwent laparoscopic-assisted PNL. All underwent standard PNL. The stone-free rate, complication rate and need for secondary intervention were evaluated. PNL was successfully completed in all. A second ultrasound-guided intraoperative puncture was required in 2 patients. Re-look PNL was required in 1 patient and the same patient later required shock wave lithotripsy for complete stone clearance. The remaining 12 patients (92.3%) were rendered stone-free in a single sitting. PNL is a feasible and effective modality in anomalous kidneys. Preoperative planning with CT and image-guided PCN is helpful in these situations. Laparoscopic-assisted PNL can be safely performed in patients where access to a renal collecting system by fluoroscopy or image-guided assistance (ultrasound or CT scan) is not possible. Copyright (c) 2010 S. Karger AG, Basel.

Ectopic osteogenesis and angiogenesis regulated by porous architecture of hydroxyapatite scaffolds with similar interconnecting structure in vivo

PubMed Central

Li, Jinyu; Zhi, Wei; Xu, Taotao; Shi, Feng; Duan, Ke; Wang, Jianxin; Mu, Yandong; Weng, Jie

2016-01-01

The macro-pore sizes of porous scaffold play a key role for regulating ectopic osteogenesis and angiogenesis but many researches ignored the influence of interconnection between macro-pores with different sizes. In order to accurately reveal the relationship between ectopic osteogenesis and macro-pore sizes in dorsal muscle and abdominal cavities of dogs, hydroxyapatite (HA) scaffolds with three different macro-pore sizes of 500–650, 750–900 and 1100–1250 µm were prepared via sugar spheres-leaching process, which also had similar interconnecting structure determined by keeping the d/s ratio of interconnecting window diameter to macro-pore size constant. The permeability test showed that the seepage flow of fluid through the porous scaffolds increased with the increase of macro-pore sizes. The cell growth in three scaffolds was not affected by the macro-pore sizes. The in vivo ectopic implantation results indicated that the macro-pore sizes of HA scaffolds with the similar interconnecting structure have impact not only the speed of osteogenesis and angiogenesis but also the space distribution of newly formed bone. The scaffold with macro-pore sizes of 750–900 µm exhibited much faster angiogenesis and osteogenesis, and much more uniformly distribution of new bone than those with other macro-pore sizes. This work illustrates the importance of a suitable macro-pore sizes in HA scaffolds with the similar interconnecting structure which provides the environment for ectopic osteogenesis and angiogenesis. PMID:27699059

Induction of Pancreatic Differentiation by Signals from Blood Vessels

NASA Astrophysics Data System (ADS)

Lammert, Eckhard; Cleaver, Ondine; Melton, Douglas

2001-10-01

Blood vessels supply developing organs with metabolic sustenance. Here, we demonstrate a role for blood vessels as a source of developmental signals during pancreatic organogenesis. In vitro experiments with embryonic mouse tissues demonstrate that blood vessel endothelium induces insulin expression in isolated endoderm. Removal of the dorsal aorta in Xenopus laevis embryos results in the failure of insulin expression in vivo. Furthermore, using transgenic mice, we show that ectopic vascularization in the posterior foregut leads to ectopic insulin expression and islet hyperplasia. These results indicate that vessels not only provide metabolic sustenance, but also provide inductive signals for organ development.

Rac-WAVE2 signaling is involved in the invasive and metastatic phenotypes of murine melanoma cells.

PubMed

Kurisu, Shusaku; Suetsugu, Shiro; Yamazaki, Daisuke; Yamaguchi, Hideki; Takenawa, Tadaomi

2005-02-17

WAVEs (WASP-family verprolin-homologous proteins) regulate the actin cytoskeleton through activation of Arp2/3 complex. As cell motility is regulated by actin cytoskeleton rearrangement and is required for tumor invasion and metastasis, blocking actin polymerization may be an effective strategy to prevent tumor dissemination. We show that WAVEs, especially WAVE2, are essential for invasion and metastasis of melanoma cells. Malignant B16F10 mouse melanoma cells expressed more WAVE1 and WAVE2 proteins and showed higher Rac activity than B16 parental cells, which are neither invasive nor metastatic. The effect of WAVE2 silencing by RNA interference (RNAi) on the highly invasive nature of B16F10 cells was more dramatic than that of WAVE1 RNAi. Membrane ruffling, cell motility, invasion into the extracellular matrix, and pulmonary metastasis of B16F10 cells were suppressed by WAVE2 RNAi. WAVE2 RNAi also had a profound effect on invasion induced by a constitutively active form of Rac (RacCA). In addition, ectopic expression of both RacCA and WAVE2 in B16 cells resulted in further increase in the invasiveness than that observed in B16 cells expressing only RacCA. Thus, WAVE2 acts as the primary effector downstream of Rac to achieve invasion and metastasis, suggesting that suppression of WAVE2 activity holds a promise for preventing cancer invasion and metastasis.

Ectopic Pregnancy

MedlinePlus

... Safe Videos for Educators Search English Español Ectopic Pregnancy KidsHealth / For Parents / Ectopic Pregnancy What's in this ... loss) lower back pain What Causes an Ectopic Pregnancy? An ectopic pregnancy usually happens because a fertilized ...

Apoptosis-Inducing-Factor-Dependent Mitochondrial Function Is Required for T Cell but Not B Cell Function.

PubMed

Milasta, Sandra; Dillon, Christopher P; Sturm, Oliver E; Verbist, Katherine C; Brewer, Taylor L; Quarato, Giovanni; Brown, Scott A; Frase, Sharon; Janke, Laura J; Perry, S Scott; Thomas, Paul G; Green, Douglas R

2016-01-19

The role of apoptosis inducing factor (AIF) in promoting cell death versus survival remains controversial. We report that the loss of AIF in fibroblasts led to mitochondrial electron transport chain defects and loss of proliferation that could be restored by ectopic expression of the yeast NADH dehydrogenase Ndi1. Aif-deficiency in T cells led to decreased peripheral T cell numbers and defective homeostatic proliferation, but thymic T cell development was unaffected. In contrast, Aif-deficient B cells developed and functioned normally. The difference in the dependency of T cells versus B cells on AIF for function and survival correlated with their metabolic requirements. Ectopic Ndi1 expression rescued homeostatic proliferation of Aif-deficient T cells. Despite its reported roles in cell death, fibroblasts, thymocytes and B cells lacking AIF underwent normal death. These studies suggest that the primary role of AIF relates to complex I function, with differential effects on T and B cells. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of Sema3–Npn-1 signaling during diaphragm innervation and muscle development

PubMed Central

Huettl, Rosa-Eva; Hanuschick, Philipp; Amend, Anna-Lena; Alberton, Paolo; Aszodi, Attila; Huber, Andrea B.

2016-01-01

ABSTRACT Correct innervation of the main respiratory muscle in mammals, namely the thoracic diaphragm, is a crucial pre-requisite for the functionality of this muscle and the viability of the entire organism. Systemic impairment of Sema3A–Npn-1 (Npn-1 is also known as NRP1) signaling causes excessive branching of phrenic nerves in the diaphragm and into the central tendon region, where the majority of misguided axons innervate ectopic musculature. To elucidate whether these ectopic muscles are a result of misguidance of myoblast precursors due to the loss of Sema3A–Npn-1 signaling, we conditionally ablated Npn-1 in somatic motor neurons, which led to a similar phenotype of phrenic nerve defasciculation and, intriguingly, also formation of innervated ectopic muscles. We therefore hypothesize that ectopic myocyte fusion is caused by additional factors released by misprojecting growth cones. Slit2 and its Robo receptors are expressed by phrenic motor axons and migrating myoblasts, respectively, during innervation of the diaphragm. In vitro analyses revealed a chemoattractant effect of Slit2 on primary diaphragm myoblasts. Thus, we postulate that factors released by motor neuron growth cones have an influence on the migration properties of myoblasts during establishment of the diaphragm. PMID:27466379

Short Vegetative Phase-Like MADS-Box Genes Inhibit Floral Meristem Identity in Barley1[W][OA

PubMed Central

Trevaskis, Ben; Tadege, Million; Hemming, Megan N.; Peacock, W. James; Dennis, Elizabeth S.; Sheldon, Candice

2007-01-01

Analysis of the functions of Short Vegetative Phase (SVP)-like MADS-box genes in barley (Hordeum vulgare) indicated a role in determining meristem identity. Three SVP-like genes are expressed in vegetative tissues of barley: Barley MADS1 (BM1), BM10, and Vegetative to Reproductive Transition gene 2. These genes are induced by cold but are repressed during floral development. Ectopic expression of BM1 inhibited spike development and caused floral reversion in barley, with florets at the base of the spike replaced by tillers. Head emergence was delayed in plants that ectopically express BM1, primarily by delayed development after the floral transition, but expression levels of the barley VRN1 gene (HvVRN1) were not affected. Ectopic expression of BM10 inhibited spike development and caused partial floral reversion, where florets at the base of the spike were replaced by inflorescence-like structures, but did not affect heading date. Floral reversion occurred more frequently when BM1 and BM10 ectopic expression lines were grown in short-day conditions. BM1 and BM10 also inhibited floral development and caused floral reversion when expressed in Arabidopsis (Arabidopsis thaliana). We conclude that SVP-like genes function to suppress floral meristem identity in winter cereals. PMID:17114273

Distal-less induces elemental color patterns in Junonia butterfly wings.

PubMed

Dhungel, Bidur; Ohno, Yoshikazu; Matayoshi, Rie; Iwasaki, Mayo; Taira, Wataru; Adhikari, Kiran; Gurung, Raj; Otaki, Joji M

2016-01-01

The border ocellus, or eyespot, is a conspicuous color pattern element in butterfly wings. For two decades, it has been hypothesized that transcription factors such as Distal-less (Dll) are responsible for eyespot pattern development in butterfly wings, based on their expression in the prospective eyespots. In particular, it has been suggested that Dll is a determinant for eyespot size. However, functional evidence for this hypothesis has remained incomplete, due to technical difficulties. Here, we show that ectopically expressed Dll induces ectopic elemental color patterns in the adult wings of the blue pansy butterfly, Junonia orithya (Lepidoptera, Nymphalidae). Using baculovirus-mediated gene transfer, we misexpressed Dll protein fused with green fluorescent protein (GFP) in pupal wings, resulting in ectopic color patterns, but not the formation of intact eyespots. Induced changes included clusters of black and orange scales (a basic feature of eyespot patterns), black and gray scales, and inhibition of cover scale development. In contrast, ectopic expression of GFP alone did not induce any color pattern changes using the same baculovirus-mediated gene transfer system. These results suggest that Dll plays an instructive role in the development of color pattern elements in butterfly wings, although Dll alone may not be sufficient to induce a complete eyespot. This study thus experimentally supports the hypothesis of Dll function in eyespot development.

A small amount of dietary carbohydrate can promote the HFD-induced insulin resistance to a maximal level.

PubMed

Mei, Shuang; Yang, Xuefeng; Guo, Huailan; Gu, Haihua; Zha, Longying; Cai, Junwei; Li, Xuefeng; Liu, Zhenqi; Bennett, Brian J; He, Ling; Cao, Wenhong

2014-01-01

Both dietary fat and carbohydrates (Carbs) may play important roles in the development of insulin resistance. The main goal of this study was to further define the roles for fat and dietary carbs in insulin resistance. C57BL/6 mice were fed normal chow diet (CD) or HFD containing 0.1-25.5% carbs for 5 weeks, followed by evaluations of calorie consumption, body weight and fat gains, insulin sensitivity, intratissue insulin signaling, ectopic fat, and oxidative stress in liver and skeletal muscle. The role of hepatic gluconeogenesis in the HFD-induced insulin resistance was determined in mice. The role of fat in insulin resistance was also examined in cultured cells. HFD with little carbs (0.1%) induced severe insulin resistance. Addition of 5% carbs to HFD dramatically elevated insulin resistance and 10% carbs in HFD was sufficient to induce a maximal level of insulin resistance. HFD with little carbs induced ectopic fat accumulation and oxidative stress in liver and skeletal muscle and addition of carbs to HFD dramatically enhanced ectopic fat and oxidative stress. HFD increased hepatic expression of key gluconeogenic genes and the increase was most dramatic by HFD with little carbs, and inhibition of hepatic gluconeogenesis prevented the HFD-induced insulin resistance. In cultured cells, development of insulin resistance induced by a pathological level of insulin was prevented in the absence of fat. Together, fat is essential for development of insulin resistance and dietary carb is not necessary for HFD-induced insulin resistance due to the presence of hepatic gluconeogenesis but a very small amount of it can promote HFD-induced insulin resistance to a maximal level.

A Small Amount of Dietary Carbohydrate Can Promote the HFD-Induced Insulin Resistance to a Maximal Level

PubMed Central

Guo, Huailan; Gu, Haihua; Zha, Longying; Cai, Junwei; Li, Xuefeng; Liu, Zhenqi; Bennett, Brian J.; He, Ling; Cao, Wenhong

2014-01-01

Both dietary fat and carbohydrates (Carbs) may play important roles in the development of insulin resistance. The main goal of this study was to further define the roles for fat and dietary carbs in insulin resistance. C57BL/6 mice were fed normal chow diet (CD) or HFD containing 0.1–25.5% carbs for 5 weeks, followed by evaluations of calorie consumption, body weight and fat gains, insulin sensitivity, intratissue insulin signaling, ectopic fat, and oxidative stress in liver and skeletal muscle. The role of hepatic gluconeogenesis in the HFD-induced insulin resistance was determined in mice. The role of fat in insulin resistance was also examined in cultured cells. HFD with little carbs (0.1%) induced severe insulin resistance. Addition of 5% carbs to HFD dramatically elevated insulin resistance and 10% carbs in HFD was sufficient to induce a maximal level of insulin resistance. HFD with little carbs induced ectopic fat accumulation and oxidative stress in liver and skeletal muscle and addition of carbs to HFD dramatically enhanced ectopic fat and oxidative stress. HFD increased hepatic expression of key gluconeogenic genes and the increase was most dramatic by HFD with little carbs, and inhibition of hepatic gluconeogenesis prevented the HFD-induced insulin resistance. In cultured cells, development of insulin resistance induced by a pathological level of insulin was prevented in the absence of fat. Together, fat is essential for development of insulin resistance and dietary carb is not necessary for HFD-induced insulin resistance due to the presence of hepatic gluconeogenesis but a very small amount of it can promote HFD-induced insulin resistance to a maximal level. PMID:25055153

The critical role of myostatin in differentiation of sheep myoblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Chenxi; Xinjiang Laboratory of Animal Biotechnology, Urumqi; Li, Wenrong

Highlights: Black-Right-Pointing-Pointer Identification of the effective and specific shRNA to knockdown MSTN. Black-Right-Pointing-Pointer Overexpression of MSTN reversibly suppressed myogenic differentiation. Black-Right-Pointing-Pointer shRNA knockdown of endogenous MSTN promoted ovine myoblast differentiation. Black-Right-Pointing-Pointer MSTN inhibits myogenic differentiation through down-regulation of MyoD and Myogenin and up-regulation of Smad3. Black-Right-Pointing-Pointer Provides a promise for the generation of transgenic sheep to improve meat productivity. -- Abstract: Myostatin [MSTN, also known as growth differentiation factor 8 (GDF8)], is an inhibitor of skeletal muscle growth. Blockade of MSTN function has been reported to result in increased muscle mass in mice. However, its role in myoblast differentiation inmore » farm animals has not been determined. In the present study, we sought to determine the role of MSTN in the differentiation of primary sheep myoblasts. We found that ectopic overexpression of MSTN resulted in lower fusion index in sheep myoblasts, which indicated the repression of myoblast differentiation. This phenotypic change was reversed by shRNA knockdown of the ectopically expressed MSTN in the cells. In contrast, shRNA knockdown of the endogenous MSTN resulted in induction of myogenic differentiation. Additional studies revealed that the induction of differentiation by knocking down the ectopically or endogenously expressed MSTN was accompanied by up-regulation of MyoD and myogenin, and down-regulation of Smad3. Our results demonstrate that MSTN plays critical role in myoblast differentiation in sheep, analogous to that in mice. This study also suggests that shRNA knockdown of MSTN could be a potentially promising approach to improve sheep muscle growth, so as to increase meat productivity.« less

Detailed Anatomical and Electrophysiological Models of Human Atria and Torso for the Simulation of Atrial Activation

PubMed Central

Ferrer, Ana; Sebastián, Rafael; Sánchez-Quintana, Damián; Rodríguez, José F.; Godoy, Eduardo J.; Martínez, Laura; Saiz, Javier

2015-01-01

Atrial arrhythmias, and specifically atrial fibrillation (AF), induce rapid and irregular activation patterns that appear on the torso surface as abnormal P-waves in electrocardiograms and body surface potential maps (BSPM). In recent years both P-waves and the BSPM have been used to identify the mechanisms underlying AF, such as localizing ectopic foci or high-frequency rotors. However, the relationship between the activation of the different areas of the atria and the characteristics of the BSPM and P-wave signals are still far from being completely understood. In this work we developed a multi-scale framework, which combines a highly-detailed 3D atrial model and a torso model to study the relationship between atrial activation and surface signals in sinus rhythm. Using this multi scale model, it was revealed that the best places for recording P-waves are the frontal upper right and the frontal and rear left quadrants of the torso. Our results also suggest that only nine regions (of the twenty-one structures in which the atrial surface was divided) make a significant contribution to the BSPM and determine the main P-wave characteristics. PMID:26523732

Signaling by ectopically expressed Drosophila Src64 requires the protein-tyrosine phosphatase corkscrew and the adapter downstream of receptor kinases.

PubMed

Cooper, J A; Simon, M A; Kussick, S J

1996-11-01

Vertebrate Src can be activated by specific mutations to become oncogenic. Analogous mutations in Drosophila Src64 (DSrc) induce abnormal differentiation of photoreceptor cells when expressed ectopically in the developing Drosophila adult eye. We have investigated the roles that the adapter protein, Downstream of receptor kinases (Drk), and the SH2 domain-containing tyrosine phosphatase, Corkscrew (Csw), play in this process. We find that dominant-negative mutations in either the drk or csw genes ameliorate the developmental abnormalities induced by activated DSrc. This suggests that Drk and Csw are required downstream of, or parallel to, DSrc. Csw does not act solely as an upstream activator of DSrc. The results are discussed in relation to potential roles for the vertebrate homologues of Drk and Csw (Grb2 and SHP2, respectively) in the transformation of fibroblasts by vertebrate Src.

A New Algorithm to Diagnose Atrial Ectopic Origin from Multi Lead ECG Systems - Insights from 3D Virtual Human Atria and Torso

PubMed Central

Alday, Erick A. Perez; Colman, Michael A.; Langley, Philip; Butters, Timothy D.; Higham, Jonathan; Workman, Antony J.; Hancox, Jules C.; Zhang, Henggui

2015-01-01

Rapid atrial arrhythmias such as atrial fibrillation (AF) predispose to ventricular arrhythmias, sudden cardiac death and stroke. Identifying the origin of atrial ectopic activity from the electrocardiogram (ECG) can help to diagnose the early onset of AF in a cost-effective manner. The complex and rapid atrial electrical activity during AF makes it difficult to obtain detailed information on atrial activation using the standard 12-lead ECG alone. Compared to conventional 12-lead ECG, more detailed ECG lead configurations may provide further information about spatio-temporal dynamics of the body surface potential (BSP) during atrial excitation. We apply a recently developed 3D human atrial model to simulate electrical activity during normal sinus rhythm and ectopic pacing. The atrial model is placed into a newly developed torso model which considers the presence of the lungs, liver and spinal cord. A boundary element method is used to compute the BSP resulting from atrial excitation. Elements of the torso mesh corresponding to the locations of the placement of the electrodes in the standard 12-lead and a more detailed 64-lead ECG configuration were selected. The ectopic focal activity was simulated at various origins across all the different regions of the atria. Simulated BSP maps during normal atrial excitation (i.e. sinoatrial node excitation) were compared to those observed experimentally (obtained from the 64-lead ECG system), showing a strong agreement between the evolution in time of the simulated and experimental data in the P-wave morphology of the ECG and dipole evolution. An algorithm to obtain the location of the stimulus from a 64-lead ECG system was developed. The algorithm presented had a success rate of 93%, meaning that it correctly identified the origin of atrial focus in 75/80 simulations, and involved a general approach relevant to any multi-lead ECG system. This represents a significant improvement over previously developed algorithms. PMID:25611350

Tissue-specific roles for sonic hedgehog signaling in establishing thymus and parathyroid organ fate

PubMed Central

Bain, Virginia E.; Gordon, Julie; O'Neil, John D.; Ramos, Isaias; Richie, Ellen R.

2016-01-01

The thymus and parathyroids develop from third pharyngeal pouch (3rd pp) endoderm. Our previous studies show that Shh null mice have smaller, aparathyroid primordia in which thymus fate specification extends into the pharynx. SHH signaling is active in both dorsal pouch endoderm and neighboring neural crest (NC) mesenchyme. It is unclear which target tissue of SHH signaling is required for the patterning defects in Shh mutants. Here, we used a genetic approach to ectopically activate or delete the SHH signal transducer Smo in either pp endoderm or NC mesenchyme. Although no manipulation recapitulated the Shh null phenotype, manipulation of SHH signaling in either the endoderm or NC mesenchyme had direct and indirect effects on both cell types during fate specification and organogenesis. SHH pathway activation throughout pouch endoderm activated ectopic Tbx1 expression and partially suppressed the thymus-specific transcription factor Foxn1, identifying Tbx1 as a key target of SHH signaling in the 3rd pp. However, ectopic SHH signaling was insufficient to expand the GCM2-positive parathyroid domain, indicating that multiple inputs, some of which might be independent of SHH signaling, are required for parathyroid fate specification. These data support a model in which SHH signaling plays both positive and negative roles in patterning and organogenesis of the thymus and parathyroids. PMID:27633995

OXPHOS-Mediated Induction of NAD+ Promotes Complete Oxidation of Fatty Acids and Interdicts Non-Alcoholic Fatty Liver Disease.

PubMed

Akie, Thomas E; Liu, Lijun; Nam, Minwoo; Lei, Shi; Cooper, Marcus P

2015-01-01

OXPHOS is believed to play an important role in non-alcoholic fatty liver disease (NAFLD), however, precise mechanisms whereby OXPHOS influences lipid homeostasis are incompletely understood. We previously reported that ectopic expression of LRPPRC, a protein that increases cristae density and OXPHOS, promoted fatty acid oxidation in cultured primary hepatocytes. To determine the biological significance of that observation and define underlying mechanisms, we have ectopically expressed LRPPRC in mouse liver in the setting of NAFLD. Interestingly, ectopic expression of LRPPRC in mouse liver completely interdicted NAFLD, including inflammation. Consistent with mitigation of NAFLD, two markers of hepatic insulin resistance--ROS and PKCε activity--were both modestly reduced. As reported by others, improvement of NAFLD was associated with improved whole-body insulin sensitivity. Regarding hepatic lipid homeostasis, the ratio of NAD+ to NADH was dramatically increased in mouse liver replete with LRPPRC. Pharmacological activators and inhibitors of the cellular respiration respectively increased and decreased the [NAD+]/[NADH] ratio, indicating respiration-mediated control of the [NAD+]/[NADH] ratio. Supporting a prominent role for NAD+, increasing the concentration of NAD+ stimulated complete oxidation of fatty acids. Importantly, NAD+ rescued impaired fatty acid oxidation in hepatocytes deficient for either OXPHOS or SIRT3. These data are consistent with a model whereby augmented hepatic OXPHOS increases NAD+, which in turn promotes complete oxidation of fatty acids and protects against NAFLD.

Rh Incompatibility

MedlinePlus

... An ectopic pregnancy, a miscarriage, or an induced abortion. (An ectopic pregnancy is a pregnancy that starts ... An ectopic pregnancy, a miscarriage, or an induced abortion. (An ectopic pregnancy is a pregnancy that starts ...

Clinicopathological Features and Treatment of Ectopic Varices with Portal Hypertension

PubMed Central

Sato, Takahiro; Akaike, Jun; Toyota, Jouji; Karino, Yoshiyasu; Ohmura, Takumi

2011-01-01

Bleeding from ectopic varices, which is rare in patients with portal hypertension, is generally massive and life-threatening. Forty-three patients were hospitalized in our ward for gastrointestinal bleeding from ectopic varices. The frequency of ectopic varices was 43/1218 (3.5%) among portal hypertensive patients in our ward. The locations of the ectopic varices were rectal in thirty-two, duodenal in three, intestinal in two, vesical in three, stomal in one, and colonic in two patients. Endoscopic or interventional radiologic treatment was performed successfully for ectopic varices. Hemorrhage from ectopic varices should be kept in mind in patients with portal hypertension presenting with lower gastrointestinal bleeding. PMID:21994879

Ectopic eruption of first permanent molars: presenting features and associations.

PubMed

Mooney, G C; Morgan, A G; Rodd, H D; North, S

2007-09-01

To investigate presenting features of ectopically erupting first permanent molars and associations with other dental anomalies. Prospective convenience study. 28 panoral radiographs were collected, over a 24-month period, of 7-11 year-old children with radiographic evidence of ectopic eruption of first permanent molars who presented to a Dental Teaching Hospital in the North of England. A further 20 radiographs were collected of matched patients with no evidence of ectopic molar eruption. All radiographs were analysed under standard conditions to record the distribution and type of ectopic eruption (if present). In addition, the presence of the following dental anomalies was noted: cleft lip and/or palate; supernumerary teeth; hypodontia, and infraocclusion of primary molars. Chi-squared analysis was performed to determine any significant differences in the frequency of these dental anomalies between ectopic molar and control groups. For patients with ectopic molar eruption, the majority demonstrated ectopic eruption of either one or two first permanent molars (32% and 57% of subjects respectively). There were a similar proportion of 'jumps' and 'holds'. 92% of these were maxillary teeth and there was equal left and right distribution. Interestingly, a positive record of ectopic eruption was only documented in the dental records of 35.7% of these subjects. Children with ectopic eruption were significantly more likely to have at least one additional dental anomaly than was the case for the control group (60.7% versus 25%). Notably, primary molar infraocclusion and cleft lip/palate were significantly more frequent in the ectopic group. This study, the first in a British population, has identified a significant association between ectopic eruption of first permanent molars and other dental anomalies. A multifactorial aetiology is thus supported and clinicians should be alert to the co-existence of ectopic eruption and other dental anomalies.

Ectopic Pregnancy

MedlinePlus

... if you have risk factors for an ectopic pregnancy Causes A tubal pregnancy — the most common type of ectopic pregnancy — happens ... smoke, the greater the risk. Complications An ectopic pregnancy can cause your fallopian tube to burst open. Without treatment, ...

Management of upper urinary tract calculi in crossed fused renal ectopic anomaly

PubMed Central

Huang, Liang; Lin, Yong; Tang, Zhengyan; Lie, Dongjie; Wang, Zhao; Chen, Hequn; Wang, Guilin

2018-01-01

The aim of the present study was to summarize the management of upper urinary tract calculi in crossed fused renal ectopia (CFRE). Two patients were retrospectively studied in Xiangya Hospital (Changsha, China) and all relevant literature published in English between 1996 and 2016 was reviewed. All patients, including those reported in the literature, were characterized by age, sex, manifestation, therapy history, ectopic side, stone location, surgery and outcome. The patients had a mean age of 42.3±18.5 years, a male: Female ratio of 5:4 and the ratio of renal ectopic side was 9:8 (left:right). All patients suffered from different degrees of pain on the affected side, with or without hematuria. Up to 89% of patients presented with renal stones. These patients received treatments including conservative management in 2, extracorporeal shock wave lithotripsy (ESWL) in 2, percutaneous nephrolithotomy (PCNL) in 11, laparoscope nephrolithotomy in 1 and retrograde intrarenal surgery (RIRS) in 3. Complete stone clearance was achieved in 14 patients (73.7%). In addition, 3 patients had a history of failed ESWL. No obvious intraoperative or postoperative complications occurred. The results suggested that, for the treatment of CFRE with upper urinary tract calculi, conservative treatment and ESWL are insufficient. PCNL is a safe and effective treatment for renal calculus, and laparoscopic nephrolithotomy is an alternative choice for treating large or staghorn renal stones. RIRS may become the first line of treatment for renal stones (≤3.5 cm) due to its multiple merits, including higher stone-free rates, minimal invasion and fewer complications. PMID:29375692

Management of upper urinary tract calculi in crossed fused renal ectopic anomaly.

PubMed

Huang, Liang; Lin, Yong; Tang, Zhengyan; Lie, Dongjie; Wang, Zhao; Chen, Hequn; Wang, Guilin

2018-01-01

The aim of the present study was to summarize the management of upper urinary tract calculi in crossed fused renal ectopia (CFRE). Two patients were retrospectively studied in Xiangya Hospital (Changsha, China) and all relevant literature published in English between 1996 and 2016 was reviewed. All patients, including those reported in the literature, were characterized by age, sex, manifestation, therapy history, ectopic side, stone location, surgery and outcome. The patients had a mean age of 42.3±18.5 years, a male: Female ratio of 5:4 and the ratio of renal ectopic side was 9:8 (left:right). All patients suffered from different degrees of pain on the affected side, with or without hematuria. Up to 89% of patients presented with renal stones. These patients received treatments including conservative management in 2, extracorporeal shock wave lithotripsy (ESWL) in 2, percutaneous nephrolithotomy (PCNL) in 11, laparoscope nephrolithotomy in 1 and retrograde intrarenal surgery (RIRS) in 3. Complete stone clearance was achieved in 14 patients (73.7%). In addition, 3 patients had a history of failed ESWL. No obvious intraoperative or postoperative complications occurred. The results suggested that, for the treatment of CFRE with upper urinary tract calculi, conservative treatment and ESWL are insufficient. PCNL is a safe and effective treatment for renal calculus, and laparoscopic nephrolithotomy is an alternative choice for treating large or staghorn renal stones. RIRS may become the first line of treatment for renal stones (≤3.5 cm) due to its multiple merits, including higher stone-free rates, minimal invasion and fewer complications.

A system and method for online high-resolution mapping of gastric slow-wave activity.

PubMed

Bull, Simon H; O'Grady, Gregory; Du, Peng; Cheng, Leo K

2014-11-01

High-resolution (HR) mapping employs multielectrode arrays to achieve spatially detailed analyses of propagating bioelectrical events. A major current limitation is that spatial analyses must currently be performed "off-line" (after experiments), compromising timely recording feedback and restricting experimental interventions. These problems motivated development of a system and method for "online" HR mapping. HR gastric recordings were acquired and streamed to a novel software client. Algorithms were devised to filter data, identify slow-wave events, eliminate corrupt channels, and cluster activation events. A graphical user interface animated data and plotted electrograms and maps. Results were compared against off-line methods. The online system analyzed 256-channel serosal recordings with no unexpected system terminations with a mean delay 18 s. Activation time marking sensitivity was 0.92; positive predictive value was 0.93. Abnormal slow-wave patterns including conduction blocks, ectopic pacemaking, and colliding wave fronts were reliably identified. Compared to traditional analysis methods, online mapping had comparable results with equivalent coverage of 90% of electrodes, average RMS errors of less than 1 s, and CC of activation maps of 0.99. Accurate slow-wave mapping was achieved in near real-time, enabling monitoring of recording quality and experimental interventions targeted to dysrhythmic onset. This work also advances the translation of HR mapping toward real-time clinical application.

Arrhythmia during extracorporeal shock wave lithotripsy.

PubMed

Zeng, Z R; Lindstedt, E; Roijer, A; Olsson, S B

1993-01-01

A prospective study of arrhythmia during extracorporeal shock wave lithotripsy (ESWL) was performed in 50 patients, using an EDAP LT01 piezoelectric lithotriptor. The 12-lead standard ECG was recorded continuously for 10 min before and during treatment. One or more atrial and/or ventricular ectopic beats occurred during ESWL in 15 cases (30%). The occurrence of arrhythmia was similar during right-sided and left-sided treatment. One patient developed multifocal ventricular premature beats and ventricular bigeminy; another had cardiac arrest for 13.5 s. It was found that various irregularities of the heart rhythm can be caused even by treatment with a lithotriptor using piezoelectric energy to create the shock wave. No evidence was found, however, that the shock wave itself rather than vagal activation and the action of sedo-analgesia was the cause of the arrhythmia. For patients with severe underlying heart disease and a history of complex arrhythmia, we suggest that the ECG be monitored during treatment. In other cases, we have found continuous monitoring of oxygen saturation and pulse rate with a pulse oximeter to be perfectly reliable for raising the alarm when depression of respiration and vaso-vagal reactions occur.

Abdominal ectopic pregnancy after in vitro fertilization and single embryo transfer: a case report and systematic review.

PubMed

Yoder, Nicole; Tal, Reshef; Martin, J Ryan

2016-10-19

Ectopic pregnancy is the leading cause of maternal morbidity and mortality during the first trimester and the incidence increases dramatically with assisted-reproductive technology (ART), occurring in approximately 1.5-2.1 % of patients undergoing in-vitro fertilization (IVF). Abdominal ectopic pregnancy is a rare yet clinically significant form of ectopic pregnancy due to potentially high maternal morbidity. While risk factors for ectopic pregnancy after IVF have been studied, very little is known about risk factors specific for abdominal ectopic pregnancy. We present a case of a 30 year-old woman who had an abdominal ectopic pregnancy following IVF and elective single embryo transfer, which was diagnosed and managed by laparoscopy. We performed a systematic literature search to identify case reports of abdominal or heterotopic abdominal ectopic pregnancies after IVF. A total of 28 cases were identified. Patients' ages ranged from 23 to 38 (Mean 33.2, S.D. = 3.2). Infertility causes included tubal factor (46 %), endometriosis (14 %), male factor (14 %), pelvic adhesive disease (7 %), structural/DES exposure (7 %), and unexplained infertility (14 %). A history of ectopic pregnancy was identified in 39 % of cases. A history of tubal surgery was identified in 50 % of cases, 32 % cases having had bilateral salpingectomy. Transfer of two embryos or more (79 %) and fresh embryo transfer (71 %) were reported in the majority of cases. Heterotopic abdominal pregnancy occurred in 46 % of cases while 54 % were abdominal ectopic pregnancies. Our systematic review has revealed several trends in reported cases of abdominal ectopic pregnancy after IVF including tubal factor infertility, history of tubal ectopic and tubal surgery, higher number of embryos transferred, and fresh embryo transfers. These are consistent with known risk factors for ectopic pregnancy following IVF. Further research focusing on more homogenous population may help in better characterizing this rare IVF complication and its risks.

PRDM1 expression on the epithelial component but not on ectopic lymphoid tissues of Warthin tumour.

PubMed

Wang, Y; Zhou, J; Zhang, Y; Wang, L; Liu, Y; Fan, L; Zhu, J; Xu, X; Huang, G; Li, X; Xun, W

2015-05-01

To determine the role of PRDM1, a key molecule for modulating the immune cells, in Warthin tumour (WT) pathogenesis. Forty paraffin-embedded parotid tissues of patients (mean age: 62.08 ± 11.90) with WT were retrieved from the pathology archives of Qindu Hospital from January 2012 to December 2012. The PRDM1 expression was investigated in a cohort of WT by immunohistochemistry. PRDM1 was expressed only on the epithelial component but not on ectopic lymphoid tissue of the tumour. Statistically, PRDM1 expression rates between WT glandular epithelial cells (40/40 cases) and the tumour-adjacent tissues (0/9 cases), and WT germinal centres (0/34 cases) and tonsil tissues (10/10 cases) were significantly different (P < 0.001), respectively. The PRDM1 expression appeared to play an essential role in WT pathogenesis. A better understanding of it might give options for revealing possible novel management strategies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ectopic beats in approximate entropy and sample entropy-based HRV assessment

NASA Astrophysics Data System (ADS)

Singh, Butta; Singh, Dilbag; Jaryal, A. K.; Deepak, K. K.

2012-05-01

Approximate entropy (ApEn) and sample entropy (SampEn) are the promising techniques for extracting complex characteristics of cardiovascular variability. Ectopic beats, originating from other than the normal site, are the artefacts contributing a serious limitation to heart rate variability (HRV) analysis. The approaches like deletion and interpolation are currently in use to eliminate the bias produced by ectopic beats. In this study, normal R-R interval time series of 10 healthy and 10 acute myocardial infarction (AMI) patients were analysed by inserting artificial ectopic beats. Then the effects of ectopic beats editing by deletion, degree-zero and degree-one interpolation on ApEn and SampEn have been assessed. Ectopic beats addition (even 2%) led to reduced complexity, resulting in decreased ApEn and SampEn of both healthy and AMI patient data. This reduction has been found to be dependent on level of ectopic beats. Editing of ectopic beats by interpolation degree-one method is found to be superior to other methods.

FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension

PubMed Central

Eash, John; Olsen, Aaron; Breur, Gert; Gerrard, Dave; Hannon, Kevin

2007-01-01

Background Skeletal muscle atrophy can occur under many different conditions, including prolonged disuse or immobilization, cachexia, cushingoid conditions, secondary to surgery, or with advanced age. The mechanisms by which unloading of muscle is sensed and translated into signals controlling tissue reduction remains a major question in the field of musculoskeletal research. While the fibroblast growth factors (FGFs) and their receptors are synthesized by, and intimately involved in, embryonic skeletal muscle growth and repair, their role maintaining adult muscle status has not been examined. Methods We examined the effects of ectopic expression of FGFR1 during disuse-mediated skeletal muscle atrophy, utilizing hindlimb suspension and DNA electroporation in mice. Results We found skeletal muscle FGF4 and FGFR1 mRNA expression to be modified by hind limb suspension,. In addition, we found FGFR1 protein localized in muscle fibers within atrophying mouse muscle which appeared to be resistant to atrophy. Electroporation and ectopic expression of FGFR1 significantly inhibited the decrease in muscle fiber area within skeletal muscles of mice undergoing suspension induced muscle atrophy. Ectopic FGFR1 expression in muscle also significantly stimulated protein synthesis in muscle fibers, and increased protein degradation in weight bearing muscle fibers. Conclusion These results support the theory that FGF signaling can play a role in regulation of postnatal skeletal muscle maintenance, and could offer potentially novel and efficient therapeutic options for attenuating muscle atrophy during aging, illness and spaceflight. PMID:17425786

The role of HCG increment in the 48h prior to methotrexate treatment as a predictor for treatment success.

PubMed

Cohen, Aviad; Almog, Benny; Cohen, Yoni; Bibi, Guy; Rimon, Eli; Levin, Ishai

2017-04-01

To evaluate the role HCG change in the 48h prior to methotrexate treatment as a predictor for treatment success. Medical records of all women who were diagnosed with ectopic pregnancy between January 2001 and June 2013 were reviewed. Four hundred and nine patients received methotrexate due to ectopic pregnancy. The "single dose" methotrexate protocol with 50mg/m 2 was administered to patients with progressing ectopic pregnancy. HCG levels in days 1, 4 and 7 were used to evaluate methotrexate treatment success. The percentage of HCG change in the 48h prior to methotrexate treatment was compared between patients who were successfully treated and those who failed treatment with methotrexate. Single dose methotrexate was successful in 309 patients (75.4%, success group). The medians of HCG change in the 48h prior to methotrexate administration were significantly higher in the "failure group" (21% vs. 4%, p<0.01). In a logistic regression analysis, the of HCG percent increment prior to methotrexate administration was shown to be an independent predictor for treatment outcome. Receiver operator characteristic curve for HCG percent change was 0.751, at a cutoff value of HCG increment <12% the positive predictive value for treatment success reached 86%. Percentage of HCG increment in the 48h prior to methotrexate administration is an independent predictor for methotrexate treatment success. HCG increment <12% prior to methotrexate treatment is a good predictor for treatment success. Copyright © 2017 Elsevier B.V. All rights reserved.

Minimally Invasive Management of Ectopic Pancreas.

PubMed

Vitiello, Gerardo A; Cavnar, Michael J; Hajdu, Cristina; Khaykis, Inessa; Newman, Elliot; Melis, Marcovalerio; Pachter, H Leon; Cohen, Steven M

2017-03-01

The management of ectopic pancreas is not well defined. This study aims to determine the prevalence of symptomatic ectopic pancreas and identify those who may benefit from treatment, with a particular focus on robotically assisted surgical management. Our institutional pathology database was queried to identify a cohort of ectopic pancreas specimens. Additional clinical data regarding clinical symptomatology, diagnostic studies, and treatment were obtained through chart review. Nineteen cases of ectopic pancreas were found incidentally during surgery for another condition or found incidentally in a pathologic specimen (65.5%). Eleven patients (37.9%) reported prior symptoms, notably abdominal pain and/or gastrointestinal bleeding. The most common locations for ectopic pancreas were the duodenum and small bowel (31% and 27.6%, respectively). Three out of 29 cases (10.3%) had no symptoms, but had evidence of preneoplastic changes on pathology, while one harbored pancreatic cancer. Over the years, treatment of ectopic pancreas has shifted from open to laparoscopic and more recently to robotic surgery. Our experience is in line with existing evidence supporting surgical treatment of symptomatic or complicated ectopic pancreas. In the current era, minimally invasive and robotic surgery can be used safely and successfully for treatment of ectopic pancreas.

Ectopic mineralization of cartilage and collagen-rich tendons and ligaments in Enpp1asj-2J mice.

PubMed

Zhang, Jieyu; Dyment, Nathaniel A; Rowe, David W; Siu, Sarah Y; Sundberg, John P; Uitto, Jouni; Li, Qiaoli

2016-03-15

Generalized arterial calcification of infancy (GACI), an autosomal recessive disorder caused by mutations in the ENPP1 gene, manifests with extensive mineralization of the cardiovascular system. A spontaneous asj-2J mutant mouse has been characterized as a model for GACI. Previous studies focused on phenotypic characterization of skin and vascular tissues. This study further examined the ectopic mineralization phenotype of cartilage, collagen-rich tendons and ligaments in this mouse model. The mice were placed on either control diet or the "acceleration diet" for up to 12 weeks of age. Soft connective tissues, such as ear (elastic cartilage) and trachea (hyaline cartilage), were processed for standard histology. Assessment of ectopic mineralization in articular cartilage and fibrocartilage as well as tendons and ligaments which are attached to long bones were performed using a novel cryo-histological method without decalcification. These analyses demonstrated ectopic mineralization in cartilages as well as tendons and ligaments in the homozygous asj-2J mice at 12 weeks of age, with the presence of immature osteophytes displaying alkaline phosphatase and tartrate-resistant acid phosphatase activities as early as at 6 weeks of age. Alkaline phosphatase activity was significantly increased in asj-2J mouse serum as compared to wild type mice, indicating increased bone formation rate in these mice. Together, these data highlight the key role of ENPP1 in regulating calcification of both soft and skeletal tissues.

Ectopic expression of Msx2 in mammalian myotubes recapitulates aspects of amphibian muscle dedifferentiation.

PubMed

Yilmaz, Atilgan; Engeler, Rachel; Constantinescu, Simona; Kokkaliaris, Konstantinos D; Dimitrakopoulos, Christos; Schroeder, Timm; Beerenwinkel, Niko; Paro, Renato

2015-11-01

In contrast to urodele amphibians and teleost fish, mammals lack the regenerative responses to replace large body parts. Amphibian and fish regeneration uses dedifferentiation, i.e., reversal of differentiated state, as a means to produce progenitor cells to eventually replace damaged tissues. Therefore, induced activation of dedifferentiation responses in mammalian tissues holds an immense promise for regenerative medicine. Here we demonstrate that ectopic expression of Msx2 in cultured mouse myotubes recapitulates several aspects of amphibian muscle dedifferentiation. We found that MSX2, but not MSX1, leads to cellularization of myotubes and downregulates the expression of myotube markers, such as MHC, MRF4 and myogenin. RNA sequencing of myotubes ectopically expressing Msx2 showed downregulation of over 500 myotube-enriched transcripts and upregulation of over 300 myoblast-enriched transcripts. MSX2 selectively downregulated expression of Ptgs2 and Ptger4, two members of the prostaglandin pathway with important roles in myoblast fusion during muscle differentiation. Ectopic expression of Msx2, as well as Msx1, induced partial cell cycle re-entry of myotubes by upregulating CyclinD1 expression but failed to initiate S-phase. Finally, MSX2-induced dedifferentiation in mouse myotubes could be recapitulated by a pharmacological treatment with trichostatin A (TSA), bone morphogenetic protein 4 (BMP4) and fibroblast growth factor 1 (FGF1). Together, these observations indicate that MSX2 is a major driver of dedifferentiation in mammalian muscle cells. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

High Expression of High-Mobility Group Box 1 in Menstrual Blood: Implications for Endometriosis.

PubMed

Shimizu, Keiko; Kamada, Yasuhiko; Sakamoto, Ai; Matsuda, Miwa; Nakatsuka, Mikiya; Hiramatsu, Yuji

2017-11-01

Endometriosis is a benign gynecologic disease characterized by the presence of ectopic endometrium and associated with inflammation and immune abnormalities. However, the molecular basis for endometriosis is not well understood. To address this issue, the present study examined the expression of high-mobility group box (HMGB) 1 in menstrual blood to investigate its role in the ectopic growth of human endometriotic stromal cells (ESCs). A total of 139 patients were enrolled in this study; 84 had endometriosis and 55 were nonendometriotic gynecological patients (control). The HMGB1 levels in various fluids were measured by enzyme-linked immunosorbent assay. Expression of receptor for advanced glycation end products (RAGE) in eutopic and ectopic endometrium was assessed by immunohistochemistry, and RAGE and vascular endothelial growth factor ( VEGF) messenger RNA expression in HMGB1- and lipopolysaccharide (LPS)-treated ESCs was evaluated by real-time polymerase chain reaction. The HMGB1 concentration was higher in menstrual blood than in serum or peritoneal fluid ( P < .001 for both). RAGE was expressed in both normal and ectopic endometrium. Administration of 1000 ng/mL HMGB1 or coadministration of 100 ng/mL HMGB1 and 100 ng/mL LPS induced VEGF production in ESCs relative to the control ( P < .05). These results suggest that menstrual fluid has naturally high levels of HMGB1 and may promote endometriosis following retrograde menstruation when complexed with other factors such as LPS by inducing inflammation and angiogenesis.

Ectopic pregnancy: current clinical trends, a fifteen year study.

PubMed

Weekes, L R

1981-09-01

This paper reviews the clinical recognition, diagnosis, and management of ectopic pregnancy at the Queen of Angels Hospital for the past 15 years. The incidence of ectopic pregnancy to deliveries is 1:195. Pain is the cardinal symptom of ectopic pregnancy, and amenorrhea of some degree was present in all cases. Pelvic inflammatory disease is a factor in the development of tubal pregnancy in some women. A careful history and thorough physical examination are important in making a careful diagnosis. The only laboratory procedures which are of any value are the blood type and the Rh determination. While examination of endometrial tissue obtained by biopsy or curettage has proved useful in ectopic pregnancy diagnosis, it is not totally decisive. Culdocentesis has proved to be the diagnostic procedure of the greatest value in recognizing intraperitoneal hemorrhage and it increases the correct preoperative diagnosis from 65-70% to 95%. Laparoscopy is useful when the physician is in doubt about the nature of the problem and it has produced an increase in the number of ectopic pregnancies diagnosed. Ultrasound is another useful tool in confirming a diagnosis of ectopic pregnancy; its accuracy ranges from 70-92%. A newly developed pregnancy test is more sensitive than conventional pregnancy tests and would be positive for pregnancy. Women who have had a previous ectopic pregnancy have a higher subsequent incidence of persistent infertility, recurrent ectopic pregnancy, and pregnancy wastage; the risk of another ectopic pregnancy increases 30-50 fold. While extopic pregnancy does recur, it is true that about 1/3 of those women do have successful pregnancies. Where previous induced abortion has occurred, there is a 10-fold increased risk of ectopic pregnancy. Women who become pregnant accidentally with an IUD in place have a greater likelihood of experiencing an extrauterine pregnancy. Abdominal pregnancy is often encountered as an aborting ectopic pregnancy during the 1st trimester. In cases such as this, there can be local excision and hemostasis. Idiopathic thrombocytopenic purpura was another encountered complication. Salpingectomy is inappropriate and even dangerous when used with an ectopic pregnancy. Early diagnosis and prompt surgery can help increase the survival rate. However, conservative surgery which preserves the tube is feasible and practical using salpingotomy and partial salpingectomy. Maternal death resulting from ectopic pregnancy is usually the result of sudden massive hemorrhage. The initiation of therapy prior to rupture is helpful. Ectopic pregnancy rate has remained fairly consistent among the white population but has decreased significantly in the nonwhite population. This is likely tied to an improvement in socioeconomic status, better patient education, and a greater awareness of medical needs. To decrease the maternal mortality rate from ectopic pregnancy, obstetricians and gynecologists must be more aggressive in research and treatment of ectopic pregnancy.

Microfollicular adenoma of ectopic thyroid gland masquerading as salivary gland tumor - a diagnostic and therapeutic challenge: a case report.

PubMed

Deshmukh, Sanjay D; Khandeparkar, Siddhi G Sinai; Gulati, Harveen K; Naik, Chetana S

2014-08-07

Ectopic thyroid tissue may appear in any location along the trajectory of the thyroglossal duct from the foramen cecum to the mediastinum. Rarely, there is incomplete descent of the gland where the final resting point may be high resulting in sublingual ectopic thyroid tissue. Ectopic thyroid tissue carries a low risk of malignancy. Most recently reported neoplasms in ectopic thyroid tissue have been papillary carcinoma of thyroid. Individual case reports of clear cell type of follicular adenoma within the ectopic thyroid tissue have been described in the literature. We present a rare case of microfollicular follicular adenoma in an ectopic sublingual thyroid tissue presenting as submental swelling in a euthyroid 24-year-old Dravidian woman. Findings in this case emphasize that when confronted with a submental/sublingual mass lesion, the evaluation of thyroid function tests and ultrasonography of the neck should be included in a pre-operative workup.

The history of the diagnosis and treatment of ectopic pregnancy: a medical adventure.

PubMed

Lurie, S

1992-01-09

From its indirect reference by Abulcasis (936-1013) and until the 19th century the ectopic pregnancy was known as a universally fatal accident. By reporting successful treatment of tubal pregnancy with salpingectomy in 1884 Robert Lawson Tait (1845-1899) started an era of almost 70 years of exclusively extirpative treatment of ectopic pregnancy. The technologic revolution of the 20th century improved diagnostic capabilities so that diagnosis of unruptured ectopic pregnancy becomes feasible and even mandatory. Side by side our understanding of the natural history of ectopic pregnancy improved. Many patients with early-resolving ectopic pregnancies escape surgical treatment. Preservation of future fertility became possible with the introduction of conservative surgical procedures and with the use of methotrexate. The main achievement in the treatment of ectopic pregnancy over the past 110 years is the dramatic decrease in mortality rate: from 72-90% in 1880 to 0.14% in 1990.

Meckel's diverticulum and ectopic epithelium: Evaluation of a complex relationship

PubMed Central

Burjonrappa, Sathyaprasad; Khaing, Phue

2014-01-01

Introduction: Meckel's diverticulum is the most common congenital anomaly of the gastrointestinal tract. Currently, for any incidentally discovered Meckel's diverticulum, the management approach is based on weighing the statistical odds of future complications against the risks of a diverticulectomy. Materials and Methods: The temporal relationship between age at Meckel's diverticulectomy and the presence of ectopic epithelium was evaluated in our series. A meta-analysis of all reported recent literature on this condition was subsequently performed to evaluate the strength of the relationship between ectopic epithelium and symptomatic Meckel's diverticulum. Results: There was a paucity of ectopic epithelium in Meckel's diverticulectomy specimens in infants operated on at less than 1 year of age. Having two or more ectopic epithelia in a diverticulum does not appear to carry an additive risk for complications. The meta-analysis confirmed that ectopic epithelium was the most significant factor that influenced surgical intervention in all series of Meckel's diverticulum. Conclusion: The relationship between ectopic epithelium and the development of symptomatic Meckel's diverticulum is complex. Further understanding of the development of ectopic rests in the diverticulum will facilitate elucidating the pathophysiology in symptomatic cases. PMID:24741211

Meckel's diverticulum and ectopic epithelium: Evaluation of a complex relationship.

PubMed

Burjonrappa, Sathyaprasad; Khaing, Phue

2014-04-01

Meckel's diverticulum is the most common congenital anomaly of the gastrointestinal tract. Currently, for any incidentally discovered Meckel's diverticulum, the management approach is based on weighing the statistical odds of future complications against the risks of a diverticulectomy. The temporal relationship between age at Meckel's diverticulectomy and the presence of ectopic epithelium was evaluated in our series. A meta-analysis of all reported recent literature on this condition was subsequently performed to evaluate the strength of the relationship between ectopic epithelium and symptomatic Meckel's diverticulum. There was a paucity of ectopic epithelium in Meckel's diverticulectomy specimens in infants operated on at less than 1 year of age. Having two or more ectopic epithelia in a diverticulum does not appear to carry an additive risk for complications. The meta-analysis confirmed that ectopic epithelium was the most significant factor that influenced surgical intervention in all series of Meckel's diverticulum. The relationship between ectopic epithelium and the development of symptomatic Meckel's diverticulum is complex. Further understanding of the development of ectopic rests in the diverticulum will facilitate elucidating the pathophysiology in symptomatic cases.

Inferior ectopic pupil and typical ocular coloboma in RCS rats.

PubMed

Tsuji, Naho; Ozaki, Kiyokazu; Narama, Isao; Matsuura, Tetsuro

2011-08-01

Ocular coloboma is sometimes accompanied by corectopia in humans and therefore ectopic pupil may indicate ocular coloboma in experimental animals. The RCS strain of rats has a low incidence of microphthalmia. We found that inferior ectopic pupil is associated exclusively with small-sized eyes in this strain. The objective of the current study was to evaluate whether inferior ectopic pupil is associated with iridal coloboma and other types of ocular coloboma in RCS rats. Both eyes of RCS rats were examined clinically, and those with inferior ectopic pupils underwent morphologic and morphometric examinations. In a prenatal study, coronal serial sections of eyeballs from fetuses at gestational day 16.5 were examined by using light microscopy. Ectopic pupils in RCS rats were found exclusively in an inferior position, where the iris was shortened. Fundic examination revealed severe chorioretinal coloboma in all cases of inferior ectopic pupil. The morphologic characteristics closely resembled those of chorioretinal coloboma in humans. Histopathologic examination of primordia showed incomplete closure of the optic fissure in 4 eyeballs of RCS fetuses. Neither F(1) rats nor N(2) (progeny of RCS × BN matings) displayed any ocular anomalies, including ectopic pupils. The RCS strain is a suitable model for human ocular coloboma, and inferior ectopic pupil appears to be a strong indicator of ocular coloboma.

Inferior Ectopic Pupil and Typical Ocular Coloboma in RCS Rats

PubMed Central

Tsuji, Naho; Ozaki, Kiyokazu; Narama, Isao; Matsuura, Tetsuro

2011-01-01

Ocular coloboma is sometimes accompanied by corectopia in humans and therefore ectopic pupil may indicate ocular coloboma in experimental animals. The RCS strain of rats has a low incidence of microphthalmia. We found that inferior ectopic pupil is associated exclusively with small-sized eyes in this strain. The objective of the current study was to evaluate whether inferior ectopic pupil is associated with iridal coloboma and other types of ocular coloboma in RCS rats. Both eyes of RCS rats were examined clinically, and those with inferior ectopic pupils underwent morphologic and morphometric examinations. In a prenatal study, coronal serial sections of eyeballs from fetuses at gestational day 16.5 were examined by using light microscopy. Ectopic pupils in RCS rats were found exclusively in an inferior position, where the iris was shortened. Fundic examination revealed severe chorioretinal coloboma in all cases of inferior ectopic pupil. The morphologic characteristics closely resembled those of chorioretinal coloboma in humans. Histopathologic examination of primordia showed incomplete closure of the optic fissure in 4 eyeballs of RCS fetuses. Neither F1 rats nor N2 (progeny of RCS × BN matings) displayed any ocular anomalies, including ectopic pupils. The RCS strain is a suitable model for human ocular coloboma, and inferior ectopic pupil appears to be a strong indicator of ocular coloboma. PMID:22330254

Frozen-Thawed Embryo Transfer Cycles Have a Lower Incidence of Ectopic Pregnancy Compared With Fresh Embryo Transfer Cycles.

PubMed

Zhang, Xinyu; Ma, Caihong; Wu, Zhangxin; Tao, Liyuan; Li, Rong; Liu, Ping; Qiao, Jie

2017-01-01

To evaluate the risk of ectopic pregnancy of embryo transfer. A retrospective cohort study on the incidence of ectopic pregnancy in fresh and frozen-thawed embryo transfer cycles from January 1 st , 2010, to January 1 st , 2015. Infertile women undergoing frozen-thawed transfer cycles or fresh transfer cycles. In-vitro fertilization, fresh embryo transfer, frozen-thawed embryo transfer, ectopic pregnancy. Ectopic pregnancy rate and clinical pregnancy rate. A total of 69 756 in vitro fertilization-embryo transfer cycles from 2010 to 2015 were analyzed, including 45 960 (65.9%) fresh and 23 796 (34.1%) frozen-thawed embryo transfer cycles. The clinical pregnancy rate per embryo transfer was slightly lower in fresh embryo transfer cycles compared with frozen-thawed embryo transfer cycles (40.8% vs 43.1%, P < .001). Frozen-thawed embryo transfer is associated with a lower incidence of ectopic pregnancy per clinical pregnancy, compared with fresh embryo transfers (odds ratio = 0.31; 95% confidence interval = 0.24-0.39). Female age and body mass index have no influence on ectopic pregnancy. In the frozen-thawed embryo transfer cycles, blastocyst transfer shows a significantly lower incidence of ectopic pregnancy (0.8% vs 1.8%, P = .002) in comparison with day 3 cleavage embryo transfer. The risk of ectopic pregnancy is lower in frozen-thawed embryo transfer cycles than fresh embryo transfer cycles, and blastocyst transfer could further decrease the ectopic pregnancy rate in frozen-thawed embryo transfer cycles.

Expression of natural killer cell activity with CD107a on ectopic endometrium in woman with endometriosis compared with non-endometriosis

NASA Astrophysics Data System (ADS)

Lubis, H. P.; Aldiansyah, D.; Siregar, H. S.; Rivany, R.; Hariadi, T. S.

2018-03-01

Some factors have an important role in endometriosis pathogenesis; there is an immune cell that plays an important role in endometrial cells that have reflux. Woman with endometriosis experienced the cellular immune disorder. It is suspected that decrease of NK cell in the peritoneal fluid caused by its qualitative defect with CD107a expression as the best marker. The aim of this study was to compare expression of NK Cell activity with CD107a between awoman with endometriosis and non-endometriosis. A case-control study from March until July 2015 in Haji Adam Malik General Hospital. The case group was ectopic endometrial tissue block paraffin and control group was normal endometrial tissue block paraffin. This study included 23 patients in endometriosis group and control group respectively. A majority proportion of CD107a expression in endometriosis group was +1 (16 patients (69.6%)), while the control group was +3 (9 patients (39.1%)). Expression of NK cell activity with CD107a in patients with endometriosis was lower than the control group (p<0.05). It suggested that cellular immune factors may play a role in the pathogenesis of endometriosis.

New roles for Nanos in neural cell fate determination revealed by studies in a cnidarian.

PubMed

Kanska, Justyna; Frank, Uri

2013-07-15

Nanos is a pan-metazoan germline marker, important for germ cell development and maintenance. In flies, Nanos also acts in posterior and neural development, but these functions have not been demonstrated experimentally in other animals. Using the cnidarian Hydractinia we have uncovered novel roles for Nanos in neural cell fate determination. Ectopic expression of Nanos2 increased the numbers of embryonic stinging cell progenitors, but decreased the numbers of neurons. Downregulation of Nanos2 had the opposite effect. Furthermore, Nanos2 blocked maturation of committed, post-mitotic nematoblasts. Hence, Nanos2 acts as a switch between two differentiation pathways, increasing the numbers of nematoblasts at the expense of neuroblasts, but preventing nematocyte maturation. Nanos2 ectopic expression also caused patterning defects, but these were not associated with deregulation of Wnt signaling, showing that the basic anterior-posterior polarity remained intact, and suggesting that numerical imbalance between nematocytes and neurons might have caused these defects, affecting axial patterning only indirectly. We propose that the functions of Nanos in germ cells and in neural development are evolutionarily conserved, but its role in posterior patterning is an insect or arthropod innovation.

Submandibular ectopic thyroid with normally located thyroid gland.

PubMed

Yılmaz, Mahmut Sinan; Aytürk, Semra; Güven, Mehmet; Dilek, Fatma Hüsniye

2014-01-01

Ectopic thyroid is a rare developmental anomaly of the thyroid gland which is defined as the presence of thyroid tissue at a site other than the pretracheal area. Nearly 1 to 3% of all ectopic thyroids are located in the lateral neck. Simultaneous submandibular ectopic thyroid tissue presenting with a functional orthotopic thyroid gland is extremely rare. In this article, we report a 37-year-old female case admitted to our clinic with a complaint of swollen neck in whom ultrasonography revealed submandibular ectopic thyroid tissue presenting with an orthotopic thyroid gland.

Ectopic pregnancy.

PubMed

Carr, R J; Evans, P

2000-03-01

Ectopic pregnancy occurs in approximately 2% of all pregnancies in the United States, and is the nation's leading cause of first trimester maternal death. Its incidence has increased sixfold in the past 25 years, despite significant improvements in techniques for early diagnosis and management. This article reviews the epidemiology, risk factors, and common clinical presentations of ectopic pregnancy. Both traditional and newly developed strategies for diagnosis and management are described. The primary care physician is in an excellent position to screen for and diagnose ectopic pregnancy, and to counsel patients regarding treatment options and future risks. With the increasing trend toward outpatient nonsurgical management of ectopics, it is expected that the roll of the primary care physician in managing patients with ectopic pregnancy will continue to increase.

Use of radiation to discourage ectopic bone. A nine-year study in surgery about the hip

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coventry, M.B.; Scanlon, P.W.

1981-02-01

Patients who had total hip arthroplasty were categorized according to the risk of development of ectopic bone. Radiation therapy was administered after operation to those considered to be at high risk of formation of ectopic bone. The dosage used was 2000 rads given in ten fractions (875 rets). Forty-eight hips in forty-two patients were treated from 1970 to 1977. Massive formation of ectopic bone did not occur in any hip when the radiation was given relatively early after operation. Thus, we believe that radiation aids in the prevention of formation of ectopic bone. Radiation was found to be of doubtfulmore » value, however, hence the ectopic bone was visible on radiography.« less

Alteration of Nrf2 and Glutamate Cysteine Ligase expression contribute to lesions growth and fibrogenesis in ectopic endometriosis.

PubMed

Marcellin, L; Santulli, P; Chouzenoux, S; Cerles, O; Nicco, C; Dousset, B; Pallardy, M; Kerdine-Römer, S; Just, P A; Chapron, C; Batteux, F

2017-09-01

The redox-sensitive nuclear factor erythroid-derived 2-like 2 (NRF2) controls endogenous antioxidant enzymes' transcription and protects against oxidative damage which is triggered by inflammation and known to favor progression of endometriosis. Glutamate Cysteine Ligase (GCL), a target gene of NRF2, is the first enzyme in the synthesis cascade of glutathione, an important endogenous antioxidant. Sixty-one patients, with thorough surgical examination of the abdominopelvic cavity, were recruited for the study: 31 with histologically-proven endometriosis and 30 disease-free women taken as controls. Expressions of NRF2 and GCL were investigated by quantitative RT-PCR and immunohistochemistry in eutopic and ectopic endometria from endometriosis-affected women and in endometrium of disease-free women. Ex vivo stromal and epithelial cells were extracted and purified from endometrial and endometriotic biopsies to explore expression of NRF2 and GCL in both stromal and epithelial compartments by western blot. Finally, in order to strengthen the role of NRF2 in endometriosis pathogenesis, we evaluated the drop of NRF2 expression in a mouse model of endometriosis using NRF2 knockout (NRF2 -/- ) mice. The mRNA levels of NRF2 and GCL were significantly lower in ectopic endometria of endometriosis-affected women compared to eutopic endometria of disease-free women. The immunohistochemical analysis confirmed the decreased expression of both NRF2 and GCL in ectopic endometriotic tissues compared to eutopic endometria of endometriosis-affected and disease-free women. Immunoblotting revealed a significant decreased of NRF2 and GCL expression in epithelial and stroma cells from ectopic lesions of endometriosis-affected women compared to eutopic endometria from controls. Using a murine model of endometriosis, NRF2 -/- implants were more fibrotic compared to wild-type with an increased weight and volume. These findings indicate that expression of the transcription factor NRF2 and its effector GCL are both profoundly deregulated in endometriotic lesions towards increased growth and fibrogenetic processes. Copyright © 2017 Elsevier Inc. All rights reserved.

Simultaneous anterior and posterior serosal mapping of gastric slow-wave dysrhythmias induced by vasopressin.

PubMed

Du, Peng; O'Grady, Gregory; Paskaranandavadivel, Niranchan; Tang, Shou-Jiang; Abell, Thomas; Cheng, Leo K

2016-06-06

What is the central question of this study? This study aimed to provide the first comparison of simultaneous high-resolution mapping of anterior and posterior gastric serosa over sustained periods. What is the main finding and its importance? Episodes of spontaneous gastric slow-wave dysrhythmias increased significantly following intravenous infusion of vasopressin compared with the baseline state. A number of persistent dysrhythmias were defined, including ectopic activation, conduction block, rotor, retrograde and collision/merger of wavefronts. Slow-wave dysrhythmias could occur either simultaneously or independently on the anterior and posterior gastric serosa, and interacted depending on activation-repolarization and frequency dynamics. High-resolution mapping enables mechanistic insights into gastric slow-wave dysrhythmias and is now achieving clinical translation. However, previous studies have focused mainly on dysrhythmias occurring on the anterior gastric wall. The present study simultaneously mapped the anterior and posterior gastric serosa during episodes of dysrhythmias induced by vasopressin to aid understanding of dysrhythmia initiation, maintenance and termination. High-resolution mapping (8 × 16 electrodes on each serosa; 20-74 cm 2 ) was performed in anaesthetized dogs. Baseline recordings (21 ± 8 min) were followed by intravenous infusion of vasopressin (0.1-0.5 IU ml -1 at 60-190 ml h -1 ) and further recordings (22 ± 13 min). Slow-wave activation maps, amplitudes, velocity, interval and frequency were calculated, and differences compared between baseline and postinfusion. All dogs demonstrated an increased prevalence of dysrhythmic events following infusion of vasopressin (17 versus 51%). Both amplitude and velocity demonstrated significant differences (baseline versus postinfusion: 3.6 versus 2.2 mV; 7.7 versus 6.5 mm s -1 ; P < 0.05 for both). Dysrhythmias occurred simultaneously or independently on the anterior and posterior serosa, and then interacted according to frequency dynamics. A number of persistent dysrhythmias were compared, including the following: ectopic activation (n = 2 animals), conduction block (n = 1), rotor (n = 2), retrograde (n = 3) and collision/merger of wavefronts (n = 2). We conclude that infusion of vasopressin induces gastric dysrhythmias, which occur across a heterogeneous range of frequencies and patterns. The results demonstrate that different classes of gastric dysrhythmias may arise simultaneously or independently in one or both surfaces of the serosa, then interact according to their relative frequencies. These results will help to inform interpretation of clinical dysrhythmia. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

A Three-Dimensional Human Atrial Model with Fiber Orientation. Electrograms and Arrhythmic Activation Patterns Relationship

PubMed Central

Tobón, Catalina; Ruiz-Villa, Carlos A.; Heidenreich, Elvio; Romero, Lucia; Hornero, Fernando; Saiz, Javier

2013-01-01

The most common sustained cardiac arrhythmias in humans are atrial tachyarrhythmias, mainly atrial fibrillation. Areas of complex fractionated atrial electrograms and high dominant frequency have been proposed as critical regions for maintaining atrial fibrillation; however, there is a paucity of data on the relationship between the characteristics of electrograms and the propagation pattern underlying them. In this study, a realistic 3D computer model of the human atria has been developed to investigate this relationship. The model includes a realistic geometry with fiber orientation, anisotropic conductivity and electrophysiological heterogeneity. We simulated different tachyarrhythmic episodes applying both transient and continuous ectopic activity. Electrograms and their dominant frequency and organization index values were calculated over the entire atrial surface. Our simulations show electrograms with simple potentials, with little or no cycle length variations, narrow frequency peaks and high organization index values during stable and regular activity as the observed in atrial flutter, atrial tachycardia (except in areas of conduction block) and in areas closer to ectopic activity during focal atrial fibrillation. By contrast, cycle length variations and polymorphic electrograms with single, double and fragmented potentials were observed in areas of irregular and unstable activity during atrial fibrillation episodes. Our results also show: 1) electrograms with potentials without negative deflection related to spiral or curved wavefronts that pass over the recording point and move away, 2) potentials with a much greater proportion of positive deflection than negative in areas of wave collisions, 3) double potentials related with wave fragmentations or blocking lines and 4) fragmented electrograms associated with pivot points. Our model is the first human atrial model with realistic fiber orientation used to investigate the relationship between different atrial arrhythmic propagation patterns and the electrograms observed at more than 43000 points on the atrial surface. PMID:23408928

Endometrial seedlings. A survival instinct? Immunomodulation and its role in the pathophysiology of endometriosis.

PubMed

Portelli, M; Pollacco, J; Sacco, K; Schembri-Wismayer, P; Calleja-Agius, J

2011-12-01

Endometriosis occurs when ectopic cells from the endometrium implant within the peritoneum. It is considered as a disease of multifactorial aetiology and affects 7-10% of women of reproductive age worldwide. In endometriosis, the immune system is thought to be dysfunctional and various studies have shown cytokine imbalance. Commonly upregulated cytokines include Tumour necrosis factor-alpha, interferon gamma and interleukin-10. Through analysis of the molecular makeup of the peritoneal fluid, a change is shown to occur, conferring resistance from macrophages and lymphocytes to endometrial cells. This is possibly due to a reduced Inter-cellular adhesion molecule-1 synthesis. Survival of ectopic endometrial cells also arises through the expression of human leukocyte antigens. Apart from the survival of ectopic/eutopic cells in endometriosis, there is marked cellular proliferation, which has also been attributed to a change in the expression of proteins such as Bcl-2-Associated X protein, B-cell lymphoma-2 protein, transforming growth factor-beta and the enzyme aromatase. Danazol and aromatase inhibitors modulate the immune system, thus allowing partial restoration of cytokine levels. Pharmacogenomics may be the way forward in developing novel treatment modalities for endometriosis.

Immunocytochemical characterization of ectopic enamel deposits and cementicles in human teeth.

PubMed

Bosshardt, Dieter D; Nanci, Antonio

2003-02-01

Despite the relative frequency and clinical relevance of radicular enamel deposits and cementicles, their etiology and nature are unknown. The purpose of the present study was therefore to evaluate the presence and distribution of mineralization-associated non-collagenous matrix proteins (NCPs) in various types of root-associated ectopic mineralizations. Human teeth were processed for embedding in epoxy or acrylic resins. Tissue sections were incubated with antibodies to amelogenins (AMEL), bone sialoprotein (BSP), and osteopontin (OPN). Radicular enamel deposits contained residual organic matrix that labeled for AMEL. In contrast, BSP and OPN were not detected in the residual enamel matrix, they were found in the cementum deposited on its surface as well as in collagen-free cementicle-like structures in the adjacent periodontal ligament. True cementicles consisted of a collagenous matrix intermixed with a non-collagenous ground substance. Labeling for BSP and OPN was mainly associated with the interfibrillar ground substance. No immunoreactivity for AMEL was detected in cementicles. These data indicate that ectopic enamel deposits on the root retain a high amount of AMEL, whereas cementicles contain BSP and OPN, two NCPs typically found in bone and cementum. These NCPs may, like in their normal tissue counterparts, play a role in the mineralization process.

Lrp5/6 are required for cerebellar development and for suppressing TH expression in Purkinje cells via β-catenin.

PubMed

Huang, Ying; Zhang, Qiong; Song, Ning-Ning; Zhang, Lei; Sun, Yu-Ling; Hu, Ling; Chen, Jia-Ying; Zhu, Weidong; Li, Jue; Ding, Yu-Qiang

2016-01-15

The cerebellum is responsible for coordinating motor functions and has a unique laminated architecture. Purkinje cells are inhibitory neurons and represent the only output from the cerebellar cortex. Tyrosine hydroxylase (TH) is the key enzyme for the synthesis of catecholamines, including dopamine and noradrenaline, and it is normally not expressed in cerebellar neurons. We report here that the low-density lipoprotein receptors (Lrp) 5 and 6, Wnt co-receptors, are required for the development of the cerebellum and for suppressing ectopic TH expression in Purkinje cells. Simultaneous inactivation of Lrp 5 and 6 by Nestin-Cre results in defective lamination and foliation of the cerebellum during postnatal development. Surprisingly, TH is ectopically expressed by Purkinje cells, although they still keep its other neurochemical characteristics. These phenotypes are also observed in the cerebellum of GFAP-Cre;β-catenin(flox/flox) mice, and AAV2-Cre-mediated gene deletion leads to ectopic TH expression in Purkinje cells of β-catenin(flox/flox) mice as well. Our results revealed a new role of the canonical Lrp5/6-β-catenin pathway in regulating the morphogenesis of the cerebellum during postnatal development.

Human Chorionic Gonadotropine in Cul-de-sac Fluid in Tubal Ectopic Pregnacy; A New Diagnostic Approach.

PubMed

Karahasanoglu, Ayse; Uzun, Isil; Ozdemir, Mucize; Yazicioglu, Fehmi

2016-04-01

Although new diagnostic abilities are being utilised increasingly yet early detection of tubal pregnancy remains a challenge. The use of highly sensitive hCG kits has facilitated the early diagnosis of a pregnancy. But it takes time to determine the localisation of the pregnancy. Early diagnosis of ectopic pregnancy may reduce the morbidity of ectopic pregnancy. This study was conducted to analyse the cul-de-sac and serum βhCG ratio in tubal ectopic pregnancy cases which may be a new diagnostic approach for ectopic pregnancy. Between January 2004 and July 2011, 263 patients with ectopic pregnancy were included in the study. Risk factors of patients and treatment modalities were evaluated. hCG was measured in peripheral serum and peritoneal fluid, obtained by puncture of Douglas pouch in 52 patients with tubal ectopic pregnancy. hCG level was determined in the cul-de-sac fluid and in the maternal serum for comparison. Tubectomy (5.3%), history of abortion (9.5%), history of previous surgery (14.8%), previous cesarean section (8%) and pelvic infamatorry disease (15.9 %) were the important risk factors for ectopic pregnancy in our cases. In 51 of 52 patients with tubal pregnancy, the cul-de-sac hCG vaule and the serum hCG value ratio was >1. It is concluded that the ratio of hCG in cul-de -sac and serum can be used for the verification of tubal ectopic pregnancy in addition to other diagnostic methods. This may help rapid confirmation of the diagnosis of ectopic pregnancy.

Prevalence of ectopic intrathyroidal thymus in Japan: the Fukushima health management survey.

PubMed

Fukushima, Toshihiko; Suzuki, Satoru; Ohira, Tetsuya; Shimura, Hiroki; Midorikawa, Sanae; Ohtsuru, Akira; Sakai, Akira; Abe, Masafumi; Yamashita, Shunichi; Suzuki, Shinichi

2015-05-01

Ectopic intrathyroidal thymus is thought to be a rare entity, often discovered incidentally, and is due to aberrant thymic migration during embryogenesis. The aim of this study was to determine the prevalence of ectopic intrathyroidal thymus in children using ultrasound screening. This study was cross-sectional and was conducted with the initial preliminary survey of the Fukushima Health Management Survey between October 9, 2011, and March 31, 2012, after the Fukushima Daiichi Nuclear Power Plant accident. A total of 37,816 children were examined in the survey. Diagnostic criteria are based on the ultrasonographic appearance of ectopic intrathyroidal thymus, which were round, oval, or polygonal hypoechoic or hyperechoic areas, with multiple granular and punctate echogenic foci. A total of 375 (0.99%) cases (164 girls) with ectopic intrathyroidal thymus were observed. The mean age was 7.0 years (range 0-18 years). Ectopic intrathyroidal thymus was located in the right (n=180), left (n=178), or bilateral (n=17) thyroid lobes. The incidence of ectopic intrathyroidal thymus was inversely correlated with age and body mass index. The results reflect the prevalence of ectopic intrathyroidal thymus using ultrasonography in the general population. Further examination will be needed by way of longitudinal follow-up.

