Growth enhancement in transgenic tilapia by ectopic expression of tilapia growth hormone.

PubMed

Martínez, R; Estrada, M P; Berlanga, J; Guillén, I; Hernández, O; Cabrera, E; Pimentel, R; Morales, R; Herrera, F; Morales, A; Piña, J C; Abad, Z; Sánchez, V; Melamed, P; Lleonart, R; de la Fuente, J

1996-03-01

The generation of transgenic fish with the transfer of growth hormone (GH) genes has opened new possibilities for the manipulation of growth in economically important fish species. The tilapia growth hormone (tiGH) cDNA was linked to the human cytomegalovirus (CMV) enhancer-promoter and used to generate transgenic tilapia by microinjection into one-cell embryos. Five transgenic tilapia were obtained from 40 injected embryos. A transgenic animal containing one copy of the transgene per cell was selected to establish a transgenic line. The transgene was stably transmitted to F1 and F2 generations in a Mendelian fashion. Ectopic, low-level expression of tiGH was detected in gonad and muscle cells of F1 transgenic tilapia by immunohystochemical analysis of tissue sections. Nine-month-old transgenic F1 progeny were 82% larger than nontransgenic fish at p = .001. These results showed that low-level ectopic expression of tiGH resulted in a growth acceleration in transgenic tilapia. Tilapia GH gene transfer is an alternative for growth acceleration in tilapia.

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.

Thiazolidinedione treatment and constitutive-PPARγ activation induces ectopic adipogenesis and promotes age-related thymic involution

PubMed Central

Youm, Yun-Hee; Yang, Hyunwon; Amin, Raj; Smith, Steven R.; Leff, Todd; Dixit, Vishwa Deep

2010-01-01

Age-related thymic involution is characterized by reduction in T cell production together with ectopic adipocyte development within the hematopoietic and thymic niches. PPARγ is required for adipocyte development, glucose homeostasis and is a target for several insulin-sensitizing drugs. Our prior studies showed that age-related elevation of PPARγ expression in thymic stromal cells is associated with thymic involution. Here, using clinically relevant pharmacological and genetic manipulations in mouse models, we provide evidence that activation of PPARγ leads to reduction in thymopoiesis. Treatment of aged mice with anti-hyperglycemic PPARγ-ligand class of Thiazolidinedione drug, Rosiglitazone caused robust thymic expression of classical pro-adipogenic transcripts. Rosiglitazone reduced thymic cellularity, lowered the naïve T cell number and T cell receptor excision circles (TRECs) indicative of compromised thymopoiesis. To directly investigate whether PPARγ activation induces thymic involution, we created transgenic mice with constitutive-active PPARγ (CA-PPARg) fusion protein in cells of adipogenic lineage. Importantly, CA-PPARγ transgene was expressed in thymus and in Fibroblast Specific Protein-1/S100A4 (FSP1+) cells, a marker of secondary mesenchymal cells. The CAPPARγ fusion protein mimicked the liganded PPARγ receptor and the transgenic mice displayed increased ectopic thymic adipogenesis and reduced thymopoiesis. Furthermore, the reduction in thymopoiesis in CA-PPARγ mice was associated with higher bone marrow adiposity and lower hematopoietic stem cell progenitor pool. Consistent with lower thymic output, CAPPARγ transgenic mice had restricted T cell receptor (TCR) repertoire diversity. Collectively, our data suggest that activation of PPARγ accelerates thymic aging and thymus-specific PPARγ antagonist may forestall age-related decline in T cell diversity. PMID:20374200

[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

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.

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

PRL-3 Is Involved in Estrogen- and IL-6-Induced Migration of Endometrial Stromal Cells From Ectopic Endometrium.

PubMed

Ren, Shifan; Zhou, Yefang; Fang, Xiaoling; She, Xiaoling; Wu, Yilin; Wu, Xianqing

2016-05-24

To investigate the role of phosphatase of regenerating liver-3 (PRL-3) in the 17β-estradiol (E2)- and interleukin 6 (IL-6)-induced migration of endometrial stromal cells (ESCs) from ectopic endometrium. Ectopic endometrial tissues were collected from patients with endometriosis, and PRL-3 expression in ectopic and eutopic endometrium was examined by immunohistochemistry. Endometrial stromal cells isolated from ectopic endometrium were treated with E2, progesterone (P), IL-6, or sodium orthovanadate (Sov) to inhibit PRL-3. Total RNA and protein were extracted from ESCs after treatment for quantitative real-time polymerase chain reaction and Western blot analyses. Cell migration was assessed using a scratch wound assay. Phosphatase of regenerating liver 3 protein was highly expressed in the endometrial glandular cells (EGCs) and ESCs in ectopic endometrium, whereas its weak expression was observed only in EGCs in eutopic endometrium. Both E2 and IL-6 treatment significantly increased PRL-3 messenger RNA and protein expression, and P treatment significantly inhibited PRL-3 expression. However, E2-induced PRL-3 expression in ESCs from ectopic endometrium was significantly blocked by IL-6 antibody. Moreover, E2- and IL-6-enhanced cell migration was completely abrogated by Sov treatment. Furthermore, Sov treatment could significantly promote PTEN expression but inhibit E2- and IL-6-induced p-AKT activation. Phosphatase of regenerating liver 3 plays a key role in the E2- and IL-6-induced migration of ESCs from ectopic endometrium, a process that is involved in the PTEN-AKT signaling pathway. © The Author(s) 2016.

Immortalization of pig fibroblast cells by transposon-mediated ectopic expression of porcine telomerase reverse transcriptase.

PubMed

He, Shan; Li, Yangyang; Chen, Yang; Zhu, Yue; Zhang, Xinyu; Xia, Xiaoli; Sun, Huaichang

2016-08-01

Pigs are the most economically important livestock, but pig cell lines useful for physiological studies and/or vaccine development are limited. Although several pig cell lines have been generated by oncogene transformation or human telomerase reverse transcriptase (TERT) immortalization, these cell lines contain viral sequences and/or antibiotic resistance genes. In this study, we established a new method for generating pig cell lines using the Sleeping Beauty (SB) transposon-mediated ectopic expression of porcine telomerase reverse transcriptase (pTERT). The performance of the new method was confirmed by generating a pig fibroblast cell (PFC) line. After transfection of primary PFCs with the SB transposon system, one cell clone containing the pTERT expression cassette was selected by dilution cloning and passed for different generations. After passage for more than 40 generations, the cell line retained stable expression of ectopic pTERT and continuous growth potential. Further characterization showed that the cell line kept the fibroblast morphology, growth curve, population doubling time, cloning efficiency, marker gene expression pattern, cell cycle distribution and anchorage-dependent growth property of the primary cells. These data suggest that the new method established is useful for generating pig cell lines without viral sequence and antibiotic resistant gene.

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 ...

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.

Ectopic expression of SUPERMAN suppresses development of petals and stamens.

PubMed

Yun, Jae-Young; Weigel, Detlef; Lee, Ilha

2002-01-01

The floral regulatory gene SUPERMAN (SUP) encodes a C2H2 type zinc finger protein that is required for maintaining boundaries between floral organs in Arabidopsis. It has been proposed that the main function of SUP is to balance cell proliferation in the third and fourth whorl of developing flowers, thereby maintaining the boundaries between the two whorls. To gain further insight into the function of SUP, we have ectopically expressed SUP using the promoter of APETALA1 (AP1), a gene that is initially expressed throughout floral meristems and later becomes restricted to the first and second whorls. Flowers of AP1::SUP plants have fewer floral organs, consistent with an effect of SUP on cell proliferation. In addition, the AP1::SUP transgene caused the conversion of petals to sepals and suppressed the development of stamens. The expression of the B function homeotic gene APETALA3 (AP3) and its regulator UNUSUAL FLORAL ORGANS (UFO) were delayed and reduced in AP1::SUP flowers. However, SUP does not act merely through UFO, as constitutive expression of UFO did not rescue the defects in petal and stamen development in AP1::SUP flowers. Together, these results suggest that SUP has both indirect and direct effects on the expression of B function homeotic genes.

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 ...

Ectopic Expression of Xylella fastidiosa rpfF Conferring Production of Diffusible Signal Factor in Transgenic Tobacco and Citrus Alters Pathogen Behavior and Reduces Disease Severity.

PubMed

Caserta, R; Souza-Neto, R R; Takita, M A; Lindow, S E; De Souza, A A

2017-11-01

The pathogenicity of Xylella fastidiosa is associated with its ability to colonize the xylem of host plants. Expression of genes contributing to xylem colonization are suppressed, while those necessary for insect vector acquisition are increased with increasing concentrations of diffusible signal factor (DSF), whose production is dependent on RpfF. We previously demonstrated that transgenic citrus plants ectopically expressing rpfF from a citrus strain of X. fastidiosa subsp. pauca exhibited less susceptibility to Xanthomonas citri subsp. citri, another pathogen whose virulence is modulated by DSF accumulation. Here, we demonstrate that ectopic expression of rpfF in both transgenic tobacco and sweet orange also confers a reduction in disease severity incited by X. fastidiosa and reduces its colonization of those plants. Decreased disease severity in the transgenic plants was generally associated with increased expression of genes conferring adhesiveness to the pathogen and decreased expression of genes necessary for active motility, accounting for the reduced population sizes achieved in the plants, apparently by limiting pathogen dispersal through the plant. Plant-derived DSF signal molecules in a host plant can, therefore, be exploited to interfere with more than one pathogen whose virulence is controlled by DSF signaling.

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

Ectopic Six3 expression in the dragon eye goldfish.

PubMed

Ma, Dong-Mei; Zhu, Hua-Ping; Gui, Jian-Fang

2008-02-01

For goldfish (Carassius auratus), there are many varieties with different eye phenotypes due to artificial selection and adaptive evolution. Dragon eye is a variant eye characterized by a large-size eyeball protruding out of the socket similar to the eye of dragon in Chinese legends. In this study, anatomical structure of the goldfish dragon eye was compared with that of the common eye, and a stretching of the retina was observed in the enlarged dragon eye. Moreover, the homeobox-containing transcription factor Six3 cDNAs were cloned from the two types of goldfish, and the expression patterns were analyzed in both normal eye and dragon eye goldfish. No amino acid sequence differences were observed between the two deduced peptides, and the expression pattern of Six3 protein in dragon eye is quite similar to common eye during embryogenesis, but from 2 days after hatching, ectopic Six3 expression began to occur in the dragon eye, especially in the outer nuclear layer cells. With eye development, more predominant Six3 distribution was detected in the outer nuclear layer cells of dragon eye than that of normal eye, and fewer cell-layers in outer nuclear layer were observed in dragon eye retina than in normal eye retina. The highlight of this study is that higher Six3 expression occurs in dragon eye goldfish than in normal eye goldfish during retinal development of larvae.

Restrictions in Cell Cycle Progression of Adult Vestibular Supporting Cells in Response to Ectopic Cyclin D1 Expression

PubMed Central

Loponen, Heidi; Ylikoski, Jukka; Albrecht, Jeffrey H.; Pirvola, Ulla

2011-01-01

Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27Kip1 and p21Cip1 expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells. PMID:22073316

Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression.

PubMed

Loponen, Heidi; Ylikoski, Jukka; Albrecht, Jeffrey H; Pirvola, Ulla

2011-01-01

Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27(Kip1) and p21(Cip1) expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells.

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, ...

Epigenetically induced ectopic expression of UNCX impairs the proliferation and differentiation of myeloid cells

PubMed Central

Daniele, Giulia; Simonetti, Giorgia; Fusilli, Caterina; Iacobucci, Ilaria; Lonoce, Angelo; Palazzo, Antonio; Lomiento, Mariana; Mammoli, Fabiana; Marsano, Renè Massimiliano; Marasco, Elena; Mantovani, Vilma; Quentmeier, Hilmar; Drexler, Hans G; Ding, Jie; Palumbo, Orazio; Carella, Massimo; Nadarajah, Niroshan; Perricone, Margherita; Ottaviani, Emanuela; Baldazzi, Carmen; Testoni, Nicoletta; Papayannidis, Cristina; Ferrari, Sergio; Mazza, Tommaso; Martinelli, Giovanni; Storlazzi, Clelia Tiziana

2017-01-01

We here describe a leukemogenic role of the homeobox gene UNCX, activated by epigenetic modifications in acute myeloid leukemia (AML). We found the ectopic activation of UNCX in a leukemia patient harboring a t(7;10)(p22;p14) translocation, in 22 of 61 of additional cases [a total of 23 positive patients out of 62 (37.1%)], and in 6 of 75 (8%) of AML cell lines. UNCX is embedded within a low-methylation region (canyon) and encodes for a transcription factor involved in somitogenesis and neurogenesis, with specific expression in the eye, brain, and kidney. UNCX expression turned out to be associated, and significantly correlated, with DNA methylation increase at its canyon borders based on data in our patients and in archived data of patients from The Cancer Genome Atlas. UNCX-positive and -negative patients displayed significant differences in their gene expression profiles. An enrichment of genes involved in cell proliferation and differentiation, such as MAP2K1 and CCNA1, was revealed. Similar results were obtained in UNCX-transduced CD34+ cells, associated with low proliferation and differentiation arrest. Accordingly, we showed that UNCX expression characterizes leukemia cells at their early stage of differentiation, mainly M2 and M3 subtypes carrying wild-type NPM1. We also observed that UNCX expression significantly associates with an increased frequency of acute promyelocytic leukemia with PML-RARA and AML with t(8;21)(q22;q22.1); RUNX1-RUNX1T1 classes, according to the World Health Organization disease classification. In summary, our findings suggest a novel leukemogenic role of UNCX, associated with epigenetic modifications and with impaired cell proliferation and differentiation in AML. PMID:28411256

Epigenetically induced ectopic expression of UNCX impairs the proliferation and differentiation of myeloid cells.

PubMed

Daniele, Giulia; Simonetti, Giorgia; Fusilli, Caterina; Iacobucci, Ilaria; Lonoce, Angelo; Palazzo, Antonio; Lomiento, Mariana; Mammoli, Fabiana; Marsano, Renè Massimiliano; Marasco, Elena; Mantovani, Vilma; Quentmeier, Hilmar; Drexler, Hans G; Ding, Jie; Palumbo, Orazio; Carella, Massimo; Nadarajah, Niroshan; Perricone, Margherita; Ottaviani, Emanuela; Baldazzi, Carmen; Testoni, Nicoletta; Papayannidis, Cristina; Ferrari, Sergio; Mazza, Tommaso; Martinelli, Giovanni; Storlazzi, Clelia Tiziana

2017-07-01

We here describe a leukemogenic role of the homeobox gene UNCX , activated by epigenetic modifications in acute myeloid leukemia (AML). We found the ectopic activation of UNCX in a leukemia patient harboring a t(7;10)(p22;p14) translocation, in 22 of 61 of additional cases [a total of 23 positive patients out of 62 (37.1%)], and in 6 of 75 (8%) of AML cell lines. UNCX is embedded within a low-methylation region (canyon) and encodes for a transcription factor involved in somitogenesis and neurogenesis, with specific expression in the eye, brain, and kidney. UNCX expression turned out to be associated, and significantly correlated, with DNA methylation increase at its canyon borders based on data in our patients and in archived data of patients from The Cancer Genome Atlas. UNCX -positive and -negative patients displayed significant differences in their gene expression profiles. An enrichment of genes involved in cell proliferation and differentiation, such as MAP2K1 and CCNA1 , was revealed. Similar results were obtained in UNCX -transduced CD34 + cells, associated with low proliferation and differentiation arrest. Accordingly, we showed that UNCX expression characterizes leukemia cells at their early stage of differentiation, mainly M2 and M3 subtypes carrying wild-type NPM1 We also observed that UNCX expression significantly associates with an increased frequency of acute promyelocytic leukemia with PML-RARA and AML with t(8;21)(q22;q22.1); RUNX1-RUNX1T1 classes, according to the World Health Organization disease classification. In summary, our findings suggest a novel leukemogenic role of UNCX , associated with epigenetic modifications and with impaired cell proliferation and differentiation in AML. Copyright© 2017 Ferrata Storti Foundation.

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.

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.

Ectopic Expression of α6 and δ GABAA Receptor Subunits in Hilar Somatostatin Neurons Increases Tonic Inhibition and Alters Network Activity in the Dentate Gyrus

PubMed Central

Tong, Xiaoping; Peng, Zechun; Zhang, Nianhui; Cetina, Yliana; Huang, Christine S.; Wallner, Martin; Otis, Thomas S.

2015-01-01

The role of GABAA receptor (GABAAR)-mediated tonic inhibition in interneurons remains unclear and may vary among subgroups. Somatostatin (SOM) interneurons in the hilus of the dentate gyrus show negligible expression of nonsynaptic GABAAR subunits and very low tonic inhibition. To determine the effects of ectopic expression of tonic GABAAR subtypes in these neurons, Cre-dependent viral vectors were used to express GFP-tagged GABAAR subunits (α6 and δ) selectively in hilar SOM neurons in SOM-Cre mice. In single-transfected animals, immunohistochemistry demonstrated strong expression of either the α6 or δ subunit; in cotransfected animals, both subunits were consistently expressed in the same neurons. Electrophysiology revealed a robust increase of tonic current, with progressively larger increases following transfection of δ, α6, and α6/δ subunits, respectively, indicating formation of functional receptors in all conditions and likely coassembly of the subunits in the same receptor following cotransfection. An in vitro model of repetitive bursting was used to determine the effects of increased tonic inhibition in hilar SOM interneurons on circuit activity in the dentate gyrus. Upon cotransfection, the frequency of GABAAR-mediated bursting in granule cells was reduced, consistent with a reduction in synchronous firing among hilar SOM interneurons. Moreover, in vivo studies of Fos expression demonstrated reduced activation of α6/δ-cotransfected neurons following acute seizure induction by pentylenetetrazole. The findings demonstrate that increasing tonic inhibition in hilar SOM interneurons can alter dentate gyrus circuit activity during strong stimulation and suggest that tonic inhibition of interneurons could play a role in regulating excessive synchrony within the network. SIGNIFICANCE STATEMENT In contrast to many hippocampal interneurons, somatostatin (SOM) neurons in the hilus of the dentate gyrus have very low levels of nonsynaptic GABAARs and exhibit

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 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.

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

p38 phosphorylation in medullary microglia mediates ectopic orofacial inflammatory pain in rats.

PubMed

Kiyomoto, Masaaki; Shinoda, Masamichi; Honda, Kuniya; Nakaya, Yuka; Dezawa, Ko; Katagiri, Ayano; Kamakura, Satoshi; Inoue, Tomio; Iwata, Koichi

2015-08-12

Orofacial inflammatory pain is likely to accompany referred pain in uninflamed orofacial structures. The ectopic pain precludes precise diagnosis and makes treatment problematic, because the underlying mechanism is not well understood. Using the established ectopic orofacial pain model induced by complete Freund's adjuvant (CFA) injection into trapezius muscle, we analyzed the possible role of p38 phosphorylation in activated microglia in ectopic orofacial pain. Mechanical allodynia in the lateral facial skin was induced following trapezius muscle inflammation, which accompanied microglial activation with p38 phosphorylation and hyperexcitability of wide dynamic range (WDR) neurons in the trigeminal spinal subnucleus caudalis (Vc). Intra-cisterna successive administration of a p38 mitogen-activated protein kinase selective inhibitor, SB203580, suppressed microglial activation and its phosphorylation of p38. Moreover, SB203580 administration completely suppressed mechanical allodynia in the lateral facial skin and enhanced WDR neuronal excitability in Vc. Microglial interleukin-1β over-expression in Vc was induced by trapezius muscle inflammation, which was significantly suppressed by SB203580 administration. These findings indicate that microglia, activated via p38 phosphorylation, play a pivotal role in WDR neuronal hyperexcitability, which accounts for the mechanical hypersensitivity in the lateral facial skin associated with trapezius muscle inflammation.

Transient ectopic expression of the histone demethylase JMJD3 accelerates the differentiation of human pluripotent stem cells

PubMed Central

Wakabayashi, Shunichi; Soma, Atsumi; Sato, Saeko; Nakatake, Yuhki; Oda, Mayumi; Murakami, Miyako; Sakota, Miki; Chikazawa-Nohtomi, Nana

2016-01-01

Harnessing epigenetic regulation is crucial for the efficient and proper differentiation of pluripotent stem cells (PSCs) into desired cell types. Histone H3 lysine 27 trimethylation (H3K27me3) functions as a barrier against cell differentiation through the suppression of developmental gene expression in PSCs. Here, we have generated human PSC (hPSC) lines in which genome-wide reduction of H3K27me3 can be induced by ectopic expression of the catalytic domain of the histone demethylase JMJD3 (called JMJD3c). We found that transient, forced demethylation of H3K27me3 alone triggers the upregulation of mesoendodermal genes, even when the culture conditions for the hPSCs are not changed. Furthermore, transient and forced expression of JMJD3c followed by the forced expression of lineage-defining transcription factors enabled the hPSCs to activate tissue-specific genes directly. We have also shown that the introduction of JMJD3c facilitates the differentiation of hPSCs into functional hepatic cells and skeletal muscle cells. These results suggest the utility of the direct manipulation of epigenomes for generating desired cell types from hPSCs for cell transplantation therapy and platforms for drug screenings. PMID:27802135

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.

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.

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 expression of pMADS3 in transgenic petunia phenocopies the petunia blind mutant.

PubMed Central

Tsuchimoto, S; van der Krol, A R; Chua, N H

1993-01-01

We cloned a MADS-box gene, pMADS3, from Petunia hybrida, which shows high sequence homology to the Arabidopsis AGAMOUS and Antirrhinum PLENA. pMADS3 is expressed exclusively in stamens and carpels of wild-type petunia plants. In the petunia mutant blind, which shows homeotic conversions of corolla limbs into antheroid structures with pollen grains and small parts of sepals into carpelloid tissue, pMADS3 is expressed in all floral organs as well as in leaves. Ectopic expression of pMADS3 in transgenic petunia leads to phenocopies of the blind mutant, i.e., the formation of antheroid structures on limbs and carpelloid tissue on sepals. Transgenic tobacco plants that overexpress pMADS3 exhibit an even more severe phenotype, with the sepals forming a carpel-like structure encasing the interior floral organs. Our results identify BLIND as a negative regulator of pMADS3, which specifies stamens and carpels during petunia flower development. PMID:8104573

Optimized transitory ectopic expression of promastigote surface antigen protein in Nicotiana benthamiana, a potential anti-leishmaniasis vaccine candidate.

PubMed

Lacombe, Séverine; Bangratz, Martine; Brizard, Jean-Paul; Petitdidier, Elodie; Pagniez, Julie; Sérémé, Drissa; Lemesre, Jean-Loup; Brugidou, Christophe

2018-01-01

In recent years, plants have been shown to be an efficient alternative expression system for high-value pharmaceuticals such as vaccines. However, constitutive expression of recombinant protein remains uncertain on their level of production and biological activity. To overcome these problems, transitory expression systems have been developed. Here, a series of experiments were performed to determine the most effective conditions to enhance vaccine antigen transient accumulation in Nicotiana benthamiana leaves using the promastigote surface antigen (PSA) from the parasitic protozoan Leishmania infantum. This protein has been previously identified as the major antigen of a licensed canine anti-leishmaniasis vaccine. The classical prokaryote Escherichia coli biosystem failed in accumulating PSA. Consequently, the standard plant system based on N. benthamiana has been optimized for the production of putatively active PSA. First, the RNA silencing defense mechanism set up by the plant against PSA ectopic expression was abolished by using three viral suppressors acting at different steps of the RNA silencing pathway. Then, we demonstrated that the signal peptide at the N-terminal side of the PSA is required for its accumulation. The PSA ER signaling and retention with the PSA signal peptide and the KDEL motif, respectively were optimized to significantly increase its accumulation. Finally, we demonstrate that the production of recombinant PSA in N. benthamiana leaves allows the conservation of its immunogenic property. These approaches demonstrate that based on these optimizations, plant based systems can be used to effectively produce the biological active PSA protein. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Ectopic transgene expression in the retina of four transgenic mouse lines

PubMed Central

Gábriel, Robert; Erdélyi, Ferenc; Szabó, Gábor; Lawrence, J. Josh

2017-01-01

Retinal expression of transgenes was examined in four mouse lines. Two constructs were driven by the choline acetyltransferase (ChAT) promoter: green fluorescent protein conjugated to tau protein (tau-GFP) or cytosolic yellow fluorescent protein (YFP) generated through CRE recombinase-induced expression of Rosa26 (ChAT-CRE/ Rosa26YFP). Two other constructs targeted inhibitory interneurons: GABAergic horizontal and amacrine cells identified by glutamic acid decarboxylase (GAD65-GFP) or parvalbumin (PV) cells (PV-CRE/Rosa26YFP). Animals were transcardially perfused and retinal sections prepared. Antibodies against PV, calretinin (CALR), calbindin (CALB), and tyrosine hydroxylase (TH) were used to counterstain transgene-expressing cells. In PVxRosa and ChAT-tauGFP constructs, staining appeared in vertically oriented row of processes resembling Müller cells. In the ChATxRosa construct, populations of amacrine cells and neurons in the ganglion cell layer were labeled. Some cones also exhibited GFP fluorescence. CALR, PV and TH were found in none of these cells. Occasionally, we found GFP/ CALR and GFP/PV double-stained cells in the ganglion cell layer (GCL). In the GAD65-GFP construct, all layers of the neuroretina were labeled, except photoreceptors. Not all horizontal cells expressed GFP. We did not find GFP/TH double-labeled cells and GFP was rarely present in CALR-and CALB-containing cells. Many PV-positive neurons were also labeled for GFP, including small diameter amacrines. In the GCL, single labeling for GFP and PV was ascertained, as well as several CALR/PV double-stained neurons. In the GCL, cells triple labeled with GFP/CALR/ CALB were sparse. In conclusion, only one of the four transgenic constructs exhibited an expression pattern consistent with endogenous retinal protein expression, while the others strongly suggested ectopic gene expression. PMID:26563404

Enhanced drought and heat stress tolerance of tobacco plants with ectopically enhanced cytokinin oxidase/dehydrogenase gene expression

PubMed Central

Macková, Hana; Hronková, Marie; Dobrá, Jana; Turečková, Veronika; Novák, Ondřej; Lubovská, Zuzana; Motyka, Václav; Haisel, Daniel; Hájek, Tomáš; Prášil, Ilja Tom; Gaudinová, Alena; Štorchová, Helena; Ge, Eva; Werner, Tomáš; Schmülling, Thomas; Vanková, Radomíra

2013-01-01

Responses to drought, heat, and combined stress were compared in tobacco (Nicotiana tabacum L.) plants ectopically expressing the cytokinin oxidase/dehydrogenase CKX1 gene of Arabidopsis thaliana L. under the control of either the predominantly root-expressed WRKY6 promoter or the constitutive 35S promoter, and in the wild type. WRKY6:CKX1 plants exhibited high CKX activity in the roots under control conditions. Under stress, the activity of the WRKY6 promoter was down-regulated and the concomitantly reduced cytokinin degradation coincided with raised bioactive cytokinin levels during the early phase of the stress response, which might contribute to enhanced stress tolerance of this genotype. Constitutive expression of CKX1 resulted in an enlarged root system, a stunted, dwarf shoot phenotype, and a low basal level of expression of the dehydration marker gene ERD10B. The high drought tolerance of this genotype was associated with a relatively moderate drop in leaf water potential and a significant decrease in leaf osmotic potential. Basal expression of the proline biosynthetic gene P5CSA was raised. Both wild-type and WRKY6:CKX1 plants responded to heat stress by transient elevation of stomatal conductance, which correlated with an enhanced abscisic acid catabolism. 35S:CKX1 transgenic plants exhibited a small and delayed stomatal response. Nevertheless, they maintained a lower leaf temperature than the other genotypes. Heat shock applied to drought-stressed plants exaggerated the negative stress effects, probably due to the additional water loss caused by a transient stimulation of transpiration. The results indicate that modulation of cytokinin levels may positively affect plant responses to abiotic stress through a variety of physiological mechanisms. PMID:23669573

Treatment of collagenase-induced osteoarthritis with a viral vector encoding TSG-6 results in ectopic bone formation.

PubMed

Broeren, Mathijs G A; Di Ceglie, Irene; Bennink, Miranda B; van Lent, Peter L E M; van den Berg, Wim B; Koenders, Marije I; Blaney Davidson, Esmeralda N; van der Kraan, Peter M; van de Loo, Fons A J

2018-01-01

Tumor necrosis factor-inducible gene 6 (TSG-6) has anti-inflammatory and chondroprotective effects in mouse models of inflammatory arthritis. Because cartilage damage and inflammation are also observed in osteoarthritis (OA), we determined the effect of viral overexpression of TSG-6 in experimental osteoarthritis. Bone marrow-derived cells were differentiated to multinucleated osteoclasts in the presence of recombinant TSG-6 or after transduction with a lentiviral TSG-6 expression vector. Multi-nucleated osteoclasts were analyzed after tartrate resistant acid phosphatase staining and resorption activity was determined on dentin slices. Collagenase-induced osteoarthritis (CIOA) was induced in C57BL/6 mice after intra-articular injection of an adenoviral TSG-6 or control luciferase expression vector. Inflammation-related protease activity was measured using bioluminescent Prosense probes. After a second adenovirus injection, cartilage damage was assessed in histological sections stained with Safranin-O. Ectopic bone formation was scored in X-ray images of the affected knees. TSG-6 did not inhibit the formation of multi-nucleated osteoclasts, but caused a significant reduction in the resorption activity on dentin slices. Adenoviral TSG-6 gene therapy in CIOA could not reduce the cartilage damage compared to the luciferase control virus and no significant difference in inflammation-related protease activity was noted between the TSG-6 and control treated group. Instead, X-ray analysis and histological analysis revealed the presence of ectopic bone formation in the TSG-6 treated group. Gene therapy based on the expression of TSG-6 could not provide cartilage protection in experimental osteoarthritis, but instead resulted in increased ectopic bone formation.

Behavior of ectopic surface: effects of β-adrenergic stimulation and uncoupling

PubMed Central

Arutunyan, Ara; Pumir, Alain; Krinsky, Valentin; Swift, Luther; Sarvazyan, Narine

2011-01-01

By using both experimental and theoretical means, we have addressed the progression of ectopic activity from individual cardiac cells to a multicellular two-dimensional network. Experimental conditions that favor ectopic activity have been created by local perfusion of a small area of cardiomyocyte network (I-zone) with an isoproterenol-heptanol containing solution. The application of this solution initially slowed down and then fully blocked wave propagation inside the I-zone. After a brief lag period, ectopically active cells appeared in the I-zone, followed by evolution of the ectopic clusters into slowly propagating waves. The changing pattern of colliding and expanding ectopic waves confined to the I-zone persisted for as long as the isoproterenol-heptanol environment was present. On restoration of the control environment, the ectopic waves from the I-zone broke out into the surrounding network causing arrhythmias. The observed sequence of events was also modeled by FitzHugh-Nagumo equations and included a cell’s arrangement of two adjacent square regions of 20 × 20 cells. The control zone consisted of well-connected, excitable cells, and the I-zone was made of weakly coupled cells (heptanol effect), which became spontaneously active as time evolved (isoproterenol effect). The dynamic events in the system have been studied numerically with the use of a finite difference method. Together, our experimental and computational data have revealed that the combination of low coupling, increased excitability, and spatial heterogeneity can lead to the development of ectopic waves confined to the injured network. This transient condition appears to serve as an essential step for the ectopic activity to “mature” before escaping into the surrounding control network. PMID:12893638

Behavior of ectopic surface: effects of beta-adrenergic stimulation and uncoupling.

PubMed

Arutunyan, Ara; Pumir, Alain; Krinsky, Valentin; Swift, Luther; Sarvazyan, Narine

2003-12-01

By using both experimental and theoretical means, we have addressed the progression of ectopic activity from individual cardiac cells to a multicellular two-dimensional network. Experimental conditions that favor ectopic activity have been created by local perfusion of a small area of cardiomyocyte network (I-zone) with an isoproterenol-heptanol containing solution. The application of this solution initially slowed down and then fully blocked wave propagation inside the I-zone. After a brief lag period, ectopically active cells appeared in the I-zone, followed by evolution of the ectopic clusters into slowly propagating waves. The changing pattern of colliding and expanding ectopic waves confined to the I-zone persisted for as long as the isoproterenol-heptanol environment was present. On restoration of the control environment, the ectopic waves from the I-zone broke out into the surrounding network causing arrhythmias. The observed sequence of events was also modeled by FitzHugh-Nagumo equations and included a cell's arrangement of two adjacent square regions of 20 x 20 cells. The control zone consisted of well-connected, excitable cells, and the I-zone was made of weakly coupled cells (heptanol effect), which became spontaneously active as time evolved (isoproterenol effect). The dynamic events in the system have been studied numerically with the use of a finite difference method. Together, our experimental and computational data have revealed that the combination of low coupling, increased excitability, and spatial heterogeneity can lead to the development of ectopic waves confined to the injured network. This transient condition appears to serve as an essential step for the ectopic activity to "mature" before escaping into the surrounding control network.

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

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 ...

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.

Complete adult neurogenesis within a Wallerian degenerating nerve expressed as an ectopic ganglion.

PubMed

Nakano, Tomonori; Kurimoto, Shigeru; Kato, Shuichi; Asano, Kenichi; Hirata, Takuma; Kiyama, Hiroshi; Hirata, Hitoshi

2018-06-01

Neurogenesis in the adult peripheral nervous system remains to be demonstrated. We transplanted embryonic neural stem cells into a Wallerian degenerating nerve graft and observed development of a nodular structure consisting of neurons, glia, and Schwann cells. Histological analysis revealed a structure loosely resembling the spinal cord, including a synaptic network that formed along the neuron. Furthermore, the new axons reinnervated the paralysed muscle, forming both de novo and revived neuromuscular junctions. Reinnervation of the paralysed muscle resulted in significantly greater mean wet muscle weight and muscle fibre cross-sectional area on the cell transplantation side than on the surgical control side (body weight 0.071 ± 0.011% vs. 0.051 ± 0.007%, p = .006; area 355.6 ± 345.2 vs. 114.0 ± 132.0 μm 2 , p < .001). Electrophysiological experiments demonstrated a functional connection between the neurons and muscle; hence, we identified this nodule as an ectopic ganglion. Surprisingly, in green rat experiments, most of these glial cells, but none of the neurons, expressed enhanced green fluorescent protein, suggesting that the cells constituting the ectopic ganglion were derived from both transplanted stem cells and endogenous stem cells. Such adult neurogenesis in a peripheral nerve related to neural stem cell transplantation has not been reported previously, and these results form the basis for a novel regenerative medicine approach in paralysed muscle. Copyright © 2018 John Wiley & Sons, Ltd.

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.

Ectopically expressing MdPIP1;3, an aquaporin gene, increased fruit size and enhanced drought tolerance of transgenic tomatoes.

PubMed

Wang, Lin; Li, Qing-Tian; Lei, Qiong; Feng, Chao; Zheng, Xiaodong; Zhou, Fangfang; Li, Lingzi; Liu, Xuan; Wang, Zhi; Kong, Jin

2017-12-19

Water deficit severely reduces apple growth and production, is detrimental to fruit quality and size. This problem is exacerbated as global warming is implicated in producing more severe drought stress. Thus water-efficiency has becomes the major target for apple breeding. A desired apple tree can absorb and transport water efficiently, which not only confers improved drought tolerance, but also guarantees fruit size for higher income returns. Aquaporins, as water channels, control water transportation across membranes and can regulate water flow by changing their amount and activity. The exploration of molecular mechanism of water efficiency and the gene wealth will pave a way for molecular breeding of drought tolerant apple tree. In the current study, we screened out a drought inducible aquaporin gene MdPIP1;3, which specifically enhanced its expression during fruit expansion in 'Fuji' apple (Malus domestica Borkh. cv. Red Fuji). It localized on plasma membranes and belonged to PIP1 subfamily. The tolerance to drought stress enhanced in transgenic tomato plants ectopically expressing MdPIP1;3, showing that the rate of losing water in isolated transgenic leaves was slower than wild type, and stomata of transgenic plants closed sensitively to respond to drought compared with wild type. Besides, length and diameter of transgenic tomato fruits increased faster than wild type, and in final, fruit sizes and fresh weights of transgenic tomatoes were bigger than wild type. Specially, in cell levels, fruit cell size from transgenic tomatoes was larger than wild type, showing that cell number per mm 2 in transgenic fruits was less than wild type. Altogether, ectopically expressing MdPIP1;3 enhanced drought tolerance of transgenic tomatoes partially via reduced water loss controlled by stomata closure in leaves. In addition, the transgenic tomato fruits are larger and heavier with larger cells via more efficient water transportation across membranes. Our research will

Ectopic expression of the gastric inhibitory polypeptide receptor gene is a sufficient genetic event to induce benign adrenocortical tumor in a xenotransplantation model.

PubMed

Mazzuco, Tania L; Chabre, Olivier; Sturm, Nathalie; Feige, Jean-Jacques; Thomas, Michaël

2006-02-01

Aberrant expression of ectopic G protein-coupled receptors (GPCRs) in adrenal cortex tissue has been observed in several cases of ACTH-independent macronodular adrenal hyperplasias and adenomas associated with Cushing's syndrome. Although there is clear clinical evidence for the implication of these ectopic receptors in abnormal regulation of cortisol production, whether this aberrant GPCR expression is the cause or the consequence of the development of an adrenal hyperplasia is still an open question. To answer it, we genetically engineered primary bovine adrenocortical cells to have them express the gastric inhibitory polypeptide receptor. After transplantation of these modified cells under the renal capsule of adrenalectomized immunodeficient mice, tissues formed had their functional and histological characteristics analyzed. We observed the formation of an enlarged and hyperproliferative adenomatous adrenocortical tissue that secreted cortisol in a gastric inhibitory polypeptide-dependent manner and induced a mild Cushing's syndrome with hyperglycemia. Moreover, we show that tumor development was ACTH independent. Thus, a single genetic event, inappropriate expression of a nonmutated GPCR gene, is sufficient to initiate the complete phenotypic alterations that ultimately lead to the formation of a benign adrenocortical tumor.

Ectopic expression of Arabidopsis broad-spectrum resistance gene RPW8.2 improves the resistance to powdery mildew in grapevine (Vitis vinifera).

PubMed

Hu, Yang; Li, Yajuan; Hou, Fengjuan; Wan, Dongyan; Cheng, Yuan; Han, Yongtao; Gao, Yurong; Liu, Jie; Guo, Ye; Xiao, Shunyuan; Wang, Yuejin; Wen, Ying-Qiang

2018-02-01

Powdery mildew is the most economically important disease of cultivated grapevines worldwide. Here, we report that the Arabidopsis broad-spectrum disease resistance gene RPW8.2 could improve resistance to powdery mildew in Vitis vinifera cv. Thompson Seedless. The RPW8.2-YFP fusion gene was stably expressed in grapevines from either the constitutive 35S promoter or the native promoter (NP) of RPW8.2. The grapevine shoots and plantlets transgenic for 35S::RPW8.2-YFP showed reduced rooting and reduced growth at later development stages in the absence of any pathogens. Infection tests with an adapted grapevine powdery mildew isolate En NAFU1 showed that hyphal growth and sporulation were significantly restricted in transgenic grapevines expressing either of the two constructs. The resistance appeared to be attributable to the ectopic expression of RPW8.2, and associated with the enhanced encasement of the haustorial complex (EHC) and onsite accumulation of H 2 O 2 . In addition, the RPW8.2-YFP fusion protein showed focal accumulation around the fungal penetration sites. Transcriptome analysis revealed that ectopic expression of RPW8.2 in grapevines not only significantly enhanced salicylic acid-dependent defense signaling, but also altered expression of other phytohormone-associated genes. Taken together, our results indicate that RPW8.2 could be utilized as a transgene for improving resistance against powdery mildew in grapevines. Copyright © 2017 Elsevier B.V. All rights reserved.

