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Sample records for caudal proliferating growth

  1. Caudal bupivacaine supplemented with caudal or intravenous clonidine in children undergoing hypospadias repair

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing; Henneberg, Steen Winther; Walther-Larsen, Søren

    2004-01-01

    Clonidine is used increasingly in paediatric anaesthetic practice to prolong the duration of action of caudal block with a local anaesthetic agent. Which route of administration of clonidine is the most beneficial remains unknown. We compared the effects of caudal and i.v. clonidine on postoperat...... on postoperative analgesia produced by caudal bupivacaine after hypospadias repair....

  2. The caudal septum replacement graft.

    Science.gov (United States)

    Foda, Hossam M T

    2008-01-01

    To describe a technique for reconstructing the lost tip support in cases involving caudal septal and premaxillary deficiencies. The study included 120 patients with aesthetic and functional nasal problems resulting from the loss of caudal septal and premaxillary support. An external rhinoplasty approach was performed to reconstruct the lost support using a cartilaginous caudal septum replacement graft and premaxillary augmentation with Mersilene mesh. The majority of cases (75%) involved revisions in patients who had previously undergone 1 or more nasal surgical procedures. A caudal septum replacement graft was combined with premaxillary augmentation in 93 patients (77.5%). The mean follow-up period was 3 years (range, 1-12 years). The technique succeeded in correcting the external nasal deformities in all patients and resulted in a significant improvement in breathing in 74 patients (86%) with preoperative nasal obstruction. There were no cases of infection, displacement, or extrusion. The caudal septum replacement graft proved to be very effective in restoring the lost tip support in patients with caudal septal deficiency. Combining the graft with premaxillary augmentation using Mersilene mesh helped increase support and stability over long-term follow-up.

  3. Five cases of caudal regression with an aberrant abdominal umbilical artery: Further support for a caudal regression-sirenomelia spectrum.

    Science.gov (United States)

    Duesterhoeft, Sara M; Ernst, Linda M; Siebert, Joseph R; Kapur, Raj P

    2007-12-15

    Sirenomelia and caudal regression have sparked centuries of interest and recent debate regarding their classification and pathogenetic relationship. Specific anomalies are common to both conditions, but aside from fusion of the lower extremities, an aberrant abdominal umbilical artery ("persistent vitelline artery") has been invoked as the chief anatomic finding that distinguishes sirenomelia from caudal regression. This observation is important from a pathogenetic viewpoint, in that diversion of blood away from the caudal portion of the embryo through the abdominal umbilical artery ("vascular steal") has been proposed as the primary mechanism leading to sirenomelia. In contrast, caudal regression is hypothesized to arise from primary deficiency of caudal mesoderm. We present five cases of caudal regression that exhibit an aberrant abdominal umbilical artery similar to that typically associated with sirenomelia. Review of the literature identified four similar cases. Collectively, the series lends support for a caudal regression-sirenomelia spectrum with a common pathogenetic basis and suggests that abnormal umbilical arterial anatomy may be the consequence, rather than the cause, of deficient caudal mesoderm. (c) 2007 Wiley-Liss, Inc.

  4. Caudal bupivacaine supplemented with caudal or intravenous clonidine in children undergoing hypospadias repair: a double-blind study

    DEFF Research Database (Denmark)

    Hansen, T G; Henneberg, S W; Walther-Larsen, S

    2004-01-01

    Clonidine is used increasingly in paediatric anaesthetic practice to prolong the duration of action of caudal block with a local anaesthetic agent. Which route of administration of clonidine is the most beneficial remains unknown. We compared the effects of caudal and i.v. clonidine on postoperat...... on postoperative analgesia produced by caudal bupivacaine after hypospadias repair....

  5. Effects of growth-promoting factors on proliferation of mouse ...

    African Journals Online (AJOL)

    AJL

    2012-02-16

    Feb 16, 2012 ... Key words: Growth-promoting factors, mouse spermatogonial stem cells (SSCs), proliferation. INTRODUCTION ... insulin-like growth factor-1 (IGF-1) can stimulate mitotic ...... A Model for Analysis of Spermatogenesis. Zool. Sci.

  6. Caudal regression syndrome : a case report

    International Nuclear Information System (INIS)

    Lee, Eun Joo; Kim, Hi Hye; Kim, Hyung Sik; Park, So Young; Han, Hye Young; Lee, Kwang Hun

    1998-01-01

    Caudal regression syndrome is a rare congenital anomaly, which results from a developmental failure of the caudal mesoderm during the fetal period. We present a case of caudal regression syndrome composed of a spectrum of anomalies including sirenomelia, dysplasia of the lower lumbar vertebrae, sacrum, coccyx and pelvic bones,genitourinary and anorectal anomalies, and dysplasia of the lung, as seen during infantography and MR imaging

  7. Caudal regression syndrome : a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Joo; Kim, Hi Hye; Kim, Hyung Sik; Park, So Young; Han, Hye Young; Lee, Kwang Hun [Chungang Gil Hospital, Incheon (Korea, Republic of)

    1998-07-01

    Caudal regression syndrome is a rare congenital anomaly, which results from a developmental failure of the caudal mesoderm during the fetal period. We present a case of caudal regression syndrome composed of a spectrum of anomalies including sirenomelia, dysplasia of the lower lumbar vertebrae, sacrum, coccyx and pelvic bones,genitourinary and anorectal anomalies, and dysplasia of the lung, as seen during infantography and MR imaging.

  8. A caudal proliferating growth center contributes to both poles of the forming heart tube

    NARCIS (Netherlands)

    van den Berg, G.; Abu-Issa, R.; de Boer, B.A.; Hutson, M.R.; de Boer, P.A.J.; Soufan, A.T.; Ruijter, J.M.; Kirby, M.L.; van den Hoff, M.J.B.; Moorman, A.F.M.

    2009-01-01

    Recent studies have shown that the primary heart tube continues to grow by addition of cells from the coelomic wall. This growth occurs concomitantly with embryonic folding and formation of the coelomic cavity, making early heart formation morphologically complex. A scarcity of data on localized

  9. Caudal ropivacaine in infants

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing; Ilett, K F; Reid, C

    2001-01-01

    Ropivacaine is a new long-acting amino-amide local anesthetic. However, there are no data on its use in infants. In the current study, the authors investigated the pharmacokinetics of caudal ropivacaine in 30 infants younger than 12 months.......Ropivacaine is a new long-acting amino-amide local anesthetic. However, there are no data on its use in infants. In the current study, the authors investigated the pharmacokinetics of caudal ropivacaine in 30 infants younger than 12 months....

  10. Genetics Home Reference: caudal regression syndrome

    Science.gov (United States)

    ... umbilical artery: Further support for a caudal regression-sirenomelia spectrum. Am J Med Genet A. 2007 Dec ... AK, Dickinson JE, Bower C. Caudal dysgenesis and sirenomelia-single centre experience suggests common pathogenic basis. Am ...

  11. Ontogenetic scaling of caudal fin shape in Squalus acanthias (Chondrichthyes, Elasmobranchii): a geometric morphometric analysis with implications for caudal fin functional morphology.

    Science.gov (United States)

    Reiss, Katie L; Bonnan, Matthew F

    2010-07-01

    The shark heterocercal caudal fin and its contribution to locomotion are of interest to biologists and paleontologists. Current hydrodynamic data show that the stiff dorsal lobe leads the ventral lobe, both lobes of the tail are synchronized during propulsion, and tail shape reflects its overall locomotor function. Given the difficulties surrounding the analysis of shark caudal fins in vivo, little is known about changes in tail shape related to ontogeny and sex in sharks. A quantifiable analysis of caudal fin shape may provide an acceptable proxy for inferring gross functional morphology where direct testing is difficult or impossible. We examined ontogenetic and sex-related shape changes in the caudal fins of 115 Squalus acanthias museum specimens, to test the hypothesis that significant shape changes in the caudal fin shape occur with increasing size and between the sexes. Using linear and geometric morphometrics, we examined caudal shape changes within the context of current hydrodynamic models. We found no statistically significant linear or shape difference between sexes, and near-isometric scaling trends for caudal dimensions. These results suggest that lift and thrust increase linearly with size and caudal span. Thin-plate splines results showed a significant allometric shape change associated with size and caudal span: the dorsal lobe elongates and narrows, whereas the ventral lobe broadens and expands ventrally. Our data suggest a combination of caudal fin morphology with other body morphology aspects, would refine, and better elucidate the hydrodynamic factors (if any) that underlie the significant shape changes we report here for S. acanthias.

  12. Fibroblast growth factor-mediated proliferation of central nervous system precursors depends on endogenous production of insulin-like growth factor I

    International Nuclear Information System (INIS)

    Drago, J.; Murphy, M.; Carroll, S.M.; Harvey, R.P.; Bartlett, P.F.

    1991-01-01

    Fibroblast growth factor stimulates proliferation and subsequent differentiation of precursor cells isolated from the neuroepithelium of embryonic day 10 mice in vitro. Here we show that fibroblast growth factor-induced proliferation is dependent on the presence of insulin-like growth factors (IGFs) and that IGF-I is endogenously produced by the neuroepithelial cells. Blocking of endogenous IGF-I activity with anti-IGF-I antibodies results in complete inhibition of fibroblast growth factor-mediated proliferation and in cell death. IGF-I alone acts as a survival agent. These observations correlate with the detection of transcripts for IGF-I and basic fibroblast growth factor in freshly isolated neuroepithelium and are consistent with an autocrine action of these factors in early brain development in vivo

  13. The anatomy and histology of caudal autotomy and regeneration in lizards.

    Science.gov (United States)

    Gilbert, Emily A B; Payne, Samantha L; Vickaryous, Matthew K

    2013-01-01

    Abstract Caudal autotomy-the ability to self-detach the tail-is a dramatic adaptation common to many structural-grade lizards. For most species, tail loss is followed by the equally dramatic phenomenon of tail regeneration. Here we review the anatomy and histology of caudal autotomy and regeneration in lizards, drawing heavily from research published over the past 2 decades. The autotomous tail is characterized by various structural adaptations, which act to minimize blood loss and trauma to adjacent tissues. The early phase of wound healing involves a leukocytic response but limited inflammation. Reepithelialization via a specialized wound epithelium is not only critical for scar-free healing but also necessary for subsequent tissue patterning and regenerative outgrowth. Regeneration begins with the formation of the blastema, a mass of proliferating mesenchymal-like cells. As the blastema expands, it is invaded by blood vessels and the spinal cord. Whereas the replacement tail outwardly resembles the original appendage, it differs in several notable respects, including the tissue composition and organization of the skeleton, muscular system, and spinal cord. Increasingly, the lizard tail is being recognized among biomedical scientists as an important model for the study of wound healing and multitissue restoration.

  14. Traction suture modification to tongue-in-groove caudal septoplasty.

    Science.gov (United States)

    Indeyeva, Y A; Lee, T S; Gordin, E; Chan, D; Ducic, Y

    2018-02-01

    Caudal septal deviation leads to unfavorable esthetic as well as functional effects on the nasal airway. A modification to the tongue-in-groove (TIG) technique to correct these caudal septal deformities is described. With placement of a temporary suspension suture to the caudal septum, manual traction is applied, assuring that the caudal septum remains in the midline position while it is being secured with multiple through-and-through, trans-columellar and trans-septal sutures. From 2003 to 2016, 148 patients underwent endonasal septoplasty using this modified technique, with excellent functional and cosmetic outcomes and a revision rate of 1.4%. This modified TIG technique replaces the periosteal suture that secures the caudal septum to the midline nasal crest in the original TIG technique. This simplifies the procedure and minimizes the risk of securing the caudal septum off-midline when used in endonasal septoplasty. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  15. Development of the caudal exoskeleton of the pliomerid trilobite Hintzeia plicamarginis new species

    Science.gov (United States)

    Simpson, A.G.; Hughes, N.C.; Kopaska-Merkel, D. C.; Ludvigsen, R.

    2005-01-01

    The later juvenile ontogeny of the caudal plate of the early Ordovician pliomerid trilobite Hintzeia plicamarginis new species likely comprised an initial phase during which the rate of appearance of new segments subterminally exceeded that of segment release into the thorax, a short phase of constant segment numbers, and a later phase during which release occurred but in which no new segments appeared. A distinct terminal region became manifest in the second phase. During the second and third phases growth coefficients for individual segments were about 1.1-1.2 per instar. Although the shapes of segments varied during growth, the pattern of ontogenetic shape change appears to have been broadly similar among segments. This suggests an homonomous trunk segment morphology regardless of thoracic or caudal identity in maturity. These results imply that control of trunk exoskeletal segment appearance and articulation were decoupled in this trilobite, and that the terminal region had a distinct mature morphology. H. plicamarginis is described as a new species. ?? Blackwell Publishing, Inc.

  16. Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1980-01-01

    The influence of two prostaglandin (PG) analogues, 16,16-dimethyl PG E2 and 16,16-dimethyl PG F2 alpha and of the cyclo-oxygenase inhibitor, flurbiprofen, on epithelial cell proliferation was assessed using a stathmokinetic technique. The epithelia examined were those of the jejunal crypts, the colonic crypts and that of dimethylhydrazine-induced adenocarcinomas of rat colon. The influence of the two prostaglandin analogues, and of flurbiprofen, on the growth of a human colorectal tumour propagated as xenografts in immune-deprived mice was also assessed. The PG E2 analogue transiently inhibited xenograft growth, but was without effect on the mitotic rate in the rat tissues. The PG F2 alpha analogue was also found to inhibit xenograft growth but, unlike the PG E2 analogue, it was found to be a strong inhibitor of cell proliferation in rat colonic tumours, and an accelerator of proliferation in jejunal-crypt cells. The only statistically significant effect of flurbiprofen was to accelerate cell division in the rat colonic tumours.

  17. Tumor cell proliferation kinetics and tumor growth rate

    Energy Technology Data Exchange (ETDEWEB)

    Tubiana, M

    1989-01-01

    The present knowledge on the growth rate and the proliferation kinetics of human tumor is based on the measurement of the tumor doubling times (DT) in several hundred patients and on the determination of the proportion of proliferating cells with radioactive thymidine or by flow cytometry in large numbers of patients. The results show that the DT of human tumor varies widely, from less than one week to over one year with a median value of approximately 2 months. The DTs are significantly correlated with the histological type. They depend upon (1) the duration of the cell cycle whose mean duration is 2 days with small variations from tumor to tumor, (2) the proportion of proliferating cells and consequently the cell birth rate which varies widely among tumors and which is significantly correlated to the DT, (3) the cell loss factors which also vary widely and which are the greatest when proliferation is most intensive. These studies have several clinical implications: (a) they have further increased our understanding of the natural history of human tumor, (b) they have therapeutic implications since tumor responsiveness and curability by radiation and drugs are strongly influenced by the cell kinetic parameters of the tumor, (c) the proportion of proliferating cells is of great prognostic value in several types of human cancers. The investigation of the molecular defects, which are correlated with the perturbation of control of cell proliferation, should lead to significant fundamental and therapeutic advances. (orig.).

  18. The role of hormones and growth factors in the cellular proliferation control in mammals

    International Nuclear Information System (INIS)

    Armelin, H.A.

    1978-01-01

    A review is done about fibroblast proliferation, its control by classic hormones and hormonal growth factors, showing their main implications and the stage of this research at present. The control exerted on fibronlast proliferation by hormonal growth factors and classic hormones is demonstrated. The existence of basic mechanisms valid for all types of cells is suggested. Experiences are carried out with the aim of finding growth mutants useful in the elucidation of the biochemical mechanisms involved in growth regulation. Radiactive precursors and autoradiographic techniques are used in the research. (M.A.) [pt

  19. Cyclophilin A enhances cell proliferation and tumor growth of liver fluke-associated cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Sawanyawisuth Kanlayanee

    2011-08-01

    Full Text Available Abstract Background Cyclophilin A (CypA expression is associated with malignant phenotypes in many cancers. However, the role and mechanisms of CypA in liver fluke-associated cholangiocarcinoma (CCA are not presently known. In this study, we investigated the expression of CypA in CCA tumor tissues and CCA cell lines as well as regulation mechanisms of CypA in tumor growth using CCA cell lines. Methods CypA expression was determined by real time RT-PCR, Western blot or immunohistochemistry. CypA silence or overexpression in CCA cells was achieved using gene delivery techniques. Cell proliferation was assessed using MTS assay or Ki-67 staining. The effect of silencing CypA on CCA tumor growth was determined in nude mice. The effect of CypA knockdown on ERK1/2 activation was assessed by Western blot. Results CypA was upregulated in 68% of CCA tumor tissues. Silencing CypA significantly suppressed cell proliferation in several CCA cell lines. Likewise, inhibition of CypA peptidyl-prolyl cis-trans isomerase (PPIase activity using cyclosporin A (CsA decreased cell proliferation. In contrast, overexpression of CypA resulted in 30% to 35% increases in proliferation of CCA cell lines. Interestingly, neither silence nor overexpression of CypA affected cell proliferation of a non-tumor human cholangiocyte cell line, MMNK1. Suppression of CypA expression attenuated ERK1/2 activity in CCA M139 cells by using both transient and stable knockdown methods. In the in vivo study, there was a 43% reduction in weight of tumors derived from CypA-silenced CCA cell lines compared with control vector CCA tumors in mice; these tumors with stable CypA silencing showed a reduced cell proliferation. Conclusions CypA is upregulated in majority of CCA patients' tissues and confers a significant growth advantage in CCA cells. Suppression of CypA expression decreases proliferation of CCA cell lines in vitro and reduces tumor growth in the nude mouse model. Inhibition of Cyp

  20. Comparison between the intravenous and caudal routes of sufentanil in children undergoing orchidopexy and further evaluation of the association of caudal adrenaline and neostigmine

    Directory of Open Access Journals (Sweden)

    Gabriela Rocha Lauretti

    2014-01-01

    Full Text Available Background: The aim of this study was to compare the intravenous (IV and caudal routes of administration of sufentanil for children undergoing orchidopexy and also to evaluate the effects on addition of caudal adrenaline and neostigmine. Materials and Methods: Sixty patients scheduled for orchidopexy were divided into the following groups: 1 Group IVSu received IV 0.5 μg/kg sufentanil and caudal saline; 2 Group CSu received caudal 0.5 μg/kg sufentanil and IV saline; 3 Group CSuAdr received caudal sufentanil plus adrenaline 5 μg/ml (1:200,000 and IV saline; 4 Group CSuNeo received caudal sufentanil plus neostigmine, and IV saline; and 5 Group CSuNeoAdr received caudal sufentanil plus neostigmine plus adrenaline, and IV saline. Heart rate and mean blood pressure >15% was treated with increasing isoflurane concentration. Consumption of isoflurane, side effects, quality of sleep, time to first administration of analgesic, and number of doses of 24-h rescue analgesic were recorded. Results: Groups were demographically similar. Isoflurane consumption showed the following association: Group IVSu = Group CSuNeo = Group CSuNeoAdr Group CSuNeo = Group CSuNeoAdr (P < 0.005. Incidence of adverse effects was similar among groups. Conclusion: Caudal sufentanil alone was no better than when administered in the IV route, and would just be justified by the association of neostigmine, but not adrenaline. Neostigmine association resulted in better perioperative analgesia.

  1. Eletrophysiological study of the caudal nerve on developing rats Estudo eletrofisiológico do nervo caudal em ratos em desenvolvimento

    Directory of Open Access Journals (Sweden)

    Juliana Netto Maia

    2010-04-01

    Full Text Available PURPOSE: To non-invasively study the sensory nerve conduction of the caudal nerve of normal developing rats. METHODS: Twenty normal Wistar male rats served as subjects. Caudal nerve conduction studies were performed at 60 days from birth and weekly at end of six consecutive weeks. The caudal nerve was stimulated distally and nerve potentials were recorded proximally on the animal's tail using common "alligator" clips as surface electrodes. RESULTS: The amplitude and the conduction velocity of the caudal nerve sensory action potential increased linearly from 29±6 µV to 85±13 µV and from 34±3 m/s to 44±4 m/s, respectively, between the 8th and the 15th week of life. The equations of linear regressions were as followed: Amplitude (µV = 8.1 × weeks - 34 (R² = 0.99 and NCV (m/s = 1.2 × weeks + 25 (R² = 0.86. CONCLUSIONS: It was possible to study non-invasively the sensitive conduction of the caudal nerve of normal developing rats and describe reference values. The technique and data may be used as animal model in physiological and pathological studies.OBJETIVO: Estudar de forma não invasiva a condução nervosa sensitiva do nervo caudal em ratos normais em desenvolvimento. MÉTODOS: Vinte ratos machos Wistar foram utilizados. A conducão nervosa foi realizada a partir dos 60 dias, semanal durante seis semanas consecutivas. O nervo caudal foi estimulado distalmente, os potenciais foram registrados proximalmente na cauda do animal usando garras comum do tipo "jacaré" como eletrodos de superficie. RESULTADOS: A amplitude do potencial de ação de nervo sensitivo a velocidade de condução nervosa do nervo caudal cresceu linearmente de 29 ± 6 µV para 85 ± 13 µV e de 34 ± 3 m/s para 44 ± 4 m/s, respectivamente, entre a 8º e a 15º semana da vida do animal. As equações de regressão linear foram as seguintes: Amplitude (µV = 8,1 × semanas - 34 (R² = 0,99 e velocidade de conducao nervosa (m/s = 1,2 × semanas + 25 (R² = 0

  2. Caudal anesthesia in pediatric surgical practice.

    Science.gov (United States)

    Rahman, S; Siddiqui, M A; Haque, M; Majumder, S K; Ali, M S; Majid, M A; Hasan, M R

    2006-07-01

    Prospective study was carried out on 100 patients since May 2005 in my private practice and in the department of pediatric surgery of MMCH. Under caudal anesthesia along with or without ketaminie induction and gas inhalation all the patients underwent different surgical procedure namely anorectal surgery (eg. anoplasty, rectal polyp), urogenital surgery (Circumcision, hypospadias, meatotomy), groin surgery (hernia, hydrocele) and foot & leg surgery. Calculated dose schedule of drugs used in anesthesia and volume were maintained. Time of giving anesthesia and time of starting analgesia were recorded. Per-operative and postoperative analgesia were evaluated. Every parent was explained regarding the merit of caudal anesthesia calculated and compared with that of general anesthesia. Application of caudal anesthesia with or without ketamine & diazepam induction can be used safely and cost effectively and may be put into protocol in many of the pediatric surgical practice both in institute and also in private practice.

  3. Plasma rich in growth factors promotes dermal fibroblast proliferation, migration and biosynthetic activity.

    Science.gov (United States)

    Anitua, E; Pino, A; Orive, G

    2016-11-02

    The use of plasma rich in growth factors (PRGF) has gained importance in many medical fields due to its regenerative potential. The aim of this study is to evaluate the effects of PRGF on primary skin fibroblasts assessing cell proliferation, migration and secretion of growth factors. The age of the patients from who PRGF was prepared was also studied to determine whether it influenced the outcomes. Human dermal fibroblasts were isolated from three healthy volunteers. Using PRGF-Endoret technology, PRGF was prepared from two groups of different ages (18-35 years and 50+ years). The effects of increasing concentration of PRGF (5%, 10% and 20%) on cell proliferation and migration was evaluated. Biosynthetic behaviour of cells was also analysed measuring vascular endothelial growth factor (VEGF), transforming growth factor b1 (TGFb1) and pro-collagen type I secreted levels with or without PRGF treatment. Mean platelet enrichment reached 2.4X and 2X in 18-35 and 50+ groups respectively. A dose-dependent response was observed in proliferation assays achieving the highest levels with 20% PRGF. Migration was also promoted in cells but not in a dose-dependent manner. Cell proliferation and migration outcomes obtained with PRGF (from both groups) were significantly higher compared to non-stimulated groups (pPRGF, however, with the exception of VEGF, no statistical significances were observed between the different age groups. Results from this study concluded that PRGF is safe and effective in stimulating skin regeneration by enhancing proliferation, migration and expression of pivotal bioactive molecules involved in wound healing and haemostasis.

  4. Caudal epidural anesthesia during intracavitary brachytherapy for cervical cancer

    International Nuclear Information System (INIS)

    Isoyama-Shirakawa, Yuko; Abe, Madoka; Nakamura, Katsumasa

    2015-01-01

    It has been suggested that pain control during intracavitary brachytherapy for cervical cancer is insufficient in most hospitals in Japan. Our hospital began using caudal epidural anesthesia during high-dose-rate (HDR) intracavitary brachytherapy in 2011. The purpose of the present study was to retrospectively investigate the effects of caudal epidural anesthesia during HDR intracavitary brachytherapy for cervical cancer patients. Caudal epidural anesthesia for 34 cervical cancer patients was performed during HDR intracavitary brachytherapy between October 2011 and August 2013. We used the patients' self-reported Numeric Rating Scale (NRS) score at the first session of HDR intracavitary brachytherapy as a subjective evaluation of pain. We compared NRS scores of the patients with anesthesia with those of 30 patients who underwent HDR intracavitary brachytherapy without sacral epidural anesthesia at our hospital between May 2010 and August 2011. Caudal epidural anesthesia succeeded in 33 patients (97%), and the NRS score was recorded in 30 patients. The mean NRS score of the anesthesia group was 5.17 ± 2.97, significantly lower than that of the control group's 6.80 ± 2.59 (P = 0.035). The caudal epidural block resulted in no side-effects. Caudal epidural anesthesia is an effective and safe anesthesia option during HDR intracavitary brachytherapy for cervical cancer. (author)

  5. Bryostatin I inhibits growth and proliferation of pancreatic cancer ...

    African Journals Online (AJOL)

    Purpose: To evaluate the effect of bryostatin I on proliferation of pancreatic cancer cells as well as tumor growth in mice tumor xenograft model. Methods: Activation of NF-κB was evaluated by preparing nuclear material extract using nuclear extract kit (Carlsbad, CA, USA) followed by enzyme-linked immunosorbent assay ...

  6. Sindrome de regresión caudal

    OpenAIRE

    Maldonado, A.; Pastor, A.; Sorni, A.; Pastor Durán, Xavier; Palomeque,A.

    1995-01-01

    El síndrome de regresión caudal o de agenesia sacra se caracteriza por un déficit funcional de los esfínteres y de la muscultatura de los miembros inferiores. Se suele asociar con otras malformaciones, como son las esqueléticas, genitourinarias y del tracto intestinal. La diabetes mellitus materna es uno de los factores predisponentes más destacados. Aquí se presenta un caso de síndrome de regresión caudal con insufiencia renal secundaria a la uropatía malformativa asociada. Se comentan los d...

  7. Caudal analgesia for herniotomy: Comparative evaluation of two ...

    African Journals Online (AJOL)

    Objective: There is currently a wide range of volume schemes for bupivacaine caudal anesthesia. This study evaluated the quality of caudal analgesia achieved with a dosing scheme of 0.75 ml/kg compared with 0.5 ml/kg of 0.25% plain bupivacaine for herniotomy. Methods: After the institutional approval, American Society ...

  8. Parotid salivary duct stenosis following caudal maxillectomy.

    Science.gov (United States)

    Mestrinho, Lisa A; Faísca, Pedro B; Niza, Maria M R E

    2014-01-01

    Parotid salivary duct dilation was diagnosed in a 9-year-old male dog. The dog had undergone caudal maxillectomy on the ipsilateral side 2-years prior to presentation. Treatment consisted of parotid salivary duct excision and superficial parotidectomy that lead to the resolution of clinical signs. Transient facial neuropraxia was observed immediately after surgery and resolved spontaneously after 2-weeks. Parotid salivary duct dilation should be considered as a chronic postoperative complication following caudal maxillectomy.

  9. Actuation of a robotic fish caudal fin for low reaction torque

    Science.gov (United States)

    Yun, Dongwon; Kim, Kyung-Soo; Kim, Soohyun; Kyung, Jinho; Lee, Sunghee

    2011-07-01

    In this paper, a novel caudal fin for actuating a robotic fish is presented. The proposed caudal fin waves in a vertical direction with a specific spatial shape, which is determined by a so-called shape factor. For a specific shape factor, a traveling wave with a vertical phase difference is formed on a caudal fin during fin motion. It will be shown by the analysis that the maximum reaction torque at the joint of a caudal fin varies depending on the shape factors. Compared with a conventional plate type caudal fin, the proposed fin with a shape factor of 2π can eliminate the reaction torque perfectly, while keeping the propulsion force unchanged. The benefits of the proposed fin will be demonstrated by experiments.

  10. Comparison of collagen fibre architecture between slow-twitch cranial and fast-twitch caudal parts of broiler M. latissimus dorsi.

    Science.gov (United States)

    Nakamura, Y N; Iwamoto, H; Tabata, S; Ono, Y

    2003-07-01

    1. Collagen fibre architectures of perimysium and endomysium in the slow-twitch cranial and fast-twitch caudal parts of broiler M. latissimus dorsi were compared. 2. Type I and III collagens were distributed in both perimysium and endomysium as indicated by their positive immunohistochemical reactions to polyclonal antibodies. 3. Cells invested by endomysium with no myofibres were larger in the cranial part because of the presence of larger slow-twitch myofibres. The honeycomb structure of endomysium was divided into several parts by thick perimysium. 4. The thick perimysial collagen fibres with parallel fibrils, which were interconnected by the loose reticular fibrils and thin fibres, were more numerous and thicker in the cranial part than the caudal. 5. Thick endomysial sidewall of cells in the cranial part was composed of a rougher reticulum of slightly thicker collagen fibrils compared with the thin sidewall in the caudal part. 6. These results indicated that both perimysial constitutions of collagen fibres and endomysial collagen fibrils had attained much larger growth in the slow-twitch cranial part than the fast-twitch caudal in broiler latissimus dorsi muscle.

  11. Regulation of proliferation of embryonic heart mesenchyme: Role of transforming growth factor-beta 1 and the interstitial matrix

    International Nuclear Information System (INIS)

    Choy, M.; Armstrong, M.T.; Armstrong, P.B.

    1990-01-01

    Proliferation of atrioventricular cushion mesenchyme of the embryonic avian heart maintained in three-dimensional aggregate culture is stimulated by interaction with the interstitial matrix. Chicken serum or transforming growth factor-beta 1, which stimulates proliferation, induces matrix deposition in regions of the aggregate showing high labeling indices with tritiated thymidine. Dispersed heart mesenchyme interstitial matrix introduced into serum-free culture is incorporated into the aggregate and stimulates cellular proliferation similar to serum or transforming growth factor-beta 1. Proliferation is reversibly inhibited by the peptide Gly-Arg-Gly-Asp-Ser-Pro. It is suggested that transforming growth factor-beta 1 stimulates the production of interstitial matrix and that a sufficient stimulus for proliferation in this system is the presence of the matrix, which acts as the adhesive support for cellular anchorage

  12. Caudal Septal Stabilization Suturing Technique to Treat Crooked Noses.

    Science.gov (United States)

    Baykal, Bahadir; Erdim, Ibrahim; Guvey, Ali; Oghan, Fatih; Kayhan, Fatma Tulin

    2016-10-01

    To rotate the nasal axis and septum to the midline using an L-strut graft and a novel caudal septal stabilization suturing technique to treat crooked noses. Thirty-six patients were included in the study. First, an L-strut graft was prepared by excising the deviated cartilage site in all patients. Second, multiple stabilization suturing, which we describe as a caudal septal stabilization suturing technique with a "fishing net"-like appearance, was applied between the anterior nasal spine and caudal septum in all patients. This new surgical technique, used to rotate the caudal septum, was applied to 22 I-type and 14 C-type crooked noses. Correction rates for the crooked noses were compared between the 2 inclination types with angular estimations. Deviation angles were measured using the AutoCAD 2012 software package and frontal (anterior) views, with the Frankfurt horizontal line parallel to the ground. Nasal axis angles showing angle improvement graded 4 categories as excellent, good, acceptable, and unsuccessful for evaluations at 6 months after surgery in the study. The success rate in the C-type nasal inclination was 86.7% (±21.9) and 88% (±16.7) in the I-type. The overall success rate of L-strut grafting and caudal septal stabilization suturing in crooked nose surgeries was 87.5% (±18.6). "Unsuccessful" results were not reported in any of the patients. L-strut grafting and caudal septal stabilization suturing techniques are efficacious in crooked noses according to objective measurement analysis results. However, a longer follow-up duration in a larger patient population is needed.

  13. Induction of growth and proliferation of fibroblast cells in magnetic field

    Directory of Open Access Journals (Sweden)

    Naghmeh Ezatti

    2015-02-01

    Full Text Available Background: Tissue engineering is generally defined as developing and changing the laboratory growth of molecules and cells in tissues or organs to replace and repair the damaged part of body. This study was carried out to stimulate the growth of cultured fibroblast cells by a physical electromagnetic method. Methods: First, an air-core coil was prepared and the cell culture plate was placed comfortably into the mold, then the plate containing the culture medium and human fibroblast cell along with air-core coil were placed in an incubator and then connected to the power supply. Thus, the sample underwent electromagnetic field at different times, and cell proliferation was studied by MTTassay. Results: Microscopic images indicated that the cells undergoing electromagnetic field (0.35 amps had a significant growth compared to the cells in control group in a definit range of stimulation. Conclusion: In conclusion, electromagnetic stimulation in a definite range led to cell proliferation and could be used as a positive factor in tissue engineering.

  14. Sensory nerve conduction in the caudal nerves of rats with diabetes Condução nervosa sensorial no nervo caudal de ratos com diabetes experimental

    OpenAIRE

    Celina Cordeiro de Carvalho; Juliana Netto Maia; Otávio Gomes Lins; Sílvia Regina Arruda de Moraes

    2011-01-01

    PURPOSE: To investigate sensory nerve conduction of the caudal nerve in normal and diabetic rats. METHODS: Diabetes was induced in twenty 8-weeks old Wistar male rats. Twenty normal rats served as controls. Caudal nerve conduction studies were made before diabetes induction and the end of each week for six consecutive weeks. The caudal nerve was stimulated distally and nerve potentials were recorded proximally on the animal's tail using common "alligator" clips as surface electrodes. RESULTS:...

  15. Platelet-released growth factors inhibit proliferation of primary keratinocytes in vitro.

    Science.gov (United States)

    Bayer, Andreas; Tohidnezhad, Mersedeh; Berndt, Rouven; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Jahr, Holger; Cremer, Jochen; Rademacher, Franziska; Simanski, Maren; Gläser, Regine; Harder, Jürgen

    2018-01-01

    Autologous thrombocyte concentrate lysates as platelet-released growth factors (PRGF) or Vivostat Platelet Rich Fibrin (PRF ® ) represent important tools in modern wound therapy, especially in the treatment of chronic, hard-to-heal or infected wounds. Nevertheless, underlying cellular and molecular mechanisms of the beneficial clinical effects of a local wound therapy with autologous thrombocyte concentrate lysates are poorly understood. Recently, we have demonstrated that PRGF induces antimicrobial peptides in primary keratinocytes and accelerates keratinocytes' differentiation. In the present study we analyzed the influence of PRGF on primary human keratinocytes' proliferation. Using the molecular proliferation marker Ki-67 we observed a concentration- and time dependent inhibition of Ki-67 gene expression in PRGF treated primary keratinocytes. These effects were independent from the EGFR- and the IL-6-R pathway. Inhibition of primary keratinocytes' proliferation by PRGF treatment was confirmed in colorimetric cell proliferation assays. Together, these data indicate that the clinically observed positive effects of autologous thrombocytes concentrates in the treatment of chronic, hard-to-heal wounds are not based on an increased keratinocytes proliferation. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. Prenatal diagnosis of Caudal Regression Syndrome : a case report

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    Celikaslan Nurgul

    2001-12-01

    Full Text Available Abstract Background Caudal regression is a rare syndrome which has a spectrum of congenital malformations ranging from simple anal atresia to absence of sacral, lumbar and possibly lower thoracic vertebrae, to the most severe form which is known as sirenomelia. Maternal diabetes, genetic predisposition and vascular hypoperfusion have been suggested as possible causative factors. Case presentation We report a case of caudal regression syndrome diagnosed in utero at 22 weeks' of gestation. Prenatal ultrasound examination revealed a sudden interruption of the spine and "frog-like" position of lower limbs. Termination of pregnancy and autopsy findings confirmed the diagnosis. Conclusion Prenatal ultrasonographic diagnosis of caudal regression syndrome is possible at 22 weeks' of gestation by ultrasound examination.

  17. Variations in the formation of the human caudal spinal cord.

    Science.gov (United States)

    Saraga-Babić, M; Sapunar, D; Wartiovaara, J

    1995-01-01

    Collection of 15 human embryos between 4-8 developmental weeks was used to histologically investigate variations in the development of the caudal part of the spinal cord and the neighboring axial organs (notochord and vertebral column). In the 4-week embryo, two types of neurulation were parallelly observed along the anteroposterior body axis: primary in the areas cranial to the neuroporus caudalis and secondary in the more caudal tail regions. In the 5-week embryos, both parts of the neural tube fused, forming only one continuous lumen in the developing spinal cord. In the three examined embryos we found anomalous pattern of spinal cord formation. Caudal parts of these spinal cords displayed division of their central canal into two or three separate lumina, each surrounded by neuroepithelial layer. In the caudal area of the spinal cord, derived by secondary neurulation, formation of separate lumina was neither connected to any anomalous notochord or vertebral column formation, nor the appearance of any major axial disturbances. We suggest that development of the caudal part of the spinal cord differs from its cranial region not only in the type of neurulation, but also in the destiny of its derivatives and possible modes of abnormality formation.

  18. Effect of ketoprofen, lidocaine local anesthesia, and combined xylazine and lidocaine caudal epidural anesthesia during castration of beef cattle on stress responses, immunity, growth, and behavior.

    Science.gov (United States)

    Ting, S T L; Earley, B; Hughes, J M L; Crowe, M A

    2003-05-01

    To determine the effects of burdizzo castration alone or in combination with ketoprofen (K), local anesthesia (LA), or caudal epidural anesthesia (EPI) on plasma cortisol, acute-phase proteins, interferon-gamma production, growth, and behavior of beef cattle, 50 Holstein x Friesian bulls (13 mo old, 307 +/- 5.3 kg) were assigned to (n = 10/treatment): 1) control (handled; C); 2) burdizzo castration (B); 3) B following K (3 mg/ kg of BW i.v.; BK); 4) B following LA (8 mL into each testis and 3 mL s.c. along the line where the jaws of the burdizzo were applied with 2% lidocaine HCl; BLA); and 5) B following EPI (0.05 mg/kg of BW of xylazine HCl and 0.4 mg/kg of BW of lidocaine HCl as caudal epidural; BEPI). The area under the cortisol curve against time was lower (P castration groups than in C. On d 7, haptoglobin and fibrinogen concentrations remained higher (P castration increased plasma cortisol and acute-phase proteins, and suppressed immune function and growth rates. Local anesthesia prolonged the increase in acute-phase proteins. Ketoprofen was more effective than LA or EPI in decreasing cortisol and partially reversed the reduction in ADG following castration. The use of K or EPI was more effective than LA in decreasing pain-associated behavioral responses observed during the first 6 h after treatment. Systemic analgesia with ketoprofen, a non-steroidal antiinflammatory drug, was more effective in reducing inflammatory responses associated with castration than LA or EPI.

  19. Sirenomelia and caudal malformations in two families.

    Science.gov (United States)

    Gerard, Marion; Layet, Valérie; Costa, Teresa; Roumazeilles, Yves; Chenal, Pierre; Cailliez, Daniel; Gerard, Bénédicte

    2012-07-01

    We report on two families with co-occurrence of sirenomelia and caudal malformations. In the first family, the mother had undergone surgery for a short form of imperforate anus. Her first pregnancy was terminated because of bilateral renal agenesis with oligohydramnios. Her second pregnancy was interrupted because of sirenomelia. The second family was referred to us because of caudal malformation in their two children. The parents' spinal radiographs were normal. The first pregnancy resulted in a girl with imperforate anus, absence of S3-S5 and coccyx, abnormal pelvic floor, and an almost bifid anteriorly located bladder. The second pregnancy resulted in a baby girl with sirenomelia. No diabetes was present during the pregnancies in either of these two families. These families confirm the hypothesis that major genes are responsible for the embryogenesis of the caudal part of the embryo, with variable expression, as has been already described in sirenomelia mouse models (CYP26A1, BMP7/tsg). Molecular studies are underway in these families and in sporadic cases in our laboratory to explore the genetic basis of sirenomelia in humans. Copyright © 2012 Wiley Periodicals, Inc.

  20. A novel transgenic mouse model of growth plate dysplasia reveals that decreased chondrocyte proliferation due to chronic ER stress is a key factor in reduced bone growth

    Directory of Open Access Journals (Sweden)

    Benedetta Gualeni

    2013-11-01

    Disease mechanisms leading to different forms of chondrodysplasia include extracellular matrix (ECM alterations and intracellular stress resulting in abnormal changes to chondrocyte proliferation and survival. Delineating the relative contribution of these two disease mechanisms is a major challenge in understanding disease pathophysiology in genetic skeletal diseases and a prerequisite for developing effective therapies. To determine the influence of intracellular stress and changes in chondrocyte phenotype to the development of chondrodysplasia, we targeted the expression of the G2320R mutant form of thyroglobulin to the endoplasmic reticulum (ER of resting and proliferating chondrocytes. Previous studies on this mutant protein have shown that it induces intracellular aggregates and causes cell stress and death in the thyroid gland. The expression and retention of this exogenous mutant protein in resting and proliferating chondrocytes resulted in a chronic cell stress response, growth plate dysplasia and reduced bone growth, without inducing any alterations to the architecture and organization of the cartilage ECM. More significantly, the decreased bone growth seemed to be the direct result of reduced chondrocyte proliferation in the proliferative zone of growth plates in transgenic mice, without transcriptional activation of a classical unfolded protein response (UPR or apoptosis. Overall, these data show that mutant protein retention in the ER of resting and proliferative zone chondrocytes is sufficient to cause disrupted bone growth. The specific disease pathways triggered by mutant protein retention do not necessarily involve a prototypic UPR, but all pathways impact upon chondrocyte proliferation in the cartilage growth plate.

  1. Cranial and caudal mesenteric arteries of the paca (Cuniculus paca, L. 1766

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    Isabela Cristina de Souza Marques

    2013-03-01

    Full Text Available The paca (Cuniculus paca, Linnaeus, 1766 is a medium-sized rodent that occurs in Brazil; however, there is little information regarding its morphology. The goal of this study was to describe the origin and branching of the cranial and caudal mesenteric arteries of this rodent in order to contribute to comparative anatomy studies. Ten animals (males and females were used. After death, their thoracic inlet was opened between the fourth and sixth ribs to expose the thoracic aorta, which was cannulated caudally. A stained, neoprene latex solution was then injected, in order to fill the arterial system, and the preparations were fixed in a 10% aqueous formalin solution for over 72h. The fixed specimens were dissected to identify the cranial and caudal mesenteric arteries. The cranial mesenteric artery started at the abdominal aorta, caudally to the celiac artery, and originated in the following arterial branches: caudal pancreatic duodenal, pancreatic, jejunal, ileum colic and cecal. The origin of the caudal mesenteric artery occurred next to the end of abdominal aorta and this vessel issued the left colic artery and cranial rectal artery from which the sigmoid arteries initiated. It was found that there was little difference in the branching pattern of the arteries compared to other rodents and domestic mammals.

  2. Mathematical Model of Growth Factor Driven Haptotaxis and Proliferation in a Tissue Engineering Scaffold

    KAUST Repository

    Pohlmeyer, J. V.

    2013-01-29

    Motivated by experimental work (Miller et al. in Biomaterials 27(10):2213-2221, 2006, 32(11):2775-2785, 2011) we investigate the effect of growth factor driven haptotaxis and proliferation in a perfusion tissue engineering bioreactor, in which nutrient-rich culture medium is perfused through a 2D porous scaffold impregnated with growth factor and seeded with cells. We model these processes on the timescale of cell proliferation, which typically is of the order of days. While a quantitative representation of these phenomena requires more experimental data than is yet available, qualitative agreement with preliminary experimental studies (Miller et al. in Biomaterials 27(10):2213-2221, 2006) is obtained, and appears promising. The ultimate goal of such modeling is to ascertain initial conditions (growth factor distribution, initial cell seeding, etc.) that will lead to a final desired outcome. © 2013 Society for Mathematical Biology.

  3. Characterization of a novel caudal vertebral interbody fusion in a rat tail model: An implication for future material and mechanical testing

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    Yu-Cheng Yeh

    2017-02-01

    Conclusion: The rat caudal disc interbody fusion model proved to be an efficient, repeatable and easily accessible model. Future research into adjuvant treatments like growth factor injection and alternative fusion materials under conditions of osteoporosis using this model would be worthwhile.

  4. DIABETES MELLITUS AND ITS ROLE IN CAUDAL REGRESSION SYNDROME

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    Sandeep

    2016-03-01

    Full Text Available BACKGROUND Caudal regression syndrome also called as sacral agenesis or hypoplasia of the sacrum is a congenital disorder in which there is abnormal development of the lower part of the vertebral column 1 due to which there is a plethora of abnormalities such as gross motor deficiencies and other genitor-urinary malformations which in deed depends on the extent of malformations that is seen. Caudal regression syndrome is rare, with an estimated incidence of 1:7500-100,000. The aim of the study is to find the frequency of manifestations and the manifestations itself. METHODS Fifty patients who were pregnant and were diagnosed with diabetes mellitus were identified and were referred to the Department of Medicine. RESULTS In the present study the frequency of manifestations of caudal regression syndrome is 8 in 100 diagnosed patients. CONCLUSION The malformations in the babies born to diabetic mothers are high in the population of costal Karnataka and Kerala.

  5. Prospective Randomized Controlled Comparison of Caudal ...

    African Journals Online (AJOL)

    Background: Bupivacaine and ropivacaine are commonly used agents for caudal anesthesia in pediatric patients. Several studies have shown different motor and cardiovascular effects of two drugs. Aim: The primary objective of this study was to evaluate the efficacy of both drugs and secondary objective was to compare ...

  6. Sirt6 regulates postnatal growth plate differentiation and proliferation via Ihh signaling.

    Science.gov (United States)

    Piao, Jinying; Tsuji, Kunikazu; Ochi, Hiroki; Iwata, Munetaka; Koga, Daisuke; Okawa, Atsushi; Morita, Sadao; Takeda, Shu; Asou, Yoshinori

    2013-10-23

    Sirtuin 6 (Sirt6) is a mammalian homologue of NAD⁺-dependent histone deacetylase Sir2. Although Sirt6⁻/⁻ mice exhibit growth retardation, the role of Sirt6 in cartilage metabolism is unclear. The aim of this study was to investigate the Sirt6 signaling pathway in cartilage metabolism. Immunohistological evaluation of the tibial growth plate in Sirt6⁻/⁻ mice exhibited impaired proliferation and differentiation of chondrocytes, reduced expression of Indian hedgehog (Ihh), and a senescent phenotype. When Sirt6 was knocked down in chondrocytes in vitro, expression of Ihh and its downstream genes were reduced. Impaired differentiation by Sirt6 silencing was completely rescued by administration of a Hh signal agonist. When sirtuins were activated, chondrocyte differentiation was enhanced together with activation of Ihh signal, and these effects were abrogated by Sirt6 silencing. ChIP assay revealed the affinity of ATF4 to the Ihh promoter was markedly decreased by Sirt6 knockdown. These data indicate Sirt6 directly controls proliferation and differentiation of chondrocytes.

  7. Sprouty2 controls proliferation of palate mesenchymal cells via fibroblast growth factor signaling

    International Nuclear Information System (INIS)

    Matsumura, Kaori; Taketomi, Takaharu; Yoshizaki, Keigo; Arai, Shinsaku; Sanui, Terukazu; Yoshiga, Daigo; Yoshimura, Akihiko; Nakamura, Seiji

    2011-01-01

    Research highlights: → Sprouty2-deficient mice exhibit cleft palate as a result of failure of palatal shelf elevation. → We examined palate cell proliferation in Sprouty2-deficient mice. → Palate mesenchymal cell proliferation was increased in Sprouty2 KO mice. → Sprouty2 plays roles in murine palatogenesis by regulating cell proliferation. -- Abstract: Cleft palate is one of the most common craniofacial deformities. The fibroblast growth factor (FGF) plays a central role in reciprocal interactions between adjacent tissues during palatal development, and the FGF signaling pathway has been shown to be inhibited by members of the Sprouty protein family. In this study, we report the incidence of cleft palate, possibly caused by failure of palatal shelf elevation, in Sprouty2-deficient (KO) mice. Sprouty2-deficient palates fused completely in palatal organ culture. However, palate mesenchymal cell proliferation estimated by Ki-67 staining was increased in Sprouty2 KO mice compared with WT mice. Sprouty2-null palates expressed higher levels of FGF target genes, such as Msx1, Etv5, and Ptx1 than WT controls. Furthermore, proliferation and the extracellular signal-regulated kinase (Erk) activation in response to FGF was enhanced in palate mesenchymal cells transfected with Sprouty2 small interfering RNA. These results suggest that Sprouty2 regulates palate mesenchymal cell proliferation via FGF signaling and is involved in palatal shelf elevation.

  8. Sprouty2 controls proliferation of palate mesenchymal cells via fibroblast growth factor signaling

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, Kaori [Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Taketomi, Takaharu, E-mail: taketomi@dent.kyushu-u.ac.jp [Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Yoshizaki, Keigo [Section of Orthodontics, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Arai, Shinsaku [Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Sanui, Terukazu [Section of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Yoshiga, Daigo [Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Yoshimura, Akihiko [Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo 102-0075 (Japan); Nakamura, Seiji [Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

    2011-01-28

    Research highlights: {yields} Sprouty2-deficient mice exhibit cleft palate as a result of failure of palatal shelf elevation. {yields} We examined palate cell proliferation in Sprouty2-deficient mice. {yields} Palate mesenchymal cell proliferation was increased in Sprouty2 KO mice. {yields} Sprouty2 plays roles in murine palatogenesis by regulating cell proliferation. -- Abstract: Cleft palate is one of the most common craniofacial deformities. The fibroblast growth factor (FGF) plays a central role in reciprocal interactions between adjacent tissues during palatal development, and the FGF signaling pathway has been shown to be inhibited by members of the Sprouty protein family. In this study, we report the incidence of cleft palate, possibly caused by failure of palatal shelf elevation, in Sprouty2-deficient (KO) mice. Sprouty2-deficient palates fused completely in palatal organ culture. However, palate mesenchymal cell proliferation estimated by Ki-67 staining was increased in Sprouty2 KO mice compared with WT mice. Sprouty2-null palates expressed higher levels of FGF target genes, such as Msx1, Etv5, and Ptx1 than WT controls. Furthermore, proliferation and the extracellular signal-regulated kinase (Erk) activation in response to FGF was enhanced in palate mesenchymal cells transfected with Sprouty2 small interfering RNA. These results suggest that Sprouty2 regulates palate mesenchymal cell proliferation via FGF signaling and is involved in palatal shelf elevation.

  9. Prospective Randomized Controlled Comparison of Caudal ...

    African Journals Online (AJOL)

    including 50 consecutive patients in the age group of 1‑10 years, who underwent urogenital surgeries ... The duration of absolute analgesia was defined as the time from caudal injection until the pain score was >2. Motor block was assessed by modified Bromage scale. .... double-blind, phase III, controlled trial comparing.

  10. Caudal Regression Syndrome/neurogenic bladder presented as ...

    African Journals Online (AJOL)

    Burhan M. Edrees

    Impaired development in the caudal region will affect the general health status of ... mities within the spinal cord, brain, or nervous supply. A number .... The parenchyma of left ... The findings have shown non-functioning right kidney; however,.

  11. Note: Dynamic analysis of a robotic fish motion with a caudal fin with vertical phase differences

    Science.gov (United States)

    Yun, Dongwon; Kim, Kyung-Soo; Kim, Soohyun; Kyung, Jinho; Lee, Sunghwi

    2013-03-01

    In this paper, a robotic fish with a caudal fin with vertical phase differences is studied, especially focusing on the energy consumption. Energies for thrusting a conventional robotic fish and one with caudal fin with vertical phase differences are obtained and compared each other. It is shown that a robotic fish with a caudal fin with vertical phase differences can save more energy, which implies the efficient thrusting via a vertically waving caudal fin.

  12. Mathematical Model of Growth Factor Driven Haptotaxis and Proliferation in a Tissue Engineering Scaffold

    KAUST Repository

    Pohlmeyer, J. V.; Waters, S. L.; Cummings, L. J.

    2013-01-01

    nutrient-rich culture medium is perfused through a 2D porous scaffold impregnated with growth factor and seeded with cells. We model these processes on the timescale of cell proliferation, which typically is of the order of days. While a quantitative

  13. The untold story of the caudal skeleton in the electric eel (ostariophysi: gymnotiformes: electrophorus.

    Directory of Open Access Journals (Sweden)

    Carlos David de Santana

    Full Text Available Alternative hypotheses had been advanced as to the components forming the elongate fin coursing along the ventral margin of much of the body and tail from behind the abdominal region to the posterior margin of the tail in the Electric Eel, Electrophorus electricus. Although the original species description indicated that this fin was a composite of the caudal fin plus the elongate anal fin characteristic of other genera of the Gymnotiformes, subsequent researchers proposed that the posterior region of the fin was formed by the extension of the anal fin posteriorly to the tip of the tail, thereby forming a "false caudal fin." Examination of ontogenetic series of the genus reveal that Electrophorus possesses a true caudal fin formed of a terminal centrum, hypural plate and a low number of caudal-fin rays. The confluence of the two fins is proposed as an additional autapomorphy for the genus. Under all alternative proposed hypotheses of relationships within the order Gymnotiformes, the presence of a caudal fin in Electrophorus optimized as being independent of the occurence of the morphologically equivalent structure in the Apteronotidae. Possible functional advantages to the presence of a caudal fin in the genus are discussed.

  14. Multidetector row computed tomography and ultrasound characteristics of caudal vena cava duplication in dogs.

    Science.gov (United States)

    Bertolini, Giovanna; Diana, Alessia; Cipone, Mario; Drigo, Michele; Caldin, Marco

    2014-01-01

    Caudal vena cava duplication has been rarely reported in small animals. The purpose of this retrospective study was to describe characteristics of duplicated caudal vena cava in a large group of dogs. Computed tomography (CT) and ultrasound databases from two hospitals were searched for canine reports having the diagnosis "double caudal vena cava." One observer reviewed CT images for 71 dogs and two observers reviewed ultrasound images for 21 dogs. In all CT cases, the duplication comprised two vessels that were bilaterally symmetrical and approximately the same calibre (similar to Type I complete duplication in humans). In all ultrasound cases, the duplicated caudal vena cava appeared as a distinct vessel running on the left side of the abdominal segment of the descending aorta and extending from the left common iliac vein to the left renal vein. The prevalence of caudal vena cava duplication was 0.46% for canine ultrasound studies and 2.08% for canine CT studies performed at these hospitals. Median body weight for affected dogs was significantly lower than that of unaffected dogs (P dogs, caudal vena cava duplication should be differentiated from other vascular anomalies when planning surgeries and for avoiding misdiagnoses. © 2014 American College of Veterinary Radiology.

  15. Rat disc torsional mechanics: effect of lumbar and caudal levels and axial compression load.

    Science.gov (United States)

    Espinoza Orías, Alejandro A; Malhotra, Neil R; Elliott, Dawn M

    2009-03-01

    Rat models with altered loading are used to study disc degeneration and mechano-transduction. Given the prominent role of mechanics in disc function and degeneration, it is critical to measure mechanical behavior to evaluate changes after model interventions. Axial compression mechanics of the rat disc are representative of the human disc when normalized by geometry, and differences between the lumbar and caudal disc have been quantified in axial compression. No study has quantified rat disc torsional mechanics. Compare the torsional mechanical behavior of rat lumbar and caudal discs, determine the contribution of combined axial load on torsional mechanics, and compare the torsional properties of rat discs to human lumbar discs. Cadaveric biomechanical study. Cyclic torsion without compressive load followed by cyclic torsion with a fixed compressive load was applied to rat lumbar and caudal disc levels. The apparent torsional modulus was higher in the lumbar region than in the caudal region: 0.081+/-0.026 (MPa/degrees, mean+/-SD) for lumbar axially loaded; 0.066+/-0.028 for caudal axially loaded; 0.091+/-0.033 for lumbar in pure torsion; and 0.056+/-0.035 for caudal in pure torsion. These values were similar to human disc properties reported in the literature ranging from 0.024 to 0.21 MPa/degrees. Use of the caudal disc as a model may be appropriate if the mechanical focus is within the linear region of the loading regime. These results provide support for use of this animal model in basic science studies with respect to torsional mechanics.

  16. Homeobox A7 increases cell proliferation by up-regulation of epidermal growth factor receptor expression in human granulosa cells

    Directory of Open Access Journals (Sweden)

    Yanase Toshihiko

    2010-06-01

    Full Text Available Abstract Background Homeobox (HOX genes encode transcription factors, which regulate cell proliferation, differentiation, adhesion, and migration. The deregulation of HOX genes is frequently associated with human reproductive system disorders. However, knowledge regarding the role of HOX genes in human granulosa cells is limited. Methods To determine the role of HOXA7 in the regulation and associated mechanisms of cell proliferation in human granulosa cells, HOXA7 and epidermal growth factor receptor (EGFR expressions were examined in primary granulosa cells (hGCs, an immortalized human granulosa cell line, SVOG, and a granulosa tumor cell line, KGN, by real-time PCR and Western blotting. To manipulate the expression of HOXA7, the HOXA7 specific siRNA was used to knockdown HOXA7 in KGN. Conversely, HOXA7 was overexpressed in SVOG by transfection with the pcDNA3.1-HOAX7 vector. Cell proliferation was measured by the MTT assay. Results Our results show that HOXA7 and EGFR were overexpressed in KGN cells compared to hGCs and SVOG cells. Knockdown of HOXA7 in KGN cells significantly decreased cell proliferation and EGFR expression. Overexpression of HOXA7 in SVOG cells significantly promoted cell growth and EGFR expression. Moreover, the EGF-induced KGN proliferation was abrogated, and the activation of downstream signaling was diminished when HOXA7 was knocked down. Overexpression of HOXA7 in SVOG cells had an opposite effect. Conclusions Our present study reveals a novel mechanistic role for HOXA7 in modulating granulosa cell proliferation via the regulation of EGFR. This finding contributes to the knowledge of the pro-proliferation effect of HOXA7 in granulosa cell growth and differentiation.

  17. Platelet-rich plasma stimulated by pulse electric fields: Platelet activation, procoagulant markers, growth factor release and cell proliferation.

    Science.gov (United States)

    Frelinger, A L; Torres, A S; Caiafa, A; Morton, C A; Berny-Lang, M A; Gerrits, A J; Carmichael, S L; Neculaes, V B; Michelson, A D

    2016-01-01

    Therapeutic use of activated platelet-rich plasma (PRP) has been explored for wound healing, hemostasis and antimicrobial wound applications. Pulse electric field (PEF) stimulation may provide more consistent platelet activation and avoid complications associated with the addition of bovine thrombin, the current state of the art ex vivo activator of therapeutic PRP. The aim of this study was to compare the ability of PEF, bovine thrombin and thrombin receptor activating peptide (TRAP) to activate human PRP, release growth factors and induce cell proliferation in vitro. Human PRP was prepared in the Harvest SmartPreP2 System and treated with vehicle, PEF, bovine thrombin, TRAP or Triton X-100. Platelet activation and procoagulant markers and microparticle generation were measured by flow cytometry. Released growth factors were measured by ELISA. The releasates were tested for their ability to stimulate proliferation of human epithelial cells in culture. PEF produced more platelet-derived microparticles, P-selectin-positive particles and procoagulant annexin V-positive particles than bovine thrombin or TRAP. These differences were associated with higher levels of released epidermal growth factor after PEF than after bovine thrombin or TRAP but similar levels of platelet-derived, vascular-endothelial, and basic fibroblast growth factors, and platelet factor 4. Supernatant from PEF-treated platelets significantly increased cell proliferation compared to plasma. In conclusion, PEF treatment of fresh PRP results in generation of microparticles, exposure of prothrombotic platelet surfaces, differential release of growth factors compared to bovine thrombin and TRAP and significant cell proliferation. These results, together with PEF's inherent advantages, suggest that PEF may be a superior alternative to bovine thrombin activation of PRP for therapeutic applications.

  18. Caudal Duplication Syndrome: the Vital Role of a Multidisciplinary Approach and Staged Correction.

    Science.gov (United States)

    Samuk, Inbal; Levitt, Marc; Dlugy, Elena; Kravarusic, Dragan; Ben-Meir, David; Rajz, Gustavo; Konen, Osnat; Freud, Enrique

    2016-12-01

    Caudal duplication syndrome is a rare entity that describes the association between congenital anomalies involving caudal structures and may have a wide spectrum of clinical manifestations. A full-term male presented with combination of anomalies including anorectal malformation, duplication of the colon and lower urinary tract, split of the lower spine, and lipomyelomeningocele with tethering of the cord. We report this exceptional case of caudal duplication syndrome with special emphasis on surgical strategy and approach combining all disciplines involved. The purpose of this report is to present the pathology, assessment, and management strategy of this complex case.

  19. Caudal Duplication Syndrome: the Vital Role of a Multidisciplinary Approach and Staged Correction

    Science.gov (United States)

    Samuk, Inbal; Levitt, Marc; Dlugy, Elena; Kravarusic, Dragan; Ben-Meir, David; Rajz, Gustavo; Konen, Osnat; Freud, Enrique

    2015-01-01

    Caudal duplication syndrome is a rare entity that describes the association between congenital anomalies involving caudal structures and may have a wide spectrum of clinical manifestations. A full-term male presented with combination of anomalies including anorectal malformation, duplication of the colon and lower urinary tract, split of the lower spine, and lipomyelomeningocele with tethering of the cord. We report this exceptional case of caudal duplication syndrome with special emphasis on surgical strategy and approach combining all disciplines involved. The purpose of this report is to present the pathology, assessment, and management strategy of this complex case. PMID:28018799

  20. Homeorhetic hormones, metabolites and accelerated growth ...

    African Journals Online (AJOL)

    Blood samples were drawn from surgically implanted catheters in the caudal aorta and vena cava during normal growth, maintenance (zero) growth and accelerated growth.These samples were assayed for glucose, free fatty acids, glycerol, alanine, lysine, growth hormone, insulin and thyroxine. It was found that during the ...

  1. ADAM12-S stimulates bone growth in transgenic mice by modulating chondrocyte proliferation and maturation

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Albrechtsen, Reidar; Rudkjaer, Lise

    2006-01-01

    ADAM12-S transgenic mice exhibit a pronounced increase in the length of bones, such as femur, tibia, and vertebrae. The effect of ADAM12-S on longitudinal bone growth involves the modulation of chondrocyte proliferation and maturation, likely through proteolytic activities and altered cell......: Transgenic mice expressing the secreted form of human ADAM12, ADAM12-S, or a truncated metalloprotease-deficient form of ADAM12-S in the circulation were used to study the effects of ADAM12 on the skeleton. In addition, murine chondrocyte cultures were used to study the effect of ADAM12-S on cell...... studies showed that ADAM12-S inhibits chondrocyte adhesion to fibronectin and collagen type II. CONCLUSIONS: ADAM12-S stimulates bone growth in mice by modulating chondrocyte proliferation and maturation through mechanisms probably involving both metalloprotease and adhesion activities....

  2. Accessory caudal axial and pelvic ribs

    International Nuclear Information System (INIS)

    Bohutova, J.; Kolar, J.; Vitovec, J.; Vyhnanek, L.

    1980-01-01

    Accessory caudal ribs are reported as an extremely curious anomaly in five patients. Once the fracture of this rib was a source of pains after injury. The different shapes of the ribs are documented in this clinical survey which is the most extensive in the present literature. Anomalous ribs arise due to inappropriate segmentation during the embryonal development of the axial skeleton. (orig.) [de

  3. Caudal regulates the spatiotemporal dynamics of pair-rule waves in Tribolium.

    Directory of Open Access Journals (Sweden)

    Ezzat El-Sherif

    2014-10-01

    Full Text Available In the short-germ beetle Tribolium castaneum, waves of pair-rule gene expression propagate from the posterior end of the embryo towards the anterior and eventually freeze into stable stripes, partitioning the anterior-posterior axis into segments. Similar waves in vertebrates are assumed to arise due to the modulation of a molecular clock by a posterior-to-anterior frequency gradient. However, neither a molecular candidate nor a functional role has been identified to date for such a frequency gradient, either in vertebrates or elsewhere. Here we provide evidence that the posterior gradient of Tc-caudal expression regulates the oscillation frequency of pair-rule gene expression in Tribolium. We show this by analyzing the spatiotemporal dynamics of Tc-even-skipped expression in strong and mild knockdown of Tc-caudal, and by correlating the extension, level and slope of the Tc-caudal expression gradient to the spatiotemporal dynamics of Tc-even-skipped expression in wild type as well as in different RNAi knockdowns of Tc-caudal regulators. Further, we show that besides its absolute importance for stripe generation in the static phase of the Tribolium blastoderm, a frequency gradient might serve as a buffer against noise during axis elongation phase in Tribolium as well as vertebrates. Our results highlight the role of frequency gradients in pattern formation.

  4. GP88 (PC-Cell Derived Growth Factor, progranulin stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells

    Directory of Open Access Journals (Sweden)

    Sabnis Gauri

    2011-06-01

    Full Text Available Abstract Background Aromatase inhibitors (AI that inhibit breast cancer cell growth by blocking estrogen synthesis have become the treatment of choice for post-menopausal women with estrogen receptor positive (ER+ breast cancer. However, some patients display de novo or acquired resistance to AI. Interactions between estrogen and growth factor signaling pathways have been identified in estrogen-responsive cells as one possible reason for acquisition of resistance. Our laboratory has characterized an autocrine growth factor overexpressed in invasive ductal carcinoma named PC-Cell Derived Growth Factor (GP88, also known as progranulin. In the present study, we investigated the role GP88 on the acquisition of resistance to letrozole in ER+ breast cancer cells Methods We used two aromatase overexpressing human breast cancer cell lines MCF-7-CA cells and AC1 cells and their letrozole resistant counterparts as study models. Effect of stimulating or inhibiting GP88 expression on proliferation, anchorage-independent growth, survival and letrozole responsiveness was examined. Results GP88 induced cell proliferation and conferred letrozole resistance in a time- and dose-dependent fashion. Conversely, naturally letrozole resistant breast cancer cells displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. GP88 overexpression, or exogenous addition blocked the inhibitory effect of letrozole on proliferation, and stimulated survival and soft agar colony formation. In letrozole resistant cells, silencing GP88 by siRNA inhibited cell proliferation and restored their sensitivity to letrozole. Conclusion Our findings provide information on the role of an alternate growth and survival factor on the acquisition of aromatase inhibitor resistance in ER+ breast cancer.

  5. Computed tomographic characteristics of collateral venous pathways in dogs with caudal vena cava obstruction.

    Science.gov (United States)

    Specchi, Swan; d'Anjou, Marc-André; Carmel, Eric Norman; Bertolini, Giovanna

    2014-01-01

    Collateral venous pathways develop in dogs with obstruction or increased blood flow resistance at any level of the caudal vena cava in order to maintain venous drainage to the right atrium. The purpose of this retrospective study was to describe the sites, causes of obstruction, and configurations of venous collateral pathways for a group of dogs with caudal vena cava obstruction. Computed tomography databases from two veterinary hospitals were searched for dogs with a diagnosis of caudal vena cava obstruction and multidetector row computed tomographic angiographic (CTA) scans that included the entire caudal vena cava. Images for each included dog were retrieved and collateral venous pathways were characterized using image postprocessing and a classification system previously reported for humans. A total of nine dogs met inclusion criteria and four major collateral venous pathways were identified: deep (n = 2), portal (n = 2), intermediate (n = 7), and superficial (n = 5). More than one collateral venous pathway was present in 5 dogs. An alternative pathway consisting of renal subcapsular collateral veins, arising mainly from the caudal pole of both kidneys, was found in three dogs. In conclusion, findings indicated that collateral venous pathway patterns similar to those described in humans are also present in dogs with caudal vena cava obstruction. These collateral pathways need to be distinguished from other vascular anomalies in dogs. Postprocessing of multidetector-row CTA images allowed delineation of the course of these complicated venous pathways and may be a helpful adjunct for treatment planning in future cases. © 2014 American College of Veterinary Radiology.

  6. Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation

    International Nuclear Information System (INIS)

    Yu, Lingling; Zhao, Yingmin; Gu, Xin; Wang, Jijun; Pang, Lei; Zhang, Yanqing; Li, Yaoyao; Jia, Xiaoqin; Wang, Xin; Gu, Jian; Yu, Duonan

    2016-01-01

    Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment. - Highlights: • LPS alone in culture is required for the proliferation of murine myeloid tumor cells. • Bone marrow stromal cells as a feeder layer is also required for the proliferation of myeloid tumor cells. • However, the growth of myeloid tumor cells is inhibited when LPS and stromal cells are both available in culture. • Thus LPS can either facilitate or attenuate tumor growth through its direct effect or modulation of tumor microenvironment.

  7. Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Lingling [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Zhao, Yingmin [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Gu, Xin; Wang, Jijun; Pang, Lei; Zhang, Yanqing; Li, Yaoyao; Jia, Xiaoqin; Wang, Xin [Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Gu, Jian [Department of Hematology, Yangzhou University School of Clinical Medicine, Yangzhou 225001 (China); Yu, Duonan, E-mail: duonan@yahoo.com [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Disease, Yangzhou 225001 (China); Institute of Comparative Medicine, Yangzhou University, Yangzhou 225001 (China); Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonosis, Yangzhou 225001 (China)

    2016-06-10

    Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment. - Highlights: • LPS alone in culture is required for the proliferation of murine myeloid tumor cells. • Bone marrow stromal cells as a feeder layer is also required for the proliferation of myeloid tumor cells. • However, the growth of myeloid tumor cells is inhibited when LPS and stromal cells are both available in culture. • Thus LPS can either facilitate or attenuate tumor growth through its direct effect or modulation of tumor microenvironment.

  8. Rostro-Caudal Organization of Connectivity between Cingulate Motor Areas and Lateral Frontal Regions

    Directory of Open Access Journals (Sweden)

    Kep Kee Loh

    2018-01-01

    Full Text Available According to contemporary views, the lateral frontal cortex is organized along a rostro-caudal functional axis with increasingly complex cognitive/behavioral control implemented rostrally, and increasingly detailed motor control implemented caudally. Whether the medial frontal cortex follows the same organization remains to be elucidated. To address this issue, the functional connectivity of the 3 cingulate motor areas (CMAs in the human brain with the lateral frontal cortex was investigated. First, the CMAs and their representations of hand, tongue, and eye movements were mapped via task-related functional magnetic resonance imaging (fMRI. Second, using resting-state fMRI, their functional connectivity with lateral prefrontal and lateral motor cortical regions of interest (ROIs were examined. Importantly, the above analyses were conducted at the single-subject level to account for variability in individual cingulate morphology. The results demonstrated a rostro-caudal functional organization of the CMAs in the human brain that parallels that in the lateral frontal cortex: the rostral CMA has stronger functional connectivity with prefrontal regions and weaker connectivity with motor regions; conversely, the more caudal CMAs have weaker prefrontal and stronger motor connectivity. Connectivity patterns of the hand, tongue and eye representations within the CMAs are consistent with that of their parent CMAs. The parallel rostral-to-caudal functional organization observed in the medial and lateral frontal cortex could likely contribute to different hierarchies of cognitive-motor control.

  9. Metformin inhibits the proliferation of human prostate cancer PC-3 cells via the downregulation of insulin-like growth factor 1 receptor

    International Nuclear Information System (INIS)

    Kato, Haruo; Sekine, Yoshitaka; Furuya, Yosuke; Miyazawa, Yoshiyuki; Koike, Hidekazu; Suzuki, Kazuhiro

    2015-01-01

    Metformin is a biguanide drug that is widely used for the treatment of type 2 diabetes. Recent studies have shown that metformin inhibits cancer cell proliferation and tumor growth both in vitro and in vivo. The anti-tumor mechanisms of metformin include activation of the AMP-activated protein kinase/mTOR pathway and direct inhibition of insulin/insulin-like growth factor (IGF)-mediated cellular proliferation. However, the anti-tumor mechanism in prostate cancer remains unclear. Because activation of the IGF-1 receptor (IGF-1R) is required for prostate cell proliferation, IGF-1R inhibitors may be of therapeutic value. Accordingly, we examined the effects of metformin on IGF-1R signaling in prostate cancer cells. Metformin significantly inhibited PC-3 cell proliferation, migration, and invasion. IGF-1R mRNA expression decreased significantly after 48 h of treatment, and IGF-1R protein expression decreased in a similar manner. IGF-1R knockdown by siRNA transfection led to inhibited proliferation, migration and invasion of PC-3 cells. IGF-1 activated both ERK1/2 and Akt, but these effects were attenuated by metformin treatment. In addition, intraperitoneal treatment with metformin significantly reduced tumor growth and IGF-1R mRNA expression in PC-3 xenografts. Our results suggest that metformin is a potent inhibitor of the IGF-1/IGF-1R system and may be beneficial in prostate cancer treatment. - Highlights: • Metformin inhibited PC-3 cell proliferation, migration, and invasion. • Metformin decreased IGF-1R mRNA and protein expressions in PC-3 cells. • Metformin inhibited IGF-1 induced ERK and Akt phosphorylations in PC-3 cells. • Metformin treatment inhibited PC-3 cell growth and IGF-1R expression in vivo. • Metformin may be a potent inhibitor of the IGF-1/IGF-1R signaling

  10. Metformin inhibits the proliferation of human prostate cancer PC-3 cells via the downregulation of insulin-like growth factor 1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Haruo, E-mail: hal.kato@gunma-u.ac.jp; Sekine, Yoshitaka; Furuya, Yosuke; Miyazawa, Yoshiyuki; Koike, Hidekazu; Suzuki, Kazuhiro

    2015-05-22

    Metformin is a biguanide drug that is widely used for the treatment of type 2 diabetes. Recent studies have shown that metformin inhibits cancer cell proliferation and tumor growth both in vitro and in vivo. The anti-tumor mechanisms of metformin include activation of the AMP-activated protein kinase/mTOR pathway and direct inhibition of insulin/insulin-like growth factor (IGF)-mediated cellular proliferation. However, the anti-tumor mechanism in prostate cancer remains unclear. Because activation of the IGF-1 receptor (IGF-1R) is required for prostate cell proliferation, IGF-1R inhibitors may be of therapeutic value. Accordingly, we examined the effects of metformin on IGF-1R signaling in prostate cancer cells. Metformin significantly inhibited PC-3 cell proliferation, migration, and invasion. IGF-1R mRNA expression decreased significantly after 48 h of treatment, and IGF-1R protein expression decreased in a similar manner. IGF-1R knockdown by siRNA transfection led to inhibited proliferation, migration and invasion of PC-3 cells. IGF-1 activated both ERK1/2 and Akt, but these effects were attenuated by metformin treatment. In addition, intraperitoneal treatment with metformin significantly reduced tumor growth and IGF-1R mRNA expression in PC-3 xenografts. Our results suggest that metformin is a potent inhibitor of the IGF-1/IGF-1R system and may be beneficial in prostate cancer treatment. - Highlights: • Metformin inhibited PC-3 cell proliferation, migration, and invasion. • Metformin decreased IGF-1R mRNA and protein expressions in PC-3 cells. • Metformin inhibited IGF-1 induced ERK and Akt phosphorylations in PC-3 cells. • Metformin treatment inhibited PC-3 cell growth and IGF-1R expression in vivo. • Metformin may be a potent inhibitor of the IGF-1/IGF-1R signaling.

  11. IL-13-induced proliferation of airway epithelial cells: mediation by intracellular growth factor mobilization and ADAM17

    Directory of Open Access Journals (Sweden)

    Sandifer Tracy

    2007-07-01

    Full Text Available Abstract Background The pleiotrophic cytokine interleukin (IL-13 features prominently in allergic and inflammatory diseases. In allergic asthma, IL-13 is well established as an inducer of airway inflammation and tissue remodeling. We demonstrated previously that IL-13 induces release of transforming growth factor-α (TGFα from human bronchial epithelial cells, with proliferation of these cells mediated by the autocrine/paracrine action of this growth factor. TGFα exists as an integral membrane protein and requires proteolytic processing to its mature form, with a disintegrin and metalloproteinase (ADAM17 responsible for this processing in a variety of tissues. Methods In this study, normal human bronchial epithelial (NHBE cells grown in air/liquid interface (ALI culture were used to examine the mechanisms whereby IL-13 induces release of TGFα and cellular proliferation. Inhibitors and antisense RNA were used to examine the role of ADAM17 in these processes, while IL-13-induced changes in the intracellular expression of TGFα and ADAM17 were visualized by confocal microscopy. Results IL-13 was found to induce proliferation of NHBE cells, and release of TGFα, in an ADAM17-dependent manner; however, this IL-13-induced proliferation did not appear to result solely from ADAM17 activation. Rather, IL-13 induced a change in the location of TGFα expression from intracellular to apical regions of the NHBE cells. The apical region was also found to be a site of significant ADAM17 expression, even prior to IL-13 stimulation. Conclusion Results from this study indicate that ADAM17 mediates IL-13-induced proliferation and TGFα shedding in NHBE cells. Furthermore, they provide the first example wherein a cytokine (IL-13 induces a change in the intracellular expression pattern of a growth factor, apparently inducing redistribution of intracellular stores of TGFα to the apical region of NHBE cells where expression of ADAM17 is prominent. Thus, IL-13

  12. Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca).

    Science.gov (United States)

    Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W; Hou, Rong; Shen, Wei

    2015-01-01

    It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro.

  13. Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca)

    Science.gov (United States)

    Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W.; Hou, Rong; Shen, Wei

    2015-01-01

    It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro. PMID:26375397

  14. Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca.

    Directory of Open Access Journals (Sweden)

    Jun-Jie Wang

    Full Text Available It has been widely known that the giant panda (Ailuropoda melanoleuca is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF, a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro.

  15. Caudal articular process dysplasia of thoracic vertebrae in neurologically normal French bulldogs, English bulldogs, and Pugs: Prevalence and characteristics.

    Science.gov (United States)

    Bertram, Simon; Ter Haar, Gert; De Decker, Steven

    2018-02-20

    The aims of this study were to evaluate the prevalence and anatomical characteristics of thoracic caudal articular process dysplasia in French bulldogs, English bulldogs and Pugs presenting for problems unrelated to spinal disease. In this retrospective cross-sectional study, computed tomography scans of the thoracic vertebral column of these three breeds were reviewed for the presence and location of caudal articular process hypoplasia and aplasia, and compared between breeds. A total of 271 dogs met the inclusion criteria: 108 French bulldogs, 63 English bulldogs, and 100 Pugs. A total of 70.4% of French bulldogs, 84.1% of English bulldogs, and 97.0% of Pugs showed evidence of caudal articular process dysplasia. Compared to French and English bulldogs, Pugs showed a significantly higher prevalence of caudal articular process aplasia, but also a lower prevalence of caudal articular process hypoplasia, a higher number of affected vertebrae per dog and demonstrated a generalized and bilateral spatial pattern more frequently. Furthermore, Pugs showed a significantly different anatomical distribution of caudal articular process dysplasia along the vertebral column, with a high prevalence of caudal articular process aplasia between T10 and T13. This area was almost completely spared in French and English bulldogs. As previously suggested, caudal articular process dysplasia is a common finding in neurologically normal Pugs but this also seems to apply to French and English bulldogs. The predisposition of clinically relevant caudal articular process dysplasia in Pugs is possibly not only caused by the higher prevalence of caudal articular process dysplasia, but also by breed specific anatomical characteristics. © 2018 American College of Veterinary Radiology.

  16. Cell-cell adhesion mediated by binding of membrane-anchored transforming growth factor α to epidermal growth factor receptors promotes cell proliferation

    International Nuclear Information System (INIS)

    Anklesaria, P.; Greenberger, J.S.; Teixido, J.; Laiho, M.; Massague, J.; Pierce, J.H.

    1990-01-01

    The precursor for transforming growth factor α, pro-TGF-α, is a cell surface glycoprotein that can establish contact with epidermal growth factor (EGF) receptors on adjacent cells. To examine whether the pro-TGF-α/EGF receptor pair can simultaneously mediate cell adhesion and promote cell proliferation, the authors have expressed pro-TGF-α in a bone marrow stromal cell line labeled with [ 35 S] cysteine. Expression of pro-TGF-α allows these cells to support long-term attachment of an EGF/interleukin-3-dependent hematopoietic progenitor cell line that expresses EGF receptors but is unable to adhere to normal stroma. This interaction is inhibited by soluble EGF receptor ligands. Further, the hematopoietic progenitor cells replicate their DNA while they are attached to the stromal cell layer and become foci of sustained cell proliferation. Thus, pro-TGF-α and the EGF receptor can function as mediators of intercellular adhesion and this interaction may promote a mitogenic response. They propose the term juxtacrine to designate this form of stimulation between adjacent cells

  17. Comparison of Caudal Analgesia and Intravenous Diclofenac for ...

    African Journals Online (AJOL)

    Background: Effective postoperative pain management is a vital determinant to when a child can be safely discharged from the hospital after day case surgery. This study compared the effect of caudal bupivacaine block with intravenous diclofenac for postoperative pain relief in children aged 1-7years undergoing ...

  18. Caudal dysgenesis, sirenomelia, and situs inversus totalis: a primitive defect in blastogenesis.

    Science.gov (United States)

    Rougemont, Anne-Laure; Bouron-Dal Soglio, Dorothée; Désilets, Valérie; Jovanovic, Mubina; Perreault, Gilles; Laurier Oligny, Luc; Fournet, Jean-Christophe

    2008-06-01

    Caudal dysgenesis (CD) constitutes a heterogeneous spectrum of congenital caudal anomalies, including varying degrees of agenesis of the vertebral column, as well as anorectal and genitourinary anomalies. Sirenomelia, characterized by a fusion of the lower limbs, could represent the most severe end of this spectrum. The two main debated pathogenic hypotheses are an aberrant vascular supply versus a primary axial mesoderm defect. We present the autopsy findings of two fetuses of non-diabetic mothers, with normal karyotype. Both fetuses presented situs inversus associated with a CD, in one case consisting of sirenomelia, establishing a very rare association profile that might be random. This association also suggests the occurrence of a common pathogenic mechanism, in accordance to recent genetic data, such as displayed in the Kif3A murine mutation phenotype. Some cases of sirenomelia and CD could represent developmental field defects of blastogenesis involving the caudal mesoderm, rather than being related to vascular insufficiency.

  19. Flow-structure Interaction Modeling of a Fish Caudal Fin during Steady Swimming

    Science.gov (United States)

    Liu, Geng; Geng, Biao; Zheng, Xudong; Xue, Qian; Dong, Haibo

    2017-11-01

    It's widely thought that the flexibilities of fish fins play critical roles in propulsive performance enhancement (such as thrust augment and efficiency improvement) in nature. In order to explore the formation mechanisms of the fish fin's flexible morphing and its hydrodynamic benefits as well, a high-fidelity flow-structure/membrane interaction modeling of the fish caudal fin is conducted in this work. Following the realistic configuration of the fish caudal fin, a thin membrane supported by a series of beams is constructed. The material properties of the membrane and the beams are reversely determined by the realistic fin morphing obtained from the high-speed videos and the high fidelity flow-structure interaction simulations. With the accurate material property, we investigate the interplay between structure, kinematics and fluid flow in caudal fin propulsion. Detailed analyses on the relationship between the flexural stiffness, fin morphing patterns, hydrodynamic forces and vortex dynamics are then conducted.

  20. Conjoined twin piglets with duplicated cranial and caudal axes.

    Science.gov (United States)

    McManus, C A; Partlow, G D; Fisher, K R

    1994-06-01

    Twins with doubling of the cranial and caudal poles, yet having a single thorax, are rare. One set of diprosopus, dipygus porcine conjoined twins was studied. In addition to the conjoining anomaly, these twins also exhibited ambiguous internal reproductive features. The twins had two snouts, three eyes, a single thorax, and were duplicated from the umbilicus caudally. Radiography indicated a single vertebral column in the cervical region. The vertebral columns were separate caudally from this point. There was a total of six limbs--one pair of forelimbs and two pairs of hindlimbs. Many medial structures failed to develop in these twins. Medial cranial nerves V-XII were absent or displaced although apparently normal laterally. The medial palates were present but shortened, whereas the medial mandibular rami had folded back on themselves rostrally to form a midline mass between the two chins. Each twin had only one lateral kidney and one lateral testis. Medial scrotal sacs were present but devoid of a testis. There was a midline, "uterine"-like structure which crossed between the twins. However, histological analysis of this structure revealed it to be dysplastic testicular tissue. The relationship between the abnormal reproductive features in these twins and the conjoining is unclear. The anatomy of these twins, in addition to the literature reviewed, illustrates the internal anatomical heterogeneity of grossly similar conjoined twins. A review of the literature also suggests that conjoined twinning may be more common in swine than was previously suspected.

  1. microRNA 21-mediated suppression of Sprouty1 by Pokemon affects liver cancer cell growth and proliferation.