Ectopic Pregnancy

MedlinePlus

... woman is pregnant. If you have an ectopic pregnancy, the fertilized egg grows in the wrong place, ... tubes. The result is usually a miscarriage. Ectopic pregnancy can be a medical emergency if it ruptures. ...

Ectopic hepatic parenchyma attached to the diaphragm: simulating a pulmonary mass in a cat.

PubMed

Dhaliwal, Ravinder S; Lacey, Janice K

2009-01-01

A case of an ectopic lobe of the liver connected to a normal diaphragm is described. A 9-year-old, castrated male cat underwent thoracotomy for a pulmonary mass. The removed mass was attached to the diaphragm that histologically was ectopic liver. The ectopic liver had no connection with the main liver. Because the occurrence of ectopic supradiaphragmatic hepatic tissue is a possibility, this should be considered as a differential diagnosis for caudal pulmonary or caudal mediastinal masses in a cat. This report describes, to the authors' knowledge, the first case of ectopic hepatic tissue attached to the diaphragm of a cat. The authors also characterize the asymptomatic clinical presentation and radiographic findings of this cat and suggest further imaging with computed tomography in unusual case presentations.

A System and Method for Online High-Resolution Mapping of Gastric Slow-Wave Activity

PubMed Central

Bull, Simon H.; O’Grady, Gregory; Du, Peng

2015-01-01

High-resolution (HR) mapping employs multielectrode arrays to achieve spatially detailed analyses of propagating bioelectrical events. A major current limitation is that spatial analyses must currently be performed “off-line” (after experiments), compromising timely recording feedback and restricting experimental interventions. These problems motivated development of a system and method for “online” HR mapping. HR gastric recordings were acquired and streamed to a novel software client. Algorithms were devised to filter data, identify slow-wave events, eliminate corrupt channels, and cluster activation events. A graphical user interface animated data and plotted electrograms and maps. Results were compared against off-line methods. The online system analyzed 256-channel serosal recordings with no unexpected system terminations with a mean delay 18 s. Activation time marking sensitivity was 0.92; positive predictive value was 0.93. Abnormal slow-wave patterns including conduction blocks, ectopic pacemaking, and colliding wave fronts were reliably identified. Compared to traditional analysis methods, online mapping had comparable results with equivalent coverage of 90% of electrodes, average RMS errors of less than 1 s, and CC of activation maps of 0.99. Accurate slow-wave mapping was achieved in near real-time, enabling monitoring of recording quality and experimental interventions targeted to dysrhythmic onset. This work also advances the translation of HR mapping toward real-time clinical application. PMID:24860024

The ginsenoside PPD exerts anti-endometriosis effects by suppressing estrogen receptor-mediated inhibition of endometrial stromal cell autophagy and NK cell cytotoxicity.

PubMed

Zhang, Bing; Zhou, Wen-Jie; Gu, Chun-Jie; Wu, Ke; Yang, Hui-Li; Mei, Jie; Yu, Jia-Jun; Hou, Xiao-Fan; Sun, Jian-Song; Xu, Feng-Yuan; Li, Da-Jin; Jin, Li-Ping; Li, Ming-Qing

2018-05-14

Endometriosis (EMS) is an estrogen-dependent gynecological disease with a low autophagy level of ectopic endometrial stromal cells (eESCs). Impaired NK cell cytotoxic activity is involved in the clearance obstruction of the ectopic endometrial tissue in the abdominopelvic cavity. Protopanaxadiol (PPD) and protopanaxatriol (PPT) are two metabolites of ginsenosides, which have profound biological functions, such as anti-cancer activities. However, the role and mechanism of ginsenosides and metabolites in endometriosis are completely unknown. Here, we found that the compounds PPD, PPT, ginsenoside-Rg3 (G-Rg3), ginsenoside-Rh2 (G-Rh2), and esculentoside A (EsA) led to significant decreases in the viability of eESCs, particularly PPD (IC50 = 30.64 µM). In vitro and in vivo experiments showed that PPD promoted the expression of progesterone receptor (PR) and downregulated the expression of estrogen receptor α (ERα) in eESCs. Treatment with PPD obviously induced the autophagy of eESCs and reversed the inhibitory effect of estrogen on eESC autophagy. In addition, eESCs pretreated with PPD enhanced the cytotoxic activity of NK cells in response to eESCs. PPD decreased the numbers and suppressed the growth of ectopic lesions in a mouse EMS model. These results suggest that PPD plays a role in anti-EMS activation, possibly by restricting estrogen-mediated autophagy regulation and enhancing the cytotoxicity of NK cells. This result provides a scientific basis for potential therapeutic strategies to treat EMS by PPD or further structural modification.

Secondary abdominal appendicular ectopic pregnancy.

PubMed

Nama, Vivek; Gyampoh, Bright; Karoshi, Mahantesh; McRae, Reynold; Opemuyi, Isaac

2007-01-01

Although the case fatality rate for ectopic pregnancies has decreased to 0.08% in industrialized countries, it still represents 3.8% of maternal mortality in the United States alone. In developing countries, the case fatality rate varies from 3% to 27%. Laparoscopic management of tubal pregnancies is now the standard form of treatment where this technology is available. Abdominal pregnancies are rare, and secondary implantation of tubal ectopic pregnancies is the most common cause of abdominal gestations. We present an interesting case of secondary implantation of a tubal ectopic pregnancy to highlight the appendix as a possible secondary implantation site after a tubal ectopic pregnancy.

The utility of neck ultrasound and sestamibi scans in patients with secondary and tertiary hyperparathyroidism.

PubMed

Alkhalili, Eyas; Tasci, Yunus; Aksoy, Erol; Aliyev, Shamil; Soundararajan, Saranya; Taskin, Eren; Siperstein, Allan; Berber, Eren

2015-03-01

Secondary hyperparathyroidism (SHPT) and tertiary hyperparathyroidism (THPT) are disease entities in patients with chronic kidney disease that are caused by parathyroid hyperplasia. The role of preoperative localization studies in patients undergoing parathyroidectomy for these conditions remains poorly defined. To evaluate the utility of surgeon-performed neck ultrasound (US) as well as sestamibi scans in the localization of parathyroid glands in patients with SHPT/THPT. A retrospective analysis of patients with SHPT/THPT who underwent parathyroidectomy at a single institution. Results of preoperative localization studies were compared to intraoperative findings. One hundred and three patients underwent parathyroidectomy for SHPT/THPT. All patients underwent surgeon-performed neck US, while 92 (89%) underwent sestamibi scans. US failed to localize any of the parathyroids in 4 patients (3.8%), while sestamibi was negative in 11 (12%). Forty-seven ectopic glands were identified in 38 patients in whom sestamibi was performed. In five patients (13%), ectopic glands were identified by both modalities, by US only in 6 (16%), by sestamibi only in 8 (21%), and by neither study in 19 patients (50%). US showed new thyroid nodules in 19 patients (18.4 %), leading to lobectomy or thyroidectomy at the time of parathyroidectomy in 16 patients (15.5%). Pathology showed malignancy in 7 patients (6.8%). US and MIBI offer little benefit in localizing ectopic glands and rarely change the conduct of a standard four-gland exploration. Although there was a benefit of US in the assessment of thyroid nodules, in only 8.7% of patients was sestamibi of benefit in identifying ectopic glands.

Ectopic expression of hoxb2 after retinoic acid treatment or mRNA injection: disruption of hindbrain and craniofacial morphogenesis in zebrafish embryos.

PubMed

Yan, Y L; Jowett, T; Postlethwait, J H

1998-12-01

To investigate pattern formation in the vertebrate hindbrain, we isolated a full length hoxb2 cDNA clone from zebrafish. In a gene phylogeny, zebrafish hoxb2 clusters with human HOXB2, and it maps on linkage group 3 along with several other loci whose orthologues are syntenic with human HOXB2. In the hindbrain, hoxb2 is expressed at high levels in rhombomere 3 (r3), lower levels in r4, still lower in r5, and at undetectable levels in r6. In r7, r8, and the rostral spinal cord, hoxb2 is expressed at a lower level than in r5. Lateral cells appearing to emanate from r4 express both hoxb2 and dlx2, suggesting that they are neural crest. Overexpression of hoxb2 by mRNA injections into early cleavage stage embryos resulted in abnormal morphogenesis of the midbrain and rostral hindbrain, abnormal patterning in r4, fusion of cartilage elements arising from pharyngeal arches 1 and 2, and ectopic expression of krx20 and valentino (but not pax2, rtk1, or hoxb1) in the rostral hindbrain, midbrain, and, surprisingly, the eye. Treatments with retinoic acid produced a phenotype similar to that of ectopic hoxb2 expression, including ectopic krx20 (but not valentino) expression in the eye, and fusion of cartilages from pharyngeal arches 1 and 2. The results suggest that hoxb2 plays an important role in the patterning of hindbrain and pharyngeal arches in the zebrafish.

Cx43-hemichannel function and regulation in physiology and pathophysiology: insights from the bovine corneal endothelial cell system and beyond

PubMed Central

D'hondt, Catheleyne; Iyyathurai, Jegan; Himpens, Bernard; Leybaert, Luc; Bultynck, Geert

2014-01-01

Intercellular communication in primary bovine corneal endothelial cells (BCECs) is mainly driven by the release of extracellular ATP through Cx43 hemichannels. Studying the characteristics of Ca2+-wave propagation in BCECs, an important form of intercellular communication, in response to physiological signaling events has led to the discovery of important insights in the functional properties and regulation of native Cx43 hemichannels. Together with ectopic expression models for Cx43 hemichannels and truncated/mutated Cx43 versions, it became very clear that loop/tail interactions play a key role in controlling the activity of Cx43 hemichannels. Interestingly, the negative regulation of Cx43 hemichannels by enhanced actin/myosin contractility seems to impinge upon loss of these loop/tail interactions essential for opening Cx43 hemichannels. Finally, these molecular insights have spurred the development of novel peptide tools that can selectively inhibit Cx43 hemichannels, but neither Cx43 gap junctions nor hemichannels formed by other Cx isoforms. These tools now set the stage to hunt for novel physiological functions for Cx43 hemichannels in primary cells and tissues and to tackle disease conditions associated with excessive, pathological Cx43-hemichannel openings. PMID:25309448

Human Chorionic Gonadotropine in Cul-de-sac Fluid in Tubal Ectopic Pregnacy; A New Diagnostic Approach

PubMed Central

Karahasanoglu, Ayse; Ozdemir, Mucize; Yazicioglu, Fehmi

2016-01-01

Introduction Although new diagnostic abilities are being utilised increasingly yet early detection of tubal pregnancy remains a challenge. The use of highly sensitive hCG kits has facilitated the early diagnosis of a pregnancy. But it takes time to determine the localisation of the pregnancy. Early diagnosis of ectopic pregnancy may reduce the morbidity of ectopic pregnancy. Aim This study was conducted to analyse the cul-de-sac and serum βhCG ratio in tubal ectopic pregnancy cases which may be a new diagnostic approach for ectopic pregnancy. Materials and Methods Between January 2004 and July 2011, 263 patients with ectopic pregnancy were included in the study. Risk factors of patients and treatment modalities were evaluated. hCG was measured in peripheral serum and peritoneal fluid, obtained by puncture of Douglas pouch in 52 patients with tubal ectopic pregnancy. hCG level was determined in the cul-de-sac fluid and in the maternal serum for comparison. Results Tubectomy (5.3%), history of abortion (9.5%), history of previous surgery (14.8%), previous cesarean section (8%) and pelvic infamatorry disease (15.9 %) were the important risk factors for ectopic pregnancy in our cases. In 51 of 52 patients with tubal pregnancy, the cul-de-sac hCG vaule and the serum hCG value ratio was >1. Conclusion It is concluded that the ratio of hCG in cul-de –sac and serum can be used for the verification of tubal ectopic pregnancy in addition to other diagnostic methods. This may help rapid confirmation of the diagnosis of ectopic pregnancy. PMID:27190895

Triple ectopic thyroid: A rare entity

PubMed Central

Nilegaonkar, Sujit; Naik, Chetna; Sonar, Sameer; Hirawe, Deepti

2011-01-01

Ectopic thyroid tissue is an uncommon congenital aberration. It is extremely rare to have three ectopic foci at three different sites. The thyroid scan has been used successfully to diagnose ectopic thyroid tissue. We report a case of ectopic thyroid tissue at base of tongue, another at the level of hyoid and third one as aberrant tissue at suprahyoid location in a 16 year old female who presented with swelling in front of neck. This patient was clinically diagnosed as thyroglossal cyst and was being planned for surgery. Preoperative thyroid scan helped in establishing diagnosis of ectopic thyroid which was the only functioning thyroid tissue. Thus, it prevented unnecessary surgery. Therefore it is suggested that thyroid scan and USG/CT scan must be done as routine work up in neck swellings pre operatively to avoid unnecessary surgeries. PMID:23559716

Regulatory role of AINTEGUMENTA in organ initiation and growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krizek, Beth Allyn; Lebioda, Lukasz

2005-03-01

Although several members of the plant-specific AP2/ERF family of transcription factors are important developmental regulators, many genes in this large protein family remain uncharacterized. Here, we present a phylogenetic analysis of the18 genes that make up the AP2 subgroup of this family. We report expression analyses of seven Arabidopsis genes most closely related to the floral development gene AINTEGUMENTA and show that all AINTEGUMENTA-like (AIL) genes are transcribed in multiple tissues during development. They are expressed primarily in young actively dividing tissues of a plant and not in mature leaves or stems. The spatial distribution of AIL5, AIL6, and AIL7more » mRNA in inflorescences was characterized by in situ hybridization. Each of these genes is expressed in a spatially and temporally distinct pattern within inflorescence meristems and flowers. Ectopic expression of AIL5 resulted in a larger floral organ phenotype, similar to that resulting from ectopic expression of ANT. Our results are consistent with AIL genes having roles in specification of meristematic or division-competent states.« less

Human Chorionic Gonadotropin and Breast Cancer

PubMed Central

Schüler-Toprak, Susanne; Treeck, Oliver; Ortmann, Olaf

2017-01-01

Breast cancer is well known as a malignancy being strongly influenced by female steroids. Pregnancy is a protective factor against breast cancer. Human chorionic gonadotropin (HCG) is a candidate hormone which could mediate this antitumoral effect of pregnancy. For this review article, all original research articles on the role of HCG in breast cancer were considered, which are listed in PubMed database and were written in English. The role of HCG in breast cancer seems to be a paradox. Placental heterodimeric HCG acts as a protective agent by imprinting a permanent genomic signature of the mammary gland determining a refractory condition to malignant transformation which is characterized by cellular differentiation, apoptosis and growth inhibition. On the other hand, ectopic expression of β-HCG in various cancer entities is associated with poor prognosis due to its tumor-promoting function. Placental HCG and ectopically expressed β-HCG exert opposite effects on breast tumorigenesis. Therefore, mimicking pregnancy by treatment with HCG is suggested as a strategy for breast cancer prevention, whereas targeting β-HCG expressing tumor cells seems to be an option for breast cancer therapy. PMID:28754015

The peripheral nervous system supports blood cell homing and survival in the Drosophila larva

PubMed Central

Makhijani, Kalpana; Alexander, Brandy; Tanaka, Tsubasa; Rulifson, Eric; Brückner, Katja

2011-01-01

Interactions of hematopoietic cells with their microenvironment control blood cell colonization, homing and hematopoiesis. Here, we introduce larval hematopoiesis as the first Drosophila model for hematopoietic colonization and the role of the peripheral nervous system (PNS) as a microenvironment in hematopoiesis. The Drosophila larval hematopoietic system is founded by differentiated hemocytes of the embryo, which colonize segmentally repeated epidermal-muscular pockets and proliferate in these locations. Importantly, we show that these resident hemocytes tightly colocalize with peripheral neurons and we demonstrate that larval hemocytes depend on the PNS as an attractive and trophic microenvironment. atonal (ato) mutant or genetically ablated larvae, which are deficient for subsets of peripheral neurons, show a progressive apoptotic decline in hemocytes and an incomplete resident hemocyte pattern, whereas supernumerary peripheral neurons induced by ectopic expression of the proneural gene scute (sc) misdirect hemocytes to these ectopic locations. This PNS-hematopoietic connection in Drosophila parallels the emerging role of the PNS in hematopoiesis and immune functions in vertebrates, and provides the basis for the systematic genetic dissection of the PNS-hematopoietic axis in the future. PMID:22071105

Ectopic recurrence of craniopharyngioma: Reporting three new cases.

PubMed

Yang, Yang; Shrestha, David; Shi, Xiang-En; Zhou, Zhongqing; Qi, Xueling; Qian, Hai

2015-04-01

Ectopic recurrence of craniopharyngioma is extremely rare following transcranial procedures of primary tumour. Here we describe 3 new cases of ectopic recurrence along the surgical route after transcranial gross total resection of primary tumour. All 3 cases are male adults--2 of them had papillary-type tumour with the other being adamantinomatous. All ectopic tumours were safely resected via repeated craniotomy. Long-term surveillance of patients with resected craniopharyngioma is essential.

[Early diagnosis of ectopic pregnancy].

PubMed

Belics, Zoran; Gérecz, Balázs; Csákány, M György

2014-07-20

Ectopic pregnancy is a high-risk condition that occurs in 2% of reported pregnancies. This percentage is fivefold higher than that registered in the 1970s. Since 1970 there has been a two-fold increase in the ratio of ectopic pregnancies to all reported pregnancies in Hungary and in 2012 7.4 ectopic pregnancies per thousand registered pregnancies were reported. Recently, the majority (80%) of cases can be diagnosed in early stage, and the related mortality objectively decreased in the past few decades to 3.8/10,000 ectopic pregnancies. If a woman with positive pregnancy test has abdominal pain and/or vaginal bleeding the physician should perform a work-up to safely exclude the possibility of ectopic pregnancy. The basis of diagnosis is ultrasonography, especially vaginal ultrasound examination and measurement of the β-subunit of human chorionic gonadotropin. The ultrasound diagnosis is based on the visualization of an ectopic mass rather than the inability to visualize an intrauterine pregnancy. In some questionable cases the diagnostic uterine curettage or laparoscopy may be useful. The actuality of this topic is justified by practical difficulties in obtaining correct diagnosis, especially in the early gestational time.

Single point biochemical measurement algorithm for early diagnosis of ectopic pregnancy.

PubMed

Butler, Stephen A; Abban, Thomas K A; Borrelli, Paola T A; Luttoo, Jameel M; Kemp, Bryn; Iles, Ray K

2013-09-01

Tubal rupture as a result of an ectopic pregnancy is the leading cause of first trimester maternal mortality. Currently, the diagnosis of ectopic pregnancy depends on transvaginal ultrasound and serial serum measurements of human chorionic gonadotrophin (hCG), which requires follow up. The objective of this study was to examine whether single point measurements at presentation could distinguish between women with ectopic pregnancy, viable pregnancy, and spontaneous miscarriage. Serum total hCG (hCGt), hyperglycosylated hCG (hCGh), free beta subunit of hCG (hCGβ), progesterone (P), and CA-125 were measured by chemiluminescence immunoassay over a 3 month period in 441 women presenting at the emergency room with abdominal pain and a positive pregnancy test. Patient outcomes were followed and confirmed by histology. 65 samples were excluded due to poor sample storage, or lost to follow up. The pregnancy outcomes were 175 viable pregnancies, 175 spontaneous miscarriages, and 26 ectopic pregnancies. A serum hCGt <3736 mIU/mL cut off was 100% sensitive, with 76% specificity, for distinguishing ectopic pregnancy from viable pregnancy; but did not differentiate spontaneous miscarriage. Serum CA125 <41.98 U/mL produced 100% sensitivity and 43% specificity in distinguishing ectopic pregnancy from spontaneous miscarriage. Sequential application of hCGt and CA-125 cut off followed by ultrasound could detect 100% of ectopic pregnancies with 87% specificity for all intrauterine pregnancies. The combination of serum hCGt <3736 mIU/mL, followed by CA125 <41.98 U/mL is a promising algorithm for detecting all ectopic pregnancy at initial presentation. © 2013.

Evaluation of cystoscopic-guided laser ablation of intramural ectopic ureters in female dogs.

PubMed

Berent, Allyson C; Weisse, Chick; Mayhew, Philipp D; Todd, Kimberly; Wright, Monika; Bagley, Demetrius

2012-03-15

To describe and evaluate the short- and long-term outcomes in female dogs after cystoscopic-guided laser ablation of ectopic ureters (CLA-EU). Prospective case series. 32 incontinent female dogs with intramural ectopic ureters. A diagnosis of intramural ectopic ureters was made via cystoscopy and fluoroscopy in all patients. Transurethral CLA-EU (via diode laser [n = 27] or Holmium:yttrium aluminum garnet laser [3]) was performed to relocate the ectopic ureteral orifice cranially into the urinary bladder. All vaginal anomalies were treated with the laser concurrently. Follow-up evaluation was standardized and included urinary continence scoring, serial bacteriologic culture of urine samples, and a follow-up cystoscopy 6 to 8 weeks after CLA-EU. Ectopic ureteral orifices of all dogs were initially located in the urethra. Eighteen of 30 dogs had bilateral ectopic ureters, and 12 had unilateral ectopic ureters. All dogs had other concurrent urinary anomalies. At the time of last follow-up (median, 2.7 years after CLA-EU, [range, 12 to 62 months]), 14 of 30 (47%) dogs did not require any additional treatments following CLA-EU to maintain urinary continence. For the 16 residually incontinent dogs, the addition of medical management, transurethral bulking-agent injection, or placement of a hydraulic occluder was effective in 3, 2, and 4 dogs, respectively, improving the overall urinary continence rate to 77% (23/30 dogs). One dog had evidence of polypoid cystitis at the neoureteral orifice 6 weeks after CLA-EU that was resolved at 3 months. CLA-EU provided an effective, safe, and minimally invasive alternative to surgery for intramural ectopic ureters in female dogs.

Mitochondrial F1Fo-ATP synthase translocates to cell surface in hepatocytes and has high activity in tumor-like acidic and hypoxic environment.

PubMed

Ma, Zhan; Cao, Manlin; Liu, Yiwen; He, Yiqing; Wang, Yingzhi; Yang, Cuixia; Wang, Wenjuan; Du, Yan; Zhou, Muqing; Gao, Feng

2010-08-01

F1Fo-ATP synthase was originally thought to exclusively locate in the inner membrane of the mitochondria. However, recent studies prove the existence of ectopic F1Fo-ATP synthase on the outside of the cell membrane. Ectopic ATP synthase was proposed as a marker for tumor target therapy. Nevertheless, the protein transport mechanism of the ectopic ATP synthase is still unclear. The specificity of the ectopic ATP synthase, with regard to tumors, is questioned because of its widespread expression. In the current study, we constructed green fluorescent protein-ATP5B fusion protein and introduced it into HepG2 cells to study the localization of the ATP synthase. The expression of ATP5B was analyzed in six cell lines with different 'malignancies'. These cells were cultured in both normal and tumor-like acidic and hypoxic conditions. The results suggested that the ectopic expression of ATP synthase is a consequence of translocation from the mitochondria. The expression and catalytic activity of ectopic ATP synthase were similar on the surface of malignant cells as on the surface of less malignant cells. Interestingly, the expression of ectopic ATP synthase was not up-regulated in tumor-like acidic and hypoxic microenvironments. However, the catalytic activity of ectopic ATP synthase was up-regulated in tumor-like microenvironments. Therefore, the specificity of ectopic ATP synthase for tumor target therapy relies on the high level of catalytic activity that is observed in acidic and hypoxic microenvironments in tumor tissues.

Comparison of ectopic pregnancy risk among transfers of embryos vitrified on day 3, day 5, and day 6.

PubMed

Du, Tong; Chen, Hong; Fu, Rong; Chen, Qiuju; Wang, Yun; Mol, Ben W; Kuang, Yanping; Lyu, Qifeng

2017-07-01

To compare ectopic pregnancy risk among transfers of embryos vitrified on day 3, day 5, and day 6. Retrospective cohort study. Academic tertiary-care medical center. A total of 10,736 pregnancies after 23,730 frozen-thawed embryo transfer (FET) cycles of in vitro fertilization/intracytoplasmic sperm injection from March 2003 to May 2015. The ectopic pregnancy rate was compared among pregnancies resulting from transfers of embryos vitrified on day 3, day 5, and day 6. Generalized estimation equation regression models were used to calculate unadjusted and adjusted odds ratios and 95% confidence intervals for the association between ectopic pregnancy and selected patient and treatment characteristics. We studied this association in both the group that achieved pregnancy and the group that underwent an FET cycle. Odds of ectopic pregnancy. The overall rate of ectopic pregnancy was 2.8% (304/10,736). Ectopic pregnancy rates after day-3, day-5, and day-6 vitrified embryo transfers were 3.1% (287/9,224), 2.0% (11/562), and 0.6% (6/950), respectively. After adjusting for confounders, the risks of ectopic pregnancy in day-3 and day-5 vitrified embryo transfers were both significantly higher than in day-6 vitrified embryo transfers. The associations were similar when we did calculations per cycle. In women undergoing FET, day-6 vitrified embryo transfer is associated with a significantly lower risk of ectopic pregnancy than both day-3 and day-5 vitrified embryo transfers. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Magnetic resonance imaging - A troubleshooter in obstetric emergencies: A pictorial review

PubMed Central

Gupta, Rohini; Bajaj, Sunil Kumar; Kumar, Nishith; Chandra, Ranjan; Misra, Ritu Nair; Malik, Amita; Thukral, Brij Bhushan

2016-01-01

The application of magnetic resonance imaging (MRI) in pregnancy faced initial skepticism of physicians because of fetal safety concerns. The perceived fetal risk has been found to be unwarranted and of late, the modality has attained acceptability. Its role in diagnosing fetal anomalies is well recognized and following its safety certification in pregnancy, it is finding increasing utilization during pregnancy and puerperium. However, the use of MRI in maternal emergency obstetric conditions is relatively limited as it is still evolving. In early gestation, ectopic implantation is one of the major life-threatening conditions that are frequently encountered. Although ultrasound (USG) is the accepted mainstay modality, the diagnostic predicament persists in many cases. MRI has a role where USG is indeterminate, particularly in the extratubal ectopic pregnancy. Later in gestation, MRI can be a useful adjunct in placental disorders like previa, abruption, and adhesion. It is a good problem-solving tool in adnexal masses such as ovarian torsion and degenerated fibroid, which have a higher incidence during pregnancy. Catastrophic conditions like uterine rupture can also be preoperatively and timely diagnosed. MRI has a definite role to play in postpartum and post-abortion life-threatening conditions, e.g., retained products of conception, and gestational trophoblastic disease, especially when USG is inconclusive or inadequate. PMID:27081223

Rac1 Dosage Is Crucial for Normal Endochondral Bone Growth.

PubMed

Suzuki, Dai; Bush, Jason R; Bryce, Dawn-Marie; Kamijo, Ryutaro; Beier, Frank

2017-10-01

Rac1, a member of the small Rho GTPase family, plays multiple cellular roles. Studies of mice conditionally lacking Rac1 have revealed essential roles for Rac1 in various tissues, including cartilage and limb mesenchyme, where Rac1 loss produces dwarfism and long bone shortening. To gain further insight into the role of Rac1 in skeletal development, we have used transgenic mouse lines to express a constitutively active (ca) Rac1 mutant protein in a Cre recombinase-dependent manner. Overexpression of caRac1 in limb bud mesenchyme or chondrocytes leads to reduced body weight and shorter bones compared with control mice. Histological analysis of growth plates showed that caRac1;Col2-Cre mice displayed ectopic hypertrophic chondrocytes in the proliferative zone and enlarged hypertrophic zones. These mice also displayed a reduced proportion of proliferating cell nuclear antigen-positive cells in the proliferative zone and nuclear β-catenin localization in the ectopic hypertrophic chondrocytes. Importantly, overexpression of caRac1 partially rescued the phenotypes of Rac1fl/fl;Col2-Cre and Rac1fl/fl;Prx1-Cre conditional knockout mice, including body weight, bone length, and growth plate disorganization. These results suggest that tight regulation of Rac1 activity is necessary for normal cartilage development. Copyright © 2017 Endocrine Society.

42 CFR 136.55 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2013 CFR

2013-10-01

... pregnancies. 136.55 Section 136.55 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... devices and termination of ectopic pregnancies. Federal funds are available for drugs or devices to... an ectopic pregnancy. ...

42 CFR 136.55 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2011 CFR

2011-10-01

... pregnancies. 136.55 Section 136.55 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... devices and termination of ectopic pregnancies. Federal funds are available for drugs or devices to... an ectopic pregnancy. ...

42 CFR 136.55 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... pregnancies. 136.55 Section 136.55 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... devices and termination of ectopic pregnancies. Federal funds are available for drugs or devices to... an ectopic pregnancy. ...

42 CFR 136.55 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2012 CFR

2012-10-01

... pregnancies. 136.55 Section 136.55 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... devices and termination of ectopic pregnancies. Federal funds are available for drugs or devices to... an ectopic pregnancy. ...

42 CFR 136.55 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2014 CFR

2014-10-01

... pregnancies. 136.55 Section 136.55 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... devices and termination of ectopic pregnancies. Federal funds are available for drugs or devices to... an ectopic pregnancy. ...

Ectopic Pregnancy

MedlinePlus

... are experiencing a typical pregnancy or an ectopic pregnancy. Abnormal bleeding and pelvic pain should be reported to your obstetrician–gynecologist ( ... health care professional suspects you may have ectopic pregnancy, he or she may perform a pelvic exam perform an ultrasound exam to see where ...

Severe hypertension and hypokalemia as first clinical manifestations in ectopic Cushing's syndrome.

PubMed

Fernández-Rodríguez, Eva; Villar-Taibo, Rocío; Pinal-Osorio, Iria; Cabezas-Agrícola, José Manuel; Anido-Herranz, Urbano; Prieto, Alma; Casanueva, Felipe F; Araujo-Vilar, David

2008-08-01

Ectopic ACTH production occurs in about 10% of all cases of Cushing's syndrome, and about 25% of cases of ACTH-dependent Cushing's syndrome. Diverse tumor types are able to produce ACTH ectopically, including small cell lung carcinoma. Ectopic ACTH secretion by malignant neoplasm has been reported to have earlier and more aggressive metabolic effects. We report a 59-year-old male patient with severe hypertension, metabolic alkalosis and hypokalemia as the first clinical manifestations of an ACTH-secreting small cell lung carcinoma, although the typical phenotypic features of Cushing's syndrome were not present. Ectopic Cushing's syndrome should always be ruled out in patients with severe hypertension and hypokalemia.

Canonical WNT signalling determines lineage specificity in Wilms tumour.

PubMed

Fukuzawa, R; Anaka, M R; Weeks, R J; Morison, I M; Reeve, A E

2009-02-26

Wilms tumours (WTs) have two distinct types of histology with or without ectopic mesenchymal elements, suggesting that WTs arise from either the mesenchymal or epithelial nephrogenic lineages. Regardless of the presence or absence of CTNNB1 mutations, nuclear accumulation of beta-catenin is often observed in WTs with ectopic mesenchymal elements. Here, we addressed the relationship between the WNT-signalling pathway and lineage in WTs by examining CTNNB1 and WT1 mutations, nuclear accumulation of beta-catenin, tumour histology and gene expression profiles. In addition, we screened for mutations in WTX, which has been proposed to be a negative regulator of the canonical WNT-signalling pathway. Unsupervised clustering analysis identified two classes of tumours: mesenchymal lineage WNT-dependent tumours, and epithelial lineage WNT-independent tumours. In contrast to the mesenchymal lineage specificity of CTNNB1 mutations, WTX mutations were surprisingly observed in both lineages. WTX-mutant WTs with ectopic mesenchymal elements had nuclear accumulation of beta-catenin, upregulation of WNT target genes and an association with CTNNB1 mutations in exon 7 or 8. However, epithelial lineage WTs with WTX mutations had no indications of active WNT signalling, suggesting that the involvement of WTX in the WNT-signalling pathway may be lineage dependent, and that WTX may have an alternative function to its role in the canonical WNT-signalling pathway.

Ectopical expression of FABP4 gene can induce bovine muscle-derived stem cells adipogenesis.

PubMed

Zhang, Le; Zhao, Yanfang; Ning, Yue; Wang, Hongbao; Zan, Linsen

2017-01-08

Fatty acid binding protein 4 (FABP4) plays a key role in Fatty acid catabolism in mammals. Findings from our previous studies have indicated that FABP4 neither affect the differentiation of bovine preadipocytes nor does it change the expression of upstream genes. To investigate whether ectopically expressed FABP4 can induces Muscle-Derived Stem Cells (MDSCs) lipid synthesis and understand the regulatory mechanism behind it. In this study, adenoviruses infection is achieved to ectopically expressed FABP4 in bovine MDSCs, RNA-seq analyses at the very early stages of induction were performed to reveal gene expression level changes during MDSCs transdifferentiation. Results showed FABP4 can induce bovine Muscle-Derived Stem Cells transdifferentiation into adipocyte-like cells, 23 genes' expression levels changed after 24 h inducing although there is no significant change in cell phenotypes. Along with induction time, more differently expressed genes (256 genes changes after 48 h induction) were screened out. These genes should be at the downstream of signal pathways and be regulated by the 23 genes identified before. Our findings may provide a unique new model for studying the molecular control of cattle cross-talk between adipose and skeletal muscle. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Unus pro omnibus, omnes pro uno: A novel, evidence-based, unifying theory for the pathogenesis of endometriosis.

PubMed

Laganà, Antonio Simone; Vitale, Salvatore Giovanni; Salmeri, Francesca Maria; Triolo, Onofrio; Ban Frangež, Helena; Vrtačnik-Bokal, Eda; Stojanovska, Lily; Apostolopoulos, Vasso; Granese, Roberta; Sofo, Vincenza

2017-06-01

The theory of retrograde menstruation as aetiopathogenesis of endometriosis formulated by John Sampson in 1927 shows clear shortcomings: this does not explain why retrograde menstruation is a physiological process that affects 90% of women, while endometriosis occurs in only 10% of cases; it also does not explain the endometriotic foci distant from the pelvis, nor explains the cases of endometriosis in male patients. The immunological alterations of the peritoneal fluid explains the effects of disease, such as the inhibition of the physiological processes of cytolysis, but does not explain the cause. There is evidence to support the hypothesis that ectopic müllerian remnants of the endometrium, endocervix and endosalpinx are items from the genital ridge leaked during organogenesis. It is known that tissues derived from coelomatic epithelial and mesenchymal cells have the potential to metaplastically differentiate into epithelium and stroma. In addition, the phenotype of the ectopic endometrial cells is significantly different from those ectopic. There is scientific evidence that, during organogenesis, the genes of the Homeobox and Wingless family play a fundamental role in the differentiation of the ducts of Muller and development of the anatomical structure of the urogenital tract. We present here a hypothesis that deregulation of genes and the Wnt signaling pathway Wnt/β-catenin leads to aberrations and deregulation within the mesoderm, thus, may cause aberrant placement of stem cells. In addition, immune cells, adhesion molecules, extracellular matrix metalloproteinase and pro-inflammatory cytokines activate/alter peritoneal microenvironment, creating the conditions for differentiation, adhesion, proliferation and survival of ectopic endometrial cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

Atrial ectopic activity in cryptogenic ischemic stroke and TIA: a risk factor for recurrence.

PubMed

Pinho, João; Braga, Carlos Galvão; Rocha, Sofia; Santos, Ana Filipa; Gomes, André; Cabreiro, Ana; Magalhães, Sónia; Ferreira, Carla

2015-02-01

To characterize atrial ectopic activity in patients with cryptogenic ischemic stroke (CIS) or transient ischemic attack (TIA) and determine its prognostic significance. Retrospective cohort study, in which 184 patients with CIS or TIA who had performed 24-hour Holter electrocardiogram were included. The median follow-up was 27.5 months. Baseline clinical and imagiologic characteristics, etiologic investigation results, and ischemic stroke and TIA recurrences information were collected. Number of atrial premature complexes (APCs) per hour was categorized as less than 10 APCs/hour, 10-30 APCs/hour, and more than 30 APCs/hour. Most of the patients had less than 10 APCs/hour (82.6%), 8.2% had 10-30 APCs/hour, and 9.2% had more than 30 APCs/hour. Patients with more than 30 APCs/hour had a greater median left atrium diameter than patients with 30 APCs/hour or less (42 mm vs. 38 mm; 95% confidence interval [CI], .50-7.00; P = .003). Annual recurrence rate of CIS or TIA was 2.9% in patients with less than 10 APCs/hour, 11.0% in 10-30 APCs/hour, and 22.6% in more than 30 APCs/hour (P = .001). More than 30 APCs/hour were independently associated with recurrence risk in multivariate survival analysis (hazard ratio, 3.40; 95% CI, 1.12-10.32; P = .030). In patients with CIS or TIA, frequent atrial ectopic activity (>30 APCs/h) was independently associated with increased risk of stroke or TIA recurrence. Further studies need to validate frequent atrial ectopic activity as a risk factor for recurrence in cryptogenic stroke and confirm its role as a predictor of occult atrial fibrillation. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Ectopic High Expression of E2-EPF Ubiquitin Carrier Protein Indicates a More Unfavorable Prognosis in Brain Glioma.

PubMed

Zhang, Xiaohui; Zhao, Fangbo; Zhang, Shujun; Song, Yichun

2017-04-01

Ubiquitination of proteins meant for elimination is a primary method of eukaryotic cellular protein degradation. The ubiquitin carrier protein E2-EPF is a key degradation enzyme that is highly expressed in many tumors. However, its expression and prognostic significance in brain glioma are still unclear. The aim of this study was to reveal how the level of E2-EPF relates to prognosis in brain glioma. Thirty low-grade and 30 high-grade brain glioma samples were divided into two tissue microarrays each. Levels of E2-EPF protein were examined by immunohistochemistry and immunofluorescence. Quantitative real-time polymerase chain reaction was used to analyze the level of E2-EPF in 60 glioma and 3 normal brain tissue samples. The relationship between E2-EPF levels and prognosis was analyzed by Kaplan-Meier survival curves. E2-EPF levels were low in normal brain tissue samples but high in glioma nuclei. E2-EPF levels gradually increased as glioma grade increased (p < 0.05). Ectopic E2-EPF levels in high-grade glioma were significantly higher than in low-grade glioma (p < 0.01). The 5-year survival rate of glioma patients with high E2-EPF levels was shorter than in patients with low expression (p < 0.05). Furthermore, the 5-year survival rate of patients with ectopic E2-EPF was significantly shorter than patients with only nuclear E2-EPF (p < 0.01). These results suggest that higher E2-EPF levels, especially ectopic, are associated with higher grade glioma and shorter survival. E2-EPF levels may play a key role in predicting the prognosis for patients with brain glioma.

Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity

PubMed Central

Garcia, Emmanuel; Becker, Veronika G. C.; McCullough, Danielle J.; Stabley, John N.; Gittemeier, Elizabeth M.; Opoku-Acheampong, Alexander B.; Sieman, Dietmar W.

2016-01-01

Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10−9 to 10−4 M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes. PMID:27125846

Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity.

PubMed

Garcia, Emmanuel; Becker, Veronika G C; McCullough, Danielle J; Stabley, John N; Gittemeier, Elizabeth M; Opoku-Acheampong, Alexander B; Sieman, Dietmar W; Behnke, Bradley J

2016-07-01

Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10(-9) to 10(-4) M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes. Copyright © 2016 the American Physiological Society.

P wave detection in ECG signals using an extended Kalman filter: an evaluation in different arrhythmia contexts.

PubMed

Rahimpour, M; Mohammadzadeh Asl, B

2016-07-01

Monitoring atrial activity via P waves, is an important feature of the arrhythmia detection procedure. The aim of this paper is to present an algorithm for P wave detection in normal and some abnormal records by improving existing methods in the field of signal processing. In contrast to the classical approaches, which are completely blind to signal dynamics, our proposed method uses the extended Kalman filter, EKF25, to estimate the state variables of the equations modeling the dynamic of an ECG signal. This method is a modified version of the nonlinear dynamical model previously introduced for a generation of synthetic ECG signals and fiducial point extraction in normal ones. It is capable of estimating the separate types of activity of the heart with reasonable accuracy and performs well in the presence of morphological variations in the waveforms and ectopic beats. The MIT-BIH Arrhythmia and QT databases have been used to evaluate the performance of the proposed method. The results show that this method has Se  =  98.38% and Pr  =  96.74% in the overall records (considering normal and abnormal rhythms).

Ectopic Male Breast Cancer: A Case Report

PubMed Central

Samanta, Dipti Rani; Upadhyay, Ashish; Sheet, Saikat; Senapati, Surendra Nath

2015-01-01

Carcinoma of male breast constitutes 1% of total breast malignancy. Carcinoma arising from ectopic breast tissue in male is an extremely rare entity and can be misdiagnosed. Ectopic breast tissue may be supernumerary or aberrant one. Despite morphologic difference, ectopic breast tissue presents characteristics analogous to orthoptic breast in terms of functional and pathologic degeneration. Most of the ectopic breast tissue occurs in thoracic or abdominal portion of milk line. If found in a location outside the milk line, it proves a diagnostic dilemma. We are reporting a case of 60-year-old male who presented with a fixed mass of size 10cm×8cm, in right chest wall infraclavicular area of 6 months duration. Histopathology of the mass revealed invasive duct carcinoma. He had no evidence of malignant or occult primary lesion in the bilateral mammary glands. Due to the paucity of the literature, incidence of ectopic male breast cancer and its management is not well understood. There is high probability of misdiagnosis of this disease. To the best of our knowledge this is the first described case of ectopic male breast cancer in the chest wall, not along the milk line, which is being reported here for documentation. PMID:26436033

Ectopic pregnancy morbidity and mortality in low-income women, 2004-2008.

PubMed

Stulberg, D B; Cain, L; Dahlquist, I H; Lauderdale, D S

2016-03-01

Does the risk of adverse outcomes at the time of ectopic pregnancy vary by race/ethnicity among women receiving Medicaid, the public health insurance program for low-income people in the USA? Among Medicaid beneficiaries with ectopic pregnancy, 11% experienced at least one complication, and women from all racial/ethnic minority groups were significantly more likely than whites to experience complications. In this population of Medicaid recipients, African American women are significantly more likely than whites to experience ectopic pregnancy, but the risk of adverse outcomes has not previously been assessed. We conducted a cross-sectional observational study of all women (n = 19 135 106) ages 15-44 enrolled in Medicaid for any amount of time during 2004-2008 who lived in one of the following 14 US states: Arizona; California; Colorado; Florida; Illinois; Indiana; Iowa; Louisiana; Massachusetts; Michigan; Minnesota; Mississippi; New York; and Texas. We analyzed Medicaid claims records for inpatient and outpatient encounters and identified ectopic pregnancies with a principal diagnosis code for ectopic pregnancy from 2004-2008. We calculated the ectopic pregnancy complication rate as the number of ectopic pregnancies with at least one complication (blood transfusion, hysterectomy, any sterilization, or length-of-stay (LOS) > 2 days) divided by the total number of ectopic pregnancies. We used Poisson regression to assess the risk of ectopic pregnancy complication by race/ethnicity. Secondary outcomes were each individual complication, and ectopic pregnancy-related death. We calculated the ectopic pregnancy mortality ratio as the number of deaths divided by live births. Ectopic pregnancy-associated complications occurred in 11% of cases. Controlling for age and state, the risk of any complication was significantly higher among women who were black (incidence risk ratio [IRR] 1.47, 95% CI 1.43-1.53, P < 0.0001), Hispanic (IRR 1.16, 95% CI 1.12-1.21, P < 0.0001), Asian (IRR 1.34, 95% CI 1.24-1.45, P < 0.0001), American Indian/Alaskan Native (IRR 1.34 95% CI 1.16-1.55, P < 0.0001), and Native Hawaiian/Pacific Islander (IRR 1.61, 95% CI 1.39-1.87, P < 0.0001) compared with white women. The ectopic pregnancy mortality ratio was 0.48 per 100 000 live births, similar to that reported in previous US surveillance. This is a secondary analysis of insurance claims. Among women at higher baseline risk of pregnancy complications due to their economic status, women from racial/ethnic minority groups face an additional risk of ectopic pregnancy adverse outcomes compared with whites. Systematic changes to reduce racial disparities are an essential part of improving maternal health in the USA. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (1 K08 HD060663 to D.B.S.). The authors report no conflict of interest. Not applicable. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Risk of ectopic pregnancy lowest with transfer of single frozen blastocyst.

PubMed

Li, Z; Sullivan, E A; Chapman, M; Farquhar, C; Wang, Y A

2015-09-01

What type of transferred embryo is associated with a lower rate of ectopic pregnancy? The lowest risk of ectopic pregnancy was associated with the transfer of blastocyst, frozen and single embryo compared with cleavage stage, fresh and multiple embryos. Ectopic pregnancy is a recognized complication following assisted reproductive technology (ART) treatment. It has been estimated that the rate of ectopic pregnancy is doubled in pregnancies following ART treatment compared with spontaneous pregnancies. However, it was not clear whether the excess rate of ectopic pregnancy following ART treatment is related to the underlying demographic factors of women undergoing ART treatment, the number of embryos transferred or the developmental stage of the embryo. A population-based cohort study of pregnancies following autologous treatment cycles between January 2009 and December 2011 were obtained from the Australian and New Zealand Assisted Reproduction Technology Database (ANZARD). The ANZARD collects ART treatment information and clinical outcomes annually from all fertility centres in Australia and New Zealand. Between 2009 and 2011, a total of 44 102 pregnancies were included in the analysis. The rate of ectopic pregnancy was compared by demographic and ART treatment factors. Generalized linear regression of Poisson distribution was used to estimate the likelihood of ectopic pregnancy. Odds ratios, adjusted odds ratios (AOR) and 95% confidence intervals (CI) were calculated. The overall rate of ectopic pregnancy was 1.4% for women following ART treatment in Australia and New Zealand. Pregnancies following single embryo transfers had 1.2% ectopic pregnancies, significantly lower than double embryo transfers (1.8%) (P < 0.01). The highest ectopic pregnancy rate was 1.9% for pregnancies from transfers of fresh cleavage embryo, followed by transfers of frozen cleavage embryo (1.7%), transfers of fresh blastocyst (1.3%), and transfers of frozen blastocyst (0.8%). Compared with fresh blastocyst transfer, the likelihood of ectopic pregnancy was 30% higher for fresh cleavage stage embryo transfers (AOR 1.30, 95% CI 1.07-1.59) and was consistent across subfertility groups. Transfer of frozen blastocyst was associated with a significantly decreased risk of ectopic pregnancy (AOR 0.70, 95% CI 0.54-0.91) compared with transfer of fresh blastocyst. A limitation of this population-based study is the lack of information available on clinical- specific protocols and processes for embryo transfer (i.e. embryo quality, cryopreservation protocol, transfer techniques, etc.) and the potential impact on outcomes. The lowest risk of ectopic pregnancy was associated with the transfer of a single frozen blastocyst. This finding adds to the increasing evidence of better perinatal outcomes following frozen embryo transfers. The approach of freezing all embryos in the initiated fresh cycle and transfer of a single frozen blastocyst in the subsequent thaw cycle may improve the overall pregnancy and birth outcomes following ART treatment, in part by reducing the ectopic pregnancy rate. There is no funding for this study. Authors declared no competing interest related to this study. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Role of GLI2 in hypopituitarism phenotype.

PubMed

Arnhold, Ivo J P; França, Marcela M; Carvalho, Luciani R; Mendonca, Berenice B; Jorge, Alexander A L

2015-06-01

GLI2 is a zinc-finger transcription factor involved in the Sonic Hedgehog pathway. Gli2 mutant mice have hypoplastic anterior and absent posterior pituitary glands. We reviewed the literature for patients with hypopituitarism and alterations in GLI2. Twenty-five patients (16 families) had heterozygous truncating mutations, and the phenotype frequently included GH deficiency, a small anterior pituitary lobe and an ectopic/undescended posterior pituitary lobe on magnetic resonance imaging and postaxial polydactyly. The inheritance pattern was autosomal dominant with incomplete penetrance and variable expressivity. The mutation was frequently inherited from an asymptomatic parent. Eleven patients had heterozygous non-synonymous GLI2 variants that were classified as variants of unknown significance, because they were either absent from or had a frequency lower than 0.001 in the databases. In these patients, the posterior pituitary was also ectopic, but none had polydactyly. A third group of variants found in patients with hypopituitarism were considered benign because their frequency was ≥ 0.001 in the databases. GLI2 is a large and polymorphic gene, and sequencing may identify variants whose interpretation may be difficult. Incomplete penetrance implies in the participation of other genetic and/or environmental factors. An interaction between Gli2 mutations and prenatal ethanol exposure has been demonstrated in mice dysmorphology. In conclusion, a relatively high frequency of GLI2 mutations and variants were identified in patients with congenital GH deficiency without other brain defects, and most of these patients presented with combined pituitary hormone deficiency and an ectopic posterior pituitary lobe. Future studies may clarify the relative role and frequency of GLI2 alterations in the aetiology of hypopituitarism. © 2015 Society for Endocrinology.

The homeobox gene mirror links EGF signalling to embryonic dorso-ventral axis formation through notch activation.

PubMed

Jordan, K C; Clegg, N J; Blasi, J A; Morimoto, A M; Sen, J; Stein, D; McNeill, H; Deng, W M; Tworoger, M; Ruohola-Baker, H

2000-04-01

Recent studies in vertebrates and Drosophila melanogaster have revealed that Fringe-mediated activation of the Notch pathway has a role in patterning cell layers during organogenesis. In these processes, a homeobox-containing transcription factor is responsible for spatially regulating fringe (fng) expression and thus directing activation of the Notch pathway along the fng expression border. Here we show that this may be a general mechanism for patterning epithelial cell layers. At three stages in Drosophila oogenesis, mirror (mirr) and fng have complementary expression patterns in the follicle-cell epithelial layer, and at all three stages loss of mirr enlarges, and ectopic expression of mirr restricts, fng expression, with consequences for follicle-cell patterning. These morphological changes are similar to those caused by Notch mutations. Ectopic expression of mirr in the posterior follicle cells induces a stripe of rhomboid (rho) expression and represses pipe (pip), a gene with a role in the establishment of the dorsal-ventral axis, at a distance. Ectopic Notch activation has a similar long-range effect on pip. Our results suggest that Mirror and Notch induce secretion of diffusible morphogens and we have identified TGF-beta (encoded by dpp) as such a molecule in germarium. We also found that mirr expression in dorsal follicle cells is induced by the EGF-receptor (EGFR) pathway and that mirr then represses pip expression in all but the ventral follicle cells, connecting EGFR activation in the dorsal follicle cells to repression of pip in the dorsal and lateral follicle cells. Our results suggest that the differentiation of ventral follicle cells is not a direct consequence of germline signalling, but depends on long-range signals from dorsal follicle cells, and provide a link between early and late events in Drosophila embryonic dorsal-ventral axis formation.

MECHANISMS IN ENDOCRINOLOGY: Skeletal muscle lipotoxicity in insulin resistance and type 2 diabetes: a causal mechanism or an innocent bystander?

PubMed

Brøns, Charlotte; Grunnet, Louise Groth

2017-02-01

Dysfunctional adipose tissue is associated with an increased risk of developing type 2 diabetes (T2D). One characteristic of a dysfunctional adipose tissue is the reduced expandability of the subcutaneous adipose tissue leading to ectopic storage of fat in organs and/or tissues involved in the pathogenesis of T2D that can cause lipotoxicity. Accumulation of lipids in the skeletal muscle is associated with insulin resistance, but the majority of previous studies do not prove any causality. Most studies agree that it is not the intramuscular lipids per se that causes insulin resistance, but rather lipid intermediates such as diacylglycerols, fatty acyl-CoAs and ceramides and that it is the localization, composition and turnover of these intermediates that play an important role in the development of insulin resistance and T2D. Adipose tissue is a more active tissue than previously thought, and future research should thus aim at examining the exact role of lipid composition, cellular localization and the dynamics of lipid turnover on the development of insulin resistance. In addition, ectopic storage of fat has differential impact on various organs in different phenotypes at risk of developing T2D; thus, understanding how adipogenesis is regulated, the interference with metabolic outcomes and what determines the capacity of adipose tissue expandability in distinct population groups is necessary. This study is a review of the current literature on the adipose tissue expandability hypothesis and how the following ectopic lipid accumulation as a consequence of a limited adipose tissue expandability may be associated with insulin resistance in muscle and liver. © 2017 European Society of Endocrinology.

Epigallocatechin gallate (EGCG) stimulates autophagy in vascular endothelial cells: a potential role for reducing lipid accumulation.

PubMed

Kim, Hae-Suk; Montana, Vedrana; Jang, Hyun-Ju; Parpura, Vladimir; Kim, Jeong-a

2013-08-02

Epigallocatechin gallate (EGCG) is a major polyphenol in green tea that has beneficial effects in the prevention of cardiovascular disease. Autophagy is a cellular process that protects cells from stressful conditions. To determine whether the beneficial effect of EGCG is mediated by a mechanism involving autophagy, the roles of the EGCG-stimulated autophagy in the context of ectopic lipid accumulation were investigated. Treatment with EGCG increased formation of LC3-II and autophagosomes in primary bovine aortic endothelial cells (BAEC). Activation of calmodulin-dependent protein kinase kinase β was required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation was significantly impaired by knockdown of calmodulin-dependent protein kinase kinase β. This effect is most likely due to cytosolic Ca(2+) load. To determine whether EGCG affects palmitate-induced lipid accumulation, the effects of EGCG on autophagic flux and co-localization of lipid droplets and autophagolysosomes were examined. EGCG normalized the palmitate-induced impairment of autophagic flux. Accumulation of lipid droplets by palmitate was markedly reduced by EGCG. Blocking autophagosomal degradation opposed the effect of EGCG in ectopic lipid accumulation, suggesting the action of EGCG is through autophagosomal degradation. The mechanism for this could be due to the increased co-localization of lipid droplets and autophagolysosomes. Co-localization of lipid droplets with LC3 and lysosome was dramatically increased when the cells were treated with EGCG and palmitate compared with the cells treated with palmitate alone. Collectively, these findings suggest that EGCG regulates ectopic lipid accumulation through a facilitated autophagic flux and further imply that EGCG may be a potential therapeutic reagent to prevent cardiovascular complications.

Dominant Suppression of β1 Integrin by Ectopic CD98-ICD Inhibits Hepatocellular Carcinoma Progression

PubMed Central

Wu, Bo; Zhou, Yang; Wang, Yu; Yang, Xiang-Min; Liu, Zhen-Yu; Li, Jiang-Hua; Feng, Fei; Chen, Zhi-Nan; Jiang, Jian-Li

2016-01-01

Hepatocellular carcinoma (HCC) is currently the third most common cause of cancer-related death in the Asia-Pacific region. Our previous work showed that knockdown of CD98 significantly inhibits malignant HCC cell phenotypes in vitro and in vivo. The level of CD98 in the membrane is tightly regulated to mediate complex processes associated with cell–cell communication and intracellular signaling. In addition, the intracellular domain of CD98 (CD98-ICD) seems to be of vital importance for recycling CD98 to the membrane after it is endocytosed. The intracellular and transmembrane domains of CD98 associate with β-integrins (primarily β1 but also β3), and this association is essential for CD98 mediation of integrin-like signaling and complements dominant suppression of β1-integrin. We speculated that isolated CD98-ICD would similarly suppress β1-integrin activation and inhibit the malignant behaviors of cancer cells. In particular, the exact role of CD98-ICD has not been studied independently in HCC. In this study, we found that ectopic expression of CD98-ICD inhibited the malignant phenotypes of HCC cells, and the mechanism possibly involves β1-integrin suppression. Moreover, the expression levels of CD98, β1-integrin-A (the activated form of β1-integrin) and Ki-67 were significantly increased in HCC tissues relative to those of normal liver tissues. Therefore, our preliminary study indicates that ectopic CD98-ICD has an inhibitory role in the malignant development of HCC, and shows that CD98-ICD acts as a dominant negative mutant of CD98 that attenuates β1-integrin activation. CD98-ICD may emerge as a promising candidate for antitumor treatment. PMID:27834933

42 CFR 136a.55 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2011 CFR

2011-10-01

... pregnancies. 136a.55 Section 136a.55 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... and devices and termination of ectopic pregnancies. Federal funds are available for drugs or devices... termination of an ectopic pregnancy. ...

42 CFR 136a.55 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... pregnancies. 136a.55 Section 136a.55 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... and devices and termination of ectopic pregnancies. Federal funds are available for drugs or devices... termination of an ectopic pregnancy. ...

42 CFR 136a.55 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2012 CFR

2012-10-01

... pregnancies. 136a.55 Section 136a.55 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... and devices and termination of ectopic pregnancies. Federal funds are available for drugs or devices... termination of an ectopic pregnancy. ...

42 CFR 136a.55 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2014 CFR

2014-10-01

... pregnancies. 136a.55 Section 136a.55 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... and devices and termination of ectopic pregnancies. Federal funds are available for drugs or devices... termination of an ectopic pregnancy. ...

42 CFR 136a.55 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2013 CFR

2013-10-01

... pregnancies. 136a.55 Section 136a.55 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... and devices and termination of ectopic pregnancies. Federal funds are available for drugs or devices... termination of an ectopic pregnancy. ...

The Role(s) of Heparan Sulfate Proteoglycan(s) in the wnt-1 Signaling Pathway

DTIC Science & Technology

1998-08-01

First , the sequence of the cDNA, when compared to the genomic site of insertion of the P-element, revealed that the P-element is inserted 686 bp...stages 8 to 13 (Yoffe et al. 1995). We first examined whether ectopic expression of Wgts effectively restores the naked cuticle as it does in wg and...by Kjell~n and Lindahl, 1991) . HS/heparin N-deacetylase/N-sulfotransferase catalyzes N-deacetylation and N-sulfation that is the first and key step

A Novel Mechanism of Estrogen Action in Breast Cancer Cells Mediated Through ER-FE65 Complex Formation

DTIC Science & Technology

2013-03-01

Deletion analyses mapped the ERα binding domain to the phosphotyrosine binding domain 2. Ectopic Fe65 increased the transcriptional activity of the...ERα in a PTB2 dependent manner in reporter assays. Fe65 knockdown decreased and its stable expression increased the activity of endogenous ERα in...Furthermore, Fe65 expression decreased the antagonistic activity of tamoxifen, suggesting a potential role for Fe65 in tamoxifen resistance. While a role of

Sonography of Methotrexate for Ectopics

NASA Astrophysics Data System (ADS)

Urzicǎ, Denise; Dorohoi, Dana-Ortansa

2007-04-01

Treatment unruptured ectopic pregnancy with methotrexate (MTX) and citrovorum factor is now an established alternative to surgical therapy. Serial measurements of serum beta-HCG and early ultrasound examination have allowed detection of early and unruptured tubal ectopic pregnancies, permitting treatment without removal of the tube. It is believed that preserving the tube increases the chance of subsequent live births. Our findings suggest that outpatient transvaginal intratubal methorexate administration can provide a safe and effective alternative to surgical treatment for patients with early and unruptured tubal ectopic pregnancy.

Tendon Mineralization Is Progressive and Associated with Deterioration of Tendon Biomechanical Properties, and Requires BMP-Smad Signaling in the Mouse Achilles Tendon Injury Model

PubMed Central

Zhang, Kairui; Asai, Shuji; Hast, Michael W.; Liu, Min; Usami, Yu; Iwamoto, Masahiro; Soslowsky, Louis J.; Enomoto-Iwamoto, Motomi

2016-01-01

Ectopic tendon mineralization can develop following tendon rupture or trauma surgery. The pathogenesis of ectopic tendon mineralization and its clinical impact have not been fully elucidated yet. In this study, we utilized a mouse Achilles tendon injury model to determine whether ectopic tendon mineralization alters the biomechanical properties of the tendon and whether BMP signaling is involved in this condition. A complete transverse incision was made at the midpoint of the right Achilles tendon in 8-week-old CD1 mice and the gap was left open. Ectopic cartilaginous mass formation was found in the injured tendon by 4 weeks post-surgery and ectopic mineralization was detected at 8–10 weeks post-surgery. Ectopic mineralization grew over time and volume of the mineralized materials of 25-weeks samples was about 2.5 fold bigger than that of 10-weeks samples, indicating that injury-induced ectopic tendon mineralization is progressive. In vitro mechanical testing showed that max force, max stress and mid-substance modulus in the 25-weeks samples were significantly lower than the 10-weeks samples. We observed substantial increases in expression of bone morphogenetic protein family genes in injured tendons 1 week post-surgery. Immunohistochemical analysis showed that phosphorylation of both Smad1 and Smad3 were highly increased in injured tendons as early as 1 week post-injury and remained high in ectopic chondrogenic lesions 4 weeks post-injury. Treatment with the BMP receptor kinase inhibitor (LDN193189) significantly inhibited injury-induced tendon mineralization. These findings indicate that injury-induced ectopic tendon mineralization is progressive, involves BMP signaling and associated with deterioration of tendon biomechanical properties. PMID:26825318

Developing a knowledge base to support the annotation of ultrasound images of ectopic pregnancy.

PubMed

Dhombres, Ferdinand; Maurice, Paul; Friszer, Stéphanie; Guilbaud, Lucie; Lelong, Nathalie; Khoshnood, Babak; Charlet, Jean; Perrot, Nicolas; Jauniaux, Eric; Jurkovic, Davor; Jouannic, Jean-Marie

2017-01-31

Ectopic pregnancy is a frequent early complication of pregnancy associated with significant rates of morbidly and mortality. The positive diagnosis of this condition is established through transvaginal ultrasound scanning. The timing of diagnosis depends on the operator expertise in identifying the signs of ectopic pregnancy, which varies dramatically among medical staff with heterogeneous training. Developing decision support systems in this context is expected to improve the identification of these signs and subsequently improve the quality of care. In this article, we present a new knowledge base for ectopic pregnancy, and we demonstrate its use on the annotation of clinical images. The knowledge base is supported by an application ontology, which provides the taxonomy, the vocabulary and definitions for 24 types and 81 signs of ectopic pregnancy, 484 anatomical structures and 32 technical elements for image acquisition. The knowledge base provides a sign-centric model of the domain, with the relations of signs to ectopic pregnancy types, anatomical structures and the technical elements. The evaluation of the ontology and knowledge base demonstrated a positive feedback from a panel of 17 medical users. Leveraging these semantic resources, we developed an application for the annotation of ultrasound images. Using this application, 6 operators achieved a precision of 0.83 for the identification of signs in 208 ultrasound images corresponding to 35 clinical cases of ectopic pregnancy. We developed a new ectopic pregnancy knowledge base for the annotation of ultrasound images. The use of this knowledge base for the annotation of ultrasound images of ectopic pregnancy showed promising results from the perspective of clinical decision support system development. Other gynecological disorders and fetal anomalies may benefit from our approach.

Diagnostic dilemma in ovarian pregnancy: a case series.

PubMed

Begum, Jasmina; Pallavee, P; Samal, Sunita

2015-04-01

Ovarian pregnancy is a rare form of ectopic pregnancy but it is the most common type of nontubal ectopic pregnancy. Many times it is operated with a misdiagnosis of ruptured tubal ectopic pregnancy or hemorrhagic corpus luteum. The high resolution transvaginal ultrasonography is a valuable tool for diagnosis of ectopic pregnancy but ovarian pregnancy still remains a diagnostic problem and a continuous challenge to the gynecologist. The correct diagnosis is made at the time of surgery and confirmation is by histopathological report. Here we report three cases of primary ovarian ectopic pregnancies, consistent with the Spiegelberg's criteria. Out of this, two cases have corroboration of ovarian ectopic pregnancy with use of intrauterine contraceptive device and one case by chance without any preexisting risk factors, probably due to interference in the release of ovum from the follicle. In all the three cases, emergency laparotomy was done for ruptured tubal ectopic pregnancy and the diagnosis of ruptured primary ovarian pregnancy was made at the time of surgery, this was subsequently confirmed by histopathology report. In the era where wider usage of intrauterine devices, ovulatory drugs and assisted reproductive techniques are rife, there is a possibility of an increase in the incidence of this rare entity, so ovarian ectopic pregnancy should be kept in mind as a possibility. Thereby early diagnosis by high resolution transvaginal ultrasound and laparoscopy can decrease the risk of complications like rupture, secondary implantation, hemorrhagic shock and maternal mortality.

42 CFR 441.207 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2014 CFR

2014-10-01

... pregnancies. 441.207 Section 441.207 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... APPLICABLE TO SPECIFIC SERVICES Abortions § 441.207 Drugs and devices and termination of ectopic pregnancies... and for medical procedures necessary for the termination of an ectopic pregnancy. ...

42 CFR 441.207 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... pregnancies. 441.207 Section 441.207 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... APPLICABLE TO SPECIFIC SERVICES Abortions § 441.207 Drugs and devices and termination of ectopic pregnancies... and for medical procedures necessary for the termination of an ectopic pregnancy. ...

42 CFR 441.207 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2012 CFR

2012-10-01

... pregnancies. 441.207 Section 441.207 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... APPLICABLE TO SPECIFIC SERVICES Abortions § 441.207 Drugs and devices and termination of ectopic pregnancies... and for medical procedures necessary for the termination of an ectopic pregnancy. ...

42 CFR 441.207 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2011 CFR

2011-10-01

... pregnancies. 441.207 Section 441.207 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... APPLICABLE TO SPECIFIC SERVICES Abortions § 441.207 Drugs and devices and termination of ectopic pregnancies... and for medical procedures necessary for the termination of an ectopic pregnancy. ...

42 CFR 441.207 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2013 CFR

2013-10-01

... pregnancies. 441.207 Section 441.207 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... APPLICABLE TO SPECIFIC SERVICES Abortions § 441.207 Drugs and devices and termination of ectopic pregnancies... and for medical procedures necessary for the termination of an ectopic pregnancy. ...

A microprocessor-based cardiotachometer

NASA Technical Reports Server (NTRS)

Donaldson, J. A.; Crosier, W. G.

1979-01-01

The development of a highly accurate and reliable cardiotachometer for measuring the heart rate of test subjects is discussed. It measures heart rate over the range of 30 to 250 beats/minute and gives instantaneous (beat to beat) updates on the system output so that occasional noise artifacts or ectopic beats could be more easily identified except that occasional missed beats caused by switching ECG leads should not cause a change in the output. The cardiotachometer uses an improved analog filter and R-wave detector and an Intel 8080A microprocessor to handle all of the logic and arithmetic necessary. By using the microprocessor, future hardware modifications could easily be made if functional changes were needed.

Left-Right Asymmetric Morphogenesis in the Xenopus Digestive System

USGS Publications Warehouse

Muller, Jennifer K.; Prather, D.R.; Nascone-Yoder, N. M.

2003-01-01

The morphogenetic mechanisms by which developing organs become left-right asymmetric entities are unknown. To investigate this issue, we compared the roles of the left and right sides of the Xenopus embryo during the development of anatomic asymmetries in the digestive system. Although both sides contribute equivalently to each of the individual digestive organs, during the initial looping of the primitive gut tube, the left side assumes concave topologies where the right side becomes convex. Of interest, the concave surfaces of the gut tube correlate with expression of the LR gene, Pitx2, and ectopic Pitx2 mRNA induces ectopic concavities in a localized manner. A morphometric comparison of the prospective concave and convex surfaces of the gut tube reveals striking disparities in their rate of elongation but no significant differences in cell proliferation. These results provide insight into the nature of symmetry-breaking morphogenetic events during left-right asymmetric organ development. ?? 2003 Wiley-Liss, Inc.

Brca1 regulates in vitro differentiation of mammary epithelial cells.

PubMed

Kubista, Marion; Rosner, Margit; Kubista, Ernst; Bernaschek, Gerhard; Hengstschläger, Markus

2002-07-18

Murine Brca1 is widely expressed during development in different tissues. Why alterations of BRCA1 lead specifically to breast and ovarian cancer is currently not clarified. Here we show that Brca1 protein expression is upregulated during mammary epithelial differentiation of HC11 cells, during differentiation of C2C12 myoblasts into myotubes and during neuronal differentiation of N1E-115 cells. Ectopic overexpression of BRCA1 and downregulation of endogenous Brca1 expression specifically affect the regulation of mammary epithelial cell differentiation. Accelerated mammary epithelial cell differentiation upon high ectopic BRCA1 expression is not a consequence of the anti-proliferative capacity of this tumor suppressor and independent of functional p53. Overexpression of the BRCA1 variant lacking the large central exon 11 has no effects on mammary epithelial cell differentiation. These data provide new insights into the cellular role of Brca1.

PreImplantation Factor in endometriosis: A potential role in inducing immune privilege for ectopic endometrium

PubMed Central

Scarpellini, Fabio; Marconi, Daniela; Rossi, Gabriele; Simmilion, Cedric; Mueller, Michael D.; Barnea, Eytan R.

2017-01-01

Endometriosis is a chronic inflammatory condition characterised by the growth of endometrial epithelial and stromal cells outside the uterine cavity. In addition to Sampson’s theory of retrograde menstruation, endometriosis pathogenesis is facilitated by a privileged inflammatory microenvironment, with T regulatory FoxP3+ expressing T cells (Tregs) being a significant factor. PreImplantation Factor (PIF) is a peptide essential for pregnancy recognition and development. An immune modulatory function of the synthetic PIF analog (sPIF) has been successfully confirmed in multiple animal models. We report that PIF is expressed in the epithelial ectopic cells in close proximity to FoxP3+ stromal cells. We provide evidence that PIF interacts with FoxP3+ cells and modulates cell viability, dependent on cell source and presence of inflammatory mediators. Our finding represent a novel PIF-based mechanism in endometriosis that has potential for novel therapeutics. PMID:28902871

Formation of ectopic osteogenesis in weightlessness

NASA Technical Reports Server (NTRS)

1977-01-01

An ectopic osteogenesis experiment aboard the Cosmos-936 biosatellite is described. Decalcified, lyophilized femur and tibia were implanted under the fascia or in the anterior wall of the abdomen in rats. Bone formation before and after the tests is described and illustrated. The extent of formation of ectopic bone in weightlessness did not differ significantly from that in the ground controls, but the bone marrow of the ectopic bone of the flight rats consisted exclusively of fat cells. The deficit of support-muscle loading was considered to cause the disturbance in skeletal bone tissue development.

Papillary Carcinoma in Median Aberrant Thyroid (Ectopic) - Case Report

PubMed Central

K, Shashidhar; Deshmane, Vijaya Laxmi; Kumar, Veerendra; Arjunan, Ravi

2014-01-01

Median ectopic thyroid may be encountered anywhere from the foramen caecum to the diaphragm. Non lingual median aberrant thyroid (incomplete descent) usually found in the infrahyoid region and malignant transformation in this ectopic thyroid tissue is very rare. We report an extremely rare case of papillary carcinoma in non lingual median aberrant thyroid in a 25-year-old female. The differentiation between a carcinoma arising in the median ectopic thyroid tissue and a metastatic papillary carcinoma from an occult primary in the main thyroid gland is also discussed. PMID:25121039

Papillary carcinoma in median aberrant thyroid (ectopic) - case report.

PubMed

Hebbar K, Ashwin; K, Shashidhar; Deshmane, Vijaya Laxmi; Kumar, Veerendra; Arjunan, Ravi

2014-06-01

Median ectopic thyroid may be encountered anywhere from the foramen caecum to the diaphragm. Non lingual median aberrant thyroid (incomplete descent) usually found in the infrahyoid region and malignant transformation in this ectopic thyroid tissue is very rare. We report an extremely rare case of papillary carcinoma in non lingual median aberrant thyroid in a 25-year-old female. The differentiation between a carcinoma arising in the median ectopic thyroid tissue and a metastatic papillary carcinoma from an occult primary in the main thyroid gland is also discussed.

Combined use of serum HCG and sonography in the diagnosis of ectopic pregnancy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kadar, N.; Taylor, K.J.W.; Rosenfield, A.T.

1983-09-01

During an 18 month period, 320 patients were referred with clinical suspicion of an ectopic pregnancy. This study is based on 19 patients with ectopic pregnancy who had both a sonographic examination of the pelvis and determination of serum beta human chorionic gonadotropin (HCG) before surgery. Emphasis is focused on the spectrum of sonographic appearances that may occur in ectopic gestation. These are illustrated, and the sonographic criteria that have been used both for a positive diagnosis and for the exclusion of ectopic pregnancy in the past are analyzed. It is suggested that the accuracy of sonography can be increasedmore » by determining the serum HCG level on the day of the scan and by interpreting the findings with reference to the discriminatory HCG zone.« less

Ruptured ectopic pregnancy with contralateral adnexal torsion after spontaneous conception.

PubMed

DiLuigi, Andrea J; Maier, Donald B; Benadiva, Claudio A

2008-11-01

To describe a case of ruptured ectopic pregnancy and contralateral adnexal torsion after spontaneous conception. Case report. Tertiary university medical center. A 23-year-old multiparous female with severe bilateral pelvic pain and a positive pregnancy test. Operative laparoscopy with detorsion of left adnexa, drainage of left ovarian hemorrhagic corpus luteum cyst, right salpingectomy, and dilation and curettage. Laparoscopy revealed a 5 cm hemorrhagic corpus luteum cyst of the left ovary, torsion of the left ovary and fallopian tube, and a ruptured right ampullary ectopic pregnancy. Normal perfusion of left ovary and fallopian tube after detorsion, resolution of left ovarian hemorrhagic corpus luteum cyst, patent left fallopian tube with chromopertubation, and successful removal of ectopic pregnancy. This is a unique case of adnexal torsion and contralateral ectopic pregnancy occurring after spontaneous conception.

Simulation of Ectopic Pacemakers in the Heart: Multiple Ectopic Beats Generated by Reentry inside Fibrotic Regions

PubMed Central

Gouvêa de Barros, Bruno; Weber dos Santos, Rodrigo; Alonso, Sergio

2015-01-01

The inclusion of nonconducting media, mimicking cardiac fibrosis, in two models of cardiac tissue produces the formation of ectopic beats. The fraction of nonconducting media in comparison with the fraction of healthy myocytes and the topological distribution of cells determines the probability of ectopic beat generation. First, a detailed subcellular microscopic model that accounts for the microstructure of the cardiac tissue is constructed and employed for the numerical simulation of action potential propagation. Next, an equivalent discrete model is implemented, which permits a faster integration of the equations. This discrete model is a simplified version of the microscopic model that maintains the distribution of connections between cells. Both models produce similar results when describing action potential propagation in homogeneous tissue; however, they slightly differ in the generation of ectopic beats in heterogeneous tissue. Nevertheless, both models present the generation of reentry inside fibrotic tissues. This kind of reentry restricted to microfibrosis regions can result in the formation of ectopic pacemakers, that is, regions that will generate a series of ectopic stimulus at a fast pacing rate. In turn, such activity has been related to trigger fibrillation in the atria and in the ventricles in clinical and animal studies. PMID:26583127

Unilateral Atraumatic Expulsion of an Ectopic Pregnancy in a Case of Bilateral Ectopic Pregnancy

PubMed Central

Mogekwu, Oluremi; Ahmed, Ammar; Bano, Farida

2017-01-01

Ectopic pregnancy occurs in 1-2% of pregnancies. The fallopian tube is the most common site; however, bilateral tubal ectopic pregnancy is an extremely rare phenomenon, seen in approximately 1/200,000 pregnancies. It is usually the result of assisted reproductive techniques (ART). Ultrasound (USS) and serial beta-hCG levels have shown poor efficacy for accurate diagnosis. Laparoscopy is the diagnostic gold standard. The majority of cases are managed surgically with bilateral salpingectomy. A 26-year-old female presented to our early pregnancy unit with pain and vaginal bleeding at 5-week gestation after IVF. USS was inconclusive and her b-hCG levels rose with worsening pain; therefore, a decision was made for diagnostic laparoscopy. Although there was a clear right sided ectopic pregnancy, the left tube was swollen and therefore a methylene blue dye test was carried out to confirm blockage. Atraumatic milking, to expose the dye, expelled necrotic tissue which histology confirmed to be a second ectopic pregnancy. She made a good recovery with falling beta-hCG levels and left tubal preservation. As the use of ART increases, bilateral ectopic pregnancies will become more common. Novel and established techniques should be used to help confirm the diagnosis and assist in tubal preservation. PMID:29090103

SOX2 plays a critical role in EGFR-mediated self-renewal of human prostate cancer stem-like cells.