Combined VEGF and LMP-1 delivery enhances osteoprogenitor cell differentiation and ectopic bone formation.

PubMed

Wang, Xiuli; Cui, Fuai; Madhu, Vedavathi; Dighe, Abhijit S; Balian, Gary; Cui, Quanjun

2011-02-01

A novel strategy to enhance bone repair is to combine angiogenic factors and osteogenic factors. We combined vascular endothelial growth factor (VEGF) and LIM mineralization protein-1 (LMP-1) by using an internal ribosome entry site to link the genes within a single plasmid. We then evaluated the effects on osteoblastic differentiation in vitro and ectopic bone formation in vivo with a subcutaneously placed PLAGA scaffold loaded with a cloned mouse osteoprogenitor cell line, D1, transfected with plasmids containing VEGF and LMP-1 genes. The cells expressing both genes elevated mRNA expression of RunX2 and β-catenin and alkaline phosphatase activity compared to cells from other groups. In vivo, X-ray and micro-CT analysis of the retrieved implants revealed more ectopic bone formation at 2 and 3 weeks but not at 4 weeks compared to other groups. The results indicate that the combination of the therapeutic growth factors potentiates cell differentiation and may promote osteogenesis.

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

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.

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.

Alteration of flower color in Iris germanica L. 'Fire Bride' through ectopic expression of phytoene synthase gene (crtB) from Pantoea agglomerans.

PubMed

Jeknić, Zoran; Jeknić, Stevan; Jevremović, Slađana; Subotić, Angelina; Chen, Tony H H

2014-08-01

Genetic modulation of the carotenogenesis in I. germanica 'Fire Bride' by ectopic expression of a crtB gene causes several flower parts to develop novel orange and pink colors. Flower color in tall bearded irises (Iris germanica L.) is determined by two distinct biochemical pathways; the carotenoid pathway, which imparts yellow, orange and pink hues and the anthocyanin pathway, which produces blue, violet and maroon flowers. Red-flowered I. germanica do not exist in nature and conventional breeding methods have thus far failed to produce them. With a goal of developing iris cultivars with red flowers, we transformed a pink iris I. germanica, 'Fire Bride', with a bacterial phytoene synthase gene (crtB) from Pantoea agglomerans under the control of the promoter region of a gene for capsanthin-capsorubin synthase from Lilium lancifolium (Llccs). This approach aimed to increase the flux of metabolites into the carotenoid biosynthetic pathway and lead to elevated levels of lycopene and darker pink or red flowers. Iris callus tissue ectopically expressing the crtB gene exhibited a color change from yellow to pink-orange and red, due to accumulation of lycopene. Transgenic iris plants, regenerated from the crtB-transgenic calli, showed prominent color changes in the ovaries (green to orange), flower stalk (green to orange), and anthers (white to pink), while the standards and falls showed no significant differences in color when compared to control plants. HPLC and UHPLC analysis confirmed that the color changes were primarily due to the accumulation of lycopene. In this study, we showed that ectopic expression of a crtB can be used to successfully alter the color of certain flower parts in I. germanica 'Fire Bride' and produce new flower traits.

Does adenosine deaminase activity play a role in the early diagnosis of ectopic pregnancy?

PubMed

Turkmen, G G; Karçaaltıncaba, D; Isık, H; Fidancı, V; Kaayalp, D; Tımur, H; Batıoglu, S

2016-01-01

Early diagnosis of ectopic pregnancy (EP) is important due to life-threatening consequences in the first trimester of pregnancy. In this study we aimed to investigate the role of adenosine deaminase (ADA) activity in the prediction of EP. Forty-one patients with unruptured ectopic pregnancy comprised the case group and forty-two first trimester pregnant women with shown foetal heart beating in ultrasound comprised the control group. The mean ADA level in EP (10.9 ± 3.0 IU/L) was higher than that in control group (9.2 ± 3.6 IU/L) (p = 0.018). Receiver operating characteristics or ROC curve identified ADA value of 10.95 IU/L as optimal threshold for the prediction of EP with 56% sensitivity and 67% specificity. High ADA levels are valuable in the early diagnosis of EP. However more comprehensive studies are required.

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

Ectopic Expression of Pumpkin NAC Transcription Factor CmNAC1 Improves Multiple Abiotic Stress Tolerance in Arabidopsis

PubMed Central

Cao, Haishun; Wang, Li; Nawaz, Muhammad A.; Niu, Mengliang; Sun, Jingyu; Xie, Junjun; Kong, Qiusheng; Huang, Yuan; Cheng, Fei; Bie, Zhilong

2017-01-01

Drought, cold and salinity are the major environmental stresses that limit agricultural productivity. NAC transcription factors regulate the stress response in plants. Pumpkin (Cucurbita moschata) is an important cucurbit vegetable crop and it has strong resistance to abiotic stress; however, the biological functions of stress-related NAC genes in this crop are largely unknown. This study reports the function of CmNAC1, a stress-responsive pumpkin NAC domain protein. The CmNAC1-GFP fusion protein was transiently expressed in tobacco leaves for subcellular localization analysis, and we found that CmNAC1 is localized in the nucleus. Transactivation assay in yeast cells revealed that CmNAC1 functions as a transcription activator, and its transactivation domain is located in the C-terminus. CmNAC1 was ubiquitously expressed in different organs, and its transcript was induced by salinity, cold, dehydration, H2O2, and abscisic acid (ABA) treatment. Furthermore, the ectopic expression (EE) of CmNAC1 in Arabidopsis led to ABA hypersensitivity and enhanced tolerance to salinity, drought and cold stress. In addition, five ABA-responsive elements were enriched in CmNAC1 promoter. The CmNAC1-EE plants exhibited different root architecture, leaf morphology, and significantly high concentration of ABA compared with WT Arabidopsis under normal conditions. Our results indicated that CmNAC1 is a critical factor in ABA signaling pathways and it can be utilized in transgenic breeding to improve the abiotic stress tolerance of crops. PMID:29234347

Ectopic expression of different cytokinin-regulated transcription factor genes of Arabidopsis thaliana alters plant growth and development.

PubMed

Köllmer, Ireen; Werner, Tomáš; Schmülling, Thomas

2011-08-15

The plant hormone cytokinin rapidly alters the steady state transcript levels of a number of transcription factor genes suggesting that these might have a function in mediating cytokinin effects. Here we report the analysis of Arabidopsis thaliana plants with an altered expression level of four different cytokinin-regulated transcription factor genes. These include GATA22 (also known as CGA1/GNL), two genes coding for members of the homeodomain zip (HD zip) class II transcription factor family (HAT4, HAT22), and bHLH64. Ectopic expression of the GATA22 gene induced the development of chloroplasts in root tissue where it is normally suppressed and led to the formation of shorter and less branched roots. Overexpression of HAT22 lowered the seedlings chlorophyll content and caused an earlier onset of leaf senescence. Enhanced expression of the HAT4 gene led to severe defects in inflorescence stem development and to a decrease in root growth and branching, while hat4 insertional mutants developed a larger root system. 35S:bHLH64 transgenic plants showed a pleiotropic phenotype, consisting of larger rosettes, reduced chlorophyll content and an elongated and thickened hypocotyl. Flower development was strongly disturbed leading to sterile plants. The results are consistent with specific functions of these transcription factor genes in regulating part of the cytokinin activities and suggest their action as convergence point with other signalling pathways, particularly those of gibberellin and light. Copyright © 2011 Elsevier GmbH. All rights reserved.

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.

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 lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium.

PubMed

Humby, Frances; Bombardieri, Michele; Manzo, Antonio; Kelly, Stephen; Blades, Mark C; Kirkham, Bruce; Spencer, Jo; Pitzalis, Costantino

2009-01-13

Follicular structures resembling germinal centres (GCs) that are characterized by follicular dendritic cell (FDC) networks have long been recognized in chronically inflamed tissues in autoimmune diseases, including the synovium of rheumatoid arthritis (RA). However, it is debated whether these ectopic structures promote autoimmunity and chronic inflammation driving the production of pathogenic autoantibodies. Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific markers of RA, predict a poor prognosis, and have been suggested to be pathogenic. Therefore, the main study objectives were to determine whether ectopic lymphoid structures in RA synovium: (i) express activation-induced cytidine deaminase (AID), the enzyme required for somatic hypermutation and class-switch recombination (CSR) of Ig genes; (ii) support ongoing CSR and ACPA production; and (iii) remain functional in a RA/severe combined immunodeficiency (SCID) chimera model devoid of new immune cell influx into the synovium. Using immunohistochemistry (IHC) and quantitative Taqman real-time PCR (QT-PCR) in synovial tissue from 55 patients with RA, we demonstrated that FDC+ structures invariably expressed AID with a distribution resembling secondary lymphoid organs. Further, AID+/CD21+ follicular structures were surrounded by ACPA+/CD138+ plasma cells, as demonstrated by immune reactivity to citrullinated fibrinogen. Moreover, we identified a novel subset of synovial AID+/CD20+ B cells outside GCs resembling interfollicular large B cells. In order to gain direct functional evidence that AID+ structures support CSR and in situ manufacturing of class-switched ACPA, 34 SCID mice were transplanted with RA synovium and humanely killed at 4 wk for harvesting of transplants and sera. Persistent expression of AID and Igamma-Cmu circular transcripts (identifying ongoing IgM-IgG class-switching) was observed in synovial grafts expressing FDCs/CD21L. Furthermore, synovial mRNA levels of AID were

Elevated ATF4 Expression, in the Absence of Other Signals, Is Sufficient for Transcriptional Induction via CCAAT Enhancer-binding Protein-activating Transcription Factor Response Elements*

PubMed Central

Shan, Jixiu; Örd, Daima; Örd, Tõnis; Kilberg, Michael S.

2009-01-01

Protein limitation in vivo or amino acid deprivation of cells in culture causes a signal transduction cascade consisting of activation of the kinase GCN2 (general control nonderepressible 2), phosphorylation of eukaryotic initiation factor 2, and increased synthesis of activating transcription factor (ATF) 4 by a translational control mechanism. In a self-limiting transcriptional program, ATF4 transiently activates a wide range of downstream target genes involved in transport, cellular metabolism, and other cell functions. Simultaneous activation of other signal transduction pathways by amino acid deprivation led to the question of whether or not the increased abundance of ATF4 alone was sufficient to trigger the transcriptional control mechanisms. Using 293 cells that ectopically express ATF4 in a tetracycline-inducible manner showed that ATF4 target genes were activated in the absence of amino acid deprivation. Ectopic expression of ATF4 alone resulted in effective recruitment of the general transcription machinery, but some reduction in histone modification was observed. These data document that ATF4 alone is sufficient to trigger the amino acid-responsive transcriptional control program. However, the absolute amount of ectopic ATF4 required to achieve the same degree of transcriptional activation observed after amino acid limitation was greater, suggesting that other factors may serve to enhance ATF4 function. PMID:19509279

[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.

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.

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

Ectopic Activation of Wnt/β-Catenin Signaling in Lens Fiber Cells Results in Cataract Formation and Aberrant Fiber Cell Differentiation

PubMed Central

Antosova, Barbora; Smolikova, Jana; Borkovcova, Romana; Strnad, Hynek; Lachova, Jitka; Machon, Ondrej; Kozmik, Zbynek

2013-01-01

The Wnt/β-catenin signaling pathway controls many processes during development, including cell proliferation, cell differentiation and tissue homeostasis, and its aberrant regulation has been linked to various pathologies. In this study we investigated the effect of ectopic activation of Wnt/β-catenin signaling during lens fiber cell differentiation. To activate Wnt/β-catenin signaling in lens fiber cells, the transgenic mouse referred to as αA-CLEF was generated, in which the transactivation domain of β-catenin was fused to the DNA-binding protein LEF1, and expression of the transgene was controlled by αA-crystallin promoter. Constitutive activation of Wnt/β-catenin signaling in lens fiber cells of αA-CLEF mice resulted in abnormal and delayed fiber cell differentiation. Moreover, adult αA-CLEF mice developed cataract, microphthalmia and manifested downregulated levels of γ-crystallins in lenses. We provide evidence of aberrant expression of cell cycle regulators in embryonic lenses of αA-CLEF transgenic mice resulting in the delay in cell cycle exit and in the shift of fiber cell differentiation to the central fiber cell compartment. Our results indicate that precise regulation of the Wnt/β-catenin signaling activity during later stages of lens development is essential for proper lens fiber cell differentiation and lens transparency. PMID:24205179

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

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.

Ectopic Expression of GsPPCK3 and SCMRP in Medicago sativa Enhances Plant Alkaline Stress Tolerance and Methionine Content

PubMed Central

Zhao, Yang; Zhao, Chaoyue; DuanMu, Huizi; Yu, Yang; Ji, Wei; Zhu, Yanming

2014-01-01

So far, it has been suggested that phosphoenolpyruvate carboxylases (PEPCs) and PEPC kinases (PPCKs) fulfill several important non-photosynthetic functions. However, the biological functions of soybean PPCKs, especially in alkali stress response, are not yet well known. In previous studies, we constructed a Glycine soja transcriptional profile, and identified three PPCK genes (GsPPCK1, GsPPCK2 and GsPPCK3) as potential alkali stress responsive genes. In this study, we confirmed the induced expression of GsPPCK3 under alkali stress and investigated its tissue expression specificity by using quantitative real-time PCR analysis. Then we ectopically expressed GsPPCK3 in Medicago sativa and found that GsPPCK3 overexpression improved plant alkali tolerance, as evidenced by lower levels of relative ion leakage and MDA content and higher levels of chlorophyll content and root activity. In this respect, we further co-transformed the GsPPCK3 and SCMRP genes into alfalfa, and demonstrated the increased alkali tolerance of GsPPCK3-SCMRP transgenic lines. Further investigation revealed that GsPPCK3-SCMRP co-overexpression promoted the PEPC activity, net photosynthetic rate and citric acid content of transgenic alfalfa under alkali stress. Moreover, we also observed the up-regulated expression of PEPC, CS (citrate synthase), H+-ATPase and NADP-ME genes in GsPPCK3-SCMRP transgenic alfalfa under alkali stress. As expected, we demonstrated that GsPPCK3-SCMRP transgenic lines displayed higher methionine content than wild type alfalfa. Taken together, results presented in this study supported the positive role of GsPPCK3 in plant response to alkali stress, and provided an effective way to simultaneously improve plant alkaline tolerance and methionine content, at least in legume crops. PMID:24586886

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 expression of ORANGE promotes carotenoid accumulation and fruit development in tomato.

PubMed

Yazdani, Mohammad; Sun, Zhaoxia; Yuan, Hui; Zeng, Shaohua; Thannhauser, Theodore W; Vrebalov, Julia; Ma, Qiyue; Xu, Yimin; Fei, Zhangjun; Van Eck, Joyce; Tian, Shiping; Tadmor, Yaakov; Giovannoni, James J; Li, Li

2018-05-05

Carotenoids are critically important to plants and humans. The ORANGE (OR) gene is a key regulator for carotenoid accumulation, but its physiological roles in crops remain elusive. In this study, we generated transgenic tomato ectopically overexpressing the Arabidopsis wild-type OR (AtOR WT ) and a 'golden SNP'-containing OR (AtOR H is ). We found that AtOR H is initiated chromoplast formation in very young fruit and stimulated carotenoid accumulation at all fruit developmental stages, uncoupled from other ripening activities. The elevated levels of carotenoids in the AtOR lines were distributed in the same subplastidial fractions as in wild-type tomato, indicating an adaptive response of plastids to sequester the increased carotenoids. Microscopic analysis revealed that the plastid sizes were increased in both AtOR WT and AtOR H is lines at early fruit developmental stages. Moreover, AtOR overexpression promoted early flowering, fruit set and seed production. Ethylene production and the expression of ripening-associated genes were also significantly increased in the AtOR transgenic fruit at ripening stages. RNA-Seq transcriptomic profiling highlighted the primary effects of OR overexpression on the genes in the processes related to RNA, protein and signalling in tomato fruit. Taken together, these results expand our understanding of OR in mediating carotenoid accumulation in plants and suggest additional roles of OR in affecting plastid size as well as flower and fruit development, thus making OR a target gene not only for nutritional biofortification of agricultural products but also for alteration of horticultural traits. © 2018 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Ectopic Expression of BnaC.CP20.1 Results in Premature Tapetal Programmed Cell Death in Arabidopsis.

PubMed

Song, Liping; Zhou, Zhengfu; Tang, Shan; Zhang, Zhiqiang; Xia, Shengqian; Qin, Maomao; Li, Bao; Wen, Jing; Yi, Bin; Shen, Jinxiong; Ma, Chaozhi; Fu, Tingdong; Tu, Jinxing

2016-09-01

Tapetal programmed cell death (PCD) is essential in pollen grain development, and cysteine proteases are ubiquitous enzymes participating in plant PCD. Although the major papain-like cysteine proteases (PLCPs) have been investigated, the exact functions of many PLCPs are still poorly understood in PCD. Here, we identified a PLCP gene, BnaC.CP20.1, which was closely related to XP_013596648.1 from Brassica oleracea. Quantitative real-time PCR analysis revealed that BnaC.CP20.1 expression was down-regulated in male-sterile lines in oilseed rape, suggesting a connection between this gene and male sterility. BnaC.CP20.1 is especially active in the tapetum and microspores in Brassica napus from the uninucleate stage until formation of mature pollen grains during anther development. On expression of BnaC.CP20.1 prior to the tetrad stage, BnA9::BnaC.CP20.1 transgenic lines in Arabidopsis thaliana showed a male-sterile phenotype with shortened siliques containing fewer or no seeds by self-crossing. Scanning electron microscopy indicated that the reticulate exine was defective in aborted microspores. Callose degradation was delayed and microspores were not released from the tetrad in a timely fashion. Additionally, the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay indicated that BnaC.CP20.1 ectopic expression led to premature tapetal PCD. Transmission electron microscopy analyses further demonstrated that the pollen abortion was due to the absence of tectum connections to the bacula in the transgenic anthers. These findings suggest that timely expression of BnaC.CP20.1 is necessary for tapetal degeneration and pollen wall formation. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Unanswered questions on ectopic pregnancy.

PubMed

Jonas, E G

1980-07-19

In a previous article (3 May, p. 1127), the British Medical Journal attempted to assess the demography of ectopic pregnancy and noted that a rise in incidence might lead to a better diagnosis of the condition. Cited as possible causes of ectopic pregnancy are pelvic sepsis and IUD usage. There is clinical confirmation of the relationship between pelvic sepsis and IUD usage. A review of the records of 325 consecutive patients diagnosed as having ectopic pregnancy in 4 large London Hospitals during the period 1967-79 revealed that PID (Pelvic Inflammatory Disease) was uncommon (11%). 12% of the remaining patients had IUDs and a further 2% were progestogen-only contraceptive failures. As regards the role of IUDs in ectopic pregnancy, failed intrauterine contraception is hypothesized to result in pregnancy, but with an incidence of ectopic, mainly tubal, implantation by reasons of disturbed ovum migration along the oviduct. The physiology of the human oviduct is not well known. Further research should be done on the many common aberations of human reproduction, iatrogenic and spontaneous.

TNFRp55 deficiency promotes the development of ectopic endometriotic-like lesions in mice.

PubMed

Vallcaneras, Sandra; Ghersa, Federica; Bastón, Juan; Delsouc, María Belén; Meresman, Gabriela; Casais, Marilina

2017-09-01

Endometriosis is an inflammatory disease depending on estradiol, with TNF-α being one of the most representative cytokines involved in its pathogenesis. TNF-α acts through its bond to the TNFRp55 and TNFRp75 membrane receptors. The aim of this study was to analyze the effect of the TNFRp55 deficiency on the development of ectopic endometriotic-like lesions. Endometriosis was induced surgically in mice of the C57BL/6 strain, wild type (WT) and TNFRp55-/- (KO). After four weeks, the peritoneal fluid was collected and the lesions were counted, measured with a caliper, removed, weighed, fixed or kept at -80°C. We evaluated the cell proliferation by proliferating cell nuclear antigen (PCNA) immunohistochemistry and apoptosis by TUNEL technique in the ectopic lesions. MMP-2 and MMP-9 activities (factors involved in invasiveness) were measured by zymography in the peritoneal fluid; estradiol and progesterone levels were measured by radioimmunoassay in the lesions and in the peritoneal fluid. We found that in KO animals the mean number of lesions established per mouse, the lesion volume, weight and cell proliferation increased and apoptosis decreased. In addition, the activity of MMP-2 and the estradiol level increased, whereas the progesterone level was not significantly modified. In conclusion, the deficiency of TNFRp55 promoted the establishment and development of endometriosis through an increase in the lesion size and high levels of estradiol which correlate with an increase in the MMP-2 activity. This is evidence of the possible association of the deregulation of the TNFRp55 expression and the survival of the endometriotic tissue in ectopic sites. © 2017 Society for Endocrinology.

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

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.

Clustered metallothionein genes are co-regulated in rice and ectopic expression of OsMT1e-P confers multiple abiotic stress tolerance in tobacco via ROS scavenging

PubMed Central

2012-01-01

Background Metallothioneins (MT) are low molecular weight, cysteine rich metal binding proteins, found across genera and species, but their function(s) in abiotic stress tolerance are not well documented. Results We have characterized a rice MT gene, OsMT1e-P, isolated from a subtractive library generated from a stressed salinity tolerant rice genotype, Pokkali. Bioinformatics analysis of the rice genome sequence revealed that this gene belongs to a multigenic family, which consists of 13 genes with 15 protein products. OsMT1e-P is located on chromosome XI, away from the majority of other type I genes that are clustered on chromosome XII. Various members of this MT gene cluster showed a tight co-regulation pattern under several abiotic stresses. Sequence analysis revealed the presence of conserved cysteine residues in OsMT1e-P protein. Salinity stress was found to regulate the transcript abundance of OsMT1e-P in a developmental and organ specific manner. Using transgenic approach, we found a positive correlation between ectopic expression of OsMT1e-P and stress tolerance. Our experiments further suggest ROS scavenging to be the possible mechanism for multiple stress tolerance conferred by OsMT1e-P. Conclusion We present an overview of MTs, describing their gene structure, genome localization and expression patterns under salinity and development in rice. We have found that ectopic expression of OsMT1e-P enhances tolerance towards multiple abiotic stresses in transgenic tobacco and the resultant plants could survive and set viable seeds under saline conditions. Taken together, the experiments presented here have indicated that ectopic expression of OsMT1e-P protects against oxidative stress primarily through efficient scavenging of reactive oxygen species. PMID:22780875

Clustered metallothionein genes are co-regulated in rice and ectopic expression of OsMT1e-P confers multiple abiotic stress tolerance in tobacco via ROS scavenging.

PubMed

Kumar, Gautam; Kushwaha, Hemant Ritturaj; Panjabi-Sabharwal, Vaishali; Kumari, Sumita; Joshi, Rohit; Karan, Ratna; Mittal, Shweta; Pareek, Sneh L Singla; Pareek, Ashwani

2012-07-10

Metallothioneins (MT) are low molecular weight, cysteine rich metal binding proteins, found across genera and species, but their function(s) in abiotic stress tolerance are not well documented. We have characterized a rice MT gene, OsMT1e-P, isolated from a subtractive library generated from a stressed salinity tolerant rice genotype, Pokkali. Bioinformatics analysis of the rice genome sequence revealed that this gene belongs to a multigenic family, which consists of 13 genes with 15 protein products. OsMT1e-P is located on chromosome XI, away from the majority of other type I genes that are clustered on chromosome XII. Various members of this MT gene cluster showed a tight co-regulation pattern under several abiotic stresses. Sequence analysis revealed the presence of conserved cysteine residues in OsMT1e-P protein. Salinity stress was found to regulate the transcript abundance of OsMT1e-P in a developmental and organ specific manner. Using transgenic approach, we found a positive correlation between ectopic expression of OsMT1e-P and stress tolerance. Our experiments further suggest ROS scavenging to be the possible mechanism for multiple stress tolerance conferred by OsMT1e-P. We present an overview of MTs, describing their gene structure, genome localization and expression patterns under salinity and development in rice. We have found that ectopic expression of OsMT1e-P enhances tolerance towards multiple abiotic stresses in transgenic tobacco and the resultant plants could survive and set viable seeds under saline conditions. Taken together, the experiments presented here have indicated that ectopic expression of OsMT1e-P protects against oxidative stress primarily through efficient scavenging of reactive oxygen species.

An Activated Form of UFO Alters Leaf Development and Produces Ectopic Floral and Inflorescence Meristems

PubMed Central

Risseeuw, Eddy; Venglat, Prakash; Xiang, Daoquan; Komendant, Kristina; Daskalchuk, Tim; Babic, Vivijan; Crosby, William; Datla, Raju

2013-01-01

Plants are unique in their ability to continuously produce new meristems and organ primordia. In Arabidopsis, the transcription factor LEAFY (LFY) functions as a master regulator of a gene network that is important for floral meristem and organ specification. UNUSUAL FLORAL ORGANS (UFO) is a co-activator of LEAFY and is required for proper activation of APETALA3 in the floral meristem during the specification of stamens and petals. The ufo mutants display defects in other parts of the flower and the inflorescence, suggestive of additional roles. Here we show that the normal determinacy of the developing Arabidopsis leaves is affected by the expression of a gain-of-function UFO fusion protein with the VP16 transcriptional activator domain. In these lines, the rosette and cauline leaf primordia exhibit reiterated serration, and upon flowering produce ectopic meristems that develop into flowers, bract leaves and inflorescences. These striking phenotypes reveal that developing leaves maintain the competency to initiate flower and inflorescence programs. Furthermore, the gain-of-function phenotypes are dependent on LFY and the SEPALLATA (SEP) MADS-box transcription factors, indicative of their functional interactions with UFO. The findings of this study also suggest that UFO promotes the establishment of the lateral meristems and primordia in the peripheral zone of the apical and floral meristems by enhancing the activity of LFY. These novel phenotypes along with the mutant phenotypes of UFO orthologs in other plant species suggest a broader function for UFO in plants. PMID:24376756

An activated form of UFO alters leaf development and produces ectopic floral and inflorescence meristems.

PubMed

Risseeuw, Eddy; Venglat, Prakash; Xiang, Daoquan; Komendant, Kristina; Daskalchuk, Tim; Babic, Vivijan; Crosby, William; Datla, Raju

2013-01-01

Plants are unique in their ability to continuously produce new meristems and organ primordia. In Arabidopsis, the transcription factor LEAFY (LFY) functions as a master regulator of a gene network that is important for floral meristem and organ specification. UNUSUAL FLORAL ORGANS (UFO) is a co-activator of LEAFY and is required for proper activation of APETALA3 in the floral meristem during the specification of stamens and petals. The ufo mutants display defects in other parts of the flower and the inflorescence, suggestive of additional roles. Here we show that the normal determinacy of the developing Arabidopsis leaves is affected by the expression of a gain-of-function UFO fusion protein with the VP16 transcriptional activator domain. In these lines, the rosette and cauline leaf primordia exhibit reiterated serration, and upon flowering produce ectopic meristems that develop into flowers, bract leaves and inflorescences. These striking phenotypes reveal that developing leaves maintain the competency to initiate flower and inflorescence programs. Furthermore, the gain-of-function phenotypes are dependent on LFY and the SEPALLATA (SEP) MADS-box transcription factors, indicative of their functional interactions with UFO. The findings of this study also suggest that UFO promotes the establishment of the lateral meristems and primordia in the peripheral zone of the apical and floral meristems by enhancing the activity of LFY. These novel phenotypes along with the mutant phenotypes of UFO orthologs in other plant species suggest a broader function for UFO in plants.

Ectopic vesicular glutamate release at the optic nerve head and axon loss in mouse experimental glaucoma.

PubMed

Fu, Christine T; Sretavan, David W

2012-11-07

Although clinical and experimental observations indicate that the optic nerve head (ONH) is a major site of axon degeneration in glaucoma, the mechanisms by which local retinal ganglion cell (RGC) axons are injured and damage spreads among axons remain poorly defined. Using a laser-induced ocular hypertension (LIOH) mouse model of glaucoma, we found that within 48 h of intraocular pressure elevation, RGC axon segments within the ONH exhibited ectopic accumulation and colocalization of multiple components of the glutamatergic presynaptic machinery including the vesicular glutamate transporter VGLUT2, several synaptic vesicle marker proteins, glutamate, the soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex and active zone cytomatrix components, as well as ultrastructurally identified, synaptophysin-containing vesicles. Ectopic vesicle exocytosis and glutamate release were detected in acute preparations of the LIOH ONH. Immunolocalization and analysis using the ionotropic receptor channel-permeant cation agmatine indicated that ONH axon segments and glia expressed glutamate receptors, and these receptors were more active after LIOH compared with controls. Pharmacological antagonism of glutamate receptors and neuronal activity resulted in increased RGC axon sparing in vivo. Furthermore, in vivo RGC-specific genetic disruption of the vesicular glutamate transporter VGLUT2 or the obligatory NMDA receptor subunit NR1 promoted axon survival in experimental glaucoma. As the inhibition of ectopic glutamate vesicular release or glutamate receptivity can independently modify the severity of RGC axon loss, synaptic release mechanisms may provide useful therapeutic entry points into glaucomatous axon degeneration.

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

Novel DLK-independent neuronal regeneration in Caenorhabditis elegans shares links with activity-dependent ectopic outgrowth

PubMed Central

Awal, Mehraj R.; Shay, James; McLoed, Melissa M.; Mazur, Eric; Gabel, Christopher V.

2016-01-01

During development, a neuron transitions from a state of rapid growth to a stable morphology, and neurons within the adult mammalian CNS lose their ability to effectively regenerate in response to injury. Here, we identify a novel form of neuronal regeneration, which is remarkably independent of DLK-1/DLK, KGB-1/JNK, and other MAPK signaling factors known to mediate regeneration in Caenorhabditis elegans, Drosophila, and mammals. This DLK-independent regeneration in C. elegans has direct genetic and molecular links to a well-studied form of endogenous activity-dependent ectopic axon outgrowth in the same neuron type. Both neuron outgrowth types are triggered by physical lesion of the sensory dendrite or mutations disrupting sensory activity, calcium signaling, or genes that restrict outgrowth during neuronal maturation, such as SAX-1/NDR kinase or UNC-43/CaMKII. These connections suggest that ectopic outgrowth represents a powerful platform for gene discovery in neuronal regeneration. Moreover, we note numerous similarities between C. elegans DLK-independent regeneration and lesion conditioning, a phenomenon producing robust regeneration in the mammalian CNS. Both regeneration types are triggered by lesion of a sensory neurite via reduction of neuronal activity and enhanced by disrupting L-type calcium channels or elevating cAMP. Taken as a whole, our study unites disparate forms of neuronal outgrowth to uncover fresh molecular insights into activity-dependent control of the adult nervous system’s intrinsic regenerative capacity. PMID:27078101

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

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.

Ectopic expression of ABSCISIC ACID 2/GLUCOSE INSENSITIVE 1 in Arabidopsis promotes seed dormancy and stress tolerance.

PubMed

Lin, Pei-Chi; Hwang, San-Gwang; Endo, Akira; Okamoto, Masanori; Koshiba, Tomokazu; Cheng, Wan-Hsing

2007-02-01

Abscisic acid (ABA) is an important phytohormone that plays a critical role in seed development, dormancy, and stress tolerance. 9-cis-Epoxycarotenoid dioxygenase is the key enzyme controlling ABA biosynthesis and stress tolerance. In this study, we investigated the effect of ectopic expression of another ABA biosynthesis gene, ABA2 (or GLUCOSE INSENSITIVE 1 [GIN1]) encoding a short-chain dehydrogenase/reductase in Arabidopsis (Arabidopsis thaliana). We show that ABA2-overexpressing transgenic plants with elevated ABA levels exhibited seed germination delay and more tolerance to salinity than wild type when grown on agar plates and/or in soil. However, the germination delay was abolished in transgenic plants showing ABA levels over 2-fold higher than that of wild type grown on 250 mm NaCl. The data suggest that there are distinct mechanisms underlying ABA-mediated inhibition of seed germination under diverse stress. The ABA-deficient mutant aba2, with a shorter primary root, can be restored to normal root growth by exogenous application of ABA, whereas transgenic plants overexpressing ABA2 showed normal root growth. The data reflect that the basal levels of ABA are essential for maintaining normal primary root elongation. Furthermore, analysis of ABA2 promoter activity with ABA2::beta-glucuronidase transgenic plants revealed that the promoter activity was enhanced by multiple prolonged stresses, such as drought, salinity, cold, and flooding, but not by short-term stress treatments. Coincidently, prolonged drought stress treatment led to the up-regulation of ABA biosynthetic and sugar-related genes. Thus, the data support ABA2 as a late expression gene that might have a fine-tuning function in mediating ABA biosynthesis through primary metabolic changes in response to stress.

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 ...

Transketolase-like 1 ectopic expression is associated with DNA hypomethylation and induces the Warburg effect in melanoma cells.

PubMed

Jayachandran, Aparna; Lo, Pu-Han; Chueh, Anderly C; Prithviraj, Prashanth; Molania, Ramyar; Davalos-Salas, Mercedes; Anaka, Matthew; Walkiewicz, Marzena; Cebon, Jonathan; Behren, Andreas

2016-02-22

The metabolism of cancer cells is often reprogrammed by dysregulation of metabolic enzymes. Transketolase-like 1 (TKTL1) is a homodimeric transketolase linking the pentose-phosphate pathway with the glycolytic pathway. It is generally silenced at a transcriptional level in somatic tissues. However, in human cancers its expression is associated with the acquisition of a glycolytic phenotype (the Warburg effect) by cancer cells that contributes to the progression of malignant tumors. In melanoma, defective promoter methylation results in the expression of genes and their products that can affect the tumor cell's phenotype including the modification of immune and functional characteristics. The present study evaluates the role of TKTL1 as a mediator of disease progression in melanoma associated with a defective methylation phenotype. The expression of TKTL1 in metastatic melanoma tumors and cell lines was analysed by qRT-PCR and immunohistochemistry. The promoter methylation status of TKTL1 in melanoma cells was evaluated by quantitative methylation specific PCR. Using qRT-PCR, the effect of a DNA demethylating agent 5-aza-2'-deoxycytidine (5aza) on the expression of TKTL1 was examined. Biochemical and molecular analyses such as glucose consumption, lactate production, invasion, proliferation and cell cycle progression together with ectopic expression and siRNA mediated knockdown were used to investigate the role of TKTL1 in melanoma cells. Expression of TKTL1 was highly restricted in normal adult tissues and was overexpressed in a subset of metastatic melanoma tumors and derived cell lines. The TKTL1 promoter was activated by hypomethylation and treatment with 5aza induced TKTL1 expression in melanoma cells. Augmented expression of TKTL1 in melanoma cells was associated with a glycolytic phenotype. Loss and gain of function studies revealed that TKTL1 contributed to enhanced invasion of melanoma cells. Our data provide evidence for an important role of TKTL1 in

Ectopic expression of class 1 KNOX genes induce adventitious shoot regeneration and alter growth and development of tobacco (Nicotiana tabacum L) and European plum (Prunus domestica L).

PubMed

Srinivasan, C; Liu, Zongrang; Scorza, Ralph

2011-04-01

Transgenic plants of tobacco (Nicotiana tabacum L) and European plum (Prunus domestica L) were produced by transforming with the apple class 1 KNOX genes (MdKN1 and MdKN2) or corn KNOX1 gene. Transgenic tobacco plants were regenerated in vitro from transformed leaf discs cultured in a medium lacking cytokinin. Ectopic expression of KNOX genes retarded shoot growth by suppressing elongation of internodes in transgenic tobacco plants. Expression of each of the three KNOX1 genes induced malformation and extensive lobbing in tobacco leaves. In situ regeneration of adventitious shoots was observed from leaves and roots of transgenic tobacco plants expressing each of the three KNOX genes. In vitro culture of leaf explants and internode sections excised from in vitro grown MdKN1 expressing tobacco shoots regenerated adventitious shoots on MS (Murashige and Skoog 1962) basal medium in the absence of exogenous cytokinin. Transgenic plum plants that expressed the MdKN2 or corn KNOX1 gene grew normally but MdKN1 caused a significant reduction in plant height, leaf shape and size and produced malformed curly leaves. A high frequency of adventitious shoot regeneration (96%) was observed in cultures of leaf explants excised from corn KNOX1-expressing transgenic plum shoots. In contrast to KNOX1-expressing tobacco, leaf and internode explants of corn KNOX1-expressing plum required synthetic cytokinin (thidiazuron) in the culture medium to induce adventitious shoot regeneration. The induction of high-frequency regeneration of adventitious shoots in vitro from leaves and stem internodal sections of plum through the ectopic expression of a KNOX1 gene is the first such report for a woody perennial fruit trees.

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.

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

Activation of the CXCL16/CXCR6 Axis by TNF-α Contributes to Ectopic Endometrial Stromal Cells Migration and Invasion.

PubMed

Peng, Yaoming; Ma, Junyan; Lin, Jun

2018-01-01

The activation of systemic and local inflammatory mechanisms, including elevated levels of chemokines and proinflammatory cytokines in endometriosis progression, is becoming more evident in the recent years. Here, we report the involvement of CXC chemokine 16 (CXCL16) and its sole receptor, CXC chemokine receptor 6 (CXCR6), in pathophysiology of endometriosis. Expression of CXCL16, but not CXCR6, was significantly upregulated in endometriotic lesions when compared to control endometrium. Additionally, serum CXCL16 was significantly elevated in women with endometriosis when compared to control group. Moreover, blockade of the CXCL16/CXCR6 axis by CXCR6 small-interfering RNA reduced the migration and invasion of ectopic endometrial stromal cells (EESCs) followed by decreased phosphorylation of ERK1/2. Furthermore, TNF-α treatment induced the expression of CXCL16 in EESCs. In conclusion, these results suggest that CXCL16/CXCR6 axis, whose expression was enhanced by TNF-α, may be associated with the increased motility of EESCs, through regulation of ERK1/2 signaling, thus contributing to the development of endometriosis. These findings indicate that the CXCL16/CXCR6 axis may contribute to the progression of endometriosis and could be served as a potential target for diagnosis and treatment.

Ectopic expression of anti-HIV-1 shRNAs protects CD8{sup +} T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation

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

Kamata, Masakazu, E-mail: masa3k@ucla.edu; Kim, Patrick Y.; Ng, Hwee L.