    Science.gov (United States)

    Jin, Xiu-Li; Sun, Qin-Sheng; Liu, Feng; Yang, Hong-Wei; Liu, Min; Liu, Hong-Xia; Xu, Wei; Jiang, Yu-Yang

    2013-07-01

    Transcriptional repressor Pokemon is a critical factor in embryogenesis, development, cell proliferation, differentiation, and oncogenesis, thus behaving as an oncogene. Oncomine database suggests a potential correlation between the expressions of Pokemon and Sprouty1. This study investigated the regulatory role of Pokemon in Sprouty1 expression and the effect on liver cancer cell growth and proliferation, revealing a novel miR-21-mediated regulatory circuit. In normal (HL-7702) and cancer (QGY-7703) liver cell lines, Sprouty1 expression is inversely correlated with Pokemon levels. Targeted expression or siRNA-mediated silencing showed that Pokemon is a repressor of Sprouty1 expression at both mRNA and protein levels, but Pokemon cannot affect the promoter activity of Sprouty1. Sprouty1 is a target of miR-21 and interestingly, we found that miR-21 is up-regulated by Pokemon in liver cancer cells. Luciferase reporter assays showed that Pokemon up-regulated miR-21 transcription in a dose-dependent manner, and ChIP assay exhibited a direct binding of Pokemon to the miR-21 promoter at -747 to -399 bp. Site-directed mutagenesis of the GC boxes at -684 to -679 bp and -652 to -647 bp of miR-21 promoter abolished the regulatory activity by Pokemon. Furthermore, we found that the modulation of Pokemon and miR-21 expression affected the growth and proliferation of liver cancer cells QGY-7703. In summary, our findings demonstrate that Pokemon suppresses Sprouty1 expression through a miR-21-mediated mechanism, affecting the growth and proliferation of liver cancer cells. This study recognized miR-21 and Sprouty1 as novel targets of the Pokemon regulatory network. Copyright © 2013 Wiley Periodicals, Inc.

  2. Neuronal M3 muscarinic acetylcholine receptors are essential for somatotroph proliferation and normal somatic growth.

    Science.gov (United States)

    Gautam, Dinesh; Jeon, Jongrye; Starost, Matthew F; Han, Sung-Jun; Hamdan, Fadi F; Cui, Yinghong; Parlow, Albert F; Gavrilova, Oksana; Szalayova, Ildiko; Mezey, Eva; Wess, Jürgen

    2009-04-14

    The molecular pathways that promote the proliferation and maintenance of pituitary somatotrophs and other cell types of the anterior pituitary gland are not well understood at present. However, such knowledge is likely to lead to the development of novel drugs useful for the treatment of various human growth disorders. Although muscarinic cholinergic pathways have been implicated in regulating somatotroph function, the physiological relevance of this effect and the localization and nature of the receptor subtypes involved in this activity remain unclear. We report the surprising observation that mutant mice that selectively lack the M(3) muscarinic acetylcholine receptor subtype in the brain (neurons and glial cells; Br-M3-KO mice) showed a dwarf phenotype associated with a pronounced hypoplasia of the anterior pituitary gland and a marked decrease in pituitary and serum growth hormone (GH) and prolactin. Remarkably, treatment of Br-M3-KO mice with CJC-1295, a synthetic GH-releasing hormone (GHRH) analog, rescued the growth deficit displayed by Br-M3-KO mice by restoring normal pituitary size and normal serum GH and IGF-1 levels. These findings, together with results from M(3) receptor/GHRH colocalization studies and hypothalamic hormone measurements, support a model in which central (hypothalamic) M(3) receptors are required for the proper function of hypothalamic GHRH neurons. Our data reveal an unexpected and critical role for central M(3) receptors in regulating longitudinal growth by promoting the proliferation of pituitary somatotroph cells.

  3. Evaluation of Anesthesia Profile in Pediatric Patients after Inguinal Hernia Repair with Caudal Block or Local Wound Infiltration.

    Science.gov (United States)

    Gavrilovska-Brzanov, Aleksandra; Kuzmanovska, Biljana; Kartalov, Andrijan; Donev, Ljupco; Lleshi, Albert; Jovanovski-Srceva, Marija; Spirovska, Tatjana; Brzanov, Nikola; Simeonov, Risto

    2016-03-15

    The aim of this study is to evaluate anesthesia and recovery profile in pediatric patients after inguinal hernia repair with caudal block or local wound infiltration. In this prospective interventional clinical study, the anesthesia and recovery profile was assessed in sixty pediatric patients undergoing inguinal hernia repair. Enrolled children were randomly assigned to either Group Caudal or Group Local infiltration. For caudal blocks, Caudal Group received 1 ml/kg of 0.25% bupivacaine; Local Infiltration Group received 0.2 ml/kg 0.25% bupivacaine. Investigator who was blinded to group allocation provided postoperative care and assessments. Postoperative pain was assessed. Motor functions and sedation were assessed as well. The two groups did not differ in terms of patient characteristic data and surgical profiles and there weren't any hemodynamic changes between groups. Regarding the difference between groups for analgesic requirement there were two major points - on one hand it was statistically significant p < 0.05 whereas on the other hand time to first analgesic administration was not statistically significant p = 0.40. There were significant differences in the incidence of adverse effects in caudal and local group including: vomiting, delirium and urinary retention. Between children undergoing inguinal hernia repair, local wound infiltration insures safety and satisfactory analgesia for surgery. Compared to caudal block it is not overwhelming. Caudal block provides longer analgesia, however complications are rather common.

  4. Cardiocirculatory intraoperative assessment during single-shot caudal anaesthesia in children: comparison between levobupivacaine and ropivacaine

    Directory of Open Access Journals (Sweden)

    A. Gentili

    2012-06-01

    Full Text Available Background: Caudal block with levobupivacaine or ropivacaine is the most commonly used regional anaesthesia in children. Methods: The aim of study was to compare the cardiocirculatory profile induced in two matched groups of young patients, submitted to caudal anaesthesia with levobupivacaine or ropivacaine for an elective subumbilical surgery. Sixty children were enrolled: thirty received levopubivacaine 0.25% and thirty ropivacaine 0.2%. Intraoperative heart rate (HR, systolic blood pressure (SBP, diastolic blood pressure (DBP were monitored at following times: Ta0 (after anaesthesia induction, Ta1 (after caudal anaesthesia, Ta2 (five minutes later, Ta3 (ten minutes later, Ts1 (at surgical incision, Ts2, Ts3, Ts4, Ts5 (every 10 minutes during surgery, Taw (at the awakening. Results: In both groups the cardiocirculatory trend remained within normal ranges at all times considered, demonstrating the safety of the method with both drugs. Both groups showed a similar trend at the different monitoring times: low decrease in HR, SBP and DBP after caudal block, slight increase in parameters after skin incision, slight decrease during surgery, increase at awakening. Regarding SBP and DBP, the levobupivacaine group children generally showed higher levels compared to the ropivacaine group, especially for DBP. Conclusions: Paediatric caudal anaesthesia is an effective method with an very infrequent complication rate. Possible hypotheses for differing haemodynamic behaviour could include a stronger vasoconstriction reflex of innervated areas during caudal anaesthesia with levobupivacaine and a lower levobupivacaine induced block of the sympathetic fibers, related to different pharmacokinetic profile of low concentrations of the local anaesthetics used in paediatric epidural space.

  5. Comparison of dysphagia outcomes between rostral and caudal lateral medullary infarct patients.

    Science.gov (United States)

    Chun, Min Ho; Kim, Daeha; Chang, Min Cheol

    2017-11-01

    A detailed knowledge of dysphagia outcomes in lateral medullary infarct (LMI) patients would enable proper establishment of swallowing therapy goals and strategies. However, little is known about the impact of infarct location on dysphagia outcomes in patients with LMI. Twenty patients with rostral LMI (rostral group) and 20 patients with caudal LMI (caudal group) participated in the study. All patients underwent swallowing therapy, which included compensatory treatments and strengthening exercises, for >3 months. Dysphagia evaluation was performed twice (during the subacute stage and six months after stroke onset) using videofluoroscopic swallowing studies. Dysphagia degree was assessed using the functional dysphagia scale (FDS), the penetration-aspiration scale (PAS) and the American Speech-Language-Hearing Association (ASHA) National Outcome Measurement System (NOMS) swallowing scale. In the subacute stage, the rostral group had significantly higher FDS and PAS scores and a significantly lower ASHA NOMS score than the caudal group. Patients from both groups showed significant improvement from the initial evaluation to the six-month evaluation. There were no significant differences in these scale scores between the two groups at the six-month evaluation. In the subacute stage, patients in the rostral group had more severe dysphagia than those in the caudal group. Dysphagia improved in both groups after 3-6 months of swallowing therapy. At six months after onset, there were no significant differences in dysphagia severity between the two groups. Recovery from dysphagia after LMI was observed regardless of the infarct location.

  6. The Oligo Fucoidan Inhibits Platelet-Derived Growth Factor-Stimulated Proliferation of Airway Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Chao-Huei Yang

    2016-01-01

    Full Text Available In the pathogenesis of asthma, the proliferation of airway smooth muscle cells (ASMCs is a key factor in airway remodeling and causes airway narrowing. In addition, ASMCs are also the effector cells of airway inflammation. Fucoidan extracted from marine brown algae polysaccharides has antiviral, antioxidant, antimicrobial, anticlotting, and anticancer properties; however, its effectiveness for asthma has not been elucidated thus far. Platelet-derived growth factor (PDGF-treated primary ASMCs were cultured with or without oligo-fucoidan (100, 500, or 1000 µg/mL to evaluate its effects on cell proliferation, cell cycle, apoptosis, and Akt, ERK1/2 signaling pathway. We found that PDGF (40 ng/mL increased the proliferation of ASMCs by 2.5-fold after 48 h (p < 0.05. Oligo-fucoidan reduced the proliferation of PDGF-stimulated ASMCs by 75%–99% after 48 h (p < 0.05 and induced G1/G0 cell cycle arrest, but did not induce apoptosis. Further, oligo-fucoidan supplementation reduced PDGF-stimulated extracellular signal-regulated kinase (ERK1/2, Akt, and nuclear factor (NF-κB phosphorylation. Taken together, oligo-fucoidan supplementation might reduce proliferation of PDGF-treated ASMCs through the suppression of ERK1/2 and Akt phosphorylation and NF-κB activation. The results provide basis for future animal experiments and human trials.

  7. [Role of connective tissue growth factor (CTGF) in proliferation and migration of pancreatic cancer cells].

    Science.gov (United States)

    Bai, Yu-chun; Kang, Quan; Luo, Qing; Wu, Dao-qi; Ye, Wei-xia; Lin, Xue-mei; Zhao, Yong

    2011-10-01

    To explore the expression of connective tissue growth factor (CTGF) in pancreatic cancer and its influence on the proliferation and migration of cancer cells. The expression of CTGF in pancreatic cell line PANC-1 cells was analyzed by real-time PCR and in pancreatic carcinoma (50 cases) tissues by immunohistochemistry. The ability of proliferation and migration in vitro of PANC-1 cells was tested by MTT assay, scratch test and Boyden chamber test after the CTGF gene was overexpressed by Ad5-CTGF or silenced with Ad5-siCTGF transfection. CTGF was overexpressed in both pancreatic cancer cells and tissues. Overxpression of CTGF leads to increased proliferation and migration of PANC-1 cells. The CTGF-transfected PANC-1 cells showed apparent stronger proliferation ability and scratch-repair ability than that of empty vector controls. The results of Boyden chamber test showed that there were 34 cells/field (200× magnificantion) of the CTGF-transfected overexpressing cells, much more than the 11 cells/field of the empty vector control cells; and 6 cells/microscopic field of the Ad5-siCTGF-transfected silenced cells, much less than the 15 cells/field of the control cells. CTGF is overexpressed in both pancreatic cancer cells in vitro and in vivo, indicating that it may play an important role in the cell proliferation and migration in pancreatic cancer.

  8. Growth/differentiation factor 15 promotes EGFR signalling, and regulates proliferation and migration in the hippocampus of neonatal and young adult mice.

    Science.gov (United States)

    Carrillo-García, Carmen; Prochnow, Sebastian; Simeonova, Ina K; Strelau, Jens; Hölzl-Wenig, Gabriele; Mandl, Claudia; Unsicker, Klaus; von Bohlen Und Halbach, Oliver; Ciccolini, Francesca

    2014-02-01

    The activation of epidermal growth factor receptor (EGFR) affects multiple aspects of neural precursor behaviour, including proliferation and migration. Telencephalic precursors acquire EGF responsiveness and upregulate EGFR expression at late stages of development. The events regulating this process and its significance are still unclear. We here show that in the developing and postnatal hippocampus (HP), growth/differentiation factor (GDF) 15 and EGFR are co-expressed in primitive precursors as well as in more differentiated cells. We also provide evidence that GDF15 promotes responsiveness to EGF and EGFR expression in hippocampal precursors through a mechanism that requires active CXC chemokine receptor (CXCR) 4. Besides EGFR expression, GDF15 ablation also leads to decreased proliferation and migration. In particular, lack of GDF15 impairs both processes in the cornu ammonis (CA) 1 and only proliferation in the dentate gyrus (DG). Importantly, migration and proliferation in the mutant HP were altered only perinatally, when EGFR expression was also affected. These data suggest that GDF15 regulates migration and proliferation by promoting EGFR signalling in the perinatal HP and represent a first description of a functional role for GDF15 in the developing telencephalon.

  9. Cell proliferation along vascular islands during microvascular network growth

    Directory of Open Access Journals (Sweden)

    Kelly-Goss Molly R

    2012-06-01

    Full Text Available Abstract Background Observations in our laboratory provide evidence of vascular islands, defined as disconnected endothelial cell segments, in the adult microcirculation. The objective of this study was to determine if vascular islands are involved in angiogenesis during microvascular network growth. Results Mesenteric tissues, which allow visualization of entire microvascular networks at a single cell level, were harvested from unstimulated adult male Wistar rats and Wistar rats 3 and 10 days post angiogenesis stimulation by mast cell degranulation with compound 48/80. Tissues were immunolabeled for PECAM and BRDU. Identification of vessel lumens via injection of FITC-dextran confirmed that endothelial cell segments were disconnected from nearby patent networks. Stimulated networks displayed increases in vascular area, length density, and capillary sprouting. On day 3, the percentage of islands with at least one BRDU-positive cell increased compared to the unstimulated level and was equal to the percentage of capillary sprouts with at least one BRDU-positive cell. At day 10, the number of vascular islands per vascular area dramatically decreased compared to unstimulated and day 3 levels. Conclusions These results show that vascular islands have the ability to proliferate and suggest that they are able to incorporate into the microcirculation during the initial stages of microvascular network growth.

  10. Transforming growth factor β inhibits platelet derived growth factor-induced vascular smooth muscle cell proliferation via Akt-independent, Smad-mediated cyclin D1 downregulation.

    Directory of Open Access Journals (Sweden)

    Abel Martin-Garrido

    Full Text Available In adult tissue, vascular smooth muscle cells (VSMCs exist in a differentiated phenotype, which is defined by the expression of contractile proteins and lack of proliferation. After vascular injury, VSMC adopt a synthetic phenotype associated with proliferation, migration and matrix secretion. The transition between phenotypes is a consequence of the extracellular environment, and in particular, is regulated by agonists such as the pro-differentiating cytokine transforming growth factor β (TGFβ and the pro-proliferative cytokine platelet derived growth factor (PDGF. In this study, we investigated the interplay between TGFβ and PDGF with respect to their ability to regulate VSMC proliferation. Stimulation of human aortic VSMC with TGFβ completely blocked proliferation induced by all isoforms of PDGF, as measured by DNA synthesis and total cell number. Mechanistically, PDGF-induced Cyclin D1 mRNA and protein expression was inhibited by TGFβ. TGFβ had no effect on PDGF activation of its receptor and ERK1/2, but inhibited Akt activation. However, constitutively active Akt did not reverse the inhibitory effect of TGFβ on Cyclin D1 expression even though inhibition of the proteasome blocked the effect of TGFβ. siRNA against Smad4 completely reversed the inhibitory effect of TGFβ on PDGF-induced Cyclin D1 expression and restored proliferation in response to PDGF. Moreover, siRNA against KLF5 prevented Cyclin D1 upregulation by PDGF and overexpression of KLF5 partially reversed TGFβ-induced inhibition of Cyclin D1 expression. Taken together, our results demonstrate that KLF5 is required for PDGF-induced Cyclin D1 expression, which is inhibited by TGFβ via a Smad dependent mechanism, resulting in arrest of VSMCs in the G1 phase of the cell cycle.

  11. Transforming growth factor β inhibits platelet derived growth factor-induced vascular smooth muscle cell proliferation via Akt-independent, Smad-mediated cyclin D1 downregulation.

    Science.gov (United States)

    Martin-Garrido, Abel; Williams, Holly C; Lee, Minyoung; Seidel-Rogol, Bonnie; Ci, Xinpei; Dong, Jin-Tang; Lassègue, Bernard; Martín, Alejandra San; Griendling, Kathy K

    2013-01-01

    In adult tissue, vascular smooth muscle cells (VSMCs) exist in a differentiated phenotype, which is defined by the expression of contractile proteins and lack of proliferation. After vascular injury, VSMC adopt a synthetic phenotype associated with proliferation, migration and matrix secretion. The transition between phenotypes is a consequence of the extracellular environment, and in particular, is regulated by agonists such as the pro-differentiating cytokine transforming growth factor β (TGFβ) and the pro-proliferative cytokine platelet derived growth factor (PDGF). In this study, we investigated the interplay between TGFβ and PDGF with respect to their ability to regulate VSMC proliferation. Stimulation of human aortic VSMC with TGFβ completely blocked proliferation induced by all isoforms of PDGF, as measured by DNA synthesis and total cell number. Mechanistically, PDGF-induced Cyclin D1 mRNA and protein expression was inhibited by TGFβ. TGFβ had no effect on PDGF activation of its receptor and ERK1/2, but inhibited Akt activation. However, constitutively active Akt did not reverse the inhibitory effect of TGFβ on Cyclin D1 expression even though inhibition of the proteasome blocked the effect of TGFβ. siRNA against Smad4 completely reversed the inhibitory effect of TGFβ on PDGF-induced Cyclin D1 expression and restored proliferation in response to PDGF. Moreover, siRNA against KLF5 prevented Cyclin D1 upregulation by PDGF and overexpression of KLF5 partially reversed TGFβ-induced inhibition of Cyclin D1 expression. Taken together, our results demonstrate that KLF5 is required for PDGF-induced Cyclin D1 expression, which is inhibited by TGFβ via a Smad dependent mechanism, resulting in arrest of VSMCs in the G1 phase of the cell cycle.

  12. Caudal regression with sirenomelia and dysplasia renofacialis (Potter's syndrome)

    International Nuclear Information System (INIS)

    Noeldge, G.; Billmann, P.; Boehm, N.; Freiburg Univ.

    1982-01-01

    A case of caudal regression in combination with sirenomelia and dysplasia renofacialis (Potter's syndrome) is reported. The formal pathogenesis of these malformations and clinical facts are shown and discussed. Findings of plain films, postmortal angiography and pathologic-anatomical changes are demonstrated. (orig.) [de

  13. Alteration of Na-K pump activity in supersensitive rat caudal artery following 6-hydroxydopamine (6-OHDA) treatment

    International Nuclear Information System (INIS)

    Wong, S.K.; Foley, D.H.

    1986-01-01

    Contractile response and the Na-K pump activity, measured as ouabain-sensitive 86 Rb-uptake, were determined in caudal artery strips of rats pretreated with 6-OHDA. At 6-7 days after 6-OHDA treatment, the potencies of norepinephrine and serotonin in causing contraction of rat caudal artery were significantly increased by 2.3 - and 1.7 - fold respectively. There was, however, no change in maximum contractile response to either agent. Treatment with 6-OHDA also reduced endogenous catecholamine content of the caudal artery to 7% of the control. Analysis of ouabain-inhibitable 86 Rb-uptake of rat caudal artery by the double-reciprocal plots showed that both the rate of 86 Rb-uptake and the affinity for rubidium were depressed after 6-OHDA treatment. The results indicate that 6-OHDA induced supersensitivity in the rat caudal artery is associated with a decrease in the Na-K pump activity. These data provide additional support to the concept that inhibition of the Na-K pump may result in partial depolarization of the cell membrane which leads to supersensitivity of smooth muscle to excitatory drugs

  14. Aguas de un mismo caudal

    Directory of Open Access Journals (Sweden)

    Carlos Morales

    2015-01-01

    Full Text Available Borges, creía que “el periodismo distorsiona la mentalidad del escritor”, el autor de este artículo, plantea en cambio que son “aguas de un mismo caudal, que muy a menudo viajan juntas”, varias han sido, y son, las concepciones que han expuesto célebres protagonistas de estos dos hechos escriturales a favor y en contra del ejercicio del periodismo para mejorar o perjudicar al escritor. El aparente divorcio entre literatura y periodismo radica cabalmente en el intento equivocado de separarlos. En verdad son lo mismo y bien podríamos clasificar al periodismo como un género dentro de la literatura.

  15. The association between caudal anesthesia and increased risk of postoperative surgical complications in boys undergoing hypospadias repair.

    Science.gov (United States)

    Taicher, Brad M; Routh, Jonathan C; Eck, John B; Ross, Sherry S; Wiener, John S; Ross, Allison K

    2017-07-01

    Recent reports have suggested that caudal anesthesia may be associated with an increased risk of postoperative surgical complications. We examined our experience with caudal anesthesia in hypospadias repair to evaluate for increased risk of urethrocutaneous fistula or glanular dehiscence. All hypospadias repairs performed by a single surgeon in 2001-2014 were reviewed. Staged or revision surgeries were excluded. Patient age, weight, hypospadias severity, surgery duration, month and year of surgery, caudal anesthesia use, and postoperative complications were recorded. Bivariate and multivariate statistical analyses were performed. We identified 395 single-stage primary hypospadias repairs. Mean age was 15.6 months; 326 patients had distal (83%) and 69 had proximal (17%) hypospadias. Caudal anesthetics were used in 230 (58%) cases; 165 patients (42%) underwent local penile block at the discretion of the surgeon and/or anesthesiologist. Complications of urethrocutaneous fistula or glanular deshiscence occurred in 22 patients (5.6%) and were associated with caudal anesthetic use (OR 16.5, 95% CI 2.2-123.8, P = 0.007), proximal hypospadias (OR 8.2, 95% CI 3.3-20.0, P anesthesia was associated with an over 13-fold increase in the odds of developing postoperative surgical complications in boys undergoing hypospadias repair even after adjusting for urethral meatus location. Until further investigation occurs, clinicians should carefully consider the use of caudal anesthesia for children undergoing hypospadias repair. © 2017 John Wiley & Sons Ltd.

  16. Ultrasound as a Screening Tool for Performing Caudal Epidural Injections

    International Nuclear Information System (INIS)

    Nikooseresht, Mahshid; Hashemi, Masoud; Mohajerani, Seyed Amir; Shahandeh, Farideh; Agah, Mahvash

    2014-01-01

    The caudal approach to the epidural space has been used for decades to treat low back pain caused by lumbosacral root compression. The use of fluoroscopy during epidural steroid injection is the preferred method for placing the needle more accurately in the sacral hiatus, but it carries the risk of radiation hazard. The aim of the study was to assess the anatomical structure of the sacral hiatus and the feasibility of caudal epidural injections under ultrasound guidance. Two hundred and forty patients (male = 100, female = 140) with low back pain and sciatica who were candidates for caudal epidural injection were enrolled into this study. Ultrasound images of the sacral hiatus and bilateral cornua were obtained by a real-time linear array ultrasound transducer. The distance between bilateral cornua and the anterior and posterior wall of the sacrum were measured at the base (sacral hiatus). Under the guide of ultrasonography, we defined the injection successful if turbulence of medication fluid was observed in the sacral canal, but correct placement of the needle and injectant was confirmed on fluoroscopic view as the gold standard technique. The epidurogram showed that the injection was successful in 230 of the 240 patients (95.8%). In eight patients, the injection was not in the correct place in the sacral canal. The sacral hiatus could not be identified by ultrasound images in only two patients who had a closed sacral hiatus identified by fluoroscopy. The mean distance of the sacral hiatus was 4.7 ± 1.7 mm and the mean distance between bilateral cornua was 18.0 ± 2.8 mm. The mean duration of the procedure was 10.8 ± 6.8 minutes. No major complication was observed in the next month. In conclusion, ultrasound could be used as a safe, fast and reliable modality to observe the anatomic variation of the sacral hiatus and to perform caudal epidural injections

  17. Caudal pneumaticity and pneumatic hiatuses in the sauropod dinosaurs Giraffatitan and Apatosaurus.

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    Mathew J Wedel

    Full Text Available Skeletal pneumaticity is found in the presacral vertebrae of most sauropod dinosaurs, but pneumaticity is much less common in the vertebrae of the tail. We describe previously unrecognized pneumatic fossae in the mid-caudal vertebrae of specimens of Giraffatitan and Apatosaurus. In both taxa, the most distal pneumatic vertebrae are separated from other pneumatic vertebrae by sequences of three to seven apneumatic vertebrae. Caudal pneumaticity is not prominent in most individuals of either of these taxa, and its unpredictable development means that it may be more widespread than previously recognised within Sauropoda and elsewhere in Saurischia. The erratic patterns of caudal pneumatization in Giraffatitan and Apatosaurus, including the pneumatic hiatuses, show that pneumatic diverticula were more broadly distributed in the bodies of the living animals than are their traces in the skeleton. Together with recently published evidence of cryptic diverticula--those that leave few or no skeletal traces--in basal sauropodomorphs and in pterosaurs, this is further evidence that pneumatic diverticula were widespread in ornithodirans, both across phylogeny and throughout anatomy.

  18. Postoperative analgesia in children when using clonidine or fentanyl with ropivacaine given caudally

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    Usha Shukla

    2011-01-01

    Full Text Available Background: The aim of the study was to compare the efficacy of clonidine and fentanyl as an additive to ropivacaine given via single shot caudal epidural in pediatric patients for postoperative pain relief. Materials and Methods: In the present double blind study, 90 children of ASA-I-II aged 3-8 years scheduled for infraumblical surgical procedures were randomly allocated to two groups to receive either ropivacaine 0.25% 1 ml/kg+clonidine 2 μg/kg (group I or ropivacaine 0.25% 1 μl/kg+fentanyl 1 μg/kg (group II. Caudal block was performed after the induction of general anesthesia. Postoperatively patients were observed for analgesia, sedation, hemodynamics, and side effects/complications. Results: Both the groups were similar with respect to patient and various block characteristics. The analgesic properties and hemodynamics were also comparable in both groups (P > 0.05. Side effects such as respiratory depression, vomiting bradycardia were significantly less in group I than group II (P < 0.05 ensuing more patient comfort. Conclusions: The analgesic properties of clonidine and fentanyl as additives to ropivacaine in single shot caudal epidural in children are comparable but clonidine offers a more favorable side effect profile. The use of clonidine as additive to ropivacaine in caudal epidural is superior choice to fentanyl because of lack of unwanted side effects and increased patient comfort.

  19. Caudal ecológico del río Chambas en la provincia Ciego de Ávila

    OpenAIRE

    Brown Manrique, Oscar; Gallardo Ballat, Yurisbel; Williams Harriote, Patricio W.; Torres Martínez, Yuneisi

    2016-01-01

    La investigación se desarrolló en el río Chambas de la provincia Ciego de Ávila con el objetivo de determinar el caudal ecológico mediante cinco metodologías: Curva de Permanencia de Caudales, Rafael Heras, Tennant, Franquet y Perímetro Mojado. Se analizó una serie de 21 años de gastos medios mensuales en el periodo comprendido de 1976 al 1986, obtenidos de la estación hidrométrica Puente Circuito Norte. Los principales resultados demostraron que los caudales promedios del río Chambas present...

  20. Caudal Regression and Encephalocele: Rare Manifestations of Expanded Goldenhar Complex

    Directory of Open Access Journals (Sweden)

    Gabriella D’Angelo

    2017-01-01

    Full Text Available Oculoauriculovertebral spectrum, or Goldenhar Syndrome, is a condition characterized by variable degrees of uni- or bilateral involvement of craniofacial structures, ocular anomalies, and vertebral defects. Its expressivity is variable; therefore, the term “expanded Goldenhar complex” has been coined. The Goldenhar Syndrome usually involves anomalies in craniofacial structures, but it is known that nervous system anomalies, including encephalocele or caudal regression, may, rarely, occur in this condition. We report two rare cases of infants affected by Goldenhar Syndrome, associated with neural tube defects, specifically caudal regression syndrome and nasal encephaloceles, to underline the extremely complex and heterogeneous clinical features of this oculoauriculovertebral spectrum. These additional particular cases could increase the number of new variable spectrums to be included in the “expanded Goldenhar complex.”

  1. Clofibric acid, a peroxisome proliferator-activated receptor alpha ligand, inhibits growth of human ovarian cancer.

    Science.gov (United States)

    Yokoyama, Yoshihito; Xin, Bing; Shigeto, Tatsuhiko; Umemoto, Mika; Kasai-Sakamoto, Akiko; Futagami, Masayuki; Tsuchida, Shigeki; Al-Mulla, Fahd; Mizunuma, Hideki

    2007-04-01

    Recent reports have shown that peroxisome proliferator-activated receptor (PPAR)alpha ligands reduce growth of some types of malignant tumors and prevent carcinogenesis. In this study, we investigated the inhibitory effect of clofibric acid (CA), a ligand for PPARalpha on growth of ovarian malignancy, in in vivo and in vitro experiments using OVCAR-3 and DISS cells derived from human ovarian cancer and aimed to elucidate the molecular mechanism of its antitumor effect. CA treatment significantly suppressed the growth of OVCAR-3 tumors xenotransplanted s.c. and significantly prolonged the survival of mice with malignant ascites derived from DISS cells as compared with control. CA also dose-dependently inhibited cell proliferation of cultured cell lines. CA treatment increased the expression of carbonyl reductase (CR), which promotes the conversion of prostaglandin E(2) (PGE(2)) to PGF(2alpha), in implanted OVCAR-3 tumors as well as cultured cells. CA treatment decreased PGE(2) level as well as vascular endothelial growth factor (VEGF) amount in both of OVCAR-3-tumor and DISS-derived ascites. Reduced microvessel density and induced apoptosis were found in solid OVCAR-3 tumors treated by CA. Transfection of CR expression vector into mouse ovarian cancer cells showed significant reduction of PGE(2) level as well as VEGF expression. These results indicate that CA produces potent antitumor effects against ovarian cancer in conjunction with a reduction of angiogenesis and induction of apoptosis. We conclude that CA could be an effective agent in ovarian cancer and should be tested alone and in combination with other anticancer drugs.

  2. Caudal Regression Syndrome with Partial Agenesis of the Corpus callosum and Partial Lobar Holoprosencephaly

    Science.gov (United States)

    Hashami, Hilal Al; Bataclan, Maria F; Mathew, Mariam; Krishnan, Lalitha

    2010-01-01

    Caudal regression syndrome is a rare fetal condition of diabetic pregnancy. Although the exact mechanism is not known, hyperglycaemia during embryogenesis seems to act as a teratogen. Independently, caudal regression syndrome (CRS), agenesis of the corpus callosum (ACC) and partial lobar holoprosencephaly (HPE) have been reported in infants of diabetic mothers. To our knowledge, a combination of all these three conditions has not been reported so far. PMID:21509087

  3. Comparing caudal and penile nerve blockade using bupivacaine in ...

    African Journals Online (AJOL)

    Background: Caudal anaesthesia is recommended for most surgical procedures of the lower part of the body, mainly below the umbilicus. It has been well established that a dorsal penile nerve block immediately after surgery decreases postoperative pain in children undergoing hypospadias repair. This study aimed to ...

  4. Lateral prefrontal cortex is organized into parallel dorsal and ventral streams along the rostro-caudal axis.

    Science.gov (United States)

    Blumenfeld, Robert S; Nomura, Emi M; Gratton, Caterina; D'Esposito, Mark

    2013-10-01

    Anatomical connectivity differences between the dorsal and ventral lateral prefrontal cortex (PFC) of the non-human primate strongly suggests that these regions support different functions. However, after years of study, it remains unclear whether these regions are functionally distinct. In contrast, there has been a groundswell of recent studies providing evidence for a rostro-caudal functional organization, along the lateral as well as dorsomedial frontal cortex. Thus, it is not known whether dorsal and ventral regions of lateral PFC form distinct functional networks and how to reconcile any dorso-ventral organization with the medio-lateral and rostro-caudal axes. Here, we used resting-state connectivity data to identify parallel dorsolateral and ventrolateral streams of intrinsic connectivity with the dorsomedial frontal cortex. Moreover, we show that this connectivity follows a rostro-caudal gradient. Our results provide evidence for a novel framework for the intrinsic organization of the frontal cortex that incorporates connections between medio-lateral, dorso-ventral, and rostro-caudal axes.

  5. Computed tomography in the evaluation of caudal cervical spondylomyelopathy of the Doberman Pinscher

    International Nuclear Information System (INIS)

    Sharp, N.J.H.; Cofone, M.; Robertson, I.D.; DeCarlo, A.; Smith, G.K.; Thrall, D.E.

    1995-01-01

    Caudal cervical spondylomyelopathy is a common neurologic disorder of Doberman pinschers which has a number of striking similarities to cervical spondylotic myelopathy in humans. Diagnosis of this human disease is facilitated considerably by the use of computed tomographic (CT) myelography. Sixteen Doberman pinscher dogs with caudal cervical spondylomyelopathy were studied by conventional myelography followed by CT myelography. A close correlation was noted between the CT myelographic appearance of the cervical spinal cord in these dogs, and that reported for human cervical spondylotic myelopathy. Five dogs had atrophy of the spinal cord, and in another there was an accumulation of contrast medium within the spinal cord. These features are often associated with a poor response to surgical decompression in humans with cervical spondylotic myelopathy. The CT examination provided information that could not be obtained by conventional myelography alone and should be considered as an additional diagnostic procedure in dogs with caudal cervical spondylomyelopathy

  6. Sensory nerve conduction in the caudal nerves of rats with diabetes Condução nervosa sensorial no nervo caudal de ratos com diabetes experimental

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    Celina Cordeiro de Carvalho

    2011-04-01

    Full Text Available PURPOSE: To investigate sensory nerve conduction of the caudal nerve in normal and diabetic rats. METHODS: Diabetes was induced in twenty 8-weeks old Wistar male rats. Twenty normal rats served as controls. Caudal nerve conduction studies were made before diabetes induction and the end of each week for six consecutive weeks. The caudal nerve was stimulated distally and nerve potentials were recorded proximally on the animal's tail using common "alligator" clips as surface electrodes. RESULTS: After induction, nerve conduction velocities (NCV increased slower in the diabetic than in the control group. Sensory nerve action potentials (SNAP conduction velocities increased slower in the diabetic than in the control group (slope of regression line: 0.5 vs 1.3m/s per week; NCV in the 15th week = 39±3m/s vs 44±4m/s. Tukey's tests showed differences between groups at the 11th, 13th and 15th weeks old. From the 10th week on, SNAP amplitudes increased faster in the diabetic than in the control group (slopes of the regression line: 10 vs 8µV per week; SNAP amplitudes in the 15th week: 107±23µV vs 85±13µV. Differences at the 12th, 13th and 15th weeks were significant. CONCLUSION: In diabetic rats nerve conduction velocities were slower whereas amplitudes were larger than in normal rats.OBJETIVO: Investigar a condução nervosa sensorial do nervo caudal em ratos normais e diabéticos. MÉTODOS: O diabetes foi induzido em vinte ratos Wistar com idade de oito semanas. Vinte ratos serviram como controle. Os estudos da condução do nervo caudal foram feitos antes da indução do diabetes e ao final de cada semana, durante seis semanas consecutivas. O nervo caudal foi estimulado distalmente e potenciais foram registrados proximalmente na cauda do animal, usando clipes comuns "jacaré" como eletrodos de superfície. RESULTADOS: Após a indução, a velocidade de condução nervosa (VCN aumentou mais lentamente no grupo diabético que no controle

  7. Comparison of caudal bupivacaine and bupivacaine-tramadol for postoperative analgesia in children with hypospadias repair

    International Nuclear Information System (INIS)

    Khan, S.; Memon, M.I.

    2008-01-01

    To compare the effects after caudal bupivacaine alone and bupivacaine-tramadol in young children with hypospadias repair. Randomized controlled trial. Sixty children aged between 13-53 months coming for hypospadias repair were divided randomly into two groups A and B. A caudal block was performed immediately after induction of general anaesthesia. The patients in group A received 0.125% bupivacaine 1 ml/kg with tramadol 1 mg/kg body weight caudally. Group B patients received 0.25% bupivacaine 1 ml/kg body weight caudally. Anaesthesia was discontinued after completion of surgery. In the recovery area, ventilatory frequency and pain scores were recorded at 1 hourly interval for first 6 hours and then every 2 hours for next 6 hours postoperatively. A modified TPPPS (Toddler-Preschool Postoperative Pain Scale) was used to assess the pain. Episodes of vomiting, facial flush and pruritus were noted, if present. The duration of analgesia was significantly prolonged in group A patients (p-value=0.001). A low frequency of postoperative vomiting was observed in both groups i.e. 10% in group A and 6.66% in group B (p-value=0.64). No respiratory depression, flushing and pruritus were observed. Low dose combination of bupivacaine and tramadol, when administered caudally, had an additive effect and provided prolonged and effective postoperative analgesia with minimal side effects. The risk of toxicity from bupivacaine decreased when combined with tramadol in low doses. (author)

  8. Eosinophil peroxidase signals via epidermal growth factor-2 to induce cell proliferation.

    LENUS (Irish Health Repository)

    Walsh, Marie-Therese

    2011-11-01

    Eosinophils exert many of their inflammatory effects in allergic disorders through the degranulation and release of intracellular mediators, including a set of cationic granule proteins that include eosinophil peroxidase. Studies suggest that eosinophils are involved in remodeling. In previous studies, we showed that eosinophil granule proteins activate mitogen-activated protein kinase signaling. In this study, we investigated the receptor mediating eosinophil peroxidase-induced signaling and downstream effects. Human cholinergic neuroblastoma IMR32 and murine melanoma B16.F10 cultures, real-time polymerase chain reaction, immunoprecipitations, and Western blotting were used in the study. We showed that eosinophil peroxidase caused a sustained increase in both the expression of epidermal growth factor-2 (HER2) and its phosphorylation at tyrosine 1248, with the consequent activation of extracellular-regulated kinase 1\\/2. This, in turn, promoted a focal adhesion kinase-dependent egress of the cyclin-dependent kinase inhibitor p27(kip) from the nucleus to the cytoplasm. Eosinophil peroxidase induced a HER2-dependent up-regulation of cell proliferation, indicated by an up-regulation of the nuclear proliferation marker Ki67. This study identifies HER2 as a novel mediator of eosinophil peroxidase signaling. The results show that eosinophil peroxidase, at noncytotoxic levels, can drive cell-cycle progression and proliferation, and contribute to tissue remodeling and cell turnover in airway disease. Because eosinophils are a feature of many cancers, these findings also suggest a role for eosinophils in tumorigenesis.

  9. Electrophysical properties, synaptic transmission and neuromodulation in serotonergic caudal raphe neurons.

    Science.gov (United States)

    Li, Y W; Bayliss, D A

    1998-06-01

    1. We studied electrophysiological properties, synaptic transmission and modulation by 5-hydroxytryptamine (5-HT) of caudal raphe neurons using whole-cell recording in a neonatal rat brain slice preparation; recorded neurons were identified as serotonergic by post-hoc immunohistochemical detection of tryptophan hydroxylase, the 5-HT-synthesizing enzyme. 2. Serotonergic neurons fired spontaneously (approximately 1 Hz), with maximal steady state firing rates of < 4 Hz. 5-Hydroxytryptamine caused hyperpolarization and cessation of spike activity in these neurons by activating inwardly rectifying K+ conductance via somatodendritic 5-HT1A receptors. 3. Unitary glutamatergic excitatory post-synaptic potentials (EPSP) and currents (EPSC) were evoked in serotonergic neurons by local electrical stimulation. Evoked EPSC were potently inhibited by 5-HT, an effect mediated by presynaptic 5-HT1B receptors. 4. In conclusion, serotonergic caudal raphe neurons are spontaneously active in vitro; they receive prominent glutamatergic synaptic inputs. 5-Hydroxytryptamine regulates serotonergic neuronal activity of the caudal raphe by decreasing spontaneous activity via somatodendritic 5-HT1A receptors and by inhibiting excitatory synaptic transmission onto these neurons via presynaptic 5-HT1B receptors. These local modulatory mechanisms provide multiple levels of feedback autoregulation of serotonergic raphe neurons by 5-HT.

  10. Endogenous growth factor stimulation of hemocyte proliferation induces resistance to Schistosoma mansoni challenge in the snail host.

    Science.gov (United States)

    Pila, Emmanuel A; Gordy, Michelle A; Phillips, Valerie K; Kabore, Alethe L; Rudko, Sydney P; Hanington, Patrick C

    2016-05-10

    Digenean trematodes are a large, complex group of parasitic flatworms that infect an incredible diversity of organisms, including humans. Larval development of most digeneans takes place within a snail (Gastropoda). Compatibility between snails and digeneans is often very specific, such that suitable snail hosts define the geographical ranges of diseases caused by these worms. The immune cells (hemocytes) of a snail are sentinels that act as a crucial barrier to infection by larval digeneans. Hemocytes coordinate a robust and specific immunological response, participating directly in parasite killing by encapsulating and clearing the infection. Hemocyte proliferation and differentiation are influenced by unknown digenean-specific exogenous factors. However, we know nothing about the endogenous control of hemocyte development in any gastropod model. Here, we identify and functionally characterize a progranulin [Biomphalaria glabrata granulin (BgGRN)] from the snail B. glabrata, a natural host for the human blood fluke Schistosoma mansoni Granulins are growth factors that drive proliferation of immune cells in organisms, spanning the animal kingdom. We demonstrate that BgGRN induces proliferation of B. glabrata hemocytes, and specifically drives the production of an adherent hemocyte subset that participates centrally in the anti-digenean defense response. Additionally, we demonstrate that susceptible B. glabrata snails can be made resistant to infection with S. mansoni by first inducing hemocyte proliferation with BgGRN. This marks the functional characterization of an endogenous growth factor of a gastropod mollusc, and provides direct evidence of gain of resistance in a snail-digenean infection model using a defined factor to induce snail resistance to infection.

  11. Regionalizacion de caudales mensuales en la región hidrográfica del Titicaca Puno Perú

    OpenAIRE

    Lujano Laura, Apolinario; Autoridad Nacional del Agua – Perú; Quispe Aragón, José Pitágoras; Autoridad Nacional del Agua – Perú; Lujano Laura, Efraín; Universidad Peruana Unión – Perú

    2017-01-01

    RESUMENLa presente investigación se realizó en la Región Hidrográfica del Titicaca, Perú. El objetivo principal fue desarrollar modelos regionales de caudales medios mensuales y de persistencia de los principales ríos, aplicado a la problemática de la estimación de caudales en cuencas sin registro hidrométrico. Se tomaron como variables independientes las características climáticas y fisiográficas de las cuencas en estudio y como variable dependiente los caudales medios mensuales y de persist...

  12. Evaluation of gradual occlusion of the caudal vena cava in clinically normal dogs.

    Science.gov (United States)

    Peacock, John T; Fossum, Theresa W; Bahr, Anne M; Miller, Matthew W; Edwards, John F

    2003-11-01

    To devise a technique for gradual occlusion of the caudal vena cava in dogs and determine effects of complete occlusion of the caudal vena cava. 8 mixed-breed hounds that weighed between 25 and 30 kg. Baseline evaluation of dogs included serum biochemical analyses and determination of glomerular filtration rate (GFR) with dynamic renal scintigraphy and plasma clearance analysis. An occluder was placed around the vena cava in the region cranial to the renal veins. The occluder was attached to a vascular access port. The vena cava was gradually occluded over 2 weeks. The GFR was measured every 2 weeks after surgery, and venograms were performed every 3 weeks after surgery. Blood samples were collected every 48 hours for the first week and then weekly thereafter to measure BUN and creatinine concentrations and activities of alanine transaminase, alkaline phosphatase, and creatinine kinase. Dogs were euthanatized 6 weeks after surgery, and tissues were submitted for histologic examination. The GFR and biochemical data were compared with baseline values. Gradual occlusion of the caudal vena cava was easily and consistently performed with this method, and adverse clinical signs were not detected. Formation of collateral vessels allowed overall GFR to remain constant despite a decrease in function of the left kidney. Measured biochemical values did not deviate from reference ranges. Gradual occlusion of the caudal vena cava may allow removal of adrenal gland tumors with vascular invasion that would otherwise be difficult or impossible to resect.

  13. Organ and Effective Dose Coefficients for Cranial and Caudal Irradiation Geometries: Neutrons

    Science.gov (United States)

    Veinot, K. G.; Eckerman, K. F.; Hertel, N. E.; Hiller, M. M.

    2017-09-01

    With the introduction of new recommendations by ICRP Publication 103, the methodology for determining the protection quantity, effective dose, has been modified. The modifications include changes to the defined organs and tissues, the associated tissue weighting factors, radiation weighting factors, and the introduction of reference sex-specific computational phantoms (ICRP Publication 110). Computations of equivalent doses in organs and tissues are now performed in both the male and female phantoms and the sex-averaged values used to determine the effective dose. Dose coefficients based on the ICRP 103 recommendations were reported in ICRP Publication 116, the revision of ICRP Publication 74 and ICRU Publication 57. The coefficients were determined for the following irradiation geometries: anterior-posterior (AP), posterior-anterior (PA), right and left lateral (RLAT and LLAT), rotational (ROT), and isotropic (ISO). In this work, the methodology of ICRP Publication 116 was used to compute dose coefficients for neutron irradiation of the body with parallel beams directed upward from below the feet (caudal) and directed downward from above the head (cranial). These geometries may be encountered in the workplace from personnel standing on contaminated surfaces or volumes and from overhead sources. Calculations of organ and tissue absorbed doses for caudal and cranial exposures to neutrons ranging in energy from 10-9 MeV to 10 GeV have been performed using the MCNP6 radiation transport code and the adult reference voxel phantoms of ICRP Publication 110. At lower energies the effective dose per particle fluence for cranial and caudal exposures is less than AP orientations while above about 30 MeV the cranial and caudal values are greater.

  14. Evaluation of caudal dexamethasone with ropivacaine for post-operative analgesia in paediatric herniotomies: A randomised controlled study

    Directory of Open Access Journals (Sweden)

    Santosh Choudhary

    2016-01-01

    Full Text Available Background and Aims: Caudal analgesia is one of the most popular regional blocks in paediatric patients undergoing infra-umbilical surgeries but with the drawback of short duration of action after single shot local anaesthetic injection. We evaluated whether caudal dexamethasone 0.1 mg/kg as an adjuvant to the ropivacaine improved analgesic efficacy after paediatric herniotomies. Methods: Totally 128 patients of 1–5 years age group, American Society of Anaesthesiologists physical status I and II undergoing elective inguinal herniotomy were randomly allocated to two groups in double-blind manner. Group A received 1 ml/kg of 0.2% ropivacaine caudally and Group B received 1 ml/kg of 0.2% ropivacaine, in which 0.1 mg/kg dexamethasone was added for caudal analgesia. Post operative pain by faces, legs, activity, cry and consolability tool score, rescue analgesic requirement and adverse effects were noted for 24 h. Results: Results were statistically analysed using Student's t-test. Pain scores measured at 1, 2, 4, and 6 h post-operative, were lower in Group B as compared to Group A. Mean duration of analgesia in Group A was 248.4 ± 54.1 min and in Group B was 478.046 ± 104.57 min with P = 0.001. Rescue analgesic requirement was more in Group A as compared to Group B. Adverse effects after surgery were comparable between the two groups. Conclusion: Caudal dexamethasone added to ropivacaine is a good alternative to prolong post-operative analgesia with less pain score compared to caudal ropivacaine alone.

  15. Comparative study of caudal bupivacaine versus bupivacaine with tramadol for postoperative analgesia in paediatric cancer patients

    Institute of Scientific and Technical Information of China (English)

    Mohammed Hegazy; Ayman A. Ghoneim

    2013-01-01

    Objective: Caudal epidural analgesia has become very common analgesic technique in paediatric surgery. Add-ing tramadol to bupivacaine for caudal injection prolongs duration of analgesia with minimal side effects. The aim of the study was to investigate the different effects of caudal bupivacaine versus bupivacaine with thamadol for postoperative analgesia in paediatric cancer patients. Methods: A prospective randomized controlled trial was conducted over 40 paediatric cancer pa-tients who were recruited from Children Cancer Hospital of Egypt (57357 Hospital). Patients were randomized into 2 groups: bupivacaine group (group B, 20 patients) to receive single shot caudal block of 1 mL/kg 0.1875% bupivacaine; tramadol group (group T, 20 patients) prepared as group B with the addition of 1 mg/kg caudal tramadol. Results: The mean duration of analgesia was significantly longer among group T than group B [(24 ± 13.7) hours versus (7 ± 3.7) hours respectively with P = 0.001]. Group T showed a significantly lower mean FLACC score than group B (2.2 ± 0.9 versus 3.6 ± 0.6 with P = 0.002). The difference in FLACC score was comparable on arrival, and after 2 and 4 hours. At 8 and 12 hours the group B recorded significantly higher scores (P = 0.002 and 0.0001 respectively). There were no significant differences between the groups as regards sedation score [the median in both groups was 1 (0–1) with P value = o.8]. No one developed facial flush or pruritis. Conclusion: Caudal injection of low dose tramadol 1 mg/kg with bupivacaine 0.1875% is proved to be effective, long standing technique for postoperative analgesia in major paediatric cancer surgery and almost devoid of side effect.

  16. Evaluation of Anesthesia Profile in Pediatric Patients after Inguinal Hernia Repair with Caudal Block or Local Wound Infiltration

    Directory of Open Access Journals (Sweden)

    Aleksandra Gavrilovska-Brzanov

    2016-02-01

    CONCLUSIONS: Between children undergoing inguinal hernia repair, local wound infiltration insures safety and satisfactory analgesia for surgery. Compared to caudal block it is not overwhelming. Caudal block provides longer analgesia, however complications are rather common.

  17. Proliferation of NS0 cells in protein-free medium: the role of cell-derived proteins, known growth factors and cellular receptors.

    Science.gov (United States)

    Spens, Erika; Häggström, Lena

    2009-05-20

    NS0 cells proliferate without external supply of growth factors in protein-free media. We hypothesize that the cells produce their own factors to support proliferation. Understanding the mechanisms behind this autocrine regulation of proliferation may open for the novel approaches to improve animal cell processes. The following proteins were identified in NS0 conditioned medium (CM): cyclophilin A, cyclophilin B (CypB), cystatin C, D-dopachrome tautomerase, IL-25, isopentenyl-diphosphate delta-isomerase, macrophage migration inhibitory factor (MIF), beta(2)-microglobulin, Niemann pick type C2, secretory leukocyte protease inhibitor, thioredoxin-1, TNF-alpha, tumour protein translationally controlled 1 and ubiquitin. Further, cDNA microarray analysis indicated that the genes for IL-11, TNF receptor 6, TGF-beta receptor 1 and the IFN-gamma receptor were transcribed. CypB, IFN-alpha/beta/gamma, IL-11, IL-25, MIF, TGF-beta and TNF-alpha as well as the known growth factors EGF, IGF-I/II, IL-6, leukaemia inhibitory factor and oncostatin M (OSM) were excluded as involved in autocrine regulation of NS0 cell proliferation. The receptors for TGF-beta, IGF and OSM are however present in NS0 cell membranes since TGF-beta(1) caused cell death, and IGF-I/II and OSM improved cell growth. Even though no ligand was found, the receptor subunit gp130, active in signal transduction of the IL-6 like proteins, was shown to be essential for NS0 cells as demonstrated by siRNA gene silencing.

  18. Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor α signalling and results in tamoxifen insensitive proliferation

    International Nuclear Information System (INIS)

    Moerkens, Marja; Zhang, Yinghui; Wester, Lynn; Water, Bob van de; Meerman, John HN

    2014-01-01

    Tamoxifen resistance is a major problem in the treatment of estrogen receptor (ER) α -positive breast cancer patients. Although the mechanisms behind tamoxifen resistance are still not completely understood, clinical data suggests that increased expression of receptor tyrosine kinases is involved. Here, we studied the estrogen and anti-estrogen sensitivity of human breast cancer MCF7 cells that have a moderate, retroviral-mediated, ectopic expression of epidermal growth factor receptor (MCF7-EGFR). Proliferation of MCF7-EGFR and parental cells was induced by 17β-estradiol (E2), epidermal growth factor (EGF) or a combination of these. Inhibition of proliferation under these conditions was investigated with 4-hydroxy-tamoxifen (TAM) or fulvestrant at 10 -12 to 10 -6 M. Cells were lysed at different time points to determine the phosphorylation status of EGFR, MAPK 1/3 , AKT and the expression of ERα. Knockdown of target genes was established using smartpool siRNAs. Transcriptomics analysis was done 6 hr after stimulation with growth factors using Affymetrix HG-U133 PM array plates. While proliferation of parental MCF7 cells could only be induced by E2, proliferation of MCF7-EGFR cells could be induced by either E2 or EGF. Treatment with TAM or fulvestrant did significantly inhibit proliferation of MCF7-EGFR cells stimulated with E2 alone. EGF treatment of E2/TAM treated cells led to a marked cell proliferation thereby overruling the anti-estrogen-mediated inhibition of cell proliferation. Under these conditions, TAM however did still inhibit ERα- mediated transcription. While siRNA-mediated knock-down of EGFR inhibited the EGF- driven proliferation under TAM/E2/EGF condition, knock down of ERα did not. The TAM resistant cell proliferation mediated by the conditional EGFR-signaling may be dependent on the PI3K/Akt pathway but not the MEK/MAPK pathway, since a MEK inhibitor (U0126), did not block the proliferation. Transcriptomic analysis under the various E2/TAM

  19. Basic fibroblast growth factor enhances cell proliferation in the dentate gyrus of neonatal rats following hypoxic-ischemic brain damage.

    Science.gov (United States)

    Zhu, Huan; Qiao, Lixing; Sun, Yao; Yin, Liping; Huang, Li; Jiang, Li; Li, Jiaqing

    2018-04-23

    Perinatal hypoxic-ischemic insult is considered a major contributor to child mortality and morbidity and leads to neurological deficits in newborn infants. There has been a lack of promising neurotherapeutic interventions for hypoxic-ischemic brain damage (HIBD) for clinical application in infants. The present study aimed to investigate the correlation between neurogenesis and basic fibroblast growth factor (bFGF) in the hippocampal dentate gyrus (DG) region in neonatal rats following HIBD. Cell proliferation was examined by detecting BrdU signals, and the role of bFGF in cell proliferation in the DG region following neonatal HIBD was investigated. Cell proliferation was induced by HIBD in the hippocampal DG of neonatal rats. Furthermore, bFGF gene expression was upregulated in the hippocampus in neonatal rats, particularly between 7 and 14 days after HIBD. Moreover, intraperitoneal injection of exogenous bFGF enhanced cell proliferation in the hippocampal DG following neonatal HIBD. Taken together, these data indicate that cell proliferation in the DG could be induced by neonatal HIBD, and bFGF promotes proliferation following neonatal HIBD. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Caudal dysgenesis and sirenomelia-single centre experience suggests common pathogenic basis.

    Science.gov (United States)

    Thottungal, Anjana D; Charles, Adrian K; Dickinson, Jan E; Bower, Carol

    2010-10-01

    Abnormally formed lower limbs with varying degrees of fusion are the major feature of sirenomelia whereas maldeveloped lower limbs without fusion are found in association with caudal dysgenesis (CD). The relationship between these two entities has been a topic of debate for many years. The presence of a single umbilical artery originating from the abdominal aorta was considered a major feature distinguishing sirenomelia from CD. Based on this finding, the vascular steal theory was put forward as the causative mechanism of sirenomelia. CD and sirenomelia were considered to be two entirely different entities with distinct pathogenic mechanisms. However, it is now clear that a single umbilical artery can be found in some patients of CD and normal umbilical arteries in some patients of sirenomelia. The hypothesis of primary deficiency of caudal mesoderm caused by early developmental disruption suggests that sirenomelia and CD are two ends of a spectrum of maldevelopment of caudal mesoderm. In this paper we report on the clinical and pathological features of 16 patients of CD and 9 patients of sirenomelia from our institution and review the literature. This series of cases is notable for the significant association with neural tube defects, refining the renal and urogenital pathology associated with these conditions, and supporting the concept of a continuum of the disease spectrum. Copyright © 2010 Wiley-Liss, Inc.

  1. Systematization, distribution and territory of the caudal cerebral artery on the brain's surface of the turkey (Meleagris gallopavo

    Directory of Open Access Journals (Sweden)

    Amarílis Díaz de Carvalho

    2014-10-01

    Full Text Available Thirty Meleagris gallopavo heads with their neck segments were used. Animals were contained and euthanized with the association of mebezonium iodide, embutramide and tetracaine hydrochloride (T 61, Intervet by intravenous injection. The arterial system was rinsed with cold saline solution (15°C, with 5000IU heparin and filled with red-colored latex. The samples were fixed in 20% formaldehyde for seven days. The brains were removed with a segment of cervical spinal cord and after, the dura-mater was removed and the arteries dissected. The cerebral carotid arteries, after the intercarotid anastomosis, were projected around the hypophysis, until they reached the tuber cinereum and divided into their terminal branches, the caudal branch and the rostral branch. The rostral branch was projected rostrolateralwards and gave off, in sequence, two collateral branches, the caudal cerebral and the middle cerebral arteries and the terminal branch was as cerebroethmoidal artery. The caudal cerebral artery of one antimere formed the interhemispheric artery, which gave off dorsal hemispheric branches to the convex surface of both antimeres. Its dorsal tectal mesencephalic branch, of only one antimere, originated the dorsal cerebellar artery. In the interior of the cerebral transverse fissure, after the origin of the dorsal tectal mesencephalic artery, the caudal cerebral artery emitted occipital hemispheric branches, pineal branches and medial hemispheric branches, on both antimeres. The caudal cerebral artery's territory comprehended the entire surface of the dorsal hemioptic lobe, the rostral surface of the cerebellum, the diencephalic structures, the caudal pole and the medial surface of the cerebral hemisphere and in the convex surface, the sagittal eminence except for its most rostral third. Due to the asymmetry found in the caudal cerebral arteries' ramifications, the models were classified into three types and their respective subtypes.

  2. Caudal block and emergence delirium in pediatric patients: Is it analgesia or sedation?

    Directory of Open Access Journals (Sweden)

    Aparna Sinha

    2012-01-01

    Full Text Available Background: Emergence delirium (ED although a short-lived and self-limiting phenomenon, makes a child prone to injury in the immediate postoperative period and hence is a cause of concern not only to the pediatric anesthesiologist, surgeons, and post anesthesia care unit staff but also amongst parents. Additional medication to quieten the child offsets the potential benefits of rapid emergence and delays recovery in day care settings. There is conflicting evidence of influence of analgesia and sedation following anesthesia on emergence agitation. We hypothesized that an anesthetic technique which improves analgesia and prolongs emergence time will reduce the incidence of ED. We selected ketamine as adjuvant to caudal block for this purpose. Methods: This randomized, double blind prospective study was performed in 150 premedicated children ASA I, II, aged 2 to 8 years who were randomly assigned to either group B (caudal with bupivacaine, BK (bupivacaine and ketamine, or NC (no caudal, soon after LMA placement. Recovery characteristics and complications were recorded. Results: Emergence time, duration of pain relief, and Pediatric Anesthesia Emergence Delirium (PAED scores were significantly higher in the NC group (P<0.05. Duration of analgesia and emergence time were significantly more in group BK than groups B and NC. However, the discharge readiness was comparable between all groups. No patient in BK group required to be given any medication to treat ED. Conclusion: Emergence time as well as duration of analgesia have significant influence on incidence of emergence delirium. Ketamine, as caudal adjuvant is a promising agent to protect against ED in children, following sevoflurane anesthesia.

  3. MicroRNA-26a modulates transforming growth factor beta-1-induced proliferation in human fetal lung fibroblasts

    International Nuclear Information System (INIS)

    Li, Xiaoou; Liu, Lian; Shen, Yongchun; Wang, Tao; Chen, Lei; Xu, Dan; Wen, Fuqiang

    2014-01-01

    Highlights: • Endogenous miR-26a inhibits TGF-beta 1 induced proliferation of lung fibroblasts. • miR-26a induces G1 arrest through directly targeting 3′-UTR of CCND2. • TGF indispensable receptor, TGF-beta R I, is regulated by miR-26a. • miR-26a acts through inhibiting TGF-beta 2 feedback loop to reduce TGF-beta 1. • Collagen type I and connective tissue growth factor are suppressed by miR-26a. - Abstract: MicroRNA-26a is a newly discovered microRNA that has a strong anti-tumorigenic capacity and is capable of suppressing cell proliferation and activating tumor-specific apoptosis. However, whether miR-26a can inhibit the over-growth of lung fibroblasts remains unclear. The relationship between miR-26a and lung fibrosis was explored in the current study. We first investigated the effect of miR-26a on the proliferative activity of human lung fibroblasts with or without TGF-beta1 treatment. We found that the inhibition of endogenous miR-26a promoted proliferation and restoration of mature miR-26a inhibited the proliferation of human lung fibroblasts. We also examined that miR-26a can block the G1/S phase transition via directly targeting 3′-UTR of CCND2, degrading mRNA and decreasing protein expression of Cyclin D2. Furthermore, we showed that miR-26a mediated a TGF-beta 2-TGF-beta 1 feedback loop and inhibited TGF-beta R I activation. In addition, the overexpression of miR-26a also significantly suppressed the TGF-beta 1-interacting-CTGF–collagen fibrotic pathway. In summary, our studies indicated an essential role of miR-26a in the anti-fibrotic mechanism in TGF-beta1-induced proliferation in human lung fibroblasts, by directly targeting Cyclin D2, regulating TGF-beta R I as well as TGF-beta 2, and suggested the therapeutic potential of miR-26a in ameliorating lung fibrosis

  4. MicroRNA-26a modulates transforming growth factor beta-1-induced proliferation in human fetal lung fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaoou [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Liu, Lian [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Shen, Yongchun; Wang, Tao; Chen, Lei; Xu, Dan [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Wen, Fuqiang, E-mail: wenfuqiang.scu@gmail.com [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China)

    2014-11-28

    Highlights: • Endogenous miR-26a inhibits TGF-beta 1 induced proliferation of lung fibroblasts. • miR-26a induces G1 arrest through directly targeting 3′-UTR of CCND2. • TGF indispensable receptor, TGF-beta R I, is regulated by miR-26a. • miR-26a acts through inhibiting TGF-beta 2 feedback loop to reduce TGF-beta 1. • Collagen type I and connective tissue growth factor are suppressed by miR-26a. - Abstract: MicroRNA-26a is a newly discovered microRNA that has a strong anti-tumorigenic capacity and is capable of suppressing cell proliferation and activating tumor-specific apoptosis. However, whether miR-26a can inhibit the over-growth of lung fibroblasts remains unclear. The relationship between miR-26a and lung fibrosis was explored in the current study. We first investigated the effect of miR-26a on the proliferative activity of human lung fibroblasts with or without TGF-beta1 treatment. We found that the inhibition of endogenous miR-26a promoted proliferation and restoration of mature miR-26a inhibited the proliferation of human lung fibroblasts. We also examined that miR-26a can block the G1/S phase transition via directly targeting 3′-UTR of CCND2, degrading mRNA and decreasing protein expression of Cyclin D2. Furthermore, we showed that miR-26a mediated a TGF-beta 2-TGF-beta 1 feedback loop and inhibited TGF-beta R I activation. In addition, the overexpression of miR-26a also significantly suppressed the TGF-beta 1-interacting-CTGF–collagen fibrotic pathway. In summary, our studies indicated an essential role of miR-26a in the anti-fibrotic mechanism in TGF-beta1-induced proliferation in human lung fibroblasts, by directly targeting Cyclin D2, regulating TGF-beta R I as well as TGF-beta 2, and suggested the therapeutic potential of miR-26a in ameliorating lung fibrosis.

  5. Metameric pattern of intervertebral disc/vertebral body is generated independently of Mesp2/Ripply-mediated rostro-caudal patterning of somites in the mouse embryo.

    Science.gov (United States)

    Takahashi, Yu; Yasuhiko, Yukuto; Takahashi, Jun; Takada, Shinji; Johnson, Randy L; Saga, Yumiko; Kanno, Jun

    2013-08-15

    The vertebrae are derived from the sclerotome of somites. Formation of the vertebral body involves a process called resegmentation, by which the caudal half of a sclerotome is combined with the rostral half of the next sclerotome. To elucidate the relationship between resegmentation and rostro-caudal patterning of somite, we used the Uncx4.1-LacZ transgene to characterize the resegmentation process. Our observations suggested that in the thoracic and lumbar vertebrae, the Uncx4.1-expressing caudal sclerotome gave rise to the intervertebral disc (IVD) and rostral portion of the vertebral body (VB). In the cervical vertebrae, the Uncx4.1-expressing caudal sclerotome appeared to contribute to the IVD and both caudal and rostral ends of the VB. This finding suggests that the rostro-caudal gene expression boundary does not necessarily coincide with the resegmentation boundary. This conclusion was supported by analyses of Mesp2 KO and Ripply1/2 double KO embryos lacking rostral and caudal properties, respectively. Resegmentation was not observed in Mesp2 KO embryos, but both the IVD and whole VB were formed from the caudalized sclerotome. Expression analysis of IVD marker genes including Pax1 in the wild-type, Mesp2 KO, and Ripply1/2 DKO embryos also supported the idea that a metameric pattern of IVD/VB is generated independently of Mesp2/Ripply-mediated rostro-caudal patterning of somite. However, in the lumbar region, IVD differentiation appeared to be stimulated by the caudal property and suppressed by the rostral property. Therefore, we propose that rostro-caudal patterning of somites is not a prerequisite for metameric patterning of the IVD and VB, but instead required to stimulate IVD differentiation in the caudal half of the sclerotome. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Organ and effective dose coefficients for cranial and caudal irradiation geometries: photons

    International Nuclear Information System (INIS)

    Veinot, K.G.; Eckerman, K.F.; Hertel, N.E.

    2016-01-01

    With the introduction of new recommendations of the International Commission on Radiological Protection (ICRP) in Publication 103, the methodology for determining the protection quantity, effective dose, has been modified. The modifications include changes to the defined organs and tissues, the associated tissue weighting factors, radiation weighting factors and the introduction of reference sex-specific computational phantoms. Computations of equivalent doses in organs and tissues are now performed in both the male and female phantoms and the sex-averaged values used to determine the effective dose. Dose coefficients based on the ICRP 103 recommendations were reported in ICRP Publication 116, the revision of ICRP Publication 74 and ICRU Publication 57. The coefficients were determined for the following irradiation geometries: anterior-posterior (AP), posterior-anterior (PA), right and left lateral (RLAT and LLAT), rotational (ROT) and isotropic (ISO). In this work, the methodology of ICRP Publication 116 was used to compute dose coefficients for photon irradiation of the body with parallel beams directed upward from below the feet (caudal) and directed downward from above the head (cranial). These geometries may be encountered in the workplace from personnel standing on contaminated surfaces or volumes and from overhead sources. Calculations of organ and tissue kerma and absorbed doses for caudal and cranial exposures to photons ranging in energy from 10 keV to 10 GeV have been performed using the MCNP6.1 radiation transport code and the adult reference phantoms of ICRP Publication 110. As with calculations reported in ICRP 116, the effects of charged-particle transport are evident when compared with values obtained by using the kerma approximation. At lower energies the effective dose per particle fluence for cranial and caudal exposures is less than AP orientations while above ∼30 MeV the cranial and caudal values are greater. (authors)

  7. Unusual caudal vena cava thrombosis in a cow, secondary to Trueperella (Arcanobacterium pyogenes infection

    Directory of Open Access Journals (Sweden)

    Rodrigo Garcia Motta

    Full Text Available Abstract: The caudal vena cava thrombosis, or pulmonary thromboembolism, in cattle is correlated with lactic acidosis, caused by diets rich in grains and highly fermentable, associated or not to septic situations, used in feedlots of beef or high-producing dairy cattle. This paper reports an unusual caudal vena cava thrombosis in a cow, secondary to Trueperella (Arcanobacterium pyogenes infection, resulting in reduced milk production, anorexia, pale mucous membranes, ruminal atony, sternal decubitus and autoauscultation position. The heart was enlarged at necropsy, presence of clots distributed along the thoracic cavity, adherence between lung and pleura, abscesses, emphysema, petechiae, suffusions and ecchymosis in lungs, thickening of the caudal vena cava wall, hepatomegaly with chronic passive congestion ("nutmeg" aspect, and rumenitis. In lab, the actinomycete Trueperella (Arcanobacterium pyogenes was isolated from liver and lung samples, probably resulting through dissemination of the bacteria of the rumen content, what reaffirms the opportunistic behavior of this actinomycete.

  8. 8-Nitro-cGMP promotes bone growth through expansion of growth plate cartilage.

    Science.gov (United States)

    Hoshino, Marie; Kaneko, Kotaro; Miyamoto, Yoichi; Yoshimura, Kentaro; Suzuki, Dai; Akaike, Takaaki; Sawa, Tomohiro; Ida, Tomoaki; Fujii, Shigemoto; Ihara, Hideshi; Tanaka, Junichi; Tsukuura, Risa; Chikazu, Daichi; Mishima, Kenji; Baba, Kazuyoshi; Kamijo, Ryutaro

    2017-09-01

    In endochondral ossification, growth of bones occurs at their growth plate cartilage. While it is known that nitric oxide (NO) synthases are required for proliferation of chondrocytes in growth plate cartilage and growth of bones, the precise mechanism by which NO facilitates these process has not been clarified yet. C-type natriuretic peptide (CNP) also positively regulate elongation of bones through expansion of the growth plate cartilage. Both NO and CNP are known to use cGMP as the second messenger. Recently, 8-nitro-cGMP was identified as a signaling molecule produced in the presence of NO in various types of cells. Here, we found that 8-nitro-cGMP is produced in proliferating chondrocytes in the growth plates, which was enhanced by CNP, in bones cultured ex vivo. In addition, 8-nitro-cGMP promoted bone growth with expansion of the proliferating zone as well as increase in the number of proliferating cells in the growth plates. 8-Nitro-cGMP also promoted the proliferation of chondrocytes in vitro. On the other hand, 8-bromo-cGMP enhanced the growth of bones with expansion of hypertrophic zone of the growth plates without affecting either the width of proliferating zone or proliferation of chondrocytes. These results indicate that 8-nitro-cGMP formed in growth plate cartilage accelerates chondrocyte proliferation and bone growth as a downstream molecule of NO. Copyright © 2017. Published by Elsevier Inc.

  9. Plasma concentrations and pharmacokinetics of bupivacaine with and without adrenaline following caudal anaesthesia in infants

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing; Morton, N S; Cullen, P M

    2001-01-01

    The aim of this study was to determine whether the use of adrenaline 1/400000 added to 0.25% bupivacaine significantly delays the systemic absorption of the drug from the caudal epidural space in young infants.......The aim of this study was to determine whether the use of adrenaline 1/400000 added to 0.25% bupivacaine significantly delays the systemic absorption of the drug from the caudal epidural space in young infants....

  10. Efficacy of clonidine as an adjuvant to bupivacaine for caudal analgesia in children undergoing sub-umbilical surgery

    Directory of Open Access Journals (Sweden)

    Aruna Parameswari

    2010-01-01

    Full Text Available Caudal epidural analgesia with bupivacaine is very popular in paediatric anaesthesia for providing intra- and postoperative analgesia. Several adjuvants have been used to prolong the action of bupivacaine. We evaluated the efficacy of clonidine added to bupivacaine in prolonging the analgesia produced by caudal bupivacaine in children undergoing sub-umbilical surgery. One hundred children, age one to three years, undergoing sub-umbilical surgery, were prospectively randomized to one of two groups: caudal analgesia with 1 ml/kg of 0.25% bupivacaine in normal saline (Group A or caudal analgesia with 1 ml/kg of 0.25% bupivacaine with 1 μg/kg of clonidine in normal saline (Group B. Post-operative pain was assessed for 24 hours using the FLACC scale. The mean duration of analgesia was significantly longer in Group B (593.4 ± 423.3 min than in Group A (288.7 ± 259.1 min; P < 0.05. The pain score assessed using FLACC scale was compared between the two groups, and children in Group B had lower pain scores, which was statistically significant. The requirement of rescue medicine was lesser in Group B. Clonidine in a dose of 1 μg/kg added to 0.25% bupivacaine for caudal analgesia, during sub-umbilical surgeries, prolongs the duration of analgesia of bupivacaine, without any side effects.

  11. Kaempferol suppresses bladder cancer tumor growth by inhibiting cell proliferation and inducing apoptosis.

    Science.gov (United States)

    Dang, Qiang; Song, Wenbin; Xu, Defeng; Ma, Yanmin; Li, Feng; Zeng, Jin; Zhu, Guodong; Wang, Xinyang; Chang, Luke S; He, Dalin; Li, Lei

    2015-09-01

    The effects of the flavonoid compound, kaempferol, which is an inhibitor of cancer cell proliferation and an inducer of cell apoptosis have been shown in various cancers, including lung, pancreatic, and ovarian, but its effect has never been studied in bladder cancer. Here, we investigated the effects of kaempferol on bladder cancer using multiple in vitro cell lines and in vivo mice studies. The MTT assay results on various bladder cancer cell lines showed that kaempferol enhanced bladder cancer cell cytotoxicity. In contrast, when analyzed by the flow cytometric analysis, DNA ladder experiment, and TUNEL assay, kaempferol significantly was shown to induce apoptosis and cell cycle arrest. These in vitro results were confirmed in in vivo mice studies using subcutaneous xenografted mouse models. Consistent with the in vitro results, we found that treating mice with kaempferol significant suppression in tumor growth compared to the control group mice. Tumor tissue staining results showed decreased expressions of the growth related markers, yet increased expressions in apoptosis markers in the kaempferol treated group mice tissues compared to the control group mice. In addition, our in vitro and in vivo data showed kaempferol can also inhibit bladder cancer invasion and metastasis. Further mechanism dissection studies showed that significant down-regulation of the c-Met/p38 signaling pathway is responsible for the kaempferol mediated cell proliferation inhibition. All these findings suggest kaempferol might be an effective and novel chemotherapeutic drug to apply for the future therapeutic agent to combat bladder cancer. © 2014 Wiley Periodicals, Inc.

  12. The PTHrP-Ihh feedback loop in the embryonic growth plate allows PTHrP to control hypertrophy and Ihh to regulate proliferation.

    Science.gov (United States)

    van Donkelaar, C C; Huiskes, R

    2007-01-01

    Growth plate and long bone development is governed by biochemical signaling pathways of which the PTHrP-Ihh system is the best known. Other factors, such as BMPs, FGFs and mechanical loading, may interact with this system. This study aims at elucidating the relative importance of PTHrP and Ihh for controlling proliferation, and hypertrophy in fetal growth plate cartilage. We assessed the question why reduced Ihh expression leads to more pronounced effects on the number of non-hypertrophic cells and total bone formation, compared to PTHrP down-regulation. Using few basic equations, constituted from literature data, this paper shows how the PTHrP-Ihh feedback system can control different aspects of tissue differentiation at distinct locations. In particular, it is shown that (mechanical or biochemical) perturbations will affect proliferation via Ihh-related parameters, whereas changes in PTHrP-related parameters selectively interact with hypertrophy. This is contra-intuitive, since PTHrP acts to keep cells proliferating. In this context, the critical PTHrP level for keeping cells proliferating has been reconsidered. In addition, an explanation is provided for the aforementioned difference in effect between reduced Ihh and PTHrP expression.

  13. Caudal Regression Syndrome with Partial Agenesis of the Corpus callosum and Partial Lobar Holoprosencephaly: Case report.

    Science.gov (United States)

    Hashami, Hilal Al; Bataclan, Maria F; Mathew, Mariam; Krishnan, Lalitha

    2010-04-01

    Caudal regression syndrome is a rare fetal condition of diabetic pregnancy. Although the exact mechanism is not known, hyperglycaemia during embryogenesis seems to act as a teratogen. Independently, caudal regression syndrome (CRS), agenesis of the corpus callosum (ACC) and partial lobar holoprosencephaly (HPE) have been reported in infants of diabetic mothers. To our knowledge, a combination of all these three conditions has not been reported so far.

  14. Incertidumbres en Mediciones de Caudal con Perfiladores de Corriente Acústicos Doppler desde Plataformas Móviles

    OpenAIRE

    Tarrab, Leticia

    2014-01-01

    Tesis (DCI)--FCEFN-UNC, 2013 Determina la incertidumbre en las mediciones de caudal con Perfiladores de Corriente Acústicos Doppler (ADCP) desde plataformas móviles a los fines de optimizar las técnicas de medición y elaborar recomendaciones para minimizar los errores (sesgo e incertidumbre aleatoria) en el uso de las técnicas de medición de caudales.

  15. Dinosaur speed demon: the caudal musculature of Carnotaurus sastrei and implications for the evolution of South American abelisaurids.

    Directory of Open Access Journals (Sweden)

    W Scott Persons

    Full Text Available In the South American abelisaurids Carnotaurus sastrei, Aucasaurus garridoi, and, to a lesser extent Skorpiovenator bustingorryi, the anterior caudal ribs project at a high dorsolateral inclination and have interlocking lateral tips. This unique morphology facilitated the expansion of the caudal hypaxial musculature at the expense of the epaxial musculature. Distinct ridges on the ventrolateral surfaces of the caudal ribs of Aucasaurus garridoi are interpreted as attachment scars from the intra caudofemoralis/ilio-ischiocaudalis septa, and confirm that the M. caudofemoralis of advanced South American abelisaurids originated from a portion of the caudal ribs. Digital muscle models indicate that, relative to its overall body size, Carnotaurus sastrei had a substantially larger M. caudofemoralis than any other theropod yet studied. In most non-avian theropods, as in many extant sauropsids, the M. caudofemoralis served as the primary femoral retractor muscle during the locomotive power stroke. This large investment in the M. caudofemoralis suggests that Carnotaurus sastrei had the potential for great cursorial abilities, particularly short-burst sprinting. However, the tightly interlocking morphology of the anterior caudal vertebrae implies a reduced ability to make tight turns. Examination of these vertebral traits in evolutionary context reveals a progressive sequence of increasing caudofemoral mass and tail rigidity among the Abelisauridae of South America.

  16. MODELO AUTORREGRESIVO BILINEAL APLICADO A LA PREDICCIÓN MENSUAL DE CAUDALES EN COLOMBIA

    Directory of Open Access Journals (Sweden)

    Juan David Cadavid

    2013-12-01

    Full Text Available Se aplica un modelo estocástico bilineal, el cual inicialmente es propuesto para análisis de retornos financieros y otros sistemas complejos combinando la alta no linealidad y multiplicidad del ruido. Este modelo, por su carácter aleatorio, no tiene componente determinística que permita considerar la persistencia de los caudales en una aplicación a la Hidrología. Por lo tanto, se propone el acoplamiento entre la parte determinística de un modelo autorregresivo de orden 2 y el modelo estocástico bilineal como componente aleatorio, y se obtiene un modelo autorregresivo bilineal (MAB. El MAB se empleó para la predicción de caudales en ventanas de 3, 6 y 12 meses en 12 ríos de Colombia de diferentes regiones del país. El MAB tiene una estructura simple y muestra una mejora sustancial en la disminución de los errores para los caudales máximos y mínimos en el período de validación respecto de los modelos estocásticos tradicionales.

  17. Postoperative Analgesia in Children- Comparative Study between Caudal Bupivacaine and Bupivacaine plus Tramadol

    Directory of Open Access Journals (Sweden)

    Meena Doda

    2009-01-01

    Full Text Available Thirty children, ASAI-II, aged between 2yrs-5yrs, undergoing sub umbilical operation (inguinal and penile surgery were selected for this double blind study. They were randomly divided in two groups, group Aand group B. Group A(n15 received 0.25%bupivacaine 0.5ml.kg -1 and Group B (n=15 received 0.25% bupivaeaine 0.5ml.kg -1 and tramadol 2mg.kg -1 as single shot caudal block. Postoperative pain was assessed by a modified TPPPS (Toddler-Preschool Postoperative Pain Scale and analgesic given only when the score was more than 3. In the first 24 hrs it was observed that the mean duration of time interval between the caudal block and first dose of analgesic was significantly long(9. lhrs in Group B as compared to Group A (6.3hrs which was much shorter(p< 0.01.There was no significant haemodynamie changes, motor weakness or respiratory depression in both groups. This study con-cluded that addition of tramadol 2mg.kg -1 to caudal 0.25% bupivacaine 0.5ml.kg -1 significantly prolong the duration of postoperative analgesia in children withoutprodueing much adverse effects.

  18. Comparison of caudal ropivacaine-morphine and paravertebral catheter for major upper abdominal surgery in infants.

    Science.gov (United States)

    Sato, Makoto; Iida, Takafumi; Kikuchi, Chika; Sasakawa, Tomoki; Kunisawa, Takayuki

    2017-05-01

    The caudal epidural block is one of the most commonly used regional anesthetic techniques in children. Administration of morphine via caudal injection enables analgesia, even for upper abdominal surgery. The thoracic paravertebral block has also been successfully used to treat perioperative pain during upper abdominal procedures in pediatric patients. In the current study, we compared the two regional techniques for upper abdominal surgery in infants to determine whether one of them was preferable to the other. Consecutive patients under 12 months of age who underwent upper abdominal surgery were retrospectively divided according to the chosen postoperative analgesia: Group C, caudal ropivacaine-morphine; Group P, paravertebral catheter. We analyzed the following outcomes: requirement for additional analgesics, pain scores, need for mechanical ventilation and oxygen dosage, postoperative blood pressure and heart rate, time to pass first stool, time until first full meal, and complications. Twenty-one consecutive patients were included: 10 in Group C and 11 in Group P. Median age at surgery was 80 (47.5-270.0) and 84.5 (34.3-287.5) days, respectively. No difference was found between the two groups in requirement for additional analgesics at 24 h after surgery (median 1 in Group C vs 1 in Group P, P = 0.288, 95% CI: -2 to 1). BOPS pain scores were only lower in Group P when compared to Group C at 24 h after surgery (median 1 vs 2, P = 0.041, 95% CI: -2 to 0). None of the patients had perioperative complications. In this small series, there was no significant difference between caudal ropivacaine-morphine and paravertebral catheter for postoperative care in infants undergoing upper abdominal surgery. Further prospective studies are needed to compare the efficacy and incidence of complications of caudal block and paravertebral catheter for postoperative analgesia. © 2017 John Wiley & Sons Ltd.

  19. Differential contributions of dorso-ventral and rostro-caudal prefrontal white matter tracts to cognitive control in healthy older adults.

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    Maren Strenziok

    Full Text Available Prefrontal cortex mediates cognitive control by means of circuitry organized along dorso-ventral and rostro-caudal axes. Along the dorso-ventral axis, ventrolateral PFC controls semantic information, whereas dorsolateral PFC encodes task rules. Along the rostro-caudal axis, anterior prefrontal cortex encodes complex rules and relationships between stimuli, whereas posterior prefrontal cortex encodes simple relationships between stimuli and behavior. Evidence of these gradients of prefrontal cortex organization has been well documented in fMRI studies, but their functional correlates have not been examined with regard to integrity of underlying white matter tracts. We hypothesized that (a the integrity of specific white matter tracts is related to cognitive functioning in a manner consistent with the dorso-ventral and rostro-caudal organization of the prefrontal cortex, and (b this would be particularly evident in healthy older adults. We assessed three cognitive processes that recruit the prefrontal cortex and can distinguish white matter tracts along the dorso-ventral and rostro-caudal dimensions -episodic memory, working memory, and reasoning. Correlations between cognition and fractional anisotropy as well as fiber tractography revealed: (a Episodic memory was related to ventral prefrontal cortex-thalamo-hippocampal fiber integrity; (b Working memory was related to integrity of corpus callosum body fibers subserving dorsolateral prefrontal cortex; and (c Reasoning was related to integrity of corpus callosum body fibers subserving rostral and caudal dorsolateral prefrontal cortex. These findings confirm the ventrolateral prefrontal cortex's role in semantic control and the dorsolateral prefrontal cortex's role in rule-based processing, in accordance with the dorso-ventral prefrontal cortex gradient. Reasoning-related rostral and caudal superior frontal white matter may facilitate different levels of task rule complexity. This study is the

  20. Differential contributions of dorso-ventral and rostro-caudal prefrontal white matter tracts to cognitive control in healthy older adults.