PubMed

Rybak, Adrian P; Tang, Damu

2013-12-01

SOX2 is an essential transcription factor for stem cells and plays a role in tumorigenesis, however its role in prostate cancer stem cells (PCSCs) remains unclear. We report here a significant upregulation of SOX2 at both mRNA and protein levels in DU145 PCSCs propagated as suspension spheres in vitro. The expression of SOX2 in DU145 PCSCs is positively regulated by epidermal growth factor receptor (EGFR) signaling. Activation of EGFR signaling, following the addition of epidermal growth factor (EGF) or ectopic expression of a constitutively-active EGFR mutant (EGFRvIII), increased SOX2 expression and the self-renewal of DU145 PCSCs. Conversely, a small molecule EGFR inhibitor (AG1478) blocked EGFR activation, reduced SOX2 expression and inhibited PCSC self-renewal activity, implicating SOX2 in mediating EGFR-dependent self-renewal of PCSCs. In line with this notion, ectopic SOX2 expression enhanced EGF-induced self-renewal of DU145 PCSCs, while SOX2 knockdown reduced PCSC self-renewal with EGF treatment no longer capable of enhancing their propagation. Furthermore, SOX2 knockdown reduced the capacity of DU145 PCSCs to grow under anchorage-independent conditions. Finally, DU145 PCSCs generated xenograft tumors more aggressively with elevated levels of SOX2 expression compared to xenograft tumors derived from non-PCSCs. Collectively, we provide evidence that SOX2 plays a critical role in EGFR-mediated self-renewal of DU145 PCSCs. © 2013.

The Bmp signaling pathway regulates development of left-right asymmetry in amphioxus.

PubMed

Soukup, Vladimir; Kozmik, Zbynek

2018-02-01

Establishment of asymmetry along the left-right (LR) body axis in vertebrates requires interplay between Nodal and Bmp signaling pathways. In the basal chordate amphioxus, the left-sided activity of the Nodal signaling has been attributed to the asymmetric morphogenesis of paraxial structures and pharyngeal organs, however the role of Bmp signaling in LR asymmetry establishment has not been addressed to date. Here, we show that Bmp signaling is necessary for the development of LR asymmetric morphogenesis of amphioxus larvae through regulation of Nodal signaling. Loss of Bmp signaling results in loss of the left-sided expression of Nodal, Gdf1/3, Lefty and Pitx and in gain of ectopic expression of Cerberus on the left side. As a consequence, the larvae display loss of the offset arrangement of axial structures, loss of the left-sided pharyngeal organs including the mouth, and ectopic development of the right-sided organs on the left side. Bmp inhibition thus phenocopies inhibition of Nodal signaling and results in the right isomerism. We conclude that Bmp and Nodal pathways act in concert to specify the left side and that Bmp signaling plays a fundamental role during LR development in amphioxus. Copyright © 2017 Elsevier Inc. All rights reserved.

Diagnosis and treatment of ectopic pregnancy.

PubMed

Epee-Bekima, Mathias; Overton, Caroline

2013-03-01

The most common site of localisation of an ectopic pregnancy is the fallopian tube. Rarely an ectopic pregnancy can be found in the ovary, a caesarean section scar, the abdomen or the cervix. Risk factors are previous ectopic pregnancy, PID, endometriosis, previous pelvic surgery, the presence of a coil and infertility. However, a third of women with an ectopic pregnancy have no known risk factors. NICE recommends a low threshold for offering a pregnancy test to women of childbearing age when they attend the surgery. Symptoms and signs appear when the tube starts to tear. When the tube ruptures, the woman will quickly become unwell and haemodynamically unstable because of rapid intra-abdominal blood loss. The most common symptoms of ectopic pregnancy are pelvic or abdominal pain, amenorrhoea, missed period or abnormal period and vaginal bleeding. A positive diagnosis of a urinary tract infection or gastroenteritis does not exclude an ectopic pregnancy. Signs of suspected ectopic pregnancy include pelvic, abdominal, adnexal or cervical motion tenderness, rebound tenderness and abdominal distension. Women who are haemodynamically unstable, or in whom there is significant concern about the degree of pain or bleeding, should be referred directly to A&E, irrespective of the result of the pregnancy test. Stable patients with bleeding who have pain or a pregnancy of six weeks gestation or more or a pregnancy of uncertain gestation should be referred immediately to an early pregnancy assessment (EPA) service, or out-of-hours gynaecology service if the EPA service is not available. Diagnosis is confirmed by transvaginal ultrasound scan to identify the location of the pregnancy.

[Cornual ectopic pregnancy. A report of a case and five-year-retrospective review].

PubMed

Ramírez Arreola, Leonardo; Nieto Galicia, Leyza Angélica; Escobar Valencia, Alfredo; Cerón Saldaña, Miguel Angel

2007-04-01

This article presents a clinical report of a cornual ectopic pregnancy as well as a five-year restrospective review of ectopic gestations at Hospital General de Matamoros Dr. Alfredo Pumarejo L, Tamaulipas, Mexico. The list with histopatological reports was checked up from January 2001 to May 2006. There were 66 results, of which only 31 files were complete. The presentation ages in these patients were between 16 and 39 years old, with a media of 25.6 years old and a mode of 21 years. The circumstances why patients attended to the hospital were: transvaginal bleeding and abdominal pain in 14 cases (45.1%), abdominal pain only in 12 cases (38.7%), and transvaginal bleeding only in five cases (16.2%). The clinical presentation was acute in 19 patients (61.3%), and it was insidious in 12 (38.7%). All women presented menstrual delay. Diagnoses were done by clinical findings in 12 women (38.7%), by clinical findings and ultrasonography in 18 (58.1%), and due to clinical findings and culdocentesis in just one patient (3.2%). Ectopic pregnancy was located in different places on each patient, such as: ampula, 24 cases (77.5%); isthmus, four patients (12.8%); fimbria, one case (3.2%); ovary, one woman (3.2%), and cornual in one patient (3.2%). Twenty-seven cases of broken ectopic pregnancies (87%), were found as transoperative findings, and the other four (13%) were not broken ectopic. There were not demises. Cornual ectopic pregnancy represents 1.5% of the ectopic gestations, as it is reported in the literature.

Orthodontic treatment of a stubborn palatally ectopic canine: a case report.

PubMed

Al-Musfir, Tumadher M; Morris, David O

2014-03-01

This is a case report that highlights a different treatment approach in dealing with palatally ectopic canines. The modified transpalatal arch with an 'active' arm was used to align a palatally ectopic canine with 'push' mechanics after the initial use of more conventional 'pull' mechanics (piggy-back archwire technique) had failed.

Ectopic canine associated with a dentigerous cyst in the maxilla.

PubMed

Thakur, Jagdeep S; Mohindroo, Narinder K; Sharma, Dev R; Minhas, Ravinder S; Thakur, Anamika

2011-06-01

Ectopic eruption of a tooth is common in the dental arch, palate, and nose, but it is rare in the maxillary antrum. We present the case of a 35-year-old man with an ectopic canine and an associated dentigerous cyst in the maxillary sinus that masqueraded as an antrochoanal polyp.

Ectopic Pregnancy and Emergency Contraceptive Pills: A Systematic Review

PubMed Central

Cleland, Kelly; Raymond, Elizabeth; Trussell, James; Cheng, Linan; Zhu, Haoping

2014-01-01

Objective To evaluate the existing data to estimate the rate of ectopic pregnancy among emergency contraceptive pill treatment failures. Data Sources Our initial reference list was generated from a 2008 Cochrane review of emergency contraception. In August 2009, we searched Biosys Previews, the Cochrane Database of Systematic Reviews, Medline, Global Health Database, Health Source: Popline, and Wanfang Data (a Chinese database). Methods of Study Selection This study included data from 136 studies which followed a defined population of women treated one time with emergency contraceptive pills (either mifepristone or levonorgestrel), and in which the number and location of pregnancies were ascertained. Results Data from each article were abstracted independently by two reviewers. In the studies of mifepristone, 3 out of 494 (0.6%) pregnancies were ectopic; in the levonorgestrel studies, 3 out of 307 (1%) were ectopic. Conclusion The rate of ectopic pregnancy when treatment with emergency contraceptive pills fails does not exceed the rate observed in the general population. Since emergency contraceptive pills are effective in lowering the risk of pregnancy, their use should reduce the chance that an act of intercourse will result in ectopic pregnancy. PMID:20502299

Dscam1-mediated self-avoidance counters netrin-dependent targeting of dendrites in Drosophila.

PubMed

Matthews, Benjamin J; Grueber, Wesley B

2011-09-13

Dendrites and axons show precise targeting and spacing patterns for proper reception and transmission of information in the nervous system. Self-avoidance promotes complete territory coverage and nonoverlapping spacing between processes from the same cell [1, 2]. Neurons that lack Drosophila Down syndrome cell adhesion molecule 1 (Dscam1) show aberrant overlap, fasciculation, and accumulation of dendrites and axons, demonstrating a role in self-recognition and repulsion leading to self-avoidance [3-11]. Fasciculation and accumulation of processes suggested that Dscam1 might promote process spacing by counterbalancing developmental signals that otherwise promote self-association [9, 12]. Here we show that Dscam1 functions to counter Drosophila sensory neuron dendritic targeting signals provided by secreted Netrin-B and Frazzled, a netrin receptor. Loss of Dscam1 function resulted in aberrant dendrite accumulation at a Netrin-B-expressing target, whereas concomitant loss of Frazzled prevented accumulation and caused severe deficits in dendritic territory coverage. Netrin misexpression was sufficient to induce ectopic dendritic targeting in a Frazzled-dependent manner, whereas Dscam1 was required to prevent ectopic accumulation, consistent with separable roles for these receptors. Our results suggest that Dscam1-mediated self-avoidance counters extrinsic signals that are required for normal dendritic patterning, but whose action would otherwise favor neurite accumulation. Counterbalancing roles for Dscam1 may be deployed in diverse contexts during neural circuit formation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Dscam1-mediated self-avoidance counters Netrin-dependent targeting of dendrites in Drosophila

PubMed Central

Matthews, Benjamin J.; Grueber, Wesley B.

2011-01-01

SUMMARY Dendrites and axons show precise targeting and spacing patterns for proper reception and transmission of information in the nervous system. Self-avoidance promotes complete territory coverage and non-overlapping spacing between processes from the same cell [1, 2]. Neurons that lack Drosophila Down syndrome cell adhesion molecule 1 (Dscam1) show aberrant overlap, fasciculation, and accumulation of dendrites and axons, demonstrating a role in self-recognition and repulsion leading to self-avoidance [3–11]. Fasciculation and accumulation of processes suggested that Dscam1 might promote process spacing by counterbalancing developmental signals that otherwise promote self-association [9, 12]. Here we show that Dscam1 functions to counter sensory neuron dendritic targeting signals provided by secreted Netrin-B and Frazzled, a netrin receptor. Loss of Dscam1 function resulted in aberrant dendrite accumulation at a Netrin-B expressing target, whereas concomitant loss of Frazzled prevented accumulation and caused severe deficits in dendritic territory coverage. Netrin misexpression was sufficient to induce ectopic dendritic targeting in a Frazzled-dependent manner, whereas Dscam1 was required to prevent ectopic accumulation, consistent with separable roles for these receptors. Our results suggest that Dscam1-mediated self-avoidance counter extrinsic signals that are required for normal dendritic patterning, but whose action would otherwise favor neurite accumulation. Counterbalancing roles for Dscam1 may be deployed in diverse contexts during neural circuit formation. PMID:21871804

Fibroadenoma in Axillary Ectopic Breast Tissue Mimicking Lymphadenopathy

PubMed Central

Maheshwari, Ujwala M

2017-01-01

Swellings in the axilla especially in women are always viewed with suspicion owing to a large number of these being associated with breast carcinoma presenting as nodal metastasis. In a country like India, tuberculous lymphadenopathy is also amongst the first differentials. We present a case of a woman with right sided axillary swelling mimicking lymphadenopathy which on Fine Needle Aspiration Cytology (FNAC) turned out to be fibroadenoma of the ectopic breast tissue. This condition is a rare occurrence in Ectopic Breast Tissue (EBT) as opposed to that in the normal breast, the most common pathology affecting ectopic breast being carcinomas. PMID:28511397

Papillary carcinoma in ectopic thyroid detected by Tl-201 scintigraphy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michigishi, T.; Mizukami, Y.; Mura, T.

1991-05-01

A 37-year-old man with papillary carcinoma in an ectopic thyroid is presented. Excisional biopsy revealed the cervical mass to be a metastasis from thyroid cancer. X-ray, ultrasonography, and computed tomography, however, failed to identify the primary tumor in the thyroid. Incidental TI-201 uptake was noted in the midline of the anterior neck, and a palpable nodule was discovered in this area. Fine needle aspiration cytology demonstrated Class V papillary adenocarcinoma, and subsequent surgery confirmed a papillary carcinoma in the ectopic thyroid. This case suggests the usefulness of TI-201 scintigraphy for the detection of ectopic thyroid malignancy.

Ectopic Cushing's syndrome secondary to olfactory neuroblastoma.

PubMed

Yu, Kenny; Roncaroli, Federico; Kearney, Tara; Ewins, David; Beeharry, Deepa; Naylor, Thomas; Ray, David; Bhalla, Rajiv; Gnanalingham, Kanna

2018-05-01

We present the case of a patient with Cushing's syndrome secondary to ectopic ACTH secretion. A MR of the head showed a left-sided nasal mass extending down from the cribriform plate. The patient underwent endoscopic resection with nearly complete removal of the mass. Histological examination showed an ACTH-secreting olfactory neuroblastoma (ONB). The patient's cortisol levels returned to normal range after surgery and have remained normal for over a year. ONB is a rare cause for ectopic ACTH secretion. This case highlights the diagnostic and management difficulties in patients with ectopic ACTH secretion, and provides a brief review of ONB.

Dual ectopic thyroid associated with thyroid hemiagenesis.

PubMed

Nakamura, Shigenori; Masuda, Teruyuki; Ishimori, Masatoshi

2018-01-01

We report a case of a 15-year-old girl with a midline neck mass that was first noted 2 or 3 years previously. She had been treated with levothyroxine (L-T4) for congenital hypothyroidism until 11 years of age. Ultrasonography revealed an atrophic right thyroid (1.0 × 1.6 × 2.6 cm in size) and a mass (2.3 × 1.0 × 3.5 cm in size) in the upper part of the neck. No left lobe of the thyroid was detected. On further evaluation, Tc-99m pertechnetate thyroid scintigraphy and CT showed ectopic thyroid tissue in the lingual region and infrahyoid region. Thus, she was diagnosed as having dual ectopic thyroid and thyroid hemiagenesis. The atrophic right thyroid was thought be non-functional. Treatment with L-T4 was started to reduce the size of the dual ectopic thyroid tissue. This may be the first reported case of dual ectopic thyroid associated with hemiagenesis detected only by ultrasonography. Ultrasonography can confirm the presence or absence of orthotopic thyroid tissue in patients with ectopic thyroid.The cause of congenital hypothyroidism should be examined.Clinical manifestation of ectopic thyroid may appear when the treatment with L-T4 is discontinued.Annual follow-up is needed in all children when their thyroid hormone replacement is stopped.

Ectopic KNOX Expression Affects Plant Development by Altering Tissue Cell Polarity and Identity[OPEN

PubMed Central

Rebocho, Alexandra B.

2016-01-01

Plant development involves two polarity types: tissue cell (asymmetries within cells are coordinated across tissues) and regional (identities vary spatially across tissues) polarity. Both appear altered in the barley (Hordeum vulgare) Hooded mutant, in which ectopic expression of the KNOTTED1-like Homeobox (KNOX) gene, BKn3, causes inverted polarity of differentiated hairs and ectopic flowers, in addition to wing-shaped outgrowths. These lemma-specific effects allow the spatiotemporal analysis of events following ectopic BKn3 expression, determining the relationship between KNOXs, polarity, and shape. We show that tissue cell polarity, based on localization of the auxin transporter SISTER OF PINFORMED1 (SoPIN1), dynamically reorients as ectopic BKn3 expression increases. Concurrently, ectopic expression of the auxin importer LIKE AUX1 and boundary gene NO APICAL MERISTEM is activated. The polarity of hairs reflects SoPIN1 patterns, suggesting that tissue cell polarity underpins oriented cell differentiation. Wing cell files reveal an anisotropic growth pattern, and computational modeling shows how polarity guiding growth can account for this pattern and wing emergence. The inverted ectopic flower orientation does not correlate with SoPIN1, suggesting that this form of regional polarity is not controlled by tissue cell polarity. Overall, the results suggest that KNOXs trigger different morphogenetic effects through interplay between tissue cell polarity, identity, and growth. PMID:27553356

A Multistate Toggle Switch Defines Fungal Cell Fates and Is Regulated by Synergistic Genetic Cues

PubMed Central

Anderson, Matthew Z.; Porman, Allison M.; Wang, Na; Mancera, Eugenio; Bennett, Richard J.

2016-01-01

Heritable epigenetic changes underlie the ability of cells to differentiate into distinct cell types. Here, we demonstrate that the fungal pathogen Candida tropicalis exhibits multipotency, undergoing stochastic and reversible switching between three cellular states. The three cell states exhibit unique cellular morphologies, growth rates, and global gene expression profiles. Genetic analysis identified six transcription factors that play key roles in regulating cell differentiation. In particular, we show that forced expression of Wor1 or Efg1 transcription factors can be used to manipulate transitions between all three cell states. A model for tristability is proposed in which Wor1 and Efg1 are self-activating but mutually antagonistic transcription factors, thereby forming a symmetrical self-activating toggle switch. We explicitly test this model and show that ectopic expression of WOR1 can induce white-to-hybrid-to-opaque switching, whereas ectopic expression of EFG1 drives switching in the opposite direction, from opaque-to-hybrid-to-white cell states. We also address the stability of induced cell states and demonstrate that stable differentiation events require ectopic gene expression in combination with chromatin-based cues. These studies therefore experimentally test a model of multistate stability and demonstrate that transcriptional circuits act synergistically with chromatin-based changes to drive cell state transitions. We also establish close mechanistic parallels between phenotypic switching in unicellular fungi and cell fate decisions during stem cell reprogramming. PMID:27711197

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srisuttee, Ratakorn; Koh, Sang Seok; Department of Functional Genomics, University of Science and Technology, Daejeon 305-333

Highlights: Black-Right-Pointing-Pointer Up-regulation of SIRT1 protein and activity sensitizes Hep3B-HBX cells to oxidative stress-induced apoptosis. Black-Right-Pointing-Pointer Nuclear localization of SIRT1 is not required for oxidation-induced apoptosis. Black-Right-Pointing-Pointer Ectopic expression and enhanced activity of SIRT1 attenuate JNK phosphorylation. Black-Right-Pointing-Pointer Inhibition of SIRT1 activity restores resistance to oxidation-induced apoptosis through JNK activation. -- Abstract: We previously showed that SIRT1 deacetylase inhibits proliferation of hepatocellular carcinoma cells expressing hepatitis B virus (HBV) X protein (HBX), by destabilization of {beta}-catenin. Here, we report another role for SIRT1 in HBX-mediated resistance to oxidative stress. Ectopic expression and enhanced activity of SIRT1 sensitize Hep3B cells stablymore » expressing HBX to oxidative stress-induced apoptosis. SIRT1 mutant analysis showed that nuclear localization of SIRT1 is not required for sensitization of oxidation-mediated apoptosis. Furthermore, ectopic expression of SIRT1 and treatment with resveratrol (a SIRT1 activator) attenuated JNK phosphorylation, which is a prerequisite for resistance to oxidative stress-induced apoptosis. Conversely, suppression of SIRT1 activity with nicotinamide inhibited the effect of resveratrol on JNK phosphorylation, leading to restoration of resistance to oxidation-induced apoptosis. Taken together, these results suggest that up-regulation of SIRT1 under oxidative stress may be a therapeutic strategy for treatment of hepatocellular carcinoma cells related to HBV through inhibition of JNK activation.« less

A painful perineal lump: an unusual case of ectopic breast tissue

PubMed Central

Yongue, G; Leff, D; Lamb, BW; Karim, S; Aref, F; Vashisht, R

2011-01-01

We report the case of a 40-year-old lady who presented with an episodically painful perineal lump. Clinical and radiological investigations were inconclusive. Excision biopsy confirmed an ectopic breast mass. Ectopic breast tissue is difficult to diagnose but close attention to clinical findings can help to guide further investigation and diagnosis. PMID:22004627

Potential link between excess added sugar intake and ectopic fat: a systematic review of randomized controlled trials

USDA-ARS?s Scientific Manuscript database

Context: The effect of added sugar intake on ectopic fat accumulation is a subject of debate. Objective: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to examine the potential effect of added sugar intake on ectopic fat depots. Data Sources: MEDLINE, CA...

Long-term effectiveness of surgical treatment of ectopic atrial tachycardia.

PubMed

Prager, N A; Cox, J L; Lindsay, B D; Ferguson, T B; Osborn, J L; Cain, M E

1993-07-01

The purpose of this study was to determine the long-term clinical outcome of patients with ectopic atrial tachycardias treated surgically. Ectopic atrial tachycardia is an uncommon arrhythmia that can be symptomatic and is associated with the development of a cardiomyopathy. Management strategies are not well defined because of the paucity of data on the long-term effectiveness of pharmacologic and nonpharmacologic therapies. The long-term clinical impact of medical and surgical therapy was determined in 15 consecutive patients with ectopic atrial tachycardia. All 15 patients were initially treated with antiarrhythmic drugs (mean 5.7 +/- 2.2 drugs/patient). An effective drug regimen was identified in only 5 (33%) of the 15 patients; the remaining 10 patients were treated surgically. In each, individualized surgical procedures were guided by computer-assisted intraoperative mapping, with atrial plaques comprising up to 156 electrodes. Focal ablation was performed in four patients and atrial isolation procedures in six. The 10 patients treated surgically were followed up a mean of 4 +/- 3.2 years. Ectopic atrial tachycardia recurred in one patient. A permanent pacemaker was implanted in two patients, one of whom also required reoperation for constrictive pericarditis. There were no operative deaths. Ectopic atrial tachycardia recurred in three (60%) of the five patients discharged on antiarrhythmic drug therapy during a mean follow-up interval of 6.4 +/- 4.3 years. There was one nonarrhythmic death. Map-guided surgery demonstrated long-term efficacy in abolishing symptoms in 9 of the 10 patients with ectopic atrial tachycardia. Results demonstrate that surgery is effective for patients with ectopic atrial tachycardias who are not easily treated with antiarrhythmic drugs.

Serum β-hCG levels post-treatment of ectopic pregnancy with a single dose of intramuscular methotrexate.

PubMed

Hadinata, Ignatius E; Doyle, Lex W; Thompson, Derrick; Reti, Leslie

2015-04-01

The cytotoxic management of ectopic pregnancy using a single dose of intramuscular methotrexate injection has been well established as effective for a select number of women with unruptured tubal ectopic pregnancy where there are minimal symptoms. The purpose of this study was to create centile curves of serum β-hCG levels following successful treatment with a single dose of 50 mg/m(2) of intramuscular methotrexate to treat ectopic pregnancy. Data were retrieved from women treated at the Royal Women's Hospital for ectopic pregnancy between 2006 and 2012. Only women with minimal symptoms, initial serum β-hCG ≤5000 IU/L and ectopic mass size of ≤35 mm on ultrasound were included. Two hundred and fifty-three cases of ectopic pregnancy were analysed. Initial β-hCG of women in the study ranged from 18 to 3995 IU/L with a median of 497 (25th to 75th centiles; 222-1160) IU/L. The median levels of β-hCG levels at day 4, 7 and 14 postmethotrexate injection were 73.8, 47.2 and 10.4% of the initial β-hCG level, respectively. The 90th centiles of β-hCG levels at day 4, 7 and 14 were 124.7, 93.8 and 40.0% of initial β-hCG level, respectively. Whilst no comparison with those unsuccessfully treated was made, pending further validation studies, the use of these curves may reduce the reliance on specialist units and streamline care for many women with ectopic pregnancy, such as those whose β-hCG regress in line with centile values without crossing a certain threshold. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

A rare case of an ACTH/CRH co-secreting midgut neuroendocrine tumor mimicking Cushing's disease.

PubMed

Streuli, Regina; Krull, Ina; Brändle, Michael; Kolb, Walter; Stalla, Günter; Theodoropoulou, Marily; Enzler-Tschudy, Annette; Bilz, Stefan

2017-01-01

Ectopic ACTH/CRH co-secreting tumors are a very rare cause of Cushing's syndrome and only a few cases have been reported in the literature. Differentiating between Cushing's disease and ectopic Cushing's syndrome may be particularly difficult if predominant ectopic CRH secretion leads to pituitary corticotroph hyperplasia that may mimic Cushing's disease during dynamic testing with both dexamethasone and CRH as well as bilateral inferior petrosal sinus sampling (BIPSS). We present the case of a 24-year-old man diagnosed with ACTH-dependent Cushing's syndrome caused by an ACTH/CRH co-secreting midgut NET. Both high-dose dexamethasone testing and BIPSS suggested Cushing's disease. However, the clinical presentation with a rather rapid onset of cushingoid features, hyperpigmentation and hypokalemia led to the consideration of ectopic ACTH/CRH-secretion and prompted a further workup. Computed tomography (CT) of the abdomen revealed a cecal mass which was identified as a predominantly CRH-secreting neuroendocrine tumor. To the best of our knowledge, this is the first reported case of an ACTH/CRH co-secreting tumor of the cecum presenting with biochemical features suggestive of Cushing's disease. The discrimination between a Cushing's disease and ectopic Cushing's syndrome is challenging and has many caveats.Ectopic ACTH/CRH co-secreting tumors are very rare.Dynamic tests as well as BIPSS may be compatible with Cushing's disease in ectopic CRH-secretion.High levels of CRH may induce hyperplasia of the corticotroph cells in the pituitary. This could be the cause of a preserved pituitary response to dexamethasone and CRH.Clinical features of ACTH-dependent hypercortisolism with rapid development of Cushing's syndrome, hyperpigmentation, high circulating levels of cortisol with associated hypokalemia, peripheral edema and proximal myopathy should be a warning flag of ectopic Cushing's syndrome and lead to further investigations.

Dysregulated endocardial TGFβ signaling and mesenchymal transformation result in heart outflow tract septation failure.

PubMed

Ma, Mancheong; Li, Peng; Shen, Hua; Estrada, Kristine D; Xu, Jian; Kumar, S Ram; Sucov, Henry M

2016-01-01

Heart outflow tract septation in mouse embryos carrying mutations in retinoic acid receptor genes fails with complete penetrance. In this mutant background, ectopic TGFβ signaling in the distal outflow tract is responsible for septation failure, but it was uncertain what tissue was responsive to ectopic TGFβ and why this response interfered with septation. By combining RAR gene mutation with tissue-specific Cre drivers and a conditional type II TGFβ receptor (Tgfbr2) allele, we determined that ectopic activation of TGFβ signaling in the endocardium is responsible for septation defects. Ectopic TGFβ signaling results in ectopic mesenchymal transformation of the endocardium and thereby in improperly constituted distal OFT cushions. Our analysis highlights the interactions between myocardium, endocardium, and neural crest cells in outflow tract morphogenesis, and demonstrates the requirement for proper TGFβ signaling in outflow tract cushion organization and septation. Copyright © 2015. Published by Elsevier Inc.

Calvarial ectopic meningothelial meningioma

PubMed Central

Vital, Roberto Bezerra; Hamamoto Filho, Pedro Tadao; Lapate, Renan Luiz; Martins, Vinícius Zanin; de Oliveira Lima, Flávio; Romero, Flávio Ramalho; Zanini, Marco Antônio

2015-01-01

Background Meningiomas are the most common benign neoplasm of the brain whereas ectopic presentation, although reported, is rare. Among these ectopic tumors, there are a group of purely intraosseous meningiomas, which usually are diagnosed differentially from common primary osseous tumor such as fibrous dysplasia and osteoid osteoma. Case description We report a 62-year-old female with a history of headaches and 6 months of progressive right parietal bulging, with no neurological signs. Parietal craniotomy was performed with immediate titanium cranioplasty of the parietal convexity. Histopathology exams revealed an ectopic intradiploic meningioma without invasion of cortical layers, with positive staining for progesterone receptors and epithelial membrane antigen. Conclusions Ectopic intraosseous meningiomas remain a rare neoplasm with only a few cases reported. The main theories to justify the unusual topography appear to be embryological remains of neuroectodermal tissue or cellular dedifferentiation. Surgical treatment seems the best curative option. PMID:25805612

Syringomyelia with intramedullary ectopic choroid plexus: Case report.

PubMed

Duan, Hongzhou; Zhang, Jiayong; Xu, Feifan; Zhang, Zongqiang; Zhao, Xiaowen

2018-06-01

Intramedullary ectopic choroid plexus is rarely reported, here, we reported a rare case of symptomatic syringomyelia resulted of intramedullary ectopic choroid plexus. The patient was a 30-year-old female who presented with a 2-month history of progressive pain of upper back and bilateral ankle joint and progressive loss of upper-extremity function. MRI examination showed an intramedullary cystic lesion at T2-T4 without enhancement. Operative exploration was indicated. A reddish vascular villus-like lesion was found being located in the left dorsal part of the cyst, which was enblock removed and was confirmed as an ectopic choroid plexus tissue by pathological examination. The patient recovered uneventful and the symptom resolved during follow-up. Although ectopic choroid plexus is extremely rare, it should be taken into acount in the differential diagnosis of pathogenesis in syringomyelia or intramedullary cyst, aggressive surgical exploration should be considered when necessary. Copyright © 2018 Elsevier B.V. All rights reserved.

Pericardial Fat is Associated With Atrial Conduction: The Framingham Heart Study

PubMed Central

Friedman, Daniel J.; Wang, Na; Meigs, James B.; Hoffmann, Udo; Massaro, Joseph M.; Fox, Caroline S.; Magnani, Jared W.

2014-01-01

Background Obesity is associated with altered atrial electrophysiology and a prominent risk factor for atrial fibrillation. Body mass index, the most widely used adiposity measure, has been related to atrial electrical remodeling. We tested the hypothesis that pericardial fat is independently associated with electrocardiographic measures of atrial conduction. Methods and Results We performed a cross‐sectional analysis of 1946 Framingham Heart Study participants (45% women) to determine the relation between pericardial fat and atrial conduction as measured by P wave indices (PWI): PR interval, P wave duration (P‐duration), P wave amplitude (P‐amplitude), P wave area (P‐area), and P wave terminal force (P‐terminal). We performed sex‐stratified linear regression analyses adjusted for relevant clinical variables and ectopic fat depots. Each 1‐SD increase in pericardial fat was significantly associated with PR interval (β=1.7 ms, P=0.049), P‐duration (β=2.3 ms, P<0.001), and P‐terminal (β=297 μV·ms, P<0.001) among women; and P‐duration (β=1.2 ms, P=0.002), P‐amplitude (β=−2.5 μV, P<0. 001), and P‐terminal (β=160 μV·ms, P=0.002) among men. Among both sexes, pericardial fat was significantly associated with P‐duration in analyses additionally adjusting for visceral fat or intrathoracic fat; a similar but non‐significant trend existed with P‐terminal. Among women, pericardial fat was significantly associated with P wave area after adjustment for visceral and intrathoracic fat. Conclusions Pericardial fat is associated with atrial conduction as quantified by PWI, even with adjustment for extracardiac fat depots. Further studies are warranted to identify the mechanisms through which pericardial fat may modify atrial electrophysiology and promote subsequent risk for arrhythmogenesis. PMID:24595189

Crossed Unfused Ectopic Pelvic Kidneys: A Case Illustration.

PubMed

Degheili, Jad A; AbuSamra, Murad M; El-Merhi, Fadi; El-Hajj, Albert

2018-01-01

Crossed unfused ectopia constitutes a very rare variant of ectopic kidneys, with an approximate incidence of 1 : 75000. We hereby describe a rare case of an incidental finding of crossed unfused ectopic kidneys, in a 45-year-old gentleman incidentally found to have a bladder lesion. The unique blood supply of his kidneys has also been described. The present case also highlights the different subtypes of renal ectopia, the different embryological hypotheses behind their presentation, and the various systematic anomalies, associated with them. Variations in vasculature of ectopic kidneys have been only described in case reports and are crucial to recognize in case any further intervention is needed.

Lactational ectopic breast tissue of the vulva: case report and brief historical review.

PubMed

Pieh-Holder, Kelly L

2013-04-01

Ectopic breast tissue is defined as glands of breast tissue located outside of the normal anatomic breasts. Historically, ectopic breast tissue has been thought to arise from a remnant of the embryonic mammary ridge along the "milk line" or the midaxillary line from the axilla to the groin, including the vulvar region. Extramammary tissue displays the same pathologic and physiologic changes as normal breast tissue and is often discovered in multiparous women as the result of swelling from lactational activity. We present a case report of a gravid patient with lactating vulvar mass and a brief historical perspective of vulvar ectopic breast tissue.

Failure rate of single dose methotrexate in managment of ectopic pregnancy.

PubMed

Sendy, Feras; AlShehri, Eman; AlAjmi, Amani; Bamanie, Elham; Appani, Surekha; Shams, Taghreed

2015-01-01

Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67%)) received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225) of the patients. 28% (63/225) were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63) of failure received a second dose of methotrexate, and 37% (23/63) underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate.

Ectopic Molar Pregnancy: Diagnostic Efficacy of Magnetic Resonance Imaging and Review of the Literature.

PubMed

Yamada, Yasushi; Ohira, Satoshi; Yamazaki, Teruyuki; Shiozawa, Tanri

2016-01-01

Ectopic molar pregnancy is extremely rare, and preoperative diagnosis is difficult. Our literature search found only one report of molar pregnancy diagnosed preoperatively. Moreover, there is no English literature depicting magnetic resonance image (MRI) findings of ectopic molar pregnancy. We report a case of ectopic molar pregnancy preoperatively diagnosed using MRI. A literature review of 31 cases of ectopic molar pregnancy demonstrated that lesions have been found in the fallopian tube (19 cases, 61%), ovary (5 cases, 16%), cornu (3 cases, 10%), peritoneum (2 cases, 6%), uterine cervix (1 case, 3%), and cesarean scar (1 case, 3%). Abdominal pain and abnormal vaginal bleeding were reported in 70% and 61% of the patients, respectively. Twenty-one cases (67%) presented with rupture and hemoperitoneum. All patients underwent surgical resection or dilatation and curettage. Methotrexate therapy was performed in one case because residual trophoblastic tissue was suspected. A second operation was performed in one case of ovarian molar pregnancy because serum hCG levels increased again after primary focal ovarian resection. No patients developed metastatic disease or relapsed. These findings suggest the prognosis of ectopic molar pregnancy to be favorable.

Radiographic assessment of dental anomalies in patients with ectopic maxillary canines.

PubMed

Sørensen, Helle Budtz; Artmann, Lone; Larsen, Helle Juul; Kjaer, Inger

2009-03-01

The aetiology of palatally and labially located ectopic maxillary canines is multifactorial. Accordingly, early prediction of this eruptional disturbance is in most cases not possible. The purpose of this study was to analyse dental deviations in cases with either palatal or labial ectopic canines. Panoramic and intra-oral radiographs from 50 patients with palatally located (38 females and 12 males) and 19 patients with labially located ectopic canines (11 females and 8 males), aged 10 years, 2 months-18 years, 1 month, were analysed. Dental deviations registered were crown and root malformations, agenesis, and eruption deviations. Registrations were performed in the maxillary incisor field and in the dentition in general. The study documented that palatally as well as labially located ectopic canines can occur in dentitions without other dental deviations. Dental deviations occurred in approximately two-thirds of all cases, more often in females and in cases with palatally located canines. More than half of the females with palatally located canines had deviations in the maxillary incisors and in the dentition in general. Dental deviations may be considered a risk factor for maxillary canine ectopia. Early identification of patients at risk and appropriate interceptive treatment may reduce ectopic eruption of maxillary canines.

Upper gastrointestinal ectopic variceal bleeding treated with various endoscopic modalities: Case reports and literature review.

PubMed

Park, Sang Woo; Cho, Eunae; Jun, Chung Hwan; Choi, Sung Kyu; Kim, Hyun Soo; Park, Chang Hwan; Rew, Jong Sun; Cho, Sung Bum; Kim, Hee Joon; Han, Mingui; Cho, Kyu Man

2017-01-01

Ectopic variceal bleeding is a rare (2-5%) but fatal gastrointestinal bleed in patients with portal hypertension. Patients with ectopic variceal bleeding manifest melena, hematochezia, or hematemesis, which require urgent managements. Definitive therapeutic modalities of ectopic varices are not yet standardized because of low incidence. Various therapeutic modalities have been applied on the basis of the experiences of experts or availability of facilities, with varying results. We have encountered eight cases of gastrointestinal ectopic variceal bleeding in five patients in the last five years. All patients were diagnosed with liver cirrhosis presenting melena or hematemesis. All patients were treated with various endoscopic modalities (endoscopic variceal obturation [EVO] with cyanoacrylate in five cases, endoscopic variceal band ligation (EVL) in two cases, hemoclipping in one case). Satisfactory hemostasis was achieved without radiologic interventions in all cases. EVO and EVL each caused one case of portal biliopathy, and EVL induced ulcer bleeding in one case. EVO generally accomplished better results of variceal obturations than EVL or hemoclipping, without serious adverse events. EVO may be an effective modality for control of ectopic variceal bleeding without radiologic intervention or surgery.

[Management of ectopic pregnancy in Conakry, Guinea].

PubMed

Sy, T; Diallo, Y; Toure, A; Diallo, F B; Balde, A A; Hyjazi, Y; Diallo, M S

2009-12-01

Ectopic pregnancy is one of the most frequent hemorrhagic emergencies encountered in gynecology and obstetrics. The purpose of this 16-month descriptive prospective study at the Ignace Deen Gynecology-Obstetric clinic at Conakry University Hospital in Guinea was to assess diagnostic techniques and therapeutic attitudes regarding ectopic pregnancy in a low-resource setting. The frequency of ectopic pregnancy was 1.4%. Mean patient age was 28.9 years. Ectopic pregnancy was often observed at the second or third pregnancy (47.1%) in women who were giving birth for the second or third time (36.0%) and had a history of sexually transmitted infections (88.2%) or abortions (43.1%). Most women had no schooling (60.8 %), were poor and lived in a marital home (86.3%). Presenting symptoms included the classic triad of amenorrhea (98.0%), abdominopelvic pain (92.2%), and vaginal bleeding (62.7%). Definitive diagnosis was achieved by ultrasound examination in 76.6% of cases and by puncture of the Douglas pouch in 84%. The most frequent site of ectopic pregnancy was the ampulla of the uterine tube (66.9%). Abdominal and ovarian pregnancy was observed in 3 and 4 of the 51 cases respectively. Surgical management was performed in all cases. The most frequent procedure was salpingectomy (80.3%). Proper treatment of sexually transmitted infections (STI), start-up of post-abortion care facilities, and provision of information during early consultation at the first signs of pregnancy would help reduce the frequency and improve the prognosis of ectopic pregnancy.

E2F1-mediated human POMC expression in ectopic Cushing's syndrome.

PubMed

Araki, Takako; Liu, Ning-Ai; Tone, Yukiko; Cuevas-Ramos, Daniel; Heltsley, Roy; Tone, Masahide; Melmed, Shlomo

2016-11-01

Cushing's syndrome is caused by excessive adrenocorticotropic hormone (ACTH) secretion derived from pituitary corticotroph tumors (Cushing disease) or from non-pituitary tumors (ectopic Cushing's syndrome). Hypercortisolemic features of ectopic Cushing's syndrome are severe, and no definitive treatment for paraneoplastic ACTH excess is available. We aimed to identify subcellular therapeutic targets by elucidating transcriptional regulation of the human ACTH precursor POMC (proopiomelanocortin) and ACTH production in non-pituitary tumor cells and in cell lines derived from patients with ectopic Cushing's syndrome. We show that ectopic hPOMC transcription proceeds independently of pituitary-specific Tpit/Pitx1 and demonstrate a novel E2F1-mediated transcriptional mechanism regulating hPOMC We identify an E2F1 cluster binding to the proximal hPOMC promoter region (-42 to +68), with DNA-binding activity determined by the phosphorylation at Ser-337. hPOMC mRNA expression in cancer cells was upregulated (up to 40-fold) by the co-expression of E2F1 and its heterodimer partner DP1. Direct and indirect inhibitors of E2F1 activity suppressed hPOMC gene expression and ACTH by modifying E2F1 DNA-binding activity in ectopic Cushing's cell lines and primary tumor cells, and also suppressed paraneoplastic ACTH and cortisol levels in xenografted mice. E2F1-mediated hPOMC transcription is a potential target for suppressing ACTH production in ectopic Cushing's syndrome. © 2016 Society for Endocrinology.

Irish women's experience of Ectopic pregnancy.

PubMed

Spillane, N; Meaney, S; O' Donoghue, K

2018-06-01

Ectopic pregnancy can become a life threatening condition. Due to the specific nature of Ectopic pregnancy the grief experienced may well be overlooked compared to other pregnancy losses. Fertility concerns for the future and recovery from surgical or medical treatment may instead become the focus of care. The objective of this study was to gain insight into women's experience of Ectopic pregnancy. A qualitative semi-structured interview format was utilised. Seven women who had experienced an Ectopic pregnancy in a large tertiary-level Irish maternity hospital were interviewed. This sample was recruited purposively ensuring inclusion of women whose treatment included expectant, medical or surgical management. Interpretative phenomenological analysis was employed as the analytic strategy as it has an ideographic approach which allows us to gain insight into the women's experiences of Ectopic pregnancy. Key findings were the importance of clear information on treatment options, the diagnostic scan was highlighted as important as it helped the women emotionally detach from the pregnancy. Lack of bereavement counselling and satisfactory completion of outpatient care hindered closure and recovery for these women. There was increased apprehension about fertility and women reported feeling reluctant to conceive again. Women reported difficulty coming to terms with their diagnosis which in turn impacted their recovery and illustrated women's reservations to embark on future pregnancies. This study has implications for the care of women who experience Ectopic pregnancy particularly in relation to how they are managed from diagnosis to completion of treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

ANALYSIS OF TMEFF2 ALLOGRAFTS AND TRANSGENIC MOUSE MODELS REVEALS ROLES IN PROSTATE REGENERATION AND CANCER

PubMed Central

Corbin, JM.; Overcash, RF.; Wren, JD.; Coburn, A.; Tipton, GJ.; Ezzell, JA.; McNaughton, KK.; Fung, KM; Kosanke, SD.; Ruiz-Echevarria, MJ

2015-01-01

BACKGROUND Previous results from our lab indicate a tumor suppressor role for the transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) in prostate cancer (PCa). Here, we further characterize this role and uncover new functions for TMEFF2 in cancer and adult prostate regeneration. METHODS The role of TMEFF2 was examined in PCa cells using Matrigel™ cultures and allograft models of PCa cells. In addition, we developed a transgenic mouse model that expresses TMEFF2 from a prostate specific promoter. Anatomical, histological and metabolic characterizations of the transgenic mouse prostate were conducted. The effect of TMEFF2 in prostate regeneration was studied by analyzing branching morphogenesis in the TMEFF2-expressing mouse lobes and alterations in branching morphogenesis were correlated with the metabolomic profiles of the mouse lobes. The role of TMEFF2 in prostate tumorigenesis in whole animals was investigated by crossing the TMEFF2 transgenic mice with the TRAMP mouse model of PCa and analyzing the histopathological changes in the progeny. RESULTS Ectopic expression of TMEFF2 impairs growth of PCa cells in Matrigel or allograft models. Surprisingly, while TMEFF2 expression in the TRAMP mouse did not have a significant effect on the glandular prostate epithelial lesions, the double TRAMP/TMEFF2 transgenic mice displayed an increased incidence of neuroendocrine type tumors. In addition, TMEFF2 promoted increased branching specifically in the dorsal lobe of the prostate suggesting a potential role in developmental processes. These results correlated with data indicating an alteration in the metabolic profile of the dorsal lobe of the transgenic TMEFF2 mice. CONCLUSIONS Collectively, our results confirm the tumor suppressor role of TMEFF2 and suggest that ectopic expression of TMEFF2 in mouse prostate leads to additional lobe-specific effects in prostate regeneration and tumorigenesis. This points to a complex and multifunctional role for TMEFF2 during PCa progression. PMID:26417683

Analysis of TMEFF2 allografts and transgenic mouse models reveals roles in prostate regeneration and cancer.

PubMed

Corbin, Joshua M; Overcash, Ryan F; Wren, Jonathan D; Coburn, Anita; Tipton, Greg J; Ezzell, Jennifer A; McNaughton, Kirk K; Fung, Kar-Ming; Kosanke, Stanley D; Ruiz-Echevarria, Maria J

2016-01-01

Previous results from our lab indicate a tumor suppressor role for the transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) in prostate cancer (PCa). Here, we further characterize this role and uncover new functions for TMEFF2 in cancer and adult prostate regeneration. The role of TMEFF2 was examined in PCa cells using Matrigel(TM) cultures and allograft models of PCa cells. In addition, we developed a transgenic mouse model that expresses TMEFF2 from a prostate specific promoter. Anatomical, histological, and metabolic characterizations of the transgenic mouse prostate were conducted. The effect of TMEFF2 in prostate regeneration was studied by analyzing branching morphogenesis in the TMEFF2-expressing mouse lobes and alterations in branching morphogenesis were correlated with the metabolomic profiles of the mouse lobes. The role of TMEFF2 in prostate tumorigenesis in whole animals was investigated by crossing the TMEFF2 transgenic mice with the TRAMP mouse model of PCa and analyzing the histopathological changes in the progeny. Ectopic expression of TMEFF2 impairs growth of PCa cells in Matrigel or allograft models. Surprisingly, while TMEFF2 expression in the TRAMP mouse did not have a significant effect on the glandular prostate epithelial lesions, the double TRAMP/TMEFF2 transgenic mice displayed an increased incidence of neuroendocrine type tumors. In addition, TMEFF2 promoted increased branching specifically in the dorsal lobe of the prostate suggesting a potential role in developmental processes. These results correlated with data indicating an alteration in the metabolic profile of the dorsal lobe of the transgenic TMEFF2 mice. Collectively, our results confirm the tumor suppressor role of TMEFF2 and suggest that ectopic expression of TMEFF2 in mouse prostate leads to additional lobe-specific effects in prostate regeneration and tumorigenesis. This points to a complex and multifunctional role for TMEFF2 during PCa progression. © 2015 Wiley Periodicals, Inc.

RUNX2 correlates with subtype-specific breast cancer in a human tissue microarray, and ectopic expression of Runx2 perturbs differentiation in the mouse mammary gland

PubMed Central

McDonald, Laura; Ferrari, Nicola; Terry, Anne; Bell, Margaret; Mohammed, Zahra M.; Orange, Clare; Jenkins, Alma; Muller, William J.; Gusterson, Barry A.; Neil, James C.; Edwards, Joanne; Morris, Joanna S.; Cameron, Ewan R.; Blyth, Karen

2014-01-01

RUNX2, a master regulator of osteogenesis, is oncogenic in the lymphoid lineage; however, little is known about its role in epithelial cancers. Upregulation of RUNX2 in cell lines correlates with increased invasiveness and the capacity to form osteolytic disease in models of breast and prostate cancer. However, most studies have analysed the effects of this gene in a limited number of cell lines and its role in primary breast cancer has not been resolved. Using a human tumour tissue microarray, we show that high RUNX2 expression is significantly associated with oestrogen receptor (ER)/progesterone receptor (PR)/HER2-negative breast cancers and that patients with high RUNX2 expression have a poorer survival rate than those with negative or low expression. We confirm RUNX2 as a gene that has a potentially important functional role in triple-negative breast cancer. To investigate the role of this gene in breast cancer, we made a transgenic model in which Runx2 is specifically expressed in murine mammary epithelium under the control of the mouse mammary tumour virus (MMTV) promoter. We show that ectopic Runx2 perturbs normal development in pubertal and lactating animals, delaying ductal elongation and inhibiting lobular alveolar differentiation. We also show that the Runx2 transgene elicits age-related, pre-neoplastic changes in the mammary epithelium of older transgenic animals, suggesting that elevated RUNX2 expression renders such tissue more susceptible to oncogenic changes and providing further evidence that this gene might have an important, context-dependent role in breast cancer. PMID:24626992

Enhanced epithelial to mesenchymal transition (EMT) and upregulated MYC in ectopic lesions contribute independently to endometriosis.

PubMed

Proestling, Katharina; Birner, Peter; Gamperl, Susanne; Nirtl, Nadine; Marton, Erika; Yerlikaya, Gülen; Wenzl, Rene; Streubel, Berthold; Husslein, Heinrich

2015-07-22

Epithelial to mesenchymal transition (EMT) is a process in which epithelial cells lose polarity and cell-to-cell contacts and acquire the migratory and invasive abilities of mesenchymal cells. These abilities are thought to be prerequisites for the establishment of endometriotic lesions. A hallmark of EMT is the functional loss of E-cadherin (CDH1) expression in epithelial cells. TWIST1, a transcription factor that represses E-cadherin transcription, is among the EMT inducers. SNAIL, a zinc-finger transcription factor, and its close relative SLUG have similar properties to TWIST1 and are thus also EMT inducers. MYC, which is upregulated by estrogens in the uterus by an estrogen response cis-acting element (ERE) in its promoter, is associated with proliferation in endometriosis. The role of EMT and proliferation in the pathogenesis of endometriosis was evaluated by analyzing TWIST1, CDH1 and MYC expression. CDH1, TWIST1, SNAIL and SLUG mRNA expression was analyzed by qRT-PCR from 47 controls and 74 patients with endometriosis. Approximately 42 ectopic and 62 eutopic endometrial tissues, of which 30 were matched samples, were collected during the same surgical procedure. We evaluated TWIST1 and MYC protein expression by immunohistochemistry (IHC) in the epithelial and stromal tissue of 69 eutopic and 90 ectopic endometrium samples, of which 49 matched samples were analyzed from the same patient. Concordant expression of TWIST1/SNAIL/SLUG and CDH1 but also of TWIST1 and MYC was analyzed. We found that TWIST1, SNAIL and SLUG are overexpressed (p < 0.001, p = 0.016 and p < 0.001) in endometriosis, while CDH1 expression was concordantly reduced in these samples (p < 0.001). Similar to TWIST1, the epithelial expression of MYC was also significantly enhanced in ectopic endometrium compared to eutopic tissues (p = 0.008). We found exclusive expression of either TWIST1 or MYC in the same samples (p = 0.003). Epithelial TWIST1 is overexpressed in endometriosis and may contribute to the formation of endometriotic lesions by inducing epithelial to mesenchymal transition, as CDH1 was reduced in ectopic lesions. We found exclusive expression of either TWIST1 or MYC in the same samples, indicating that EMT and proliferation contribute independently of each other to the formation of endometriotic lesions.

Neurologic impairment from ectopic bone in the lumbar canal: a potential complication of off-label PLIF/TLIF use of bone morphogenetic protein-2 (BMP-2).

PubMed

Wong, David A; Kumar, Anant; Jatana, Sanjay; Ghiselli, Gary; Wong, Katherine

2008-01-01

Bone morphogenetic protein-2 (BMP-2) (Infuse) has been approved for use in anterior lumbar fusion in conjunction with an LT cage. However, off-label use is seen with anterior cervical fusion, posterior lumbar interbody fusion (PLIF), and transforaminal lumbar interbody fusion (TLIF). The Federal Food and Drug Administration trial of BMP-2 in a PLIF application was halted because of a high incidence of ectopic bone forming in the neural canal (75%). The authors did not find a correlation between ectopic bone and increased leg pain. They concluded that the ectopic bone was a radiographic phenomenon and not associated with clinical findings. Complications using BMP in the cervical spine have been reported. Heretofore, there has not been a similar warning voiced for use of BMP in a lumbar PLIF or TLIF. The purpose was to report five cases of ectopic bone in the canal associated with PLIF/TLIF off-label use of BMP-2 potentially contributing to abnormal neurologic findings. This is an observational cohort study of patients referred to a tertiary care private medical center. This was a retrospective chart review of patients referred to a tertiary spine institute with complications after surgery where BMP-2 had been used in an off-label PLIF or TLIF application. Patient demographics, operating room (OR) notes from the index BMP surgery, imaging studies, and current clinical status were reviewed. Five cases of ectopic bone in the spinal canal with potential neurologic compromise were identified. It does appear that ectopic bone in the spinal canal associated with BMP-2 use in PLIF or TLIF may contribute to symptomatic neurologic findings in rare cases. Revision surgeries are difficult. This article challenges a previous publication, which concluded that the high incidence of ectopic bone was of no clinical significance. Isolating BMP anteriorly in the disc space using layered barriers of bone graft between the BMP and the annular defect may reduce the incidence of ectopic bone in the spinal canal. Surgeons need to weigh the benefits versus risks of any technology used off label when making treatment decisions with their patients.

Perineurial Glial Plasticity and the Role of TGF-β in the Development of the Blood-Nerve Barrier.

PubMed

Morris, Angela D; Lewis, Gwendolyn M; Kucenas, Sarah

2017-05-03

Precisely orchestrated interactions between spinal motor axons and their ensheathing glia are vital for forming and maintaining functional spinal motor nerves. Following perturbations to peripheral myelinating glial cells, centrally derived oligodendrocyte progenitor cells (OPCs) ectopically exit the spinal cord and myelinate peripheral nerves in myelin with CNS characteristics. However, whether remaining peripheral ensheathing glia, such as perineurial glia, properly encase the motor nerve despite this change in glial cell and myelin composition, remains unknown. Using zebrafish mutants in which OPCs migrate out of the spinal cord and myelinate peripheral motor axons, we assayed perineurial glial development, maturation, and response to injury. Surprisingly, in the presence of OPCs, perineurial glia exited the CNS normally. However, aspects of their development, response to injury, and function were altered compared with wildtype larvae. In an effort to better understand the plasticity of perineurial glia in response to myelin perturbations, we identified transforming growth factor-β1 as a partial mediator of perineurial glial development. Together, these results demonstrate the incredible plasticity of perineurial glia in the presence of myelin perturbations. SIGNIFICANCE STATEMENT Peripheral neuropathies can result from damage or dysregulation of the insulating myelin sheath surrounding spinal motor axons, causing pain, inefficient nerve conduction, and the ectopic migration of oligodendrocyte progenitor cells (OPCs), the resident myelinating glial cell of the CNS, into the periphery. How perineurial glia, the ensheathing cells that form the protective blood-nerve barrier, are impacted by this myelin composition change is unknown. Here, we report that certain aspects of perineurial glial development and injury responses are mostly unaffected in the presence of ectopic OPCs. However, perineurial glial function is disrupted along nerves containing centrally derived myelin, demonstrating that, although perineurial glial cells display plasticity despite myelin perturbations, the blood-nerve barrier is compromised in the presence of ectopic OPCs. Copyright © 2017 the authors 0270-6474/17/374790-18$15.00/0.

Crossed Unfused Ectopic Pelvic Kidneys: A Case Illustration

PubMed Central

AbuSamra, Murad M.; El-Merhi, Fadi

2018-01-01

Crossed unfused ectopia constitutes a very rare variant of ectopic kidneys, with an approximate incidence of 1 : 75000. We hereby describe a rare case of an incidental finding of crossed unfused ectopic kidneys, in a 45-year-old gentleman incidentally found to have a bladder lesion. The unique blood supply of his kidneys has also been described. The present case also highlights the different subtypes of renal ectopia, the different embryological hypotheses behind their presentation, and the various systematic anomalies, associated with them. Variations in vasculature of ectopic kidneys have been only described in case reports and are crucial to recognize in case any further intervention is needed. PMID:29854552

Locations of ectopic beats coincide with spatial gradients of NADH in a regional model of low-flow reperfusion.

PubMed

Kay, Matthew; Swift, Luther; Martell, Brian; Arutunyan, Ara; Sarvazyan, Narine

2008-05-01

We studied the origins of ectopic beats during low-flow reperfusion after acute regional ischemia in excised rat hearts. The left anterior descending coronary artery was cannulated. Perfusate was delivered to the cannula using an high-performance liquid chromatography pump. This provided not only precise control of flow rate but also avoided mechanical artifacts associated with vessel occlusion and deocclusion. Optical mapping of epicardial transmembrane potential served to identify activation wavefronts. Imaging of NADH fluorescence was used to quantify local ischemia. Our experiments suggest that low-flow reperfusion of ischemic myocardium leads to a highly heterogeneous ischemic substrate and that the degree of ischemia between adjacent patches of tissue changes in time. In contrast to transient ectopic activity observed during full-flow reperfusion, persistent ectopic arrhythmias were observed during low-flow reperfusion. The origins of ectopic beats were traceable to areas of high spatial gradients of changes in NADH fluorescence caused by low-flow reperfusion.

Tethered Hsp90 Inhibitors Carrying Optical or Radioiodinated Probes Reveal Selective Internalization of Ectopic Hsp90 in Malignant Breast Tumor Cells

PubMed Central

Barrott, Jared J.; Hughes, Philip F.; Osada, Takuya; Yang, Xiao-Yi; Hartman, Zachary C.; Loiselle, David R.; Spector, Neil L.; Neckers, Len; Rajaram, Narasimhan; Hu, Fangyao; Ramanujam, Nimmi; Vaidyanathan, Ganesan; Zalutsky, Michael R.; Lyerly, H. Kim; Haystead, Timothy A.

2013-01-01

Summary Hsp90 inhibitors have demonstrated unusual selectivity for tumor cells despite its ubiquitous expression. This phenomenon has remained unexplained but could be influenced by ectopically expressed Hsp90 in tumors. We have synthesized novel Hsp90 inhibitors that can carry optical or radioiodinated probes via a PEG tether. We show that these tethered inhibitors selectively recognize cells expressing ectopic Hsp90 and become internalized. The internalization process is blocked by Hsp90 antibodies, suggesting that active cycling of the protein is occurring at the plasma membrane. In mice, we show exquisite accumulation of the fluor-tethered versions within breast tumors at very sensitive levels. Cell-based assays with the radiolabeled version showed picomolar detection in cells that express ectopic Hsp90. Our findings show that fluor-tethered or radiolabeled inhibitors targeting ectopic Hsp90 can be used to detect breast cancer malignancies through non-invasive imaging. PMID:24035283

Lack of Evidence That Male Fetal Microchimerism is Present in Endometriosis

PubMed Central

Fassbender, Amelie; Debiec-Rychter, Maria; Bree, Rieta Van; Vermeesch, Joris Robert; Meuleman, Christel; Tomassetti, Carla; Peeraer, Karen; D’Hooghe, Thomas; Lebovic, Dan I.

2015-01-01

Introduction: Fetal microchimerism has been implicated in the etiology of autoimmune diseases. This study was done to test the hypothesis that male fetal microchimerism is present in eutopic and ectopic endometrium (EM) obtained from women with endometriosis but not in eutopic EM from women without endometriosis. Methods: A total of 31 patients were selected, including women with endometriosis (paired eutopic and ectopic EM; n = 19) and women without endometriosis (eutopic EM; n = 12). Tricolor interphase fluorescence in situ hybridization analysis was performed by cohybridization of CEP Y SpectrumAqua and CEP X SpectrumGreen (SG)/CEP Y SpectrumOrange probes. Results: Ectopic EM from women with endometriosis had 75% XX chromosomes (double SG signals) and 25% X chromosomes (single SG signal). Y chromosomes were not observed in any of the eutopic/ectopic endometrial tissues from cases or controls. Conclusions: We were unable to confirm our hypothesis that male fetal microchimerism is present in eutopic and/or ectopic EM obtained from women with endometriosis. PMID:25749809

Early Ectopic Recurrence of Craniopharyngioma in the Cerebellopontine Angle.

PubMed

Mahdi, Mohamad-Motaz Al; Krauss, Joachim K; Nakamura, Makoto; Brandis, Almuth; Hong, Bujung

2018-01-01

Ectopic recurrence of craniopharyngioma in the cerebellopontine angle after surgical resection of a suprasellar craniopharyngioma is rare. Thus, only 5 cases were reported with a delay ranging between 4 and 26 years after removal of the primary tumor. We report a unique case of ectopic recurrence of craniopharyngioma in the cerebellopontine angle, which occurred at only 4 months after surgical resection of the primary tumor. A 24-year-old man underwent resection of a suprasellar craniopharyngioma via a right pterional approach four months earlier. During follow-up, cerebral magnetic resonance imaging (MRI) showed a round homogeneous contrast-enhancing tumor in the right cerebellopontine angle with neither relation to the internal auditory canal nor to the dura mater. After microsurgical resection, histopathological findings revealed ectopic recurrence of craniopharyngioma with similar tumors like the primary tumor. Although infrequent, craniopharyngioma may disseminate via the cerebrospinal fluid during surgical resection and grow in an ectopic place. Early follow-up and MRI scan following resection of a craniopharyngioma is recommended.

Complications of misdiagnosis of maxillary canine ectopic eruption.

PubMed

Garib, Daniela Gamba; Janson, Guilherme; Baldo, Taiana de Oliveira; dos Santos, Patrícia Bittencourt Dutra

2012-08-01

Ectopic eruption of maxillary canines can be associated with root resorption of adjacent teeth. This case report describes and discusses an interesting case of a 15-year-old girl with a Class III malocclusion and an impacted maxillary canine. Because of the unfavorable position of the ectopic canine and the severe root resorption of the maxillary left central and lateral incisors, the treatment options included extraction of the maxillary permanent canines. The mandibular first premolars were extracted to compensate for the Class III malocclusion. A panoramic radiograph taken earlier in the mixed dentition already indicated a possible eruption disturbance of the maxillary left permanent canine. The importance of early diagnosis of maxillary canine ectopic eruption is highlighted in this case report. The early identification of radiographic signs of an ectopic pathway of eruption should be followed by deciduous canine extraction to prevent canine retention and maxillary incisor root resorption. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Recruitment of TRF2 to laser-induced DNA damage sites.

PubMed

Huda, Nazmul; Abe, Satoshi; Gu, Ling; Mendonca, Marc S; Mohanty, Samarendra; Gilley, David

2012-09-01

Several lines of evidence suggest that the telomere-associated protein TRF2 plays critical roles in the DNA damage response. TRF2 is rapidly and transiently phosphorylated by an ATM-dependent pathway in response to DNA damage and this DNA damage-induced phosphoryation is essential for the DNA-PK-dependent pathway of DNA double-strand break repair (DSB). However, the type of DNA damage that induces TRF2 localization to the damage sites, the requirement for DNA damage-induced phosphorylation of TRF2 for its recruitment, as well as the detailed kinetics of TRF2 accumulation at DNA damage sites have not been fully investigated. In order to address these questions, we used an ultrafast femtosecond multiphoton laser and a continuous wave 405-nm single photon laser to induce DNA damage at defined nuclear locations. Our results showed that DNA damage produced by a femtosecond multiphoton laser was sufficient for localization of TRF2 to these DNA damage sites. We also demonstrate that ectopically expressed TRF2 was recruited to DNA lesions created by a 405-nm laser. Our data suggest that ATM and DNA-PKcs kinases are not required for TRF2 localization to DNA damage sites. Furthermore, we found that phosphorylation of TRF2 at residue T188 was not essential for its recruitment to laser-induced DNA damage sites. Thus, we provide further evidence that a protein known to function in telomere maintenance, TRF2, is recruited to sites of DNA damage and plays critical roles in the DNA damage response. Copyright © 2012 Elsevier Inc. All rights reserved.

Protein S-Nitrosylation Regulates Xylem Vessel Cell Differentiation in Arabidopsis.

PubMed

Kawabe, Harunori; Ohtani, Misato; Kurata, Tetsuya; Sakamoto, Tomoaki; Demura, Taku

2018-01-01

Post-translational modifications of proteins have important roles in the regulation of protein activity. One such modification, S-nitrosylation, involves the covalent binding of nitric oxide (NO)-related species to a cysteine residue. Recent work showed that protein S-nitrosylation has crucial functions in plant development and environmental responses. In the present study, we investigated the importance of protein S-nitrosylation for xylem vessel cell differentiation using a forward genetics approach. We performed ethyl methanesulfonate mutagenesis of a transgenic Arabidopsis 35S::VND7-VP16-GR line in which the activity of VASCULAR-RELATED NAC-DOMAIN7 (VND7), a key transcription factor involved in xylem vessel cell differentiation, can be induced post-translationally by glucocorticoid treatment, with the goal of obtaining suppressor mutants that failed to differentiate ectopic xylem vessel cells; we named these mutants suppressor of ectopic vessel cell differentiation induced by VND7 (seiv) mutants. We found the seiv1 mutant to be a recessive mutant in which ectopic xylem cell differentiation was inhibited, especially in aboveground organs. In seiv1 mutants, a single nucleic acid substitution (G to A) leading to an amino acid substitution (E36K) was present in the gene encoding S-NITROSOGLUTATHIONE REDUCTASE 1 (GSNOR1), which regulates the turnover of the natural NO donor, S-nitrosoglutathione. An in vitro S-nitrosylation assay revealed that VND7 can be S-nitrosylated at Cys264 and Cys320 located near the transactivation activity-related domains, which were shown to be important for transactivation activity of VND7 by transient reporter assay. Our results suggest crucial roles for GSNOR1-regulated protein S-nitrosylation in xylem vessel cell differentiation, partly through the post-translational modification of VND7. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Deficient of a clock gene, brain and muscle Arnt-like protein-1 (BMAL1), induces dyslipidemia and ectopic fat formation.

PubMed

Shimba, Shigeki; Ogawa, Tomohiro; Hitosugi, Shunsuke; Ichihashi, Yuya; Nakadaira, Yuki; Kobayashi, Munehiro; Tezuka, Masakatsu; Kosuge, Yasuhiro; Ishige, Kumiko; Ito, Yoshihisa; Komiyama, Kazuo; Okamatsu-Ogura, Yuko; Kimura, Kazuhiro; Saito, Masayuki

2011-01-01

A link between circadian rhythm and metabolism has long been discussed. Circadian rhythm is controlled by positive and negative transcriptional and translational feedback loops composed of several clock genes. Among clock genes, the brain and muscle Arnt-like protein-1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) play important roles in the regulation of the positive rhythmic transcription. In addition to control of circadian rhythm, we have previously shown that BMAL1 regulates adipogenesis. In metabolic syndrome patients, the function of BMAL1 is dysregulated in visceral adipose tissue. In addition, analysis of SNPs has revealed that BMAL1 is associated with susceptibility to hypertension and type II diabetes. Furthermore, the significant roles of BMAL1 in pancreatic β cells proliferation and maturation were recently reported. These results suggest that BMAL1 regulates energy homeostasis. Therefore, in this study, we examined whether loss of BMAL1 function is capable of inducing metabolic syndrome. Deficient of the Bmal1 gene in mice resulted in elevation of the respiratory quotient value, indicating that BMAL1 is involved in the utilization of fat as an energy source. Indeed, lack of Bmal1 reduced the capacity of fat storage in adipose tissue, resulting in an increase in the levels of circulating fatty acids, including triglycerides, free fatty acids, and cholesterol. Elevation of the circulating fatty acids level induced the formation of ectopic fat in the liver and skeletal muscle in Bmal1 -/- mice. Interestingly, ectopic fat formation was not observed in tissue-specific (liver or skeletal muscle) Bmal1 -/- mice even under high fat diet feeding condition. Therefore, we were led to conclude that BMAL1 is a crucial factor in the regulation of energy homeostasis, and disorders of the functions of BMAL1 lead to the development of metabolic syndrome.

Ectopic expression of Triticum aestivum SERK genes (TaSERKs) control plant growth and development in Arabidopsis.

PubMed

Singh, Akanksha; Khurana, Paramjit

2017-09-28

Somatic embryogenesis receptor kinases (SERKs) belong to a small gene family of receptor-like kinases involved in signal transduction. A total of 54 genes were shortlisted from the wheat genome survey sequence of which 5 were classified as SERKs and 49 were identified as SERK-like (SERLs). Tissue- specific expression of TaSERKs at major developmental stages of wheat corroborates their indispensable role during somatic and zygotic embryogenesis. TaSERK transcripts show inherent differences in their hormonal sensitivities, i.e. TaSERK2 and TaSERK3 elicits auxin- specific responses while TaSERK1, 4 and 5 were more specific towards BR-mediated regulation. The ectopic expression of TaSERK1, 2, 3, 4 and 5 in Arabidopsis led to enhanced plant height, larger silique size and increased seed yield. Zygotic embryogenesis specific genes showed a differential pattern in TaSERK Arabidopsis transgenics specifically in the silique tissues. Elongated hypocotyls and enhanced root growth were observed in the overexpression transgenic lines of all five TaSERKs. The inhibitory action of auxin and brassinosteroid in all the TaSERK transgenic lines indicates their role in regulating root development. The results obtained imply redundant functions of TaSERKs in maintaining plant growth and development.

The RECG1 DNA Translocase Is a Key Factor in Recombination Surveillance, Repair, and Segregation of the Mitochondrial DNA in Arabidopsis[OPEN

PubMed Central

Le Ret, Monique; Bergdoll, Marc; Bichara, Marc; Dietrich, André

2015-01-01

The mitochondria of flowering plants have considerably larger and more complex genomes than the mitochondria of animals or fungi, mostly due to recombination activities that modulate their genomic structures. These activities most probably participate in the repair of mitochondrial DNA (mtDNA) lesions by recombination-dependent processes. Rare ectopic recombination across short repeats generates new genomic configurations that contribute to mtDNA heteroplasmy, which drives rapid evolution of the sequence organization of plant mtDNAs. We found that Arabidopsis thaliana RECG1, an ortholog of the bacterial RecG translocase, is an organellar protein with multiple roles in mtDNA maintenance. RECG1 targets to mitochondria and plastids and can complement a bacterial recG mutant that shows defects in repair and replication control. Characterization of Arabidopsis recG1 mutants showed that RECG1 is required for recombination-dependent repair and for suppression of ectopic recombination in mitochondria, most likely because of its role in recovery of stalled replication forks. The analysis of alternative mitotypes present in a recG1 line and of their segregation following backcross allowed us to build a model to explain how a new stable mtDNA configuration, compatible with normal plant development, can be generated by stoichiometric shift. PMID:26462909

Targeted CRISPR disruption reveals a role for RNase MRP RNA in human preribosomal RNA processing

PubMed Central

Goldfarb, Katherine C.; Cech, Thomas R.

2017-01-01

MRP RNA is an abundant, essential noncoding RNA whose functions have been proposed in yeast but are incompletely understood in humans. Mutations in the genomic locus for MRP RNA cause pleiotropic human diseases, including cartilage hair hypoplasia (CHH). Here we applied CRISPR–Cas9 genome editing to disrupt the endogenous human MRP RNA locus, thereby attaining what has eluded RNAi and RNase H experiments: elimination of MRP RNA in the majority of cells. The resulting accumulation of ribosomal RNA (rRNA) precursor—analyzed by RNA fluorescent in situ hybridization (FISH), Northern blots, and RNA sequencing—implicates MRP RNA in pre-rRNA processing. Amelioration of pre-rRNA imbalance is achieved through rescue of MRP RNA levels by ectopic expression. Furthermore, affinity-purified MRP ribonucleoprotein (RNP) from HeLa cells cleaves the human pre-rRNA in vitro at at least one site used in cells, while RNP isolated from cells with CRISPR-edited MRP loci loses this activity, and ectopic MRP RNA expression restores cleavage activity. Thus, a role for RNase MRP in human pre-rRNA processing is established. As demonstrated here, targeted CRISPR disruption is a valuable tool for functional studies of essential noncoding RNAs that are resistant to RNAi and RNase H-based degradation. PMID:28115465

Supradiaphragmatic ectopic liver: delayed traumatic hepatic hernia mimics pulmonary tumor.

PubMed

Huang, C-S; Hsu, W-H; Hsia, C-Y

2007-06-01

We present a rare case of a 63-year-old woman, the oldest one in the literature, with supradiaphragmatic ectopic liver that mimics a pulmonary nodule. The chest roentgenogram and chest computer tomography showed a lobulated tumor nearby the diaphragm. Pathological examination of the resected tumor disclosed only remarkable fatty liver change. Ectopic liver should be kept in mind to differentiate for the pulmonary tumor nearby the diaphragm.

Ectopic Multinodular Goiter: Multidetector Computed Tomography Findings

PubMed Central

Karakaya, Afak Durur; Kantarci, Mecit; Yalcin, Ahmet; Demir, Berrin

2008-01-01

The thyroid is the first endocrine gland to form during embryogenesis. At this stage, incomplete or anomalous migration of thyroid tissue causes ectopic localization of the gland. In our case, a 55-year-old woman who was evaluated via ultrasonography (USG) and multi-detector computed tomography (MDCT) had no thyroid gland at the normal location, but did have ectopic thyroid tissue in the left submandibular and submental regions. PMID:25610021

Failure Rate of Single Dose Methotrexate in Managment of Ectopic Pregnancy

PubMed Central

Sendy, Feras; AlShehri, Eman; AlAjmi, Amani; Bamanie, Elham; Appani, Surekha; Shams, Taghreed

2015-01-01

Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67%)) received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225) of the patients. 28% (63/225) were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63) of failure received a second dose of methotrexate, and 37% (23/63) underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate. PMID:25861275

Association of ectopic fat with abdominal aorto-illiac and coronary artery calcification in african ancestry men.

PubMed

Kuipers, Allison L; Zmuda, Joseph M; Carr, J Jeffrey; Terry, James G; Nair, Sangeeta; Cvejkus, Ryan; Bunker, Clareann H; Patrick, Alan L; Wassel, Christina L; Miljkovic, Iva

2017-08-01

There is strong evidence that fat accumulating in non-adipose sites, "ectopic fat", is associated with cardiovascular disease (CVD), including vascular calcification. Most previous studies of this association have assessed only a single ectopic fat depot. Therefore, our aim was to assess the association of total, regional, and ectopic fat with abdominal aorto-illiac calcification (AAC) and coronary artery calcification (CAC) in 798 African ancestry men. Participants (mean age 62) were from the Tobago Bone Health Study cohort. Adiposity was assessed via clinical examination, dual x-ray absorptiometry, and computed tomography (CT). Ectopic fat depots included: abdominal visceral adipose tissue (VAT), liver attenuation, and calf intermuscular adipose tissue (IMAT). Vascular calcification was assessed by CT and quantified as present versus absent. Associations were tested using multiple logistic regression adjusted for traditional cardiovascular risk factors. Models of ectopic fat were additionally adjusted for total body fat and standing height. All adiposity measures, except VAT, were associated with AAC. Lower liver attenuation or greater calf IMAT was associated with 1.2-1.3-fold increased odds of AAC (p < 0.03 for both), though calf IMAT was a stronger predictor than liver attenuation (p < 0.001) when entered in a single model. No ectopic fat measure was associated with CAC. Greater adiposity in the skeletal muscle and liver, but not in the visceral compartment, was associated with increased odds of AAC in African ancestry men. These results highlight the potential importance of both quantity and location of adiposity accumulation throughout the body. Copyright © 2017 Elsevier B.V. All rights reserved.

Ectopic Varices in the Gastrointestinal Tract: Short- and Long-Term Outcomes of Percutaneous Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macedo, Thanila A., E-mail: macedo.thanila@mayo.edu; Andrews, James C.; Kamath, Patrick S.