Chimeric antigen receptors (CARs) are artificially engineered receptors that confer a desired specificity to immune effector T cells. As an HIV-1-specific CAR, CD4ζ CAR has been extensively tested in vitro as well as in clinical trials. T cells modified with this CAR mediated highly potent anti-HIV-1 activities in vitro and were well-tolerated in vivo, but exerted limited effects on viral load and reservoir size due to poor survival and/or functionality of the transduced cells in patients. We hypothesize that ectopic expression of CD4ζ on CD8{sup +} T cells renders them susceptible to HIV-1 infection, resulting in poor survival of those cells. To testmore » this possibility, highly purified CD8{sup +} T cells were genetically modified with a CD4ζ-encoding lentiviral vector and infected with HIV-1. CD8{sup +} T cells were vulnerable to HIV-1 infection upon expression of CD4ζ as evidenced by elevated levels of p24{sup Gag} in cells and culture supernatants. Concurrently, the number of CD4ζ-modified CD8{sup +} T cells was reduced relative to control cells upon HIV-1 infection. To protect these cells from HIV-1 infection, we co-expressed two anti-HIV-1 shRNAs previously developed by our group together with CD4ζ. This combination vector was able to suppress HIV-1 infection without impairing HIV-1-dependent effector activities of CD4ζ. In addition, the number of CD4ζ-modified CD8{sup +} T cells maintained similar levels to that of the control even under HIV-1 infection. These results suggest that protecting CD4ζ-modified CD8{sup +} T cells from HIV-1 infection is required for prolonged HIV-1-specific immune surveillance. - Highlights: • Ectopic expression of CD4ζ CAR in CD8{sup +} T cells renders them susceptible to HIV-1 infection. • Co-expression of two anti-HIV-1 shRNAs protects CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection. • Protecting CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection suppresses its cytopathic effect.« less

Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells.

PubMed

Wang, Rui; Kozhaya, Lina; Mercer, Frances; Khaitan, Alka; Fujii, Hodaka; Unutmaz, Derya

2009-08-11

The molecules that define human regulatory T cells (Tregs) phenotypically and functionally remain to be fully characterized. We recently showed that activated human Tregs express mRNA for a transmembrane protein called glycoprotein A repetitions predominant (GARP, or LRRC32). Here, using a GARP-specific mAb, we demonstrate that expression of GARP on activated Tregs correlates with their suppressive capacity. However, GARP was not induced on T cells activated in the presence of TGFbeta, which expressed high levels of FOXP3 and lacked suppressive function. Ectopic expression of FOXP3 in conventional T cells was also insufficient for induction of GARP expression in most donors. Functionally, silencing GARP in Tregs only moderately attenuated their suppressive activity. CD25+ T cells sorted for high GARP expression displayed more potent suppressive activity compared with CD25+GARP- cells. Remarkably, CD25+GARP- T cells expanded in culture contained 3-5 fold higher IL-17-secreting cells compared with either CD25+GARP+ or CD25-GARP- cells, suggesting that high GARP expression can potentially discriminate Tregs from those that have switched to Th17 lineage. We also determined whether GARP expression correlates with FOXP3-expressing T cells in human immunodeficiency virus (HIV) -infected subjects. A subset of HIV+ individuals with high percentages of FOXP3+ T cells did not show proportionate increase in GARP+ T cells. This finding suggests that higher FOXP3 levels observed in these HIV+ individuals is possibly due to immune activation rather than to an increase in Tregs. Our findings highlight the significance of GARP both in dissecting duality of Treg/Th17 cell differentiation and as a marker to identify bona fide Tregs during diseases with chronic immune activation.

Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells

PubMed Central

Wang, Rui; Kozhaya, Lina; Mercer, Frances; Khaitan, Alka; Fujii, Hodaka; Unutmaz, Derya

2009-01-01

The molecules that define human regulatory T cells (Tregs) phenotypically and functionally remain to be fully characterized. We recently showed that activated human Tregs express mRNA for a transmembrane protein called glycoprotein A repetitions predominant (GARP, or LRRC32). Here, using a GARP-specific mAb, we demonstrate that expression of GARP on activated Tregs correlates with their suppressive capacity. However, GARP was not induced on T cells activated in the presence of TGFβ, which expressed high levels of FOXP3 and lacked suppressive function. Ectopic expression of FOXP3 in conventional T cells was also insufficient for induction of GARP expression in most donors. Functionally, silencing GARP in Tregs only moderately attenuated their suppressive activity. CD25+ T cells sorted for high GARP expression displayed more potent suppressive activity compared with CD25+GARP− cells. Remarkably, CD25+GARP− T cells expanded in culture contained 3–5 fold higher IL-17-secreting cells compared with either CD25+GARP+ or CD25−GARP− cells, suggesting that high GARP expression can potentially discriminate Tregs from those that have switched to Th17 lineage. We also determined whether GARP expression correlates with FOXP3-expressing T cells in human immunodeficiency virus (HIV) −infected subjects. A subset of HIV+ individuals with high percentages of FOXP3+ T cells did not show proportionate increase in GARP+ T cells. This finding suggests that higher FOXP3 levels observed in these HIV+ individuals is possibly due to immune activation rather than to an increase in Tregs. Our findings highlight the significance of GARP both in dissecting duality of Treg/Th17 cell differentiation and as a marker to identify bona fide Tregs during diseases with chronic immune activation. PMID:19666573

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.

The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome.

PubMed Central

de Keyzer, Y; Lenne, F; Auzan, C; Jégou, S; René, P; Vaudry, H; Kuhn, J M; Luton, J P; Clauser, E; Bertagna, X

1996-01-01

Ectopic ACTH secretion occurs in highly differentiated and rather indolent tumors like bronchial carcinoids or, in contrast, in various types of aggressive and poorly differentiated neuroendocrine tumors. We explored this phenomenon using the recently cloned human pituitary V3 vasopressin receptor as an alternate molecular marker of the corticotroph phenotype. Expression of V3 receptor, corticotrophin releasing hormone (CRH) receptor, and proopiomelanocortin (POMC) genes was examined in tumors of pituitary and nonpituitary origin. A comparative RT-PCR approach revealed signals for both V3 receptor and CHR receptor mRNAs in 17 of 18 ACTH-secreting pituitary adenomas, and 6 of 6 normal pituitaries; in six growth hormone- or prolactin-secreting adenomas, a very faint V3 receptor signal was observed in three cases, and CRH receptor signal was undetected in all. Six of eight bronchial carcinoids responsible for the ectopic ACTH syndrome had both POMC and V3 receptor signals as high as those in ACTH-secreting pituitary adenomas; in contrast, no POMC signal and only a very faint V3 receptor signal were detected in six of eight nonsecreting bronchial carcinoids. Northern blot analysis showed V3 receptor mRNA of identical size in ACTH-secreting bronchial carcinoids and pituitary tumors. Other types of nonpituitary tumors responsible for ectopic ACTH syndrome presented much lower levels of both POMC and V3 receptor gene expression than those found in ACTH-secreting bronchial carcinoids. In contrast with the V3 receptor, CRH receptor mRNA was detected in the majority of neuroendocrine tumors irrespective of their POMC status. These results show that expression of the V3 receptor gene participates in the corticotroph phenotype. Its striking association with ACTH-secreting bronchial carcinoids defines a subset of nonpituitary tumors in which ectopic POMC gene expression is but one aspect of a wider process of corticotroph cell differentiation, and opens new possibilities of

The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome.

PubMed

de Keyzer, Y; Lenne, F; Auzan, C; Jégou, S; René, P; Vaudry, H; Kuhn, J M; Luton, J P; Clauser, E; Bertagna, X

1996-03-01

Ectopic ACTH secretion occurs in highly differentiated and rather indolent tumors like bronchial carcinoids or, in contrast, in various types of aggressive and poorly differentiated neuroendocrine tumors. We explored this phenomenon using the recently cloned human pituitary V3 vasopressin receptor as an alternate molecular marker of the corticotroph phenotype. Expression of V3 receptor, corticotrophin releasing hormone (CRH) receptor, and proopiomelanocortin (POMC) genes was examined in tumors of pituitary and nonpituitary origin. A comparative RT-PCR approach revealed signals for both V3 receptor and CHR receptor mRNAs in 17 of 18 ACTH-secreting pituitary adenomas, and 6 of 6 normal pituitaries; in six growth hormone- or prolactin-secreting adenomas, a very faint V3 receptor signal was observed in three cases, and CRH receptor signal was undetected in all. Six of eight bronchial carcinoids responsible for the ectopic ACTH syndrome had both POMC and V3 receptor signals as high as those in ACTH-secreting pituitary adenomas; in contrast, no POMC signal and only a very faint V3 receptor signal were detected in six of eight nonsecreting bronchial carcinoids. Northern blot analysis showed V3 receptor mRNA of identical size in ACTH-secreting bronchial carcinoids and pituitary tumors. Other types of nonpituitary tumors responsible for ectopic ACTH syndrome presented much lower levels of both POMC and V3 receptor gene expression than those found in ACTH-secreting bronchial carcinoids. In contrast with the V3 receptor, CRH receptor mRNA was detected in the majority of neuroendocrine tumors irrespective of their POMC status. These results show that expression of the V3 receptor gene participates in the corticotroph phenotype. Its striking association with ACTH-secreting bronchial carcinoids defines a subset of nonpituitary tumors in which ectopic POMC gene expression is but one aspect of a wider process of corticotroph cell differentiation, and opens new possibilities of

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.

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.

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.

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

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: 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

Hematopoietic Stem Cell Regeneration Enhanced by Ectopic Expression of ROS-detoxifying Enzymes in Transplant Mice

PubMed Central

Miao, Weimin; XuFeng, Richard; Park, Moo-Rim; Gu, Haihui; Hu, Linping; Kang, Jin Wook; Ma, Shihui; Liang, Paulina H; Li, Yanxin; Cheng, Haizi; Yu, Hui; Epperly, Michael; Greenberger, Joel; Cheng, Tao

2013-01-01

High levels of reactive oxygen species (ROS) can exhaust hematopoietic stem cells (HSCs). Thus, maintaining a low state of redox in HSCs by modulating ROS-detoxifying enzymes may augment the regeneration potential of HSCs. Our results show that basal expression of manganese superoxide dismutase (MnSOD) and catalase were at low levels in long-term and short-term repopulating HSCs, and administration of a MnSOD plasmid and lipofectin complex (MnSOD-PL) conferred radiation protection on irradiated recipient mice. To assess the intrinsic role of elevated MnSOD or catalase in HSCs and hematopoietic progenitor cells, the MnSOD or catalase gene was overexpressed in mouse hematopoietic cells via retroviral transduction. The impact of MnSOD and catalase on hematopoietic progenitor cells was mild, as measured by colony-forming units (CFUs). However, overexpressed catalase had a significant beneficial effect on long-term engraftment of transplanted HSCs, and this effect was further enhanced after an insult of low-dose γ-irradiation in the transplant mice. In contrast, overexpressed MnSOD exhibited an insignificant effect on long-term engraftment of transplanted HSCs, but had a significant beneficial effect after an insult of sublethal irradiation. Taken together, these results demonstrate that HSC function can be enhanced by ectopic expression of ROS-detoxifying enzymes, especially after radiation exposure in vivo. PMID:23295952

Identification of Genes in the Phenylalanine Metabolic Pathway by Ectopic Expression of a MYB Transcription Factor in Tomato Fruit[W

PubMed Central

Dal Cin, Valeriano; Tieman, Denise M.; Tohge, Takayuki; McQuinn, Ryan; de Vos, Ric C.H.; Osorio, Sonia; Schmelz, Eric A.; Taylor, Mark G.; Smits-Kroon, Miriam T.; Schuurink, Robert C.; Haring, Michel A.; Giovannoni, James; Fernie, Alisdair R.; Klee, Harry J.

2011-01-01

Altering expression of transcription factors can be an effective means to coordinately modulate entire metabolic pathways in plants. It can also provide useful information concerning the identities of genes that constitute metabolic networks. Here, we used ectopic expression of a MYB transcription factor, Petunia hybrida ODORANT1, to alter Phe and phenylpropanoid metabolism in tomato (Solanum lycopersicum) fruits. Despite the importance of Phe and phenylpropanoids to plant and human health, the pathway for Phe synthesis has not been unambiguously determined. Microarray analysis of ripening fruits from transgenic and control plants permitted identification of a suite of coregulated genes involved in synthesis and further metabolism of Phe. The pattern of coregulated gene expression facilitated discovery of the tomato gene encoding prephenate aminotransferase, which converts prephenate to arogenate. The expression and biochemical data establish an arogenate pathway for Phe synthesis in tomato fruits. Metabolic profiling and 13C flux analysis of ripe fruits further revealed large increases in the levels of a specific subset of phenylpropanoid compounds. However, while increased levels of these human nutrition-related phenylpropanoids may be desirable, there were no increases in levels of Phe-derived flavor volatiles. PMID:21750236

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

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 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.

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.

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 Cdx2 expression in murine esophagus models an intermediate stage in the emergence of Barrett's esophagus.

PubMed

Kong, Jianping; Crissey, Mary Ann; Funakoshi, Shinsuke; Kreindler, James L; Lynch, John P

2011-04-06

Barrett's esophagus (BE) is an intestinal metaplasia that occurs in the setting of chronic acid and bile reflux and is associated with a risk for adenocarcinoma. Expression of intestine-specific transcription factors in the esophagus likely contributes to metaplasia development. Our objective was to explore the effects of an intestine-specific transcription factor when expressed in the mouse esophageal epithelium. Transgenic mice were derived in which the transcription factor Cdx2 is expressed in squamous epithelium using the murine Keratin-14 gene promoter. Effects of the transgene upon cell proliferation and differentiation, gene expression, and barrier integrity were explored. K14-Cdx2 mice express the Cdx2 transgene in esophageal squamous tissues. Cdx2 expression was associated with reduced basal epithelial cell proliferation and altered cell morphology. Ultrastructurally two changes were noted. Cdx2 expression was associated with dilated space between the basal cells and diminished cell-cell adhesion caused by reduced Desmocollin-3 mRNA and protein expression. This compromised epithelial barrier function, as the measured trans-epithelial electrical resistance (TEER) of the K14-Cdx2 epithelium was significantly reduced compared to controls (1189 Ohm*cm(2) ±343.5 to 508 Ohm*cm(2)±92.48, p = 0.0532). Secondly, basal cells with features of a transitional cell type, intermediate between keratinocytes and columnar Barrett's epithelial cells, were observed. These cells had reduced keratin bundles and increased endoplasmic reticulum levels, suggesting the adoption of secretory-cell features. Moreover, at the ultrastructural level they resembled "Distinctive" cells associated with multilayered epithelium. Treatment of the K14-Cdx2 mice with 5'-Azacytidine elicited expression of BE-associated genes including Cdx1, Krt18, and Slc26a3/Dra, suggesting the phenotype could be advanced under certain conditions. We conclude that ectopic Cdx2 expression in keratinocytes

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: 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

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

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.

Management Strategies for Aggressive Cushing's Syndrome: From Macroadenomas to Ectopics

PubMed Central

Pozza, Carlotta; Graziadio, Chiara; Giannetta, Elisa; Lenzi, Andrea; Isidori, Andrea M.

2012-01-01

Cushing's syndrome (CS) is a rare but severe clinical condition represented by an excessive endogenous cortisol secretion and hence excess circulating free cortisol, characterized by loss of the normal feedback regulation and circadian rhythm of the hypothalamic-pituitary axis due to inappropriate secretion of ACTH from a pituitary tumor (Cushing's disease, CD) or an ectopic source (ectopic ACTH secretion, EAS). The remaining causes (20%) are ACTH independent. As soon as the diagnosis is established, the therapeutic goal is the removal of the tumor. Whenever surgery is not curative, management of patients with CS requires a major effort to control hypercortisolemia and associated symptoms. A multidisciplinary approach that includes endocrinologists, neurosurgeons, oncologists, and radiotherapists should be adopted. This paper will focus on traditional and novel medical therapy for aggressive ACTH-dependent CS. Several drugs are able to reduce cortisol levels. Their mechanism of action involves blocking adrenal steroidogenesis (ketoconazole, metyrapone, aminoglutethimide, mitotane, etomidate) or inhibiting the peripheral action of cortisol through blocking its receptors (mifepristone “RU-486”). Other drugs include centrally acting agents (dopamine agonists, somatostatin receptor agonists, retinoic acid, peroxisome proliferator-activated receptor γ “PPAR-γ” ligands) and novel chemotherapeutic agents (temozolomide and tyrosine kinase inhibitors) which have a significant activity against aggressive pituitary or ectopic tumors. PMID:22934113

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.

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.

[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.

The tripartite leader sequence is required for ectopic expression of HAdV-B and HAdV-E E3 CR1 genes.

PubMed

Bair, Camden R; Kotha Lakshmi Narayan, Poornima; Kajon, Adriana E

2017-05-01

The unique repertoire of genes that characterizes the early region 3 (E3) of the different species of human adenovirus (HAdV) likely contributes to their distinct pathogenic traits. The function of many E3 CR1 proteins remains unknown possibly due to unidentified intrinsic properties that make them difficult to express ectopically. This study shows that the species HAdV-B- and HAdV-E-specific E3 CR1 genes can be expressed from vectors carrying the HAdV tripartite leader (TPL) sequence but not from traditional mammalian expression vectors. Insertion of the TPL sequence upstream of the HAdV-B and HAdV-E E3 CR1 open reading frames was sufficient to rescue protein expression from pCI-neo constructs in transfected 293T cells. The detection of higher levels of HAdV-B and HAdV-E E3 CR1 transcripts suggests that the TPL sequence may enhance gene expression at both the transcriptional and translational levels. Our findings will facilitate the characterization of additional AdV E3 proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of Transgenic Cloned Pig Models of Skin Inflammation by DNA Transposon-Directed Ectopic Expression of Human β1 and α2 Integrin

PubMed Central

Staunstrup, Nicklas Heine; Madsen, Johannes; Primo, Maria Nascimento; Li, Juan; Liu, Ying; Kragh, Peter M.; Li, Rong; Schmidt, Mette; Purup, Stig; Dagnæs-Hansen, Frederik; Svensson, Lars; Petersen, Thomas K.; Callesen, Henrik; Bolund, Lars; Mikkelsen, Jacob Giehm

2012-01-01

Integrins constitute a superfamily of transmembrane signaling receptors that play pivotal roles in cutaneous homeostasis by modulating cell growth and differentiation as well as inflammatory responses in the skin. Subrabasal expression of integrins α2 and/or β1 entails hyperproliferation and aberrant differentiation of keratinocytes and leads to dermal and epidermal influx of activated T-cells. The anatomical and physiological similarities between porcine and human skin make the pig a suitable model for human skin diseases. In efforts to generate a porcine model of cutaneous inflammation, we employed the Sleeping Beauty DNA transposon system for production of transgenic cloned Göttingen minipigs expressing human β1 or α2 integrin under the control of a promoter specific for subrabasal keratinocytes. Using pools of transgenic donor fibroblasts, cloning by somatic cell nuclear transfer was utilized to produce reconstructed embryos that were subsequently transferred to surrogate sows. The resulting pigs were all transgenic and harbored from one to six transgene integrants. Molecular analyses on skin biopsies and cultured keratinocytes showed ectopic expression of the human integrins and localization within the keratinocyte plasma membrane. Markers of perturbed skin homeostasis, including activation of the MAPK pathway, increased expression of the pro-inflammatory cytokine IL-1α, and enhanced expression of the transcription factor c-Fos, were identified in keratinocytes from β1 and α2 integrin-transgenic minipigs, suggesting the induction of a chronic inflammatory phenotype in the skin. Notably, cellular dysregulation obtained by overexpression of either β1 or α2 integrin occurred through different cellular signaling pathways. Our findings mark the creation of the first cloned pig models with molecular markers of skin inflammation. Despite the absence of an overt psoriatic phenotype, these animals may possess increased susceptibility to severe skin damage

Ectopic expression of a fruit phytoene synthase from Citrus paradisi Macf. promotes abiotic stress tolerance in transgenic tobacco.

PubMed

Cidade, Luciana C; de Oliveira, Tahise M; Mendes, Amanda F S; Macedo, Amanda F; Floh, Eny I S; Gesteira, Abelmon S; Soares-Filho, Walter S; Costa, Marcio G C

2012-12-01

Abscisic acid (ABA) is an important regulator of plant responses to environmental stresses and an absolute requirement for stress tolerance. Recently, a third phytoene synthase (PSY3) gene paralog was identified in monocots and demonstrated to play a specialized role in stress-induced ABA formation, thus suggesting that the first committed step in carotenogenesis is a key limiting step in ABA biosynthesis. To examine whether the ectopic expression of PSY, other than PSY3, would similarly affect ABA level and stress tolerance, we have produced transgenic tobacco containing a fruit-specific PSY (CpPSY) of grapefruit (Citrus paradisi Macf.). The transgenic plants contained a single- or double-locus insertion and expressed CpPSY at varying transcript levels. In comparison with the wild-type plants, the CpPSY expressing transgenic plants showed a significant increase on root length and shoot biomass under PEG-, NaCl- and mannitol-induced osmotic stress. The enhanced stress tolerance of transgenic plants was correlated with the increased endogenous ABA level and expression of stress-responsive genes, which in turn was correlated with the CpPSY copy number and expression level in different transgenic lines. Collectively, these results provide further evidence that PSY is a key enzyme regulating ABA biosynthesis and that the altered expression of other PSYs in transgenic plants may provide a similar function to that of the monocot's PSY3 in ABA biosynthesis and stress tolerance. The results also pave the way for further use of CpPSY, as well as other PSYs, as potential candidate genes for engineering tolerance to drought and salt stress in crop plants.

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.

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.

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

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

Overexpression or ectopic expression of MUC2 is the common property of mucinous carcinomas of the colon, pancreas, breast, and ovary.

PubMed

Hanski, C; Hofmeier, M; Schmitt-Gräff, A; Riede, E; Hanski, M L; Borchard, F; Sieber, E; Niedobitek, F; Foss, H D; Stein, H; Riecken, E O

1997-08-01

Mucinous carcinomas of the colorectum have been reported to overexpress the intestinal mucin MUC2. The purpose of this study was to determine whether this alteration is shared by mucinous tumours of the ovary, breast, and pancreas. A total of 40 breast carcinomas (22 of mucinous and 18 of ductal invasive type), 39 ovarian adenocarcinomas (16 mucinous, 23 serous), 47 colorectal carcinomas (25 mucinous and 22 non-mucinous), and 41 pancreatic adenocarcinomas (14 mucinous, 27 non-mucinous) were investigated by immunohistochemistry with the anti-MUC2 monoclonal antibody 4F1 and the expression pattern was ranked. MUC2 mucin is expressed in the normal colonic epithelium; in the normal epithelium of the breast, ovary, and pancreas, it was not detectable by immunohistochemistry or by reverse transcriptase-polymerase chain reaction (RT-PCR). In agreement with previous reports, the colonic mucinous carcinomas differed significantly from the non-mucinous carcinomas by strong MUC2 expression. In all mucinous carcinomas of the ovary, breast, and pancreas, de novo expression of the MUC2 gene was observed, which differentiated mucinous and non-mucinous carcinomas of these tissues (P < 0.001). The overexpression or ectopic expression of the MUC2 gene exhibited by mucinous carcinomas of four organs indicates a common genetic lesion associated with the mucinous tumour phenotype.

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

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

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.

Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis

PubMed Central

Bombardieri, Michele; Greenhill, Claire J.; McLeod, Louise; Nerviani, Alessandra; Rocher-Ros, Vidalba; Cardus, Anna; Williams, Anwen S.; Pitzalis, Costantino; Jenkins, Brendan J.

2015-01-01

Ectopic lymphoid-like structures (ELSs) reminiscent of secondary lymphoid organs often develop at sites of chronic inflammation where they contribute to immune-mediated pathology. Through evaluation of synovial tissues from rheumatoid arthritis (RA) patients, we now show that low interleukin-27 (IL-27) expression corresponds with an increased incidence of ELS and gene signatures associated with their development and activity. The presence of synovial ELS was also noted in mice deficient in the IL-27 receptor (IL-27R) after the onset of inflammatory arthritis. Here, pathology was associated with increased synovial expression of pro-inflammatory cytokines, homeostatic chemokines, and transcriptional regulators linked with lymphoid neogenesis. In both clinical and experimental RA, synovial ELS coincided with the heightened local expression of cytokines and transcription factors of the Th17 and T follicular helper (Tfh) cell lineages, and included podoplanin-expressing T cells within lymphoid aggregates. IL-27 inhibited the differentiation of podoplanin-expressing Th17 cells, and an increased number of these cells were observed in IL-27R–deficient mice with inflammatory arthritis. Thus, IL-27 appears to negatively regulate ELS development in RA through control of effector T cells. These studies open new opportunities for patient stratification and treatment. PMID:26417004

[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).

Ectopic norrin induces growth of ocular capillaries and restores normal retinal angiogenesis in Norrie disease mutant mice.

PubMed

Ohlmann, Andreas; Scholz, Michael; Goldwich, Andreas; Chauhan, Bharesh K; Hudl, Kristiane; Ohlmann, Anne V; Zrenner, Eberhart; Berger, Wolfgang; Cvekl, Ales; Seeliger, Mathias W; Tamm, Ernst R

2005-02-16

Norrie disease is an X-linked retinal dysplasia that presents with congenital blindness, sensorineural deafness, and mental retardation. Norrin, the protein product of the Norrie disease gene (NDP), is a secreted protein of unknown biochemical function. Norrie disease (Ndp(y/-)) mutant mice that are deficient in norrin develop blindness, show a distinct failure in retinal angiogenesis, and completely lack the deep capillary layers of the retina. We show here that the transgenic expression of ectopic norrin under control of a lens-specific promoter restores the formation of a normal retinal vascular network in Ndp(y/-) mutant mice. The improvement in structure correlates with restoration of neuronal function in the retina. In addition, lenses of transgenic mice with ectopic expression of norrin show significantly more capillaries in the hyaloid vasculature that surrounds the lens during development. In vitro, lenses of transgenic mice in coculture with microvascular endothelial cells induce proliferation of the cells. Transgenic mice with ectopic expression of norrin show more bromodeoxyuridine-labeled retinal progenitor cells at embryonic day 14.5 and thicker retinas at postnatal life than wild-type littermates, indicating a putative direct neurotrophic effect of norrin. These data provide direct evidence that norrin induces growth of ocular capillaries and that pharmacologic modulation of norrin might be used for treatment of the vascular abnormalities associated with Norrie disease or other vascular disorders of the retina.

Ectopic Cdx2 Expression in Murine Esophagus Models an Intermediate Stage in the Emergence of Barrett's Esophagus

PubMed Central

Kong, Jianping; Crissey, Mary Ann; Funakoshi, Shinsuke; Kreindler, James L.; Lynch, John P.

2011-01-01

Barrett's esophagus (BE) is an intestinal metaplasia that occurs in the setting of chronic acid and bile reflux and is associated with a risk for adenocarcinoma. Expression of intestine-specific transcription factors in the esophagus likely contributes to metaplasia development. Our objective was to explore the effects of an intestine-specific transcription factor when expressed in the mouse esophageal epithelium. Transgenic mice were derived in which the transcription factor Cdx2 is expressed in squamous epithelium using the murine Keratin-14 gene promoter. Effects of the transgene upon cell proliferation and differentiation, gene expression, and barrier integrity were explored. K14-Cdx2 mice express the Cdx2 transgene in esophageal squamous tissues. Cdx2 expression was associated with reduced basal epithelial cell proliferation and altered cell morphology. Ultrastructurally two changes were noted. Cdx2 expression was associated with dilated space between the basal cells and diminished cell-cell adhesion caused by reduced Desmocollin-3 mRNA and protein expression. This compromised epithelial barrier function, as the measured trans-epithelial electrical resistance (TEER) of the K14-Cdx2 epithelium was significantly reduced compared to controls (1189 Ohm*cm2 ±343.5 to 508 Ohm*cm2±92.48, p = 0.0532). Secondly, basal cells with features of a transitional cell type, intermediate between keratinocytes and columnar Barrett's epithelial cells, were observed. These cells had reduced keratin bundles and increased endoplasmic reticulum levels, suggesting the adoption of secretory-cell features. Moreover, at the ultrastructural level they resembled “Distinctive” cells associated with multilayered epithelium. Treatment of the K14-Cdx2 mice with 5′-Azacytidine elicited expression of BE-associated genes including Cdx1, Krt18, and Slc26a3/Dra, suggesting the phenotype could be advanced under certain conditions. We conclude that ectopic Cdx2 expression in keratinocytes

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

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

High accumulation of anthocyanins via the ectopic expression of AtDFR confers significant salt stress tolerance in Brassica napus L.

PubMed

Kim, Jihye; Lee, Won Je; Vu, Tien Thanh; Jeong, Chan Young; Hong, Suk-Whan; Lee, Hojoung

2017-08-01

The ectopic expression of AtDFR results in increased accumulation of anthocyanins leading to enhanced salinity and drought stress tolerance in B. napus plants. Flavonoids with antioxidant effects confer many additional benefits to plants. Evidence indicates that flavonoids, including anthocyanins, protect tissues against oxidative stress from various abiotic stressors. We determined whether increases in anthocyanins increased abiotic stress tolerance in Brassica napus, because the values of B. napus L. and its cultivation area are increasing worldwide. We overexpressed Arabidopsis dihydroflavonol-4-reductase (DFR) in B. napus. Increased DFR transcript levels for AtDFR-OX B. shoots correlated with higher anthocyanin accumulation. AtDFR-OX Brassica shoots exhibited lower reactive oxygen species (ROS) accumulation than wild-type (WT) shoots under high NaCl and mannitol concentrations. This was corroborated by 3,3-diaminobenzidine staining for ROS scavenging activity in 1,1-diphenyl-2-picryl-hydrazyl assays. Shoots of the AtDFR-OX B. napus lines grown in a high salt medium exhibited enhanced salt tolerance and higher chlorophyll content than similarly grown WT plants. Our observations suggested that the AtDFR gene can be effectively manipulated to modulate salinity and drought stress tolerance by directing to high accumulation of anthocyanins in oilseed plants.

A challenging case of an ectopic parathyroid adenoma.

PubMed

Panchani, Roopal; Varma, Tarun; Goyal, Ashutosh; Gupta, Nitinranjan; Saini, Ashish; Tripathi, Sudhir

2012-12-01

The occurrence of ectopic parathyroid adenomas is not uncommon (3-4% of all parathyroid adenomas). A 42-year-old female diagnosed as having GH secreting pituitary adenoma presented with an ectopic mediastinal parathyroid adenoma located between left (Lt) pulmonary artery and Lt main bronchus. The aim of presenting this case is not to appreciate the rarity of the condition but to rather discuss some of the vital practical problems faced during its management. Patient presenting in endocrine OPD with nausea, vomiting, drowsiness and chronic constipation was investigated biochemically and with various imaging modalities and accordingly managed. Patient was also investigated from the perspective of MEN 1 syndrome. Baseline routine investigations revealed hypercalcemia (corrected S. Ca- 16.9 mg/dl) due to primary hyperparathyroidism (PHP, PTH-1190 ng/L) with adenoma located between Lt main bronchus and Lt pulmonary artery. Patient was medically managed and after proper preoperative preparation, surgical excision by open thoracotomy was planned but two days before surgery she developed pulmonary embolism and was shifted to ICU where she died after 20 days. An accurate preoperative localization by various imaging procedures plays a decisive role in case of ectopic adenomas in the chest. Ectopic parathyroid adenomas are frequent cause of failed initial surgery. The best surgical approach to these ectopic adenomas is still controversial. Equally effective newer medical treatment modalities are also required in patients who are awaiting or are unfit for surgery. Lastly combination of MEN 1 with ectopic parathyroid adenoma is rare.

Compartmentalization of the somite and myogenesis in chick embryos are influenced by wnt expression.

PubMed

Wagner, J; Schmidt, C; Nikowits, W; Christ, B

2000-12-01

Muscles of the body and bones of the axial skeleton derive from specialized regions of somites. Somite development is influenced by adjacent structures. In particular, the dorsal neural tube and the overlying ectoderm have been shown to be necessary for the induction of myogenic precursor cells in the dermomyotome. Members of the Wnt family of signaling molecules, which are expressed in the dorsal neural tube and the ectoderm, are postulated to be responsible for this process. It is shown here that ectopically implanted Wnt-1-, -3a-, and -4-expressing cells alter the process of somite compartmentalization in vivo. An enlarged dorsal compartment results from the implantation of Wnt-expressing cells ventrally between the neural tube/notochord and epithelial somites, at the expense of the ventral compartment, the sclerotome. Thus, ectopic Wnt expression is able to override the influence of ventralizing signals arising from notochord and floor plate. This shift of the border between the two compartments was identified by an increase in the domain of Pax-3 expression and a complete loss of Pax-1 expression in somites close to the ectopic Wnt signal. The expanded expression of MyoD and desmin provides evidence that it is the myotome which increases as a result of Wnt signaling. Paraxis expression is also drastically amplified after implantation of Wnt-expressing cells indicating that Wnts are involved in the formation and maintenance of somite epithelium and suggesting that Paraxis is activated through Wnt signaling pathways. Taken together these results suggest that ectopic Wnts disturb the normal balance of signaling molecules within the somite, resulting in an enhanced recruitment of somitic cells into the myogenic lineage. Copyright 2000 Academic Press.

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.

Stable Ectopic Expression of ST6GALNAC5 Induces Autocrine MET Activation and Anchorage-Independence in MDCK Cells.

PubMed

Chu, Chia; Bottaro, Donald P; Betenbaugh, Michael J; Shiloach, Joseph

2016-01-01

The epithelial-mesenchymal transition (EMT) is a complex cancer progression that can boost the metastatic potential of transformed cells by inducing migration, loss of cell adhesion, and promoting proliferation under anchorage-independent conditions. A DNA microarray analysis was performed comparing parental anchorage-dependent MDCK cells and anchorage-independent MDCK cells that were engineered to express human siat7e (ST6GALNAC5). The comparison identified several genes involved in the EMT process that were differentially expressed between the anchorage-dependent and the anchorage-independent MDCK cell lines. The hepatocyte growth factor gene (hgf) was found to be over-expressed in the engineered MDCK-siat7e cells at both transcription and protein expression levels. Phosphorylation analysis of the MET receptor tyrosine kinase confirmed the activation of an autocrine loop of the HGF/ MET signaling pathway in the MDCK-siat7e cells. When MET activities were suppressed by using the small-molecular inhibitor drug PF-02341066 (Crizotinib), the anchorage-independent MDCK-siat7e cells reverted to the cellular morphology of the parental anchorage-dependent MDCK cells. These observations indicate that the MET receptor plays a central role in the growth properties of the MDCK cells and its phosphorylation status is likely dependent on sialylation. Further investigation of the downstream signaling targets in the MET network showed that the degree of MDCK cell adhesion correlated with secretion levels of a matrix metalloproteinase, MMP1, suggesting a role of metalloproteinases in the EMT process. These results demonstrate that in addition to its application in biotechnology processes, MDCK-siat7e may serve as a model cell for metastasis studies to decipher the sequence of events leading up to the activation of EMT.

Use of Toll-Like Receptor Agonists to Induce Ectopic Lymphoid Structures in Myasthenia Gravis Mouse Models

PubMed Central

Robinet, Marieke; Villeret, Bérengère; Maillard, Solène; Cron, Mélanie A.; Berrih-Aknin, Sonia; Le Panse, Rozen

2017-01-01

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction. MG symptoms are characterized by muscle weaknesses. The thymus of MG patients is very often abnormal and possesses all the characteristics of tertiary lymphoid organs such as neoangiogenesis processes, overexpression of inflammatory cytokines and chemokines, and infiltration of B lymphocytes leading to ectopic germinal center (GC) development. We previously demonstrated that injections of mice with polyinosinic–polycytidylic acid [Poly(I:C)], a synthetic double-stranded RNA mimicking viral infection, induce thymic changes and trigger MG symptoms. Upon Poly(I:C) injections, we observed increased thymic expressions of α-AChR, interferon-β and chemokines such as CXCL13 and CCL21 leading to B-cell recruitment. However, these changes were only transient. In order to develop an experimental MG model associated with thymic GCs, we used Poly(I:C) in the classical experimental autoimmune MG model induced by immunizations with purified AChR emulsified in complete Freund’s adjuvant. We observed that Poly(I:C) strongly favored the development of MG as almost all mice displayed MG symptoms. Nevertheless, we did not observe any ectopic GC development. We next challenged mice with Poly(I:C) together with other toll-like receptor (TLR) agonists known to be involved in GC development and that are overexpressed in MG thymuses. Imiquimod and CpG oligodeoxynucleotides that activate TLR7 and TLR9, respectively, did not induce thymic changes. In contrast, lipopolysaccharide that activates TLR4 potentiated Poly(I:C) effects and induced a significant expression of CXCL13 mRNA in the thymus associated with a higher recruitment of B cells that induced over time thymic B-lymphoid structures. Altogether, these data suggest that tertiary lymphoid genesis in MG thymus could result from a combined activation of TLR signaling pathways. PMID

Ectopic application of recombinant BMP-2 and BMP-4 can change patterning of developing chick facial primordia.

PubMed

Barlow, A J; Francis-West, P H

1997-01-01

The facial primordia initially consist of buds of undifferentiated mesenchyme, which give rise to a variety of tissues including cartilage, muscle and nerve. These must be arranged in a precise spatial order for correct function. The signals that control facial outgrowth and patterning are largely unknown. The bone morphogenetic proteins Bmp-2 and Bmp-4 are expressed in discrete regions at the distal tips of the early facial primordia suggesting possible roles for BMP-2 and BMP-4 during chick facial development. We show that expression of Bmp-4 and Bmp-2 is correlated with the expression of Msx-1 and Msx-2 and that ectopic application of BMP-2 and BMP-4 can activate Msx-1 and Msx-2 gene expression in the developing facial primordia. We correlate this activation of gene expression with changes in skeletal development. For example, activation of Msx-1 gene expression across the distal tip of the mandibular primordium is associated with an extension of Fgf-4 expression in the epithelium and bifurcation of Meckel's cartilage. In the maxillary primordium, extension of the normal domain of Msx-1 gene expression is correlated with extended epithelial expression of shh and bifurcation of the palatine bone. We also show that application of BMP-2 can increase cell proliferation of the mandibular primordia. Our data suggest that BMP-2 and BMP-4 are part of a signalling cascade that controls outgrowth and patterning of the facial primordia.

Evidence for the ectopic synthesis of melanin in human adipose tissue.