    Science.gov (United States)

    Strenziok, Maren; Greenwood, Pamela M; Santa Cruz, Sophia A; Thompson, James C; Parasuraman, Raja

    2013-01-01

    Prefrontal cortex mediates cognitive control by means of circuitry organized along dorso-ventral and rostro-caudal axes. Along the dorso-ventral axis, ventrolateral PFC controls semantic information, whereas dorsolateral PFC encodes task rules. Along the rostro-caudal axis, anterior prefrontal cortex encodes complex rules and relationships between stimuli, whereas posterior prefrontal cortex encodes simple relationships between stimuli and behavior. Evidence of these gradients of prefrontal cortex organization has been well documented in fMRI studies, but their functional correlates have not been examined with regard to integrity of underlying white matter tracts. We hypothesized that (a) the integrity of specific white matter tracts is related to cognitive functioning in a manner consistent with the dorso-ventral and rostro-caudal organization of the prefrontal cortex, and (b) this would be particularly evident in healthy older adults. We assessed three cognitive processes that recruit the prefrontal cortex and can distinguish white matter tracts along the dorso-ventral and rostro-caudal dimensions -episodic memory, working memory, and reasoning. Correlations between cognition and fractional anisotropy as well as fiber tractography revealed: (a) Episodic memory was related to ventral prefrontal cortex-thalamo-hippocampal fiber integrity; (b) Working memory was related to integrity of corpus callosum body fibers subserving dorsolateral prefrontal cortex; and (c) Reasoning was related to integrity of corpus callosum body fibers subserving rostral and caudal dorsolateral prefrontal cortex. These findings confirm the ventrolateral prefrontal cortex's role in semantic control and the dorsolateral prefrontal cortex's role in rule-based processing, in accordance with the dorso-ventral prefrontal cortex gradient. Reasoning-related rostral and caudal superior frontal white matter may facilitate different levels of task rule complexity. This study is the first to

  1. Effect of growth factors (BMP-4/7 & bFGF on proliferation & osteogenic differentiation of bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    Shaohui Yuan

    2013-01-01

    Full Text Available Background & objectives: BMP (bone morphogenetic protein-4/7 and bFGF (basic fibroblast growth factor significantly promote the osteogenic activity and the proliferation of rabbit BMSCs (bone marrow stromal cells, respectively. However, their synergistic effects on the proliferation and the differentiation of BMSCs remain unclear. In the present study, the effects of bFGF and BMP-4/7 were investigated on the proliferation and the differentiation of rat BMSCs in vitro. Methods: BMSCs were isolated from New Zealand white rabbits and cultured to the third passage. The samples were divided into five groups according to the material implanted: (A 80 ng/ml BMP-4/7; (B 80 ng/ml bFGF; (C 30 ng/ml BMP-4/7 and 30 ng/ml bFGF; (D 50 ng/ml BMP-4/7 and 50 ng/ml bFGF; and (E 80 ng/ml BMP-4/7 and 80 ng/ml bFGF. Cell proliferation was analyzed using methyl thiazolyl tetrazolium (MTT assay. Alkaline phosphatase activity and osteocalcin (OC dynamics were also measured. Results: BMP-4/7 alone significantly (P<0.05 promoted the proliferation of BMSCs. At the same time, it also promoted or inhibited the osteogenic differentiation of BMSCs. The synergistic effects of BMP-4/7 and bFGF significantly promoted both the proliferation and the osteogenic differentiation of BMSCs. The treatment of the synergistic effects was dose and time dependent. Interpretation & conclusions: A rational combination of BMP-4/7 and bFGF can promote the proliferation and the osteogenic differentiation of BMSCs. In addition, the synergistic functions are effective.

  2. Effect of caudal epidural steroid or saline injection in chronic lumbar radiculopathy: multicentre, blinded, randomised controlled trial

    DEFF Research Database (Denmark)

    Iversen, Trond; Solberg, Tore K; Romner, Bertil

    2011-01-01

    To assess the efficacy of caudal epidural steroid or saline injection in chronic lumbar radiculopathy in the short (6 weeks), intermediate (12 weeks), and long term (52 weeks).......To assess the efficacy of caudal epidural steroid or saline injection in chronic lumbar radiculopathy in the short (6 weeks), intermediate (12 weeks), and long term (52 weeks)....

  3. Vitrification of caudal fin explants from zebrafish adult specimens.

    Science.gov (United States)

    Cardona-Costa, J; Roig, J; Perez-Camps, M; García-Ximénez, F

    2006-01-01

    No data on vitrification of tissue samples are available in fishes. Three vitrification solutions were compared: V1: 20% ethylene glycol and 20% dimethyl sulphoxide; V2: 25% propylene glycol and 20% dimethyl sulphoxide, and; V3: 20% propylene glycol and 13% methanol, all three prepared in Hanks' buffered salt solution plus 20 percent FBS, following the same one step vitrification procedure developed in mammals. Caudal fin tissue pieces were vitrified into 0.25 ml plastic straws in 30s and stored in liquid nitrogen for 3 days minimum, warmed (10s in nitrogen vapour and 5s in a 25 degree C water bath) and cultured (L-15 plus 20% FBS at 28.5 degree C). At the third day of culture, both attachment and outgrowing rates were recorded. V3 led to the worst results (8% of attachment rate). V1 and V2 allow higher attachment rates (V1: 63% vs V2: 50%. P < 0.05) but not significantly different outgrowing rates (83% to 94%). Vitrification of caudal fin pieces is advantageous in fish biodiversity conservation, particularly in the wild, due to the simplicity of procedure and equipment.

  4. Seminal plasma enhances cervical adenocarcinoma cell proliferation and tumour growth in vivo.

    Directory of Open Access Journals (Sweden)

    Jason R Sutherland

    Full Text Available Cervical cancer is one of the leading causes of cancer-related death in women in sub-Saharan Africa. Extensive evidence has shown that cervical cancer and its precursor lesions are caused by Human papillomavirus (HPV infection. Although the vast majority of HPV infections are naturally resolved, failure to eradicate infected cells has been shown to promote viral persistence and tumorigenesis. Furthermore, following neoplastic transformation, exposure of cervical epithelial cells to inflammatory mediators either directly or via the systemic circulation may enhance progression of the disease. It is well recognised that seminal plasma contains an abundance of inflammatory mediators, which are identified as regulators of tumour growth. Here we investigated the role of seminal plasma in regulating neoplastic cervical epithelial cell growth and tumorigenesis. Using HeLa cervical adenocarcinoma cells, we found that seminal plasma (SP induced the expression of the inflammatory enzymes, prostaglandin endoperoxide synthase (PTGS1 and PTGS2, cytokines interleukin (IL -6, and -11 and vascular endothelial growth factor-A (VEGF-A. To investigate the role of SP on tumour cell growth in vivo, we xenografted HeLa cells subcutaneously into the dorsal flank of nude mice. Intra-peritoneal administration of SP rapidly and significantly enhanced the tumour growth rate and size of HeLa cell xenografts in nude mice. As observed in vitro, we found that SP induced expression of inflammatory PTGS enzymes, cytokines and VEGF-A in vivo. Furthermore we found that SP enhances blood vessel size in HeLa cell xenografts. Finally we show that SP-induced cytokine production, VEGF-A expression and cell proliferation are mediated via the induction of the inflammatory PTGS pathway.

  5. Caudal regression with sirenomelia and dysplasia renofacialis (Potter's syndrome)

    Energy Technology Data Exchange (ETDEWEB)

    Noeldge, G.; Billmann, P.; Boehm, N.

    1982-05-01

    A case of caudal regression in combination with sirenomelia and dysplasia renofacialis (Potter's syndrome) is reported. The formal pathogenesis of these malformations and clinical facts are shown and discussed. Findings of plain films, postmortal angiography and pathologic-anatomical changes are demonstrated.

  6. A Late Cretaceous theropod caudal vertebra from the Sultanate of Oman

    NARCIS (Netherlands)

    Schulp, Anne S.; Hanna, Samir S.; Hartman, Axel Frans; Jagt, John W M

    2000-01-01

    A caudal vertebra collected from conglomerates of the Al-Khod Formation (Late Cretaceous) in the Al-Khod area, Sultanate of Oman, is assigned to a medium-sized theropod dinosaur. The Al-Khod discovery represents one of the very few dinosaur records from the Middle East.

  7. Effects of Plasma Rich in Growth Factors and Platelet-Rich Fibrin on Proliferation and Viability of Human Gingival Fibroblasts

    Directory of Open Access Journals (Sweden)

    Surena Vahabi

    2016-01-01

    Full Text Available Objectives: Platelet preparations are commonly used to enhance bone and soft tissue regeneration. Considering the existing controversies on the efficacy of platelet products for tissue regeneration, more in vitro studies are required. The aim of the present study was to compare the in vitro effects of plasma rich in growth factors (PRGF and platelet-rich fibrin (PRF on proliferation and viability of human gingival fibroblasts (HGFs.Materials and Methods: Anitua's PRGF and Choukran's PRF were prepared according to the standard protocols. After culture periods of 24, 48 and 72 hours, proliferation of HGFs was evaluated by the methyl thiazol tetrazolium assay. Statistical analysis was performed using one-way ANOVA followed by Tukey-Kramer’s multiple comparisons and P-values<0.05 were considered statistically significant.Results: PRGF treatment induced statistically significant (P<0.001 proliferation of HGF cells compared to the negative control (100% viability at 24, 48 and 72 hours in values of 123%±2.25%, 102%±2.8% and 101%±3.92%, respectively. The PRF membrane treatment of HGF cells had a statistically significant effect on cell proliferation (21%±1.73%, P<0.001 at 24 hours compared to the negative control. However, at 48 and 72 hours after treatment, PRF had a negative effect on HGF cell proliferation and caused 38% and 60% decrease in viability and proliferation compared to the negative control, respectively. The HGF cell proliferation was significantly higher in PRGF than in PRF group (P< 0.001.Conclusion: This study demonstrated that PRGF had a strong stimulatory effect on HGF cell viability and proliferation compared to PRF.

  8. Wnt/β-Catenin Signaling Defines Organizing Centers that Orchestrate Growth and Differentiation of the Regenerating Zebrafish Caudal Fin

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    Daniel Wehner

    2014-02-01

    Full Text Available Zebrafish regenerate their fins via the formation of a population of progenitor cells, the blastema. Wnt/β-catenin signaling is essential for blastemal cell proliferation and patterning of the overlying epidermis. Yet, we find that β-catenin signaling is neither active in the epidermis nor the majority of the proliferative blastemal cells. Rather, tissue-specific pathway interference indicates that Wnt signaling in the nonproliferative distal blastema is required for cell proliferation in the proximal blastema, and signaling in cells lining the osteoblasts directs osteoblast differentiation. Thus, Wnt signaling regulates epidermal patterning, blastemal cell proliferation, and osteoblast maturation indirectly via secondary signals. Gene expression profiling, chromatin immunoprecipitation, and functional rescue experiments suggest that Wnt/β-catenin signaling acts through Fgf and Bmp signaling to control epidermal patterning, whereas retinoic acid and Hedgehog signals mediate its effects on blastemal cell proliferation. We propose that Wnt signaling orchestrates fin regeneration by defining organizing centers that instruct cellular behaviors of adjacent tissues.

  9. A Dictyostelium chalone uses G proteins to regulate proliferation.

    Science.gov (United States)

    Bakthavatsalam, Deenadayalan; Choe, Jonathan M; Hanson, Nana E; Gomer, Richard H

    2009-07-27

    Several studies have shown that organ size, and the proliferation of tumor metastases, may be regulated by negative feedback loops in which autocrine secreted factors called chalones inhibit proliferation. However, very little is known about chalones, and how cells sense them. We previously identified two secreted proteins, AprA and CfaD, which act as chalones in Dictyostelium. Cells lacking AprA or CfaD proliferate faster than wild-type cells, and adding recombinant AprA or CfaD to cells slows their proliferation. We show here that cells lacking the G protein components Galpha8, Galpha9, and Gbeta proliferate faster than wild-type cells despite secreting normal or high levels of AprA and CfaD. Compared with wild-type cells, the proliferation of galpha8-, galpha9- and gbeta- cells are only weakly inhibited by recombinant AprA (rAprA). Like AprA and CfaD, Galpha8 and Gbeta inhibit cell proliferation but not cell growth (the rate of increase in mass and protein per nucleus), whereas Galpha9 inhibits both proliferation and growth. galpha8- cells show normal cell-surface binding of rAprA, whereas galpha9- and gbeta- cells have fewer cell-surface rAprA binding sites, suggesting that Galpha9 and Gbeta regulate the synthesis or processing of the AprA receptor. Like other ligands that activate G proteins, rAprA induces the binding of [3H]GTP to membranes, and GTPgammaS inhibits the binding of rAprA to membranes. Both AprA-induced [3H]GTP binding and the GTPgammaS inhibition of rAprA binding require Galpha8 and Gbeta but not Galpha9. Like aprA- cells, galpha8- cells have reduced spore viability. This study shows that Galpha8 and Gbeta are part of the signal transduction pathway used by AprA to inhibit proliferation but not growth in Dictyostelium, whereas Galpha9 is part of a differealnt pathway that regulates both proliferation and growth, and that a chalone signal transduction pathway uses G proteins.

  10. Régimen natural de caudales del río Ayuquila-Armería en el occidente de México

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    Demetrio Meza Rodríguez

    2017-07-01

    Full Text Available El caudal superficial a nivel cuenca, constituye hoy en día un proceso clave para los estudios hidrológicos de cualquier índole. El presente trabajo explora la reconstrucción del régimen natural de caudales de la cuenca del Río Ayuquila-Armería para el periodo 1963‑1991, su importancia radica en que el método usado, puede ser extrapolado a otras cuencas en México y Latinoamérica, donde se carece de datos hidrométricos puntuales. El campo de interés está centrado en la técnica de reconstrucción del caudal natural basándose en las precipitaciones y las temperaturas, en situaciones donde se carece de información hidrológica puntual, utilizando el modelo determinístico “precipitación-escurrimiento”. Es un modelo que requiere de pocos parámetros para su implementación, usando los procesos climáticos y físicos en el ámbito espacial y temporal, con la utilización del Sistemas de Información Geográfica (l. A partir de caudales calibrados en la misma área geográfica, es posible extrapolar el modelo de predicción a toda la cuenca. El resultado fue una base de datos de 29 años de régimen natural de caudales, con un caudal aproximado de 71.5 (m3 s-1, y con un volumen anual de 2254 (hm3 año-1, donde se observaron las pautas estacionales y su fluctuación a lo largo del año. El uso de esta metodología servirá de apoyo para la nueva norma NMX-AA-159-SCFI-2012, donde el principio científico para la determinación de caudal ecológico es el paradigma del régimen hidrológico natural.

  11. Lactoferrin promote primary rat osteoblast proliferation and differentiation via up-regulation of insulin-like growth factor-1 expression.

    Science.gov (United States)

    Hou, Jian-ming; Wu, Man; Lin, Qing-ming; Lin, Fan; Xue, Ying; Lan, Xu-hua; Chen, En-yu; Wang, Mei-li; Yang, Hai-yan; Wang, Feng-xiong

    2014-08-01

    The aim of this study was to explore the effect of lactoferrin (LF) in primary fetal rat osteoblasts proliferation and differentiation and investigate the underlying molecular mechanisms. Primary rat osteoblasts were obtained from the calvarias of neonatal rats. Osteoblasts were treated with LF (0.1-1000 μg/mL), or OSI-906 [a selective inhibitor of insulin-like growth factor 1 (IGF-1) receptor and insulin receptor]. The IGF-1 was then knocked down by small hairpin RNA (shRNA) technology and then was treated with recombinant human IGF-1 or LF. Cell proliferation and differentiation were measured by MTT assay and alkaline phosphatase (ALP) assay, respectively. The expression of IGF-1 and IGF binding protein 2 (IGFBP2) mRNA were analyzed using real-time PCR. LF promotes the proliferation and differentiation of osteoblasts in a certain range (1-100 μg/mL) in time- and dose-dependent manner. The mRNA level of IGF-1 was significantly increased, while the expression of IGFBP2 was suppressed by LF treatment. Knockdown of IGF-1 by shRNA in primary rat osteoblast dramatically decreased the abilities of proliferation and differentiation of osteoblasts and blocked the proliferation and differentiation effect of LF in osteoblasts. OSI906 (5 μM) blocked the mitogenic and differentiation of LF in osteoblasts. Proliferation and differentiation of primary rat osteoblasts in response to LF are mediated in part by stimulating of IGF-1 gene expression and alterations in the gene expression of IGFBP2.

  12. Smad2 and Smad3 Regulate Chondrocyte Proliferation and Differentiation in the Growth Plate.

    Directory of Open Access Journals (Sweden)

    Weiguang Wang

    2016-10-01

    Full Text Available TGFβs act through canonical and non-canonical pathways, and canonical signals are transduced via Smad2 and Smad3. However, the contribution of canonical vs. non-canonical pathways in cartilage is unknown because the role of Smad2 in chondrogenesis has not been investigated in vivo. Therefore, we analyzed mice in which Smad2 is deleted in cartilage (Smad2CKO, global Smad3-/- mutants, and crosses of these strains. Growth plates at birth from all mutant strains exhibited expanded columnar and hypertrophic zones, linked to increased proliferation in resting chondrocytes. Defects were more severe in Smad2CKO and Smad2CKO;Smad3-/- (Smad2/3 mutant mice than in Smad3-/- mice, demonstrating that Smad2 plays a role in chondrogenesis. Increased levels of Ihh RNA, a key regulator of chondrocyte proliferation and differentiation, were seen in prehypertrophic chondrocytes in the three mutant strains at birth. In accordance, TGFβ treatment decreased Ihh RNA levels in primary chondrocytes from control (Smad2fx/fx mice, but inhibition was impaired in cells from mutants. Consistent with the skeletal phenotype, the impact on TGFβ-mediated inhibition of Ihh RNA expression was more severe in Smad2CKO than in Smad3-/- cells. Putative Smad2/3 binding elements (SBEs were identified in the proximal Ihh promoter. Mutagenesis demonstrated a role for three of them. ChIP analysis suggested that Smad2 and Smad3 have different affinities for these SBEs, and that the repressors SnoN and Ski were differentially recruited by Smad2 and Smad3, respectively. Furthermore, nuclear localization of the repressor Hdac4 was decreased in growth plates of Smad2CKO and double mutant mice. TGFβ induced association of Hdac4 with Smad2, but not with Smad3, on the Ihh promoter. Overall, these studies revealed that Smad2 plays an essential role in the development of the growth plate, that both Smads 2 and 3 inhibit Ihh expression in the neonatal growth plate, and suggested they accomplish

  13. Smad2 and Smad3 Regulate Chondrocyte Proliferation and Differentiation in the Growth Plate

    Science.gov (United States)

    Wang, Weiguang; Song, Buer; Anbarchian, Teni; Shirazyan, Anna

    2016-01-01

    TGFβs act through canonical and non-canonical pathways, and canonical signals are transduced via Smad2 and Smad3. However, the contribution of canonical vs. non-canonical pathways in cartilage is unknown because the role of Smad2 in chondrogenesis has not been investigated in vivo. Therefore, we analyzed mice in which Smad2 is deleted in cartilage (Smad2CKO), global Smad3-/- mutants, and crosses of these strains. Growth plates at birth from all mutant strains exhibited expanded columnar and hypertrophic zones, linked to increased proliferation in resting chondrocytes. Defects were more severe in Smad2CKO and Smad2CKO;Smad3-/- (Smad2/3) mutant mice than in Smad3-/- mice, demonstrating that Smad2 plays a role in chondrogenesis. Increased levels of Ihh RNA, a key regulator of chondrocyte proliferation and differentiation, were seen in prehypertrophic chondrocytes in the three mutant strains at birth. In accordance, TGFβ treatment decreased Ihh RNA levels in primary chondrocytes from control (Smad2fx/fx) mice, but inhibition was impaired in cells from mutants. Consistent with the skeletal phenotype, the impact on TGFβ-mediated inhibition of Ihh RNA expression was more severe in Smad2CKO than in Smad3-/- cells. Putative Smad2/3 binding elements (SBEs) were identified in the proximal Ihh promoter. Mutagenesis demonstrated a role for three of them. ChIP analysis suggested that Smad2 and Smad3 have different affinities for these SBEs, and that the repressors SnoN and Ski were differentially recruited by Smad2 and Smad3, respectively. Furthermore, nuclear localization of the repressor Hdac4 was decreased in growth plates of Smad2CKO and double mutant mice. TGFβ induced association of Hdac4 with Smad2, but not with Smad3, on the Ihh promoter. Overall, these studies revealed that Smad2 plays an essential role in the development of the growth plate, that both Smads 2 and 3 inhibit Ihh expression in the neonatal growth plate, and suggested they accomplish this by binding to

  14. Artérias mesentéricas cranial e caudal da paca (Cuniculus paca, L. 1766

    Directory of Open Access Journals (Sweden)

    Isabela Cristina de Souza Marques

    2012-10-01

    Full Text Available http://dx.doi.org/10.5007/2175-7925.2013v26n1p165 A paca (Cuniculus paca, Linnaeus, 1766 é um roedor de porte médio, que embora pertença à fauna brasileira, poucas são as informações sobre sua morfologia na literatura especializada. Nesse sentido, objetivou-se descrever a origem e as ramificações de suas artérias mesentéricas cranial e caudal no intuito de contribuir com estudos de anatomia comparativa. Foram utilizados dez animais, entre machos e fêmeas, que após o óbito, tiveram sua parede torácica rebatida entre a quarta e a sexta costelas, para a exposição da aorta torácica, a qual foi canulada no sentido caudal e procedeu-se a injeção de solução de neoprene do tipo látex, corado convenientemente, para o preenchimento de todo o sistema arterial. Estas preparações foram fixadas em solução aquosa de formol a 10% por período superior à 72h; em seguida, as peças foram dissecadas e as artérias mesentéricas cranial e caudal identificadas. A artéria mesentérica cranial se originava da aorta abdominal, caudalmente à artéria celíaca, emitindo os seguintes ramos arteriais: pancreaticoduodenal caudal, pancreáticos, jejunais, íleocólicos e cecais. A origem da artéria mesentérica caudal ocorria próximo ao final da aorta abdominal, e este vaso emitia a artéria cólica esquerda e a artéria retal cranial, da qual partiam as artérias sigmóideas. Constatou-se que houve pouca variação no padrão de ramificação das artérias em relação aos referidos roedores e mamíferos domésticos.

  15. Sirenomelia phenotype in bmp7;shh compound mutants: a novel experimental model for studies of caudal body malformations.

    Science.gov (United States)

    Garrido-Allepuz, Carlos; González-Lamuño, Domingo; Ros, Maria A

    2012-01-01

    Sirenomelia is a severe congenital malformation of the lower body characterized by the fusion of the legs into a single lower limb. This striking external phenotype consistently associates severe visceral abnormalities, most commonly of the kidneys, intestine, and genitalia that generally make the condition lethal. Although the causes of sirenomelia remain unknown, clinical studies have yielded two major hypotheses: i) a primary defect in the generation of caudal mesoderm, ii) a primary vascular defect that leaves the caudal part of the embryo hypoperfused. Interestingly, Sirenomelia has been shown to have a genetic basis in mice, and although it has been considered a sporadic condition in humans, recently some possible familial cases have been reported. Here, we report that the removal of one or both functional alleles of Shh from the Bmp7-null background leads to a sirenomelia phenotype that faithfully replicates the constellation of external and internal malformations, typical of the human condition. These mutants represent an invaluable model in which we have analyzed the pathogenesis of sirenomelia. We show that the signaling defect predominantly impacts the morphogenesis of the hindgut and the development of the caudal end of the dorsal aortas. The deficient formation of ventral midline structures, including the interlimb mesoderm caudal to the umbilicus, leads to the approximation and merging of the hindlimb fields. Our study provides new insights for the understanding of the mechanisms resulting in caudal body malformations, including sirenomelia.

  16. Sirenomelia phenotype in bmp7;shh compound mutants: a novel experimental model for studies of caudal body malformations.

    Directory of Open Access Journals (Sweden)

    Carlos Garrido-Allepuz

    Full Text Available Sirenomelia is a severe congenital malformation of the lower body characterized by the fusion of the legs into a single lower limb. This striking external phenotype consistently associates severe visceral abnormalities, most commonly of the kidneys, intestine, and genitalia that generally make the condition lethal. Although the causes of sirenomelia remain unknown, clinical studies have yielded two major hypotheses: i a primary defect in the generation of caudal mesoderm, ii a primary vascular defect that leaves the caudal part of the embryo hypoperfused. Interestingly, Sirenomelia has been shown to have a genetic basis in mice, and although it has been considered a sporadic condition in humans, recently some possible familial cases have been reported. Here, we report that the removal of one or both functional alleles of Shh from the Bmp7-null background leads to a sirenomelia phenotype that faithfully replicates the constellation of external and internal malformations, typical of the human condition. These mutants represent an invaluable model in which we have analyzed the pathogenesis of sirenomelia. We show that the signaling defect predominantly impacts the morphogenesis of the hindgut and the development of the caudal end of the dorsal aortas. The deficient formation of ventral midline structures, including the interlimb mesoderm caudal to the umbilicus, leads to the approximation and merging of the hindlimb fields. Our study provides new insights for the understanding of the mechanisms resulting in caudal body malformations, including sirenomelia.

  17. Diagnosis and management of cranial and caudal nuchal bursitis in four horses.

    Science.gov (United States)

    García-López, José M; Jenei, Thomas; Chope, Kate; Bubeck, Kirstin A

    2010-10-01

    4 horses with a history of neck pain, abnormal head carriage, and related inability to perform were examined. Cranial nuchal bursitis was diagnosed in 2 horses, and caudal nuchal bursitis was diagnosed in the other 2. All 4 horses had prominent swelling in the region between the frontal bone and temporal fossa (ie, the poll) and abnormal head carriage. Ultrasonographic examination revealed fluid distention and synovial thickening of the cranial or caudal nuchal bursa in all 4 horses. Ultrasonography-guided aspiration of the affected region was performed successfully in 3 horses. Radiography revealed bony remodeling and mineralization over the dorsal aspect of the atlas in 1 horse and a radiolucency at the axis in another. Nuclear scintigraphy revealed an increase in radioisotope uptake at the level of C2 in 1 horse. Although a septic process was considered among the differential diagnoses in all horses, a septic process could only be confirmed in 1 horse. All horses were refractory to conservative management consisting of intrabursal injection of anti-inflammatory medications. Bursoscopic debridement and lavage of the affected bursae resulted in resolution of the clinical signs in all horses, and they all returned to their intended use. Cranial and caudal nuchal bursitis, of nonseptic or septic origin, should be considered as a differential diagnosis in horses with head and neck pain. Horses undergoing surgical intervention consisting of nuchal bursoscopy have the opportunity to return to their original degree of exercise.

  18. Cryptorchidism as a caudal developmental field defect. A new description of cryptorchidism associated with malformations and dysplasias of the kidneys, the ureters and the spine from T10 to S5

    DEFF Research Database (Denmark)

    Cortes, D; Thorup, J M; Beck, B L

    1998-01-01

    individuals with tritonmelia, the male variant of sirenomelia. Sirenomelia/tritonmelia is an extreme degree of abnormal differentiation of the caudal developmental field, also called caudal dysplasia, the caudal regression syndrome and the caudal regression malformation sequence. Caudal developmental field...

  19. Serum from Chronic Hepatitis B Patients Promotes Growth and Proliferation via the IGF-II/IGF-IR/MEK/ERK Signaling Pathway in Hepatocellular Carcinoma Cells.

    Science.gov (United States)

    Ji, Yuanyuan; Wang, Zhidong; Chen, Haiyan; Zhang, Lei; Zhuo, Fei; Yang, Qingqing

    2018-05-09

    Chronic hepatitis B virus (HBV) infection (CHB) plays a central role in the etiology of hepatocellular carcinoma (HCC). Emerging evidence implicates insulin-like growth factor (IGF)-II as a major risk factor for the growth and development of HCC. However, the relationship between HBV infection and IGF-II functions remains to be elucidated. Levels of circulating IGF-II and IGF-I receptor (IGF-IR) in healthy donors (HDs) and CHB patients were tested by ELISA. Human HCC cell lines (HepG-2, SMMC-7721, MHCC97-H) were incubated with serum from HDs and CHB patients at various concentrations for 24, 48, and 72 h. MTT and plate colony formation assays, BrdU ELISA, ELISA, small-interfering RNA (siRNA) transfection, quantitative real-time PCR, and western blot were applied to assess the functional and molecular mechanisms in HCC cell lines. Serum levels of IGF-II and IGF-IR were significantly higher in CHB patients than in HDs. Additionally, serum from CHB patients directly induced cell growth, proliferation, IGF-II secretion, and HDGF-related protein-2 (HRP-2) and nuclear protein 1 (NUPR1) mRNA and protein expression in HCC cells. Moreover, serum from CHB patients increased IGF-II-induced cell growth, proliferation, and HRP-2 and NUPR1 mRNA and protein expression in HCC cells. Blockade of IGF-IR clearly inhibited the above effects. Most importantly, interference with IGF-II function markedly repressed the cell proliferation and HRP-2 and NUPR1 mRNA and protein expression induced by serum from CHB patients. Furthermore, serum from CHB patients induced ERK phosphorylation via IGF-IR, with the MEK inhibitor PD98059 significantly decreasing CHB patient serum-induced IGF-II secretion, cell proliferation, and HRP-2 and NUPR1 mRNA and protein expression. Serum from CHB patients increases cell growth and proliferation and enhances HRP-2 and NUPR1 expression in HCC cells via the IGF-II/IGF-IR/MEK/ERK signaling pathway. These findings help to explain the molecular mechanisms

  20. Enhancing proliferation and optimizing the culture condition for human bone marrow stromal cells using hypoxia and fibroblast growth factor-2

    Directory of Open Access Journals (Sweden)

    Jung-Seok Lee

    2018-04-01

    Full Text Available This study aimed to determine the cellular characteristics and behaviors of human bone marrow stromal cells (hBMSCs expanded in media in a hypoxic or normoxic condition and with or without fibroblast growth factor-2 (FGF-2 treatment. hBMSCs isolated from the vertebral body and expanded in these four groups were evaluated for cellular proliferation/migration, colony-forming units, cell-surface characterization, in vitro differentiation, in vivo transplantation, and gene expression. Culturing hBMSCs using a particular environmental factor (hypoxia and with the addition of FGF-2 increased the cellular proliferation rate while enhancing the regenerative potential, modulated the multipotency-related processes (enhanced chondrogenesis-related processes/osteogenesis, but reduced adipogenesis, and increased cellular migration and collagen formation. The gene expression levels in the experimental samples showed activation of the hypoxia-inducible factor-1 pathway and glycolysis in the hypoxic condition, with this not being affected by the addition of FGF-2. The concurrent application of hypoxia and FGF-2 could provide a favorable condition for culturing hBMSCs to be used in clinical applications associated with bone tissue engineering, due to the enhancement of cellular proliferation and regenerative potential. Keywords: Bone marrow stromal cells, Hypoxia, Fibroblast growth factor, Tissue regeneration, Microenvironment interactions

  1. Effects of Plasma Rich in Growth Factors and Platelet-Rich Fibrin on Proliferation and Viability of Human Gingival Fibroblasts

    Science.gov (United States)

    Vahabi, Surena; Vaziri, Shahram; Torshabi, Maryam

    2015-01-01

    Objectives: Platelet preparations are commonly used to enhance bone and soft tissue regeneration. Considering the existing controversies on the efficacy of platelet products for tissue regeneration, more in vitro studies are required. The aim of the present study was to compare the in vitro effects of plasma rich in growth factors (PRGF) and platelet-rich fibrin (PRF) on proliferation and viability of human gingival fibroblasts (HGFs). Materials and Methods: Anitua’s PRGF and Choukran’s PRF were prepared according to the standard protocols. After culture periods of 24, 48 and 72 hours, proliferation of HGFs was evaluated by the methyl thiazol tetrazolium assay. Statistical analysis was performed using one-way ANOVA followed by Tukey-Kramer’s multiple comparisons and P-valuesPRGF treatment induced statistically significant (PPRGF than in PRF group (PPRGF had a strong stimulatory effect on HGF cell viability and proliferation compared to PRF. PMID:26877740

  2. Postoperative analgesia in children when using clonidine in addition to fentanyl with bupivacaine given caudally.

    Science.gov (United States)

    Jarraya, Anouar; Elleuch, Sahar; Zouari, Jawhar; Smaoui, Mohamed; Laabidi, Sofiene; Kolsi, Kamel

    2016-01-01

    The aim of the study was to evaluate the efficacy of clonidine in association with fentanyl as an additive to bupivacaine 0.25% given via single shot caudal epidural in pediatric patients for postoperative pain relief. In the present prospective randomized double blind study, 40 children of ASA-I-II aged 1-5 years scheduled for infraumblical surgical procedures were randomly allocated to two groups to receive either bupivacaine 0.25% (1 ml/kg) with fentanyl 1 μg/kg and clonidine 1μg/kg (group I) or bupivacaine 0.25% (1 ml/kg) with fentanyl 1 μg/kg (group II). Caudal block was performed after the induction of general anesthesia. Postoperatively patients were observed for analgesia, sedation, hemodynamic parameters, and side effects or complications. Both the groups were similar with respect to patient and various block characteristics. Heart rate and blood pressure were not different in 2 groups. Significantly prolonged duration of post-operative analgesia was observed in group I (Pbupivacaine in single shot caudal epidural in children may provide better and longer analgesia after infraumblical surgical procedures.

  3. Stimulating Neoblast-Like Cell Proliferation in Juvenile Fasciola hepatica Supports Growth and Progression towards the Adult Phenotype In Vitro

    Science.gov (United States)

    Rathinasamy, Vignesh; Toet, Hayley; McCammick, Erin; O’Connor, Anna; Marks, Nikki J.; Mousley, Angela; Brennan, Gerard P.; Halton, David W.; Spithill, Terry W.; Maule, Aaron G.

    2016-01-01

    Fascioliasis (or fasciolosis) is a socioeconomically important parasitic disease caused by liver flukes of the genus Fasciola. Flukicide resistance has exposed the need for new drugs and/or a vaccine for liver fluke control. A rapidly improving ‘molecular toolbox’ for liver fluke encompasses quality genomic/transcriptomic datasets and an RNA interference platform that facilitates functional genomics approaches to drug/vaccine target validation. The exploitation of these resources is undermined by the absence of effective culture/maintenance systems that would support in vitro studies on juvenile fluke development/biology. Here we report markedly improved in vitro maintenance methods for Fasciola hepatica that achieved 65% survival of juvenile fluke after 6 months in standard cell culture medium supplemented with 50% chicken serum. We discovered that this long-term maintenance was dependent upon fluke growth, which was supported by increased proliferation of cells resembling the “neoblast” stem cells described in other flatworms. Growth led to dramatic morphological changes in juveniles, including the development of the digestive tract, reproductive organs and the tegument, towards more adult-like forms. The inhibition of DNA synthesis prevented neoblast-like cell proliferation and inhibited growth/development. Supporting our assertion that we have triggered the development of juveniles towards adult-like fluke, mass spectrometric analyses showed that growing fluke have an excretory/secretory protein profile that is distinct from that of newly-excysted juveniles and more closely resembles that of ex vivo immature and adult fluke. Further, in vitro maintained fluke displayed a transition in their movement from the probing behaviour associated with migrating stage worms to a slower wave-like motility seen in adults. Our ability to stimulate neoblast-like cell proliferation and growth in F. hepatica underpins the first simple platform for their long-term in

  4. Stimulating Neoblast-Like Cell Proliferation in Juvenile Fasciola hepatica Supports Growth and Progression towards the Adult Phenotype In Vitro.

    Science.gov (United States)

    McCusker, Paul; McVeigh, Paul; Rathinasamy, Vignesh; Toet, Hayley; McCammick, Erin; O'Connor, Anna; Marks, Nikki J; Mousley, Angela; Brennan, Gerard P; Halton, David W; Spithill, Terry W; Maule, Aaron G

    2016-09-01

    Fascioliasis (or fasciolosis) is a socioeconomically important parasitic disease caused by liver flukes of the genus Fasciola. Flukicide resistance has exposed the need for new drugs and/or a vaccine for liver fluke control. A rapidly improving 'molecular toolbox' for liver fluke encompasses quality genomic/transcriptomic datasets and an RNA interference platform that facilitates functional genomics approaches to drug/vaccine target validation. The exploitation of these resources is undermined by the absence of effective culture/maintenance systems that would support in vitro studies on juvenile fluke development/biology. Here we report markedly improved in vitro maintenance methods for Fasciola hepatica that achieved 65% survival of juvenile fluke after 6 months in standard cell culture medium supplemented with 50% chicken serum. We discovered that this long-term maintenance was dependent upon fluke growth, which was supported by increased proliferation of cells resembling the "neoblast" stem cells described in other flatworms. Growth led to dramatic morphological changes in juveniles, including the development of the digestive tract, reproductive organs and the tegument, towards more adult-like forms. The inhibition of DNA synthesis prevented neoblast-like cell proliferation and inhibited growth/development. Supporting our assertion that we have triggered the development of juveniles towards adult-like fluke, mass spectrometric analyses showed that growing fluke have an excretory/secretory protein profile that is distinct from that of newly-excysted juveniles and more closely resembles that of ex vivo immature and adult fluke. Further, in vitro maintained fluke displayed a transition in their movement from the probing behaviour associated with migrating stage worms to a slower wave-like motility seen in adults. Our ability to stimulate neoblast-like cell proliferation and growth in F. hepatica underpins the first simple platform for their long-term in vitro study

  5. Stimulating Neoblast-Like Cell Proliferation in Juvenile Fasciola hepatica Supports Growth and Progression towards the Adult Phenotype In Vitro.

    Directory of Open Access Journals (Sweden)

    Paul McCusker

    2016-09-01

    Full Text Available Fascioliasis (or fasciolosis is a socioeconomically important parasitic disease caused by liver flukes of the genus Fasciola. Flukicide resistance has exposed the need for new drugs and/or a vaccine for liver fluke control. A rapidly improving 'molecular toolbox' for liver fluke encompasses quality genomic/transcriptomic datasets and an RNA interference platform that facilitates functional genomics approaches to drug/vaccine target validation. The exploitation of these resources is undermined by the absence of effective culture/maintenance systems that would support in vitro studies on juvenile fluke development/biology. Here we report markedly improved in vitro maintenance methods for Fasciola hepatica that achieved 65% survival of juvenile fluke after 6 months in standard cell culture medium supplemented with 50% chicken serum. We discovered that this long-term maintenance was dependent upon fluke growth, which was supported by increased proliferation of cells resembling the "neoblast" stem cells described in other flatworms. Growth led to dramatic morphological changes in juveniles, including the development of the digestive tract, reproductive organs and the tegument, towards more adult-like forms. The inhibition of DNA synthesis prevented neoblast-like cell proliferation and inhibited growth/development. Supporting our assertion that we have triggered the development of juveniles towards adult-like fluke, mass spectrometric analyses showed that growing fluke have an excretory/secretory protein profile that is distinct from that of newly-excysted juveniles and more closely resembles that of ex vivo immature and adult fluke. Further, in vitro maintained fluke displayed a transition in their movement from the probing behaviour associated with migrating stage worms to a slower wave-like motility seen in adults. Our ability to stimulate neoblast-like cell proliferation and growth in F. hepatica underpins the first simple platform for their long

  6. Platelet-released growth factors can accelerate tenocyte proliferation and activate the anti-oxidant response element.

    Science.gov (United States)

    Tohidnezhad, M; Varoga, D; Wruck, C J; Brandenburg, L O; Seekamp, A; Shakibaei, M; Sönmez, T T; Pufe, Thomas; Lippross, S

    2011-05-01

    Little is know about the pathophysiology of acute and degenerative tendon injuries. Although most lesions are uncomplicated, treatment is long and unsatisfactory in a considerable number of cases. Besides the common growth factors that were shown to be relevant for tendon integrity more recently protection against oxidative stress was shown to promote tendon healing. To improve tendon regeneration, many have advocated the use of platelet-rich plasma (PRP), a thrombocyte concentrate that can serve as an autologous source of growth factors. In this study, we investigated the effect of platelet-released growth factors (PRGF) on tenocytes. Tenocytes were isolated from the Achilles tendon of postnatal rats. Tenocyte cell cultures were stimulated with PRGF. We used a CyQuant assay and WST assay to analyse tendon cell growth and viability in different concentrations of PRGF. Migration and proliferation of cells grown in PRGF were assessed by a scratch test. A dual-luciferase assay was used to demonstrate the activation of the anti-oxidant response element (ARE) in tenocytes. A positive effect of PRGF could be shown on tendon cell growth and migratory capacity. PRGF activated the Nrf2-ARE pathway in a dose-dependent manner. Here, we provide evidence of a biological effect of PRGF on tenocytes by the promotion of tenocyte growth and activation of the Nrf2-ARE pathway. This is a novel aspect of the action of platelet concentrates on tendon growth.

  7. Sistematização da origem, da distribuição e dos territórios da artéria cerebral caudal na superfície do encéfalo em gatos Systematization of the origin, distribution and territory of the caudal cerebral artery on the surface of the encephalon in cats

    Directory of Open Access Journals (Sweden)

    Eduardo Maurício Mendes de Lima

    2010-09-01

    Full Text Available Foram estudados 26 encéfalos de gatos, adultos, sem diferenciação de sexo, sem raça definida, corados com látex e fixados por solução aquosa de formaldeído. As artérias cerebrais caudais, direita e esquerda, apresentaram-se únicas em 96,1 e 88,4% dos casos, respectivamente. Em 69,2% dos casos no antímero direito e 80,8% no esquerdo, a artéria cerebral caudal originou-se pela anastomose entre o ramo caudal da artéria carótida interna, com maior contribuição, e o ramo terminal da artéria basilar. Em 88,4% dos casos no antímero direito e em 84,6% no esquerdo, a artéria cerebral caudal originou a artéria tectal rostral e um ramo caudal. O ramo caudal bifurcou-se e vascularizou os colículos rostrais e caudais dos corpos quadrigêmeos e em alguns casos contribuiu na formação do plexo coroide do terceiro ventrículo. A artéria tectal rostral seguiu ventralmente ao lobo piriforme e durante seu trajeto liberou ramos para o hipocampo e, no antímero esquerdo, supriu a superfície dorsal do tálamo, contribuindo para a formação do plexo coroide do terceiro ventrículo.In this study were used 26 brains of adult cats, without sex differentiation and definable race, colored with latex and fixed in formaldehyde aqueous solution. The right and left caudal cerebral arteries were single in 96.1% and 88.4% of the sample, respectively. In 69.2% of the samples on the right side and 80.8% on the left, the caudal cerebral artery fin from the anastomosis behind the caudal branch of the internal carotid artery, with a large contribution, and the basal artery terminal branch. In 88.4% of the samples on the right side and 84.6% on the left, the caudal cerebral artery showed the tectal rostral artery and one caudal branche. The caudal branch forked in two branches that supplied the rostral and caudal colliculis of the quadruplet bodies and formed the choroid plexus of the third ventricle. The tectal rostral artery followed ventrally to the

  8. Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Gang [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Hitomi, Hirofumi, E-mail: hitomi@kms.ac.jp [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Hosomi, Naohisa [Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa (Japan); Lei, Bai; Nakano, Daisuke [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Deguchi, Kazushi; Mori, Hirohito; Masaki, Tsutomu [Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Ma, Hong [Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Griendling, Kathy K. [Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA (United States); Nishiyama, Akira [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan)

    2011-10-15

    Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. -- Highlights: {yields} Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. {yields} Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. {yields} Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. {yields} Results provide possible mechanisms of vascular remodeling in hypertension with DM.

  9. Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

    Directory of Open Access Journals (Sweden)

    Ribeiro-Resende Victor

    2012-07-01

    Full Text Available Abstract Background Among the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC, satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that support neuronal survival and axonal growth following peripheral nerve injury. Fibroblast growth factor-2 (FGF-2 is the main mitogenic factor for SCs and is released in large amounts by bone marrow-derived cells, as well as by growing axons and endoneurial fibroblasts during development and regeneration of the peripheral nervous system (PNS. Results Here we show that bone marrow-derived cell treatment induce an increase in the expression of FGF-2 in the sciatic nerve, dorsal root ganglia and the dorsolateral (DL region of the lumbar spinal cord (LSC in a model of sciatic nerve transection and connection into a hollow tube. SCs in culture in the presence of bone marrow derived conditioned media (CM resulted in increased proliferation and migration. This effect was reduced when FGF-2 was neutralized by pretreating BMMC or CM with a specific antibody. The increased expression of FGF-2 was validated by RT-PCR and immunocytochemistry in co-cultures of bone marrow derived cells with sciatic nerve explants and regenerating nerve tissue respectivelly. Conclusion We conclude that FGF-2 secreted by BMMC strongly increases early glial proliferation, which can potentially improve PNS regeneration.

  10. Ecomorphological inferences in early vertebrates: reconstructing Dunkleosteus terrelli (Arthrodira, Placodermi) caudal fin from palaeoecological data.

    Science.gov (United States)

    Ferrón, Humberto G; Martínez-Pérez, Carlos; Botella, Héctor

    2017-01-01

    Our knowledge about the body morphology of many extinct early vertebrates is very limited, especially in regard to their post-thoracic region. The prompt disarticulation of the dermo-skeletal elements due to taphonomic processes and the lack of a well-ossified endoskeleton in a large number of groups hinder the preservation of complete specimens. Previous reconstructions of most early vertebrates known from partial remains have been wholly based on phylogenetically closely related taxa. However, body design of fishes is determined, to a large extent, by their swimming mode and feeding niche, making it possible to recognise different morphological traits that have evolved several times in non-closely related groups with similar lifestyles. Based on this well-known ecomorphological correlation, here we propose a useful comparative framework established on extant taxa for predicting some anatomical aspects in extinct aquatic vertebrates from palaeoecological data and vice versa. For this, we have assessed the relationship between the locomotory patterns and the morphological variability of the caudal region in extant sharks by means of geometric morphometrics and allometric regression analysis. Multivariate analyses reveal a strong morphological convergence in non-closely related shark species that share similar modes of life, enabling the characterization of the caudal fin morphology of different ecological subgroups. In addition, interspecific positive allometry, affecting mainly the caudal fin span, has been detected. This phenomenon seems to be stronger in sharks with more pelagic habits, supporting its role as a compensation mechanism for the loss of hydrodynamic lift associated with the increase in body size, as previously suggested for many other living and extinct aquatic vertebrates. The quantification of shape change per unit size in each ecological subgroup has allowed us to establish a basis for inferring not only qualitative aspects of the caudal fin

  11. Ecomorphological inferences in early vertebrates: reconstructing Dunkleosteus terrelli (Arthrodira, Placodermi caudal fin from palaeoecological data

    Directory of Open Access Journals (Sweden)

    Humberto G. Ferrón

    2017-12-01

    Full Text Available Our knowledge about the body morphology of many extinct early vertebrates is very limited, especially in regard to their post-thoracic region. The prompt disarticulation of the dermo-skeletal elements due to taphonomic processes and the lack of a well-ossified endoskeleton in a large number of groups hinder the preservation of complete specimens. Previous reconstructions of most early vertebrates known from partial remains have been wholly based on phylogenetically closely related taxa. However, body design of fishes is determined, to a large extent, by their swimming mode and feeding niche, making it possible to recognise different morphological traits that have evolved several times in non-closely related groups with similar lifestyles. Based on this well-known ecomorphological correlation, here we propose a useful comparative framework established on extant taxa for predicting some anatomical aspects in extinct aquatic vertebrates from palaeoecological data and vice versa. For this, we have assessed the relationship between the locomotory patterns and the morphological variability of the caudal region in extant sharks by means of geometric morphometrics and allometric regression analysis. Multivariate analyses reveal a strong morphological convergence in non-closely related shark species that share similar modes of life, enabling the characterization of the caudal fin morphology of different ecological subgroups. In addition, interspecific positive allometry, affecting mainly the caudal fin span, has been detected. This phenomenon seems to be stronger in sharks with more pelagic habits, supporting its role as a compensation mechanism for the loss of hydrodynamic lift associated with the increase in body size, as previously suggested for many other living and extinct aquatic vertebrates. The quantification of shape change per unit size in each ecological subgroup has allowed us to establish a basis for inferring not only qualitative aspects of

  12. Intermittent hypoxia induces the proliferation of rat vascular smooth muscle cell with the increases in epidermal growth factor family and erbB2 receptor

    International Nuclear Information System (INIS)

    Kyotani, Yoji; Ota, Hiroyo; Itaya-Hironaka, Asako; Yamauchi, Akiyo; Sakuramoto-Tsuchida, Sumiyo; Zhao, Jing; Ozawa, Kentaro; Nagayama, Kosuke; Ito, Satoyasu; Takasawa, Shin; Kimura, Hiroshi; Uno, Masayuki; Yoshizumi, Masanori

    2013-01-01

    Obstructive sleep apnea is characterized by intermittent hypoxia (IH), and associated with cardiovascular diseases, such as stroke and heart failure. These cardiovascular diseases have a relation to atherosclerosis marked by the proliferation of vascular smooth muscle cells (VSMCs). In this study, we investigated the influence of IH on cultured rat aortic smooth muscle cell (RASMC). The proliferation of RASMC was significantly increased by IH without changing the level of apoptosis. In order to see what induces RASMC proliferation, we investigated the influence of normoxia (N)-, IH- and sustained hypoxia (SH)-treated cell conditioned media on RASMC proliferation. IH-treated cell conditioned medium significantly increased RASMC proliferation compared with N-treated cell conditioned medium, but SH-treated cell conditioned medium did not. We next investigated the epidermal growth factor (EGF) family as autocrine growth factors. Among the EGF family, we found significant increases in mRNAs for epiregulin (ER), amphiregulin (AR) and neuregulin-1 (NRG1) in IH-treated cells and mature ER in IH-treated cell conditioned medium. We next investigated the changes in erbB family receptors that are receptors for ER, AR and NRG1, and found that erbB2 receptor mRNA and protein expressions were increased by IH, but not by SH. Phosphorylation of erbB2 receptor at Tyr-1248 that mediates intracellular signaling for several physiological effects including cell proliferation was increased by IH, but not by SH. In addition, inhibitor for erbB2 receptor suppressed IH-induced cell proliferation. These results provide the first demonstration that IH induces VSMC proliferation, and suggest that EGF family, such as ER, AR and NRG1, and erbB2 receptor could be involved in the IH-induced VSMC proliferation. - Highlights: ●In vitro system for intermittent hypoxia (IH) and sustained hypoxia (SH). ●IH, but not SH, induces the proliferation of rat vascular smooth muscle cell. ●Epiregulin m

  13. Intermittent hypoxia induces the proliferation of rat vascular smooth muscle cell with the increases in epidermal growth factor family and erbB2 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Kyotani, Yoji, E-mail: cd147@naramed-u.ac.jp [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522 (Japan); Ota, Hiroyo [Second Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8522 (Japan); Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Itaya-Hironaka, Asako; Yamauchi, Akiyo; Sakuramoto-Tsuchida, Sumiyo [Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Zhao, Jing; Ozawa, Kentaro; Nagayama, Kosuke; Ito, Satoyasu [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Takasawa, Shin [Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Kimura, Hiroshi [Second Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8522 (Japan); Uno, Masayuki [Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522 (Japan); Yoshizumi, Masanori [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan)

    2013-11-15

    Obstructive sleep apnea is characterized by intermittent hypoxia (IH), and associated with cardiovascular diseases, such as stroke and heart failure. These cardiovascular diseases have a relation to atherosclerosis marked by the proliferation of vascular smooth muscle cells (VSMCs). In this study, we investigated the influence of IH on cultured rat aortic smooth muscle cell (RASMC). The proliferation of RASMC was significantly increased by IH without changing the level of apoptosis. In order to see what induces RASMC proliferation, we investigated the influence of normoxia (N)-, IH- and sustained hypoxia (SH)-treated cell conditioned media on RASMC proliferation. IH-treated cell conditioned medium significantly increased RASMC proliferation compared with N-treated cell conditioned medium, but SH-treated cell conditioned medium did not. We next investigated the epidermal growth factor (EGF) family as autocrine growth factors. Among the EGF family, we found significant increases in mRNAs for epiregulin (ER), amphiregulin (AR) and neuregulin-1 (NRG1) in IH-treated cells and mature ER in IH-treated cell conditioned medium. We next investigated the changes in erbB family receptors that are receptors for ER, AR and NRG1, and found that erbB2 receptor mRNA and protein expressions were increased by IH, but not by SH. Phosphorylation of erbB2 receptor at Tyr-1248 that mediates intracellular signaling for several physiological effects including cell proliferation was increased by IH, but not by SH. In addition, inhibitor for erbB2 receptor suppressed IH-induced cell proliferation. These results provide the first demonstration that IH induces VSMC proliferation, and suggest that EGF family, such as ER, AR and NRG1, and erbB2 receptor could be involved in the IH-induced VSMC proliferation. - Highlights: ●In vitro system for intermittent hypoxia (IH) and sustained hypoxia (SH). ●IH, but not SH, induces the proliferation of rat vascular smooth muscle cell. ●Epiregulin m

  14. EGF signalling pathway regulates colon cancer stem cell proliferation and apoptosis.

    Science.gov (United States)

    Feng, Y; Dai, X; Li, X; Wang, H; Liu, J; Zhang, J; Du, Y; Xia, L

    2012-10-01

    Cancer stem cells (CSCs) compose a subpopulation of cells within a tumour that can self-renew and proliferate. Growth factors such as epidermal growth factor (EGF) and basic fibroblast growth factor (b-FGF) promote cancer stem cell proliferation in many solid tumours. This study assesses whether EGF, bFGF and IGF signalling pathways are essential for colon CSC proliferation and self-renewal. Colon CSCs were cultured in serum-free medium (SFM) with one of the following growth factors: EGF, bFGF or IGF. Characteristics of CSC gene expression were evaluated by real time PCR. Tumourigenicity of CSCs was determined using a xenograft model in vivo. Effects of EGF receptor inhibitors, Gefitinib and PD153035, on CSC proliferation, apoptosis and signalling were evaluated using fluorescence-activated cell sorting and western blotting. Colon cancer cell HCT116 transformed to CSCs in SFM. Compared to other growth factors, EGF was essential to support proliferation of CSCs that expressed higher levels of progenitor genes (Musashi-1, LGR5) and lower levels of differential genes (CK20). CSCs promoted more rapid tumour growth than regular cancer cells in xenografts. EGFR inhibitors suppressed proliferation and induced apoptosis of CSCs by inhibiting autophosphorylation of EGFR and downstream signalling proteins, such as Akt kinase, extracellular signal-regulated kinase 1/2 (ERK 1/2). This study indicates that EGF signalling was essential for formation and maintenance of colon CSCs. Inhibition of the EGF signalling pathway may provide a useful strategy for treatment of colon cancer. © 2012 Blackwell Publishing Ltd.

  15. Destruction of the medial forebrain bundle caudal to the site of stimulation reduces rewarding efficacy but destruction rostrally does not.

    Science.gov (United States)

    Gallistel, C R; Leon, M; Lim, B T; Sim, J C; Waraczynski, M

    1996-08-01

    Rats with an electrode in the medial forebrain bundle (MFB) in or near the ventral tegmental area and another at the level of the rostral hypothalamus sustained large electrolytic lesions at either the rostral or the caudal electrode. The rewarding efficacy of stimulation through the other electrode was determined before and after the lesion. Massive damage to the MFB in the rostral lateral hypothalamus (LH) generally had little effect on the rewarding efficacy of more caudal stimulation, whereas large lesions in the caudal MFB generally reduced the rewarding efficacy of LH stimulation by 35-60%. Similar reductions were produced by knife cuts in the caudal MFB. These results appear to be inconsistent with the hypothesis that the reward fibers consist either of descending or ascending fibers coursing in or near the MFB. It is suggested that the reward fibers are collaterals from neurons with both their somata and their behaviorally significant terminals located primarily in the midbrain.

  16. 3',5'-Cyclic diguanylic acid (c-di-GMP) inhibits basal and growth factor-stimulated human colon cancer cell proliferation

    International Nuclear Information System (INIS)

    Karaolis, David K.R.; Cheng, Kunrong; Lipsky, Michael; Elnabawi, Ahmed; Catalano, Jennifer; Hyodo, Mamoru; Hayakawa, Yoshihiro; Raufman, Jean-Pierre

    2005-01-01

    The novel cyclic dinucleotide, 3',5'-cyclic diguanylic acid, cGpGp (c-di-GMP), is a naturally occurring small molecule that regulates important signaling mechanisms in prokaryotes. Recently, we showed that c-di-GMP has 'drug-like' properties and that c-di-GMP treatment might be a useful antimicrobial approach to attenuate the virulence and pathogenesis of Staphylococcus aureus and prevent or treat infection. In the present communication, we report that c-di-GMP (≤50 μM) has striking properties regarding inhibition of cancer cell proliferation in vitro. c-di-GMP inhibits both basal and growth factor (acetylcholine and epidermal growth factor)-induced cell proliferation of human colon cancer (H508) cells. Toxicity studies revealed that exposure of normal rat kidney cells and human neuroblastoma cells to c-di-GMP at biologically relevant doses showed no lethal cytotoxicity. Cyclic dinucleotides, such as c-di-GMP, represent an attractive and novel 'drug-platform technology' that can be used not only to develop new antimicrobial agents, but also to develop novel therapeutic agents to prevent or treat cancer

  17. A Dictyostelium chalone uses G proteins to regulate proliferation

    Directory of Open Access Journals (Sweden)

    Hanson Nana E

    2009-07-01

    Full Text Available Abstract Background Several studies have shown that organ size, and the proliferation of tumor metastases, may be regulated by negative feedback loops in which autocrine secreted factors called chalones inhibit proliferation. However, very little is known about chalones, and how cells sense them. We previously identified two secreted proteins, AprA and CfaD, which act as chalones in Dictyostelium. Cells lacking AprA or CfaD proliferate faster than wild-type cells, and adding recombinant AprA or CfaD to cells slows their proliferation. Results We show here that cells lacking the G protein components Galpha8, Galpha9, and Gbeta proliferate faster than wild-type cells despite secreting normal or high levels of AprA and CfaD. Compared with wild-type cells, the proliferation of galpha8-, galpha9- and gbeta- cells are only weakly inhibited by recombinant AprA (rAprA. Like AprA and CfaD, Galpha8 and Gbeta inhibit cell proliferation but not cell growth (the rate of increase in mass and protein per nucleus, whereas Galpha9 inhibits both proliferation and growth. galpha8- cells show normal cell-surface binding of rAprA, whereas galpha9- and gbeta- cells have fewer cell-surface rAprA binding sites, suggesting that Galpha9 and Gbeta regulate the synthesis or processing of the AprA receptor. Like other ligands that activate G proteins, rAprA induces the binding of [3H]GTP to membranes, and GTPgammaS inhibits the binding of rAprA to membranes. Both AprA-induced [3H]GTP binding and the GTPgammaS inhibition of rAprA binding require Galpha8 and Gbeta but not Galpha9. Like aprA- cells, galpha8- cells have reduced spore viability. Conclusion This study shows that Galpha8 and Gbeta are part of the signal transduction pathway used by AprA to inhibit proliferation but not growth in Dictyostelium, whereas Galpha9 is part of a differealnt pathway that regulates both proliferation and growth, and that a chalone signal transduction pathway uses G proteins.

  18. Orexin inputs to caudal raphé neurons involved in thermal, cardiovascular, and gastrointestinal regulation.

    Science.gov (United States)

    Berthoud, Hans-Rudolf; Patterson, Laurel M; Sutton, Gregory M; Morrison, Christopher; Zheng, Huiyuan

    2005-02-01

    Orexin-expressing neurons in the lateral hypothalamus with their wide projections throughout the brain are important for the regulation of sleep and wakefulness, ingestive behavior, and the coordination of these behaviors in the environmental context. To further identify downstream effector targets of the orexin system, we examined in detail orexin-A innervation of the caudal raphe nuclei in the medulla, known to harbor sympathetic preganglionic motor neurons involved in thermal, cardiovascular, and gastrointestinal regulation. All three components of the caudal raphe nuclei, raphe pallidus, raphe obscurus, and parapyramidal nucleus, are innervated by orexin-A-immunoreactive fibers. Using confocal microscopy, we demonstrate close anatomical appositions between varicose orexin-A immunoreactive axon profiles and sympathetic premotor neurons identified with either a transneuronal retrograde pseudorabies virus tracer injected into the interscapular brown fat pads, or with in situ hybridization of pro-TRH mRNA. Furthermore, orexin-A injected into the fourth ventricle induced c-Fos expression in the raphe pallidus and parapyramidal nucleus. These findings suggest that orexin neurons in the hypothalamus can modulate brown fat thermogenesis, cardiovascular, and gastrointestinal functions by acting directly on neurons in the caudal raphe nuclei, and support the idea that orexin's simultaneous stimulation of food intake and sympathetic activity might have evolved as a mechanism to stay alert while foraging.

  19. M2 macrophages induce ovarian cancer cell proliferation via a heparin binding epidermal growth factor/matrix metalloproteinase 9 intercellular feedback loop.

    Science.gov (United States)

    Carroll, Molly J; Kapur, Arvinder; Felder, Mildred; Patankar, Manish S; Kreeger, Pamela K

    2016-12-27

    In ovarian cancer, a high ratio of anti-inflammatory M2 to pro-inflammatory M1 macrophages correlates with poor patient prognosis. The mechanisms driving poor tumor outcome as a result of the presence of M2 macrophages in the tumor microenvironment remain unclear and are challenging to study with current techniques. Therefore, in this study we utilized a micro-culture device previously developed by our lab to model concentrated paracrine signaling in order to address our hypothesis that interactions between M2 macrophages and ovarian cancer cells induce tumor cell proliferation. Using the micro-culture device, we determined that co-culture with M2-differentiated primary macrophages or THP-1 increased OVCA433 proliferation by 10-12%. This effect was eliminated with epidermal growth factor receptor (EGFR) or heparin-bound epidermal growth factor (HB-EGF) neutralizing antibodies and HBEGF expression in peripheral blood mononuclear cells from ovarian cancer patients was 9-fold higher than healthy individuals, suggesting a role for HB-EGF in tumor progression. However, addition of HB-EGF at levels secreted by macrophages or macrophage-conditioned media did not induce proliferation to the same extent, indicating a role for other factors in this process. Matrix metalloproteinase-9, MMP-9, which cleaves membrane-bound HB-EGF, was elevated in co-culture and its inhibition decreased proliferation. Utilizing inhibitors and siRNA against MMP9 in each population, we determined that macrophage-secreted MMP-9 released HB-EGF from macrophages, which increased MMP9 in OVCA433, resulting in a positive feedback loop to drive HB-EGF release and increase proliferation in co-culture. Identification of multi-cellular interactions such as this may provide insight into how to most effectively control ovarian cancer progression.

  20. Fluoroscopically guided caudal epidural steroid injection for management of degenerative lumbar spinal stenosis: short-term and long-term results

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joon Woo; Myung, Jae Sung; Kang, Heung Sik [Seoul National University Bundang Hospital, Department of Radiology, Seong Nam, Gyeongi-do (Korea); Park, Kun Woo; Yeom, Jin S. [Seoul National University Bundang Hospital, Department of Orthopaedic Surgery, Seong Nam, Gyeongi-do (Korea); Kim, Ki-Jeong; Kim, Hyun-Jib [Seoul National University Bundang Hospital, Department of Neurosurgery, Seong Nam, Gyeongi-do (Korea)

    2010-07-15

    To evaluate the short-term and long-term effects of fluoroscopically guided caudal epidural steroid injection (ESI) for the management of degenerative lumbar spinal stenosis (DLSS) and to analyze outcome predictors. All patients who underwent caudal ESI in 2006 for DLSS were included in the study. Response was based on chart documentation (aggravated, no change, slightly improved, much improved, no pain). In June 2009 telephone interviews were conducted, using formatted questions including the North American Spine Society (NASS) patient satisfaction scale. For short-term and long-term effects, age difference was evaluated by the Mann-Whitney U test, and gender, duration of symptoms, level of DLSS, spondylolisthesis, and previous operations were evaluated by Fisher's exact test. Two hundred and sixteen patients (male: female = 75:141; mean age 69.2 years; range 48{proportional_to}91 years) were included in the study. Improvements (slightly improved, much improved, no pain) were seen in 185 patients (85.6%) after an initial caudal ESI and in 189 patients (87.5%) after a series of caudal ESIs. Half of the patients (89/179, 49.8%) replied positively to the NASS patient satisfaction scale (1 or 2). There were no significant outcome predictors for either the short-term or the long-term responses. Fluoroscopically guided caudal ESI was effective for the management of DLSS (especially central canal stenosis) with excellent short-term and good long-term results, without significant outcome predictors. (orig.)

  1. [Magnetic resonance imaging features of a caudal cruciate ligament rupture associated with a suspected bone bruise lesion in a dog].

    Science.gov (United States)

    Schmohl, M; Konar, M; Tassani-Prell, M; Rupp, S

    2014-04-16

    In this case study we describe a surgically confirmed caudal cruciate ligament rupture in a 10-year-old Border Collie. Magnetic resonance imaging (MRI) demonstrated a complete rupture of the caudal cruciate ligament, a suspected bone bruise lesion on the proximolateral tibia and a muscle strain injury of the M. flexor digitorum lateralis. In human medicine, bone bruise lesions in MRI have been described as "footprint injuries" and can thereby explain the mechanism of trauma in ligament injuries. The combination of the MRI findings in this case can help to understand how the rarely diagnosed isolated rupture of the caudal cruciate ligament occurred in this dog.

  2. Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

    Science.gov (United States)

    Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

    2015-07-01

    It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

  3. Caudal venous return through a left azygos vein in a dog

    International Nuclear Information System (INIS)

    Sammarco, C.D.; Regan, J.; Ward, C.R.; Buchanan, J.D.

    1995-01-01

    The Clinical, radiologic and echocardiographic findings in a one-year old dog with mild subvalvular aortic stenosis and aberrant caudal vena circulation are described. Aberrant systemic venous return to the right side of the heart usually has little clinical significance, but the unusual features in survey radiographs, contrast angiograms and contrast echocardiograms constitute the reasons for this report

  4. Mullerian papilloma-like proliferation arising in cystic pelvic endosalpingiosis.

    Science.gov (United States)

    McCluggage, W Glenn; O'Rourke, Declan; McElhenney, Clodagh; Crooks, Michael

    2002-09-01

    This report describes an unusual epithelial proliferation occurring in pelvic cystic endosalpingiosis. A cyst mass lined by a layer of ciliated epithelial cells involved the posterior surface of the cervix and vagina. The epithelial proliferation within the wall resembled a mullerian papilloma with fibrous and fibrovascular cores lined by bland cuboidal epithelial cells. Other areas had a microglandular growth pattern resembling cervical microglandular hyperplasia, and focally there was a solid growth pattern. Foci of typical endosalpingiosis involved the surface of both ovaries and pelvic soft tissues. The cystic lesion recurred after partial cystectomy and drainage and was followed up radiologically and with periodic fine-needle aspiration. Part of the wall of the cyst removed 11 years after the original surgery showed an identical epithelial proliferation. MIB1 staining showed a proliferation index of less than 5%, contrasting with the higher proliferation index of a typical serous borderline tumor. The differential diagnosis is discussed. As far as we are aware, this is the first report of such a benign epithelial proliferation involving cystic endosalpingiosis. Copyright 2002, Elsevier Science (USA). All rights reserved.

  5. Effect of concentrated growth factor combined with guided bone regeneration on cell proliferation and bone resorption in patients with severe periodontitis

    Directory of Open Access Journals (Sweden)

    Qiang Gao

    2017-10-01

    Full Text Available Objective: To study the effect of concentrated growth factor (CGF combined with guided bone regeneration on cell proliferation and bone resorption in patients with severe periodontitis. Methods: Patients with severe periodontitis who were treated in Stomatology Department of Shenmu Hospital between May 2014 and February 2017 were selected as the research subjects and randomly divided into two groups, surgery + CGF group received concentrated growth factor combined with guided bone regeneration, and pure surgery group received guided bone regeneration. The contents of inflammatory response, cell proliferation and bone resorption markers in gingival crevicular fluid were determined 1 week after treatment. Results: 1 week after treatment, HMGB1, ICAM1, E-selectin, Smac, FasL, Caspase-8, Caspase-9, Caspase-3, RANKL and NTX contents in gingival crevicular fluid of surgery + CGF group were significantly lower than those of pure surgery group while PD-L1, hBD-3, Wnt3a, BGP and OPG contents were significantly higher than those of pure surgery group. Conclusion: Concentrated growth factor combined with guided bone regeneration for severe periodontitis can inhibit inflammatory response, apoptosis and bone resorption, which is beneficial to the reconstruction of periodontal tissue.

  6. NSAIDs and Cell Proliferation in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Raj Ettarh

    2010-06-01

    Full Text Available Colon cancer is common worldwide and accounts for significant morbidity and mortality in patients. Fortunately, epidemiological studies have demonstrated that continuous therapy with NSAIDs offers real promise of chemoprevention and adjunct therapy for colon cancer patients. Tumour growth is the result of complex regulation that determines the balance between cell proliferation and cell death. How NSAIDs affect this balance is important for understanding and improving treatment strategies and drug effectiveness. NSAIDs inhibit proliferation and impair the growth of colon cancer cell lines when tested in culture in vitro and many NSAIDs also prevent tumorigenesis and reduce tumour growth in animal models and in patients, but the relationship to inhibition of tumour cell proliferation is less convincing, principally due to gaps in the available data. High concentrations of NSAIDs are required in vitro to achieve cancer cell inhibition and growth retardation at varying time-points following treatment. However, the results from studies with colon cancer cell xenografts are promising and, together with better comparative data on anti-proliferative NSAID concentrations and doses (for in vitro and in vivo administration, could provide more information to improve our understanding of the relationships between these agents, dose and dosing regimen, and cellular environment.

  7. Knockdown of NF-E2-related factor 2 inhibits the proliferation and growth of U251MG human glioma cells in a mouse xenograft model.

    Science.gov (United States)

    Ji, Xiang-Jun; Chen, Sui-Hua; Zhu, Lin; Pan, Hao; Zhou, Yuan; Li, Wei; You, Wan-Chun; Gao, Chao-Chao; Zhu, Jian-Hong; Jiang, Kuan; Wang, Han-Dong

    2013-07-01

    NF-E2-related factor 2 (Nrf2) is a pivotal transcription factor of cellular responses to oxidative stress and recent evidence suggests that Nrf2 plays an important role in cancer pathobiology. However, the underlying mechanism has yet to be elucidated, particularly in glioma. In the present study, we investigated the role of Nrf2 in the clinical prognosis, cell proliferation and tumor growth of human glioblastoma multiforme (GBM). We detected overexpression of Nrf2 protein levels in GBM compared to normal brain tissues. Notably, higher protein levels of Nrf2 were significantly associated with poorer overall survival and 1-year survival for GBM patients. Furthermore, we constructed the plasmid Si-Nrf2 and transduced it into U251MG cells to downregulate the expression of Nrf2 and established stable Nrf2 knockdown cells. The downregulation of Nrf2 suppressed cell proliferation in vitro and tumor growth in mouse xenograft models. We performed immunohistochemistry staining to detect the protein levels of Nrf2, Ki-67, caspase-3 and CD31 in the xenograft tumors and found that the expression levels of Nrf2 and Ki-67 were much lower in the Si-Nrf2 group compared to the Si-control group. In addition, the number of caspase-3-positive cells was significantly increased in the Si-Nrf2 group. By analysis of microvessel density (MVD) assessed by CD31, the MVD value in the Si-Nrf2 group decreased significantly compared to the Si-control group. These findings indicate that the knockdown of Nrf2 may suppress tumor growth by inhibiting cell proliferation, increasing cell apoptosis and inhibiting angiogenesis. These results highlight the potential of Nrf2 as a candidate molecular target to control GBM cell proliferation and tumor growth.

  8. Proliferating fibroblasts and HeLa cells co-cultured in vitro reciprocally influence growth patterns, protein expression, chromatin features and cell survival.

    Science.gov (United States)

    Delinasios, John G; Angeli, Flora; Koumakis, George; Kumar, Shant; Kang, Wen-Hui; Sica, Gigliola; Iacopino, Fortunata; Lama, Gina; Lamprecht, Sergio; Sigal-Batikoff, Ina; Tsangaris, George T; Farfarelos, Christos D; Farfarelos, Maria C; Vairaktaris, Eleftherios; Vassiliou, Stavros; Delinasios, George J

    2015-04-01

    to identify biological interactions between proliferating fibroblasts and HeLa cells in vitro. Fibroblasts were isolated from both normal and tumour human tissues. Coverslip co-cultures of HeLa and fibroblasts in various ratios with medium replacement every 48 h were studied using fixed cell staining with dyes such as Giemsa and silver staining, with immunochemistry for Ki-67 and E-cadherin, with dihydrofolate reductase (DHFR) enzyme reaction, as well as live cell staining for non-specific esterases and lipids. Other techniques included carmine cell labeling, autoradiography and apoptosis assessment. Under conditions of feeding and cell: cell ratios allowing parallel growth of human fibroblasts and HeLa cells, co-cultured for up to 20 days, a series of phenomena occur consecutively: profound affinity between the two cell types and exchange of small molecules; encircling of the HeLa colonies by the fibroblasts and enhanced growth of both cell types at their contact areas; expression of carbonic anhydrase in both cell types and high expression of non-specific esterases and cytoplasmic argyrophilia in the surrounding fibroblasts; intense production and secretion of lipid droplets by the surrounding fibroblasts; development of a complex net of argyrophilic projections of the fibroblasts; E-cadherin expression in the HeLa cells; from the 10th day onwards, an increasing detachment of batches of HeLa cells at the peripheries of colonies and appearance of areas with many multi-nucleated and apoptotic HeLa cells, and small HeLa fragments; from the 17th day, appearance of fibroblasts blocked at the G2-M phase. Co-cultures at approximately 17-20 days display a cell-cell fight with foci of (a) sparse growth of both cell types, (b) overgrowth of the fibroblasts and (c) regrowth of HeLa in small colonies. These results indicate that during their interaction with HeLa cells in vitro, proliferating fibroblasts can be activated against HeLa. This type of activation is not observed

  9. Excessive Cellular Proliferation Negatively Impacts Reprogramming Efficiency of Human Fibroblasts.

    Science.gov (United States)

    Gupta, Manoj K; Teo, Adrian Kee Keong; Rao, Tata Nageswara; Bhatt, Shweta; Kleinridders, Andre; Shirakawa, Jun; Takatani, Tomozumi; Hu, Jiang; De Jesus, Dario F; Windmueller, Rebecca; Wagers, Amy J; Kulkarni, Rohit N

    2015-10-01

    The impact of somatic cell proliferation rate on induction of pluripotent stem cells remains controversial. Herein, we report that rapid proliferation of human somatic fibroblasts is detrimental to reprogramming efficiency when reprogrammed using a lentiviral vector expressing OCT4, SOX2, KLF4, and cMYC in insulin-rich defined medium. Human fibroblasts grown in this medium showed higher proliferation, enhanced expression of insulin signaling and cell cycle genes, and a switch from glycolytic to oxidative phosphorylation metabolism, but they displayed poor reprogramming efficiency compared with cells grown in normal medium. Thus, in contrast to previous studies, our work reveals an inverse correlation between the proliferation rate of somatic cells and reprogramming efficiency, and also suggests that upregulation of proteins in the growth factor signaling pathway limits the ability to induce pluripotency in human somatic fibroblasts. The efficiency with which human cells can be reprogrammed is of interest to stem cell biology. In this study, human fibroblasts cultured in media containing different concentrations of growth factors such as insulin and insulin-like growth factor-1 exhibited variable abilities to proliferate, with consequences on pluripotency. This occurred in part because of changes in the expression of proteins involved in the growth factor signaling pathway, glycolysis, and oxidative phosphorylation. These findings have implications for efficient reprogramming of human cells. ©AlphaMed Press.

  10. Caudal fin allometry in the white shark Carcharodon carcharias: implications for locomotory performance and ecology

    Science.gov (United States)

    Lingham-Soliar, Theagarten

    2005-05-01

    Allometric scaling analysis was employed to investigate the consequences of size evolution on hydrodynamic performance and ecology in the white shark Carcharodon carcharias. Discriminant analysis using the power equation y=axb was negative for caudal fin span (S) versus fork length (FL) in C. carcharias. In contrast in two delphinid species, Delphinus capensis and Tursiops aduncus, the span of the flukes versus fork length rises in positive allometric fashion, and strong positive allometry of S versus √A (area) was also recorded. The latter reflects a high lift/drag ratio. S versus √A in C. carcharias displays negative allometry and consequently a lower lift/drag ratio. A lower aspect ratio (AR) caudal fin in C. carcharias compared to that of the delphinids (mean 3.33 and 4.1, respectively) and other thunniform swimmers provides the potential for better maneuverability and acceleration. The liver in sharks is frequently associated with a buoyancy function and was found to be positively allometric in C. carcharias. The overall findings suggest that the negatively allometric caudal fin morphometrics in C. carcharias are unlikely to have deleterious evolutionary fitness consequences for predation. On the contrary, when considered in the context of positive liver allometry in C. carcharias it is hereby suggested that buoyancy may play a dominant role in larger white sharks in permitting slow swimming while minimizing energy demands needed to prevent sinking. In contrast hydrodynamic lift is considered more important in smaller white sharks. Larger caudal fin spans and higher lift/drag ratio in smaller C. carcharias indicate greater potential for prolonged, intermediate swimming speeds and for feeding predominantly on fast-moving fish, in contrast to slow-swimming search patterns of larger individuals for predominantly large mammalian prey. Such data may provide some answers to the lifestyle and widespread habitat capabilities of this still largely mysterious animal.

  11. Comparison of preemptive intravenous paracetamol and caudal block in terms of analgesic and hemodynamic parameters in children

    Directory of Open Access Journals (Sweden)

    Serbülent Gökhan Beyaz

    2012-06-01

    Full Text Available Objectives: Paracetamol has a widespread use for feverand symptomatic relief of pain in children. The aim ofthis study was to compare analgesic effects of preemptiveintravenous (i.v. paracetamol, and caudal block withlevobupivacaine.Materials and methods: A total of 60 children with ASAI-II physical status, aged 5-15 years and undergoing inguinalhernia repair, were randomly allocated to threegroups so that each group contained 20 patients. Group Pchildren received i.v. 15mg/kg paracetamol. Group C receivedonly caudal block with levobupivacaine, and GroupPC received both i.v. paracetamol, and caudal block withlevobupivacaine. Pain level assessed by modified EasternOntario Children’s Hospital pain scale (mCHEOPs,sedation status by Ramsey sedation scale at postoperative5, 15, 30 min and 1,3, and 6th hours.Results: No significant differences were found in age,gender distribution, body weight, ASA status, type andduration of surgery between three groups (p>0.05. Althoughsignificant difference were found in mCHEOPsscores within groups by repeated measures, no differenceof pain scores was observed between three groups(p>0.05. There were no significant differences in the hemodynamicparameters (heart rate, blood pressure bothwithin groups and between groups (p>0.05.Conclusions: Preemptive intravenous paracetamol hadsimilar analgesic effects compared with caudal block withlevobupivacaine with regard to postoperative pain scoresin children undergoing inguinal hernia repair. No hemodynamicor other adverse effects were observed withintravenous paracetamol. J Clin Exp Invest 2012; 3(2:202-208

  12. Opposing roles of C/EBPbeta and AP-1 in the control of fibroblast proliferation and growth arrest-specific gene expression

    DEFF Research Database (Denmark)

    Gagliardi, Mark; Maynard, Scott; Miyake, Tetsuaki

    2003-01-01

    in the levels of AP-1 proteins. Therefore, C/EBPbeta is a negative regulator of AP-1 expression and activity in CEF. The expression of cyclin D1 and cell proliferation were stimulated by the dominant negative mutant of C/EBPbeta but not in the presence of TAM67, a dominant negative mutant of c-Jun and AP-1. CEF......Chicken embryo fibroblasts (CEF) express several growth arrest-specific (GAS) gene products in G0. In contact-inhibited cells, the expression of the most abundant of these proteins, the p20K lipocalin, is activated at the transcriptional level by C/EBPbeta. In this report, we describe the role of C....../EBPbeta in CEF proliferation. We show that the expression of a dominant negative mutant of C/EBPbeta (designated Delta184-C/EBPbeta) completely inhibited p20K expression at confluence and stimulated the proliferation of CEF without inducing transformation. Mouse embryo fibroblasts nullizygous for C/EBPbeta had...

  13. Conjoined legs: Sirenomelia or caudal regression syndrome?

    Directory of Open Access Journals (Sweden)

    Sakti Prasad Das

    2013-01-01

    Full Text Available Presence of single umbilical persistent vitelline artery distinguishes sirenomelia from caudal regression syndrome. We report a case of a12-year-old boy who had bilateral umbilical arteries presented with fusion of both legs in the lower one third of leg. Both feet were rudimentary. The right foot had a valgus rocker-bottom deformity. All toes were present but rudimentary. The left foot showed absence of all toes. Physical examination showed left tibia vara. The chest evaluation in sitting revealed pigeon chest and elevated right shoulder. Posterior examination of the trunk showed thoracic scoliosis with convexity to right. The patient was operated and at 1 year followup the boy had two separate legs with a good aesthetic and functional results.

  14. Conjoined legs: Sirenomelia or caudal regression syndrome?

    Science.gov (United States)

    Das, Sakti Prasad; Ojha, Niranjan; Ganesh, G Shankar; Mohanty, Ram Narayan

    2013-07-01

    Presence of single umbilical persistent vitelline artery distinguishes sirenomelia from caudal regression syndrome. We report a case of a12-year-old boy who had bilateral umbilical arteries presented with fusion of both legs in the lower one third of leg. Both feet were rudimentary. The right foot had a valgus rocker-bottom deformity. All toes were present but rudimentary. The left foot showed absence of all toes. Physical examination showed left tibia vara. The chest evaluation in sitting revealed pigeon chest and elevated right shoulder. Posterior examination of the trunk showed thoracic scoliosis with convexity to right. The patient was operated and at 1 year followup the boy had two separate legs with a good aesthetic and functional results.

  15. CARACTERÍSTICAS DE LA CIRCULACIÓN TROPOSFÉRICA ASOCIADA A LAS VARIACIONES INTERANUALES DEL CAUDAL DEL RÍO TECKA – GUALJAINA, ARGENTINA

    Directory of Open Access Journals (Sweden)

    Mariana P. Torrero

    2016-06-01

    Full Text Available La cuenca del río Tecka – Gualjaina se localiza al Noroeste de la provincia de Chubut, Argentina y desarrolla una superficie de 5.318 km2. El trabajo explora los forzantes del sistema atmósfera-océano asociados a la variabilidad interanual del caudal para la temporada de máximo caudal (de junio a noviembre, que representa el 80% del total anual, y de mínimo caudal (de diciembre a mayo. El balance hídrico de la cuenca arrojó condiciones de aridez, por lo que el comportamiento temporal del caudal depende del de la precipitación. En el registro disponible 1956-2013 la serie de máximo caudal presentó tendencia negativa, con un cambio de régimen en las anomalías de caudal a comienzos de los 80, pasando de un predominio positivo antes a otro negativo después. La serie de mínimo caudal mostró ser más estacionaria, sin tendencia significativa. Los ciclos dominantes en ambas series temporales sólo se observaron en la alta frecuencia interanual ( 2 años y 4-5 años. Las teleconexiones y forzantes asociados a las series de caudal se analizaron para el período 1979-2013 mediante el reanálisis del ERA-Interim. Las variaciones interanuales del caudal máximo estuvieron asociadas a teleconexión troposférica de baja frecuencia (interanual simétrica respecto del Ecuador, posiblemente asociada a variaciones en la convección tropical entre aproximadamente 10oN-10oS y 150oE-180oE, inducidas por variaciones de temperatura superficial del mar en el Pacífico occidental ecuatorial (entre 180oO-150oO. La teleconexión afectó la posición e intensidad de las corrientes en chorro subtropical y polar, alterando la trayectoria de sistemas baroclínicos invernales que precipitan en la región. Las variaciones interanuales del mínimo caudal estuvieron asociadas a una variabilidad de altas latitudes simétricamente anular, modulada por un tren de onda 3 en latitudes medias sobre el Pacífico Sur y el Atlántico Sur. Estas características pudieron

  16. 1,8-cineole inhibits both proliferation and elongation of BY-2 cultured tobacco cells.

    Science.gov (United States)

    Yoshimura, Hiroko; Sawai, Yu; Tamotsu, Satoshi; Sakai, Atsushi

    2011-03-01

    Volatile monoterpenes such as 1,8-cineole inhibit the growth of Brassica campestris seedlings in a dose-dependent manner, and the growth-inhibitory effects are more severe for roots than hypocotyls. The preferential inhibition of root growth may be explained if the compounds inhibit cell proliferation more severely than cell elongation because root growth requires both elongation and proliferation of the constituent cells, whereas hypocotyl growth depends exclusively on elongation of existing cells. In order to examine this possibility, BY-2 suspension-cultured tobacco (Nicotiana tabacum) cells were treated with 1,8-cineole, and the inhibitory effects on cell proliferation and on cell elongation were assessed quantitatively. Treatment with 1,8-cineole lowered both the mitotic index and elongation of the cells in a dose-dependent manner, and the half-maximal inhibitory concentration (IC₅₀) for cell elongation was lower than that for cell proliferation. Moreover, 1,8-cineole also inhibited starch synthesis, with IC₅₀ lower than that for cell proliferation. Thus, the inhibitory effects of 1,8-cineole were not specific to cell proliferation; rather, 1,8-cineole seemed inhibitory to a variety of physiological activities when it was in direct contact with target cells. Based on these results, possible mechanisms for the mode of action of 1,8-cineole and for its preferential inhibition on root growth are discussed.