2005-04-15

To evaluate the results of percutaneous management of ectopic varices, a retrospective review was carried out of 14 patients (9 men, 5 women; mean age 58 years) who between 1992 and 2001 underwent interventional radiological techniques for management of bleeding ectopic varices. A history of prior abdominal surgery was present in 12 of 14 patients. The interval between the surgery and percutaneous intervention ranged from 2 to 38 years. Transhepatic portal venography confirmed ectopic varices to be the source of portal hypertension-related gastrointestinal bleeding. Embolization of the ectopic varices was performed by a transhepatic approach with coil embolization of themore » veins draining into the ectopic varices. Transjugular intrahepatic portosystemic shunt (TIPS) was performed in the standard fashion. Eighteen procedures (12 primary coil embolizations, 1 primary TIPS, 2 re-embolizations, 3 secondary TIPS) were performed in 13 patients. One patient was not a candidate for percutaneous treatment. All interventions but one (re-embolization) were technically successful. In 2 of 18 interventions, re-bleeding occurred within 72 hr (both embolization patients). Recurrent bleeding (23 days to 27 months after initial intervention) was identified in 9 procedures (8 coil embolizations, 1 TIPS due to biliary fistula). One patient had TIPS revision because of ultrasound surveillance findings. New encephalopathy developed in 2 of 4 TIPS patients. Percutaneous coil embolization is a simple and safe treatment for bleeding ectopic varices; however, recurrent bleeding is frequent and reintervention often required. TIPS can offer good control of bleeding at the expense of a more complex procedure and associated risk of encephalopathy.« less

Development of functional ectopic compound eyes in scarabaeid beetles by knockdown of orthodenticle.

PubMed

Zattara, Eduardo E; Macagno, Anna L M; Busey, Hannah A; Moczek, Armin P

2017-11-07

Complex traits like limbs, brains, or eyes form through coordinated integration of diverse cell fates across developmental space and time, yet understanding how complexity and integration emerge from uniform, undifferentiated precursor tissues remains limited. Here, we use ectopic eye formation as a paradigm to investigate the emergence and integration of novel complex structures following massive ontogenetic perturbation. We show that down-regulation via RNAi of a single head patterning gene- orthodenticle -induces ectopic structures externally resembling compound eyes at the middorsal adult head of both basal and derived scarabaeid beetle species (Onthophagini and Oniticellini). Scanning electron microscopy documents ommatidial organization of these induced structures, while immunohistochemistry reveals the presence of rudimentary ommatidial lenses, crystalline cones, and associated neural-like tissue within them. Further, RNA-sequencing experiments show that after orthodenticle down-regulation, the transcriptional signature of the middorsal head-the location of ectopic eye induction-converges onto that of regular compound eyes, including up-regulation of several retina-specific genes. Finally, a light-aversion behavioral assay to assess functionality reveals that ectopic compound eyes can rescue the ability to respond to visual stimuli when wild-type eyes are surgically removed. Combined, our results show that knockdown of a single gene is sufficient for the middorsal head to acquire the competence to ectopically generate a functional compound eye-like structure. These findings highlight the buffering capacity of developmental systems, allowing massive genetic perturbations to be channeled toward orderly and functional developmental outcomes, and render ectopic eye formation a widely accessible paradigm to study the evolution of complex systems. Published under the PNAS license.

FGF2 cooperates with IL-17 to promote autoimmune inflammation.

PubMed

Shao, Xinrui; Chen, Siyuan; Yang, Daping; Cao, Mengtao; Yao, Yikun; Wu, Zhengxi; Li, Ningli; Shen, Nan; Li, Xiaoxia; Song, Xinyang; Qian, Youcun

2017-08-01

IL-17 is a pro-inflammatory cytokine implicated a variety of autoimmune diseases. We have recently reported that FGF2 cooperates with IL-17 to protect intestinal epithelium during dextran sodium sulfate (DSS)-induced colitis. Here, we report a pathogenic role of the FGF2-IL-17 cooperation in the pathogenesis of autoimmune arthritis. Combined treatment with FGF2 and IL-17 synergistically induced ERK activation as well as the production of cytokines and chemokines in human synovial intimal resident fibroblast-like synoviocytes (FLS). Furthermore, ectopic expression of FGF2 in mouse joints potentiated IL-17-induced inflammatory cytokine and chemokine production in the tissue. In the collagen-induced arthritis (CIA) model, while ectopic expression of FGF2 in vivo exacerbated tissue inflammation and disease symptom in the wild-type controls, the effect was largely blunted in Il17a -/- mice. Taken together, our study suggests that FGF2 cooperates with IL-17 to promote the pathogenesis of autoimmune arthritis by cooperating with IL-17 to induce inflammatory response.

Novel phosphate-activated macrophages prevent ectopic calcification by increasing extracellular ATP and pyrophosphate

PubMed Central

Villa-Bellosta, Ricardo; Hamczyk, Magda R.; Andrés, Vicente

2017-01-01

Purpose Phosphorus is an essential nutrient involved in many pathobiological processes. Less than 1% of phosphorus is found in extracellular fluids as inorganic phosphate ion (Pi) in solution. High serum Pi level promotes ectopic calcification in many tissues, including blood vessels. Here, we studied the effect of elevated Pi concentration on macrophage polarization and calcification. Macrophages, present in virtually all tissues, play key roles in health and disease and display remarkable plasticity, being able to change their physiology in response to environmental cues. Methods and results High-throughput transcriptomic analysis and functional studies demonstrated that Pi induces unpolarized macrophages to adopt a phenotype closely resembling that of alternatively-activated M2 macrophages, as revealed by arginine hydrolysis and energetic and antioxidant profiles. Pi-induced macrophages showed an anti-calcifying action mediated by increased availability of extracellular ATP and pyrophosphate. Conclusion We conclude that the ability of Pi-activated macrophages to prevent calcium-phosphate deposition is a compensatory mechanism protecting tissues from hyperphosphatemia-induced pathologic calcification. PMID:28362852

Fermentation performance optimization in an ectopic fermentation system.

PubMed

Yang, Xiaotong; Geng, Bing; Zhu, Changxiong; Li, Hongna; He, Buwei; Guo, Hui

2018-07-01

Ectopic fermentation systems (EFSs) were developed for wastewater treatment. Previous studies have investigated the ability of thermophilic bacteria to improve fermentation performance in EFS. Continuing this research, we evaluated EFS performance using principle component analysis and investigated the addition of different proportions of cow dung. Viable bacteria communities were clustered and identified using BOX-AIR-based repetitive extragenic palindromic-PCR and 16S rDNA analysis. The results revealed optimal conditions for the padding were maize straw inoculated with thermophilic bacteria. Adding 20% cow dung yielded the best pH values (6.94-8.56), higher temperatures, increased wastewater absorption, improved litter quality, and greater microbial quantities. The viable bacteria groups were enriched by the addition of thermophilic consortium, and exogenous strains G21, G14, G4-1, and CR-15 were detected in fermentation process. The proportion of Bacillus species in treatment groups reached 70.37% after fermentation, demonstrating that thermophilic bacteria, especially Bacillus, have an important role in EFS, supporting previous predictions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ectopically tethered CP190 induces large-scale chromatin decondensation

NASA Astrophysics Data System (ADS)

Ahanger, Sajad H.; Günther, Katharina; Weth, Oliver; Bartkuhn, Marek; Bhonde, Ramesh R.; Shouche, Yogesh S.; Renkawitz, Rainer

2014-01-01

Insulator mediated alteration in higher-order chromatin and/or nucleosome organization is an important aspect of epigenetic gene regulation. Recent studies have suggested a key role for CP190 in such processes. In this study, we analysed the effects of ectopically tethered insulator factors on chromatin structure and found that CP190 induces large-scale decondensation when targeted to a condensed lacO array in mammalian and Drosophila cells. In contrast, dCTCF alone, is unable to cause such a decondensation, however, when CP190 is present, dCTCF recruits it to the lacO array and mediates chromatin unfolding. The CP190 induced opening of chromatin may not be correlated with transcriptional activation, as binding of CP190 does not enhance luciferase activity in reporter assays. We propose that CP190 may mediate histone modification and chromatin remodelling activity to induce an open chromatin state by its direct recruitment or targeting by a DNA binding factor such as dCTCF.

A TAD boundary is preserved upon deletion of the CTCF-rich Firre locus.

PubMed

Barutcu, A Rasim; Maass, Philipp G; Lewandowski, Jordan P; Weiner, Catherine L; Rinn, John L

2018-04-13

The binding of the transcriptional regulator CTCF to the genome has been implicated in the formation of topologically associated domains (TADs). However, the general mechanisms of folding the genome into TADs are not fully understood. Here we test the effects of deleting a CTCF-rich locus on TAD boundary formation. Using genome-wide chromosome conformation capture (Hi-C), we focus on one TAD boundary on chromosome X harboring ~ 15 CTCF binding sites and located at the long non-coding RNA (lncRNA) locus Firre. Specifically, this TAD boundary is invariant across evolution, tissues, and temporal dynamics of X-chromosome inactivation. We demonstrate that neither the deletion of this locus nor the ectopic insertion of Firre cDNA or its ectopic expression are sufficient to alter TADs in a sex-specific or allele-specific manner. In contrast, Firre's deletion disrupts the chromatin super-loop formation of the inactive X-chromosome. Collectively, our findings suggest that apart from CTCF binding, additional mechanisms may play roles in establishing TAD boundary formation.

Ectopic pregnancy: exploration of its global research architecture using density-equalising mapping and socioeconomic benchmarks

PubMed Central

Brüggmann, Dörthe; Kollascheck, Jana; Quarcoo, David; Bendels, Michael H; Klingelhöfer, Doris; Louwen, Frank; Jaque, Jenny M; Groneberg, David A

2017-01-01

Objective About 2% of all pregnancies are complicated by the implantation of the zygote outside the uterine cavity and termed ectopic pregnancy. Whereas a multitude of guidelines exists and related research is constantly growing, no thorough assessment of the global research architecture has been performed yet. Hence, we aim to assess the associated scientific activities in relation to geographical and chronological developments, existing research networks and socioeconomic parameters. Design Retrospective, descriptive study. Setting On the basis of the NewQIS platform, scientometric methods were combined with novel visualising techniques such as density-equalising mapping to assess the scientific output on ectopic pregnancy. Using the Web of Science, we identified all related entries from 1900 to 2012. Results 8040 publications were analysed. The USA and the UK were dominating the field in regard to overall research activity (2612 and 723 publications), overall citation numbers and country-specific H-Indices (US: 80, UK: 42). Comparison to economic power of the most productive countries demonstrated that Israel invested more resources in ectopic pregnancy-related research than other nations (853.41 ectopic pregnancy-specific publications per 1000 billlion US$ gross domestic product (GDP)), followed by the UK (269.97). Relation to the GDP per capita index revealed 49.3 ectopic pregnancy-specific publications per US$1000 GDP per capita for the USA in contrast to 17.31 for the UK. Semiqualitative indices such as country-specific citation rates ranked Switzerland first (24.7 citations per ectopic pregnancy-specific publication), followed by the Scandinavian countries Finland and Sweden. Low-income countries did not exhibit significant research activities. Conclusions This is the first in-depth analysis of global ectopic pregnancy research since 1900. It offers unique insights into the global scientific landscape. Besides the USA and the UK, Scandinavian countries and Switzerland can also be regarded as leading nations with regard to their relative socioeconomic input. PMID:29025848

A rare case of an ACTH/CRH co-secreting midgut neuroendocrine tumor mimicking Cushing's disease

PubMed Central

Streuli, Regina; Krull, Ina; Brändle, Michael; Kolb, Walter; Stalla, Günter; Theodoropoulou, Marily; Enzler-Tschudy, Annette

2017-01-01

Ectopic ACTH/CRH co-secreting tumors are a very rare cause of Cushing’s syndrome and only a few cases have been reported in the literature. Differentiating between Cushing’s disease and ectopic Cushing’s syndrome may be particularly difficult if predominant ectopic CRH secretion leads to pituitary corticotroph hyperplasia that may mimic Cushing’s disease during dynamic testing with both dexamethasone and CRH as well as bilateral inferior petrosal sinus sampling (BIPSS). We present the case of a 24-year-old man diagnosed with ACTH-dependent Cushing’s syndrome caused by an ACTH/CRH co-secreting midgut NET. Both high-dose dexamethasone testing and BIPSS suggested Cushing’s disease. However, the clinical presentation with a rather rapid onset of cushingoid features, hyperpigmentation and hypokalemia led to the consideration of ectopic ACTH/CRH-secretion and prompted a further workup. Computed tomography (CT) of the abdomen revealed a cecal mass which was identified as a predominantly CRH-secreting neuroendocrine tumor. To the best of our knowledge, this is the first reported case of an ACTH/CRH co-secreting tumor of the cecum presenting with biochemical features suggestive of Cushing’s disease. Learning points: The discrimination between a Cushing’s disease and ectopic Cushing’s syndrome is challenging and has many caveats. Ectopic ACTH/CRH co-secreting tumors are very rare. Dynamic tests as well as BIPSS may be compatible with Cushing’s disease in ectopic CRH-secretion. High levels of CRH may induce hyperplasia of the corticotroph cells in the pituitary. This could be the cause of a preserved pituitary response to dexamethasone and CRH. Clinical features of ACTH-dependent hypercortisolism with rapid development of Cushing’s syndrome, hyperpigmentation, high circulating levels of cortisol with associated hypokalemia, peripheral edema and proximal myopathy should be a warning flag of ectopic Cushing’s syndrome and lead to further investigations. PMID:28680643

β-hCG resolution times during expectant management of tubal ectopic pregnancies.

PubMed

Mavrelos, D; Memtsa, M; Helmy, S; Derdelis, G; Jauniaux, E; Jurkovic, D

2015-05-21

A subset of women with a tubal ectopic pregnancy can be safely managed expectantly. Expectant management involves a degree of disruption with hospital visits to determine serum β-hCG (β-human chorionic gonadotrophin) concentration until the pregnancy test becomes negative and expectant management is considered complete. The length of time required for the pregnancy test to become negative and the parameters that influence this interval have not been described. Information on the likely length of follow up would be useful for women considering expectant management of their tubal ectopic pregnancy. This was a retrospective study at a tertiary referral center in an inner city London Hospital. We included women who were diagnosed with a tubal ectopic pregnancy by transvaginal ultrasound between March 2009 and March 2014. During the study period 474 women were diagnosed with a tubal ectopic pregnancy and 256 (54 %) of them fulfilled our management criteria for expectant management. A total of 158 (33 %) women had successful expectant management and in those cases we recorded the diameter of the ectopic pregnancy (mm), the maximum serum β-hCG (IU/L) and levels during follow up until resolution as well as the interval to resolution (days). The median interval from maximum serum β-hCG concentration to resolution was 18.0 days (IQR 11.0-28.0). The maximum serum β-hCG concentration and the rate of decline of β-hCG were independently associated with the length of follow up. Women's age and size of ectopic pregnancy did not have significant effects on the length of follow up. Women undergoing expectant management of ectopic pregnancy can be informed that the likely length of follow up is under 3 weeks and that it positively correlates with initial β-hCG level at the time of diagnosis.

Differential roles of HIC-5 isoforms in the regulation of cell death and myotube formation during myogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao Zhengliang; Deblis, Ryan; Glenn, Honor

2007-11-15

Hic-5 is a LIM-Only member of the paxillin superfamily of focal adhesion proteins. It has been shown to regulate a range of biological processes including: senescence, tumorigenesis, steroid hormone action, integrin signaling, differentiation, and apoptosis. To better understand the roles of Hic-5 during development, we initiated a detailed analysis of Hic-5 expression and function in C{sub 2}C{sub 12} myoblasts, a well-established model for myogenesis. We have found that: (1) myoblasts express at least 6 distinct Hic-5 isoforms; (2) the two predominant isoforms, Hic-5{alpha} and Hic-5{beta}, are differentially expressed during myogenesis; (3) any experimentally induced change in Hic-5 expression results inmore » a substantial increase in apoptosis during differentiation; (4) ectopic expression of Hic-5{alpha} is permissive to differentiation while expression of either Hic-5{beta} or antisense Hic-5 blocks myoblast fusion but not chemodifferentiation; (5) Hic-5 localizes to focal adhesions in C{sub 2}C{sub 12} myoblasts and perturbation of Hic-5 leads to defects in cell spreading; (6) alterations in Hic-5 expression interfere with the normal dynamics of laminin expression; and (7) ectopic laminin, but not fibronectin, can rescue the Hic-5-induced blockade of myoblast survival and differentiation. Our data demonstrate differential roles for individual Hic-5 isoforms during myogenesis and support the hypothesis that Hic-5 mediates these effects via integrin signaling.« less

Primary and repeated surgeries for ectopic pregnancies and distribution by patient age, surgeon age, and hospital levels: an 11-year nationwide population-based descriptive study in Taiwan.

PubMed

Hsu, Ming-I; Tang, Chao-Hsiun; Hsu, Pei-Yang; Huang, Yu-Tung; Long, Cheng-Yu; Huang, Kuan-Hui; Wu, Ming-Ping

2012-01-01

To describe the changing trend, repeat operation rate, and distribution of laparoscopy, as compared with laparotomy, in treating ectopic pregnancy, according to patient age, preoperative conditions, surgeon age, and hospital accreditation level, in Taiwan over 11-years. Retrospective cohort study (Canadian Task Force classification II-2). Population-based nationwide insurance database. Women who underwent either laparotomy or laparoscopy because of ectopic pregnancy. Women who had National Health Insurance (NHI) underwent various surgical procedures to treat ectopic pregnancy. Data for this study were obtained from the Inpatient Expenditures by Admissions files of the NHI Research Database, released by the NHI program in Taiwan between 1997 and 2007. A total of 43 170 women with 44 928 operations were identified. Only the primary surgeries, via either laparotomy or laparoscopy, performed because of ectopic pregnancy were included for analysis. The annual number of procedures to treat ectopic pregnancies decreased in the later years of the 11-year study. Laparotomy decreased significantly, from 81.2% in 1997 to 26.2% in 2007, whereas laparoscopic procedures increased significantly, from 18.8% in 1997 to 73.8% in 2007, as evidenced at log-linear regression analysis (p < .001). The rate of repeat operations because of persistent ectopic pregnancy was higher in the laparoscopy group than in the laparotomy group (0.38% vs 0.14 %; p < .001). Patients were more likely to undergo the same type of operation for the repeated surgery (i.e., laparotomy to laparotomy in 73.1% or laparoscopy to laparoscopy in 80.2%; p = 0.43). Use of laparoscopy (58.1%) and laparotomy (41.9%) differed according to patient age, preoperative comorbidities, surgeon age, and hospital accreditation level and ownership type. With older patients, those with preoperative anemia or shock, and elder surgeons, there was a greater chance that laparotomy would be performed. The probability of undergoing laparotomy was greater in patients in regional hospitals, local hospitals, and office-based clinics compared with those in medical centers. There has been considerable change in the type of surgical approach used to treat ectopic pregnancy in Taiwan over the past 11 years. Laparoscopy is preferred to laparotomy, and has become the standard surgical approach to treating ectopic pregnancies in Taiwan. However, laparoscopy is associated with a higher rate of repeat operations. The laparoscopic approach signifies a profound change in treating ectopic pregnancies among patients, surgeons, and hospital types. Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.

The Bladder Tumor Suppressor Protein TERE1 (UBIAD1)Modulates Cell Cholesterol: Implications for Tumor Progression

PubMed Central

McGarvey, Terry; Wang, Huiyi; Lal, Priti; Puthiyaveettil, Raghunath; Tomaszewski, John; Sepulveda, Jorge; Labelle, Ed; Weiss, Jayne S.; Nickerson, Michael L.; Kruth, Howard S.; Brandt, Wolfgang; Wessjohann, Ludger A.; Malkowicz, S. Bruce

2011-01-01

Convergent evidence implicates the TERE1 protein in human bladder tumor progression and lipid metabolism. Previously, reduced TERE1 expression was found in invasive urologic cancers and inhibited cell growth upon re-expression. A role in lipid metabolism was suggested by TERE1 binding to APOE, a cholesterol carrier, and to TBL2, a candidate protein in triglyceride disorders. Natural TERE1 mutations associate with Schnyder's corneal dystrophy, characterized by lipid accumulation. TERE1 catalyzes menaquinone synthesis, known to affect cholesterol homeostasis. To explore this relationship, we altered TERE1 and TBL2 dosage via ectopic expression and interfering RNA and measured cholesterol by Amplex red. Protein interactions of wild-type and mutant TERE1 with GST-APOE were evaluated by binding assays and molecular modeling. We conducted a bladder tumor microarray TERE1 expression analysis and assayed tumorigenicity of J82 cells ectopically expressing TERE1. TERE1 expression was reduced in a third of invasive specimens. Ectopic TERE1 expression in J82 bladder cancer cells dramatically inhibited nude mouse tumorigenesis. TERE1 and TBL2 proteins inversely modulated cellular cholesterol in HEK293 and bladder cancer cells from 20% to 50%. TERE1 point mutations affected APOE interactions, and resulted in cholesterol levels that differed from wild type. Elevated tumor cell cholesterol is known to affect apoptosis and growth signaling; thus, loss of TERE1 in invasive bladder cancer may represent a defect in menaquinone-mediated cholesterol homeostasis that contributes to progression. PMID:21740188

Ectopic ERK Expression Induces Phenotypic Conversion of C10 Cells and Alters DNA Methyltransferase Expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sontag, Ryan L.; Weber, Thomas J.

2012-05-04

In some model systems constitutive extracellular signal regulated kinase (ERK) activation is sufficient to promote an oncogenic phenotype. Here we investigate whether constitutive ERK expression influences phenotypic conversion in murine C10 type II alveolar epithelial cells. C10 cells were stably transduced with an ERK1-green fluorescent protein (ERK1-GFP) chimera or empty vector and ectopic ERK expression was associated with the acquisition of soft agar focus-forming potential in late passage, but not early passage cells. Late passage ERK1-GFP cells exhibited a significant increase in the expression of DNA methyl transferases (DNMT1 and 3b) and a marked increase in sensitivity to 5-azacytidine (5-azaC)-mediatedmore » toxicity, relative to early passage ERK1-GFP cells and vector controls. The expression of xeroderma pigmentosum complementation group A (XPA) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) were significantly increased in late passage cells, suggesting enhanced DNA damage recognition and repair activity which we interpret as a reflection of genomic instability. Phospho-ERK levels were dramatically decreased in late passage ERK1-GFP cells, relative to early passage and vector controls, and phospho-ERK levels were restored by treatment with sodium orthovanadate, indicating a role for phosphatase activity in this response. Collectively these observations suggest that ectopic ERK expression promotes phenotypic conversion of C10 cells that is associated with latent effects on epigenetic programming and phosphatase activities.« less

Ectopic pregnancy

MedlinePlus

Tubal pregnancy; Cervical pregnancy; Tubal ligation - ectopic pregnancy ... In most pregnancies, the fertilized egg travels through the fallopian tube to the womb (uterus). If the movement of the egg ...

The Intertwined Roles of Transcription and Repair Proteins

PubMed Central

Fong, Yick W.; Cattoglio, Claudia; Tjian, Robert

2014-01-01

Transcription is apparently risky business. Its intrinsic mutagenic potential must be kept in check by networks of DNA repair factors that monitor the transcription process to repair DNA lesions that could otherwise compromise transcriptional fidelity and genome integrity. Intriguingly, recent studies point to an even more direct function of DNA repair complexes as co-activators of transcription and the unexpected role of “scheduled” DNA damage/repair at gene promoters. Paradoxically, spontaneous DNA double-strand breaks also induce ectopic transcription that is essential for repair. Thus, transcription, DNA damage and repair may be more physically and functionally intertwined than previously appreciated. PMID:24207023

Transcervical excision of thymoma and video-assisted thoracoscopic extended thymectomy (VATET) for ectopic cervical thymoma with myasthenia gravis: report of a case.

PubMed

Kumazawa, Sachiko; Ishibashi, Hironori; Takahashi, Ken; Okubo, Kenichi

2016-12-01

Myasthenia gravis is the most common disease associated with thymoma, but it is rarely accompanied by ectopic thymoma. We describe a 47-year-old woman who presented with an ectopic cervical thymoma with myasthenia gravis. She was admitted to our neurology department with ptosis, diplopia, and mandibular muscle fatigue, and was diagnosed with myasthenia gravis. The mass was located posterior to the right lobe of thyroid gland on computed tomography and was diagnosed as ectopic thymoma on fine-needle aspiration biopsy examination. Transcervical excision of thymoma and VATET were performed. The patient has been free of neurological symptoms and has displayed no evidence of recurrent thymoma for 2 years.

Intranasal tooth: ectopic eruption 1 year after maxillofacial trauma

PubMed Central

Agrawal, Mamta; Khan, Tayyeb Sultan; Gupta, Tulika; Khanna, Shally

2014-01-01

Injury to the permanent central incisors due to trauma in the maxillofacial region, though common, may result in an uncommon sequel. We report a case of traumatic injury in a 5-year-old child with displacement of the tooth bud into the nasal floor. The identification of ectopic tooth buds poses little diagnostic challenge due to the available imaging facilities, however, in the present case the ectopic bud remained unnoticed and resulted in ectopic eruption of the tooth in the nasal cavity 1 year later. This report highlights a rare case of nasal eruption of a permanent tooth and places stress on the need for close attention to detail during maxillofacial trauma for early detection and proper management. PMID:25103317

Intranasal tooth: ectopic eruption 1 year after maxillofacial trauma.

PubMed

Agrawal, Mamta; Khan, Tayyeb Sultan; Gupta, Tulika; Khanna, Shally

2014-08-06

Injury to the permanent central incisors due to trauma in the maxillofacial region, though common, may result in an uncommon sequel. We report a case of traumatic injury in a 5-year-old child with displacement of the tooth bud into the nasal floor. The identification of ectopic tooth buds poses little diagnostic challenge due to the available imaging facilities, however, in the present case the ectopic bud remained unnoticed and resulted in ectopic eruption of the tooth in the nasal cavity 1 year later. This report highlights a rare case of nasal eruption of a permanent tooth and places stress on the need for close attention to detail during maxillofacial trauma for early detection and proper management. 2014 BMJ Publishing Group Ltd.

Scary gas: a spectrum of soft tissue gas encountered in the axial body (part II).

PubMed

Sandstrom, Claire K; Osman, Sherif F; Linnau, Ken F

2017-08-01

Ectopic gas in the mediastinum, subperitoneal abdomen, and superficial soft tissues is concerning and can be seen in the setting of trauma, iatrogenic injuries, infection, and inflammation. It can spread along different dissection pathways and may present remotely from the involved organ as described in part one. Recognition of ectopic gas on imaging and differentiating it from other causes of benign gas is very important as these conditions associated with ectopic gas can lead to rapid patient deterioration and usually require urgent surgery. In part two, the different causes of ectopic and benign gas in the torso are reviewed as well as the imaging features that can help to narrow the differential diagnosis.

Effects of early afterdepolarizations on excitation patterns in an accurate model of the human ventricles

PubMed Central

Seemann, Gunnar; Panfilov, Alexander V.; Vandersickel, Nele

2017-01-01

Early Afterdepolarizations, EADs, are defined as the reversal of the action potential before completion of the repolarization phase, which can result in ectopic beats. However, the series of mechanisms of EADs leading to these ectopic beats and related cardiac arrhythmias are not well understood. Therefore, we aimed to investigate the influence of this single cell behavior on the whole heart level. For this study we used a modified version of the Ten Tusscher-Panfilov model of human ventricular cells (TP06) which we implemented in a 3D ventricle model including realistic fiber orientations. To increase the likelihood of EAD formation at the single cell level, we reduced the repolarization reserve (RR) by reducing the rapid delayed rectifier Potassium current and raising the L-type Calcium current. Varying these parameters defined a 2D parametric space where different excitation patterns could be classified. Depending on the initial conditions, by either exciting the ventricles with a spiral formation or burst pacing protocol, we found multiple different spatio-temporal excitation patterns. The spiral formation protocol resulted in the categorization of a stable spiral (S), a meandering spiral (MS), a spiral break-up regime (SB), spiral fibrillation type B (B), spiral fibrillation type A (A) and an oscillatory excitation type (O). The last three patterns are a 3D generalization of previously found patterns in 2D. First, the spiral fibrillation type B showed waves determined by a chaotic bi-excitable regime, i.e. mediated by both Sodium and Calcium waves at the same time and in same tissue settings. In the parameter region governed by the B pattern, single cells were able to repolarize completely and different (spiral) waves chaotically burst into each other without finishing a 360 degree rotation. Second, spiral fibrillation type A patterns consisted of multiple small rotating spirals. Single cells failed to repolarize to the resting membrane potential hence prohibiting the Sodium channel gates to recover. Accordingly, we found that Calcium waves mediated these patterns. Third, a further reduction of the RR resulted in a more exotic parameter regime whereby the individual cells behaved independently as oscillators. The patterns arose due to a phase-shift of different oscillators as disconnection of the cells resulted in continuation of the patterns. For all patterns, we computed realistic 9 lead ECGs by including a torso model. The B and A type pattern exposed the behavior of Ventricular Tachycardia (VT). We conclude that EADs at the single cell level can result in different types of cardiac fibrillation at the tissue and 3D ventricle level. PMID:29216239

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gonsalves, M., E-mail: michael.gonsalves@stgeorges.nhs.uk; Belli, A., E-mail: Anna.Belli@stgeorges.nhs.u

Obstetric hemorrhage remains a major cause of maternal morbidity and mortality worldwide. Traditionally, in cases of obstetric hemorrhage refractory to conservative treatment, obstetricians have resorted to major surgery with the associated risks of general anesthesia, laparotomy, and, in the case of hysterectomy, loss of fertility. Over the past two decades, the role of pelvic arterial embolization has evolved from a novel treatment option to playing a key role in the management of obstetric hemorrhage. To date, interventional radiology offers a minimally invasive, fertility-preserving alternative to conventional surgical treatment. We review current literature regarding the role of interventional radiology in postpartummore » hemorrhage, abnormal placentation, abortion, and cervical ectopic pregnancy. We discuss techniques, success rates, and complications.« less

Effects of Prolonged Spaceflight on Atrial Size, Atrial Electrophysiology, and Risk of Atrial Fibrillation.

PubMed

Khine, Htet W; Steding-Ehrenborg, Katarina; Hastings, Jeffrey L; Kowal, Jamie; Daniels, James D; Page, Richard L; Goldberger, Jeffery J; Ng, Jason; Adams-Huet, Beverley; Bungo, Michael W; Levine, Benjamin D

2018-05-01

The prevalence of atrial fibrillation (AF) in active astronauts is ≈5%, similar to the general population but at a younger age. Risk factors for AF include left atrial enlargement, increased number of premature atrial complexes, and certain parameters on signal-averaged electrocardiography, such as P-wave duration, root mean square voltage for the terminal 20 ms of the signal-averaged P wave, and P-wave amplitude. We aimed to evaluate changes in atrial structure, supraventricular beats, and atrial electrophysiology to determine whether spaceflight could increase the risk of AF. Thirteen astronauts underwent cardiac magnetic resonance imaging to assess atrial structure and function before and after 6 months in space and high-resolution Holter monitoring for multiple 48-hour time periods before flight, during flight, and on landing day. Left atrial volume transiently increased after 6 months in space (12±18 mL; P =0.03) without changing atrial function. Right atrial size remained unchanged. No changes in supraventricular beats were noted. One astronaut had a large increase in supraventricular ectopic beats but none developed AF. Filtered P-wave duration did not change over time, but root mean square voltage for the terminal 20 ms decreased on all fight days except landing day. No changes in P-wave amplitude were seen in leads II or V 1 except landing day for lead V 1 . Six months of spaceflight may be sufficient to cause transient changes in left atrial structure and atrial electrophysiology that increase the risk of AF. However, there was no definite evidence of increased supraventricular arrhythmias and no identified episodes of AF. © 2018 American Heart Association, Inc.

Intrinsic neurophysiological properties of hilar ectopic and normotopic dentate granule cells in human temporal lobe epilepsy and a rat model.

PubMed

Althaus, A L; Sagher, O; Parent, J M; Murphy, G G

2015-02-15

Hilar ectopic dentate granule cells (DGCs) are a salient feature of aberrant plasticity in human temporal lobe epilepsy (TLE) and most rodent models of the disease. Recent evidence from rodent TLE models suggests that hilar ectopic DGCs contribute to hyperexcitability within the epileptic hippocampal network. Here we investigate the intrinsic excitability of DGCs from humans with TLE and the rat pilocarpine TLE model with the objective of comparing the neurophysiology of hilar ectopic DGCs to their normotopic counterparts in the granule cell layer (GCL). We recorded from 36 GCL and 7 hilar DGCs from human TLE tissue. Compared with GCL DGCs, hilar DGCs in patient tissue exhibited lower action potential (AP) firing rates, more depolarized AP threshold, and differed in single AP waveform, consistent with an overall decrease in excitability. To evaluate the intrinsic neurophysiology of hilar ectopic DGCs, we made recordings from retrovirus-birthdated, adult-born DGCs 2-4 mo after pilocarpine-induced status epilepticus or sham treatment in rats. Hilar DGCs from epileptic rats exhibited higher AP firing rates than normotopic DGCs from epileptic or control animals. They also displayed more depolarized resting membrane potential and wider AP waveforms, indicating an overall increase in excitability. The contrasting findings between disease and disease model may reflect differences between the late-stage disease tissue available from human surgical specimens and the earlier disease stage examined in the rat TLE model. These data represent the first neurophysiological characterization of ectopic DGCs from human hippocampus and prospectively birthdated ectopic DGCs in a rodent TLE model. Copyright © 2015 the American Physiological Society.

Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery.

PubMed

Fasshauer, Mathias; Lincke, Thomas; Witzigmann, Helmut; Kluge, Regine; Tannapfel, Andrea; Moche, Michael; Buchfelder, Michael; Petersenn, Stephan; Kratzsch, Juergen; Paschke, Ralf; Koch, Christian A

2006-04-27

ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled (111)In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide scan positive in atypical locations may benefit from explorative radioguided surgery using (111)In-pentetreotide and a gamma probe.

Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery

PubMed Central

Fasshauer, Mathias; Lincke, Thomas; Witzigmann, Helmut; Kluge, Regine; Tannapfel, Andrea; Moche, Michael; Buchfelder, Michael; Petersenn, Stephan; Kratzsch, Juergen; Paschke, Ralf; Koch, Christian A

2006-01-01

Background ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. Case presentation A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled 111In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. Conclusion This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide scan positive in atypical locations may benefit from explorative radioguided surgery using 111In-pentetreotide and a gamma probe. PMID:16643652

Osteophyte formation and matrix mineralization in a TMJ osteoarthritis mouse model are associated with ectopic hedgehog signaling

PubMed Central

Bechtold, Till E.; Saunders, Cheri; Decker, Rebekah S.; Um, Hyo-Bin; Cottingham, Naiga; Salhab, Imad; Kurio, Naito; Billings, Paul C.; Pacifici, Maurizio; Nah, Hyun-Duck; Koyama, Eiki

2016-01-01

The temporomandibular joint (TMJ) is a diarthrodial joint that relies on lubricants for frictionless movement and long-term function. It remains unclear what temporal and causal relationships may exist between compromised lubrication and onset and progression of TMJ disease. Here we report that Proteoglycan 4 (Prg4)-null TMJs exhibit irreversible osteoarthritis-like changes over time and are linked to formation of ectopic mineralized tissues and osteophytes in articular disc, mandibular condyle and glenoid fossa. In the presumptive layer of mutant glenoid fossa’s articulating surface, numerous chondrogenic cells and/or chondrocytes emerged ectopically within the type I collagen-expressing cell population, underwent endochondral bone formation accompanied by enhanced Ihh expression, became entrapped into temporal bone mineralized matrix, and thereby elicited excessive chondroid bone formation. As the osteophytes grew, the roof of the glenoid fossa/eminence became significantly thicker and flatter, resulting in loss of its characteristic concave shape for accommodation of condyle and disc. Concurrently, the condyles became flatter and larger and exhibited ectopic bone along their neck, likely supporting the enlarged condylar heads. Articular discs lost their concave configuration, and ectopic cartilage developed and articulated with osteophytes. In glenoid fossa cells in culture, hedgehog signaling stimulated chondrocyte maturation and mineralization including alkaline phosphatase, while treatment with hedgehog inhibitor HhAntag prevented such maturation process. In sum, our data indicate that Prg4 is needed for TMJ integrity and long-term postnatal function. In its absence, progenitor cells near presumptive articular layer and disc undergo ectopic chondrogenesis and generate ectopic cartilage, possibly driven by aberrant activation of Hh signaling. The data suggest also that the Prg4-null mice represent a useful model to study TMJ osteoarthritis-like degeneration and clarify its pathogenesis. PMID:26945615

Extrauterine Choriocarcinoma in the Fallopian Tube Following Infertility Treatment: Implications for the Management of Early-Detected Ectopic Pregnancies.

PubMed

Jwa, Seung Chik; Kamiyama, Shigeru; Takayama, Hisako; Tokunaga, Yoshimitsu; Sakumoto, Tetsuro; Higashi, Masahiro

Extrauterine choriocarcinoma in the fallopian tube is very rare and is often diagnosed and treated as an ectopic tubal pregnancy. A 34-year-old woman who initially became pregnant after infertility treatment using ovulation induction with clomiphene citrate and intrauterine insemination was later diagnosed with an extrauterine choriocarcinoma in the left fallopian tube. Because of suspected left ectopic tubal pregnancy based on ultrasonography findings and a high level of β-human chorionic gonadotropin (β-hCG; 7054.3 mIU/mL), the patient underwent diagnostic laparoscopy at a gestational age of 6 weeks. Left salpingectomy was performed based on the operative diagnosis of an ectopic tubal pregnancy. No signs of tubal rupture or leakage of contents from the fallopian tube were observed during the operation. Her serum β-hCG dropped to 10.3 mIU/mL at 15 days postoperatively. Histopathology demonstrated an extrauterine choriocarcinoma in the removed fallopian tube, and the patient was referred to a regional oncologic hospital to receive additional adjuvant chemotherapy. This case indicates that conservative treatment for ectopic pregnancy should be chosen carefully, and that histopathology diagnosis and appropriate β-hCG monitoring following treatment are important not only to diagnose persistent ectopic pregnancy, but also to rule out the possibility of a tubal choriocarcinoma. Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.

Effects of aerobic exercise on ectopic lipids in patients with growth hormone deficiency before and after growth hormone replacement therapy.

PubMed

Christ, Emanuel R; Egger, Andrea; Allemann, Sabin; Buehler, Tania; Kreis, Roland; Boesch, Chris

2016-01-21

Growth hormone replacement therapy (GHRT) increases exercise capacity and insulin resistance while it decreases fat mass in growth hormone-deficient patients (GHD). Ectopic lipids (intramyocellular (IMCL) and intrahepatocellular lipids (IHCL) are related to insulin resistance. The effect of GHRT on ectopic lipids is unknown. It is hypothesized that exercise-induced utilization of ectopic lipids is significantly decreased in GHD patients and normalized by GHRT. GHD (4 females, 6 males) and age/gender/waist-matched control subjects (CS) were studied. VO2max was assessed on a treadmill and insulin sensitivity determined by a two-step hyperinsulinaemic-euglycaemic clamp. Visceral (VAT) and subcutaneous (SAT) fat were quantified by MR-imaging. IHCL and IMCL were measured before and after a 2 h exercise at 50-60% of VO2max using MR-spectroscopy (∆IMCL, ∆IHCL). Identical investigations were performed after 6 months of GHRT. VO2max was similar in GHD and CS and significantly increased after GHRT; GHRT significantly decreased SAT and VAT. 2 h-exercise resulted in a decrease in IMCL (significant in CS and GHRT) and a significant increase in IHCL in CS and GHD pre and post GHRT. GHRT didn't significantly impact on ∆IMCL and ∆IHCL. We conclude that aerobic exercise affects ectopic lipids in patients and controls. GHRT increases exercise capacity without influencing ectopic lipids.

An Ectopic Breast Tissue Presenting with Fibroadenoma in Axilla

PubMed Central

Amaranathan, Anandhi; Balaguruswamy, Kanchana; Bhat, Ramachandra V.; Bora, Manash Kumar

2013-01-01

Introduction. The congenital anomalies of breast, especially the polymastia (supernumerary breast) and polythelia (supernumerary nipple), always do not fail to amuse the clinicians because of their varied presentations, associated renal anomalies, and pathologies arising from them. The axillary polymastia is a variant of ectopic breast tissue (EBT). Ectopic breast tissue can undergo the same physiological and pathological processes as the normally located breast. The incidence of fibroadenoma developing in ectopic breast is reported as a rare entity, the most common being the carcinoma. Case Presentation. A 31-year-old Dravidian female presented with a lump of 4 cm in the right axilla for the past year which gradually increased in size, giving discomfort. Our initial differential diagnosis was fibroadenoma, lipoma, and lymphadenopathy. Further investigation and histopathological report of excision biopsy confirmed it as a fibroadenoma on ectopic breast tissue in the axilla. Patient has no associated urological or cardiac anomaly. Conclusion. This case has been reported for its rarity and to reemphasise the importance of screening of EBT for any pathology during routine screening of breast. PMID:23607040

An ectopic breast tissue presenting with fibroadenoma in axilla.

PubMed

Amaranathan, Anandhi; Balaguruswamy, Kanchana; Bhat, Ramachandra V; Bora, Manash Kumar

2013-01-01

Introduction. The congenital anomalies of breast, especially the polymastia (supernumerary breast) and polythelia (supernumerary nipple), always do not fail to amuse the clinicians because of their varied presentations, associated renal anomalies, and pathologies arising from them. The axillary polymastia is a variant of ectopic breast tissue (EBT). Ectopic breast tissue can undergo the same physiological and pathological processes as the normally located breast. The incidence of fibroadenoma developing in ectopic breast is reported as a rare entity, the most common being the carcinoma. Case Presentation. A 31-year-old Dravidian female presented with a lump of 4 cm in the right axilla for the past year which gradually increased in size, giving discomfort. Our initial differential diagnosis was fibroadenoma, lipoma, and lymphadenopathy. Further investigation and histopathological report of excision biopsy confirmed it as a fibroadenoma on ectopic breast tissue in the axilla. Patient has no associated urological or cardiac anomaly. Conclusion. This case has been reported for its rarity and to reemphasise the importance of screening of EBT for any pathology during routine screening of breast.

The Flexibility of Ectopic Lipids

PubMed Central

Loher, Hannah; Kreis, Roland; Boesch, Chris; Christ, Emanuel

2016-01-01

In addition to the subcutaneous and the visceral fat tissue, lipids can also be stored in non-adipose tissue such as in hepatocytes (intrahepatocellular lipids; IHCL), skeletal (intramyocellular lipids; IMCL) or cardiac muscle cells (intracardiomyocellular lipids; ICCL). Ectopic lipids are flexible fuel stores that can be depleted by physical exercise and repleted by diet. They are related to obesity and insulin resistance. Quantification of IMCL was initially performed invasively, using muscle biopsies with biochemical and/or histological analysis. 1H-magnetic resonance spectroscopy (1H-MRS) is now a validated method that allows for not only quantifying IMCL non-invasively and repeatedly, but also assessing IHCL and ICCL. This review summarizes the current available knowledge on the flexibility of ectopic lipids. The available evidence suggests a complex interplay between quantitative and qualitative diet, fat availability (fat mass), insulin action, and physical exercise, all important factors that influence the flexibility of ectopic lipids. Furthermore, the time frame of the intervention on these parameters (short-term vs. long-term) appears to be critical. Consequently, standardization of physical activity and diet are critical when assessing ectopic lipids in predefined clinical situations. PMID:27649157

The Flexibility of Ectopic Lipids.

PubMed

Loher, Hannah; Kreis, Roland; Boesch, Chris; Christ, Emanuel

2016-09-14

In addition to the subcutaneous and the visceral fat tissue, lipids can also be stored in non-adipose tissue such as in hepatocytes (intrahepatocellular lipids; IHCL), skeletal (intramyocellular lipids; IMCL) or cardiac muscle cells (intracardiomyocellular lipids; ICCL). Ectopic lipids are flexible fuel stores that can be depleted by physical exercise and repleted by diet. They are related to obesity and insulin resistance. Quantification of IMCL was initially performed invasively, using muscle biopsies with biochemical and/or histological analysis. ¹H-magnetic resonance spectroscopy (¹H-MRS) is now a validated method that allows for not only quantifying IMCL non-invasively and repeatedly, but also assessing IHCL and ICCL. This review summarizes the current available knowledge on the flexibility of ectopic lipids. The available evidence suggests a complex interplay between quantitative and qualitative diet, fat availability (fat mass), insulin action, and physical exercise, all important factors that influence the flexibility of ectopic lipids. Furthermore, the time frame of the intervention on these parameters (short-term vs. long-term) appears to be critical. Consequently, standardization of physical activity and diet are critical when assessing ectopic lipids in predefined clinical situations.

Virilization caused by an ectopic adrenal tumor located behind the iliopsoas muscle.

PubMed

Mavroudis, Konstantinos; Aloumanis, Kyriakos; Papapetrou, Peter D; Voros, Dionisios; Spanos, Iraklis

2007-06-01

Virilization due to androgen-secreting neoplasms in women is a result of androgen overproduction from benign or malignant tumors that are found in the ovaries or rarely in the adrenal glands. Virilizing tumors that arise from ectopic adrenal tissue are extremely rare. We describe a very rare case of an ectopic androgen-producing adrenal tumor. Case report study. Endocrinology outpatient department of university-affiliated teaching hospital. A 45-year-old woman with symptoms of virilization of abrupt onset and rapid progression, with high serum androgen hormone levels and normal glucocorticoid secretion. Basal hormonal levels, stimulation and suppression tests, imaging techniques, and selective venous sampling. Localization and surgical removal of the source of androgen production. An ectopic mass was detected behind the left iliopsoas muscle. The patient was operated on and an oblong-shaped lesion, weighing 6 g, was removed. Histologically, the tissue was identified to be of adrenal origin. Postoperatively the androgen levels decreased to normal levels. This case illustrates difficulties in detecting and localizing the rare contingence of an ectopic adrenocortical androgen-secreting tumor.

Submandibular Lateral Ectopic Thyroid Tissue: Ultrasonography, Computed Tomography, and Scintigraphic Findings

PubMed Central

Çeliker, Metin; Beyazal Çeliker, Fatma; Turan, Arzu; Beyazal, Mehmet; Beyazal Polat, Hatice

2015-01-01

Ectopic thyroid can be encountered anywhere between the base of tongue and pretracheal region. The most common form is euthyroid neck mass. Herein, we aimed to present the findings of a female case with ectopic thyroid tissue localized in the left submandibular region. A 44-year-old female patient, who underwent bilateral subtotal thyroidectomy four years ago with the diagnosis of multinodular goiter, was admitted to our hospital due to a mass localized in the left submandibular area that gradually increased in the last six months. Neck ultrasonography, contrast-enhanced computed tomography, and scintigraphic examination were performed on the patient. On thyroid scintigraphy with Tc-99m pertechnetate, thyroid tissue activity uptake showing massive radioactivity was observed in the normal localization of the thyroid gland and in the submandibular localization. The focus in the submandibular region was excised. Pathological examination of the specimen showed normal thyroid follicle cells with no signs of malignancy. The submandibular mass is a rarely encountered lateral ectopic thyroid tissue. Accordingly, ectopic thyroid tissue should also be considered in the differential diagnosis of masses in the submandibular region. PMID:26634164

Ectopic mineralization disorders of the extracellular matrix of connective tissue: molecular genetics and pathomechanisms of aberrant calcification.

PubMed

Li, Qiaoli; Jiang, Qiujie; Uitto, Jouni

2014-01-01

Ectopic mineralization of connective tissues is a complex process leading to deposition of calcium phosphate complexes in the extracellular matrix, particularly affecting the skin and the arterial blood vessels and common in age-associated disorders. A number of initiating and contributing metabolic and environmental factors are linked to aberrant mineralization in these diseases, making the identification of precise pathomechanistic pathways exceedingly difficult. However, there has been significant recent progress in understanding the ectopic mineralization processes through study of heritable single-gene disorders, which have allowed identification of discrete pathways and contributing factors leading to aberrant connective tissue mineralization. These studies have provided support for the concept of an intricate mineralization/anti-mineralization network present in peripheral connective tissues, providing a perspective to development of pharmacologic approaches to limit the phenotypic consequences of ectopic mineralization. This overview summarizes the current knowledge of ectopic heritable mineralization disorders, with accompanying animal models, focusing on pseudoxanthoma elasticum and generalized arterial calcification of infancy, two autosomal recessive diseases manifesting with extensive connective tissue mineralization in the skin and the cardiovascular system. © 2013.

Ectopic mineralization disorders of the extracellular matrix of connective tissue: Molecular genetics and pathomechanisms of aberrant calcification

PubMed Central

Li, Qiaoli; Jiang, Qiujie; Uitto, Jouni

2013-01-01

Ectopic mineralization of connective tissues is a complex process leading to deposition of calcium phosphate complexes in the extracellular matrix, particularly affecting the skin and the arterial blood vessels and common in age-associated disorders. A number of initiating and contributing metabolic and environmental factors are linked to aberrant mineralization in these diseases, making the identification of precise pathomechanistic pathways exceedingly difficult. However, there has been significant recent progress in understanding the ectopic mineralization processes through study of heritable single-gene disorders, which have allowed identification of discreet pathways and contributing factors leading to aberrant connective tissue mineralization. These studies have provided support for the concept of an intricate mineralization/anti-mineralization network present in peripheral connective tissues, providing a perspective to development of pharmacologic approaches to limit the phenotypic consequences of ectopic mineralization. This overview summarizes the current knowledge of ectopic heritable mineralization disorders, with accompanying animal models, focusing on pseudoxanthoma elasticum and generalized arterial calcification of infancy, two autosomal recessive diseases manifesting with extensive connective tissue mineralization in the skin and the cardiovascular system. PMID:23891698

Clinical audit of ectopic pregnancy.

PubMed

Hamid, Alaa Aldin Abdel; Yousry, Almraghy; El Radi, Safwat Abd; Shabaan, Omar Mamdouh; Mazen, Elzahry; Nabil, Halal

2017-03-01

The aim of this study was to determine the risk factors of ectopic pregnancy in cases presented to the Woman's Health Hospital (WHH) in Assuit University, and to perform clinical audit on strategies for management of ectopic pregnancy in the WHH. This descriptive hospital based study was conducted at the Woman's Health Hospital (WHH) of Assuit University (Egypt). There were 210 patients who were admitted to the WHH with the diagnosis of ectopic pregnancy in the period between February 1, 2015 through the end of October 2015. Data were analyzed by SPSS version 21, using descriptive statistics, Mann-Whitney U test, and Chi square. Ectopic pregnancy affects woman in the reproductive age. There are many risk factors that increase the chance of its occurrence; however, it may also occur in the absence of any risk factors (14.0%). Internal VD (72.5%) is the most frequent risk factor; other risk factors include history of abortion, previous CS, ovulation induction, history of infertility, or previous history of EP. Clinical audit is an important item of any adequate health care. As regards to the clinical audit of EP management, we are not adhering to the guidelines.

Wnt5a and Wnt11 regulate mammalian anterior-posterior axis elongation

PubMed Central

Andre, Philipp; Song, Hai; Kim, Wantae; Kispert, Andreas; Yang, Yingzi

2015-01-01

Mesoderm formation and subsequent anterior-posterior (A-P) axis elongation are fundamental aspects of gastrulation, which is initiated by formation of the primitive streak (PS). Convergent extension (CE) movements and epithelial-mesenchymal transition (EMT) are important for A-P axis elongation in vertebrate embryos. The evolutionarily conserved planar cell polarity (PCP) pathway regulates CE, and Wnts regulate many aspects of gastrulation including CE and EMT. However, the Wnt ligands that regulate A-P axis elongation in mammalian development remain unknown. Wnt11 and Wnt5a regulate axis elongation in lower vertebrates, but only Wnt5a, not Wnt11, regulates mammalian PCP signaling and A-P axis elongation in development. Here, by generating Wnt5a; Wnt11 compound mutants, we show that Wnt11 and Wnt5a play redundant roles during mouse A-P axis elongation. Both genes regulate trunk notochord extension through PCP-controlled CE of notochord cells, establishing a role for Wnt11 in mammalian PCP. We show that Wnt5a and Wnt11 are required for proper patterning of the neural tube and somites by regulating notochord formation, and provide evidence that both genes are required for the generation and migration of axial and paraxial mesodermal precursor cells by regulating EMT. Axial and paraxial mesodermal precursors ectopically accumulate in the PS at late gastrula stages in Wnt5a−/−; Wnt11−/− embryos and these cells ectopically express epithelial cell adhesion molecules. Our data suggest that Wnt5a and Wnt11 regulate EMT by inducing p38 (Mapk14) phosphorylation. Our findings provide new insights into the role of Wnt5a and Wnt11 in mouse early development and also in cancer metastasis, during which EMT plays a crucial role. PMID:25813538

Ectopic lens material in an otherwise healthy 5-week-old infant.

PubMed

Rigaudy, Axelle; Parulekar, Manoj; Gibbon, Caspar; Quinn, Anthony

2018-06-21

To report the unusual finding of ectopic lens material in an otherwise healthy 5-week-old infant. Case report and literature review. An asymptomatic 5-week-old female infant was found to have unilateral ectopic lens material in the retrolental space of the left eye associated with a posterior capsular defect. The abnormality is likely embryological in origin, and the established progression for similar conditions means long-term monitoring is required to ensure the best possible visual outcome.

The role of TGF-β in the pathophysiology of peritoneal endometriosis.

PubMed

Young, Vicky J; Ahmad, S F; Duncan, W Colin; Horne, Andrew W

2017-09-01

Endometriosis is estimated to affect 6-10% of women of reproductive age and it is associated with chronic pelvic pain, dysmenorrhoea and subfertility. It is currently managed surgically or medically but symptoms recur in up to 75% of cases and available medical treatments have undesirable side effects. Endometriosis is defined as the presence of endometrial tissue outside the uterus with lesions typically found on the peritoneum. The aetiology of endometriosis is uncertain but there is increasing evidence that transforming growth factor (TGF)-β plays a major role. A descriptive review was undertaken of the published literature on the expression pattern of TGF-β ligands and signalling molecules in women with and without endometriosis, and on the potential roles of TGF-β signalling in the development and progression of peritoneal endometriosis. The current understanding of the TGF-β signalling pathway is summarized. We searched the Pubmed database using the terms 'transforming growth factor beta' and 'endometriosis' for studies published between 1995 and 2016. The initial search identified 99 studies and these were used as the basic material for this review. We also extended our remit for important older publications. In addition, we searched the reference lists of studies used in this review for additional studies we judged as relevant. Studies which were included in the review focused on peritoneal endometriosis only as increasing evidence suggests that ovarian and deep endometriosis may have a differing pathophysiology. Thus, a final 95 studies were included in the review. TGF-β1 is reported to be increased in the peritoneal fluid, serum, ectopic endometrium and peritoneum of women with endometriosis compared to women without endometriosis, and TGF-β1-null mice have reduced endometriosis lesion growth when compared to their wild-type controls. Studies in mice and women have indicated that increasing levels of TGF-β ligands are associated with decreased immune cell activity within the peritoneum, together with an increase in ectopic endometrial cell survival, attachment, invasion and proliferation, during endometriosis lesion development. TGF-β1 has been associated with changes in ectopic endometrial and peritoneal cell metabolism and the initiation of neoangiogenesis, further fuelling endometriosis lesion development. Together these studies suggest that TGF-β1 plays a major role in the development of peritoneal endometriosis lesions and that targeting this pathway may be of therapeutic potential. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

The Association Between Prepregnancy Parental Support and Control and Adolescent Girls’ Pregnancy Resolution Decisions

PubMed Central

Madkour, Aubrey Spriggs; Xie, Yiqiong; Harville, Emily W.

2013-01-01

Purpose To examine the influence of prepregnancy parental support and control on adolescent girls’ pregnancy resolution decisions. Methods Data from the National Longitudinal Study of Adolescent Health were analyzed. Girls whose first pregnancy reported in wave IV occurred after wave I and before age 20 were included (n = 1,107). Participants self-reported pregnancy disposition (abortion, ectopic or tubal pregnancy, miscarriage, stillbirth, live birth) for each pregnancy; responses were dichotomized as abortion versus other. Girls’ perceptions of parental support and control were measured at wave I. Controls were included for wave I age, age at pregnancy, year at the end of pregnancy, race/ethnicity, and parent characteristics (i.e., education, religious affiliation, age at first marriage, and educational expectations). Weighted multivariable logistic regression models were performed. Results Approximately 18% of girls reporting a teen pregnancy reported having an abortion. In crude analyses, parental support was marginally negatively related to abortion (odds ratio [OR] =.83, p =.06) and parental control was significantly negatively related to abortion (OR = .78, p = .02). In multivariable analyses, higher parental control was significantly negatively related to abortion versus other pregnancy outcomes (adjusted OR .80, 95% confidence interval .66–.98). Perceived parental support was unassociated with pregnancy resolution decisions. The only other factor associated with abortion decisions was parent education: odds of choosing abortion versus other pregnancy outcomes were significantly higher for adolescent girls whose parents had a bachelor’s degree or greater versus those with lower educational attainment. Conclusions Pregnant adolescents with less educated parents or parents exercising greater control were less likely to have an abortion. PMID:23763966

Expression of GRIM-19 in adenomyosis and its possible role in pathogenesis.

PubMed

Wang, Jing; Deng, Xiaohui; Yang, Yang; Yang, Xingsheng; Kong, Beihua; Chao, Lan

2016-04-01

To study the expression of the gene associated with retinoid-interferon (IFN)-induced mortality 19 (GRIM-19) in the endometrial tissue of patients with adenomyosis and to describe the possible pathogenic mechanisms of this phenomenon. Experimental study using human samples and cell lines. University-affiliated hospital. Ectopic and eutopic endometrial tissues were obtained from 30 patients with adenomyosis, whereas normal endometrial specimens were obtained from 10 control patients without adenomyosis. Patients with rapid pathology report-confirmed adenomyosis were recruited, and eutopic and ectopic endometrial tissue samples were collected from patients who had undergone hysterectomies by either the transabdominal or laparoscopic method at Qilu Hospital. Normal endometrial tissue was collected from a group of control patients without adenomyosis. Immunohistochemistry (IHC) was performed to evaluate the expression of GRIM-19, phospho-signal transducer and activator of transcription 3 (Y705) (Y705) (pSTAT3(Y705)), and vascular endothelial growth factor (VEGF) in endometrial tissue samples. The protein levels of GRIM-19, pSTAT3(Y705), STAT3, and VEGF were detected by Western blot. Apoptosis in endometrial specimens was assayed by TUNEL. Immunohistochemistry with an antibody directed against CD34 was performed to detect new blood vessels in the endometrial tissue. GRIM-19 small interfering RNA and a recombinant plasmid carrying GRIM-19 were constructed to evaluate the effects of GRIM-19 on the downstream factors pSTAT3(Y705), STAT3, and VEGF in Ishikawa cells. The expression of GRIM-19 was down-regulated in the eutopic endometria of patients with adenomyosis compared with the endometria of patients in the control group, and it was further reduced in the endometrial glandular epithelial cells of adenomyotic lesions. Apoptosis was reduced in the eutopic endometrium compared with the control group, and it was significantly reduced in ectopic endometrial tissues. In addition, the ectopic and eutopic endometria of patients with adenomyosis displayed a much higher microvessel density. In the eutopic and ectopic endometria of patients with adenomyosis, the expression levels of pSTAT3(Y705) and VEGF were significantly higher than in the controls. Furthermore, down-regulation of GRIM-19 in Ishikawa cells significantly promoted the activation of both pSTAT3(Y705) and its dependent gene VEGF. Aberrant expression of GRIM-19 may be associated with adenomyosis through the regulation of apoptosis and angiogenesis. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Ectopic breast cancer: case report and review of the literature.

PubMed

Francone, Elisa; Nathan, Marco J; Murelli, Federica; Bruno, Maria Santina; Traverso, Enrico; Friedman, Daniele

2013-08-01

Ectopic breast tissue comes in two forms: supernumerary and aberrant. Despite morphologic differences, ectopic breast tissue presents characteristics analogous to orthotopic breast tissue in terms of function and, most importantly, pathologic degeneration. Data in the literature concerning its precise incidence, the probability of malignant degeneration, and its standardized management are scarce and controversial. This study selected more than 100 years of literature, and this report discusses a case of ectopic breast cancer treatment, suggesting novel therapeutic advice that could bring considerable clinical advantages, improve cosmetic results, and reduce the psychological impact on patients. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Ovarian ectopic pregnancy: diagnosis, treatment, correlation to Carnegie stage 16 and review based on a clinical case.

PubMed

Kraemer, Bernhard; Kraemer, Elizabeth; Guengoer, Ersin; Juhasz-Boess, Ingolf; Solomayer, Erich-Franz; Wallwiener, Diethelm; Rajab, Taufiek Konrad

2009-07-01

To present a case of a vital ectopic pregnancy after 8 weeks that was located in the right ovary. Case study and literature review. Hospital outpatient clinic. A 29-year-old primigravida presented with lower abdominal pain and mild vaginal bleeding at 8 weeks after her last menstrual period. Wedge resection of the ovary which did not affect subsequent fertility. Conservative treatment options and preservation of patient's reproductive capacity. The embryo was laparoscopically removed in toto and visualized. Therefore, macroscopic correlation to Carnegie stage 16 of development was possible. Approximately 3% of all ectopic pregnancies are located in the ovaries. Preoperative diagnosis of this extremely rare condition is challenging, because the ectopic tumor often resembles cysts of the corpus luteum. At surgery, the trophoblast tissue or the embryo can rarely be visualized completely.

Acute hemorrhage related to a residual cervical pregnancy: management with curettage, tamponade, and cerclage.

PubMed

Pereira, Nigel; Grias, Irene; Foster, Sarah E; Della Badia, Carl R

2013-01-01

Cervical ectopic pregnancy is uncommon, with no universally accepted protocol for conservative management of acute hemorrhage due to residual cervical ectopic pregnancy. Herein is presented the case of a 33-year-old woman with profuse vaginal bleeding 3 months after receiving treatment including intraamniotic potassium chloride injection, systemic methotrexate, and uterine artery embolization because of a cervical ectopic pregnancy. A residual cervical pregnancy was suspected. Hemorrhage was controlled using curettage, tamponade with a Bakri balloon, and cerclage. The balloon and cerclage were removed on postoperative day 2, with no recurrence of symptoms. Our experience suggests that a combination of curettage, balloon tamponade, and cerclage may be considered in the management of cervical ectopic pregnancies with acute hemorrhage, in particular in patients desiring future childbearing. Copyright © 2013 AAGL. Published by Elsevier Inc. All rights reserved.

An unusual case of ectopic ACTH syndrome.

PubMed

Willhauck, M J; Pöpperl, G; Rachinger, W; Giese, A; Auernhammer, C J; Spitzweg, C

2012-02-01

Ectopic ACTH-syndrome is a rare cause of Cushing's disease. Despite extensive diagnostic procedures the source of ACTH secretion often remains occult. This case describes a 45-year old woman with an ectopic Cushing's syndrome. Extensive imaging procedures including CT scan of chest and abdomen, octreotide scan and MRI of the chest and pituitary did not reveal the source of ACTH secretion. In consideration of an occult source of ACTH secretion we started a therapeutic trial with cabergoline (0.5 mg/d), a dopamine receptor agonist, which has been shown to be effective in ectopic Cushing's syndrome. 2 months after cabergoline treatment had been initiated, ACTH and cortisol levels normalized in association with significant improvement of the clinical symptoms. During follow-up a [(68)Ga-DOTA-dPhe(1), Tyr(3)]-octreotate ([(68)Ga-DOTA]-TATE) PET-CT was performed revealing a somatostatin receptor positive lesion in the right sphenoidal sinus suggesting the source of ACTH secretion. The patient was cured by transnasal resection of the polypoid lesion, which was immunohistochemically characterized as an ACTH-positive neuroendocrine tumor. This case report demonstrates the management of ectopic ACTH-syndrome by molecularly -targeted therapy with dopamine receptor -agonists as well as improved detection of the ectopic ACTH source by novel imaging modalities, such as [(68)Ga-DOTA]-TATE PET specifically targeting somatostatin receptor subtype-2 with high affinity. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Early serum interleukin-8 evaluation may prove useful in localizing abnormally implanted human gestations after in vitro fertilization.

PubMed

Morelli, Sara S; Keegan, Debbra A; Krey, Lewis C; Katz, Joseph; Liu, Mengling; Noyes, Nicole

2008-12-01

To determine whether early measurement of the serum cytokines interleukin-2 receptor (IL-2R), IL-6, and IL-8 along with human chorionic gonadotropin (hCG) and progesterone (P(4)) can differentiate an ectopic from an intrauterine gestation. Retrospective analysis. University-based fertility center. 75 women who underwent treatment with in vitro fertilization (IVF) and subsequently had an ectopic gestation (n = 15), spontaneous abortion (SAB) (n = 30), or term delivery (TD) (n = 30). Serum samples were obtained 14 (day 28) and 21 (day 35) days after oocyte retrieval. Serum concentrations of IL-2R, IL-6, IL-8, P(4), and hCG. Median hCG readings on day 28 and day 35 were statistically significantly lower in the ectopic gestation group than in those with spontaneous abortion or term delivery. On day 28, median IL-8 levels were lower in the ectopic gestation group when compared with all intrauterine gestations combined. No statistically significant differences in IL-2R or IL-6 levels were noted between groups. Despite P(4) supplementation, median day-35 P(4) levels were lower in ectopic gestation than in the spontaneous abortion and term delivery cycles. In the setting of a rise or plateau in hCG levels, low day-28 IL-8 and day-35 P(4) levels suggested an extrauterine implantation. This assay combination may facilitate earlier diagnosis of an ectopic gestation when pregnancy location is unclear.

Morphological, diagnostic and surgical features of ectopic thyroid gland: a review of literature.

PubMed

Guerra, Germano; Cinelli, Mariapia; Mesolella, Massimo; Tafuri, Domenico; Rocca, Aldo; Amato, Bruno; Rengo, Sandro; Testa, Domenico

2014-01-01

Ectopic thyroid tissue remains a rare developmental abnormality involving defective or aberrant embryogenesis of the thyroid gland during its passage from the floor of the primitive foregut to its usual final position in pre-tracheal region of the neck. Its specific prevalence accounts about 1 case per 100.000-300.000 persons and one in 4.000-8.000 patients with thyroid disease show this condition. The cause of this defect is not fully known. Despite genetic factors have been associated with thyroid gland morphogenesis and differentiation, just recently some mutation has been associated with human thyroid ectopy. Lingual region in the most common site of thyroid ectopy but ectopic thyroid tissue were found in other head and neck locations. Nevertheless, aberrant ectopic thyroid tissue has been found in other places distant from the neck region. Ectopic tissue is affected by different pathological changes that occur in the normal eutopic thyroid. Patients may present insidiously or as an emergency. Diagnostic management of thyroid ectopy is performed by radionuclide thyroid imaging, ultrasonography, CT scan, MRI, biopsy and thyroid function tests. Asymptomatic euthyroid patients with ectopic thyroid do not usually require therapy but are kept under observation. For those with symptoms, treatment depends on size of the gland, nature of symptoms, thyroid function status and histological findings. Surgical excision is often required as treatment for this condition. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Coordination of Recombination with Meiotic Progression in the Caenorhabditis elegans Germline by KIN-18, a TAO Kinase That Regulates the Timing of MPK-1 Signaling

PubMed Central

Yin, Yizhi; Donlevy, Sean; Smolikove, Sarit

2016-01-01

Meiosis is a tightly regulated process requiring coordination of diverse events. A conserved ERK/MAPK-signaling cascade plays an essential role in the regulation of meiotic progression. The Thousand And One kinase (TAO) kinase is a MAPK kinase kinase, the meiotic role of which is unknown. We have analyzed the meiotic functions of KIN-18, the homolog of mammalian TAO kinases, in Caenorhabditis elegans. We found that KIN-18 is essential for normal meiotic progression; mutants exhibit accelerated meiotic recombination as detected both by analysis of recombination intermediates and by crossover outcome. In addition, ectopic germ-cell differentiation and enhanced levels of apoptosis were observed in kin-18 mutants. These defects correlate with ectopic activation of MPK-1 that includes premature, missing, and reoccurring MPK-1 activation. Late progression defects in kin-18 mutants are suppressed by inhibiting an upstream activator of MPK-1 signaling, KSR-2. However, the acceleration of recombination events observed in kin-18 mutants is largely MPK-1-independent. Our data suggest that KIN-18 coordinates meiotic progression by modulating the timing of MPK-1 activation and the progression of recombination events. The regulation of the timing of MPK-1 activation ensures the proper timing of apoptosis and is required for the formation of functional oocytes. Meiosis is a conserved process; thus, revealing that KIN-18 is a novel regulator of meiotic progression in C. elegans would help to elucidate TAO kinase’s role in germline development in higher eukaryotes. PMID:26510792

“Real time” genetic manipulation: a new tool for ecological field studies

PubMed Central

Schäfer, Martin; Brütting, Christoph; Gase, Klaus; Reichelt, Michael; Baldwin, Ian; Meldau, Stefan

2014-01-01

Summary Field experiments with transgenic plants often reveal the functional significance of genetic traits important for plant performance in their natural environments. Until now, only constitutive overexpression, ectopic expression and gene silencing methods have been used to analyze gene-related phenotypes in natural habitats. These methods do not allow sufficient control over gene expression to study ecological interactions in real-time, genetic traits playing essential roles in development, or dose-dependent effects. We applied the sensitive dexamethasone (DEX)-inducible pOp6/LhGR expression system to the ecological model plant Nicotiana attenuata and established a lanolin-based DEX application method to facilitate ectopic gene expression and RNAi mediated gene silencing in the field and under challenging conditions (e.g. high temperature, wind and UV radiation). Fully established field-grown plants were used to silence phytoene desaturase and thereby cause photobleaching only in specific plant sectors, and to activate expression of the cytokinin (CK) biosynthesis gene isopentenyl transferase (ipt). We used ipt expression to analyze the role of CK’s in both the glasshouse and field to understand resistance to the native herbivore Tupiocoris notatus, which attack plants at small spatial scales. By spatially restricting ipt expression and elevating CK levels in single leaves, T. notatus damage increased, demonstrating CK’s role in this plant-herbivore interaction at a small scale. As the arena of most ecological interactions is highly constrained in time and space, these tools will advance the genetic analysis of dynamic traits that matter for plant performance in nature. PMID:23906159

Body Composition and Ectopic Lipid Changes With Biochemical Control of Acromegaly.

PubMed

Bredella, Miriam A; Schorr, Melanie; Dichtel, Laura E; Gerweck, Anu V; Young, Brian J; Woodmansee, Whitney W; Swearingen, Brooke; Miller, Karen K

2017-11-01

Acromegaly is characterized by growth hormone (GH) and insulinlike growth factor-1 (IGF-1) hypersecretion, and GH and IGF-1 play important roles in regulating body composition and glucose homeostasis. The purpose of our study was to investigate body composition including ectopic lipids, measures of glucose homeostasis, and gonadal steroids in patients with active acromegaly compared with age-, body mass index (BMI)-, and sex-matched controls and to determine changes in these parameters after biochemical control of acromegaly. Cross-sectional study of 20 patients with active acromegaly and 20 healthy matched controls. Prospective study of 16 patients before and after biochemical control of acromegaly. Body composition including ectopic lipids by magnetic resonance imaging/proton magnetic resonance spectroscopy; measures of glucose homeostasis by an oral glucose tolerance test; gonadal steroids. Patients with active acromegaly had lower mean intrahepatic lipid (IHL) and higher mean fasting insulin and insulin area under the curve (AUC) values than controls. Men with acromegaly had lower mean total testosterone, sex hormone-binding globulin, and estradiol values than male controls. After therapy, homeostasis model assessment of insulin resistance, fasting insulin level, and insulin AUC decreased despite an increase in IHL and abdominal and thigh adipose tissues and a decrease in muscle mass. Patients with acromegaly were characterized by insulin resistance and hyperinsulinemia but lower IHL compared with age-, BMI-, and sex-matched healthy controls. Biochemical control of acromegaly improved insulin resistance but led to a less favorable anthropometric phenotype with increased IHL and abdominal adiposity and decreased muscle mass. Copyright © 2017 Endocrine Society

Somatic hypermutation and antigen-driven selection of B cells are altered in autoimmune diseases.

PubMed

Zuckerman, Neta S; Hazanov, Helena; Barak, Michal; Edelman, Hanna; Hess, Shira; Shcolnik, Hadas; Dunn-Walters, Deborah; Mehr, Ramit

2010-12-01

B cells have been found to play a critical role in the pathogenesis of several autoimmune (AI) diseases. A common feature amongst many AI diseases is the formation of ectopic germinal centers (GC) within the afflicted tissue or organ, in which activated B cells expand and undergo somatic hypermutation (SHM) and antigen-driven selection on their immunoglobulin variable region (IgV) genes. However, it is not yet clear whether these processes occurring in ectopic GCs are identical to those in normal GCs. The analysis of IgV mutations has aided in revealing many aspects concerning B cell expansion, mutation and selection in GC reactions. We have applied several mutation analysis methods, based on lineage tree construction, to a large set of data, containing IgV productive and non-productive heavy and light chain sequences from several different tissues, to examine three of the most profoundly studied AI diseases - Rheumatoid Arthritis (RA), Multiple Sclerosis (MS) and Sjögren's Syndrome (SS). We have found that RA and MS sequences exhibited normal mutation spectra and targeting motifs, but a stricter selection compared to normal controls, which was more apparent in RA. SS sequence analysis results deviated from normal controls in both mutation spectra and indications of selection, also showing differences between light and heavy chain IgV and between different tissues. The differences revealed between AI diseases and normal control mutation patterns may result from the different microenvironmental influences to which ectopic GCs are exposed, relative to those in normal secondary lymphoid tissues. Copyright © 2010 Elsevier Ltd. All rights reserved.

Molecular analysis of the mouse agouti gene and the role of dominant agouti-locus mutations in obesity and insulin resistance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klebig, M.L.; Woychik, R.P.; Wilkinson, J.E.

1994-09-01

The lethal yellow (A{sup y/-}) and viable yellow (A{sup vy/-}) mouse agouti mutants have a predominantly yellow pelage and display a complex syndrome that includes obesity, hyperinsulinemia, and insulin resistance, hallmark features of obesity-associated noninsulin-dependent diabetes mellitus (NIDDM) in humans. A new dominant agouti allele, A{sup iapy}, has recently been identified; like the A{sup vy} allele, it is homozygous viable and confers obesity and yellow fur in heterozygotes. The agouti gene was cloned and characterized at the molecular level. The gene is expressed in the skin during hair growth and is predicted to encode a 131 amino acid protein, thatmore » is likely to be a secreted factor. In both Ay/- and A{sup iapy}/- mice, the obesity and other dominant pleiotropic effects are associated with an ectopic expression of agouti in many tissues where the gene product is normally not produced. In Ay, a 170-kb deletion has occurred that causes an upstream promoter to drive the ectopic expression of the wild-type agouti coding exons. In A{sup iapy}, the coding region of the gene is expressed from a cryptic promoter within the LTR of an intracisternal A-particle (IAP), which has integrated within the region just upstream of the first agouti coding exon. Transgenic mice ubiquitously expressing the cloned agouti gene under the influence of the beta-actin and phosphoglycerate kinase promoters display obesity, hyperinsulinemia, and yellow coat color. This demonstrates unequivocally that ectopic expression of agouti is responsible for the yellow obese syndrome.« less

Decoy receptor 3 promotes cell adhesion and enhances endometriosis development.

PubMed

Tsai, Hsiao-Wen; Huang, Ming-Ting; Wang, Peng-Hui; Huang, Ben-Shian; Chen, Yi-Jen; Hsieh, Shie-Liang

2018-02-01

Endometriosis is a multifactorial inflammatory disease with persistent activation of the nuclear factor-κB (NF-κB) signalling pathway. Aberrant adhesion of endometrium is the essential step in the progression of endometriosis, but the molecular mechanism of ectopic growth of endometrium is still unclear. Decoy receptor 3 (DcR3)/TNFRSF6B, a pleiotropic immunomodulator regulated by oestrogen, is able to activate focal adhesion kinase to promote cell adhesion. We found that DcR3 is upregulated in human ectopic endometrial cells via activation of the Akt-NF-κB signalling pathway, and its expression level correlates positively with that of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and homing cell adhesion molecule (HCAM; CD44). In a multivariate regression model, DcR3 expression level was the most significant parameter associated with endometriosis severity. Knockdown of DcR3 not only downregulated the expression of ICAM-1 and HCAM, but also reduced cell adhesion and migration. In vivo investigation further showed that DcR3 promoted the growth and spread of endometrium, whereas knockdown of DcR3 by lentivirus-delivered short hairpin RNA inhibited ectopic adhesion of endometrium and abrogated endometriosis progression. These observations are in support of DcR3 playing a critical role in the pathogenesis of endometriosis, and the inhibition of DcR3 expression being a promising approach for the treatment of endometriosis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

MicroRNA203a suppresses glioma tumorigenesis through an ATM-dependent interferon response pathway

PubMed Central

Yang, Chuan He; Wang, Yinan; Sims, Michelle; Cai, Chun; He, Ping; Häcker, Hans; Yue, Junming; Cheng, Jinjun; Boop, Frederick A.; Pfeffer, Lawrence M.