PubMed

Randhawa, Manpreet; Huff, Tom; Valencia, Julio C; Younossi, Zobair; Chandhoke, Vikas; Hearing, Vincent J; Baranova, Ancha

2009-03-01

Melanin is a common pigment in animals. In humans, melanin is produced in melanocytes, in retinal pigment epithelium (RPE) cells, in the inner ear, and in the central nervous system. Previously, we noted that human adipose tissue expresses several melanogenesis-related genes. In the current study, we confirmed the expression of melanogenesis-related mRNAs and proteins in human adipose tissue using real-time polymerase chain reaction and immunohistochemical staining. TYR mRNA signals were also detected by in situ hybridization in visceral adipocytes. The presence of melanin in human adipose tissue was revealed both by Fontana-Masson staining and by permanganate degradation of melanin coupled with liquid chromatography/ultraviolet/mass spectrometry determination of the pyrrole-2,3,5-tricarboxylic acid (PTCA) derivative of melanin. We also compared melanogenic activities in adipose tissues and in other human tissues using the L-[U-(14)C] tyrosine assay. A marked heterogeneity in the melanogenic activities of individual adipose tissue extracts was noted. We hypothesize that the ectopic synthesis of melanin in obese adipose may serve as a compensatory mechanism that uses its anti-inflammatory and its oxidative damage-absorbing properties. In conclusion, our study demonstrates for the first time that the melanin biosynthesis pathway is functional in adipose tissue.

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.

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.

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.

Impeding Xist expression from the active X chromosome improves mouse somatic cell nuclear transfer.

PubMed

Inoue, Kimiko; Kohda, Takashi; Sugimoto, Michihiko; Sado, Takashi; Ogonuki, Narumi; Matoba, Shogo; Shiura, Hirosuke; Ikeda, Rieko; Mochida, Keiji; Fujii, Takashi; Sawai, Ken; Otte, Arie P; Tian, X Cindy; Yang, Xiangzhong; Ishino, Fumitoshi; Abe, Kuniya; Ogura, Atsuo

2010-10-22

Cloning mammals by means of somatic cell nuclear transfer (SCNT) is highly inefficient because of erroneous reprogramming of the donor genome. Reprogramming errors appear to arise randomly, but the nature of nonrandom, SCNT-specific errors remains elusive. We found that Xist, a noncoding RNA that inactivates one of the two X chromosomes in females, was ectopically expressed from the active X (Xa) chromosome in cloned mouse embryos of both sexes. Deletion of Xist on Xa showed normal global gene expression and resulted in about an eight- to ninefold increase in cloning efficiency. We also identified an Xist-independent mechanism that specifically down-regulated a subset of X-linked genes through somatic-type repressive histone blocks. Thus, we have identified nonrandom reprogramming errors in mouse cloning that can be altered to improve the efficiency of SCNT methods.

Spi-C has opposing effects to PU.1 on gene expression in progenitor B cells.

PubMed

Schweitzer, Brock L; Huang, Kelly J; Kamath, Meghana B; Emelyanov, Alexander V; Birshtein, Barbara K; DeKoter, Rodney P

2006-08-15

The Ets transcription factor Spi-C, expressed in B cells and macrophages, is closely related to PU.1 and has the ability to recognize the same DNA consensus sequence. However, the function of Spi-C has yet to be determined. The purpose of this study is to further examine Spi-C activity in B cell development. First, using retroviral vectors to infect PU.1(-/-) fetal liver progenitors, Spi-C was found to be inefficient at inducing cytokine-dependent proliferation and differentiation of progenitor B (pro-B) cells or macrophages relative to PU.1 or Spi-B. Next, Spi-C was ectopically expressed in fetal liver-derived, IL-7-dependent pro-B cell lines. Wild-type (WT) pro-B cells ectopically expressing Spi-C (WT-Spi-C) have several phenotypic characteristics of pre-B cells such as increased CD25 and decreased c-Kit surface expression. In addition, WT-Spi-C pro-B cells express increased levels of IgH sterile transcripts and reduced levels of expression and transcription of the FcgammaRIIb gene. Gel-shift analysis suggests that Spi-C, ectopically expressed in pro-B cells, can bind PU.1 consensus sites in the IgH intronic enhancer and FcgammaRIIb promoter. Transient transfection analysis demonstrated that PU.1 functions to repress the IgH intronic enhancer and activate the FcgammaRIIb promoter, while Spi-C opposes these activities. WT-Spi-C pro-B cells have reduced levels of dimethylation on lysine 9 of histone H3 within the IgH 3' regulatory region, indicating that Spi-C can contribute to removal of repressive features in the IgH locus. Overall, these studies suggest that Spi-C may promote B cell differentiation by modulating the activity of PU.1-dependent genes.

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

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.

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.

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.

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.

Usefulness of ventricular endocardial electric reconstruction from body surface potential maps to noninvasively localize ventricular ectopic activity in patients

NASA Astrophysics Data System (ADS)

Lai, Dakun; Sun, Jian; Li, Yigang; He, Bin

2013-06-01

As radio frequency (RF) catheter ablation becomes increasingly prevalent in the management of ventricular arrhythmia in patients, an accurate and rapid determination of the arrhythmogenic site is of important clinical interest. The aim of this study was to test the hypothesis that the inversely reconstructed ventricular endocardial current density distribution from body surface potential maps (BSPMs) can localize the regions critical for maintenance of a ventricular ectopic activity. Patients with isolated and monomorphic premature ventricular contractions (PVCs) were investigated by noninvasive BSPMs and subsequent invasive catheter mapping and ablation. Equivalent current density (CD) reconstruction (CDR) during symptomatic PVCs was obtained on the endocardial ventricular surface in six patients (four men, two women, years 23-77), and the origin of the spontaneous ectopic activity was localized at the location of the maximum CD value. Compared with the last (successful) ablation site (LAS), the mean and standard deviation of localization error of the CDR approach were 13.8 and 1.3 mm, respectively. In comparison, the distance between the LASs and the estimated locations of an equivalent single moving dipole in the heart was 25.5 ± 5.5 mm. The obtained CD distribution of activated sources extending from the catheter ablation site also showed a high consistency with the invasively recorded electroanatomical maps. The noninvasively reconstructed endocardial CD distribution is suitable to predict a region of interest containing or close to arrhythmia source, which may have the potential to guide RF catheter ablation.

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.

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

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

Induction by agrin of ectopic and functional postsynaptic-like membrane in innervated muscle

PubMed Central

Jones, G.; Meier, T.; Lichtsteiner, M.; Witzemann, V.; Sakmann, B.; Brenner, H. R.

1997-01-01

Two factors secreted from the nerve terminal, agrin and neuregulin, have been postulated to induce localization of the acetylcholine receptors (AChRs) to the subsynaptic membrane in skeletal muscle fibers. The principal function ascribed to neuregulin is induction of AChR subunit gene expression and to agrin is the aggregation of AChRs. Here we report that when myoblasts engineered to secrete an agrin fragment were placed into the nerve-free region of denervated rodent muscle, the host muscle fibers expressed AChR ɛ-subunit gene transcripts, characteristic of the neuromuscular synapse in adult muscle. Transcripts were colocalized with agrin deposits and AChR clusters that were resistant to electrical muscle activity. More directly, single innervated muscle fibers injected intracellularly with agrin expression plasmids in their extrasynaptic region developed a functional ectopic postsynaptic membrane with clusters of adult-type AChR channels and acetylcholinesterase and accumulation of myonuclei. The results demonstrate that agrin is the principal neural signal that induces the formation of the subsynaptic apparatus in the muscle fiber and controls locally, either indirectly or directly, the transcription of AChR subunit genes and the aggregation of AChRs. PMID:9122251

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.

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

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 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

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

Dominant expression of interleukin-10 and transforming growth factor-beta genes in activated T-cells of chronic active Epstein-Barr virus infection.

PubMed

Ohga, Shouichi; Nomura, Akihiko; Takada, Hidetoshi; Tanaka, Tamami; Furuno, Kenji; Takahata, Yasushi; Kinukawa, Naoko; Fukushima, Noriyasu; Imai, Shosuke; Hara, Toshiro

2004-11-01

Chronic active Epstein-Barr virus (EBV) infection is a chronic mononucleosis syndrome associated with clonal proliferation of EBV-carrying T-/natural killer (NK)-cells. High levels of circulating EBV and activated T-cells are sustained during the prolonged disease course, whereas it is not clear how ectopic EBV infection in T-/NK-cells has been established and maintained. To assess the biological role of activated T-cells in chronic active EBV infection (CAEBV), EBV DNA and cellular gene expressions in peripheral T-cells were quantified in CAEBV and infectious mononucleosis (IM) patients. In CAEBV, HLA-DR(+) T-cells had higher viral load and larger amounts of IFN gamma, IL-10, transforming growth factor-beta (TGF beta), and cytotoxic T lymphocyte antigen-4 (CTLA4) mRNA than HLA-DR(-)T-cells. HLA-DR(+) T cells of IM patients transcribed more IFN gamma and IL-10 than their HLA-DR(-)T cells. Expression levels of IFN gamma and forkhead box p3 (Foxp3) in CAEBV HLA-DR(+) T-cells were higher than in IM HLA-DR(+) T-cells. The effective variables to discriminate the positivity of HLA-DR were IL-10, IFN gamma, CTLA4, TGF beta, and IL-2 in the order of statistical weight. EBV load in CAEBV T-cells correlated with the expression levels of only IL-10 and TGF beta. These results suggest that CAEBV T-cells are activated to transcribe IFN gamma, IL-10, and TGF beta excessively, and the latter two genes are expressed preferentially in the EBV-infected subsets. The dominant expression of regulatory cytokines in T-cells may imply a viral evasion mechanism in the disease.

Induction of ectopic taste buds by SHH reveals the competency and plasticity of adult lingual epithelium

PubMed Central

Castillo, David; Seidel, Kerstin; Salcedo, Ernesto; Ahn, Christina; de Sauvage, Frederic J.; Klein, Ophir D.; Barlow, Linda A.

2014-01-01

Taste buds are assemblies of elongated epithelial cells, which are innervated by gustatory nerves that transmit taste information to the brain stem. Taste cells are continuously renewed throughout life via proliferation of epithelial progenitors, but the molecular regulation of this process remains unknown. During embryogenesis, sonic hedgehog (SHH) negatively regulates taste bud patterning, such that inhibition of SHH causes the formation of more and larger taste bud primordia, including in regions of the tongue normally devoid of taste buds. Here, using a Cre-lox system to drive constitutive expression of SHH, we identify the effects of SHH on the lingual epithelium of adult mice. We show that misexpression of SHH transforms lingual epithelial cell fate, such that daughter cells of lingual epithelial progenitors form cell type-replete, onion-shaped taste buds, rather than non-taste, pseudostratified epithelium. These SHH-induced ectopic taste buds are found in regions of the adult tongue previously thought incapable of generating taste organs. The ectopic buds are composed of all taste cell types, including support cells and detectors of sweet, bitter, umami, salt and sour, and recapitulate the molecular differentiation process of endogenous taste buds. In contrast to the well-established nerve dependence of endogenous taste buds, however, ectopic taste buds form independently of both gustatory and somatosensory innervation. As innervation is required for SHH expression by endogenous taste buds, our data suggest that SHH can replace the need for innervation to drive the entire program of taste bud differentiation. PMID:24993944

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.

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.

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

Argonaute2 and LaminB modulate gene expression by controlling chromatin topology

PubMed Central

Nazer, Ezequiel; Dale, Ryan K.; Chinen, Madoka; Radmanesh, Behram

2018-01-01

Drosophila Argonaute2 (AGO2) has been shown to regulate expression of certain loci in an RNA interference (RNAi)-independent manner, but its genome-wide function on chromatin remains unknown. Here, we identified the nuclear scaffolding protein LaminB as a novel interactor of AGO2. When either AGO2 or LaminB are depleted in Kc cells, similar transcription changes are observed genome-wide. In particular, changes in expression occur mainly in active or potentially active chromatin, both inside and outside LaminB-associated domains (LADs). Furthermore, we identified a somatic target of AGO2 transcriptional repression, no hitter (nht), which is immersed in a LAD located within a repressive topologically-associated domain (TAD). Null mutation but not catalytic inactivation of AGO2 leads to ectopic expression of nht and downstream spermatogenesis genes. Depletion of either AGO2 or LaminB results in reduced looping interactions within the nht TAD as well as ectopic inter-TAD interactions, as detected by 4C-seq analysis. Overall, our findings reveal coordination of AGO2 and LaminB function to dictate genome architecture and thereby regulate gene expression. PMID:29529026

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.

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.

Endometrial Expression of Steroidogenic Factor 1 Promotes Cystic Glandular Morphogenesis

PubMed Central

Vasquez, Yasmin M.; Wu, San-Pin; Anderson, Matthew L.; Hawkins, Shannon M.; Creighton, Chad J.; Ray, Madhumita; Tsai, Sophia Y.; Tsai, Ming-Jer; Lydon, John P.

2016-01-01

Epigenetic silencing of steroidogenic factor 1 (SF1) is lost in endometriosis, potentially contributing to de novo local steroidogenesis favoring inflammation and growth of ectopic endometrial tissue. In this study, we examine the impact of SF1 expression in the eutopic uterus by a novel mouse model that conditionally expresses SF1 in endometrium. In vivo SF1 expression promoted the development of enlarged endometrial glands and attenuated estrogen and progesterone responsiveness. Endometriosis induction by autotransplantation of uterine tissue to the mesenteric membrane resulted in the increase in size of ectopic lesions from SF1-expressing mice. By integrating the SF1-dependent transcriptome with the whole genome binding profile of SF1, we identified uterine-specific SF1-regulated genes involved in Wingless and Progesterone receptor-Hedgehog-Chicken ovalbumin upstream promoter transcription factor II signaling for gland development and epithelium-stroma interaction, respectively. The present results indicate that SF1 directly contributes to the abnormal uterine gland morphogenesis, an inhibition of steroid hormone signaling and activation of an immune response, in addition to previously postulated estrogen production. PMID:27018534

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

PubMed

Mai, Ronald; Hagedorn, Manolo Gunnar; Gelinsky, Michael; Werner, Carsten; Turhani, Dritan; Späth, Heike; Gedrange, Tomas; Lauer, Günter

2006-09-01

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

[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.

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.

Homeobox protein TLX3 activates miR-125b expression to promote T-cell acute lymphoblastic leukemia

PubMed Central

Renou, Laurent; Boelle, Pierre-Yves; Deswarte, Caroline; Spicuglia, Salvatore; Benyoucef, Aissa; Calvo, Julien; Uzan, Benjamin; Belhocine, Mohamed; Cieslak, Agata; Landman-Parker, Judith; Baruchel, Andre; Asnafi, Vahid; Pflumio, Françoise; Ballerini, Paola

2017-01-01

The oncogenic mechanisms driven by aberrantly expressed transcription factors in T-cell acute leukemia (T-ALL) are still elusive. MicroRNAs (miRNAs) play an important role in normal development and pathologies. Here, we examined the expression of 738 miRNA species in 41 newly diagnosed pediatric T-ALLs and in human thymus-derived cells. We found that expression of 2 clustered miRNAs, miR-125b/99a, peaks in primitive T cells and is upregulated in the T leukemia homeobox 3 (TLX3)–positive subtype of T-ALL. Using loss- and gain-of-function approaches, we established functional relationships between TLX3 and miR-125b. Both TLX3 and miR-125b support in vitro cell growth and in vivo invasiveness of T-ALL. Besides, ectopic expression of TLX3 or miR-125b in human hematopoietic progenitor cells enhances production of T-cell progenitors and favors their accumulation at immature stages of T-cell development resembling the differentiation arrest observed in TLX3 T-ALL. Ectopic miR-125b also remarkably accelerated leukemia in a xenograft model, suggesting that miR125b is an important mediator of the TLX3-mediated transformation program that takes place in immature T-cell progenitors. Mechanistically, TLX3-mediated activation of miR-125b may impact T-cell differentiation in part via repression of Ets1 and CBFβ genes, 2 regulators of T-lineage. Finally, we established that TLX3 directly regulates miR-125b production through binding and transactivation of LINC00478, a long noncoding RNA gene, which is the host of miR-99a/Let-7c/miR-125b. Altogether, our results reveal an original functional link between TLX3 and oncogenic miR-125b in T-ALL development. PMID:29296717

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.

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 overexpression of LAPTM5 results in lysosomal targeting and induces Mcl-1 down-regulation, Bak activation, and mitochondria-dependent apoptosis in human HeLa cells

PubMed Central

Jun, Do Youn; Kim, Hyejin; Jang, Won Young; Lee, Ji Young; Fukui, Kiyoshi; Kim, Young Ho

2017-01-01

Human lysosomal-associated protein multispanning membrane 5 (LAPTM5) was identified by an ordered differential display-polymerase chain reaction (ODD-PCR) as an up-regulated cDNA fragment during 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced differentiation of U937 cells into monocytes/macrophages. After TPA-treatment, the levels of LAPTM5 mRNA and protein increased and reached a maximum at 18–36 h. In healthy human tissues, LAPTM5 mRNA was expressed at high levels in hematopoietic cells and tissues, at low levels in the lung and fetal liver, and was not detected in other non-hematopoietic tissues. LAPTM5 mRNA was detected in immature malignant cells of myeloid lineage, such as K562, HL-60, U937, and THP-1 cells, and in unstimulated peripheral T cells, but was absent or barely detectable in lymphoid malignant or non-hematopoietic malignant cells. The LAPTM5 level in HL-60 cells increased more significantly during TPA-induced monocyte/macrophage differentiation than during DMSO-induced granulocyte differentiation. Ectopic expression of GFP-LAPTM5 or LAPTM5 in HeLa cells exhibited the localization of LAPTM5 to the lysosome. In HeLa cells overexpressing LAPTM5, the Mcl-1 and Bid levels declined markedly and apoptosis was induced via Bak activation, Δψm loss, activation of caspase-9, -8 and -3, and PARP degradation without accompanying necrosis. However, these LAPTM5-induced apoptotic events except for the decline of Bid level were completely abrogated by concomitant overexpression of Mcl-1. The pan-caspase inhibitor (z-VAD-fmk) could suppress the LAPTM5-induced apoptotic sub-G1 peak by ~40% but failed to block the induced Δψm loss, whereas the broad-range inhibitor of cathepsins (Cathepsin Inhibitor I) could suppress the LAPTM5-induced apoptotic sub-G1 peak and Δψm loss, by ~22% and ~23%, respectively, suggesting that the LAPTM5-mediated Δψm loss was exerted at least in part in a cathepsin-dependent manner. Together, these results demonstrate that

Ectopic Expression of a Glycine soja myo-Inositol Oxygenase Gene (GsMIOX1a) in Arabidopsis Enhances Tolerance to Alkaline Stress

PubMed Central

Chen, Chen; Sun, Xiaoli; Duanmu, Huizi; Yu, Yang; Liu, Ailin; Xiao, Jialei; Zhu, Yanming

2015-01-01

Myo-inositol participates in various aspects of plant physiology, and myo-inositol oxygenase is the key enzyme of the myo-inositol oxygenation pathway. Previous studies indicated that myo-inositol oxygenase may play a role in plant responses to abiotic stresses. In this study, we focused on the functional characterization of GsMIOX1a, a remarkable alkaline stress-responsive gene of Glycine soja 07256, based on RNA-seq data. Using quantitative real-time PCR, we demonstrated that GsMIOX1a is rapidly induced by alkaline stress and expressed predominantly in flowers. We also elucidated the positive function of GsMIOX1a in the alkaline response in the wild type, atmiox1 mutant as well as GsMIOX1a-overexpressing Arabidopsis. We determined that atmiox1 mutant decreased Arabidopsis tolerance to alkaline stress, whereas GsMIOX1a overexpression increased tolerance. Moreover, the expression levels of some alkaline stress-responsive and inducible marker genes, including H+-Ppase, NADP-ME, KIN1 and RD29B, were also up-regulated in GsMIOX1a overexpression lines compared with the wild type and atmiox1 mutant. Together, these results suggest that the GsMIOX1a gene positively regulates plant tolerance to alkaline stress. This is the first report to demonstrate that ectopic expression of myo-inositol oxygenase improves alkaline tolerance in plants. PMID:26091094

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.

Endogenous and ectopic expression of telomere regulating genes in chicken embryonic fibroblasts

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

Michailidis, Georgios; Saretzki, Gabriele; Hall, Judith

In this study, we compared the endogenous expression of genes encoding telomere regulating proteins in cultured chicken embryonic fibroblasts (CEFs) and 10-day-old chicken embryos. CEFs maintained in vitro senesced and senescence was accompanied by reduced telomere length, telomerase activity, and expression of the chicken (c) TRF1 gene. There was no change in TRF2 gene expression although the major TRF2 transcript identified in 10-day-old chicken embryos encoded a truncated TRF2 protein (TRF2'), containing an N-terminal dimerisation domain but lacking a myb-related DNA binding domain and nuclear localisation signal. Senescence of the CEFs in vitro was associated with the loss of themore » TRF2' transcript, indicative of a novel function for the encoded protein. Senescence was also coupled with decreased expression of RAD51, but increased RAD52 expression. These data support that RAD51 independent recombination mechanisms do not function in vitro to maintain chicken telomeres. To attempt to rescue the CEFs from replicative senescence, we stably transfected passage 3 CEFs with the human telomerase reverse transcriptase (hTERT) catalytic subunit. While hTERT expression was detected in the stable transfectants neither telomerase activity nor the stabilisation of telomere length was observed, and the transfectant cells senesced at the same passage number as the untransfected cells. These data indicate that the human TERT is incompatible with the avian telomere maintenance apparatus and suggest the functioning of a species specific telomere system in the avian.« less

Experimental variation of the level and the ratio of angiogenic and osteogenic signaling affects the spatiotemporal expression of bone-specific markers and organization of bone formation in ectopic sites.

PubMed

Moser, Norman; Goldstein, Jan; Kauffmann, Phillip; Epple, Matthias; Schliephake, Henning

2018-04-01

The aim of the present study was to test the hypothesis that the ratio of angiogenic and osteogenic signaling affects ectopic bone formation when delivered in different amounts. Porous composite PDLLA/CaCO 3 scaffolds were loaded with rhBMP2 and rhVEGF in different dosage combinations and implanted into the gluteal muscles of 120 adult male Wistar rats. Bone formation and expression of alkaline phosphatase and Runx2 were quantified by histomorphometry. Spatial distribution across the scaffolds was assessed by using a grid that discriminated between the periphery and center of the scaffolds. The evaluation showed that the combined delivery of bone morphogenetic protein BMP2 and VEGF in different dosage combinations did not enhance the overall quantity of ectopic bone formation compared to the delivery of BMP2 alone. The addition of VEGF generally upregulated Runx2 after 4 weeks, which may have retarded terminal osteogenic differentiation. However, slow combined delivery of 1.5-2.0 μg BMP2 combined with 50 ng VEGF165 over a period of 5 weeks supported a more even distribution of bone formation across the implanted scaffolds whereas higher amounts of VEGF did not elicit this effect. The findings suggest that structural organization rather than the quantity of ectopic bone formation is affected by the dosage and the ratio of BMP2 and VEGF levels at the observed intervals. The development of carriers for dual growth factor delivery has to take into account the necessity to carefully balance the ratio of growth release.

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

Enhanced expression of the urokinase-type plasminogen activator gene and reduced colony formation in soft agar by ectopic expression of PU.1 in HT1080 human fibrosarcoma cells.

PubMed Central

Kondoh, N.; Yamada, T.; Kihara-Negishi, F.; Yamamoto, M.; Oikawa, T.

1998-01-01

To investigate the cell biological function of PU.1, a member of the Ets family of transcription factors, a vector capable of expressing the protein was transfected into HT1080 human fibrosarcoma cells. Exogenous expression of PU.1 in HT1080 cells reduced colony-forming efficiency but stimulated cell migration in soft agar, although it did not affect cell growth in adherent culture. Expression of the urokinase-type plasminogen activator (uPA) mRNA, which is known to be correlated with cell migration and invasion, was enhanced in PU.1 transfectants compared with mock transfectants. Run-on analysis demonstrated that uPA transcription was unaffected by PU.1, suggesting that this enhancement mainly occurs at a post-transcriptional level. On the other hand, treatment of HT1080 cells with the synthetic glucocorticoid dexamethasone (DEX; 10(-7) M) significantly reduced uPA gene expression at a transcriptional level. Furthermore, DEX inhibited cell migration in soft agar without affecting cell growth. These negative effects of DEX on uPA expression and cell migration were alleviated by the expression of PU.1 in HT1080 cells, whereas expression of the N-ras oncogene, which is responsible for maintenance of the transformed phenotypes in HT1080 cells, was unaffected by PU.1 expression or DEX treatment in the cells. Our results suggest that expression of PU.1 can stimulate uPA gene expression at the post-transcriptional level, which may subsequently lead to activation of cell motility and/or reduced cell-cell adhesion, but reduces anchorage-independent growth of HT1080 cells. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9743289

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.

Induction of ectopic taste buds by SHH reveals the competency and plasticity of adult lingual epithelium.

PubMed

Castillo, David; Seidel, Kerstin; Salcedo, Ernesto; Ahn, Christina; de Sauvage, Frederic J; Klein, Ophir D; Barlow, Linda A

2014-08-01

Taste buds are assemblies of elongated epithelial cells, which are innervated by gustatory nerves that transmit taste information to the brain stem. Taste cells are continuously renewed throughout life via proliferation of epithelial progenitors, but the molecular regulation of this process remains unknown. During embryogenesis, sonic hedgehog (SHH) negatively regulates taste bud patterning, such that inhibition of SHH causes the formation of more and larger taste bud primordia, including in regions of the tongue normally devoid of taste buds. Here, using a Cre-lox system to drive constitutive expression of SHH, we identify the effects of SHH on the lingual epithelium of adult mice. We show that misexpression of SHH transforms lingual epithelial cell fate, such that daughter cells of lingual epithelial progenitors form cell type-replete, onion-shaped taste buds, rather than non-taste, pseudostratified epithelium. These SHH-induced ectopic taste buds are found in regions of the adult tongue previously thought incapable of generating taste organs. The ectopic buds are composed of all taste cell types, including support cells and detectors of sweet, bitter, umami, salt and sour, and recapitulate the molecular differentiation process of endogenous taste buds. In contrast to the well-established nerve dependence of endogenous taste buds, however, ectopic taste buds form independently of both gustatory and somatosensory innervation. As innervation is required for SHH expression by endogenous taste buds, our data suggest that SHH can replace the need for innervation to drive the entire program of taste bud differentiation. © 2014. Published by The Company of Biologists Ltd.

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 expression of specific GA2 oxidase mutants promotes yield and stress tolerance in rice.

PubMed

Lo, Shuen-Fang; Ho, Tuan-Hua David; Liu, Yi-Lun; Jiang, Mirng-Jier; Hsieh, Kun-Ting; Chen, Ku-Ting; Yu, Lin-Chih; Lee, Miin-Huey; Chen, Chi-Yu; Huang, Tzu-Pi; Kojima, Mikiko; Sakakibara, Hitoshi; Chen, Liang-Jwu; Yu, Su-May

2017-07-01

A major challenge of modern agricultural biotechnology is the optimization of plant architecture for enhanced productivity, stress tolerance and water use efficiency (WUE). To optimize plant height and tillering that directly link to grain yield in cereals and are known to be tightly regulated by gibberellins (GAs), we attenuated the endogenous levels of GAs in rice via its degradation. GA 2-oxidase (GA2ox) is a key enzyme that inactivates endogenous GAs and their precursors. We identified three conserved domains in a unique class of C 20 GA2ox, GA2ox6, which is known to regulate the architecture and function of rice plants. We mutated nine specific amino acids in these conserved domains and observed a gradient of effects on plant height. Ectopic expression of some of these GA2ox6 mutants moderately lowered GA levels and reprogrammed transcriptional networks, leading to reduced plant height, more productive tillers, expanded root system, higher WUE and photosynthesis rate, and elevated abiotic and biotic stress tolerance in transgenic rice. Combinations of these beneficial traits conferred not only drought and disease tolerance but also increased grain yield by 10-30% in field trials. Our studies hold the promise of manipulating GA levels to substantially improve plant architecture, stress tolerance and grain yield in rice and possibly in other major crops. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Ectopic expression of a novel CD22 splice-variant regulates survival and proliferation in malignant T cells from cutaneous T cell lymphoma (CTCL) patients

PubMed Central

Bagdonaite, Ieva; Wandall, Hans H.; Litvinov, Ivan V.; Nastasi, Claudia; Becker, Jürgen C.; Dabelsteen, Sally; Geisler, Carsten; Bonefeld, Charlotte M.; Zhang, Qian; Wasik, Mariusz A.; Zhou, Youwen; Sasseville, Denis; Ødum, Niels; Woetmann, Anders

2015-01-01

CD22 is a member of the Sialic acid-binding Ig-like lectin (Siglec) family of lectins described to be exclusively present in B lymphocytes and B cell-derived neoplasms. Here, we describe a novel splice form of CD22 (designated CD22ΔN), which lacks the N-terminal domain as demonstrated by exon-specific RT-PCR and differential recognition by anti-CD22 antibodies. Importantly, CD22ΔN mRNA is expressed in skin lesions from 39 out of 60 patients with cutaneous T cell lymphoma (CTCL), whereas few patients (6 out of 60) expresses full-length, wild type CD22 (CD22wt). In addition, IHC staining of tumor biopsies confirmed the expression of CD22 in CD4+ T cells. Moreover, four out of four malignant T cell lines express CD22: Two cell lines express CD22ΔN (MyLa2059 and PB2B) and two express CD22wt (MAC-1 and MAC-2A). siRNA-mediated silencing of CD22 impairs proliferation and survival of malignant T cells, demonstrating a functional role for both CD22ΔN and CD22wt in these cells. In conclusion, we provide the first evidence for an ectopic expression of CD22 and a novel splice variant regulating malignant proliferation and survival in CTCL. Analysis of expression and function of CD22 in cutaneous lymphomas may form the basis for development of novel targeted therapies for our patients. PMID:25957418

Ectopic expression of a novel CD22 splice-variant regulates survival and proliferation in malignant T cells from cutaneous T cell lymphoma (CTCL) patients.

PubMed

Bagdonaite, Ieva; Wandall, Hans H; Litvinov, Ivan V; Nastasi, Claudia; Becker, Jürgen C; Dabelsteen, Sally; Geisler, Carsten; Bonefeld, Charlotte M; Zhang, Qian; Wasik, Mariusz A; Zhou, Youwen; Sasseville, Denis; Ødum, Niels; Woetmann, Anders

2015-06-10

CD22 is a member of the Sialic acid-binding Ig-like lectin (Siglec) family of lectins described to be exclusively present in B lymphocytes and B cell-derived neoplasms. Here, we describe a novel splice form of CD22 (designated CD22∆N), which lacks the N-terminal domain as demonstrated by exon-specific RT-PCR and differential recognition by anti-CD22 antibodies. Importantly, CD22∆N mRNA is expressed in skin lesions from 39 out of 60 patients with cutaneous T cell lymphoma (CTCL), whereas few patients (6 out of 60) expresses full-length, wild type CD22 (CD22wt). In addition, IHC staining of tumor biopsies confirmed the expression of CD22 in CD4+ T cells. Moreover, four out of four malignant T cell lines express CD22: Two cell lines express CD22∆N (MyLa2059 and PB2B) and two express CD22wt (MAC-1 and MAC-2A). siRNA-mediated silencing of CD22 impairs proliferation and survival of malignant T cells, demonstrating a functional role for both CD22∆N and CD22wt in these cells.In conclusion, we provide the first evidence for an ectopic expression of CD22 and a novel splice variant regulating malignant proliferation and survival in CTCL. Analysis of expression and function of CD22 in cutaneous lymphomas may form the basis for development of novel targeted therapies for our patients.

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.

A block in lineage differentiation of immortal human mammary stem / progenitor cells by ectopically-expressed oncogenes

PubMed Central

Zhao, Xiangshan; Malhotra, Gautam K.; Band, Hamid; Band, Vimla

2011-01-01

Introduction: Emerging evidence suggests a direct role of cancer stem cells (CSCs) in the development of breast cancer. In vitro cellular models that recapitulate properties of CSCs are therefore highly desirable. We have previously shown that normal human mammary epithelial cells (hMECs) immortalized with human telomerase reverse transcriptase (hTERT) possess properties of mammary stem / progenitor cells. Materials and Methods: In the present study, we used this cell system to test the idea that other known hMEC-immortalizing oncogenes (RhoA, HPVE6, HPVE7, p53 mutant, and treatment with γ-radiation), share with hTERT, the ability to maintain mammary stem / progenitor cells. Results: The results presented here demonstrate that similar to hMECs immortalized with hTERT, all hMEC cell lines immortalized using various oncogenic strategies express stem / progenitor cell markers. Furthermore, analyses using 2D and 3D culture assays demonstrate that all the immortal cell lines retain their ability to self-renew and to differentiate along the luminal lineage. Remarkably, the stem / progenitor cell lines generated using various oncogenic strategies exhibit a block in differentiation along the myoepithelial lineage, a trait that is retained on hTERT-immortalized stem / progenitors. The inability to differentiate along the myoepithelial lineage could be induced by ectopic mutant p53 expression in hTERT-immortalized hMEC. Conclusions: Our studies demonstrate that stem / progenitor cell characteristics of hMECs are maintained upon immortalization by using various cancer-relevant oncogenic strategies. Oncogene-immortalized hMECs show a block in their ability to differentiate along the myoepithelial lineage. Abrogation of the myoepithelial differentiation potential by a number of distinct oncogenic insults suggests a potential explanation for the predominance of luminal and rarity of myoepithelial breast cancers. PMID:22279424

A block in lineage differentiation of immortal human mammary stem / progenitor cells by ectopically-expressed oncogenes.

PubMed

Zhao, Xiangshan; Malhotra, Gautam K; Band, Hamid; Band, Vimla

2011-01-01

Emerging evidence suggests a direct role of cancer stem cells (CSCs) in the development of breast cancer. In vitro cellular models that recapitulate properties of CSCs are therefore highly desirable. We have previously shown that normal human mammary epithelial cells (hMECs) immortalized with human telomerase reverse transcriptase (hTERT) possess properties of mammary stem / progenitor cells. In the present study, we used this cell system to test the idea that other known hMEC-immortalizing oncogenes (RhoA, HPVE6, HPVE7, p53 mutant, and treatment with γ-radiation), share with hTERT, the ability to maintain mammary stem / progenitor cells. The results presented here demonstrate that similar to hMECs immortalized with hTERT, all hMEC cell lines immortalized using various oncogenic strategies express stem / progenitor cell markers. Furthermore, analyses using 2D and 3D culture assays demonstrate that all the immortal cell lines retain their ability to self-renew and to differentiate along the luminal lineage. Remarkably, the stem / progenitor cell lines generated using various oncogenic strategies exhibit a block in differentiation along the myoepithelial lineage, a trait that is retained on hTERT-immortalized stem / progenitors. The inability to differentiate along the myoepithelial lineage could be induced by ectopic mutant p53 expression in hTERT-immortalized hMEC. Our studies demonstrate that stem / progenitor cell characteristics of hMECs are maintained upon immortalization by using various cancer-relevant oncogenic strategies. Oncogene-immortalized hMECs show a block in their ability to differentiate along the myoepithelial lineage. Abrogation of the myoepithelial differentiation potential by a number of distinct oncogenic insults suggests a potential explanation for the predominance of luminal and rarity of myoepithelial breast cancers.

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.

Failure of in vitro-differentiated mesenchymal stem cells from the synovial membrane to form ectopic stable cartilage in vivo.

PubMed

De Bari, Cosimo; Dell'Accio, Francesco; Luyten, Frank P

2004-01-01

We previously reported the identification in a nude mouse assay of molecular markers predictive of the capacity of articular cartilage-derived cells (ACDCs) to form ectopic stable cartilage that is resistant to vascular invasion and endochondral ossification. In the present study, we investigated whether in vitro-differentiated mesenchymal stem cells (MSCs) from the synovial membrane (SM) express the stable-chondrocyte markers and form ectopic stable cartilage in vivo. Chondrogenesis was induced in micromass culture with the addition of transforming growth factor beta1 (TGFbeta1). After acquisition of the cartilage phenotype, micromasses were implanted subcutaneously into nude mice. Alternatively, cells were released enzymatically and either replated in monolayer or injected intramuscularly into nude mice. Marker analysis was performed by quantitative reverse transcription-polymerase chain reaction. Cell death was detected with TUNEL assay. Cartilage-like micromasses and released cells expressed the stable-chondrocyte markers at levels comparable with those expressed by stable ACDCs. The released cells lost chondrocyte marker expression by 24 hours in monolayer and failed to form cartilage when injected intramuscularly into nude mice. Instead, myogenic differentiation was detected. When intact TGFbeta1-treated micromasses were implanted subcutaneously, they partially lost their cartilage phenotype and underwent cell death and neoangiogenesis within 1 week. At later time points (15-40 days), we retrieved neither cartilage nor bone, and human cells were not detectable. The chondrocyte-like phenotype of human SM MSCs, induced in vitro under specific conditions, appears to be unstable and is not sufficient to obtain ectopic formation of stable cartilage in vivo. Studies in animal models of joint surface defect repair are necessary to evaluate the stability of the SM MSC chondrocyte-like phenotype within the joint environment.

Non-invasive localization of atrial ectopic beats by using simulated body surface P-wave integral maps

PubMed Central

Godoy, Eduardo J.; Lozano, Miguel; Martínez-Mateu, Laura; Atienza, Felipe; Saiz, Javier; Sebastian, Rafael

2017-01-01

Non-invasive localization of continuous atrial ectopic beats remains a cornerstone for the treatment of atrial arrhythmias. The lack of accurate tools to guide electrophysiologists leads to an increase in the recurrence rate of ablation procedures. Existing approaches are based on the analysis of the P-waves main characteristics and the forward body surface potential maps (BSPMs) or on the inverse estimation of the electric activity of the heart from those BSPMs. These methods have not provided an efficient and systematic tool to localize ectopic triggers. In this work, we propose the use of machine learning techniques to spatially cluster and classify ectopic atrial foci into clearly differentiated atrial regions by using the body surface P-wave integral map (BSPiM) as a biomarker. Our simulated results show that ectopic foci with similar BSPiM naturally cluster into differentiated non-intersected atrial regions and that new patterns could be correctly classified with an accuracy of 97% when considering 2 clusters and 96% for 4 clusters. Our results also suggest that an increase in the number of clusters is feasible at the cost of decreasing accuracy. PMID:28704537

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.

Damage-induced ectopic recombination in the yeast Saccharomyces cerevisiae.

PubMed

Kupiec, M; Steinlauf, R

1997-06-09

Mitotic recombination in the yeast Saccharomyces cerevisiae is induced when cells are irradiated with UV or X-rays, reflecting the efficient repair of damage by recombinational repair mechanisms. We have used multiply marked haploid strains that allow the simultaneous detection of several types of ectopic recombination events. We show that inter-chromosomal ectopic conversion of lys2 heteroalleles and, to a lesser extent, direct repeat recombination (DRR) between non-tandem repeats, are increased by DNA-damaging agents; in contrast, ectopic recombination of the naturally occurring Ty element is not induced. We have tested several hypotheses that could explain the preferential lack of induction of Ty recombination by DNA-damaging agents. We have found that the lack of induction cannot be explained by a cell cycle control or by an effect of the mating-type genes. We also found no role for the flanking long terminal repeats (LTRs) of the Ty in preventing the induction. Ectopic conversion, DRR, and forward mutation of artificial repeats show different kinetics of induction at various positions of the cell cycle, reflecting different mechanisms of recombination. We discuss the mechanistic and evolutionary aspects of these results.