  17. 3-Deoxysappanchalcone Promotes Proliferation of Human Hair Follicle Dermal Papilla Cells and Hair Growth in C57BL/6 Mice by Modulating WNT/β-Catenin and STAT Signaling

    Science.gov (United States)

    Kim, Young Eun; Choi, Hyung Chul; Lee, In-Chul; Yuk, Dong Yeon; Lee, Hyosung; Choi, Bu Young

    2016-01-01

    3-Deoxysappanchalcone (3-DSC) has been reported to possess anti-allergic, antiviral, anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of 3-DSC on the proliferation of human hair follicle dermal papilla cells (HDPCs) and mouse hair growth in vivo. A real-time cell analyzer system, luciferase assay, Western blot and real-time polymerase chain reaction (PCR) were employed to measure the biochemical changes occurring in HDPCs in response to 3-DSC treatment. The effect of 3-DSC on hair growth in C57BL/6 mice was also examined. 3-DSC promoted the proliferation of HDPCs, similar to Tofacitinib, an inhibitor of janus-activated kinase (JAK). 3-DSC promoted phosphorylation of β-catenin and transcriptional activation of the T-cell factor. In addition, 3-DSC potentiated interleukin-6 (IL-6)-induced phosphorylation and subsequent transactivation of signal transducer and activator of transcription-3 (STAT3), thereby increasing the expression of cyclin-dependent kinase-4 (Cdk4), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). On the contrary, 3-DSC attenuated STAT6 mRNA expression and IL4-induced STAT6 phosphorylation in HDPCs. Finally, we observed that topical application of 3-DSC promoted the anagen phase of hair growth in C57BL/6 mice. 3-DSC stimulates hair growth possibly by inducing proliferation of follicular dermal papilla cells via modulation of WNT/β-catenin and STAT signaling. PMID:27795451

  18. Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines

    International Nuclear Information System (INIS)

    Girroir, Elizabeth E.; Hollingshead, Holly E.; Billin, Andrew N.; Willson, Timothy M.; Robertson, Gavin P.; Sharma, Arun K.; Amin, Shantu; Gonzalez, Frank J.; Peters, Jeffrey M.

    2008-01-01

    The development of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands for the treatment of diseases including metabolic syndrome, diabetes and obesity has been hampered due to contradictory findings on their potential safety. For example, while some reports show that ligand activation of PPARβ/δ promotes the induction of terminal differentiation and inhibition of cell growth, other reports suggest that PPARβ/δ ligands potentiate tumorigenesis by increasing cell proliferation. Some of the contradictory findings could be due in part to differences in the ligand examined, the presence or absence of serum in cell cultures, differences in cell lines or differences in the method used to quantify cell growth. For these reasons, this study examined the effect of ligand activation of PPARβ/δ on cell growth of two human cancer cell lines, MCF7 (breast cancer) and UACC903 (melanoma) in the presence or absence of serum using two highly specific PPARβ/δ ligands, GW0742 or GW501516. Culturing cells in the presence of either GW0742 or GW501516 caused upregulation of the known PPARβ/δ target gene angiopoietin-like protein 4 (ANGPTL4). Inhibition of cell growth was observed in both cell lines cultured in the presence of either GW0742 or GW501516, and the presence or absence of serum had little influence on this inhibition. Results from the present studies demonstrate that ligand activation of PPARβ/δ inhibits the growth of both MCF7 and UACC903 cell lines and provide further evidence that PPARβ/δ ligands are not mitogenic in human cancer cell lines

  19. The Mu opioid receptor promotes opioid and growth factor-induced proliferation, migration and Epithelial Mesenchymal Transition (EMT in human lung cancer.

    Directory of Open Access Journals (Sweden)

    Frances E Lennon

    Full Text Available Recent epidemiologic studies implying differences in cancer recurrence based on anesthetic regimens raise the possibility that the mu opioid receptor (MOR can influence cancer progression. Based on our previous observations that overexpression of MOR in human non-small cell lung cancer (NSCLC cells increased tumor growth and metastasis, this study examined whether MOR regulates growth factor receptor signaling and epithelial mesenchymal transition (EMT in human NSCLC cells. We utilized specific siRNA, shRNA, chemical inhibitors and overexpression vectors in human H358 NSCLC cells that were either untreated or treated with various concentrations of DAMGO, morphine, fentanyl, EGF or IGF. Cell function assays, immunoblot and immunoprecipitation assays were then performed. Our results indicate MOR regulates opioid and growth factor-induced EGF receptor signaling (Src, Gab-1, PI3K, Akt and STAT3 activation which is crucial for consequent human NSCLC cell proliferation and migration. In addition, human NSCLC cells treated with opioids, growth factors or MOR overexpression exhibited an increase in snail, slug and vimentin and decrease ZO-1 and claudin-1 protein levels, results consistent with an EMT phenotype. Further, these effects were reversed with silencing (shRNA or chemical inhibition of MOR, Src, Gab-1, PI3K, Akt and STAT3 (p<0.05. Our data suggest a possible direct effect of MOR on opioid and growth factor-signaling and consequent proliferation, migration and EMT transition during lung cancer progression. Such an effect provides a plausible explanation for the epidemiologic findings.

  20. Early growth response 4 is involved in cell proliferation of small cell lung cancer through transcriptional activation of its downstream genes.

    Directory of Open Access Journals (Sweden)

    Taisuke Matsuo

    Full Text Available Small cell lung cancer (SCLC is aggressive, with rapid growth and frequent bone metastasis; however, its detailed molecular mechanism remains poorly understood. Here, we report the critical role of early growth factor 4 (EGR4, a DNA-binding, zinc-finger transcription factor, in cell proliferation of SCLC. EGR4 overexpression in HEK293T cells conferred significant upregulation of specific splice variants of the parathyroid hormone-related protein (PTHrP gene, resulting in enhancement of the secretion of PTHrP protein, a known mediator of osteolytic bone metastasis. More importantly, depletion of EGR4 expression by siRNA significantly suppressed growth of the SCLC cell lines, SBC-5, SBC-3 and NCI-H1048. On the other hand, introduction of EGR4 into NIH3T3 cells significantly enhanced cell growth. We identified four EGR4 target genes, SAMD5, RAB15, SYNPO and DLX5, which were the most significantly downregulated genes upon depletion of EGR4 expression in all of the SCLC cells examined, and demonstrated the direct recruitment of EGR4 to their promoters by ChIP and luciferase reporter analysis. Notably, knockdown of the expression of these genes by siRNA remarkably suppressed the growth of all the SCLC cells. Taken together, our findings suggest that EGR4 likely regulates the bone metastasis and proliferation of SCLC cells via transcriptional regulation of several target genes, and may therefore be a promising target for the development of anticancer drugs for SCLC patients.

  1. Nuclear PIM1 confers resistance to rapamycin-impaired endothelial proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Walpen, Thomas; Kalus, Ina [Research Unit, Division Internal Medicine, University Hospital Zuerich, 8091 Zuerich (Switzerland); Schwaller, Juerg [Department of Biomedicine, University of Basel, 4031 Basel (Switzerland); Peier, Martin A. [Research Unit, Division Internal Medicine, University Hospital Zuerich, 8091 Zuerich (Switzerland); Battegay, Edouard J. [Research Unit, Division Internal Medicine, University Hospital Zuerich, 8091 Zuerich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), 8057 Zuerich (Switzerland); Humar, Rok, E-mail: Rok.Humar@usz.ch [Research Unit, Division Internal Medicine, University Hospital Zuerich, 8091 Zuerich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), 8057 Zuerich (Switzerland)

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer Pim1{sup -/-} endothelial cell proliferation displays increased sensitivity to rapamycin. Black-Right-Pointing-Pointer mTOR inhibition by rapamycin enhances PIM1 cytosolic and nuclear protein levels. Black-Right-Pointing-Pointer Truncation of Pim1 beyond serine 276 results in nuclear localization of the kinase. Black-Right-Pointing-Pointer Nuclear PIM1 increases endothelial proliferation independent of rapamycin. -- Abstract: The PIM serine/threonine kinases and the mTOR/AKT pathway integrate growth factor signaling and promote cell proliferation and survival. They both share phosphorylation targets and have overlapping functions, which can partially substitute for each other. In cancer cells PIM kinases have been reported to produce resistance to mTOR inhibition by rapamycin. Tumor growth depends highly on blood vessel infiltration into the malignant tissue and therefore on endothelial cell proliferation. We therefore investigated how the PIM1 kinase modulates growth inhibitory effects of rapamycin in mouse aortic endothelial cells (MAEC). We found that proliferation of MAEC lacking Pim1 was significantly more sensitive to rapamycin inhibition, compared to wildtype cells. Inhibition of mTOR and AKT in normal MAEC resulted in significantly elevated PIM1 protein levels in the cytosol and in the nucleus. We observed that truncation of the C-terminal part of Pim1 beyond Ser 276 resulted in almost exclusive nuclear localization of the protein. Re-expression of this Pim1 deletion mutant significantly increased the proliferation of Pim1{sup -/-} cells when compared to expression of the wildtype Pim1 cDNA. Finally, overexpression of the nuclear localization mutant and the wildtype Pim1 resulted in complete resistance to growth inhibition by rapamycin. Thus, mTOR inhibition-induced nuclear accumulation of PIM1 or expression of a nuclear C-terminal PIM1 truncation mutant is sufficient to increase endothelial cell proliferation

  2. Three-dimensional motion pattern of the caudal lumbar and lumbosacral portions of the vertebral column of dogs.

    Science.gov (United States)

    Benninger, Monika I; Seiler, Gabriela S; Robinson, Leanne E; Ferguson, Stephen J; Bonél, Harald M; Busato, André R; Lang, Johann

    2004-05-01

    To evaluate the 3-dimensional motion pattern including main and coupled motions of the caudal lumbar and lumbosacral portions of the vertebral column of dogs. Vertebral columns of 9 German Shepherd Dogs (GSDs) and 16 dogs of other breeds with similar body weights and body conditions. Main and coupled motions of the caudal lumbar and lumbosacral portions of the vertebral column (L4 to S1) were determined by use of a testing apparatus that permitted precise application of known pure moments to the vertebral column. Motion was compared between GSDs and dogs of other breeds. All specimens had a similar motion pattern consisting of main motion and a certain amount of coupled motion including translation. Vertebral columns of GSDs had significantly less main motion in all directions than that of dogs of other breeds. Translation was similar in GSDs and dogs of other breeds and was smallest at the lumbosacral motion segment. Results indicated that motion in the caudal lumbar and lumbosacral portions of the vertebral column of dogs is complex and provided a basis for further studies evaluating abnormal vertebral columns.

  3. Differential role of PTEN in transforming growth factor β (TGF-β) effects on proliferation and migration in prostate cancer cells.

    Science.gov (United States)

    Kimbrough-Allah, Mawiyah N; Millena, Ana C; Khan, Shafiq A

    2018-04-01

    Transforming growth factor-β (TGF-β) acts as a tumor suppressor in normal epithelial cells but as a tumor promoter in advanced prostate cancer cells. PI3-kinase pathway mediates TGF-β effects on prostate cancer cell migration and invasion. PTEN inhibits PI3-kinase pathway and is frequently mutated in prostate cancers. We investigated possible role(s) of PTEN in TGF-β effects on proliferation and migration in prostate cancer cells. Expression of PTEN mRNA and proteins were determined using RT-PCR and Western blotting in RWPE1 and DU145 cells. We also studied the role of PTEN in TGF-β effects on cell proliferation and migration in DU145 cells after transient silencing of endogenous PTEN. Conversely, we determined the role of PTEN in cell proliferation and migration after over-expression of PTEN in PC3 cells which lack endogenous PTEN. TGF-β1 and TGF-β3 had no effect on PTEN mRNA levels but both isoforms increased PTEN protein levels in DU145 and RWPE1 cells indicating that PTEN may mediate TGF-β effects on cell proliferation. Knockdown of PTEN in DU145 cells resulted in significant increase in cell proliferation which was not affected by TGF-β isoforms. PTEN overexpression in PC3 cells inhibited cell proliferation. Knockdown of endogenous PTEN enhanced cell migration in DU145 cells, whereas PTEN overexpression reduced migration in PC3 cells and reduced phosphorylation of AKT in response to TGF-β. We conclude that PTEN plays a role in inhibitory effects of TGF-β on cell proliferation whereas its absence may enhance TGF-β effects on activation of PI3-kinase pathway and cell migration. © 2018 Wiley Periodicals, Inc.

  4. ETOH inhibits embryonic neural stem/precursor cell proliferation via PLD signaling

    International Nuclear Information System (INIS)

    Fujita, Yuko; Hiroyama, Masami; Sanbe, Atsushi; Yamauchi, Junji; Murase, Shoko; Tanoue, Akito

    2008-01-01

    While a mother's excessive alcohol consumption during pregnancy is known to have adverse effects on fetal neural development, little is known about the underlying mechanism of these effects. In order to investigate these mechanisms, we investigated the toxic effect of ethanol (ETOH) on neural stem/precursor cell (NSC) proliferation. In cultures of NSCs, phospholipase D (PLD) is activated following stimulation with epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2). Exposure of NSCs to ETOH suppresses cell proliferation, while it has no effect on cell death. Phosphatidic acid (PA), which is a signaling messenger produced by PLD, reverses ETOH inhibition of NSC proliferation. Blocking the PLD signal by 1-butanol suppresses the proliferation. ETOH-induced suppression of NSC proliferation and the protective effect of PA for ETOH-induced suppression are mediated through extracellular signal-regulated kinase signaling. These results indicate that exposure to ETOH impairs NSC proliferation by altering the PLD signaling pathway

  5. Modified Labial Button Technique for Maintaining Occlusion After Caudal Mandibular Fracture/Temporomandibular Joint Luxation in the Cat.

    Science.gov (United States)

    Goodman, Alice E; Carmichael, Daniel T

    2016-03-01

    Maxillofacial trauma in cats often results in mandibular symphyseal separation in addition to injuries of the caudal mandible and/or temporomandibular joint (TMJ). Caudal mandibular and TMJ injuries are difficult to access and stabilize using direct fixation techniques, thus indirect fixation is commonly employed. The immediate goals of fixation include stabilization for return to normal occlusion and function with the long-term objective of bony union. Indirect fixation techniques commonly used for stabilization of caudal mandibular and temporomandibular joint fracture/luxation include maxillomandibular fixation (MMF) with acrylic composite, interarcade wiring, tape muzzles, and the bignathic encircling and retaining device (BEARD) technique. This article introduces a modification of the previously described "labial reverse suture through buttons" technique used by Koestlin et al and the "labial locking with buttons" technique by Rocha et al. In cases with minimally displaced subcondylar and pericondylar fractures without joint involvement, the labial button technique can provide sufficient stabilization for healing. Advantages of the modified labial button technique include ease of application, noninvasive nature, and use of readily available materials. The construct can remain in place for a variable of amount of time, depending on its intended purpose. It serves as an alternative to the tape muzzle, which is rarely tolerated by cats. This technique can be easily used in conjunction with other maxillomandibular repairs, such as cerclage wire fixation of mandibular symphyseal separation. The purpose of this article is to demonstrate a modified labial button technique for maintaining occlusion of feline caudal mandibular fractures/TMJ luxations in a step-by-step fashion.

  6. Simvastatin inhibits the proliferation of human prostate cancer PC-3 cells via down-regulation of the insulin-like growth factor 1 receptor

    International Nuclear Information System (INIS)

    Sekine, Yoshitaka; Furuya, Yosuke; Nishii, Masahiro; Koike, Hidekazu; Matsui, Hiroshi; Suzuki, Kazuhiro

    2008-01-01

    Recently, statins have been being studied for their proapoptic and antimetastatic effects. However, the exact mechanisms of their anticancer action are still unclear. Dolichyl phosphate is a nonsterol isoprenoid derivative in the mevalonate pathway that affects the expression of the Insulin-like growth factor 1 receptor (IGF-1R). IGF-1R activation is required for prostate cell proliferation; therefore, IGF-1R inhibitory agents may be of preventive and/or therapeutic value. In this study, the effects of simvastatin on IGF-1R signaling in prostate cancer PC-3 cells were examined. Simvastatin suppressed proliferation and induced apoptosis of PC-3, and the expression of IGF-1R was suppressed by simvastatin. Knockdown of IGF-1R by siRNA led to inhibition of proliferation of PC-3. Simvastatin also inhibited IGF-1-induced activation of both ERK and Akt signaling and IGF-1-induced PC-3 cell proliferation. Our results suggest statins are potent inhibitors of the IGF-1/IGF-1R system in prostate cancer cells and may be beneficial in prostate cancer treatment

  7. FHOD1 formin is upregulated in melanomas and modifies proliferation and tumor growth

    International Nuclear Information System (INIS)

    Peippo, Minna; Gardberg, Maria; Lamminen, Tarja; Kaipio, Katja; Carpén, Olli; Heuser, Vanina D.

    2017-01-01

    The functional properties of actin-regulating formin proteins are diverse and in many cases cell-type specific. FHOD1, a formin expressed predominantly in cells of mesenchymal lineage, bundles actin filaments and participates in maintenance of cell shape, migration and cellular protrusions. FHOD1 participates in cancer-associated epithelial to mesenchymal transition (EMT) in oral squamous cell carcinoma and breast cancer. The role of FHOD1 in melanomas has not been characterized. Here, we show that FHOD1 expression is typically strong in cutaneous melanomas and cultured melanoma cells while the expression is low or absent in benign nevi. By using shRNA to knockdown FHOD1 in melanoma cells, we discovered that FHOD1 depleted cells are larger, rounder and have smaller focal adhesions and inferior migratory capacity as compared to control cells. Importantly, we found FHOD1 depleted cells to have reduced colony-forming capacity and attenuated tumor growth in vivo, a finding best explained by the reduced proliferation rate caused by cell cycle arrest. Unexpectedly, FHOD1 depletion did not prevent invasive growth at the tumor margins. These results suggest that FHOD1 participates in key cellular processes that are dysregulated in malignancy, but may not be essential for melanoma cell invasion.

  8. UAP56 is an important mediator of Angiotensin II/platelet derived growth factor induced vascular smooth muscle cell DNA synthesis and proliferation

    International Nuclear Information System (INIS)

    Sahni, Abha; Wang, Nadan; Alexis, Jeffrey

    2013-01-01

    Highlights: ► Knockdown of UAP56 inhibits Angiotensin II/PDGF induced vascular smooth muscle cell proliferation. ► UAP56 is a positive regulator of E2F transcriptional activation. ► UAP56 is present in the vessel wall of low flow carotid arteries. -- Abstract: Angiotensin (Ang) II and platelet-derived growth factor (PDGF) are important mediators of pathologic vascular smooth muscle cell (VSMC) proliferation. Identifying downstream mediators of Ang II and PDGF signaling may provide insights for therapies to improve vascular proliferative diseases. We have previously demonstrated that breakpoint cluster region (Bcr) is an important mediator of Ang II/PDGF signaling in VSMC. We have recently reported that the DExD/H box protein UAP56 is an interacting partner of Bcr in regulating VSMC DNA synthesis. We hypothesized that UAP56 itself is an important regulator of VSMC proliferation. In this report we demonstrate that knockdown of UAP56 inhibits Ang II/PDGF induced VSMC DNA synthesis and proliferation, and inhibits E2F transcriptional activity. In addition, we demonstrate that UAP56 is present in the vessel wall of low-flow carotid arteries. These findings suggest that UAP56 is a regulator of VSMC proliferation and identify UAP56 as a target for preventing vascular proliferative disease

  9. Single dose caudal tramadol with bupivacaine and bupivacaine alone in pediatric inguinoscrotal surgeries

    International Nuclear Information System (INIS)

    Khalid, A.; Siddiqui, S.Z.; Aftab, S.

    2007-01-01

    To determine the postoperative analgesic effect of Tramadol when given with caudally administered Bupivacaine in children undergoing inguinoscrotal surgeries. A total of 60 children, undergoing inguinoscrotal surgeries, aged from 1 to 12 years, ASA 1 and 2, were included. The patients were divided into two equal groups. The group given Bupivacaine with Tramadol was called group BT and the group which was given only Bupivacaine was labeled as group B. Group BT was given 0.25%, 0.8 ml/kg Bupivacaine and Tramadol 2 mg/kg while the other group B was given 0.25%, 0.8 ml/kg Bupivacaine through caudal route after induction of general anesthesia. No other analgesic was given intraoperatively. The postoperative pain was evaluated by using visual analogue scale/Ocher face scale/CHEOPS and sedation was assessed by 5 points sedation score at immediate postoperative period 1,2,3,4,6,12 and 24 hours. Supplemental analgesia in the form of paracetamol suppositories and syrup ibuprofen was given accordingly. SaO 2, pulse, blood pressure, and motor block were monitored in all the patients. Addition of Tramadol with Bupivacaine resulted in meaningfully increased postoperative analgesic period (16.06 +- 4.04 hours). No other side effects like respiratory depression, pruritus, urinary retention were found in both the groups except for nausea and vomiting. The demand for supplemental analgesia was more in the patients belonging to B group than BT group. The sedation scores were similar in both the groups. The use of Tramadol as an additive with local anesthetics can prolong the postoperative analgesic period when administered caudally. Its use is safe in children. (author)

  10. Insulin-like growth factor I (IGF-1) Ec/Mechano Growth factor--a splice variant of IGF-1 within the growth plate.

    Science.gov (United States)

    Schlegel, Werner; Raimann, Adalbert; Halbauer, Daniel; Scharmer, Daniela; Sagmeister, Susanne; Wessner, Barbara; Helmreich, Magdalena; Haeusler, Gabriele; Egerbacher, Monika

    2013-01-01

    Human insulin-like growth factor 1 Ec (IGF-1Ec), also called mechano growth factor (MGF), is a splice variant of insulin-like growth factor 1 (IGF-1), which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation.

  11. Comparison of the effect of sevoflurane and halothane anesthesia on the fall in hear rate as a predictor of successful single shot caudal epidural in children

    International Nuclear Information System (INIS)

    Mercan, A.; Ture, H.; Sayin, Murat M.; Koner, O.; Aykac, B.; Sozubir, S.

    2009-01-01

    Objective was to investigate the effect of sevoflurane anesthesia on heart rate (HR) fall with the injection of the initial drug in caudal space to confirm the correct needle placement. After the ethical approval was obtained from the hospital's ethics committee, a prospective randomized, clinical study was designed in Yeditepe University Hospital, in 2007. Children aged 1-12 years, scheduled for infraumblical surgery under general anesthesia and caudal block were included in the study. Anesthesia was induced and maintained by sevoflurane in group S (n=8) and by halothane in group H (n=82). Baseline HR was recorded before the caudal block was performed. The HR changes during the initial dose and total drug injection was recorded followed by 2 more HR recordings taken 5 and 10 minutes after caudal injection. The success of the block was recorded by a blind observer. There were 167 children included in the study. Caudal block success was 96.5% in group S and 97.6% in group H. Basal HR was 110.9+-10.9 in group S and 105.9+-10.1 in group H. Following the initial drug injection, mean HR was 109.8+-10.9 in group S and 102.9+-9.9 in group H. It was significantly lower than the baseline in group. The only significant decrease in the HR of the patients in group S was at the tenth minute following caudal injection. The decrease in HR with drug injection has no value to predict the success of caudal block under sevoflurane anesthesia. (author)

  12. Cyp26b1 within the growth plate regulates bone growth in juvenile mice

    International Nuclear Information System (INIS)

    Minegishi, Yoshiki; Sakai, Yasuo; Yahara, Yasuhito; Akiyama, Haruhiko; Yoshikawa, Hideki; Hosokawa, Ko; Tsumaki, Noriyuki

    2014-01-01

    Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1 Δchon cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone

  13. Differential migration and proliferation of geometrical ensembles of cell clusters

    International Nuclear Information System (INIS)

    Kumar, Girish; Chen, Bo; Co, Carlos C.; Ho, Chia-Chi

    2011-01-01

    Differential cell migration and growth drives the organization of specific tissue forms and plays a critical role in embryonic development, tissue morphogenesis, and tumor invasion. Localized gradients of soluble factors and extracellular matrix have been shown to modulate cell migration and proliferation. Here we show that in addition to these factors, initial tissue geometry can feedback to generate differential proliferation, cell polarity, and migration patterns. We apply layer by layer polyelectrolyte assembly to confine multicellular organization and subsequently release cells to demonstrate the spatial patterns of cell migration and growth. The cell shapes, spreading areas, and cell-cell contacts are influenced strongly by the confining geometry. Cells within geometric ensembles are morphologically polarized. Symmetry breaking was observed for cells on the circular pattern and cells migrate toward the corners and in the direction parallel to the longest dimension of the geometric shapes. This migration pattern is disrupted when actomyosin based tension was inhibited. Cells near the edge or corner of geometric shapes proliferate while cells within do not. Regions of higher rate of cell migration corresponded to regions of concentrated growth. These findings demonstrate that multicellular organization can result in spatial patterns of migration and proliferation.

  14. Effectiveness of caudal septal extension graft application in endonasal septoplasty

    Directory of Open Access Journals (Sweden)

    Yunus Karadavut

    Full Text Available Abstract Introduction Septal deviation is a common disease seen in daily otorhinolaryngology practice and septoplasty is a commonly performed surgical procedure. Caudal septum deviation is also a challenging pathology for ear, nose, and throat specialists. Many techniques are defined for caudal septal deviation. Objective To evaluate the effectiveness of caudal septal extension graft (CSEG application in patients who underwent endonasal septoplasty for a short and deviated nasal septum. Methods Forty patients with nasal septal deviation, short nasal septum, and weak nasal tip support who underwent endonasal septoplasty with or without CSEG placement between August 2012 and June 2013 were enrolled in this study. Twenty patients underwent endonasal septoplasty with CSEG placement. The rest of the group, who rejected auricular or costal cartilage harvest for CSEG placement, underwent only endonasal septoplasty without any additional intervention. Using the Nasal Obstruction Symptom Evaluation (NOSE and Rhinoplasty Outcome Evaluation (ROE questionnaires, pre- and post-operative acoustic rhinometer measurements were evaluated to assess the effect of CESG placement on nasal obstruction. Results In the control group, preoperative and postoperative minimal cross-sectional areas (MCA1 were 0.44 ± 0.10 cm2 and 0.60 ± 0.11 cm2, respectively (p < 0.001. In the study group, pre- and postoperative MCA1 values were 0.45 ± 0.16 cm2 and 0.67 ± 0.16 cm2, respectively (p < 0.01. In the control group, the nasal cavity volume (VOL1 value was 1.71 ± 0.21 mL preoperatively and 1.94 ± 0.17 mL postoperatively (p < 0.001. In the study group, pre- and postoperative VOL1s were 1.72 ± 0.15 mL and 1.97 ± 0.12 mL, respectively (p < 0.001. Statistical analysis of postoperative MCA1 and VOL1 values in the study and the control groups could not detect any significant intergroup difference (p = 0.093 and 0.432, respectively. In the study group, mean nasolabial angles were

  15. Bryostatin I inhibits growth and proliferation of pancreatic cancer ...

    African Journals Online (AJOL)

    ). ... µM reduced MIApaCa 2 cell proliferation from 87 to 26 %. ... tumors in the treatment and untreated groups was 123.67 ± 22.56 and ... κB expression, and therefore, needs to be further investigated for therapeutic application in pancreatic.

  16. Caudal duplication syndrome: imaging evaluation of a rare entity in an adult patient

    Directory of Open Access Journals (Sweden)

    Tianshen Hu, BS

    2016-03-01

    Full Text Available Several theories have been put forth to explain the complex yet symmetrical malformations and the myriad of clinical presentations of caudal duplication syndrome. Hereby, reported case is a 28-year-old female, gravida 2 para 2, with congenital caudal malformation who has undergone partial reconstructive surgeries in infancy to connect her 2 colons. She presented with recurrent left lower abdominal pain associated with nausea, vomiting, and subsequent feculent anal discharge. Imaging reveals duplication of the urinary bladder, urethra, and colon with with cloacal malformations and fistulae from the left-sided cloaca, uterus didelphys with separate cervices and vaginal canals, right-sided aortic arch and descending thoracic aorta, and dysraphic midline sacrococcygeal defect. Hydronephrosis of the left kidney with left hydroureter and inflammation of one of the colons were suspected to be the cause of the patient’s acute complaints. She improved symptomatically over the course of her hospitalization stay with conservative treatments. The management for this syndrome is individualized and may include surgical intervention to fuse or excise the duplicated organs.

  17. Activation of a Neospora caninum EGFR-Like Kinase Facilitates Intracellular Parasite Proliferation

    Directory of Open Access Journals (Sweden)

    Xiaoxia Jin

    2017-10-01

    Full Text Available The Apicomplexan parasite Neospora caninum, an obligate intracellular protozoan, causes serious diseases in a number of mammalian species, especially in cattle. Infection with N. caninum is associated with abortions in both dairy and beef cattle worldwide which have a major economic impact on the cattle industry. However, the mechanism by which N. caninum proliferates within host cells is poorly understood. Epidermal growth factor receptor (EGFR is a protein kinase ubiquitously expressed, present on cell surfaces in numerous species, which has been confirmed to be essential in signal transduction involved in cell growth, proliferation, survival, and many other intracellular processes. However, the presence of EGFR in N. caninum and its role in N. caninum proliferation remain unclear. In the present study, we identified a putative EGFR-like kinase in N. caninum, which could be activated in tachyzoites by infection or treatment with rNcMIC3 [containing four epidermal growth factor (EGF domains] or human EGF. Blockade of EGFR-like in tachyzoites by AG1478 significantly reduced parasite proliferation in host cells. Our data suggested that the activation of tachyzoite EGFR-like might facilitate the intracellular proliferation of N. caninum.

  18. Insulin-like growth factor I (IGF-1 Ec/Mechano Growth factor--a splice variant of IGF-1 within the growth plate.

    Directory of Open Access Journals (Sweden)

    Werner Schlegel

    Full Text Available Human insulin-like growth factor 1 Ec (IGF-1Ec, also called mechano growth factor (MGF, is a splice variant of insulin-like growth factor 1 (IGF-1, which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation.

  19. Inhibition of Cell Proliferation and Growth of Pancreatic Cancer by Silencing of Carbohydrate Sulfotransferase 15 In Vitro and in a Xenograft Model.

    Directory of Open Access Journals (Sweden)

    Kazuki Takakura

    Full Text Available Chondroitin sulfate E (CS-E, a highly sulfated glycosaminoglycan, is known to promote tumor invasion and metastasis. Because the presence of CS-E is detected in both tumor and stromal cells in pancreatic ductal adenocarcinoma (PDAC, multistage involvement of CS-E in the development of PDAC has been considered. However, its involvement in the early stage of PDAC progression is still not fully understood. In this study, to clarify the direct role of CS-E in tumor, but not stromal, cells of PDAC, we focused on carbohydrate sulfotransferase 15 (CHST15, a specific enzyme that biosynthesizes CS-E, and investigated the effects of the CHST15 siRNA on tumor cell proliferation in vitro and growth in vivo. CHST15 mRNA is highly expressed in the human pancreatic cancer cell lines PANC-1, MIA PaCa-2, Capan-1 and Capan-2. CHST15 siRNA significantly inhibited the expression of CHST15 mRNA in these four cells in vitro. Silencing of the CHST15 gene in the cells was associated with significant reduction of proliferation and up-regulation of the cell cycle inhibitor-related gene p21CIP1/WAF1. In a subcutaneous xenograft tumor model of PANC-1 in nude mice, a single intratumoral injection of CHST15 siRNA almost completely suppressed tumor growth. Reduced CHST15 protein signals associated with tumor necrosis were observed with the treatment with CHST15 siRNA. These results provide evidence of the direct action of CHST15 on the proliferation of pancreatic tumor cells partly through the p21CIP1/WAF1 pathway. Thus, CHST15-CS-E axis-mediated tumor cell proliferation could be a novel therapeutic target in the early stage of PDAC progression.

  20. Growth of SJL/J-derived transplantable reticulum cell sarcoma as related to its ability to induce T-cell proliferation in the host- III. Studies on thymectomized and congenitally athymic SJL mice

    International Nuclear Information System (INIS)

    Katz, I.R.; Chapman-Alexander, J.; Jacobson, E.B.; Lerman, S.P.; Thorbecke, G.J.

    1981-01-01

    When SJL mice are irradiated and reconstituted with syngeneic bone marrow (XBM) they support growth of transplantable reticulum cell sarcoma to approximately 60% of that in normal mice. The ability to support RCS growth gradually improves with time after irradiation and reaches 90% of normal by 8-12 weeks. However, if the mice are thymectomized 4 weeks prior to treatment (Tx-XBM) they initially show 50% which increases to only 65% of growth in normal mice after 12 weeks. The ability of lymphoid cells from these mice to proliferate in vitro in response to irradiated RCS cells is normal 4 weeks after treatment in XBM, but remains <10% of normal in Tx-XBM mice. Nude mice of SJL background also show greatly diminished RCS growth. It is concluded that T cells promote RCS growth in vivo possibly via their tendency to proliferate upon exposure to RCS

  1. PHA665752, a small-molecule inhibitor of c-Met, inhibits hepatocyte growth factor-stimulated migration and proliferation of c-Met-positive neuroblastoma cells

    International Nuclear Information System (INIS)

    Crosswell, Hal E; Dasgupta, Anindya; Alvarado, Carlos S; Watt, Tanya; Christensen, James G; De, Pradip; Durden, Donald L; Findley, Harry W

    2009-01-01

    c-Met is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF), and both c-Met and its ligand are expressed in a variety of tissues. C-Met/HGF/SF signaling is essential for normal embryogenesis, organogenesis, and tissue regeneration. Abnormal c-Met/HGF/SF signaling has been demonstrated in different tumors and linked to aggressive and metastatic tumor phenotypes. In vitro and in vivo studies have demonstrated inhibition of c-Met/HGF/SF signaling by the small-molecule inhibitor PHA665752. This study investigated c-Met and HGF expression in two neuroblastoma (NBL) cell lines and tumor tissue from patients with NBL, as well as the effects of PHA665752 on growth and motility of NBL cell lines. The effect of the tumor suppressor protein PTEN on migration and proliferation of tumor cells treated with PHA665752 was also evaluated. Expression of c-Met and HGF in NBL cell lines SH-EP and SH-SY5Y and primary tumor tissue was assessed by immunohistochemistry and quantitative RT-PCR. The effect of PHA665752 on c-Met/HGF signaling involved in NBL cell proliferation and migration was evaluated in c-Met-positive cells and c-Met-transfected cells. The transwell chemotaxis assay and the MTT assay were used to measure migration and proliferation/cell-survival of tumor cells, respectively. The PPAR-γ agonist rosiglitazone was used to assess the effect of PTEN on PHA665752-induced inhibition of NBL cell proliferation/cell-survival and migration High c-Met expression was detected in SH-EP cells and primary tumors from patients with advanced-stage disease. C-Met/HGF signaling induced both migration and proliferation of SH-EP cells. Migration and proliferation/cell-survival were inhibited by PHA665752 in a dose-dependent manner. We also found that induced overexpression of PTEN following treatment with rosiglitazone significantly enhanced the inhibitory effect of PHA665752 on NBL-cell migration and proliferation. c-Met is highly expressed in most tumors from

  2. Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro

    International Nuclear Information System (INIS)

    Xu, Yang; Pang, Xiaoyan; Dong, Mei; Wen, Fang; Zhang, Yi

    2013-01-01

    Highlights: •Nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest. •Nesfatin-1 enhances HO-8910 cell apoptosis. •Nesfatin-1 inhibits HO-8910 cell proliferation via mTOR and RhoA/ROCK signaling pathway. •The first report of nesfatin-1-mediated proliferation in ovarian epithelial carcinoma. -- Abstract: Nesfatin-1, an 82-amino-acid peptide derived from a 396-amino-acid precursor protein nucleobindin 2 (NUCB2), was originally identified in hypothalamic nuclei involved in the regulation of food intake. It was recently reported that nesfatin-1 is a novel depot specific adipokine preferentially produced by subcutaneous tissue, with obesity- and food deprivation-regulated expression. Although a relation between ovarian cancer mortality and obesity has been previously established, a role of nesfatin-1 in ovarian epithelial carcinoma remains unknown. The aim of the present study is to examine the effect of nesfatin-1 on ovary carcinoma cells proliferation. We found that nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest, this inhibition could be abolished by nesfatin-1 neutralizing antibody. Nesfatin-1 enhances HO-8910 cell apoptosis, activation of mammalian target of rapamycin (mTOR) and RhoA/ROCK signaling pathway block the effects of nesfatin-1-induced apoptosis, therefore reverses the inhibition of HO-8910 cell proliferation by nesfatin-1. In conclusion, the present study demonstrated that nesfatin-1 can inhibit the proliferation in human ovarian epithelial carcinoma cell line HO-8910 cells through inducing apoptosis via mTOR and RhoA/ROCK signaling pathway. This study provides a novel regulatory signaling pathway of nesfatin-1-regulated ovarian epithelial carcinoma growth and may contribute to ovarian cancer prevention and therapy, especially in obese patients

  3. Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yang; Pang, Xiaoyan; Dong, Mei; Wen, Fang, E-mail: wenfang64@hotmail.com; Zhang, Yi, E-mail: syzi960@yahoo.com

    2013-11-01

    Highlights: •Nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest. •Nesfatin-1 enhances HO-8910 cell apoptosis. •Nesfatin-1 inhibits HO-8910 cell proliferation via mTOR and RhoA/ROCK signaling pathway. •The first report of nesfatin-1-mediated proliferation in ovarian epithelial carcinoma. -- Abstract: Nesfatin-1, an 82-amino-acid peptide derived from a 396-amino-acid precursor protein nucleobindin 2 (NUCB2), was originally identified in hypothalamic nuclei involved in the regulation of food intake. It was recently reported that nesfatin-1 is a novel depot specific adipokine preferentially produced by subcutaneous tissue, with obesity- and food deprivation-regulated expression. Although a relation between ovarian cancer mortality and obesity has been previously established, a role of nesfatin-1 in ovarian epithelial carcinoma remains unknown. The aim of the present study is to examine the effect of nesfatin-1 on ovary carcinoma cells proliferation. We found that nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest, this inhibition could be abolished by nesfatin-1 neutralizing antibody. Nesfatin-1 enhances HO-8910 cell apoptosis, activation of mammalian target of rapamycin (mTOR) and RhoA/ROCK signaling pathway block the effects of nesfatin-1-induced apoptosis, therefore reverses the inhibition of HO-8910 cell proliferation by nesfatin-1. In conclusion, the present study demonstrated that nesfatin-1 can inhibit the proliferation in human ovarian epithelial carcinoma cell line HO-8910 cells through inducing apoptosis via mTOR and RhoA/ROCK signaling pathway. This study provides a novel regulatory signaling pathway of nesfatin-1-regulated ovarian epithelial carcinoma growth and may contribute to ovarian cancer prevention and therapy, especially in obese patients.

  4. Increased classical endoplasmic reticulum stress is sufficient to reduce chondrocyte proliferation rate in the growth plate and decrease bone growth.

    Directory of Open Access Journals (Sweden)

    Louise H W Kung

    Full Text Available Mutations in genes encoding cartilage oligomeric matrix protein and matrilin-3 cause a spectrum of chondrodysplasias called multiple epiphyseal dysplasia (MED and pseudoachondroplasia (PSACH. The majority of these diseases feature classical endoplasmic reticulum (ER stress and activation of the unfolded protein response (UPR as a result of misfolding of the mutant protein. However, the importance and the pathological contribution of ER stress in the disease pathogenesis are unknown. The aim of this study was to investigate the generic role of ER stress and the UPR in the pathogenesis of these diseases. A transgenic mouse line (ColIITgcog was generated using the collagen II promoter to drive expression of an ER stress-inducing protein (Tgcog in chondrocytes. The skeletal and histological phenotypes of these ColIITgcog mice were characterised. The expression and intracellular retention of Tgcog induced ER stress and activated the UPR as characterised by increased BiP expression, phosphorylation of eIF2α and spliced Xbp1. ColIITgcog mice exhibited decreased long bone growth and decreased chondrocyte proliferation rate. However, there was no disruption of chondrocyte morphology or growth plate architecture and perturbations in apoptosis were not apparent. Our data demonstrate that the targeted induction of ER stress in chondrocytes was sufficient to reduce the rate of bone growth, a key clinical feature associated with MED and PSACH, in the absence of any growth plate dysplasia. This study establishes that classical ER stress is a pathogenic factor that contributes to the disease mechanism of MED and PSACH. However, not all the pathological features of MED and PSACH were recapitulated, suggesting that a combination of intra- and extra-cellular factors are likely to be responsible for the disease pathology as a whole.

  5. Comparative proteome approach demonstrates that platelet-derived growth factor C and D efficiently induce proliferation while maintaining multipotency of hMSCs

    Energy Technology Data Exchange (ETDEWEB)

    Sotoca, Ana M., E-mail: a.sotoca@science.ru.nl [Department of Cell and Applied Biology, Radboud University, Heijendaalseweg 135, 6525 AJ Nijmegen (Netherlands); Roelofs-Hendriks, Jose [Department of Cell and Applied Biology, Radboud University, Heijendaalseweg 135, 6525 AJ Nijmegen (Netherlands); Boeren, Sjef [Laboratory of Biochemistry, Wageningen University, Dreijenlaan 3, 6703 HA Wageningen (Netherlands); Kraan, Peter M. van der [Department of Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Vervoort, Jacques [Laboratory of Biochemistry, Wageningen University, Dreijenlaan 3, 6703 HA Wageningen (Netherlands); Zoelen, Everardus J.J. van; Piek, Ester [Department of Cell and Applied Biology, Radboud University, Heijendaalseweg 135, 6525 AJ Nijmegen (Netherlands)

    2013-10-15

    This is the first study that comprehensively describes the effects of the platelet-derived growth factor (PDGF) isoforms C and D during in vitro expansion of human mesenchymal stem cells (hMSCs). Our results show that PDGFs can enhance proliferation of hMSCs without affecting their multipotency. It is of great value to culture and expand hMSCs in a safe and effective manner without losing their multipotency for manipulation and further development of cell-based therapies. Moreover, differential effects of PDGF isoforms have been observed on lineage-specific differentiation induced by BMP2 and Vitamin D3. Based on label-free LC-based quantitative proteomics approach we have furthermore identified specific pathways induced by PDGFs during the proliferation process, showing the importance of bioinformatics tools to study cell function. - Highlights: • PDGFs (C and D) significantly increased the number of multipotent undifferentiated hMSCs. • Enhanced proliferation did not impair the ability to undergo lineage-specific differentiation. • Proteomic analysis confirmed the overall signatures of the ‘intact’ cells.

  6. Proliferation-dependent changes in amino acid transport and glucose metabolism in glioma cell lines

    International Nuclear Information System (INIS)

    Sasajima, Toshio; Miyagawa, Tadashi; Oku, Takamitsu; Gelovani, Juri G.; Finn, Ronald; Blasberg, Ronald

    2004-01-01

    Amino acid imaging is increasingly being used for assessment of brain tumor malignancy, extent of disease, and prognosis. This study explores the relationship between proliferative activity, amino acid transport, and glucose metabolism in three glioma cell lines (U87, Hs683, C6) at different phases of growth in culture. Growth phase was characterized by direct cell counting, proliferation index determined by flow cytometry, and [ 3 H]thymidine (TdR) accumulation, and was compared with the uptake of two non-metabolized amino acids ([ 14 C]aminocyclopentane carboxylic acid (ACPC) and [ 14 C]aminoisobutyric acid (AIB)), and [ 18 F]fluorodeoxyglucose (FDG). Highly significant relationships between cell number (density), proliferation index, and TdR accumulation rate were observed in all cell lines (r>0.99). Influx (K 1 ) of both ACPC and AIB was directly related to cell density, and inversely related to the proliferation index and TdR accumulation in all cell lines. The volume of distribution (V d ) for ACPC and AIB was lowest during rapid growth and highest during the near-plateau growth phase in all cell lines. FDG accumulation in Hs683 and C6 cells was unaffected by proliferation rate, growth phase, and cell density, whereas FDG accumulation was correlated with TdR accumulation, growth phase, and cell density in U87 cells. This study demonstrates that proliferation rate and glucose metabolism are not necessarily co-related in all glioma cell lines. The values of K 1 and V d for ACPC and AIB under different growth conditions suggest that these tumor cell lines can up-regulate amino acid transporters in their cell membranes when their growth conditions become adverse and less than optimal. (orig.)

  7. Ligands for the peroxisome proliferator-activated receptor-γ have inhibitory effects on growth of human neuroblastoma cells in vitro

    International Nuclear Information System (INIS)

    Valentiner, Ursula; Carlsson, Margarita; Erttmann, Rudolf; Hildebrandt, Herbert; Schumacher, Udo

    2005-01-01

    The thiazolidinedione (TZD) or glitazone class of peroxisome proliferator-activated-γ (PPAR-γ) ligands not only induce adipocyte differentiation and increase insulin sensitivity, but also exert growth inhibitory effects on several carcinoma cell lines in vitro as well as in vivo. In the current study the in vitro effect of four PPAR-γ agonists (ciglitazone, pioglitazone, troglitazone, rosiglitazone) on the cell growth of seven human neuroblastoma cell lines (Kelly, LAN-1, LAN-5, LS, IMR-32, SK-N-SH, SH-SY5Y) was investigated. Growth rates were assessed by a colorimetric XTT-based assay kit. Expression of PPAR-γ protein was examined by immunohistochemistry and Western blot analysis. All glitazones inhibited in vitro growth and viability of the human neuroblastoma cell lines in a dose-dependent manner showing considerable effects only at high concentrations (10 μM and 100 μM). Effectiveness of the glitazones on neuroblastoma cell growth differed depending on the cell line and the agent. The presence of PPAR-γ protein was demonstrated in all cell lines. Our findings indicate that ligands for PPAR-γ may be useful therapeutic agents for the treatment of neuroblastoma. Thus the effect of glitazones on the growth of neuroblastoma should now be investigated in an in vivo animal model

  8. Minimally invasive transcriptome profiling in salmon: detection of biological response in rainbow trout caudal fin following exposure to environmental chemical contaminants.

    Science.gov (United States)

    Veldhoen, Nik; Stevenson, Mitchel R; Skirrow, Rachel C; Rieberger, Kevin J; van Aggelen, Graham; Meays, Cynthia L; Helbing, Caren C

    2013-10-15

    An increasing number of anthropogenic chemicals have demonstrated potential for disruption of biological processes critical to normal growth and development of wildlife species. Both anadromous and freshwater salmon species are at risk of exposure to environmental chemical contaminants that may affect migratory behavior, environmental fitness, and reproductive success. A sensitive metric in determination of the presence and impact of such environmental chemical contaminants is through detection of changes in the status of gene transcript levels using a targeted quantitative real-time polymerase chain reaction assay. Ideally, the wildlife assessment strategy would incorporate conservation-centered non-lethal practices. Herein, we describe the development of such an assay for rainbow trout, Oncorhynchus mykiss, following an acute 96 h exposure to increasing concentrations of either 17α-ethinyl estradiol or cadmium. The estrogenic screen included measurement of mRNA encoding estrogen receptor α and β isoforms, vitellogenin, vitelline envelope protein γ, cytochrome p450 family 19 subfamily A, aryl hydrocarbon receptor, and the stress indicator, catalase. The metal exposure screen included evaluation of the latter two mRNA transcripts along with those encoding the metallothionein A and B isoforms. Exposure-dependent transcript abundance profiles were detected in both liver and caudal fin supporting the use of the caudal fin as a non-lethally obtained tissue source. The potential for both transcriptome profiling and genotypic sex determination from fin biopsy was extended, in principle, to field-captured Chinook salmon (Oncorhynchus tshawytscha). Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Rostro-caudal and dorso-ventral gradients in medial and lateral prefrontal cortex during cognitive control of affective and cognitive interference.

    Science.gov (United States)

    Rahm, Christoffer; Liberg, Benny; Wiberg-Kristoffersen, Maria; Aspelin, Peter; Msghina, Mussie

    2013-04-01

    Characterizing the anatomical substrates of major brain functions such as cognition and emotion is of utmost importance to the ongoing efforts of understanding the nature of psychiatric ailments and their potential treatment. The aim of our study was to investigate how the brain handles affective and cognitive interferences on cognitive processes. Functional magnetic resonance imaging investigation was performed on healthy individuals, comparing the brain oxygenation level dependent activation patterns during affective and cognitive counting Stroop tasks. The affective Stroop task activated rostral parts of medial prefrontal cortex (PFC) and rostral and ventral parts of lateral PFC, while cognitive Stroop activated caudal parts of medial PFC and caudal and dorsal parts of lateral PFC. Our findings suggest that the brain may handle affective and cognitive interference on cognitive processes differentially, with affective interference preferentially activating rostral and ventral PFC networks and cognitive interference activating caudal and dorsal PFC networks. © 2013 The Authors. Scandinavian Journal of Psychology © 2013 The Scandinavian Psychological Associations.

  10. Hydrodynamics of a robotic fish tail: effects of the caudal peduncle, fin ray motions and the flow speed.

    Science.gov (United States)

    Ren, Ziyu; Yang, Xingbang; Wang, Tianmiao; Wen, Li

    2016-02-08

    Recent advances in understanding fish locomotion with robotic devices have included the use of biomimetic flapping based and fin undulatory locomotion based robots, treating two locomotions separately from each other. However, in most fish species, patterns of active movements of fins occur in concert with the body undulatory deformation during swimming. In this paper, we describe a biomimetic robotic caudal fin programmed with individually actuated fin rays to mimic the fin motion of the Bluegill Sunfish (Lepomis macrochirus) and coupled with heave and pitch oscillatory motions adding to the robot to mimic the peduncle motion which is derived from the undulatory fish body. Multiple-axis force and digital particle image velocimetry (DPIV) experiments from both the vertical and horizontal planes behind the robotic model were conducted under different motion programs and flow speeds. We found that both mean thrust and lift could be altered by changing the phase difference (φ) from 0° to 360° between the robotic caudal peduncle and the fin ray motion (spanning from 3 mN to 124 mN). Notably, DPIV results demonstrated that the caudal fin generated multiple wake flow patterns in both the vertical and horizontal planes by varying φ. Vortex jet angle and thrust impulse also varied significantly both in these two planes. In addition, the vortex shedding position along the spanwise tail direction could be shifted around the mid-sagittal position between the upper and lower lobes by changing the phase difference. We hypothesize that the fish caudal fin may serve as a flexible vectoring propeller during swimming and may be critical for the high maneuverability of fish.

  11. Beta cell proliferation and growth factors

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis; Svensson, C; Møldrup, Annette

    1999-01-01

    Formation of new beta cells can take place by two pathways: replication of already differentiated beta cells or neogenesis from putative islet stem cells. Under physiological conditions both processes are most pronounced during the fetal and neonatal development of the pancreas. In adulthood little...... increase in the beta cell number seems to occur. In pregnancy, however, a marked hyperplasia of the beta cells is observed both in rodents and man. Increased mitotic activity has been seen both in vivo and in vitro in islets exposed to placental lactogen (PL), prolactin (PRL) and growth hormone (GH...... and activation of the tyrosine kinase JAK2 and the transcription factors STAT1 and 3. The activation of the insulin gene however also requires the distal part of the receptor and activation of calcium uptake and STAT5. In order to identify putative autocrine growth factors or targets for growth factors we have...

  12. The use of tubular retractors for translaminar discectomy for cranially and caudally extruded discs

    Directory of Open Access Journals (Sweden)

    Arvind G Kulkarni

    2018-01-01

    Full Text Available Background: The conventional interlaminar approach is adequate for access to most disc herniations in lumbar spine surgery. The access to cranially and caudally migrated disc fragments, by conventional interlaminar fenestration, requires an extension of the fenestration with the potential destruction of the facet joint complex and consequent postsurgical instability. To describe the technique and results of the translaminar technique of targeted discectomy using tubular retractors for the surgical treatment of cranially and caudally extruded discs. Materials and Methods: The study period extended from January 2008 to December 2014. All patients with lumbar herniated discs who failed conservative management were selected for surgery and underwent routine erect radiographs and magnetic resonance imaging (MRI of the lumbar spine. The patients with cranially or caudally migrated discs were included in this study. The technique involves approaching migrated disc through an oval window (sculpted through an 18 mm tubular retractor using a burr in the lamina precisely over the location of the migrated disc as predicted by the preoperative MRI (inferior lamina for inferior migration and superior lamina for superior migration. The perioperative parameters studied were operative time, blood loss, complications, Oswestry Disability Index (ODI, and visual analog scale (VAS for leg pain before surgery and at last followup. In the study, 4 patients underwent a postoperative computed tomography-scan with a three-dimensional reconstruction to visualize the oval window and to rule out any pars fracture. All technical difficulties and complications were analyzed. Results: 17 patients in the age group of 41–58 years underwent the translaminar technique of targeted discectomy. The migration of disc was cranial in 12 patients and caudal in 5 patients. Fourteen of the affected discs were at the L4–L5 level and three were at the L5-S1 level. The mean VAS (leg pain

  13. Cyp26b1 within the growth plate regulates bone growth in juvenile mice

    Energy Technology Data Exchange (ETDEWEB)

    Minegishi, Yoshiki [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Department of Plastic and Reconstructive Surgery, University of Fukui Hospital, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193 (Japan); Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Sakai, Yasuo [Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Department of Plastic Surgery, Bellland General Hospital, 500-3 Higashiyama Naka-ku, Sakai, Osaka 599-8247 (Japan); Yahara, Yasuhito [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Akiyama, Haruhiko [Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagito, Gifu 501-1194 (Japan); Yoshikawa, Hideki [Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Hosokawa, Ko [Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tsumaki, Noriyuki, E-mail: ntsumaki@cira.kyoto-u.ac.jp [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Japan Science and Technology Agency, CREST, Tokyo 102-0075 (Japan)

    2014-11-07

    Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1{sup Δchon} cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone.

  14. Ethylene Inhibits Cell Proliferation of the Arabidopsis Root Meristem1[OPEN

    Science.gov (United States)

    Street, Ian H.; Aman, Sitwat; Zubo, Yan; Ramzan, Aleena; Wang, Xiaomin; Shakeel, Samina N.; Kieber, Joseph J.; Schaller, G. Eric

    2015-01-01

    The root system of plants plays a critical role in plant growth and survival, with root growth being dependent on both cell proliferation and cell elongation. Multiple phytohormones interact to control root growth, including ethylene, which is primarily known for its role in controlling root cell elongation. We find that ethylene also negatively regulates cell proliferation at the root meristem of Arabidopsis (Arabidopsis thaliana). Genetic analysis indicates that the inhibition of cell proliferation involves two pathways operating downstream of the ethylene receptors. The major pathway is the canonical ethylene signal transduction pathway that incorporates CONSTITUTIVE TRIPLE RESPONSE1, ETHYLENE INSENSITIVE2, and the ETHYLENE INSENSITIVE3 family of transcription factors. The secondary pathway is a phosphorelay based on genetic analysis of receptor histidine kinase activity and mutants involving the type B response regulators. Analysis of ethylene-dependent gene expression and genetic analysis supports SHORT HYPOCOTYL2, a repressor of auxin signaling, as one mediator of the ethylene response and furthermore, indicates that SHORT HYPOCOTYL2 is a point of convergence for both ethylene and cytokinin in negatively regulating cell proliferation. Additional analysis indicates that ethylene signaling contributes but is not required for cytokinin to inhibit activity of the root meristem. These results identify key elements, along with points of cross talk with cytokinin and auxin, by which ethylene negatively regulates cell proliferation at the root apical meristem. PMID:26149574

  15. Quantitative analysis of neurological effects induced by cranio-caudal gamma-irradiation of rats

    International Nuclear Information System (INIS)

    Davydov, B.I.; Ushakov, I.B.; Karpov, V.N.

    1987-01-01

    A study was made of the frequency and duration of neurological disorders after cranio-caudal irradiation of rats with doses of 7.5-500 Gy delivered to the head. As the mean effective dose increased the neurological disorders occurred in the following order: tremor, rotatory movements hyperkinesia, opisthotonos, and convulsions. The europhysiological disorders observed were subjected to a pathophysiological analysis

  16. Development of bioengineering system for stem cell proliferation

    Science.gov (United States)

    Park, H. S.; Shah, R.; Shah, C.

    2016-08-01

    From last decades, intensive research in the field of stem cells proliferation had been promoted due to the unique property of stem cells to self-renew themselves into multiples and has potential to replicate into an organ or tissues and so it's highly demanding though challenging. Bioreactor, a mechanical device, works as a womb for stem cell proliferation by providing nutritious environment for the proper growth of stem cells. Various factors affecting stem cells growth are the bioreactor mechanism, feeding of continuous nutrients, healthy environment, etc., but it always remains a challenge for controlling biological parameters. The present paper unveils the design of mechanical device commonly known as bioreactor in tissues engineering and biotech field, use for proliferation of stem cells and imparts the proper growing condition for stem cells. This high functional bioreactor provides automation mixing of cell culture and stem cells. This design operates in conjunction with mechanism of reciprocating motion. Compare to commercial bioreactors, this proposed design is more convenient, easy to operate and less maintenance is required as bioreactor culture bag is made of polyethylene which is single use purpose. Development of this bioengineering system will be beneficial for better growth and expansion of stem cell

  17. Terbinafine: effects on platelet-derived growth factor-stimulated smooth muscle cells in vitro and myointimal proliferation in vivo

    International Nuclear Information System (INIS)

    McCarthy, L.; Van Halen, R.G.; St Denny, I.H.; Glinka, K.G.; Handley, D.A.; Stuetz, A.; Nemecek, G.M.

    1987-01-01

    Terbinafine (T; (E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic agent with antimitogenic activity in fibroblasts, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated aortic smooth muscle cell DNA synthesis in vitro and myointimal proliferation in vivo. Exposure of smooth muscle cells to 1-25 μM T resulted in a concentration-dependent inhibition of PDGF-induced mitogenesis as determined by [ 3 H]thymidine incorporation or cell number. The IC 50 for T was approximately 5 μM. The inhibitory effect of terbinafine persisted in the presence of 0.4-8.0 μg/ml cholesterol or 130 μg/ml mevalonate. Administration of T to rats for 2 d before and 14 d after balloon catheter carotid injury resulted in a 40% decrease in lesion area. These observations indicate that T is both a potent in vitro antagonist of the smooth muscle cell mitogenic response to PDGF and an effective, well-tolerated, orally active inhibitor of myointimal proliferation in vivo

  18. Terbinafine: effects on platelet-derived growth factor-stimulated smooth muscle cells in vitro and myointimal proliferation in vivo

    Energy Technology Data Exchange (ETDEWEB)

    McCarthy, L.; Van Halen, R.G.; St. Denny, I.H.; Glinka, K.G.; Handley, D.A.; Stuetz, A.; Nemecek, G.M.

    1987-05-01

    Terbinafine (T; (E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic agent with antimitogenic activity in fibroblasts, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated aortic smooth muscle cell DNA synthesis in vitro and myointimal proliferation in vivo. Exposure of smooth muscle cells to 1-25 ..mu..M T resulted in a concentration-dependent inhibition of PDGF-induced mitogenesis as determined by (/sup 3/H)thymidine incorporation or cell number. The IC/sub 50/ for T was approximately 5 ..mu..M. The inhibitory effect of terbinafine persisted in the presence of 0.4-8.0 ..mu..g/ml cholesterol or 130 ..mu..g/ml mevalonate. Administration of T to rats for 2 d before and 14 d after balloon catheter carotid injury resulted in a 40% decrease in lesion area. These observations indicate that T is both a potent in vitro antagonist of the smooth muscle cell mitogenic response to PDGF and an effective, well-tolerated, orally active inhibitor of myointimal proliferation in vivo.

  19. Carbon nanotubes functionalized with fibroblast growth factor accelerate proliferation of bone marrow-derived stromal cells and bone formation

    International Nuclear Information System (INIS)

    Hirata, Eri; Takita, Hiroko; Watari, Fumio; Yokoyama, Atsuro; Ménard-Moyon, Cécilia; Venturelli, Enrica; Bianco, Alberto

    2013-01-01

    Multi-walled carbon nanotubes (MWCNTs) were functionalized with fibroblast growth factor (FGF) and the advantages of their use as scaffolds for bone augmentation were evaluated in vitro and in vivo. The activity of FGF was assessed by measuring the effect on the proliferation of rat bone marrow stromal cells (RBMSCs). The presence of FGF enhanced the proliferation of RBMSCs and the FGF covalently conjugated to the nanotubes (FGF–CNT) showed the same effect as FGF alone. In addition, FGF–CNT coated sponges were implanted between the parietal bone and the periosteum of rats and the formation of new bone was investigated. At day 14 after implantation, a larger amount of newly formed bone was clearly observed in most pores of FGF–CNT coated sponges. These findings indicated that MWCNTs accelerated new bone formation in response to FGF, as well as the integration of particles into new bone during its formation. Scaffolds coated with FGF–CNT could be considered as promising novel substituting materials for bone regeneration in future tissue engineering applications. (paper)

  20. Carbon nanotubes functionalized with fibroblast growth factor accelerate proliferation of bone marrow-derived stromal cells and bone formation

    Science.gov (United States)

    Hirata, Eri; Ménard-Moyon, Cécilia; Venturelli, Enrica; Takita, Hiroko; Watari, Fumio; Bianco, Alberto; Yokoyama, Atsuro

    2013-11-01

    Multi-walled carbon nanotubes (MWCNTs) were functionalized with fibroblast growth factor (FGF) and the advantages of their use as scaffolds for bone augmentation were evaluated in vitro and in vivo. The activity of FGF was assessed by measuring the effect on the proliferation of rat bone marrow stromal cells (RBMSCs). The presence of FGF enhanced the proliferation of RBMSCs and the FGF covalently conjugated to the nanotubes (FGF-CNT) showed the same effect as FGF alone. In addition, FGF-CNT coated sponges were implanted between the parietal bone and the periosteum of rats and the formation of new bone was investigated. At day 14 after implantation, a larger amount of newly formed bone was clearly observed in most pores of FGF-CNT coated sponges. These findings indicated that MWCNTs accelerated new bone formation in response to FGF, as well as the integration of particles into new bone during its formation. Scaffolds coated with FGF-CNT could be considered as promising novel substituting materials for bone regeneration in future tissue engineering applications.

  1. Effects of gintonin on the proliferation, migration, and tube formation of human umbilical-vein endothelial cells: involvement of lysophosphatidic-acid receptors and vascular-endothelial-growth-factor signaling

    Directory of Open Access Journals (Sweden)

    Sung-Hee Hwang

    2016-10-01

    Conclusion: The gintonin-mediated proliferation, migration, and vascular-endothelial-growth-factor release in HUVECs via LPA-receptor activation may be one of in vitro mechanisms underlying ginseng-induced angiogenic and wound-healing effects.

  2. Breast fibroblasts modulate epithelial cell proliferation in three-dimensional in vitro co-culture

    International Nuclear Information System (INIS)

    Sadlonova, Andrea; Novak, Zdenek; Johnson, Martin R; Bowe, Damon B; Gault, Sandra R; Page, Grier P; Thottassery, Jaideep V; Welch, Danny R; Frost, Andra R

    2005-01-01

    Stromal fibroblasts associated with in situ and invasive breast carcinoma differ phenotypically from fibroblasts associated with normal breast epithelium, and these alterations in carcinoma-associated fibroblasts (CAF) may promote breast carcinogenesis and cancer progression. A better understanding of the changes that occur in fibroblasts during carcinogenesis and their influence on epithelial cell growth and behavior could lead to novel strategies for the prevention and treatment of breast cancer. To this end, the effect of CAF and normal breast-associated fibroblasts (NAF) on the growth of epithelial cells representative of pre-neoplastic breast disease was assessed. NAF and CAF were grown with the nontumorigenic MCF10A epithelial cells and their more transformed, tumorigenic derivative, MCF10AT cells, in direct three-dimensional co-cultures on basement membrane material. The proliferation and apoptosis of MCF10A cells and MCF10AT cells were assessed by 5-bromo-2'-deoxyuridine labeling and TUNEL assay, respectively. Additionally, NAF and CAF were compared for expression of insulin-like growth factor II as a potential mediator of their effects on epithelial cell growth, by ELISA and by quantitative, real-time PCR. In relatively low numbers, both NAF and CAF suppressed proliferation of MCF10A cells. However, only NAF and not CAF significantly inhibited proliferation of the more transformed MCF10AT cells. The degree of growth inhibition varied among NAF or CAF from different individuals. In greater numbers, NAF and CAF have less inhibitory effect on epithelial cell growth. The rate of epithelial cell apoptosis was not affected by NAF or CAF. Mean insulin-like growth factor II levels were not significantly different in NAF versus CAF and did not correlate with the fibroblast effect on epithelial cell proliferation. Both NAF and CAF have the ability to inhibit the growth of pre-cancerous breast epithelial cells. NAF have greater inhibitory capacity than CAF

  3. The Effects of Single-Dose Rectal Midazolam Application on Postoperative Recovery, Sedation, and Analgesia in Children Given Caudal Anesthesia Plus Bupivacaine

    Directory of Open Access Journals (Sweden)

    Sedat Saylan

    2014-01-01

    Full Text Available Background. This study aimed to compare the effects of rectal midazolam addition after applying bupivacaine and caudal anesthesia on postoperative analgesia time, the need for additional analgesics, postoperative recovery, and sedation and to find out its adverse effects in children having lower abdominal surgery. Methods. 40 children between 2 and 10 years of ASA I-II were randomized, and they received caudal anesthesia under general anesthesia. Patients underwent the application of caudal block in addition to saline and 1 mL/kg bupivacaine 0.25%. In the postoperative period, Group C (n = 20 was given 5 mL saline, and Group M (n = 20 was given 0.30 mg/kg rectal midazolam diluted with 5 mL saline. Sedation scale and postoperative pain scale (CHIPPS of the patients were evaluated. The patients were observed for their analgesic need, first analgesic time, and adverse effects for 24 hours. Results. Demographic and hemodynamic data of the two groups did not differ. Postoperative sedation scores in both groups were significantly lower compared with the preoperative period. There was no significant difference between the groups in terms of sedation and sufficient analgesia. Conclusions. We conclude that caudal anesthesia provided sufficient analgesia in peroperative and postoperative periods, and rectal midazolam addition did not create any differences. This trial is registered with ClinicalTrials.gov NCT02127489.

  4. Histological variations in myoepithelial cells and arrectores pilorum muscles among caudal, metatarsal and preorbital glands in Hokkaido sika deer (Cervus nippon yesoensis Heude, 1884).

    Science.gov (United States)

    Ozaki, Nobuo; Suzuki, Masatsugu; Ohtaishi, Noriyuki

    2004-03-01

    The morphological characteristics of myoepithelial cells and arrectores pilorum muscles were investigated in caudal, metatarsal and preorbital glands of Hokkaido sika deer (Cervus nippon yesoensis Heude, 1884) using immunohistochemistry for alpha-smooth muscle actin. In the metatarsal, preorbital and general skin glands, myoepithelial cell layers continuously embraced the secretory epithelium, while in the caudal gland, discontinuous myoepithelial cell rows surrounded the apocrine tubules. There was a trend that the widths of the myoepithelial cells of the caudal and preorbital glands appeared to be thinner than those of the metatarsal and general skin glands. In the metatarsal gland, the arrectores pilorum muscles were highly developed and considerably larger than those in other skin glands.

  5. Comparison of the therapeutic effect between a transforminal along with a caudal epidural injection, as well as two-level transforaminal epidural injections ina radiculopathy patient

    International Nuclear Information System (INIS)

    Hwang, Jung Han; Hwang, Cheol Mog; Cho, Young Jun; Kim, Keun Won; Kim, Young Joong; Seo, Jae Young; Lim, Seong Joo; Kang, Byeong Seong

    2017-01-01

    The aim of this study was to evaluate the therapeutic effect of a transforaminal epidural steroid injection (TFESI) along with a caudal epidural steroid injection (ESI), compared to two-level TFESIs in a multi-level radiculopathy patient. A total of 895 lumbar ESIs were performed in 492 patients with multi-level radiculopathy from January 2012 to January 2015. Before injections were performed, the initial Numeric Rating Scale (NRS) score was assessed in all patients, categorized into no pain (excellent), mild (good, NRS: 1-3), moderate (fair, NRS: 4-6), and severe pain (poor, NRS: 7-10). Therapeutic effects were examined for two groups: one-level TFESI along with caudal and ESI two-level TFESIs. Patient outcomes were assessed by NRS in a serial follow-up at one, three, and six months. One TFESI along with caudal ESI was performed in 274 patients and two TFESIs for 218. For the former group with one TFESI along with caudal ESI, excellent results were shown: 219 (79.9%) patients after one month, 200 (72.9%) after three, and 193 (70.4%) after six months. In the patient group with two TFESIs (n = 218) the outcomes were also very good: 152 (69.7%) after one month, 131 (60.0%) after three months, and 123 (56.4%) patients after six months. The therapeutic effect of one TFESI along with caudal ESI was better than two TFESIs in for one, threes, and six months (p < 0.01). Transforaminal epidural steroid with caudal epidural injection is a more effective tool for lumbosacral radiculopathy than two level transforaminal injections in multi-level radiculopathy patients

  6. Comparison of the therapeutic effect between a transforminal along with a caudal epidural injection, as well as two-level transforaminal epidural injections ina radiculopathy patient

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Jung Han; Hwang, Cheol Mog; Cho, Young Jun; Kim, Keun Won; Kim, Young Joong; Seo, Jae Young; Lim, Seong Joo [Dept. of Diagnostic Radiology, Konyang University Hospital, Deajeon (Korea, Republic of); Kang, Byeong Seong [Dept. of Radiology, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan (Korea, Republic of)

    2017-01-15

    The aim of this study was to evaluate the therapeutic effect of a transforaminal epidural steroid injection (TFESI) along with a caudal epidural steroid injection (ESI), compared to two-level TFESIs in a multi-level radiculopathy patient. A total of 895 lumbar ESIs were performed in 492 patients with multi-level radiculopathy from January 2012 to January 2015. Before injections were performed, the initial Numeric Rating Scale (NRS) score was assessed in all patients, categorized into no pain (excellent), mild (good, NRS: 1-3), moderate (fair, NRS: 4-6), and severe pain (poor, NRS: 7-10). Therapeutic effects were examined for two groups: one-level TFESI along with caudal and ESI two-level TFESIs. Patient outcomes were assessed by NRS in a serial follow-up at one, three, and six months. One TFESI along with caudal ESI was performed in 274 patients and two TFESIs for 218. For the former group with one TFESI along with caudal ESI, excellent results were shown: 219 (79.9%) patients after one month, 200 (72.9%) after three, and 193 (70.4%) after six months. In the patient group with two TFESIs (n = 218) the outcomes were also very good: 152 (69.7%) after one month, 131 (60.0%) after three months, and 123 (56.4%) patients after six months. The therapeutic effect of one TFESI along with caudal ESI was better than two TFESIs in for one, threes, and six months (p < 0.01). Transforaminal epidural steroid with caudal epidural injection is a more effective tool for lumbosacral radiculopathy than two level transforaminal injections in multi-level radiculopathy patients.

  7. Origens e distribuições das artérias mesentéricas cranial e caudal em fetos de javalis (Sus scrofa scrofa, Linnaeus – 1758

    Directory of Open Access Journals (Sweden)

    Andrea Regina Abrantes Gomes

    2013-01-01

    Full Text Available http://dx.doi.org/10.5007/2175-7925.2013v26n1p159 Estudou-se o comportamento anatômico das artérias mesentéricas cranial e caudal em 21 fetos de javalis, fêmeas e machos, nos quais foi injetada, através da aorta torácica, solução de Neoprene Látex “450”, corada com pigmento específico e, em seguida, eles foram fixados em solução de formol a 10%. A análise dos resultados permitiu afirmar que a artéria mesentérica cranial originou-se da aorta abdominal, caudalmente à artéria celíaca, emitiu ramos adrenais direito e esquerdo, pancreáticos, e as artérias pancreático-duodenal caudal, jejunais, cólicas média e direita, e ileocecocólica. A artéria mesentérica caudal surgiu da aorta abdominal, de seu terço caudal, e emitiu as artérias cólica esquerda e retal cranial. Foram verificadas anastomoses entre artérias jejunais, cólica esquerda e retal cranial, e cólicas esquerda e média. Nas três espécies, as artérias mesentéricas cranial e caudal, pancreático-duodenal caudal, jejunais, cólicas direita e média, e ileocecocólica apresentaram padrões vasculares semelhantes, visto que as diferenças quanto a emissão de ramos ou surgimento isolado ou em tronco comum não alteraram o suprimento sanguíneo.

  8. Segmental distribution of high-volume caudal anesthesia in neonates, infants, and toddlers as assessed by ultrasonography.

    Science.gov (United States)

    Lundblad, Märit; Lönnqvist, Per-Arne; Eksborg, Staffan; Marhofer, Peter

    2011-02-01

    The aim of this prospective, age-stratified, observational study was to determine the cranial extent of spread of a large volume (1.5 ml·kg(-1) , ropivacaine 0.2%), single-shot caudal epidural injection using real-time ultrasonography. Fifty ASA I-III children were included in the study, stratified in three age groups; neonates, infants (1-12 months), and toddlers (1-4 years). The caudal blocks were performed during ultrasonographic observation of the spread of local anesthetic (LA) in the epidural space. A significant inverse relationship was found between age, weight, and height, and the maximal cranial level reached by 1.5 ml·kg(-1) of LA. In neonates, 93% of the blocks reached a cranial level of ≥Th12 vs 73% and 25% in infants and toddlers, respectively. Based on our data, a predictive equation of segmental spread was generated: Dose (ml/spinal segment) = 0.1539·(BW in kg)-0.0937. This study found an inverse relationship between age, weight, and height and the number of segments covered by a caudal injection of 1.5 ml·kg(-1) of ropivacaine 0.2% in children 0-4 years of age. However, the cranial spread of local anesthetics within the spinal canal as assessed by immediate ultrasound visualization was found to be in poor agreement with previously published predictive equations that are based on actual cutaneous dermatomal testing. © 2010 Blackwell Publishing Ltd.

  9. Systematization, description and territory of the caudal cerebral artery of the brain in broad-snouted Caiman (Caiman latirostris

    Directory of Open Access Journals (Sweden)

    Lygia Almeida

    2011-09-01

    Full Text Available Thirty heads with the neck segment of Caiman latirostris were used. The animals were provided from a creation center called Mister Caiman, under the authorization of the Brazilian Institute of Environment and Renewable Natural Resources (Ibama. Animals were sacrificed according to the slaughtering routine of the abattoir, and the heads were sectioned at the level of the third cervical vertebra. The arterial system was washed with cold saline solution, with drainage through jugular veins. Subsequently, the system was filled with red colored latex injection. Pieces were than fixed in 20% formaldehyde, for seven days. The brains were removed, with a spinal cord segment, the duramater removed and the arteries dissected. At the level of the hypophysis, the internal carotid artery gave off a rostral branch, and a short caudal branch, continuing, naturally, as the caudal cerebral artery. This artery projected laterodorsalwards and, as it overpassed the optic tract, gave off its I (the first central branch. Penetrated in the cerebral transverse fissure, emitting the diencephalic artery and next its II (second central branch. Still inside the fissure, originated occipital hemispheric branches and a pineal branch. Emerged from the cerebral transverse fissure, over the occipital pole of the cerebral hemisphere. Projected rostralwards, sagital to the cerebral longitudinal fissure, as interhemispheric artery. This artery gave off medial and convex hemispheric branches to the respective surfaces of the cerebral hemispheres, anastomosed with its contralateral homologous, forming the common ethmoidal artery. This artery entered the fissure between the olfactory peduncles, emerging ventrally and dividing into ethmoidal arteries, right and left, which progressed towards the nasal cavities, vascularizing them. The territory of the caudal cerebral artery included the most caudal area of the base of the cerebral hemisphere, its convex surface, the olfactory

  10. Effect of magnesium added to local anesthetics for caudal anesthesia on postoperative pain in pediatric surgical patients: A systematic review and meta-analysis with Trial Sequential Analysis.

    Science.gov (United States)

    Kawakami, Hiromasa; Mihara, Takahiro; Nakamura, Nobuhito; Ka, Koui; Goto, Takahisa

    2018-01-01

    Magnesium has been investigated as an adjuvant for neuraxial anesthesia, but the effect of caudal magnesium on postoperative pain is inconsistent. The aim of this systematic review and meta-analysis was to evaluate the analgesic effect of caudal magnesium. We searched six databases, including trial registration sites. Randomized clinical trials reporting the effect of caudal magnesium on postoperative pain after general anesthesia were eligible. The risk ratio for use of rescue analgesics after surgery was combined using a random-effects model. We also assessed adverse events. The I2 statistic was used to assess heterogeneity. We assessed risk of bias with Cochrane domains. We controlled type I and II errors due to sparse data and repetitive testing with Trial Sequential Analysis. We assessed the quality of evidence with GRADE. Four randomized controlled trials (247 patients) evaluated the need for rescue analgesics. In all four trials, 50 mg of magnesium was administered with caudal ropivacaine. The results suggested that the need for rescue analgesia was reduced significantly by caudal magnesium administration (risk ratio 0.45; 95% confidence interval 0.24-0.86). There was considerable heterogeneity as indicated by an I2 value of 62.5%. The Trial Sequential Analysis-adjusted confidence interval was 0.04-5.55, indicating that further trials are required. The quality of evidence was very low. The rate of adverse events was comparable between treatment groups. Caudal magnesium may reduce the need for rescue analgesia after surgery, but further randomized clinical trials with a low risk of bias and a low risk of random errors are necessary to assess the effect of caudal magnesium on postoperative pain and adverse events. University Hospital Medical Information Network Clinical Trials Registry UMIN000025344.

  11. A randomized double-blinded comparison between dexmedetomidine and clonidine as an adjuvant to caudal ropivacaine in children for below umbilical surgery

    Directory of Open Access Journals (Sweden)

    Ganapathi Mavuri

    2017-01-01

    Full Text Available Background: Alpha-2 adenoreceptors as an adjuvant to local anesthetic during caudal analgesia in children prolongs the duration of analgesia. This study was designed to compare the analgesic efficacy and adverse effects of dexmedetomidine and clonidine when added to ropivacaine for caudal analgesia in children undergoing lower abdominal surgeries. Methods: In a prospective study, Seventy-eight children received block with either 0.2% ropivacaine 1.5 mg/kg (Group R; n = 26 or 0.2% ropivacaine 1.5 mg/kg + 1 mcg/kg clonidine (Group RC; n = 26 or 0.2% ropivacaine 1.5 mg/kg + dexmedetomidine 1 mcg/kg (Group RD; n = 26. Results: Duration of analgesia was 7.15 ± 1.00 h in Group R, 11.57 ± 1.27 h in Group R + C, and 14.73 ± 1.53 h in Group R + D (P 0.05. Conclusion: Addition of clonidine and dexmedetomidine to caudal ropivacaine significantly prolongs the duration of analgesia without adverse effects.

  12. Transforming growth factor alpha (TGFα regulates granulosa cell tumor (GCT cell proliferation and migration through activation of multiple pathways.

    Directory of Open Access Journals (Sweden)

    Cheng Wang

    Full Text Available Granulosa cell tumors (GCTs are the most common ovarian estrogen producing tumors, leading to symptoms of excessive estrogen such as endometrial hyperplasia and endometrial adenocarcinoma. These tumors have malignant potential and often recur. The etiology of GCT is unknown. TGFα is a potent mitogen for many different cells. However, its function in GCT initiation, progression and metastasis has not been determined. The present study aims to determine whether TGFα plays a role in the growth of GCT cells. KGN cells, which are derived from an invasive GCT and have many features of normal granulosa cells, were used as the cellular model. Immunohistochemistry, Western blot and RT-PCR results showed that the ErbB family of receptors is expressed in human GCT tissues and GCT cell lines. RT-PCR results also indicated that TGFα and EGF are expressed in the human granulosa cells and the GCT cell lines, suggesting that TGFα might regulate GCT cell function in an autocrine/paracrine manner. TGFα stimulated KGN cell DNA synthesis, cell proliferation, cell viability, cell cycle progression, and cell migration. TGFα rapidly activated EGFR/PI3K/Akt and mTOR pathways, as indicated by rapid phosphorylation of Akt, TSC2, Rictor, mTOR, P70S6K and S6 proteins following TGFα treatment. TGFα also rapidly activated the EGFR/MEK/ERK pathway, and P38 MAPK pathways, as indicated by the rapid phosphorylation of EGFR, MEK, ERK1/2, P38, and CREB after TGFα treatment. Whereas TGFα triggered a transient activation of Akt, it induced a sustained activation of ERK1/2 in KGN cells. Long-term treatment of KGN cells with TGFα resulted in a significant increase in cyclin D2 and a decrease in p27/Kip1, two critical regulators of granulosa cell proliferation and granulosa cell tumorigenesis. In conclusion, TGFα, via multiple signaling pathways, regulates KGN cell proliferation and migration and may play an important role in the growth and metastasis of GCTs.

  13. Unique caudal plumage of Jeholornis and complex tail evolution in early birds

    OpenAIRE

    O’Connor, Jingmai; Wang, Xiaoli; Sullivan, Corwin; Zheng, Xiaoting; Tubaro, Pablo; Zhang, Xiaomei; Zhou, Zhonghe

    2013-01-01

    The Early Cretaceous bird Jeholornis was previously only known to have a distally restricted ornamental frond of tail feathers. We describe a previously unrecognized fan-shaped tract of feathers situated dorsal to the proximal caudal vertebrae. The position and morphology of these feathers is reminiscent of the specialized upper tail coverts observed in males of some sexually dimorphic neornithines. As in the neornithine tail, the unique “two-tail” plumage in Jeholornis probably evolved as th...

  14. GATA-3 is involved in the development of serotonergic neurons in the caudal raphe nuclei

    NARCIS (Netherlands)

    J. van der Wees (Jacqueline); A. Karis (Alar); E. Goedknegt; M. Rutteman; F.G. Grosveld (Frank); J.H. van Doorninck (Hikke); C.I. de Zeeuw (Chris)

    1999-01-01

    textabstractAbstract The GATA-3 transcription factor shows a specific and restricted expression pattern in the developing and adult mouse brain. In the present study we investigated the role of GATA-3 in the caudal raphe system, which is known to operate as a modulator of motor activity. We

  15. Multivalent conjugates of basic fibroblast growth factor enhance in vitro proliferation and migration of endothelial cells.

    Science.gov (United States)

    Zbinden, Aline; Browne, Shane; Altiok, Eda I; Svedlund, Felicia L; Jackson, Wesley M; Healy, Kevin E

    2018-05-01

    Growth factors hold great promise for regenerative therapies. However, their clinical use has been halted by poor efficacy and rapid clearance from tissue, necessitating the delivery of extremely high doses to achieve clinical effectiveness which has raised safety concerns. Thus, strategies to either enhance growth factor activity at low doses or to increase their residence time within target tissues are necessary for clinical success. In this study, we generated multivalent conjugates (MVCs) of basic fibroblast growth factor (bFGF), a key growth factor involved in angiogenesis and wound healing, to hyaluronic acid (HyA) polymer chains. Multivalent bFGF conjugates (mvbFGF) were fabricated with minimal non-specific interaction observed between bFGF and the HyA chain. The hydrodynamic radii of mvbFGF ranged from ∼50 to ∼75 nm for conjugation ratios of bFGF to HyA chains at low (10 : 1) and high (30 : 1) feed ratios, respectively. The mvbFGF demonstrated enhanced bioactivity compared to unconjugated bFGF in assays of cell proliferation and migration, processes critical to angiogenesis and tissue regeneration. The 30 : 1 mvbFGF outperformed the 10 : 1 conjugate, which could be due to either FGF receptor clustering or interference with receptor mediated internalization and signal deactivation. This study simultaneously investigated the role of both protein to polymer ratio and multivalent conjugate size on their bioactivity, and determined that increasing the protein-to-polymer ratio and conjugate size resulted in greater cell bioactivity.