2017-01-01

Glioblastoma (GBM) is a deadly and incurable brain tumor. Although microRNAs (miRNAs) play critical roles in regulating the cancer cell phenotype, the underlying mechanisms of how they regulate tumorigenesis are incompletely understood. We previously showed that miR-203a is expressed at relatively low levels in GBM patients, and ectopic miR-203a expression in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by interferon (IFN) or temozolomide in vitro, and inhibited GBM tumorigenesis in vivo. Here we show that ectopic expression of miR-203a in GBM cell lines promotes the IFN response pathway as evidenced by increased IFN production and IFN-stimulated gene (ISG) expression, and high basal tyrosine phosphorylation of multiple STAT proteins. Importantly, we identified that miR-203a directly suppressed the protein levels of ataxia-telangiectasia mutated (ATM) kinase that negatively regulates IFN production. We found that high ATM expression in GBM correlates with poor patient survival and that ATM expression is inversely correlated with miR-203a expression. Knockout of ATM expression and inhibition of ATM function in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by therapeutic agents in vitro, and markedly suppressed GBM tumor growth and promoted animal survival. In contrast, restoring ATM levels in GBM cells ectopically expressing miR-203a increased tumorigenicity and decreased animal survival. Our study suggests that low miR-203a expression in GBM suppresses the interferon response through an ATM-dependent pathway. PMID:29348882

MicroRNA203a suppresses glioma tumorigenesis through an ATM-dependent interferon response pathway.

PubMed

Yang, Chuan He; Wang, Yinan; Sims, Michelle; Cai, Chun; He, Ping; Häcker, Hans; Yue, Junming; Cheng, Jinjun; Boop, Frederick A; Pfeffer, Lawrence M

2017-12-22

Glioblastoma (GBM) is a deadly and incurable brain tumor. Although microRNAs (miRNAs) play critical roles in regulating the cancer cell phenotype, the underlying mechanisms of how they regulate tumorigenesis are incompletely understood. We previously showed that miR-203a is expressed at relatively low levels in GBM patients, and ectopic miR-203a expression in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by interferon (IFN) or temozolomide in vitro , and inhibited GBM tumorigenesis in vivo . Here we show that ectopic expression of miR-203a in GBM cell lines promotes the IFN response pathway as evidenced by increased IFN production and IFN-stimulated gene (ISG) expression, and high basal tyrosine phosphorylation of multiple STAT proteins. Importantly, we identified that miR-203a directly suppressed the protein levels of ataxia-telangiectasia mutated (ATM) kinase that negatively regulates IFN production. We found that high ATM expression in GBM correlates with poor patient survival and that ATM expression is inversely correlated with miR-203a expression. Knockout of ATM expression and inhibition of ATM function in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by therapeutic agents in vitro , and markedly suppressed GBM tumor growth and promoted animal survival. In contrast, restoring ATM levels in GBM cells ectopically expressing miR-203a increased tumorigenicity and decreased animal survival. Our study suggests that low miR-203a expression in GBM suppresses the interferon response through an ATM-dependent pathway.

The Role of SncN and Ski in Mammary Epithelial Cell Transformation

DTIC Science & Technology

2005-07-01

cellular activities through the Smad proteins. Upon phosphorylation by the active TGFβ receptor kinases, Smad2 and Smad3 oligomerize with Smad4, translocate...sequence in sense and antisense orientation with an intervening linker . Primer pairs were designed to generate single-strand overhangs upon annealing...nuclear protein, based on studies of ectopically expressed SnoN and endogenous SnoN in cancer cell lines. In the nucleus, SnoN binds to Smad2, Smad3 , and

Gene array analysis reveals a common Runx transcriptional program controlling cell adhesion and survival

PubMed Central

Wotton, Sandy; Terry, Anne; Kilbey, Anna; Jenkins, Alma; Herzyk, Pawel; Cameron, Ewan; Neil, James C.

2008-01-01

The Runx genes play divergent roles in development and cancer, where they can act either as oncogenes or tumour suppressors. We compared the effects of ectopic Runx expression in established fibroblasts, where all three genes produce an indistinguishable phenotype entailing epithelioid morphology and increased cell survival under stress conditions. Gene array analysis revealed a strongly overlapping transcriptional signature, with no examples of opposing regulation of the same target gene. A common set of 50 highly regulated genes was identified after further filtering on regulation by inducible RUNX1-ER. This set revealed a strong bias towards genes with annotated roles in cancer and development, and a preponderance of targets encoding extracellular or surface proteins, reflecting the marked effects of Runx on cell adhesion. Furthermore, in silico prediction of resistance to glucocorticoid growth inhibition was confirmed in fibroblasts and lymphoid cells expressing ectopic Runx. The effects of fibroblast expression of common RUNX1 fusion oncoproteins (RUNX1-ETO, TEL-RUNX1, CBFB-MYH11) were also tested. While two direct Runx activation target genes were repressed (Ncam1, Rgc32), the fusion proteins appeared to disrupt regulation of down-regulated targets (Cebpd, Id2, Rgs2) rather than impose constitutive repression. These results elucidate the oncogenic potential of the Runx family and reveal novel targets for therapeutic inhibition. PMID:18560354

Ectopic Expression of the Wild Grape WRKY Transcription Factor VqWRKY52 in Arabidopsis thaliana Enhances Resistance to the Biotrophic Pathogen Powdery Mildew But Not to the Necrotrophic Pathogen Botrytis cinerea.

PubMed

Wang, Xianhang; Guo, Rongrong; Tu, Mingxing; Wang, Dejun; Guo, Chunlei; Wan, Ran; Li, Zhi; Wang, Xiping

2017-01-01

WRKY transcription factors are known to play important roles in plant responses to biotic stresses. We previously showed that the expression of the WRKY gene, VqWRKY52 , from Chinese wild Vitis quinquangularis was strongly induced 24 h post inoculation with powdery mildew. In this study, we analyzed the expression levels of VqWRKY52 following treatment with the defense related hormones salicylic acid (SA) and methyl jasmonate, revealing that VqWRKY52 was strongly induced by SA but not JA. We characterized the VqWRKY52 gene, which encodes a WRKY III gene family member, and found that ectopic expression in Arabidopsis thaliana enhanced resistance to powdery mildew and Pseudomonas syringae pv. tomato DC3000, but increased susceptibility to Botrytis cinerea , compared with wild type (WT) plants. The transgenic A. thaliana lines displayed strong cell death induced by the biotrophic powdery mildew pathogen, the hemibiotrophic P. syringe pathogen and the necrotrophic pathogen B. cinerea . In addition, the relative expression levels of various defense-related genes were compared between the transgenic A. thaliana lines and WT plants following the infection by different pathogens. Collectively, the results indicated that VqWRKY52 plays essential roles in the SA dependent signal transduction pathway and that it can enhance the hypersensitive response cell death triggered by microbial pathogens.

Evidence that the notochord may be pivotal in the development of sacral and anorectal malformations.

PubMed

Qi, Bao Quan; Beasley, Spencer W; Frizelle, Francis A

2003-09-01

The notochord is known to organize normal development of central axial structures, such as the spinal cord, vertebral column, and anorectum, but its role in abnormal development of these organs has not been well documented. The current study has used Ethylenethiourea to induce anorectal malformations in fetal rats, allowing investigation of abnormalities of the notochord and their relationship to the axial structural abnormalities that occur. Timed-mated pregnant rats were fed Ethylenethiourea by gavage on gestational day 10. Their embryos were harvested on gestational days 13 to 16 and sectioned in either the transverse or sagittal plane. Sections were stained with H and E and examined serially. Anorectal malformations were identified in 29 of 34 embryos and neural tube defects in 24, ranging from an accessory neural tube to lumbo-sacral rachischisis. There was no tail or only a rudimentary tail in the majority of embryos. Abnormalities of the notochord in the lumbo-sacral area included ventro-dorsal branching, ventral deviation, and ectopic notochordal tissue. Most abnormal notochord branches and ectopic notochordal tissue were abnormally close to or in contact with the wall of the cloaca or neural tube. Given the known role of the notochord in controlling normal development, this study would suggest that abnormal notochord development may be pivotal in producing neural tube defects and anorectal malformations, possibly by altering sonic hedgehog signalling.

Targeted CRISPR disruption reveals a role for RNase MRP RNA in human preribosomal RNA processing.

PubMed

Goldfarb, Katherine C; Cech, Thomas R

2017-01-01

MRP RNA is an abundant, essential noncoding RNA whose functions have been proposed in yeast but are incompletely understood in humans. Mutations in the genomic locus for MRP RNA cause pleiotropic human diseases, including cartilage hair hypoplasia (CHH). Here we applied CRISPR-Cas9 genome editing to disrupt the endogenous human MRP RNA locus, thereby attaining what has eluded RNAi and RNase H experiments: elimination of MRP RNA in the majority of cells. The resulting accumulation of ribosomal RNA (rRNA) precursor-analyzed by RNA fluorescent in situ hybridization (FISH), Northern blots, and RNA sequencing-implicates MRP RNA in pre-rRNA processing. Amelioration of pre-rRNA imbalance is achieved through rescue of MRP RNA levels by ectopic expression. Furthermore, affinity-purified MRP ribonucleoprotein (RNP) from HeLa cells cleaves the human pre-rRNA in vitro at at least one site used in cells, while RNP isolated from cells with CRISPR-edited MRP loci loses this activity, and ectopic MRP RNA expression restores cleavage activity. Thus, a role for RNase MRP in human pre-rRNA processing is established. As demonstrated here, targeted CRISPR disruption is a valuable tool for functional studies of essential noncoding RNAs that are resistant to RNAi and RNase H-based degradation. © 2017 Goldfarb and Cech; Published by Cold Spring Harbor Laboratory Press.

Expression and regulation of estrogen-converting enzymes in ectopic human endometrial tissue.

PubMed

Fechner, Sabine; Husen, Bettina; Thole, Hubert; Schmidt, Markus; Gashaw, Isabella; Kimmig, Rainer; Winterhager, Elke; Grümmer, Ruth

2007-10-01

To investigate the regulation of estrogen-converting enzymes in human ectopic endometrial tissue. Animal study. Academic medical center. Sixty female nude mice with implanted human endometrial tissue. Twenty-two premenopausal women undergoing endometrial biopsy or hysterectomy. Human endometrial tissue was implanted into the peritoneal cavity of nude mice, and the effect of therapeutic drugs on transcription of steroid receptors and estrogen-converting enzymes was analyzed. Transcript levels of steroid hormone receptors, 17beta-hydroxysteroid dehydrogenase type 1 and 2, aromatase, and steroid sulfatase as well as proliferation rate were analyzed in the human ectopic endometrial tissue. Steroid receptors and estrogen-converting enzymes were expressed in the ectopic human endometrial fragments. Application of medroxyprogesterone acetate, dydrogesterone, danazol, and the aromatase inhibitor finrozole significantly inhibited aromatase transcription. In addition, danazol caused a significant decrease in transcription of steroid sulfatase, and finrozole, of 17beta-hydroxysteroid dehydrogenase type 1 in parallel to a decrease in proliferation rate in the ectopic human endometrial tissue. Pharmacological regulation of transcription of estrogen-converting enzymes in human endometrium cultured in nude mice may help to develop new therapeutic concepts based on local regulation of estrogen metabolism in endometriosis.

Outcomes of conception subsequent to methotrexate treatment for an unruptured ectopic pregnancy.

PubMed

Svirsky, Ran; Ben-Ami, Ido; Berkovitch, Matitiahu; Halperin, Reuvit; Rozovski, Uri

2017-11-01

To assess the risk of adverse pregnancy outcomes in subsequent pregnancies among women treated with methotrexate for ectopic pregnancy. In a retrospective single-center study, data were assessed for women treated with methotrexate for ectopic pregnancy at Asaf Harofe Medical Center, Zerifin, Israel, between May 2004 and May 2014. Overall, 226 women were treated with methotrexate for ectopic pregnancy and subsequently conceived. The median time from treatment to conception was 10 months (range 1-120 months), and 127 women conceived within 12 months of treatment. Except for early missed abortion-which affected 23 (10.2%) pregnancies-adverse pregnancy outcomes such as fetal malformations were rare. The frequency of early abortion was lowest for women who conceived within 6 months of treatment with methotrexate (3/93, 3.2%), increased between 6 and 23 months (15/83, 18.1%), and remained high thereafter (7/50, 14.0%; P=0.006). The frequency of fetal malformation in a subsequent pregnancy was low among women treated with methotrexate for ectopic pregnancy. The frequency of early missed abortion was lowest during the first 6 months after treatment with methotrexate. © 2017 International Federation of Gynecology and Obstetrics.

Rh Factor: How It Can Affect Your Pregnancy

MedlinePlus

... antibodies after a miscarriage , ectopic pregnancy , or induced abortion . If an Rh-negative woman gets pregnant after ... ectopic pregnancy or a first-trimester miscarriage or abortion after invasive procedures, such as amniocentesis, CVS, fetal ...

Single-Session CT-Guided Percutaneous Microwave Ablation of Bilateral Adrenal Gland Hyperplasia Due to Ectopic ACTH Syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarma, Asha, E-mail: ashasarma@gmail.com; Shyn, Paul B., E-mail: pshyn@partners.org; Vivian, Mark A.

Bilateral adrenalectomy is currently the only available treatment for adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (ectopic ACTH syndrome) that is refractory to pharmacologic therapy. We describe two patients with refractory ectopic ACTH syndrome who were treated with CT-guided percutaneous microwave ablation of both hyperplastic adrenal glands in a single session: One was not a surgical candidate, and the other had undergone unsuccessful surgery. Following the procedure, both patients achieved substantial decreases in serum cortisol, symptomatic improvement, and decreased anti-hypertensive medication requirements.

A case of ectopic intraabdominal fascioliasis presented with acute abdomen.

PubMed

Tanir, Gönül; Karaman, Ayşe; Tüfekçı, Sehra Birgül; Erdoğan, Duygu; Tuygun, Nilden; Ozkan, Ayşegül Taylan

2011-06-01

Human fascioliasis with Fasciola species occurs worldwide and is most common among rural people who tend sheep and eat uncooked water vegetables, particularly watercress. The natural history of the acute phase begins with ingestion of metacercariae encysted on various kinds of aquatic vegetation such as watercress. Fascioliasis primarily involves the liver, bile ducts, gallbladder, and occasionally ectopic sites. We describe herein a case of ectopic fascioliasis. This uncommon form of disease was peritonitis; both visceral and parietal peritoneal layers were affected with the formation of multiple nodules and ascites.

Study of Chlamydia trachomatis in Military Women; Prevalence, Risk Factors, and a Cost Benefit Analysis of Early Diagnosis and Treatment

DTIC Science & Technology

1999-09-01

ectopic pregnancy, and infertility represent a large disease burden 1,3. Infection rates for young, sexually active women range from 5-20%. In men...Hospitalizations (PASBA) for PID (ICD9 codes 614 and 615), infertility (ICD9 code 628), and 18 * ectopic pregnancy (ICD9 code 633) in Army enlisted females...trachomatisinfections in women has been lim- flammatory disease, infertility , and ectopic pregnancy. ited by the need for access to a medical clinic and a To design

Proteomics Identification of Annexin A2 as a Key Mediator in the Metastasis and Proangiogenesis of Endometrial Cells in Human Adenomyosis*

PubMed Central

Zhou, Shengtao; Yi, Tao; Liu, Rui; Bian, Ce; Qi, Xiaorong; He, Xiang; Wang, Kui; Li, Jingyi; Zhao, Xia; Huang, Canhua; Wei, Yuquan

2012-01-01

Adenomyosis is a common estrogen-dependent disorder of females characterized by a downward extension of the endometrium into the uterine myometrium and neovascularization in ectopic lesions. It accounts for chronic pelvic pain, dysmenorrhea, menorrhagia, and infertility in 8.8–61.5% women worldwide. However, the molecular mechanisms for adenomyosis development remain poorly elucidated. Here, we utilized a two-dimensional polyacrylamide gel electrophoresis/MS-based proteomics analysis to compare and identify differentially expressed proteins in matched ectopic and eutopic endometrium of adenomyosis patients. A total of 93 significantly altered proteins were identified by tandem MS analysis. Further cluster analysis revealed a group of estrogen-responsive proteins as dysregulated in adenomyosis, among which annexin A2, a member of annexin family proteins, was found up-regulated most significantly in the ectopic endometrium of adenomyosis compared with its eutopic counterpart. Overexpression of ANXA2 was validated in ectopic lesions of human adenomyosis and was found to be tightly correlated with markers of epithelial to mesenchymal transition and dysmenorrhea severity of adenomyosis patients. Functional analysis demonstrated that estrogen could remarkably up-regulate ANXA2 and induce epithelial to mesenchymal transition in an in vitro adenomyosis model. Enforced expression of ANXA2 could mediate phenotypic mesenchymal-like cellular changes, with structural and functional alterations in a β-catenin/T-cell factor (Tcf) signaling-associated manner, which could be reversed by inhibition of ANXA2 expression. We also proved that enforced expression of ANXA2 enhanced the proangiogenic capacity of adenomyotic endometrial cells through HIF-1α/VEGF-A pathway. In vivo, we demonstrated that ANXA2 inhibition abrogated endometrial tissue growth, metastasis, and angiogenesis in an adenomyosis nude mice model and significantly alleviated hyperalgesia. Taken together, our data unraveled a dual role for ANXA2 in the pathogenesis of human adenomyosis through conferring endometrial cells both metastatic potential and proangiogenic capacity, which could serve as a potential therapeutic target for the treatment of adenomyosis patients. PMID:22493182

Intraductal papilloma in an axillary lymph node of a patient with human immunodeficiency virus: a case report and review of the literature.

PubMed

Cottom, Hannah; Rengabashyam, Bhavani; Turton, Philip E; Shaaban, Abeer M

2014-05-23

Inclusions of ectopic breast tissue in axillary lymph nodes are reported very infrequently and typically are only identified microscopically as an incidental finding. Furthermore the development of a benign proliferative lesion in the form of an intraductal papilloma from intranodal ectopic breast tissue is an extremely rare phenomenon with only three previous cases reported. This report describes an unusual and rare case of an intraductal papilloma arising in an axillary lymph node of a patient known to have the human immunodeficiency virus. A 40-year-old Black African woman underwent excision of an enlarged palpable axillary lymph node. In the preceding 7 years she had received at least six separate surgical excisions to her ipsilateral breast for papillomatosis. The last surgical intervention was performed 1 year prior to presentation with an enlarged axillary lymph node. Histological examination of her axillary lymph node revealed a papillomatous proliferative epithelial lesion within an apparent encompassing duct, resembling a mammary intraductal papilloma. In the surrounding lymphoid tissue small groups of duct-like structures were additionally noted. Immunostaining with a panel of myoepithelial markers in conjunction with oestrogen receptor produced a mixed heterogeneous staining pattern in both the papillomatous lesion and the peripheral duct-like structures. This confirmed the diagnosis of a benign intraductal papilloma within an axillary lymph node, considered to have arisen from ectopic breast tissue. This case demonstrates that intranodal ectopic breast tissue has the potential to undergo benign proliferative change albeit extremely rarely. Therefore this possibility must be considered to ensure the correct diagnosis is made. In addition, to the best of our knowledge, this is the first case report which has described recurrent intraductal papillomas and the subsequent development of an intraductal papilloma within an ipsilateral axillary lymph node, in a patient who is human immunodeficiency virus positive. There is minimal literature investigating the specific types of breast pathologies experienced by patients infected with human immunodeficiency virus and it remains unexplored as to whether human immunodeficiency virus may lead to proliferative papillomatous epithelial changes. This report considers the role of the human papillomavirus and recommends that further investigatory studies are required.

Endometrial cysteine-rich secretory protein 3 is inhibited by human chorionic gonadotrophin, and is increased in the decidua of tubal ectopic pregnancy.

PubMed

Horne, A W; Duncan, W C; King, A E; Burgess, S; Lourenco, P C; Cornes, P; Ghazal, P; Williams, A R; Udby, L; Critchley, H O D

2009-05-01

Ectopic pregnancy (EP) remains a considerable cause of morbidity and occasional mortality. Currently, there is no reliable test to differentiate ectopic from intrauterine gestation. We have previously used array technology to demonstrate that differences in gene expression in decidualized endometrium from women with ectopic and intrauterine gestations could be used to identify candidate diagnostic biomarkers for EP. The aim of this study was to further investigate the decidual gene with the highest fold increase in EP, cysteine-rich secretory protein-3 (CRISP-3). Decidualized endometrium from gestation-matched women undergoing surgical termination of pregnancy (n = 8), evacuation of uterus for miscarriage (n = 6) and surgery for EP (n = 11) was subjected to quantitative RT-PCR, morphological assessment, immunohistochemistry and western blot analysis. Sera were analysed for progesterone and human chorionic gonadotrophin (hCG) levels. Immortalized endometrial epithelial cells were cultured with physiological concentrations of hCG. CRISP-3 mRNA and protein expression were greater in endometrium from ectopic when compared with intrauterine pregnancies (P < 0.05). CRISP-3 protein was localized to epithelium and granulocytes of endometrium. CRISP-3 serum concentrations were not different in women with ectopic compared with intrauterine pregnancies. CRISP-3 expression in endometrium was not related to the degree of decidualization or to serum progesterone levels. Endometrial CRISP-3 expression was inversely proportional to serum hCG concentrations (P < 0.001). Stimulation of endometrial epithelial cells with hCG in vitro caused a reduction in CRISP-3 expression (P < 0.01). The measurement of CRISP-3 in endometrium could provide an additional tool in the diagnosis of failing early pregnancy of unknown location. The absence of a local reduction in expression of CRISP-3 in decidualized endometrium of women with EP may be due to reduced exposure to hCG due to the ectopic location of the trophoblast.

Absence of catalytic domain in a putative protein kinase C (PkcA) suppresses tip dominance in Dictyostelium discoideum

PubMed Central

Mohamed, Wasima; Ray, Sibnath; Brazill, Derrick; Baskar, Ramamurthy

2017-01-01

A number of organisms possess several isoforms of protein kinase C but little is known about the significance of any specific isoform during embryogenesis and development. To address this we characterized a PKC ortholog (PkcA; DDB_G0288147) in Dictyostelium discoideum. pkcA expression switches from prestalk in mound to prespore in slug, indicating a dynamic expression pattern. Mutants lacking the catalytic domain of PkcA (pkcA−) did not exhibit tip dominance. A striking phenotype of pkcA− was the formation of an aggregate with a central hollow, and aggregates later fragmented to form small mounds, each becoming a fruiting body. Optical density wave patterns of cAMP in the late aggregates showed several cAMP wave generation centers. We attribute these defects in pkcA− to impaired cAMP signaling, altered cell motility and decreased expression of the cell adhesion molecules – CadA and CsaA. pkcA− slugs showed ectopic expression of ecmA in the prespore region. Further, the use of a PKC-specific inhibitor, GF109203X that inhibits the activity of catalytic domain phenocopied pkcA−. PMID:26183108

Therapeutic experience of severe and recurrent secondary hyperparathyroidism in a patient on hemodialysis for 18 years: A case report.

PubMed

Zhu, Mingwen; Zhang, Zongming; Lin, Fangcai; Miao, Jieping; Wang, Pei; Zhang, Chong; Yu, Hongwei; Deng, Hai; Liu, Zhuo; Liu, Limin; Wan, Baijiang; Yang, Haiyan; Song, Mengmeng; Zhao, Yue; Jiang, Nan; Zhang, Zichao; Zhang, Zhenya; Pan, Lijie

2018-05-01

For patients with refractory secondary hyperparathyroidism (SHPT), parathyroidectomy (PTX) has received increasing attention. However, evidence-based medicine shows that there is still controversy regarding surgical methods, efficacy, and safety. We retrospectively analyzed the process of diagnosis and treatment in one patient with severe SHPT and long-term chronic renal failure (CRF), so as to further improve the therapeutic effect. A 61-year-old female with SHPT and CRF manifested as no urine for 18 years, underwent PTX 4 times since September 2010, with satisfactory final recovery. The first operation involved resection of 3 parathyroid glands in the normal position; the second operation involved removal of an ectopic parathyroid gland, combined with parathyroid gland autotransplantation; the third operation was performed to resect suspected recurrent parathyroid gland; the fourth operation involved partial excision of the autotransplanted parathyroid glands. Accurate preoperative localized diagnosis and optimal surgical approach play key roles in the prevention and treatment of SHPT; postoperative recurrence of SHPT caused by ectopic or autotransplanted parathyroid gland should receive more attention.

Pineal and ectopic pineal tumors: the role of radiation therapy. [X ray; /sup 60/Co

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rao, Y.T.R.; Medini, E.; Haselow, R.E.

Seventeen patients with pineal tumors and one ectopic (suprasellar) germinoma were treated with radiation therapy. Surgery was restricted to decompression in 16 patients, and only two patients had resection of the tumor. Thirteen of 18 patients are alive without evidence for disease with a ten-year surrvival rate of 88%. The tumor dose ranged from 4000 rads to 6000 rads. No age or dose dependence in survival was noted, but patients with whole brain irradiation or generous volume to include ventricular system had better survival. No case of spinal metastasis was noted. The possibility of increased incidence of meningeal seeding followingmore » surgical intervention is considered. From their data, the authors feel that radiation therapy with or without surgical decompression should be the primary treatment for pinealoma. Surgery can be used for diagnosis and/or treatment of patients who show delayed response to radiation. Recommendation is made for the use of whole brain irradiation to 4000 rads followed by a boost to the tumor area to 5000 rads.« less

Nuclear Glycolytic Enzyme Enolase of Toxoplasma gondii Functions as a Transcriptional Regulator

PubMed Central

Mouveaux, Thomas; Oria, Gabrielle; Werkmeister, Elisabeth; Slomianny, Christian; Fox, Barbara A.; Bzik, David J.; Tomavo, Stanislas

2014-01-01

Apicomplexan parasites including Toxoplasma gondii have complex life cycles within different hosts and their infectivity relies on their capacity to regulate gene expression. However, little is known about the nuclear factors that regulate gene expression in these pathogens. Here, we report that T. gondii enolase TgENO2 is targeted to the nucleus of actively replicating parasites, where it specifically binds to nuclear chromatin in vivo. Using a ChIP-Seq technique, we provide evidence for TgENO2 enrichment at the 5′ untranslated gene regions containing the putative promoters of 241 nuclear genes. Ectopic expression of HA-tagged TgENO1 or TgENO2 led to changes in transcript levels of numerous gene targets. Targeted disruption of TgENO1 gene results in a decrease in brain cyst burden of chronically infected mice and in changes in transcript levels of several nuclear genes. Complementation of this knockout mutant with ectopic TgENO1-HA fully restored normal transcript levels. Our findings reveal that enolase functions extend beyond glycolytic activity and include a direct role in coordinating gene regulation in T. gondii. PMID:25153525

Calcific Aortic Valve Stenosis: Methods, Models, and Mechanisms

PubMed Central

Miller, Jordan D.; Weiss, Robert M.; Heistad, Donald D.

2011-01-01

Calcific aortic valve stenosis (CAVS) is a major health problem facing aging societies. The identification of osteoblast-like and osteoclast-like cells in human tissue has led to a major paradigm shift in the field. CAVS was thought to be a passive, degenerative process, whereas now the progression of calcification in CAVS is considered to be actively regulated. Mechanistic studies examining the contributions of true ectopic osteogenesis, non-osseous calcification, and ectopic osteoblast-like cells (that appear to function differently from skeletal osteoblasts) to valvular dysfunction have been facilitated by the development of mouse models of CAVS. Recent studies also suggest that valvular fibrosis, as well as calcification, may play an important role in restricting cusp movement, and CAVS may be more appropriately viewed as a fibrocalcific disease. High resolution echocardiography and magnetic resonance imaging have emerged as useful tools for testing the efficacy of pharmacological and genetic interventions in vivo. Key studies in humans and animals are reviewed that have shaped current paradigms in the field of CAVS, and suggest promising future areas for research. PMID:21617136

Laparoscopy

MedlinePlus

... Laparoscopy may be done to remove an ectopic pregnancy. • Pelvic floor disorders —Laparoscopic surgery can be used to ... vagina. Chronic Pelvic Pain: Persistent pain in the pelvic region that has ... fluid. Ectopic Pregnancy: A pregnancy in which the fertilized egg begins ...

Expression of a repressor form of the Arabidopsis thaliana transcription factor TCP16 induces the formation of ectopic meristems.

PubMed

Uberti-Manassero, Nora G; Coscueta, Ezequiel R; Gonzalez, Daniel H

2016-11-01

Plants that express a fusion of the Arabidopsis thaliana class I TCP transcription factor TCP16 to the EAR repressor domain develop several phenotypic alterations, including rounder leaves, short petioles and pedicels, and delayed elongation of sepals, petals and anthers. In addition, these plants develop lobed cotyledons and ectopic meristems. Ectopic meristems are formed on the adaxial side of cotyledon petioles and arise from a cleft that is formed at this site. Analysis of the expression of reporter genes indicated that meristem genes are reactivated at the site of emergence of ectopic meristems, located near the bifurcation of cotyledon veins. The plants also show increased transcript levels of the boundary-specific CUP-SHAPED COTYLEDON (CUC) genes. The results suggest that TCP16 is able to modulate the induction of meristematic programs and the differentiation state of plant cells. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

High Titers ofChlamydia trachomatis Antibodies in Brazilian Women with Tubal Occlusion or Previous Ectopic Pregnancy

PubMed Central

Machado, A. C. S.; Guimarães, E. M. B.; Sakurai, E.; Fioravante, F. C. R.; Amaral, W. N.; Alves, M. F. C.

2007-01-01

Objective. To evaluate serum chlamydia antibody titers (CATs) in tubal occlusion or previous ectopic pregnancy and the associated risk factors.Methods. The study population consisted of 55 women wih tubal damage and 55 parous women. CAT was measured using the whole-cell inclusion immunofluorescence test and cervical chlamydial DNA detected by PCR. Odds ratios were calculated to assess variables associated withC. trachomatis infection.Results. The prevalence of chlamydial antibodies and antibody titers in women with tubal occlusion or previous ectopic pregnancy was significantly higher (P < .01) than in parous women. Stepwise logistic regression analysis showed that chlamydia IgG antibodies were associated with tubal damage and with a larger number of lifetime sexual partners.Conclusions. Chlamydia antibody titers were associated with tubal occlusion, prior ectopic pregnancy, and with sexual behavior, suggesting that a chlamydia infection was the major contributor to the tubal damage in these women. PMID:17541464

Surgical treatment for ectopic atrial tachycardia.

PubMed

Graffigna, A; Vigano, M; Pagani, F; Salerno, G

1992-08-01

Atrial tachycardia is an infrequent but potentially dangerous arrhythmia which often determines cardiac enlargement. Surgical ablation of the arrhythmia is effective and safe, provided a careful atrial mapping is performed and the surgical technique is tailored to the individual focus location. Eight patients underwent surgical ablation of ectopic atrial tachycardia between 1977 and 1990. Different techniques were adopted for each patient according to the anatomical location of the focus and possibly associated arrhythmias. Whenever possible, a closed heart procedure was chosen. In 1 patient a double focal origin was found and treated by separate procedures. In 1 patient with ostium secundum atrial septal defect and atrial flutter, surgical isolation of the right appendage and the ectopic focus was performed. In all patients ectopic atrial tachycardia was ablated with maintenance of the sinoatrial and atrioventricular nodal function as well as internodal conduction. In follow-up up to December 1991, no recurrency was recorded.

Usefulness of postoperative hip irradiation in the prevention of heterotopic bone formation in a high risk group of patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacLennan, I.; Keys, H.M.; Evarts, C.M.

1984-01-01

Heterotopic ossification is a complication of total hip arthroplasty in 14 to 30% of patients. Significant functional impairment will occur in up to 28% of patients with ectopic bone. The high risk group includes those with preexisting heterotopic bone in either hip, those suffering from hypertrophic osteoarthritis or ankylosing spondylitis and patients who have had multiple procedures on the hip. Fifty-eight patients (67 hips) were irradiated after surgical removal of ectopic bone (53 hips) or received radiation prophylaxis of heterotopic ossification (14 hips). Ninety-five percent of patients had either no bone visible or insignificant amounts of ectopic bone visible onmore » postoperative hip X-rays. Only 5% of patients showed significant persistence of ectopic bone. Postoperative hip function was dramatically improved compared to preoperative function in all patients treated. The importance of early commencement of irradiation is emphasized.« less

Frequency of Cushing's syndrome due to ACTH-secreting adrenal medullary lesions: a retrospective study over 10 years from a single center.

PubMed

Falhammar, Henrik; Calissendorff, Jan; Höybye, Charlotte

2017-01-01

Cushing's syndrome due to ectopic adrenocorticotropic hormone production from adrenal medullary lesions has occasionally been described. We retrospectively reviewed all 164 cases of Cushing's syndrome and 77 cases of pheochromocytomas during 10 years. Of all cases with Cushing's syndrome, only two cases (1.2 %) were due to ectopic adrenocorticotropic hormone production from adrenal medullary lesions (one case of pheochromocytoma and one case of adrenal medullary hyperplasia). Of all pheochromocytomas only the above-mentioned case (1.3 %) also gave rise to an ectopic adrenocorticotropic hormone syndrome. The clinical presentation of adrenocorticotropic hormone-secreting pheochromocytoma and adrenal medullary hyperplasia can be anything from mild to dramatic. These are rare conditions important to bear in mind in the workup of a patient with Cushing's syndrome or with pheochromocytoma. The identification of ectopic adrenocorticotropic hormone secretion from adrenal medullary lesions can be life-saving.

Bleeding due to ectopic varices in a urinary diversion: A multidisciplinary diagnostic and therapeutic challenge

PubMed Central

Acosta, Eduardo Mariano Albers; Reyes, Alfonsi Friera; Menéndez, Ricardo Brime

2015-01-01

The ectopic varices in patients with portal hypertension are those that occur at any level of the gastrointestinal (GI) tract, regardless of the varices that occur at the esophageal level. These ectopic varices account for 2–5% of the causes of GI bleeding varices. The risk of bleeding is quadrupled compared to the esophagogastric area, with a mortality of up to 40%. The transjugular intrahepatic portosystemic shunt, should be considered in cases secondary to recurrent bleeding varices. We present a case report of an urological emergency of bleeding in a urinary diversion secondary to ectopic varices successfully treated through the placement of transjugular intrahepatic portosystemic shunt. The condition described here is rare, but important, as it can be a life-threatening complication of portal hypertension. This kind of complication should be known by urologic surgeons managing patients with urinary diversions. PMID:26834901

Robotic partial nephrectomy for duplex kidney with ectopic ureter draining in the vagina in an adult patient with urinary incontinence.

PubMed

Mahmood, Humza; Hadjipavlou, Marios; Das, Raj; Anderson, Chris

2017-02-06

A duplex kidney system with an ectopic ureter draining into the vagina is a congenital malformation that typically presents as refractory urinary incontinence. Diagnosis is often difficult to establish and delayed due to a low incidence. We present the case of a patient aged 26 years with a life-long history of persistent urinary incontinence. Initial presentation was at childhood; however, the diagnosis went undetermined for 22 years. CT urography revealed a duplex kidney with an atrophic upper pole associated with an ectopic ureter that drained into the vaginal vault. This is the first description of such a case being managed successfully via a robot-assisted partial nephrectomy approach. Ectopic ureteral duplication should be considered in the differential diagnosis for young women with refractory urinary incontinence. Robotic partial nephrectomy is a safe and effective technique to manage such cases. 2017 BMJ Publishing Group Ltd.

Low levels of LTR retrotransposon deletion by ectopic recombination in the gigantic genomes of salamanders.

PubMed

Frahry, Matthew Blake; Sun, Cheng; Chong, Rebecca A; Mueller, Rachel Lockridge

2015-02-01

Across the tree of life, species vary dramatically in nuclear genome size. Mutations that add or remove sequences from genomes-insertions or deletions, or indels-are the ultimate source of this variation. Differences in the tempo and mode of insertion and deletion across taxa have been proposed to contribute to evolutionary diversity in genome size. Among vertebrates, most of the largest genomes are found within the salamanders, an amphibian clade with genome sizes ranging from ~14 to ~120 Gb. Salamander genomes have been shown to experience slower rates of DNA loss through small (i.e., <30 bp) deletions than do other vertebrate genomes. However, no studies have addressed DNA loss from salamander genomes resulting from larger deletions. Here, we focus on one type of large deletion-ectopic-recombination-mediated removal of LTR retrotransposon sequences. In ectopic recombination, double-strand breaks are repaired using a "wrong" (i.e., ectopic, or non-allelic) template sequence-typically another locus of similar sequence. When breaks occur within the LTR portions of LTR retrotransposons, ectopic-recombination-mediated repair can produce deletions that remove the internal transposon sequence and the equivalent of one of the two LTR sequences. These deletions leave a signature in the genome-a solo LTR sequence. We compared levels of solo LTRs in the genomes of four salamander species with levels present in five vertebrates with smaller genomes. Our results demonstrate that salamanders have low levels of solo LTRs, suggesting that ectopic-recombination-mediated deletion of LTR retrotransposons occurs more slowly than in other vertebrates with smaller genomes.

Dacryocystitis following a nasolacrimal duct obstruction caused by an ectopic intranasal tooth in a dog.

PubMed

Voelter-Ratson, Katrin; Hagen, Regine; Grundmann, Stefan; Spiess, Bernhard Martin

2015-09-01

To describe a nasolacrimal duct (NLD) obstruction secondary to an ectopic tooth in a 5-year-old male Border collie. The dog was presented with a 1-month history of mucopurulent discharge from the left eye (OS) preceded by a lifelong history of epiphora OS. Treatment with neomycin/polymyxin B/dexamethasone ophthalmic solution had not improved the clinical signs, and the NLD was not patent when irrigated by the referring veterinarian. A complete ophthalmologic examination was performed followed by dacryocystorhinography and computed tomography (CT). The ophthalmologic examination revealed marked mucopurulent discharge, mild conjunctivitis, slightly elevated STT measurements, and a negative Jones test OS. Both nasolacrimal puncta OS could be cannulated without resistance for approximately 1.5 cm. Upon irrigation, copious amounts of mucopurulent discharge were exited through the corresponding punctum, while no fluid could be detected at the nares. Dacryocystorhinography was performed. Radiographs revealed an ectopic left canine tooth within the left nasal cavity. A cystic dilation of the NLD was observed proximal to the ectopic tooth. Computed tomography was performed to determine the exact position of the tooth and possible involvement of adjacent structures; CT confirmed the previous imaging findings. Treatment with systemic antibiotics, NSAIDs, and ofloxacin ophthalmic solution led to resolution of the clinical signs within several days. Surgery was declined by the owner. This is the first case report describing a blocked NLD due to an ectopic tooth in a dog. Ectopic teeth should be included as a differential diagnosis in cases of dacryocystitis and chronic epiphora in dogs. © 2014 American College of Veterinary Ophthalmologists.

Cytomorphology and sonographic features of ectopic thymic tissue diagnosed in paediatric FNA biopsies.

PubMed

Escobar, F A; Pantanowitz, L; Picarsic, J L; Craig, F E; Simons, J P; Viswanathan, P A; Yilmaz, S; Monaco, S E

2018-03-26

Ectopic thymic tissue can arise as an asymptomatic neck mass, which may be detected on imaging studies. The aim of this study was to determine the incidence of ectopic thymic tissue in paediatric FNAs and to the correlate clinical, radiological and cytomorphological findings. FNAs in children with neck and mediastinal lesions performed between January 2012 and July 2016 were reviewed for cases of ectopic thymus. These were then evaluated and correlated with the cytology findings. Of 739 FNAs, 13 (1.8%) cases from 11 patients showed ectopic thymic tissue. The targeted lesions were in the thyroid (n = 7), submandibular region (n = 1), superior mediastinum (n = 1) and paratracheal region (n = 1). The most common indication was for microcalcifications concerning for papillary thyroid carcinoma on ultrasound (n = 6). Imaging findings included fusiform lesions with linear and punctuate bright echoes. The cytology evaluation showed small lymphocytes with discohesive epithelioid cells in most cases, and proteinaceous fluid in the cystic case. There were rare macrophages and Hassall's corpuscles. Flow cytometry and/or immunostains were performed in all cases, supporting thymic origin. Ectopic thymic tissue is rarely present as a neck mass or thyroid nodule on FNA biopsy. The ultrasound imaging findings reveal a well-defined fusiform lesion with punctate bright echoes that could be misinterpreted as papillary thyroid carcinoma. The aspirates show a small lymphoid population, immunophenotypically compatible with thymic T-cells, in addition to scattered epithelial cells. Therefore, knowledge of the typical ultrasonographic and cytopathological features can help make a definitive diagnosis and avoid more invasive procedures in paediatric patients. © 2018 John Wiley & Sons Ltd.

Trends in ectopic pregnancy, hydatidiform mole and miscarriage in the largest obstetrics and gynaecology hospital in China from 2003 to 2013.

PubMed

Li, Xue-Lian; Du, Dan-Feng; Chen, Shang-Jie; Zheng, Sai-Hua; Lee, Arier C; Chen, Qi

2016-05-20

Ectopic pregnancies, miscarriages and hydatidiform moles are the major types of pathological pregnancies in the early gestations of pregnancy and constitute an important public health problem. The trends and incidences of these pathological pregnancies may vary by ethnicity and geographical regions. This has not been fully investigated in the Chinese population. In this study we retrospectively report the trends of pathological pregnancies in Chinese population. Data on 22,511 women with ectopic pregnancy, hydatidiform mole and miscarriage were collected from the largest obstetrics and gynaecology hospital in China from 2003 to 2013. Data included age at diagnosis and the annual number of women with diagnosed ectopic pregnancy, hydatidiform mole and miscarriage. The total number of ectopic pregnancy, hydatidiform mole and miscarriage was increased 3.5folds in 2013 compared to 2003. Ectopic pregnancy is the leading pathological pregnancy and miscarriage is increasing at a greater rate among the pathological pregnancies. The median age of women with hydatidiform mole at diagnosis significantly increased from 25.5 years to 29 years (p = 0.002), however the median age for other pathological pregnancies was not different between 2003 and 2013. The number of women with hydatidiform mole at diagnosis who were over 40 years old has increased. The mean maternal age is increased from 28.1 years old in 2003 to 29.4 years old in 2013 in this hospital. We speculate that the increased maternal age may contribute to the increase in these pathological pregnancies between 2003 and 2013 in China.

Non-linear imaging techniques visualize the lipid profile of C. elegans

NASA Astrophysics Data System (ADS)

Mari, Meropi; Petanidou, Barbara; Palikaras, Konstantinos; Fotakis, Costas; Tavernarakis, Nektarios; Filippidis, George

2015-07-01

The non-linear techniques Second and Third Harmonic Generation (SHG, THG) have been employed simultaneously to record three dimensional (3D) imaging and localize the lipid content of the muscular areas (ectopic fat) of Caenorhabditis elegans (C. elegans). Simultaneously, Two-Photon Fluorescence (TPEF) was used initially to localize the stained lipids with Nile Red, but also to confirm the THG potential to image lipids successfully. In addition, GFP labelling of the somatic muscles, proves the initial suggestion of the existence of ectopic fat on the muscles and provides complementary information to the SHG imaging of the pharynx. The ectopic fat may be related to a complex of pathological conditions including type-2 diabetes, hypertension and cardiovascular diseases. The elucidation of the molecular path leading to the development of metabolic syndrome is a vital issue with high biological significance and necessitates accurate methods competent of monitoring lipid storage distribution and dynamics in vivo. THG microscopy was employed as a quantitative tool to monitor the lipid accumulation in non-adipose tissues in the pharyngeal muscles of 12 unstained specimens while the SHG imaging revealed the anatomical structure of the muscles. The ectopic fat accumulation on the pharyngeal muscles increases in wild type (N2) C. elegans between 1 and 9 days of adulthood. This suggests a correlation of the ectopic fat accumulation with the aging. Our results can provide new evidence relating the deposition of ectopic fat with aging, but also validate SHG and THG microscopy modalities as new, non-invasive tools capable of localizing and quantifying selectively lipid accumulation and distribution.

Towards ontology-based decision support systems for complex ultrasound diagnosis in obstetrics and gynecology.

PubMed

Maurice, P; Dhombres, F; Blondiaux, E; Friszer, S; Guilbaud, L; Lelong, N; Khoshnood, B; Charlet, J; Perrot, N; Jauniaux, E; Jurkovic, D; Jouannic, J-M

2017-05-01

We have developed a new knowledge base intelligent system for obstetrics and gynecology ultrasound imaging, based on an ontology and a reference image collection. This study evaluates the new system to support accurate annotations of ultrasound images. We have used the early ultrasound diagnosis of ectopic pregnancies as a model clinical issue. The ectopic pregnancy ontology was derived from medical texts (4260 ultrasound reports of ectopic pregnancy from a specialist center in the UK and 2795 Pubmed abstracts indexed with the MeSH term "Pregnancy, Ectopic") and the reference image collection was built on a selection from 106 publications. We conducted a retrospective analysis of the signs in 35 scans of ectopic pregnancy by six observers using the new system. The resulting ectopic pregnancy ontology consisted of 1395 terms, and 80 images were collected for the reference collection. The observers used the knowledge base intelligent system to provide a total of 1486 sign annotations. The precision, recall and F-measure for the annotations were 0.83, 0.62 and 0.71, respectively. The global proportion of agreement was 40.35% 95% CI [38.64-42.05]. The ontology-based intelligent system provides accurate annotations of ultrasound images and suggests that it may benefit non-expert operators. The precision rate is appropriate for accurate input of a computer-based clinical decision support and could be used to support medical imaging diagnosis of complex conditions in obstetrics and gynecology. Copyright © 2017. Published by Elsevier Masson SAS.

42 CFR 50.308 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2014 CFR

2014-10-01

... pregnancies. 50.308 Section 50.308 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... pregnancies. Federal financial participation is available with respect to the cost of drugs or devices to... an ectopic pregnancy. ...

42 CFR 50.308 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2011 CFR

2011-10-01

... pregnancies. 50.308 Section 50.308 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... pregnancies. Federal financial participation is available with respect to the cost of drugs or devices to... an ectopic pregnancy. ...

42 CFR 50.308 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... pregnancies. 50.308 Section 50.308 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... pregnancies. Federal financial participation is available with respect to the cost of drugs or devices to... an ectopic pregnancy. ...

42 CFR 50.308 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2012 CFR

2012-10-01

... pregnancies. 50.308 Section 50.308 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... pregnancies. Federal financial participation is available with respect to the cost of drugs or devices to... an ectopic pregnancy. ...

42 CFR 50.308 - Drugs and devices and termination of ectopic pregnancies.

Code of Federal Regulations, 2013 CFR

2013-10-01

... pregnancies. 50.308 Section 50.308 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... pregnancies. Federal financial participation is available with respect to the cost of drugs or devices to... an ectopic pregnancy. ...

Computing the stability of steady-state solutions of mathematical models of the electrical activity in the heart.

PubMed

Tveito, Aslak; Skavhaug, Ola; Lines, Glenn T; Artebrant, Robert

2011-08-01

Instabilities in the electro-chemical resting state of the heart can generate ectopic waves that in turn can initiate arrhythmias. We derive methods for computing the resting state for mathematical models of the electro-chemical process underpinning a heartbeat, and we estimate the stability of the resting state by invoking the largest real part of the eigenvalues of a linearized model. The implementation of the methods is described and a number of numerical experiments illustrate the feasibility of the methods. In particular, we test the methods for problems where we can compare the solutions with analytical results, and problems where we have solutions computed by independent software. The software is also tested for a fairly realistic 3D model. Copyright © 2011 Elsevier Ltd. All rights reserved.

Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models

PubMed Central

Varela, Marta; Hancox, Jules C.; Aslanidi, Oleg V.

2016-01-01

Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are effective in terminating AF. PMID:27984585

Zebrafish pronephros tubulogenesis and epithelial identity maintenance are reliant on the polarity proteins Prkc iota and zeta

PubMed Central

Gerlach, Gary F.; Wingert, Rebecca A.

2014-01-01

The zebrafish pronephros provides an excellent in vivo system to study the mechanisms of vertebrate nephron development. When and how renal progenitors in the zebrafish embryo undergo tubulogenesis to form nephrons is poorly understood, but is known to involve a mesenchymal to epithelial transition (MET) and the acquisition of polarity. Here, we determined the precise timing of these events in pronephros tubulogenesis. As the ternary polarity complex is an essential regulator of epithelial cell polarity across tissues, we performed gene knockdown studies to assess the roles of the related factors atypical protein kinase C iota and zeta (prkcι, prkcζ). We found that prkcι and prkcζ serve partially redundant functions to establish pronephros tubule epithelium polarity. Further, the loss of prkcι or the combined knockdown of prkcι/ζ disrupted proximal tubule morphogenesis and podocyte migration due to cardiac defects that prevented normal fluid flow to the kidney. Surprisingly, tubule cells in prkcι/ζ morphants displayed ectopic expression of the transcription factor pax2a and the podocyte-associated genes wt1a, wt1b, and podxl, suggesting that prkcι/ζ are needed to maintain renal epithelial identity. Knockdown of genes essential for cardiac contractility and vascular flow to the kidney, such as tnnt2a, or elimination of pronephros fluid output through knockdown of the intraflagellar transport gene ift88, was not associated with ectopic pronephros gene expression, thus suggesting a unique role for prkcι/ζ in maintaining tubule epithelial identity separate from the consequence of disruptions to renal fluid flow. Interestingly, knockdown of pax2a, but not wt1a, was sufficient to rescue ectopic tubule gene expression in prkcι/ζ morphants. These data suggest a model in which the redundant activities of prkcι and prkcζ are essential to establish tubule epithelial polarity and also serve to maintain proper epithelial cell type identity in the tubule by inhibiting pax2a expression. These studies provide a valuable foundation for further analysis of MET during nephrogenesis, and have implications for understanding the pathways that affect nephron epithelial cells during kidney disease and regeneration. PMID:25446529

mRNA-binding protein TIA-1 reduces cytokine expression in human endometrial stromal cells and is down-regulated in ectopic endometrium.

PubMed

Karalok, Hakan Mete; Aydin, Ebru; Saglam, Ozlen; Torun, Aysenur; Guzeloglu-Kayisli, Ozlem; Lalioti, Maria D; Kristiansson, Helena; Duke, Cindy M P; Choe, Gina; Flannery, Clare; Kallen, Caleb B; Seli, Emre

2014-12-01

Cytokines and growth factors play important roles in endometrial function and the pathogenesis of endometriosis. mRNAs encoding cytokines and growth factors undergo rapid turnover; primarily mediated by adenosine- and uridine-rich elements (AREs) located in their 3'-untranslated regions. T-cell intracellular antigen (TIA-1), an mRNA-binding protein, binds to AREs in target transcripts, leading to decreased gene expression. The purpose of this article was to determine whether TIA-1 plays a role in the regulation of endometrial cytokine and growth factor expression during the normal menstrual cycle and whether TIA-1 expression is altered in women with endometriosis. Eutopic endometrial tissue obtained from women without endometriosis (n = 30) and eutopic and ectopic endometrial tissues from women with endometriosis (n = 17) were immunostained for TIA-1. Staining intensities were evaluated by histological scores (HSCOREs). The regulation of endometrial TIA-1 expression by immune factors and steroid hormones was studied by treating primary cultured human endometrial stromal cells (HESCs) with vehicle, lipopolysaccharide, TNF-α, IL-6, estradiol, or progesterone, followed by protein blot analyses. HESCs were engineered to over- or underexpress TIA-1 to test whether TIA-1 regulates IL-6 or TNF-α expression in these cells. We found that TIA-1 is expressed in endometrial stromal and glandular cells throughout the menstrual cycle and that this expression is significantly higher in the perimenstrual phase. In women with endometriosis, TIA-1 expression in eutopic and ectopic endometrium was reduced compared with TIA-1 expression in eutopic endometrium of unaffected control women. Lipopolysaccharide and TNF-α increased TIA-1 expression in HESCs in vitro, whereas IL-6 or steroid hormones had no effect. In HESCs, down-regulation of TIA-1 resulted in elevated IL-6 and TNF-α expression, whereas TIA-1 overexpression resulted in decreased IL-6 and TNF-α expression. Endometrial TIA-1 is regulated throughout the menstrual cycle, TIA-1 modulates the expression of immune factors in endometrial cells, and downregulation of TIA-1 may contribute to the pathogenesis of endometriosis.

mRNA-Binding Protein TIA-1 Reduces Cytokine Expression in Human Endometrial Stromal Cells and Is Down-Regulated in Ectopic Endometrium

PubMed Central

Karalok, Hakan Mete; Aydin, Ebru; Saglam, Ozlen; Torun, Aysenur; Guzeloglu-Kayisli, Ozlem; Lalioti, Maria D.; Kristiansson, Helena; Duke, Cindy M. P.; Choe, Gina; Flannery, Clare; Kallen, Caleb B.

2014-01-01

Background: Cytokines and growth factors play important roles in endometrial function and the pathogenesis of endometriosis. mRNAs encoding cytokines and growth factors undergo rapid turnover; primarily mediated by adenosine- and uridine-rich elements (AREs) located in their 3′-untranslated regions. T-cell intracellular antigen (TIA-1), an mRNA-binding protein, binds to AREs in target transcripts, leading to decreased gene expression. Objective: The purpose of this article was to determine whether TIA-1 plays a role in the regulation of endometrial cytokine and growth factor expression during the normal menstrual cycle and whether TIA-1 expression is altered in women with endometriosis. Methods: Eutopic endometrial tissue obtained from women without endometriosis (n = 30) and eutopic and ectopic endometrial tissues from women with endometriosis (n = 17) were immunostained for TIA-1. Staining intensities were evaluated by histological scores (HSCOREs). The regulation of endometrial TIA-1 expression by immune factors and steroid hormones was studied by treating primary cultured human endometrial stromal cells (HESCs) with vehicle, lipopolysaccharide, TNF-α, IL-6, estradiol, or progesterone, followed by protein blot analyses. HESCs were engineered to over- or underexpress TIA-1 to test whether TIA-1 regulates IL-6 or TNF-α expression in these cells. Results: We found that TIA-1 is expressed in endometrial stromal and glandular cells throughout the menstrual cycle and that this expression is significantly higher in the perimenstrual phase. In women with endometriosis, TIA-1 expression in eutopic and ectopic endometrium was reduced compared with TIA-1 expression in eutopic endometrium of unaffected control women. Lipopolysaccharide and TNF-α increased TIA-1 expression in HESCs in vitro, whereas IL-6 or steroid hormones had no effect. In HESCs, down-regulation of TIA-1 resulted in elevated IL-6 and TNF-α expression, whereas TIA-1 overexpression resulted in decreased IL-6 and TNF-α expression. Conclusions: Endometrial TIA-1 is regulated throughout the menstrual cycle, TIA-1 modulates the expression of immune factors in endometrial cells, and downregulation of TIA-1 may contribute to the pathogenesis of endometriosis. PMID:25140393

The Role of Retinal Determination Gene Network (RDGN) in Hormone Signaling Transduction and Prostate Tumorigenesis

DTIC Science & Technology

2012-10-01

support with our hypothesis, expressions of AR co-repressors (48-50), HDAC1, HDAC3 or SirT1 inhibit the ligand-induced AR activation at different...signaling and androgen-dependent growth. We hypothesis that DACH1/Six1/Eya pathway is an endogenous regulator of AR trans- activation and contributes to...mechanism. Inhibitory function of Eya1 on AR transactivation required a phosphates activity and could be enhanced by ectopic expression of co-repressors

WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility

PubMed Central

Yan, Catherine; Martinez-Quiles, Narcisa; Eden, Sharon; Shibata, Tomoyuki; Takeshima, Fuminao; Shinkura, Reiko; Fujiwara, Yuko; Bronson, Roderick; Snapper, Scott B.; Kirschner, Marc W.; Geha, Raif; Rosen, Fred S.; Alt, Frederick W.

2003-01-01

The Wiskott–Aldrich syndrome related protein WAVE2 is implicated in the regulation of actin-cytoskeletal reorganization downstream of the small Rho GTPase, Rac. We inactivated the WAVE2 gene by gene-targeted mutation to examine its role in murine development and in actin assembly. WAVE2-deficient embryos survived until approximately embryonic day 12.5 and displayed growth retardation and certain morphological defects, including malformations of the ventricles in the developing brain. WAVE2-deficient embryonic stem cells displayed normal proliferation, whereas WAVE2-deficient embryonic fibroblasts exhibited severe growth defects, as well as defective cell motility in response to PDGF, lamellipodium formation and Rac-mediated actin polymerization. These results imply a non-redundant role for WAVE2 in murine embryogenesis and a critical role for WAVE2 in actin-based processes downstream of Rac that are essential for cell movement. PMID:12853475

WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility.

PubMed

Yan, Catherine; Martinez-Quiles, Narcisa; Eden, Sharon; Shibata, Tomoyuki; Takeshima, Fuminao; Shinkura, Reiko; Fujiwara, Yuko; Bronson, Roderick; Snapper, Scott B; Kirschner, Marc W; Geha, Raif; Rosen, Fred S; Alt, Frederick W

2003-07-15

The Wiskott-Aldrich syndrome related protein WAVE2 is implicated in the regulation of actin-cytoskeletal reorganization downstream of the small Rho GTPase, Rac. We inactivated the WAVE2 gene by gene-targeted mutation to examine its role in murine development and in actin assembly. WAVE2-deficient embryos survived until approximately embryonic day 12.5 and displayed growth retardation and certain morphological defects, including malformations of the ventricles in the developing brain. WAVE2-deficient embryonic stem cells displayed normal proliferation, whereas WAVE2-deficient embryonic fibroblasts exhibited severe growth defects, as well as defective cell motility in response to PDGF, lamellipodium formation and Rac-mediated actin polymerization. These results imply a non-redundant role for WAVE2 in murine embryogenesis and a critical role for WAVE2 in actin-based processes downstream of Rac that are essential for cell movement.

Esthesioneuroblastoma (Olfactory Neuroblastoma) with Ectopic ACTH Syndrome: a multidisciplinary case presentation from the Joan Karnell cancer center of Pennsylvania Hospital.

PubMed

Mintzer, David M; Zheng, Sarah; Nagamine, Michiko; Newman, Jason; Benito, Maria

2010-01-01

The case of a patient with recurrent esthesioneuroblastoma complicated by ectopic adrenocorticotropic hormone production is presented, including the workup and management of this uncommon complication of an uncommon disease.

Ectopic pinealoma: an unusual clinical presentation and a histochemical comparison with a seminoma of the testis

PubMed Central

Beeley, J. M.; Daly, J. J.; Timperley, W. R.; Warner, J.

1973-01-01

A patient with ectopic pinealoma first presented with apparent anorexia nervosa and hypernatraemic coma. A history of diabetes insipidus two months previously was not known on admission to hospital. The diabetes insipidus was unmasked by the administration of steroids. Neuroendocrinal and neuropathological aspects of the case are discussed with reference to the march of symptoms due to the growth of the tumour. Histochemical evidence is presented supporting the similarity between ectopic pinealoma and seminoma which suggests that they may more properly be referred to as atypical teratomas. Images PMID:4356733

[Successive ectopic pregnancies associated with tubal shistosomiasis in a French traveler].

PubMed

Laroche, Justine; Mottet, Nicolas; Malincenco, Marianna; Gay, Catherine; Royer, Pierre Yves; Riethmuller, Didier

2016-01-01

Schistosomiasis is the second endemic parasitic disease in the world and is a common cause of urogenital infections. Ectopic pregnancies due to tubal obstruction by schistosoma's eggs are usually reported in Africa. Schistosomiasis also affects travelers but infection of the female genital tract is less frequently described. We report an unusual clinical case of two successive ectopic pregnancies with tubal schistosomiasis in a French woman, seven years after a travel to Mali. The first event was discovered after histologic examination of salpingectomy and the second event required a controlateral salpingotomy with an injection of methotrexate, two months later.

Treating non-tubal ectopic pregnancy.

PubMed

Chetty, Maya; Elson, Janine

2009-08-01

The purpose of this review is to examine the current state of knowledge regarding the treatment of non-tubal ectopic pregnancies. This review looks at the management of cervical, caesarean scar, ovarian, interstitial, cornual and abdominal pregnancies. Traditionally these pregnancies have been diagnosed late and managed by open surgery. Earlier diagnosis has led to the use of minimal access techniques, medical and conservative management for all types of non-tubal pregnancies. Increased awareness and the experience of specialised centres have led to an improved understanding of the best way to manage non-tubal ectopic pregnancies and the development of new techniques.

Simple ectopic kidney in three dogs.

PubMed

Choi, Jiyoung; Lee, Heechun; Lee, Youngwon; Choi, Hojung

2012-10-01

Simple ectopic kidney was diagnosed in three dogs by means of radiography and ultrasonography. A 2-year-old castrated male Schnauzer, a 13-year-old female Schnauzer and a 9-year-old male Jindo were referred with vomiting, hematuria and ocular discharge, respectively. In all three dogs, oval-shaped masses with soft tissue density were observed in the mid to caudal abdomen bilaterally or unilaterally, and kidney silhouettes were not identified at the proper anatomic places on abdominal radiographs. Ultrasonography confirmed the masses were malpositioned kidney. The ectopic kidneys had relatively small size, irregular shape and short ureter but showed normal function on excretory urography.

Single-Tooth Osteotomy Combined Wide Linear Corticotomy Under Local Anesthesia for Correcting Anterior Protrusion With Ectopically Erupted Canine.

PubMed

Iskenderoglu, Nur Serife; Choi, Byung-Joon; Seo, Kyung Won; Lee, Yeon-Ji; Lee, Baek-Soo; Kim, Seong-Hun

2017-01-01

This article presents the alternative surgical treatments of both anterior protrusion by carrying out retraction on mandibular anterior fragment, meanwhile applying retraction force on maxilla anterior teeth and ectopically erupted canine with using platelet-rich fibrin (PRF). Anterior segmental osteotomy was combined with linear corticotomy under local anesthesia. The correction of right ectopic canine was achieved through 2 stages. First, dento-osseous osteotomy on palatal side was performed. Then second osteotomy with immediate manual repositioning of the canine with concomitant first premolar extraction was enhanced with PRF, which was prepared by centrifuging patient's blood, applied into buccal side of high canine during osteotomy. Mandibular retraction was accomplished by anterior segmental osteotomy. Single-tooth osteotomy is a more effective surgical method for ankylosed or ectopically erupted tooth in orthodontic treatment. It can reduce the total orthodontic treatment time and root resorption, 1 common complication. Significant improved bone formation was seen with the addition of PRF on noncritical size defects in the animal model. It is reasonable to think that PRF can promote bone regeneration. So early bone formation also can reduce the complication such as postoperative infection. As an alternative to anterior protrusion and ectopically erupted canine treatment, segmental osteotomy and corticotomy combined platelet-rich plasma can enhance orthodontic treatment outcome.

Nimesulide, a COX-2 inhibitor, does not reduce lesion size or number in a nude mouse model of endometriosis.

PubMed

Hull, M L; Prentice, A; Wang, D Y; Butt, R P; Phillips, S C; Smith, S K; Charnock-Jones, D S

2005-02-01

Women with endometriosis have elevated levels of cyclooxygenase-2 (COX-2) in peritoneal macrophages and endometriotic tissue. Inhibition of COX-2 has been shown to reduce inflammation, angiogenesis and cellular proliferation. It may also downregulate aromatase activity in ectopic endometrial lesions. Ectopic endometrial establishment and growth are therefore likely to be suppressed in the presence of COX-2 inhibitors. We hypothesized that COX-2 inhibition would reduce the size and number of ectopic human endometrial lesions in a nude mouse model of endometriosis. The selective COX-2 inhibitor, nimesulide, was administered to estrogen-supplemented nude mice implanted with human endometrial tissue. Ten days after implantation, the number and size of ectopic endometrial lesions were evaluated and compared with lesions from a control group. Immunohistochemical assessment of vascular development and macrophage and myofibroblast infiltration in control and treated lesions was performed. There was no difference in the number or size of ectopic endometrial lesions in control and nimesulide-treated nude mice. Nimesulide did not induce a visually identifiable difference in blood vessel development or macrophage or myofibroblast infiltration in nude mouse explants. The hypothesized biological properties of COX-2 inhibition did not influence lesion number or size in the nude mouse model of endometriosis.

Catheter ablation of junctional ectopic tachycardia in children, with preservation of atrioventricular conduction.

PubMed

Emmel, M; Sreeram, N; Brockmeier, K

2005-04-01

Idiopathic junctional ectopic tachycardia is a rare arrhythmia in children. Several studies have demonstrated that drug therapy is often ineffective and sometimes the only achieved effect is rate control. Early presentation and frequent recurrence are associated with adverse outcome. Three consecutive children, aged 9, 7 and 12 years respectively, underwent radiofrequency catheter ablation for junctional ectopic tachycardia, after having failed antiarrhythmic drug therapy. The entire His bundle was plotted out and marked, using the Localisa navigation system. The arrhythmia was readily and repeatedly inducible using intravenous isoprenaline infusion and the site of earliest retrograde conduction during tachycardia could be assessed. Ablations were performed in sinus rhythm, empirically targeting the site of earliest retrograde conduction during tachycardia. This approach was successful in abolishing tachyarrhythmia in the first two patients, in whom the successful ablation site was located superoparaseptally. In the third patient, junctional ectopic tachycardia was inducible, despite abolishing retrograde atrial activation, in a septal location on the tricuspid valve annulus. Further ablations in the superoparaseptal region, closer to the His bundle, were successful in rendering tachyarrhythmia noninducible. Over a median follow-up of 10 months, none of the patients has had recurrence of arrhythmia, despite discontinuing all antiarrhythmic medications. Radio frequency catheter ablation of junctional ectopic tachycardia is feasible with preservation of atrioventricular conduction.

Ectopic Osteoid and Bone Formation by Three Calcium-Phosphate Ceramics in Rats, Rabbits and Dogs

PubMed Central

Wang, Liao; Zhang, Bi; Bao, Chongyun; Habibovic, Pamela; Hu, Jing; Zhang, Xingdong

2014-01-01

Calcium phosphate ceramics with specific physicochemical properties have been shown to induce de novo bone formation upon ectopic implantation in a number of animal models. In this study we explored the influence of physicochemical properties as well as the animal species on material-induced ectopic bone formation. Three bioceramics were used for the study: phase-pure hydroxyapatite (HA) sintered at 1200°C and two biphasic calcium phosphate (BCP) ceramics, consisting of 60 wt.% HA and 40 wt.% TCP (β-Tricalcium phosphate), sintered at either 1100°C or 1200°C. 108 samples of each ceramic were intramuscularly implanted in dogs, rabbits, and rats for 6, 12, and 24 weeks respectively. Histological and histomorphometrical analyses illustrated that ectopic bone and/or osteoid tissue formation was most pronounced in BCP sintered at 1100°C and most limited in HA, independent of the animal model. Concerning the effect of animal species, ectopic bone formation reproducibly occurred in dogs, while in rabbits and rats, new tissue formation was mainly limited to osteoid. The results of this study confirmed that the incidence and the extent of material-induced bone formation are related to both the physicochemical properties of calcium phosphate ceramics and the animal model. PMID:25229501

Esthesioneuroblastoma (Olfactory Neuroblastoma) with Ectopic ACTH Syndrome: A Multidisciplinary Case Presentation from the Joan Karnell Cancer Center of Pennsylvania Hospital

PubMed Central

Zheng, Sarah; Nagamine, Michiko; Newman, Jason; Benito, Maria

2010-01-01

The case of a patient with recurrent esthesioneuroblastoma complicated by ectopic adrenocorticotropic hormone production is presented, including the workup and management of this uncommon complication of an uncommon disease. PMID:20053760

Serum Human Chorionic Gonadotropin (β- hCG) Clearance Curves in Women with Successfully Expectantly Managed Tubal Ectopic Pregnancies: A Retrospective Cohort Study

PubMed Central

Helmy, Samir; Mavrelos, Dimitrios; Sawyer, Elinor; Ben-Nagi, Jara; Koch, Marianne; Day, Andrea; Jurkovic, Davor

2015-01-01

Objective To establish clearance curves for serum β -hCG in women with successfully expectantly managed tubal ectopic pregnancies. Design Retrospective cohort study. Non- viable tubal ectopic pregnancy was diagnosed on transvaginal ultrasound. If initial serum β hCG was less than 5000 IU/L and patients were asymptomatic, expectant management was offered. Patients underwent serial β hCG measurements until serum β hCG was less than 20 IU/l, or the urine pregnancy test was negative. Setting Early Pregnancy and Gynaecology Assessment Unit, Kings College Hospital, London (December 1998 to July 2006). Patients We included 161 women with diagnosed non-viable tubal ectopic pregnancy who underwent successful expectant management. Main outcome measure Serum β hCG level. Results Mean initial serum β- hCG was 488 IU/L (41 - 4883) and median serum β hCG clearance time was 19 days (5 - 82). The average half-life of β hCG clearance was 82.5 hours (±SD 50.2) in patients with steadily declining serum β- hCG levels compared to 106.7 hours (±SD 72.0) in patients with primarily plateauing β-hCG levels in the declining phase. However, these differences were not significant (p>0.05). Conclusion We identified a median follow-up of 19 days until serum β hCG clearance in women with tubal ectopic pregnancy and successful expectant management. Although non- significant, women with initially plateauing serum β hCG showed a longer follow-up time until clearance compared to women with steadily declining β hCG levels. This information may serve as a guideline enabling clinicians to predict the length of follow-up for women with tubal ectopic pregnancy and expectant management. PMID:26135923

Endoscopic Endonasal Surgery for Remission of Cushing Disease Caused by Ectopic Intracavernous Macroadenoma: Case Report and Literature Review.

PubMed

Koutourousiou, Maria; Winstead, Welby I

2017-02-01

Complete surgical resection of an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is the gold standard of treatment of Cushing disease. Ectopic location of these adenomas is an extremely rare condition that may compromise the diagnosis and surgical success. We present the first case of an ectopic intracavernous ACTH-secreting macroadenoma totally resected with endoscopic endonasal surgery (EES). A 36-year-old woman presented with Cushing syndrome. Increased ACTH, serum cortisol, and free urine cortisol levels were identified; however, pituitary magnetic resonance imaging failed to show a pituitary tumor; instead, a parasellar lesion in the left cavernous sinus (CS) was noticed. Inferior petrosal sinus sampling showed a significant central to peripheral and lateralized left-sided ACTH gradient. The patient underwent EES. No tumor was found in the sella; however, the left CS was widely explored and a tumor was found lateral to the paraclival segment of the carotid artery. There were no complications after EES. Pathology confirmed the diagnosis of an ACTH-secreting adenoma. During the immediate postoperative course, serum cortisol levels decreased lower than 5 μg/dL. Postoperative magnetic resonance imaging showed complete tumor resection. At 20 months follow-up, the patient remained in clinical and biochemical remission of Cushing disease. Only 12 cases of ectopic intracavernous ACTH-secreting adenomas have been reported and all were microadenomas. The presence of an ectopic ACTH-secreting macroadenoma in the CS represents a surgical challenge. EES is the ideal approach for complete resection of ectopic intracavernous adenomas, allowing for a wide exploration of the CS with no surgical complications. Copyright © 2016 Elsevier Inc. All rights reserved.

[Ectopic pregnancy at the Ignace Deen University Hospital in Conakry: epidemiologic, social, demographic, therapeutic, and prognostic aspects].

PubMed

Baldé, I S; Diallo, F B; Conté, I; Diallo, M H; Sylla, I; Diallo, B S; Diallo, T S; Sy, T

2014-01-01

The objectives of this study were to calculate the frequency of ectopic pregnancy in the department, define its epidemiological, diagnostic, therapeutic, and prognostic aspects, and determine a clear therapeutic approach appropriate to our setting. In this prospective study, we compiled all cases of ectopic pregnancy seen in 2011 and 2012 in the obstetrics-gynecology department at Ignace Deen University Hospital in Conakry. Ectopic pregnancies represented 1.3% of all deliveries over this period. In the 111 cases in this population, women aged 30-34 years accounted for 31.5%, those pregnant for the first time 40.5%, nulliparous women 35.1%, married women 72.1%, those without schooling 43.2%), and those with a history of sexually transmitted infection 57.6% (these categories are not exclusive, and the same women may be included in several). Secondary amenorrhea with abdominopelvic pain and metrorrhagia was the reason for admission in 56.5% of cases. Ultrasound in early pregnancy is infrequent in Conakry. Almost all of our patients underwent emergency surgery (80.2%) More than half of the ectopic pregnancies were located in the ampulla of the uterine tubes (73.0%). There were three abdominal pregnancies and 2 ovarian. In all cases the treatment was surgical, most often salpingectomy. Postoperative complications occurred in 35.1% of cases, most often anemia (27.9% of all cases) requiring blood transfusion in 11.7% of all cases before, during, or after surgery. The maternal death rate was 1.8%. Ectopic pregnancy remains a major concern at Ignace Deen CHU. Reduction of its frequency requires increased population awareness of sexually transmitted infections and illegal abortions. Management should be prompt and appropriate.

Obesity and exercise-induced ectopic ventricular arrhythmias in apparently healthy middle aged adults.

PubMed

Sabbag, Avi; Sidi, Yechezkel; Kivity, Shaye; Beinart, Roy; Glikson, Michael; Segev, Shlomo; Goldenberg, Ilan; Maor, Elad

2016-03-01

Obesity and overweight are strongly associated with cardiovascular morbidity and mortality. However, there are limited data on the association between excess weight and the risk of ectopic ventricular activity. We investigated the association between body mass index (BMI) and the risk for ectopic ventricular activity (defined as multiple ventricular premature beats (≥3), ventricular bigeminy, nonsustained ventricular tachycardia or sustained ventricular tachycardia) during exercise stress testing among 22,516 apparently healthy men and women who attended periodic health screening examinations between the years 2000 and 2014. All subjects had completed maximal exercise stress testing annually according to the Bruce protocol. Subjects were divided at baseline into three groups: normal weight (BMI ≥ 18.5 kg/m(2) and<25; N = 9,994), overweight (BMI ≥ 25 and < 30; N = 9,613) and obese (BMI ≥ 30; N = 2,906). The mean age of study subjects was 47 ± 10 years and 72% were men. Kaplan-Meier survival analysis showed that the cumulative probability for the development of exercise-induced ectopic ventricular activity arrhythmias was highest among obese subjects, intermediate among overweight subjects and lowest among subjects with normal weight (3.4%, 2.7% and 2.2% respectively; p < 0.001). Multivariate binary logistic regression with repeated measures of 92,619 ESTs, showed that obese subjects were 33% more likely to have ectopic ventricular arrhythmias during exercise compared with subjects with normal weight (p = 0.005), and that each 1 kg/m(2) increase in BMI was associated with a significant 4% (p = 0.002) increased adjusted risk for exercise-induced ventricular arrhythmias. Obesity is independently associated with increased likelihood of ectopic ventricular arrhythmia during exercise. © The European Society of Cardiology 2015.

Population-based study on the effect of socioeconomic factors and race on management and outcomes of 35,535 inpatient ectopic pregnancies.