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.

Tissue transglutaminase regulates focal adhesion kinase/AKT activation by modulating PTEN expression in pancreatic cancer cells.

PubMed

Verma, Amit; Guha, Sushovan; Wang, Huamin; Fok, Jansina Y; Koul, Dimpy; Abbruzzese, James; Mehta, Kapil

2008-04-01

Pancreatic ductal adenocarcinoma (PDAC) progresses rapidly and exhibits profound resistance to treatment. We recently reported that a great majority of PDAC tumors and tumor cell lines express elevated levels of tissue transglutaminase (TG2). Here, we provide first evidence that TG2 expression in PDAC cells results in constitutive activation of focal adhesion kinase/AKT by modulating the expression of the tumor suppressor phosphatase PTEN. Using PDAC cell lines, we determined the effect of TG2 overexpression on PTEN stability and functions. We confirmed the correlation between TG2 expression and PTEN levels in a few (n=51) PDAC tumor samples. We observed that expression of TG2 is inversely correlated with PTEN expression in PDAC cells. Ectopic expression of TG2 inhibited PTEN phosphorylation and promoted its degradation by ubiquitin-proteasomal pathway. Conversely, down-regulation of TG2 by small interfering RNA up-regulated PTEN expression. Clinical relevance of these results was evident in an athymic nude mouse model where down-regulation of endogenous TG2 caused a significant retardation in PDAC xenograft growth. Importantly, the analysis of 51 tumor samples from patients with stage II PDAC revealed that overexpression of TG2 was associated with loss of PTEN expression (P=0.023; odds ratio, 4.1). In multivariate analysis, TG2-mediated loss of PTEN was a prognostic factor for overall survival in patients with stage II pancreatic ductal carcinoma independent of tumor stage/lymph node status and tumor differentiation (P=0.01). TG2 expression in PDAC promotes degradation of PTEN by ubiquitin-proteasomal pathway and results in constitutive activation of focal adhesion kinase/AKT cell survival signaling.

Co-ordinated expression of MMP-2 and its putative activator, MT1-MMP, in human placentation.

PubMed

Bjørn, S F; Hastrup, N; Lund, L R; Danø, K; Larsen, J F; Pyke, C

1997-08-01

The spatial expression of mRNA for matrix metalloproteinase 2 (MMP-2), its putative activator, the membrane-type 1 matrix metalloproteinase (MT1-MMP), and the MMP-2 substrate type IV collagen was investigated in human placentas of both normal and tubal ectopic pregnancies and in cyclic endometrium using in-situ hybridization. Cytokeratin staining applied to adjacent sections was used to identify epithelial and trophoblast cells. In both normal and tubal pregnancies MT1-MMP, MMP-2 and type IV collagen mRNA were highly expressed and co-localized in the extravillous cytotrophoblasts of anchoring villi, in cytotrophoblasts that had penatrated into the placental bed and in cytotrophoblastic cell islands. In addition, the decidual cells of normal pregnancies in some areas co-expressed MT1-MMP and MMP-2 mRNA, with moderate signals for both components. Fibroblast-like stromal cells in tubal pregnancies were positive for MMP-2 mRNA but generally negative for MT1-MMP mRNA. The consistent co-localization of MT1-MMP with MMP-2 and type IV collagen in the same subset of cytotrophoblasts strongly suggests that all three components co-operate in the tightly regulated fetal invasion process. The co-expression of MT1-MMP and MMP-2 mRNA in some of the decidual cells indicates that these cells are also actively involved in the placentation process.

Ectopic expression of a polyalanine expansion mutant of poly(A)-binding protein N1 in muscle cells in culture inhibits myogenesis

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

Wang Qishan; Bag, Jnanankur

2006-02-17

Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset dominant genetic disease caused by the expansion of a GCG trinucleotide repeat that encodes the polyalanine tract at the N-terminus of the nuclear poly(A)-binding protein (PABPN1). Presence of intranuclear inclusions (INIs) containing PABPN1 aggregates in the skeletal muscles is the hallmark of OPMD. Here, we show that ectopic expression of the mutant PABPN1 produced INIs in a muscle cell culture model and reduced expression of several muscle-specific proteins including {alpha}-actin, slow troponin C, muscle creatine kinase, and two myogenic transcription factors, myogenin and MyoD. However, the levels of two upstream regulators of themore » MyoD gene, the Myf-5 and Pax3/7, were not affected, but both proteins co-localized with the PABPN1 aggregates in the mutant PABPN1 overexpressing cells. In these cells, although myogenin and MyoD levels were reduced, these two transcription factors did not co-localize with the mutant PABPN1 aggregates. Therefore, sequestration of Myf5 and Pax3/7 by the mutant PABPN1 aggregates was a specific effect on these factors. Our results suggest that trapping of these two important myogenic determinants may interfere with an early step in myogenesis.« less

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.

Ectopic Terpene Synthase Expression Enhances Sesquiterpene Emission in Nicotiana attenuata without Altering Defense or Development of Transgenic Plants or Neighbors1[W

PubMed Central

Schuman, Meredith C.; Palmer-Young, Evan C.; Schmidt, Axel; Gershenzon, Jonathan; Baldwin, Ian T.

2014-01-01

Sesquiterpenoids, with approximately 5,000 structures, are the most diverse class of plant volatiles with manifold hypothesized functions in defense, stress tolerance, and signaling between and within plants. These hypotheses have often been tested by transforming plants with sesquiterpene synthases expressed behind the constitutively active 35S promoter, which may have physiological costs measured as inhibited growth and reduced reproduction or may require augmentation of substrate pools to achieve enhanced emission, complicating the interpretation of data from affected transgenic lines. Here, we expressed maize (Zea mays) terpene synthase10 (ZmTPS10), which produces (E)-α-bergamotene and (E)-β-farnesene, or a point mutant ZmTPS10M, which produces primarily (E)-β-farnesene, under control of the 35S promoter in the ecological model plant Nicotiana attenuata. Transgenic N. attenuata plants had specifically enhanced emission of target sesquiterpene(s) with no changes detected in their emission of any other volatiles. Treatment with herbivore or jasmonate elicitors induces emission of (E)-α-bergamotene in wild-type plants and also tended to increase emission of (E)-α-bergamotene and (E)-β-farnesene in transgenics. However, transgenics did not differ from the wild type in defense signaling or chemistry and did not alter defense chemistry in neighboring wild-type plants. These data are inconsistent with within-plant and between-plant signaling functions of (E)-β-farnesene and (E)-α-bergamotene in N. attenuata. Ectopic sesquiterpene emission was apparently not costly for transgenics, which were similar to wild-type plants in their growth and reproduction, even when forced to compete for common resources. These transgenics would be well suited for field experiments to investigate indirect ecological effects of sesquiterpenes for a wild plant in its native habitat. PMID:25187528

Wnt/β-Catenin Regulates the Activity of Epiprofin/Sp6, SHH, FGF, and BMP to Coordinate the Stages of Odontogenesis

PubMed Central

Aurrekoetxea, Maitane; Irastorza, Igor; García-Gallastegui, Patricia; Jiménez-Rojo, Lucia; Nakamura, Takashi; Yamada, Yoshihiko; Ibarretxe, Gaskon; Unda, Fernando J.

2016-01-01

Background: We used an in vitro tooth development model to investigate the effects of overactivation of the Wnt/β-catenin pathway during odontogenesis by bromoindirubin oxime reagent (BIO), a specific inhibitor of GSK-3 activity. Results: Overactivating the Wnt/β-catenin pathway at tooth initiation upregulated and ectopically expressed the epithelial markers Sonic Hedgehog (Shh), Epiprofin (Epfn), and Fibroblast growth factor8 (Fgf8), which are involved in the delimitation of odontogenic fields in the oral ectoderm. This result indicated an ectopic extension of the odontogenic potential. During tooth morphogenesis, Fibroblast growth factor4 (Fgf4), Fibroblast growth factor10 (Fgf10), Muscle segment homeobox 1 (Msx-1), Bone Morphogenetic protein 4 (Bmp4), and Dickkopf WNT signaling pathway inhibitor 1 (Dkk-1) were overexpressed in first molars cultured with BIO. Conversely, the expression levels of Wingless integration site 10b (Wnt-10b) and Shh were reduced. Additionally, the odontoblast differentiation markers Nestin and Epfn showed ectopic overexpression in the dental mesenchyme of BIO-treated molars. Moreover, alkaline phosphatase activity increased in the dental mesenchyme, again suggesting aberrant, ectopic mesenchymal cell differentiation. Finally, Bmp4 downregulated Epfn expression during dental morphogenesis. Conclusions: We suggest the presence of a positive feedback loop wherein Epfn and β-catenin activate each other. The balance of the expression of these two molecules is essential for proper tooth development. We propose a possible link between Wnt, Bmp, and Epfn that would critically determine the correct patterning of dental cusps and the differentiation of odontoblasts and ameloblasts. PMID:27066482

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.

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

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.

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.

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.

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.

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. ...

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

Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing's syndrome.

PubMed

Lecoq, Anne-Lise; Stratakis, Constantine A; Viengchareun, Say; Chaligné, Ronan; Tosca, Lucie; Deméocq, Vianney; Hage, Mirella; Berthon, Annabel; Faucz, Fabio R; Hanna, Patrick; Boyer, Hadrien-Gaël; Servant, Nicolas; Salenave, Sylvie; Tachdjian, Gérard; Adam, Clovis; Benhamo, Vanessa; Clauser, Eric; Guiochon-Mantel, Anne; Young, Jacques; Lombès, Marc; Bourdeau, Isabelle; Maiter, Dominique; Tabarin, Antoine; Bertherat, Jérôme; Lefebvre, Hervé; de Herder, Wouter; Louiset, Estelle; Lacroix, André; Chanson, Philippe; Bouligand, Jérôme; Kamenický, Peter

2017-09-21

GIP-dependent Cushing's syndrome is caused by ectopic expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in cortisol-producing adrenal adenomas or in bilateral macronodular adrenal hyperplasias. Molecular mechanisms leading to ectopic GIPR expression in adrenal tissue are not known. Here we performed molecular analyses on adrenocortical adenomas and bilateral macronodular adrenal hyperplasias obtained from 14 patients with GIP-dependent adrenal Cushing's syndrome and one patient with GIP-dependent aldosteronism. GIPR expression in all adenoma and hyperplasia samples occurred through transcriptional activation of a single allele of the GIPR gene. While no abnormality was detected in proximal GIPR promoter methylation, we identified somatic duplications in chromosome region 19q13.32 containing the GIPR locus in the adrenocortical lesions derived from 3 patients. In 2 adenoma samples, the duplicated 19q13.32 region was rearranged with other chromosome regions, whereas a single tissue sample with hyperplasia had a 19q duplication only. We demonstrated that juxtaposition with cis-acting regulatory sequences such as glucocorticoid response elements in the newly identified genomic environment drives abnormal expression of the translocated GIPR allele in adenoma cells. Altogether, our results provide insight into the molecular pathogenesis of GIP-dependent Cushing's syndrome, occurring through monoallelic transcriptional activation of GIPR driven in some adrenal lesions by structural variations.

ID4 promotes AR expression and blocks tumorigenicity of PC3 prostate cancer cells.

PubMed

Komaragiri, Shravan Kumar; Bostanthirige, Dhanushka H; Morton, Derrick J; Patel, Divya; Joshi, Jugal; Upadhyay, Sunil; Chaudhary, Jaideep

2016-09-09

Deregulation of tumor suppressor genes is associated with tumorigenesis and the development of cancer. In prostate cancer, ID4 is epigenetically silenced and acts as a tumor suppressor. In normal prostate epithelial cells, ID4 collaborates with androgen receptor (AR) and p53 to exert its tumor suppressor activity. Previous studies have shown that ID4 promotes tumor suppressive function of AR whereas loss of ID4 results in tumor promoter activity of AR. Previous study from our lab showed that ectopic ID4 expression in DU145 attenuates proliferation and promotes AR expression suggesting that ID4 dependent AR activity is tumor suppressive. In this study, we examined the effect of ectopic expression of ID4 on highly malignant prostate cancer cell, PC3. Here we show that stable overexpression of ID4 in PC3 cells leads to increased apoptosis and decreased cell proliferation and migration. In addition, in vivo studies showed a decrease in tumor size and volume of ID4 overexpressing PC3 cells, in nude mice. At the molecular level, these changes were associated with increased androgen receptor (AR), p21, and AR dependent FKBP51 expression. At the mechanistic level, ID4 may regulate the expression or function of AR through specific but yet unknown AR co-regulators that may determine the final outcome of AR function. Copyright © 2016 Elsevier Inc. All rights reserved.

ID4 promotes AR expression and blocks tumorigenicity of PC3 prostate cancer cells

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

Komaragiri, Shravan Kumar; Bostanthirige, Dhanushka H.; Morton, Derrick J.

Deregulation of tumor suppressor genes is associated with tumorigenesis and the development of cancer. In prostate cancer, ID4 is epigenetically silenced and acts as a tumor suppressor. In normal prostate epithelial cells, ID4 collaborates with androgen receptor (AR) and p53 to exert its tumor suppressor activity. Previous studies have shown that ID4 promotes tumor suppressive function of AR whereas loss of ID4 results in tumor promoter activity of AR. Previous study from our lab showed that ectopic ID4 expression in DU145 attenuates proliferation and promotes AR expression suggesting that ID4 dependent AR activity is tumor suppressive. In this study, wemore » examined the effect of ectopic expression of ID4 on highly malignant prostate cancer cell, PC3. Here we show that stable overexpression of ID4 in PC3 cells leads to increased apoptosis and decreased cell proliferation and migration. In addition, in vivo studies showed a decrease in tumor size and volume of ID4 overexpressing PC3 cells, in nude mice. At the molecular level, these changes were associated with increased androgen receptor (AR), p21, and AR dependent FKBP51 expression. At the mechanistic level, ID4 may regulate the expression or function of AR through specific but yet unknown AR co-regulators that may determine the final outcome of AR function. - Highlights: • ID4 expression induces AR expression in PC3 cells, which generally lack AR. • ID4 expression increased apoptosis and decreased cell proliferation and invasion. • Overexpression of ID4 reduces tumor growth of subcutaneous xenografts in vivo. • ID4 induces p21 and FKBP51 expression- co-factors of AR tumor suppressor activity.« less

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.

[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.

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 .

Donor-Specific Antibodies Are Produced Locally in Ectopic Lymphoid Structures in Cardiac Allografts.

PubMed

Huibers, M M H; Gareau, A J; Beerthuijzen, J M T; Siera-de Koning, E; van Kuik, J; Kamburova, E G; Vink, A; de Jonge, N; Lee, T D G; Otten, H G; de Weger, R A

2017-01-01

Cardiac allograft vasculopathy (CAV) is a transplant pathology, limiting graft survival after heart transplantation. CAV arteries are surrounded by ectopic lymphoid structures (ELS) containing B cells and plasma cells. The aim of this study was to characterize the antigenic targets of antibodies produced in ELS. Coronary arteries and surrounding epicardial tissue from 56 transplant recipients were collected during autopsy. Immunofluorescence was used to identify antibody-producing plasma cells. Immunoglobulin levels in tissue lysates were measured by enzyme-linked immunosorbent assay and analyzed for donor-specific HLA antibodies by Luminex assay. Cytokine and receptor expression levels were quantified using quantitative polymerase chain reaction. Plasma cells in ELS were polyclonal and produced IgG and/or IgM antibodies. In epicardial tissue, IgG (p < 0.05) and IgM levels were higher in transplant patients with larger ELS than smaller ELS. In 4 of 21 (19%) patients with ELS, donor-specific HLA type II antibodies were detected locally. Cytokine and receptor expression (CXCR3, interferon γ and TGF-β) was higher in large ELS in the epicardial tissue than in other vessel wall layers, suggesting active recruitment and proliferation of T and B lymphocytes. ELS exhibited active plasma cells producing locally manufactured antibodies that, in some cases, were directed against the donor HLA, potentially mediating rejection with major consequences for the graft. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Ras/Mitogen-activated Protein Kinase (MAPK) Signaling Modulates Protein Stability and Cell Surface Expression of Scavenger Receptor SR-BI*

PubMed Central

Wood, Peta; Mulay, Vishwaroop; Darabi, Masoud; Chan, Karen Cecilia; Heeren, Joerg; Pol, Albert; Lambert, Gilles; Rye, Kerry-Anne; Enrich, Carlos; Grewal, Thomas

2011-01-01

The mitogen-activated protein kinase (MAPK) Erk1/2 has been implicated to modulate the activity of nuclear receptors, including peroxisome proliferator activator receptors (PPARs) and liver X receptor, to alter the ability of cells to export cholesterol. Here, we investigated if the Ras-Raf-Mek-Erk1/2 signaling cascade could affect reverse cholesterol transport via modulation of scavenger receptor class BI (SR-BI) levels. We demonstrate that in Chinese hamster ovary (CHO) and human embryonic kidney (HEK293) cells, Mek1/2 inhibition reduces PPARα-inducible SR-BI protein expression and activity, as judged by reduced efflux onto high density lipoprotein (HDL). Ectopic expression of constitutively active H-Ras and Mek1 increases SR-BI protein levels, which correlates with elevated PPARα Ser-21 phosphorylation and increased cholesterol efflux. In contrast, SR-BI levels are insensitive to Mek1/2 inhibitors in PPARα-depleted cells. Most strikingly, Mek1/2 inhibition promotes SR-BI degradation in SR-BI-overexpressing CHO cells and human HuH7 hepatocytes, which is associated with reduced uptake of radiolabeled and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyane-labeled HDL. Loss of Mek1/2 kinase activity reduces SR-BI expression in the presence of bafilomycin, an inhibitor of lysosomal degradation, indicating down-regulation of SR-BI via proteasomal pathways. In conclusion, Mek1/2 inhibition enhances the PPARα-dependent degradation of SR-BI in hepatocytes. PMID:21525007

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

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.

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 Complex Structural Variation on Chromosome 27 Leads to the Ectopic Expression of HOXB8 and the Muffs and Beard Phenotype in Chickens

PubMed Central

Wang, Yanqiang; Luo, Chenglong; Liu, Ranran; Qu, Hao; Shu, Dingming; Wen, Jie; Crooijmans, Richard P. M. A.; Zhao, Yiqiang; Hu, Xiaoxiang; Li, Ning

2016-01-01

Muffs and beard (Mb) is a phenotype in chickens where groups of elongated feathers gather from both sides of the face (muffs) and below the beak (beard). It is an autosomal, incomplete dominant phenotype encoded by the Muffs and beard (Mb) locus. Here we use genome-wide association (GWA) analysis, linkage analysis, Identity-by-Descent (IBD) mapping, array-CGH, genome re-sequencing and expression analysis to show that the Mb allele causing the Mb phenotype is a derived allele where a complex structural variation (SV) on GGA27 leads to an altered expression of the gene HOXB8. This Mb allele was shown to be completely associated with the Mb phenotype in nine other independent Mb chicken breeds. The Mb allele differs from the wild-type mb allele by three duplications, one in tandem and two that are translocated to that of the tandem repeat around 1.70 Mb on GGA27. The duplications contain total seven annotated genes and their expression was tested during distinct stages of Mb morphogenesis. A continuous high ectopic expression of HOXB8 was found in the facial skin of Mb chickens, strongly suggesting that HOXB8 directs this regional feather-development. In conclusion, our results provide an interesting example of how genomic structural rearrangements alter the regulation of genes leading to novel phenotypes. Further, it again illustrates the value of utilizing derived phenotypes in domestic animals to dissect the genetic basis of developmental traits, herein providing novel insights into the likely role of HOXB8 in feather development and differentiation. PMID:27253709

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.

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.

Atrial Fibrosis Hampers Non-invasive Localization of Atrial Ectopic Foci From Multi-Electrode Signals: A 3D Simulation Study

PubMed Central

Godoy, Eduardo Jorge; Lozano, Miguel; García-Fernández, Ignacio; Ferrer-Albero, Ana; MacLeod, Rob; Saiz, Javier; Sebastian, Rafael

2018-01-01

Introduction: Focal atrial tachycardia is commonly treated by radio frequency ablation with an acceptable long-term success. Although the location of ectopic foci tends to appear in specific hot-spots, they can be located virtually in any atrial region. Multi-electrode surface ECG systems allow acquiring dense body surface potential maps (BSPM) for non-invasive therapy planning of cardiac arrhythmia. However, the activation of the atria could be affected by fibrosis and therefore biomarkers based on BSPM need to take these effects into account. We aim to analyze the effect of fibrosis on a BSPM derived index, and its potential application to predict the location of ectopic foci in the atria. Methodology: We have developed a 3D atrial model that includes 5 distributions of patchy fibrosis in the left atrium at 5 different stages. Each stage corresponds to a different amount of fibrosis that ranges from 2 to 40%. The 25 resulting 3D models were used for simulation of Focal Atrial Tachycardia (FAT), triggered from 19 different locations described in clinical studies. BSPM were obtained for all simulations, and the body surface potential integral maps (BSPiM) were calculated to describe atrial activations. A machine learning (ML) pipeline using a supervised learning model and support vector machine was developed to learn the BSPM patterns of each of the 475 activation sequences and relate them to the origin of the FAT source. Results: Activation maps for stages with more than 15% of fibrosis were greatly affected, producing conduction blocks and delays in propagation. BSPiMs did not always cluster into non-overlapped groups since BSPiMs were highly altered by the conduction blocks. From stage 3 (15% fibrosis) the BSPiMs showed differences for ectopic beats placed around the area of the pulmonary veins. Classification results were mostly above 84% for all the configurations studied when a large enough number of electrodes were used to map the torso. However, the

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

Hepatitis C virus Core overcomes all-trans retinoic acid-induced apoptosis in human hepatoma cells by inhibiting p14 expression via DNA methylation

PubMed Central

Kwak, Juri; Choi, Jung-Hye; Jang, Kyung Lib

2017-01-01

All-trans retinoic acid (ATRA), the most biologically active metabolite of vitamin A, is known to induce p14 expression via promoter hypomethylation to activate the p14-MDM2-p53 pathway, which leads to activation of the p53-dependent apoptotic pathway and subsequent induction of apoptosis in human hepatoma cells. In the present study, we found that hepatitis C virus (HCV) Core derived from ectopic expression or HCV infection overcomes ATRA-induced apoptosis in p53-positive hepatoma cells. For this effect, HCV Core upregulated both protein levels and enzyme activities of DNA methyltransferase 1 (DNMT1), DNMT3a, and DNMT3b and thereby repressed p14 expression via promoter hypermethylation, resulting in inactivation of the pathway leading to p53 accumulation in the presence of ATRA. As a result, HCV Core prevented ATRA from activating several apoptosis-related molecules, including Bax, p53 upregulated modulator of apoptosis, caspase-9, caspase-3, and poly (ADP-ribose) polymerase. In addition, complementation of p14 in the Core-expressing cells by either ectopic expression or treatment with 5-Aza-2′dC almost completely abolished the potential of HCV Core to suppress ATRA-induced apoptosis. Based on these observations, we conclude that HCV Core executes its oncogenic potential by suppressing the p53-dependent apoptosis induced by ATRA in human hepatoma cells. PMID:29156743

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

Hormonal therapy deregulates prostaglandin-endoperoxidase synthase 2 (PTGS2) expression in endometriotic tissues.

PubMed

Santulli, Pietro; Borghese, Bruno; Noël, Jean-Christophe; Fayt, Isabelle; Anaf, Vincent; de Ziegler, Dominique; Batteux, Frederic; Vaiman, Daniel; Chapron, Charles

2014-03-01

Endometriosis is a common gynecologic condition characterized by an important inflammatory process mediated by the prostaglandin pathway. Oral contraceptives are the treatment of choice for symptomatic endometriotic women. However the effects of oral contraceptives use and prostaglandin pathway in endometriotic women are actually still unknown. To investigate the expression of prostaglandin pathway key genes in endometriotic tissue, affected or not by hormonal therapy, as compared with healthy endometrial tissue. This was a comparative laboratory study. This study was conducted in a tertiary-care university hospital. Seventy-six women, with (n = 46) and without (n = 30) histologically proven endometriosis. Prostaglandin-endoperoxidase synthase (PTGS)1, PTGS2, prostaglandin E receptor (PTGER)1, PTGER2, PTGER3, and PTGER4 mRNA levels in endometrium of disease-free women and in eutopic and ectopic endometrium of endometriosis-affected women. PTGS2 expression was further investigated by immunohistochemistry, using specific monoclonal antibodies. PTGS2 expression was analyzed at mRNA and protein levels and correlated with taking hormonal treatment. PTGS2 expression was significantly increased in eutopic and ectopic endometrium as compared with healthy tissue (induction of 9.6- and 6.3-fold, respectively; P = .001). PTGS2 immunoreactivity increased gradually from normal endometrium to eutopic and ectopic endometrium (h-score of 96.7 ± 55.0, 128.3 ± 66.1, and 226.7 ± 62.6, respectively, P < .001). PTGER2, PTGER3, and PTGER4 expression increased significantly and gradually from normal to eutopic and ectopic endometrium, whereas PTGER1 remained unchanged. Patients under hormonal treatment had a higher PTGS2 expression at transcriptional and protein levels as compared with those without treatment (P = .002 and P = .025, respectively). Prostaglandin pathway is strongly deregulated in eutopic and ectopic endometrium of women suffering from endometriosis for the benefit of

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

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.

Ultrasound diagnosis of ectopic pregnancy

PubMed Central

2015-01-01

Abstract Ectopic pregnancy (EP) remains the number one cause of first trimester maternal death. Traditionally, laparoscopy has been the gold standard for diagnosis of EP. The advent of high‐resolution transvaginal scan (TVS) means more clinically stable women with EPs are diagnosed earlier, well before surgery becomes necessary in many cases. Early diagnosis by TVS is therefore potentially life saving and can reduce surgical morbidity by allowing elective surgery or even non‐surgical conservative treatment options. Combining transabdominal and transvaginal scanning confers no benefit over transvaginal scanning alone. Reports that reads “…empty uterus, ectopic pregnancy cannot be excluded” should be a thing of the past. Diagnosis of EP should be based upon the positive identification of an adnexal mass using TVS rather than the absence of an intra‐uterine gestational sac. A systematic approach to scanning the early pregnancy pelvis will diagnose the vast majority of EPs at the initial scan. Ultrasound, and in particular TVS, is fast becoming the new gold standard for diagnosis of all types of EP. In modern management, laparoscopy should be seen as the operative tool of choice while TVS the diagnostic tool of choice. PMID:28191110

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

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.

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. ...

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

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.

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

Acute mesenteric ischemia and hepatic infarction after treatment of ectopic Cushing's syndrome.

PubMed

Takayasu, Shinobu; Murasawa, Shingo; Yamagata, Satoshi; Kageyama, Kazunori; Nigawara, Takeshi; Watanuki, Yutaka; Kimura, Daisuke; Tsushima, Takao; Sakamoto, Yoshiyuki; Hakamada, Kenichi; Terui, Ken; Daimon, Makoto

2017-01-01

Patients with Cushing's syndrome and excess exogenous glucocorticoids have an increased risk for venous thromboembolism, as well as arterial thrombi. The patients are at high risk of thromboembolic events, especially during active disease and even in cases of remission and after surgery in Cushing's syndrome and withdrawal state in glucocorticoid users. We present a case of Cushing's syndrome caused by adrenocorticotropic hormone-secreting lung carcinoid tumor. Our patient developed acute mesenteric ischemia after video-assisted thoracoscopic surgery despite administration of sufficient glucocorticoid and thromboprophylaxis in the perioperative period. In addition, our patient developed hepatic infarction after surgical resection of the intestine. Then, the patient was supported by total parenteral nutrition. Our case report highlights the risk of microthrombi, which occurred in our patient after treatment of ectopic Cushing's syndrome. Guidelines on thromboprophylaxis and/or antiplatelet therapy for Cushing's syndrome are acutely needed. The present case showed acute mesenteric thromboembolism and hepatic infarction after treatment of ectopic Cushing's syndrome.Patients with Cushing's syndrome are at increased risk for thromboembolic events and increased morbidity and mortality.An increase in thromboembolic risk has been observed during active disease, even in cases of remission and postoperatively in Cushing's syndrome.Thromboprophylaxis and antiplatelet therapy should be considered in treatment of glucocorticoid excess or glucocorticoid withdrawal.

Nerve-independent and ectopically additional induction of taste buds in organ culture of fetal tongues.

PubMed

Honda, Kotaro; Tomooka, Yasuhiro

2016-10-01

An improved organ culture system allowed to observe morphogenesis of mouse lingual papillae and taste buds relatively for longer period, in which fetal tongues were analyzed for 6 d. Taste cells were defined as eosinophobic epithelial cells expressing CK8 and Sox2 within lingual epithelium. Addition of glycogen synthase kinase 3 beta inhibitor CHIR99021 induced many taste cells and buds in non-gustatory and gustatory stratified lingual epithelium. The present study clearly demonstrated induction of taste cells and buds ectopically and without innervation.

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.

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.

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.

Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing’s syndrome

PubMed Central

Lecoq, Anne-Lise; Stratakis, Constantine A.; Viengchareun, Say; Chaligné, Ronan; Tosca, Lucie; Hage, Mirella; Berthon, Annabel; Faucz, Fabio R.; Hanna, Patrick; Boyer, Hadrien-Gaël; Servant, Nicolas; Salenave, Sylvie; Tachdjian, Gérard; Adam, Clovis; Benhamo, Vanessa; Clauser, Eric; Guiochon-Mantel, Anne; Young, Jacques; Lombès, Marc; Bourdeau, Isabelle; Maiter, Dominique; Tabarin, Antoine; Bertherat, Jérôme; Lefebvre, Hervé; Louiset, Estelle; Lacroix, André; Bouligand, Jérôme; Kamenický, Peter

2017-01-01

GIP-dependent Cushing’s syndrome is caused by ectopic expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in cortisol-producing adrenal adenomas or in bilateral macronodular adrenal hyperplasias. Molecular mechanisms leading to ectopic GIPR expression in adrenal tissue are not known. Here we performed molecular analyses on adrenocortical adenomas and bilateral macronodular adrenal hyperplasias obtained from 14 patients with GIP-dependent adrenal Cushing’s syndrome and one patient with GIP-dependent aldosteronism. GIPR expression in all adenoma and hyperplasia samples occurred through transcriptional activation of a single allele of the GIPR gene. While no abnormality was detected in proximal GIPR promoter methylation, we identified somatic duplications in chromosome region 19q13.32 containing the GIPR locus in the adrenocortical lesions derived from 3 patients. In 2 adenoma samples, the duplicated 19q13.32 region was rearranged with other chromosome regions, whereas a single tissue sample with hyperplasia had a 19q duplication only. We demonstrated that juxtaposition with cis-acting regulatory sequences such as glucocorticoid response elements in the newly identified genomic environment drives abnormal expression of the translocated GIPR allele in adenoma cells. Altogether, our results provide insight into the molecular pathogenesis of GIP-dependent Cushing’s syndrome, occurring through monoallelic transcriptional activation of GIPR driven in some adrenal lesions by structural variations. PMID:28931750

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.

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.

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

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.

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

Arabidopsis and tobacco plants ectopically expressing the soybean antiquitin-like ALDH7 gene display enhanced tolerance to drought, salinity, and oxidative stress.

PubMed

Rodrigues, Simone M; Andrade, Maxuel O; Gomes, Ana Paula Soares; Damatta, Fabio M; Baracat-Pereira, Maria C; Fontes, Elizabeth P B

2006-01-01

Despite extensive studies in eukaryotic aldehyde dehydrogenases, functional information about the ALDH7 antiquitin-like proteins is lacking. A soybean antiquitin homologue gene, designated GmTP55, has been isolated which encodes a dehydrogenase motif-containing 55 kDa protein induced by dehydration and salt stress. GmTP55 is closely related to the stress-induced plant antiquitin-like proteins that belong to the ALDH7 family. Transgenic tobacco (Nicotiana tabacum) and Arabidopsis (Arabidopsis thaliana) plants constitutively expressing GmTP55 have been obtained in order to examine the physiological role of this enzyme under a variety of stress conditions. Ectopic expression of GmTP55 in both Arabidopsis and tobacco conferred tolerance to salinity during germination and to water deficit during plant growth. Under salt stress, the germination efficiency of both transgenic tobacco and Arabidopsis seeds was significantly higher than that of their control counterparts. Likewise, under progressive drought, the transgenic tobacco lines apparently kept the shoot turgidity to a normal level, which contrasted with the leaf wilt phenotype of control plants. The transgenic plants also exhibited an enhanced tolerance to H(2)O(2)- and paraquat-induced oxidative stress. Both GmTP55-expressing Arabidopsis and tobacco seeds germinated efficiently in medium supplemented with H(2)O(2), whereas the germination of control seeds was drastically impaired. Similarly, transgenic tobacco leaf discs treated with paraquat displayed a significant reduction in the necrotic lesions as compared with control leaves. These transgenic lines also exhibited a lower concentration of lipid peroxidation-derived reactive aldehydes under oxidative stress. These results suggest that antiquitin may be involved in adaptive responses mediated by a physiologically relevant detoxification pathway in plants.

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

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.

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.

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.

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.

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.

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

A high affinity RIM-binding protein/Aplip1 interaction prevents the formation of ectopic axonal active zones.

PubMed

Siebert, Matthias; Böhme, Mathias A; Driller, Jan H; Babikir, Husam; Mampell, Malou M; Rey, Ulises; Ramesh, Niraja; Matkovic, Tanja; Holton, Nicole; Reddy-Alla, Suneel; Göttfert, Fabian; Kamin, Dirk; Quentin, Christine; Klinedinst, Susan; Andlauer, Till Fm; Hell, Stefan W; Collins, Catherine A; Wahl, Markus C; Loll, Bernhard; Sigrist, Stephan J

2015-08-14

Synaptic vesicles (SVs) fuse at active zones (AZs) covered by a protein scaffold, at Drosophila synapses comprised of ELKS family member Bruchpilot (BRP) and RIM-binding protein (RBP). We here demonstrate axonal co-transport of BRP and RBP using intravital live imaging, with both proteins co-accumulating in axonal aggregates of several transport mutants. RBP, via its C-terminal Src-homology 3 (SH3) domains, binds Aplip1/JIP1, a transport adaptor involved in kinesin-dependent SV transport. We show in atomic detail that RBP C-terminal SH3 domains bind a proline-rich (PxxP) motif of Aplip1/JIP1 with submicromolar affinity. Pointmutating this PxxP motif provoked formation of ectopic AZ-like structures at axonal membranes. Direct interactions between AZ proteins and transport adaptors seem to provide complex avidity and shield synaptic interaction surfaces of pre-assembled scaffold protein transport complexes, thus, favouring physiological synaptic AZ assembly over premature assembly at axonal membranes.

Monoacylglycerols are components of root waxes and can be produced in the aerial cuticle by ectopic expression of a suberin-associated acyltransferase.

PubMed

Li, Yonghua; Beisson, Fred; Ohlrogge, John; Pollard, Mike

2007-07-01

The interface between plants and the environment is provided for aerial organs by epicuticular waxes that have been extensively studied. By contrast, little is known about the nature, biosynthesis, and role of waxes at the root-rhizosphere interface. Waxes isolated by rapid immersion of Arabidopsis (Arabidopsis thaliana) roots in organic solvents were rich in saturated C18-C22 alkyl esters of p-hydroxycinnamic acids, but also contained significant amounts of both alpha- and beta-isomers of monoacylglycerols with C22 and C24 saturated acyl groups and the corresponding free fatty acids. Production of these compounds in root waxes was positively correlated to the expression of sn-glycerol-3-P acyltransferase5 (GPAT5), a gene encoding an acyltransferase previously shown to be involved in aliphatic suberin synthesis. This suggests a direct metabolic relationship between suberin and some root waxes. Furthermore, when ectopically expressed in Arabidopsis, GPAT5 produced very-long-chain saturated monoacylglycerols and free fatty acids as novel components of cuticular waxes. The crystal morphology of stem waxes was altered and the load of total stem wax compounds was doubled, although the major components typical of the waxes found on wild-type plants decreased. These results strongly suggest that GPAT5 functions in vivo as an acyltransferase to a glycerol-containing acceptor and has access to the same pool of acyl intermediates and/or may be targeted to the same membrane domain as that of wax synthesis in aerial organs.

Interleukin-4 induces expression of eotaxin in endometriotic stromal cells.

PubMed

Ouyang, Zhuo; Osuga, Yutaka; Hirota, Yasushi; Hirata, Tetsuya; Yoshino, Osamu; Koga, Kaori; Yano, Tetsu; Taketani, Yuji

2010-06-01

To study the relationship between eotaxin and interleukin-4 (IL-4) in the pathophysiology of endometriosis. Comparative and laboratory study. University teaching hospital reproductive endocrinology and infertility practice. Ectopic endometrial tissues were collected from women with endometriosis. Ectopic endometrial stromal cells (ESCs) were isolated and cultured with IL-4. Ectopic endometriotic tissues were immunostained for eotaxin and IL-4. Gene expression of eotaxin was determined by standard and real-time reverse-transcriptase polymerase chain reaction. Secretion of eotaxin from ESC was measured using specific ELISA. The immunostained sections were examined. Interleukin-4 (IL-4) increased mRNA expression and protein secretion of eotaxin from ESC in a dose-dependent manner. Immunohistochemical analysis showed that eotaxin-positive cells colocalized with IL-4-positive cells and accumulated around the blood vessels in the stroma of endometriotic tissue. IL-4 induces eotaxin in ESCs, which might promote angiogenesis and the subsequent development of endometriosis. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Interferon regulatory factor-1 binds c-Cbl, enhances mitogen activated protein kinase signaling and promotes retinoic acid-induced differentiation of HL-60 human myelo-monoblastic leukemia cells.

PubMed

Shen, Miaoqing; Bunaciu, Rodica P; Congleton, Johanna; Jensen, Holly A; Sayam, Lavanya G; Varner, Jeffrey D; Yen, Andrew

2011-12-01

All-trans retinoic acid (RA) and interferons (IFNs) have efficacy in treating certain leukemias and lymphomas, respectively, motivating interest in their mechanism of action to improve therapy. Both RA and IFNs induce interferon regulatory factor-1 (IRF-1). We find that in HL-60 myeloblastic leukemia cells which undergo mitogen activated protien kinase (MAPK)-dependent myeloid differentiation in response to RA, IRF-1 propels differentiation. RA induces MAPK-dependent expression of IRF-1. IRF-1 binds c-Cbl, a MAPK related adaptor. Ectopic IRF-1 expression causes CD38 expression and activation of the Raf/MEK/ERK axis, and enhances RA-induced differentiation by augmenting CD38, CD11b, respiratory burst and G0 arrest. Ectopic IRF-1 expression also decreases the activity of aldehyde dehydrogenase 1, a stem cell marker, and enhances RA-induced ALDH1 down-regulation. Interestingly, expression of aryl hydrocarbon receptor (AhR), which is RA-induced and known to down-regulate Oct4 and drive RA-induced differentiation, also enhances IRF-1 expression. The data are consistent with a model whereby IRF-1 acts downstream of RA and AhR to enhance Raf/MEK/ERK activation and propel differentiation.