  16. CHIP promotes thyroid cancer proliferation via activation of the MAPK and AKT pathways

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Li [Department of Pharmacy, Urumchi General Hospital of Lanzhou Military Region, Urumchi, Xinjiang 830000 (China); Liu, Lianyong [Medical College of Soochow University, Suzhou, Jiangsu 215123 (China); Department of Endocrinology, Shanghai Punan Hospital, Shanghai 200125 (China); He, Xiaohua; Shen, Yunling; Liu, Xuerong; Wei, Jing; Yu, Fang [Department of Endocrinology, Urumchi General Hospital of Lanzhou Military Region, Urumchi, Xinjiang 830000 (China); Tian, Jianqing, E-mail: jianqing0991@163.com [Department of Endocrinology, Urumchi General Hospital of Lanzhou Military Region, Urumchi, Xinjiang 830000 (China)

    2016-08-26

    The carboxyl terminus of Hsp70-interacting protein (CHIP) is a U box-type ubiquitin ligase that plays crucial roles in various biological processes, including tumor progression. To date, the functional mechanism of CHIP in thyroid cancer remains unknown. Here, we obtained evidence of upregulation of CHIP in thyroid cancer tissues and cell lines. CHIP overexpression markedly enhanced thyroid cancer cell viability and colony formation in vitro and accelerated tumor growth in vivo. Conversely, CHIP knockdown impaired cell proliferation and tumor growth. Notably, CHIP promoted cell growth through activation of MAPK and AKT pathways, subsequently decreasing p27 and increasing cyclin D1 and p-FOXO3a expression. Our findings collectively indicate that CHIP functions as an oncogene in thyroid cancer, and is therefore a potential therapeutic target for this disease. - Highlights: • CHIP is significantly upregulated in thyroid cancer cells. • Overexpression of CHIP facilitates proliferation and tumorigenesis of thyroid cancer cells. • Silencing of CHIP inhibits the proliferation and tumorigenesis of thyroid cancer cells. • CHIP promotes thyroid cancer cell proliferation via activating the MAPK and AKT pathways.

  17. Involvement of H- and N-Ras isoforms in transforming growth factor-β1-induced proliferation and in collagen and fibronectin synthesis

    International Nuclear Information System (INIS)

    Martinez-Salgado, Carlos; Fuentes-Calvo, Isabel; Garcia-Cenador, Begona; Santos, Eugenio; Lopez-Novoa, Jose M.

    2006-01-01

    Transforming growth factor β1 (TGF-β1) has a relevant role in the origin and maintenance of glomerulosclerosis and tubule-interstitial fibrosis. TGF-β and Ras signaling pathways are closely related: TGF-β1 overcomes Ras mitogenic effects and Ras counteracts TGF-β signaling. Tubule-interstitial fibrosis is associated to increases in Ras, Erk, and Akt activation in a renal fibrosis model. We study the role of N- and H-Ras isoforms, and the involvement of the Ras effectors Erk and Akt, in TGF-β1-mediated extracellular matrix (ECM) synthesis and proliferation, using embrionary fibroblasts from double knockout (KO) mice for H- and N-Ras (H-ras -/- /N-ras -/- ) isoforms and from heterozygote mice (H-ras +/- /N-ras +/- ). ECM synthesis is increased in basal conditions in H-ras -/- /N-ras -/- fibroblasts, this increase being higher after stimulation with TGF-β1. TGF-β1-induced fibroblast proliferation is smaller in H-ras -/- /N-ras -/- than in H-ras +/- /N-ras +/- fibroblasts. Erk activation is decreased in H-ras -/- /N-ras -/- fibroblasts; inhibition of Erk activation reduces fibroblast proliferation. Akt activation is higher in double KO fibroblasts than in heterozygotes; inhibition of Akt activation also inhibits ECM synthesis. We suggest that H- and N-Ras isoforms downregulate ECM synthesis, and mediate proliferation, in part through MEK/Erk activation. PI3K-Akt pathway activation may be involved in the increase in ECM synthesis observed in the absence of H- and N-Ras

  18. Homocysteine inhibits hepatocyte proliferation via endoplasmic reticulum stress.

    Directory of Open Access Journals (Sweden)

    Xue Yu

    Full Text Available Homocysteine is an independent risk factor for coronary, cerebral, and peripheral vascular diseases. Recent studies have shown that levels of homocysteine are elevated in patients with impaired hepatic function, but the precise role of homocysteine in the development of hepatic dysfunction is unclear. In this study, we examined the effect of homocysteine on hepatocyte proliferation in vitro. Our results demonstrated that homocysteine inhibited hepatocyte proliferation by up-regulating protein levels of p53 as well as mRNA and protein levels of p21(Cip1 in primary cultured hepatocytes. Homocysteine induced cell growth arrest in p53-positive hepatocarcinoma cell line HepG2, but not in p53-null hepatocarcinoma cell line Hep3B. A p53 inhibitor pifithrin-α inhibited the expression of p21(Cip1 and attenuated homocysteine-induced cell growth arrest. Homocysteine induced TRB3 expression via endoplasmic reticulum stress pathway, resulting in Akt dephosphorylation. Knock-down of endogenous TRB3 significantly suppressed the inhibitory effect of homocysteine on cell proliferation and the phosphorylation of Akt. LiCl reversed homocysteine-mediated cell growth arrest by inhibiting TRB3-mediated Akt dephosphorylation. These results demonstrate that both TRB3 and p21(Cip1 are critical molecules in the homocysteine signaling cascade and provide a mechanistic explanation for impairment of liver regeneration in hyperhomocysteinemia.

  19. CDX2 Stimulates the Proliferation of Porcine Intestinal Epithelial Cells by Activating the mTORC1 and Wnt/β-Catenin Signaling Pathways.

    Science.gov (United States)

    Fan, Hong-Bo; Zhai, Zhen-Ya; Li, Xiang-Guang; Gao, Chun-Qi; Yan, Hui-Chao; Chen, Zhe-Sheng; Wang, Xiu-Qi

    2017-11-18

    Caudal type homeobox 2 (CDX2) is expressed in intestinal epithelial cells and plays a role in gut development and homeostasis by regulating cell proliferation. However, whether CDX2 cooperates with the mammalian target of rapamycin complex 1 (mTORC1) and Wnt/β-catenin signaling pathways to stimulate cell proliferation remains unknown. The objective of this study was to investigate the effect of CDX2 on the proliferation of porcine jejunum epithelial cells (IPEC-J2) and the correlation between CDX2, the mTORC1 and Wnt/β-catenin signaling pathways. CDX2 overexpression and knockdown cell culture models were established to explore the regulation of CDX2 on both pathways. Pathway-specific antagonists were used to verify the effects. The results showed that CDX2 overexpression increased IPEC-J2 cell proliferation and activated both the mTORC1 and Wnt/β-catenin pathways, and that CDX2 knockdown decreased cell proliferation and inhibited both pathways. Furthermore, the mTORC1 and Wnt/β-catenin pathway-specific antagonist rapamycin and XAV939 (3,5,7,8-tetrahydro-2-[4-(trifluoromethyl)]-4H -thiopyrano[4,3-d]pyrimidin-4-one) both suppressed the proliferation of IPEC-J2 cells overexpressing CDX2, and that the combination of rapamycin and XAV939 had an additive effect. Regardless of whether the cells were treated with rapamycin or XAV939 alone or in combination, both mTORC1 and Wnt/β-catenin pathways were down-regulated, accompanied by a decrease in CDX2 expression. Taken together, our data indicate that CDX2 stimulates porcine intestinal epithelial cell proliferation by activating the mTORC1 and Wnt/β-catenin signaling pathways.

  20. Olive phenolics as c-Met inhibitors: (--Oleocanthal attenuates cell proliferation, invasiveness, and tumor growth in breast cancer models.

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    Mohamed R Akl

    Full Text Available Dysregulation of the Hepatocyte growth factor (HGF/c-Met signaling axis upregulates diverse tumor cell functions, including cell proliferation, survival, scattering and motility, epithelial-to-mesenchymal transition (EMT, angiogenesis, invasion, and metastasis. (--Oleocanthal is a naturally occurring secoiridoid from extra-virgin olive oil, which showed antiproliferative and antimigratory activity against different cancer cell lines. The aim of this study was to characterize the intracellular mechanisms involved in mediating the anticancer effects of (--oleocanthal treatment and the potential involvement of c-Met receptor signaling components in breast cancer. Results showed that (--oleocanthal inhibits the growth of human breast cancer cell lines MDA-MB-231, MCF-7 and BT-474 while similar treatment doses were found to have no effect on normal human MCF10A cell growth. In addition, (--oleocanthal treatment caused a dose-dependent inhibition of HGF-induced cell migration, invasion and G1/S cell cycle progression in breast cancer cell lines. Moreover, (--oleocanthal treatment effects were found to be mediated via inhibition of HGF-induced c-Met activation and its downstream mitogenic signaling pathways. This growth inhibitory effect is associated with blockade of EMT and reduction in cellular motility. Further results from in vivo studies showed that (--oleocanthal treatment suppressed tumor cell growth in an orthotopic model of breast cancer in athymic nude mice. Collectively, the findings of this study suggest that (--oleocanthal is a promising dietary supplement lead with potential for therapeutic use to control malignancies with aberrant c-Met activity.

  1. Leptin Regulates Proliferation and Apoptosis in Human Prostate

    Directory of Open Access Journals (Sweden)

    Eduardo Leze

    2012-01-01

    Full Text Available This paper aimed to evaluate the leptin role on the cellular proliferation and the expression of fibroblast growth factor 2, aromatase enzyme, and apoptotic genes in the human prostate tissue. Methods. Fifteen samples of hyperplasic prostate tissue were divided in four symmetric parts maintained in RPMI medium supplemented with 10% fetal bovine serum, 1 ng/mL of gentamicin, and added with 50 ng/mL leptin (L or not (C. After 3 hours of incubation, gene expression was evaluated by real time RT-PCR. Cellular proliferation was evaluated by immunohistochemistry for PCNA. Results. The leptin treatment led to an increase cellular proliferation (C=21.8±0.5; L=64.8±0.9; P<0.0001 and in the expression of Bax (C=0.4±0.1; L=0.9±0.2; P<0.05 while Bcl-2 (C=19.9±5.6; L=5.6±1.8; P<0.05, Bcl-x (C=0.2±0.06; L=0.07±0.02; P<0.05, and aromatase expressions (C=1.9±0.6; L=0.4±0.1; P<0.04 were significantly reduced. Conclusion. Leptin has an important role in maintaining the physiological growth of the prostate since it stimulates both cellular proliferation and apoptosis, with the decrement in the aromatase gene expression.

  2. Role of early growth response 1 in arteriogenesis: impact on vascular cell proliferation and leukocyte recruitment in vivo.

    Science.gov (United States)

    Pagel, Judith-Irina; Ziegelhoeffer, Tibor; Heil, Matthias; Fischer, Silvia; Fernández, Borja; Schaper, Wolfgang; Preissner, Klaus T; Deindl, Elisabeth

    2012-03-01

    Based on previous findings that early growth response 1 (Egr-1) participates in leukocyte recruitment and cell proliferation in vitro, this study was designed to investigate its mode of action during arteriogenesis in vivo. In a model of peripheral arteriogenesis, Egr-1 was significantly upregulated in growing collaterals of wild-type (WT) mice, both on mRNA and protein level. Egr-1(-/-) mice demonstrated delayed arteriogenesis after femoral artery ligation. They further showed increased levels of monocytes and granulocytes in the circulation, but reduced levels in adductor muscles under baseline conditions. After femoral artery ligation, elevated numbers of macrophages were detected in the perivascular zone of collaterals in Egr-1(-/-) mice and mRNA of leukocyte recruitment mediators was upregulated. Other Egr family members (Egr-2 to -4) were significantly upregulated only in Egr-1(-/-) mice, suggesting a mechanism of counterbalancing Egr-1 deficiency. Moreover, splicing factor-1, downregulated in WT mice after femoral artery ligation in the process of increased vascular cell proliferation, was upregulated in Egr-1(-/-) mice. αSM-actin on the other hand, significantly downregulated in WT mice, showed no differential expression in Egr-1(-/-) mice. While cell cycle regulator cyclin E and cdc20 were upregulated in Egr-1(-/-) mice, cyclin D1 expression decreased below the detection limit in collaterals, and the proliferation marker ki67 was not differentially expressed. In conclusion, compensation for deficiency in Egr-1 function in leukocyte recruitment can presumably be mediated by other transcription factors; however, Egr-1 is indispensable for effective vascular cell cycle progression in arteriogenesis.

  3. Cystatin C deficiency suppresses tumor growth in a breast cancer model through decreased proliferation of tumor cells.

    Science.gov (United States)

    Završnik, Janja; Butinar, Miha; Prebanda, Mojca Trstenjak; Krajnc, Aleksander; Vidmar, Robert; Fonović, Marko; Grubb, Anders; Turk, Vito; Turk, Boris; Vasiljeva, Olga

    2017-09-26

    Cysteine cathepsins are proteases that, in addition to their important physiological functions, have been associated with multiple pathologies, including cancer. Cystatin C (CstC) is a major endogenous inhibitor that regulates the extracellular activity of cysteine cathepsins. We investigated the role of cystatin C in mammary cancer using CstC knockout mice and a mouse model of breast cancer induced by expression of the polyoma middle T oncoprotein (PyMT) in the mammary epithelium. We showed that the ablation of CstC reduced the rate of mammary tumor growth. Notably, a decrease in the proliferation of CstC knockout PyMT tumor cells was demonstrated ex vivo and in vitro , indicating a role for this protease inhibitor in signaling pathways that control cell proliferation. An increase in phosphorylated p-38 was observed in CstC knockout tumors, suggesting a novel function for cystatin C in cancer development, independent of the TGF-β pathway. Moreover, proteomic analysis of the CstC wild-type and knockout PyMT primary cell secretomes revealed a decrease in the levels of 14-3-3 proteins in the secretome of knock-out cells, suggesting a novel link between cysteine cathepsins, cystatin C and 14-3-3 proteins in tumorigenesis, calling for further investigations.

  4. MiR-34a inhibits colon cancer proliferation and metastasis by inhibiting platelet-derived growth factor receptor α.

    Science.gov (United States)

    Li, Chunyan; Wang, Yulin; Lu, Shuming; Zhang, Zhuqing; Meng, Hua; Liang, Lina; Zhang, Yan; Song, Bo

    2015-11-01

    The microRNA (miRNA), miR‑34a is significant in colon cancer progression. In the present study, the role of miR‑34a in colon cancer cell proliferation and metastasis was investigated. It was found that the expression of miR‑34a in colon cancer tissues and cell lines was lower when compared with that of normal tissues and cells. Further research demonstrated that miR‑34a inhibited cell proliferation, induced G1 phase arrest, and suppressed metastasis and epithelial mesenchymal transition in colon cancer cells. Bioinformatic prediction indicated that platelet‑derived growth factor receptor α (PDGFRA) was a potential target gene of miR‑34a and a luciferase assay identified that PDGFRA was a novel direct target gene of miR‑34a. In addition, assays of western blot analyses and quantitative reverse‑transcription polymerase chain reaction confirmed that miR‑34a decreased PDGFRA mRNA expression and protein levels in colon cancer cells. Assessment of cellular function indicated that miR‑34a inhibited colon cancer progression via PDGFRA. These findings demonstrate that miR‑34a may act as a negative regulator in colon cancer by targeting PDGFRA.

  5. Proliferation Potential of 18-Month-Old Callus of Ananas comosus L. cv. Moris

    Directory of Open Access Journals (Sweden)

    A.E. De Silva

    2006-01-01

    Full Text Available Differential effect of plant growth regulators and additives in proliferation of 18-month-old calli of Ananas comosus L. cv. Moris were assessed in vitro. The proliferation of callus relied on the growth regulators and additives. Of the different auxins supplemented in the Murashige and Skoog (MS media, 32.22 μM α-naphthaleneacetic acid (NAA gave the highest mean fresh weight of callus (46.817 g. Medium supplemented with 2,4-dichlorophenoxyacetic acid (2,4-D was inferior to NAA, while b-naphthoxy acetic acid (BNOA and p-chlorophenoxy acetic acid (4-CPA were not effective in proliferating 18-months old callus. Addition of casein hydrolysate and coconut water to NAA supplemented medium showed better proliferation and production of callus. However, in terms of callus production, NAA at 32.22 μM was economically better.

  6. Norepinephrine accumulation by the rat caudal artery in the presence of hypertensive plasma

    International Nuclear Information System (INIS)

    Freas, W.; Thompson, D.A.; Hart, J.L.; Muldoon, S.M.

    1986-01-01

    We have partially isolated endogenous factors from canine plasma which inhibit 3 H-norepinephrine (NE) accumulation by the canine saphenous vein. The purpose of this study is to determine if these circulating factors may account for the observed differences in 3 H-NE uptake by hypertensive and normotensive blood vessels. Three models of hypertension were examined in this study. Blood vessels were compared from SHR and WKY rats, deoxycorticosterone acetate (DOCA) and control rats, and reduced renal mass (RRM) and control rats. There was no significant difference in 3 H-NE accumulation between blood vessels obtained from RRM and paired control rats. However, both the SHR and DOCA hypertensive caudal arteries and aorta accumulated significantly more 3 H-NE than their corresponding control tissues. There was not a significant change in 3 H-NE accumulation between hypertensive and control vena cava and mesenteric arteries. Normotensive and hypertensive plasma inhibited 3 H-NE accumulation by the rat caudal artery. However, there was not a correlation between blood pressure of plasma donor rats and accumulation of 3 H-NE. Therefore, although there are differences in 3 H-NE accumulation between hypertensive and normotensive blood vessels, plasma does not contain a factor responsible for this observed difference

  7. Vitreous humor and albumin augment the proliferation of cultured retinal precursor cells

    DEFF Research Database (Denmark)

    Yang, Jing; Klassen, Henry; Pries, Mette

    2008-01-01

    concentrations of vitreous fluid supplementation was quantified by using a (3)H-thymidine incorporation assay. Active components of vitreous fluid were partially characterized by gel filtration chromatography (GFC) and UV spectral analysis. The effect of each vitreous fraction on proliferation was determined...... Da, consistent with ascorbic acid. Ascorbic acid was confirmed in vitreous fluid by UV spectral analysis. Growth-augmenting activity was present in higher molecular mass vitreous fractions, consistent with protein components. Albumin, the major protein in vitreous fluid, was found to augment...... proliferation. Because vitreous-associated augmentation of retinal precursor proliferation remains an epidermal growth factor-dependent phenomenon, the proliferative status of transplanted cells in the vitreous cavity is likely determined by a combination of factors. (c) 2008 Wiley-Liss, Inc....

  8. The insulin-like growth factors I and II stimulate proliferation of different types of Schwann cells

    DEFF Research Database (Denmark)

    Sondell, M; Svenningsen, Åsa Fex; Kanje, M

    1997-01-01

    in combination with BrdU immunocytochemistry showed that around 93% of the proliferating cells in the nerve segments were Schwann cells. Immunostaining for BrdU and GFAP (glial fibrillary acid protein) showed that IGF-II enhanced proliferation of Schwann cells surrounding unmyelinated nerve fibres. In contrast......, truncated IGF-I promoted proliferation of Schwann cells of myelinated nerve fibres while insulin increased proliferation of both cell types....

  9. Caudal dysplasia syndrome and sirenomelia: are they part of a spectrum?

    Science.gov (United States)

    Bruce, Jocelyn H; Romaguera, Rita L; Rodriguez, Maria M; González-Quintero, Víctor H; Azouz, E Michel

    2009-01-01

    Caudal dysplasia syndrome (CDS) is associated with hypoplastic lower extremities, caudal vertebrae, sacrum, neural tube, and urogenital organs. Sirenomelia is characterized by a single lower extremity, absent sacrum, urogenital anomalies, and imperforate anus. There is controversy in the medical literature about whether sirenomelia and CDS are part of the spectrum of the same malformation. Patients with CDS and sirenomelia were identified from our pathology files from 1991 to 2006. Maternal history, pathologic examination, and radiographs were collected and tabulated. We found 9 cases with CDS and 6 with sirenomelia. Fully 7 of 9 patients with CDS (77.7%) versus none of sirenomelic babies were infants of diabetic mothers. Congenital heart disease was present in 5 patients with CDS (55.5%) and none of the infants with sirenomelia. Of 9 children with CDS 2 (22.2%) had bilateral renal agenesis versus 66% of sirenomelics. Single umbilical artery was found in 33% of cases with CDS and 100% of children with sirenomelia. External genitalia were ambiguous in 2 of 9 patients (22.2%) with CDS and in all patients with sirenomelia. Imperforate anus was found in 10 cases (66.6%) divided as 4 of 9 babies with CDS (44.4%) and all patients with sirenomelia. Three patients with CDS had concomitant maternal diabetes mellitus and chronic hypertension. These babies also had cleft lip and palate. Congenital heart disease was found in 55.5% of cases with CDS and none of the children with sirenomelia. We conclude that although CDS and sirenomelia share many similar features, they are two different entities.

  10. Interaction of osteoblast-like cells with serum and fibronectin: effects on cell motility and proliferation in vitro

    International Nuclear Information System (INIS)

    Zuk, A.

    1986-01-01

    Osteoblast migration and proliferation are believed to occur during bone remodelling, in particular after osteoclastic bone resorption and prior to osteoblastic bone formation. In order to study migration and proliferation in vitro, the model of Alessandri et al. (1983) was modified. The model entailed seeding osteoblast-like cells into wells cut in agar and quantifying migration and proliferation peripheral to the well. Cell morphology also was described. The data indicated that on growth surfaces enriched with varying concentrations of fetal calf serum (FSC), the quantification of migration and proliferation was related both to percent cell attachment and to FCS-concentration. Because few osteoblast-like cells incorporated ( 3 H-TdR), it was concluded that the appearance of cells peripheral to the well was due to migration, and not to proliferation. Cell morphology and myosin distribution and organization indicated that osteoblast-like cells at the periphery of the cell culture (i.e. leading edge) may have been directionally migrating whereas cells behind the leading edge may have been engaged in non-directional migration. The migration, proliferation, and morphology of osteoblast-like cells cultured on fibronectin (FN) enriched growth surfaces also was examined. The quantification of migration and proliferation was related to the FN-concentration applied to the growth surface. Because few osteoblast-like cells incorporated 3 H-TdR and cell morphology indicated migration, it was concluded that osteoblast-like cells on FN-enriched growth surfaces are specialized, in part, for migration

  11. Ultrasound guided TAP block versus ultrasound guided caudal block for pain relief in children undergoing lower abdominal surgeries

    Directory of Open Access Journals (Sweden)

    Wafaa Mohamed Alsadek

    2015-04-01

    Conclusion: TAP block and caudal block under ultrasound guidance proved to be safe with no recorded complications either intra or postoperatively. Patient and parent satisfaction was markedly observed in case of TAP block.

  12. Transforming growth factor β-activated kinase 1 inhibitor suppresses the proliferation in triple-negative breast cancer through TGF-β/TGFR pathway.

    Science.gov (United States)

    Zhang, Liangyu; Fu, Zelong; Li, Xia; Tang, Haitao; Luo, Jiesi; Zhang, Dehui; Zhuang, Yongzhi; Han, Zhiyang; Yin, Mingzhu

    2017-09-01

    Breast cancer is one of the most invasive cancer types in female population. The functional activity of Transforming growth factor β-activated kinase 1 (TAK1) in breast cancer progression increasingly attracts attention as it provides a potential target for antibreast cancer drug development. However, the fundamental role of TAK1 for triple-negative breast cancer (TNBC) progression and the effect of potential anti-TAK1 drug candidate needs to be further evaluated. Herein, we focused on the role of TAK1 in human breast cancer cells, and we hypothesized that the inhibition of TAK1 activation can repress the growth of human TNBC cells. We found that the TAK1 is robustly activated within cancer cell population of clinic-derived TNBC samples and the human breast cancer cell lines in culture. Furthermore, we determined the effect of 5Z-7-oxozeaenol (5Z-O), a TAK1-specific small molecule inhibitor, on proliferation of human TNBC cell line. 5Z-O treatment significantly suppressed the proliferation of human TNBC cells. Collectively, these demonstrate the role of TAK1 in human breast cancer and the antiproliferate effect of TAK1 inhibitor. Our study sets the stage for further research on TAK1 as a promising target for development of anti-TNBC drugs and therapeutic strategies. © 2017 John Wiley & Sons A/S.

  13. Gene regulation by growth factors

    International Nuclear Information System (INIS)

    Metz, R.; Gorham, J.; Siegfried, Z.; Leonard, D.; Gizang-Ginsberg, E.; Thompson, M.A.; Lawe, D.; Kouzarides, T.; Vosatka, R.; MacGregor, D.; Jamal, S.; Greenberg, M.E.; Ziff, E.B.

    1988-01-01

    To coordinate the proliferation and differentiation of diverse cell types, cells of higher eukaryotes communicate through the release of growth factors. These peptides interact with specific transmembrane receptors of other cells and thereby generate intracellular messengers. The many changes in cellular physiology and activity that can be induced by growth factors imply that growth factor-induced signals can reach the nucleus and control gene activity. Moreover, current evidence also suggests that unregulated signaling along such pathways can induce aberrant proliferation and the formation of tumors. This paper reviews investigations of growth factor regulation of gene expression conducted by the authors' laboratory

  14. Heparin-Binding EGF-like Growth Factor (HB-EGF) stimulates the proliferation of Müller glia-derived progenitor cells in avian and murine retinas

    Science.gov (United States)

    Todd, Levi; Volkov, Leo I.; Zelinka, Chris; Squires, Natalie; Fischer, Andy J.

    2015-01-01

    Müller glia can be stimulated to de-differentiate, proliferate and form Müller glia-derived progenitor cells (MGPCs) that regenerate retinal neurons. In the zebrafish retina, Heparin-Binding EGF-like Growth Factor (HB-EGF) may be one of the key factors that stimulate the formation of proliferating MGPCs. Currently nothing is known about the influence of HB-EGF on the proliferative potential of Müller glia in retinas of birds and rodents. In the chick retina, we found that levels of both hb-egf and egf-receptor are rapidly and transiently up-regulated following NMDA-induced damage. Although intraocular injections of HB-EGF failed to stimulate cell-signaling or proliferation of Müller glia in normal retinas, HB-EGF stimulated proliferation of MGPCs in damaged retinas. By comparison, inhibition of the EGF-receptor (EGFR) decreased the proliferation of MGPCs in damaged retinas. HB-EGF failed to act synergistically with FGF2 to stimulate the formation of MGPCs in the undamaged retina and inhibition of EGF-receptor did not suppress FGF2-mediated formation of MGPCs. In the mouse retina, HB-EGF stimulated the proliferation of Müller glia following NMDA-induced damage. Furthermore, HB-EGF stimulated not only MAPK-signaling in Müller glia/MGPCs, but also activated mTor- and Jak/Stat-signaling. We propose that levels of expression of EGFR are rate-limiting to the responses of Müller glia to HB-EGF and the expression of EGFR can be induced by retinal damage, but not by FGF2-treatment. We conclude that HB-EGF is mitogenic to Müller glia in both chick and mouse retinas, and HB-EGF is an important player in the formation of MGPCs in damaged retinas. PMID:26500021

  15. Hypothyroidism in utero stimulates pancreatic beta cell proliferation and hyperinsulinaemia in the ovine fetus during late gestation.

    Science.gov (United States)

    Harris, Shelley E; De Blasio, Miles J; Davis, Melissa A; Kelly, Amy C; Davenport, Hailey M; Wooding, F B Peter; Blache, Dominique; Meredith, David; Anderson, Miranda; Fowden, Abigail L; Limesand, Sean W; Forhead, Alison J

    2017-06-01

    Thyroid hormones are important regulators of growth and maturation before birth, although the extent to which their actions are mediated by insulin and the development of pancreatic beta cell mass is unknown. Hypothyroidism in fetal sheep induced by removal of the thyroid gland caused asymmetric organ growth, increased pancreatic beta cell mass and proliferation, and was associated with increased circulating concentrations of insulin and leptin. In isolated fetal sheep islets studied in vitro, thyroid hormones inhibited beta cell proliferation in a dose-dependent manner, while high concentrations of insulin and leptin stimulated proliferation. The developing pancreatic beta cell is therefore sensitive to thyroid hormone, insulin and leptin before birth, with possible consequences for pancreatic function in fetal and later life. The findings of this study highlight the importance of thyroid hormones during pregnancy for normal development of the fetal pancreas. Development of pancreatic beta cell mass before birth is essential for normal growth of the fetus and for long-term control of carbohydrate metabolism in postnatal life. Thyroid hormones are also important regulators of fetal growth, and the present study tested the hypotheses that thyroid hormones promote beta cell proliferation in the fetal ovine pancreatic islets, and that growth retardation in hypothyroid fetal sheep is associated with reductions in pancreatic beta cell mass and circulating insulin concentration in utero. Organ growth and pancreatic islet cell proliferation and mass were examined in sheep fetuses following removal of the thyroid gland in utero. The effects of triiodothyronine (T 3 ), insulin and leptin on beta cell proliferation rates were determined in isolated fetal ovine pancreatic islets in vitro. Hypothyroidism in the sheep fetus resulted in an asymmetric pattern of organ growth, pancreatic beta cell hyperplasia, and elevated plasma insulin and leptin concentrations. In pancreatic

  16. Effect of thidiazuron on in vivo shoot proliferation of popular banana ...

    African Journals Online (AJOL)

    SARAH

    2014-09-30

    Sep 30, 2014 ... Mzuzu underscore the need for further studies to determine alternative best cytokine-based growth regulators. Key words: Thidiazuron, in vivo proliferation, Sucker growth, Banana. INTRODUCTION. In vivo macropropagation is an alternative technique for mass production of banana planting materials.

  17. Influence of vesicoureteral reflux and urinary tract infection on renal growth in children with upper urinary tract duplication

    International Nuclear Information System (INIS)

    Hannerz, L.; Wikstad, I.; Celsi, G.; Aperia, A.; St. Goeran's Children's Hospital, Stockholm

    1989-01-01

    The growth of the renal parenchyma was examined in children with duplicated outflow systems, vesicoureteral reflux (VUR), urinary tract infection (UTI) and no sign of obstruction. Ten patients with reflux occurring only in the caudal system (group A) and 4 patients with reflux both to the caudal and the apical system (group B) were studied shortly after their first UTI (study 1) and then 1.5 to 9 years later (study 2). The frequency of UTI was relatively high during the follow-up period. At urography, renal length and renal area were normal in group A in studies 1 and 2. Parenchymal thickness of the apical pole (APT/L) did not differ from normal values in any of the studies. Parenchymal thickness of the caudal pole (CPT/L) was significantly smaller than normal in both studies. There was also a significant decrease in CPT/L between study 1 and 2. UTI during the first year of life was associated with a greater reduction in CPT/L. The determination of renal length and renal area in children with a duplicated ureter, VUR and UTI, does not identify subjects at risk of developing renal growth retardation while serial determinations of parenchymal thickness appear to be an appropriate method. (orig.)

  18. The X protein of hepatitis B virus activates hepatoma cell proliferation through repressing melanoma inhibitory activity 2 gene

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yilin; Yang, Yang; Cai, Yanyan; Liu, Fang; Liu, Yingle; Zhu, Ying [State Key Laboratory of Virology, College of Life Sciences, and Chinese-French Liver Disease Research Institute at Zhongnan Hospital, Wuhan University, Wuhan 430072 (China); Wu, Jianguo, E-mail: jwu@whu.edu.cn [State Key Laboratory of Virology, College of Life Sciences, and Chinese-French Liver Disease Research Institute at Zhongnan Hospital, Wuhan University, Wuhan 430072 (China)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer We demonstrated that HBV represses MIA2 gene expression both invitro and in vivo. Black-Right-Pointing-Pointer The X protein of HBV plays a major role in such regulation. Black-Right-Pointing-Pointer Knock-down of MIA2 in HepG2 cells activates cell growth and proliferation. Black-Right-Pointing-Pointer HBx activates cell proliferation, over-expression of MIA2 impaired such regulation. Black-Right-Pointing-Pointer HBx activates hepatoma cell proliferation through repressing MIA2 expression. -- Abstract: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer deaths globally. Chronic hepatitis B virus (HBV) infection accounts for over 75% of all HCC cases; however, the molecular pathogenesis of HCC is not well understood. In this study, we found that the expression of the newly identified gene melanoma inhibitory activity 2 (MIA2) was reduced by HBV infection invitro and invivo, and that HBV X protein (HBx) plays a major role in this regulation. Recent studies have revealed that MIA2 is a potential tumor suppressor, and that, in most HCCs, MIA2 expression is down-regulated or lost. We found that the knock-down of MIA2 in HepG2 cells activated cell growth and proliferation, suggesting that MIA2 inhibits HCC cell growth and proliferation. In addition, the over-expression of HBx alone induced cell proliferation, whereas MIA2 over-expression impaired the HBx-mediated induction of proliferation. Taken together, our results suggest that HBx activates hepatoma cell growth and proliferation through repression of the potential tumor suppressor MIA2.

  19. Regulation of pancreatic beta-cell mass and proliferation by SOCS-3

    DEFF Research Database (Denmark)

    Lindberg, K; Rønn, S G; Tornehave, D

    2005-01-01

    Growth hormone and prolactin are important growth factors for pancreatic beta-cells. The effects exerted by these hormones on proliferation and on insulin synthesis and secretion in beta-cells are largely mediated through the Janus kinase (JAK)/signal transducer and activator of transcription (ST...

  20. Autoradiographical investigations of the proliferation of gynaecological carcinomas

    International Nuclear Information System (INIS)

    Wehweck, H.

    1981-01-01

    23 biopsies and operation preparations of gynaecological tumours were examined autoradiographically: 8 with an external short-time preirradiation of up to 750 R, one with a curative radiotherapy 1 1/2 years ago. Besides the determination of quantitative parameters of growth kinetics another main concern was to find out the interdependence between the proliferation behaviour of the tumour cells and the histological differentiation of the tumour parenchyma and the topographical location of the malignant cells in the tissue. Possible effects of a previous radiotherapy on the cell proliferation are discussed. (orig./MG) [de

  1. Dynamics of growth of Вопе in sheep of romni-marsh breed

    OpenAIRE

    Slesarcnco, In; Nikitchenko, V.; Nikitchenko, D.

    2007-01-01

    A study was carried out on the growth of bones in young male sheep of the romni-marsh breed aged 4, 7, 10 and 48 months old. It was found out that in the axial region of male sheep, the thoracic region has the most intensive growth in the postnatal period from which the intensity of growth decreases in the cranial and caudal area. With the increase in the relative weight of bones of the limbs, their weight (in relation to the weight of bones of the carcass) decreases, with this; the more dist...

  2. Overexpression of microRNA-375 impedes platelet-derived growth factor-induced proliferation and migration of human fetal airway smooth muscle cells by targeting Janus kinase 2.

    Science.gov (United States)

    Ji, Yamei; Yang, Xin; Su, Huixia

    2018-02-01

    The abnormal proliferation and migration of airway smooth muscle (ASM) cells play a critical role in airway remodeling during the development of asthma. MicroRNAs (miRNAs) have emerged as critical regulators of ASM cell proliferation and migration in airway remodeling. In this study, we aimed to investigate the potential role of miR-375 in the regulation of platelet-derived growth factor (PDGF)-induced fetal ASM cell proliferation and migration. Our results showed that miR-375 expression was significantly decreased in fetal ASM cells that were treated with PDGF. Functional data showed that overexpression of miR-375 inhibited the proliferation and migration of fetal ASM cells, whereas inhibition of miR-375 enhanced the proliferation and migration of fetal ASM cells. The results of bioinformatics analysis and a dual-luciferase reporter assay showed that miR-375 binds directly to the 3'-untranslated region of Janus kinase 2 (JAK2). Further data confirmed that miR-375 negatively regulates the expression of JAK2 in fetal ASM cells. Moreover, miR-375 also impeded the PDGF-induced activation of signal transducer and activator of transcription 3 (STAT3) in fetal ASM cells. However, restoration of JAK2 expression partially reversed the inhibitory effect of miR-375 on fetal ASM cell proliferation and migration. Overall, our results demonstrate that miR-375 inhibits fetal ASM cell proliferation and migration by targeting JAK2/STAT3 signaling. Our study provides a potential therapeutic target for the development of novel treatment strategies for pediatric asthma. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Expression of various growth factors for cell proliferation and cytodifferentiation during fracture repair of bone

    Directory of Open Access Journals (Sweden)

    M Fukuda

    2009-12-01

    Full Text Available We examined immunohistochemically the fracture repair process in rat tibial bone using antibodies to PCNA, BMP2, TGF-b 1,-2,-3, TGF-b R1,- R2, bFGF, bFGFR, PDGF, VEGF, and S-100. The peak level of cell proliferation as revealed by PCNA labelling appeared first in primitive mesenchymal cells and inflammatory cells at the fracture edges and neighboring periosteum at 2-days after fracture, followed by the peaks of periosteal primitive fibroblasts and chondroblasts, which appeared at fracture edges at 3- and 4-days after fracture, respectively. BMP2 was weakly positive in primitive mesenchymal cells, osteoblasts and chondroblasts. At 3-days post-fracture, periosteal osteoblasts produced osteoid tissue and callus with marrow spaces lined by osteoblasts and osteoclasts, and all primitive mesenchymal cells and osteoblasts were positive for TGF-b 1,-2,-3, and TGF-b R1,-R2. They were also positive for vascular growth factors bFGF, FGFR and PDGF, but negative for VEGF, and the peak of PCNA labelling of vascular endothelial cells in the marrow space was delayed to 4-days after fracture. Chondroblasts at fracture edges produced hypertrophic chondrocytes at 5-days after fracture and they were positive for TGF-b 1,-2,-3, and TGF-b R1,-R2. Primitive chondroblasts were positive for vascular growth factors VEGF as well as bFGF, FGFR, and the peak of PCNA labelling of vascular endothelial cells in the cartilage was at 5-days after fracture. Hypertrophic chondrocytes were also positive for these growth factors but negative for bFGF and bFGFR. S-100 protein-induced calcification was only positive on chondroblasts and hypertrophic chondrocytes. At 7-days after fracture, bone began to be formed from the cartilage at fracture edges, by a process similar to bone formation in the growth plate. Enchondral ossification established a bridge between both fracture edges and periosteal membranous ossification encompassed the fracture site like a sheath at 14- day after

  4. A novel approach to brachycephalic syndrome. 3. Isolated laser-assisted turbinectomy of caudal aberrant turbinates (CAT LATE).

    Science.gov (United States)

    Schuenemann, Riccarda; Pohl, Sabine; Oechtering, Gerhard U

    2017-01-01

    To describe isolated laser-assisted turbinectomy of caudal aberrant turbinates (CAT LATE) as a new minimally invasive surgical procedure for the treatment of brachycephalic dogs with obstructing caudal aberrant turbinates (CAT). Prospective clinical study. Brachycephalic dogs (24 Pugs, 1 English Bulldog) with CAT but adequate air spaces between the lamellae of the nonobstructing ventral nasal concha. A rhinoscopically guided diode laser fiber introduced from anterior was used to dissect CAT within the nasopharyngeal meatus, while leaving the intranasal turbinates intact. Small grasping forceps were used to extract the dissected CAT from anterior or to push it through the nasopharyngeal meatus for extraction from posterior. Isolated CAT LATE was successfully performed on 32 CAT in 25 dogs. Intranasally applied xylometazoline helped shrink the ventral concha, making the approach and extraction easier. Minor bleeding was the only complication observed. It is possible to remove CAT with endoscopically applied diode-laser energy while leaving the nonobstructing ventral nasal concha intact. © 2017 The American College of Veterinary Surgeons.

  5. Dynamics of cell proliferation and apoptosis reflect different life strategies in hydrothermal vent and cold seep vestimentiferan tubeworms.

    Science.gov (United States)

    Pflugfelder, Bettina; Cary, S Craig; Bright, Monika

    2009-07-01

    Deep-sea vestimentiferan tubeworms, which live in symbiosis with bacteria, exhibit different life strategies according to their habitat. At unstable and relatively short-lived hydrothermal vents, they grow extremely fast, whereas their close relatives at stable and long-persisting cold seeps grow slowly and live up to 300 years. Growth and age differences are thought to occur because of ecological and physiological adaptations. However, the underlying mechanisms of cell proliferation and death, which are closely linked to homeostasis, growth, and longevity, are unknown. Here, we show by immunohistochemical and ultrastructural cell cycle analyses that cell proliferation activities of the two species studied are higher than in any other characterized invertebrate, being only comparable with tumor and wound-healing processes. The slow growth in Lamellibrachia luymesi from cold seeps results from balanced activities of proliferation and apoptosis in the epidermis. In contrast, Riftia pachyptila from hydrothermal vents grows fast because apoptosis is down-regulated in this tissue. The symbiont-housing organ, the trophosome, exhibits a complex cell cycle and terminal differentiation pattern in both species, and growth is regulated by proliferation. These mechanisms have similarities to the up- and down-regulation of proliferation or apoptosis in various types of tumor, although they occur in healthy animals in this study, thus providing significant insights into the underlying mechanisms of growth and longevity.

  6. Metals in the caudal scutes of Morelet's crocodile (Crocodylus moreletii) from the southern Gulf of Mexico.

    Science.gov (United States)

    Trillanes, C E; Pérez-Jiménez, J C; Rosíles-Martínez, R; González-Jáuregui, M

    2014-10-01

    Caudal scutes were collected from 92 Morelet's crocodiles (Crocodylus moreletii) between May and August 2012, in three Wildlife Management and Use Units (UMAs, from its name in Spanish) and three wild sites in Campeche, Mexico. The UMAs are intensive, with an ex situ approach to manage crocodiles in captivity. The concentrations of arsenic, mercury, lead, nickel, cadmium and chromium were analyzed in each sample. As and Pb were detected in all samples, Hg in 86 and Ni in 74. The metal concentrations estimated were higher than most of the concentrations reported for skin, tail tip and caudal scutes in other crocodilians around the world. The concentration of As, Pb and Ni was significantly greater in the free-ranging groups than in the captive groups in UMAs (p < 0.05). Negative linear relationship was estimated between the snout-vent length and the concentration of Pb (in five groups) and Ni (in three groups). In this region C. moreletii is exposed to metals contamination and more studies are necessary to establish if represents a risk to their populations.

  7. Localization of Proliferating Cells in the Inter-Vertebral Region of the Developing and Adult Vertebrae of Lizards in Relation to Growth and Regeneration.

    Science.gov (United States)

    Alibardi, Lorenzo

    2016-04-01

    New cartilaginous tissues in lizards is formed during the regeneration of the tail or after vertebral damage. In order to understand the origin of new cartilaginous cells in the embryo and after injury of adult vertebrae we have studied the distribution of proliferating cartilaginous cells in the vertebral column of embryos and adults of the lizard Anolis lineatopus using autoradiography for H3-thymidine and light and ultrastructural immunocytochemistry for 5BrdU. Proliferating sclerotomal cells initially surround the notochord in a segmental pattern and give rise to the chondrocytes of the vertebral centrum that replace the original chordal cells. Qualitative observations show that proliferating sclerotomal cells dilute the labeling up to 13 days post-injection but a few maintain the labeling as long labeling retention cells and remain in the inter-centra and perichondrium after birth. These cells supply new chondroblasts for post-natal growth of vertebrae but can also proliferate in case of vertebral damage or tail amputation in lizards, a process that sustains tail regeneration. The lack of somitic organization in the regenerating tail impedes the re-formation of a segmental vertebral column that is instead replaced by a continuous cartilaginous tube. It is hypothesized that long labeling retaining cells might represent stem/primordial cells, and that their permanence in the inter-vertebral cartilages and the nearby perichondrium in adult lizards pre-adapt these reptiles to elicit a broad cartilage regeneration in case of injury of the vertebrae. © 2016 Wiley Periodicals, Inc.

  8. Novel role of NPY in neuroimmune interaction and lung growth after intrauterine growth restriction.

    Science.gov (United States)

    Thangaratnarajah, Chansutha; Dinger, Katharina; Vohlen, Christina; Klaudt, Christian; Nawabi, Jawed; Lopez Garcia, Eva; Kwapiszewska, Grazyna; Dobner, Julia; Nüsken, Kai D; van Koningsbruggen-Rietschel, Silke; von Hörsten, Stephan; Dötsch, Jörg; Alejandre Alcázar, Miguel A

    2017-09-01

    Individuals with intrauterine growth restriction (IUGR) are at risk for chronic lung disease. Using a rat model, we showed in our previous studies that altered lung structure is related to IL-6/STAT3 signaling. As neuropeptide Y (NPY), a coneurotransmitter of the sympathetic nervous system, regulates proliferation and immune response, we hypothesized that dysregulated NPY after IUGR is linked to IL-6, impaired myofibroblast function, and alveolar growth. IUGR was induced in rats by isocaloric low-protein diet; lungs were analyzed on embryonic day (E) 21, postnatal day (P) 3, P12, and P23. Finally, primary neonatal lung myofibroblasts (pnF) and murine embryonic fibroblasts (MEF) were used to assess proliferation, apoptosis, migration, and IL-6 expression. At E21, NPY and IL-6 expression was decreased, and AKT/PKC and STAT3/AMPKα signaling was reduced. Early reduction of NPY/IL-6 was associated with increased chord length in lungs after IUGR at P3, indicating reduced alveolar formation. At P23, however, IUGR rats exhibited a catch-up of body weight and alveolar growth coupled with more proliferating myofibroblasts. These structural findings after IUGR were linked to activated NPY/PKC, IL-6/AMPKα signaling. Complementary, IUGR-pnF showed increased survival, impaired migration, and reduced IL-6 compared with control-pnF (Co-pnF). In contrast, NPY induced proliferation, migration, and increased IL-6 synthesis in fibroblasts. Additionally, NPY -/- mice showed reduced IL-6 signaling and less proliferation of lung fibroblasts. Our study presents a novel role of NPY during alveolarization: NPY regulates 1 ) IL-6 and lung STAT3/AMPKα signaling, and 2 ) proliferation and migration of myofibroblasts. These new insights in pulmonary neuroimmune interaction offer potential strategies to enable lung growth. Copyright © 2017 the American Physiological Society.

  9. The effect of different growth media, carbon source and pgrs on dendrobium broga giant orchid's protocorm-like bodies (plbs) proliferation supported with sem and tem analysis

    International Nuclear Information System (INIS)

    Uddain, J.; Gnasekaran, P.; Zakaria, L.

    2015-01-01

    Dendrobium Broga Giant (Dendrobium Bobby Messina * Dendrobium Superbiens) is a new orchid hybrid in Malaysia. The aim of this study was to investigate the effect of different growth media, carbon sources and PGRs on Dendrobium Broga Giant orchid's protocorm-like bodies (PLBs) proliferation supported with SEM and TEM analysis. The PLBs were cultured on different strength of semi-solid and liquid MS medium and the proliferation rate was recorded based on the fresh weight basis. The maximum PLBs proliferation (12.31% 0.57) was obtained in MS semi-solid medium. PLBs were cultured on MS semi-solid media supplemented with different sucrose concentrations (0, 10, 20, 30 and 40 g L-1). The highest proliferation rate of PLBs (15.48% 1.20) was recorded from MS supplemented with 20 g L-1 sucrose. Different concentrations of BAP (0, 0.5, 1.0, 2.0 mg.L-1) and NAA (0, 0.5, 1.0, 2.0 mgL-1) were added to MS semi-solid medium. Combinations of 1.0 mg L-1 BAP and 0.5 mg.L-1 NAA produced higher PLBs proliferation. Micromorphological studies by SEM and TEM displayed trichome, leaf primordial, stomata, various sizes of mitochondria, vacuoles, different shapes of chloroplast were found in PLBs which ameliorated the slow proliferation nature of plantlets. (author)

  10. Effects of growth-promoting factors on proliferation of mouse ...

    African Journals Online (AJOL)

    SSCs) in vitro are critical to our understanding of male infertility, genetic resources and endangered species conservation. To investigate the effects of growth-promoting factors, epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1) and ...

  11. Andrographolide reduces proliferation and migration of lens epithelial cells by modulating PI3K/Akt pathway.

    Science.gov (United States)

    Kayastha, Forum; Madhu, Hardik; Vasavada, Abhay; Johar, Kaid

    2014-11-01

    Lens epithelial cell proliferation, migration, and transdifferentiation are involved in the development of subcapsular cataracts and postoperative capsular opacification (PCO). PI3K/Akt pathway is involved in the proliferation and migration of lens epithelial cells. Andrographolide is the main bioactive component of Andrographis paniculata and is known to possess anti-proliferative and anti-migratory activities. The purpose of this study is to evaluate the effect of andrographolide on proliferation and migration induced by growth factors (TGF-β and bFGF) in the lens epithelial cell line, FHL 124. We have also evaluated the role of the PI3K/Akt pathway and its alteration by andrographolide during proliferation and migration of lens epithelial cells. The results showed that andrographolide significantly inhibited proliferation in a dose and time dependent manner. The growth factors, TGF-β and bFGF, induced migration of lens epithelial cells, which was lowered by andrographolide. The growth factors also up regulated phosphorylated Akt (Ser473) and Akt (Thr308), which was abolished by simultaneous treatment of andrographolide. Similar changes were also observed with the PI3K inhibitor, LY290042. Our findings suggest that andrographolide reduces proliferation, migration, and phosphorylated Akt levels in lens epithelial cells. Hence andrographolide can be utilized for the prevention of PCO. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. EGCG Inhibits Proliferation, Invasiveness and Tumor Growth by Up-Regulation of Adhesion Molecules, Suppression of Gelatinases Activity, and Induction of Apoptosis in Nasopharyngeal Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Chih-Yeu Fang

    2015-01-01

    Full Text Available (−-Epigallocatechin-3-gallate (EGCG, a major green tea polyphenol, has been shown to inhibit the proliferation of a variety of tumor cells. Epidemiological studies have shown that drinking green tea can reduce the incidence of nasopharyngeal carcinoma (NPC, yet the underlying mechanism is not well understood. In this study, the inhibitory effect of EGCG was tested on a set of Epstein Barr virus-negative and -positive NPC cell lines. Treatment with EGCG inhibited the proliferation of NPC cells but did not affect the growth of a non-malignant nasopharyngeal cell line, NP460hTert. Moreover, EGCG treated cells had reduced migration and invasive properties. The expression of the cell adhesion molecules E-cadherin and β-catenin was found to be up-regulated by EGCG treatment, while the down-regulation of matrix metalloproteinases (MMP-2 and MMP-9 were found to be mediated by suppression of extracellular signal-regulated kinase (ERK phosphorylation and AP-1 and Sp1 transactivation. Spheroid formation by NPC cells in suspension was significantly inhibited by EGCG. Oral administration of EGCG was capable of suppressing tumor growth in xenografted mice bearing NPC tumors. Treatment with EGCG was found to elevate the expression of p53 and p21, and eventually led to apoptosis of NPC cells via caspase 3 activation. The nuclear translocation of NF-κB and β-catenin was also suppressed by EGCG treatment. These results indicate that EGCG can inhibit the proliferation and invasiveness, and induce apoptosis, of NPC cells, making it a promising agent for chemoprevention or adjuvant therapy of NPC.

  13. Proliferation of the Golgi apparatus in tobacco BY-2 cells during cell proliferation after release from the stationary phase of growth.

    Science.gov (United States)

    Abiodun, Moses; Matsuoka, Ken

    2013-08-01

    We have recently developed a new method aimed at mass photo-conversion of photo-convertible fluorescence protein (PFP) fluorescence in transformed tobacco BY-2 cells. Using this method we reported recently that the Golgi apparatus is generated by the de novo formation from ER and the division of pre-existing Golgi stacks with similar extents In this work we report that the proliferation of the Golgi apparatus in tobacco cells that enter the growing cycle from the non-dividing cycle is quite similar to that in rapidly growing cells and that de novo formation from the ER and division of pre-existing stacks seems to contribute almost equally to the proliferation.

  14. GATA4 Regulates Epithelial Cell Proliferation to Control Intestinal Growth and Development in MiceSummary

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    Bridget M. Kohlnhofer

    2016-03-01

    Full Text Available Background & Aims: The embryonic small intestinal epithelium is highly proliferative, and although much is known about mechanisms regulating proliferation in the adult intestine, the mechanisms controlling epithelial cell proliferation in the developing intestine are less clear. GATA4, a transcription factor that regulates proliferation in other developing tissues, is first expressed early in the developing gut in midgut endoderm. GATA4 function within midgut endoderm and the early intestinal epithelium is unknown. Methods: By using Sonic Hedgehog Cre to eliminate GATA4 in the midgut endoderm of mouse embryos, we determined the impact of loss of GATA4 on intestinal development, including epithelial cell proliferation, between embryonic day (E9.5 and E18.5. Results: We found that intestinal length and width were decreased in GATA4 mutants compared with controls. GATA4-deficient intestinal epithelium contained fewer cells, and epithelial girth was decreased. We further observed a decreased proportion of proliferating epithelial cells at E10.5 and E11.5 in GATA4 mutants. We showed that GATA4 binds to chromatin containing GATA4 consensus binding sites within cyclin D2 (Ccnd2, cyclin-dependent kinase 6 (Cdk6, and frizzled 5 (Fzd5. Moreover, Ccnd2, Cdk6, and Fzd5 transcripts were reduced at E11.5 in GATA4 mutant tissue. Villus morphogenesis was delayed, and villus structure was abnormal in GATA4 mutant intestine. Conclusions: Our data identify GATA4 as an essential regulator of early intestinal epithelial cell proliferation. We propose that GATA4 controls proliferation in part by directly regulating transcription of cell-cycle mediators. Our data further suggest that GATA4 affects proliferation through transcriptional regulation of Fzd5, perhaps by influencing the response of the epithelium to WNT signaling. Keywords: Transcriptional Regulation, WNT Signaling, Villus Morphogenesis

  15. Minimally invasive transcriptome profiling in salmon: Detection of biological response in rainbow trout caudal fin following exposure to environmental chemical contaminants

    Energy Technology Data Exchange (ETDEWEB)

    Veldhoen, Nik; Stevenson, Mitchel R. [Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 3055, STN CSC, Victoria, BC V8W 3P6 (Canada); Skirrow, Rachel C. [Pacific and Yukon Laboratory for Environmental Testing, Pacific Environmental Science Centre, Environment Canada, 2645 Dollarton Highway, North Vancouver, BC V7H 1B1 (Canada); Rieberger, Kevin J. [Environmental Sustainability and Strategic Policy Division, Water Protection and Sustainability Branch, British Columbia Ministry of Environment, P.O. Box 9362 Stn Prov Govt, Victoria, BC V8W 9M2 (Canada); Aggelen, Graham van [Pacific and Yukon Laboratory for Environmental Testing, Pacific Environmental Science Centre, Environment Canada, 2645 Dollarton Highway, North Vancouver, BC V7H 1B1 (Canada); Meays, Cynthia L. [Environmental Sustainability and Strategic Policy Division, Water Protection and Sustainability Branch, British Columbia Ministry of Environment, P.O. Box 9362 Stn Prov Govt, Victoria, BC V8W 9M2 (Canada); Helbing, Caren C., E-mail: chelbing@uvic.ca [Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 3055, STN CSC, Victoria, BC V8W 3P6 (Canada)

    2013-10-15

    Highlights: •A minimally-invasive tail fin biopsy assay was developed for use in fish. •Quantitative real time polymerase reaction provided gene expression readout. •Results were comparable to classical liver tissue responses. •The approach was used on two salmonid species and can be coupled with genomic sex determination using an additional biopsy for maximal information. -- Abstract: An increasing number of anthropogenic chemicals have demonstrated potential for disruption of biological processes critical to normal growth and development of wildlife species. Both anadromous and freshwater salmon species are at risk of exposure to environmental chemical contaminants that may affect migratory behavior, environmental fitness, and reproductive success. A sensitive metric in determination of the presence and impact of such environmental chemical contaminants is through detection of changes in the status of gene transcript levels using a targeted quantitative real-time polymerase chain reaction assay. Ideally, the wildlife assessment strategy would incorporate conservation-centered non-lethal practices. Herein, we describe the development of such an assay for rainbow trout, Oncorhynchus mykiss, following an acute 96 h exposure to increasing concentrations of either 17α-ethinyl estradiol or cadmium. The estrogenic screen included measurement of mRNA encoding estrogen receptor α and β isoforms, vitellogenin, vitelline envelope protein γ, cytochrome p450 family 19 subfamily A, aryl hydrocarbon receptor, and the stress indicator, catalase. The metal exposure screen included evaluation of the latter two mRNA transcripts along with those encoding the metallothionein A and B isoforms. Exposure-dependent transcript abundance profiles were detected in both liver and caudal fin supporting the use of the caudal fin as a non-lethally obtained tissue source. The potential for both transcriptome profiling and genotypic sex determination from fin biopsy was extended, in

  16. Minimally invasive transcriptome profiling in salmon: Detection of biological response in rainbow trout caudal fin following exposure to environmental chemical contaminants

    International Nuclear Information System (INIS)

    Veldhoen, Nik; Stevenson, Mitchel R.; Skirrow, Rachel C.; Rieberger, Kevin J.; Aggelen, Graham van; Meays, Cynthia L.; Helbing, Caren C.

    2013-01-01

    Highlights: •A minimally-invasive tail fin biopsy assay was developed for use in fish. •Quantitative real time polymerase reaction provided gene expression readout. •Results were comparable to classical liver tissue responses. •The approach was used on two salmonid species and can be coupled with genomic sex determination using an additional biopsy for maximal information. -- Abstract: An increasing number of anthropogenic chemicals have demonstrated potential for disruption of biological processes critical to normal growth and development of wildlife species. Both anadromous and freshwater salmon species are at risk of exposure to environmental chemical contaminants that may affect migratory behavior, environmental fitness, and reproductive success. A sensitive metric in determination of the presence and impact of such environmental chemical contaminants is through detection of changes in the status of gene transcript levels using a targeted quantitative real-time polymerase chain reaction assay. Ideally, the wildlife assessment strategy would incorporate conservation-centered non-lethal practices. Herein, we describe the development of such an assay for rainbow trout, Oncorhynchus mykiss, following an acute 96 h exposure to increasing concentrations of either 17α-ethinyl estradiol or cadmium. The estrogenic screen included measurement of mRNA encoding estrogen receptor α and β isoforms, vitellogenin, vitelline envelope protein γ, cytochrome p450 family 19 subfamily A, aryl hydrocarbon receptor, and the stress indicator, catalase. The metal exposure screen included evaluation of the latter two mRNA transcripts along with those encoding the metallothionein A and B isoforms. Exposure-dependent transcript abundance profiles were detected in both liver and caudal fin supporting the use of the caudal fin as a non-lethally obtained tissue source. The potential for both transcriptome profiling and genotypic sex determination from fin biopsy was extended, in

  17. [The crooked nose: correction of dorsal and caudal septal deviations].

    Science.gov (United States)

    Foda, H M T

    2010-09-01

    The deviated nose represents a complex cosmetic and functional problem. Septal surgery plays a central role in the successful management of the externally deviated nose. This study included 800 patients seeking rhinoplasty to correct external nasal deviations; 71% of these suffered from variable degrees of nasal obstruction. Septal surgery was necessary in 736 (92%) patients, not only to improve breathing, but also to achieve a straight, symmetric external nose. A graduated surgical approach was adopted to allow correction of the dorsal and caudal deviations of the nasal septum without weakening its structural support to the nasal dorsum or nasal tip. The approach depended on full mobilization of deviated cartilage, followed by straightening of the cartilage and its fixation in the corrected position by using bony splinting grafts through an external rhinoplasty approach.

  18. Effect of nalbuphine as an adjuvant on levobupivacaine induced caudal analgesia in children undergoing surgical procedures, controlled randomized double blinded

    Directory of Open Access Journals (Sweden)

    Riham Hussein Saleh

    2016-01-01

    Conclusion: Caudal epidural nalbuphine is safe in pediatric surgeries including the lower half of the body and effectively reduces postoperative pain. However it may cause early postoperative sedation, yet without respiratory depression.

  19. Insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-5 mediate TGF-β- and myostatin-induced suppression of proliferation in porcine embryonic myogenic cell cultures

    International Nuclear Information System (INIS)

    Kamanga-Sollo, E.; Pampusch, M.S.; White, M.E.; Hathaway, M.R.; Dayton, W.R.

    2005-01-01

    We have previously shown that cultured porcine embryonic myogenic cells (PEMC) produce both insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-5 and secrete these proteins into their media. Exogenously added recombinant porcine (rp) IGFBP-3 and rpIGFBP-5 act via IGF-dependent and IGF-independent mechanisms to suppress proliferation of PEMC cultures. Furthermore, immunoneutralization of endogenous IGFBP-3 and IGFBP-5 in the PEMC culture medium results in increased DNA synthesis rate suggesting that endogenous IGFBP-3 and IGFBP-5 suppress PEMC proliferation. TGF-β superfamily members myostatin and TGF-β 1 have also been shown to suppress proliferation of myogenic cells, and treatment of cultured PEMC with either TGF-β 1 or myostatin significantly (P 1 and myostatin. Here, we show that immunoneutralization of IGFBP-5 also significantly (P 1 or myostatin-treated PEMC cultures restores Long-R3-IGF-I-stimulated DNA synthesis rates to 90% of the levels observed in control cultures receiving no TGF-β 1 or myostatin treatment (P 1 or myostatin-treated PEMC cultures, phosphosmad2 levels in these cultures were not affected. These findings strongly suggest that IGFBP-3 and IGFBP-5 affect processes downstream from receptor-mediated Smad phosphorylation that facilitate the ability of TGF-β and myostatin to suppress proliferation of PEMC

  20. The Termination Level of the Dural Sac Relevant to Caudal Epidural Block in Lumbosacral Transitional Vertebrae: A Comparison between Sacralization and Lumbarization Groups.

    Science.gov (United States)

    Jeon, Ji Young; Jeong, Yu Mi; Lee, Sheen-Woo; Kim, Jeong Ho; Choi, Hye-Young; Ahn, Yong

    2018-01-01

    Lumbosacral transitional vertebrae (LSTV) are a relatively common variant and have been considered as one of the reasons for back pain. It is not unusual for clinicians to encounter patients with LSTV who require caudal epidural block (CEB) for pain management. We investigated the termination level of the dural sac (DS) and anatomical features of the lumbosacral region relevant to CEB in patients with LSTV and compared these findings between sacralization and lumbarization groups. A retrospective evaluation. A university hospital with inpatient and outpatient LSTV cases presenting low back pain. Four hundred ninety-four LSTV patients were included and categorized into sacralization (n = 201) or lumbarization groups (n = 293). Magnetic resonance imaging (MRI) of all of the LSTV patients were reviewed to determine the level of DS termination, the shortest distance between the apex of the sacral hiatus and DS, and the presence and the caudal level of sacral perineural cysts. Each lumbosacral vertebra column was divided into 3 equal portions (upper, middle, and lower thirds). The MRI findings in both of the groups were compared and analyzed. The distribution frequency of the levels of DS termination demonstrated a significant difference between the 2 groups. The mean caudal DS level in the lumbarization group was significantly lower than the sacralization group (lower third of the S2 [131 {44.7%} of 293 patients] vs. lower third of the S1 [78 {38.8%} of 201 patients]). The DS terminated at the S3 in more than 19% of the lumbarization group, whereas in only one case of the sacralization group. Although the incidence of perineural cysts was not significantly different between the 2 groups, the mean level of caudal margin of perineural cysts in the lumbarization group was significantly lower than the sacralization group (middle third of the S3 [10 {35.7%} of 28 cases] vs. middle third of the S2 [11 {44%} of 25 cases]). This study reveals several limitations including the

  1. Combined Stimulation with the Tumor Necrosis Factor α and the Epidermal Growth Factor Promotes the Proliferation of Hepatocytes in Rat Liver Cultured Slices

    Directory of Open Access Journals (Sweden)

    Francis Finot

    2012-01-01

    Full Text Available The culture liver slices are mainly used to investigate drug metabolism and xenobiotic-mediated liver injuries while apoptosis and proliferation remain unexplored in this culture model. Here, we show a transient increase in LDH release and caspase activities indicating an ischemic injury during the slicing procedure. Then, caspase activities decrease and remain low in cultured slices demonstrating a low level of apoptosis. The slicing procedure is also associated with the G0/G1 transition of hepatocytes demonstrated by the activation of stress and proliferation signalling pathways including the ERK1/2 and JNK1/2/3 MAPKinases and the transient upregulation of c-fos. The cells further progress up to mid-G1 phase as indicated by the sequential induction of c-myc and p53 mRNA levels after the slicing procedure and at 24 h of culture, respectively. The stimulation by epidermal growth factor induces the ERK1/2 phosphorylation but fails to activate expression of late G1 and S phase markers such as cyclin D1 and Cdk1 indicating that hepatocytes are arrested in mid-G1 phase of the cell cycle. However, we found that combined stimulation by the proinflammatory cytokine tumor necrosis factor α and the epidermal growth factor promotes the commitment to DNA replication as observed in vivo during the liver regeneration.

  2. Thiazolidinediones abrogate cervical cancer growth

    Energy Technology Data Exchange (ETDEWEB)

    Wuertz, Beverly R., E-mail: knier003@umn.edu; Darrah, Lindsay, E-mail: ldarrah@obgynmn.com; Wudel, Justin, E-mail: drwudel@drwudel.com; Ondrey, Frank G., E-mail: ondre002@umn.edu

    2017-04-15

    Peroxisome proliferator-activated receptor gamma (PPAR γ) is activated by thiazolidinedione drugs (TZDs) and can promote anti-cancer properties. We used three TZDs (pioglitazone, rosiglitazone, and ciglitazone) to target cervical cancer cell lines and a nude mouse animal model. Each agent increased activation of PPAR γ, as judged by a luciferase reporter gene assay in three HPV-associated cell lines (CaSki, SiHa, and HeLa cells) while decreasing cellular proliferation in a dose-dependent manner. They also promoted Oil Red O accumulation in treated cell lines and upregulated the lipid differentiation marker adipsin. Interestingly, xenograft HeLa tumors in nude mice treated with 100 mg/kg/day pioglitazone exhibited decreased growth compared to control mice or mice treated with standard cervical chemotherapy. In conclusion, TZDs slow tumor cell growth in vitro and in vivo with decreases in cell proliferation and increases in PPAR γ and adipsin. These agents may be interesting treatments or treatment adjuncts for HPV-associated cancers or perhaps even precancerous conditions. - Highlights: • Thiazolidinediones decreases cervical cancer proliferation. • Pioglitazone increases cervical cancer differentiation. • Pioglitazone decreases tumor growth in mice. • Pioglitazone may be a useful treatment adjunct.

  3. Effects of ketamine and midazolam on emergence agitation after sevoflurane anaesthesia in children receiving caudal block: a randomized trial

    Directory of Open Access Journals (Sweden)

    Ayse Ozcan

    2014-11-01

    Full Text Available Background and objectives: Emergence agitation is a common postanaesthetic problem in children after sevoflurane anaesthesia. We aimed to compare the effects of ketamine and midazolam administered intravenously, before the end of surgery, for prevention of emergence agitation in children who received caudal block for pain relief under sevoflurane anaesthesia. Methods: 62 American Society of Anesthesiologists patient classification status I children, aged 2–7 years, scheduled for inguinal hernia repair, circumcision or orchidopexy were enrolled to the study. Anaesthesia was induced with sevoflurane 8% in a mixture of 50% oxygen and nitrous oxide. After achieving adequate depth of anaesthesia, a laryngeal mask was placed and then caudal block was performed with 0.75 mL kg−1, 0.25% bupivacaine. At the end of the surgery, ketamine 0.25 mg kg−1, midazolam 0.03 mg kg−1 and saline were given to ketamine, midazolam and control groups, respectively. Agitation was assessed using Paediatric Anaesthesia Emergence Delirium scale and postoperative pain was evaluated with modified Children's Hospital of Eastern Ontario Pain Scale. Results and conclusions: Modified Children's Hospital of Eastern Ontario Pain Scale scores were found higher in control group than in ketamine and midazolam groups. Paediatric Anaesthesia Emergence Delirium scores were similar between groups. Modified Children's Hospital of Eastern Ontario Pain Scale and Paediatric Anaesthesia Emergence Delirium scores showed a significant decrease by time in all groups during follow-up in postanaesthesia care unit. The present study resulted in satisfactory Paediatric Anaesthesia Emergence Delirium scores which are below 10 in all groups. As a conclusion, neither ketamine nor midazolam added to caudal block under sevoflurane anaesthesia did show further effect on emergence agitation. In addition, pain relief still seems to be the major factor in preventing emergence agitation after

  4. Spatiotemporal distribution of proliferation, proapoptotic and antiapoptotic factors in the early human limb development.

    Science.gov (United States)

    Bečić, Tina; Bilan, Kanito; Mardešić, Snježana; Vukojević, Katarina; Saraga-Babić, Mirna

    2016-06-01

    Involvement of proliferation and apoptosis in the human limb development was analyzed electronmicroscopically and immunohistochemically in histological sections of 8 human embryos, 4(th) -10(th) week old, using apoptotic (caspase-3, AIF, BAX), anti-apoptotic (Bcl-2) and proliferation (Ki-67) markers, and TUNEL method. The data were analyzed by Mann-Whitney test, Kruskal-Wallis and Dunn's post hoc test. Initially, developing human limbs consisted of mesenchymal core and surface ectoderm with apical ectodermal ridge (AER). During progression of development, strong proliferation activity gradually decreased in the mesenchyme (from 78% to 68%) and in the epithelium (from 62% to 42%), while in the differentiating finger cartilages proliferation was constantly low (26-7%). Apoptotic caspase-3 and AIF-positive cells characterized mesenchyme and AER at earliest stages, while during digit separation they appeared in interdigital mesenchyme as well. Strong Bcl-2 expression was observed in AER, subridge mesenchyme and phalanges, while BAX expression charaterized limb areas undergoing apoptosis. Ultrastructurally, proliferating cells showed mitotic figures, while apoptotic cells were characterized by nuclear fragmentation. Macrophages were observed around the apoptotic cells. We suggest that intense proliferation enables growth and elongation of human limb primordia, and differential growth of digits. Both caspase-3 and AIF-dependant pathways of cell death control the extent of AER and numer of cells in the subridge mesenchyme at earliest developmental stages, as well as process of digit separation at later stages of limb development. Spatio-temporal co-expresson of Bcl-2 and BAX indicates their role in suppression of apoptosis and selective stimulation of growth during human limb morphogenesis. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. An Evolutionarily Conserved Network Mediates Development of the zona limitans intrathalamica, a Sonic Hedgehog-Secreting Caudal Forebrain Signaling Center

    Directory of Open Access Journals (Sweden)

    Elena Sena

    2016-10-01

    Full Text Available Recent studies revealed new insights into the development of a unique caudal forebrain-signaling center: the zona limitans intrathalamica (zli. The zli is the last brain signaling center to form and the first forebrain compartment to be established. It is the only part of the dorsal neural tube expressing the morphogen Sonic Hedgehog (Shh whose activity participates in the survival, growth and patterning of neuronal progenitor subpopulations within the thalamic complex. Here, we review the gene regulatory network of transcription factors and cis-regulatory elements that underlies formation of a shh-expressing delimitated domain in the anterior brain. We discuss evidence that this network predates the origin of chordates. We highlight the contribution of Shh, Wnt and Notch signaling to zli development and discuss implications for the fact that the morphogen Shh relies on primary cilia for signal transduction. The network that underlies zli development also contributes to thalamus induction, and to its patterning once the zli has been set up. We present an overview of the brain malformations possibly associated with developmental defects in this gene regulatory network (GRN.

  6. Amlexanox Blocks the Interaction between S100A4 and Epidermal Growth Factor and Inhibits Cell Proliferation.

    Directory of Open Access Journals (Sweden)

    Ching Chang Cho

    Full Text Available The human S100A4 protein binds calcium, resulting in a change in its conformation to promote the interaction with its target protein. Human epidermal growth factor (EGF is the target protein of S100A4 and a critical ligand of the receptor EGFR. The EGF/EGFR system promotes cell survival, differentiation, and growth by activating several signaling pathways. Amlexanox is an anti-inflammatory and anti-allergic drug that is used to treat recurrent aphthous ulcers. In the present study, we determined that amlexanox interacts with S100A4 using heteronuclear single quantum correlation titration. We elucidated the interactions of S100A4 with EGF and amlexanox using fluorescence and nuclear magnetic resonance spectroscopy. We generated two binary models (for the S100A4-EGF and S100A4-amlexanox complexes and observed that amlexanox and EGF share a similar binding region in mS100A4. We also used a WST-1 assay to investigate the bioactivity of S100A4, EGF, and amlexanox, and found that amlexanox blocks the binding between S100A4 and EGF, and is therefore useful for the development of new anti-proliferation drugs.

  7. Ontogeny of head and caudal fin shape of an apex marine predator: The tiger shark (Galeocerdo cuvier).

    Science.gov (United States)

    Fu, Amy L; Hammerschlag, Neil; Lauder, George V; Wilga, Cheryl D; Kuo, Chi-Yun; Irschick, Duncan J

    2016-05-01

    How morphology changes with size can have profound effects on the life history and ecology of an animal. For apex predators that can impact higher level ecosystem processes, such changes may have consequences for other species. Tiger sharks (Galeocerdo cuvier) are an apex predator in tropical seas, and, as adults, are highly migratory. However, little is known about ontogenetic changes in their body form, especially in relation to two aspects of shape that influence locomotion (caudal fin) and feeding (head shape). We captured digital images of the heads and caudal fins of live tiger sharks from Southern Florida and the Bahamas ranging in body size (hence age), and quantified shape of each using elliptical Fourier analysis. This revealed changes in the shape of the head and caudal fin of tiger sharks across ontogeny. Smaller juvenile tiger sharks show an asymmetrical tail with the dorsal (upper) lobe being substantially larger than the ventral (lower) lobe, and transition to more symmetrical tail in larger adults, although the upper lobe remains relatively larger in adults. The heads of juvenile tiger sharks are more conical, which transition to relatively broader heads over ontogeny. We interpret these changes as a result of two ecological transitions. First, adult tiger sharks can undertake extensive migrations and a more symmetrical tail could be more efficient for swimming longer distances, although we did not test this possibility. Second, adult tiger sharks expand their diet to consume larger and more diverse prey with age (turtles, mammals, and elasmobranchs), which requires substantially greater bite area and force to process. In contrast, juvenile tiger sharks consume smaller prey, such as fishes, crustaceans, and invertebrates. Our data reveal significant morphological shifts in an apex predator, which could have effects for other species that tiger sharks consume and interact with. © 2016 Wiley Periodicals, Inc.

  8. Cell cycles and proliferation patterns in Haematococcus pluvialis

    Science.gov (United States)

    Zhang, Chunhui; Liu, Jianguo; Zhang, Litao

    2017-09-01

    Most studies on Haematococcus pluvialis have been focused on cell growth and astaxanthin accumulation; far less attention has been paid to cell cycles and proliferation patterns. The purpose of this study was to clarify cell cycles and proliferation patterns in H. pluvialis microscopically using a camera and video recorder system. The complicated life history of H. pluvialis can be divided into two stages: the motile stage and the non-motile stage. All the cells can be classified into forms as follows: motile cell, nonmotile cell, zoospore and aplanospore. The main cell proliferation, both in the motile phase and non-motile phase in H. pluvialis, is by asexual reproduction. Under normal growth conditions, a motile cell usually produces two, sometimes four, and exceptionally eight zoospores. Under unfavorable conditions, the motile cell loses its flagella and transforms into a non-motile cell, and the non-motile cell usually produces 2, 4 or 8 aplanospores, and occasionally 20-32 aplanospores, which further develop into non-motile cells. Under suitable conditions, the non-motile cell is also able to release zoospores. The larger non-motile cells produce more than 16 zoospores, and the smaller ones produce 4 or 8 zoospores. Vegetative reproduction is by direct cell division in the motile phase and by occasional cell budding in the non-motile phase. There is, as yet, no convincing direct evidence for sexual reproduction.

  9. Radiographic evaluation of caudal vena cava size in dogs

    International Nuclear Information System (INIS)

    Lehmkuhl, L.B.; Bonagura, J.D.; Biller, D.S.; Hartman, W.M.

    1997-01-01

    Dilation of the caudal vena cava (CVC) on lateral thoracic radiographs is often interpreted as suggestive of right-sided congestive heart failure, To quantitate the clinical utility of evaluating CVC size as an indicator of right-sided heart disease, we compared the ratio of the diameter of the CVC as measured on a left lateral thoracic radiograph to the descending aorta (Ao), length of the thoracic vertebra above the tracheal bifurcation (VL), and width of the right fourth rib (R4) in 35 dogs with right heart disease and 35 control dogs, Each CVC ratio(CVC/Ao, CVC/VL, CVC/R4) was statistically larger in dogs with right heart disease, Response operating characteristic curves and likelihood ratios were used to determine ratios helpful in identifying dogs with right heart disease. A CVC/Ao > 1.50, CVC/VL > 1.30, or CVC/R4 > 3.50 are strongly suggestive of a right-sided heart abnormality in a patient

  10. Endothelial cell proliferation in swine experimental aneurysm after coil embolization.

    Directory of Open Access Journals (Sweden)

    Yumiko Mitome-Mishima

    Full Text Available After coil embolization, recanalization in cerebral aneurysms adversely influences long-term prognosis. Proliferation of endothelial cells on the coil surface may reduce the incidence of recanalization and further improve outcomes after coil embolization. We aimed to map the expression of proliferating tissue over the aneurysmal orifice and define the temporal profile of tissue growth in a swine experimental aneurysm model. We compared the outcomes after spontaneous thrombosis with those of coil embolization using histological and morphological techniques. In aneurysms that we not coiled, spontaneous thrombosis was observed, and weak, easily detachable proliferating tissue was evident in the aneurysmal neck. In contrast, in the coil embolization group, histological analysis showed endothelial-like cells lining the aneurysmal opening. Moreover, immunohistochemical and morphological analysis suggested that these cells were immature endothelial cells. Our results indicated the existence of endothelial cell proliferation 1 week after coil embolization and showed immature endothelial cells in septal tissue between the systemic circulation and the aneurysm. These findings suggest that endothelial cells are lead to and proliferate in the former aneurysmal orifice. This is the first examination to evaluate the temporal change of proliferating tissue in a swine experimental aneurysm model.

  11. Laparoscopic Radical Extended Right Hemicolectomy Using a Caudal-to-Cranial Approach.

    Science.gov (United States)

    Zou, Liaonan; Xiong, Wenjun; Mo, Delong; He, Yaobin; Li, Hongming; Tan, Ping; Wang, Wei; Wan, Jin

    2016-08-01

    Due to the emphasis of oncologic principle, a medial-to-lateral approach for laparoscopic right hemicolectomy was recommended.1 (,) 2 This approach, however, is technically challenging and involves several limitations with overweight patients, whose mesocolon may be too thick for identification of the vessel landmarks. Moreover, it is difficult for inexperienced surgeons to enter the retroperitoneum space accurately. This report describes a caudal-to-cranial approach for laparoscopic radical extended right hemicolectomy. First, a "yellow-white borderline" between the right mesostenium and retroperitoneum in the right iliac fossa is dissected as the entry for separation of the fusion fascial space between the visceral and parietal peritoneum.3 The right Toldt's fascia is dissected and expanded medial to the periphery of the superior mesenteric vein (SMV), cranial to the pancreas head, and lateral to the ascending colon. The posterior paries of ileocolic vessels (ICVs), right colic vessels (RCVs), and Henle's trunk are exposed. Second, the mesocolon between the ICV and SMV is dissected safely, and the ICV, RCV, and right gastroepiploic vessels as well as the right branch of the middle colic vessel are divided and ligated easily because of the separated retroperitoneal space. The lymph nodes along the SMV are dissected using a caudal-to-cranial approach. Third, the greater omental is dissected for full mobilization of the mesocolon containing 10 cm of normal colon distal to the lesion followed by complete mobilization of the lateral attachments of the ascending colon. In this study, 10 men and 8 women with hepatic flexure cancer underwent laparoscopic extended right hemicolectomy using a caudal-to-cranial approach. No conversion was recorded. The overall complication rate was 11.2 %, including one case of pulmonary infection and one case of urinary tract infection, both of which were cured with conservative measures. The mean age of the patients was 61.3 ± 12.7

  12. Neuronal models for evaluation of proliferation in vitro using high content screening

    International Nuclear Information System (INIS)

    Mundy, William R.; Radio, Nicholas M.; Freudenrich, Theresa M.

    2010-01-01

    In vitro test methods can provide a rapid approach for the screening of large numbers of chemicals for their potential to produce toxicity (hazard identification). In order to identify potential developmental neurotoxicants, a battery of in vitro tests for neurodevelopmental processes such as cell proliferation, differentiation, growth, and synaptogenesis has been proposed. The development of in vitro approaches for toxicity testing will require choosing a model system that is appropriate to the endpoint of concern. This study compared several cell lines as models for neuronal proliferation. The sensitivities of neuronal cell lines derived from three species (PC12, rat; N1E-115, mouse; SH-SY5Y, human) to chemicals known to affect cell proliferation were assessed using a high content screening system. After optimizing conditions for cell growth in 96-well plates, proliferation was measured as the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into replicating DNA during S phase. BrdU-labeled cells were detected by immunocytochemistry and cell counts were obtained using automated image acquisition and analysis. The three cell lines showed approximately 30-40% of the population in S phase after a 4 h pulse of BrdU. Exposure to the DNA polymerase inhibitor aphidicolin for 20 h prior to the 4 h pulse of BrdU significantly decreased proliferation in all three cell lines. The sensitivities of the cell lines were compared by exposure to eight chemicals known to affect proliferation (positive controls) and determination of the concentration inhibiting proliferation by 50% of control (I 50 ). PC12 cells were the most sensitive to chemicals; 6 out of 8 chemicals (aphidicolin, cadmium, cytosine arabinoside, dexamethasone, 5-fluorouracil, and methylmercury) inhibited proliferation at the concentrations tested. SH-SY5Y cells were somewhat less sensitive to chemical effects, with five out of eight chemicals inhibiting proliferation; dexamethasone had no effect, and cadmium

  13. α-Ketoglutarate Promotes Pancreatic Progenitor-Like Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Jing Song

    2018-03-01

    Full Text Available A major source of β cell generation is pancreatic progenitor-like cell differentiation. Multiple studies have confirmed that stem cell metabolism plays important roles in self-renewal and proliferation. In the absence of glucose, glutamine provides the energy for cell division and growth. Furthermore, α-ketoglutarate (αKG, a precursor for glutamine synthesis, is sufficient for enabling glutamine-independent cell proliferation. We have demonstrated that αKG contributes to the large-scale proliferation of pancreatic progenitor-like cells that can provide an ample amount of clinically relevant β cells. We compared the mRNA expression of a subset of genes, the abundance of ATP, reactive oxide species, mitochondrial number, and the colony-forming frequency between mouse pancreatic CD133+ and CD133− cells. We employed Real-Time PCR, immunostaining and passage assays to investigate self-renewal and proliferation of pancreatic progenitor-like cells in a 3D culture system in the presence and absence of αKG. The energy metabolism of CD133+ cells was more prone to oxidative phosphorylation. However, in the 3D culture system, when αKG was supplemented to the culture medium, the proliferation of the pancreatic progenitor-like cells was significantly elevated. We confirmed that the presence of αKG correlated with the up-regulation of Ten-Eleven Translocation (Tet. αKG can promote the proliferation of pancreatic progenitor-like cells via the up-regulation of Tet.

  14. α-Ketoglutarate Promotes Pancreatic Progenitor-Like Cell Proliferation.

    Science.gov (United States)

    Song, Jing; Ma, Dongshen; Xing, Yun; Tang, Shanshan; Alahdal, Murad; Guo, Jiamin; Pan, Yi; Zhang, Yanfeng; Shen, Yumeng; Wu, Qiong; Lu, Zhou; Jin, Liang

    2018-03-22

    A major source of β cell generation is pancreatic progenitor-like cell differentiation. Multiple studies have confirmed that stem cell metabolism plays important roles in self-renewal and proliferation. In the absence of glucose, glutamine provides the energy for cell division and growth. Furthermore, α-ketoglutarate (αKG), a precursor for glutamine synthesis, is sufficient for enabling glutamine-independent cell proliferation. We have demonstrated that αKG contributes to the large-scale proliferation of pancreatic progenitor-like cells that can provide an ample amount of clinically relevant β cells. We compared the mRNA expression of a subset of genes, the abundance of ATP, reactive oxide species, mitochondrial number, and the colony-forming frequency between mouse pancreatic CD133⁺ and CD133 - cells. We employed Real-Time PCR, immunostaining and passage assays to investigate self-renewal and proliferation of pancreatic progenitor-like cells in a 3D culture system in the presence and absence of αKG. The energy metabolism of CD133⁺ cells was more prone to oxidative phosphorylation. However, in the 3D culture system, when αKG was supplemented to the culture medium, the proliferation of the pancreatic progenitor-like cells was significantly elevated. We confirmed that the presence of αKG correlated with the up-regulation of Ten-Eleven Translocation (Tet). αKG can promote the proliferation of pancreatic progenitor-like cells via the up-regulation of Tet.