PubMed

Papillon-Smith, Jessica; Imam, Basel; Patenaude, Valerie; Abenhaim, Haim Arie

2014-01-01

To evaluate whether socioeconomic variables influence the management and outcomes of ectopic pregnancies. Retrospective cohort study (Canadian Task Force classification II-2). Hospitals in the United States participating in the Health Care Cost and Utilization Project. Women (n = 35 535) with a primary discharge diagnosis of ectopic pregnancy. Effect of socioeconomic factors and race/ethnicity on management and adverse outcomes of ectopic pregnancy. During the 9-year study, 35 535 ectopic pregnancies were identified. The development of hemoperitoneum in 8706 patients (24.50%) was the most common complication. Asian race was the sociodemographic variable most predictive of hemoperitoneum (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.24-1.61; p < .01) and transfusion (OR, 1.62; 95% CI, 1.39-1.89; p < .01), and Medicare status was most influential on prolonged hospitalization (OR, 1.83; 95% CI, 1.36-2.47; p < .01). Major complications were not affected by socioeconomic factors. Laparotomy in 25 075 patients (70.6%) was the most common treatment option. Patients of Asian or Pacific Islander descent were least likely to be treated non-surgically (OR, 0.62; 95% CI, 0.51-0.76; p < .01), whereas Medicare recipients were most likely to be treated non-surgically (OR, 1.70; 95% CI, 1.32-2.18; p < .01). All non-white groups were less likely to undergo a laparoscopic approach. Major complications from ectopic pregnancy are not influenced by socioeconomic variables; however, less serious complications and management approaches are persistently affected. Copyright © 2014 AAGL. Published by Elsevier Inc. All rights reserved.

Transcriptome analysis of ectopic chloroplast development in green curd cauliflower (Brassica oleracea L. var. botrytis).

PubMed

Zhou, Xiangjun; Fei, Zhangjun; Thannhauser, Theodore W; Li, Li

2011-11-23

Chloroplasts are the green plastids where photosynthesis takes place. The biogenesis of chloroplasts requires the coordinate expression of both nuclear and chloroplast genes and is regulated by developmental and environmental signals. Despite extensive studies of this process, the genetic basis and the regulatory control of chloroplast biogenesis and development remain to be elucidated. Green cauliflower mutant causes ectopic development of chloroplasts in the curd tissue of the plant, turning the otherwise white curd green. To investigate the transcriptional control of chloroplast development, we compared gene expression between green and white curds using the RNA-seq approach. Deep sequencing produced over 15 million reads with lengths of 86 base pairs from each cDNA library. A total of 7,155 genes were found to exhibit at least 3-fold changes in expression between green and white curds. These included light-regulated genes, genes encoding chloroplast constituents, and genes involved in chlorophyll biosynthesis. Moreover, we discovered that the cauliflower ELONGATED HYPOCOTYL5 (BoHY5) was expressed higher in green curds than white curds and that 2616 HY5-targeted genes, including 1600 up-regulated genes and 1016 down-regulated genes, were differently expressed in green in comparison to white curd tissue. All these 1600 up-regulated genes were HY5-targeted genes in the light. The genome-wide profiling of gene expression by RNA-seq in green curds led to the identification of large numbers of genes associated with chloroplast development, and suggested the role of regulatory genes in the high hierarchy of light signaling pathways in mediating the ectopic chloroplast development in the green curd cauliflower mutant.

Transcriptome analysis of ectopic chloroplast development in green curd cauliflower (Brassica oleracea L. var. botrytis)

PubMed Central

2011-01-01

Background Chloroplasts are the green plastids where photosynthesis takes place. The biogenesis of chloroplasts requires the coordinate expression of both nuclear and chloroplast genes and is regulated by developmental and environmental signals. Despite extensive studies of this process, the genetic basis and the regulatory control of chloroplast biogenesis and development remain to be elucidated. Results Green cauliflower mutant causes ectopic development of chloroplasts in the curd tissue of the plant, turning the otherwise white curd green. To investigate the transcriptional control of chloroplast development, we compared gene expression between green and white curds using the RNA-seq approach. Deep sequencing produced over 15 million reads with lengths of 86 base pairs from each cDNA library. A total of 7,155 genes were found to exhibit at least 3-fold changes in expression between green and white curds. These included light-regulated genes, genes encoding chloroplast constituents, and genes involved in chlorophyll biosynthesis. Moreover, we discovered that the cauliflower ELONGATED HYPOCOTYL5 (BoHY5) was expressed higher in green curds than white curds and that 2616 HY5-targeted genes, including 1600 up-regulated genes and 1016 down-regulated genes, were differently expressed in green in comparison to white curd tissue. All these 1600 up-regulated genes were HY5-targeted genes in the light. Conclusions The genome-wide profiling of gene expression by RNA-seq in green curds led to the identification of large numbers of genes associated with chloroplast development, and suggested the role of regulatory genes in the high hierarchy of light signaling pathways in mediating the ectopic chloroplast development in the green curd cauliflower mutant. PMID:22112144

Targeting MYCN-Driven Transcription By BET-Bromodomain Inhibition.

PubMed

Henssen, Anton; Althoff, Kristina; Odersky, Andrea; Beckers, Anneleen; Koche, Richard; Speleman, Frank; Schäfers, Simon; Bell, Emma; Nortmeyer, Maike; Westermann, Frank; De Preter, Katleen; Florin, Alexandra; Heukamp, Lukas; Spruessel, Annika; Astrahanseff, Kathy; Lindner, Sven; Sadowski, Natalie; Schramm, Alexander; Astorgues-Xerri, Lucile; Riveiro, Maria E; Eggert, Angelika; Cvitkovic, Esteban; Schulte, Johannes H

2016-05-15

Targeting BET proteins was previously shown to have specific antitumoral efficacy against MYCN-amplified neuroblastoma. We here assess the therapeutic efficacy of the BET inhibitor, OTX015, in preclinical neuroblastoma models and extend the knowledge on the role of BRD4 in MYCN-driven neuroblastoma. The efficacy of OTX015 was assessed in in vitro and in vivo models of human and murine MYCN-driven neuroblastoma. To study the effects of BET inhibition in the context of high MYCN levels, MYCN was ectopically expressed in human and murine cells. The effect of OTX015 on BRD4-regulated transcriptional pause release was analyzed using BRD4 and H3K27Ac chromatin immunoprecipitation coupled with DNA sequencing (ChIP-Seq) and gene expression analysis in neuroblastoma cells treated with OTX015 compared with vehicle control. OTX015 showed therapeutic efficacy against preclinical MYCN-driven neuroblastoma models. Similar to previously described BET inhibitors, concurrent MYCN repression was observed in OTX015-treated samples. Ectopic MYCN expression, however, did not abrogate effects of OTX015, indicating that MYCN repression is not the only target of BET proteins in neuroblastoma. When MYCN was ectopically expressed, BET inhibition still disrupted MYCN target gene transcription without affecting MYCN expression. We found that BRD4 binds to super-enhancers and MYCN target genes, and that OTX015 specifically disrupts BRD4 binding and transcription of these genes. We show that OTX015 is effective against mouse and human MYCN-driven tumor models and that BRD4 not only targets MYCN, but specifically occupies MYCN target gene enhancers as well as other genes associated with super-enhancers. Clin Cancer Res; 22(10); 2470-81. ©2015 AACR. ©2015 American Association for Cancer Research.

Inflammatory and age-related pathologies in mice with ectopic expression of human PARP-1.

PubMed

Mangerich, Aswin; Herbach, Nadja; Hanf, Benjamin; Fischbach, Arthur; Popp, Oliver; Moreno-Villanueva, María; Bruns, Oliver T; Bürkle, Alexander

2010-06-01

Poly(ADP-ribose) polymerase-1 (PARP-1) is a sensor for DNA strand breaks and some unusual DNA structures and catalyzes poly(ADP-ribosyl)ation of nuclear proteins with NAD(+) serving as substrate. PARP-1 is involved in the regulation of genomic integrity, transcription, inflammation, and cell death. Due to its versatile role, PARP-1 is discussed both as a longevity factor and as an aging-promoting factor. Recently, we generated a mouse model with ectopic integration of full-length hPARP-1 [Mangerich, A., Scherthan, H., Diefenbach, J., Kloz, U., van der Hoeven, F., Beneke, S. and Bürkle, A., 2009. A caveat in mouse genetic engineering: ectopic gene targeting in ES cells by bidirectional extension of the homology arms of a gene replacement vector carrying human PARP-1. Transgenic Res. 18, 261-279]. Here, we show that hPARP-1 mice exhibit impaired survival rates accompanied by reduced hair growth and premature development of several inflammation and age-associated pathologies, such as adiposity, kyphosis, nephropathy, dermatitis, pneumonitis, cardiomyopathy, hepatitis, and anemia. Moreover, mutant male mice showed impaired glucose tolerance, yet without developing manifest diabetes. Overall tumor burden was comparable in wild-type and hPARP-1 mice, but tumor spectrum was shifted in mutant mice, showing lower incidence of sarcomas, but increased incidence of carcinomas. Furthermore, DNA repair was delayed in splenocytes of hPARP-1 mice, and gene expression of pro-inflammatory cytokines was dysregulated. Our results suggest that in hPARP-1 mice impaired DNA repair, accompanied by a continuous low-level increase in pro-inflammatory stimuli, causes development of chronic diseases leading to impaired survival. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

ADAP deficiency impairs megakaryocyte polarization with ectopic proplatelet release and causes microthrombocytopenia.

PubMed

Spindler, Markus; van Eeuwijk, Judith M M; Schurr, Yvonne; Nurden, Paquita; Nieswandt, Bernhard; Stegner, David; Reinhold, Annegret; Bender, Markus

2018-06-27

Bone marrow megakaryocytes (MKs) produce platelets by extending proplatelets into sinusoidal blood vessels. Defects in thrombopoiesis can lead to thrombocytopenia associated with increased bleeding tendency. Recently, the platelet disorder congenital autosomal recessive small-platelet thrombocytopenia (CARST) was described which is caused by mutations in the ADAP (Adhesion and degranulation promoting adaptor protein; synonym: FYB, SLAP130/120) gene, and characterized by microthrombocytopenia and bleeding symptoms. In this study we used constitutive ADAP-deficient mice (Adap -/- ) as a model to investigate mechanisms underlying the microthrombocytopenia in CARST. We show that Adap -/- mice display several characteristics of human CARST, with moderate thrombocytopenia and smaller-sized platelets. Adap -/- platelets had a shorter life span than control platelets, and macrophage depletion, but not splenectomy, increased platelet counts in mutant mice to control levels. Whole sternum 3D confocal imaging and intravital two-photon microscopy revealed altered morphology of ADAP-deficient MKs with signs of fragmentation and ectopic release of (pro)platelet-like particles into the bone marrow compartment. In addition, cultured bone marrow-derived MKs lacking ADAP showed reduced spreading on extracellular matrix proteins as well as activation of β1 integrins, impaired podosome formation, and displayed defective polarization of the demarcation membrane system in vitro. MK-/platelet-specific ADAP deficient mice (PF4-cre) also produced less and smaller-sized platelets and released platelets ectopically. These data demonstrate that the abnormal platelet production in the mutant mice is a MK-intrinsic defect. Taken together, these results point to a so far unidentified role of ADAP in the process of MK polarization and platelet biogenesis. Copyright © 2018 American Society of Hematology.

Small Heat Shock Proteins Can Release Light Dependence of Tobacco Seed during Germination1[OPEN

PubMed Central

Koo, Hyun Jo; Park, Soo Min; Kim, Keun Pill; Suh, Mi Chung; Lee, Mi Ok; Lee, Seong-Kon; Xinli, Xia

2015-01-01

Small heat shock proteins (sHSPs) function as ATP-independent molecular chaperones, and although the production and function of sHSPs have often been described under heat stress, the expression and function of sHSPs in fundamental developmental processes, such as pollen and seed development, have also been confirmed. Seed germination involves the breaking of dormancy and the resumption of embryo growth that accompany global changes in transcription, translation, and metabolism. In many plants, germination is triggered simply by imbibition of water; however, different seeds require different conditions in addition to water. For small-seeded plants, like Arabidopsis (Arabidopsis thaliana), lettuce (Lactuca sativa), tomato (Solanum lycopersicum), and tobacco (Nicotiana tabacum), light is an important regulator of seed germination. The facts that sHSPs accumulate during seed development, sHSPs interact with various client proteins, and seed germination accompanies synthesis and/or activation of diverse proteins led us to investigate the role of sHSPs in seed germination, especially in the context of light dependence. In this study, we have built transgenic tobacco plants that ectopically express sHSP, and the effect was germination of the seeds in the dark. Administering heat shock to the seeds also resulted in the alleviation of light dependence during seed germination. Subcellular localization of ectopically expressed sHSP was mainly observed in the cytoplasm, whereas heat shock-induced sHSPs were transported to the nucleus. We hypothesize that ectopically expressed sHSPs in the cytoplasm led the status of cytoplasmic proteins involved in seed germination to function during germination without additional stimulus and that heat shock can be another signal that induces seed germination. PMID:25604531

Ectopic bone formation and chondrodysplasia in transgenic mice carrying the rat C3(1)/T{sub AG} fusion gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Green, J.E.; Maroulakou, I.G.; Anver, M.

Transgenic mice expressing the SV40 large T-antigen (T{sup AG}) under the regultory control of the hormone-responsive rat C3(1) prostatein promoter develop unusual bone and cartilage lesions, as well as ectopic bone and cartilage formation. Two lines of transgenic animals have been propagated in which the expression of the transgene in chondrocytes results in a mild to moderate generalized disorganization of cartilage growth which appears to affect multiple tissues, including the trachea, ear pinna and articular cartilage. The epiphyseal plates are also affected with normal architecture of the zones of proliferation and maturation, but marked elongation of the zone of hypertrophy.more » Immunocytochemistry demonstrates that expression of T{sup AG} is limited to the zone of hypertropny in the epiphyseal plates, suggesting that the chondrocytes become hormone-responsive at this particular stage of differentiation. Normal mineralization and trabecular formation in long bone appears to occur. Ectopic bone and cartilage formation occurs in the foot pads of the fore- and hind- feet over the course of several months. This is preceded by proliferation of sweat gland epithelial cells followed by the appearance of nodules of cartilage and bone. The nodules are closely associated with proliferating epithelium but are not contiguous with bony structures normally found in the feet. The roles of BMP`s, growth factors, oncogenes and hormones in the development of these lesions will be presented. These transgenic animals may provide new insights into hormone-responsiveness of chondrocytes, as well as factors involved in the processes of bone and cartilage differentiation and growth. These transgenic animals may serve as a useful model for human heterotopic bone formation.« less

IL-27 triggers IL-10 production in Th17 cells via a c-Maf/RORγt/Blimp-1 signal to promote the progression of endometriosis

PubMed Central

Chang, Kai-Kai; Liu, Li-Bing; Jin, Li-Ping; Zhang, Bing; Mei, Jie; Li, Hui; Wei, Chun-Yan; Zhou, Wen-Jie; Zhu, Xiao-Yong; Shao, Jun; Li, Da-Jin; Li, Ming-Qing

2017-01-01

Endometriosis is an estrogen-dependent inflammatory disease. The anti-inflammatory cytokine IL-10 is also increased in endometriosis. IL-10 production by Th17 cells is critical for limiting autoimmunity and inflammatory responses. However, the mechanism of inducing IL-10-producing Th17 cells is still largely unknown. The present study investigated the differentiation mechanism and role of IL-10-producing Th17 cells in endometriosis. Here, we report that IL-10+Th17 cells are significantly increased in the peritoneal fluid of women with endometriosis, along with an elevation of IL-27, IL-6 and TGF-β. Compared with peripheral CD4+ T cells, endometrial CD4+ T cells highly expressed IL-27 receptors, especially the ectopic endometrium. Under external (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and local (estrogen, IL-6 and TGF-β) environmental regulation, IL-27 from macrophages and endometrial stromal cells (ESCs) induces IL-10 production in Th17 cells in vitro and in vivo. This process may be mediated through the interaction between c-musculoaponeurotic fibrosarconna (c-Maf) and retinoic acid-related orphan receptor gamma t (RORγt), and associated with the upregulation of downstream B lymphocyte-induced maturation protein-1 (Blimp-1). IL-10+Th17 cells, in turn, stimulate the proliferation and implantation of ectopic lesions and accelerate the progression of endometriosis. These results suggest that IL-27 is a pivotal regulator in endometriotic immune tolerance by triggering Th17 cells to produce IL-10 and promoting the rapid growth and implantation of ectopic lesions. This finding provides a scientific basis for potential therapeutic strategies aimed at preventing the development of endometriosis, especially for patients with high levels of IL-10+Th17 cells. PMID:28300844

Ectopic expression of UGT84A2 delayed flowering by indole-3-butyric acid-mediated transcriptional repression of ARF6 and ARF8 genes in Arabidopsis.

PubMed

Zhang, Gui-Zhi; Jin, Shang-Hui; Li, Pan; Jiang, Xiao-Yi; Li, Yan-Jie; Hou, Bing-Kai

2017-12-01

Ectopic expression of auxin glycosyltransferase UGT84A2 in Arabidopsis can delay flowering through increased indole-3-butyric acid and suppressed transcription of ARF6, ARF8 and flowering-related genes FT, SOC1, AP1 and LFY. Auxins are critical regulators for plant growth and developmental processes. Auxin homeostasis is thus an important issue for plant biology. Here, we identified an indole-3-butyric acid (IBA)-specific glycosyltransferase, UGT84A2, and characterized its role in Arabidopsis flowering development. UGT84A2 could catalyze the glycosylation of IBA, but not indole-3-acetic acid (IAA). UGT84A2 transcription expression was clearly induced by IBA. When ectopically expressing in Arabidopsis, UGT84A2 caused obvious delay in flowering. Correspondingly, the increase of IBA level, the down-regulation of AUXIN RESPONSE FACTOR 6 (ARF6) and ARF8, and the down-regulation of flowering-related genes such as FLOWERING LOCUS T (FT), SUPPRESSOR OF OVEREXPRESSION OF CO1(SOC1), APETALA1 (AP1), and LEAFY(LFY) were observed in transgenic plants. When exogenously applying IBA to wild-type plants, the late flowering phenotype, the down-regulation of ARF6, ARF8 and flowering-related genes recurred. We examined the arf6arf8 double mutants and found that the expression of flowering-related genes was also substantially decreased in these mutants. Together, our results suggest that glycosyltransferase UGT84A2 may be involved in flowering regulation through indole-3-butyric acid-mediated transcriptional repression of ARF6, ARF8 and downstream flowering pathway genes.

Genetic Analysis of Hedgehog Signaling in Ventral Body Wall Development and the Onset of Omphalocele Formation

PubMed Central

Matsumaru, Daisuke; Haraguchi, Ryuma; Miyagawa, Shinichi; Motoyama, Jun; Nakagata, Naomi; Meijlink, Frits; Yamada, Gen

2011-01-01

Background An omphalocele is one of the major ventral body wall malformations and is characterized by abnormally herniated viscera from the body trunk. It has been frequently found to be associated with other structural malformations, such as genitourinary malformations and digit abnormalities. In spite of its clinical importance, the etiology of omphalocele formation is still controversial. Hedgehog (Hh) signaling is one of the essential growth factor signaling pathways involved in the formation of the limbs and urogenital system. However, the relationship between Hh signaling and ventral body wall formation remains unclear. Methodology/Principal Findings To gain insight into the roles of Hh signaling in ventral body wall formation and its malformation, we analyzed phenotypes of mouse mutants of Sonic hedgehog (Shh), GLI-Kruppel family member 3 (Gli3) and Aristaless-like homeobox 4 (Alx4). Introduction of additional Alx4Lst mutations into the Gli3Xt/Xt background resulted in various degrees of severe omphalocele and pubic diastasis. In addition, loss of a single Shh allele restored the omphalocele and pubic symphysis of Gli3Xt/+; Alx4Lst/Lst embryos. We also observed ectopic Hh activity in the ventral body wall region of Gli3Xt/Xt embryos. Moreover, tamoxifen-inducible gain-of-function experiments to induce ectopic Hh signaling revealed Hh signal dose-dependent formation of omphaloceles. Conclusions/Significance We suggest that one of the possible causes of omphalocele and pubic diastasis is ectopically-induced Hh signaling. To our knowledge, this would be the first demonstration of the involvement of Hh signaling in ventral body wall malformation and the genetic rescue of omphalocele phenotypes. PMID:21283718

Requirements for FGF3 and FGF10 during inner ear formation.

PubMed

Alvarez, Yolanda; Alonso, Maria Teresa; Vendrell, Victor; Zelarayan, Laura Cecilia; Chamero, Pablo; Theil, Thomas; Bösl, Michael R; Kato, Shigeaki; Maconochie, Mark; Riethmacher, Dieter; Schimmang, Thomas

2003-12-01

Members of the fibroblast growth factor (FGF) gene family control formation of the body plan and organogenesis in vertebrates. FGF3 is expressed in the developing hindbrain and has been shown to be involved in inner ear development of different vertebrate species, including zebrafish, Xenopus, chick and mouse. In the mouse, insertion of a neomycin resistance gene into the Fgf3 gene via homologous recombination results in severe developmental defects during differentiation of the otic vesicle. We have addressed the precise roles of FGF3 and other FGF family members during formation of the murine inner ear using both loss- and gain-of-function experiments. We generated a new mutant allele lacking the entire FGF3-coding region but surprisingly found no evidence for severe defects either during inner ear development or in the mature sensory organ, suggesting the functional involvement of other FGF family members during its formation. Ectopic expression of FGF10 in the developing hindbrain of transgenic mice leads to the formation of ectopic vesicles, expressing some otic marker genes and thus indicating a role for FGF10 during otic vesicle formation. Expression analysis of FGF10 during mouse embryogenesis reveals a highly dynamic pattern of expression in the developing hindbrain, partially overlapping with FGF3 expression and coinciding with formation of the inner ear. However, FGF10 mutant mice have been reported to display only mild defects during inner ear differentiation. We thus created double mutant mice for FGF3 and FGF10, which form severely reduced otic vesicles, suggesting redundant roles of these FGFs, acting in combination as neural signals for otic vesicle formation.

The Role of Serum Beta hCG in Early Diagnosis and Management Strategy of Ectopic Pregnancy.

PubMed

Surampudi, Kameswari; Gundabattula, Sirisha Rao

2016-07-01

The presentation of Ectopic Pregnancy (EP) can be highly variable and serum Beta hCG estimation plays an important role in early diagnosis. Aim of the study was to determine the trends of hCG levels in EP and to explore the role of hCG in decisions related to management and follow-up of EPs. A retrospective study of women who had EPs from January 2006 to December 2012 at an advanced tertiary care centre in southern India was carried out. These women had undergone treatment based on the hospital protocol. The study identified 337 women with EP. Thirty one surgically confirmed cases were diagnosed below the discriminatory zone of 1500 mIU/ml. Among women who had Beta hCG estimations 48 hours apart, plateauing was observed in 22.5% while decrease >15% was noted in 26.8%. Almost half (47.9%) of the cases had an increase >15% and a few (2.8%) demonstrated an initial fall followed by a rise in titres. In 23.9% of these women, there was a rise >53% similar to intrauterine pregnancy. The average pre-treatment Beta hCG was 429.8, 3866.2 and 12961.5 mIU/ml for those who received expectant, medical and direct surgical treatment respectively. 43 women with relative contraindications received medical management and 39 were lost to follow-up after medical and expectant management. Excluding them, the success rate of these two modalities was 76.6% and 85.0% respectively. No single level of Beta hCG is diagnostic of EP and serial levels can demonstrate atypical trends in some cases. Hence, interpretation of these results should be done in conjunction with clinical and sonographic findings to arrive at a correct diagnosis.

The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells.

PubMed

Collombat, Patrick; Xu, Xiaobo; Ravassard, Philippe; Sosa-Pineda, Beatriz; Dussaud, Sébastien; Billestrup, Nils; Madsen, Ole D; Serup, Palle; Heimberg, Harry; Mansouri, Ahmed

2009-08-07

We have previously reported that the loss of Arx and/or Pax4 gene activity leads to a shift in the fate of the different endocrine cell subtypes in the mouse pancreas, without affecting the total endocrine cell numbers. Here, we conditionally and ectopically express Pax4 using different cell-specific promoters and demonstrate that Pax4 forces endocrine precursor cells, as well as mature alpha cells, to adopt a beta cell destiny. This results in a glucagon deficiency that provokes a compensatory and continuous glucagon+ cell neogenesis requiring the re-expression of the proendocrine gene Ngn3. However, the newly formed alpha cells fail to correct the hypoglucagonemia since they subsequently acquire a beta cell phenotype upon Pax4 ectopic expression. Notably, this cycle of neogenesis and redifferentiation caused by ectopic expression of Pax4 in alpha cells is capable of restoring a functional beta cell mass and curing diabetes in animals that have been chemically depleted of beta cells.

Neonatal Bartter syndrome and unilateral ectopic renal cyst as new renal causes of hydrops fetalis: two case reports and review of the literature.

PubMed

Çetinkaya, Merih; Durmaz, Oguzhan; Büyükkale, Gökhan; Ozbek, Sibel; Acar, Deniz; Kilicaslan, Isin; Kavuncuoglu, Sultan

2013-07-01

Non-immune hydrops fetalis (NIHF) is a challenging entity as it represents the end stage of several different disorders. Renal and genitourinary causes of NIHF are rare and include congenital renal malformations, tumors and ureter-urethra disorders. Herein, two NIHF cases with different renal causes were presented. The first case that had antenatal NIHF was diagnosed neonatal Bartter syndrome. The second case of NIHF with antenatal large cyst in the surrenal gland area required surgery and ectopic renal cyst was diagnosed. To our best of knowledge, these are the first reports of NIHF associated with neonatal Bartter syndrome and ectopic renal cyst in neonates. Although it may be coincidental, these cases suggest that both neonatal Bartter syndrome and unilateral ectopic renal cyst may cause NIHF development in neonates by several different mechanisms. Therefore, these two rare entities should be suspected in cases of NIHF with similar findings.

Previous tubal ectopic pregnancy raises the incidence of repeated ectopic pregnancies in in vitro fertilization-embryo transfer patients.

PubMed

Weigert, Monika; Gruber, Diego; Pernicka, Elisabeth; Bauer, Peter; Feichtinger, Wilfried

2009-01-01

To investigate the incidence of Tubal Ectopic Pregnancies (TEP) in IVF-ET patients with respect to the status of the fallopian tubes after a previous TEP. This retrospective study compares patients undergoing 481 IVF-ET cycles after conservatively or surgically treated TEP(s) with a Control Group (idiopathic or male factor for IVF-ET indication). Medical reports of surgery and/or hysterosalpingograms prior to the IVF cycles classified the status of the fallopian tubes. 12 TEPs (8.95%/Pregnancies (PR)) occurred in the Study Group. In the Control Group one TEP (0.75%/PR; p < 0.001) was found. Smoking increased the probability of TEPs (p = 0.0028) and of pathological pregnancies (abortion, biochemical and ectopic PR; (p = 0.0411)). For statistic evolution logistic regression (PROC GENMOD) and a repeated measure model were applied. Women with a previous TEP should be informed about the significantly increased risk for a further TEP in IVF-ET treatment, especially if they are smoking.

High-dose bone morphogenetic protein-induced ectopic abdomen bone growth.

PubMed

Deutsch, Harel

2010-02-01

Infuse [bone morphogenetic protein (BMP)] is increasingly used in spinal fusion surgery. The authors report a rare complication of BMP use. This is a case report. A 55-year-old male underwent a thoracic T8 to the pelvis fusion for degenerative lumbar disc disease and pseudarthrosis at another institution. The procedure involved an anterior and posterior approach with the use of multiple units of BMP. The patient presented to our institution with complaints of weight loss, pain, tenderness, and increasing solid growth in the left lower quadrant several months after his surgery. A computed tomography revealed ectopic bone growth in the retroperitoneal area and pelvis contiguous to the anterior lumbar exposure. The anterior wound was re-explored, and a large sheet of ectopic bone was removed from the retroperitoneal space. We report a rare case of extraspinal ectopic bone growth because of the use of multiple packages of BMP. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Neuroendocrine carcinoma of the ampulla of Vater causing ectopic adrenocorticotropic hormone-dependent Cushing's syndrome.

PubMed

Kato, Akihisa; Hayashi, Kazuki; Naitoh, Itaru; Seno, Kyoji; Okada, Yukiko; Ban, Tesshin; Kondo, Hiromu; Nishi, Yuji; Umemura, Shuichiro; Hori, Yasuki; Natsume, Makoto; Joh, Takashi

2016-07-01

Ectopic adrenocorticotropic hormone (ACTH) is rarely secreted by neuroendocrine tumors. Although neuroendocrine tumors may occur at any site in the gastrointestinal system, they very rarely occur in the ampulla of Vater and have a poor prognosis. The present study described the first Cushing's syndrome as a result of ectopic ACTH arising from the ampulla of Vater neuroendocrine carcinoma. A 69-year-old female was admitted with clinical features of Cushing's syndrome, confirmed biochemically by hypokalemia, and elevated levels of ACTH and cortisol. In further investigations, a tumor of the ampulla of Vater and liver metastases were detected. Pathological analysis of the biopsy confirmed a neuroendocrine carcinoma, which was immunohistochemically positive for chromogranin A, synaptophysin, cluster of differentiation 56 and ACTH. Therefore, the present study diagnosed a functional and metastatic neuroendocrine carcinoma of the ampulla of Vater with ectopic ACTH production causing Cushing's syndrome. The patient succumbed to mortality 4 months later, despite administration of combined chemotherapy with irinotecan and cisplatin.

Status epilepticus increases mature granule cells in the molecular layer of the dentate gyrus in rats★

PubMed Central

Liang, Zhaoliang; Gao, Fei; Wang, Fajun; Wang, Xiaochen; Song, Xinyu; Liu, Kejing; Zhan, Ren-Zhi

2013-01-01

Enhanced neurogenesis in the dentate gyrus of the hippocampus following seizure activity, especially status epilepticus, is associated with ectopic residence and aberrant integration of newborn granule cells. Hilar ectopic granule cells may be detrimental to the stability of dentate circuitry by means of their electrophysiological properties and synaptic connectivity. We hypothesized that status epilepticus also increases ectopic granule cells in the molecular layer. Status epilepticus was induced in male Sprague-Dawley rats by intraperitoneal injection of pilocarpine. Immunostaining showed that many doublecortin-positive cells were present in the molecular layer and the hilus 7 days after the induction of status epilepticus. At least 10 weeks after status epilepticus, the estimated number of cells positive for both prospero homeobox protein 1 and neuron-specific nuclear protein in the hilus was significantly increased. A similar trend was also found in the molecular layer. These findings indicate that status epilepticus can increase the numbers of mature and ectopic newborn granule cells in the molecular layer. PMID:25206705

Prediction of Tubal Ectopic Pregnancy Using Offline Analysis of 3-Dimensional Transvaginal Ultrasonographic Data Sets: An Interobserver and Diagnostic Accuracy Study.

PubMed

Infante, Fernando; Espada Vaquero, Mercedes; Bignardi, Tommaso; Lu, Chuan; Testa, Antonia C; Fauchon, David; Epstein, Elisabeth; Leone, Francesco P G; Van den Bosch, Thierry; Martins, Wellington P; Condous, George

2018-06-01

To assess interobserver reproducibility in detecting tubal ectopic pregnancies by reading data sets from 3-dimensional (3D) transvaginal ultrasonography (TVUS) and comparing it with real-time 2-dimensional (2D) TVUS. Images were initially classified as showing pregnancies of unknown location or tubal ectopic pregnancies on real time 2D TVUS by an experienced sonologist, who acquired 5 3D volumes. Data sets were analyzed offline by 5 observers who had to classify each case as ectopic pregnancy or pregnancy of unknown location. The interobserver reproducibility was evaluated by the Fleiss κ statistic. The performance of each observer in predicting ectopic pregnancies was compared to that of the experienced sonologist. Women were followed until they were reclassified as follows: (1) failed pregnancy of unknown location; (2) intrauterine pregnancy; (3) ectopic pregnancy; or (4) persistent pregnancy of unknown location. Sixty-one women were included. The agreement between reading offline 3D data sets and the first real-time 2D TVUS was very good (80%-82%; κ = 0.89). The overall interobserver agreement among observers reading offline 3D data sets was moderate (κ = 0.52). The diagnostic performance of experienced observers reading offline 3D data sets had accuracy of 78.3% to 85.0%, sensitivity of 66.7% to 81.3%, specificity of 79.5% to 88.4%, positive predictive value of 57.1% to 72.2%, and negative predictive value of 87.5% to 91.3%, compared to the experienced sonologist's real-time 2D TVUS: accuracy of 94.5%, sensitivity of 94.4%, specificity of 94.5%, positive predictive value of 85.0%, and negative predictive value of 98.1%. The diagnostic accuracy of 3D TVUS by reading offline data sets for predicting ectopic pregnancies is dependent on experience. Reading only static 3D data sets without clinical information does not match the diagnostic performance of real time 2D TVUS combined with clinical information obtained during the scan. © 2017 by the American Institute of Ultrasound in Medicine.

Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses.

PubMed

Du, William W; Yang, Weining; Chen, Yu; Wu, Zhong-Kai; Foster, Francis Stuart; Yang, Zhenguo; Li, Xiangmin; Yang, Burton B

2017-05-07

Circular RNAs are a subclass of non-coding RNAs detected within mammalian cells. This study was designed to test the roles of a circular RNA circ-Foxo3 in senescence using in vitro and in vivo approaches. Using the approaches of molecular and cellular biology, we show that a circular RNA generated from a member of the forkhead family of transcription factors, Foxo3, namely circ-Foxo3, was highly expressed in heart samples of aged patients and mice, which was correlated with markers of cellular senescence. Doxorubicin-induced cardiomyopathy was aggravated by ectopic expression of circ-Foxo3 but was relieved by silencing endogenous circ-Foxo3. We also found that silencing circ-Foxo3 inhibited senescence of mouse embryonic fibroblasts and that ectopic expression of circ-Foxo3 induced senescence. We found that circ-Foxo3 was mainly distributed in the cytoplasm, where it interacted with the anti-senescent protein ID-1 and the transcription factor E2F1, as well as the anti-stress proteins FAK and HIF1α. We conclude that ID-1, E2F1, FAK, and HIF1α interact with circ-Foxo3 and are retained in the cytoplasm and could no longer exert their anti-senescent and anti-stress roles, resulting in increased cellular senescence. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Whole exome sequencing in an Italian family with isolated maxillary canine agenesis and canine eruption anomalies.

PubMed

Barbato, Ersilia; Traversa, Alice; Guarnieri, Rosanna; Giovannetti, Agnese; Genovesi, Maria Luce; Magliozzi, Maria Rosa; Paolacci, Stefano; Ciolfi, Andrea; Pizzi, Simone; Di Giorgio, Roberto; Tartaglia, Marco; Pizzuti, Antonio; Caputo, Viviana

2018-07-01

The aim of this study was the clinical and molecular characterization of a family segregating a trait consisting of a phenotype specifically involving the maxillary canines, including agenesis, impaction and ectopic eruption, characterized by incomplete penetrance and variable expressivity. Clinical standardized assessment of 14 family members and a whole-exome sequencing (WES) of three affected subjects were performed. WES data analyses (sequence alignment, variant calling, annotation and prioritization) were carried out using an in-house implemented pipeline. Variant filtering retained coding and splice-site high quality private and rare variants. Variant prioritization was performed taking into account both the disruptive impact and the biological relevance of individual variants and genes. Sanger sequencing was performed to validate the variants of interest and to carry out segregation analysis. Prioritization of variants "by function" allowed the identification of multiple variants contributing to the trait, including two concomitant heterozygous variants in EDARADD (c.308C>T, p.Ser103Phe) and COL5A1 (c.1588G>A, p.Gly530Ser), specifically associated with a more severe phenotype (i.e. canine agenesis). Differently, heterozygous variants in genes encoding proteins with a role in the WNT pathway were shared by subjects showing a phenotype of impacted/ectopic erupted canines. This study characterized the genetic contribution underlying a complex trait consisting of isolated canine anomalies in a medium-sized family, highlighting the role of WNT and EDA cell signaling pathways in tooth development. Copyright © 2018 Elsevier Ltd. All rights reserved.

BIG LEAF is a regulator of organ size and adventitious root formation in poplar

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yordanov, Yordan S.; Ma, Cathleen; Yordanova, Elena

Here we report the discovery through activation tagging and subsequent characterization of the BIG LEAF (BL) gene from poplar. In poplar, BL regulates leaf size via positively affecting cell proliferation. Up and downregulation of the gene led to increased and decreased leaf size, respectively, and these phenotypes corresponded to increased and decreased cell numbers. BL function encompasses the early stages of leaf development as native BL expression was specific to the shoot apical meristem and leaf primordia and was absent from the later stages of leaf development and other organs. Consistently, BL downregulation reduced leaf size at the earliest stagesmore » of leaf development. Ectopic expression in mature leaves resulted in continued growth most probably via sustained cell proliferation and thus the increased leaf size. In contrast to the positive effect on leaf growth, ectopic BL expression in stems interfered with and significantly reduced stem thickening, suggesting that BL is a highly specific activator of growth. Additionally, stem cuttings from BL overexpressing plants developed roots, whereas the wild type was difficult to root, demonstrating that BL is a positive regulator of adventitious rooting. Large transcriptomic changes in plants that overexpressed BL indicated that BL may have a broad integrative role, encompassing many genes linked to organ growth. Here, we conclude that BL plays a fundamental role in control of leaf size and thus may be a useful tool for modifying plant biomass productivity and adventitious rooting.« less

BIG LEAF is a regulator of organ size and adventitious root formation in poplar

PubMed Central

Yordanov, Yordan S.; Ma, Cathleen; Yordanova, Elena; Meilan, Richard; Strauss, Steven H.; Busov, Victor B.

2017-01-01

Here we report the discovery through activation tagging and subsequent characterization of the BIG LEAF (BL) gene from poplar. In poplar, BL regulates leaf size via positively affecting cell proliferation. Up and downregulation of the gene led to increased and decreased leaf size, respectively, and these phenotypes corresponded to increased and decreased cell numbers. BL function encompasses the early stages of leaf development as native BL expression was specific to the shoot apical meristem and leaf primordia and was absent from the later stages of leaf development and other organs. Consistently, BL downregulation reduced leaf size at the earliest stages of leaf development. Ectopic expression in mature leaves resulted in continued growth most probably via sustained cell proliferation and thus the increased leaf size. In contrast to the positive effect on leaf growth, ectopic BL expression in stems interfered with and significantly reduced stem thickening, suggesting that BL is a highly specific activator of growth. In addition, stem cuttings from BL overexpressing plants developed roots, whereas the wild type was difficult to root, demonstrating that BL is a positive regulator of adventitious rooting. Large transcriptomic changes in plants that overexpressed BL indicated that BL may have a broad integrative role, encompassing many genes linked to organ growth. We conclude that BL plays a fundamental role in control of leaf size and thus may be a useful tool for modifying plant biomass productivity and adventitious rooting. PMID:28686626

SOX2 regulates self-renewal and tumorigenicity of stem-like cells of head and neck squamous cell carcinoma.

PubMed

Lee, S H; Oh, S-Y; Do, S I; Lee, H J; Kang, H J; Rho, Y S; Bae, W J; Lim, Y C

2014-11-25

Head and neck squamous cell carcinomas (HNSCCs) display cellular heterogeneity and contain cancer stem cells (CSCs). Sex-determining region Y [SRY]-box (SOX)2 is an important regulator of embryonic stem cell fate and is aberrantly expressed in several types of human tumours. Nonetheless, the role of SOX2 in HNSCC remains unclear. We created cells ectopically expressing SOX2 from previously established HNSCC cells and examined the cell proliferation, self-renewal capacity, and chemoresistance of these cells compared with control cells. In addition, we knocked down SOX2 in primary spheres obtained from HNSCC tumour tissue and assessed the attenuation of stemness-associated traits in these cells in vitro and in vivo. Furthermore, we examined the clinical relevance of SOX2 expression in HNSCC patients. SOX2 is aberrantly expressed in primary tissue of HNSCC patients but not in healthy tissue. SOX2 expression correlated with tumour recurrence and poor prognosis of HNSCC patients. Ectopic expression of SOX2 induced cell proliferation via cyclin B1 expression and stemness-associated features, such as self-renewal and chemoresistance. In addition, a knockdown of SOX2 in HNSCC CSCs attenuated their self-renewal capacity, chemoresistance (through ABCG2 suppression), invasion capacity (via snail downregulation), and in vivo tumorigenicity. These results suggest that SOX2 may have important roles in the 'stemness' and progression of HNSCC. Targeting SOX2-positive tumour cells (CSCs) could be a new therapeutic strategy in HNSCCs.

BIG LEAF is a regulator of organ size and adventitious root formation in poplar

DOE PAGES

Yordanov, Yordan S.; Ma, Cathleen; Yordanova, Elena; ...

2017-07-07

Here we report the discovery through activation tagging and subsequent characterization of the BIG LEAF (BL) gene from poplar. In poplar, BL regulates leaf size via positively affecting cell proliferation. Up and downregulation of the gene led to increased and decreased leaf size, respectively, and these phenotypes corresponded to increased and decreased cell numbers. BL function encompasses the early stages of leaf development as native BL expression was specific to the shoot apical meristem and leaf primordia and was absent from the later stages of leaf development and other organs. Consistently, BL downregulation reduced leaf size at the earliest stagesmore » of leaf development. Ectopic expression in mature leaves resulted in continued growth most probably via sustained cell proliferation and thus the increased leaf size. In contrast to the positive effect on leaf growth, ectopic BL expression in stems interfered with and significantly reduced stem thickening, suggesting that BL is a highly specific activator of growth. Additionally, stem cuttings from BL overexpressing plants developed roots, whereas the wild type was difficult to root, demonstrating that BL is a positive regulator of adventitious rooting. Large transcriptomic changes in plants that overexpressed BL indicated that BL may have a broad integrative role, encompassing many genes linked to organ growth. Here, we conclude that BL plays a fundamental role in control of leaf size and thus may be a useful tool for modifying plant biomass productivity and adventitious rooting.« less

Ectopic Overexpression of SsCBF1, a CRT/DRE-Binding Factor from the Nightshade Plant Solanum lycopersicoides, Confers Freezing and Salt Tolerance in Transgenic Arabidopsis

PubMed Central

Zhang, Lili; Li, Zhenjun; Li, Jingfu; Wang, Aoxue

2013-01-01

The C-repeat (CRT)/dehydration-responsive element (DRE) binding factor (CBF/DREB1) transcription factors play a key role in cold response. However, the detailed roles of many plant CBFs are far from fully understood. A CBF gene (SsCBF1) was isolated from the cold-hardy plant Solanum lycopersicoides. A subcellular localization study using GFP fusion protein indicated that SsCBF1 is localized in the nucleus. We delimited the SsCBF1 transcriptional activation domain to the C-terminal segment comprising amino acid residues 193–228 (SsCBF1193–228). The expression of SsCBF1 could be dramatically induced by cold, drought and high salinity. Transactivation assays in tobacco leaves revealed that SsCBF1 could specifically bind to the CRT cis-elements in vivo to activate the expression of downstream reporter genes. The ectopic overexpression of SsCBF1 conferred increased freezing and high-salinity tolerance and late flowering phenotype to transgenic Arabidopsis. RNA-sequencing data exhibited that a set of cold and salt stress responsive genes were up-regulated in transgenic Arabidopsis. Our results suggest that SsCBF1 behaves as a typical CBF to contribute to plant freezing tolerance. Increased resistance to high-salinity and late flowering phenotype derived from SsCBF1 OE lines lend more credence to the hypothesis that plant CBFs participate in diverse physiological and biochemical processes related to adverse conditions. PMID:23755095

BIG LEAF is a regulator of organ size and adventitious root formation in poplar.

PubMed

Yordanov, Yordan S; Ma, Cathleen; Yordanova, Elena; Meilan, Richard; Strauss, Steven H; Busov, Victor B

2017-01-01

Here we report the discovery through activation tagging and subsequent characterization of the BIG LEAF (BL) gene from poplar. In poplar, BL regulates leaf size via positively affecting cell proliferation. Up and downregulation of the gene led to increased and decreased leaf size, respectively, and these phenotypes corresponded to increased and decreased cell numbers. BL function encompasses the early stages of leaf development as native BL expression was specific to the shoot apical meristem and leaf primordia and was absent from the later stages of leaf development and other organs. Consistently, BL downregulation reduced leaf size at the earliest stages of leaf development. Ectopic expression in mature leaves resulted in continued growth most probably via sustained cell proliferation and thus the increased leaf size. In contrast to the positive effect on leaf growth, ectopic BL expression in stems interfered with and significantly reduced stem thickening, suggesting that BL is a highly specific activator of growth. In addition, stem cuttings from BL overexpressing plants developed roots, whereas the wild type was difficult to root, demonstrating that BL is a positive regulator of adventitious rooting. Large transcriptomic changes in plants that overexpressed BL indicated that BL may have a broad integrative role, encompassing many genes linked to organ growth. We conclude that BL plays a fundamental role in control of leaf size and thus may be a useful tool for modifying plant biomass productivity and adventitious rooting.

Improvement of metabolic disorders by an EP2 receptor agonist via restoration of the subcutaneous adipose tissue in pulmonary emphysema.

PubMed

Tsuji, Takao; Yamaguchi, Kazuhiro; Kikuchi, Ryota; Nakamura, Hiroyuki; Misaka, Ryoichi; Nagai, Atsushi; Aoshiba, Kazutetsu

2017-05-01

Chronic obstructive pulmonary disease (COPD) is often associated with co-morbidities. Metabolic disorders like hyperlipidemia and diabetes occur also in underweight COPD patients, although the mechanism is uncertain. Subcutaneous adipose tissue (SAT) plays an important role in energy homeostasis, since restricted capacity to increase fat cell number with increase in fat cell size occurring instead, is associated with lipotoxicity and metabolic disorders. The aim of this study is to show the protective role of SAT for the metabolic disorders in pulmonary emphysema of a murine model. We found ectopic fat accumulation and impaired glucose homeostasis with wasting of SAT in a murine model of elastase-induced pulmonary emphysema (EIE mice) reared on a high-fat diet. ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, improved angiogenesis and subsequently adipogenesis, and finally improved ectopic fat accumulation and glucose homeostasis with restoration of the capacity for storage of surplus energy in SAT. These results suggest that metabolic disorders like hyperlipidemia and diabetes occured in underweight COPD is partially due to the less capacity for storage of surplus energy in SAT, though the precise mechanism is uncertained. Our data pave the way for the development of therapeutic interventions for metabolic disorders in emphysema patients, e.g., use of pro-angiogenic agents targeting the capacity for storage of surplus energy in the subcutaneous adipose tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

Inactivation of Msx1 and Msx2 in neural crest reveals an unexpected role in suppressing heterotopic bone formation in the head

PubMed Central

Roybal, Paul G.; Wu, Nancy L.; Sun, Jingjing; Ting, Man-chun; Schaefer, Christopher; Maxson, Robert E.

2011-01-01

In an effort to understand the morphogenetic forces that shape the bones of the skull, we inactivated Msx1 and Msx2 conditionally in neural crest. We show that Wnt1-Cre inactivation of up to three Msx1/2 alleles results in a progressively larger defect in the neural crest-derived frontal bone. Unexpectedly, in embryos lacking all four Msx1/2 alleles, the large defect is filled in with mispatterned bone consisting of ectopic islands of bone between the reduced frontal bones, just anterior to the parietal bones. The bone is derived from neural crest, not mesoderm, and, from DiI cell marking experiments, originates in a normally non-osteogenic layer of cells through which the rudiment elongates apically. Associated with the heterotopic osteogeneis is an upregulation of Bmp signaling in this cell layer. Prevention of this upregulation by implantation of noggin-soaked beads in head explants also prevented heterotopic bone formation. These results suggest that Msx genes have a dual role in calvarial development: They are required for the differentiation and proliferation of osteogenic cells within rudiments, and they are also required to suppress an osteogenic program in a cell layer within which the rudiments grow. We suggest that the inactivation of this repressive activity may be one cause of Wormian bones, ectopic bones that are a feature of a variety of pathological conditions in which calvarial bone development is compromised. PMID:20398647

Abdominal aortic aneurysm with ectopic renal artery origins: a case report.

PubMed

Kotsis, T; Mylonas, S; Katsenis, K; Arapoglou, V; Dimakakos, P

2007-01-01

The coexistense of an abdominal aortic aneurysm with ectopic main renal vasculature complicates aortic surgery and mandates a focused imaging evaluation and a carefully planned operation to minimize renal ischemia. We present the case of a 75-year-old man with an abdominal aortic aneurysm and a right kidney with two ectopic main renal arteries, one originating from the aneurysmal distal aorta and the other from the right common iliac artery; the patient underwent a surgical repair and followed an uneventful course with no deterioration of renal function. The preoperative and intraoperative details are reported, along with a review of the literature.

Preoperative Localization of Mediastinal Parathyroid Adenoma with Intra-arterial Methylene Blue.

PubMed

Salman, Rida; Sebaaly, Mikhael G; Wehbe, Mohammad Rachad; Sfeir, Pierre; Khalife, Mohamad; Al-Kutoubi, Aghiad

2017-06-01

Ectopic parathyroid is found in 16% of patients with hyperparathyroidism. 2% of ectopic parathyroid adenomas are not accessible to standard cervical excision. In such cases, video-assisted thoracoscopic resection is the recommended definitive treatment. We present a case of mediastinal parathyroid adenoma localized preoperatively by injecting methylene blue within a branch of the internal mammary artery that is supplying the adenoma. Intra-arterial methylene blue injection facilitated visualization and resection of the adenoma. The preoperative intra-arterial infusion of methylene blue appears to be an effective and safe method for localization of ectopic mediastinal parathyroid adenomas and allows rapid identification during thoracoscopic resection.

Preoperative Localization of Mediastinal Parathyroid Adenoma with Intra-arterial Methylene Blue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salman, Rida; Sebaaly, Mikhael G.; Wehbe, Mohammad Rachad

Ectopic parathyroid is found in 16% of patients with hyperparathyroidism. 2% of ectopic parathyroid adenomas are not accessible to standard cervical excision. In such cases, video-assisted thoracoscopic resection is the recommended definitive treatment. We present a case of mediastinal parathyroid adenoma localized preoperatively by injecting methylene blue within a branch of the internal mammary artery that is supplying the adenoma. Intra-arterial methylene blue injection facilitated visualization and resection of the adenoma. The preoperative intra-arterial infusion of methylene blue appears to be an effective and safe method for localization of ectopic mediastinal parathyroid adenomas and allows rapid identification during thoracoscopic resection.

Expression of human olfactory receptor 10J5 in heart aorta, coronary artery, and endothelial cells and its functional role in angiogenesis.

PubMed

Kim, Sung-Hee; Yoon, Yeo Cho; Lee, Ae Sin; Kang, NaNa; Koo, JaeHyung; Rhyu, Mee-Ra; Park, Jae-Ho

2015-05-01

ORs are ectopically expressed in non-chemosensory tissues including muscle, kidney, and keratinocytes; however, their physiological roles are largely unknown. We found that human olfactory receptor 10J5 (OR10J5) is expressed in the human aorta, coronary artery, and umbilical vein endothelial cells (HUVEC). Lyral induces Ca(2+) and phosphorylation of AKT in HUVEC. A knockdown study showed the inhibition of the lyral-induced Ca(2+) and the phosphorylation AKT and implied that these processes are mediated by OR10J5. In addition, lyral enhanced migration of HUVEC, which were also inhibited by RNAi in a migration assay. In addition, matrigel plug assay showed that lyral enhanced angiogenesis in vivo. Together these data demonstrate the physiological role of OR10J5 in angiogenesis and represent roles of ORs in HUVEC cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Prevalence of Ectopic Breast Tissue and Tumor: A 20-Year Single Center Experience.

PubMed

Famá, Fausto; Cicciú, Marco; Sindoni, Alessandro; Scarfó, Paola; Pollicino, Andrea; Giacobbe, Giuseppa; Buccheri, Giancarlo; Taranto, Filippo; Palella, Jessica; Gioffré-Florio, Maria

2016-08-01

Ectopic breast tissue, which includes both supernumerary breast and aberrant breast tissue, is the most common congenital breast abnormality. Ectopic breast cancers are rare neoplasms that occur in 0.3% to 0.6% of all cases of breast cancer. We retrospectively report, using a large series of breast abnormalities diagnosed and treated, our clinical experience on the management of the ectopic breast cancer. In 2 decades, we observed 327 (2.7%) patients with ectopic breast tissue out of a total of 12,177 subjects undergoing a breast visit for lesions. All patients were classified into 8 classes, according to the classification of Kajava, and assessed by a physician examination, ultrasounds, and, when appropriate, further studies with fine needle aspiration cytology and mammography. All specimens were submitted to the anatomo-pathologist. The most frequent benign histological diagnosis was fibrocystic disease. A rare granulosa cell tumor was also found in the right anterior thoracic wall of 1 patient. Four malignancies were also diagnosed in 4 women: an infiltrating lobular cancer in 1 patient with a lesion classified as class I, and an infiltrating apocrine carcinoma, an infiltrating ductal cancer, and an infiltrating ductal cancer with tubular pattern, occurring in 3 patients with lesions classified as class IV. Only 1 recurrence was observed. We recommend an earlier surgical approach for patients with lesions from class I to IV. Copyright © 2016 Elsevier Inc. All rights reserved.

[Ectopic breast fibroadenoma. Case report].

PubMed

Senatore, G; Zanotti, S; Cambrini, P; Montroni, I; Pellegrini, A; Montanari, E; Santini, D; Taffurelli, M

2010-03-01

Among the rare anomalies of the breast development, polythelia is the most common, between 1% and 5% of women and men present supernumerary nipples. Polymastia, usually presenting as ectopic breast tissue without areola-nipple complex, is seen mostly along the milk line, extending from the axilla to the pubic region. Ectopic breast tissue is functionally analogous to mammary gland and it is subjected to the same alterations and diseases, whether benign or malignant, that affect normal breast tissue. We report the case of a 21 years-old female evaluated by the medical staff after founding a solid nodular mass by suspect axillary lymphadenopathy. Differential diagnosis with lymphoma is the major problem in these cases. The mass was removed and the intraoperative histological examination showed fibroadenoma in axillary supernumerary breast. Presence of ectopic breast tissue is a rare condition; development of benign mass or malignant degeneration is possible, but it is very unusual. In case of polymastia diagnosis is simple; in case of isolated nodule, without local inflammation or infection, there are greater difficulties. Ultrasonography is diagnostic in case of breast fibroadenoma, but it might be inadequate in ectopic localizations owing to the shortage of mammary tissue around the mass. Preoperative diagnosis is important to plan an adequate surgical treatment; lumpectomy is indicated in case of benign tissue; in case of malignancy, therapy is based on the standard treatment used for breast cancer (surgery, chemotherapy and radiation therapy).

The Tea4-PP1 landmark promotes local growth by dual Cdc42 GEF recruitment and GAP exclusion.

PubMed

Kokkoris, Kyriakos; Gallo Castro, Daniela; Martin, Sophie G

2014-05-01

Cell polarization relies on small GTPases, such as Cdc42, which can break symmetry through self-organizing principles, and landmarks that define the axis of polarity. In fission yeast, microtubules deliver the Tea1-Tea4 complex to mark cell poles for growth, but how this complex activates Cdc42 is unknown. Here, we show that ectopic targeting of Tea4 to cell sides promotes the local activation of Cdc42 and cell growth. This activity requires that Tea4 binds the type I phosphatase (PP1) catalytic subunit Dis2 or Sds21, and ectopic targeting of either catalytic subunit is similarly instructive for growth. The Cdc42 guanine-nucleotide-exchange factor Gef1 and the GTPase-activating protein Rga4 are required for Tea4-PP1-dependent ectopic growth. Gef1 is recruited to ectopic Tea4 and Dis2 locations to promote Cdc42 activation. By contrast, Rga4 is locally excluded by Tea4, and its forced colocalization with Tea4 blocks ectopic growth, indicating that Rga4 must be present, but at sites distinct from Tea4. Thus, a Tea4-PP1 landmark promotes local Cdc42 activation and growth both through Cdc42 GEF recruitment and by creating a local trough in a Cdc42 GAP.

Ectopic ACTH syndrome caused by pulmonary carcinoid tumourlets.

PubMed

Povedano, S T; Pastor, C V; Seoane, C P; Reina, L J; Moreno, M A; Ortega, R P; López-Rubio, F; López, P B

2001-06-01

The differential diagnosis of Cushing's syndrome is a major challenge to clinical endocrinologists, especially those infrequent cases referred to as occult ectopic ACTH syndromes. Although bronchial carcinoids are well known to be a cause of Cushing's syndrome due to ectopic ACTH secretion, very few cases of carcinoid tumourlets causing an ACTH ectopic syndrome have been reported, and their origin remains controversial. For some authors, tumourlets and typical carcinoids represent distinct pathological entities, whilst others hold that tumourlets are merely microscopic carcinoid tumours. We report a patient with an aggressive Cushing's syndrome that required bilateral adrenalectomy, diagnosed 22 years before a 3-cm lung nodule became apparent on routine chest X-ray. The biopsy after lung surgery revealed a typical peripheral bronchial carcinoid surrounded by tumourlets. Both tumourlets and carcinoid tumour showed strongly positive ACTH immunostaining. Recently, Arioglu et al. (1998) reported a case of Cushing's syndrome caused by pulmonary carcinoid tumourlets, concluding that this entity should be considered in the differential diagnosis of occult ectopic ACTH syndrome. Furthermore, we consider that the carcinoid tumourlets found in our patient, were the initial source of ACTH, leading to Cushing's syndrome with a rapid onset, and that a loss of cell proliferation control in one of such tumourlets many years later, could have resulted in the development of a typical carcinoid tumour, reinforcing the theory of a common origin of these lesions.

Treatment of ectopic eruption of maxillary permanent first molars.

PubMed

Taloumis, L J; Allinder, J R

1993-01-01

A review of treatment of the ectopic maxillary permanent first molar is presented; prevalence and possible etiologies of the condition are explained. A step-by-step procedure for correctly diagnosing and treating the problem is suggested. A case is described in which diagnosis and treatment followed the principles outlined.

In Vivo Multiparametric Ultrasound Imaging of Structural and Functional Tumor Modifications during Therapy.

PubMed

Dizeux, Alexandre; Payen, Thomas; Le Guillou-Buffello, Delphine; Comperat, Eva; Gennisson, Jean-Luc; Tanter, Mickael; Oelze, Michael; Bridal, S Lori

2017-09-01

Longitudinal imaging techniques are needed that can meaningfully probe the tumor microenvironment and its spatial heterogeneity. Contrast-enhanced ultrasound, shear wave elastography and quantitative ultrasound are ultrasound-based techniques that provide information on the vascular function and micro-/macroscopic tissue structure. Modifications of the tumor microenvironment induced by cytotoxic and anti-angiogenic molecules in ectopic murine Lewis lung carcinoma tumors were monitored. The most heterogenous structures were found in tumors treated with anti-angiogenic drug that simultaneously accumulated the highest levels of necrosis and fibrosis. The anti-angiogenic group presented the highest number of correlations between parameters related to vascular function and those related to the micro-/macrostructure of the tumor microenvironment. Results suggest how patterns of multiparametric ultrasound modifications can be related to provide a more insightful marker of changes occurring within tumors during therapy. Copyright © 2017. Published by Elsevier Inc.

Cleavage of cohesin rings coordinates the separation of centrioles and chromatids.

PubMed

Schöckel, Laura; Möckel, Martin; Mayer, Bernd; Boos, Dominik; Stemmann, Olaf

2011-07-10

Cohesin pairs sister chromatids by forming a tripartite Scc1-Smc1-Smc3 ring around them. In mitosis, cohesin is removed from chromosome arms by the phosphorylation-dependent prophase pathway. Centromeric cohesin is protected by shugoshin 1 and protein phosphatase 2A (Sgo1-PP2A) and opened only in anaphase by separase-dependent cleavage of Scc1 (refs 4-6). Following chromosome segregation, centrioles loosen their tight orthogonal arrangement, which licenses later centrosome duplication in S phase. Although a role of separase in centriole disengagement has been reported, the molecular details of this process remain enigmatic. Here, we identify cohesin as a centriole-engagement factor. Both premature sister-chromatid separation and centriole disengagement are induced by ectopic activation of separase or depletion of Sgo1. These unscheduled events are suppressed by expression of non-cleavable Scc1 or inhibition of the prophase pathway. When endogenous Scc1 is replaced by artificially cleavable Scc1, the corresponding site-specific protease triggers centriole disengagement. Separation of centrioles can alternatively be induced by ectopic cleavage of an engineered Smc3. Thus, the chromosome and centrosome cycles exhibit extensive parallels and are coordinated with each other by dual use of the cohesin ring complex.

Neural differentiation promoted by truncated trkC receptors in collaboration with p75(NTR).

PubMed

Hapner, S J; Boeshore, K L; Large, T H; Lefcort, F

1998-09-01

trkC receptors, which serve critical functions during the development of the nervous system, are alternatively spliced to yield isoforms containing the catalytic tyrosine kinase domain (TK+) and truncated isoforms which lack this domain (TK-). To test for potential differences in their roles during early stages of neural development, TK+ and TK- isoforms were ectopically expressed in cultures of neural crest, the stem cell population that gives rise to the vast majority of the peripheral nervous system. NT-3 activation of ectopically expressed trkC TK+ receptors promoted both proliferation of neural crest cells and neuronal differentiation. Strikingly, the trkC TK- isoform was significantly more effective at promoting neuronal differentiation, but had no effect on proliferation. Furthermore, the trkC TK- response was dependent on a conserved receptor cytoplasmic domain and required the participation of the p75(NTR) neurotrophin receptor. Antibody-mediated receptor dimerization of TK+ receptors, but not TK- receptors, was sufficient to stimulate differentiation. These data identify a phenotypic response to activation of the trkC TK- receptor and demonstrate a functional interaction with p75(NTR), indicating there may be multiple trkC receptor-mediated systems guiding neuronal differentiation. Copyright 1998 Academic Press.

Transmembrane voltage potential controls embryonic eye patterning in Xenopus laevis

PubMed Central

Pai, Vaibhav P.; Aw, Sherry; Shomrat, Tal; Lemire, Joan M.; Levin, Michael

2012-01-01

Uncovering the molecular mechanisms of eye development is crucial for understanding the embryonic morphogenesis of complex structures, as well as for the establishment of novel biomedical approaches to address birth defects and injuries of the visual system. Here, we characterize change in transmembrane voltage potential (Vmem) as a novel biophysical signal for eye induction in Xenopus laevis. During normal embryogenesis, a striking hyperpolarization demarcates a specific cluster of cells in the anterior neural field. Depolarizing the dorsal lineages in which these cells reside results in malformed eyes. Manipulating Vmem of non-eye cells induces well-formed ectopic eyes that are morphologically and histologically similar to endogenous eyes. Remarkably, such ectopic eyes can be induced far outside the anterior neural field. A Ca2+ channel-dependent pathway transduces the Vmem signal and regulates patterning of eye field transcription factors. These data reveal a new, instructive role for membrane voltage during embryogenesis and demonstrate that Vmem is a crucial upstream signal in eye development. Learning to control bioelectric initiators of organogenesis offers significant insight into birth defects that affect the eye and might have significant implications for regenerative approaches to ocular diseases. PMID:22159581

Regulation of Compound Leaf Development by PHANTASTICA in Medicago truncatula1[C][W][OPEN

PubMed Central

Ge, Liangfa; Peng, Jianling; Berbel, Ana; Madueño, Francisco; Chen, Rujin

2014-01-01

Plant leaves, simple or compound, initiate as peg-like structures from the peripheral zone of the shoot apical meristem, which requires class I KNOTTED-LIKE HOMEOBOXI (KNOXI) transcription factors to maintain its activity. The MYB domain protein encoded by the ASYMMETRIC LEAVES1/ROUGH SHEATH2/PHANTASTICA (ARP) gene, together with other factors, excludes KNOXI gene expression from incipient leaf primordia to initiate leaves and specify leaf adaxial identity. However, the regulatory relationship between ARP and KNOXI is more complex in compound-leafed species. Here, we investigated the role of ARP and KNOXI genes in compound leaf development in Medicago truncatula. We show that the M. truncatula phantastica mutant exhibited severe compound leaf defects, including curling and deep serration of leaf margins, shortened petioles, increased rachises, petioles acquiring motor organ characteristics, and ectopic development of petiolules. On the other hand, the M. truncatula brevipedicellus mutant did not exhibit visible compound leaf defects. Our analyses show that the altered petiole development requires ectopic expression of ELONGATED PETIOLULE1, which encodes a lateral organ boundary domain protein, and that the distal margin serration requires the auxin efflux protein M. truncatula PIN-FORMED10 in the M. truncatula phantastica mutant. PMID:24218492

Induced stem cell neoplasia in a cnidarian by ectopic expression of a POU domain transcription factor.

PubMed

Millane, R Cathriona; Kanska, Justyna; Duffy, David J; Seoighe, Cathal; Cunningham, Stephen; Plickert, Günter; Frank, Uri

2011-06-01

The evolutionary origin of stem cell pluripotency is an unresolved question. In mammals, pluripotency is limited to early embryos and is induced and maintained by a small number of key transcription factors, of which the POU domain protein Oct4 is considered central. Clonal invertebrates, by contrast, possess pluripotent stem cells throughout their life, but the molecular mechanisms that control their pluripotency are poorly defined. To address this problem, we analyzed the expression pattern and function of Polynem (Pln), a POU domain gene from the marine cnidarian Hydractinia echinata. We show that Pln is expressed in the embryo and adult stem cells of the animal and that ectopic expression in epithelial cells induces stem cell neoplasms and loss of epithelial tissue. Neoplasm cells downregulated the transgene but expressed the endogenous Pln gene and also Nanos, Vasa, Piwi and Myc, which are all known cnidarian stem cell markers. Retinoic acid treatment caused downregulation of Pln and the differentiation of neoplasm cells to neurosensory and epithelial cells. Pln downregulation by RNAi led to differentiation. Collectively, our results suggest an ancient role of POU proteins as key regulators of animal stem cells.

Acoustic holograms of active regions

NASA Astrophysics Data System (ADS)

Chou, Dean-Yi

2008-10-01

We propose a method to study solar magnetic regions in the solar interior with the principle of optical holography. A magnetic region in the solar interior scatters the solar background acoustic waves. The scattered waves and background waves could form an interference pattern on the solar surface. We investigate the feasibility of detecting this interference pattern on the solar surface, and using it to construct the three-dimensional scattered wave from the magnetic region with the principle of optical holography. In solar acoustic holography, the background acoustic waves play the role of reference wave; the magnetic region plays the role of the target object; the interference pattern, acoustic power map, on the solar surface plays the role of the hologram.

Molecular pathogenesis of ovarian clear cell carcinoma.

PubMed

Gounaris, Ioannis; Brenton, James D

2015-01-01

Ovarian clear cell carcinoma is a distinct subtype of epithelial ovarian cancer, characterized by an association with endometriosis, glycogen accumulation and resistance to chemotherapy. Key driver events, including ARID1A mutations and HNF1B overexpression, have been recently identified and their functional characterization is ongoing. Additionally, the role of glycogen in promoting the malignant phenotype is coming under scrutiny. Appreciation of the notion that ovarian clear cell carcinoma is essentially an ectopic uterine cancer will hopefully lead to improved animal models of the disease, in turn paving the way for effective treatments.

Ectopic drainage from the inferior vena cava to the left atrium together with a partial anomalous pulmonary venous connection.

PubMed

Wu, Yuan; Xu, Shuangyue; Guo, Hongwei; Yan, Guoliang; Qi, Zhongquan; Shan, Zhonggui

2014-07-01

We report a case of a 44-year-old male patient with ectopic drainage from the inferior vena cava to the left atrium accompanied by partial anomalous pulmonary venous drainage. After the patient was hospitalized, his diagnosis was confirmed by Doppler echocardiography and angiography. A pericardial patch was used to divert the blood to the atrium. The surgical procedure was successful, and the patient began a rehabilitation program 8 days later. This type of ectopic drainage pattern is an unusual and infrequent clinical finding. The definitive diagnosis should be made by Doppler ultrasound combined with angiography. Copyright © 2014 Elsevier Inc. All rights reserved.

[Prenatal diagnosis of a right thoracic congenital ectopic kidney with a diaphragmatic hernia: a combination with a good prognosis].

PubMed

Cessans, C; Pharamin, J; Crouzet, K; Kessler, S; Puget, C; Bouali, O; Galinier, P; Marcoux, M-O

2015-11-01

Ectopic intrathoracic kidney is a rare congenital anomaly, usually asymptomatic. This anomaly is sometimes associated with a diaphragmatic hernia. Few cases of this combination have been described, often in the absence of a prenatal diagnosis. We report on the case of a female newborn infant who was diagnosed with an ectopic intrathoracic right kidney and a diaphragmatic hernia upon 33 weeks of gestation. The patient underwent surgery on the first day of life and the respiratory and renal outcomes were simple. We review the literature and discuss the seemingly good prognosis of this combination. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Scary gas: intravascular, intracranial, and intraspinal ectopic gas (part III).

PubMed

Sandstrom, Claire K; Osman, Sherif F; Linnau, Ken F

2017-08-01

While ectopic gas can be a sign of dangerous disease requiring immediate medical or surgical intervention, it can also be an incidental and benign finding. Intravenous gas and spinal vacuum gas are common and almost always benign. Intravascular gas is most often related to instrumentation and, if intraarticular, can cause end-organ ischemia; however, treatment is usually supportive. Pneumocephalus arises from a communication with paranasal sinuses or mastoids more often than from meningeal infection and can usually be managed nonoperatively. In part 3 of this series, the different causes of ectopic gas in the vessels, skull, and spine are reviewed, as are the imaging features that can help to narrow the differential diagnosis.

Torso-Tank Validation of High-Resolution Electrogastrography (EGG): Forward Modelling, Methodology and Results.

PubMed

Calder, Stefan; O'Grady, Greg; Cheng, Leo K; Du, Peng

2018-04-27

Electrogastrography (EGG) is a non-invasive method for measuring gastric electrical activity. Recent simulation studies have attempted to extend the current clinical utility of the EGG, in particular by providing a theoretical framework for distinguishing specific gastric slow wave dysrhythmias. In this paper we implement an experimental setup called a 'torso-tank' with the aim of expanding and experimentally validating these previous simulations. The torso-tank was developed using an adult male torso phantom with 190 electrodes embedded throughout the torso. The gastric slow waves were reproduced using an artificial current source capable of producing 3D electrical fields. Multiple gastric dysrhythmias were reproduced based on high-resolution mapping data from cases of human gastric dysfunction (gastric re-entry, conduction blocks and ectopic pacemakers) in addition to normal test data. Each case was recorded and compared to the previously-presented simulated results. Qualitative and quantitative analyses were performed to define the accuracy showing [Formula: see text] 1.8% difference, [Formula: see text] 0.99 correlation, and [Formula: see text] 0.04 normalised RMS error between experimental and simulated findings. These results reaffirm previous findings and these methods in unison therefore present a promising morphological-based methodology for advancing the understanding and clinical applications of EGG.

Ectopic expression of Msx-2 in posterior limb bud mesoderm impairs limb morphogenesis while inducing BMP-4 expression, inhibiting cell proliferation, and promoting apoptosis.

PubMed

Ferrari, D; Lichtler, A C; Pan, Z Z; Dealy, C N; Upholt, W B; Kosher, R A

1998-05-01

During early stages of chick limb development, the homeobox-containing gene Msx-2 is expressed in the mesoderm at the anterior margin of the limb bud and in a discrete group of mesodermal cells at the midproximal posterior margin. These domains of Msx-2 expression roughly demarcate the anterior and posterior boundaries of the progress zone, the highly proliferating posterior mesodermal cells underneath the apical ectodermal ridge (AER) that give rise to the skeletal elements of the limb and associated structures. Later in development as the AER loses its activity, Msx-2 expression expands into the distal mesoderm and subsequently into the interdigital mesenchyme which demarcates the developing digits. The domains of Msx-2 expression exhibit considerably less proliferation than the cells of the progress zone and also encompass several regions of programmed cell death including the anterior and posterior necrotic zones and interdigital mesenchyme. We have thus suggested that Msx-2 may be in a regulatory network that delimits the progress zone by suppressing the morphogenesis of the regions of the limb mesoderm in which it is highly expressed. In the present study we show that ectopic expression of Msx-2 via a retroviral expression vector in the posterior mesoderm of the progress zone from the time of initial formation of the limb bud severely impairs limb morphogenesis. Msx-2-infected limbs are typically very narrow along the anteroposterior axis, are occasionally truncated, and exhibit alterations in the pattern of formation of skeletal elements, indicating that as a consequence of ectopic Msx-2 expression the morphogenesis of large portions of the posterior mesoderm has been suppressed. We further show that Msx-2 impairs limb morphogenesis by reducing cell proliferation and promoting apoptosis in the regions of the posterior mesoderm in which it is ectopically expressed. The domains of ectopic Msx-2 expression in the posterior mesoderm also exhibit ectopic expression of BMP-4, a secreted signaling molecule that is coexpressed with Msx-2 during normal limb development in the anterior limb mesoderm, the posterior necrotic zone, and interdigital mesenchyme. This indicates that Msx-2 regulates BMP-4 expression and that the suppressive effects of Msx-2 on limb morphogenesis might be mediated in part by BMP-4. These studies indicate that during normal limb development Msx-2 is a key component of a regulatory network that delimits the boundaries of the progress zone by suppressing the morphogenesis of the regions of the limb mesoderm in which it is highly expressed, thus restricting the outgrowth and formation of skeletal elements and associated structures to the progress zone. We also report that rather large numbers of apoptotic cells as well as proliferating cells are present throughout the AER during all stages of normal limb development we have examined, indicating that many of the cells of the AER are continuously undergoing programmed cell death at the same time that new AER cells are being generated by cell proliferation. Thus, a balance between cell proliferation and programmed cell death may play a very important role in maintaining the activity of the AER. Copyright 1998 Academic Press.

A Retroperitoneal Neuroendocrine Tumor in Ectopic Pancreatic Tissue

PubMed Central

Okasha, Hussein Hassan; Al-Bassiouni, Fahim; El-Ela, Monir Abo; Al-Gemeie, Emad Hamza; Ezzat, Reem

2013-01-01

Ectopic pancreas is the relatively uncommon presence of pancreatic tissue outside the normal location of the pancreas. We report a case of abdominal pain due to retroperitoneal neuroendocrine tumor arising from heterotopic pancreatic tissue between the duodenal wall and the head of the pancreas. Patient underwent surgical enucleation of the tumor. PMID:24949389

Ectopic lobe of right lung with abscess formation in children: a visual diagnosis case.

PubMed

Wu, Chyi-Sen; Wan, Kong-Sang

2013-08-01

We report a 9-year-old boy who had chest pain of 3 weeks' duration caused by ectopic lobe of the right lung with abscess formation. The diagnosis was supported by chest computed tomography and video-assisted thoracoscopy. The child responded well to the operation and fully recovered.

Tissue reaction of deproteinized bovine bone matrix grafting in ectopic site: histological study on sheep.

PubMed

Grossi, João Ricardo Almeida; Bonacin, Rodrigo; Crivelaro, Viviane Rozeira; Giovanini, Allan Fernando; Zielak, João César; Deliberador, Tatiana Miranda

2016-12-01

The aim of this paper was to evaluate through histological analysis of the tissue reaction of deproteinized bovine bone matrix (DBBM) when inserted into the site of intramuscular ectopic sheep. In this study, 16 sheep received 3 groups and these were divided into 2 experimental times: Group 1-sham group, Group 2-particulate autogenous bone and Group 3-DBBM granules. All animals underwent surgical procedures for insertion of materials in an ectopic site (muscles of the lower back and after 3 and 6 months postoperatively, the samples were evaluated by histological analysis. The results indicated that the Sham group showed dense collagen fibers and thin, characterizing fibrosis at 3 and 6 months. In the autograft group there was a significant amount of collagen deposition and decreased inflammation at 6 months postoperatively. Group of DBBM, it was noted the presence of dense connective tissue and surrounding remaining particles was observed the formation of with osteoid characteristic tissue. The DBBM demonstrated biocompatibility, osteoconductivity and small osteogenesis capacity on ectopic site.

Ectopic Thymic Cyst of the Subglottis: Considerations for Diagnosis and Management.