Ectopic Expression of JcWRKY Confers Enhanced Resistance in Transgenic Tobacco Against Macrophomina phaseolina.

PubMed

Agarwal, Parinita; Patel, Khantika; Agarwal, Pradeep K

2018-04-01

Plants possess an innate immune system comprising of a complex network of closely regulated defense responses involving differential gene expression mediated by transcription factors (TFs). The WRKYs comprise of an important plant-specific TF family, which is involved in regulation of biotic and abiotic defenses. The overexpression of JcWRKY resulted in improved resistance in transgenic tobacco against Macrophomina phaseolina. The production of reactive oxygen species (ROS) and its detoxification through antioxidative system in the transgenics facilitates defense against Macrophomina. The enhanced catalase activity on Macrophomina infection limits the spread of infection. The transcript expression of antioxidative enzymes gene (CAT and SOD) and salicylic acid (SA) biosynthetic gene ICS1 showed upregulation during Macrophomina infection and combinatorial stress. The enhanced transcript of pathogenesis-related genes PR-1 indicates the accumulation of SA during different stresses. The PR-2 and PR-5 highlight the activation of defense responses comprising of activation of hydrolytic cleavage of glucanases and thaumatin-like proteins causing disruption of fungal cells. The ROS homeostasis in coordination with signaling molecules regulate the defense responses and inhibit fungal growth.

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

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.

Strontium-doped hydroxyapatite polysaccharide materials effect on ectopic bone formation

PubMed Central

Aid-Launais, R.; Sagardoy, T.; Siadous, R.; Bareille, R.; Rey, S.; Pechev, S.; Etienne, L.; Kalisky, J.; de Mones, E.; Letourneur, D.; Amedee Vilamitjana, J.

2017-01-01

Previous studies performed using polysaccharide-based matrices supplemented with hydroxyapatite (HA) particles showed their ability to form in subcutaneous and intramuscular sites a mineralized and osteoid tissue. Our objectives are to optimize the HA content in the matrix and to test the combination of HA with strontium (Sr-HA) to increase the matrix bioactivity. First, non-doped Sr-HA powders were combined to the matrix at three different ratios and were implanted subcutaneously for 2 and 4 weeks. Interestingly, matrices showed radiolucent properties before implantation. Quantitative analysis of micro-CT data evidenced a significant increase of mineralized tissue formed ectopically with time of implantation and allowed us to select the best ratio of HA to polysaccharides of 30% (w/w). Then, two Sr-substitution of 8% and 50% were incorporated in the HA powders (8Sr-HA and 50Sr-HA). Both Sr-HA were chemically characterized and dispersed in matrices. In vitro studies performed with human mesenchymal stem cells (MSCs) demonstrated the absence of cytotoxicity of the Sr-doped matrices whatever the amount of incorporated Sr. They also supported osteoblastic differentiation and activated the expression of one late osteoblastic marker involved in the mineralization process i.e. osteopontin. In vivo, subcutaneous implantation of these Sr-doped matrices induced osteoid tissue and blood vessels formation. PMID:28910401

Systems-level effects of ectopic galectin-7 reconstitution in cervical cancer and its microenvironment.

PubMed

Higareda-Almaraz, Juan Carlos; Ruiz-Moreno, Juan S; Klimentova, Jana; Barbieri, Daniela; Salvador-Gallego, Raquel; Ly, Regina; Valtierra-Gutierrez, Ilse A; Dinsart, Christiane; Rabinovich, Gabriel A; Stulik, Jiri; Rösl, Frank; Rincon-Orozco, Bladimiro

2016-08-24

Galectin-7 (Gal-7) is negatively regulated in cervical cancer, and appears to be a link between the apoptotic response triggered by cancer and the anti-tumoral activity of the immune system. Our understanding of how cervical cancer cells and their molecular networks adapt in response to the expression of Gal-7 remains limited. Meta-analysis of Gal-7 expression was conducted in three cervical cancer cohort studies and TCGA. In silico prediction and bisulfite sequencing were performed to inquire epigenetic alterations. To study the effect of Gal-7 on cervical cancer, we ectopically re-expressed it in the HeLa and SiHa cervical cancer cell lines, and analyzed their transcriptome and SILAC-based proteome. We also examined the tumor and microenvironment host cell transcriptomes after xenotransplantation into immunocompromised mice. Differences between samples were assessed with the Kruskall-Wallis, Dunn's Multiple Comparison and T tests. Kaplan-Meier and log-rank tests were used to determine overall survival. Gal-7 was constantly downregulated in our meta-analysis (p < 0.0001). Tumors with combined high Gal-7 and low galectin-1 expression (p = 0.0001) presented significantly better prognoses (p = 0.005). In silico and bisulfite sequencing assays showed de novo methylation in the Gal-7 promoter and first intron. Cells re-expressing Gal-7 showed a high apoptosis ratio (p < 0.05) and their xenografts displayed strong growth retardation (p < 0.001). Multiple gene modules and transcriptional regulators were modulated in response to Gal-7 reconstitution, both in cervical cancer cells and their microenvironments (FDR < 0.05 %). Most of these genes and modules were associated with tissue morphogenesis, metabolism, transport, chemokine activity, and immune response. These functional modules could exert the same effects in vitro and in vivo, even despite different compositions between HeLa and SiHa samples. Gal-7 re-expression affects the regulation of

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.

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.

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.

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.

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.

Expression of Notch pathway genes in mammalian epidermis and modulation by beta-catenin.

PubMed

Ambler, Carrie A; Watt, Fiona M

2007-06-01

The Notch pathway is required for hair follicle maintenance and is activated through beta-catenin induced transcription of the Notch ligand Jagged1. We show that hair follicles in the resting phase express low levels of Jagged1 and Hes1, and other Notch target genes are undetectable. In growing (anagen) follicles, Jagged1 and Hes1 expression increases, Hes5 and HeyL are expressed in distinct cell layers, and Hey2 is expressed in the dermal papilla. When beta-catenin is activated by means of an inducible transgene, Jagged1, Hes1, Hes5, HeyL, and Hey2 are up-regulated, the sites of expression being the same in beta-catenin induced ectopic follicles as in anagen follicles. beta-Catenin also induces Hey1 in dermal papilla cells. beta-Catenin-induced up-regulation of Jagged1 precedes induction of other Notch target genes. The different sites of expression of Hes and Hey genes suggest input from additional signaling pathways. Copyright 2007 Wiley-Liss, Inc.

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.

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.

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.

Meta-analysis of expression of l(3)mbt tumor-associated germline genes supports the model that a soma-to-germline transition is a hallmark of human cancers.

PubMed

Feichtinger, Julia; Larcombe, Lee; McFarlane, Ramsay J

2014-05-15

Evidence is starting to emerge indicating that tumorigenesis in metazoans involves a soma-to-germline transition, which may contribute to the acquisition of neoplastic characteristics. Here, we have meta-analyzed gene expression profiles of the human orthologs of Drosophila melanogaster germline genes that are ectopically expressed in l(3)mbt brain tumors using gene expression datasets derived from a large cohort of human tumors. We find these germline genes, some of which drive oncogenesis in D. melanogaster, are similarly ectopically activated in a wide range of human cancers. Some of these genes normally have expression restricted to the germline, making them of particular clinical interest. Importantly, these analyses provide additional support to the emerging model that proposes a soma-to-germline transition is a general hallmark of a wide range of human tumors. This has implications for our understanding of human oncogenesis and the development of new therapeutic and biomarker targets with clinical potential. © 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

HIF-1α activates hypoxia-induced BCL-9 expression in human colorectal cancer cells

PubMed Central

Chen, Tian-Rui; Wei, Hai-feng; Song, Dian-Wen; Liu, Tie-Long; Yang, Xing-Hai; Fu, Chuan-Gang; Hu, Zhi-qian; Zhou, Wang; Yan, Wang-Jun; Xiao, Jian-Ru

2017-01-01

B-cell CLL/lymphoma 9 protein (BCL-9), a multi-functional co-factor in Wnt signaling, induced carcinogenesis as well as promoting tumor progression, metastasis and chemo-resistance in colorectal cancer (CRC). However, the mechanisms for increased BCL-9 expression in CRC were not well understood. Here, we report that hypoxia, a hallmark of solid tumors, induced BCL-9 mRNA expression in human CRC cells. Analysis of BCL-9 promoter revealed two functional hypoxia-responsive elements (HRE-B and HRE-C) that can be specifically bound with and be transactivated by hypoxia inducible factors (HIF) -1α but not HIF-2α. Consistently, ectopic expression of HIF-1α but not HIF-2α transcriptionally induced BCL-9 expression levels in cells. Knockdown of endogenous HIF-1α but not HIF-2α by siRNA largely abolished the induction of HIF by hypoxia. Furthermore, there was a strong association of HIF-1α expression with BCL-9 expression in human CRC specimens. In summary, results from this study demonstrated that hypoxia induced BCL-9 expression in human CRC cells mainly through HIF-1α, which could be an important underlying mechanism for increased BCL-9 expression in CRC. PMID:27121066

Ectopic Cushing syndrome: Report of 9 cases.

PubMed

Araujo Castro, Marta; Palacios García, Nuria; Aller Pardo, Javier; Izquierdo Alvarez, Cristina; Armengod Grao, Laura; Estrada García, Javier

2018-05-01

Ectopic Cushing's syndrome (ECS) is a rare condition caused by ACTH secretion by extrapituitary tumors. Its low frequency makes it difficult to acquire experience in its management. The aim of this study was to describe patients with ECS seen at the endocrinology department of a tertiary hospital over 15 years. This was a retrospective study of the clinical, biochemical and radiographic data, treatment, and course of patients with ECS seen from 2000 to 2015. Nine patients (6 of them female) with a mean age of 47 years were included in the study. The clinical syndrome developed in less than 3 months in all cases but one, and most patients also had edema, hyperpigmentation and/or hypokalemia. Mean urinary free cortisol and ACTH levels were 2,840μg/24h and 204pg/mL respectively. The ectopic origin was confirmed by a combination of dynamic non-invasive tests and radiographic studies in most cases. The tumor responsible could be identified in 8 cases, and 7 patients had metastatic dissemination. Primary treatment was surgery in one patient, surgery combined with systemic therapy in 3, and chemotherapy in the other 3 patients. Bilateral adrenalectomy was required in 4 patients to control hypercortisolism. After a mean follow-up of 40 months, 3 patients died, 5 were still alive, and one had been lost to follow-up. Our study confirms that ECS covers a wide spectrum of tumors of different aggressiveness and nature. The ectopic origin of Cushing's syndrome can usually, be suspected and confirmed in most cases without the need for invasive tests. Control of both hypercortisolism and the tumor requires multiple treatment modalities, and multidisciplinary management is recommended. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

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.

[Perineal ectopic testis: report of four paediatric cases].

PubMed

Jlidi, Said; Echaieb, Anis; Ghorbel, Sofiene; Khemakhem, Rachid; Ben Khalifa, Sonia; Chaouachi, Béji

2004-09-01

Perineal ectopic testis is a rare congenital malformation in which the testis is abnormally situated between the penoscrotal raphe and the genitofemoral fold. The authors report four new cases in children aged 2 months, 6 months, 2 years and 5 years. The abnormality was associated with an inguinal hernia in one case. The diagnosis was based on the presence of an empty scrotum or perineal swelling. Treatment, via an inguinal incision, consisted of orchidopexy in a dartos pouch with a favourable course in every case. The aetiopathogenesis of perineal ectopic testis is controversial. It can be easily diagnosed by palpation of the testis in the perineal region. Orchidopexy in a dartos pouch must be performed early, and does not raise any particular problems because of the sufficient length of the spermatic cord. The functional prognosis, always difficult to define, appears to be identical to that of other sites.

Association of anti-Chlamydia antibodies with ectopic pregnancy in Benin city, Nigeria: a case-control study.

PubMed

Agholor, K; Omo-Aghoja, L; Okonofua, F

2013-06-01

Ectopic pregnancy remains a major public health problem especially in many developing countries where it is a significant contributor to pregnancy related morbidity and mortality. To determine the association between prior Chlamydia trachomatis infection and the risk of ectopic pregnancy. A case-control study from two tertiary health care facilities in Benin City, Nigeria. Ninety eight women with ectopic pregnancy (cases) and another 98 women with uncomplicated intrauterine pregnancy (controls) matched for age, were interviewed using a semi-structured questionnaire and evaluated for serological evidence of prior Chlamydia trachomatis infection. The antibody titres in cases (48%) were significantly higher than in controls (16.3%) (p<0.001). However, the association between Chlamydia antibodies and ectopic pregnancy was attenuated when the effects of indicators of previous pelvic infections, socio-demographic characteristics, contraceptive and sexual history were controlled for. Primary level of education (OR = 6.32; CI, 2.31 - 17.3), three or more lifetime sexual partners (OR = 5.71; CI, 2.39 - 13.65) and prior history of vaginal discharge (OR = 5.00; CI, 2.03 - 12.3) were more likely to be associated with ectopic pregnancy than with the presence of antibodies to Chlamydia trachomatis (OR = 2.82; 95% CI, 1.33 - 5.95). The Population Attributable Risk was 30.9%. Chlamydial infections play only a limited role in the pathogenesis of ectopic pregnancy.

Human Cytomegalovirus Nuclear Egress Proteins Ectopically Expressed in the Heterologous Environment of Plant Cells are Strictly Targeted to the Nuclear Envelope.

PubMed

Lamm, Christian E; Link, Katrin; Wagner, Sabrina; Milbradt, Jens; Marschall, Manfred; Sonnewald, Uwe

2016-03-10

In all eukaryotic cells, the nucleus forms a prominent cellular compartment containing the cell's nuclear genome. Although structurally similar, animal and plant nuclei differ substantially in details of their architecture. One example is the nuclear lamina, a layer of tightly interconnected filament proteins (lamins) underlying the nuclear envelope of metazoans. So far no orthologous lamin genes could be detected in plant genomes and putative lamin-like proteins are only poorly described in plants. To probe for potentially conserved features of metazoan and plant nuclear envelopes, we ectopically expressed the core nuclear egress proteins of human cytomegalovirus pUL50 and pUL53 in plant cells. pUL50 localizes to the inner envelope of metazoan nuclei and recruits the nuclear localized pUL53 to it, forming heterodimers. Upon expression in plant cells, a very similar localization pattern of both proteins could be determined. Notably, pUL50 is specifically targeted to the plant nuclear envelope in a rim-like fashion, a location to which coexpressed pUL53 becomes strictly corecruited from its initial nucleoplasmic distribution. Using pUL50 as bait in a yeast two-hybrid screening, the cytoplasmic re-initiation supporting protein RISP could be identified. Interaction of pUL50 and RISP could be confirmed by coexpression and coimmunoprecipitation in mammalian cells and by confocal laser scanning microscopy in plant cells, demonstrating partial pUL50-RISP colocalization in areas of the nuclear rim and other intracellular compartments. Thus, our study provides strong evidence for conserved structural features of plant and metazoan nuclear envelops and identifies RISP as a potential pUL50-interacting plant protein.

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.

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.

Ectopic cross-talk between thyroid and retinoic acid signaling: A possible etiology for spinal neural tube defects.

PubMed

Li, Huili; Bai, Baoling; Zhang, Qin; Bao, Yihua; Guo, Jin; Chen, Shuyuan; Miao, Chunyue; Liu, Xiaozhen; Zhang, Ting

2015-12-01

Previous studies have highlighted the connections between neural tube defects (NTDs) and both thyroid hormones (TH) and vitamin A. However, whether the two hormonal signaling pathways interact in NTDs has remained unclear. We measured the expression levels of TH signaling genes in human fetuses with spinal NTDs associated with maternal hyperthyroidism as well as levels of retinoic acid (RA) signaling genes in mouse fetuses exposed to an overdose of RA using NanoString or real-time PCR on spinal cord tissues. Interactions between the two signaling pathways were detected by ChIP assays. The data revealed attenuated DIO2/DIO3 switching in fetuses with NTDs born to hyperthyroid mothers. The promoters of the RA signaling genes CRABP1 and RARB were ectopically occupied by increased RXRG and RXRB but displayed decreased levels of inhibitory histone modifications, suggesting that elevated TH signaling abnormally stimulates RA signaling genes. Conversely, in the mouse model, the observed decrease in Dio3 expression could be explained by increased levels of inhibitory histone modifications in the Dio3 promoter region, suggesting that overactive RA signaling may ectopically derepress TH signaling. This study thus raises in vivo a possible abnormal cross-promotion between two different hormonal signals through their common RXRs and the subsequent recruitment of histone modifications, prompting further investigation into their involvement in the etiology of spinal NTDs. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Repression of the expression of PPP3CC by ZEB1 confers activation of NF-κB and contributes to invasion and growth in glioma cells.

PubMed

Wang, Hongquan; Zhao, Shuli; Chen, Bo; Fu, Chuhua; Dang, Yanwei; Fang, Peihai; Wang, Jun; Wang, Ning; Liu, Lijun

2018-02-01

Gliomas are highly malignant brain tumors. Aberrant activation of NF-κB plays a crucial role in tumor progression. ELISA assay was used to detect NF-κB activity in glimoas cells with different treatments. PPP3CC expression was evaluated by qRT-PCR and western blot assay. Kaplan-Meier analysis estimated the overall survival rates according to the protein level of PPP3CC. Transwell and MTS assay were performed to determine cell invasion and growth. Chromatin immunoprecipitation combined with luciferase reporter assays illustrated the transcriptional regulation of PPP3CC. We showed that PPP3CC decrease was responsible for constitutive activation of NF-κB in gliomas. Restored PPP3CC expression inhibited activation of NF-κB. PPP3CC was frequently decreased in gliomas and that repression of the expression of PPP3CC correlated glioma progression. The ectopic expression of PPP3CC inhibited the invasive potential of glioma cells, and inhibited glioma cells proliferation in vitro and growth in vivo. Additionally, the expression of Zinc finger E-box-binding homeobox 1(ZEB1) was increased in gliomas and was negatively correlated with clinical outcomes of glioma patients. ZEB1 inversely correlated with the expression of PPP3CC. ZEB1 was also confirmed to physically bind to the PPP3CC promoter. ZEB1 knockdown resulted in an increase in the expression of PPP3CC and elevation of PPP3CC promoter activity in glioma cells. These findings indicated that the down-regulation of PPP3CC by ZEB1 resulted in activation of NF-κB is a critical oncogenic event in gliomas. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Effect of Recombinant Tyrosine Hydroxylase Expression on the Neurogenic Differentiation Potency of Mesenchymal Stem Cells

PubMed Central

Duruksu, Gokhan; Karaoz, Erdal

2018-01-01

Objective Tyrosine hydroxylase (TH) is a rate-limiting enzyme in dopamine synthesis, making the enhancement of its activity a target for ensuring sufficient dopamine levels. Rat bone marrow mesenchymal stem cells (rBM-MSCs) are known to synthesize TH after differentiating into neuronal cells through chemical induction, but the effect of its ectopic expression on these cells has not yet been determined. This study investigated the effects of ectopic recombinant TH expression on the stemness characteristics of rBM-MSCs. Methods After cloning, a cell line with stable TH expression was maintained, and the proliferation, the gene expression profile, and differentiation potential of rBM-MSCs were analyzed. Analysis of the cells showed an increment in the proliferation rate that could be reversed by the neutralization of TH. Results The constitutive expression of TH in rBM-MSCs was successfully implemented, without significantly affecting their osteogenic and adipogenic differentiation potential. TH expression improved the expression of other neuronal markers, such as glial fibrillary acidic protein, β-tubulin, nestin, and c-Fos, confirming the neurogenic differentiation capacity of the stem cells. The expression of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) significantly increased after the chemical induction of neurogenic differentiation. Conclusion In this study, the expression of recombinant TH improved the neuroprotective effect of MSCs by upregulating the expression of BDNF and CNTF. Although the neuronal markers were upregulated, the expression of recombinant TH alone in rBM-MSCs was not sufficient for MSCs to differentiate into neurogenic cell lines. PMID:29656620

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.

A Novel Low-Molecular-Weight Compound Enhances Ectopic Bone Formation and Fracture Repair

PubMed Central

Wong, Eugene; Sangadala, Sreedhara; Boden, Scott D.; Yoshioka, Katsuhito; Hutton, William C.; Oliver, Colleen; Titus, Louisa

2013-01-01

Background: Use of recombinant human bone morphogenetic protein-2 (rhBMP-2) is expensive and may cause local side effects. A small synthetic molecule, SVAK-12, has recently been shown in vitro to potentiate rhBMP-2-induced transdifferentiation of myoblasts into the osteoblastic phenotype. The aims of this study were to test the ability of SVAK-12 to enhance bone formation in a rodent ectopic model and to test whether a single percutaneous injection of SVAK-12 can accelerate callus formation in a rodent femoral fracture model. Methods: Collagen disks with rhBMP-2 alone or with rhBMP-2 and SVAK-12 were implanted in a standard athymic rat chest ectopic model, and radiographic analysis was performed at four weeks. In a second set of rats (Sprague-Dawley), SVAK-12 was percutaneously injected into the site of a closed femoral fracture. The fractures were analyzed radiographically and biomechanically (with torsional testing) five weeks after surgery. Results: In the ectopic model, there was dose-dependent enhancement of rhBMP-2 activity with use of SVAK-12 at doses of 100 to 500 μg. In the fracture model, the SVAK-12-treated group had significantly higher radiographic healing scores than the untreated group (p = 0.028). Biomechanical testing revealed that the fractured femora in the 200 to 250-μg SVAK-12 group were 43% stronger (p = 0.008) and 93% stiffer (p = 0.014) than those in the control group. In summary, at five weeks the femoral fracture group injected with SVAK-12 showed significantly improved radiographic and biomechanical evidence of healing compared with the controls. Conclusions: A single local dose of a low-molecular-weight compound, SVAK-12, enhanced bone-healing in the presence of low-dose exogenous rhBMP-2 (in the ectopic model) and endogenous rhBMPs (in the femoral fracture model). Clinical Relevance: This study demonstrates that rhBMP-2 responsiveness can be enhanced by a novel small molecule, SVAK-12. Local application of anabolic small molecules has

[The modification of electrophysiology affected by ectopic synapse in ON-retinal bipolar cells of RCS rats].

PubMed

Zhang, Chen-xing; Yin, Zheng-qin; Weng, Chuan-huang; Zeng, Yu-xiao

2011-03-01

To study the influence of the ectopic synapse for electrophysiological characteristics modification in ON retinal bipolar cells (ON-RBCs) of RCS rat. Immunofluorescence of the retinal frozen section was taken in P60 d, P90 d of RCS rat (RCS) and control rat (CTR) with the anti-mGluR6 and anti-Synaptophysin, Lucifer Yellow staining solo ON-RBCs was taken in all the group. The whole cell recording was performed in the retinal slice of P60 d, P90 d in RCS and CTR. The modification of the passive membrane properties and the outward currents properties in RCS-ON-RBCs, CTR-ON-RBCs and CTR-OFF-RBCs were observed. RCS-ON-RBCs stretched out the ectopic neurite in different direction and the activity of synapse could be detected around the ectopic neurite. From Pn60d, passive membrane properties of RCS-ON-RBCs kept immature, The RMP in RCS-ON-RBCs and CTR-ON-RBCs were (-61.8 ± 3.07), (-50.44 ± 1.36) mV and (-63.1 ± 2.59), (-48.37 ± 3.69) mV when P60 d and P90 d, there ware significantly higher than CTR group (t = 2.191, 2.435, 5.817, 6.912;P < 0.05). The IR in RCS-ON-RBCs and CTR-ON-RBCs were (323.3 ± 42.6), (337.6 ± 71.3) MΩ and (321.2 ± 58.6), (340.3 ± 62.8) MΩ when P60 d and P90 d, there ware significantly higher than CTR group (t = 3.561, 1.987, 5.211, 4.034; P < 0.05). Outward currents were recorded when giving hyper- and depolarized voltage steps. In retinal degeneration, the amplitude of outward currents in RCS-ON-RBCs is significantly different with CTR-ON-RBCs (t = 5.561, 6.341; P < 0.05) or CTR-OFF-RBCs (t = 5.357, 6.997; P < 0.05). The ectopic neurite from RCS-ON-RBCs has the possibility for translating the signal. In retinitis pigmentosa, the modification of electrophysiology characteristics in RCS-ON-RBCs was significantly different with CTR-ON-RBCs and CTR-OFF-RBCs. Influence with the ectopic neurite is the possible cause.

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.

[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.

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.

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.

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.

Increased activity of TNAP compensates for reduced adenosine production and promotes ectopic calcification in the genetic disease ACDC

PubMed Central

Jin, Hui; Hilaire, Cynthia St.; Huang, Yuting; Yang, Dan; Dmitrieva, Natalia I.; Negro, Alejandra; Schwartzbeck, Robin; Liu, Yangtengyu; Yu, Zhen; Walts, Avram; Davaine, Jean-Michel; Lee, Duck-Yeon; Donahue, Danielle; Hsu, Kevin S.; Chen, Jessica; Cheng, Tao; Gahl, William; Chen, Guibin; Boehm, Manfred

2017-01-01

ACDC (arterial calcification due to deficiency of CD73) is an autosomal recessive disease resulting from loss-of-function mutations in NT5E, which encodes CD73, a 5′-ectonucleotidase that converts extracellular adenosine monophosphate to adenosine. ACDC patients display progressive calcification of lower extremity arteries, causing limb ischemia. Tissue-nonspecific alkaline phosphatase (TNAP), which converts pyrophosphate (PPi) to inorganic phosphate (Pi), and extracellular purine metabolism play important roles in other inherited forms of vascular calcification. Compared to cells from healthy subjects, induced pluripotent stem cell–derived mesenchymal stromal cells (iMSCs) from ACDC patients displayed accelerated calcification and increased TNAP activity when cultured under conditions that promote osteogenesis. TNAP activity generated adenosine in iMSCs derived from ACDC patients but not in iMSCs from control subjects, which have CD73. In response to osteogenic stimulation, ACDC patient–derived iMSCs had decreased amounts of the TNAP substrate PPi, an inhibitor of extracellular matrix calcification, and exhibited increased activation of AKT, mechanistic target of rapamycin (mTOR), and the 70-kDa ribosomal protein S6 kinase (p70S6K), a pathway that promotes calcification. In vivo, teratomas derived from ACDC patient cells showed extensive calcification and increased TNAP activity. Treating mice bearing these teratomas with an A2b adenosine receptor agonist, the mTOR inhibitor rapamycin, or the bisphosphonate etidronate reduced calcification. These results show that an increase of TNAP activity in ACDC contributes to ectopic calcification by disrupting the extracellular balance of PPi and Pi and identify potential therapeutic targets for ACDC. PMID:27965423

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.

Ectopic expression of bacterial amylopullulanase enhances bioethanol production from maize grain.

PubMed

Nahampun, Hartinio N; Lee, Chang Joo; Jane, Jay-Lin; Wang, Kan

2013-09-01

Heterologous expression of amylopullulanase in maize seeds leads to partial starch degradation into fermentable sugars, which enhances direct bioethanol production from maize grain. Utilization of maize in bioethanol industry in the United States reached ±13.3 billion gallons in 2012, most of which was derived from maize grain. Starch hydrolysis for bioethanol industry requires the addition of thermostable alpha amylase and amyloglucosidase (AMG) enzymes to break down the α-1,4 and α-1,6 glucosidic bonds of starch that limits the cost effectiveness of the process on an industrial scale due to its high cost. Transgenic plants expressing a thermostable starch-degrading enzyme can overcome this problem by omitting the addition of exogenous enzymes during the starch hydrolysis process. In this study, we generated transgenic maize plants expressing an amylopullulanase (APU) enzyme from the bacterium Thermoanaerobacter thermohydrosulfuricus. A truncated version of the dual functional APU (TrAPU) that possesses both alpha amylase and pullulanase activities was produced in maize endosperm tissue using a seed-specific promoter of 27-kD gamma zein. A number of analyses were performed at 85 °C, a temperature typically used for starch processing. Firstly, enzymatic assay and thin layer chromatography analysis showed direct starch hydrolysis into glucose. In addition, scanning electron microscopy illustrated porous and broken granules, suggesting starch autohydrolysis. Finally, bioethanol assay demonstrated that a 40.2 ± 2.63 % (14.7 ± 0.90 g ethanol per 100 g seed) maize starch to ethanol conversion was achieved from the TrAPU seeds. Conversion efficiency was improved to reach 90.5 % (33.1 ± 0.66 g ethanol per 100 g seed) when commercial amyloglucosidase was added after direct hydrolysis of TrAPU maize seeds. Our results provide evidence that enzymes for starch hydrolysis can be produced in maize seeds to enhance bioethanol production.

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.

Xenopus msx-1 regulates dorso-ventral axis formation by suppressing the expression of organizer genes.

PubMed

Takeda, M; Saito, Y; Sekine, R; Onitsuka, I; Maeda, R; Maéno, M

2000-06-01

We demonstrated previously that Xmsx-1 is involved in mesoderm patterning along the dorso-ventral axis, under the regulation of BMP-4 signaling. When Xmsx-1 RNA was injected into the dorsal blastomeres, a mass of muscle tissue formed instead of notochord. This activity was similar to that of Xwnt-8 reported previously. In this study, we investigated whether the activity of Xmsx-1 is related to the ventralizing signal and myogenesis promoting factor, Xwnt-8. Whole-mount in situ hybridization showed that Xmsx-1, Xwnt-8, and XmyoD were expressed in overlapping areas, including the ventro-lateral marginal zone at mid-gastrula stage. The expression of XmyoD was induced by the ectopic expression of either Xmsx-1 or Xwnt-8 in dorsal blastomeres, and Xwnt-8 was induced by the ectopic expression of Xmsx-1. On the other hand, the expression of Xmsx-1 was not affected by the loading of pCSKA-Xwnt-8 or dominant-negative Xwnt-8 (DN-Xwnt-8) RNA. In addition, Xmsx-1 RNA did not abrogate the formation of notochord if coinjected with DN-Xwnt-8 RNA. These results suggest that Xmsx-1 functions upstream of the Xwnt-8 signal. Furthermore, the antagonistic function of Xmsx-1 to the expression of organizer genes, such as Xlim-1 and goosecoid, was shown by in situ hybridization analysis and luciferase reporter assay using the goosecoid promoter construct. Finally if Xmsx-1/VP-16 fusion RNA, which was expected to function as a dominant-negative Xmsx-1, was injected into ventral blastomeres, a partial secondary axis formed in a significant number of embryos. In such embryos, the activity of luciferase, under the control of goosecoid promoter sequence, was significantly elevated at gastrula stage. These results led us to conclude that Xmsx-1 plays a central role in establishing dorso-ventral axis in gastrulating embryo, by suppressing the expression of organizer genes.

The inhibitor of kappa B kinase-epsilon regulates MMP-3 expression levels and can promote lung metastasis.

PubMed

Seccareccia, E; Pinard, M; Wang, N; Li, S; Burnier, J; Dankort, D; Brodt, P

2014-08-18

The factors that determine the ability of metastatic tumor cells to expand and grow in specific secondary site(s) are not yet fully understood. Matrix metalloproteinases (MMP) were identified as potential regulators of the site-specificity of metastasis. We found that lung carcinoma cells ectopically expressing high levels of the receptor for the type I insulin like growth factor receptor (M27(R) cells) had a significant reduction in MMP-3 expression levels and this coincided with reduced metastasis to the lung. We used these cells to further investigate signaling pathways regulating MMP-3 expression and the role that MMP-3 plays in lung metastasis. We show that ectopic IκB kinase ɛ (IKKɛ) expression in these cells partly restored MMP-3 expression levels and also sensitized MMP-3 transcription to induction by phorbol 12-myristate 13-acetate (PMA). This increase in MMP-3 production was due to increased activation of several signal transduction mediators, including protein kinase C alpha, ERK2, Akt and the transcription factor p65. Furthermore, reconstitution of MMP-3 expression in M27(R) cells restored their ability to colonize the lung whereas silencing of MMP-3 in M27 cells reduced metastases. Collectively, our results implicate IKKɛ as a central regulator of PMA-induced cell signaling and MMP-3 expression and identify MMP-3 as an enabler of tumor cell expansion in the lung.Oncogenesis (2014) 3, e116; doi:10.1038/oncsis.2014.28; published online 18 August 2014.

Exploiting cancer’s phenotypic guise against itself: targeting ectopically expressed peptide G-protein coupled receptors for lung cancer therapy

PubMed Central

Khan, Mahjabin; Huang, Tao; Lin, Cheng-Yuan; Wu, Jiang; Fan, Bao-Min; Bian, Zhao-Xiang

2017-01-01

Lung cancer, claiming millions of lives annually, has the highest mortality rate worldwide. This advocates the development of novel cancer therapies that are highly toxic for cancer cells but negligibly toxic for healthy cells. One of the effective treatments is targeting overexpressed surface receptors of cancer cells with receptor-specific drugs. The receptors-in-focus in the current review are the G-protein coupled receptors (GPCRs), which are often overexpressed in various types of tumors. The peptide subfamily of GPCRs is the pivot of the current article owing to the high affinity and specificity to and of their cognate peptide ligands, and the proven efficacy of peptide-based therapeutics. The article summarizes various ectopically expressed peptide GPCRs in lung cancer, namely, Cholecystokinin-B/Gastrin receptor, the Bombesin receptor family, Bradykinin B1 and B2 receptors, Arginine vasopressin receptors 1a, 1b and 2, and the Somatostatin receptor type 2. The autocrine growth and pro-proliferative pathways they mediate, and the distinct tumor-inhibitory effects of somatostatin receptors are then discussed. The next section covers how these pathways may be influenced or ‘corrected’ through therapeutics (involving agonists and antagonists) targeting the overexpressed peptide GPCRs. The review proceeds on to Nano-scaled delivery platforms, which enclose chemotherapeutic agents and are decorated with peptide ligands on their external surface, as an effective means of targeting cancer cells. We conclude that targeting these overexpressed peptide GPCRs is potentially evolving as a highly promising form of lung cancer therapy. PMID:29262666

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

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

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.

Ectopic Prolactinoma Presenting as Bacterial Meningitis: A Diagnostic Conundrum.

PubMed

Akinduro, Oluwaseun O; Akinduro, Olutomi T; Gupta, Vivek; Reimer, Ronald; Olomu, Osarenoma

2018-04-01

Prolactinomas may rarely present with meningitis and cerebrospinal fluid (CSF) rhinorrhea secondary to erosion of the wall of the sella turcica. It is even more uncommon for this abnormal communication to be caused by an ectopic prolactinoma arising from the sphenoid sinus and eroding into the sella. This atypical growth pattern makes diagnosis very difficult because there may be no displacement of the normal pituitary gland. The first reported case of a patient with an ectopic prolactinoma originating within the sphenoid sinus presenting primarily with meningitis is presented, and the management strategy and surgical and nonsurgical treatment options are discussed. A 48-year-old woman presented with confusion, low-pressure headache, and fever. A lumbar puncture revealed Streptococcus pneumoniae meningitis, and she was placed on intravenous penicillin G. After initiation of antibiotics, she noticed salty tasting postnasal fluid leakage. Imaging was remarkable for bony erosion of the sphenoid sinus wall by a soft tissue mass growing from within the sinus, with no disruption of the normal pituitary gland. A biopsy was then performed with an endoscopic transnasal transsphenoidal approach, and the CSF leak was repaired with a pedicled nasoseptal flap. The final pathology was prolactinoma, and she was placed on cabergoline. Ectopic prolactinomas may rarely present as meningitis secondary to retrograde transmission of bacteria through a bony defect in the sphenoid sinus, and must be included in the differential diagnosis of any sphenoid sinus mass. Management should first address the infection, followed by surgical repair of the bony defect. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Ectopic Thyroid Tissue in Submandibular and Infrahyoid Region

PubMed Central

Mutlu, Vahit

2014-01-01

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. Submandibular ectopic thyroid tissue with a coexisting normally located thyroid gland is extremely rare. In this case aimed to present the findings of the 65-years-old female patient who is bilateral subtotal thyroidectomy operation performed for multinodular goiter of 12 years ago. Case, painless mass in the right submandibular and infrahyoid region for 6 months was admitted to our clinic with complaints. Result of contrast-enhanced neck computed tomography, ultrasound-guided fine-needle aspiration biopsy and thyroid scintigraphy were found of functional residual thyroid tissue in the normal localization as well as 2×3 cm mass in the submandibular area and 1×2 cm mass lesion in the infrahyoid region. The patient referred to excisional biopsy. Normal thyroid follicules and no evidence of malignancy were found in specimen pathologically. Postoperative follow-up of thyroid function tests were normal. PMID:25610328

A Phenotypic Screen in Zebrafish Identifies a Novel Small-Molecule Inducer of Ectopic Tail Formation Suggestive of Alterations in Non-Canonical Wnt/PCP Signaling

PubMed Central

Gebruers, Evelien; Cordero-Maldonado, María Lorena; Gray, Alexander I.; Clements, Carol; Harvey, Alan L.; Edrada-Ebel, Ruangelie; de Witte, Peter A. M.; Crawford, Alexander D.; Esguerra, Camila V.

2013-01-01

Zebrafish have recently emerged as an attractive model for the in vivo bioassay-guided isolation and characterization of pharmacologically active small molecules of natural origin. We carried out a zebrafish-based phenotypic screen of over 3000 plant-derived secondary metabolite extracts with the goal of identifying novel small-molecule modulators of the BMP and Wnt signaling pathways. One of the bioactive plant extracts identified in this screen – Jasminum gilgianum, an Oleaceae species native to Papua New Guinea – induced ectopic tails during zebrafish embryonic development. As ectopic tail formation occurs when BMP or non-canonical Wnt signaling is inhibited during the tail protrusion process, we suspected a constituent of this extract to act as a modulator of these pathways. A bioassay-guided isolation was carried out on the basis of this zebrafish phenotype, identifying para-coumaric acid methyl ester (pCAME) as the active compound. We then performed an in-depth phenotypic analysis of pCAME-treated zebrafish embryos, including a tissue-specific marker analysis of the secondary tails. We found pCAME to synergize with the BMP-inhibitors dorsomorphin and LDN-193189 in inducing ectopic tails, and causing convergence-extension defects in compound-treated embryos. These results indicate that pCAME may interfere with non-canonical Wnt signaling. Inhibition of Jnk, a downstream target of Wnt/PCP signaling (via morpholino antisense knockdown and pharmacological inhibition with the kinase inhibitor SP600125) phenocopied pCAME-treated embryos. However, immunoblotting experiments revealed pCAME to not directly inhibit Jnk-mediated phosphorylation of c-Jun, suggesting additional targets of SP600125, and/or other pathways, as possibly being involved in the ectopic tail formation activity of pCAME. Further investigation of pCAME’s mechanism of action will help determine this compound’s pharmacological utility. PMID:24349481

Transcription of fgf8 is regulated by activating and repressive cis-elements at the midbrain-hindbrain boundary in zebrafish embryos.