  15. Control of cell proliferation by a porous chitosan scaffold with multiple releasing capabilities

    Science.gov (United States)

    Cai, Shu-Jyun; Li, Ching-Wen; Weihs, Daphne; Wang, Gou-Jen

    2017-01-01

    Abstract The aim of this study was to develop a porous chitosan scaffold with long-acting drug release as an artificial dressing to promote skin wound healing. The dressing was fabricated by pre-freezing at different temperatures (−20 and −80 °C) for different periods of time, followed by freeze-drying to form porous chitosan scaffolds with different pore sizes. The chitosan scaffolds were then used to investigate the effect of the controlled release of fibroblast growth factor-basic (bFGF) and transforming growth factor-β1 (TGFβ1) on mouse fibroblast cells (L929) and bovine carotid endothelial cells (BEC). The biocompatibility of the prepared chitosan scaffold was confirmed with WST-1 proliferation and viability assay, which demonstrated that the material is suitable for cell growth. The results of this study show that the pore sizes of the porous scaffolds prepared by freeze-drying can change depending on the pre-freezing temperature and time via the formation of ice crystals. In this study, the scaffolds with the largest pore size were found to be 153 ± 32 μm and scaffolds with the smallest pores to be 34 ± 9 μm. Through cell culture analysis, it was found that the concentration that increased proliferation of L929 cells for bFGF was 0.005 to 0.1 ng/mL, and the concentration for TGFβ1 was 0.005 to 1 ng/mL. The cell culture of the chitosan scaffold and growth factors shows that 3.75 ng of bFGF in scaffolds with pore sizes of 153 ± 32 μm can promote L929 cell proliferation, while 400 pg of TGFβ1 in scaffolds with pore size of 34 ± 9 μm can enhance the proliferation of L929 cells, but also inhibit BEC proliferation. It is proposed that the prepared chitosan scaffolds can form a multi-drug (bFGF and TGFβ1) release dressing that has the ability to control wound healing via regulating the proliferation of different cell types. PMID:29230255

  16. Metformin Antagonizes Cancer Cell Proliferation by Suppressing Mitochondrial-Dependent Biosynthesis.

    Directory of Open Access Journals (Sweden)

    Takla Griss

    2015-12-01

    Full Text Available Metformin is a biguanide widely prescribed to treat Type II diabetes that has gained interest as an antineoplastic agent. Recent work suggests that metformin directly antagonizes cancer cell growth through its actions on complex I of the mitochondrial electron transport chain (ETC. However, the mechanisms by which metformin arrests cancer cell proliferation remain poorly defined. Here we demonstrate that the metabolic checkpoint kinases AMP-activated protein kinase (AMPK and LKB1 are not required for the antiproliferative effects of metformin. Rather, metformin inhibits cancer cell proliferation by suppressing mitochondrial-dependent biosynthetic activity. We show that in vitro metformin decreases the flow of glucose- and glutamine-derived metabolic intermediates into the Tricarboxylic Acid (TCA cycle, leading to reduced citrate production and de novo lipid biosynthesis. Tumor cells lacking functional mitochondria maintain lipid biosynthesis in the presence of metformin via glutamine-dependent reductive carboxylation, and display reduced sensitivity to metformin-induced proliferative arrest. Our data indicate that metformin inhibits cancer cell proliferation by suppressing the production of mitochondrial-dependent metabolic intermediates required for cell growth, and that metabolic adaptations that bypass mitochondrial-dependent biosynthesis may provide a mechanism of tumor cell resistance to biguanide activity.

  17. Ultrasound versus fluoroscopy-guided caudal epidural steroid injection for the treatment of chronic low back pain with radiculopathy: A randomised, controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Arindam Kumar Hazra

    2016-01-01

    Full Text Available Background and Aims: Caudal epidural steroid administration is an effective treatment for chronic low back pain (LBP. Fluoroscopy guidance is the gold standard for pain procedures. Ultrasound guidance is recently being used in pain clinic procedures. We compared the fluoroscopy guidance and ultrasound guidance for caudal epidural steroid injection with respect to the time needed for correct placement of the needle and clinical effectiveness in patients with chronic LBP. Methods: Fifty patients with chronic LBP with radiculopathy, not responding to conventional medical management, were randomly allocated to receive injection depot methyl prednisolone (40 mg through caudal route either using ultrasound guidance (Group U, n = 25 or fluoroscopy guidance (Group F, n = 25. Pre-procedural visual analogue scale (VAS score and Oswestry Disability Index (ODI were noted. During the procedure, the time needed for correct placement of needle was observed. Adverse events, if any, were also noted. All patients were followed up for next 2 months to evaluate Visual Analogue Scale (VAS score and ODI at the 2nd week and again at the end of 1st and 2nd month. Results: The needle-placement time was less using ultrasound guidance as compared to fluoroscopy guidance (119 ± 7.66 vs. 222.28 ± 29.65 s, respectively,P< 0.001. Significant reduction in VAS score and ODI (clinical improvement was noted in the follow-up time points and comparable between the groups at all time points. Conclusion: Ultrasound guidance can be a safe alternative tool for achieving faster needle placement in caudal epidural space. Clinical effectiveness (reduction of VAS and ODI scores remains comparable between both the techniques.

  18. Caudal anesthesia in a patient with peritonitis: Is it safe??

    Directory of Open Access Journals (Sweden)

    H Kako

    2016-01-01

    Full Text Available Neuraxial anesthesia combined with general anesthesia has become a widely accepted method of providing effective postoperative analgesia and decreasing intraoperative anesthetic needs in the pediatric population. In clinical practice, there still appears to be hesitancy for the use of a neuraxial technique (spinal or epidural in patients at risk for bacteremia or with an on-going systemic infection. However, evidence-based medicine lacks any data to support an increase in the risk of infectious complications following neuraxial anesthesia. We present two pediatric patients with intra-abdominal infectious processes who received caudal epidural blockade for postoperative operative analgesia. The use of neuraxial techniques in patients at risk for bacteremia is reviewed, evidence-based medicine regarding the risks of infection discussed, and the potential favorable effects of neuraxial blockade on the neurohumoral response to sepsis and the systemic inflammatory responses presented.

  19. Epidermal growth factor in the rat prostate

    DEFF Research Database (Denmark)

    Tørring, Niels; Jørgensen, P E; Poulsen, Steen Seier

    1998-01-01

    Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate.......Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate....

  20. Plasma rich in growth factors (PRGF-Endoret) stimulates proliferation and migration of primary keratocytes and conjunctival fibroblasts and inhibits and reverts TGF-beta1-Induced myodifferentiation.

    Science.gov (United States)

    Anitua, Eduardo; Sanchez, Mikel; Merayo-Lloves, Jesus; De la Fuente, Maria; Muruzabal, Francisco; Orive, Gorka

    2011-08-01

    Plasma rich in growth factors (PRGF-Endoret) technology is an autologous platelet-enriched plasma obtained from patient's own blood, which after activation with calcium chloride allows the release of a pool of biologically active proteins that influence and promote a range of biological processes including cell recruitment, and growth and differentiation. Because ocular surface wound healing is mediated by different growth factors, we decided to explore the potential of PRGF-Endoret technology in stimulating the biological processes related with fibroblast-induced tissue repair. Furthermore, the anti-fibrotic properties of this technology were also studied. Blood from healthy donors was collected, centrifuged and, whole plasma column (WP) and the plasma fraction with the highest platelet concentration (F3) were drawn off, avoiding the buffy coat. Primary human cells including keratocytes and conjunctival fibroblasts were used to perform the "in vitro" investigations. The potential of PRGF-Endoret in promoting wound healing was evaluated by means of a proliferation and migration assays. Fibroblast cells were induced to myofibroblast differentiation after the treatment with 2.5 ng/mL of TGF-β1. The capability of WP and F3 to prevent and inhibit TGF-β1-induced differentiation was evaluated. Results show that this autologous approach significantly enhances proliferation and migration of both keratocytes and conjunctival fibroblasts. In addition, plasma rich in growth factors prevents and inhibits TGF-β1-induced myofibroblast differentiation. No differences were found between WP and F3 plasma fractions. These results suggest that PRGF-Endoret could reduce scarring while stimulating wound healing in ocular surface. F3 or whole plasma column show similar biological effects in keratocytes and conjunctival fibroblast cells.

  1. In vitro PROLIFERATION ABILITY OF AXILLARY BUDS IN Musa spp

    African Journals Online (AJOL)

    AISA

    The proliferation rate of Axillary and apical buds and other growth parameters ... types of buds after four to five sub cultures in all the varieties except for CRBP 39 where the axillary bud exhibits ..... propagation, conservation and exchange.

  2. TAM receptors support neural stem cell survival, proliferation and neuronal differentiation.

    Science.gov (United States)

    Ji, Rui; Meng, Lingbin; Jiang, Xin; Cvm, Naresh Kumar; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

    2014-01-01

    Tyro3, Axl and Mertk (TAM) receptor tyrosine kinases play multiple functional roles by either providing intrinsic trophic support for cell growth or regulating the expression of target genes that are important in the homeostatic regulation of immune responses. TAM receptors have been shown to regulate adult hippocampal neurogenesis by negatively regulation of glial cell activation in central nervous system (CNS). In the present study, we further demonstrated that all three TAM receptors were expressed by cultured primary neural stem cells (NSCs) and played a direct growth trophic role in NSCs proliferation, neuronal differentiation and survival. The cultured primary NSCs lacking TAM receptors exhibited slower growth, reduced proliferation and increased apoptosis as shown by decreased BrdU incorporation and increased TUNEL labeling, than those from the WT NSCs. In addition, the neuronal differentiation and maturation of the mutant NSCs were impeded, as characterized by less neuronal differentiation (β-tubulin III+) and neurite outgrowth than their WT counterparts. To elucidate the underlying mechanism that the TAM receptors play on the differentiating NSCs, we examined the expression profile of neurotrophins and their receptors by real-time qPCR on the total RNAs from hippocampus and primary NSCs; and found that the TKO NSC showed a significant reduction in the expression of both nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), but accompanied by compensational increases in the expression of the TrkA, TrkB, TrkC and p75 receptors. These results suggest that TAM receptors support NSCs survival, proliferation and differentiation by regulating expression of neurotrophins, especially the NGF.

  3. Evaluación de requerimientos ecológicos para el diseño de regímenes ambientales de caudales fluviales

    Directory of Open Access Journals (Sweden)

    Juan Manuel Diez-Hernández

    2008-11-01

    Full Text Available Las sociedades avanzadas medioambientalmente están reclamando progresivamente una gestión fluvial auténticamente integral, que implemente Planes de Manejo de Cuencas Hidrográficas fundamentados en el paradigma del Régimen Ambiental de Caudales (RAC. Este trabajo sugiere una metodología genérica para establecer RAC confiables, que posibiliten el aprovechamiento hídrico a un coste ecológico admisible. Adicionalmente, plantea los criterios y técnicas preferentes para la evaluación de los requerimientos ecosistémicos de caudal, los cuales componen el RAC mediante el Régimen de Caudales Ecológicos (RCE. La adaptación de estos procedimientos para los ríos de Colombia favorecerá la conservación de su valiosa biodiversidad. / The environmentally advanced societies are claiming progressively an authentically integral fluvial management, that implements Watershed Management Programs based on the paradigm of the Environmental Flows Regime (EFR. This work suggests a generic methodology for the reliable EFR setting, that facilitate the water use with an environmental acceptable cost. Additionally, it outlines the approaches and outstanding techniques for the evaluation of instream flow requirements, which constitute the EFR by means of the Instream Flow Regime (IFR. The adaptation of these approaches to the Colombian rivers will contribute to the conservation of their valuable biodiversity.

  4. Serum from plasma rich in growth factors regenerates rabbit corneas by promoting cell proliferation, migration, differentiation, adhesion and limbal stemness.

    Science.gov (United States)

    Etxebarria, Jaime; Sanz-Lázaro, Sara; Hernáez-Moya, Raquel; Freire, Vanesa; Durán, Juan A; Morales, María-Celia; Andollo, Noelia

    2017-12-01

    To evaluate the regenerating potential and the mechanisms through which the autologous serum derived from plasma rich in growth factors (s-PRGF) favours corneal wound healing in vitro and in vivo. We compared the effect of various concentrations of s-PRGF versus fetal bovine serum (FBS) and control treatment in rabbit primary corneal epithelial and stromal cells and wounded rabbit corneas. Cell proliferation was measured using an enzymatic colorimetric assay. In vitro and in vivo wound-healing progression was assessed by image-analysis software. Migration and invasion were evaluated using transfilter assays. Histological structure was analysed in stained sections. Protein expression was evaluated by immunohistochemistry. s-PRGF promoted the robust proliferation of epithelial cultures at any concentration, similar to FBS. Likewise, s-PRGF and FBS produced similar re-epithelialization rates in in vitro wound-healing assays. In vivo, s-PRGF treatment accelerated corneal wound healing in comparison with control treatment. This difference was significant only for 100% s-PRGF treatment in our healthy rabbit model. Histological analysis confirmed normal epithelialization in all cases. Immunohistochemistry showed a higher expression of cytokeratins 3/76 and 15, zonula occludens-1 and alpha-smooth muscle actin proteins as a function of s-PRGF concentration. Notably, keratocyte density in the anterior third of the stroma increased with increase in s-PRGF concentration, suggesting an in vivo chemotactic effect of s-PRGF on keratocytes that was further confirmed in vitro. s-PRGF promotes proliferation and migration and influences limbal stemness, adhesion and fibrosis during corneal healing. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  5. Wingless promotes proliferative growth in a gradient-independent manner.

    Science.gov (United States)

    Baena-Lopez, Luis Alberto; Franch-Marro, Xavier; Vincent, Jean-Paul

    2009-10-06

    Morphogens form concentration gradients that organize patterns of cells and control growth. It has been suggested that, rather than the intensity of morphogen signaling, it is its gradation that is the relevant modulator of cell proliferation. According to this view, the ability of morphogens to regulate growth during development depends on their graded distributions. Here, we describe an experimental test of this model for Wingless, one of the key organizers of wing development in Drosophila. Maximal Wingless signaling suppresses cellular proliferation. In contrast, we found that moderate and uniform amounts of exogenous Wingless, even in the absence of endogenous Wingless, stimulated proliferative growth. Beyond a few cell diameters from the source, Wingless was relatively constant in abundance and thus provided a homogeneous growth-promoting signal. Although morphogen signaling may act in combination with as yet uncharacterized graded growth-promoting pathways, we suggest that the graded nature of morphogen signaling is not required for proliferation, at least in the developing Drosophila wing, during the main period of growth.

  6. Yorkie regulates epidermal wound healing in Drosophila larvae independently of cell proliferation and apoptosis.

    Science.gov (United States)

    Tsai, Chang-Ru; Anderson, Aimee E; Burra, Sirisha; Jo, Juyeon; Galko, Michael J

    2017-07-01

    Yorkie (Yki), the transcriptional co-activator of the Hippo signaling pathway, has well-characterized roles in balancing apoptosis and cell division during organ growth control. Yki is also required in diverse tissue regenerative contexts. In most cases this requirement reflects its well-characterized roles in balancing apoptosis and cell division. Whether Yki has repair functions outside of the control of cell proliferation, death, and growth is not clear. Here we show that Yki and Scalloped (Sd) are required for epidermal wound closure in the Drosophila larval epidermis. Using a GFP-tagged Yki transgene we show that Yki transiently translocates to some epidermal nuclei upon wounding. Genetic analysis strongly suggests that Yki interacts with the known wound healing pathway, Jun N-terminal kinase (JNK), but not with Platelet Derived Growth Factor/Vascular-Endothelial Growth Factor receptor (Pvr). Yki likely acts downstream of or parallel to JNK signaling and does not appear to regulate either proliferation or apoptosis in the larval epidermis during wound repair. Analysis of actin structures after wounding suggests that Yki and Sd promote wound closure through actin regulation. In sum, we found that Yki regulates an epithelial tissue repair process independently of its previously documented roles in balancing proliferation and apoptosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Effect of young maternal age and skeletal growth on placental growth and development.

    Science.gov (United States)

    Hayward, C E; Greenwood, S L; Sibley, C P; Baker, P N; Jones, R L

    2011-12-01

    Teenagers are susceptible to delivering small-for-gestational-age infants. Previous studies implicate continued skeletal growth as a contributory factor, and impaired placental development was the primary cause of fetal growth restriction in growing adolescent sheep. The aims of this study were to examine the impact of young maternal age and growth on placental development. Placentas were collected from 31 teenagers, of which 12 were growing and 17 non-growing based on knee height measurements. An adult control group (n = 12) was included. Placental weight and morphometric measurements of villous, syncytiotrophoblast, fibrin and vessel areas, as well as indices of proliferation and apoptosis, were analysed in relation to maternal growth and age. Growing teenagers had a higher birthweight:placental weight ratio than non-growing teenagers (p adult and teenage pregnancies. Maternal smoking, a potential confounding factor, did not exert a major influence on the placental parameters examined, except for a stimulatory effect on placental proliferation (p development, and is consistent with our recent observations that maternal growth was not detrimental to fetal growth. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Desarrollo osteológico de la columna vertebral y del complejo caudal de larvas de Lutjanus guttatus (Perciformes: Lutjanidae en condiciones de cultivo

    Directory of Open Access Journals (Sweden)

    Luz Estela Rodríguez-Ibarra

    2015-03-01

    Full Text Available El pargo flamenco (Lutjanus guttatus es una especie de importancia comercial en México con un gran potencial para su cultivo. El estudio osteológico en estadios tempranos de esta especie bajo condiciones controladas, es una herramienta importante para el conocimiento de su estructura ósea normal y poder detectar las malformaciones que se puedan presentar. El objetivo del presente trabajo se realizó para conocer y describir el desarrollo osteológico normal de la columna vertebral y el complejo caudal de 540 larvas de 2.1 a 17.5mm de longitud total (LT bajo condiciones de cultivo a 28°C, 5.74mg/L de oxígeno y 32.2UPS de salinidad. Diariamente se tomó una muestra de 15 organismos desde el día uno hasta el 36 después de la eclosión (DDE y se procesaron con las técnicas de clareado y tinción de cartílago (azul aciano y hueso (rojo alizarina para llevar a cabo la descripción de las estructuras. La columna vertebral se divide en región abdominal con diez vértebras y región caudal compuesta por 14 vértebras incluido el urostilo. El desarrollo del esqueleto axial inicia con la formación de los arcos neurales y hemales a los 3.8mm de LT. A los 4.1mm de LT empieza la formación de los hipurales y parahipural que son elementos caudales. Entre los 5.3 y 5.8mm de LT se observó en pre-flexión y flexión del notocordio y la formación de todos los hipurales. La osificación de las vértebras en la región abdominal y en algunos arcos neurales inició a los 9.5mm de LT. A los 10.2mm de LT se osificó la región caudal y todos los arcos neurales y hemales. A los 11.2mm LT se osificaron todas las vértebras abdominales con sus respectivos arcos neurales y los parapófisis, mientras que los elementos del esqueleto caudal que se osificaron fueron los hipurales, parahipurales y las espinas hemales modificadas. A los 15.5mm de LT se osificaron los radios de la aleta caudal y 12 espinas neurales y 3 hemales. El proceso de osificación de las

  9. Targeting of GIT1 by miR-149* in breast cancer suppresses cell proliferation and metastasis in vitro and tumor growth in vivo

    Directory of Open Access Journals (Sweden)

    Dong Y

    2017-12-01

    Full Text Available Yan Dong,1,* Cai Chang,2,* Jingtian Liu,3 Jinwei Qiang4 1Department of Ultrasonography, Jinshan Hospital, 2Department of Ultrasonography, Cancer Center, 3Department of General Surgery, 4Department of Radiology, Jinshan Hospital, Fudan University, Shanghai, China *These authors contributed equally to this work Abstract: Breast cancer remains a major cause of cancer-related death in women worldwide. Dysregulation of microRNAs (miRNAs is involved in the initiation and progression of breast cancer. Moreover, it was found that GIT1 was widely involved in the development of many human cancers. Herein, we aimed to investigate the expression changes of miR-149* and GIT1 and the functional effects of miR-149*/GIT1 link in breast cancer. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR and Western blot (WB were used to examine the expression levels of miR-149* and GIT1. Dual luciferase reporter assay was utilized to confirm the target interaction between miR-149* and GIT1. The biological functions, including cell proliferation, invasion, and migration, of miR-149* and GIT1 were determined by MTT assay and Transwell assays, respectively. Eventually, the tumor xenograft model in nude mice injected with stable transfected MDA-MB-231 cells was established to verify the effects of miR-149* and GIT1 on tumor growth. Our results showed that miR-149* expression was decreased, whereas GIT1 expression was increased in clinical samples of breast cancer. Based on the inverse expression trend between miR-149* and GIT1, we further demonstrated that miR-149* indeed directly targets GIT1. Subsequently, it was observed that inhibition of miR-149* significantly promoted cell proliferation, invasion, and migration, but the ability of cell proliferation, invasion, and migration was obviously declined after silencing of GIT1 in MDA-MB-231 cells transfected with miR-149* mimic and/or si-GIT1. Finally, it was also found that elevated miR-149* decelerated

  10. Paris polyphylla extract inhibits proliferation and promotes apoptosis ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of Paris polyphylla extract (PPE) on proliferation and apoptosis in A549 human lung cancer cells. Methods: Morphological changes were examined by microscopy in A549 cells after exposure to PPE. Trypan blue staining of living cells was used to aid the construction of the cell growth curve ...

  11. Studies on the age-dependent proliferation kinetics of the epithelium of the rat small intestine

    International Nuclear Information System (INIS)

    Kranz, D.; Dietze, F.; Laue, R.; Fuhrmann, I.

    1980-01-01

    The small intestine of 244 Wistar rats, aged 6 days, 6 weeks, 6, 12, 23, and 28 months, respectively. were investigated autoradiographically as to their age-dependent cell proliferation kinetics of the mucosal epithelial cells. There were age-dependent differences concerning the hourly regeneration ratio of the crypt cells and the migration velocity of the enterocytes. Both parameters became greater while the existing non growth fraction became smaller with increasing age. The non growth fraction seems to be a reserve being involved into the proliferating pool if required

  12. Nitric oxide from inflammatory origin impairs neural stem cell proliferation by inhibiting epidermal growth factor receptor signaling

    Directory of Open Access Journals (Sweden)

    Bruno Pereira Carreira

    2014-10-01

    Full Text Available Neuroinflammation is characterized by activation of microglial cells, followed by production of nitric oxide (NO, which may have different outcomes on neurogenesis, favoring or inhibiting this process. In the present study, we investigated how the inflammatory mediator NO can affect proliferation of neural stem cells (NSC, and explored possible mechanisms underlying this effect. We investigated which mechanisms are involved in the regulation of NSC proliferation following treatment with an inflammatory stimulus (LPS plus IFN-γ, using a culture system of subventricular zone (SVZ-derived NSC mixed with microglia cells obtained from wild-type mice (iNOS+/+ or from iNOS knockout mice (iNOS-/-. We found an impairment of NSC cell proliferation in iNOS+/+ mixed cultures, which was not observed in iNOS-/- mixed cultures. Furthermore, the increased release of NO by activated iNOS+/+ microglial cells decreased the activation of the ERK/MAPK signaling pathway, which was concomitant with an enhanced nitration of the EGF receptor. Preventing nitrogen reactive species formation with MnTBAP, a scavenger of peroxynitrite, or using the peroxynitrite degradation catalyst FeTMPyP, cell proliferation and ERK signaling were restored to basal levels in iNOS+/+ mixed cultures. Moreover, exposure to the NO donor NOC-18 (100 µM, for 48 h, inhibited SVZ-derived NSC proliferation. Regarding the antiproliferative effect of NO, we found that NOC-18 caused the impairment of signaling through the ERK/MAPK pathway, which may be related to increased nitration of the EGF receptor in NSC. Using MnTBAP nitration was prevented, maintaining ERK signaling, rescuing NSC proliferation. We show that NO from inflammatory origin leads to a decreased function of the EGF receptor, which compromised proliferation of NSC. We also demonstrated that NO-mediated nitration of the EGF receptor caused a decrease in its phosphorylation, thus preventing regular proliferation signaling through the

  13. EGFR/Ras Signaling Controls Drosophila Intestinal Stem Cell Proliferation via Capicua-Regulated Genes.

    Directory of Open Access Journals (Sweden)

    Yinhua Jin

    2015-12-01

    Full Text Available Epithelial renewal in the Drosophila intestine is orchestrated by Intestinal Stem Cells (ISCs. Following damage or stress the intestinal epithelium produces ligands that activate the epidermal growth factor receptor (EGFR in ISCs. This promotes their growth and division and, thereby, epithelial regeneration. Here we demonstrate that the HMG-box transcriptional repressor, Capicua (Cic, mediates these functions of EGFR signaling. Depleting Cic in ISCs activated them for division, whereas overexpressed Cic inhibited ISC proliferation and midgut regeneration. Epistasis tests showed that Cic acted as an essential downstream effector of EGFR/Ras signaling, and immunofluorescence showed that Cic's nuclear localization was regulated by EGFR signaling. ISC-specific mRNA expression profiling and DNA binding mapping using DamID indicated that Cic represses cell proliferation via direct targets including string (Cdc25, Cyclin E, and the ETS domain transcription factors Ets21C and Pointed (pnt. pnt was required for ISC over-proliferation following Cic depletion, and ectopic pnt restored ISC proliferation even in the presence of overexpressed dominant-active Cic. These studies identify Cic, Pnt, and Ets21C as critical downstream effectors of EGFR signaling in Drosophila ISCs.

  14. P44/WDR77 restricts the sensitivity of proliferating cells to TGFβ signaling

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Pengfei [Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, Hubei 430022 (China); Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States); Gao, Shen [Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States); Gu, Zhongping [Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038 (China); Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States); Huang, Tao [Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, Hubei 430022 (China); Wang, Zhengxin, E-mail: zhenwang@mdanderson.org [Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States)

    2014-07-18

    Highlights: • P44/WDR77 causes proliferating cells to become non-responsive to TGFβ signaling. • P44/WDR77 down-regulates TβRII and TβR2 expression. • P44/WDR77 down-regulated TGFβ signaling correlates with lung tumorigenesis. - Abstract: We previously reported that a novel WD-40 domain-containing protein, p44/WDR77, drives quiescent epithelial cells to re-enter the cell cycle and plays an essential role for growth of lung and prostate cancer cells. Transforming growth factor beta (TGFβ) signaling is important in the maintenance of non-transformed cells in the quiescent or slowly cycling stage. However, both non-transformed proliferating cells and human cancer cells are non-responsive to endogenous TGFβ signaling. The mechanism by which proliferating cells become refractory to TGFβ inhibition is not well established. Here, we found that silencing p44/WDR77 increased cellular sensitivity to TGFβ signaling and that this was inversely correlated with decreased cell proliferation. Smad2 or 3 phosphorylation, TGFβ-mediated transcription, and TGFβ2 and TGFβ receptor type II (TβRII) expression were dramatically induced by silencing of p44/WDR77. These data support the hypothesis that p44/WDR77 down-regulates the expression of the TGFβ ligand and its receptor, thereby leading to a cellular non-response to TGFβ signaling. Finally, we found that p44/WDR77 expression was correlated with cell proliferation and decreased TGFβ signaling during lung tumorigenesis. Together, these results suggest that p44/WDR77 expression causes the non-sensitivity of proliferating cells to TGFβ signaling, thereby contributing to cellular proliferation during lung tumorigenesis.

  15. Sirenomelia and severe caudal regression syndrome.

    Science.gov (United States)

    Seidahmed, Mohammed Z; Abdelbasit, Omer B; Alhussein, Khalid A; Miqdad, Abeer M; Khalil, Mohammed I; Salih, Mustafa A

    2014-12-01

    To describe cases of sirenomelia and severe caudal regression syndrome (CRS), to report the prevalence of sirenomelia, and compare our findings with the literature. Retrospective data was retrieved from the medical records of infants with the diagnosis of sirenomelia and CRS and their mothers from 1989 to 2010 (22 years) at the Security Forces Hospital, Riyadh, Saudi Arabia. A perinatologist, neonatologist, pediatric neurologist, and radiologist ascertained the diagnoses. The cases were identified as part of a study of neural tube defects during that period. A literature search was conducted using MEDLINE. During the 22-year study period, the total number of deliveries was 124,933 out of whom, 4 patients with sirenomelia, and 2 patients with severe forms of CRS were identified. All the patients with sirenomelia had single umbilical artery, and none were the infant of a diabetic mother. One patient was a twin, and another was one of triplets. The 2 patients with CRS were sisters, their mother suffered from type II diabetes mellitus and morbid obesity on insulin, and neither of them had a single umbilical artery. Other associated anomalies with sirenomelia included an absent radius, thumb, and index finger in one patient, Potter's syndrome, abnormal ribs, microphthalmia, congenital heart disease, hypoplastic lungs, and diaphragmatic hernia. The prevalence of sirenomelia (3.2 per 100,000) is high compared with the international prevalence of one per 100,000. Both cases of CRS were infants of type II diabetic mother with poor control, supporting the strong correlation of CRS and maternal diabetes.

  16. Effects of supplementation with green tea by-products on growth performance, meat quality, blood metabolites and immune cell proliferation in goats.

    Science.gov (United States)

    Ahmed, S T; Lee, J-W; Mun, H-S; Yang, C-J

    2015-12-01

    Forty-eight castrated male goats were used to determine the effects of feeding green tea by-products (GTB) on growth performance, meat quality, blood metabolites and immune cell proliferation. Experimental treatments consisted of basal diets supplemented with four levels of GTB (0%, 0.5%, 1.0% or 2.0%). Four replicate pens were assigned to each treatment with three goats per replicate. Increasing dietary GTB tended to linearly increase the overall average weight gain and feed intake (p = 0.09). Water holding capacity, pH and sensory attributes of meat were not affected by GTB supplementation, while cooking loss was reduced both linearly and quadratically (p goat meat were improved by GTB supplementation. Increasing dietary GTB quadratically increased protein and decreased crude fat (p goat meat. The proportions of monounsaturated fatty acid, polyunsaturated fatty acid (PUFA) and n-6 PUFA increased linearly (p meat were lower in the 2.0% GTB-supplemented group in all storage periods (p meat quality, blood metabolites and immune cell proliferation when supplemented as a feed additive in goat diet. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

  17. SerpinB1 Promotes Pancreatic β Cell Proliferation

    Energy Technology Data Exchange (ETDEWEB)

    El Ouaamari, Abdelfattah; Dirice, Ercument; Gedeon, Nicholas; Hu, Jiang; Zhou, Jian-Ying; Shirakawa, Jun; Hou, Lifei; Goodman, Jessica; Karampelias, Christos; Qiang, Guifeng; Boucher, Jeremie; Martinez, Rachael; Gritsenko, Marina A.; De Jesus, Dario F.; Kahraman, Sevim; Bhatt, Shweta; Smith, Richard D.; Beer, Hans-Dietmar; Jungtrakoon, Prapaporn; Gong, Yanping; Goldfine, Allison B.; Liew, Chong Wee; Doria, Alessandro; Andersson, Olov; Qian, Wei-Jun; Remold-O’Donnell, Eileen; Kulkarni, Rohit N.

    2016-01-01

    Compensatory β-cell growth in response to insulin resistance is a common feature in diabetes. We recently reported that liver-derived factors participate in this compensatory response in the liver insulin receptor knockout (LIRKO) mouse, a model of significant islet hyperplasia. Here we show that serpinB1 is a liver-derived secretory protein that controls β-cell proliferation. SerpinB1 is abundant in the hepatocyte secretome and sera derived from LIRKO mice. SerpinB1 and small molecule compounds that partially mimic serpinB1 activity enhanced proliferation of zebrafish, mouse and human β-cells. We report that serpinB1-induced β-cell replication requires protease inhibition activity and mice lacking serpinB1 exhibit attenuated β-cell replication in response to insulin resistance. Finally, SerpinB1-treatment of islets modulated signaling proteins in growth and survival pathways such as MAPK, PKA and GSK3. Together, these data implicate SerpinB1 as a protein that can potentially be harnessed to enhance functional β-cell mass in patients with diabetes.

  18. Arsenic and urinary bladder cell proliferation

    International Nuclear Information System (INIS)

    Luster, Michael I.; Simeonova, Petia P.

    2004-01-01

    Epidemiologic studies have demonstrated that a close association exists between the elevated levels of arsenic in drinking water and the incidence of certain cancers, including transitional cell carcinomas of the urinary bladder. We have employed in vitro and in vivo models to examine the effects of sodium arsenite on the urinary bladder epithelium. Mice exposed to 0.01% sodium arsenite in drinking water demonstrated hyperproliferation of the bladder uroepithelium within 4 weeks after initiating treatment. This occurred in the absence of amorphous precipitates and was accompanied by the accumulation of trivalent arsenite (iAs 3+ ), and to a lesser extent dimethylarsenic (DMA), arsenate (iAs 5+ ), and monomethylarsenic (MMA) in bladder tissue. In contrast to the bladder, urinary secretion was primarily in the form of DMA and MMA. Arsenic-induced cell proliferation in the bladder epithelium was correlated with activation of the MAP kinase pathway, leading to extracellular signal-regulated kinase (ERK) kinase activity, AP-1 activation, and expression of AP-1-associated genes involved in cell proliferation. Activation of the MAP kinase pathway involved both epidermal growth factor (EGF) receptor-dependent and -independent events, the latter involving Src activation. Studies summarized in this review suggest that arsenic accumulates in urinary bladder epithelium causing activation of specific signaling pathways that lead to chronic increased cell proliferation. This may play a non-epigenetic role in carcinogenesis by increasing the proliferation of initiated cells or increasing the mutational rate

  19. Effect of temperature on the proliferation of Gymnodinium breve and Gomphosphaeria aponina

    Energy Technology Data Exchange (ETDEWEB)

    Eng-Wilmot, D.L.; Hitchcock, W.S.; Martin, D.F.

    1977-01-01

    The effect of temperature on the growth and proliferation of two marine microorganisms, the toxigenic dinoflagellate Gymnodinium breve, and a potential bio-control organism, the blue-green alga Gomphosphaeria aponina, was determined by culturing the organisms in thermal gradients established by heating and cooling the opposite ends of an aluminum bar that had been adapted to hold culture tubes. Gradients were linear and stable for the duration of each trial. There was no relationship between variations in light and growth of the organisms. Gymnodinium breve showed optimum growth at 22/sup 0/C, and prolifereated over a range of temperatures (17/sup 0/ to 30/sup 0/C). Below 17/sup 0/C cultures of G. breve declined in growth, and at 4/sup 0/C the organisms died within 5 h. Above 31/sup 0/C there was rapid decline in viability of cells, and at 33.5/sup 0/C the organism died within 24 h. Gomphosphaeria aponina showed optimum growth between 24/sup 0/ and 29/sup 0/C, with a maximum at 27/sup 0/C. Growth at temperatures greater than 31/sup 0/C was minimal, but the organism survived. Limitation may be due to repression of the bio-synthesis of an iron-transport compound.

  20. Uterine epithelial cell proliferation and endometrial hyperplasia: evidence from a mouse model.

    Science.gov (United States)

    Gao, Yang; Li, Shu; Li, Qinglei

    2014-08-01

    In the uterus, epithelial cell proliferation changes during the estrous cycle and pregnancy. Uncontrolled epithelial cell proliferation results in implantation failure and/or cancer development. Transforming growth factor-β (TGF-β) signaling is a fundamental regulator of diverse biological processes and is indispensable for multiple reproductive functions. However, the in vivo role of TGF-β signaling in uterine epithelial cells remains poorly defined. We have shown that in the uterus, conditional deletion of the Type 1 receptor for TGF-β (Tgfbr1) using anti-Müllerian hormone receptor type 2 (Amhr2) Cre leads to myometrial defects. Here, we describe enhanced epithelial cell proliferation by immunostaining of Ki67 in the uteri of these mice. The aberration culminated in endometrial hyperplasia in aged females. To exclude the potential influence of ovarian steroid hormones, the proliferative status of uterine epithelial cells was assessed following ovariectomy. Increased uterine epithelial cell proliferation was also revealed in ovariectomized Tgfbr1 Amhr2-Cre conditional knockout mice. We further demonstrated that transcript levels for fibroblast growth factor 10 (Fgf10) were markedly up-regulated in Tgfbr1 Amhr2-Cre conditional knockout uteri. Consistently, treatment of primary uterine stromal cells with TGF-β1 significantly reduced Fgf10 mRNA expression. Thus, our findings suggest a potential involvement of TGFBR1-mediated signaling in the regulation of uterine epithelial cell proliferation, and provide genetic evidence supporting the role of uterine epithelial cell proliferation in the pathogenesis of endometrial hyperplasia. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Hydrogen sulfide (H2S)/cystathionine γ-lyase (CSE) pathway contributes to the proliferation of hepatoma cells

    International Nuclear Information System (INIS)

    Pan, Yan; Ye, Shuang; Yuan, Dexiao; Zhang, Jianghong; Bai, Yang; Shao, Chunlin

    2014-01-01

    Highlights: • Inhibition of H 2 S/CSE pathway strongly stimulates cellular apoptosis. • Inhibition of H 2 S/CSE pathway suppresses cell growth by blocking EGFR pathway. • H 2 S/CSE pathway is critical for maintaining the proliferation of hepatoma cells. - Abstract: Hydrogen sulfide (H 2 S)/cystathionine γ-lyase (CSE) pathway has been demonstrated to play vital roles in physiology and pathophysiology. However, its role in tumor cell proliferation remains largely unclear. Here we found that CSE over-expressed in hepatoma HepG2 and PLC/PRF/5 cells. Inhibition of endogenous H 2 S/CSE pathway drastically decreased the proliferation of HepG2 and PLC/PRF/5 cells, and it also enhanced ROS production and mitochondrial disruption, pronounced DNA damage and increased apoptosis. Moreover, this increase of apoptosis was associated with the activation of p53 and p21 accompanied by a decreased ratio of Bcl-2/Bax and up-regulation of phosphorylated c-Jun N-terminal kinase (JNK) and caspase-3 activity. In addition, the negative regulation of cell proliferation by inhibition of H 2 S/CSE system correlated with the blockage of cell mitogenic and survival signal transduction of epidermal growth factor receptor (EGFR) via down-regulating the extracellular-signal-regulated kinase 1/2 (ERK1/2) activation. These results demonstrate that H 2 S/CSE and its downstream pathway contribute to the proliferation of hepatoma cells, and inhibition of this pathway strongly suppress the excessive growth of hepatoma cells by stimulating mitochondrial apoptosis and suppressing cell growth signal transduction

  2. Efficient inhibition of fibroblast proliferation and collagen expression by ERK2 siRNAs

    International Nuclear Information System (INIS)

    Li, Fengfeng; Fan, Cunyi; Cheng, Tao; Jiang, Chaoyin; Zeng, Bingfang

    2009-01-01

    Transforming growth factor-β1 and fibroblast growth factor-2 play very important roles in fibroblast proliferation and collagen expression. These processes lead to the formation of joint adhesions through the SMAD and MAPK pathways, in which ERK2 is supposed to be crucial. Based on these assumptions, lentivirus (LV)-mediated small interfering RNAs (siRNAs) targeting ERK2 were used to suppress the proliferation and collagen expression of rat joint adhesion tissue fibroblasts (RJATFs). Among four siRNAs examined, siRNA1 caused an 84% reduction in ERK2 expression (p < 0.01) and was selected as the most efficient siRNA for use in this study. In subsequent experiments, significant downregulation of types I and III collagen were observed by quantitative RT-PCR and Western blot analyses. MTT assays and flow cytometry revealed marked inhibition of RJATF proliferation, but no apoptosis. In conclusion, LV-mediated ERK2 siRNAs may represent novel therapies or drug targets for preventing joint adhesion formation.

  3. Platelets promote osteosarcoma cell growth through activation of the platelet-derived growth factor receptor-Akt signaling axis.

    Science.gov (United States)

    Takagi, Satoshi; Takemoto, Ai; Takami, Miho; Oh-Hara, Tomoko; Fujita, Naoya

    2014-08-01

    The interactions of tumor cells with platelets contribute to the progression of tumor malignancy, and the expression levels of platelet aggregation-inducing factors positively correlate with the metastatic potential of osteosarcoma cells. However, it is unclear how tumor-platelet interaction contributes to the proliferation of osteosarcomas. We report here that osteosarcoma-platelet interactions induce the release of platelet-derived growth factor (PDGF) from platelets, which promotes the proliferation of osteosarcomas. Co-culture of platelets with MG63 or HOS osteosarcoma cells, which could induce platelet aggregation, enhanced the proliferation of each cell line in vitro. Analysis of phospho-antibody arrays revealed that co-culture of MG63 cells with platelets induced the phosphorylation of platelet derived growth factor receptor (PDGFR) and Akt. The addition of supernatants of osteosarcoma-platelet reactants also increased the growth of MG63 and HOS cells as well as the level of phosphorylated-PDGFR and -Akt. Sunitinib or LY294002, but not erlotinib, significantly inhibited the platelet-induced proliferation of osteosarcoma cells, indicating that PDGF released from platelets plays an important role in the proliferation of osteosarcomas by activating the PDGFR and then Akt. Our results suggest that inhibitors that specifically target osteosarcoma-platelet interactions may eradicate osteosarcomas. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  4. Caudal léxico en alumnos universitarios : Implicancias para la interacción textual

    OpenAIRE

    Piatti, Vanesa; Fernicola, Alfredo; Melillo, Oscar Roberto; Peralta, Diego

    2011-01-01

    En este trabajo se comunican los resultados preliminares de una investigación en curso. Específicamente se refiere a los resultados encontrados en pruebas de que examinan el caudal léxico, por el interés de sus relaciones con la interacción textual. En razón de ello en la elaboración de esta comunicación se ha tenido particularmente en cuenta el modelo de comprensión lectora proporcionado por Kintsch y Rawson (2005) sobre los diferentes niveles de procesamiento cuando se lee. Los autores d...

  5. Diacylglycerol kinase α mediates 17-β-estradiol-induced proliferation, motility, and anchorage-independent growth of Hec-1A endometrial cancer cell line through the G protein-coupled estrogen receptor GPR30.

    Science.gov (United States)

    Filigheddu, Nicoletta; Sampietro, Sara; Chianale, Federica; Porporato, Paolo E; Gaggianesi, Miriam; Gregnanin, Ilaria; Rainero, Elena; Ferrara, Michele; Perego, Beatrice; Riboni, Francesca; Baldanzi, Gianluca; Graziani, Andrea; Surico, Nicola

    2011-12-01

    Increased levels of endogenous and/or exogenous estrogens are one of the well known risk factors of endometrial cancer. Diacylglycerol kinases (DGKs) are a family of enzymes which phosphorylate diacylglycerol (DAG) to produce phosphatidic acid (PA), thus turning off and on DAG-mediated and PA-mediated signaling pathways, respectively. DGK α activity is stimulated by growth factors and oncogenes and is required for chemotactic, proliferative, and angiogenic signaling in vitro. Herein, using either specific siRNAs or the pharmacological inhibitor R59949, we demonstrate that DGK α activity is required for 17-β-estradiol (E2)-induced proliferation, motility, and anchorage-independent growth of Hec-1A endometrial cancer cell line. Impairment of DGK α activity also influences basal cell proliferation and growth in soft agar of Hec-1A, while it has no effects on basal cell motility. Moreover, we show that DGK α activity induced by E2, as well as its observed effects, are mediated by the G protein-coupled estrogen receptor GPR30 (GPER). These findings suggest that DGK α may be a potential target in endometrial cancer therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Isorhynchophylline protects against pulmonary arterial hypertension and suppresses PASMCs proliferation

    International Nuclear Information System (INIS)

    Guo, Haipeng; Zhang, Xin; Cui, Yuqian; Deng, Wei; Xu, Dachun; Han, Hui; Wang, Hao; Chen, Yuguo; Li, Yu; Wu, Dawei

    2014-01-01

    Highlights: • We focus on PASMCs proliferation in the pathogenesis of PAH. • Isorhynchophylline inhibited PASMCs proliferation and alleviated PAH. • IRN blocked PDGF-Rβ phosphorylation and its downstream signal transduction. • IRN regulated cyclins and CDKs to arrest cell cycle in the G0/G1 phase. • We reported IRN has the potential to be a candidate for PAH treatment. - Abstract: Increased pulmonary arterial smooth muscle cells (PASMCs) proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Isorhynchophylline (IRN) is a tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla. It has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether IRN can influence the development of PAH. Here we examined the effect of IRN on monocrotaline (MCT) induced PAH in rats. Our data demonstrated that IRN prevented MCT induced PAH in rats, as assessed by right ventricular (RV) pressure, the weight ratio of RV to (left ventricular + septum) and RV hypertrophy. IRN significantly attenuated the percentage of fully muscularized small arterioles, the medial wall thickness, and the expression of smooth muscle α-actin (α-SMA) and proliferating cell nuclear antigen (PCNA). In vitro studies, IRN concentration-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of PASMCs. Fluorescence-activated cell-sorting analysis showed that IRN caused G0/G1 phase cell cycle arrest. IRN-induced growth inhibition was associated with downregulation of Cyclin D1 and CDK6 as well as an increase in p27Kip1 levels in PDGF-BB-stimulated PASMCs. Moreover, IRN negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, ERK1/2, Akt/GSK3β, and signal transducers and activators of transcription 3 (STAT3). These results demonstrate that IRN could inhibit PASMCs proliferation and

  7. Isorhynchophylline protects against pulmonary arterial hypertension and suppresses PASMCs proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Haipeng; Zhang, Xin [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012 (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China); Cui, Yuqian [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China); Deng, Wei [Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Xu, Dachun [Department of Cardiology, Shanghai Tenth People’s Hospital of Tongji University, Shanghai 200072 (China); Han, Hui; Wang, Hao [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012 (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China); Chen, Yuguo [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China); Li, Yu, E-mail: qlliyu@126.com [Department of Respiratory, Qilu Hospital of Shandong University, Jinan 250012 (China); Wu, Dawei, E-mail: wdwu55@163.com [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012 (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China)

    2014-07-18

    Highlights: • We focus on PASMCs proliferation in the pathogenesis of PAH. • Isorhynchophylline inhibited PASMCs proliferation and alleviated PAH. • IRN blocked PDGF-Rβ phosphorylation and its downstream signal transduction. • IRN regulated cyclins and CDKs to arrest cell cycle in the G0/G1 phase. • We reported IRN has the potential to be a candidate for PAH treatment. - Abstract: Increased pulmonary arterial smooth muscle cells (PASMCs) proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Isorhynchophylline (IRN) is a tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla. It has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether IRN can influence the development of PAH. Here we examined the effect of IRN on monocrotaline (MCT) induced PAH in rats. Our data demonstrated that IRN prevented MCT induced PAH in rats, as assessed by right ventricular (RV) pressure, the weight ratio of RV to (left ventricular + septum) and RV hypertrophy. IRN significantly attenuated the percentage of fully muscularized small arterioles, the medial wall thickness, and the expression of smooth muscle α-actin (α-SMA) and proliferating cell nuclear antigen (PCNA). In vitro studies, IRN concentration-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of PASMCs. Fluorescence-activated cell-sorting analysis showed that IRN caused G0/G1 phase cell cycle arrest. IRN-induced growth inhibition was associated with downregulation of Cyclin D1 and CDK6 as well as an increase in p27Kip1 levels in PDGF-BB-stimulated PASMCs. Moreover, IRN negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, ERK1/2, Akt/GSK3β, and signal transducers and activators of transcription 3 (STAT3). These results demonstrate that IRN could inhibit PASMCs proliferation and

  8. The role of vascular endothelial growth factor in proliferation of odontogenic cysts and tumors: An immunohistochemical study.

    Science.gov (United States)

    Gupta, Bhavana; Chandra, Shaleen; Singh, Anil; Sah, Kunal; Raj, Vineet; Gupta, Vivek

    2016-01-01

    Vascular endothelial growth factor (VEGF) is capable of initiating angiogenesis in blood vessels and may act as mitogenic agent for epithelium of odontogenic cysts and tumors. This study was conducted to evaluate the role of epithelial VEGF expression in odontogenic cysts and ameloblastoma and its correlation with argyrophilic nucleolar organizer region counts to assess its role in their biological behavior. In this retrospective cross-sectional study, 45 histologically confirmed cases, 15 cases of each of keratocystic odontogenic tumors (KCOTs), dentigerous cysts, and ameloblastomas were examined for immunohistochemical expression for epithelial VEGF, and argyrophilic nucleolar organizer regions (AgNORs) (used as secondary marker in this study) staining was done for comparing the proliferative capacity with VEGF. KCOT shows mild expression within the basal layers and strong expression in the suprabasal layer whereas, in dentigerous cysts, a majority showed no VEGF expression whereas ameloblastomas showed strong expression in all cases by stellate reticulum-like cells at the center of the follicles and suprabasal layers of epithelium. The results of AgNOR counts were higher in KCOTs as compared to ameloblastoma and least in dentigerous cysts. VEGF expression by the epithelium of odontogenic cysts and tumors may play a role in epithelial proliferation via autocrine mechanism as reflected by increased AgNOR counts. The angiogenic activity via paracrine pathway may be responsible for the difference in growth rate and neoplastic behavior of the lesions.

  9. Linking gene regulation to cell behaviors in the posterior growth zone of sequentially segmenting arthropods.

    Science.gov (United States)

    Williams, Terri A; Nagy, Lisa M

    2017-05-01

    Virtually all arthropods all arthropods add their body segments sequentially, one by one in an anterior to posterior progression. That process requires not only segment specification but typically growth and elongation. Here we review the functions of some of the key genes that regulate segmentation: Wnt, caudal, Notch pathway, and pair-rule genes, and discuss what can be inferred about their evolution. We focus on how these regulatory factors are integrated with growth and elongation and discuss the importance and challenges of baseline measures of growth and elongation. We emphasize a perspective that integrates the genetic regulation of segment patterning with the cellular mechanisms of growth and elongation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Parametric study of the swimming performance of a fish robot propelled by a flexible caudal fin

    Energy Technology Data Exchange (ETDEWEB)

    Low, K H; Chong, C W, E-mail: mkhlow@ntu.edu.s, E-mail: ch0018ee@ntu.edu.s [School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798 (Singapore)

    2010-12-15

    In this paper, we aim to study the swimming performance of fish robots by using a statistical approach. A fish robot employing a carangiform swimming mode had been used as an experimental platform for the performance study. The experiments conducted aim to investigate the effect of various design parameters on the thrust capability of the fish robot with a flexible caudal fin. The controllable parameters associated with the fin include frequency, amplitude of oscillation, aspect ratio and the rigidity of the caudal fin. The significance of these parameters was determined in the first set of experiments by using a statistical approach. A more detailed parametric experimental study was then conducted with only those significant parameters. As a result, the parametric study could be completed with a reduced number of experiments and time spent. With the obtained experimental result, we were able to understand the relationship between various parameters and a possible adjustment of parameters to obtain a higher thrust. The proposed statistical method for experimentation provides an objective and thorough analysis of the effects of individual or combinations of parameters on the swimming performance. Such an efficient experimental design helps to optimize the process and determine factors that influence variability.

  11. Parametric study of the swimming performance of a fish robot propelled by a flexible caudal fin.

    Science.gov (United States)

    Low, K H; Chong, C W

    2010-12-01

    In this paper, we aim to study the swimming performance of fish robots by using a statistical approach. A fish robot employing a carangiform swimming mode had been used as an experimental platform for the performance study. The experiments conducted aim to investigate the effect of various design parameters on the thrust capability of the fish robot with a flexible caudal fin. The controllable parameters associated with the fin include frequency, amplitude of oscillation, aspect ratio and the rigidity of the caudal fin. The significance of these parameters was determined in the first set of experiments by using a statistical approach. A more detailed parametric experimental study was then conducted with only those significant parameters. As a result, the parametric study could be completed with a reduced number of experiments and time spent. With the obtained experimental result, we were able to understand the relationship between various parameters and a possible adjustment of parameters to obtain a higher thrust. The proposed statistical method for experimentation provides an objective and thorough analysis of the effects of individual or combinations of parameters on the swimming performance. Such an efficient experimental design helps to optimize the process and determine factors that influence variability.

  12. Parametric study of the swimming performance of a fish robot propelled by a flexible caudal fin

    International Nuclear Information System (INIS)

    Low, K H; Chong, C W

    2010-01-01

    In this paper, we aim to study the swimming performance of fish robots by using a statistical approach. A fish robot employing a carangiform swimming mode had been used as an experimental platform for the performance study. The experiments conducted aim to investigate the effect of various design parameters on the thrust capability of the fish robot with a flexible caudal fin. The controllable parameters associated with the fin include frequency, amplitude of oscillation, aspect ratio and the rigidity of the caudal fin. The significance of these parameters was determined in the first set of experiments by using a statistical approach. A more detailed parametric experimental study was then conducted with only those significant parameters. As a result, the parametric study could be completed with a reduced number of experiments and time spent. With the obtained experimental result, we were able to understand the relationship between various parameters and a possible adjustment of parameters to obtain a higher thrust. The proposed statistical method for experimentation provides an objective and thorough analysis of the effects of individual or combinations of parameters on the swimming performance. Such an efficient experimental design helps to optimize the process and determine factors that influence variability.

  13. Whether the weather drives patterns of endemic amphibian chytridiomycosis: a pathogen proliferation approach.

    Directory of Open Access Journals (Sweden)

    Kris A Murray

    Full Text Available The pandemic amphibian disease chytridiomycosis often exhibits strong seasonality in both prevalence and disease-associated mortality once it becomes endemic. One hypothesis that could explain this temporal pattern is that simple weather-driven pathogen proliferation (population growth is a major driver of chytridiomycosis disease dynamics. Despite various elaborations of this hypothesis in the literature for explaining amphibian declines (e.g., the chytrid thermal-optimum hypothesis it has not been formally tested on infection patterns in the wild. In this study we developed a simple process-based model to simulate the growth of the pathogen Batrachochytrium dendrobatidis (Bd under varying weather conditions to provide an a priori test of a weather-linked pathogen proliferation hypothesis for endemic chytridiomycosis. We found strong support for several predictions of the proliferation hypothesis when applied to our model species, Litoria pearsoniana, sampled across multiple sites and years: the weather-driven simulations of pathogen growth potential (represented as a growth index in the 30 days prior to sampling; GI30 were positively related to both the prevalence and intensity of Bd infections, which were themselves strongly and positively correlated. In addition, a machine-learning classifier achieved ~72% success in classifying positive qPCR results when utilising just three informative predictors 1 GI30, 2 frog body size and 3 rain on the day of sampling. Hence, while intrinsic traits of the individuals sampled (species, size, sex and nuisance sampling variables (rainfall when sampling influenced infection patterns obtained when sampling via qPCR, our results also strongly suggest that weather-linked pathogen proliferation plays a key role in the infection dynamics of endemic chytridiomycosis in our study system. Predictive applications of the model include surveillance design, outbreak preparedness and response, climate change scenario

  14. Whether the weather drives patterns of endemic amphibian chytridiomycosis: a pathogen proliferation approach.

    Science.gov (United States)

    Murray, Kris A; Skerratt, Lee F; Garland, Stephen; Kriticos, Darren; McCallum, Hamish

    2013-01-01

    The pandemic amphibian disease chytridiomycosis often exhibits strong seasonality in both prevalence and disease-associated mortality once it becomes endemic. One hypothesis that could explain this temporal pattern is that simple weather-driven pathogen proliferation (population growth) is a major driver of chytridiomycosis disease dynamics. Despite various elaborations of this hypothesis in the literature for explaining amphibian declines (e.g., the chytrid thermal-optimum hypothesis) it has not been formally tested on infection patterns in the wild. In this study we developed a simple process-based model to simulate the growth of the pathogen Batrachochytrium dendrobatidis (Bd) under varying weather conditions to provide an a priori test of a weather-linked pathogen proliferation hypothesis for endemic chytridiomycosis. We found strong support for several predictions of the proliferation hypothesis when applied to our model species, Litoria pearsoniana, sampled across multiple sites and years: the weather-driven simulations of pathogen growth potential (represented as a growth index in the 30 days prior to sampling; GI30) were positively related to both the prevalence and intensity of Bd infections, which were themselves strongly and positively correlated. In addition, a machine-learning classifier achieved ~72% success in classifying positive qPCR results when utilising just three informative predictors 1) GI30, 2) frog body size and 3) rain on the day of sampling. Hence, while intrinsic traits of the individuals sampled (species, size, sex) and nuisance sampling variables (rainfall when sampling) influenced infection patterns obtained when sampling via qPCR, our results also strongly suggest that weather-linked pathogen proliferation plays a key role in the infection dynamics of endemic chytridiomycosis in our study system. Predictive applications of the model include surveillance design, outbreak preparedness and response, climate change scenario modelling and

  15. Marcadores de proliferação celular na avaliação do crescimento do tumor sólido e ascítico de Ehrlich Cell proliferation markers for evaluating the growth of solid and ascitic forms of Ehrlich tumor

    Directory of Open Access Journals (Sweden)

    A.E. Silva

    2006-08-01

    Full Text Available Twenty BALB/c mice were inoculated with cell suspension of Ehrlich tumor. Ten mice were inoculated in the cushion plant (solid form and the other 10 in the peritoneum (ascitic form. Animals were euthanized on different times (7 and 14 days. Cytological and histological slides, immunohistochemical (PCNA analysis and NORs silver impregnation technique were performed. The results showed more proliferation on the 7th day in the ascitic form and on 14th day in the solid form, using both analyses (PCNA and AgNORs. The alterations observed in the Ehrlich tumor’s proliferation activity suggested that the growth curve is different between ascitic and solid forms. In the first one, the proliferation peak occurs on the seventh day and in the solid tumor the growth curve was more delayed, showing increased proliferative potential after seven days.

  16. Indirect caudal lymphography using a new water-soluble contrast agent - animal experimental studies in pigs

    International Nuclear Information System (INIS)

    Apitzsch, D.E.; Kroll, H.U.; Zuehlke, H.V.

    1981-01-01

    Animal experiments on caudal lymphography in pigs are presented, using a new water-soluble contrast medium which is renally excreted. Indirect cutaneous administration renders possible the radiological visualization of the entire lymphatic drainage system of the lower limb, the retro-peritoneal space and the thoracic duct. Visualization of the lymphatic system is rapid, homogeneous and can be repeated as often as desired. The quality of the lymphogram is as good as that obtained by the current methods in common use. (orig.)

  17. Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Nahyun Choi

    2018-02-01

    Full Text Available Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs. We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif ligand 1 (CXCL1, platelet-derived endothelial cell growth factor (PD-ECGF, and platelet-derived growth factor-C (PDGF-C. Minoxidil increased extracellular signal–regulated kinases 1/2 (ERK1/2 phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration.

  18. Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells

    Science.gov (United States)

    Choi, Nahyun; Shin, Soyoung; Song, Sun U.; Sung, Jong-Hyuk

    2018-01-01

    Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP) and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs). We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif) ligand 1 (CXCL1), platelet-derived endothelial cell growth factor (PD-ECGF), and platelet-derived growth factor-C (PDGF-C). Minoxidil increased extracellular signal–regulated kinases 1/2 (ERK1/2) phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration. PMID:29495622

  19. Growth hormone is a growth factor for the differentiated pancreatic beta-cell

    DEFF Research Database (Denmark)

    Linde, S; Welinder, B S; Billestrup, N

    1989-01-01

    The regulation of the growth of the pancreatic beta-cell is poorly understood. There are previous indications of a role of GH in the growth and insulin production of the pancreatic islets. In the present study we present evidence for a direct long-term effect of GH on proliferation and insulin...

  20. [Regulation of airway stem cell proliferation in idiopathic pulmonary fibrosis].

    Science.gov (United States)

    Yang, S X; Wu, Q; Sun, X; Li, X; Li, K; Xu, L; Li, Y; Zhang, Q Y; Zhang, Y C; Chen, H Y

    2016-09-01

    To investigate the effect of fibroblasts on regulating airway stem cell proliferation in idiopathic pulmonary fibrosis. Lung cell suspension was prepared from β-actin-GFP mice. Airway stem cells were obtained by fluorescence activated cell sorting and co-cultured with lung fibroblasts. The fibroblasts were treated with TGF-β inhibitor SB43142. The expression of growth factors FGF1/2 and the effect of FGF1/2 on stem cell proliferation were observed. The cloning efficiency of airway stem cells, when co-cultured with normal lung fibroblast cells for 8 days, was (3.5±1.1)%, while the cloning efficiency was reduced to (0.04±0.04)% when co-cultured with lung fibroblasts from idiopathic pulmonary fibrosis patients. The difference between the 2 groups was statistically significant(P=0.002 5). TGF-β receptor inhibitor SB431542 increased lung fibroblast growth factors FGF1/2 expression.FGF1 mRNA expression was increased to the experimental group 0.005 5 from 0.000 2 in the control group.FGF2 mRNA expression of the amount raised to the experimental group 0.000 15 from 0.000 8 in the control group.FGF1/2 promoted the growth of airway stem cells. After FGF1/2 was co-cultured with normal lung fibroblast cells for 8 days, the cloning efficiency of airway stem cells was (0.3±0.1)%. During the development of idiopathic pulmonary fibrosis, fibroblast secreted FGF1/2 regulate airway stem cell proliferation.

  1. Effects of simulated microgravity on circadian rhythm of caudal arterial pressure and heart rate in rats and their underlying mechanism

    Directory of Open Access Journals (Sweden)

    Li CHEN

    2016-04-01

    Full Text Available Objective  To explore the effects of simulated microgravity on the circadian rhythm of rats' caudal arterial pressure and heart rate, and their underlying mechanism. Methods  Eighteen male SD rats (aged 8 weeks were randomly assigned to control (CON and tail suspension (SUS group (9 each. Rats with tail suspension for 28 days were adopted as the animal model to simulate microgravity. Caudal arterial pressure and heart rate of rats were measured every 3 hours. The circadian difference of abdominal aorta contraction was measured by aortic ring test. Western blotting was performed to determine and compare the protein expression level of clock genes such as Per2 (Period2, Bmal1 (Aryl hydrocarbon receptor nuclear translocatorlike and dbp (D element binding protein in suprachiasmatic nucleus (SCN and abdominal aorta of rats in CON and SUS group at different time points. Results  Compared with CON group, the caudal arterial pressure, both systolic and diastolic pressure, decreased significantly and the diurnal variability disappeared, meanwhile the heart rate increased obviously and also the diurnal variability disappeared in rats of SUS group. Compared with CON group, the contraction reactivity of abdominal aorta decreased with disappearence of the diurnal variability, and also the clock genes expression in SCN and abdominal aorta showed no diurnal variability in rats of SUS group. Conclusion  Simulated microgravity may lead to circadian rhythm disorders in rats' cardiovascular system, which may be associated with the changes of the clock genes expression. DOI: 10.11855/j.issn.0577-7402.2016.04.06

  2. Prediction of water flows in Colorado River, Argentina Predicción de caudales en río Colorado, Argentina

    Directory of Open Access Journals (Sweden)

    Jorge O Pierini

    2012-11-01

    Full Text Available The identification of suitable models for predicting daily water flow is important for planning and management of water storage in reservoirs of Argentina. Long-term prediction of water flow is crucial for regulating reservoirs and hydroelectric plants, for assessing environmental protection and sustainable development, for guaranteeing correct operation of public water supply in cities like Catriel, 25 de Mayo, Colorado River and potentially also Bahía Blanca. In this paper, we analyze in Buta Ranquil flow time series upstream reservoir and hydroelectric plant in order to model and predict daily fluctuations. We compare results obtained by using a three-layer artificial neural network (ANN, and an autoregressive (AR model, using 18 years of data, of which the last 3 years are used for model validation by means of the root mean square error (RMSE, and measure of certainty (Skill. Our results point out to the better performance to predict daily water flow or refill them of the ANN model performance respect to the AR model.La identificación de modelos adecuados para predecir caudales diarios es importante para la planificación y la gestión de almacenamiento de agua en los embalses de la Argentina. La predicción a largo plazo del caudal es crucial para la regulación de los embalses y centrales hidroeléctricas, evaluar la protección del medio ambiente y el desarrollo sostenible, garantizar el correcto funcionamiento del abastecimiento público de agua en ciudades como Catriel, 25 de Mayo, río Colorado y también, eventualmente, en Bahía Blanca. En este trabajo, se analizan series de tiempo de caudales de agua, arriba del embalse y de la planta hidroeléctrica en Buta Ranquil, para modelar y predecir las fluctuaciones diarias. Se comparan los resultados obtenidos mediante el uso de una red neuronal artificial (ANN de tres capas y un modelo autoregresivo (AR, con 18 anos de datos, cuyos últimos 3 anos se utilizan para la validación del

  3. Early decrease in dietary protein:energy ratio by fat addition and ontogenetic changes in muscle growth mechanisms of rainbow trout: short- and long-term effects.

    Science.gov (United States)

    Alami-Durante, Hélène; Cluzeaud, Marianne; Duval, Carine; Maunas, Patrick; Girod-David, Virginia; Médale, Françoise

    2014-09-14

    As the understanding of the nutritional regulation of muscle growth mechanisms in fish is fragmentary, the present study aimed to (1) characterise ontogenetic changes in muscle growth-related genes in parallel to changes in muscle cellularity; (2) determine whether an early decrease in dietary protein:energy ratio by fat addition affects the muscle growth mechanisms of rainbow trout (Oncorhynchus mykiss) alevins; and (3) determine whether this early feeding of a high-fat (HF) diet to alevins had a long-term effect on muscle growth processes in juveniles fed a commercial diet. Developmental regulation of hyperplasia and hypertrophy was evidenced at the molecular (expression of myogenic regulatory factors, proliferating cell nuclear antigen and myosin heavy chains (MHC)) and cellular (number and diameter of white muscle fibres) levels. An early decrease in dietary protein:energy ratio by fat addition stimulated the body growth of alevins but led to a fatty phenotype, with accumulation of lipids in the anterior part, and less caudal muscle when compared at similar body weights, due to a decrease in both the white muscle hyperplasia and maximum hypertrophy of white muscle fibres. These HF diet-induced cellular changes were preceded by a very rapid down-regulation of the expression of fast-MHC. The present study also demonstrated that early dietary composition had a long-term effect on the subsequent muscle growth processes of juveniles fed a commercial diet for 3 months. When compared at similar body weights, initially HF diet-fed juveniles indeed had a lower mean diameter of white muscle fibres, a smaller number of large white muscle fibres, and lower expression levels of MyoD1 and myogenin. These findings demonstrated the strong effect of early feed composition on the muscle growth mechanisms of trout alevins and juveniles.

  4. Cell proliferation alterations in Chlorella cells under stress conditions

    International Nuclear Information System (INIS)

    Rioboo, Carmen; O'Connor, Jose Enrique; Prado, Raquel; Herrero, Concepcion; Cid, Angeles

    2009-01-01

    Very little is known about growth and proliferation in relation to the cell cycle regulation of algae. The lack of knowledge is even greater when referring to the potential toxic effects of pollutants on microalgal cell division. To assess the effect of terbutryn, a triazine herbicide, on the proliferation of the freshwater microalga Chlorella vulgaris three flow cytometric approaches were used: (1) in vivo cell division using 5-,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) staining was measured, (2) the growth kinetics were determined by cytometric cell counting and (3) cell viability was evaluated with the membrane-impermeable double-stranded nucleic acid stain propidium iodide (PI). The results obtained in the growth kinetics study using CFSE to identify the microalgal cell progeny were consistent with those determined by cytometric cell counting. In all C. vulgaris cultures, each mother cell had undergone only one round of division through the 96 h of assay and the cell division occurred during the dark period. Cell division of the cultures exposed to the herbicide was asynchronous. Terbutryn altered the normal number of daughter cells (4 autospores) obtained from each mother cell. The number was only two in the cultures treated with 250 nM. The duration of the lag phase after the exposure to terbutryn could be dependent on the existence of a critical cell size to activate cytoplasmic division. Cell size, complexity and fluorescence of chlorophyll a of the microalgal cells presented a marked light/dark (day/night) cycle, except in the non-dividing 500 nM cultures, where terbutryn arrested cell division at the beginning of the cycle. Viability results showed that terbutryn has an algastatic effect in C. vulgaris cells at this concentration. The rapid and precise determination of cell proliferation by CFSE staining has allowed us to develop a model for assessing both the cell cycle of C. vulgaris and the in vivo effects of pollutants on growth and

  5. Cell proliferation alterations in Chlorella cells under stress conditions

    Energy Technology Data Exchange (ETDEWEB)

    Rioboo, Carmen [Laboratorio de Microbiologia, Facultad de Ciencias, Universidad de A Coruna, Campus da Zapateira s/n, 15008 A Coruna (Spain); O' Connor, Jose Enrique [Laboratorio de Citomica, Unidad Mixta de Investigacion CIPF-UVEG, Centro de Investigacion Principe Felipe, Avda. Autopista del Saler, 16, 46013 Valencia (Spain); Prado, Raquel; Herrero, Concepcion [Laboratorio de Microbiologia, Facultad de Ciencias, Universidad de A Coruna, Campus da Zapateira s/n, 15008 A Coruna (Spain); Cid, Angeles, E-mail: cid@udc.es [Laboratorio de Microbiologia, Facultad de Ciencias, Universidad de A Coruna, Campus da Zapateira s/n, 15008 A Coruna (Spain)

    2009-09-14

    Very little is known about growth and proliferation in relation to the cell cycle regulation of algae. The lack of knowledge is even greater when referring to the potential toxic effects of pollutants on microalgal cell division. To assess the effect of terbutryn, a triazine herbicide, on the proliferation of the freshwater microalga Chlorella vulgaris three flow cytometric approaches were used: (1) in vivo cell division using 5-,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) staining was measured, (2) the growth kinetics were determined by cytometric cell counting and (3) cell viability was evaluated with the membrane-impermeable double-stranded nucleic acid stain propidium iodide (PI). The results obtained in the growth kinetics study using CFSE to identify the microalgal cell progeny were consistent with those determined by cytometric cell counting. In all C. vulgaris cultures, each mother cell had undergone only one round of division through the 96 h of assay and the cell division occurred during the dark period. Cell division of the cultures exposed to the herbicide was asynchronous. Terbutryn altered the normal number of daughter cells (4 autospores) obtained from each mother cell. The number was only two in the cultures treated with 250 nM. The duration of the lag phase after the exposure to terbutryn could be dependent on the existence of a critical cell size to activate cytoplasmic division. Cell size, complexity and fluorescence of chlorophyll a of the microalgal cells presented a marked light/dark (day/night) cycle, except in the non-dividing 500 nM cultures, where terbutryn arrested cell division at the beginning of the cycle. Viability results showed that terbutryn has an algastatic effect in C. vulgaris cells at this concentration. The rapid and precise determination of cell proliferation by CFSE staining has allowed us to develop a model for assessing both the cell cycle of C. vulgaris and the in vivo effects of pollutants on growth and

  6. Skeletal muscle Kv7 (KCNQ) channels in myoblast differentiation and proliferation

    International Nuclear Information System (INIS)

    Roura-Ferrer, Meritxell; Sole, Laura; Martinez-Marmol, Ramon; Villalonga, Nuria; Felipe, Antonio

    2008-01-01

    Voltage-dependent K + channels (Kv) are involved in myocyte proliferation and differentiation by triggering changes in membrane potential and regulating cell volume. Since Kv7 channels may participate in these events, the purpose of this study was to investigate whether skeletal muscle Kv7.1 and Kv7.5 were involved during proliferation and myogenesis. Here we report that, while myotube formation did not regulate Kv7 channels, Kv7.5 was up-regulated during cell cycle progression. Although, Kv7.1 mRNA also increased during the G 1 -phase, pharmacological evidence mainly involves Kv7.5 in myoblast growth. Our results indicate that the cell cycle-dependent expression of Kv7.5 is involved in skeletal muscle cell proliferation

  7. Ihh signaling regulates mandibular symphysis development and growth.

    Science.gov (United States)

    Sugito, H; Shibukawa, Y; Kinumatsu, T; Yasuda, T; Nagayama, M; Yamada, S; Minugh-Purvis, N; Pacifici, M; Koyama, E

    2011-05-01

    Symphyseal secondary cartilage is important for mandibular development, but the molecular mechanisms underlying its formation remain largely unknown. Here we asked whether Indian hedgehog (Ihh) regulates symphyseal cartilage development and growth. By embryonic days 16.5 to 18.5, Sox9-expressing chondrocytes formed within condensed Tgfβ-1/Runx2-expressing mesenchymal cells at the prospective symphyseal joint site, and established a growth-plate-like structure with distinct Ihh, collagen X, and osteopontin expression patterns. In post-natal life, mesenchymal cells expressing the Ihh receptor Patched1 were present anterior to the Ihh-expressing secondary cartilage, proliferated, differentiated into chondrocytes, and contributed to anterior growth of alveolar bone. In Ihh-null mice, however, symphyseal development was defective, mainly because of enhanced chondrocyte maturation and reduced proliferation of chondroprogenitor cells. Proliferation was partially restored in dual Ihh;Gli3 mutants, suggesting that Gli3 is normally a negative regulator of symphyseal development. Thus, Ihh signaling is essential for symphyseal cartilage development and anterior mandibular growth.

  8. Effect of Lactobacillus reuteri on the proliferation of Propionibacterium acnes and Staphylococcus epidermidis.

    Science.gov (United States)

    Kang, Mi-Sun; Oh, Jong-Suk; Lee, Seok-Woo; Lim, Hoi-Soon; Choi, Nam-Ki; Kim, Seon-Mi

    2012-02-01

    While it is generally accepted that Propionibacterium acnes is involved in the development of acne, other bacteria including Staphylococcus epidermidis have also been isolated from the acne lesion. The interaction between Lactobacillus reuteri, a probiotic bacterium, and acnegenic bacteria is unclear. This study examined the effects of L. reuteri on the proliferation of P. acnes and S. epidermidis. Human-derived L. reuteri strains (KCTC 3594 and KCTC 3678) and rat-derived L. reuteri KCTC 3679 were used. All strains exhibited significant inhibitory effects on the growth of P. acnes and S. epidermidis. The proliferation of P. acnes was decreased by 2-log scales after incubation with L. reuteri for 24 h. In addition, the proliferation of S. epidermidis was decreased by 3-log scales after incubation with L. reuteri for 24 h, whereas the growth of L. reuteri was unaffected by P. acnes or S. epidermidis. Among the L. reuteri strains examined, L. reuteri KCTC 3679 had the strongest inhibitory effect on the growth of P. acnes and S. epidermidis, followed by L. reuteri KCTC 3594 and L. reuteri KCTC 3678. Interestingly, reuterin, an antimicrobial factor, was produced only by L. reuteri KCTC 3594. The most pronounced the antibacterial activities of L. reuteri were attributed to the production of organic acids. Overall, these results suggest that L. reuteri may be a useful probiotic agent to control the growth of bacteria involved in acne inflammation and prevent acne.

  9. Analgesia pós-operatória em correção cirúrgica de pé torto congênito: comparação entre bloqueio nervoso periférico e bloqueio peridural caudal Analgesia postoperatoria en corrección quirúrgica de pie jorobado congénito: comparación entre bloqueo nervioso periférico y bloqueo epidural caudal Postoperative analgesia for the surgical correction of congenital clubfoot: comparison between peripheral nerve block and caudal epidural block

    Directory of Open Access Journals (Sweden)

    Monica Rossi Rodrigues

    2009-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O procedimento de correção de pé torto congênito (PTC cursa com dor pós-operatória intensa. A técnica mais utilizada em crianças é a peridural caudal associada à anestesia geral. Tem como limitação a curta duração da analgesia pós-operatória. Os bloqueios de nervos periféricos têm sido apontados como procedimentos com baixa incidência de complicações e tempo prolongado de analgesia. O objetivo do estudo foi comparar o tempo de analgesia dos bloqueios nervosos periféricos e bloqueio caudal e o consumo de morfina nas primeiras 24 horas após a correção de PTC em crianças. MÉTODO: Estudo randômico, encoberto, em crianças submetidas à intervenção cirúrgica para liberação póstero-medial de PTC, alocadas em 4 grupos conforme a técnica anestésica: Caudal (ACa; Bloqueios isquiático e femoral (IF; Bloqueios isquiático e safeno (IS; Bloqueio isquiático e anestesia local (IL, associados à anestesia geral. Nas primeiras 24 horas os pacientes receberam dipirona e paracetamol via oral e foram avaliados por anestesiologista que desconhecia a técnica empregada. Conforme escores da escala CHIPPS (Children's and infants postoperative pain scale era administrada morfina via oral (0,19 mg.kg-1 por dia. RESULTADOS: Foram estudadas 118 crianças distribuídas nos grupos ACa (30, IF (32, IS (28 IL (28. O tempo médio entre o bloqueio e a primeira dose de morfina foi 6,16 horas no grupo ACa, 7,05 horas no IF, 7,58 horas no IS e 8,18 horas no IL. O consumo de morfina foi 0,3 mg.kg-1 por dia nos quatro grupos. Não houve diferença significativa entre os grupos. CONCLUSÕES: Os bloqueios nervosos periféricos não promoveram maior tempo de analgesia, tampouco redução no consumo de morfina nas primeiras 24 horas em crianças submetidas à correção de PTC quando comparados ao bloqueio peridural caudal.JUSTIFICATIVA Y OBJETIVOS: El procedimiento de corrección de pie jorobado congénito (PJC, debuta

  10. Skeletal muscle-derived progenitors capable of differentiating into cardiomyocytes proliferate through myostatin-independent TGF-β family signaling

    International Nuclear Information System (INIS)

    Nomura, Tetsuya; Ueyama, Tomomi; Ashihara, Eishi; Tateishi, Kento; Asada, Satoshi; Nakajima, Norio; Isodono, Koji; Takahashi, Tomosaburo; Matsubara, Hiroaki; Oh, Hidemasa

    2008-01-01

    The existence of skeletal muscle-derived stem cells (MDSCs) has been suggested in mammals; however, the signaling pathways controlling MDSC proliferation remain largely unknown. Here we report the isolation of myosphere-derived progenitor cells (MDPCs) that can give rise to beating cardiomyocytes from adult skeletal muscle. We identified that follistatin, an antagonist of TGF-β family members, was predominantly expressed in MDPCs, whereas myostatin was mainly expressed in myogenic cells and mature skeletal muscle. Although follistatin enhanced the replicative growth of MDPCs through Smad2/3 inactivation and cell cycle progression, disruption of myostatin did not increase the MDPC proliferation. By contrast, inhibition of activin A (ActA) or growth differentiation factor 11 (GDF11) signaling dramatically increased MDPC proliferation via down-regulation of p21 and increases in the levels of cdk2/4 and cyclin D1. Thus, follistatin may be an effective progenitor-enhancing agent neutralizing ActA and GDF11 signaling to regulate the growth of MDPCs in skeletal muscle

  11. Caudal epidural injections for lumbar prolapsed inter vertebral disc: assessment with urdu version of oswestry disability index

    International Nuclear Information System (INIS)

    Pasha, I.F.; Qureshi, M.A.; Farooq, M.

    2014-01-01

    Background/Aims: Oswestry Disability index is an established tool for assessment of Spinal Disability. It has been translated into many languages and but not to Urdu. The aim of this prospective observational study was translation, application and validation of Urdu version of the Oswestry Disability Index (Urdu ODI) for our specific cultural background. Methods: Urdu version of ODI was developed and applied for outcome assessment in 50 patients, suffering from lumbar prolapsed inter vertebral discs and treated with caudal epidural steroid injection. All patients having mechanical low backache with radiculopathy and single level disc prolapse at L-4-5 or L5- S 1 on Magnetic Resonance Imaging (MRI) were included in the study. Single Steroid Injection with local anesthetic was injected into sacral caudal epidural space through sacral hiatus. A Performa was made for each patient and records were kept in a custom built Microsoft access database. Outcome was assessed using Urdu ODI and validation by comparing with Numeric rating Scale 0-10 at each visit. Results: Fifty patients received caudal epidural injections, 23 (46%) were male and 27 (54%) were female. The mean age was 34 years, with the range being 21-55. Low mechanical backache with right sided radiculopathy was in 29 (58%) and left sided in 21 (42%) patients. The commonest involved disc was L4-S in 28 (56%) and L5-S1 in 22 (44%) patients Pain was assessed with Numeric Rating Scale (NRS) of ten points. This was mean 7.35, range 9-6 at presentation and mean improvement was 4.15 with range 5-3 at fist week, 3.80 with range 5-2 at first month and 3.05 with range 4-1 after six months. Functional disability assessment was done using Urdu ODI. The mean Urdu ODI at the time of presentation was 66.23% with range 81%-48%. The mean functional status was found to be 38.64% with range 26%-45% at the end of the first week, 43.65% with range 31%-48% after one month and 44.85% with range 28%-48% after six months. So there was

  12. Interleukin 1 is an autocrine regulator of human endothelial cell growth

    International Nuclear Information System (INIS)

    Cozzolino, F.; Torcia, M.; Aldinucci, D.; Ziche, M.; Bani, D.; Almerigogna, F.; Stern, D.M.

    1990-01-01

    Proliferation of endothelial cells is regulated through the autocrine production of growth factors and the expression of cognate surface receptors. In this study, the authors demonstrate that interleukin 1 (IL-1) is an inhibitor of endothelial growth in vitro and in vivo. IL-1 arrested growing, cultured endothelial cells in G 1 phase; inhibition of proliferation was dose dependent and occurred in parallel with occupancy of endothelial surface IL-1 receptors. In an angiogenesis model, IL-1 could inhibit fibroblast growth factor-induced vessel formation. The autocrine nature of the IL-1 effect on endothelial proliferation was demonstrated by the observation that occupancy of cell-surface receptors by endogenous IL-1 depressed cell growth. The potential significance of this finding was emphasized by the detection of IL-1 in the native endothelium of human umbilical veins. A mechanism by which IL-1 may exert its inhibitory effect on endothelial cell growth was suggested by studies showing that IL-1 decreased the expression of high-affinity fibroblast growth factor binding sites on endothelium. These results point to a potentially important role of IL-1 in regulating blood vessel growth the suggest that autocrine production of inhibitory factors may be a mechanism controlling proliferation of normal cells

  13. MicroRNA-20b-5p inhibits platelet-derived growth factor-induced proliferation of human fetal airway smooth muscle cells by targeting signal transducer and activator of transcription 3.

    Science.gov (United States)

    Tang, Jin; Luo, Lingying

    2018-06-01

    Pediatric asthma is still a health threat to the pediatric population in recent years. The airway remodeling induced by abnormal airway smooth muscle (ASM) cell proliferation is an important cause of asthma. MicroRNAs (miRNAs) are important regulators of ASM cell proliferation. Numerous studies have reported that miR-20b-5p is a critical regulator for cell proliferation. However, whether miR-20b-5p is involved in regulating ASM cell proliferation remains unknown. In this study, we aimed to investigate the potential role of miR-20b-5p in regulating the proliferation of fetal ASM cell induced by platelet-derived growth factor (PDGF). Here, we showed that miR-20b-5p was significantly decreased in fetal ASM cells treated with PDGF. Biological experiments showed that the overexpression of miR-20b-5p inhibited the proliferation while miR-20b-5p inhibition markedly promoted the proliferation of fetal ASM cells. Bioinformatics analysis and luciferase reporter assay showed that miR-20b-5p directly targeted the 3'-UTR of signal transducer and activator of transcription 3 (STAT3). Further data showed that miR-20b-5p negatively regulated the expression of STAT3 in fetal ASM cells. Moreover, miR-20b-5p regulates the transcriptional activity of STAT3 in fetal ASM cells. Overexpression of STAT3 reversed the inhibitory effect of miR-20b-5p overexpression on fetal ASM cell proliferation while the knockdown of STAT3 abrogated the promoted effect of miR-20b-5p inhibition on fetal ASM cell proliferation. Overall, our results show that miR-20b-5p impedes PDGF-induced proliferation of fetal ASM cells through targeting STAT3. Our study suggests that miR-20b-5p may play an important role in airway remodeling during asthma and suggests that miR-20b-5p may serve as a potential therapeutic target for pediatric asthma. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  14. Growth activity in human septal cartilage: age-dependent incorporation of labeled sulfate in different anatomic locations

    International Nuclear Information System (INIS)

    Vetter, U.; Pirsig, W.; Heinze, E.