PubMed

Ahmad, Iram; Kirby, Patricia; Liming, Bryan

2018-03-01

To share the diagnostic and management challenges created by an extremely rare airway lesion-the subglottic ectopic thymic cyst. Case report and literature review. We review the presentation, management, and clinical course of an infant who presented with a subglottic mass that was histologically confirmed as a thymic cyst. A brief literature review supplements the case presentation Results: We present the third described case of an ectopic thymic cyst presenting as a subglottic mass. The differential diagnosis of subglottic masses in neonates consists primarily of subglottic hemangioma and mucous retention cysts. Otolaryngologists must be prepared for unexpected findings when dealing with critical airways. We compare the presentation and management of our patient with the 2 previously described cases. We propose an embryologic theory for the origin of these rare lesions. An ectopic thymic cyst is a rare and unexpected cause of neonatal stridor. Management of pediatric airway lesions must allow for unexpected findings at the time of diagnostic and therapeutic endoscopy. The appropriate management of subglottic thymic cysts is poorly defined, but close surveillance for recurrence is mandatory.

Direct pelvic access percutaneous nephrolithotomy in management of ectopic kidney stone: a case report and literature review.

PubMed

Mehmet, Rifaioglu Murat; Rustu, Yalcinkaya Fatih; Hanefi, Bayarogullari; Mursel, Davarci; Fusun, Aydogan; Mehmet, Inci

2013-01-01

Percutaneous nephrolithotomy (PNL) is an effective procedure for the treatment of patients with large or complex stones. PNL is challenging in anomalous kidneys, certain patients, such as those with renal ectopia. It is unable to undergo PNL in conventional technique safely in these cases. We presented a case report of laparoscopic-assisted PNL via direct pelvic puncture in a pelvic kidney stone and discussed previous published literature. A 49-year-old man presented with right lower quadrant pain and hematuria. Intravenous pyelography and three-dimensional computerized tomography revealed an opaque 2.7 × 1.7 cm pelvis renalis stone in a right side ectopic pelvic kidney with grade III hydronephrosis. Laparoscopic-assisted tubeless PNL was performed to remove the calculus. Laparoscopic-assisted PNL as a minimally invasive therapy in ectopic kidney has many advantages. Our case showed that, in pelvic ectopic kidney with pelvic stones greater than 1.5 cm in size, laparoscopic-assisted PNL via direct pelvis puncture is a safe and effective technique.

Severe Cushing's syndrome and bilateral pulmonary nodules: beyond ectopic ACTH.

PubMed

Tavares Bello, Carlos; van der Poest Clement, Emma; Feelders, Richard

2017-01-01

Cushing's syndrome is a rare disease that results from prolonged exposure to supraphysiological levels of glucocorticoids. Severe and rapidly progressive cases are often, but not exclusively, attributable to ectopic ACTH secretion. Extreme hypercortisolism usually has florid metabolic consequences and is associated with an increased infectious and thrombotic risk. The authors report on a case of a 51-year-old male that presented with severe Cushing's syndrome secondary to an ACTH-secreting pituitary macroadenoma, whose diagnostic workup was affected by concurrent subclinical multifocal pulmonary infectious nodules. The case is noteworthy for the atypically severe presentation of Cushing's disease, and it should remind the clinician of the possible infectious and thrombotic complications associated with Cushing's syndrome. Severe Cushing's syndrome is not always caused by ectopic ACTH secretion.Hypercortisolism is a state of immunosuppression, being associated with an increased risk for opportunistic infections.Infectious pulmonary infiltrates may lead to imaging diagnostic dilemmas when investigating a suspected ectopic ACTH secretion.Cushing's syndrome carries an increased thromboembolic risk that may even persist after successful surgical management.Antibiotic and venous thromboembolism prophylaxis should be considered in every patient with severe Cushing's syndrome.

Intraoral extraction of an ectopic mandibular third molar detected in the subcondylar region without a pathological cause: A case report and literature review.

PubMed

Okuyama, Kohei; Sakamoto, Yuki; Naruse, Tomofumi; Kawakita, Akiko; Yanamoto, Souichi; Furukawa, Kohei; Umeda, Masahiro

2017-09-01

To present a case report on the presence of an ectopic mandibular third molar (EMTM), the surgical treatment, and outcome. A 63-year-old woman presented with right preauricular facial swelling, limited jaw function, and pain. Radiographic assessment demonstrated an EMTM positioned in the superoposterior aspect of the ramus. Radiographically, there was a bony tunnel extending from the third molar to distal of the second molar. The patient was treated by an intraoral approach on the medial aspect of the ramus for removal of the ectopic third molar, as well as the tissue in the bony tunnel. The patient healed uneventfully. The soft tissue in the bony canal was granulation tissue, and nerve function was preserved. A literature search of EMTMs was conducted identifying 17 reported cases. Three-dimensional imaging in the management of EMTM can be beneficial in identifying position of the tooth, associated pathology, and identifying the position of neurovascular structures to aid in removal of the ectopic tooth.

Acromegaly and Cushing's syndrome associated with a foregut carcinoid tumor.

PubMed

Leveston, S A; McKeel, D W; Buckley, P J; Deschryver, K; Greider, M H; Jaffe, B M; Daughaday, W H

1981-10-01

We report an 18-yr-old youth with a metastatic foregut carcinoid tumor, Cushing's syndrome, and hypersomatotropic gigantism. Administration of cyproheptadine caused a dramatic fall in urinary cortisol excretion and plasma ACTH levels associated with clinical remission of the Cushing's syndrome. GH secretion was not affected by cyproheptadine administration. Ectopic ACTH secretion was confirmed by RIA of tumor extracts and immunohistochemical demonstration of ACTH-containing cells in hepatic metastases. There were two sources of GH production demonstrated in this patient. Ectopic secretion of GH by the carcinoid hepatic metastases was documented by both RIA and immunohistochemical techniques. A somatotrophic pituitary tumor was also present. The histological characteristics of this tumor suggest adenomatous hyperplasia rather than de novo neoplastic change as the likely mechanism of its pathogenesis. GH releasing factor-like activity was demonstrated in extracts of plasma and in extracts of the carcinoid tumor. We conclude that cyproheptadine exerted an effect on the ectopic ACTH-producing cells but not on the ectopic GH-producing cells or on adenohypophyseal GH secretion. Production of a GH releasing factor-like activity by the carcinoid tumor may have caused the pituitary somatotrophic tumor.

Zoonotic ectopic fascioliasis: review and discussion.

PubMed

Rashed, Amr A; Khalil, Hazem H M; Morsy, Ayman T A

2010-12-01

Ectopic fascioliasis (EF) has direct and indirect effects on both humans and animals. The phenomenon of EF was individual cases in the period from 1950 up to the end of last century. From the period of 2000 up to 2006, plenty of researches were on EF in the developed and undeveloped countries. Nineteen EF cases infected with the immature and few with the mature worms were 13 females and 6 males. Three cases of lymphatic, pleural and breast fascioliasis reached the adults and laid their eggs in a lymph node in the cervical region pleural cavity and breast tissues. Until recent, knowledge about the ectopic fascioliasis pathway is little. Fasciola hepatica was the commonest species in most cases. The effect of fascioliasis might be direct to liver as ectopic foci or indirect on other organs due to the metabolites and secretory excretory products. All ages and both sexes were EF infected. Watercress topped the list of water plants born encysted metacercariae followed by lettuce, mint, and alfalfa. Nearly 24 million Egyptians at risk and about 800,000 were infected. On the global scale, about 180 million are at risk of infection.

Sonographic findings of hepatobiliary fascioliasis accompanied by extrahepatic expansion and ectopic lesions.

PubMed

Teke, Memik; Önder, Hakan; Çiçek, Mutalip; Hamidi, Cihad; Göya, Cemil; Çetinçakmak, Mehmet Güli; Hattapoğlu, Salih; Ülger, Burak Veli

2014-12-01

The aim of the study was to describe the sonographic findings of hepatobiliary fascioliasis with extrahepatic expansion and ectopic lesions. The study included 45 patients with fascioliasis. All diagnoses were confirmed via serologic enzyme-linked immunosorbent assays. Sonographic findings in the hepatobiliary system, extrahepatic expansion, and ectopic lesions were defined. The most common hepatic lesions were subcapsular localized, small, confluent, multiple hypoechoic nodules with poorly defined borders. We also detected ectopic lesion in 5 patients (11.1%) and live parasites in the gallbladder and bile duct in 11 (24.4%). The large spectrum of entities in the differential diagnosis of hepatobiliary fascioliasis may lead to misdiagnosis and incorrect treatment. However, the diagnosis can be made when the characteristic sonographic features are seen, such as heterogeneity of the liver with multiple poorly defined hypoechoic-isoechoic lesions and multiple echogenic nonshadowing particles in the gallbladder or common bile ducts. Nonetheless, the differential diagnosis of fascioliasis versus other hepatic lesions may still be difficult. In these situations, pathologic confirmation should be performed to exclude the possibility of malignancy. © 2013 by the American Institute of Ultrasound in Medicine.

Osteogenesis imperfecta with ectopic mineralizations in dentin and cementum and a COL1A2 mutation.

PubMed

Kantaputra, Piranit Nik; Sirirungruangsarn, Yuddhasert; Intachai, Worrachet; Ngamphiw, Chumpol; Tongsima, Sissades; Dejkhamron, Prapai

2018-04-10

We report a Thai father (patient 1) and his daughter (patient 2) affected with osteogenesis imperfecta type IV and dentinogenesis imperfecta. Both were heterozygous for the c.1451G>A (p.Gly484Glu) mutation in COL1A2. The father, a Thai boxer, had very mild osteogenesis imperfecta with no history of low-trauma bone fractures. Scanning electron micrography of the primary teeth with DI of the patient 2, and the primary teeth with DI of another OI patient with OI showed newly recognized dental manifestations of teeth with DI. Normal dentin and cementum might have small areas of ectopic mineralizations. Teeth affected with DI have well-organized ectopic mineralizations in dentin and cementum. The "French-fries-appearance" of the crystals at the cemento-dentinal junction and abnormal cementum have never been reported to be associated with dentinogenesis imperfecta, either isolated or osteogenesis imperfecta-associated. Our study shows for the first time that abnormal collagen fibers can lead to ectopic mineralization in dentin and cementum and abnormal cementum can be a part of osteogenesis imperfecta.

Pleomorphic adenoma of a deep orbital ectopic lacrimal gland.

PubMed

Misra, Somen; Bhandari, Akshay; Misra, Neeta; Gogri, Pratik; Mahajan, Shruti

2016-10-01

Ectopic lacrimal gland, being one of the choristomas, is comprised of lacrimal gland tissue outside the lacrimal gland fossa in the fronto-lateral part of the orbital roof. Ectopic lacrimal gland is a rare condition where the gland may be found in the orbit, eyelids, ocular adnexa or within the globe. Neoplastic transformation of such tissue may occur. A sixty-two-year old male patient presented with right eye proptosis and slight nasal displacement of the globe. Computerized tomography scan revealed a well-defined hypodense lesion of size 19 x 18 x 20 mm supero-lateral to lateral rectus muscle, with mild proptosis and thinning of the right lateral orbital wall. Excisional biopsy was performed through a lateral orbitotomy approach. A well circumscribed globular mass was removed from the right orbit, well behind the fossa for the lacrimal gland in the retrobulbar space. Histopathology was suggestive of pleomorphic adenoma of lacrimal gland. Pleomorphic adenoma is an epithelial tumor of the lacrimal gland which is extremely rare from an ectopic lacrimal gland and only few cases have been reported in literature till date.

The role of Drosophila TNF Eiger in developmental and damage-induced neuronal apoptosis.

PubMed

Shklover, Jeny; Levy-Adam, Flonia; Kurant, Estee

2015-04-02

Eiger, the sole Drosophila TNF-alpha homolog, causes ectopic apoptosis through JNK pathway activation. Yet, its role in developmental apoptosis remains unclear. eiger mutant flies are viable and fertile but display compromised elimination of oncogenic cells and extracellular bacteria. Here we show that Eiger, specifically expressed in embryonic neurons and glia, is not involved in developmental neuronal apoptosis or in apoptotic cell clearance. Instead, we provide evidence that Eiger is required for damage-induced apoptosis in the embryonic CNS through regulation of the pro-apoptotic gene hid independently of the JNK pathway. Our study thus reveals a new requirement for Eiger in eliminating damaged cells during development. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

To Assess the Association between Glucose Metabolism and Ectopic Lipid Content in Different Clinical Classifications of PCOS.

PubMed

Göbl, Christian S; Ott, Johannes; Bozkurt, Latife; Feichtinger, Michael; Rehmann, Victoria; Cserjan, Anna; Heinisch, Maike; Steinbrecher, Helmut; JustKukurova, Ivica; Tuskova, Radka; Leutner, Michael; Vytiska-Binstorfer, Elisabeth; Kurz, Christine; Weghofer, Andrea; Tura, Andrea; Egarter, Christian; Kautzky-Willer, Alexandra

2016-01-01

There are emerging data indicating an association between PCOS (polycystic ovary syndrome) and metabolic derangements with potential impact on its clinical presentation. This study aims to evaluate the pathophysiological processes beyond PCOS with particular focus on carbohydrate metabolism, ectopic lipids and their possible interaction. Differences between the two established classifications of the disease should be additionally evaluated. A metabolic characterization was performed in 53 untreated PCOS patients as well as 20 controls including an extended oral glucose tolerance test (OGTT, to assess insulin sensitivity, secretion and ß-cell function) in addition to a detailed examination of ectopic lipid content in muscle and liver by nuclear magnetic resonance spectroscopy. Women with PCOS classified by the original NIH 1990 definition showed a more adverse metabolic risk profile compared to women characterized by the additional Rotterdam 2003 phenotypes. Subtle metabolic derangements were observed in both subgroups, including altered shapes of OGTT curves, impaired insulin action and hyperinsulinemia due to increased secretion and attenuated hepatic extraction. No differences were observed for ectopic lipids between the groups. However, particularly hepatocellular lipid content was significantly related to clinical parameters of PCOS like whole body insulin sensitivity, dyslipidemia and free androgen index. Subtle alterations in carbohydrate metabolism are present in both PCOS classifications, but more profound in subjects meeting the NIH 1990 criteria. Females with PCOS and controls did not differ in ectopic lipids, however, liver fat was tightly related to hyperandrogenism and an adverse metabolic risk profile.

Retroperitoneal ectopic pregnancy: a case report and review of the literature.

PubMed

Yang, Man; Cidan, Lamu; Zhang, Dan

2017-10-16

Retroperitoneal ectopic pregnancy (REP) is an extremely rare type of ectopic pregnancy, with a total of less than 20 cases reported in the English literature. However, failure to recognize REP may result in severe consequences. We report a case of 32-year-old woman with REP. She had amenorrhea, left lower abdominal pain, but no vaginal bleeding. Her urine human chorionic gonadotropin (HCG) test was positive and blood HCG level was 1880 m-international units per milliliter (mIU/mL). Transvaginal ultrasound sonography showed a left adnexal mass. Laparoscopy found an enlarged uterus, normal right uterine tube and ovary, and normal left uterine tube. The left ovary was partly covered by a blood clot, but appeared normal after removing the clot. There was a 10-mm circular peritoneal defect located lateral to the left sacrocervical ligament, anterior to the left ovarian fossa, and next to the lower edge of the left broad ligament. The patient was diagnosed of having REP with the gestational tissues covered by the peritoneum. The REP was removed by laparoscopic surgery. Bleeding was stopped by bipolar coagulation and absorbable hemostatic cellulose. The patient recovered smoothly and was discharged on the next day after surgery. Her blood HCG returned to normal range 29 days after surgery. REP is very rare, but in any suspected case of ectopic pregnancy, caution must be paid to find signs of REP when the common sites of ectopic pregnancy do not have any positive findings.

Ectopic lignification in the flax lignified bast fiber1 mutant stem is associated with tissue-specific modifications in gene expression and cell wall composition.

PubMed

Chantreau, Maxime; Portelette, Antoine; Dauwe, Rebecca; Kiyoto, Shingo; Crônier, David; Morreel, Kris; Arribat, Sandrine; Neutelings, Godfrey; Chabi, Malika; Boerjan, Wout; Yoshinaga, Arata; Mesnard, François; Grec, Sebastien; Chabbert, Brigitte; Hawkins, Simon

2014-11-01

Histochemical screening of a flax ethyl methanesulfonate population led to the identification of 93 independent M2 mutant families showing ectopic lignification in the secondary cell wall of stem bast fibers. We named this core collection the Linum usitatissimum (flax) lbf mutants for lignified bast fibers and believe that this population represents a novel biological resource for investigating how bast fiber plants regulate lignin biosynthesis. As a proof of concept, we characterized the lbf1 mutant and showed that the lignin content increased by 350% in outer stem tissues containing bast fibers but was unchanged in inner stem tissues containing xylem. Chemical and NMR analyses indicated that bast fiber ectopic lignin was highly condensed and rich in G-units. Liquid chromatography-mass spectrometry profiling showed large modifications in the oligolignol pool of lbf1 inner- and outer-stem tissues that could be related to ectopic lignification. Immunological and chemical analyses revealed that lbf1 mutants also showed changes to other cell wall polymers. Whole-genome transcriptomics suggested that ectopic lignification of flax bast fibers could be caused by increased transcript accumulation of (1) the cinnamoyl-CoA reductase, cinnamyl alcohol dehydrogenase, and caffeic acid O-methyltransferase monolignol biosynthesis genes, (2) several lignin-associated peroxidase genes, and (3) genes coding for respiratory burst oxidase homolog NADPH-oxidases necessary to increase H2O2 supply. © 2014 American Society of Plant Biologists. All rights reserved.

Ultrasound monitoring in patients undergoing in-vitro fertilization after methotrexate treatment for ectopic pregnancy.

PubMed

Provansal, M; Agostini, A; Lacroix, O; Gerbeau, S; Grillo, J-M; Gamerre, M

2009-12-01

To compare sonographic characteristics of the endometrium and follicles during in-vitro fertilization (IVF) before and after methotrexate (MTX) treatment for ectopic pregnancy. This retrospective study, conducted at Conception Hospital from January 2000 to July 2007, included all patients diagnosed with an ectopic pregnancy resulting from IVF treatment that was treated with MTX and who then underwent another IVF cycle. We compared the number and size of follicles and the endometrial thickness and quality on the day of human chorionic gonadotropin injection in the cycles before and after the MTX treatment to determine whether MTX had any effect. Eleven patients were included in the study. The median interval between the IVF cycle resulting in ectopic pregnancy and the first IVF cycle after MTX therapy was 180 (range, 150-900) days. There was no statistically significant difference between the before and after MTX treatment groups with respect to number of follicles (14 (3-20) vs. 9 (4-16), P = 0.12), follicle size (16.5 (14.7-21.7) mm vs. 17.8 (14.9-19.8) mm, P = 0.37), endometrial thickness (10.0 (9.5-12.0) mm vs. 10.0 (7.5-14.0) mm, P = 0.31) or endometrial quality (P = 0.32). Four women became pregnant during the IVF cycle following MTX treatment. Ultrasound monitoring showed no modification of the characteristics of the endometrium or follicles during IVF after MTX treatment for ectopic pregnancy. Copyright 2009 ISUOG. Published by John Wiley & Sons, Ltd.

Ectopic expression of Cripto-1 in transgenic mouse embryos causes hemorrhages, fatal cardiac defects and embryonic lethality

PubMed Central

Lin, Xiaolin; Zhao, Wentao; Jia, Junshuang; Lin, Taoyan; Xiao, Gaofang; Wang, Shengchun; Lin, Xia; Liu, Yu; Chen, Li; Qin, Yujuan; Li, Jing; Zhang, Tingting; Hao, Weichao; Chen, Bangzhu; Xie, Raoying; Cheng, Yushuang; Xu, Kang; Yao, Kaitai; Huang, Wenhua; Xiao, Dong; Sun, Yan

2016-01-01

Targeted disruption of Cripto-1 in mice caused embryonic lethality at E7.5, whereas we unexpectedly found that ectopic Cripto-1 expression in mouse embryos also led to embryonic lethality, which prompted us to characterize the causes and mechanisms underlying embryonic death due to ectopic Cripto-1 expression. RCLG/EIIa-Cre embryos displayed complex phenotypes between embryonic day 14.5 (E14.5) and E17.5, including fatal hemorrhages (E14.5-E15.5), embryo resorption (E14.5-E17.5), pale body surface (E14.5-E16.5) and no abnormal appearance (E14.5-E16.5). Macroscopic and histological examination revealed that ectopic expression of Cripto-1 transgene in RCLG/EIIa-Cre embryos resulted in lethal cardiac defects, as evidenced by cardiac malformations, myocardial thinning, failed assembly of striated myofibrils and lack of heartbeat. In addition, Cripto-1 transgene activation beginning after E8.5 also caused the aforementioned lethal cardiac defects in mouse embryos. Furthermore, ectopic Cripto-1 expression in embryonic hearts reduced the expression of cardiac transcription factors, which is at least partially responsible for the aforementioned lethal cardiac defects. Our results suggest that hemorrhages and cardiac abnormalities are two important lethal factors in Cripto-1 transgenic mice. Taken together, these findings are the first to demonstrate that sustained Cripto-1 transgene expression after E11.5 causes fatal hemorrhages and lethal cardiac defects, leading to embryonic death at E14.5-17.5. PMID:27687577

A Novel Animal Model for Pseudoxanthoma Elasticum

PubMed Central

Li, Qiaoli; Berndt, Annerose; Guo, Haitao; Sundberg, John P.; Uitto, Jouni

2013-01-01

Pseudoxanthoma elasticum is a multisystem ectopic mineralization disorder caused by mutations in the ABCC6 gene. A mouse model with targeted ablation of the corresponding gene (Abcc6tm1JfK) develops ectopic mineralization on the dermal sheath of vibrissae as biomarker of the progressive mineralization disorder. Survey of 31 mouse strains in a longitudinal aging study has identified three mouse strains with similar ectopic mineralization of the vibrissae, particularly the KK/HlJ strain. We report here that this mouse strain depicts, in addition to ectopic mineralization of the dermal sheath of vibrissae, mineral deposits in a number of internal organs. Energy dispersive X-ray analysis and topographic mapping found the presence of calcium and phosphate as the principal ions in the mineral deposits, similar to that in Abcc6tm1JfK mice, suggesting the presence of calcium hydroxyapatite. The mineralization was associated with a splice junction mutation at the 3′ end of exon 14 of the Abcc6 gene, resulting in a 5-bp deletion from the coding region and causing frame-shift of translation. As a consequence, essentially no Abcc6 protein was detected in the liver of the KK/HlJ mice, similar to that in Abcc6tm1JfK mice. Collectively, our studies found that the KK/HlJ mouse strain is characterized by ectopic mineralization due to a mutation in the Abcc6 gene and therefore provides a novel model system to study pseudoxanthoma elasticum. PMID:22846719

Methotrexate treatment in progressive tubal ectopic pregnancies and hCG-related clinicosurgical implications.

PubMed

Dogan, Askin; Gulhan, Ibrahim; Uyar, Ibrahim; Ekin, Atalay; Gezer, Cenk; Bilgin, Muzaffer; Taner, Cüneyt E; Ertas, Ibrahim E

2016-06-01

Our aim was to evaluate the relationship between the success of methotrexate treatment and β-hCG levels in progressive tubal ectopic pregnancies. We defined a retrospective cohort of 394 progressive tubal ectopic pregnancy patients treated with methotrexate. A single-dose methotrexate protocol using 50 mg/m(2) was administered to patients with progressive tubal ectopic pregnancy. Surgery was performed in patients who exhibited signs of acute abdomen due to tubal rupture. Of 394 patients that received methotrexate treatment, 335 (84.6%) responded to medical treatment, while the remaining 59 (15.36%) underwent surgery due to treatment failure. β-hCG levels in the failure group were significantly higher as compared with the success group at Day 1, Day 4, and Day 7 (2116±3157 vs. 4178±3422, 2062±3551 vs. 4935±4103, and 1532±3007 vs. 3900±4783, respectively). The receiver operating characteristics curve for β-hCG levels at Day 1 was 0.738, with a cutoff value of 1418 mIU/mL, while sensitivity and specificity values reached the optimum for treatment success (83.1% and 59.4%, respectively). Medical treatment with methotrexate achieved an 85.02% success rate for the treatment of progressive tubal ectopic pregnancy, while success rates for medical treatment decreased significantly when initial β-hCG levels were >1418 mIU/mL. Copyright © 2016. Published by Elsevier Taiwan.

Ectopic Lignification in the Flax lignified bast fiber1 Mutant Stem Is Associated with Tissue-Specific Modifications in Gene Expression and Cell Wall Composition[C][W

PubMed Central

Chantreau, Maxime; Portelette, Antoine; Dauwe, Rebecca; Kiyoto, Shingo; Crônier, David; Morreel, Kris; Arribat, Sandrine; Neutelings, Godfrey; Chabi, Malika; Boerjan, Wout; Yoshinaga, Arata; Mesnard, François; Grec, Sebastien; Chabbert, Brigitte; Hawkins, Simon

2014-01-01

Histochemical screening of a flax ethyl methanesulfonate population led to the identification of 93 independent M2 mutant families showing ectopic lignification in the secondary cell wall of stem bast fibers. We named this core collection the Linum usitatissimum (flax) lbf mutants for lignified bast fibers and believe that this population represents a novel biological resource for investigating how bast fiber plants regulate lignin biosynthesis. As a proof of concept, we characterized the lbf1 mutant and showed that the lignin content increased by 350% in outer stem tissues containing bast fibers but was unchanged in inner stem tissues containing xylem. Chemical and NMR analyses indicated that bast fiber ectopic lignin was highly condensed and rich in G-units. Liquid chromatography-mass spectrometry profiling showed large modifications in the oligolignol pool of lbf1 inner- and outer-stem tissues that could be related to ectopic lignification. Immunological and chemical analyses revealed that lbf1 mutants also showed changes to other cell wall polymers. Whole-genome transcriptomics suggested that ectopic lignification of flax bast fibers could be caused by increased transcript accumulation of (1) the cinnamoyl-CoA reductase, cinnamyl alcohol dehydrogenase, and caffeic acid O-methyltransferase monolignol biosynthesis genes, (2) several lignin-associated peroxidase genes, and (3) genes coding for respiratory burst oxidase homolog NADPH-oxidases necessary to increase H2O2 supply. PMID:25381351

Ectopic Expression of Nolz-1 in Neural Progenitors Promotes Cell Cycle Exit/Premature Neuronal Differentiation Accompanying with Abnormal Apoptosis in the Developing Mouse Telencephalon

PubMed Central

Chang, Sunny Li-Yun; Chen, Shih-Yun; Huang, Huai-Huei; Ko, Hsin-An; Liu, Pei-Tsen; Liu, Ya-Chi; Chen, Ping-Hau; Liu, Fu-Chin

2013-01-01

Nolz-1, as a murine member of the NET zinc-finger protein family, is expressed in post-mitotic differentiating neurons of striatum during development. To explore the function of Nolz-1 in regulating the neurogenesis of forebrain, we studied the effects of ectopic expression of Nolz-1 in neural progenitors. We generated the Cre-loxP dependent conditional transgenic mice in which Nolz-1 was ectopically expressed in proliferative neural progenitors. Ectopic expression of Nolz-1 in neural progenitors by intercrossing the Nolz-1 conditional transgenic mice with the nestin-Cre mice resulted in hypoplasia of telencephalon in double transgenic mice. Decreased proliferation of neural progenitor cells were found in the telencephalon, as evidenced by the reduction of BrdU−, Ki67− and phospho-histone 3-positive cells in E11.5–12.5 germinal zone of telencephalon. Transgenic Nolz-1 also promoted cell cycle exit and as a consequence might facilitate premature differentiation of progenitors, because TuJ1-positive neurons were ectopically found in the ventricular zone and there was a general increase of TuJ1 immunoreactivity in the telencephalon. Moreover, clusters of strong TuJ1-expressing neurons were present in E12.5 germinal zone. Some of these strong TuJ1-positive clusters, however, contained apoptotic condensed DNA, suggesting that inappropriate premature differentiation may lead to abnormal apoptosis in some progenitor cells. Consistent with the transgenic mouse analysis in vivo, similar effects of Nozl-1 over-expression in induction of apoptosis, inhibition of cell proliferation and promotion of neuronal differentiation were also observed in three different N18, ST14A and N2A neural cell lines in vitro. Taken together, our study indicates that ectopic expression of Nolz-1 in neural progenitors promotes cell cycle exit/premature neuronal differentiation and induces abnormal apoptosis in the developing telencephalon. PMID:24073229

Ectopic expression of nolz-1 in neural progenitors promotes cell cycle exit/premature neuronal differentiation accompanying with abnormal apoptosis in the developing mouse telencephalon.

PubMed

Chang, Sunny Li-Yun; Chen, Shih-Yun; Huang, Huai-Huei; Ko, Hsin-An; Liu, Pei-Tsen; Liu, Ya-Chi; Chen, Ping-Hau; Liu, Fu-Chin

2013-01-01

Nolz-1, as a murine member of the NET zinc-finger protein family, is expressed in post-mitotic differentiating neurons of striatum during development. To explore the function of Nolz-1 in regulating the neurogenesis of forebrain, we studied the effects of ectopic expression of Nolz-1 in neural progenitors. We generated the Cre-loxP dependent conditional transgenic mice in which Nolz-1 was ectopically expressed in proliferative neural progenitors. Ectopic expression of Nolz-1 in neural progenitors by intercrossing the Nolz-1 conditional transgenic mice with the nestin-Cre mice resulted in hypoplasia of telencephalon in double transgenic mice. Decreased proliferation of neural progenitor cells were found in the telencephalon, as evidenced by the reduction of BrdU-, Ki67- and phospho-histone 3-positive cells in E11.5-12.5 germinal zone of telencephalon. Transgenic Nolz-1 also promoted cell cycle exit and as a consequence might facilitate premature differentiation of progenitors, because TuJ1-positive neurons were ectopically found in the ventricular zone and there was a general increase of TuJ1 immunoreactivity in the telencephalon. Moreover, clusters of strong TuJ1-expressing neurons were present in E12.5 germinal zone. Some of these strong TuJ1-positive clusters, however, contained apoptotic condensed DNA, suggesting that inappropriate premature differentiation may lead to abnormal apoptosis in some progenitor cells. Consistent with the transgenic mouse analysis in vivo, similar effects of Nozl-1 over-expression in induction of apoptosis, inhibition of cell proliferation and promotion of neuronal differentiation were also observed in three different N18, ST14A and N2A neural cell lines in vitro. Taken together, our study indicates that ectopic expression of Nolz-1 in neural progenitors promotes cell cycle exit/premature neuronal differentiation and induces abnormal apoptosis in the developing telencephalon.

Current approaches for assessment and treatment of women with early miscarriage or ectopic pregnancy in Nigeria: a case for dedicated early pregnancy services.

PubMed

Iyoke, C A; Ugwu, O G; Ezugwu, F O; Onah, H E; Agbata, A T; Ajah, L C

2014-01-01

It has been suggested that women with early miscarriage or ectopic pregnancy are best cared for in dedicated units which offer rapid and definitive ultrasonographic and biochemical assessment at the initial review of the patient. To describe the current protocols for the assessment and treatment of women with early miscarriage or ectopic pregnancy as reported by Nigerian Gynecologists, and determine if dedicated early pregnancy services such as Early Pregnancy Assessment Units could be introduced to improve care. A cross-sectional survey of Nigerian Gynecologists attending the 46 th Annual Scientific Conference of the Society of Gynaecology and Obstetrics of Nigeria. This was a questionnaire-based study. Data analysis was by descriptive statistics using Statistical Package for the Social Sciences software, version 17.0 for Windows (IBM Corporation, Armonk, NY, USA). A total of 232 gynecologists working in 52 different secondary and tertiary health facilities participated in the survey. The mean age of the respondents was 42.6 ± 9.1 years (range 28-70 years). The proportion of gynecologists reporting that women with early miscarriage or ectopic pregnancy were first managed within the hospital general emergency room was 92%. The mean reported interval between arrival in hospital and first ultrasound scan was 4.9 ± 1.4 hours (range ½-8 hours). Transvaginal scan was stated as the routine initial imaging investigation by only 17.2% of respondents. Approximately 94.8% of respondents felt that dedicated early pregnancy services were feasible and should be introduced to improve the care of women with early miscarriage and ectopic pregnancy. Reported protocols for managing early miscarriage or ectopic pregnancy in many health facilities in Nigeria appear to engender unnecessary delays and avoidable costs, and dedicated early pregnancy services could be both useful and feasible in addressing these shortcomings in the way women with such conditions are currently managed.

Associations of lifetime active and passive smoking with spontaneous abortion, stillbirth and tubal ectopic pregnancy: a cross-sectional analysis of historical data from the Women's Health Initiative.

PubMed

Hyland, Andrew; Piazza, Kenneth M; Hovey, Kathleen M; Ockene, Judith K; Andrews, Christopher A; Rivard, Cheryl; Wactawski-Wende, Jean

2015-07-01

To examine the associations between tobacco exposure and adverse pregnancy outcomes using quantitative measures of lifetime active smoking and secondhand smoke (SHS) exposure. Historical reproductive data on 80 762 women who participated in the Women's Health Initiative Observational Study were examined with a cross-sectional analysis. We assessed self-reported lifetime active and passive tobacco smoke exposure, self-reported spontaneous abortions, stillbirths and ectopic pregnancies. When compared with never-smoking women, participants who were ever active smokers during their reproductive years had ORs (OR) of 1.16 (95% CI 1.08 to 1.26) for 1 or more spontaneous abortions, 1.44 (95% CI 1.20 to 1.73) for 1 or more stillbirths, and 1.43 (95% CI 1.10 to 1.86) for 1 or more ectopic pregnancies. Never-smoking women participants with the highest levels of lifetime SHS exposure, including childhood >10 years, adult home >20 years and adult work exposure >10 years, when compared with never-smoking women with no SHS exposure had adjusted ORs of 1.17 (95% CI 1.05 to 1.30) for spontaneous abortion, 1.55 (95% CI 1.21 to 1.97) for stillbirth, and 1.61 (95% CI 1.16 to 2.24) for ectopic pregnancy. Women who were ever-smokers during their reproductive years had significantly greater estimates of risk for spontaneous abortion, stillbirth and tubal ectopic pregnancy. Never-smoking women with the highest levels of lifetime exposure to SHS had significantly increased estimates of risk for spontaneous abortion, stillbirth and tubal ectopic pregnancy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Predictive factors for the methotrexate treatment outcome in ectopic pregnancy: A comparative study of 400 cases.

PubMed

Bonin, Lucie; Pedreiro, Cécile; Moret, Stéphanie; Chene, Gautier; Gaucherand, Pascal; Lamblin, Géry

2017-01-01

We sought to evaluate the global success rate of intramuscular methotrexate for the treatment of ectopic pregnancy, identify factors predictive of treatment success or failure, and study methotrexate tolerability in a large patient cohort. For this single-center retrospective observational study, we retrieved the records of all women who had a clinically or echographically confirmed ectopic pregnancy with a Fernandez score <13 and who were treated according to a 1mg/kg intramuscular single-dose methotrexate protocol. Medical treatment failure was defined by an obligation to proceed to laparoscopy. Needing a second injection was not considered to be medical treatment failure. Between February 2008 and November 2013 (69 months), 400 women received methotrexate for ectopic pregnancy. The medical treatment protocol was effective for 314 patients, i.e., an overall success rate of 78.5%. A single methotrexate dose was sufficient for 63.5% of the women and a second dose was successful for 73.2% of the remaining women. The medical treatment success rate fell as initial hCG levels climbed. The main factors associated with methotrexate failure included day (D) 0, D4 and D7 hCG levels, pretherapeutic blood progesterone, hematosalpinx at D0 and pain at D7. Early favorable kinetics of hCG levels was predictive of success. Methotrexate treatment was successful in 90% of women who had D0 hCG <1000IU/l. Methotrexate tolerability was good, with only 9% of the women reporting non-severe adverse effects. The fertility rate with delivery after medical treatment for ectopic pregnancy was 80.7%. In this study, we showed that an initial hCG value <1000IU/l and favorable early HCG kinetics were predictive factors for the successful medical treatment of ectopic pregnancy by methotrexate, and hematosalpinx and pretherapeutic blood progesterone >5ng/ml at diagnosis were predictive of its failure. We also confirmed good tolerability for single-dose methotrexate protocols. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Short-Lasting Episodes of Torsade de Pointes in the Chronic Atrioventricular Block Dog Model Have a Focal Mechanism, While Longer-Lasting Episodes Are Maintained by Re-Entry.

PubMed

Vandersickel, Nele; Bossu, Alexandre; De Neve, Jan; Dunnink, Albert; Meijborg, Veronique M F; van der Heyden, Marcel A G; Beekman, Jet D M; De Bakker, Jacques M T; Vos, Marc A; Panfilov, Alexander V

2017-12-26

This study investigated the arrhythmogenic mechanisms responsible for torsade de pointes (TdP) in the chronic atrioventricular block dog model, known for its high susceptibility for TdP. The mechanism of TdP arrhythmias has been under debate for many years. Focal activity as well as re-entry have both been mentioned in the initiation and the perpetuation of TdP. In 5 TdP-sensitive chronic atrioventricular block dogs, 56 needle electrodes were evenly distributed transmurally to record 240 unipolar local electrograms simultaneously. Nonterminating (NT) episodes were defibrillated after 10 s. Software was developed to automatically detect activation times and to create 3-dimensional visualizations of the arrhythmia. For each episode of ectopic activity (ranging from 2 beats to NT episodes), a novel methodology was created to construct directed graphs of the wave propagation and detect re-entry loops by using an iterative depth-first-search algorithm. Depending on the TdP definition (number of consecutive ectopic beats), we analyzed 29 to 54 TdP: 29 were longer than 5 beats. In the total group, 9 were NT and 45 were self-terminating. Initiation and termination were always based on focal activity. Re-entry becomes more important in the longer-lasting episodes (>14 beats), whereas in all NT TdP, re-entry was the last active mechanism. During re-entry, excitation fronts were constantly present in the heart, while during focal TdP, there was always a silent interval between 2 consecutive waves (142 ms) during which excitation fronts were absent. Interbeat intervals were significantly smaller for re-entry episodes-220 versus 310 ms in focal. Electrograms recorded in particular areas during NT TdP episodes had significantly smaller amplitude (0.38) than during focal episodes (0.59). TdP can be driven by focal activity as well as by re-entry depending on the duration of the episode. NT episodes are always maintained by re-entry, which can be identified in local unipolar electrograms by shorter interbeat intervals and smaller deflection amplitude. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Magnetophysiologic and echocardiographic comparison of blocked atrial bigeminy and 2:1 atrioventricular block in the fetus.

PubMed

Wiggins, Delonia L; Strasburger, Janette F; Gotteiner, Nina L; Cuneo, Bettina; Wakai, Ronald T

2013-08-01

Blocked atrial bigeminy (BAB) and second-degree atrioventricular block with 2:1 conduction block (2:1 AVB) both present as ventricular bradycardia and can be difficult to distinguish by echocardiography. Since the prognosis and clinical management of these rhythms are different, an accurate diagnosis is essential. To identify magnetic and mechanical heart rate and rhythm parameters that could reliably distinguish BAB from 2:1 AVB. A retrospective study of ten BAB and seven 2:1 AVB subjects was performed, using fMCG and pulsed Doppler ultrasound. Distinguishing BAB from 2:1 AVB by using fMCG was relatively straightforward because in BAB the ectopic P wave (P') occurred early, resulting in a bigeminal (short-long) atrial rhythm. The normalized coupling interval of the ectopic beat (PP' of the blocked beat to PP of the conducted beat) was 0.29 ± 0.03. In contrast, the echocardiographic assessment of inflow-outflow gave a normalized mechanical coupling interval (AA'/AA) near 0.5, which made it difficult to distinguish BAB from 2:1 AVB. Heart rate distinguished most subjects with BAB from those with 2:1 AVB (82 ± 5.7 beats/min vs 69 ± 4.2 beats/min), but was not a completely reliable indicator. In most subjects, BAB alternated with sinus rhythm or other rhythms, resulting in complex heart rate and rhythm patterns. Fetal BAB and 2:1 AV block can be difficult to distinguish using echocardiography because in many fetuses with BAB the mechanical rhythm does not accurately reflect the magnetic rhythm. fMCG provides a more reliable means of making a differential diagnosis. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Laparoscopic Finding of Ectopic Adrenocortical Tissue in a 2-Year-Old Boy with Vanishing Testis

PubMed Central

Marte, Antonio

2018-01-01

Ectopic adrenocortical tissue (EAT) along the spermatic cord is an unusual condition in children. The author reports on a 2-year-old boy with impalpable testis. On laparoscopy, EAT was detected along the hypotrophic spermatic vessels and excised. These remnants should be removed to prevent hormone production or malignant transformation. PMID:29326864

Laparoscopic Finding of Ectopic Adrenocortical Tissue in a 2-Year-Old Boy with Vanishing Testis.

PubMed

Marte, Antonio

2018-01-01

Ectopic adrenocortical tissue (EAT) along the spermatic cord is an unusual condition in children. The author reports on a 2-year-old boy with impalpable testis. On laparoscopy, EAT was detected along the hypotrophic spermatic vessels and excised. These remnants should be removed to prevent hormone production or malignant transformation.

Zebrafish pronephros tubulogenesis and epithelial identity maintenance are reliant on the polarity proteins Prkc iota and zeta.

PubMed

Gerlach, Gary F; Wingert, Rebecca A

2014-12-15

The zebrafish pronephros provides an excellent in vivo system to study the mechanisms of vertebrate nephron development. When and how renal progenitors in the zebrafish embryo undergo tubulogenesis to form nephrons is poorly understood, but is known to involve a mesenchymal to epithelial transition (MET) and the acquisition of polarity. Here, we determined the precise timing of these events in pronephros tubulogenesis. As the ternary polarity complex is an essential regulator of epithelial cell polarity across tissues, we performed gene knockdown studies to assess the roles of the related factors atypical protein kinase C iota and zeta (prkcι, prkcζ). We found that prkcι and prkcζ serve partially redundant functions to establish pronephros tubule epithelium polarity. Further, the loss of prkcι or the combined knockdown of prkcι/ζ disrupted proximal tubule morphogenesis and podocyte migration due to cardiac defects that prevented normal fluid flow to the kidney. Surprisingly, tubule cells in prkcι/ζ morphants displayed ectopic expression of the transcription factor pax2a and the podocyte-associated genes wt1a, wt1b, and podxl, suggesting that prkcι/ζ are needed to maintain renal epithelial identity. Knockdown of genes essential for cardiac contractility and vascular flow to the kidney, such as tnnt2a, or elimination of pronephros fluid output through knockdown of the intraflagellar transport gene ift88, was not associated with ectopic pronephros gene expression, thus suggesting a unique role for prkcι/ζ in maintaining tubule epithelial identity separate from the consequence of disruptions to renal fluid flow. Interestingly, knockdown of pax2a, but not wt1a, was sufficient to rescue ectopic tubule gene expression in prkcι/ζ morphants. These data suggest a model in which the redundant activities of prkcι and prkcζ are essential to establish tubule epithelial polarity and also serve to maintain proper epithelial cell type identity in the tubule by inhibiting pax2a expression. These studies provide a valuable foundation for further analysis of MET during nephrogenesis, and have implications for understanding the pathways that affect nephron epithelial cells during kidney disease and regeneration. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Mature orbital teratoma with an ectopic tooth and primary anophthalmos.

PubMed

Chawla, Bhavna; Chauhan, Kanchan; Kashyap, Seema

2013-02-01

To describe the clinicopathologic features and management of an unusual case of orbital teratoma. A 7-year-old girl presented with a history of an orbital mass since birth. CT scan showed a large mass lesion involving the right orbit, with absence of the eyeball. An ectopic tooth was identified within the tumor. Lid-sparing exenteration surgery was performed. Histopathologic examination of the excised mass showed presence of elements from all three germ layers, consistent with a diagnosis of mature orbital teratoma. Normal ocular structures were not identified on histopathology. At one year follow-up, there was no tumor recurrence. We report an extremely rare and interesting case of a mature orbital teratoma, which was associated with primary anophthalmos and an ectopic tooth.

Pregnancy Luteoma in Ectopic Pregnancy: A Case Report.

PubMed

Brar, Rupinder Kaur; Bharti, Jyotsna Naresh; Nigam, Jitendra Singh; Sehgal, Sahil; Singh, Hena Paul; Ojha, Pushpanjali

2017-01-01

Pregnancy luteoma is a rare non neoplastic condition of the ovary. It is usually asymptomatic and found incidentally during imaging in pregnancy or during cesarean section. Pregnancy luteoma can also occur after ectopic pregnancy. A 30 year old female presented to G.B. Pant Hospital, Andaman and Nicobar Islands institute of Medical Sciences, Port Blair in October 2015 with abdominal pain. After initial investigations, exploratory laporotomy was done for ruptured ectopic pregnancy. Enlarged ovary was removed along with the ruptured portion of fallopian tube. Histopathological examination revealed solid aggregates of large cells with abundant eosinophilic cytoplasm; diagnosis of pregnancy luteoma was given. It must be considered in the differential diagnosis of ovarian masses in pregnant females that early diagnosis of this entity may avoid unnecessary radical surgery.

Nephroureterectomy and ureteroneocystostomy in an alpaca with bilateral ectopic ureters diagnosed by computed tomographic excretory urography.

PubMed

Polf, Holly D; Smith, Shasta; Simpson, Katharine M; Rochat, Mark C

2015-01-01

To report diagnosis and treatment of urinary incontinence in a female Huacaya alpaca. Clinical case report. Female intact Huacaya alpaca (n = 1) METHODS: Computed tomographic (CT) excretory urography and vaginourethrography were performed to diagnose the cause of urinary incontinence. Bilateral ectopic ureters and left hydronephrosis and hydroureter were diagnosed. Left nephroureterectomy and right ureteroneocystostomy were performed with subsequent resolution of clinical signs. Pyelonephritis was identified by culture of the resected left kidney. CT excretory urography was helpful in the diagnosis of bilateral ectopic ureters in an alpaca and provided information for surgical planning. Surgical repair by ureteroneocystostomy and unilateral nephroureterectomy was successful in resolving clinical signs. © Copyright 2014 by The American College of Veterinary Surgeons.

The transposon Galileo generates natural chromosomal inversions in Drosophila by ectopic recombination.

PubMed

Delprat, Alejandra; Negre, Bàrbara; Puig, Marta; Ruiz, Alfredo

2009-11-18

Transposable elements (TEs) are responsible for the generation of chromosomal inversions in several groups of organisms. However, in Drosophila and other Dipterans, where inversions are abundant both as intraspecific polymorphisms and interspecific fixed differences, the evidence for a role of TEs is scarce. Previous work revealed that the transposon Galileo was involved in the generation of two polymorphic inversions of Drosophila buzzatii. To assess the impact of TEs in Drosophila chromosomal evolution and shed light on the mechanism involved, we isolated and sequenced the two breakpoints of another widespread polymorphic inversion from D. buzzatii, 2z(3). In the non inverted chromosome, the 2z(3) distal breakpoint was located between genes CG2046 and CG10326 whereas the proximal breakpoint lies between two novel genes that we have named Dlh and Mdp. In the inverted chromosome, the analysis of the breakpoint sequences revealed relatively large insertions (2,870-bp and 4,786-bp long) including two copies of the transposon Galileo (subfamily Newton), one at each breakpoint, plus several other TEs. The two Galileo copies: (i) are inserted in opposite orientation; (ii) present exchanged target site duplications; and (iii) are both chimeric. Our observations provide the best evidence gathered so far for the role of TEs in the generation of Drosophila inversions. In addition, they show unequivocally that ectopic recombination is the causative mechanism. The fact that the three polymorphic D. buzzatii inversions investigated so far were generated by the same transposon family is remarkable and is conceivably due to Galileo's unusual structure and current (or recent) transpositional activity.

Morphogenesis of the mouse neural plate depends on distinct roles of cofilin 1 in apical and basal epithelial domains

PubMed Central

Grego-Bessa, Joaquim; Hildebrand, Jeffrey; Anderson, Kathryn V.

2015-01-01

The genetic control of mammalian epithelial polarity and dynamics can be studied in vivo at cellular resolution during morphogenesis of the mouse neural tube. The mouse neural plate is a simple epithelium that is transformed into a columnar pseudostratified tube over the course of ∼24 h. Apical F-actin is known to be important for neural tube closure, but the precise roles of actin dynamics in the neural epithelium are not known. To determine how the organization of the neural epithelium and neural tube closure are affected when actin dynamics are blocked, we examined the cellular basis of the neural tube closure defect in mouse mutants that lack the actin-severing protein cofilin 1 (CFL1). Although apical localization of the adherens junctions, the Par complex, the Crumbs complex and SHROOM3 is normal in the mutants, CFL1 has at least two distinct functions in the apical and basal domains of the neural plate. Apically, in the absence of CFL1 myosin light chain does not become phosphorylated, indicating that CFL1 is required for the activation of apical actomyosin required for neural tube closure. On the basal side of the neural plate, loss of CFL1 has the opposite effect on myosin: excess F-actin and myosin accumulate and the ectopic myosin light chain is phosphorylated. The basal accumulation of F-actin is associated with the assembly of ectopic basal tight junctions and focal disruptions of the basement membrane, which eventually lead to a breakdown of epithelial organization. PMID:25742799

The role of acyl-CoA:diacylglycerol acyltransferase (DGAT) in energy metabolism.

PubMed

Yu, Yi-Hao; Ginsberg, Henry N

2004-01-01

Acyl-CoA:diacylglycerol acyltransferase (DGAT, EC2.3.1.20), a key enzyme in triglyceride (TG) biosynthesis, not only participates in lipid metabolism but also influences metabolic pathways of other fuel molecules. Changes in the expression and/or activity levels of DGAT may lead to changes in systemic insulin sensitivity and energy homeostasis. The synthetic role of DGAT in adipose tissue, the liver, and the intestine, sites where endogenous levels of DGAT activity and TG synthesis are high, is relatively clear. Less clear is whether DGAT plays a mediating or preventive role in the development of ectopic lipotoxicity in tissues such as muscle and the pancreas, when their supply of free fatty acids (FFAs) exceeds their needs. Future studies with tissue-specific overexpression and/or knockout in these animal models would be expected to shed additional light on these issues.

Gastrokines: stomach-specific proteins with putative homeostatic and tumor suppressor roles.

PubMed

Menheniott, Trevelyan R; Kurklu, Bayzar; Giraud, Andrew S

2013-01-15

During the past decade, a new family of stomach-specific proteins has been recognized. Known as "gastrokines" (GKNs), these secreted proteins are products of gastric mucus-producing cell lineages. GKNs are highly conserved in physical structure, and emerging data point to convergent functions in the modulation of gastric mucosal homeostasis and inflammation. While GKNs are highly prevalent in the normal stomach, frequent loss of GKN expression in gastric cancers, coupled with established antiproliferative activity, suggests putative tumor suppressor roles. Conversely, ectopic expression of GKNs in reparative lesions of Crohn's disease alludes to additional activity in epithelial wound healing and/or repair. Modes of action remain unsolved, but the recent demonstration of a GKN2-trefoil factor 1 heterodimer implicates functional interplay with trefoil factors. This review aims to provide a historical account of GKN biology and encapsulate the rapidly accumulating evidence supporting roles in gastric epithelial homeostasis and tumor suppression.

Increasing chlamydia diagnoses but little change in hospitalisations for ectopic pregnancy and infertility among women in New South Wales from 2001 to 2008.

PubMed

Liu, Bette; Donovan, Basil; Parker, Jim; Guy, Rebecca; Hocking, Jane; Kaldor, John M; Wand, Handan; Jorm, Louisa

2012-09-01

As genital chlamydia (Chlamydia trachomatis) notifications have increased in Australia, time trends in hospitalisations for ectopic pregnancy and female infertility between 2001 and 2008 in New South Wales (NSW), Australia, and their relationship to trends in chlamydia notifications in women were assessed. Annual rates of chlamydia notification, and hospitalisations for female infertility or ectopic pregnancy in women aged 15-44 years in NSW were calculated using routinely collected data. Chlamydia notifications and hospital separations occurring within each year belonging to the same woman were linked using probabilistic linkage of identifiers so that multiple notifications and admissions for one woman in each calendar year were only counted once. From 2001 to 2008, the annual rate of chlamydia diagnoses in women increased from 157 to 477 per 100000 population (P(trend)<0.001). Over the same period, the annual hospitalisation rate for women with an ectopic pregnancy decreased from 14.3 to 12.6 per 1000 births (P(trend)<0.001). This decrease was mostly in women aged 25-44 years, with no appreciable fall in women aged 15-24 years (P(trend)=0.8). Meanwhile, the hospitalisation rate for women with infertility of female origin did not follow a consistent trend: between 2001 and 2008, it fluctuated between a low of 479 and a high of 554 per 10000 women who were seeking pregnancy. These trends in ectopic pregnancy and female infertility suggest that the large increase in chlamydia notifications may not reflect hospitalisations for these two proposed chlamydia-related sequelae.

Ectopic prolactin secretion from a perivascular epithelioid cell tumor (PEComa).

PubMed

Korytnaya, Evgenia; Liu, Jiayan; Camelo-Piragua, Sandra; Sullivan, Stephen; Auchus, Richard J; Barkan, Ariel

2014-11-01

The diagnosis of ectopic pituitary hormone secretion requires abnormally high circulating hormone levels, absence of a pituitary tumor, and localization of the hormone in question to the extrapituitary malignant neoplasm. No case of a malignant solid tumor producing prolactin has been documented thus far. A 47-year-old woman presented with amenorrhea and galactorrhea of 3-year duration. Serum prolactin ranged from 300 to > 900 ng/mL, and other pituitary and thyroid indices were normal, including testing for macroprolactinemia. Pituitary magnetic resonance imaging revealed a partially empty sella but no tumor. Cabergoline 0.5 mg twice weekly did not affect her prolactinemia (1700 to 1900 ng/mL), and the medication was stopped. In the meantime, she developed abdominal pain, and a computed tomography scan showed a 17 × 13 × 8-cm mass abutting the distal stomach, proximal duodenum, and right colon. After the tumor was excised, her galactorrhea resolved, menstrual periodicity resumed within the first month, and serum prolactin fell to 5 ng/mL. Pathological examination of the excised tumor was consistent with perivascular epithelioid cell tumor. Between 5 and 10% of the tumor cells were strongly positive for prolactin on immunohistochemistry. RT-PCR detected prolactin mRNA in the tumor cell extract, confirming the diagnosis of ectopic prolactin synthesis and secretion. We present the first example of massive and symptomatic hyperprolactinemia due to ectopic prolactin production by a solid extrapituitary mesenchymal tumor confirmed with both mRNA analysis and immunohistochemistry. Ectopic prolactin secretion should be suspected in patients with a prolactin >200 ng/mL and negative sellar MRI.

To Assess the Association between Glucose Metabolism and Ectopic Lipid Content in Different Clinical Classifications of PCOS

PubMed Central

Göbl, Christian S.; Ott, Johannes; Bozkurt, Latife; Feichtinger, Michael; Rehmann, Victoria; Cserjan, Anna; Heinisch, Maike; Steinbrecher, Helmut; JustKukurova, Ivica; Tuskova, Radka; Leutner, Michael; Vytiska-Binstorfer, Elisabeth; Kurz, Christine; Weghofer, Andrea; Tura, Andrea; Egarter, Christian; Kautzky-Willer, Alexandra

2016-01-01

Aims There are emerging data indicating an association between PCOS (polycystic ovary syndrome) and metabolic derangements with potential impact on its clinical presentation. This study aims to evaluate the pathophysiological processes beyond PCOS with particular focus on carbohydrate metabolism, ectopic lipids and their possible interaction. Differences between the two established classifications of the disease should be additionally evaluated. Methods A metabolic characterization was performed in 53 untreated PCOS patients as well as 20 controls including an extended oral glucose tolerance test (OGTT, to assess insulin sensitivity, secretion and ß-cell function) in addition to a detailed examination of ectopic lipid content in muscle and liver by nuclear magnetic resonance spectroscopy. Results Women with PCOS classified by the original NIH 1990 definition showed a more adverse metabolic risk profile compared to women characterized by the additional Rotterdam 2003 phenotypes. Subtle metabolic derangements were observed in both subgroups, including altered shapes of OGTT curves, impaired insulin action and hyperinsulinemia due to increased secretion and attenuated hepatic extraction. No differences were observed for ectopic lipids between the groups. However, particularly hepatocellular lipid content was significantly related to clinical parameters of PCOS like whole body insulin sensitivity, dyslipidemia and free androgen index. Conclusions Subtle alterations in carbohydrate metabolism are present in both PCOS classifications, but more profound in subjects meeting the NIH 1990 criteria. Females with PCOS and controls did not differ in ectopic lipids, however, liver fat was tightly related to hyperandrogenism and an adverse metabolic risk profile. PMID:27505055

Plasma Steroid Metabolome Profiling for Diagnosis and Subtyping Patients with Cushing Syndrome.

PubMed

Eisenhofer, Graeme; Masjkur, Jimmy; Peitzsch, Mirko; Di Dalmazi, Guido; Bidlingmaier, Martin; Grüber, Matthias; Fazel, Julia; Osswald, Andrea; Beuschlein, Felix; Reincke, Martin

2018-03-01

Diagnosis of Cushing syndrome requires a multistep process that includes verification of hypercortisolism followed by identification of the cause of adrenocortical hyperfunction. This study assessed whether pituitary, ectopic, and adrenal subtypes of Cushing syndrome were characterized by distinct plasma steroid profiles that might assist diagnosis. In this retrospective cross-sectional study, mass spectrometric measurements of a panel of 15 plasma steroids were applied to 222 patient samples tested for Cushing syndrome. Disease was excluded in 138 and confirmed in 51 patients with pituitary Cushing syndrome, 12 with ectopic adrenocorticotropin secretion, and 21 with adrenal disease. Another 277 age- and sex-matched hypertensive and normotensive volunteers were included for comparison. Compared with patients without disease, the largest increases in plasma steroids among patients with Cushing syndrome were observed for 11-deoxycortisol (289%), 21-deoxycortisol (150%), 11-deoxycorticosterone (133%), corticosterone (124%), and cortisol (122%). Patients with ectopic disease showed the most prominent increases, but there was considerable variation for other steroids according to subtype. Patients with adrenal disease had the lowest concentrations of androgens, whereas those with ectopic and pituitary disease showed the lowest concentrations of aldosterone. Plasma 18-oxocortisol was particularly low in ectopic disease. With the use of 10 selected steroids, subjects with and without different Cushing syndrome subtypes could be discriminated nearly as closely as with the use of salivary and urinary free cortisol, dexamethasone-suppressed cortisol, and plasma adrenocorticotropin (9.5% vs 5.8% misclassification). Patients with different subtypes of Cushing syndrome show distinctive plasma steroid profiles that may offer a supplementary single-test alternative for screening purposes. © 2017 American Association for Clinical Chemistry.

Functions of ectopically transplanted invasive horse trophoblast

PubMed Central

de Mestre, Amanda M.; Hanlon, David; Adams, A. Paige; Runcan, Erin; Leadbeater, Jane C.; Erb, Hollis N.; Costa, Christina C.; Miller, Donald; Allen, W. R; Antczak, Douglas F.

2013-01-01

The invasive and fully antigenic trophoblast of the chorionic girdle portion of the equine fetal membranes has the capacity to survive and differentiate after transplantation to ectopic sites. The objectives of this study were to determine: (i) the survival time of ectopically transplanted allogeneic trophoblast cells in non-pregnant recipient mares, (ii) whether equine Chorionic Gonadotrophin (eCG) can be delivered systemically by transplanted chorionic girdle cells, and (iii) if eCG delivered by the transplanted cells is biologically active and can suppress behavioral signs associated with estrus. Ectopically transplanted chorionic girdle survived for up to 105 days with a mean lifespan of 75 days (95% CI 55–94), and secreted sufficient eCG for the hormone to be measurable in the recipients’ circulation. Immunohistochemical labeling of serial biopsies of the transplant sites and measurement of eCG profiles demonstrated that graft survival was similar to the lifespan of equine endometrial cups in normal horse pregnancy. The eCG secreted by the transplanted cells induced corpora lutea formation and sustained systemic progesterone levels in the recipient mares, effects that are also observed during pregnancy. This in turn caused suppression of estrus behavior in the recipients for up to three months. Thus, ectopically transplanted equine trophoblast provides an unusual example of sustained viability and function of an immunogenic transplant in a recipient with an intact immune system. This model highlights the importance of innate immunoregulatory capabilities of invasive trophoblast cells and describes a new method to deliver sustained circulating concentrations of eCG in non-pregnant mares. PMID:21389079

Pregnancy of unknown location: Outcome in a tertiary care hospital.

PubMed

Amer, Nuzhat; Amer, Muhammad; Kolkaila, Mohamed Abdoh; Yaqoob, Shahida

2015-10-01

To find out the outcome of a cohort of women with pregnancy of unknown location presenting to a tertiary care hospital. The prospective study was conducted from January to December, 2011, at Early Pregnancy Assessment Unit, King Faisal Military Hospital, Khamis Mushait, Saudi Arabia. Data was collected for women with early pregnancy or with history of amenorrhoea, bleeding or pain. These women were investigated with serum beta-human chorionic gonadotrophin levels twice weekly and transvaginal ultrasonography weekly. Expectant management was done for failing pregnancy of unknown location while medical or surgical management was considered for persistent pregnancy of unknown location and ectopic pregnancy. During study period, 7215 patients were admitted, and, of them, 2212(30.6%) were patients with early pregnancy. Meeting the inclusion criteria were 183(2.53%) patients who formed the study sample. There were 131(71.6%) patients presenting with amenorrhoea, 90(49.2%) had bleeding and 93(50.8%) presented with pain. Outcome of 100(54.6%) patients was failing pregnancy of unknown location, 58(31.7%) had intrauterine pregnancy, 14(7.7%) converted to ectopic pregnancy, while 11(6%) had persistent pregnancy of unknown location. All patients with persistent pregnancy of unknown location and 5(36%) patients with ectopic pregnancy were medically treated. Five (36%) patients having ectopic pregnancy were managed surgically. Management of choice for asymptomatic patients having pregnancy of unknown location is expectant management. Most of the patients suspected to have Most of the patients with persistent pregnancy of unknown location and ectopic pregnancy can be managed medically.

Ruptured ectopic pregnancy in a patient with a recent intrauterine abortion.

PubMed

Nugent, P J

1992-01-01

The case of a 33-year-old woman who presented with abdominal pain referable to the lower abdomen is discussed. She had had an uncomplicated intrauterine abortive procedure two weeks earlier. It was determined that a ruptured ectopic pregnancy was the etiology of her abdominal pain. The rare phenomenon of combined intrauterine and extrauterine pregnancy is discussed.

[Non surgical management of ectopic pregnancy].

PubMed

Kdous, Moez

2006-06-01

During the past 25 years, the incidence of ectopic pregnancy has progressively increased while the morbidity and mortality have substantialy decreased, and the treatment has progressed from salpingectomy by laparotomy to conservative surgery by laparoscopy and more recently to medical therapy with Methotrexate or expectant management. This therapeutic transition from surgical emergency to non surgical managment has been attributed to early diagnosis through the use of sensitive assays for hCG and the high definition of vaginal ultrasound. By using these sensitive diagnostic tools, we are now able to select those patients who are most likely to respond to expectant or medical managment versus those who are at high risk of rupture and require surgery. We have reviewed the scientific literature on ectopic pregnancy published over the past 20 years, with the aim to assess the value of non surgical managment of etopic pregnancy. Predictor factors of expectant managment are discussed. Medical therapy with methotrexate: results, indications, Unpleasant side effects and complications are detailed. Several protocols are defined and therapeutic supervision is etablished. The authors offred several recommandations for OB/GY wich will optimize the effectivness of non invasive methods for treatment of ectopic pregnancy.

A challenging case of an ectopic cushing syndrome.

PubMed

Menezes Nunes, Joana; Pinho, Elika; Camões, Isabel; Maciel, João; Cabral Bastos, Pedro; Souto de Moura, Conceição; Bettencourt, Paulo

2014-01-01

Bronchopulmonary carcinoids are rare pulmonary neoplasms although they account for most cases of ectopic ACTH syndromes. When feasible, the mainstay treatment is surgical resection of the tumor. We report the case of a 52-year-old woman with signs and symptoms suggestive of hypercortisolism for 12 months, admitted to our department because of community acquired pneumonia. Blood hormone analysis showed increased levels of ACTH and urinary free cortisol and nonsuppressibility to high- and low-dose dexamethasone tests. Pituitary MRI showed no lesion and no central-to-peripheral ACTH gradient was present in bilateral inferior petrosal sinus sampling. CRH stimulation test suggested an ectopic ACTH source. Thoracic CT scan revealed a nodular region measuring 12 mm located in the inferior lingular lobule of the left superior lung with negative uptake by (18)-FDG-PET scan and negative SRS. The patient was successfully treated with an atypical lung resection and histology revealed an atypical bronchial carcinoid tumor with positive ACTH immunoreactivity. This was an interesting case because the patient was admitted due to pneumonia that may have been associated with her untreated and chronic hypercortisolism and a challenging case of ectopic ACTH syndrome due to conflicting results on the diagnostic exams.

Follicular adenoma in ectopic thyroid. A case-report.

PubMed

Consalvo, Vincenzo; Barbieri, Gerarda; Rossetti, Amalia Rosaria Rita; Romano, Mafalda; Contieri, Rosaria; Tramontano, Salvatore; Rescigno, Carmela; Infranzi, Massimo; Lombardi, Domenico

2017-01-01

The term ectopic thyroid refers to the presence of thyroid tissue located far from its usual anatomic placement and with no vascular connection to the main gland. The presence of swelling in atypical locations is diagnostically differentiated from other pathologies like pleomorphic adenoma or carcinoma, inflammatory lesions like sialadenitis, neurogenic tumors, paraganglioma, fibrolipoma and lymphadenopaties of diverse etiologies. Here we present the case of a submandibular ectopic thyroid in a 67year old woman. She came to our attention for a left submandibular swelling. The anamnesis did not show related pathologies, as well as blood tests. Diagnostic image studies and a FNAC were performed. The mass was surgically removed and histopatology showed a follicular adenoma in the contest of the capsulated lesion. It is important to not underestimate these types of lesions and procede with hematochemical, instrumental tests and above all surgery that can eliminate any diagnostic uncertainty and on the whole be therapeutic. It should not be forgotten that ectopic thyroid tissue can be a site for adenoma or papillary carcinoma and thus any watch and wait strategy should be avoided. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Role of beach morphology in wave overtopping hazard assessment

NASA Astrophysics Data System (ADS)

Phillips, Benjamin; Brown, Jennifer; Bidlot, Jean-Raymond; Plater, Andrew

2017-04-01

Understanding the role of beach morphology in controlling wave overtopping volume will further minimise uncertainties in flood risk assessments at coastal locations defended by engineered structures worldwide. XBeach is used to model wave overtopping volume for a 1:200 yr joint probability distribution of waves and water levels with measured, pre- and post-storm beach profiles. The simulation with measured bathymetry is repeated with and without morphological evolution enabled during the modelled storm event. This research assesses the role of morphology in controlling wave overtopping volumes for hazardous events that meet the typical design level of coastal defence structures. Results show disabling storm-driven morphology under-represents modelled wave overtopping volumes by up to 39% under high Hs conditions, and has a greater impact on the wave overtopping rate than the variability applied within the boundary conditions due to the range of wave-water level combinations that meet the 1:200 yr joint probability criterion. Accounting for morphology in flood modelling is therefore critical for accurately predicting wave overtopping volumes and the resulting flood hazard and to assess economic losses.

Duplex System with Ectopic Ureter Opens into the Posterior Urethra: Case Report.

PubMed

Milicevic, Snjezana; Bijelic, Radojka; Krivokuca, Vladimir; Jakovljevic, Branislava

2018-04-01

Duplicated ureter or Duplex Collecting System is a congenital condition in which the ureteric bud, the embryological origin of the ureter, arises twice, resulting in two ureters draining a single kidney. This congenital anomaly is rare, and even rarer when the duplex system with ectopic ureter is present. This type of congenital anomaly is even more rarely diagnosed and surgically treated in adulthood. This case report presents a case of a 32-year-old male, who had a duplex collecting system with two ureters on the left side. Ectopic ureter, draining the upper pole of the left kidney, opened into the posterior urethra. In our patient, taking into account the clinical perspective, the renal tissue damaging of the upper pole which was not functional, partial nephrectomy and ureterectomy was successfully performed.

Pneumocystis Pneumonia Concomitant with Ectopic ACTH Syndrome Caused by a Large Cell Neuroendocrine Carcinoma of the Thymus.

PubMed

Oda, Naohiro; Miyahara, Nobuaki; Tabata, Masahiro; Minami, Daisuke; Ninomiya, Kiichiro; Kanehiro, Arihiko; Komatsubara, Motoshi; Inagaki, Kenichi; Tanimoto, Mitsune; Kiura, Katsuyuki

2017-01-01

We herein report the case of a 44-year-old man who was diagnosed with pneumocystis pneumonia (PCP) concomitant with ectopic adrenocorticotropic hormone (ACTH) syndrome, which had been caused by a large cell neuroendocrine carcinoma of the thymus. Chest computed tomography revealed ground-glass opacities in the lungs. PCP was diagnosed by a polymerase chain reaction with bronchoalveolar lavage. The levels of cortisol were slowly corrected with an adrenal enzyme inhibitor, and the exacerbation of PCP was successfully avoided. Our case indicates that in addition to prophylaxis, the early diagnosis of PCP and the slow correction of hypercortisolemia should be considered in order to prevent an exacerbation due to the reconstitution of the immune function in patients with ectopic ACTH syndrome.

Pregnancy Luteoma in Ectopic Pregnancy: A Case Report

PubMed Central

Brar, Rupinder Kaur; Bharti, Jyotsna Naresh; Nigam, Jitendra Singh; Sehgal, Sahil; Singh, Hena Paul; Ojha, Pushpanjali

2017-01-01

Background: Pregnancy luteoma is a rare non neoplastic condition of the ovary. It is usually asymptomatic and found incidentally during imaging in pregnancy or during cesarean section. Pregnancy luteoma can also occur after ectopic pregnancy. Case Presentation: A 30 year old female presented to G.B. Pant Hospital, Andaman and Nicobar Islands institute of Medical Sciences, Port Blair in October 2015 with abdominal pain. After initial investigations, exploratory laporotomy was done for ruptured ectopic pregnancy. Enlarged ovary was removed along with the ruptured portion of fallopian tube. Histopathological examination revealed solid aggregates of large cells with abundant eosinophilic cytoplasm; diagnosis of pregnancy luteoma was given. Conclusion: It must be considered in the differential diagnosis of ovarian masses in pregnant females that early diagnosis of this entity may avoid unnecessary radical surgery. PMID:29062798

Dual Pathologies of Parathyroid Adenoma and Papillary Thyroid Cancer on Fluorocholine and Fluorodeoxyglucose PET/CT.

PubMed

Thanseer, N T K; Bhadada, Sanjay Kumar; Sood, Ashwani; Parihar, Ashwin Singh; Dahiya, Divya; Singh, Priyanka; Basher, Rajender Kumar; Das, Ashim; Mittal, Bhagwant R

2018-04-01

18 F-Fluorocholine (FCH) PET/CT is evolving as a functional imaging modality for the preoperative imaging of abnormal parathyroid tissue(s) helping to localize eutopic and ectopic parathyroid tissue and limit the extent of surgery. FCH PET/CT may show incidental uptake in various thyroid lesions necessitating further evaluation, whereas the role of 18 F-fluorodeoxyglucose (FDG) PET/CT in the detection of incidental thyroid nodules is well documented. The case of a middle-aged woman with dual pathology of parathyroid adenoma and papillary thyroid cancer detected on FCH and FDG PET/CT is presented.

[Healthy obesity? Why the adiposity paradox is only seemingly paradox].

PubMed

Ströhle, Alexander; Worm, Nicolai

2014-02-01

The health consequences of being overweight have been discussed controversially. Indeed, from a metabolic point of view, overweight and obese people are quite heterogenous. The body mass index (BMI) is not suitable to predict health oriented outcomes on an individual level without taking into account further parameters such as waist circumference, blood pressure, serum glucose, serum lipids, and physical fitness. The BMI does not distinguish between metabolically healthy and metabolically unhealthy. Of upmost importance for health consequences of obesity is body fat distribution. Two types of principally different fat distribution can be identified: abdominal and gluteofemoral fat. Waist circumference and hip circumference can be utilized to distinguish between those two types. People with accumulation of body fat in the abdominal region have a markedly higher risk of developing type-2-diabetes and cardiovascular disease. Moreover, their total mortality is increased. On the other hand, waist circumference is not sufficiently capable of indicating individual risk. Instead, the amount of visceral fat is believed to be a primary risk factor because of its metabolic characteristics (i. e. increased lipolysis, diabetogenic and atherogenic adipokine profile). Recent findings point to visceral fat being more an indicator of the parallel accumulation of fat deposits in organs placed in the abdomen. The accumulation of lipids in tissues not primary intended for fat storage is called,,ectopic fat". It can be found in muscle, liver, pancreas, and kidney. The fattening of those organs is now considered to have the key role in the pathogenesis of type-2-diabetes. The pathophysiological effects of ectopic fat and the associated metabolic derangements can solve the conflicting findings concerning health consequences of BMI--at least in part. Moreover, these findings may have therapeutic consequences. The reduction of ectopic fat as well as the modification of its metabolic effects - via dietetic, bariatric or pharmaceutic means - opens up the pathway to counteract impaired glucose tolerance early and in a causal way.

Cross-regulation in the mouse HoxB complex: the expression of Hoxb2 in rhombomere 4 is regulated by Hoxb1.

PubMed

Maconochie, M K; Nonchev, S; Studer, M; Chan, S K; Pöpperl, H; Sham, M H; Mann, R S; Krumlauf, R

1997-07-15

Correct regulation of the segment-restricted patterns of Hox gene expression is essential for proper patterning of the vertebrate hindbrain. We have examined the molecular basis of restricted expression of Hoxb2 in rhombomere 4 (r4), by using deletion analysis in transgenic mice to identify an r4 enhancer from the mouse gene. A bipartite Hox/Pbx binding motif is located within this enhancer, and in vitro DNA binding experiments showed that the vertebrate labial-related protein Hoxb1 will cooperatively bind to this site in a Pbx/Exd-dependent manner. The Hoxb2 r4 enhancer can be transactivated in vivo by the ectopic expression of Hoxb1, Hoxa1, and Drosophila labial in transgenic mice. In contrast, ectopic Hoxb2 and Hoxb4 are unable to induce expression, indicating that in vivo this enhancer preferentially responds to labial family members. Mutational analysis demonstrated that the bipartite Hox/Pbx motif is required for r4 enhancer activity and the responses to retinoids and ectopic Hox expression. Furthermore, three copies of the Hoxb2 motif are sufficient to mediate r4 expression in transgenic mouse embryos and a labial pattern in Drosophila embryos. This reporter expression in Drosophila embryos is dependent upon endogenous labial and exd, suggesting that the ability of this Hox/Pbx site to interact with labial-related proteins has been evolutionarily conserved. The endogenous Hoxb2 gene is no longer upregulated in r4 in Hoxb1 homozygous mutant embryos. On the basis of these experiments we conclude that the r4-restricted domain of Hoxb2 in the hindbrain is the result of a direct cross-regulatory interaction by Hoxb1 involving vertebrate Pbx proteins as cofactors. This suggests that part of the functional role of Hoxb1 in maintaining r4 identity may be mediated by the Hoxb2 gene.

Drosophila Syd-1, Liprin-α, and Protein Phosphatase 2A B′ Subunit Wrd Function in a Linear Pathway to Prevent Ectopic Accumulation of Synaptic Materials in Distal Axons

PubMed Central

Li, Long; Tian, Xiaolin; Zhu, Mingwei; Bulgari, Dinara; Böhme, Mathias A.; Goettfert, Fabian; Wichmann, Carolin; Sigrist, Stephan J.; Levitan, Edwin S.