PubMed

Inoue, Fumitaka; Parvin, Mst Shahnaj; Yamasu, Kyo

2008-04-15

Fgf8 is expressed in the isthmic region of the developing brain, serving an organizing function in vertebrate embryos. We previously identified S4.2 downstream to the zebrafish fgf8 gene as a regulatory region that drives transcription in the anterior hindbrain. Here, we investigated the mechanism of fgf8 regulation by the S4.2 region during development. Reporter analyses in embryos revealed that S4.2 closely recapitulates fgf8 expression in the anteriormost hindbrain during somitogenesis. This region contains a sequence highly conserved in fgf8 of diverse vertebrates. Further analyses of S4.2 revealed a 342-bp core region composed of three subregions (#2, #3, and #4). Regions #3 and #4 drove expression broadly in the brain from the midbrain to r5 of the hindbrain, whereas a 28-bp sequence in #2 repressed ectopic expression in the midbrain and in r2 to r5. The enhancer function of S4.2 was absent in pax2a mutant embryos, while it was activated ectopically by pax2a misexpression in the hindbrain. We identified two sites in the core region that are bound by Pax2a in vitro and in vivo, the disruption of which abrogated the S4.2 activity. Thus, fgf8 expression in the anteriormost hindbrain involves activation and repression, with Pax2a as a pivotal regulator.

The adaptor protein Cindr regulates JNK activity to maintain epithelial sheet integrity.

PubMed

Yasin, Hannah W R; van Rensburg, Samuel H; Feiler, Christina E; Johnson, Ruth I

2016-02-15

Epithelia are essential barrier tissues that must be appropriately maintained for their correct function. To achieve this a plethora of protein interactions regulate epithelial cell number, structure and adhesion, and differentiation. Here we show that Cindr (the Drosophila Cin85 and Cd2ap ortholog) is required to maintain epithelial integrity. Reducing Cindr triggered cell delamination and movement. Most delaminating cells died. These behaviors were consistent with JNK activation previously associated with loss of epithelial integrity in response to ectopic oncogene activity. We confirmed a novel interaction between Cindr and Drosophila JNK (dJNK), which when perturbed caused inappropriate JNK signaling. Genetically reducing JNK signaling activity suppressed the effects of reducing Cindr. Furthermore, ectopic JNK signaling phenocopied loss of Cindr and was partially rescued by concomitant cindr over-expression. Thus, correct Cindr-dJNK stoichiometry is essential to maintain epithelial integrity and disturbing this balance may contribute to the pathogenesis of disease states, including cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional Expression of Aryl Hydrocarbon Receptor on Mast Cells Populating Human Endometriotic Tissues

PubMed Central

Orsaria, Maria; Marzinotto, Stefania; Londero, Ambrogio P; Bulfoni, Michela; Candotti, Veronica; Zanello, Andrea; Ballico, Maurizio; Mimmi, Maria C; Calcagno, Angelo; Marchesoni, Diego; Di Loreto, Carla; Beltrami, Antonio P; Cesselli, Daniela; Gri, Giorgia

2016-01-01

Endometriosis is an inflammatory disease characterized by the presence of ectopic endometrial tissue outside the uterus. A diffuse infiltration of mast cells (MCs) is observed throughout endometriotic lesions, but little is known about how these cells contribute to the network of molecules that modulate the growth of ectopic endometrial implants and promote endometriosis-associated inflammation. The Aryl Hydrocarbon Receptor (AhR), a transcription factor known to respond to environmental toxins and endogenous compounds, is present in MCs. In response to AhR activation, MCs produce IL-17 and reactive oxygen species, highlighting the potential impact of AhR ligands on inflammation via MCs. Here, we investigated the possibility that endometrial MCs promote an inflammatory microenvironment by sensing AhR ligands, thus sustaining endometriosis development. Using human endometriotic tissue (ET) samples, we performed the following experiments: i) examined the cytokine expression profile; ii) counted AhR-expressing MCs; iii) verified the phenotype of AhR-expressing MCs to establish whether MCs have a tolerogenic (IL-10-positive) or inflammatory (IL-17-positive) phenotype; iv) measured the presence of AhR ligands (tryptophan-derived kynurenine) and tryptophan-metabolizing enzymes (indoleamine 2,3-dioxygenase 1 (IDO1)); v) treated ET organ cultures with an AhR antagonist in vitro to measure changes in the cytokine milieu; and vi) measured the growth of endometrial stromal cells cultured with AhR-activated MC-conditioned medium. We found that ET tissue was conducive to cytokine production, orchestrating chronic inflammation and a population of AhR-expressing MCs that are both IL-17 and IL-10-positive. ET was rich in IDO1 and the AhR-ligand kynurenine compared with control tissue, possibly promoting MC activation through AhR. ET was susceptible to treatment with an AhR antagonist, and endometrial stromal cell growth was improved in the presence of soluble factors released by

Functional expression of aryl hydrocarbon receptor on mast cells populating human endometriotic tissues.

PubMed

Mariuzzi, Laura; Domenis, Rossana; Orsaria, Maria; Marzinotto, Stefania; Londero, Ambrogio P; Bulfoni, Michela; Candotti, Veronica; Zanello, Andrea; Ballico, Maurizio; Mimmi, Maria C; Calcagno, Angelo; Marchesoni, Diego; Di Loreto, Carla; Beltrami, Antonio P; Cesselli, Daniela; Gri, Giorgia

2016-09-01

Endometriosis is an inflammatory disease characterized by the presence of ectopic endometrial tissue outside the uterus. A diffuse infiltration of mast cells (MCs) is observed throughout endometriotic lesions, but little is known about how these cells contribute to the network of molecules that modulate the growth of ectopic endometrial implants and promote endometriosis-associated inflammation. The aryl hydrocarbon receptor (AhR), a transcription factor known to respond to environmental toxins and endogenous compounds, is present in MCs. In response to AhR activation, MCs produce IL-17 and reactive oxygen species, highlighting the potential impact of AhR ligands on inflammation via MCs. Here, we investigated the possibility that endometrial MCs promote an inflammatory microenvironment by sensing AhR ligands, thus sustaining endometriosis development. Using human endometriotic tissue (ET) samples, we performed the following experiments: (i) examined the cytokine expression profile; (ii) counted AhR-expressing MCs; (iii) verified the phenotype of AhR-expressing MCs to establish whether MCs have a tolerogenic (IL-10-positive) or inflammatory (IL-17-positive) phenotype; (iv) measured the presence of AhR ligands (tryptophan-derived kynurenine) and tryptophan-metabolizing enzymes (indoleamine 2,3-dioxygenase 1 (IDO1)); (v) treated ET organ cultures with an AhR antagonist in vitro to measure changes in the cytokine milieu; and (vi) measured the growth of endometrial stromal cells cultured with AhR-activated MC-conditioned medium. We found that ET tissue was conducive to cytokine production, orchestrating chronic inflammation and a population of AhR-expressing MCs that are both IL-17 and IL-10-positive. ET was rich in IDO1 and the AhR-ligand kynurenine compared with control tissue, possibly promoting MC activation through AhR. ET was susceptible to treatment with an AhR antagonist, and endometrial stromal cell growth was improved in the presence of soluble factors

Opposing Functions of the ETS Factor Family Define Shh Spatial Expression in Limb Buds and Underlie Polydactyly

PubMed Central

Lettice, Laura A.; Williamson, Iain; Wiltshire, John H.; Peluso, Silvia; Devenney, Paul S.; Hill, Alison E.; Essafi, Abdelkader; Hagman, James; Mort, Richard; Grimes, Graeme; DeAngelis, Carlo L.; Hill, Robert E.

2012-01-01

Summary Sonic hedgehog (Shh) expression during limb development is crucial for specifying the identity and number of digits. The spatial pattern of Shh expression is restricted to a region called the zone of polarizing activity (ZPA), and this expression is controlled from a long distance by the cis-regulator ZRS. Here, members of two groups of ETS transcription factors are shown to act directly at the ZRS mediating a differential effect on Shh, defining its spatial expression pattern. Occupancy at multiple GABPα/ETS1 sites regulates the position of the ZPA boundary, whereas ETV4/ETV5 binding restricts expression outside the ZPA. The ETS gene family is therefore attributed with specifying the boundaries of the classical ZPA. Two point mutations within the ZRS change the profile of ETS binding and activate Shh expression at an ectopic site in the limb bud. These molecular changes define a pathogenetic mechanism that leads to preaxial polydactyly (PPD). PMID:22340503

Not all fats are created equal: adipose vs. ectopic fat, implication in cardiometabolic diseases.

PubMed

Gaggini, Melania; Saponaro, Chiara; Gastaldelli, Amalia

2015-04-01

Adipose tissue is a recognized endocrine organ that acts not only as a fuel storage but also is able to secrete adipokines that can modulate inflammation. Most of the fat is composed of white adipocytes (WAT), although also brown/beige adipocytes (BAT/BeAT) have been found in humans. BAT is located close to the neck but also among WAT in the epicardial fat and perivascular fat. Adipocyte hypertrophy and infiltration of macrophages impair adipose tissue metabolism determining "adiposopathy" (i.e., sick fat) and increasing the risk to develop metabolic and cardiovascular diseases. The purpose of this review was to search and discuss the available literature on the impact of different types of fat and fat distribution on cardiometabolic risk. Visceral fat, but also ectopic fat, either in liver, muscle and heart, can increase the risk to develop insulin resistance, type 2 diabetes and cardiovascular diseases. Results recently published showed that BAT could have an impact on cardiometabolic risk, not only because it is implicated in energy metabolism but also because it can modulate glucose and lipid metabolism. Therapeutical interventions that can increase energy expenditure, successfully change fat distribution and reduce ectopic fat, also through BAT activation, were discussed.

Cushing's syndrome due to ectopic production of corticotropin-releasing hormone in an infant with ganglioneuroblastoma.

PubMed

Zangeneh, Farhad; Young, William F; Lloyd, Ricardo V; Chiang, Myra; Kurczynski, Elizabeth; Zangeneh, Fereydoun

2003-01-01

To report the first recognized case of Cushing's syndrome due to a corticotropin-releasing hormone (CRH)-secreting ganglioneuroblastoma, which was found in an 18-month-old boy with hypertensive encephalopathy. The clinical, biochemical, and immunohistochemical characteristics of this rare syndrome are described, and the relevant literature is reviewed. An 18-month-old boy with a history of recent weight gain was admitted because of sudden onset of right fixed esotropia and left facial palsy after episodes of emesis. Magnetic resonance imaging showed old left frontal lobe and right hypothalamic infarcts. The patient had generalized obesity, decelerated linear growth, hypertrichosis, hypertension (144/103 mm Hg), hypokalemia, and proteinuria. The 24-hour urinary excretion of free cortisol, catecholamines, and metanephrines was increased. The serum cortisol concentration after a 1-mg overnight dexamethasone suppression test (DST) was 53.7 mg/dL (normal, <5). The serum adrenocorticotropic hormone (ACTH) concentration was 7 pg/mL (normal, 10 to 60), and the CRH level was 439 pg/mL (normal, 24 to 40). An overnight high-dose DST (8 mg) failed to suppress serum cortisol; however, both cortisol and ACTH were responsive to ovine CRH stimulation. Despite discordant dynamic endocrine testing and negative somatostatin receptor scintigraphy, computed tomography showed a right 3.6- by 3.0-cm extra-adrenal retroperitoneal mass with central calcification extending 7 cm cephalocaudally. The patient underwent exploratory laparotomy, followed by chemotherapy. Findings on light microscopic and immunohistochemical examination of the retroperitoneal mass were consistent with a ganglioneuroblastoma that expressed CRH, pro-opiomelanocortin, and ACTH. The evaluation of Cushing's syndrome is one of the most complex endocrine challenges. In this case, it was due to ectopic production of CRH by a ganglioneuroblastoma. Because most CRH-producing tumors also secrete ACTH, the ectopic production

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.

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.

Chicken ovalbumin upstream promoter-transcription factor II regulates nuclear receptor, myogenic, and metabolic gene expression in skeletal muscle cells.

PubMed

Crowther, Lisa M; Wang, Shu-Ching Mary; Eriksson, Natalie A; Myers, Stephen A; Murray, Lauren A; Muscat, George E O

2011-02-24

We demonstrate that chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) mRNA is more abundantly expressed (than COUP-TFI mRNA) in skeletal muscle C2C12 cells and in (type I and II) skeletal muscle tissue from C57BL/10 mice. Consequently, we have utilized the ABI TaqMan Low Density Array (TLDA) platform to analyze gene expression changes specifically attributable to ectopic COUP-TFII (relative to vector only) expression in muscle cells. Utilizing a TLDA-based platform and 5 internal controls, we analyze the entire NR superfamily, 96 critical metabolic genes, and 48 important myogenic regulatory genes on the TLDA platform utilizing 5 internal controls. The low density arrays were analyzed by rigorous statistical analysis (with Genorm normalization, Bioconductor R, and the Empirical Bayes statistic) using the (integromics) statminer software. In addition, we validated the differentially expressed patho-physiologically relevant gene (identified on the TLDA platform) glucose transporter type 4 (Glut4). We demonstrated that COUP-TFII expression increased the steady state levels of Glut4 mRNA and protein, while ectopic expression of truncated COUP-TFII lacking helix 12 (COUP-TFΔH12) reduced Glut4 mRNA expression in C2C12 cells. Moreover, COUP-TFII expression trans-activated the Glut4 promoter (-997/+3), and ChIP analysis identified selective recruitment of COUP-TFII to a region encompassing a highly conserved SP1 binding site (in mouse, rat, and human) at nt positions -131/-118. Mutation of the SpI site ablated COUP-TFII mediated trans-activation of the Glut4 promoter. In conclusion, this study demonstrates that in skeletal muscle cells, COUP-TFII regulates several nuclear hormone receptors, and critical metabolic and muscle specific genes.

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.

HIV-1 Tat induces DNMT over-expression through microRNA dysregulation in HIV-related non Hodgkin lymphomas.

PubMed

Luzzi, Anna; Morettini, Federica; Gazaneo, Sara; Mundo, Lucia; Onnis, Anna; Mannucci, Susanna; Rogena, Emily A; Bellan, Cristiana; Leoncini, Lorenzo; De Falco, Giulia

2014-01-01

A close association between HIV infection and the development of cancer exists. Although the advent of highly active antiretroviral therapy has changed the epidemiology of AIDS-associated malignancies, a better understanding on how HIV can induce malignant transformation will help the development of novel therapeutic agents. HIV has been reported to induce the expression of DNMT1 in vitro, but still no information is available about the mechanisms regulating DNMT expression in HIV-related B-cell lymphomas. In this paper, we investigated the expression of DNMT family members (DNMT1, DNMT3a/b) in primary cases of aggressive B-cell lymphomas of HIV-positive subjects. Our results confirmed the activation of DNMT1 by HIV in vivo, and reported for the first time a marked up-regulation of DNMT3a and DNMT3b in HIV-positive aggressive B-cell lymphomas. DNMT up-regulation in HIV-positive tumors correlated with down-regulation of specific microRNAs, as the miR29 family, the miR148-152 cluster, known to regulate their expression. Literature reports the activation of DNMTs by the human polyomavirus BKV large T-antigen and adenovirus E1a, through the pRb/E2F pathway. We have previously demonstrated that the HIV Tat protein is able to bind to the pocket proteins and to inactivate their oncosuppressive properties, resulting in uncontrolled cell proliferation. Therefore, we focused on the role of Tat, due to its capability to be released from infected cells and to dysregulate uninfected ones, using an in vitro model in which Tat was ectopically expressed in B-cells. Our findings demonstrated that the ectopic expression of Tat was per se sufficient to determine DNMT up-regulation, based on microRNA down-regulation, and that this results in aberrant hypermethylation of target genes and microRNAs. These results point at a direct role for Tat in participating in uninfected B-cell lymphomagenesis, through dysregulation of the epigenetical control of gene expression.

Role of an expansin-like molecule in Dictyostelium morphogenesis and regulation of its gene expression by the signal transducer and activator of transcription protein Dd-STATa.

PubMed

Ogasawara, Shun; Shimada, Nao; Kawata, Takefumi

2009-02-01

Expansins are proteins involved in plant morphogenesis, exerting their effects on cellulose to extend cell walls. Dictyostelium is an organism that possesses expansin-like molecules, but their functions are not known. In this study, we analyzed the expL7 (expansin-like 7) gene, which has been identified as a putative target of Dd-STATa, a Dictyostelium homolog of the metazoan signal transducer and activator of transcription (STAT) proteins. Promoter fragments of the expL7 were fused to a lacZ reporter and the expression patterns determined. As expected from the behavior of the endogenous expL7 gene, the expL7/lacZ fusion gene was downregulated in Dd-STATa null slugs. In the parental strain, the expL7 promoter was activated in the anterior tip region. Mutational analysis of the promoter identified a sequence that was necessary for expression in tip cells. In addition, an activator sequence for pstAB cells was identified. These sequences act in combination with the repressor region to prevent ectopic expL7 expression in the prespore and prestalk regions of the slug and culminant. Although the expL7 null mutant showed no phenotypic change, the expL7 overexpressor showed aberrant stalk formation. These results indicate that the expansin-like molecule is important for morphogenesis in Dictyostelium.

miR-130a activates apoptotic signaling through activation of caspase-8 in taxane-resistant prostate cancer cells.

PubMed

Fujita, Yasunori; Kojima, Toshio; Kawakami, Kyojiro; Mizutani, Kosuke; Kato, Taku; Deguchi, Takashi; Ito, Masafumi

2015-10-01

The acquisition of drug resistance is one of the most malignant phenotypes of cancer and identification of its therapeutic target is a prerequisite for the development of novel therapy. MicroRNAs (miRNAs) have been implicated in various types of cancer and proposed as potential therapeutic targets for patients. In the present study, we aimed to identify miRNA that could serve as a therapeutic target for taxane-resistant prostate cancer. In order to identify miRNAs related to taxane-resistance, miRNA profiling was performed using prostate cancer PC-3 cells and paclitaxel-resistant PC-3 cell lines established from PC-3 cells. Microarray analysis of mRNA expression was also conducted to search for potential target genes of miRNA. Luciferase reporter assay was performed to examine miRNA binding to the 3'-UTR of target genes. The effects of ectopic expression of miRNA on cell growth, tubulin polymerization, drug sensitivity, and apoptotic signaling pathway were investigated in a paclitaxel-resistant PC-3 cell line. The expression of miR-130a was down-regulated in all paclitaxel-resistant cell lines compared with parental PC-3 cells. Based on mRNA microarray analysis and luciferase reporter assay, we identified SLAIN1 as a direct target gene for miR-130a. Transfection of a miR-130a precursor into a paclitaxel-resistant cell line suppressed cell growth and increased the sensitivity to paclitaxel. Lastly, ectopic expression of miR-130a did not affect the polymerized tubulin level, but activated apoptotic signaling through activation of caspase-8. Our results suggested that reduced expression of miR-130a may be involved in the paclitaxel-resistance and that miR-130a could be a therapeutic target for taxane-resistant prostate cancer patients. © 2015 Wiley Periodicals, Inc.

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.

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.

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...

Functional activity and tumor-specific expression of dual oxidase 2 in pancreatic cancer cells and human malignancies characterized with a novel monoclonal antibody.

PubMed

Wu, Yonghzong; Antony, Smitha; Hewitt, Stephen M; Jiang, Guojian; Yang, Sherry X; Meitzler, Jennifer L; Juhasz, Agnes; Lu, Jiamo; Liu, Han; Doroshow, James H; Roy, Krishnendu

2013-04-01

Dual oxidase 2 (Duox2), one of the seven members of the NADPH oxidase gene family, plays a critical role in generating H2O2 for thyroid hormone biosynthesis and as an integral part of the host defense system of the respiratory epithelium and the gastrointestinal tract. Recent evidence suggests that the regulation of Duox2 expression is under the control of pro-inflammatory cytokines and that Duox2-induced reactive oxygen species (ROS) contribute to the inflammation-related tissue injury that occurs in two pre-malignant, inflammatory conditions: chronic pancreatitis and inflammatory bowel disease. Because no reliable Duox antibodies are commercially available, we report the development of a murine monoclonal antibody (MAb) to Duox2 (clone Duox S-12) and its use for the characterization of Duox2 expression in human tumors, tumor cell lines and normal tissues. Duox S-12 specifically detected both endogenously- and ectopically-expressed Duox2 protein by immunoblotting, immunofluorescence microscopy and immunohistochemistry (where both membranous and cytoplasmic staining were present). Duox2 expression detected by Duox S-12 was functionally coupled to the generation of H(2)O(2) in pancreatic cancer cells that expressed Duox2 and its cognate maturation factor DuoxA2. Although Duox S-12 recognizes ectopically expressed Duox1 protein because of the extensive amino acid homology between Duox1 and Duox2, the lack of substantial Duox1 mRNA expression in human tumors (except thyroid cancer) allowed us to evaluate Duox2 expression across a wide range of normal and malignant tissues by immuno-histochemistry. Duox2 was expressed at elevated levels in many human cancers, most notably tumors of the prostate, lung, colon and breast while brain tumors and lymphomas demonstrated the lowest frequency of expression. The Duox-specific monoclonal antibody described here provides a promising tool for the further examination of the role of Duox-dependent reactive oxygen production in

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

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

Leaf-Like Sepals Induced by Ectopic Expression of a SHORT VEGETATIVE PHASE (SVP)-Like MADS-Box Gene from the Basal Eudicot Epimedium sagittatum

PubMed Central

Li, Zhineng; Zeng, Shaohua; Li, Yanbang; Li, Mingyang; Souer, Erik

2016-01-01

Epimedium L. (Berberidaceae, Ranales), a perennial traditional Chinese medicinal herb, has become a new popular landscape plant for ground cover and pot culture in many countries based on its excellent ornamental characteristics and, distinctive and diverse floral morphology. However, little is known about the molecular genetics of flower development in Epimedium sagittatum. Here, we describe the characterization of EsSVP that encodes a protein sharing 68, 54, and 35% similarity with SVP, AGAMOUS-like 24 (AGL24) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) in Arabidopsis, respectively. Quantitative RT-PCR (qRT-PCR) indicated that EsSVP transcripts were principally found in petiole and leaf tissues, with little expression in roots and flowers and no in fruits. The highest EsSVP expression was observed in leaves. The flowering time of 35S::EsSVP in most Arabidopsis thaliana and in all petunia plants was not affected in both photoperiod conditions, but 35S::EsSVP 5# and 35S::EsSVP 1# Arabidopsis lines induced late and early flowering under long day (LD, 14 h light/10 h dark) and short day (SD, 10 h light/14 h dark) conditions, respectively. The 35S::EsSVP Arabidopsis produced extra secondary inflorescence or floral meristems in the axils of the leaf-like sepals with excrescent trichomes, and leaf-like sepals not able to enclose the inner three whorls completely. Moreover, almost all transgenic Arabidopsis plants showed persistent sepals around the completely matured fruits. Upon ectopic expression of 35S::EsSVP in Petunia W115, sepals were enlarged, sometimes to the size of leaves; corollas were greenish and did not fully open. These results suggest that EsSVP is involved in inflorescence meristem identity and flowering time regulation in some conditions. Although, the SVP homologs might have suffered functional diversification among diverse species between core and basal eudicots, the protein functions are conserved between Arabidopsis/Petunia and Epimedium

Spermidine promotes Bacillus subtilis biofilm formation by activating expression of the matrix regulator slrR.

PubMed

Hobley, Laura; Li, Bin; Wood, Jennifer L; Kim, Sok Ho; Naidoo, Jacinth; Ferreira, Ana Sofia; Khomutov, Maxim; Khomutov, Alexey; Stanley-Wall, Nicola R; Michael, Anthony J

2017-07-21

Ubiquitous polyamine spermidine is not required for normal planktonic growth of Bacillus subtilis but is essential for robust biofilm formation. However, the structural features of spermidine required for B. subtilis biofilm formation are unknown and so are the molecular mechanisms of spermidine-stimulated biofilm development. We report here that in a spermidine-deficient B. subtilis mutant, the structural analogue norspermidine, but not homospermidine, restored biofilm formation. Intracellular biosynthesis of another spermidine analogue, aminopropylcadaverine, from exogenously supplied homoagmatine also restored biofilm formation. The differential ability of C-methylated spermidine analogues to functionally replace spermidine in biofilm formation indicated that the aminopropyl moiety of spermidine is more sensitive to C -methylation, which it is essential for biofilm formation, but that the length and symmetry of the molecule is not critical. Transcriptomic analysis of a spermidine-depleted B. subtilis speD mutant uncovered a nitrogen-, methionine-, and S -adenosylmethionine-sufficiency response, resulting in repression of gene expression related to purine catabolism, methionine and S -adenosylmethionine biosynthesis and methionine salvage, and signs of altered membrane status. Consistent with the spermidine requirement in biofilm formation, single-cell analysis of this mutant indicated reduced expression of the operons for production of the exopolysaccharide and TasA protein biofilm matrix components and SinR antagonist slrR Deletion of sinR or ectopic expression of slrR in the spermidine-deficient Δ speD background restored biofilm formation, indicating that spermidine is required for expression of the biofilm regulator slrR Our results indicate that spermidine functions in biofilm development by activating transcription of the biofilm matrix exopolysaccharide and TasA operons through the regulator slrR . © 2017 by The American Society for Biochemistry and

Identification of a regulatory T cell specific cell surface molecule that mediates suppressive signals and induces Foxp3 expression.

PubMed

Wang, Rui; Wan, Qi; Kozhaya, Lina; Fujii, Hodaka; Unutmaz, Derya

2008-07-16

Regulatory T (T(reg)) cells control immune activation and maintain tolerance. How T(regs) mediate their suppressive function is unclear. Here we identified a cell surface molecule, called GARP, (or LRRC32), which within T cells is specifically expressed in T(regs) activated through the T cell receptor (TCR). Ectopic expression of GARP in human naïve T (T(N)) cells inhibited their proliferation and cytokine secretion upon TCR activation. Remarkably, GARP over-expression in T(N) cells induced expression of T(reg) master transcription factor Foxp3 and endowed them with a partial suppressive function. The extracellular but not the cytoplasmic region of GARP, was necessary for these functions. Silencing Foxp3 in human T(reg) cells reduced expression of GARP and attenuated their suppressive function. However, GARP function was not affected when Foxp3 was downregulated in GARP-overexpressing cells, while silencing GARP in Foxp3-overexpressing cells reduced their suppressive activity. These findings reveal a novel cell surface molecule-mediated regulatory mechanism, with implications for modulating aberrant immune responses.

Expression and phosphorylation of the AS160_v2 splice variant supports GLUT4 activation and the Warburg effect in multiple myeloma

PubMed Central

2013-01-01

Background Multiple myeloma (MM) is a fatal plasma cell malignancy exhibiting enhanced glucose consumption associated with an aerobic glycolytic phenotype (i.e., the Warburg effect). We have previously demonstrated that myeloma cells exhibit constitutive plasma membrane (PM) localization of GLUT4, consistent with the dependence of MM cells on this transporter for maintenance of glucose consumption rates, proliferative capacity, and viability. The purpose of this study was to investigate the molecular basis of constitutive GLUT4 plasma membrane localization in MM cells. Findings We have elucidated a novel mechanism through which myeloma cells achieve constitutive GLUT4 activation involving elevated expression of the Rab-GTPase activating protein AS160_v2 splice variant to promote the Warburg effect. AS160_v2-positive MM cell lines display constitutive Thr642 phosphorylation, known to be required for inactivation of AS160 Rab-GAP activity. Importantly, we show that enforced expression of AS160_v2 is required for GLUT4 PM translocation and activation in these select MM lines. Furthermore, we demonstrate that ectopic expression of a full-length, phospho-deficient AS160 mutant is sufficient to impair constitutive GLUT4 cell surface residence, which is characteristic of MM cells. Conclusions This is the first study to tie AS160 de-regulation to increased glucose consumption rates and the Warburg effect in cancer. Future studies investigating connections between the insulin/IGF-1/AS160_v2/GLUT4 axis and FDG-PET positivity in myeloma patients are warranted and could provide rationale for therapeutically targeting this pathway in MM patients with advanced disease. PMID:24280290

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.

Loss of HSulf-1 expression enhances tumorigenicity by inhibiting Bim expression in ovarian cancer.

PubMed

He, Xiaoping; Khurana, Ashwani; Roy, Debarshi; Kaufmann, Scott; Shridhar, Viji

2014-10-15

The expression of human Sulfatase1 (HSulf-1) is downregulated in the majority of primary ovarian cancer tumors, but the functional consequence of this downregulation remains unclear. Using two different shRNAs (Sh1 and Sh2), HSulf-1 expression was stably downregulated in ovarian cancer OV202 cells. We found that HSulf-1-deficient OV202 Sh1 and Sh2 cells formed colonies in soft agar. In contrast, nontargeting control (NTC) shRNA-transduced OV202 cells did not form any colonies. Moreover, subcutaneous injection of OV202 HSulf-1-deficient cells resulted in tumor formation in nude mice, whereas OV202 NTC cells did not. Also, ectopic expression of HSulf-1 in ovarian cancer SKOV3 cells significantly suppressed tumor growth in nude mice. Here, we show that HSulf-1-deficient OV202 cells have markedly decreased expression of proapoptotic Bim protein, which can be rescued by restoring HSulf-1 expression in OV202 Sh1 cells. Enhanced expression of HSulf-1 in HSulf-1-deficient SKOV3 cells resulted in increased Bim expression. Decreased Bim levels after loss of HSulf-1 were due to increased p-ERK, because inhibition of ERK activity with PD98059 resulted in increased Bim expression. However, treatment with a PI3 kinase/AKT inhibitor, LY294002, failed to show any change in Bim protein level. Importantly, rescuing Bim expression in HSulf-1 knockdown cells significantly retarded tumor growth in nude mice. Collectively, these results suggest that loss of HSulf-1 expression promotes tumorigenicity in ovarian cancer through regulating Bim expression. © 2014 UICC.

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.

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

Mesenchyme-specific knockout of ESET histone methyltransferase causes ectopic hypertrophy and terminal differentiation of articular chondrocytes.

PubMed

Lawson, Kevin A; Teteak, Colin J; Zou, Junhui; Hacquebord, Jacques; Ghatan, Andrew; Zielinska-Kwiatkowska, Anna; Fernandes, Russell J; Chansky, Howard A; Yang, Liu

2013-11-08

The exact molecular mechanisms governing articular chondrocytes remain unknown in skeletal biology. In this study, we have found that ESET (an ERG-associated protein with a SET domain, also called SETDB1) histone methyltransferase is expressed in articular cartilage. To test whether ESET regulates articular chondrocytes, we carried out mesenchyme-specific deletion of the ESET gene in mice. ESET knock-out did not affect generation of articular chondrocytes during embryonic development. Two weeks after birth, there was minimal qualitative difference at the knee joints between wild-type and ESET knock-out animals. At 1 month, ectopic hypertrophy, proliferation, and apoptosis of articular chondrocytes were seen in the articular cartilage of ESET-null animals. At 3 months, additional signs of terminal differentiation such as increased alkaline phosphatase activity and an elevated level of matrix metalloproteinase (MMP)-13 were found in ESET-null cartilage. Staining for type II collagen and proteoglycan revealed that cartilage degeneration became progressively worse from 2 weeks to 12 months at the knee joints of ESET knock-out mutants. Analysis of over 14 pairs of age- and sex-matched wild-type and knock-out mice indicated that the articular chondrocyte phenotype in ESET-null mutants is 100% penetrant. Our results demonstrate that expression of ESET plays an essential role in the maintenance of articular cartilage by preventing articular chondrocytes from terminal differentiation and may have implications in joint diseases such as osteoarthritis.

Caffeic acid phenethyl ester down-regulates claudin-2 expression at the transcriptional and post-translational levels and enhances chemosensitivity to doxorubicin in lung adenocarcinoma A549 cells.

PubMed

Sonoki, Hiroyuki; Tanimae, Asami; Furuta, Takumi; Endo, Satoshi; Matsunaga, Toshiyuki; Ichihara, Kenji; Ikari, Akira

2018-06-01

Claudin-2 is highly expressed in human lung adenocarcinoma cells and involved in the promotion of proliferation. Here, we searched for a compound, which can decrease claudin-2 expression using lung adenocarcinoma A549 cells. In the screening using compounds included in royal jelly and propolis, the protein level of claudin-2 was dose-dependently decreased by caffeic acid phenethyl ester (CAPE), whereas the mRNA level and promoter activity were only decreased by 50 μM CAPE. These results suggest that CAPE down-regulates claudin-2 expression mediated by two different mechanisms. CAPE (50 μM) decreased the level of p-NF-κB, whereas it increased that of IκB. The CAPE-induced decrease in promoter activity of claudin-2 was blocked by the mutation in an NF-κB-binding site. The inhibition of NF-κB may be involved in the decrease in mRNA level of claudin-2. The CAPE (10 μM)-induced decrease in claudin-2 expression was inhibited by chloroquine, a lysosomal inhibitor. CAPE increased the expression and activity of protein phosphatase (PP) 1 and 2A. The CAPE-induced decrease in claudin-2 expression was blocked by cantharidin, a potent PPs inhibitor. The cell proliferation was suppressed by CAPE, which was partially rescued by ectopic expression of claudin-2. In addition, the toxicity and accumulation of doxorubicin in 3D spheroid cells were enhanced by CAPE, which was inhibited by ectopic expression of claudin-2. Taken together, CAPE down-regulates claudin-2 expression at the transcriptional and post-translational levels, and enhances sensitivity of cells to doxorubicin in 3D culture conditions. CAPE may be a useful adjunctive compound in the treatment of lung adenocarcinoma. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Glucose Oxidase Induces Cellular Senescence in Immortal Renal Cells through ILK by Downregulating Klotho Gene Expression

PubMed Central

Troyano-Suárez, Nuria; del Nogal-Avila, María; Mora, Inés; Sosa, Patricia; López-Ongil, Susana; Rodriguez-Puyol, Diego; Olmos, Gemma; Ruíz-Torres, María Piedad

2015-01-01

Cellular senescence can be prematurely induced by oxidative stress involved in aging. In this work, we were searching for novel intermediaries in oxidative stress-induced senescence, focusing our interest on integrin-linked kinase (ILK), a scaffold protein at cell-extracellular matrix (ECM) adhesion sites, and on the Klotho gene. Cultured renal cells were treated with glucose oxidase (GOx) for long time periods. GOx induced senescence, increasing senescence associated β-galactosidase activity and the expression of p16. In parallel, GOx increased ILK protein expression and activity. Ectopic overexpression of ILK in cells increased p16 expression, even in the absence of GOx, whereas downregulation of ILK inhibited the increase in p16 due to oxidative stress. Additionally, GOx reduced Klotho gene expression and cells overexpressing Klotho protein did not undergo senescence after GOx addition. We demonstrated a direct link between ILK and Klotho since silencing ILK expression in cells and mice increases Klotho expression and reduces p53 and p16 expression in renal cortex. In conclusion, oxidative stress induces cellular senescence in kidney cells by increasing ILK protein expression and activity, which in turn reduces Klotho expression. We hereby present ILK as a novel downregulator of Klotho gene expression. PMID:26583057

Glucose Oxidase Induces Cellular Senescence in Immortal Renal Cells through ILK by Downregulating Klotho Gene Expression.

PubMed

Troyano-Suárez, Nuria; del Nogal-Avila, María; Mora, Inés; Sosa, Patricia; López-Ongil, Susana; Rodriguez-Puyol, Diego; Olmos, Gemma; Ruíz-Torres, María Piedad

2015-01-01

Cellular senescence can be prematurely induced by oxidative stress involved in aging. In this work, we were searching for novel intermediaries in oxidative stress-induced senescence, focusing our interest on integrin-linked kinase (ILK), a scaffold protein at cell-extracellular matrix (ECM) adhesion sites, and on the Klotho gene. Cultured renal cells were treated with glucose oxidase (GOx) for long time periods. GOx induced senescence, increasing senescence associated β-galactosidase activity and the expression of p16. In parallel, GOx increased ILK protein expression and activity. Ectopic overexpression of ILK in cells increased p16 expression, even in the absence of GOx, whereas downregulation of ILK inhibited the increase in p16 due to oxidative stress. Additionally, GOx reduced Klotho gene expression and cells overexpressing Klotho protein did not undergo senescence after GOx addition. We demonstrated a direct link between ILK and Klotho since silencing ILK expression in cells and mice increases Klotho expression and reduces p53 and p16 expression in renal cortex. In conclusion, oxidative stress induces cellular senescence in kidney cells by increasing ILK protein expression and activity, which in turn reduces Klotho expression. We hereby present ILK as a novel downregulator of Klotho gene expression.

Ectopic eruption of permanent incisors after predecessor pulpectomy: five cases.

PubMed

Tannure, Patricia Nivoloni; Fidalgo, Tatiana Kelly da Silva; Barcelos, Roberta; Gleiser, Rogerio; Primo, Laura Guimaraes

2011-01-01

Pulpectomy in primary teeth is a common technique that preserves teeth in the oral environment and maintains or recovers periapical tissues to a healthy condition. This article describes the ectopic eruption of permanent incisors whose primary predecessors underwent pulpectomy using ZOE filler paste. In a group of 135 teeth that received pulpectomy therapy due to caries, 10 primary maxillary incisors had overretention and were followed for at least 3.5 years (mean time of 4.2 years), both clinically and radiographically, until the permanent teeth erupted. The proposed treatment included extraction of the overretained primary incisors based on permanent successor eruption chronology and contralateral eruption. Seven permanent teeth erupted ectopically. Autocorrection of the permanent tooth positions was observed in five cases. It can be concluded that periodic clinical and radiographic assessments are essential to verify radicular and filling paste resorptions and to avoid overretention and any subsequent malocclusion.

MAPK/ERK signal pathway involved expression of COX-2 and VEGF by IL-1β induced in human endometriosis stromal cells in vitro

PubMed Central

Huang, Fengying; Cao, Jing; Liu, Qiuhong; Zou, Ying; Li, Hongyun; Yin, Tuanfang

2013-01-01

Objective: Now there are more and more evidences that Cyclooxygenase-2 (COX-2) plays an important role in angiogenesis of endometriosis (EMs). Vascular endothelial growth factor (VEGF) has a potent angiogenic activity. However, it is worth studying about the regulating mechanism of COX-2/COX-1 and VEGF in the development of human endometriosis in vitro. The current study was designed to investigate the effect of 4 cytokines on COX-2/COX-1 expression and the effect of IL-1β on VEGF release in human endometriosis stromal cells (ESC), and to explore the related signaling pathways involved in vitro. Methods: Isolation, culture and identification of ESC. Cells were treated with 4 cytokines, and the inhibitor mitogen-activated protein-Erk (MEK) and the inhibitor p38 mitogen-activated protein kinase (MAPK) prior to adding cytokine IL-1β. COX-2 protein expression was measured by western blot and VEGF secretion was determined by ELISA. Results: Among four kinds of cytokines, IL-1β treatment increased COX-2 protein expression and VEGF release in three ESC, and TNF-α had the same effect on COX-2 protein level as IL-1β only in ectopic and eutopic ESC, and MCSF had only slight effect on ectopic ESC. In contrast, cytokines had no effect on COX-1 expression. We also demonstrated that MAPK reduced the synthesis of COX-2 by IL-1β induced. COX-2 inhibitor reduced VEGF release by IL-1β induced. Conclusions: i) In human ESC in vitro, IL-1β up-regulated the COX-2 expression through the activation of p38 MAPK pathway, and not to COX-1. ii) Up-regulation of VEGF level by IL-1β treatment was found in human endometriosis stromal cell and COX-2 inhibitor was involved in this process. PMID:24133591

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.