    1983-01-01

    Growth activity in different areas of human septal cartilage was measured by the in vitro incorporation of 35 S-labeled NaSO 4 into chondroitin sulfate. Septal cartilage without perichondrium was obtained during rhinoplasty from 36 patients aged 6 to 35 years. It could be shown that the anterior free end of the septum displays high growth activity in all age groups. The supra-premaxillary area displayed its highest growth activity during prepuberty, showing thereafter a continuous decline during puberty and adulthood. A similar age-dependent pattern in growth activity was found in the caudal prolongation of the septal cartilage. No age-dependent variations could be detected in the posterior area of the septal cartilage

  15. Biodegradable electrospun nanofibers coated with platelet-rich plasma for cell adhesion and proliferation

    International Nuclear Information System (INIS)

    Diaz-Gomez, Luis; Alvarez-Lorenzo, Carmen; Concheiro, Angel; Silva, Maite; Dominguez, Fernando; Sheikh, Faheem A.; Cantu, Travis; Desai, Raj; Garcia, Vanessa L.; Macossay, Javier

    2014-01-01

    Biodegradable electrospun poly(ε-caprolactone) (PCL) scaffolds were coated with platelet-rich plasma (PRP) to improve cell adhesion and proliferation. PRP was obtained from human buffy coat, and tested on human adipose-derived mesenchymal stem cells (MSCs) to confirm cell proliferation and cytocompatibility. Then, PRP was adsorbed on the PCL scaffolds via lyophilization, which resulted in a uniform sponge-like coating of 2.85 (S.D. 0.14) mg/mg. The scaffolds were evaluated regarding mechanical properties (Young's modulus, tensile stress and tensile strain), sustained release of total protein and growth factors (PDGF-BB, TGF-β1 and VEGF), and hemocompatibility. MSC seeded on the PRP–PCL nanofibers showed an increased adhesion and proliferation compared to pristine PCL fibers. Moreover, the adsorbed PRP enabled angiogenesis features observed as neovascularization in a chicken chorioallantoic membrane (CAM) model. Overall, these results suggest that PRP–PCL scaffolds hold promise for tissue regeneration applications. - Highlights: • Platelet-rich plasma (PRP) can be adsorbed on electrospun fibers via lyophilization. • PRP coating enhanced mesenchymal stem cell adhesion and proliferation on scaffolds. • PRP-coated scaffolds showed sustained release of growth factors. • Adsorbed PRP provided angiogenic features. • PRP-poly(ε-caprolactone) scaffolds hold promise for tissue regeneration applications

  16. Biodegradable electrospun nanofibers coated with platelet-rich plasma for cell adhesion and proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Gomez, Luis [Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15872 Santiago de Compostela (Spain); Instituto de Ortopedia y Banco de Tejidos Musculoesqueléticos, Universidad de Santiago de Compostela, 15872 Santiago de Compostela (Spain); Alvarez-Lorenzo, Carmen, E-mail: carmen.alvarez.lorenzo@usc.es [Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15872 Santiago de Compostela (Spain); Concheiro, Angel [Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15872 Santiago de Compostela (Spain); Silva, Maite [Instituto de Ortopedia y Banco de Tejidos Musculoesqueléticos, Universidad de Santiago de Compostela, 15872 Santiago de Compostela (Spain); Dominguez, Fernando [Fundación Publica Galega de Medicina Xenómica, Santiago de Compostela (Spain); Sheikh, Faheem A.; Cantu, Travis; Desai, Raj; Garcia, Vanessa L. [Department of Chemistry, University of Texas Pan American, Edinburg, TX 78541 (United States); Macossay, Javier, E-mail: jmacossay@utpa.edu [Department of Chemistry, University of Texas Pan American, Edinburg, TX 78541 (United States)

    2014-07-01

    Biodegradable electrospun poly(ε-caprolactone) (PCL) scaffolds were coated with platelet-rich plasma (PRP) to improve cell adhesion and proliferation. PRP was obtained from human buffy coat, and tested on human adipose-derived mesenchymal stem cells (MSCs) to confirm cell proliferation and cytocompatibility. Then, PRP was adsorbed on the PCL scaffolds via lyophilization, which resulted in a uniform sponge-like coating of 2.85 (S.D. 0.14) mg/mg. The scaffolds were evaluated regarding mechanical properties (Young's modulus, tensile stress and tensile strain), sustained release of total protein and growth factors (PDGF-BB, TGF-β1 and VEGF), and hemocompatibility. MSC seeded on the PRP–PCL nanofibers showed an increased adhesion and proliferation compared to pristine PCL fibers. Moreover, the adsorbed PRP enabled angiogenesis features observed as neovascularization in a chicken chorioallantoic membrane (CAM) model. Overall, these results suggest that PRP–PCL scaffolds hold promise for tissue regeneration applications. - Highlights: • Platelet-rich plasma (PRP) can be adsorbed on electrospun fibers via lyophilization. • PRP coating enhanced mesenchymal stem cell adhesion and proliferation on scaffolds. • PRP-coated scaffolds showed sustained release of growth factors. • Adsorbed PRP provided angiogenic features. • PRP-poly(ε-caprolactone) scaffolds hold promise for tissue regeneration applications.

  17. Metals and organochlorine pesticides in caudal scutes of crocodiles from Belize and Costa Rica

    Energy Technology Data Exchange (ETDEWEB)

    Rainwater, Thomas R. [Institute of Environmental and Human Health, Department of Environmental Toxicology, Texas Tech University, Lubbock, TX 79409 (United States)]. E-mail: thomas.rainwater@tiehh.ttu.edu; Wu, Ted H. [Institute of Environmental and Human Health, Department of Environmental Toxicology, Texas Tech University, Lubbock, TX 79409 (United States); Finger, Adam G. [Institute of Environmental and Human Health, Department of Environmental Toxicology, Texas Tech University, Lubbock, TX 79409 (United States); Canas, Jaclyn E. [Institute of Environmental and Human Health, Department of Environmental Toxicology, Texas Tech University, Lubbock, TX 79409 (United States); Yu Lu [Institute of Environmental and Human Health, Department of Environmental Toxicology, Texas Tech University, Lubbock, TX 79409 (United States); Reynolds, Kevin D. [Institute of Environmental and Human Health, Department of Environmental Toxicology, Texas Tech University, Lubbock, TX 79409 (United States); Coimbatore, Gopal [Institute of Environmental and Human Health, Department of Environmental Toxicology, Texas Tech University, Lubbock, TX 79409 (United States); Barr, Brady [National Geographic Channel, 1145 17th St. NW Washington, DC 20036 (United States); Platt, Steven G. [Department of Biology, Box C-64, Sul Ross State University, Alpine, TX 79832 (United States); Cobb, George P. [Institute of Environmental and Human Health, Department of Environmental Toxicology, Texas Tech University, Lubbock, TX 79409 (United States); Anderson, Todd A. [Institute of Environmental and Human Health, Department of Environmental Toxicology, Texas Tech University, Lubbock, TX 79409 (United States); McMurry, Scott T. [Institute of Environmental and Human Health, Department of Environmental Toxicology, Texas Tech University, Lubbock, TX 79409 (United States)

    2007-02-01

    Despite high animal diversity in the Neotropics and the largely unregulated use and disposal of pesticides and industrial chemicals in Central America, few data exist regarding accumulation of environmental contaminants in Central American wildlife. In this study we examined accumulation of metals and organochlorine (OC) pesticides in caudal scutes of crocodiles from Belize and Costa Rica. Scutes from Morelet's crocodiles (Crocodylus moreletii) from two sites in northern Belize were analyzed for metals, and scutes from American crocodiles (C. acutus) from one site in Costa Rica were analyzed for metals and OC pesticides. All scutes (n = 25; one scute from each of 25 individuals) contained multiple contaminants. Mercury was the predominant metal detected, occurring in all scutes examined from both species. Other metals detected include cadmium, copper, lead, and zinc. American crocodile scutes from Costa Rica contained multiple OC pesticides, including endrin, methoxychlor, p,p'-DDE, and p,p'-DDT, all of which occurred in 100% of scutes analyzed (n = 6). Mean metal and OC concentrations varied in relation to those previously reported in crocodilian scutes from other localities in North, Central, and South America. OC concentrations in American crocodile scutes were generally higher than those previously reported for other Costa Rican wildlife. Currently, caudal scutes may serve as general, non-lethal indicators of contaminant accumulation in crocodilians and their areas of occurrence. However, a better understanding of the relationships between pollutant concentrations in scutes, internal tissues, and environmental matrices at sample collection sites are needed to improve the utility of scutes in future ecotoxicological investigations.

  18. Metals and organochlorine pesticides in caudal scutes of crocodiles from Belize and Costa Rica

    International Nuclear Information System (INIS)

    Rainwater, Thomas R.; Wu, Ted H.; Finger, Adam G.; Canas, Jaclyn E.; Yu Lu; Reynolds, Kevin D.; Coimbatore, Gopal; Barr, Brady; Platt, Steven G.; Cobb, George P.; Anderson, Todd A.; McMurry, Scott T.

    2007-01-01

    Despite high animal diversity in the Neotropics and the largely unregulated use and disposal of pesticides and industrial chemicals in Central America, few data exist regarding accumulation of environmental contaminants in Central American wildlife. In this study we examined accumulation of metals and organochlorine (OC) pesticides in caudal scutes of crocodiles from Belize and Costa Rica. Scutes from Morelet's crocodiles (Crocodylus moreletii) from two sites in northern Belize were analyzed for metals, and scutes from American crocodiles (C. acutus) from one site in Costa Rica were analyzed for metals and OC pesticides. All scutes (n = 25; one scute from each of 25 individuals) contained multiple contaminants. Mercury was the predominant metal detected, occurring in all scutes examined from both species. Other metals detected include cadmium, copper, lead, and zinc. American crocodile scutes from Costa Rica contained multiple OC pesticides, including endrin, methoxychlor, p,p'-DDE, and p,p'-DDT, all of which occurred in 100% of scutes analyzed (n = 6). Mean metal and OC concentrations varied in relation to those previously reported in crocodilian scutes from other localities in North, Central, and South America. OC concentrations in American crocodile scutes were generally higher than those previously reported for other Costa Rican wildlife. Currently, caudal scutes may serve as general, non-lethal indicators of contaminant accumulation in crocodilians and their areas of occurrence. However, a better understanding of the relationships between pollutant concentrations in scutes, internal tissues, and environmental matrices at sample collection sites are needed to improve the utility of scutes in future ecotoxicological investigations

  19. Low-level laser irradiation induces in vitro proliferation of mesenchymal stem cells

    International Nuclear Information System (INIS)

    Barboza, Carlos Augusto Galvão; Ginani, Fernanda; Soares, Diego Moura; Henriques, Águida Cristina Gomes; Freitas, Roseana de Almeida

    2014-01-01

    To evaluate the effect of low-level laser irradiation on the proliferation and possible nuclear morphological changes of mouse mesenchymal stem cells. Mesenchymal stem cells derived from bone marrow and adipose tissue were submitted to two applications (T0 and T48 hours) of low-level laser irradiation (660nm; doses of 0.5 and 1.0J/cm"2). The trypan blue assay was used to evaluate cell viability, and growth curves were used to analyze proliferation at zero, 24, 48, and 72 hours. Nuclear alterations were evaluated by staining with DAPI (4'-6-diamidino-2-phenylindole) at 72 hours. Bone marrow-derived mesenchymal stem cells responded to laser therapy in a dose-dependent manner. Higher cell growth was observed when the cells were irradiated with a dose of 1.0J/cm"2, especially after 24 hours (p<0.01). Adipose-derived mesenchymal stem cells responded better to a dose of 1.0J/cm"2, but higher cell proliferation was observed after 48 hours (p<0.05) and 72 hours (p<0.01). Neither nuclear alterations nor a significant change in cell viability was detected in the studied groups. Low-level laser irradiation stimulated the proliferation of mouse mesenchymal stem cells without causing nuclear alterations. The biostimulation of mesenchymal stem cells using laser therapy might be an important tool for regenerative therapy and tissue engineering

  20. Novel, Moon and Mars, partial gravity simulation paradigms and their effects on the balance between cell growth and cell proliferation during early plant development.

    Science.gov (United States)

    Manzano, Aránzazu; Herranz, Raúl; den Toom, Leonardus A; Te Slaa, Sjoerd; Borst, Guus; Visser, Martijn; Medina, F Javier; van Loon, Jack J W A

    2018-01-01

    Clinostats and Random Positioning Machine (RPM) are used to simulate microgravity, but, for space exploration, we need to know the response of living systems to fractional levels of gravity (partial gravity) as they exist on Moon and Mars. We have developed and compared two different paradigms to simulate partial gravity using the RPM, one by implementing a centrifuge on the RPM (RPM HW ), the other by applying specific software protocols to driving the RPM motors (RPM SW ). The effects of the simulated partial gravity were tested in plant root meristematic cells, a system with known response to real and simulated microgravity. Seeds of Arabidopsis thaliana were germinated under simulated Moon (0.17  g ) and Mars (0.38  g ) gravity. In parallel, seeds germinated under simulated microgravity (RPM), or at 1  g control conditions. Fixed root meristematic cells from 4-day grown seedlings were analyzed for cell proliferation rate and rate of ribosome biogenesis using morphometrical methods and molecular markers of the regulation of cell cycle and nucleolar activity. Cell proliferation appeared increased and cell growth was depleted under Moon gravity, compared with the 1  g control. The effects were even higher at the Moon level than at simulated microgravity, indicating that meristematic competence (balance between cell growth and proliferation) is also affected at this gravity level. However, the results at the simulated Mars level were close to the 1  g static control. This suggests that the threshold for sensing and responding to gravity alteration in the root would be at a level intermediate between Moon and Mars gravity. Both partial g simulation strategies seem valid and show similar results at Moon g -levels, but further research is needed, in spaceflight and simulation facilities, especially around and beyond Mars g levels to better understand more precisely the differences and constrains in the use of these facilities for the space biology community.

  1. Low-intensity pulsed ultrasound stimulates cell proliferation, proteoglycan synthesis and expression of growth factor-related genes in human nucleus pulposus cell line

    Directory of Open Access Journals (Sweden)

    Y Kobayashi

    2009-06-01

    Full Text Available Low-intensity pulsed ultrasound (LIPUS stimulation has been shown to effect differentiation and activation of human chondrocytes. A study involving stimulation of rabbit disc cells with LIPUS revealed upregulation of cell proliferation and proteoglycan (PG synthesis. However, the effect of LIPUS on human nucleus pulposus cells has not been investigated. In the present study, therefore, we investigated whether LIPUS stimulation of a human nucleus pulposus cell line (HNPSV-1 exerted a positive effect on cellular activity. HNPSV-1 cells were encapsulated in 1.2% sodium alginate solution at 1x105 cells/ml and cultured at 10 beads/well in 6-well plates. The cells were stimulated for 20 min each day using a LIPUS generator, and the effects of LIPUS were evaluated by measuring DNA and PG synthesis. Furthermore, mRNA expression was analyzed by cDNA microarray using total RNA extracted from the cultured cells. Our study revealed no significant difference in cell proliferation between the control and the ultrasound treated groups. However, PG production was significantly upregulated in HNPSV cells stimulated at intensities of 15, 30, 60, and 120 mW/cm2 compared with the control. The results of cDNA array showed that LIPUS significantly stimulated the gene expression of growth factors and their receptors (BMP2, FGF7, TGFbetaR1 EGFRF1, VEGF. These findings suggest that LIPUS stimulation upregulates PG production in human nucleus pulposus cells by the enhancement of several matrix-related genes including growth factor-related genes. Safe and non-invasive stimulation using LIPUS may be a useful treatment for delaying the progression of disc degeneration.

  2. Effect of pirfenidone on the proliferation of rat corneal stromal cells

    Directory of Open Access Journals (Sweden)

    Jun-Jie Chen

    2015-02-01

    Full Text Available AIM: To investigate the effects of pirfenidone(PFDon the proliferation and transfomring growth factor-β1(TGF-β1expression in vitro culture rat corneal stromal cells. METHODS: Corneal stromal cells from 8 to 10wk SD rats were isolated, cultured and treated with different concentrations of PFD 0mg/mL(control group, 0.15mg/mL(experimental group Ⅰ, 0.3mg/mL(experimental group Ⅱ, 1mg/mL(experimental group Ⅲfor 48h. CCK-8 assay was performed to assess cell proliferation, while immunocytochemistry and Western Blot were used to detect the expression of ki-67 and TGF-β1 expression, respectively. RESULTS: Compared with control group, PFD significantly inhibited the proliferation in a dose-dependent manner(all P1 in a dose-dependent manner(PCONCLUSION: Pirfenidone can significantly inhibit the proliferation of rat corneal stromal cell by down regulating TGF-β1 expression, therefore, it has potential prospect in lightening the corneal wound healing reaction.

  3. A Mathematical Model Quantifies Proliferation and Motility Effects of TGF-β on Cancer Cells

    Directory of Open Access Journals (Sweden)

    Shizhen Emily Wang

    2009-01-01

    Full Text Available Transforming growth factor (TGF-β is known to have properties of both a tumour suppressor and a tumour promoter. While it inhibits cell proliferation, it also increases cell motility and decreases cell–cell adhesion. Coupling mathematical modelling and experiments, we investigate the growth and motility of oncogene-expressing human mammary epithelial cells under exposure to TGF-β. We use a version of the well-known Fisher–Kolmogorov equation, and prescribe a procedure for its parametrisation. We quantify the simultaneous effects of TGF-β to increase the tendency of individual cells and cell clusters to move randomly and to decrease overall population growth. We demonstrate that in experiments with TGF-β treated cells in vitro, TGF-β increases cell motility by a factor of 2 and decreases cell proliferation by a factor of 1/2 in comparison with untreated cells.

  4. Inosine Released from Dying or Dead Cells Stimulates Cell Proliferation via Adenosine Receptors

    Directory of Open Access Journals (Sweden)

    Yi Zhao

    2017-04-01

    Full Text Available IntroductionMany antitumor therapies induce apoptotic cell death in order to cause tumor regression. Paradoxically, apoptotic cells are also known to promote wound healing, cell proliferation, and tumor cell repopulation in multicellular organisms. We aimed to characterize the nature of the regenerative signals concentrated in the micromilieu of dead and dying cells.MethodsCultures of viable melanoma B16F10 cells, mouse fibroblasts, and primary human fibroblast-like synoviocytes (FLS in the presence of dead and dying cells, their supernatants (SNs, or purified agonists and antagonists were used to evaluate the stimulation of proliferation. Viable cell quantification was performed by either flow cytometry of harvested cells or by crystal violet staining of adherent cells. High-performance liquid chromatography and liquid chromatography coupled with mass spectrometry of cell SNs were deployed to identify the nature of growth-promoting factors. Coimplantation of living cells in the presence of SNs collected from dead and dying cells and specific agonists was used to evaluate tumor growth in vivo.ResultsThe stimulation of proliferation of few surviving cells by bystander dead cells was confirmed for melanoma cells, mouse fibroblasts, and primary FLS. We found that small soluble molecules present in the protein-free fraction of SNs of dead and dying cells were responsible for the promotion of proliferation. The nucleoside inosine released by dead and dying cells acting via adenosine receptors was identified as putative inducer of proliferation of surviving tumor cells after irradiation and heat treatment.ConclusionInosine released by dead and dying cells mediates tumor cell proliferation via purinergic receptors. Therapeutic strategies surmounting this pathway may help to reduce the rate of recurrence after radio- and chemotherapy.

  5. Testicular growth and development in puberty.

    Science.gov (United States)

    Koskenniemi, Jaakko J; Virtanen, Helena E; Toppari, Jorma

    2017-06-01

    To describe pubertal testicular growth in humans, changes in testicular cell populations that result in testicular growth, and the role of testosterone and gonadotrophins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in testicular growth. When human data were not available, studies in nonhuman primates and/or rodents were used as surrogates. Testicular growth in puberty follows a sigmoidal growth curve, with a large variation in timing of testicular growth and adult testicular volume. Testicular growth early in puberty is due to increase in Sertoli cell number and length of seminiferous tubules, whereas the largest and fastest growth results from the increase in the diameter of the seminiferous tubules first due to spermatogonial proliferation and then due to the expansion of meiotic and haploid germ cells. FSH stimulates Sertoli cell and spermatogonial proliferation, whereas LH/testosterone is mandatory to complete spermatogenesis. However, FSH and LH/testosterone work in synergy and are both needed for normal spermatogenesis. Testicular growth during puberty is rapid, and mostly due to germ cell expansion and growth in seminiferous tubule diameter triggered by androgens. Pre-treatment with FSH before the induction of puberty may improve the treatment of hypogonadotropic hypogonadism, but remains to be proven.

  6. Salinomycin inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cell in vitro and suppresses tumor growth in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Danxin; Zhang, Yu; Huang, Jie; Fan, Zirong; Shi, Fengrong; Wang, Senming, E-mail: wsenming@126.com

    2014-01-10

    Highlight: •We first evaluated the effect of salinomycin on nasopharyngeal carcinoma (NPC). •Salinomycin could inhibit Wnt/β-catenin signaling and induce apoptosis in NPC. •So salinomycin may be a good potential candidate for the chemotherapy of NPC. -- Abstract: Salinomycin (Sal) is a polyether ionophore antibiotic that has recently been shown to induce cell death in various human cancer cells. However, whether salinomycin plays a functional role in nasopharyngeal carcinoma (NPC) has not been determined to date. The present study investigated the chemotherapeutic efficacy of salinomycin and its molecular mechanisms of action in NPC cells. Salinomycin efficiently inhibited proliferation and invasion of 3 NPC cell lines (CNE-1, CNE-2, and CNE-2/DDP) and activated a extensive apoptotic process that is accompanied by activation of caspase-3 and caspase-9, and decreased mitochondrial membrane potential. Meanwhile, the protein expression level of the Wnt coreceptor lipoprotein receptor related protein 6 (LRP6) and β-catenin was down-regulated, which showed that the Wnt/β-catenin signaling was involved in salinomycin-induced apoptosis of NPC cells. In a nude mouse NPC xenograft model, the anti-tumor effect of salinomycin was associated with the downregulation of β-catenin expression. The present study demonstrated that salinomycin can effectively inhibit proliferation and invasion, and induce apoptosis of NPC cells in vitro and inhibit tumor growth in vivo, probably via the inhibition of Wnt/β-catenin signaling, suggesting salinomycin as a potential candidate for the chemotherapy of NPC.

  7. Phenolic Compounds in Extra Virgin Olive Oil Stimulate Human Osteoblastic Cell Proliferation.

    Science.gov (United States)

    García-Martínez, Olga; De Luna-Bertos, Elvira; Ramos-Torrecillas, Javier; Ruiz, Concepción; Milia, Egle; Lorenzo, María Luisa; Jimenez, Brigida; Sánchez-Ortiz, Araceli; Rivas, Ana

    2016-01-01

    In this study, we aimed to clarify the effects of phenolic compounds and extracts from different extra virgin olive oil (EVOO) varieties obtained from fruits of different ripening stages on osteoblast cells (MG-63) proliferation. Cell proliferation was increased by hydroxytyrosol, luteolin, apigenin, p-coumaric, caffeic, and ferulic acids by approximately 11-16%, as compared with controls that were treated with one vehicle alone, while (+)-pinoresinol, oleuropein, sinapic, vanillic acid and derivative (vanillin) did not affect cell proliferation. All phenolic extracts stimulated MG-63 cell growth, and they induced higher cell proliferation rates than individual compounds. The most effective EVOO phenolic extracts were those obtained from the Picual variety, as they significantly increased cell proliferation by 18-22%. Conversely, Arbequina phenolic extracts increased cell proliferation by 9-13%. A decline in osteoblast proliferation was observed in oils obtained from olive fruits collected at the end of the harvest period, as their total phenolic content decreases at this late stage. Further research on the signaling pathways of olive oil phenolic compounds involved in the processes and their metabolism should be carried out to develop new interventions and adjuvant therapies using EVOO for bone health (i.e.osteoporosis) in adulthood and the elderly.

  8. Phenolic Compounds in Extra Virgin Olive Oil Stimulate Human Osteoblastic Cell Proliferation

    Science.gov (United States)

    García-Martínez, Olga; De Luna-Bertos, Elvira; Ramos-Torrecillas, Javier; Ruiz, Concepción; Milia, Egle; Lorenzo, María Luisa; Jimenez, Brigida; Sánchez-Ortiz, Araceli; Rivas, Ana

    2016-01-01

    In this study, we aimed to clarify the effects of phenolic compounds and extracts from different extra virgin olive oil (EVOO) varieties obtained from fruits of different ripening stages on osteoblast cells (MG-63) proliferation. Cell proliferation was increased by hydroxytyrosol, luteolin, apigenin, p-coumaric, caffeic, and ferulic acids by approximately 11–16%, as compared with controls that were treated with one vehicle alone, while (+)-pinoresinol, oleuropein, sinapic, vanillic acid and derivative (vanillin) did not affect cell proliferation. All phenolic extracts stimulated MG-63 cell growth, and they induced higher cell proliferation rates than individual compounds. The most effective EVOO phenolic extracts were those obtained from the Picual variety, as they significantly increased cell proliferation by 18–22%. Conversely, Arbequina phenolic extracts increased cell proliferation by 9–13%. A decline in osteoblast proliferation was observed in oils obtained from olive fruits collected at the end of the harvest period, as their total phenolic content decreases at this late stage. Further research on the signaling pathways of olive oil phenolic compounds involved in the processes and their metabolism should be carried out to develop new interventions and adjuvant therapies using EVOO for bone health (i.e.osteoporosis) in adulthood and the elderly. PMID:26930190

  9. Proliferation of epithelial cell rests, formation of apical cysts, and regression of apical cysts after periapical wound healing.

    Science.gov (United States)

    Lin, Louis M; Huang, George T-J; Rosenberg, Paul A

    2007-08-01

    There is continuing controversy regarding the potential for inflammatory apical cysts to heal after nonsurgical endodontic therapy. Molecular cell biology may provide answers to a series of related questions. How are the epithelial cell rests of Malassez stimulated to proliferate? How are the apical cysts formed? How does the lining epithelium of apical cysts regress after endodontic therapy? Epithelial cell rests are induced to divide and proliferate by inflammatory mediators, proinflammatory cytokines, and growth factors released from host cells during periradicular inflammation. Quiescent epithelial cell rests can behave like restricted-potential stem cells if stimulated to proliferate. Formation of apical cysts is most likely caused by the merging of proliferating epithelial strands from all directions to form a three-dimensional ball mass. After endodontic therapy, epithelial cells in epithelial strands of periapical granulomas and the lining epithelium of apical cysts may stop proliferating because of a reduction in inflammatory mediators, proinflammatory cytokines, and growth factors. Epithelial cells will also regress because of activation of apoptosis or programmed cell death through deprivation of survival factors or by receiving death signals during periapical wound healing.

  10. Effects of ketamine and midazolam on emergence agitation after sevoflurane anaesthesia in children receiving caudal block: a randomized trial

    Directory of Open Access Journals (Sweden)

    Ayse Ozcan

    2014-12-01

    Full Text Available Background and objectives: Emergence agitation is a common postanaesthetic problem in children after sevoflurane anaesthesia. We aimed to compare the effects of ketamine and midazolam administered intravenously, before the end of surgery, for prevention of emergence agitation in children who received caudal block for pain relief under sevoflurane anaesthesia. Methods: 62 American Society of Anesthesiologists patient classification status I children, aged 2–7 years, scheduled for inguinal hernia repair, circumcision or orchidopexy were enrolled to the study. Anaesthesia was induced with sevoflurane 8% in a mixture of 50% oxygen and nitrous oxide. After achieving adequate depth of anaesthesia, a laryngeal mask was placed and then caudal block was performed with 0.75 mL kg−1, 0.25% bupivacaine. At the end of the surgery, ketamine 0.25 mg kg−1, midazolam 0.03 mg kg−1 and saline were given to ketamine, midazolam and control groups, respectively. Agitation was assessed using Paediatric Anaesthesia Emergence Delirium scale and postoperative pain was evaluated with modified Children's Hospital of Eastern Ontario Pain Scale. Results and conclusions: Modified Children's Hospital of Eastern Ontario Pain Scale scores were found higher in control group than in ketamine and midazolam groups. Paediatric Anaesthesia Emergence Delirium scores were similar between groups. Modified Children's Hospital of Eastern Ontario Pain Scale and Paediatric Anaesthesia Emergence Delirium scores showed a significant decrease by time in all groups during follow-up in postanaesthesia care unit. The present study resulted in satisfactory Paediatric Anaesthesia Emergence Delirium scores which are below 10 in all groups. As a conclusion, neither ketamine nor midazolam added to caudal block under sevoflurane anaesthesia did show further effect on emergence agitation. In addition, pain relief still seems to be the major factor in preventing emergence agitation after

  11. TGF-β2 inhibits AKT activation and FGF-2-induced corneal endothelial cell proliferation

    International Nuclear Information System (INIS)

    Lu Jiawei; Lu Zhenyu; Reinach, Peter

    2006-01-01

    The corneal endothelial cells form a boundary layer between anterior chamber and cornea. This single cell layer is important to maintain cornea transparency by eliciting net fluid transport into the anterior chamber. Injuries of the corneal endothelial layer in humans lead to corneal swelling and translucence. This hindrance is thought to be due to limited proliferative capacity of the endothelial layer. Fibroblast growth factor 2 (FGF-2) and transforming growth factor-beta 2 (TGF-β2) are both found in aqueous humor, and these two cytokines promote and inhibit cell growth, respectively. The intracellular signaling mechanisms by which TGF-β2 suppresses the mitogenic response to FGF-2, however, remain unclear. We have addressed this question by investigating potential crosstalk between FGF-2-induced and TGF-β2-regulated intracellular signaling events in cultured bovine corneal endothelial (BCE) cells. We found that TGF-β2 and FGF-2 oppositely affect BCE cell proliferation and TGF-β2 can override the stimulating effects of FGF-2 by increasing COX-2 expression in these cells. Consistent with these findings, overexpression of COX-2 significantly reduced FGF-2-induced cell proliferation whereas a COX-2 specific inhibitor NS398 reversed the effect of TGF-β2 on FGF-2-induced cell proliferation. The COX-2 product prostaglandin E2 (PGE-2) blocks FGF-2-induced cell proliferation. Whereas FGF-2 stimulates cell proliferation by activating the AKT pathway, TGF-β2 and PGE-2 both inhibit this pathway. In accordance with the effect of PGE-2, cAMP also inhibits FGF-2-induced AKT activation. These findings suggest that the mitogenic response to FGF-2 in vivo in the corneal endothelial layer may be inhibited by TGF-β2-induced suppression of the PI3-kinase/AKT signaling pathway

  12. Pitch Variability in Patients with Parkinson's Disease: Effects of Deep Brain Stimulation of Caudal Zona Incerta and Subthalamic Nucleus

    Science.gov (United States)

    Karlsson, Fredrik; Olofsson, Katarina; Blomstedt, Patric; Linder, Jan; van Doorn, Jan

    2013-01-01

    Purpose: The purpose of the present study was to examine the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) pitch characteristics of connected speech in patients with Parkinson's disease (PD). Method: The authors evaluated 16 patients preoperatively and 12 months after DBS surgery. Eight…

  13. Enriched Astaxanthin Extract from Haematococcus pluvialis Augments Growth Factor Secretions to Increase Cell Proliferation and Induces MMP1 Degradation to Enhance Collagen Production in Human Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Hsin-Yu Chou

    2016-06-01

    Full Text Available Among many antioxidants that are used for the repairing of oxidative stress induced skin damages, we identified the enriched astaxanthin extract (EAE from Haematococcus pluvialis as a viable ingredient. EAE was extracted from the red microalgae through supercritical fluid carbon dioxide extraction. To compare the effectiveness, EAE wastreated on human dermal fibroblasts with other components, phorbol 12-myristate 13-acetate (PMA, and doxycycline. With sirius red staining and quantitative real-time polymerase chain reaction (qRT-PCR, we found that PMA decreased the collagen concentration and production while overall the addition of doxycycline and EAE increased the collagen concentration in a trial experiments. EAE increased collagen contents through inhibited MMP1 and MMP3 mRNA expression and induced TIMP1, the antagonists of MMPs protein, gene expression. As for when tested for various proteins through western blotting, it was seen that the addition of EAE increased the expression of certain proteins that promote cell proliferation. Testing those previous solutions using growth factor assay, it was noticeable that EAE had a positive impact on cell proliferation and vascular endothelial growth factor (VEGF than doxycycline, indicating that it was a better alternative treatment for collagen production. To sum up, the data confirmed the possible applications as medical cosmetology agentsand food supplements.

  14. Dafachronic acid inhibits C. elegans germ cell proliferation in a DAF-12-dependent manner.

    Science.gov (United States)

    Mukherjee, Madhumati; Chaudhari, Snehal N; Balachandran, Riju S; Vagasi, Alexandra S; Kipreos, Edward T

    2017-12-15

    Dafachronic acid (DA) is a bile acid-like steroid hormone that regulates dauer formation, heterochrony, and lifespan in C. elegans. Here, we describe that DA is an inhibitor of C. elegans germ stem cell proliferation in adult hermaphrodites. Using a C. elegans germ cell primary culture system, we show that DA inhibits the proliferation of germ cells in vitro. Exogenous DA reduces the frequency of large tumors in adult tumorous germline mutants and decreases the proliferation of wild-type germ stem cells in adult hermaphrodites. In contrast, DA has no appreciable effect on the proliferation of larval-stage germ cells in wild type. The inhibition of adult germ cell proliferation by DA requires its canonical receptor DAF-12. Blocking DA production by inactivating the cytochrome P450 DAF-9 increases germ cell proliferation in wild-type adult hermaphrodites and the frequency of large tumors in germline tumorous mutants, suggesting that DA inhibits the rate of germ cell proliferation under normal growth conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activity

    International Nuclear Information System (INIS)

    Qi, Wentao; Weber, Christopher R; Wasland, Kaarin; Savkovic, Suzana D

    2011-01-01

    Soy consumption is associated with a lower incidence of colon cancer which is believed to be mediated by one of its of components, genistein. Genistein may inhibit cancer progression by inducing apoptosis or inhibiting proliferation, but mechanisms are not well understood. Epidermal growth factor (EGF)-induced proliferation of colon cancer cells plays an important role in colon cancer progression and is mediated by loss of tumor suppressor FOXO3 activity. The aim of this study was to assess if genistein exerts anti-proliferative properties by attenuating the negative effect of EGF on FOXO3 activity. The effect of genistein on proliferation stimulated by EGF-mediated loss of FOXO3 was examined in human colonic cancer HT-29 cells. EGF-induced FOXO3 phosphorylation and translocation were assessed in the presence of genistein. EGF-mediated loss of FOXO3 interactions with p53 (co-immunoprecipitation) and promoter of p27kip1 (ChIP assay) were examined in presence of genistein in cells with mutated p53 (HT-29) and wild type p53 (HCT116). Silencing of p53 determined activity of FOXO3 when it is bound to p53. Genistein inhibited EGF-induced proliferation, while favoring dephosphorylation and nuclear retention of FOXO3 (active state) in colon cancer cells. Upstream of FOXO3, genistein acts via the PI3K/Akt pathway to inhibit EGF-stimulated FOXO3 phosphorylation (i.e. favors active state). Downstream, EGF-induced disassociation of FOXO3 from mutated tumor suppressor p53, but not wild type p53, is inhibited by genistein favoring FOXO3-p53(mut) interactions with the promoter of the cell cycle inhibitor p27kip1 in colon cancer cells. Thus, the FOXO3-p53(mut) complex leads to elevated p27kip1 expression and promotes cell cycle arrest. These novel anti-proliferative mechanisms of genistein suggest a possible role of combining genistein with other chemoreceptive agents for the treatment of colon cancer

  16. MicroRNA-199 suppresses cell proliferation, migration and invasion by downregulating RGS17 in hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Wei; Qian, Sheng; Yang, Guowei; Zhu, Liang; Zhou, Bo; Wang, Jianhua; Liu, Rong; Yan, Zhiping; Qu, Xudong

    2018-06-15

    Hepatocellular carcinoma (HCC), the most common primary tumor of the liver, has a poor prognosis and shows rapid progression. MicroRNAs (miRNAs) play important roles in carcinogenesis and tumor progression. Regulators of G-protein signaling (RGS) are critical for defining G-protein-dependent signal fidelity. RGS17 plays an important role in the regulation of cancer cell proliferation, migration and invasion. Here, we showed that miR-199 was downregulated in a hepatocarcinoma cell line. Overexpression of miR-199 significantly suppressed HCC cell proliferation, migration, and invasion in vitro. RGS17 overexpression promoted HCC cell proliferation, migration, and invasion, and reversed the miR-199 mediated inhibition of proliferation, migration, and invasion. Dual-fluorescence reporter experiments confirmed that miR-199 downregulated RGS17 by direct interaction with the 3'-UTR of RGS17 mRNA. In vivo studies showed that miR-199 overexpression significantly inhibited the growth of tumors. Taken together, the results suggested that miR-199 inhibited tumor growth and metastasis by targeting RGS17. Published by Elsevier B.V.

  17. Wernekink Commissure Syndrome Secondary to Bilateral Caudal Paramedian Midbrain Infarction Presenting with a Unique “Heart or V” Appearance Sign: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Chenguang Zhou

    2017-08-01

    Full Text Available Wernekink commissure syndrome secondary to caudal paramedian midbrain infarction (CPMI is a rare midbrain syndrome involving the decussation of the superior cerebellar peduncle in the caudal paramedian midbrain tegmentum. The central characteristics are constant bilateral cerebellar dysfunction, variable eye movement disorders, and rare delayed palatal myoclonus. Following is a description of the case of a 60-year-old man who presented with dizziness, slurred speech, and difficulty walking. Neurological examination revealed bilateral cerebellar dysfunction and bilateral internuclear ophthalmoplegia (bilateral INO. Serial magnetic resonance imaging (MRI revealed a lesion in the caudal paramedian midbrain with a “heart-shaped” sign on fluid-attenuation inversion recovery images and a “V-shaped” appearance on diffusion-weighted imaging (DWI. An acute CPMI with a “heart or V” appearance sign was diagnosed. Upon follow-up evaluation 3 months later, a palatal tremor accompanied by involuntary head tremor was discovered. Hypertrophy and increased signal of the bilateral inferior olivary nucleus, compatible with hypertropic olivary degeneration (HOD were revealed during a subsequent MRI study.

  18. Evaluation of Artificial Caudal Fin for Fish Robot with Two Joints by Using Three-Dimensional Fluid-Structure Simulation

    Directory of Open Access Journals (Sweden)

    Yogo Takada

    2013-01-01

    Full Text Available A fish robot with image sensors is useful to research for underwater creatures such as fish. However, the propulsion velocity of a fish robot is very slow compared with live fish. It is necessary to swim at a speed several times faster than the speed of the current robots for various usages. Therefore, we are searching for the method of making the robot swim fast. The simulation before making the robot is important. We have made the computational simulation program of three-dimensional fluid-structure analysis. The flow around the caudal fin can be examined by analyzing the fin as an elastic body. We compared the results of numerical analysis with the results of PIV measurement. Both were agreed well. Because the performance of a fish robot with two joints is better than that of a fish robot with one joint, we searched for an excellent fin for the fish robot with two joints by using CFD. We confirmed that the swimming performance of a fish robot becomes very good when the caudal fin is rigid except for the root of the fin which is comparatively flexible.

  19. Verteporfin inhibits papillary thyroid cancer cells proliferation and cell cycle through ERK1/2 signaling pathway

    Science.gov (United States)

    Liao, Tian; Wei, Wen-Jun; Wen, Duo; Hu, Jia-Qian; Wang, Yu; Ma, Ben; Cao, Yi-Min; Xiang, Jun; Guan, Qing; Chen, Jia-Ying; Sun, Guo-Hua; Zhu, Yong-Xue; Li, Duan-Shu; Ji, Qing-Hai

    2018-01-01

    Verteporfin, a FDA approved second-generation photosensitizer, has been demonstrated to have anticancer activity in various tumors, but not including papillary thyroid cancer (PTC). In current pre-clinical pilot study, we investigate the effect of verteporfin on proliferation, apoptosis, cell cycle and tumor growth of PTC. Our results indicate verteporfin attenuates cell proliferation, arrests cell cycle in G2/S phase and induces apoptosis of PTC cells. Moreover, treatment of verteporfin dramatically suppresses tumor growth from PTC cells in xenograft mouse model. We further illustrate that exposure to MEK inhibitor U0126 inactivates phosphorylation of ERK1/2 and MEK in verteporfin-treated PTC cells. These data suggest verteporfin exhibits inhibitory effect on PTC cells proliferation and cell cycle partially via ERK1/2 signalling pathway, which strongly encourages the further application of verteporfin in the treatment against PTC. PMID:29721041

  20. Hyaluronan suppresses prostate tumor cell proliferation through diminished expression of N-cadherin and aberrant growth factor receptor signaling

    International Nuclear Information System (INIS)

    Bharadwaj, Alamelu G.; Goodrich, Nathaniel P.; McAtee, Caitlin O.; Haferbier, Katie; Oakley, Gregory G.; Wahl, James K.; Simpson, Melanie A.

    2011-01-01

    Hyaluronan (HA) production has been functionally implicated in prostate tumorigenesis and metastasis. We previously used prostate tumor cells overexpressing the HA synthesizing enzyme HAS3 or the clinically relevant hyaluronidase Hyal1 to show that excess HA production suppresses tumor growth, while HA turnover accelerates spontaneous metastasis from the prostate. Here, we examined pathways responsible for effects of HAS3 and Hyal1 on tumor cell phenotype. Detailed characterization of cell cycle progression revealed that expression of Hyal1 accelerated cell cycle re-entry following synchronization, whereas HAS3 alone delayed entry. Hyal1 expressing cells exhibited a significant reduction in their ability to sustain ERK phosphorylation upon stimulation by growth factors, and in their expression of the cyclin-dependent kinase inhibitor p21. In contrast, HAS3 expressing cells showed prolonged ERK phosphorylation and increased expression of both p21 and p27, in asynchronous and synchronized cultures. Changes in cell cycle regulatory proteins were accompanied by HA-induced suppression of N-cadherin, while E-cadherin expression and β-catenin expression and distribution remained unchanged. Our results are consistent with a model in which excess HA synthesis suppresses cell proliferation by promoting homotypic E-cadherin mediated cell-cell adhesion, consequently signaling to elevate cell cycle inhibitor expression and suppress G1- to S-phase transition.

  1. Evidence that transferrin supports cell proliferation by supplying iron for DNA synthesis

    International Nuclear Information System (INIS)

    Laskey, J.; Webb, I.; Schulman, H.M.; Ponka, P.

    1988-01-01

    Transferrin is essential for cell proliferation and it was suggested that it may trigger a proliferative response following its interaction with receptors, serving as a growth factor. However, since the only clearly defined function of transferrin is iron transport, it may merely serve as an iron donor. To further clarify this issue, the authors took advantage of an iron chelate, ferric salicylaldehyde isonicotinoyl hydrazone (Fe-SIH), which they developed and previously demonstrated to efficiently supply iron to cells without using physiological transferrin receptor pathway. As expected, they observed that blocking monoclonal antibodies against transferrin receptors inhibited proliferation of both Raji and murine erythroleukemia cells. This inhibited cell growth was rescued upon the addition of Fe-SIH which was also shown to deliver iron to Raji cells in the presence of blocking anti-transferrin receptor antibodies. Moreover, blocking anti-transferrin receptor antibodies inhibited [ 3 H]thymidine incorporation into DNA and this inhibition could be overcome by added Fe-SIH. In addition, Fe-SIH slightly stimulated, while SIH (an iron chelator) significantly inhibited, DNA synthesis in phytohemagglutinin-stimulated peripheral blood lymphocytes. Taken together, these results indicate that the only function of transferrin supporting cell proliferation is to supply cells with iron

  2. Nitric oxide mediated DNA double strand breaks induced in proliferating bystander cells after {alpha}-particle irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Han Wei [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Chen Shaopeng [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Wu Lijun [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China)

    2010-02-03

    Low-dose {alpha}-particle exposures comprise 55% of the environmental dose to the human population and have been shown to induce bystander responses. Previous studies showed that bystander effect could induce stimulated cell growth or genotoxicity, such as excessive DNA double strand breaks (DSBs), micronuclei (MN), mutation and decreased cell viability, in the bystander cell population. In the present study, the stimulated cell growth, detected with flow cytometry (FCM), and the increased MN and DSB, detected with p53 binding protein 1 (53BP1) immunofluorescence, were observed simultaneously in the bystander cell population, which were co-cultured with cells irradiated by low-dose {alpha}-particles (1-10 cGy) in a mixed system. Further studies indicated that nitric oxide (NO) and transforming growth factor {beta}1 (TGF-{beta}1) played very important roles in mediating cell proliferation and inducing MN and DSB in the bystander population through treatments with NO scavenger and TGF-{beta}1 antibody. Low-concentrations of NO, generated by spermidine, were proved to induce cell proliferation, DSB and MN simultaneously. The proliferation or shortened cell cycle in bystander cells gave them insufficient time to repair DSBs. The increased cell division might increase the probability of carcinogenesis in bystander cells since cell proliferation increased the probability of mutation from the mis-repaired or un-repaired DSBs.

  3. Nitric oxide mediated DNA double strand breaks induced in proliferating bystander cells after α-particle irradiation

    International Nuclear Information System (INIS)

    Han Wei; Chen Shaopeng; Yu, K.N.; Wu Lijun

    2010-01-01

    Low-dose α-particle exposures comprise 55% of the environmental dose to the human population and have been shown to induce bystander responses. Previous studies showed that bystander effect could induce stimulated cell growth or genotoxicity, such as excessive DNA double strand breaks (DSBs), micronuclei (MN), mutation and decreased cell viability, in the bystander cell population. In the present study, the stimulated cell growth, detected with flow cytometry (FCM), and the increased MN and DSB, detected with p53 binding protein 1 (53BP1) immunofluorescence, were observed simultaneously in the bystander cell population, which were co-cultured with cells irradiated by low-dose α-particles (1-10 cGy) in a mixed system. Further studies indicated that nitric oxide (NO) and transforming growth factor β1 (TGF-β1) played very important roles in mediating cell proliferation and inducing MN and DSB in the bystander population through treatments with NO scavenger and TGF-β1 antibody. Low-concentrations of NO, generated by spermidine, were proved to induce cell proliferation, DSB and MN simultaneously. The proliferation or shortened cell cycle in bystander cells gave them insufficient time to repair DSBs. The increased cell division might increase the probability of carcinogenesis in bystander cells since cell proliferation increased the probability of mutation from the mis-repaired or un-repaired DSBs.

  4. Caudal regression syndrome and sirenomelia in only one twin in two diabetic pregnancies.

    Science.gov (United States)

    Assimakopoulos, E; Athanasiadis, A; Zafrakas, M; Dragoumis, K; Bontis, J

    2004-01-01

    Many authors consider sirenomelia to be an extreme form of caudal regression syndrome (CRS), while others argue that they are two distinct entities. Maternal diabetes mellitus is considered to be an important predisposing factor for both CRS and sirenomelia. Two rare cases of diabetic, dizygotic twin pregnancies, each with one normal and one affected fetus are presented. In case 1 the affected fetus had CRS. In case 2 the affected fetus had sirenomelia. The present cases suggest that the pathogenesis of CRS and sirenomelia is more complex than previously thought, that maternal diabetes is not the only underlying pathogenetic mechanism and that genetic or epigenetic factors probably contribute to the formation of these conditions.

  5. Acute traumatic brain-stem hemorrhage produced by sudden caudal displacement of the brain

    International Nuclear Information System (INIS)

    Mirvis, S.E.; Wolf, A.L.; Thompson, R.K.

    1990-01-01

    This paper determines in an experimental canine study and a clinical review, whether acute caudal displacement of the brain following blunt trauma produces hemorrhage in the rostral anterior midline of the brain stem by tethering the basilar to the fixed carotid arteries. In four dogs, a balloon catheter was suddenly inflated over the frontal lobe; in two, the carotid-basilar vascular connections were severed prior to balloon inflation. ICP was monitored during and after balloon inflation. Hemorrhage was verified by MR imaging and direct inspection of the fixed brain specimens. Admission CT scans demonstrating acute traumatic brain stem hemorrhage (TBH) in human patients were reviewed to determine the site of TBH, predominant site of impact, and neurologic outcome

  6. Thioredoxin (Trxo1) interacts with proliferating cell nuclear antigen (PCNA) and its overexpression affects the growth of tobacco cell culture.

    Science.gov (United States)

    Calderón, Aingeru; Ortiz-Espín, Ana; Iglesias-Fernández, Raquel; Carbonero, Pilar; Pallardó, Federico Vicente; Sevilla, Francisca; Jiménez, Ana

    2017-04-01

    Thioredoxins (Trxs), key components of cellular redox regulation, act by controlling the redox status of many target proteins, and have been shown to play an essential role in cell survival and growth. The presence of a Trx system in the nucleus has received little attention in plants, and the nuclear targets of plant Trxs have not been conclusively identified. Thus, very little is known about the function of Trxs in this cellular compartment. Previously, we studied the intracellular localization of PsTrxo1 and confirmed its presence in mitochondria and, interestingly, in the nucleus under standard growth conditions. In investigating the nuclear function of PsTrxo1 we identified proliferating cellular nuclear antigen (PCNA) as a PsTrxo1 target by means of affinity chromatography techniques using purified nuclei from pea leaves. Such protein-protein interaction was corroborated by dot-blot and bimolecular fluorescence complementation (BiFC) assays, which showed that both proteins interact in the nucleus. Moreover, PsTrxo1 showed disulfide reductase activity on previously oxidized recombinant PCNA protein. In parallel, we studied the effects of PsTrxo1 overexpression on Tobacco Bright Yellow-2 (TBY-2) cell cultures. Microscopy and flow-cytometry analysis showed that PsTrxo1 overexpression increases the rate of cell proliferation in the transformed lines, with a higher percentage of the S phase of the cell cycle at the beginning of the cell culture (days 1 and 3) and at the G2/M phase after longer times of culture (day 9), coinciding with an upregulation of PCNA protein. Furthermore, in PsTrxo1 overexpressed cells there is a decrease in the total cellular glutathione content but maintained nuclear GSH accumulation, especially at the end of the culture, which is accompanied by a higher mitotic index, unlike non-overexpressing cells. These results suggest that Trxo1 is involved in the cell cycle progression of TBY-2 cultures, possibly through its link with cellular PCNA

  7. Hydrogen sulfide (H{sub 2}S)/cystathionine γ-lyase (CSE) pathway contributes to the proliferation of hepatoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Yan; Ye, Shuang; Yuan, Dexiao; Zhang, Jianghong; Bai, Yang; Shao, Chunlin, E-mail: clshao@shmu.edu.cn

    2014-05-15

    Highlights: • Inhibition of H{sub 2}S/CSE pathway strongly stimulates cellular apoptosis. • Inhibition of H{sub 2}S/CSE pathway suppresses cell growth by blocking EGFR pathway. • H{sub 2}S/CSE pathway is critical for maintaining the proliferation of hepatoma cells. - Abstract: Hydrogen sulfide (H{sub 2}S)/cystathionine γ-lyase (CSE) pathway has been demonstrated to play vital roles in physiology and pathophysiology. However, its role in tumor cell proliferation remains largely unclear. Here we found that CSE over-expressed in hepatoma HepG2 and PLC/PRF/5 cells. Inhibition of endogenous H{sub 2}S/CSE pathway drastically decreased the proliferation of HepG2 and PLC/PRF/5 cells, and it also enhanced ROS production and mitochondrial disruption, pronounced DNA damage and increased apoptosis. Moreover, this increase of apoptosis was associated with the activation of p53 and p21 accompanied by a decreased ratio of Bcl-2/Bax and up-regulation of phosphorylated c-Jun N-terminal kinase (JNK) and caspase-3 activity. In addition, the negative regulation of cell proliferation by inhibition of H{sub 2}S/CSE system correlated with the blockage of cell mitogenic and survival signal transduction of epidermal growth factor receptor (EGFR) via down-regulating the extracellular-signal-regulated kinase 1/2 (ERK1/2) activation. These results demonstrate that H{sub 2}S/CSE and its downstream pathway contribute to the proliferation of hepatoma cells, and inhibition of this pathway strongly suppress the excessive growth of hepatoma cells by stimulating mitochondrial apoptosis and suppressing cell growth signal transduction.

  8. Six1 promotes proliferation of pancreatic cancer cells via upregulation of cyclin D1 expression.

    Directory of Open Access Journals (Sweden)

    Zhaoming Li

    Full Text Available Six1 is one of the transcription factors that act as master regulators of development and are frequently dysregulated in cancers. However, the role of Six1 in pancreatic cancer is not clear. Here we show that the relative expression of Six1 mRNA is increased in pancreatic cancer and correlated with advanced tumor stage. In vitro functional assays demonstrate that forced overexpression of Six1 significantly enhances the growth rate and proliferation ability of pancreatic cancer cells. Knockdown of endogenous Six1 decreases the proliferation of these cells dramatically. Furthermore, Six1 promotes the growth of pancreatic cancer cells in a xenograft assay. We also show that the gene encoding cyclin D1 is a direct transcriptional target of Six1 in pancreatic cancer cells. Overexpression of Six1 upregulates cyclin D1 mRNA and protein, and significantly enhances the activity of the cyclin D1 promoter in PANC-1 cells. We demonstrate that Six1 promotes cell cycle progression and proliferation by upregulation of cyclin D1. These data suggest that Six1 is overexpressed in pancreatic cancer and may contribute to the increased cell proliferation through upregulation of cyclin D1.

  9. Anisomycin-induced GATA-6 degradation accompanying a decrease of proliferation of colorectal cancer cell

    Energy Technology Data Exchange (ETDEWEB)

    Ushijima, Hironori; Horyozaki, Akiko; Maeda, Masatomo, E-mail: mmaeda@nupals.ac.jp

    2016-09-09

    Transcription factor GATA-6 plays a key role in normal cell differentiation of the mesoderm and endoderm. On the other hand, GATA-6 is abnormally overexpressed in many clinical gastrointestinal cancer tissue samples, and accelerates cell proliferation or an anti-apoptotic response in cancerous tissues. We previously showed that activation of the JNK signaling cascade causes proteolysis of GATA-6. In this study, we demonstrated that anisomycin, a JNK activator, stimulates nuclear export of GATA-6 in a colorectal cancer cell line, DLD-1. Concomitantly, anisomycin remarkably inhibits the proliferation of DLD-1 cells via G2/M arrest in a plate culture. However, it did not induce apoptosis under growth arrest conditions. Furthermore, the growth of DLD-1 cells in a spheroid culture was suppressed by anisomycin. Although 5-FU showed only a slight inhibitory effect on 3D spheroid cultures, the same concentration of 5-FU together with a low concentration of anisomycin exhibited strong growth inhibition. These results suggest that the induction of GATA-6 dysfunction may be more effective for chemotherapy for colorectal cancer, although the mechanism underlying the synergistic effect of 5-FU and anisomycin remains unknown. - Highlights: • Anisomycin induces proteolysis of GATA-6 in DLD-1 cells. • Anisomycin remarkably inhibits the proliferation of DLD-1 cells via G2/M arrest. • Anisomycin suppresses the growth of spheroids of DLD-1, and enhances the effect of 5-FU.

  10. Nuclear Fuel Leasing, Recycling and proliferation: Modeling a Global View

    International Nuclear Information System (INIS)

    Crozat, M P; Choi, J; Reis, V H; Hill, R

    2004-01-01

    On February 11, 2004, U.S. President George W. Bush, in a speech to the National Defense University stated: ''The world must create a safe, orderly system to field civilian nuclear plants without adding to the danger of weapons proliferation. The world's leading nuclear exporters should ensure that states have reliable access at reasonable cost to fuel for civilian reactors, so long as those states renounce enrichment and reprocessing. Enrichment and reprocessing are not necessary for nations seeking to harness nuclear energy for peaceful purposes.'' This concept would require nations to choose one of two paths for civilian nuclear development: those that only have reactors and those that contain one or more elements of the nuclear fuel cycle, including recycling. ''Fuel cycle'' states would enrich uranium, manufacture and lease fuel to ''reactor'' states and receive the reactor states' spent fuel. All parties would accede to stringent security and safeguard standards, embedded within a newly invigorated international regime. Reactor states would be relieved of the financial, environmental (and political) burden of enriching and manufacturing fuel and dealing with spent fuel. Fuel cycle states would potentially earn money on leasing the fuel and perhaps on sales of reactors to the reactor states. Such a leasing concept is especially interesting in scenarios which envision growth in nuclear power, and an important consideration for such a nuclear growth regime is the role of recycling of civilian spent fuel. Recycling holds promise for improved management of spent fuel and efficient utilization of resources, but continues to raise the specter of a world with uncontrolled nuclear weapons proliferation. If done effectively, a fuel-leasing concept could help create a political and economic foundation for significant growth of clean, carbon-free nuclear power while providing a mechanism for significant international cooperation to reduce proliferation concern. This

  11. Nicotine as a mitogenic stimulus for pancreatic acinar cell proliferation

    Institute of Scientific and Technical Information of China (English)

    Parimal Chowdhury; Kodetthoor B Udupa

    2006-01-01

    Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of nicotine,a mitogen, in the induction of signaling pathways resulting in proliferation of pancreatic tumor cells and compares these events with those in normal acinar cells isolated from the rat pancreas. The data shows striking similarities between these two cellular systems.In addition, the editorial reviews very recent literature of the contribution of MAPK signaling in cell lines associated with human diseases. A prospective cellular model of nicotine induced activation of MAPK cascade is presented.

  12. Proliferation: myth or reality?; La proliferation: mythe ou realite?

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This article analyzes the proliferation approach, its technical condition and political motivation, and the share between the myth (political deception, assumptions and extrapolations) and the reality of proliferation. Its appreciation is complicated by the irrational behaviour of some political actors and by the significant loss of the non-use taboo. The control of technologies is an important element for proliferation slowing down but an efficient and autonomous intelligence system remains indispensable. (J.S.)

  13. Bloqueio peridural caudal: técnica anestésica de uso exclusivo em crianças? É possível sua realização em adultos? Qual o papel do ultrassom nesse contexto?

    Directory of Open Access Journals (Sweden)

    Ilana Esquenazi Najman

    2011-02-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O bloqueio peridural caudal é a mais popular entre todas as técnicas de anestesia regional em crianças. Com o avanço da idade, apenas a relativa dificuldade em localizar o hiato sacral limita seu uso. Entretanto, em adultos a técnica vem sendo largamente utilizada para controle de dor crônica com o auxílio da fluoroscopia. Assim, a habilidade em localizar o hiato e definir as variações anatômicas é o principal fator determinante do sucesso e segurança na execução do bloqueio peridural pela via caudal. Nesse contexto, o ultrassom vem ganhando espaço como guia para a realização do bloqueio caudal. O objetivo desta revisão foi elucidar o papel do ultrassom na anestesia caudal, além de demonstrar que o bloqueio caudal, muito utilizado em crianças, também é útil e pode ser usado em adultos. CONTEÚDO: Uma revisão literária sobre a anatomia da região sacral e da técnica anestésica necessária para a realização adequada do bloqueio caudal foi promovida. Além disso, artigos recentes sobre estudos realizados com bloqueios peridurais caudais guiados por ultrassom tanto em crianças quanto em adultos também foram incluídos. CONCLUSÕES: O ultrassom, apesar de suas limitações, pode ser útil como ferramenta adjuvante no posicionamento da agulha no espaço caudal. Permite a fácil identificação da anatomia sacral, além de visualização da injeção, em tempo real. Sua natureza portátil, não invasiva e livre de exposição à radiação faz dele uma tecnologia atrativa na sala operatória, principalmente na emergência de casos difíceis. Entretanto, como seu uso em bloqueios centrais do neuroeixo ainda é muito primitivo, é necessário que mais pesquisas sejam feitas para se consagre como técnica de rotina na prática anestésica.

  14. Low-level laser irradiation induces in vitro proliferation of mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Barboza, Carlos Augusto Galvão; Ginani, Fernanda [Universidade Federal do Rio Grande do Norte, Natal, RN (Brazil); Soares, Diego Moura [Universidade Federal de Pernambuco, Recife, PE (Brazil); Henriques, Águida Cristina Gomes; Freitas, Roseana de Almeida [Universidade Federal do Rio Grande do Norte, Natal, RN (Brazil)

    2014-07-01

    To evaluate the effect of low-level laser irradiation on the proliferation and possible nuclear morphological changes of mouse mesenchymal stem cells. Mesenchymal stem cells derived from bone marrow and adipose tissue were submitted to two applications (T0 and T48 hours) of low-level laser irradiation (660nm; doses of 0.5 and 1.0J/cm{sup 2}). The trypan blue assay was used to evaluate cell viability, and growth curves were used to analyze proliferation at zero, 24, 48, and 72 hours. Nuclear alterations were evaluated by staining with DAPI (4'-6-diamidino-2-phenylindole) at 72 hours. Bone marrow-derived mesenchymal stem cells responded to laser therapy in a dose-dependent manner. Higher cell growth was observed when the cells were irradiated with a dose of 1.0J/cm{sup 2}, especially after 24 hours (p<0.01). Adipose-derived mesenchymal stem cells responded better to a dose of 1.0J/cm{sup 2}, but higher cell proliferation was observed after 48 hours (p<0.05) and 72 hours (p<0.01). Neither nuclear alterations nor a significant change in cell viability was detected in the studied groups. Low-level laser irradiation stimulated the proliferation of mouse mesenchymal stem cells without causing nuclear alterations. The biostimulation of mesenchymal stem cells using laser therapy might be an important tool for regenerative therapy and tissue engineering.

  15. Persistent STAT3 Activation in Colon Cancer Is Associated with Enhanced Cell Proliferation and Tumor Growth

    Directory of Open Access Journals (Sweden)

    Florian M. Corvinus

    2005-06-01

    Full Text Available Colorectal carcinoma (CRC is a major cause of morbidity and mortality in Western countries. It has so far been molecularly defined mainly by alterations of the Wnt pathway. We show here for the first time that aberrant activities of the signal transducer and activator of transcription STAT3 actively contribute to this malignancy and, thus, are a potential therapeutic target for CRC. Constitutive STAT3 activity was found to be abundant in dedifferentiated cancer cells and infiltrating lymphocytes of CRC samples, but not in non-neoplastic colon epithelium. Cell lines derived from malignant colorectal tumors lost persistent STAT3 activity in culture. However, implantation of colon carcinoma cells into nude mice resulted in restoration of STAT3 activity, suggesting a role of an extracellular stimulus within the tumor microenvironment as a trigger for STAT activation. STAT3 activity in CRC cells triggered through interleukin-6 or through a constitutively active STAT3 mutant promoted cancer cell multiplication, whereas STAT3 inhibition through a dominant-negative variant impaired IL-6-driven proliferation. Blockade of STAT3 activation in CRCderived xenograft tumors slowed down their development, arguing for a contribution of STAT3 to colorectal tumor growth.

  16. R-spondin 2 facilitates differentiation of proliferating chondrocytes into hypertrophic chondrocytes by enhancing Wnt/β-catenin signaling in endochondral ossification

    International Nuclear Information System (INIS)

    Takegami, Yasuhiko; Ohkawara, Bisei; Ito, Mikako; Masuda, Akio; Nakashima, Hiroaki; Ishiguro, Naoki; Ohno, Kinji

    2016-01-01

    Endochondral ossification is a crucial process for longitudinal growth of bones. Differentiating chondrocytes in growth cartilage form four sequential zones of proliferation, alignment into column, hypertrophy, and substitution of chondrocytes with osteoblasts. Wnt/β-catenin signaling is essential for differentiation of proliferating chondrocytes into hypertrophic chondrocytes in growth cartilage. R-spondin 2 (Rspo2), a member of R-spondin family, is an agonist for Wnt signaling, but its role in chondrocyte differentiation remains unknown. Here we report that growth cartilage of Rspo2-knockout mice shows a decreased amount of β-catenin and increased amounts collagen type II (CII) and Sox9 in the abnormally extended proliferating zone. In contrast, expression of collagen type X (CX) in the hypertrophic zone remains unchanged. Differentiating chondrogenic ATDC5 cells, mimicking proliferating chondrocytes, upregulate Rspo2 and its putative receptor, Lgr5, in parallel. Addition of recombinant human Rspo2 to differentiating ATDC5 cells decreases expressions of Col2a1, Sox9, and Acan, as well as production of proteoglycans. In contrast, lentivirus-mediated knockdown of Rspo2 has the opposite effect. The effect of Rspo2 on chondrogenic differentiation is mediated by Wnt/β-catenin signaling, and not by Wnt/PCP or Wnt/Ca 2+ signaling. We propose that Rspo2 activates Wnt/β-catenin signaling to reduce Col2a1 and Sox9 and to facilitate differentiation of proliferating chondrocytes into hypertrophic chondrocytes in growth cartilage. - Highlights: • Rspo2 is a secreted activator of Wnt, and its knockout shows extended proliferating chondrocytes in endochondral ossification. • In proliferating chondrocytes of Rspo2-knockout mice, Sox9 and collagen type 2 are increased and β-catenin is decreased. • Rspo2 and its receptor Lgr5, as well as Sox9 and collagen type 2, are expressed in differentiating ATDC5 chondrogenic cells. • In ATDC5 cells, Rspo2 decreases expressions

  17. R-spondin 2 facilitates differentiation of proliferating chondrocytes into hypertrophic chondrocytes by enhancing Wnt/β-catenin signaling in endochondral ossification

    Energy Technology Data Exchange (ETDEWEB)

    Takegami, Yasuhiko [Division of Neurogenetics, Center of Neurological Disease and Cancer, Nagoya University Graduate School of Medicine, Nagoya (Japan); Department of Orthopaedic Surgery, Nagoya University School of Medicine, Nagoya (Japan); Ohkawara, Bisei; Ito, Mikako; Masuda, Akio [Division of Neurogenetics, Center of Neurological Disease and Cancer, Nagoya University Graduate School of Medicine, Nagoya (Japan); Nakashima, Hiroaki; Ishiguro, Naoki [Department of Orthopaedic Surgery, Nagoya University School of Medicine, Nagoya (Japan); Ohno, Kinji, E-mail: ohnok@med.nagoya-u.ac.jp [Division of Neurogenetics, Center of Neurological Disease and Cancer, Nagoya University Graduate School of Medicine, Nagoya (Japan)

    2016-04-22

    Endochondral ossification is a crucial process for longitudinal growth of bones. Differentiating chondrocytes in growth cartilage form four sequential zones of proliferation, alignment into column, hypertrophy, and substitution of chondrocytes with osteoblasts. Wnt/β-catenin signaling is essential for differentiation of proliferating chondrocytes into hypertrophic chondrocytes in growth cartilage. R-spondin 2 (Rspo2), a member of R-spondin family, is an agonist for Wnt signaling, but its role in chondrocyte differentiation remains unknown. Here we report that growth cartilage of Rspo2-knockout mice shows a decreased amount of β-catenin and increased amounts collagen type II (CII) and Sox9 in the abnormally extended proliferating zone. In contrast, expression of collagen type X (CX) in the hypertrophic zone remains unchanged. Differentiating chondrogenic ATDC5 cells, mimicking proliferating chondrocytes, upregulate Rspo2 and its putative receptor, Lgr5, in parallel. Addition of recombinant human Rspo2 to differentiating ATDC5 cells decreases expressions of Col2a1, Sox9, and Acan, as well as production of proteoglycans. In contrast, lentivirus-mediated knockdown of Rspo2 has the opposite effect. The effect of Rspo2 on chondrogenic differentiation is mediated by Wnt/β-catenin signaling, and not by Wnt/PCP or Wnt/Ca{sup 2+} signaling. We propose that Rspo2 activates Wnt/β-catenin signaling to reduce Col2a1 and Sox9 and to facilitate differentiation of proliferating chondrocytes into hypertrophic chondrocytes in growth cartilage. - Highlights: • Rspo2 is a secreted activator of Wnt, and its knockout shows extended proliferating chondrocytes in endochondral ossification. • In proliferating chondrocytes of Rspo2-knockout mice, Sox9 and collagen type 2 are increased and β-catenin is decreased. • Rspo2 and its receptor Lgr5, as well as Sox9 and collagen type 2, are expressed in differentiating ATDC5 chondrogenic cells. • In ATDC5 cells, Rspo2 decreases

  18. EVALUACIÓN DEL COMPORTAMIENTO HIDRÁULICO DE DOCE MODELOS DE GOTEROS DE BAJO CAUDAL

    OpenAIRE

    Pastor J., Rocío; Universidad Nacional Agraria La Molina, Lima, Perú.; Narro D., Ángel; Universidad Nacional Agraria La Molina, Lima, Perú.

    2015-01-01

    La investigación se realizó en el laboratorio de Riego y Drenaje de la Facultad de Ingeniería Agrícola, de la Universidad Nacional Agraria La Molina. El objetivo fue determinar el coeficiente de variación y las curvas caudal-presión de 12 modelos de goteros. Las mangueras fueron evaluadas en un banco de pruebas que consta de una estructura de soporte que sostiene a la bandeja de captación. Las dimensiones son 2,0 m de largo por 1,0 m de ancho y la estructura de conducción de 0,45 m de largo p...

  19. Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro

    DEFF Research Database (Denmark)

    Billestrup, Nils; Swanson, L W; Vale, W

    1986-01-01

    The mitogenic effect of the hypothalamic peptides growth hormone-releasing factor (GRF) and somatostatin on cultured growth hormone (GH)-producing cells (somatotrophs) was studied. Using autoradiographic detection of [3H]thymidine uptake and immunocytochemical identification of GH-producing cells...

  20. Clinicopathological and immunohistochemical characterization of papillary proliferation of the endometrium: A single institutional experience.

    Science.gov (United States)

    Park, Cheol Keun; Yoon, Gun; Cho, Yoon Ah; Kim, Hyun-Soo

    2016-06-28

    Papillary proliferation of the endometrium is an unusual lesion that is composed of papillae with fibrovascular stromal cores covered with benign-appearing glandular epithelium. We studied the clinicopathological and immunohistochemical features of four cases of endometrial papillary proliferations. All patients were postmenopausal. Two lesions were incidental findings in hysterectomy specimens, and two lesions were detected in endometrial curettage specimens. Based on the degree of architectural complexity and extent of proliferation, we classified papillary proliferations histopathologically into "simple" or "complex" growth patterns. Three cases were classified as simple papillary proliferation, and one case was classified as complex papillary proliferation. Simple papillary proliferations were characterized by slender papillae with delicate stromal cores. In contrast, complex papillary proliferations had intracystic papillary projections and cellular clusters with frequent branching and occasional cytological atypia. All cases showed coexistent metaplastic epithelial changes, including mucinous metaplasia, eosinophilic cell change, and ciliated cell metaplasia. One patient with simple papillary proliferations had coexistent well-differentiated endometrioid carcinoma. One patient had subsequent hyperplasia without atypia, and another patient had subsequent atypical hyperplasia/endometrioid intraepithelial neoplasia; both patients underwent total hysterectomy within four months. Our observations are consistent with previous data demonstrating that endometrial papillary proliferations coexist with or develop into atypical hyperplasia/endometrioid intraepithelial neoplasia or endometrioid carcinoma. It is very important for pathologists to discriminate papillary proliferations from neoplastic lesions (including atypical hyperplasia/endometrioid intraepithelial neoplasia and well-differentiated endometrioid carcinoma) and benign mimickers (including papillary

  1. TRPM8 ion channels differentially modulate proliferation and cell cycle distribution of normal and cancer prostate cells.

    Directory of Open Access Journals (Sweden)

    María Ll Valero

    Full Text Available Overexpression of the cation-permeable channel TRPM8 in prostate cancers might represent a novel opportunity for their treatment. Inhibitors of TRPM8 reduce the growth of prostate cancer cells. We have used two recently described and highly specific blockers, AMTB and JNJ41876666, and RNAi to determine the relevance of TRPM8 expression in the proliferation of non-tumor and tumor cells. Inhibition of the expression or function of the channel reduces proliferation rates and proliferative fraction in all tumor cells tested, but not of non-tumor prostate cells. We observed no consistent acceleration of growth after stimulation of the channel with menthol or icilin, indicating that basal TRPM8 expression is enough to sustain growth of prostate cancer cells.

  2. TRPM8 ion channels differentially modulate proliferation and cell cycle distribution of normal and cancer prostate cells.

    Science.gov (United States)

    Valero, María Ll; Mello de Queiroz, Fernanda; Stühmer, Walter; Viana, Félix; Pardo, Luis A

    2012-01-01

    Overexpression of the cation-permeable channel TRPM8 in prostate cancers might represent a novel opportunity for their treatment. Inhibitors of TRPM8 reduce the growth of prostate cancer cells. We have used two recently described and highly specific blockers, AMTB and JNJ41876666, and RNAi to determine the relevance of TRPM8 expression in the proliferation of non-tumor and tumor cells. Inhibition of the expression or function of the channel reduces proliferation rates and proliferative fraction in all tumor cells tested, but not of non-tumor prostate cells. We observed no consistent acceleration of growth after stimulation of the channel with menthol or icilin, indicating that basal TRPM8 expression is enough to sustain growth of prostate cancer cells.

  3. Advances in cell proliferation and apoptosis signal pathway and therapies of polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Xiao-ying LIAN

    2016-12-01

    Full Text Available Polycystic kidney disease (PKD is one of the monogenic inherited diseases. In PKD, excessive cell proliferation and fluid secretion, and disruption of the mechanisms controlling tubular diameter may all lead to cyst formation. Current evidence has demonstrated that intracellular calcium ion and cAMP imbalance drive both abnormal cell proliferation and apoptosis signal pathway. The present paper summarized the evidence implicating calcium ion and cAMP as central players in the signaling pathway of cell proliferation and apoptosis in PKD, and considered the potential therapeutic approaches targeted to slow cyst growth in PKD. DOI: 10.11855/j.issn.0577-7402.2016.11.13

  4. Longitudinal bone growth is impaired by direct involvement of caffeine with chondrocyte differentiation in the growth plate.

    Science.gov (United States)

    Choi, Hyeonhae; Choi, Yuri; Kim, Jisook; Bae, Jaeman; Roh, Jaesook

    2017-01-01

    We showed previously that caffeine adversely affects longitudinal bone growth and disrupts the histomorphometry of the growth plate during the pubertal growth spurt. However, little attention has been paid to the direct effects of caffeine on chondrocytes. Here, we investigated the direct effects of caffeine on chondrocytes of the growth plate in vivo and in vitro using a rapidly growing young rat model, and determined whether they were related to the adenosine receptor signaling pathway. A total of 15 male rats (21 days old) were divided randomly into three groups: a control group and two groups fed caffeine via gavage with 120 and 180 mg kg -1  day -1 for 4 weeks. After sacrifice, the tibia processed for the analysis of the long bone growth and proliferation of chondrocytes using tetracycline and BrdU incorporation, respectively. Caffeine-fed animals showed decreases in matrix mineralization and proliferation rate of growth plate chondrocytes compared with the control. To evaluate whether caffeine directly affects chondrocyte proliferation and chondrogenic differentiation, primary rat chondrocytes were isolated from the growth plates and cultured in either the presence or absence of caffeine at concentrations of 0.1-1 mm, followed by determination of the cellular proliferation or expression profiles of cellular differentiation markers. Caffeine caused significant decreases in extracellular matrix production, mineralization, and alkaline phosphatase activity, accompanied with decreases in gene expression of the cartilage-specific matrix proteins such as aggrecan, type II collagen and type X. Our results clearly demonstrate that caffeine is capable of interfering with cartilage induction by directly inhibiting the synthetic activity and orderly expression of marker genes relevant to chondrocyte maturation. In addition, we found that the adenosine type 1 receptor signaling pathway may be partly involved in the detrimental effects of caffeine on chondrogenic

  5. Response Function of the Crayfish Caudal Photoreceptor to Hydrodynamic Stimuli

    Science.gov (United States)

    Breite, Sally; Bahar, Sonya; Neiman, Alexander; Moss, Frank

    2002-03-01

    In its abdominal 6th ganglion the crayfish houses 2 light-sensitive neurons (caudal photoreceptors, or CPRs). It is known that these neurons work in tandem with a mechanosensory system of tiny hairs spread across the tailfan, which make synaptic contact with the photoreceptors. A stochastic resonance effect has been shown in this system in which light enhances the transduction of a weak, periodic mechanosensory (hydrodynamic) stimulus. It is not known, however, whether an optimal response from the CPR is induced by a single sine wave cycle or some other waveform. We have experimentally investigated this favorable waveform by driving a tailfan preparation with mechanical 10 Hz correlated Ornstein-Uhlenbeck noise and calculating the response function from the spike-triggered average of the applied noise waveform. We will discuss differences in the shape of the optimal waveform under dark and light conditions, as well as what seems to be a noticeable difference in the magnitude of the animals' response to a noisy stimulus in comparison with a periodic stimulus.

  6. Dose-dependent dual effects of cholesterol and desmosterol on J774 macrophage proliferation

    International Nuclear Information System (INIS)

    Rodriguez-Acebes, Sara; Cueva, Paloma de la; Ferruelo, Antonio J.; Fernandez-Hernando, Carlos; Lasuncion, Miguel A.; Martinez-Botas, Javier; Gomez-Coronado, Diego

    2008-01-01

    We addressed the ability of native, oxidized and acetylated low-density lipoproteins (nLDL, oxLDL and acLDL, respectively) and desmosterol to act as sources of sterol for the proliferation of J774A.1 macrophages. Treatment with 0.5 μM lovastatin and lipoprotein-deficient serum suppressed cell proliferation. This inhibition was effectively prevented by nLDL, but only to a lesser extent by oxLDL. AcLDL, despite its ability to deliver a higher amount of cholesterol to J774 macrophages than the other LDLs, was dependent on mevalonate supply to sustain cell proliferation. Similarly, exogenous desmosterol, which is not converted into cholesterol in J774 cells, required the simultaneous addition of mevalonate to support optimal cell growth. Expression of hydroxymethyl glutaryl coenzyme A reductase mRNA was potently down-regulated by acLDL and exogenous desmosterol, but the effect was weaker with other sterol sources. We conclude that nLDL is more efficient than modified LDL in sustaining macrophage proliferation. Despite the requirement of cholesterol or desmosterol for J774 cell proliferation, excessive provision of either sterol limits mevalonate availability, thus suppressing cell proliferation.

  7. Dose-dependent dual effects of cholesterol and desmosterol on J774 macrophage proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Acebes, Sara [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain); Cueva, Paloma de la; Ferruelo, Antonio J; Fernandez-Hernando, Carlos [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); Lasuncion, Miguel A [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain); Departamento de Bioquimica y Biologia Molecular, Universidad de Alcala, Alcala de Henares (Spain); Martinez-Botas, Javier [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain); Gomez-Coronado, Diego [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], E-mail: diego.gomez@hrc.es

    2008-12-12

    We addressed the ability of native, oxidized and acetylated low-density lipoproteins (nLDL, oxLDL and acLDL, respectively) and desmosterol to act as sources of sterol for the proliferation of J774A.1 macrophages. Treatment with 0.5 {mu}M lovastatin and lipoprotein-deficient serum suppressed cell proliferation. This inhibition was effectively prevented by nLDL, but only to a lesser extent by oxLDL. AcLDL, despite its ability to deliver a higher amount of cholesterol to J774 macrophages than the other LDLs, was dependent on mevalonate supply to sustain cell proliferation. Similarly, exogenous desmosterol, which is not converted into cholesterol in J774 cells, required the simultaneous addition of mevalonate to support optimal cell growth. Expression of hydroxymethyl glutaryl coenzyme A reductase mRNA was potently down-regulated by acLDL and exogenous desmosterol, but the effect was weaker with other sterol sources. We conclude that nLDL is more efficient than modified LDL in sustaining macrophage proliferation. Despite the requirement of cholesterol or desmosterol for J774 cell proliferation, excessive provision of either sterol limits mevalonate availability, thus suppressing cell proliferation.

  8. Epithelialization and stromalization of porcine follicular granulosa cells during real-time proliferation - a primary cell culture approach.

    Science.gov (United States)

    Ciesiółka, S; Bryja, A; Budna, J; Kranc, W; Chachuła, A; Bukowska, D; Piotrowska, H; Porowski, L; Antosik, P; Bruska, M; Brüssow, K P; Nowicki, M; Zabel, M; Kempisty, B

    2016-01-01

    The process of oocyte growth and development takes place during long stages of folliculogenesis and oogenesis. This is accompanied by biochemical and morphological changes, occurring from the preantral to antral stages during ovarian follicle differentiation. It is well known that the process of follicle growth is associated with morphological modifications of theca (TCs) and granulosa cells (GCs). However, the relationship between proliferation and/or differentiation of porcine GCs during long-term in vitro culture requires further investigation. Moreover, the expression of cytokeratins and vimentin in porcine GCs, in relation to real-time cell proliferation, has yet to be explored. Utilizing confocal microscopy, we analyzed cytokeratin 18 (CK18), cytokeratin 8 + 18 + 19 (panCK), and vimentin (Vim) expression, as well as their protein distribution, within GCs isolated from slaughtered ovarian follicles. The cells were cultured for 168 h with protein expression and cell proliferation index analyzed at 24-h intervals. We found the highest expression of CK18, panCK, and Vim occurred at 120 h of in vitro culture (IVC) as compared with other experimental time intervals. All of the investigated proteins displayed cytoplasmic distribution. Analysis of real-time cell proliferation revealed an increased cell index after the first 24 h of IVC. Additionally, during each period between 24-168 h of IVC, a significant difference in the proliferation profile, expressed as the cell index, was also observed. We concluded that higher expression of vimentin at 120 h of in vitro proliferation might explain the culmination of the stromalization process associated with growth and domination of stromal cells in GC culture. Cytokeratin expression within GC cytoplasm confirms the presence of epithelial cells as well as epithelial-related GC development during IVC. Moreover, expression of both cytokeratins and vimentin during short-term culture suggests that the process of GC proliferation

  9. KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts

    International Nuclear Information System (INIS)

    Ohshimo, Shinichiro; Yokoyama, Akihito; Hattori, Noboru; Ishikawa, Nobuhisa; Hirasawa, Yutaka; Kohno, Nobuoki

    2005-01-01

    The serum level of KL-6, a MUC1 mucin, is a clinically useful marker for various interstitial lung diseases. Previous studies demonstrated that KL-6 promotes chemotaxis of human fibroblasts. However, the pathophysiological role of KL-6 remains poorly understood. Here, we further investigate the functional aspects of KL-6 in proliferation and apoptosis of lung fibroblasts. KL-6 accelerated the proliferation and inhibited the apoptosis of all human lung fibroblasts examined. An anti-KL-6 monoclonal antibody counteracted both of these effects induced by KL-6 on human lung fibroblasts. The pro-fibroproliferative and anti-apoptotic effects of KL-6 are greater than and additive to those of the maximum effective concentrations of platelet-derived growth factor, basic fibroblast growth factor, and transforming growth factor-β. These findings indicate that increased levels of KL-6 in the epithelial lining fluid may stimulate fibrotic processes in interstitial lung diseases and raise the possibility of applying an anti-KL-6 antibody to treat interstitial lung diseases

  10. Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol.

    Science.gov (United States)

    Cruz, Pamela; Torres, Cristian; Ramírez, María Eugenia; Epuñán, María José; Valladares, Luis Emilio; Sierralta, Walter Daniel

    2010-05-01

    The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E(2)) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E(2), and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E(2) in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E(2)-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels.

  11. Non-proliferation

    International Nuclear Information System (INIS)

    Manley, I.T.

    1981-01-01

    Proliferation is a problem that can only be solved when the political problems which lead countries to contemplate, the possession of nuclear weapons are solved; in the meantime it can only be managed. Non-proliferation policy has to deal both with the political and the technical aspects of proliferation. It must seek to buy time by addressing the reasons why nations feel the political need to construct nuclear weapons, as well as delaying the moment when such nations feel capable of doing so. The subject is examined and proposals made. (author)

  12. Auxillary system for optimizing simulation and percutaneous irradiation in cranio-caudally contiguous head-neck-mediastinum fields

    International Nuclear Information System (INIS)

    Sistermanns, J.

    1994-01-01

    Percutaneous irradiation in the head and neck region via opponing lateral fields with caudally contiguous ventral and/or dorsal fields makes very high demands on simulation, instrument adjustment and documentation. At the outer boundaries of the irradiation volumes, there is always the danger of overdosage or underdosage with the familiar consequences. Four targeting systems in one plane were inserted in a perspex frame each consisting of two concentric rings and two orthogonal crossbars. Under simulation conditions, the lateral radiation fields take up one half of the targeting systems and the ventro-dorsal fields occupy the remaining half. The corresponding targeting systems project exactly on or into each other with compensation of the beam divergence. A definitively exact irradiation via cranio-caudally contiguous fields with different incident beam direction is possible by using the four targeting systems in one plane. Compensation of divergence is aimed for by rotation of the table and gantry angle modification, errors of compensation can already be checked optically from 0,5 . Deviations of 5 mm in the simulated longitudinal arrangement of the contiguous fields can be imaged on the documentation film made with therapy activity. On the one hand, the auxillary system presented allows both recognition of undesired field overlap and gaps in contiguous fields with different incident beam direction. On the other hand, it can be unequivocally documented whether the therapy is correct. Treatment errors can thus be minimized. (orig./MG) [de

  13. In vitro Proliferation Ability of Axillary Buds in Musa spp | Youmbi ...

    African Journals Online (AJOL)

    from : Pisang Mas (AA), Grande Naine (AAA), Batard and French Clair (AAB), CRBP 39 (AAAB) and Pelipita (ABB) varieties were used as explants. The proliferation rate of Axillary and apical buds and other growth parameters were measured. Results showed that no significant differences were observed between the two ...