2014-01-01

During synaptic development, presynaptic differentiation occurs as an intrinsic property of axons to form specialized areas of plasma membrane [active zones (AZs)] that regulate exocytosis and endocytosis of synaptic vesicles. Genetic and biochemical studies in vertebrate and invertebrate model systems have identified a number of proteins involved in AZ assembly. However, elucidating the molecular events of AZ assembly in a spatiotemporal manner remains a challenge. Syd-1 (synapse defective-1) and Liprin-α have been identified as two master organizers of AZ assembly. Genetic and imaging analyses in invertebrates show that Syd-1 works upstream of Liprin-α in synaptic assembly through undefined mechanisms. To understand molecular pathways downstream of Liprin-α, we performed a proteomic screen of Liprin-α-interacting proteins in Drosophila brains. We identify Drosophila protein phosphatase 2A (PP2A) regulatory subunit B′ [Wrd (Well Rounded)] as a Liprin-α-interacting protein, and we demonstrate that it mediates the interaction of Liprin-α with PP2A holoenzyme and the Liprin-α-dependent synaptic localization of PP2A. Interestingly, loss of function in syd-1, liprin-α, or wrd shares a common defect in which a portion of synaptic vesicles, dense-core vesicles, and presynaptic cytomatrix proteins ectopically accumulate at the distal, but not proximal, region of motoneuron axons. Strong genetic data show that a linear syd-1/liprin-α/wrd pathway in the motoneuron antagonizes glycogen synthase kinase-3β kinase activity to prevent the ectopic accumulation of synaptic materials. Furthermore, we provide data suggesting that the syd-1/liprin-α/wrd pathway stabilizes AZ specification at the nerve terminal and that such a novel function is independent of the roles of syd-1/liprin-α in regulating the morphology of the T-bar structural protein BRP (Bruchpilot). PMID:24948803

Drosophila Syd-1, liprin-α, and protein phosphatase 2A B' subunit Wrd function in a linear pathway to prevent ectopic accumulation of synaptic materials in distal axons.

PubMed

Li, Long; Tian, Xiaolin; Zhu, Mingwei; Bulgari, Dinara; Böhme, Mathias A; Goettfert, Fabian; Wichmann, Carolin; Sigrist, Stephan J; Levitan, Edwin S; Wu, Chunlai

2014-06-18

During synaptic development, presynaptic differentiation occurs as an intrinsic property of axons to form specialized areas of plasma membrane [active zones (AZs)] that regulate exocytosis and endocytosis of synaptic vesicles. Genetic and biochemical studies in vertebrate and invertebrate model systems have identified a number of proteins involved in AZ assembly. However, elucidating the molecular events of AZ assembly in a spatiotemporal manner remains a challenge. Syd-1 (synapse defective-1) and Liprin-α have been identified as two master organizers of AZ assembly. Genetic and imaging analyses in invertebrates show that Syd-1 works upstream of Liprin-α in synaptic assembly through undefined mechanisms. To understand molecular pathways downstream of Liprin-α, we performed a proteomic screen of Liprin-α-interacting proteins in Drosophila brains. We identify Drosophila protein phosphatase 2A (PP2A) regulatory subunit B' [Wrd (Well Rounded)] as a Liprin-α-interacting protein, and we demonstrate that it mediates the interaction of Liprin-α with PP2A holoenzyme and the Liprin-α-dependent synaptic localization of PP2A. Interestingly, loss of function in syd-1, liprin-α, or wrd shares a common defect in which a portion of synaptic vesicles, dense-core vesicles, and presynaptic cytomatrix proteins ectopically accumulate at the distal, but not proximal, region of motoneuron axons. Strong genetic data show that a linear syd-1/liprin-α/wrd pathway in the motoneuron antagonizes glycogen synthase kinase-3β kinase activity to prevent the ectopic accumulation of synaptic materials. Furthermore, we provide data suggesting that the syd-1/liprin-α/wrd pathway stabilizes AZ specification at the nerve terminal and that such a novel function is independent of the roles of syd-1/liprin-α in regulating the morphology of the T-bar structural protein BRP (Bruchpilot). Copyright © 2014 the authors 0270-6474/14/348474-14$15.00/0.

Role of day 4 HCG as an early predictor of success after methotrexate therapy for ectopic pregnancies.

PubMed

Girija, S; Manjunath, A P; Salahudin, A; Jeyaseelan, L; Gowri, V; Abu-Heija, A; Al Kharusi, L

2017-08-01

To validate whether change in serum HCG levels between days 0 and 4 confer any prognostic value during methotrexate therapy and to quantify its change. This is a retrospective study of 48 tubal ectopic pregnancies treated with single dose methotrexate protocol at University Hospital, Muscat, Oman from January 2012 to December 2013. The clinical outcome was analyzed based on the complete resolution of HCG levels or need for additional doses of methotrexate or recourse to surgery. The percentage change in HCG levels between days 0 and 4 (HCG index) of methotrexate were calculated and receiver operator characteristics curve was plotted to identify the best cutoff levels. In order to get a robust 95% confidence interval, bootstrap method using R software was done using 1000 re-sampling. ROC curve and the predictive values were estimated using MEDCALC software. The mean HCG level on day 4 is significantly higher in treatment failure group (4254±4095 IU/L vs. 2109±3646 IU/L, P=0.008). The HCG levels between day 0 and 4 decreased in 42.7% (21/48) of cases and 80.9% of these cases had treatment success. The HCG levels increased in 57.4% (27/48) of cases and 33.3% of these cases had treatment success. (P=0.001). A 10 percent decline in day 4 HCG levels predict the treatment success with sensitivity of 77% and Specificity 81%. The area under the ROC curve was 0.82 (95% CI: 0.67-0.92), (P<0.001). The success with single dose of methotrexate therapy for tubal ectopic pregnancies was predicted early in the course of treatment by following three key findings: the absolute mean HCG values on day 4, decrease in HCG level from day 0 to 4 and 10% or more fall in day 4 HCG levels. Copyright © 2017 Elsevier B.V. All rights reserved.

Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.

PubMed

Oishi, Teruyo; Uezumi, Akiyoshi; Kanaji, Arihiko; Yamamoto, Naoki; Yamaguchi, Asami; Yamada, Harumoto; Tsuchida, Kunihiro

2013-01-01

Heterotopic ossification (HO) is defined as the formation of ectopic bone in soft tissue outside the skeletal tissue. HO is thought to result from aberrant differentiation of osteogenic progenitors within skeletal muscle. However, the precise origin of HO is still unclear. Skeletal muscle contains two kinds of progenitor cells, myogenic progenitors and mesenchymal progenitors. Myogenic and mesenchymal progenitors in human skeletal muscle can be identified as CD56(+) and PDGFRα(+) cells, respectively. The purpose of this study was to investigate the osteogenic differentiation potential of human skeletal muscle-derived progenitors. Both CD56(+) cells and PDGFRα(+) cells showed comparable osteogenic differentiation potential in vitro. However, in an in vivo ectopic bone formation model, PDGFRα(+) cells formed bone-like tissue and showed successful engraftment, while CD56(+) cells did not form bone-like tissue and did not adapt to an osteogenic environment. Immunohistological analysis of human HO sample revealed that many PDGFRα(+) cells were localized in proximity to ectopic bone formed in skeletal muscle. MicroRNAs (miRNAs) are known to regulate many biological processes including osteogenic differentiation. We investigated the participation of miRNAs in the osteogenic differentiation of PDGFRα(+) cells by using microarray. We identified miRNAs that had not been known to be involved in osteogenesis but showed dramatic changes during osteogenic differentiation of PDGFRα(+) cells. Upregulation of miR-146b-5p and -424 and downregulation of miR-7 during osteogenic differentiation of PDGFRα(+) cells were confirmed by quantitative real-time RT-PCR. Inhibition of upregulated miRNAs, miR-146b-5p and -424, resulted in the suppression of osteocyte maturation, suggesting that these two miRNAs have the positive role in the osteogenesis of PDGFRα(+) cells. Our results suggest that PDGFRα(+) cells may be the major source of HO and that the newly identified miRNAs may regulate osteogenic differentiation process of PDGFRα(+) cells.

Prognostic factors in ectopic Cushing's syndrome due to neuroendocrine tumors: a multicenter study.

PubMed

Davi', Maria Vittoria; Cosaro, Elisa; Piacentini, Serena; Reimondo, Giuseppe; Albiger, Nora; Arnaldi, Giorgio; Faggiano, Antongiulio; Mantovani, Giovanna; Fazio, Nicola; Piovesan, Alessandro; Arvat, Emanuela; Grimaldi, Franco; Canu, Letizia; Mannelli, Massimo; Ambrogio, Alberto Giacinto; Pecori Giraldi, Francesca; Martini, Chiara; Lania, Andrea; Albertelli, Manuela; Ferone, Diego; Zatelli, Maria Chiara; Campana, Davide; Colao, Annamaria; Scaroni, Carla; Terzolo, Massimo; De Marinis, Laura; Cingarlini, Sara; Micciolo, Rocco; Francia, Giuseppe

2017-04-01

Evidence is limited regarding outcome of patients with ectopic Cushing's syndrome (ECS) due to neuroendocrine tumors (NETs). We assessed the prognostic factors affecting the survival of patients with NETs and ECS. Retrospective analysis of clinicopathological features, severity of hormonal syndrome, treatments from a large cohort of patients with NETs and ECS collected from 17 Italian centers. Our series included 110 patients, 58.2% female, with mean (±s.d.) age at diagnosis of 49.5 ± 15.9 years. The main sources of ectopic ACTH were bronchial carcinoids (BC) (40.9%), occult tumors (22.7%) and pancreatic (p)NETs (15.5%). Curative surgery was performed in 56.7% (70.2% of BC, 11% of pNETs). Overall survival was significantly higher in BC compared with pNETs and occult tumors ( P  = 0.033) and in G1-NETs compared with G2 and G3 ( P  = 0.007). Negative predictive factors for survival were severity of hypercortisolism ( P  < 0.02), hypokalemia ( P  = 0.001), diabetes mellitus ( P  = 0.0146) and distant metastases ( P  < 0.001). Improved survival was observed in patients who underwent NET removal ( P  < 0.001). Adrenalectomy improved short-term survival. Multiple factors affect prognosis of ECS patients: type of NET, grading, distant metastases, severity of hypercortisolism, hypokalemia and diabetes mellitus. BCs have the highest curative surgical rate and better survival compared with occult tumors and pNETs. Hypercortisolism plays a primary role in affecting outcome and quality of life; therefore, prompt and vigorous treatment of hormonal excess by NET surgery and medical therapy should be a key therapeutic goal. In refractory cases, adrenalectomy should be considered as it affects outcome positively at least in the first 2 years. © 2017 European Society of Endocrinology.

Translational repression by an RNA-binding protein promotes differentiation to infective forms in Trypanosoma cruzi.

PubMed

Romaniuk, Maria Albertina; Frasch, Alberto Carlos; Cassola, Alejandro

2018-06-01

Trypanosomes, protozoan parasites of medical importance, essentially rely on post-transcriptional mechanisms to regulate gene expression in insect vectors and vertebrate hosts. RNA binding proteins (RBPs) that associate to the 3'-UTR of mature mRNAs are thought to orchestrate master developmental programs for these processes to happen. Yet, the molecular mechanisms by which differentiation occurs remain largely unexplored in these human pathogens. Here, we show that ectopic inducible expression of the RBP TcUBP1 promotes the beginning of the differentiation process from non-infective epimastigotes to infective metacyclic trypomastigotes in Trypanosoma cruzi. In early-log epimastigotes TcUBP1 promoted a drop-like phenotype, which is characterized by the presence of metacyclogenesis hallmarks, namely repositioning of the kinetoplast, the expression of an infective-stage virulence factor such as trans-sialidase, increased resistance to lysis by human complement and growth arrest. Furthermore, TcUBP1-ectopic expression in non-infective late-log epimastigotes promoted full development into metacyclic trypomastigotes. TcUBP1-derived metacyclic trypomastigotes were infective in cultured cells, and developed normally into amastigotes in the cytoplasm. By artificial in vivo tethering of TcUBP1 to the 3' untranslated region of a reporter mRNA we were able to determine that translation of the reporter was reduced by 8-fold, while its mRNA abundance was not significantly compromised. Inducible ectopic expression of TcUBP1 confirmed its role as a translational repressor, revealing significant reduction in the translation rate of multiple proteins, a reduction of polysomes, and promoting the formation of mRNA granules. Expression of TcUBP1 truncated forms revealed the requirement of both N and C-terminal glutamine-rich low complexity sequences for the development of the drop-like phenotype in early-log epimastigotes. We propose that a rise in TcUBP1 levels, in synchrony with nutritional deficiency, can promote the differentiation of T. cruzi epimastigotes into infective metacyclic trypomastigotes.

Is the type of gonadotropin-releasing hormone suppression protocol for ovarian hyperstimulation associated with ectopic pregnancy in fresh autologous cycles for in vitro fertilization?

PubMed

Londra, Laura; Moreau, Caroline; Strobino, Donna; Bhasin, Aarti; Zhao, Yulian

2016-09-01

To evaluate the association between different ovarian hyperstimulation protocols and ectopic pregnancy (EP) in in vitro fertilization (IVF) cycles in fresh autologous embryo transfer cycles in the United States between 2008 and 2011 as reported to the Society of Assisted Reproductive Technology (SART). Historical cohort study. Not applicable. None. None. All autologous cycles that resulted in a clinical pregnancy after a fresh, intrauterine embryo transfer and described characteristics of cycles according to protocol were included: luteal GnRH agonist, GnRH agonist flare, or GnRH antagonist. Multivariate logistic regression was conducted to investigate the association between type of protocol and EP. Among 136,605 clinical pregnancies, 2,645 (1.94%) were EP. Ectopic pregnancy was more frequent with GnRH antagonist (2.4%) cycles than with GnRH agonist flare (2.1%) or luteal GnRH agonist (1.6%) cycles. After adjusting for maternal and treatment characteristics, the GnRH antagonist and the GnRH agonist flare protocols were associated with increased odds of EP (adjusted odds ratio [aOR] 1.52; 95% confidence interval [CI], 1.39-1.65; and aOR 1.25; 95% CI, 1.09-1.44, respectively) compared with luteal GnRH agonist. Analysis of differences in the factors related to EP in luteal GnRH agonist versus GnRH antagonist protocols indicated that diminished ovarian reserve was associated with an increased risk of EP in luteal GnRH agonist but not in GnRH antagonist cycles. The type of protocol used during ovarian hyperstimulation in fresh autologous cycles was associated with EP. This finding suggests a role for extrapituitary GnRH on the tubal and uterine environment during ovarian hyperstimulation treatment for IVF. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Genomic Landscape of Long Terminal Repeat Retrotransposons (LTR-RTs) and Solo LTRs as Shaped by Ectopic Recombination in Chicken and Zebra Finch.

PubMed

Ji, Yanzhu; DeWoody, J Andrew

2016-06-01

Transposable elements (TEs) are nearly ubiquitous among eukaryotic genomes, but TE contents vary dramatically among phylogenetic lineages. Several mechanisms have been proposed as drivers of TE dynamics in genomes, including the fixation/loss of a particular TE insertion by selection or drift as well as structural changes in the genome due to mutation (e.g., recombination). In particular, recombination can have a significant and directional effect on the genomic TE landscape. For example, ectopic recombination removes internal regions of long terminal repeat retrotransposons (LTR-RTs) as well as one long terminal repeat (LTR), resulting in a solo LTR. In this study, we focus on the intra-species dynamics of LTR-RTs and solo LTRs in bird genomes. The distribution of LTR-RTs and solo LTRs in birds is intriguing because avian recombination rates vary widely within a given genome. We used published linkage maps and whole genome assemblies to study the relationship between recombination rates and LTR-removal events in the chicken and zebra finch. We hypothesized that regions with low recombination rates would harbor more full-length LTR-RTs (and fewer solo LTRs) than regions with high recombination rates. We tested this hypothesis by comparing the ratio of full-length LTR-RTs and solo LTRs across chromosomes, across non-overlapping megabase windows, and across physical features (i.e., centromeres and telomeres). The chicken data statistically supported the hypothesis that recombination rates are inversely correlated with the ratio of full-length to solo LTRs at both the chromosome level and in 1-Mb non-overlapping windows. We also found that the ratio of full-length to solo LTRs near chicken telomeres was significantly lower than those ratios near centromeres. Our results suggest a potential role of ectopic recombination in shaping the chicken LTR-RT genomic landscape.

Wave particle interactions in Jupiter's magnetosphere: Implications for auroral and magnetospheric particle distributions

NASA Astrophysics Data System (ADS)

Saur, Joachim; Schreiner, Anne; Barry, Mauk; Clark, George; Kollman, Peter

2017-04-01

We investigate the occurrence and the role of wave particle interaction processes, i.e., Landau and cyclotron damping, in Jupiter's magnetosphere. Therefore we calculate kinetic length and temporal scales, which we cross-compare at various regions within Jupiter's magnetosphere. Based on these scales, we investigate the roles of possible wave particle mechanisms in each region, e.g., Jupiter's plasma sheet, the auroral acceleration region and the polar ionosphere. We thereby consider that the magnetospheric regions are coupled through convective transport, Alfven and other wave modes. We particularly focus on the role of kinetic Alfven waves in contributing to Jupiter's aurora. Our results will aid the interpretation of particle distribution functions measured by the JEDI instrument onboard the JUNO spacecraft.

Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications

PubMed Central

Torossian, Frédéric; Guerton, Bernadette; Anginot, Adrienne; Alexander, Kylie A.; Desterke, Christophe; Soave, Sabrina; Tseng, Hsu-Wen; Arouche, Nassim; Boutin, Laetitia; Kulina, Irina; Salga, Marjorie; Jose, Beulah; Pettit, Allison R.; Clay, Denis; Vlachos, Erica; Genet, Guillaume; Debaud, Charlotte; Denormandie, Philippe; Genet, François; Sims, Natalie A.; Banzet, Sébastien; Levesque, Jean-Pierre; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline

2017-01-01

Neurogenic heterotopic ossification (NHO) is the formation of ectopic bone generally in muscles surrounding joints following spinal cord or brain injury. We investigated the mechanisms of NHO formation in 64 patients and a mouse model of spinal cord injury–induced NHO. We show that marrow from human NHOs contains hematopoietic stem cell (HSC) niches, in which mesenchymal stromal cells (MSCs) and endothelial cells provide an environment supporting HSC maintenance, proliferation, and differentiation. The transcriptomic signature of MSCs from NHOs shows a neuronal imprinting associated with a molecular network required for HSC support. We demonstrate that oncostatin M (OSM) produced by activated macrophages promotes osteoblastic differentiation and mineralization of human muscle-derived stromal cells surrounding NHOs. The key role of OSM was confirmed using an experimental model of NHO in mice defective for the OSM receptor (OSMR). Our results provide strong evidence that macrophages contribute to NHO formation through the osteogenic action of OSM on muscle cells within an inflammatory context and suggest that OSM/OSMR could be a suitable therapeutic target. Altogether, the evidence of HSCs in ectopic bones growing at the expense of soft tissue in spinal cord/brain-injured patients indicates that inflammation and muscle contribute to HSC regulation by the brain-bone-blood triad. PMID:29093266

Conditions that influence the response to Fgf during otic placode induction

PubMed Central

Padanad, Mahesh S.; Bhat, Neha; Guo, BiWei; Riley, Bruce B.

2016-01-01

Despite the vital importance of Fgf for otic induction, previous attempts to study otic induction through Fgf misexpression have yielded widely varying and contradictory results. There are also discrepancies regarding the ability of Fgf to induce otic tissue in ectopic locations, raising questions about the sufficiency of Fgf and the degree to which other local factors enhance or restrict otic potential. Using heat shock-inducible transgenes to misexpress Fgf3 or Fgf8 in zebrafish, we found that the stage, distribution and level of misexpression strongly influence the response to Fgf. Fgf misexpression during gastrulation can inhibit or promote otic development, depending on context, whereas misexpression after gastrulation leads to expansion of otic markers throughout preplacodal ectoderm surrounding the head. Elevated Fgf also expands expression of the putative competence factor Foxi1, which is required for Fgf to expand other otic markers. Misexpression of downstream factors Pax2a or Pax8 also expands otic markers but cannot bypass the requirement for Fgf or Foxi1. Co-misexpression of Pax2/8 with Fgf8 potentiates formation of ectopic otic vesicles expressing a full range of otic markers. These findings document the variables critically affecting the response to Fgf and clarify the roles of foxi1 and pax2/8 in the otic response. PMID:22327005

Involvement of calprotectin (S100A8/A9) in molecular pathways associated with HNSCC

PubMed Central

Khammanivong, Ali; Sorenson, Brent S.; Ross, Karen F.; Dickerson, Erin B.; Hasina, Rifat; Lingen, Mark W.; Herzberg, Mark C.

2016-01-01

Calprotectin (S100A8/A9), a heterodimeric protein complex of calcium-binding proteins S100A8 and S100A9, plays key roles in cell cycle regulation and inflammation, with potential functions in squamous cell differentiation. While upregulated in many cancers, S100A8/A9 is downregulated in squamous cell carcinomas of the cervix, esophagus, and the head and neck (HNSCC). We previously reported that ectopic S100A8/A9 expression inhibits cell cycle progression in carcinoma cells. Here, we show that declining expression of S100A8/A9 in patients with HNSCC is associated with increased DNA methylation, less differentiated tumors, and reduced overall survival. Upon ectopic over-expression of S100A8/A9, the cancer phenotype of S100A8/A9-negative carcinoma cells was suppressed in vitro and tumor growth in vivo was significantly decreased. MMP1, INHBA, FST, LAMC2, CCL3, SULF1, and SLC16A1 were significantly upregulated in HNSCC but were downregulated by S100A8/A9 expression. Our findings strongly suggest that downregulation of S100A8/A9 through epigenetic mechanisms may contribute to increased proliferation, malignant transformation, and disease progression in HNSCC. PMID:26883112

Involvement of calprotectin (S100A8/A9) in molecular pathways associated with HNSCC.

PubMed

Khammanivong, Ali; Sorenson, Brent S; Ross, Karen F; Dickerson, Erin B; Hasina, Rifat; Lingen, Mark W; Herzberg, Mark C

2016-03-22

Calprotectin (S100A8/A9), a heterodimeric protein complex of calcium-binding proteins S100A8 and S100A9, plays key roles in cell cycle regulation and inflammation, with potential functions in squamous cell differentiation. While upregulated in many cancers, S100A8/A9 is downregulated in squamous cell carcinomas of the cervix, esophagus, and the head and neck (HNSCC). We previously reported that ectopic S100A8/A9 expression inhibits cell cycle progression in carcinoma cells. Here, we show that declining expression of S100A8/A9 in patients with HNSCC is associated with increased DNA methylation, less differentiated tumors, and reduced overall survival. Upon ectopic over-expression of S100A8/A9, the cancer phenotype of S100A8/A9-negative carcinoma cells was suppressed in vitro and tumor growth in vivo was significantly decreased. MMP1, INHBA, FST, LAMC2, CCL3, SULF1, and SLC16A1 were significantly upregulated in HNSCC but were downregulated by S100A8/A9 expression. Our findings strongly suggest that downregulation of S100A8/A9 through epigenetic mechanisms may contribute to increased proliferation, malignant transformation, and disease progression in HNSCC.

Mutations in the murine homologue of TUBB5 cause microcephaly by perturbing cell cycle progression and inducing p53-associated apoptosis.

PubMed

Breuss, Martin; Fritz, Tanja; Gstrein, Thomas; Chan, Kelvin; Ushakova, Lyubov; Yu, Nuo; Vonberg, Frederick W; Werner, Barbara; Elling, Ulrich; Keays, David A

2016-04-01

Microtubules play a crucial role in the generation, migration and differentiation of nascent neurons in the developing vertebrate brain. Mutations in the constituents of microtubules, the tubulins, are known to cause an array of neurological disorders, including lissencephaly, polymicrogyria and microcephaly. In this study we explore the genetic and cellular mechanisms that cause TUBB5-associated microcephaly by exploiting two new mouse models: a conditional E401K knock-in, and a conditional knockout animal. These mice present with profound microcephaly due to a loss of upper-layer neurons that correlates with massive apoptosis and upregulation of p53. This phenotype is associated with a delay in cell cycle progression and ectopic DNA elements in progenitors, which is dependent on the dosage of functional Tubb5. Strikingly, we report ectopic Sox2-positive progenitors and defects in spindle orientation in our knock-in mouse line, which are absent in knockout animals. This work sheds light on the functional repertoire of Tubb5, reveals that the E401K mutation acts by a complex mechanism, and demonstrates that the cellular pathology driving TUBB5-associated microcephaly is cell death. © 2016. Published by The Company of Biologists Ltd.

Traffic jam functions in a branched pathway from Notch activation to niche cell fate.

PubMed

Wingert, Lindsey; DiNardo, Stephen

2015-07-01

The niche directs key behaviors of its resident stem cells, and is thus crucial for tissue maintenance, repair and longevity. However, little is known about the genetic pathways that guide niche specification and development. The male germline stem cell niche in Drosophila houses two stem cell populations and is specified within the embryonic gonad, thus making it an excellent model for studying niche development. The hub cells that form the niche are specified early by Notch activation. Over the next few hours, these individual cells then cluster together and take up a defined position before expressing markers of hub cell differentiation. This timing suggests that there are other factors for niche development yet to be defined. Here, we have identified a role for the large Maf transcription factor Traffic jam (Tj) in hub cell specification downstream of Notch. Tj downregulation is the first detectable effect of Notch activation in hub cells. Furthermore, Tj depletion is sufficient to generate ectopic hub cells that can recruit stem cells. Surprisingly, ectopic niche cells in tj mutants remain dispersed in the absence of Notch activation. This led us to uncover a branched pathway downstream of Notch in which Bowl functions to direct hub cell assembly in parallel to Tj downregulation. © 2015. Published by The Company of Biologists Ltd.

Distinct effects of tubulin isotype mutations on neurite growth in Caenorhabditis elegans

PubMed Central

Zheng, Chaogu; Diaz-Cuadros, Margarete; Nguyen, Ken C. Q.; Hall, David H.; Chalfie, Martin

2017-01-01

Tubulins, the building block of microtubules (MTs), play a critical role in both supporting and regulating neurite growth. Eukaryotic genomes contain multiple tubulin isotypes, and their missense mutations cause a range of neurodevelopmental defects. Using the Caenorhabditis elegans touch receptor neurons, we analyzed the effects of 67 tubulin missense mutations on neurite growth. Three types of mutations emerged: 1) loss-of-function mutations, which cause mild defects in neurite growth; 2) antimorphic mutations, which map to the GTP binding site and intradimer and interdimer interfaces, significantly reduce MT stability, and cause severe neurite growth defects; and 3) neomorphic mutations, which map to the exterior surface, increase MT stability, and cause ectopic neurite growth. Structure-function analysis reveals a causal relationship between tubulin structure and MT stability. This stability affects neuronal morphogenesis. As part of this analysis, we engineered several disease-associated human tubulin mutations into C. elegans genes and examined their impact on neuronal development at the cellular level. We also discovered an α-tubulin (TBA-7) that appears to destabilize MTs. Loss of TBA-7 led to the formation of hyperstable MTs and the generation of ectopic neurites; the lack of potential sites for polyamination and polyglutamination on TBA-7 may be responsible for this destabilization. PMID:28835377

Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates.

PubMed

Shikhagaie, Medya Mara; Björklund, Åsa K; Mjösberg, Jenny; Erjefält, Jonas S; Cornelissen, Anne S; Ros, Xavier Romero; Bal, Suzanne M; Koning, Jasper J; Mebius, Reina E; Mori, Michiko; Bruchard, Melanie; Blom, Bianca; Spits, Hergen

2017-02-14

Here, we characterize a subset of ILC3s that express Neuropilin1 (NRP1) and are present in lymphoid tissues, but not in the peripheral blood or skin. NRP1 + group 3 innate lymphoid cells (ILC3s) display in vitro lymphoid tissue inducer (LTi) activity. In agreement with this, NRP1 + ILC3s are mainly located in proximity to high endothelial venules (HEVs) and express cell surface molecules involved in lymphocyte migration in secondary lymphoid tissues via HEVs. NRP1 was also expressed on mouse fetal LTi cells, indicating that NRP1 is a conserved marker for LTi cells. Human NRP1 + ILC3s are primed cells because they express CD45RO and produce higher amounts of cytokines than NRP1 - cells, which express CD45RA. The NRP1 ligand vascular endothelial growth factor A (VEGF-A) served as a chemotactic factor for NRP1 + ILC3s. NRP1 + ILC3s are present in lung tissues from smokers and patients with chronic obstructive pulmonary disease, suggesting a role in angiogenesis and/or the initiation of ectopic pulmonary lymphoid aggregates. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Ectopic expression of a Catalpa bungei (Bignoniaceae) PISTILLATA homologue rescues the petal and stamen identities in Arabidopsis pi-1 mutant.

PubMed

Jing, Danlong; Xia, Yan; Chen, Faju; Wang, Zhi; Zhang, Shougong; Wang, Junhui

2015-02-01

PISTILLATA (PI) plays crucial roles in Arabidopsis flower development by specifying petal and stamen identities. To investigate the molecular mechanisms underlying organ development of woody angiosperm in Catalpa, we isolated and identified a PI homologue, referred to as CabuPI (C. bungei PISTILLATA), from two genetically cognate C. bungei (Bignoniaceae) bearing single and double flowers. Sequence and phylogenetic analyses revealed that the gene is closest related to the eudicot PI homologues. Moreover, a highly conserved PI-motif is found in the C-terminal regions of CabuPI. Semi-quantitative and quantitative real time PCR analyses showed that the expression of CabuPI was restricted to petals and stamens. However, CabuPI expression in the petals and stamens persisted throughout all floral development stages, but the expression levels were different. In 35S::CabuPI transgenic homozygous pi-1 mutant Arabidopsis, the second and the third whorl floral organs produced normal petals and a different number of stamens, respectively. Furthermore, ectopic expression of the CabuPI in transgenic wild-type or heterozygote pi-1 mutant Arabidopsis caused the first whorl sepal partially converted into a petal-like structure. These results clearly reveal the functional conservation of PI homologues between C. bungei and Arabidopsis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

First-trimester emergencies: a radiologist's perspective.

PubMed

Phillips, Catherine H; Wortman, Jeremy R; Ginsburg, Elizabeth S; Sodickson, Aaron D; Doubilet, Peter M; Khurana, Bharti

2018-02-01

The purpose of this article is to help the practitioner ensure early diagnosis and response to emergencies in the first trimester by reviewing anatomy of the developing embryo, highlighting the sonographic appearance of common first-trimester emergencies, and discussing key management pathways for treating emergent cases. First-trimester fetal development is a stepwise process that can be challenging to evaluate in the emergency department (ED) setting. This is due, in part, to the complex anatomy of early pregnancy, subtlety of the sonographic findings, and the fact that fewer than half of patients with ectopic pregnancy present with the classic clinical findings of a positive pregnancy test, vaginal bleeding, pelvic pain, and tender adnexa. Ultrasound (US) has been the primary approach to diagnostic imaging of first-trimester emergencies, with magnetic resonance imaging (MRI) and computed tomography (CT) playing a supportive role in a small minority of cases. Familiarity with the sonographic findings diagnostic of and suspicious for early pregnancy failure, ectopic pregnancy, retained products of conception, gestational trophoblastic disease, failed intrauterine devices, and complications associated with assisted reproductive technology (ART) is critical for any emergency radiologist. Evaluation of first-trimester emergencies is challenging, and knowledge of key imaging findings and familiarity with management pathways are needed to ensure early diagnosis and response.

A Novel Nitronyl Nitroxide with Salicylic Acid Framework Attenuates Pain Hypersensitivity and Ectopic Neuronal Discharges in Radicular Low Back Pain.

PubMed

Han, Wen-Juan; Chen, Lei; Wang, Hai-Bo; Liu, Xiang-Zeng; Hu, San-Jue; Sun, Xiao-Li; Luo, Ceng

2015-01-01

Evidence has accumulated that reactive oxygen species and inflammation play crucial roles in the development of chronic pain, including radicular low back pain. Nonsteroid anti-inflammatory drugs (NSAIDs), for example, salicylic acid, aspirin, provided analgesic effects in various types of pain. However, long-term use of these drugs causes unwanted side effects, which limits their implication. Stable nitronyl (NIT) nitroxide radicals have been extensively studied as a unique and interesting class of new antioxidants for protection against oxidative damage. The present study synthesized a novel NIT nitroxide radical with salicylic acid framework (SANR) to provide synergistic effect of both antioxidation and antiinflammation. We demonstrated for the first time that both acute and repeated SANR treatment exerted dramatic analgesic effect in radicular low back pain mimicked by chronic compression of dorsal root ganglion in rats. This analgesic potency was more potent than that produced by classical NSAIDs aspirin and traditional nitroxide radical Tempol alone. Furthermore, SANR-induced behavioral analgesia is found to be mediated, at least in partial, by a reduction of ectopic spontaneous discharges in injured DRG neurons. Therefore, the synthesized NIT nitroxide radical coupling with salicylic acid framework may represent a novel potential therapeutic candidate for treatment of chronic pain, including radicular low back pain.

Mutation of a chitinase-like gene causes ectopic deposition of lignin, aberrant cell shapes, and overproduction of ethylene.

PubMed

Zhong, Ruiqin; Kays, Stanley J; Schroeder, Betty P; Ye, Zheng-Hua

2002-01-01

Chitinase-like proteins have long been proposed to play roles in normal plant growth and development, but no mutations in chitinase-like genes have been obtained previously to support this hypothesis. In this study, we have shown that the gene responsible for the elp1 mutation in Arabidopsis encodes a chitinase-like protein (AtCTL1). Mutation of this chitinase-like gene caused ectopic deposition of lignin and aberrant shapes of cells with incomplete cell walls in the pith of inflorescence stems. The AtCTL1 gene was expressed in all organs during normal plant growth and development, but it was not induced by wounding, salicylic acid, pectin fragments, or ethylene. Consistent with its ubiquitous expression pattern, mutation of the AtCTL1 gene affected many aspects of plant growth and development, including exaggerated hook curvature, reduced length and increased diameter of hypocotyls in dark-grown seedlings, and reduced root length and increased number of root hairs in light-grown seedlings. The mutant phenotypes could be rescued partially by ethylene inhibitors, and ethylene production in the mutant was significantly greater than in the wild type. Together, these results suggest that AtCTL1, a chitinase-like gene, is essential for normal plant growth and development in Arabidopsis.

Long non-coding RNA CASC15 promotes tongue squamous carcinoma progression through targeting miR-33a-5p.

PubMed

Zuo, Zhibin; Ma, Long; Gong, Zuode; Xue, Lande; Wang, Qibao

2018-05-26

Long non-coding RNAs (lncRNAs) have gained a lot of attention because they participate in several human disorders, including tumors. This study determined the role of LncRNA CASC15 (cancer susceptibility candidate 15) in the development of tongue squamous cell carcinoma (TSCC). Here, we identified that CASC15 expression was upregulated in TSCC samples and cell lines. We showed that overexpression of CASC15 promoted cell proliferation, cycle, and migration in TSCC. In addition, we revealed that miR-33a-5p expression was downregulated in TSCC tissues and cell lines. Moreover, we showed that the expression of CASC15 was negatively related with miR-33a-5p expression in TSCC tissues. Ectopic expression of miR-33a-5p suppressed cell proliferation, cycle, and migration in TSCC. Elevated expression of CASC15 suppressed miR-33a-5p expression and promoted ZEB1 expression in SCC4 cell. Ectopic expression of CASC15 promoted TSCC cell proliferation, cycle, and migration through targeting miR-33a-5p. These results suggested that lncRNA CASC15 and miR-33a-5p might be exploited as new markers of TSCC and were potential treatment targets for TSCC patients.

Ectopic expression of Arabidopsis Target of Rapamycin (AtTOR) improves water-use efficiency and yield potential in rice

NASA Astrophysics Data System (ADS)

Bakshi, Achala; Moin, Mazahar; Kumar, M. Udaya; Reddy, Aramati Bindu Madhava; Ren, Maozhi; Datla, Raju; Siddiq, E. A.; Kirti, P. B.

2017-02-01

The target of Rapamycin (TOR) present in all eukaryotes is a multifunctional protein, regulating growth, development, protein translation, ribosome biogenesis, nutrient, and energy signaling. In the present study, ectopic expression of TOR gene of Arabidopsis thaliana in a widely cultivated indica rice resulted in enhanced plant growth under water-limiting conditions conferring agronomically important water-use efficiency (WUE) trait. The AtTOR high expression lines of rice exhibited profuse tillering, increased panicle length, increased plant height, high photosynthetic efficiency, chlorophyll content and low Δ13C. Δ13C, which is inversely related to high WUE, was as low as 17‰ in two AtTOR high expression lines. These lines were also insensitive to the ABA-mediated inhibition of seed germination. The significant upregulation of 15 stress-specific genes in high expression lines indicates their contribution to abiotic stress tolerance. The constitutive expression of AtTOR is also associated with significant transcriptional upregulation of putative TOR complex-1 components, OsRaptor and OsLST8. Glucose-mediated transcriptional activation of AtTOR gene enhanced lateral root formation. Taken together, our findings indicate that TOR, in addition to its multiple cellular functions, also plays an important role in response to abiotic stress and potentially enhances WUE and yield related attributes.

Association of T-Zone Reticular Networks and Conduits with Ectopic Lymphoid Tissues in Mice and Humans

PubMed Central

Link, Alexander; Hardie, Debbie L.; Favre, Stéphanie; Britschgi, Mirjam R.; Adams, David H.; Sixt, Michael; Cyster, Jason G.; Buckley, Christopher D.; Luther, Sanjiv A.

2011-01-01

Ectopic or tertiary lymphoid tissues (TLTs) are often induced at sites of chronic inflammation. They typically contain various hematopoietic cell types, high endothelial venules, and follicular dendritic cells; and are organized in lymph node–like structures. Although fibroblastic stromal cells may play a role in TLT induction and persistence, they have remained poorly defined. Herein, we report that TLTs arising during inflammation in mice and humans in a variety of tissues (eg, pancreas, kidney, liver, and salivary gland) contain stromal cell networks consisting of podoplanin+ T-zone fibroblastic reticular cells (TRCs), distinct from follicular dendritic cells. Similar to lymph nodes, TRCs were present throughout T-cell–rich areas and had dendritic cells associated with them. They expressed lymphotoxin (LT) β receptor (LTβR), produced CCL21, and formed a functional conduit system. In rat insulin promoter–CXCL13–transgenic pancreas, the maintenance of TRC networks and conduits was partially dependent on LTβR and on lymphoid tissue inducer cells expressing LTβR ligands. In conclusion, TRCs and conduits are hallmarks of secondary lymphoid organs and of well-developed TLTs, in both mice and humans, and are likely to act as important scaffold and organizer cells of the T-cell–rich zone. PMID:21435450

[Surgical treatment of a 5 month pregnancy in the rudimentary uterine cornu].

PubMed

Bosković, V; Vrzić-Petronijević, S; Petronijević, M; Berisavac, M; Likić-Ladjević, I

2006-01-01

Cornual ectopic pregnacy is rare clinical entity with high maternal mortality. In all cases surgical treatment is indicated, and taking care of most important complication--haemorrhagic shock. Therapeutic approach is individual and depending of simptomatplogy, gestational age of pregnancy and condition of the patient in time of diagnosis. Authors are presenting the case of cornual ectopic pregnancy of five months.

Common Pediatric Urological Disorders

PubMed Central

Robson, Wm. Lane M.; Leung, Alexander K.C.; Boag, Graham S.

1991-01-01

The clinical and radiological presentations of 12 pediatric urological disorders are described. The described disorders include pyelonephritis, vesicoureteral reflux, ureteropelvic obstruction, ureterovesical obstruction, ectopic ureterocele, posterior urethral valves, multicystic dysplastic kidney, polycystic kidney disease, ectopic kidney, staghorn calculi, urethral diverticulum, and urethral meatal stenosis. ImagesFigure 1-2Figure 3Figure 3Figure 4Figure 5Figure 6-7Figure 8-9Figure 10Figure 11-12 PMID:21229068

Transcatheter Arterial Embolization Therapy for a Hypoplastic Pelvic Kidney with a Single Vaginal Ectopic Ureter to Control Incontinence: The Usefulness of Three-Dimensional CT Angiography Using Multidetector-Row Helical CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kudoh, Kouichi, E-mail: cdk70770@par.odn.ne.jp; Kadota, Masataka; Nakayama, Yoshiharu

2003-09-15

A girl with continuous urinary incontinence was successfully treated by angiographic embolization of a hypoplastic pelvic kidney with a single unilateral vaginal ectopic opening of the ureter. For this intervention, CT angiography was useful for detecting the corresponding renal artery of the hypoplastic kidney.

Ectopic expression of LEAFY COTYLEDON1-LIKE gene and localized auxin accumulation mark embryogenic competence in epiphyllous plants of Helianthus annuus × H. tuberosus

PubMed Central

Chiappetta, A.; Fambrini, M.; Petrarulo, M.; Rapparini, F.; Michelotti, V.; Bruno, L.; Greco, M.; Baraldi, R.; Salvini, M.; Pugliesi, C.; Bitonti, M. B.

2009-01-01

Background and Aims The clone EMB-2 of the interspecific hybrid Helianthus annuus × H. tuberosus provides an interesting system to study molecular and physiological aspects of somatic embryogenesis. Namely, in addition to non-epiphyllous (NEP) leaves that expand normally, EMB-2 produces epiphyllous (EP) leaves bearing embryos on the adaxial surface. This clone was used to investigate if the ectopic expression of H. annuus LEAFY COTYLEDON1-LIKE (Ha-L1L) gene and auxin activity are correlated with the establishment of embryogenic competence. Methods Ha-L1L expression was evaluated by semi-quantitative RT-PCR and in situ hybridization. The endogenous level and spatial distribution of free indole-3-acetic acid (IAA) were estimated by a capillary gas chromatography–mass spectrometry–selected ion monitoring method and an immuno-cytochemical approach. Key Results Ectopic expression of Ha-L1L was detected in specific cell domains of the adaxial epidermis of EP leaves prior to the development of ectopic embryos. Ha-L1L was expressed rapidly when NEP leaves were induced to regenerate somatic embryos by in vitro culture. Differences in auxin distribution pattern rather than in absolute level were observed between EP and A-2 leaves. More precisely, a strong IAA immuno-signal was detected in single cells or in small groups of cells along the epidermis of EP leaves and accompanied the early stages of embryo development. Changes in auxin level and distribution were observed in NEP leaves induced to regenerate by in vitro culture. Exogenous auxin treatments lightly influenced Ha-L1L transcript levels in spite of an enhancement of the regeneration frequency. Conclusions In EP leaves, Ha-L1L activity marks the putative founder cells of ectopic embryos. Although the ectopic expression of Ha-L1L seems to be not directly mediated by auxin levels per se, it was demonstrated that localized Ha-L1L expression and IAA accumulation in leaf epidermis domains represent early events of somatic embryogenesis displayed by the epiphyllous EMB-2 clone. PMID:19151043

Fertility outcomes subsequent to treatment of tubal ectopic pregnancy in younger Turkish women.

PubMed

Turan, Volkan

2011-10-01

The assessment of future fertility in patients that were hospitalized with diagnosis of tubal ectopic pregnancy. Between January 1998 and September 2008, we retrospectively reviewed 219 tubal ectopic pregnancy patients who were hospitalized. The patients using contraceptive methods, underwent previous pelvic or tubal surgery, pregnancy after in vitro fertilization, over the age of 28, and extratubal ectopic pregnancies were excluded. Patients who actively attempted to conceive were included. We called all the patients to see whether they had pregnancy in 24 months, and how long they had waited for this after the operation. Overall, we could not reach 14 patients who were treated surgically (n = 9) or medically (n = 5). Department of Obstetrics and Gynecology, Ege University, Izmir, Turkey. Women aged between 18 and 28 years that were treated because of tubal ectopic pregnancy and have concerns about infertility. Medical treatment with methotrexate (n = 34), salpingectomy (n = 62) salpingostomy (n = 37). Intrauterine pregnancy rates, ectopic pregnancy rates and mean time to pregnancy after interventions. After questionnaire: in the methotrexate group; six of 29 (20%) had no pregnancy; 23 (79%) of them conceived, but three (10%) of the pregnancies were extrauterine. Thirty-seven patients received salpingostomy and 62 patients composed the salpingectomy group. Intrauterine pregnancy rates up to 24 months were established as 65.2% in salpingectomy (n = 55) and 60.1% in the salpingostomy (n = 35) groups respectively. No significant difference was noticed when pregnancy rates were compared among three groups (P = 0.942). Mean time to pregnancy in methotrexate group was 7.8 ± 2.2 months, and in salpingostomy and salpingectomy groups was 8.7 ± 2.2 and 9.3 ± 3.1 months respectively (P = 0.841). Since we found no difference in terms of pregnancy rates among three groups, medical treatment appears to be more favored with early and accurate diagnosis. After salpingectomy, patients may conceive later in life when compared with other groups so selected patients should be assessed according to their age for the decision of assisted reproductive techniques. Copyright © 2011 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Regulation of miRNA-29c and its downstream pathways in preneoplastic progression of triple-negative breast cancer

PubMed Central

Bhardwaj, Anjana; Singh, Harpreet; Rajapakshe, Kimal; Tachibana, Kazunoshin; Ganesan, Nivetha; Pan, Yinghong; Gunaratne, Preethi H.; Coarfa, Cristian; Bedrosian, Isabelle

2017-01-01

Little is understood about the early molecular drivers of triple-negative breast cancer (TNBC), making the identification of women at risk and development of targeted therapy for prevention significant challenges. By sequencing a TNBC cell line-based breast cancer progression model we have found that miRNA-29c is progressively lost during TNBC tumorigenesis. In support of the tumor suppressive role of miRNA 29c, we found that low levels predict poor overall patient survival and, conversely, that ectopic expression of miRNA-29c in preneoplastic cell models inhibits growth. miRNA-29c exerts its growth inhibitory effects through direct binding and regulation of TGFB-induced factor homeobox 2 (TGIF2), CAMP-responsive element binding protein 5 (CREB5), and V-Akt murine thymoma viral oncogene homolog 3 (AKT3). miRNA-29c regulation of these gene targets seems to be functionally relevant, as TGIF2, CREB5, and AKT3 were able to rescue the inhibition of cell proliferation and colony formation caused by ectopic expression of miRNA-29c in preneoplastic cells. AKT3 is an oncogene of known relevance in breast cancer, and as a proof of principle we show that inhibition of phosphoinositide 3-kinase (PI3K) activity, a protein upstream of AKT3, suppressed proliferation in TNBC preneoplastic cells. We explored additional opportunities for prevention of TNBC by studying the regulation of miRNA-29c and identified DNA methylation to have a role in the inhibition of miRNA-29c during TNBC tumorigenesis. Consistent with these observations, we found 5 aza-cytadine to relieve the suppression of miRNA-29c. Together, these results demonstrate that miRNA-29c loss plays a key role in the early development of TNBC. PMID:28160548

Down-regulation of Transducin-Like Enhancer of Split protein 4 in hepatocellular carcinoma promotes cell proliferation and epithelial-Mesenchymal-Transition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Xiao-cai; Xiao, Cui-cui; Li, Hua

Background: Transducin-Like Enhancer of Split protein 4 (TLE4) has been reported to be involved in some subsets of acute myeloid leukemia and colorectal cancer. In the present study, we aimed to explore the role of TLE4 in tumorigenesis and cancer progression in hepatocellular carcinoma (HCC). Methods: The expression pattern of TLE4 in HCC was determined by Western-blot and qRT-PCR, gain-of-function and loss-of-function was used to explore the biological role of TLE4 in HCC cells. A xenograft model was established to confirm its effects on proliferation. Results: The protein expression levels of TLE4 were significantly down-regulated in HCC tissues compared tomore » matched adjacent normal liver tissues. In vitro, down-regulation of TLE4 in Huh7 or SMMC-7721 promoted cell proliferation and ectopical expression of TLE4 in Hep3B or Bel-7404 suppressed cell proliferation. In addition, the cell colony formation ability was enhanced after down-regulation of TLE4 expression in Huh-7 but suppressed after over-expression in Hep3B. Furthermore, down-regulation of TLE4 increased the cell invasion ability, as well as increased the expression level of Vimentin and decreased that of E-cadherin, indicating a phenotype of epithelial-mesenchymal transition (EMT) in HCC cells. On the contrary, ectopical expression of TLE4 in HCC cells decreased the cell invasion ability and inhibited EMT. In vivo, compared to control group, xenograft tumor volumes were significantly decreased in TLE4 overexpression group. Conclusions: These results demonstrated that TLE4 might play important regulatory roles in cellular proliferation and EMT process in HCC. - Highlights: • TLE4 is significantly down-regulated in HCC samples. • Down regulated of TLE4 in HCC cells promotes cell proliferation. • Down regulated of TLE4 in HCC cells promotes epithelial-to-mesenchymal transition.« less

3' Untranslated regions mediate transcriptional interference between convergent genes both locally and ectopically in Saccharomyces cerevisiae.

PubMed

Wang, Luwen; Jiang, Ning; Wang, Lin; Fang, Ou; Leach, Lindsey J; Hu, Xiaohua; Luo, Zewei

2014-01-01

Paired sense and antisense (S/AS) genes located in cis represent a structural feature common to the genomes of both prokaryotes and eukaryotes, and produce partially complementary transcripts. We used published genome and transcriptome sequence data and found that over 20% of genes (645 pairs) in the budding yeast Saccharomyces cerevisiae genome are arranged in convergent pairs with overlapping 3'-UTRs. Using published microarray transcriptome data from the standard laboratory strain of S. cerevisiae, our analysis revealed that expression levels of convergent pairs are significantly negatively correlated across a broad range of environments. This implies an important role for convergent genes in the regulation of gene expression, which may compensate for the absence of RNA-dependent mechanisms such as micro RNAs in budding yeast. We selected four representative convergent gene pairs and used expression assays in wild type yeast and its genetically modified strains to explore the underlying patterns of gene expression. Results showed that convergent genes are reciprocally regulated in yeast populations and in single cells, whereby an increase in expression of one gene produces a decrease in the expression of the other, and vice-versa. Time course analysis of the cell cycle illustrated the functional significance of this relationship for the three pairs with relevant functional roles. Furthermore, a series of genetic modifications revealed that the 3'-UTR sequence plays an essential causal role in mediating transcriptional interference, which requires neither the sequence of the open reading frame nor the translation of fully functional proteins. More importantly, transcriptional interference persisted even when one of the convergent genes was expressed ectopically (in trans) and therefore does not depend on the cis arrangement of convergent genes; we conclude that the mechanism of transcriptional interference cannot be explained by the transcriptional collision model, which postulates a clash between simultaneous transcriptional processes occurring on opposite DNA strands.

Activation of IRE1α-XBP1 pathway induces cell proliferation and invasion in colorectal carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin, Chun; Jin, Zhao; Chen, Nian-zhao

2016-01-29

Cell proliferation and tumor metastasis are considered as the main reasons for death in colorectal carcinoma (CRC). IRE1α-XBP1 pathway is the most conserved UPR pathways, which are activated during ER stress caused by the accumulation of unfolded or misfolded protein in the lumen of ER. Here, we demonstrated the critical role of IRE1α-XBP1 pathway and underlying molecular mechanism in cell proliferation and tumor metastasis in CRC. By the use of tissue microarray analysis of samples from 119 patients with CRC, IRE1α was determined to be an independent predictor of overall survival as higher expression of IRE1α in CRC patients showedmore » lower survival rates (p = 0.0041). RNA interference and ectopic expression of IRE1α were applied to determine the molecular effects of IRE1α in CRC cells. The silencing of IRE1α inhibited the proliferation and blocked the invasion of CRC cells in vitro, while ectopic expression of IRE1α in turn promoted cell proliferation and invasion. IRE1α-XBP1 pathway regulated the mitosis of CRC cells through the directly binding of XBP1s to Cyclin D1 promoter to activate Cyclin D1 expression. Our results reveal that IRE1α-XBP1 pathway plays an important role in tumor progression and epithelial-to-mesenchymal transition (EMT), and IRE1α could be employed as a novel prognostic marker and a promising therapeutic target for CRC. - Highlights: • IRE1 was determined to be an independent predictor of overall survival in CRC patient. • IRE1-XBP1 pathway promoted CRC cell proliferation through regulating Cyclin D1 expression. • IRE1-XBP1 pathway played important role in EMT of CRC cells.« less

3′ Untranslated Regions Mediate Transcriptional Interference between Convergent Genes Both Locally and Ectopically in Saccharomyces cerevisiae

PubMed Central

Wang, Luwen; Jiang, Ning; Wang, Lin; Fang, Ou; Leach, Lindsey J.; Hu, Xiaohua; Luo, Zewei

2014-01-01

Paired sense and antisense (S/AS) genes located in cis represent a structural feature common to the genomes of both prokaryotes and eukaryotes, and produce partially complementary transcripts. We used published genome and transcriptome sequence data and found that over 20% of genes (645 pairs) in the budding yeast Saccharomyces cerevisiae genome are arranged in convergent pairs with overlapping 3′-UTRs. Using published microarray transcriptome data from the standard laboratory strain of S. cerevisiae, our analysis revealed that expression levels of convergent pairs are significantly negatively correlated across a broad range of environments. This implies an important role for convergent genes in the regulation of gene expression, which may compensate for the absence of RNA-dependent mechanisms such as micro RNAs in budding yeast. We selected four representative convergent gene pairs and used expression assays in wild type yeast and its genetically modified strains to explore the underlying patterns of gene expression. Results showed that convergent genes are reciprocally regulated in yeast populations and in single cells, whereby an increase in expression of one gene produces a decrease in the expression of the other, and vice-versa. Time course analysis of the cell cycle illustrated the functional significance of this relationship for the three pairs with relevant functional roles. Furthermore, a series of genetic modifications revealed that the 3′-UTR sequence plays an essential causal role in mediating transcriptional interference, which requires neither the sequence of the open reading frame nor the translation of fully functional proteins. More importantly, transcriptional interference persisted even when one of the convergent genes was expressed ectopically (in trans) and therefore does not depend on the cis arrangement of convergent genes; we conclude that the mechanism of transcriptional interference cannot be explained by the transcriptional collision model, which postulates a clash between simultaneous transcriptional processes occurring on opposite DNA strands. PMID:24465217

Rac-WAVE-mediated actin reorganization is required for organization and maintenance of cell-cell adhesion.

PubMed

Yamazaki, Daisuke; Oikawa, Tsukasa; Takenawa, Tadaomi

2007-01-01

During cadherin-dependent cell-cell adhesion, the actin cytoskeleton undergoes dynamic reorganization in epithelial cells. Rho-family small GTPases, which regulate actin dynamics, play pivotal roles in cadherin-dependent cell-cell adhesion; however, the precise molecular mechanisms that underlie cell-cell adhesion formation remain unclear. Here we show that Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE)-mediated reorganization of actin, downstream of Rac plays an important role in normal development of cadherin-dependent cell-cell adhesions in MDCK cells. Rac-induced development of cadherin-dependent adhesions required WAVE2-dependent actin reorganization. The process of cell-cell adhesion is divided into three steps: formation of new cell-cell contacts, stabilization of these new contacts and junction maturation. WAVE1 and WAVE2 were expressed in MDCK cells. The functions of WAVE1 and WAVE2 were redundant in this system but WAVE2 appeared to play a more significant role. During the first step, WAVE2-dependent lamellipodial protrusions facilitated formation of cell-cell contacts. During the second step, WAVE2 recruited actin filaments to new cell-cell contacts and stabilized newly formed cadherin clusters. During the third step, WAVE2-dependent actin reorganization was required for organization and maintenance of mature cell-cell adhesions. Thus, Rac-WAVE-dependent actin reorganization is not only involved in formation of cell-cell adhesions but is also required for their maintenance.

Dexamethasone Enhances Osteogenic Differentiation of Bone Marrow- and Muscle-Derived Stromal Cells and Augments Ectopic Bone Formation Induced by Bone Morphogenetic Protein-2

PubMed Central

Yuasa, Masato; Yamada, Tsuyoshi; Taniyama, Takashi; Masaoka, Tomokazu; Xuetao, Wei; Yoshii, Toshitaka; Horie, Masaki; Yasuda, Hiroaki; Uemura, Toshimasa; Okawa, Atsushi; Sotome, Shinichi

2015-01-01

We evaluated whether dexamethasone augments the osteogenic capability of bone marrow-derived stromal cells (BMSCs) and muscle tissue-derived stromal cells (MuSCs), both of which are thought to contribute to ectopic bone formation induced by bone morphogenetic protein-2 (BMP-2), and determined the underlying mechanisms. Rat BMSCs and MuSCs were cultured in growth media with or without 10-7 M dexamethasone and then differentiated under osteogenic conditions with dexamethasone and BMP-2. The effects of dexamethasone on cell proliferation and osteogenic differentiation, and also on ectopic bone formation induced by BMP-2, were analyzed. Dexamethasone affected not only the proliferation rate but also the subpopulation composition of BMSCs and MuSCs, and subsequently augmented their osteogenic capacity during osteogenic differentiation. During osteogenic induction by BMP-2, dexamethasone also markedly affected cell proliferation in both BMSCs and MuSCs. In an in vivo ectopic bone formation model, bone formation in muscle-implanted scaffolds containing dexamethasone and BMP-2 was more than two fold higher than that in scaffolds containing BMP-2 alone. Our results suggest that dexamethasone potently enhances the osteogenic capability of BMP-2 and may thus decrease the quantity of BMP-2 required for clinical application, thereby reducing the complications caused by excessive doses of BMP-2. Highlights: 1. Dexamethasone induced selective proliferation of bone marrow- and muscle-derived cells with higher differentiation potential. 2. Dexamethasone enhanced the osteogenic capability of bone marrow- and muscle-derived cells by altering the subpopulation composition. 3. Dexamethasone augmented ectopic bone formation induced by bone morphogenetic protein-2. PMID:25659106

Transcatheter Embolotherapy with N-Butyl Cyanoacrylate for Ectopic Varices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Jin Woo; Kim, Hyo-Cheol, E-mail: angiointervention@gmail.com; Jae, Hwan Jun, E-mail: jaemdphd@gmail.com

PurposeTo address technical feasibility and clinical outcome of transcatheter embolotherapy with N-butyl cyanoacrylate (NBCA) for bleeding ectopic varices.MethodsThe institutional review board approved this retrospective study and waived informed consent. From January 2004 to June 2013, a total of 12 consecutive patients received transcatheter embolotherapy using NBCA for bleeding ectopic varices in our institute. Clinical and radiologic features of the endovascular procedures were comprehensively reviewed.ResultsPreprocedural computed tomography images revealed ectopic varices in the jejunum (n = 7), stoma (n = 2), rectum (n = 2), and duodenum (n = 1). The 12 procedures consisted of solitary embolotherapy (n = 8) and embolotherapy with portal decompression (main portal vein stenting in 3,more » transjugular intrahepatic portosystemic shunt in 1). With regard to vascular access, percutaneous transhepatic access (n = 7), transsplenic access (n = 4), and transjugular intrahepatic portosystemic shunt tract (n = 1) were used. There was no failure in either the embolotherapy or the vascular accesses (technical success rate, 100 %). Two patients died within 1 month from the procedure from preexisting fatal medical conditions. Only one patient, with a large varix that had been partially embolized by using coils and NBCA, underwent rebleeding 5.5 months after the procedure. The patient was retreated with NBCA and did not undergo any bleeding afterward for a follow-up period of 2.5 months. The remaining nine patients did not experience rebleeding during the follow-up periods (range 1.5–33.2 months).ConclusionTranscatheter embolotherapy using NBCA can be a useful option for bleeding ectopic varices.« less

Hyperthyroidism caused by an ectopic thyrotropin-secreting tumor of the nasopharynx: a case report and review of the literature.

PubMed

Tong, Anli; Xia, Weibo; Qi, Fang; Jin, Zimeng; Yang, Di; Zhang, Zhuhua; Li, Fang; Xing, Xiaoping; Lian, Xiaolan

2013-09-01

Ectopic thyrotropin (TSH)-secreting tumors are extremely rare. To our knowledge, only three cases have previously been reported so far, but the tumors were not studied ultrastructurally and in vitro. We present a case that was extensively examined to gain deeper insights in terms of the histopathological features and hormonal secretion profile of the tumor. A 49-year-old female complained of nasal obstruction for 15 years and thyrotoxicosis for one and a half years. Except for a high basal TSH with concomitantly elevated free tri-iodothyronine (FT3) and free thyroxine (FT4) levels, her pituitary hormone profile yielded normal results. Magnetic resonance imaging revealed a 2 cm × 2 cm mass in the nasopharynx, which showed an increased tracer uptake on octreotide scintigraphy. Preoperative treatment with octreotide effectively reduced serum TSH, FT3, and FT4 to normal levels. The mass was endoscopically removed via an endonasal approach. Immunophenotyping and hormone determination of cultured cells confirmed that the mass was a plurihormonal TSH-/growth hormone (GH)-/prolactin (PRL)-producing adenoma. Co-expression of TSH and GH was found in most cells. Electron microscopy showed that the adenoma was formed by a single cell type, with secretory granules of small size. In vitro studies demonstrated that octreotide reduced both TSH and GH secretion. We report an ectopic TSH-secreting tumor, which had plurihormonal secretion in vitro, including TSH, GH, and PRL. Histologically, it mimicked a TSH-secreting pituitary adenoma. Octreotide was useful in the diagnosis and treatment of this ectopic TSH-secreting tumor. Ectopic TSH-secreting tumors are extremely rare. In terms of hormone secretion profile, histological characteristics, and response to octreotide, they are similar to pituitary TSH-secreting adenomas, suggesting that they are of identical cell origin.

The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate

PubMed Central

Song, Guodong; Habibovic, Pamela; Bao, Chongyun; Hu, Jing; van Blitterswijk, Clemens A.; Yuan, Huipin; Chen, Wenchuan; Xu, Hockin H.K.

2013-01-01

Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched beagle dog model to investigate BMSC homing via blood circulation to participate in ectopic bone formation via osteoinductive biomaterial. BMSCs of male dogs were injected into female femoral marrow cavity. The survival and stable chimerism of donor BMSCs in recipients were confirmed with polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH). Biphasic calcium phosphate (BCP) granules were implanted in dorsal muscles of female dogs. Y chromosomes were detected in samples harvested from female dogs which had received male BMSCs. At 4 weeks, cells with Y-chromosomes were distributed in the new bone matrix throughout the BCP granule implant. At 6 weeks, cells with Y chromosomes were present in newly mineralized woven bone. TRAP positive osteoclast-like cells were observed in 4-week implants, and the number of such cells decreased from 4 to 6 weeks. These results show that osteoprogenitors were recruited from bone marrow and homed to ectopic site to serve as a cell source for calcium phosphate-induced bone formation. In conclusion, BMSCs were demonstrated to migrate from bone marrow through blood circulation to non-osseous bioceramic implant site to contribute to ectopic bone formation in a canine model. BCP induced new bone in muscles without growth factor delivery, showing excellent osteoinductivity that could be useful for bone tissue engineering. PMID:23298780

Vitamin K supplementation increases vitamin K tissue levels but fails to counteract ectopic calcification in a mouse model for pseudoxanthoma elasticum.

PubMed

Gorgels, Theo G M F; Waarsing, Jan H; Herfs, Marjolein; Versteeg, Daniëlle; Schoensiegel, Frank; Sato, Toshiro; Schlingemann, Reinier O; Ivandic, Boris; Vermeer, Cees; Schurgers, Leon J; Bergen, Arthur A B

2011-11-01

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder in which calcification of connective tissue leads to pathology in skin, eye and blood vessels. PXE is caused by mutations in ABCC6. High expression of this transporter in the basolateral hepatocyte membrane suggests that it secretes an as-yet elusive factor into the circulation which prevents ectopic calcification. Utilizing our Abcc6 (-/-) mouse model for PXE, we tested the hypothesis that this factor is vitamin K (precursor) (Borst et al. 2008, Cell Cycle). For 3 months, Abcc6 (-/-) and wild-type mice were put on diets containing either the minimum dose of vitamin K required for normal blood coagulation or a dose that was 100 times higher. Vitamin K was supplied as menaquinone-7 (MK-7). Ectopic calcification was monitored in vivo by monthly micro-CT scans of the snout, as the PXE mouse model develops a characteristic connective tissue mineralization at the base of the whiskers. In addition, calcification of kidney arteries was measured by histology. Results show that supplemental MK-7 had no effect on ectopic calcification in Abcc6 ( -/- ) mice. MK-7 supplementation increased vitamin K levels (in skin, heart and brain) in wild-type and in Abcc6 (-/-) mice. Vitamin K tissue levels did not depend on Abcc6 genotype. In conclusion, dietary MK-7 supplementation increased vitamin K tissue levels in the PXE mouse model but failed to counteract ectopic calcification. Hence, we obtained no support for the hypothesis that Abcc6 transports vitamin K and that PXE can be cured by increasing tissue levels of vitamin K.

A rare condition: Ectopic liver tissue with its unique blood supply encountered during laparoscopic cholecystectomy.

PubMed

Bal, Ahmet; Yilmaz, Sezgin; Yavas, Betul Demirciler; Ozdemir, Cigdem; Ozsoy, Mustafa; Akici, Murat; Kalkan, Mustafa; Ersen, Ogun; Saripinar, Baris; Arikan, Yuksel

2015-01-01

Developmental abnormalities of liver including ectopic liver tissue (ELT) are rare conditions. Few cases presenting ELT have been reported in literature till now. Even though the most common area seen is gallbladder, it is detected both abdominal and thoracic sites. There is a relationship between HCC and ectopic liver that necessitates the removal. A 51-year-old female was hospitalized because of abdominal pain. Gallstone and bile duct dilatation were determined during ultrasonographic (USG) evaluation. The patient was operated for cholecystectomy following a successful endoscopic retrograde cholangiopancreatography (ERCP). During operation, a mass located on gallbladder with its unique vascular support was identified and resected together with gallbladder. The mass had a separate vascular stalk arising from liver parenchyma substance and it was clipped with laparoscopic staples. The histopathological examination revealed that the mass adherent to gallbladder was ectopic liver confirming the intraoperative observation. The postoperative course of patient was uneventfull and she was discharged at the second day after the operation. Ectopic liver tissue is incidentally found both in abdominal and thoracic cavity. ELT can rarely be diagnosed before surgical procedures or autopsies. It can be overlooked easily by radiological techniques. Although it does not usually produce any symptom clinically, it can rarely result in serious complications such as bleeding, pyloric and portal vein obstruction. ELT also has the capacity of malignant transformation to hepatocellular carcinoma that makes it essential to be removed. Although ELT is rarely seen, it should be removed when recognized in order to prevent the complications and malignant transformation. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Primary ectopic breast cancer of the vulva, treated with local excision of the vulva and sentinel lymph node biopsy: a case report.

PubMed

Ishigaki, Takayuki; Toriumi, Yasuo; Nosaka, Ryouko; Kudou, Rei; Imawari, Yoshimi; Kamio, Makiko; Nogi, Hiroko; Shioya, Hisashi; Takeyama, Hiroshi

2017-12-01

Primary breast cancer fairly infrequently occurs in ectopic breast tissue, and primary ectopic breast cancer of the vulva is particularly rare. Only 26 cases have been published in the English-language literature, and there has been no report of primary breast carcinoma of the vulva in Japan. We report a rare case of primary ectopic breast cancer of the vulva that was treated with local excision of the vulva and sentinel lymph node biopsy (SLNB). The patient was a 72-year-old woman who had noticed a right vulvar tumor 10 years earlier. The tumor was excised by the Department of Plastic Surgery of our hospital. The histology of the vulvar tumor revealed an invasive ductal carcinoma of the breast, and immunohistochemical staining of the vulvar specimen showed the tumor cells to be 100% estrogen-receptor-positive and 100% progesterone-receptor-positive. All margins of resection were positive for neoplastic involvement. An additional local excision of the vulva and right inguinal SLNB were performed in our department. The intraoperative frozen section was negative for metastasis, and lymph node dissection was not performed. The final pathology was negative for residual disease, and a partially normal ductal component was present. Adjuvant hormonal therapy with an aromatase inhibitor was indicated post-operatively. The patient was asymptomatic and free of detectable disease at a 6-month follow-up. Due to the rarity of this diagnosis, there are no established guidelines for treatment. Although cases in which SLNB was performed are rare, we consider SLNB to be an effective alternative to inguinal node dissection for ectopic primary breast cancer of the vulva.

The Fate and Impact of Internal Waves in Nearshore Ecosystems

NASA Astrophysics Data System (ADS)

Woodson, C. B.

2018-01-01

Internal waves are widespread features of global oceans that play critical roles in mixing and thermohaline circulation. Similarly to surface waves, internal waves can travel long distances, ultimately breaking along continental margins. These breaking waves can transport deep ocean water and associated constituents (nutrients, larvae, and acidic low-oxygen waters) onto the shelf and locally enhance turbulence and mixing, with important effects on nearshore ecosystems. We are only beginning to understand the role internal waves play in shaping nearshore ecosystems. Here, I review the physics of internal waves in shallow waters and identify two commonalities among internal waves in the nearshore: exposure to deep offshore waters and enhanced turbulence and mixing. I relate these phenomena to important ecosystem processes ranging from extreme events to fertilization success to draw general conclusions about the influence of internal waves on ecosystems and the effects of internal waves in a changing climate.

The Fate and Impact of Internal Waves in Nearshore Ecosystems.

PubMed

Woodson, C B

2018-01-03

Internal waves are widespread features of global oceans that play critical roles in mixing and thermohaline circulation. Similarly to surface waves, internal waves can travel long distances, ultimately breaking along continental margins. These breaking waves can transport deep ocean water and associated constituents (nutrients, larvae, and acidic low-oxygen waters) onto the shelf and locally enhance turbulence and mixing, with important effects on nearshore ecosystems. We are only beginning to understand the role internal waves play in shaping nearshore ecosystems. Here, I review the physics of internal waves in shallow waters and identify two commonalities among internal waves in the nearshore: exposure to deep offshore waters and enhanced turbulence and mixing. I relate these phenomena to important ecosystem processes ranging from extreme events to fertilization success to draw general conclusions about the influence of internal waves on ecosystems and the effects of internal waves in a changing climate.

Lin28B promotes Müller glial cell de-differentiation and proliferation in the regenerative rat retinas

PubMed Central

Tao, Zui; Zhao, Chen; Jian, Qian; Gillies, Mark; Xu, Haiwei; Yin, Zheng Qin

2016-01-01

Retinal regeneration and repair are severely impeded in higher mammalian animals. Although Müller cells can be activated and show some characteristics of progenitor cells when injured or under pathological conditions, they quickly form gliosis scars. Unfortunately, the basic mechanisms that impede retinal regeneration remain unknown. We studied retinas from Royal College of Surgeon (RCS) rats and found that let-7 family molecules, let-7e and let-7i, were significantly overexpressed in Müller cells of degenerative retinas. It demonstrated that down-regulation of the RNA binding protein Lin28B was one of the key factors leading to the overexpression of let-7e and let-7i. Lin28B ectopic expression in the Müller cells suppressed overexpression of let-7e and let-7i, stimulated and mobilized Müller glia de-differentiation, proliferation, promoted neuronal commitment, and inhibited glial fate acquisition of de-differentiated Müller cells. ERG recordings revealed that the amplitudes of a-wave and b-wave were improved significantly after Lin28B was delivered into the subretinal space of RCS rats. In summary, down-regulation of Lin28B as well as up-regulation of let-7e and let-7i may be the main factors that impede Müller cell de-differentiation and proliferation in the retina of RCS rats. PMID:27384999

[Conservative treatment of ectopic pregnancy in a 27 years old patient with stage-Ia ovarian cancer after conservative surgical treatment and chemotherapy].

PubMed

Malinowski, Andrzej; Augustyniak, Tomasz; Bartosiak, Ilona; Maciołek-Bleniewska, Grazyna; Ciesielski, Arkadiusz

2004-01-01

We report a case of conservative treatment of ectopic pregnancy in a 27 years old patient, previously treated for ovarian cancer. Two years before she had surgery because of tumour in the left ovary. Ovarian cancer in stage la according to FIGO was confirmed. Considering the patient s young age, future reproductive plans and the early stage of cancer, the patient qualified for conservative treatment. Left adnexectomy with consequent chemotherapy (6 courses) was performed. Two years later on the ground of clinical symptoms, gynaecologic examination, sonography and changes in HCG serum concentration, ectopic pregnancy was recognised in the right tube. We applied conservative management with intramuscularly administrated Methotrexate. The patient, in good condition, was discharged from hospital on day 12 after injection of Methotrexate.

Ectopic banking of amputated great toe for delayed thumb reconstruction: case report.

PubMed

Valerio, Ian L; Hui-Chou, Helen G; Zelken, Jonathan; Basile, Patrick L; Ipsen, Derek; Higgins, James P

2014-07-01

Ectopic banking of amputated parts is a recognized technique for delayed replantation of an amputated part when the amputation stump will not permit immediate replantation. This is conventionally performed with the intent of transferring the injured part back to its anatomic position when the amputation stump is more appropriate for replantation. Current warfare conditions have led to a commonly encountered military trauma injury pattern of multiple extremity amputations with protected trunk and core structures. This pattern poses many challenges, including the limit or absence of donor sites for immediate or delayed flap reconstructive procedures. We describe a case in which we ectopically banked the great toe of an amputated lower extremity for delayed thumb reconstruction. Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Management of interstitial ectopic pregnancies with a combined intra-amniotic and systemic approach.

PubMed

Swank, Morgan L; Harken, Tabetha R; Porto, Manuel

2013-08-01

Approximately 2% of all pregnancies are ectopic; of these, 4% are interstitial or cervical. There exists no clear consensus as to whether surgical or medical management is superior. We present three cases of advanced nonfallopian tube ectopic pregnancies from 6 to 8 weeks of gestation. Our first two cases were managed with a combined intrafetal, intra-amniotic and systemic approach using methotrexate and potassium chloride, whereas our third case was managed with an intra-amniotic approach alone. Our combined approach cases were successful, with resolution of human chorionic gonadotropin in 50 and 34 days, whereas our single approach case re-presented with bleeding requiring uterine artery embolization and operative removal of products of conception. Patients presenting with advanced interstitial or cervical pregnancies who are clinically stable can be offered medical management with a combined approach.

A rare case of atypical pleomorphic adenoma arising from periocular ectopic lacrimal gland.

PubMed

Wajda, Brynn N; Mancini, Ronald; Evers, Bret; Nick Hogan, R

2018-06-23

To describe features of atypical pleomorphic adenoma, a rare clinical entity, particularly when found in ectopic periocular lacrimal gland tissue. Case report of biopsy-confirmed periocular atypical pleomorphic adenoma. A 35-year-old female presented with a unique orbital lesion found to be ectopic lacrimal gland demonstrating atypical pleomorphic adenoma on formal histopathologic review. Pleomorphic adenoma is pathologically characterized as an epithelial lesion intermixed with mesenchymal elements. It is further classified as atypical with the presence of features such as hypercellularity, regions of necrosis or hyalinization, cellular dysplasia, capsular violation, and malignant characteristics without frank local extension or distant metastases. Due to its rarity, the natural history and prognosis of atypical pleomorphic adenoma is unclear. Physicians need to recognize this entity, and complete surgical excision with strict follow-up regimens are likely warranted.

From Loschmidt daemons to time-reversed waves.

PubMed

Fink, Mathias

2016-06-13

Time-reversal invariance can be exploited in wave physics to control wave propagation in complex media. Because time and space play a similar role in wave propagation, time-reversed waves can be obtained by manipulating spatial boundaries or by manipulating time boundaries. The two dual approaches will be discussed in this paper. The first approach uses 'time-reversal mirrors' with a wave manipulation along a spatial boundary sampled by a finite number of antennas. Related to this method, the role of the spatio-temporal degrees of freedom of the wavefield will be emphasized. In a second approach, waves are manipulated from a time boundary and we show that 'instantaneous time mirrors', mimicking the Loschmidt point of view, simultaneously acting in the entire space at once can also radiate time-reversed waves. © 2016 The Author(s).

Fibroadenoma in axilla: another manifestation of ectopic breast

PubMed Central

Tiwary, Satyendra K; Kumar, Puneet; Khanna, Ajay Kumar

2015-01-01

Fibroadenoma of an accessory breast is a rare disease. The clinical significance lies in the fact that a number of cystic, inflammatory, neoplastic diseases similar to those of a normal breast have been reported in accessory breasts as well. Vigilant self-assessment and complete clinical examination are always encouraged to detect earliest malignancy in the axilla. We report two cases of ectopic breast fibroadenoma with the relevant literature. PMID:25917072