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

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.

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

Constitutive Smad signaling and Smad-dependent collagen gene expression in mouse embryonic fibroblasts lacking peroxisome proliferator-activated receptor-{gamma}

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

Ghosh, Asish K; Wei, Jun; Wu, Minghua

2008-09-19

Transforming growth factor-{beta} (TGF-{beta}), a potent inducer of collagen synthesis, is implicated in pathological fibrosis. Peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}) is a nuclear hormone receptor that regulates adipogenesis and numerous other biological processes. Here, we demonstrate that collagen gene expression was markedly elevated in mouse embryonic fibroblasts (MEFs) lacking PPAR-{gamma} compared to heterozygous control MEFs. Treatment with the PPAR-{gamma} ligand 15d-PGJ{sub 2} failed to down-regulate collagen gene expression in PPAR-{gamma} null MEFs, whereas reconstitution of these cells with ectopic PPAR-{gamma} resulted in their normalization. Compared to control MEFs, PPAR-{gamma} null MEFs displayed elevated levels of the Type I TGF-{beta} receptor (T{beta}RI),more » and secreted more TGF-{beta}1 into the media. Furthermore, PPAR-{gamma} null MEFs showed constitutive phosphorylation of cellular Smad2 and Smad3, even in the absence of exogenous TGF-{beta}, which was abrogated by the ALK5 inhibitor SB431542. Constitutive Smad2/3 phosphorylation in PPAR-{gamma} null MEFs was associated with Smad3 binding to its cognate DNA recognition sequences, and interaction with coactivator p300 previously implicated in TGF-{beta} responses. Taken together, these results indicate that loss of PPAR-{gamma} in MEFs is associated with upregulation of collagen synthesis, and activation of intracellular Smad signal transduction, due, at least in part, to autocrine TGF-{beta} stimulation.« less

Surgical correction of ectopic penis and scrotum associated with bilateral orchidopexy.

PubMed

Sobral, Daniel Santos Rocha; Silva, Helder Damásio da; Damázio, Eulálio

2017-01-01

Ectopic penis is usually associated with penoscrotal transposition, and it is rarely observed in isolation. We report a surgical approach for an extremely rare case. A 10-year-old male patient with bilateral cryptorchidism and ectopic penis and scrotum in perineal area, with no penoscrotal transposition, representing an association not yet described in literature. A previous orchiopexy failed due to ectopic scrotum. By means of an inverted Y incision, the penis was mobilized and a perineal skin flap in form of a testicular sac was prepared. Finally orchiopexy was performed. The surgery was essential to treat cryptorchidism and to improve the self-image of the patient. RESUMO O pênis ectópico geralmente ocorre associado à transposição peno-escrotal, sendo raro isoladamente. Relatamos uma abordagem cirúrgica para um caso extremamente raro. Tratava-se de paciente do sexo masculino, 10 anos, com criptorquidia bilateral e pênis e escroto ectópicos, na região perineal, sem transposição peno-escrotal, representando uma associação ainda não descrita na literatura. Orquidopexia prévia sem sucesso, devido à ectopia do escroto. Por meio de uma incisão em Y invertido, mobilizou-se o pênis e preparou-se um retalho da pele perineal em forma de bolsa testicular. Por fim, realizou-se a orquidopexia. A cirurgia foi fundamental para tratar a criptorquidia e promover ganho na autoimagem do paciente.

WEREWOLF and ENHANCER of GLABRA3 are interdependent regulators of the spatial expression pattern of GLABRA2 in Arabidopsis.

PubMed

Song, Sang-Kee; Kwak, Su-Hwan; Chang, Soo Chul; Schiefelbein, John; Lee, Myeong Min

2015-11-06

In multicellular organisms, cell fates are specified through differential regulation of transcription. Epidermal cell fates in the Arabidopsis thaliana root are precisely specified by several transcription factors, with the GLABRA2 (GL2) homeodomain protein acting at the farthest downstream in this process. To better understand the regulation of GL2 expression, we ectopically expressed WEREWOLF (WER) and ENHANCER OF GLABRA3 (EGL3) in various tissues and examined GL2 expression. Here we show that WER expressed ubiquitously in the root induced GL2 expression only in the root epidermis, whereas co-expression of WER and EGL3 induced GL2 expression in the corresponding tissues. We also found that GL3 accumulated in the nucleus at the early meristematic region and EGL3 accumulated later in the nucleus of epidermal cells. We further found that ectopic expression of WER and EGL3 in ground tissues inhibited GL2 expression in the epidermis. Our results suggest that the co-expression of WER and EGL3 is sufficient for driving GL2 and CPC expression. Copyright © 2015 Elsevier Inc. All rights reserved.

A Fast Multimodal Ectopic Beat Detection Method Applied for Blood Pressure Estimation Based on Pulse Wave Velocity Measurements in Wearable Sensors.

PubMed

Pflugradt, Maik; Geissdoerfer, Kai; Goernig, Matthias; Orglmeister, Reinhold

2017-01-14

Automatic detection of ectopic beats has become a thoroughly researched topic, with literature providing manifold proposals typically incorporating morphological analysis of the electrocardiogram (ECG). Although being well understood, its utilization is often neglected, especially in practical monitoring situations like online evaluation of signals acquired in wearable sensors. Continuous blood pressure estimation based on pulse wave velocity considerations is a prominent example, which depends on careful fiducial point extraction and is therefore seriously affected during periods of increased occurring extrasystoles. In the scope of this work, a novel ectopic beat discriminator with low computational complexity has been developed, which takes advantage of multimodal features derived from ECG and pulse wave relating measurements, thereby providing additional information on the underlying cardiac activity. Moreover, the blood pressure estimations' vulnerability towards ectopic beats is closely examined on records drawn from the Physionet database as well as signals recorded in a small field study conducted in a geriatric facility for the elderly. It turns out that a reliable extrasystole identification is essential to unsupervised blood pressure estimation, having a significant impact on the overall accuracy. The proposed method further convinces by its applicability to battery driven hardware systems with limited processing power and is a favorable choice when access to multimodal signal features is given anyway.

Aberrant expression of CKLF-like MARVEL transmembrane member 5 (CMTM5) by promoter methylation in myeloid leukemia.

PubMed

Niu, Jihong; Li, Henan; Zhang, Yao; Li, Jinlan; Xie, Min; Li, Lingdi; Qin, Xiaoying; Qin, Yazhen; Guo, Xiaohuan; Jiang, Qian; Liu, Yanrong; Chen, Shanshan; Huang, Xiaojun; Han, Wenling; Ruan, Guorui

2011-06-01

CMTM5 has been shown to exhibit tumor suppressor activities, however, its role in leukemia is unclear. Herein we firstly reported the expression and function of CMTM5 in myeloid leukemia. CMTM5 was down-regulated, or undetectable, in leukemia cell lines and bone marrow cells from leukemia patients with promoter methylation. Ectopic expression of CMTM5-v1 strongly inhibited the proliferation of K562 and MEG-01 cells. In addition, significant negative correlations were observed between CMTM5 and three leukemia-specific fusion genes (AML1-ETO, PML-RARα and BCR/ABL1). CMTM5 expression was up-regulated in patients who had undergone treatment. Therefore, CMTM5 may be involved in the pathomechanism of myeloid leukemias. Copyright © 2010 Elsevier Ltd. All rights reserved.

Peroxisome proliferator-activated receptor-β/δ inhibits human neuroblastoma cell tumorigenesis by inducing p53- and SOX2-mediated cell differentiation.

PubMed

Yao, Pei-Li; Chen, Liping; Dobrzański, Tomasz P; Zhu, Bokai; Kang, Boo-Hyon; Müller, Rolf; Gonzalez, Frank J; Peters, Jeffrey M

2017-05-01

Neuroblastoma is a common childhood cancer typically treated by inducing differentiation with retinoic acid (RA). Peroxisome proliferator-activated receptor-β/δ, (PPARβ/δ) is known to promote terminal differentiation of many cell types. In the present study, PPARβ/δ was over-expressed in three human neuroblastoma cell lines, NGP, SK-N-BE(2), and IMR-32, that exhibit high, medium, and low sensitivity, respectively, to retinoic acid-induced differentiation to determine if PPARβ/δ and retinoic acid receptors (RARs) could be jointly targeted to increase the efficacy of treatment. All-trans-RA (atRA) decreased expression of SRY (sex determining region Y)-box 2 (SOX2), a stem cell regulator and marker of de-differentiation, in NGP and SK-N-BE(2) cells with inactive or mutant tumor suppressor p53, respectively. However, atRA did not suppress SOX2 expression in IMR-32 cells carrying wild-type p53. Over-expression and/or ligand activation of PPARβ/δ reduced the average volume and weight of ectopic tumor xenografts from NGP, SK-N-BE(2), or IMR-32 cells compared to controls. Compared with that found with atRA, PPARβ/δ suppressed SOX2 expression in NGP and SK-N-BE(2) cells and ectopic xenografts, and was also effective in suppressing SOX2 expression in IMR-32 cells that exhibit higher p53 expression compared to the former cell lines. Combined, these observations demonstrate that activating or over-expressing PPARβ/δ induces cell differentiation through p53- and SOX2-dependent signaling pathways in neuroblastoma cells and tumors. This suggests that combinatorial activation of both RARα and PPARβ/δ may be suitable as an alternative therapeutic approach for RA-resistant neuroblastoma patients. Published [2016]. This article is a U.S. Government work and is in the public domain in the USA.

High Temperature Requirement A1, Transforming Growth Factor Beta 1, phosphoSmad2 and Ki67 in Eutopic and Ectopic Endometrium of Women With Endometriosis

PubMed Central

Goteri, G.; Altobelli, E.; Tossetta, G.; Zizzi, A.; Avellini, C.; Licini, C.; Lorenzi, T.; Castellucci, M.; Ciavattini, A.

2015-01-01

Increasing evidence supports the hypothesis that TGFβ1 signalling may be mediated by high temperature requirement A1 (HtrA1) serine protease, acting on important regulatory mechanisms such as cell proliferation and mobility. Evidence is now accumulating to suggest that HtrA1 is involved in the development and progression of several pathologies. The aim of this study was to evaluate: i) if HtrA1 and TGFβ1 expressions differ in eutopic and ectopic endometrium in women with endometriosis; ii) if HtrA1 correlates to TGFβ1, pSmad and Ki67. This study was carried out including 10 women with ovarian endometriosis (cases) and 10 women with non endometriotic diseases (controls). Endometrial tissue underwent immunohistochemical H-score analysis for HtrA1, TGFβ1, pSmad and Ki67 molecules. Data evaluation was performed by a nonparametric Kruskal-Wallis test and Spearman correlation was applied to evaluate the relationship among the molecules investigated in the epithelial and in the stromal compartment. The HtrA1 was significantly decreased in ectopic and eutopic endometrium of women with endometriosis when compared with control endometrium in epithelial compartment. TGFβ1was significantly increased in eutopic endometrium and decreased in ectopic endometrium in epithelial and stromal compartment. In addition, Ki67 was significantly increased and an increase, but not significant, was detected for pSMAd2 in eutopic and ectopic endometrium compared to control one. In summary, the significant direct correlation between TGFβ1 and pSmad2 as well as between HtrA1 and TGFβ1 and the very significant increase of Ki67 in stromal compartment of eutopic endometrium suggest a possible involvement of HtrA1 in the pathogenesis of endometriosis. PMID:26708185

Expression of grape ACS1 in tomato decreases ethylene and alters the balance between auxin and ethylene during shoot and root formation.

PubMed

Ye, Xia; Fu, Mengmeng; Liu, Yu; An, Dongliang; Zheng, Xianbo; Tan, Bin; Li, Jidong; Cheng, Jun; Wang, Wei; Feng, Jiancan

2018-05-04

Ethylene plays an important role in the grape rachis, where its production can be 10 times higher than in the berry. VvACS1 is the only rachis-specific ACC synthase (ACS) gene, and its expression is coincident with ethylene production in the rachis of Vitis vinifera 'Thompson seedless'. VvACS1 was cloned and ectopically expressed in tomato (Solanum lycopersicum 'Moneymaker'). Lateral buds were increased in two- or four-week-old 35s∷VvACS1 transgenic tomato plants after transplanting. Compared with wild-type (WT) plants, the transgenic tomato plants showed higher expression of the VvACS1 gene in the flowers, leaves, rachis, and fruits. There was no obvious difference of ACS activity in the fruit of tomato, and only increased ACS activity in the rachis of tomato. Ethylene production was decreased in flowers, leaves, and fruits (seven weeks after full bloom), while the relative expression of endogenous tomato ACS1 and ACS6 genes was not down-regulated by the ectopic expression of VvACS1. These results imply that post-transcriptional or post-translational regulation of ACS may occur, resulting in lower ethylene production in the transgenic tomato plants. Moreover, expression of VvACS1 in tomato resulted in decreased auxin and increased zeatin contents in the lateral buds, as well as reduced or delayed formation of adventitious roots in lateral bud cuttings. RNA-Seq and qRT-PCR analyses of rooted lateral bud cuttings indicated that the relative expression levels of the genes for zeatin O-glucosyltransferase-like, auxin repressed/dormancy-associated protein, and ERF transcription factors were higher in transgenic tomatoes than in WT, suggesting that ethylene may regulate auxin transport and distribution in shoots and that adventitious root formation employs coordination between auxin and ethylene. Copyright © 2018 Elsevier GmbH. All rights reserved.

Modulating ectopic gene expression levels by using retroviral vectors equipped with synthetic promoters.

PubMed

Ferreira, Joshua P; Peacock, Ryan W S; Lawhorn, Ingrid E B; Wang, Clifford L

2011-12-01

The human cytomegalovirus and elongation factor 1α promoters are constitutive promoters commonly employed by mammalian expression vectors. These promoters generally produce high levels of expression in many types of cells and tissues. To generate a library of synthetic promoters capable of generating a range of low, intermediate, and high expression levels, the TATA and CAAT box elements of these promoters were mutated. Other promoter variants were also generated by random mutagenesis. Evaluation using plasmid vectors integrated at a single site in the genome revealed that these various synthetic promoters were capable of expression levels spanning a 40-fold range. Retroviral vectors were equipped with the synthetic promoters and evaluated for their ability to reproduce the graded expression demonstrated by plasmid integration. A vector with a self-inactivating long terminal repeat could neither reproduce the full range of expression levels nor produce stable expression. Using a second vector design, the different synthetic promoters enabled stable expression over a broad range of expression levels in different cell lines. The online version of this article (doi:10.1007/s11693-011-9089-0) contains supplementary material, which is available to authorized users.

Tumor Suppressor p53 Stimulates the Expression of Epstein-Barr Virus Latent Membrane Protein 1.

PubMed

Wang, Qianli; Lingel, Amy; Geiser, Vicki; Kwapnoski, Zachary; Zhang, Luwen

2017-10-15

Epstein-Barr virus (EBV) is associated with multiple human malignancies. EBV latent membrane protein 1 (LMP1) is required for the efficient transformation of primary B lymphocytes in vitro and possibly in vivo The tumor suppressor p53 plays a seminal role in cancer development. In some EBV-associated cancers, p53 tends to be wild type and overly expressed; however, the effects of p53 on LMP1 expression is not clear. We find LMP1 expression to be associated with p53 expression in EBV-transformed cells under physiological and DNA damaging conditions. DNA damage stimulates LMP1 expression, and p53 is required for the stimulation. Ectopic p53 stimulates endogenous LMP1 expression. Moreover, endogenous LMP1 blocks DNA damage-mediated apoptosis. Regarding the mechanism of p53-mediated LMP1 expression, we find that interferon regulatory factor 5 (IRF5), a direct target of p53, is associated with both p53 and LMP1. IRF5 binds to and activates a LMP1 promoter reporter construct. Ectopic IRF5 increases the expression of LMP1, while knockdown of IRF5 leads to reduction of LMP1. Furthermore, LMP1 blocks IRF5-mediated apoptosis in EBV-infected cells. All of the data suggest that cellular p53 stimulates viral LMP1 expression, and IRF5 may be one of the factors for p53-mediated LMP1 stimulation. LMP1 may subsequently block DNA damage- and IRF5-mediated apoptosis for the benefits of EBV. The mutual regulation between p53 and LMP1 may play an important role in EBV infection and latency and its related cancers. IMPORTANCE The tumor suppressor p53 is a critical cellular protein in response to various stresses and dictates cells for various responses, including apoptosis. This work suggests that an Epstein-Bar virus (EBV) principal viral oncogene is activated by cellular p53. The viral oncogene blocks p53-mediated adverse effects during viral infection and transformation. Therefore, the induction of the viral oncogene by p53 provides a means for the virus to cope with infection and

Aurora A regulates the activity of HURP by controlling the accessibility of its microtubule-binding domain.

PubMed

Wong, Jim; Lerrigo, Robert; Jang, Chang-Young; Fang, Guowei

2008-05-01

HURP is a spindle-associated protein that mediates Ran-GTP-dependent assembly of the bipolar spindle and promotes chromosome congression and interkinetochore tension during mitosis. We report here a biochemical mechanism of HURP regulation by Aurora A, a key mitotic kinase that controls the assembly and function of the spindle. We found that HURP binds to microtubules through its N-terminal domain that hyperstabilizes spindle microtubules. Ectopic expression of this domain generates defects in spindle morphology and function that reduce the level of tension across sister kinetochores and activate the spindle checkpoint. Interestingly, the microtubule binding activity of this N-terminal domain is regulated by the C-terminal region of HURP: in its hypophosphorylated state, C-terminal HURP associates with the microtubule-binding domain, abrogating its affinity for microtubules. However, when the C-terminal domain is phosphorylated by Aurora A, it no longer binds to N-terminal HURP, thereby releasing the inhibition on its microtubule binding and stabilizing activity. In fact, ectopic expression of this C-terminal domain depletes endogenous HURP from the mitotic spindle in HeLa cells in trans, suggesting the physiological importance for this mode of regulation. We concluded that phosphorylation of HURP by Aurora A provides a regulatory mechanism for the control of spindle assembly and function.

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

Differentiation of EL4 lymphoma cells by tumoral environment is associated with inappropriate expression of the large chondroitin sulfate proteoglycan PG-M and the tumor-associated antigen HTgp-175.

PubMed

Rottiers, P; Verfaillie, T; Contreras, R; Revets, H; Desmedt, M; Dooms, H; Fiers, W; Grooten, J

1998-11-09

Progression to malignancy of transformed cells involves complex genetic alterations and aberrant gene expression patterns. While aberrant gene expression is often caused by alterations in individual genes, the contribution of the tumoral environment to the triggering of this gene expression is less well established. The stable but heterogeneous expression in cultured EL4/13 cells of a novel tumor-associated antigen, designated as HTgp-175, was chosen for the investigation of gene expression during tumor formation. Homogeneously HTgp-175-negative EL4/13 cells, isolated by cell sorting or obtained by subcloning, acquired HTgp-175 expression as a result of tumor formation. The tumorigenicity of HTgp-175-negative vs. HTgp-175-positive EL4 variants was identical, indicating that induction but not selection accounted for the phenotypic switch from HTgp-175-negative to HTgp-175-positive. Although mutagenesis experiments showed that the protein was not essential for tumor establishment, tumor-derived cells showed increased malignancy, linking HTgp-175 expression with genetic changes accompanying tumor progression. This novel gene expression was not an isolated event, since it was accompanied by ectopic expression of the large chondroitin sulfate proteoglycan PG-M and of normal differentiation antigens. We conclude that signals derived from the tumoral microenvironment contribute significantly to the aberrant gene expression pattern of malignant cells, apparently by fortuitous activation of differentiation processes and cause expression of novel differentiation antigens as well as of inappropriate tumor-associated and ectopic antigens.

The expression and function of epithelial membrane protein 1 in laryngeal carcinoma.

PubMed

Li, Hong; Zhang, Xiaowen; Jiang, Xuejun; Ji, Xu

2017-01-01

In this study, we compared the expression of epithelial membrane protein 1 (EMP1) on the steady-state mRNA level (by quantitative real-time PCR) and on the protein level (by western immunoblot and immunohistochemistry) in 51 pairs of laryngeal carcinoma tissues and matched cancer-free peritumor tissues, and we analyzed the correlation between EMP1 expression and different clinicopathological factors. Furthermore, we ectopically expressed EMP1 in human laryngeal carcinoma Hep-2 cells and examined the effects on cell viability, apoptosis, colonogenicity, and motility, by MTT assay, flow cytometry, colony formation assay and Transwell migration assay, respectively. EMP1 expression (on both the mRNA and protein levels) was significantly lower in the cancer tissues than in matched peritumor tissues (P<0.05). In laryngeal cancers, the level of EMP1 protein was correlated with histological grade (P<0.05), but not with age, gender, clinical stage, cancer subtype or lymph node metastasis (P>0.05). Functionally, ectopic expression of EMP1 in Hep-2 cells significantly reduced cell viability, colony formation, and migration, but enhanced apoptosis. Therefore, EMP1 is a tumor suppressor in laryngeal carcinoma. Boosting EMP1 expression in laryngeal carcinoma initiates multiple anticancer phenotypes and thus presents a promising therapeutic strategy for laryngeal cancer.

A United Kingdom national survey of trends in ectopic pregnancy management.

PubMed

Taheri, M; Bharathan, R; Subramaniam, A; Kelly, T

2014-08-01

Our national survey demonstrates increased use of medical and laparoscopic management of ectopic pregnancy in the UK. In the UK in 2000, 35% of cases were managed by laparoscopy, 63% by laparotomy and 1% with medication. A recent review in the USA revealed increasing rates of medical management and decreasing rates of laparotomy; a trend driven by both cost-effectiveness and patient choice. A total of 119 early pregnancy units were surveyed regarding the nature and management of the three most recent cases of ectopic pregnancy; in addition, feasibility of training residents was also requested. Participants reported on 124 cases with a median of five cases per month per department. A total of 57% of cases were managed laparoscopically, 31% medically, 5% by laparotomy and 6% conservatively. Out of 44 centres, 29 have the facilities for training in both intermediate laparoscopic surgery and early pregnancy ultrasound.

Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway

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

Fan, Yu; Zhan, Qian; Xu, Hongying

The KRAB–zinc-finger protein ZNF545 was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of ZNF545 in tumorigenesis remain unclear. In this study, we investigated the expression and roles of ZNF545 in multiple myeloma (MM). ZNF545 was frequently downregulated in MM tissues compared with non-tumor bone marrow tissues. ZNF545 expression was silenced by promoter methylation in MM cell lines, and could be restored by demethylation treatment. ZNF545 methylation was detected in 28.3% of MM tissues, compared with 4.3% of normal bone marrow tissues. ZNF545 transcriptionally activated the p53 signaling pathway but had no effect onmore » Akt in MM, whereas ectopic expression of ZNF545 in silenced cells suppressed their proliferation and induced apoptosis. We therefore identified ZNF545 as a novel tumor suppressor inhibiting tumor growth through activation of the p53 pathway in MM. Moreover, tumor-specific methylation of ZNF545 may represent an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. -- Highlights: •Downregulated ZNF545 in MM tissues and cell lines and ectopic expression of ZNF545 suppresses tumor growth. •Tumor-specific methylation of ZNF545 represents an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. •ZNF545 exerts its tumor suppressive effects via transcriptional activating p53 pathway.« less

Incidence of ectopic pregnancy in Benin City, Nigeria.

PubMed

Oronsaye, A U; Odiase, G I

1981-10-01

A study of 100 consecutive cases of ectopic pregnancy managed over a 21-month period in the University Department of Obstetrics and Gynaecology is reported. The results show that this is a common gynaecological emergency in the community. Although pelvic inflammatory disease appears to be an important aetiological factor, a significant proportion showed no evidence of previous pelvic sepsis. The usual surgical treatment of cases in our unit is, where possible, total salpingectomy rather than salpingo-oophorectomy.

IGF-I stimulates ERβ and aromatase expression via IGF1R/PI3K/AKT-mediated transcriptional activation in endometriosis.

PubMed

Zhou, Yan; Zeng, Cheng; Li, Xin; Wu, Pei-Li; Yin, Ling; Yu, Xiao-Lan; Zhou, Ying-Fang; Xue, Qing

2016-08-01

Estrogen receptor beta (ERβ, encoded by ESR2 gene) and cytochrome P450 aromatase (encoded by CYP19A1 gene) play critical roles in endometriosis, and the levels of insulin-like growth factor-I (IGF-I) in the peritoneal fluid are significantly higher in patients with endometriosis compared with those in normal women. However, the effects and mechanisms of IGF-I on ERβ and aromatase expression remain to be fully elucidated. In this study, human endometriotic stromal cells (ESCs) and endometrial cells (EMs) derived from ovarian endometriomas and eutopic endometrial tissues. ESCs were cultured with IGF-I, signal pathway inhibitors, and siRNAs. ERβ and aromatase expression were measured by real-time PCR and Western, respectively. The binding of c-Jun and CREB to the ESR2 and CYP19A1 promoters was assessed by chromatin immunoprecipitation assay. Animal experiments were performed in a xenograft mouse model. Levels of IGF-I mRNA in ESCs were markedly higher than those in EMs. IGF-I upregulated ERβ and aromatase expression in ESCs after stimulation of the IGF1R/PI3K/AKT pathway. Following IGF-I treatment, a marked increase in c-Jun and CREB phosphorylation occurred, enhancing binding to the ESR2 and CYP19A1 promoters. An IGF1R inhibitor in vivo reduced IGF-I-induced endometriosis graft growth and ERβ and aromatase expression. In conclusion, this is the first report to describe a mechanistic analysis of ERβ and aromatase expression regulated by IGF-I in ESCs. Moreover, an IGF1R inhibitor impeded ectopic lesion growth in nude mice. These findings suggest that an inhibitor of IGF1R might have therapeutic potential as an antiendometriotic drug. Level of IGF-I mRNA in ESCs is markedly higher than that in EMs. IGF-I up-regulates ERβ and aromatase expression via IGF1R/PI3K/AKT pathway. C-Jun and CREB are recruited to ESR2 or CYP19A1 promoter by IGF-I stimulation. IGF-1R inhibitors in vivo impede the growth of ectopic lesions in nude mice.

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.

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.

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.

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

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.

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. ...

Maternally expressed PGK-Cre transgene as a tool for early and uniform activation of the Cre site-specific recombinase.

PubMed

Lallemand, Y; Luria, V; Haffner-Krausz, R; Lonai, P

1998-03-01

A transgenic mouse strain with early and uniform expression of the Cre site-specific recombinase is described. In this strain, PGK-Crem, Cre is driven by the early acting PGK-1 promoter, but, probably due to cis effects at the integration site, the recombinase is under dominant maternal control. When Cre is transmitted by PGK-Crem females mated to males that carry a reporter transgene flanked by loxP sites, even offspring that do not inherit PGK-Cre delete the target gene. It follows that in the PGK-Crem female Cre activity commences in the diploid phase of oogenesis. In PGK-Crem crosses complete recombination was observed in all organs, including testis and ovary. We prepared a mouse stock that is homozygous for PGK-Crem and at the albino (c) locus. This strain will be useful for the early and uniform induction of ectopic and dominant negative mutations, for the in vivo removal of selective elements from targeted mutations and in connection with the manipulation of targeted loci in 'knock in' and related technologies.

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.

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.

The co-expression of GPER and Gankyrin in ovarian endometriosis and its correlation with the rASRM stages.

PubMed

Zhang, Chun; Yuan, Xiying; Zhang, Yi

2016-01-01

The aim of this study was to examine the expression of G protein-coupled estrogen receptor (GPER) and Gankyrin in ovarian endometriosis, analyze their clinicopathological significance, and investigate their correlation. Quantitative real-time polymerase chain reaction and Western blot were performed to testify mRNA and protein expression of GPER and Gankyrin in ovarian endometriosis. Immunohistochemical staining (streptavidin-peroxidase method) was conducted to determine the expression and distribution of GPER and Gankyrin protein in matched ectopic and eutopic endometrium of endometriosis and normal endometrium. We also investigated their associations with rASRM stages and the correlation between the two proteins. GPER and Gankyrin were found overexpressed in ectopic endometrium of endometriosis compared with either its eutopic counterpart or endometrium from normal patients. The immunohistochemical analysis also revealed that higher expression was observed in eutopic endometrium with or without endometriosis during proliferative phase in comparison to secretory phase. These two proteins were positively correlated with the stages of endometriosis. Moreover, a significant positive correlation was found between GPER and Gankyrin both in ectopic and eutopic endometrium of the ovarian endometriosis. GPER and Gankyrin might be implicated in the hormonal regulation of endometriosis and be associated with the severity of endometriosis. In addition, GPER and Gankyrin were found to be positively correlated, which could possibly serve as novel therapeutic targets for this disease.

Mobilizing Transit-Amplifying Cell-Derived Ectopic Progenitors Prevents Hair Loss from Chemotherapy or Radiation Therapy.

PubMed

Huang, Wen-Yen; Lai, Shih-Fan; Chiu, Hsien-Yi; Chang, Michael; Plikus, Maksim V; Chan, Chih-Chieh; Chen, You-Tzung; Tsao, Po-Nien; Yang, Tsung-Lin; Lee, Hsuan-Shu; Chi, Peter; Lin, Sung-Jan

2017-11-15

Genotoxicity-induced hair loss from chemotherapy and radiotherapy is often encountered in cancer treatment, and there is a lack of effective treatment. In growing hair follicles (HF), quiescent stem cells (SC) are maintained in the bulge region, and hair bulbs at the base contain rapidly dividing, yet genotoxicity-sensitive transit-amplifying cells (TAC) that maintain hair growth. How genotoxicity-induced HF injury is repaired remains unclear. We report here that HFs mobilize ectopic progenitors from distinct TAC compartments for regeneration in adaptation to the severity of dystrophy induced by ionizing radiation (IR). Specifically, after low-dose IR, keratin 5 + basal hair bulb progenitors, rather than bulge SCs, were quickly activated to replenish matrix cells and regenerated all concentric layers of HFs, demonstrating their plasticity. After high-dose IR, when both matrix and hair bulb cells were depleted, the surviving outer root sheath cells rapidly acquired an SC-like state and fueled HF regeneration. Their progeny then homed back to SC niche and supported new cycles of HF growth. We also revealed that IR induced HF dystrophy and hair loss and suppressed WNT signaling in a p53- and dose-dependent manner. Augmenting WNT signaling attenuated the suppressive effect of p53 and enhanced ectopic progenitor proliferation after genotoxic injury, thereby preventing both IR- and cyclophosphamide-induced alopecia. Hence, targeted activation of TAC-derived progenitor cells, rather than quiescent bulge SCs, for anagen HF repair can be a potential approach to prevent hair loss from chemotherapy and radiotherapy. Cancer Res; 77(22); 6083-96. ©2017 AACR . ©2017 American Association for Cancer Research.

[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.

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 expression of protein kinase C-β sensitizes head and neck squamous cell carcinoma to diterpene esters.

PubMed

Adams, Ryan A; D'Souza, Marjorie M A; Pierce, Carly J; Korica, Natasa; Wallwork, Ben; Parsons, Peter G; Panizza, Benedict; Boyle, Glen M

2015-03-01

The objective of this study was to examine the effect of specific Protein kinase C (PKC) isoform re-expression in solid malignancies, particularly head and neck squamous cell carcinoma cell lines, and the impact this may have on treatment with known activators of PKC. The constitutive expression of PKC isoforms were determined in six head and neck squamous cell carcinoma (SCC) cell lines. Cytotoxicity of the prototypic phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) and the novel diterpene ester PEP005 was established. Viral transduction to re-express PKCβ isoforms in two of these cell lines was performed, and its effect on the sensitivity to the compounds was quantified. Tongue and hypopharyngeal SCC cell lines were resistant to both TPA and PEP005, with the concentration required to inhibit growth by 50% (IC50) being >1,000 ng/ml. CAL-27 (tongue SCC) and FaDu (hypopharyngeal SCC) cell lines re-expressing PKCβI and -βII isoforms demonstrated IC50 of 1-5 ng/ml with TPA or PEP005. Re-expression of PKCβ in head and neck SCC cell lines leads to cells one thousand-times more sensitive to the cytotoxic effects of phorbol or diterpene esters in culture. This highlights the importance of the isoform in tumor progression and presents the potential benefit of these compounds in malignancies expressing the protein, and in combination therapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Mechanism of Telomerase Activation by v-Rel and Its Contribution to Transformation

PubMed Central

Hrdličková, Radmila; Nehyba, Jiří; Liss, Andrew S.; Bose, Henry R.

2006-01-01

Telomerase is activated during the transformation of lymphoid cells and fibroblasts by v-Rel, the oncogenic member of the Rel/NF-κB family of transcription factors. v-Rel-transformed cell lines have longer telomeres than untransformed chicken lymphoid cells and have high levels of telomerase activity. v-Rel-mediated activation of telomerase is achieved by multiple mechanisms. The expression of the gene encoding the catalytic subunit of telomerase (TERT) was directly upregulated by v-Rel. Moreover, the expression of v-Rel altered the ratio of alternatively spliced and full-length TERT transcripts in favor of the full-length forms. The activation of telomerase by v-Rel in lymphocytes was also accompanied by inactivation of nuclear inhibitors. The inhibition of telomerase activity in v-Rel-transformed cell lines led to apoptosis within 24 h. The expression of v-Rel in a macrophage cell line resulted in elevated levels of reactive oxygen species (ROS), increased telomerase activity, and increased sensitivity to telomerase inhibitors. In contrast, the ectopic expression of TERT decreased the extent of apoptosis induced by ROS. The activation of telomerase by v-Rel may, therefore, partially protect the transformed cells from apoptosis induced by ROS. PMID:16352553

Characterization of the synthesis and expression of the GTA-kinase from transformed and normal rodent cells.

PubMed

Kerr, M; Fischer, J E; Purushotham, K R; Gao, D; Nakagawa, Y; Maeda, N; Ghanta, V; Hiramoto, R; Chegini, N; Humphreys-Beher, M G

1994-08-02

The murine transformed cell line YC-8 and beta-adrenergic receptor agonist (isoproternol) treated rat and mouse parotid gland acinar cells ectopically express cell surface beta 1-4 galactosyltransferase during active proliferation. This activity is dependent upon the expression of the GTA-kinase (p58) in these cells. Using total RNA, cDNA clones for the protein coding region of the kinase were isolated by reverse transcriptase-PCR cloning. DNA sequence analysis failed to show sequence differences with the normal homolog from mouse cells although Southern blot analysis of YC-8, and a second cell line KI81, indicated changes in the restriction enzyme digestion profile relative to murine cell lines which do not express cell surface galactosyltransferase. The rat cDNA clone from isoproterenol-treated salivary glands showed a high degree of protein and nucleic acid sequence homology to the GTA-kinase from both murine and human sources. Northern blot analysis of YC-8 and a control cell line LSTRA revealed the synthesis of a major 3.0 kb mRNA from both cell lines plus the unique expression of a 4.5 kb mRNA in the YC-8 cells. Reverse transcriptase-PCR of LSTRA and YC-8 confirmed the increased steady state levels of the GTA-kinase mRNA in YC-8. In the mouse, induction of cell proliferation by isoproterenol resulted in a 50-fold increase in steady state mRNA levels for the kinase over the low level of expression in quiescent cells. Expression of the rat 3' untranslated region in rat parotid cells in vitro led to an increased rate of DNA synthesis, cell number an ectopic expression of cell surface galactosyltransferase in the sense orientation. Antisense expression or vector alone did not alter growth characteristics of acinar cells. A polyclonal antibody monospecific to a murine amino terminal peptide sequence revealed a uniform distribution of GTA-kinase over the cytoplasm of acinar and duct cells of control mouse parotid glands. However, upon growth stimulation, kinase was

Mature Luffa Leaves (Luffa cylindrica L.) as a Tool for Gene Expression Analysis by Agroinfiltration

PubMed Central

Błażejewska, Kamila; Kapusta, Małgorzata; Zielińska, Elżbieta; Tukaj, Zbigniew; Chincinska, Izabela A.

2017-01-01

We exploited the potential of cucurbits for ectopic gene expression. Agroinfiltration is a simple and commonly used method to obtain transient expression of foreign genes in plants. In contrast to in vitro transformation techniques, agroinfiltration can be used for genetic modification of mature plant tissues. Although the cucurbits are commonly used as model plants for molecular biology and biotechnology studies, to date there are no literature sources on the possibility of transient gene expression in mature cucurbit tissues. Our research has shown that mature leaves of Luffa cylindrica L. (luffa), in contrast to other cucurbit species, can be successfully transiently transformed with Agrobacterium tumefaciens. We efficiently transformed luffa leaves with a reporter gene encoding β-glucuronidase (GUS). The GUS activity in transiently transformed leaf tissues was detected within 24 h after the infiltration with bacteria. Additionally, we have shown that the activity of a transiently expressed the GUS gene can be monitored directly in the EDTA-exudates collected from the cut petioles of the agroinfiltrated leaves. The results suggest that luffa leaves can be useful as a plant expression system for studies of physiological and biochemical processes in cucurbits. PMID:28270826

Analysis of Expression Pattern and Genetic Deletion of Netrin5 in the Developing Mouse

PubMed Central

Garrett, Andrew M.; Jucius, Thomas J.; Sigaud, Liam P. R.; Tang, Fu-Lei; Xiong, Wen-Cheng; Ackerman, Susan L.; Burgess, Robert W.

2016-01-01

Boundary cap cells (BCC) are a transient, neural-crest-derived population found at the motor exit point (MEP) and dorsal root entry zone (DREZ) of the embryonic spinal cord. These cells contribute to the central/peripheral nervous system (CNS/PNS) boundary, and in their absence neurons and glia from the CNS migrate into the PNS. We found Netrin5 (Ntn5), a previously unstudied member of the netrin gene family, to be robustly expressed in BCC. We generated Ntn5 knockout mice and examined neurodevelopmental and BCC-related phenotypes. No abnormalities in cranial nerve guidance, dorsal root organization, or sensory projections were found. However, Ntn5 mutant embryos did have ectopic motor neurons (MNs) that migrated out of the ventral horn and into the motor roots. Previous studies have implicated semaphorin6A (Sema6A) in BCC signaling to plexinA2 (PlxnA2)/neuropilin2 (Nrp2) in MNs in restricting MN cell bodies to the ventral horn, particularly in the caudal spinal cord. In Ntn5 mutants, ectopic MNs are likely to be a different population, as more ectopias were found rostrally. Furthermore, ectopic MNs in Ntn5 mutants were not immunoreactive for NRP2. The netrin receptor deleted in colorectal cancer (DCC) is a potential receptor for NTN5 in MNs, as similar ectopic neurons were found in Dcc mutant mice, but not in mice deficient for other netrin receptors. Thus, Ntn5 is a novel netrin family member that is expressed in BCC, functioning to prevent MN migration out of the CNS. PMID:26858598