  14. Recovering missing data: estimating position and size of caudal vertebrae in Staurikosaurus pricei Colbert, 1970

    Directory of Open Access Journals (Sweden)

    Orlando N. Grillo

    2011-03-01

    Full Text Available Missing data is a common problem in paleontology. It makes it difficult to reconstruct extinct taxa accurately and restrains the inclusion of some taxa on comparative and biomechanical studies. Particularly, estimating the position of vertebrae on incomplete series is often non-empirical and does not allow precise estimation of missing parts. In this work we present a method for calculating the position of preserved middle sequences of caudal vertebrae in the saurischian dinosaur Staurikosaurus pricei, based on the length and height of preserved anterior and posterior caudal vertebral centra. Regression equations were used to estimate these dimensions for middle vertebrae and, consequently, to assess the position of the preserved middle sequences. It also allowed estimating these dimensions for non-preserved vertebrae. Results indicate that the preserved caudal vertebrae of Staurikosaurus may correspond to positions 1-3, 5, 7, 14-19/15-20, 24-25/25-26, and 29-47, and that at least 25 vertebrae had transverse processes. Total length of the tail was estimated in 134 cm and total body length was 220-225 cm.Dados lacunares são um problema comum na paleontologia. Eles dificultam a reconstrução acurada de táxons extintos e limitam a inclusão de alguns táxons em estudos comparativose biomecânicos. Particularmente, estimar a posição de vértebras em séries incompletas tem sido feito com base em métodos não empíricos que não permitem estimar corretamente as partes ausentes. Neste trabalho apresentamos uma metodologia que permite estimar a posição de sequências médias preservadas de vértebras caudais no dinossauro saurísquio Staurikosaurus pricei, com base no comprimento e altura dos centros das vértebras anteriores e posteriores preservadas. Equações de regressão foram usadas para estimar essas dimensões para as vértebras médias e, consequentemente, para posicionar as sequências médias preservadas e para estimar o tamanho das

  15. Molecular mechanisms involved in the inhibition of tumor cells proliferation exposed to elevated concentrations of the epidermal growth factor

    International Nuclear Information System (INIS)

    Guillen, Isabel A; Berlanga, Jorge; Camacho, Hanlet

    2013-01-01

    The EGF promotes inhibition of cell proliferation in vitro and in vivo models depending on its concentration, application schema and the type of tumor cells on which it acts. Our research hypothesis was based on the fact that the EGF varies the expression of genes involved in a negative regulation of tumor cell lines proliferation carrying high levels of its receptor (EGFR). Our objectives were, to obtain information about the effect of EGF on tumor cell proliferation in vitro and in vivo models and, know the gene expression patterns of a group of genes involved in cancer signaling pathways and EGFR. The results showed that EGF at nanomolar concentrations inhibits the tumor cells proliferation bearing high levels of EGFR and, promotes the survival of treated animals, establishing a direct relationship between the inhibition of cell proliferation, high concentrations of EGF and, high amount of EGFR in the cells. The differential gene expression profile showed a variation in a group of genes which exert a powerful control over the cell cycle progression, gene transcription and apoptosis. It was concluded that the inhibition of tumor cell proliferation by the action of EGF is due to activation of molecular mechanisms controlling cell cycle progression. This work won the Annual Award of the Cuban Academy of Sciences in 2012

  16. NSA2, a novel nucleolus protein regulates cell proliferation and cell cycle

    International Nuclear Information System (INIS)

    Zhang, Heyu; Ma, Xi; Shi, Taiping; Song, Quansheng; Zhao, Hongshan; Ma, Dalong

    2010-01-01

    NSA2 (Nop seven-associated 2) was previously identified in a high throughput screen of novel human genes associated with cell proliferation, and the NSA2 protein is evolutionarily conserved across different species. In this study, we revealed that NSA2 is broadly expressed in human tissues and cultured cell lines, and located in the nucleolus of the cell. Both of the putative nuclear localization signals (NLSs) of NSA2, also overlapped with nucleolar localization signals (NoLSs), are capable of directing nucleolar accumulation. Moreover, over-expression of the NSA2 protein promoted cell growth in different cell lines and regulated the G1/S transition in the cell cycle. SiRNA silencing of the NSA2 transcript attenuated the cell growth and dramatically blocked the cell cycle in G1/S transition. Our results demonstrated that NSA2 is a nucleolar protein involved in cell proliferation and cell cycle regulation.

  17. International aspects of non-proliferation policy

    International Nuclear Information System (INIS)

    Aucoin, P.A.

    1978-01-01

    There are currently two areas on the national scene and one on the international scene that require immediate attention. The first is relief under contracts for enrichment services, an area in which the US can still demonstrate its desire to become a stable and continuous source of supply. The second national area is the Nuclear Non-Proliferation Act of 1977. The United States must proceed very cautiously, however, for if discretion and very careful judgment are not used, the Act will immediately be branded as a blatant effort on the part of the US to control the energy options of other sovereign states. The international area is that of the International Nuclear Fuel Cycle Evaluation program. This medium exists for wise and deliberate growth of a commercial nuclear power program which can serve the global community. The next three years probably allow one remaining chance for successful containment of weapons proliferation. If we do not recognize the rights of every sovereign state to voluntarily participate and agree, we, as members of the global community, will have failed

  18. Acetylcarnitine metabolism and the partial purification and characterization of an acetylcarnitine hydrolase from bovine caudal epididymal spermatozoa

    International Nuclear Information System (INIS)

    Bruns, K.A.

    1987-01-01

    Epididymal spermatozoa are capable of utilizing extracellular substrates for energy, but carbohydrates and free or esterified fatty acids are present in only very low concentrations in epididymal fluid. Acetyl-L-carnitine has been identified in epididymal fluid in low mM concentrations in several mammalian species and could possibly be an energy substrate for epididymal spermatozoa. Evidence that extracellular acetyl-L-carnitine can be used by intact caudal epididymal spermatozoa for energy, and a model for the metabolism of acetyl-L-carnitine by epididymal spermatozoa are presented here. Intact bovine and hamster caudal epididymal spermatozoa oxidized [1- 14 C] acetyl-L-carnitine to 14 CO 2 in a time-, cell number-, and substrate concentration-dependent manner. No concomitant uptake of acetyl-D,L-[N-methyl- 3 H] carnitine was observed by cells from the same preparations. Half-maximal rates of oxidation were observed at 8 mM and 4.5 mM acetyl-L-carnitine for the two species, respectively; the rates of oxidation at these concentrations were 15.3 nmol/10 8 cells·h and 2.9 nmol/10 7 cells·h. Intact spermatozoa in incubation with [ 3 H] acetyl-L-carnitine were observed to produce [ 3 H] acetate in the medium, and addition of sodium acetate competed for the uptake of radioactive acetate by these cells

  19. MicroRNA-424 suppresses estradiol-induced cell proliferation via targeting GPER in endometrial cancer cells.

    Science.gov (United States)

    Zhang, H; Wang, X; Chen, Z; Wang, W

    2015-11-30

    Endometrial carcinoma (EC) is the most common gynecologic malignancy with increasing morbidity in recent years. MicroRNAs (miRNAs), a type of non-coding RNA, have been proven to be critical in the process of tumorigenesis. miR-424 has been reported to play a protective role in various type of cancer including endometrial carcinoma. It has been reported that high levels of estrogen increase morbidity of EC by promoting cell growth ability. The current research was designed to delineate the mechanism of miR-424 in regulating E2 (17β-estradiol)-induced cell proliferation in endometrial cancer. In this study, we confirmed that cell proliferation is increased significantly in E2-treated endometrial cancer cell lines. Moreover, miR-424 overexpression dramatically decreased E2-induced cell proliferation, indicating a pivotal role in endometrial cancer cell growth. In addition, the results suggest that miR-424 up-regulation inactivated the PI3K/AKT signaling, which was mediated by G-protein-coupled estrogen receptor-1 (GPER) in endometrial cancer. Furthermore, the luciferase report confirmed the targeting reaction between miR-424 and GPER. After transfection with the GPER overexpression vector into E2-induced endometrial cancer cells, we found that GPER significantly attenuated the inhibition effect of miR-424 in E2-induced cell growth in EC. Taken together, our study suggests that increased miR-424 suppresses E2-induced cell growth, and providing a potential therapeutic target for estrogen-associated endometrial carcinoma.

  20. Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

    Science.gov (United States)

    Mahmoud, Ahmed I; O'Meara, Caitlin C; Gemberling, Matthew; Zhao, Long; Bryant, Donald M; Zheng, Ruimao; Gannon, Joseph B; Cai, Lei; Choi, Wen-Yee; Egnaczyk, Gregory F; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Poss, Kenneth D; Lee, Richard T

    2015-08-24

    Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Fissile material proliferation risk

    International Nuclear Information System (INIS)

    Dreicer, J.S.; Rutherford, D.A.

    1996-01-01

    The proliferation risk of a facility depends on the material attractiveness, level of safeguards, and physical protection applied to the material in conjunction with an assessment of the impact of the socioeconomic circumstances and threat environment. Proliferation risk is a complementary extension of proliferation resistance. The authors believe a better determination of nuclear proliferation can be achieved by establishing the proliferation risk for facilities that contain nuclear material. Developing a method that incorporates the socioeconomic circumstances and threat environment inherent to each country enables a global proliferation assessment. To effectively reduce the nuclear danger, a broadly based set of criteria is needed that provides the capability to relatively assess a wide range of nuclear related sites and facilities in different countries and still ensure a global decrease in proliferation risk for fissile material (plutonium and highly enriched uranium)

  2. Autocrine regulation of human urothelial cell proliferation and migration during regenerative responses in vitro

    International Nuclear Information System (INIS)

    Varley, Claire; Hill, Gemma; Pellegrin, Stephanie; Shaw, Nicola J.; Selby, Peter J.; Trejdosiewicz, Ludwik K.; Southgate, Jennifer

    2005-01-01

    Regeneration of the urothelium is rapid and effective in order to maintain a barrier to urine following tissue injury. Whereas normal human urothelial (NHU) cells are mitotically quiescent and G0 arrested in situ, they rapidly enter the cell cycle upon seeding in primary culture and show reversible growth arrest at confluency. We have used this as a model to investigate the role of EGF receptor signaling in urothelial regeneration and wound-healing. Transcripts for HER-1, HER-2, and HER-3 were expressed by quiescent human urothelium in situ. Expression of HER-1 was upregulated in proliferating cultures, whereas HER-2 and HER-3 were more associated with a growth-arrested phenotype. NHU cells could be propagated in the absence of exogenous EGF, but autocrine signaling through HER-1 via the MAPK and PI3-kinase pathways was essential for proliferation and migration during urothelial wound repair. HB-EGF was expressed by urothelium in situ and HB-EGF, epiregulin, TGF-α, and amphiregulin were expressed by proliferating NHU cells. Urothelial wound repair in vitro was attenuated by neutralizing antibodies against HER-1 ligands, particularly amphiregulin. By contrast, the same ligands applied exogenously promoted migration, but inhibited proliferation, implying that HER-1 ligands provoke differential effects in NHU cells depending upon whether they are presented as soluble or juxtacrine ligands. We conclude that proliferation and migration during wound healing in NHU cells are mediated through an EGFR autocrine signalling loop and our results implicate amphiregulin as a key mediator

  3. Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

    International Nuclear Information System (INIS)

    Tang, Chunling; Yang, Liqun; Jiang, Xiaolan; Xu, Chuan; Wang, Mei; Wang, Qinrui; Zhou, Zhansong; Xiang, Zhonghuai; Cui, Hongjuan

    2014-01-01

    Highlights: • Tigecycline inhibited cell growth and proliferation in human gastric cancer cells. • Tigecycline induced autophagy not apoptosis in human gastric cancer cells. • AMPK/mTOR/p70S6K pathway was activated after tigecycline treatment. • Tigecycline inhibited tumor growth in xenograft model of human gastric cancer cells. - Abstract: Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer

  4. Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chunling; Yang, Liqun; Jiang, Xiaolan [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Xu, Chuan [Division of Scientific Research and Training, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083 (China); Wang, Mei; Wang, Qinrui [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Zhou, Zhansong, E-mail: zhouzhans@sina.com [Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Xiang, Zhonghuai [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Cui, Hongjuan, E-mail: hcui@swu.edu.cn [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China)

    2014-03-28

    Highlights: • Tigecycline inhibited cell growth and proliferation in human gastric cancer cells. • Tigecycline induced autophagy not apoptosis in human gastric cancer cells. • AMPK/mTOR/p70S6K pathway was activated after tigecycline treatment. • Tigecycline inhibited tumor growth in xenograft model of human gastric cancer cells. - Abstract: Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer.

  5. Entrapped Sediments as a Source of Phosphorus in Epilithic Cyanobacterial Proliferations in Low Nutrient Rivers

    Science.gov (United States)

    Wood, Susanna A.; Depree, Craig; Brown, Logan; McAllister, Tara; Hawes, Ian

    2015-01-01

    Proliferations of the benthic mat-forming cyanobacteria Phormidium have been reported in rivers worldwide. Phormidium commonly produces natural toxins which pose a health risk to animal and humans. Recent field studies in New Zealand identified that sites with Phormidium proliferations consistently have low concentrations of water column dissolved reactive phosphorus (DRP). Unlike other river periphyton, Phormidium mats are thick and cohesive, with water and fine sediment trapped in a mucilaginous matrix. We hypothesized that daytime photosynthetic activity would elevate pH inside the mats, and/or night time respiration would reduce dissolved oxygen. Either condition could be sufficient to facilitate desorption of phosphates from sediment incorporated within mats, thus allowing Phormidium to utilize it for growth. Using microelectrodes, optodes and pulse amplitude modulation fluorometry we demonstrated that photosynthetic activity results in elevated pH (>9) during daytime, and that night-time respiration causes oxygen depletion (river water and this, together with elevated concentrations of elements, including iron, suggest phosphorus release from entrapped sediment. Sequential extraction of phosphorus from trapped sediment was used to investigate the role of sediment at sites on the Mangatainoka River (New Zealand) with and without Phormidium proliferations. Deposition of fine sediment (sediment can provide a source of phosphorus to support Phormidium growth and proliferation. PMID:26479491

  6. miR-150 suppresses the proliferation and tumorigenicity of leukemia stem cells by targeting the Nanog signaling pathway

    Directory of Open Access Journals (Sweden)

    Dan-dan Xu

    2016-11-01

    Full Text Available Proliferation, a key feature of cancer cells, accounts for the majority of cancer-related diseases resulting in mortality. MicroRNAs (miRNAs plays important post-transcriptional modulation roles by acting on multiple signaling pathways, but the underlying mechanism in proliferation and tumorigenicity is unclear. Here, we identified the role of miR-150 in proliferation and tumorigenicity in leukemia stem cells (LSCs (CD34+CD38- cells. miR-150 expression was significantly down-regulated in LSCs from leukemia cell lines and clinical samples. Functional assays demonstrated that increased miR-150 expression inhibited proliferation and clonal and clonogenic growth, enhanced chemosensitivity, and attenuated tumorigenic activity of LSCs in vitro. Transplantation animal studies revealed that miR-150 overexpression progressively abrogates tumour growth. Immunohistochemistry assays demonstrated that miR-150 overexpression enhanced caspase-3 level and reduced Ki-67 level. Moreover, luciferase reporter assays indicated Nanog is a direct and functional target of miR-150. Nanog silencing using small interfering RNA recapitulated anti-proliferation and tumorigenicity inhibition effects. Furthermore, miR-150 directly down-regulated the expression of other cancer stem cell factors including Notch2 and CTNNB1. These results provide insights into the specific biological behaviour of miR-150 in regulating LSC proliferation and tumorigenicity. Targeting this miR-150/Nanog axis would be a helpful therapeutic strategy to treat acute myeloid leukemia.

  7. TWEAK induces liver progenitor cell proliferation

    Science.gov (United States)

    Jakubowski, Aniela; Ambrose, Christine; Parr, Michael; Lincecum, John M.; Wang, Monica Z.; Zheng, Timothy S.; Browning, Beth; Michaelson, Jennifer S.; Baestcher, Manfred; Wang, Bruce; Bissell, D. Montgomery; Burkly, Linda C.

    2005-01-01

    Progenitor (“oval”) cell expansion accompanies many forms of liver injury, including alcohol toxicity and submassive parenchymal necrosis as well as experimental injury models featuring blocked hepatocyte replication. Oval cells can potentially become either hepatocytes or biliary epithelial cells and may be critical to liver regeneration, particularly when hepatocyte replication is impaired. The regulation of oval cell proliferation is incompletely understood. Herein we present evidence that a TNF family member called TWEAK (TNF-like weak inducer of apoptosis) stimulates oval cell proliferation in mouse liver through its receptor Fn14. TWEAK has no effect on mature hepatocytes and thus appears to be selective for oval cells. Transgenic mice overexpressing TWEAK in hepatocytes exhibit periportal oval cell hyperplasia. A similar phenotype was obtained in adult wild-type mice, but not Fn14-null mice, by administering TWEAK-expressing adenovirus. Oval cell expansion induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was significantly reduced in Fn14-null mice as well as in adult wild-type mice with a blocking anti-TWEAK mAb. Importantly, TWEAK stimulated the proliferation of an oval cell culture model. Finally, we show increased Fn14 expression in chronic hepatitis C and other human liver diseases relative to its expression in normal liver, which suggests a role for the TWEAK/Fn14 pathway in human liver injury. We conclude that TWEAK has a selective mitogenic effect for liver oval cells that distinguishes it from other previously described growth factors. PMID:16110324

  8. Melatonin prevents human pancreatic carcinoma cell PANC-1-induced human umbilical vein endothelial cell proliferation and migration by inhibiting vascular endothelial growth factor expression.

    Science.gov (United States)

    Cui, Peilin; Yu, Minghua; Peng, Xingchun; Dong, Lv; Yang, Zhaoxu

    2012-03-01

    Melatonin is an important natural oncostatic agent, and our previous studies have found its inhibitory action on tumor angiogenesis, but the mechanism remains unclear. It is well known that vascular endothelial growth factor (VEGF) plays key roles in tumor angiogenesis and has become an important target for antitumor therapy. Pancreatic cancer is a representative of the most highly vascularized and angiogenic solid tumors, which responds poorly to chemotherapy and radiation. Thus, seeking new treatment strategies targeting which have anti-angiogenic capability is urgent in clinical practice. In this study, a co-culture system between human umbilical vein endothelial cells (HUVECs) and pancreatic carcinoma cells (PANC-1) was used to investigate the direct effect of melatonin on the tumor angiogenesis and its possible action on VEGF expression. We found HUVECs exhibited an increased cell proliferation and cell migration when co-cultured with PANC-1 cells, but the process was prevented when melatonin added to the incubation medium. Melatonin at concentrations of 1 μm and 1 mm inhibited the cell proliferation and migration of HUVECs and also decreased both the VEGF protein secreted to the cultured medium and the protein produced by the PANC-1 cells. In addition, the VEGF mRNA expression was also down-regulated by melatonin. Taken together, our present study shows that melatonin at pharmacological concentrations inhibited the elevated cell proliferation and cell migration of HUVECs stimulated by co-culturing them with PANC-1 cells; this was associated with a suppression of VEGF expression in PANC-1 cells. © 2011 John Wiley & Sons A/S.

  9. Insulin-like growth factors act synergistically with basic fibroblast growth factor and nerve growth factor to promote chromaffin cell proliferation

    DEFF Research Database (Denmark)

    Frödin, M; Gammeltoft, S

    1994-01-01

    We have investigated the effects of insulin-like growth factors (IGFs), basic fibroblast growth factor (bFGF), and nerve growth factor (NGF) on DNA synthesis in cultured chromaffin cells from fetal, neonatal, and adult rats by using 5-bromo-2'-deoxyuridine (BrdUrd) pulse labeling for 24 or 48 h...... implications for improving the survival of chromaffin cell implants in diseased human brain....

  10. Yongdamsagan-tang, a traditional herbal formula, inhibits cell growth through the suppression of proliferation and inflammation in benign prostatic hyperplasia epithelial-1 cells.

    Science.gov (United States)

    Park, Eunsook; Lee, Mee-Young; Seo, Chang-Seob; Jeon, Woo-Young; Shin, Hyeun-Kyoo

    2017-09-14

    Benign prostatic hyperplasia (BPH), also called benign enlargement of the prostate, is a progressive disease that is observed in most elderly men. Yongdamsagan-tang, a traditional herbal formula, is used commonly for the treatment of inflammation-related diseases. Although the therapeutic efficacy of Yongdamsagan-tang against BPH in vivo was reported previously, its underlying mechanisms are not clearly understood. In this study, we investigated the effect of Yongdamsagan-tang water extract (YSTE) and its mechanism on the growth of human BPH epithelial BPH-1 cells. YSTE was extracted from 11 herbaceous plants and its chemical composition was analyzed by High-performance liquid chromatography (HPLC). YSTE was treated in the epithelial BPH-1 cell line and then cell lysates or supernant were used to evaluate cell viability, cell cycle, proliferation and cytokine production. HPLC revealed that Baicalin and gentiopicroside were involved as the major compounds of YSTE. YSTE treatment in BPH-1 cells repressed cell viability in a dose-dependent manner. Regarding the inhibitory mechanisms of YSTE on cell growth, YSTE inhibited cell proliferation via a decrease in endogenous cyclin D1 protein levels and arrest at the S phase during cell-cycle progression. Furthermore, YSTE treatment in BPH-1 cells suppressed prostaglandin E 2 production and cyclooxygenase-2 (COX-2) protein levels. The secretion of the proinflammatory cytokines, interleukin-8 and interleukin-6, was also reduced by YSTE treatment. YSTE in BPH-1 cells showed antiproliferative and anti-inflammatory activities via cell-cycle arrest and downregulation of COX-2 expression, respectively. Taken together, the results of the present study will enhance our understanding of the mechanisms underlying the effect of YSTE in BPH. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  11. Effect of irradiance and spectral composition of radiation on in vitro shoot proliferation in Malus domestica

    International Nuclear Information System (INIS)

    Noè, N.; Eccher, T.; Bonini, L.

    1997-01-01

    Four clones of Malus domestica cv. Golden Delicious - namely Smoothee, Crielaard, Reinders and Golden B - were cultured in vitro from single-node microcuttings placed on solid medium under irradiance (PPFD) of 50 micromol m -2 s -1 . After 9 months an average shoot proliferation of 5.3 was achieved; Crielaard showed the highest rate (7.1), followed Golden B (5.4), Smoothee and Reinders (4.4). Proliferating shoots were then exposed to higher PPFD (80 micromol m -2 s -1 ) and different spectral composition of radiation using PMMA-B and PMMA-R/FR filters. High PPFD decreased the average proliferation rate to 4.5, in particular in Crielaard and Golden B, while it increased proliferation in Reinders. When a PMMA-R/FR filter was interposed, the mean proliferation rate slightly increased. PMMA-B filters decreased the overall proliferation rate to 3.0; only in Crielaard it was increased, but shoots were very small. Thus PPFD and spectral composition influenced in vitro shoot proliferation and growth and the responses were different among the clones. (author)

  12. Extracellular matrix collagen alters cell proliferation and cell cycle progression of human uterine leiomyoma smooth muscle cells.

    Science.gov (United States)

    Koohestani, Faezeh; Braundmeier, Andrea G; Mahdian, Arash; Seo, Jane; Bi, JiaJia; Nowak, Romana A

    2013-01-01

    Uterine leiomyomas (ULs) are benign tumors occurring in the majority of reproductive aged women. Despite the high prevalence of these tumors, little is known about their etiology. A hallmark of ULs is the excessive deposition of extracellular matrix (ECM), primarily collagens. Collagens are known to modulate cell behavior and function singularly or through interactions with integrins and growth factor-mediated mitogenic pathways. To better understand the pathogenesis of ULs and the role of ECM collagens in their growth, we investigated the interaction of leiomyoma smooth muscle cells (LSMCs) with two different forms of collagen, non-polymerized collagen (monomeric) and polymerized collagen (fibrillar), in the absence or presence of platelet-derived growth factor (PDGF), an abundant growth factor in ULs. Primary cultures of human LSMCS from symptomatic patients were grown on these two different collagen matrices and their morphology, cytoskeletal organization, cellular proliferation, and signaling pathways were evaluated. Our results showed that LSMCs had distinct morphologies on the different collagen matrices and their basal as well as PDGF-stimulated proliferation varied on these matrices. These differences in proliferation were accompanied by changes in cell cycle progression and p21, an inhibitory cell cycle protein. In addition we found alterations in the phosphorylation of focal adhesion kinase, cytoskeletal reorganization, and activation of the mitogen activated protein kinase (MAPK) signaling pathway. In conclusion, our results demonstrate a direct effect of ECM on the proliferation of LSMCs through interplay between the collagen matrix and the PDGF-stimulated MAPK pathway. In addition, these findings will pave the way for identifying novel therapeutic approaches for ULs that target ECM proteins and their signaling pathways in ULs.

  13. Culture Medium Supplements Derived from Human Platelet and Plasma: Cell Commitment and Proliferation Support

    Directory of Open Access Journals (Sweden)

    Anita Muraglia

    2017-11-01

    Full Text Available Present cell culture medium supplements, in most cases based on animal sera, are not fully satisfactory especially for the in vitro expansion of cells intended for human cell therapy. This paper refers to (i an heparin-free human platelet lysate (PL devoid of serum or plasma components (v-PL and (ii an heparin-free human serum derived from plasma devoid of PL components (Pl-s and to their use as single components or in combination in primary or cell line cultures. Human mesenchymal stem cells (MSC primary cultures were obtained from adipose tissue, bone marrow, and umbilical cord. Human chondrocytes were obtained from articular cartilage biopsies. In general, MSC expanded in the presence of Pl-s alone showed a low or no proliferation in comparison to cells grown with the combination of Pl-s and v-PL. Confluent, growth-arrested cells, either human MSC or human articular chondrocytes, treated with v-PL resumed proliferation, whereas control cultures, not supplemented with v-PL, remained quiescent and did not proliferate. Interestingly, signal transduction pathways distinctive of proliferation were activated also in cells treated with v-PL in the absence of serum, when cell proliferation did not occur, indicating that v-PL could induce the cell re-entry in the cell cycle (cell commitment, but the presence of serum proteins was an absolute requirement for cell proliferation to happen. Indeed, Pl-s alone supported cell growth in constitutively activated cell lines (U-937, HeLa, HaCaT, and V-79 regardless of the co-presence of v-PL. Plasma- and plasma-derived serum were equally able to sustain cell proliferation although, for cells cultured in adhesion, the Pl-s was more efficient than the plasma from which it was derived. In conclusion, the cells expanded in the presence of the new additives maintained their differentiation potential and did not show alterations in their karyotype.

  14. PPARγ1 phosphorylation enhances proliferation and drug resistance in human fibrosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Xiaojuan; Shu, Yuxin; Niu, Zhiyuan; Zheng, Wei; Wu, Haochen [State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Lu, Yan, E-mail: luyan@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Shen, Pingping, E-mail: ppshen@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Model Animal Research Center (MARC), Nanjing University, Nanjing (China)

    2014-03-10

    Post-translational regulation plays a critical role in the control of cell growth and proliferation. The phosphorylation of peroxisome proliferator-activated receptor γ (PPARγ) is the most important post-translational modification. The function of PPARγ phosphorylation has been studied extensively in the past. However, the relationship between phosphorylated PPARγ1 and tumors remains unclear. Here we investigated the role of PPARγ1 phosphorylation in human fibrosarcoma HT1080 cell line. Using the nonphosphorylation (Ser84 to alanine, S84A) and phosphorylation (Ser84 to aspartic acid, S84D) mutant of PPARγ1, the results suggested that phosphorylation attenuated PPARγ1 transcriptional activity. Meanwhile, we demonstrated that phosphorylated PPARγ1 promoted HT1080 cell proliferation and this effect was dependent on the regulation of cell cycle arrest. The mRNA levels of cyclin-dependent kinase inhibitor (CKI) p21{sup Waf1/Cip1} and p27{sup Kip1} descended in PPARγ1{sup S84D} stable HT1080 cell, whereas the expression of p18{sup INK4C} was not changed. Moreover, compared to the PPARγ1{sup S84A}, PPARγ1{sup S84D} up-regulated the expression levels of cyclin D1 and cyclin A. Finally, PPARγ1 phosphorylation reduced sensitivity to agonist rosiglitazone and increased resistance to anticancer drug 5-fluorouracil (5-FU) in HT1080 cell. Our findings establish PPARγ1 phosphorylation as a critical event in human fibrosarcoma growth. These findings raise the possibility that chemical compounds that prevent the phosphorylation of PPARγ1 could act as anticancer drugs. - Highlights: • Phosphorylation attenuates PPARγ1 transcriptional activity. • Phosphorylated PPARγ1 promotes HT1080 cells proliferation. • PPARγ1 phosphorylation regulates cell cycle by mediating expression of cell cycle regulators. • PPARγ1 phosphorylation reduces sensitivity to agonist and anticancer drug. • Our findings establish PPARγ1 phosphorylation as a critical event in HT1080

  15. Specific protein supplementation using soya, casein or whey differentially affects regional gut growth and luminal growth factor bioactivity in rats; implications for the treatment of gut injury and stimulating repair.

    Science.gov (United States)

    Marchbank, Tania; Mandir, Nikki; Calnan, Denis; Goodlad, Robert A; Podas, Theo; Playford, Raymond J

    2018-01-24

    Modulation of regional growth within specific segments of the bowel may have clinical value for several gastrointestinal conditions. We therefore examined the effects of different dietary protein sources on regional gut growth and luminal growth factor bioactivity as potential therapies. Rats were fed for 14 days on isonitrogenous and isocaloric diets comprising elemental diet (ED) alone (which is known to cause gut atrophy), ED supplemented with casein or whey or a soya protein-rich feed. Effects on regional gut growth and intraluminal growth factor activity were then determined. Despite calorie intake being similar in all groups, soya rich feed caused 20% extra total body weight gain. Stomach weight was highest on soya and casein diets. Soya enhanced diet caused greatest increase in small intestinal weight and preserved luminal growth factor activity at levels sufficient to increase proliferation in vitro. Regional small intestinal proliferation was highest in proximal segment in ED fed animals whereas distal small intestine proliferation was greater in soya fed animals. Colonic weight and proliferation throughout the colon was higher in animals receiving soya or whey supplemented feeds. We conclude that specific protein supplementation with either soya, casein or whey may be beneficial to rest or increase growth in different regions of the bowel through mechanisms that include differentially affecting luminal growth factor bioactivity. These results have implications for targeting specific regions of the bowel for conditions such as Crohn's disease and chemotherapy.

  16. Bizarre parosteal osteochondromatous proliferation of bone

    International Nuclear Information System (INIS)

    Bandiera, S.; Bacchini, P.; Bertoni, F.

    1998-01-01

    A 47-year-old man presented with a painless mass of 7 months' duration, on the plantar aspect of the great toe of the right foot. Radiographs and CT images initially suggested an osteochondroma arising from the proximal phalanx of the great toe but there was no continuity between the medullary canal of the phalanx and the lesion. The mass was excised and a histological diagnosis of bizarre parosteal osteochondromatous proliferation of bone (Nora's disease) was made. The aggressive growth of this lesion may clinically suggest a neoplasm. Histological features, however, are those of a reactive lesion. (orig.)

  17. Growth and proliferation in vitro of Vaccinium corymbosum under different irradiance and radiation spectral composition

    International Nuclear Information System (INIS)

    Noe, N.; Eccher, T.; Signore, E. del; Montoldi, A.

    1998-01-01

    Plantlets of highbush blueberry (Vaccinium corymbosum) cvs. Atlantic, Barkeley and Elizabeth, were exposed in vitro to radiation of different spectral compositions obtained by filtering the cool-white light. Red colour of leaves was the first response to the light treatments. On average, cv. Atlantic yielded the highest number of shoots per explant (10.4), followed by cv. Elizabeth (9.1) and Berkeley (6.5). No-B-PMMA increased the proliferation rate in all the 3 genotypes, especially in cv. Atlantic. Cutting wavelengths between 650 and 760 nm (no-R-PMMA filter) generally depressed the proliferation rate. No-B-PMMA induced remarkable changes in the morphology of the shoots - more elongate leaves and longer internodes - especially in cv. Atlantic

  18. C8 cross transfer for the treatment of caudal brachial plexus avulsion in three dogs.

    Science.gov (United States)

    Moissonnier, Pierre; Carozzo, Claude; Thibaut, Jean-Laurent; Escriou, Catherine; Hidalgo, Antoine; Blot, Stéphane

    2017-01-01

    To evaluate the cervical nerve 8 cross-transfer technique (C8CT) as a part of surgical treatment of caudal brachial plexus avulsion (BPA) in the dog. Case series. Client-owned dogs suspected to have caudal BPA based on neurological examination and electrophysiological testing (n = 3). The distal stump of the surgically transected contralateral C8 ventral branch (donor) was bridged to the proximal stump of the avulsed C8 ventral branch (recipient) and secured with 9-0 polypropylene suture under an operating microscope. A carpal panarthrodesis was performed on the injured limb after C8CT. Surgical exploration confirmed avulsion of nerve roots C7, C8, and T1 in all cases. There was no evidence of an iatrogenic effect on the donor forelimb. Gradual improvement in function of the affected forelimb occurred in all dogs, with eventual recovery of voluntary elbow extension. Reinnervation was evident in EMG recordings 6 months postoperatively in all three dogs. Stimulation of the donor C8 ventral branch led to motor evoked potentials in the avulsed side triceps brachialis and radial carpus extensor muscles. Variable functional outcome was observed in the 3 dogs during clinical evaluation 3-4 years after surgery. Digital abrasion wounds, distal interphalangeal infectious arthritis, and self-mutilation necessitated distal phalanx amputation of digits 3 and 4 in 2 dogs. C8CT provided partial reconnection of the donor C8 ventral branch to the avulsed brachial plexus in the 3 dogs of this series. Reinnervation resulted in active elbow extension and promoted functional recovery in the affected limb. © 2017 The American College of Veterinary Surgeons.

  19. Conserved size and periodicity of pyramidal patches in layer 2 of medial/caudal entorhinal cortex.

    Science.gov (United States)

    Naumann, Robert K; Ray, Saikat; Prokop, Stefan; Las, Liora; Heppner, Frank L; Brecht, Michael

    2016-03-01

    To understand the structural basis of grid cell activity, we compare medial entorhinal cortex architecture in layer 2 across five mammalian species (Etruscan shrews, mice, rats, Egyptian fruit bats, and humans), bridging ∼100 million years of evolutionary diversity. Principal neurons in layer 2 are divided into two distinct cell types, pyramidal and stellate, based on morphology, immunoreactivity, and functional properties. We confirm the existence of patches of calbindin-positive pyramidal cells across these species, arranged periodically according to analyses techniques like spatial autocorrelation, grid scores, and modifiable areal unit analysis. In rodents, which show sustained theta oscillations in entorhinal cortex, cholinergic innervation targeted calbindin patches. In bats and humans, which only show intermittent entorhinal theta activity, cholinergic innervation avoided calbindin patches. The organization of calbindin-negative and calbindin-positive cells showed marked differences in entorhinal subregions of the human brain. Layer 2 of the rodent medial and the human caudal entorhinal cortex were structurally similar in that in both species patches of calbindin-positive pyramidal cells were superimposed on scattered stellate cells. The number of calbindin-positive neurons in a patch increased from ∼80 in Etruscan shrews to ∼800 in humans, only an ∼10-fold over a 20,000-fold difference in brain size. The relatively constant size of calbindin patches differs from cortical modules such as barrels, which scale with brain size. Thus, selective pressure appears to conserve the distribution of stellate and pyramidal cells, periodic arrangement of calbindin patches, and relatively constant neuron number in calbindin patches in medial/caudal entorhinal cortex. © 2015 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  20. COMPARATIVE STUDY TO EVALUATE ANALGESIC EFFICACY OF CAUDAL MIDAZOLAM AND CLONIDINE POSTOPERATIVE ANALGESIA IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Ramalinga Raju A.V.S

    2017-03-01

    Full Text Available BACKGROUND Caudal epidural analgesia is one of the most popular regional techniques used in paediatric patients undergoing lower limb, anoperineal and abdominal surgical procedures for postoperative pain relief. The aim of postoperative pain relief is to provide subjective comfort and inhibit trauma-induced nociceptive impulses to blunt autonomic and reflex responses to pain and subsequently to enhance the restoration of function. Caudal epidural analgesia though practiced widely is of short duration even when used with long-acting local anaesthetics. MATERIALS AND METHODS Children of either sex undergoing elective hernia or hydrocele surgery within in the age group of 2-8 years belonging to ASA I and II were included in the study. Informed consent was obtained from the parents before procedure. RESULTS The duration of analgesia in the study group was 10.14 ± 4.69 hrs. and 6.83 ± 0.79 hrs. in the clonidine group and midazolam group. Duration of analgesia in clonidine group was significantly longer when compared to with midazolam group with a p value of <0.05. Sedation Score- There was decrease in heart rate and mean arterial pressure from baseline, but these were under allowable limits of 20%. The patient had pain scores of less than 8 for first 6-8 hrs. The patients were well sedated and were easily arousable. CONCLUSION We conclude that in our study we found that clonidine 8 μg/kg provided good analgesia for a longer duration when compared with midazolam. Clonidine also provided good sedation with minimal haemodynamic variations. This is in agreement with studies conducted to know haemodynamic stability with higher doses of clonidine.

  1. Analysis of nuclear proliferation resistance reprocessing and recycling technologies

    International Nuclear Information System (INIS)

    Paviet-Hartmann, Patricia; Cerefice, Gary; Stacey, Marcela; Bakhtiar, Steven

    2011-01-01

    The PUREX process has been progressively and continuously improved during the past three decades, and these improvements account for successful commercialization of reprocessing in a few countries. The renewed interest in nuclear energy and the international growth of nuclear electricity generation do not equate - and should not be equated - with increasing proliferation risks. Indeed, the nuclear renaissance presents a unique opportunity to enhance the culture of non-proliferation. With the recent revival of interest in nuclear technology, technical methods for prevention of nuclear proliferation are being revisited. Robust strategies to develop new advanced separation technologies are emerging worldwide for sustainability and advancement of nuclear energy with enhanced proliferation resistance. On the other hand, at this moment, there are no proliferation resistance advanced technologies. Until now proliferation resistance as it applies to reprocessing has been focused on not separating a pure stream of weapons-usable plutonium. France, as an example, has proposed a variant of the PUREX process, the COEX TM process, which does not result on a pure plutonium product stream. A further step is to implement a process based on group extraction of actinides and fission products associated with a homogeneous recycling strategy (UNEX process in the US, GANEX process in France). Such scheme will most likely not be deployable on an industrial scale before 2030 or so because it requires intensive R and D and robust flowsheets. Finally, future generation recycling schemes will handle the used nuclear fuel in fast neutron reactors. This means that the plutonium throughput of the recycling process may increase. The need is obvious for advanced aqueous recycling technologies that are intrinsically more proliferation resistant than the commercial PUREX process. In this paper, we review the actual PUREX process along with the advanced recycling technologies that will enhance

  2. Analysis of nuclear proliferation resistance reprocessing and recycling technologies

    Energy Technology Data Exchange (ETDEWEB)

    Patricia Paviet-Hartmann; Gary Cerefice; Marcela Stacey; Steven Bakhtiar

    2011-05-01

    The PUREX process has been progressively and continuously improved during the past three decades, and these improvements account for successful commercialization of reprocessing in a few countries. The renewed interest in nuclear energy and the international growth of nuclear electricity generation do not equate – and should not be equated -with increasing proliferation risks. Indeed, the nuclear renaissance presents a unique opportunity to enhance the culture of non-proliferation. With the recent revival of interest in nuclear technology, technical methods for prevention of nuclear proliferation are being revisited. Robust strategies to develop new advanced separation technologies are emerging worldwide for sustainability and advancement of nuclear energy with enhanced proliferation resistance. On the other hand, at this moment, there are no proliferation resistance advanced technologies. . Until now proliferation resistance as it applies to reprocessing has been focused on not separating a pure stream of weapons-usable plutonium. France, as an example, has proposed a variant of the PUREX process, the COEX TM process, which does not result on a pure plutonium product stream. A further step is to implement a process based on group extraction of actinides and fission products associated with a homogeneous recycling strategy (UNEX process in the US, GANEX process in France). Such scheme will most likely not be deployable on an industrial scale before 2030 or so because it requires intensive R&D and robust flowsheets. Finally, future generation recycling schemes will handle the used nuclear fuel in fast neutron reactors. This means that the plutonium throughput of the recycling process may increase. The need is obvious for advanced aqueous recycling technologies that are intrinsically more proliferation resistant than the commercial PUREX process. In this paper, we review the actual PUREX process along with the advanced recycling technologies that will enhance

  3. Functional anatomy of the caudal thoracolumbar and lumbosacral spine in the horse.

    Science.gov (United States)

    Stubbs, N C; Hodges, P W; Jeffcott, L B; Cowin, G; Hodgson, D R; McGowan, C M

    2006-08-01

    Research in spinal biomechanics and functional anatomy has advanced back pain research in man. Yet, despite the performance limiting nature of back pain in horses, there are few data for the equine spine. To describe aspects of functional anatomy of the equine thoracolumbar and lumbosacral (LS) spine and potential effects on performance. The first study investigated variations in LS vertebral formula by post mortem examination of 120 horses. Midline vertebral transection was carried out on 65 Thoroughbred (TB), 24 Standardbred (SB) and 31 other breeds. The second study investigated morphology and biomechanics of the deep stabilising epaxial muscles of 13 horses using MRI (n = 3), anatomical dissection (n = 11) and biomechanical analysis (n = 6). The spinous process angular orientation relative to the vertebral body, was analysed at vertebrae T13, T18, L3, L5, L6 and S1. LS variations were found in 33.3% of the total group, 40.0% TB and 45.2% others, but 0% SB. Sacralisation of lumbar vertebra (L) 6 with LS motion between L5 and L6 occurred in 32.3% TB and 29.0% others. Five segmental multifidus fascicles were identified originating from spinous processes and vertebral laminae running craniocaudally onto the mammillary processes and lateral border of the sacrum, crossing between 1-5 intervertebral discs. Sacrocaudalis dorsalis (SCD) lateralis muscle was an extension of multifidus from L4, L5 and L6 depending on the vertebral formula whereas SCD medialis mm originated from S3. Both inserted on caudal vertebrae. Based on the location and direction of fibres, the principal action of the deep epaxial muscles was dorsoventral sagittal rotation. This action was dependent on vertebral spinous process/body orientation. We hypothesise that equine multifidus and SCD lateralis muscles act as caudal sagittal rotators of their vertebra of origin, as is the case in man, allowing dynamic stabilisation during dorsoventral motion. Equine multifidus anatomy and function are

  4. Dynamics of growth zone patterning in the milkweed bug Oncopeltus fasciatus.

    Science.gov (United States)

    Auman, Tzach; Vreede, Barbara M I; Weiss, Aryeh; Hester, Susan D; Williams, Terri A; Nagy, Lisa M; Chipman, Ariel D

    2017-05-15

    We describe the dynamic process of abdominal segment generation in the milkweed bug Oncopeltus fasciatus We present detailed morphological measurements of the growing germband throughout segmentation. Our data are complemented by cell division profiles and expression patterns of key genes, including invected and even-skipped as markers for different stages of segment formation. We describe morphological and mechanistic changes in the growth zone and in nascent segments during the generation of individual segments and throughout segmentation, and examine the relative contribution of newly formed versus existing tissue to segment formation. Although abdominal segment addition is primarily generated through the rearrangement of a pool of undifferentiated cells, there is nonetheless proliferation in the posterior. By correlating proliferation with gene expression in the growth zone, we propose a model for growth zone dynamics during segmentation in which the growth zone is functionally subdivided into two distinct regions: a posterior region devoted to a slow rate of growth among undifferentiated cells, and an anterior region in which segmental differentiation is initiated and proliferation inhibited. © 2017. Published by The Company of Biologists Ltd.

  5. Adiponectin Is Involved in Connective Tissue Growth Factor-Induced Proliferation, Migration and Overproduction of the Extracellular Matrix in Keloid Fibroblasts.

    Science.gov (United States)

    Luo, Limin; Li, Jun; Liu, Han; Jian, Xiaoqing; Zou, Qianlei; Zhao, Qing; Le, Qu; Chen, Hongdou; Gao, Xinghua; He, Chundi

    2017-05-12

    Adiponectin, an adipocyte-derived hormone, exerts pleiotropic biological effects on metabolism, inflammation, vascular homeostasis, apoptosis and immunity. Recently, adiponectin has been suggested to attenuate the progression of human dermal fibrosis. Connective tissue growth factor (CTGF) is induced in keloids and is thought to be participated in the formation of keloid fibrosis. However, the roles played by adiponectin in keloids remain unclear. In this study, we explored the effects of adiponectin on CTGF-induced cell proliferation, migration and the deposition of extracellular matrix (ECM) and their associated intracellular signalling pathways in keloid fibroblasts (KFs). We also explored possible mechanisms of keloid pathogenesis. Primary fibroblast cultures were established from foreskin biopsies and skin biopsies from patients with keloids. The expression of adiponectin and adiponectin receptors (adipoRs) was evaluated by reverse transcription-PCR (RT-PCR), quantitative real-time RT-PCR, immunofluorescence staining, and immunohistochemical analysis. Next, KFs and normal dermal fibroblasts (NFs) were treated with CTGF in the presence or absence of adiponectin. A cell counting kit-8 (CCK-8) and the Transwell assay were used to examine cell proliferation and migration. The level of the collagen I, fibronectin (FN) and α-smooth muscle actin (α-SMA) mRNAs and proteins were determined by quantitative real-time RT-PCR and western blotting. The effects of RNA interference (RNAi) targeting the adipoR genes were detected. Phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase-protein kinase (PI3K-Akt) were examined by western blotting to further investigate the signalling pathways. Furthermore, inhibitors of signal transduction pathways were investigated. The expression levels of adiponectin and adipoRs were significantly decreased in keloids compared with those

  6. DEPDC1 promotes cell proliferation and tumor growth via activation of E2F signaling in prostate cancer.

    Science.gov (United States)

    Huang, Lin; Chen, Keng; Cai, Zhao-Peng; Chen, Fu-Chao; Shen, Hui-Yong; Zhao, Wei-Hua; Yang, Song-Jie; Chen, Xu-Biao; Tang, Guo-Xue; Lin, Xi

    2017-08-26

    DEP domain containing 1 (DEPDC1) is recently reported to be overexpressed in several types of human cancer; however the role of DEPDC1 in prostate cancer remains to be investigated. Herein, we identified that the DEPDC1 mRNA and protein expression levels were dramatically increased in prostate cancer tissues and cell lines. Overexpression of DEPDC1 promoted, but depletion of DEPDC1 inhibited cell proliferation by regulating the G1-S phase cell cycle transition. Importantly, we found that DEPDC1 was essential for the tumor growth and formation of bone metastases of prostate cancer cells in vivo. Finally, we demonstrated that DEPDC1 interacted with E2F1 and increased its transcriptional activity, leading to hyper-activation of E2F signaling in prostate cancer cells. Our findings reveal an oncogenic role of DEPDC1 in prostate cancer progression via activation of E2F signaling, and suggest DEPDC1 might be a potential therapeutic target against the disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Plasma Rich in Growth Factors Induces Cell Proliferation, Migration, Differentiation, and Cell Survival of Adipose-Derived Stem Cells.

    Science.gov (United States)

    Mellado-López, Maravillas; Griffeth, Richard J; Meseguer-Ripolles, Jose; Cugat, Ramón; García, Montserrat; Moreno-Manzano, Victoria

    2017-01-01

    Adipose-derived stem cells (ASCs) are a promising therapeutic alternative for tissue repair in various clinical applications. However, restrictive cell survival, differential tissue integration, and undirected cell differentiation after transplantation in a hostile microenvironment are complications that require refinement. Plasma rich in growth factors (PRGF) from platelet-rich plasma favors human and canine ASC survival, proliferation, and delaying human ASC senescence and autophagocytosis in comparison with serum-containing cultures. In addition, canine and human-derived ASCs efficiently differentiate into osteocytes, adipocytes, or chondrocytes in the presence of PRGF. PRGF treatment induces phosphorylation of AKT preventing ASC death induced by lethal concentrations of hydrogen peroxide. Indeed, AKT inhibition abolished the PRGF apoptosis prevention in ASC exposed to 100  μ M of hydrogen peroxide. Here, we show that canine ASCs respond to PRGF stimulus similarly to the human cells regarding cell survival and differentiation postulating the use of dogs as a suitable translational model. Overall, PRGF would be employed as a serum substitute for mesenchymal stem cell amplification to improve cell differentiation and as a preconditioning agent to prevent oxidative cell death.

  8. Sirenomelia: a review of embryogenic theories and discussion of the differences from caudal regression syndrome.

    Science.gov (United States)

    Isik Kaygusuz, Ecmel; Kurek Eken, Meryem; Sivrikoz, Oya Nermin; Cetiner, Handan

    2016-03-01

    To discuss the pathological features of sirenomelia in the light of our 10 cases and review the current theories. We identified 10 patients with sirenomelia from our hospital database. All clinical details and the autopsy features of 10 cases were noted. Of the 10 children with sirenomelia seven had bilateral renal agenesis, three had bladder agenesis and one had a renal hypoplasia. Single umbilical artery was found in 60% of children with sirenomelia. External genitalia was ambiguous in seven of 10 patients. Even though the etiology of caudal regression syndrome (CRS) and sirenomelia remains unknown we tend to believe that sirenomelia and CRS might be different entities.

  9. Keratinocytes from APP/APLP2-deficient mice are impaired in proliferation, adhesion and migration in vitro

    International Nuclear Information System (INIS)

    Siemes, Christina; Quast, Thomas; Kummer, Christiane; Wehner, Sven; Kirfel, Gregor; Mueller, Ulrike; Herzog, Volker

    2006-01-01

    Growing evidence shows that the soluble N-terminal form (sAPPα) of the amyloid precursor protein (APP) represents an epidermal growth factor fostering keratinocyte proliferation, migration and adhesion. APP is a member of a protein family including the two mammalian amyloid precursor-like proteins APLP1 and APLP2. In the mammalian epidermis, only APP and APLP2 are expressed. APP and APLP2-deficient mice die shortly after birth but do not display a specific epidermal phenotype. In this report, we investigated the epidermis of APP and/or APLP2 knockout mice. Basal keratinocytes showed reduced proliferation in vivo by about 40%. Likewise, isolated keratinocytes exhibited reduced proliferation rates in vitro, which could be completely rescued by either exogenously added recombinant sAPPα, or by co-culture with dermal fibroblasts derived from APP knockout mice. Moreover, APP-knockout keratinocytes revealed reduced migration velocity resulting from severely compromised cell substrate adhesion. Keratinocytes from double knockout mice died within the first week of culture, indicating essential functions of APP-family members for survival in vitro. Our data indicate that sAPPα has to be considered as an essential epidermal growth factor which, however, in vivo can be functionally compensated to a certain extent by other growth factors, e.g., factors released from dermal fibroblasts

  10. Predicting cellular growth from gene expression signatures.

    Directory of Open Access Journals (Sweden)

    Edoardo M Airoldi

    2009-01-01

    Full Text Available Maintaining balanced growth in a changing environment is a fundamental systems-level challenge for cellular physiology, particularly in microorganisms. While the complete set of regulatory and functional pathways supporting growth and cellular proliferation are not yet known, portions of them are well understood. In particular, cellular proliferation is governed by mechanisms that are highly conserved from unicellular to multicellular organisms, and the disruption of these processes in metazoans is a major factor in the development of cancer. In this paper, we develop statistical methodology to identify quantitative aspects of the regulatory mechanisms underlying cellular proliferation in Saccharomyces cerevisiae. We find that the expression levels of a small set of genes can be exploited to predict the instantaneous growth rate of any cellular culture with high accuracy. The predictions obtained in this fashion are robust to changing biological conditions, experimental methods, and technological platforms. The proposed model is also effective in predicting growth rates for the related yeast Saccharomyces bayanus and the highly diverged yeast Schizosaccharomyces pombe, suggesting that the underlying regulatory signature is conserved across a wide range of unicellular evolution. We investigate the biological significance of the gene expression signature that the predictions are based upon from multiple perspectives: by perturbing the regulatory network through the Ras/PKA pathway, observing strong upregulation of growth rate even in the absence of appropriate nutrients, and discovering putative transcription factor binding sites, observing enrichment in growth-correlated genes. More broadly, the proposed methodology enables biological insights about growth at an instantaneous time scale, inaccessible by direct experimental methods. Data and tools enabling others to apply our methods are available at http://function.princeton.edu/growthrate.

  11. Control of proliferation rate of N27 dopaminergic neurons using Transcranial Magnetic Stimulation orientation

    Science.gov (United States)

    Meng, Yiwen; Hadimani, Ravi; Anantharam, Vellareddy; Kanthasamy, Anumantha; Jiles, David

    2015-03-01

    Transcranial magnetic stimulation (TMS) has been used to investigate possible treatments for a variety of neurological disorders. However, the effect that magnetic fields have on neurons has not been well documented in the literature. We have investigated the effect of different orientation of magnetic field generated by TMS coils with a monophasic stimulator on the proliferation rate of N27 neuronal cells cultured in flasks and multi-well plates. The proliferation rate of neurons would increase by exposed horizontally adherent N27 cells to a magnetic field pointing upward through the neuronal proliferation layer compared with the control group. On the other hand, proliferation rate would decrease in cells exposed to a magnetic field pointing downward through the neuronal growth layer compared with the control group. We confirmed results obtained from the Trypan-blue and automatic cell counting methods with those from the CyQuant and MTS cell viability assays. Our findings could have important implications for the preclinical development of TMS treatments of neurological disorders and represents a new method to control the proliferation rate of neuronal cells.

  12. Increased p21ras activity in human fibroblasts transduced with survivin enhances cell proliferation

    International Nuclear Information System (INIS)

    Temme, Achim; Diestelkoetter-Bachert, Petra; Schmitz, Marc; Morgenroth, Agnieszka; Weigle, Bernd; Rieger, Michael A.; Kiessling, Andrea; Rieber, E. Peter

    2005-01-01

    Survivin is critically involved in mitosis and when overexpressed enhances the activity of the Aurora B kinase, a serine-threonine kinase belonging to the family of oncogenic Aurora/IpI1p-related kinases. Both proteins interact with Ras GTPase-activating protein suggesting an impact on the Ras pathway. This study aimed at defining the role of survivin in proliferation and potential transformation of cells. When survivin was overexpressed in normal human lung fibroblasts, the characteristic track lanes of fibroblasts were disturbed and the rate of cell proliferation was increased. An enhanced level of p21 ras mRNA and protein expression and concomitant rise in levels of activated p21 ras were observed. Despite increased proliferation cell survival remained dependent on serum and cells were not able to form colonies in soft agar assays. These data suggest that overexpression of survivin increases cell growth but, despite the increase in active p21 ras , is not sufficient to transform primary cells. Yet, in addition to its anti-apoptotic function it might contribute to the accelerated growth of tumour cells by increasing p21 ras activity

  13. Platelet Lysate-Modified Porous Silicon Microparticles for Enhanced Cell Proliferation in Wound Healing Applications.

    Science.gov (United States)

    Fontana, Flavia; Mori, Michela; Riva, Federica; Mäkilä, Ermei; Liu, Dongfei; Salonen, Jarno; Nicoletti, Giovanni; Hirvonen, Jouni; Caramella, Carla; Santos, Hélder A

    2016-01-13

    The new frontier in the treatment of chronic nonhealing wounds is the use of micro- and nanoparticles to deliver drugs or growth factors into the wound. Here, we used platelet lysate (PL), a hemoderivative of platelets, consisting of a multifactorial cocktail of growth factors, to modify porous silicon (PSi) microparticles and assessed both in vitro and ex vivo the properties of the developed microsystem. PL-modified PSi was assessed for its potential to induce proliferation of fibroblasts. The wound closure-promoting properties of the microsystem were then assessed in an in vitro wound healing assay. Finally, the PL-modified PSi microparticles were evaluated in an ex vivo experiment over human skin. It was shown that PL-modified PSi microparticles were cytocompatible and enhanced the cell proliferation in different experimental settings. In addition, this microsystem promoted the closure of the gap between the fibroblast cells in the wound healing assay, in periods of time comparable with the positive control, and induced a proliferation and regeneration process onto the human skin in an ex vivo experiment. Overall, our results show that PL-modified PSi microparticles are suitable microsystems for further development toward applications in the treatment of chronic nonhealing wounds.

  14. Printed Proliferation: The Implications of Additive Manufacturing and Nuclear Weapons Proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Lindsey, Nicholas C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-01-26

    The growth of additive manufacturing as a disruptive technology poses nuclear proliferation concerns worthy of serious consideration. Additive manufacturing began in the early 1980s with technological advances in polymer manipulation, computer capabilities, and computer-aided design (CAD) modeling. It was originally limited to rapid prototyping; however, it eventually developed into a complete means of production that has slowly penetrated the consumer market. Today, additive manufacturing machines can produce complex and unique items in a vast array of materials including plastics, metals, and ceramics. These capabilities have democratized the manufacturing industry, allowing almost anyone to produce items as simple as cup holders or as complex as jet fuel nozzles. Additive manufacturing, or three-dimensional (3D) printing as it is commonly called, relies on CAD files created or shared by individuals with additive manufacturing machines to produce a 3D object from a digital model. This sharing of files means that a 3D object can be scanned or rendered as a CAD model in one country, and then downloaded and printed in another country, allowing items to be shared globally without physically crossing borders. The sharing of CAD files online has been a challenging task for the export controls regime to manage over the years, and additive manufacturing could make these transfers more common. In this sense, additive manufacturing is a disruptive technology not only within the manufacturing industry but also within the nuclear nonproliferation world. This paper provides an overview of additive manufacturing concerns of proliferation.

  15. Bone growth during rapamycin therapy in young rats

    Directory of Open Access Journals (Sweden)

    He Yu-Zhu

    2009-01-01

    Full Text Available Abstract Background Rapamycin is an effective immunosuppressant widely used to maintain the renal allograft in pediatric patients. Linear growth may be adversely affected in young children since rapamycin has potent anti-proliferative and anti-angiogenic properties. Methods Weanling three week old rats were given rapamycin at 2.5 mg/kg daily by gavage for 2 or 4 weeks and compared to a Control group given equivalent amount of saline. Morphometric measurements and biochemical determinations for serum calcium, phosphate, iPTH, urea nitrogen, creatinine and insulin-growth factor I (IGF-I were obtained. Histomorphometric analysis of the growth plate cartilage, in-situ hybridization experiments and immunohistochemical studies for various proteins were performed to evaluate for chondrocyte proliferation, chondrocyte differentiation and chondro/osteoclastic resorption. Results At the end of the 2 weeks, body and tibia length measurements were shorter after rapamycin therapy associated with an enlargement of the hypertrophic zone in the growth plate cartilage. There was a decrease in chondrocyte proliferation assessed by histone-4 and mammalian target of rapamycin (mTOR expression. A reduction in parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP and an increase in Indian hedgehog (Ihh expression may explain in part, the increase number of hypertrophic chondrocytes. The number of TRAP positive multinucleated chondro/osteoclasts declined in the chondro-osseous junction with a decrease in the receptor activator of nuclear factor kappa β ligand (RANKL and vascular endothelial growth factor (VEGF expression. Although body and tibial length remained short after 4 weeks of rapamycin, changes in the expression of chondrocyte proliferation, chondrocyte differentiation and chondro/osteoclastic resorption which were significant after 2 weeks of rapamycin improved at the end of 4 weeks. Conclusion When given to young rats, 2 weeks of rapamycin

  16. Keratinocyte Growth Factor Causes Cystic Dilation of the Mammary Glands of Mice: Interactions of Keratinocyte Growth Factor, Estrogen, and Progesterone In Vivo

    OpenAIRE

    Yi, Eunhee S.; Bedoya, Adriana A.; Lee, Hyesun; Kim, Seokhyun; Housley, Regina M.; Aukerman, Sharon L.; Tarpley, John E.; Starnes, Charles; Yin, Songmei; Pierce, Glenn F.; Ulich, Thomas R.

    1994-01-01

    Keratinocyte growth factor (KGF) is a paracrine mediator of epithelial cell proliferation that has been reported to induce marked proliferation of mammary epithelium in rats. In this study, systemic administration of KGF into naive and oophorectomized mice causes mammary gland proliferation, as evidenced histologically by the appearance of cysts lined by a single layer of epithelium and by hyperplastic epithelium. Whole mount preparations of the mammary glands reveal that the histologically n...

  17. Inhibition of Proliferation of Vascular Smooth Muscle Cells by Cucurbitanes from Momordica charantia.

    Science.gov (United States)

    Tuan, Nguyen Quoc; Lee, Do-Hyung; Oh, Joonseok; Kim, Chung Sub; Heo, Kyung-Sun; Myung, Chang-Seon; Na, MinKyun

    2017-07-28

    The cucurbitaceous plant Momordica charantia L., named "bitter melon", inhabits Asia, Africa, and South America and has been used as a traditional medicine. The atypical proliferation of vascular smooth muscle cells (VSMCs) plays an important role in triggering the pathogenesis of cardiovascular diseases. Platelet-derived growth factor (PDGF) is regarded as the most powerful growth factor in promoting the intimal accumulation of VSMCs. The current study features the identification of six new cucurbitane-type triterpenoids (1-6) from the fruits of M.  charantia, utilizing diverse chromatographic and spectroscopic techniques. In particular, the 2D structure of 1 was confirmed utilizing the long-range HSQMBC NMR pulse, capable of measuring heteronuclear long-range correlations ( 4-6 J CH ). The cucurbitanes were also assessed for their inhibitory activity against PDGF-induced VSMC proliferation. This current study may constitute a basis for developing those chemotypes into sensible pharmacophores alleviating cardiovascular disorders.

  18. Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Takahara, Kiyoshi [Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Ii, Masaaki, E-mail: masaii@art.osaka-med.ac.jp [Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Inamoto, Teruo; Komura, Kazumasa; Ibuki, Naokazu; Minami, Koichiro; Uehara, Hirofumi; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi [Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Asahi, Michio [Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Azuma, Haruhito [Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka (Japan)

    2014-04-18

    Highlights: • AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells. • AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway. • High expression of the TGF-β1 gene in AdSCs. - Abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferation of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa.

  19. Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis

    International Nuclear Information System (INIS)

    Takahara, Kiyoshi; Ii, Masaaki; Inamoto, Teruo; Komura, Kazumasa; Ibuki, Naokazu; Minami, Koichiro; Uehara, Hirofumi; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi; Asahi, Michio; Azuma, Haruhito

    2014-01-01

    Highlights: • AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells. • AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway. • High expression of the TGF-β1 gene in AdSCs. - Abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferation of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa

  20. The Cx43-like connexin protein Cx40.8 is differentially localized during fin ontogeny and fin regeneration.

    Directory of Open Access Journals (Sweden)

    Sarah V Gerhart

    Full Text Available Connexins (Cx are the subunits of gap junctions, membraneous protein channels that permit the exchange of small molecules between adjacent cells. Cx43 is required for cell proliferation in the zebrafish caudal fin. Previously, we found that a Cx43-like connexin, cx40.8, is co-expressed with cx43 in the population of proliferating cells during fin regeneration. Here we demonstrate that Cx40.8 exhibits novel differential subcellular localization in vivo, depending on the growth status of the fin. During fin ontogeny, Cx40.8 is found at the plasma membrane, but Cx40.8 is retained in the Golgi apparatus during regeneration. We next identified a 30 amino acid domain of Cx40.8 responsible for its dynamic localization. One possible explanation for the differential localization is that Cx40.8 contributes to the regulation of Cx43 in vivo, perhaps modifying channel activity during ontogenetic growth. However, we find that the voltage-gating properties of Cx40.8 are similar to Cx43. Together our findings reveal that Cx40.8 exhibits differential subcellular localization in vivo, dependent on a discrete domain in its carboxy terminus. We suggest that the dynamic localization of Cx40.8 differentially influences Cx43-dependent cell proliferation during ontogeny and regeneration.

  1. Antagonism between the transcription factors NANOG and OTX2 specifies rostral or caudal cell fate during neural patterning transition.

    Science.gov (United States)

    Su, Zhenghui; Zhang, Yanqi; Liao, Baojian; Zhong, Xiaofen; Chen, Xin; Wang, Haitao; Guo, Yiping; Shan, Yongli; Wang, Lihui; Pan, Guangjin

    2018-03-23

    During neurogenesis, neural patterning is a critical step during which neural progenitor cells differentiate into neurons with distinct functions. However, the molecular determinants that regulate neural patterning remain poorly understood. Here we optimized the "dual SMAD inhibition" method to specifically promote differentiation of human pluripotent stem cells (hPSCs) into forebrain and hindbrain neural progenitor cells along the rostral-caudal axis. We report that neural patterning determination occurs at the very early stage in this differentiation. Undifferentiated hPSCs expressed basal levels of the transcription factor orthodenticle homeobox 2 (OTX2) that dominantly drove hPSCs into the "default" rostral fate at the beginning of differentiation. Inhibition of glycogen synthase kinase 3β (GSK3β) through CHIR99021 application sustained transient expression of the transcription factor NANOG at early differentiation stages through Wnt signaling. Wnt signaling and NANOG antagonized OTX2 and, in the later stages of differentiation, switched the default rostral cell fate to the caudal one. Our findings have uncovered a mutual antagonism between NANOG and OTX2 underlying cell fate decisions during neural patterning, critical for the regulation of early neural development in humans. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Stochastic models for tumoral growth

    OpenAIRE

    Escudero, Carlos

    2006-01-01

    Strong experimental evidence has indicated that tumor growth belongs to the molecular beam epitaxy universality class. This type of growth is characterized by the constraint of cell proliferation to the tumor border, and surface diffusion of cells at the growing edge. Tumor growth is thus conceived as a competition for space between the tumor and the host, and cell diffusion at the tumor border is an optimal strategy adopted for minimizing the pressure and helping tumor development. Two stoch...

  3. Growth factor and pro-inflammatory cytokine contents in platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), advanced platelet-rich fibrin (A-PRF), and concentrated growth factors (CGF).

    Science.gov (United States)

    Masuki, Hideo; Okudera, Toshimitsu; Watanebe, Taisuke; Suzuki, Masashi; Nishiyama, Kazuhiko; Okudera, Hajime; Nakata, Koh; Uematsu, Kohya; Su, Chen-Yao; Kawase, Tomoyuki

    2016-12-01

    The development of platelet-rich fibrin (PRF) drastically simplified the preparation procedure of platelet-concentrated biomaterials, such as platelet-rich plasma (PRP), and facilitated their clinical application. PRF's clinical effectiveness has often been demonstrated in pre-clinical and clinical studies; however, it is still controversial whether growth factors are significantly concentrated in PRF preparations to facilitate wound healing and tissue regeneration. To address this matter, we performed a comparative study of growth factor contents in PRP and its derivatives, such as advanced PRF (A-PRF) and concentrated growth factors (CGF). PRP and its derivatives were prepared from the same peripheral blood samples collected from healthy donors. A-PRF and CGF preparations were homogenized and centrifuged to produce extracts. Platelet and white blood cell counts in A-PRF and CGF preparations were determined by subtracting those counts in red blood cell fractions, supernatant acellular serum fractions, and A-PRF/CGF exudate fractions from those counts of whole blood samples. Concentrations of growth factors (TGF-β1, PDGF-BB, VEGF) and pro-inflammatory cytokines (IL-1β, IL-6) were determined using ELISA kits. Compared to PRP preparations, both A-PRF and CGF extracts contained compatible or higher levels of platelets and platelet-derived growth factors. In a cell proliferation assay, both A-PRF and CGF extracts significantly stimulated the proliferation of human periosteal cells without significant reduction at higher doses. These data clearly demonstrate that both A-PRF and CGF preparations contain significant amounts of growth factors capable of stimulating periosteal cell proliferation, suggesting that A-PRF and CGF preparations function not only as a scaffolding material but also as a reservoir to deliver certain growth factors at the site of application.

  4. Mesenchymal precursor cells maintain the differentiation and proliferation potentials of breast epithelial cells

    Science.gov (United States)

    2014-01-01

    Introduction Stromal-epithelial interactions play a fundamental role in tissue homeostasis, controlling cell proliferation and differentiation. Not surprisingly, aberrant stromal-epithelial interactions contribute to malignancies. Studies of the cellular and molecular mechanisms underlying these interactions require ex vivo experimental model systems that recapitulate the complexity of human tissue without compromising the differentiation and proliferation potentials of human primary cells. Methods We isolated and characterized human breast epithelial and mesenchymal precursors from reduction mammoplasty tissue and tagged them with lentiviral vectors. We assembled heterotypic co-cultures and compared mesenchymal and epithelial cells to cells in corresponding monocultures by analyzing growth, differentiation potentials, and gene expression profiles. Results We show that heterotypic culture of non-immortalized human primary breast epithelial and mesenchymal precursors maintains their proliferation and differentiation potentials and constrains their growth. We further describe the gene expression profiles of stromal and epithelial cells in co-cultures and monocultures and show increased expression of the tumor growth factor beta (TGFβ) family member inhibin beta A (INHBA) in mesenchymal cells grown as co-cultures compared with monocultures. Notably, overexpression of INHBA in mesenchymal cells increases colony formation potential of epithelial cells, suggesting that it contributes to the dynamic reciprocity between breast mesenchymal and epithelial cells. Conclusions The described heterotypic co-culture system will prove useful for further characterization of the molecular mechanisms mediating interactions between human normal or neoplastic breast epithelial cells and the stroma, and will provide a framework to test the relevance of the ever-increasing number of oncogenomic alterations identified in human breast cancer. PMID:24916766

  5. RhoA–Rho kinase and Platelet Activating Factor Stimulation of Ovine Fetal Pulmonary Vascular Smooth Muscle Cell Proliferation

    Science.gov (United States)

    Renteria, Lissette S.; Austin, Monique; Lazaro, Mariecon; Andrews, Mari Ashley; Lustina, Jennessee; Raj, J. Usha; Ibe, Basil O.

    2013-01-01

    Objectives Platelet Activating Factor (PAF) is produced by pulmonary vascular smooth muscle Cells (PVSMC). We studied effect of Rho kinase on PAF stimulation of PVSMC proliferation in an attempt to understand a role for RhoA/Rho kinase on PAF-induced ovine fetal pulmonary vascular remodeling. Our hypothesis is that PAF acts through Rho kinase, as one of its downstream signaling, to induce arterial (SMC-PA) and venous (SMC-PV) growth in the hypoxic lung environment of the fetus in utero. Materials and methods Rho kinase and MAPK effects on PAF receptor (PAFR)-mediated cell growth and PAFR expression were studied by DNA synthesis, Western and immunocytochemistry. Effects of constructs T19N and G14V on PAF-induced cell proliferation was also studied. Results Hypoxia increased PVSMC proliferation and the Rho kinase inhibitors, Y-27632 and Fasudil (HA-1077) as well as MAPK inhibitors PD 98059 and SB 203580 attenuated PAF stimulation of cell proliferation. RhoA T19N and G14V stimulated cell proliferation, but co-incubation with PAF did not affect proliferative effects of the constructs. PAFR protein expression was significantly down-regulated in both cell types by both Y-27632 and HA-1077 with comparable profiles. Also cells treated with Y-27632 showed less PAF receptor fluorescence with significant disruption of the cell morphology. Conclusions Our results show that Rho kinase nonspecifically modulates PAFR-mediated responses via a translational modification of PAFR protein and suggest that, in vivo, activation of Rho kinase by PAF may be one other pathway to sustain PAFR-mediated PVSMC growth. PMID:24033386

  6. Adipocytes enhance murine pancreatic cancer growth via a hepatocyte growth factor (HGF)-mediated mechanism.

    Science.gov (United States)

    Ziegler, Kathryn M; Considine, Robert V; True, Eben; Swartz-Basile, Deborah A; Pitt, Henry A; Zyromski, Nicholas J

    2016-04-01

    Obesity accelerates the development and progression of pancreatic cancer, though the mechanisms underlying this association are unclear. Adipocytes are biologically active, producing factors such as hepatocyte growth factor (HGF) that may influence tumor progression. We therefore sought to test the hypothesis that adipocyte-secreted factors including HGF accelerate pancreatic cancer cell proliferation. Murine pancreatic cancer cells (Pan02 and TGP-47) were grown in a) conditioned medium (CM) from murine F442A preadipocytes, b) HGF-knockdown preadipocyte CM, c) recombinant murine HGF at increasing doses, and d) CM plus HGF-receptor (c-met) inhibitor. Cell proliferation was measured using the MTT assay. ANOVA and t-test were applied; p TGP-47 cell proliferation relative to control (59 ± 12% and 34 ± 12%, p TGP-47 cells remained unchanged. Recombinant HGF dose-dependently increased Pan02, but not TGP-47, proliferation (p TGP-47 cells. These experiments demonstrate that adipocyte-derived factors accelerate murine pancreatic cancer proliferation. In the case of Pan02 cells, HGF is responsible, in part, for this proliferation. Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  7. Nuclear non proliferation and disarmament; Non-proliferation nucleaire et desarmement

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-07-01

    In the framework of the publication of a document on the ''weapons mastership, disarmament and non proliferation: the french action'', by the ministry of Foreign Affairs and the ministry of Defense, the French Documentation organization presents a whole document. This document describes and details the following topics: the conference on the treaty of non proliferation of nuclear weapons, the France, Usa and Non Governmental Organizations position, the threats of the proliferation, the french actions towards the disarmament, the disarmament in the world, a chronology and some bibliographic resources. (A.L.B.)

  8. Effect of platelet-rich plasma (PRP) concentration on proliferation, neurotrophic function and migration of Schwann cells in vitro.

    Science.gov (United States)

    Zheng, Canbin; Zhu, Qingtang; Liu, Xiaolin; Huang, Xijun; He, Caifeng; Jiang, Li; Quan, Daping; Zhou, Xiang; Zhu, Zhaowei

    2016-05-01

    Platelet-rich plasma (PRP) contains various growth factors and appears to have the potential to promote peripheral nerve regeneration, but evidence is lacking regarding its biological effect on Schwann cells (SCs). The present study was designed to investigate the effect of PRP concentration on SCs in order to determine the plausibility of using this plasma-derived therapy for peripheral nerve injury. PRP was obtained from rats by double-step centrifugation and was characterized by determining platelet numbers and growth factor concentrations. Primary cultures of rat SCs were exposed to various concentrations of PRP (40%, 20%, 10%, 5% and 2.5%). Cell proliferation assays and flow cytometry were performed to study to assess SC proliferation. Quantitative real-time PCR and ELISA analysis were performed to determine the ability of PRP to induce SCs to produce nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). Microchemotaxis assay was used to analyse the cell migration capacity. The results obtained indicated that the platelet concentration and growth factors in our PRP preparations were significantly higher than in whole blood. Cell culture experiments showed that 2.5-20% PRP significantly stimulated SC proliferation and migration compared to untreated controls in a dose-dependent manner. In addition, the expression and secretion of NGF and GDNF were significantly increased. However, the above effects of SCs were suppressed by high PRP concentrations (40%). In conclusion, the appropriate concentration of PRP had the potency to stimulate cell proliferation, induced the synthesis of neurotrophic factors and significantly increased migration of SCs dose-dependently. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

  9. Electrospun Gelatin–Chondroitin Sulfate Scaffolds Loaded with Platelet Lysate Promote Immature Cardiomyocyte Proliferation

    Directory of Open Access Journals (Sweden)

    Francesca Saporito

    2018-02-01

    Full Text Available The aim of the present work was the development of heart patches based on gelatin (G and chondroitin sulfate (CS to be used as implants to improve heart recovery after corrective surgery for critical congenital heart defects (CHD. Patches were prepared by means of electrospinning to obtain nanofibrous scaffolds and they were loaded with platelet lysate (PL as a source of growth factors to further enhance the repair process. Scaffolds were characterized for morphology and mechanical properties and for the capability to support in vitro adhesion and proliferation of dermal fibroblasts in order to assess the system’s general biocompatibility. Adhesion and proliferation of endothelial cells and cardiac cells (cardiomyocytes and cardiac fibroblasts from rat fetuses onto PL-loaded patches was evaluated. Patches presented good elasticity and high stiffness suitable for in vivo adaptation to heart contraction. CS improved adhesion and proliferation of dermal fibroblasts, as proof of their biocompatibility. Moreover, they enhanced the adhesion and proliferation of endothelial cells, a crucial mediator of cardiac repair. Cell adhesion and proliferation could be related to elastic properties, which could favor cell motility. The presence of platelet lysate and CS was crucial for the adhesion and proliferation of cardiac cells and, in particular, of cardiomyocytes: G/CS scaffold embedded with PL appeared to selectively promote proliferation in cardiomyocytes but not cardiac fibroblasts. In conclusion, G/CS scaffold seems to be a promising system to assist myocardial-repair processes in young patient, preserving cardiomyocyte viability and preventing cardiac fibroblast proliferation, likely reducing subsequent uncontrolled collagen deposition by fibroblasts following repair.

  10. Articulatory Closure Proficiency in Patients with Parkinson's Disease Following Deep Brain Stimulation of the Subthalamic Nucleus and Caudal Zona Incerta

    Science.gov (United States)

    Karlsson, Fredrik; Olofsson, Katarina; Blomstedt, Patric; Linder, Jan; Nordh, Erik; van Doorn, Jan

    2014-01-01

    Purpose: The present study aimed at comparing the effects of deep brain stimulation (DBS) treatment of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) on the proficiency in achieving oral closure and release during plosive production of people with Parkinson's disease. Method: Nineteen patients participated preoperatively and…

  11. Epidermal growth factor receptor mediated proliferation depends on increased lipid droplet density regulated via a negative regulatory loop with FOXO3/Sirtuin6

    Energy Technology Data Exchange (ETDEWEB)

    Penrose, Harrison; Heller, Sandra; Cable, Chloe [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States); Makboul, Rania [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States); Pathology Department, Assiut University, Assiut (Egypt); Chadalawada, Gita; Chen, Ying [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States); Crawford, Susan E. [Department of Pathology, Saint Louis University School of Medicine, 1402 South Grand Blvd, Saint Louis, MO 63104 (United States); Savkovic, Suzana D., E-mail: ssavkovi@tulane.edu [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States)

    2016-01-15

    The proliferation of colon cancer cells is mediated in part by epidermal growth factor receptor (EGFR) signaling and requires sustained levels of cellular energy to meet its high metabolic needs. Intracellular lipid droplets (LDs) are a source of energy used for various cellular functions and they are elevated in density in human cancer, yet their regulation and function are not well understood. Here, in human colon cancer cells, EGF stimulates increases in LD density, which depends on EGFR expression and activation as well as the individual cellular capacity for lipid synthesis. Increases in LDs are blockaded by inhibition of PI3K/mTOR and PGE2 synthesis, supporting their dependency on select upstream pathways. In colon cancer cells, silencing of the FOXO3 transcription factor leads to down regulation of SIRT6, a negative regulator of lipid synthesis, and consequent increases in the LD coat protein PLIN2, revealing that increases in LDs depend on loss of FOXO3/SIRT6. Moreover, EGF stimulates loss of FOXO3/SIRT6, which is blockaded by the inhibition of upstream pathways as well as lipid synthesis, revealing existence of a negative regulatory loop between LDs and FOXO3/SIRT6. Elevated LDs are utilized by EGF treatment and their depletion through the inhibition of lipid synthesis or silencing of PLIN2 significantly attenuates proliferation. This novel mechanism of proliferative EGFR signaling leading to elevated LD density in colon cancer cells could potentially be therapeutically targeted for the treatment of tumor progression. - Highlights: • In colon cancer cells, EGFR activation leads to increases in LD density. • EGFR signaling includes PI3K/mTOR and PGE2 leading to lipid synthesis. • Increases in LDs are controlled by a negative regulatory loop with FOXO3/SIRT6. • EGFR mediated colon cancer cell proliferation depends on increased LD density.

  12. Epidermal growth factor receptor mediated proliferation depends on increased lipid droplet density regulated via a negative regulatory loop with FOXO3/Sirtuin6

    International Nuclear Information System (INIS)

    Penrose, Harrison; Heller, Sandra; Cable, Chloe; Makboul, Rania; Chadalawada, Gita; Chen, Ying; Crawford, Susan E.; Savkovic, Suzana D.

    2016-01-01

    The proliferation of colon cancer cells is mediated in part by epidermal growth factor receptor (EGFR) signaling and requires sustained levels of cellular energy to meet its high metabolic needs. Intracellular lipid droplets (LDs) are a source of energy used for various cellular functions and they are elevated in density in human cancer, yet their regulation and function are not well understood. Here, in human colon cancer cells, EGF stimulates increases in LD density, which depends on EGFR expression and activation as well as the individual cellular capacity for lipid synthesis. Increases in LDs are blockaded by inhibition of PI3K/mTOR and PGE2 synthesis, supporting their dependency on select upstream pathways. In colon cancer cells, silencing of the FOXO3 transcription factor leads to down regulation of SIRT6, a negative regulator of lipid synthesis, and consequent increases in the LD coat protein PLIN2, revealing that increases in LDs depend on loss of FOXO3/SIRT6. Moreover, EGF stimulates loss of FOXO3/SIRT6, which is blockaded by the inhibition of upstream pathways as well as lipid synthesis, revealing existence of a negative regulatory loop between LDs and FOXO3/SIRT6. Elevated LDs are utilized by EGF treatment and their depletion through the inhibition of lipid synthesis or silencing of PLIN2 significantly attenuates proliferation. This novel mechanism of proliferative EGFR signaling leading to elevated LD density in colon cancer cells could potentially be therapeutically targeted for the treatment of tumor progression. - Highlights: • In colon cancer cells, EGFR activation leads to increases in LD density. • EGFR signaling includes PI3K/mTOR and PGE2 leading to lipid synthesis. • Increases in LDs are controlled by a negative regulatory loop with FOXO3/SIRT6. • EGFR mediated colon cancer cell proliferation depends on increased LD density.

  13. Exposure to a specific time-varying electromagnetic field inhibits cell proliferation via cAMP and ERK signaling in cancer cells.

    Science.gov (United States)

    Buckner, Carly A; Buckner, Alison L; Koren, Stan A; Persinger, Michael A; Lafrenie, Robert M

    2018-04-01

    Exposure to specific electromagnetic field (EMF) patterns can affect a variety of biological systems. We have shown that exposure to Thomas-EMF, a low-intensity, frequency-modulated (25-6 Hz) EMF pattern, inhibited growth and altered cell signaling in malignant cells. Exposure to Thomas-EMF for 1 h/day inhibited the growth of malignant cells including B16-BL6 mouse melanoma cells, MDA-MB-231, MDA-MB-468, BT-20, and MCF-7 human breast cancer and HeLa cervical cancer cells but did not affect non-malignant cells. The Thomas-EMF-dependent changes in cell proliferation were mediated by adenosine 3',5'-cyclic monophosphate (cAMP) and extracellular-signal-regulated kinase (ERK) signaling pathways. Exposure of malignant cells to Thomas-EMF transiently changed the level of cellular cAMP and promoted ERK phosphorylation. Pharmacologic inhibitors (SQ22536) and activators (forskolin) of cAMP production both blocked the ability of Thomas-EMF to inhibit cell proliferation, and an inhibitor of the MAP kinase pathway (PD98059) was able to partially block Thomas-EMF-dependent inhibition of cell proliferation. Genetic modulation of protein kinase A (PKA) in B16-BL6 cells also altered the effect of Thomas-EMF on cell proliferation. Cells transfected with the constitutively active form of PKA (PKA-CA), which interfered with ERK phosphorylation, also interfered with the Thomas-EMF effect on cell proliferation. The non-malignant cells did not show any EMF-dependent changes in cAMP levels, ERK phosphorylation, or cell growth. These data indicate that exposure to the specific Thomas-EMF pattern can inhibit the growth of malignant cells in a manner dependent on contributions from the cAMP and MAP kinase pathways. Bioelectromagnetics. 39;217-230, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Peroxisome Proliferator-Activated Receptor-γ Inhibits Transformed Growth of Non-Small Cell Lung Cancer Cells through Selective Suppression of Snail

    Directory of Open Access Journals (Sweden)

    Rashmi Choudhary

    2010-03-01

    Full Text Available Work from our laboratory and others has demonstrated that activation of the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ inhibits transformed growth of non-small cell lung cancer (NSCLC cell lines in vitro and in vivo. We have demonstrated that activation of PPARγ promotes epithelial differentiation of NSCLC by increasing expression of E-cadherin, as well as inhibiting expression of COX-2 and nuclear factor-κB. The Snail family of transcription factors, which includes Snail (Snail1, Slug (Snail2, and ZEB1, is an important regulator of epithelial-mesenchymal transition, as well as cell survival. The goal of this study was to determine whether the biological responses to rosiglitazone, a member of the thiazolidinedione family of PPARγ activators, are mediated through the regulation of Snail family members. Our results indicate that, in two independent NSCLC cell lines, rosiglitazone specifically decreased expression of Snail, with no significant effect on either Slug or ZEB1. Suppression of Snail using short hairpin RNA silencing mimicked the effects of PPARγ activation, in inhibiting anchorage-independent growth, promoting acinar formation in three-dimensional culture, and inhibiting invasiveness. This was associated with the increased expression of E-cadherin and decreased expression of COX-2 and matrix metaloproteinases. Conversely, overexpression of Snail blocked the biological responses to rosiglitazone, increasing anchorage-independent growth, invasiveness, and promoting epithelial-mesenchymal transition. The suppression of Snail expression by rosiglitazone seemed to be independent of GSK-3 signaling but was rather mediated through suppression of extracellular signal-regulated kinase activity. These findings suggest that selective regulation of Snail may be critical in mediating the antitumorigenic effects of PPARγ activators.

  15. Anti-sense suppression of epidermal growth factor receptor expression alters cellular proliferation, cell-adhesion and tumorigenicity in ovarian cancer cells.

    Science.gov (United States)

    Alper, O; De Santis, M L; Stromberg, K; Hacker, N F; Cho-Chung, Y S; Salomon, D S

    2000-11-15

    Over-expression of epidermal growth factor receptor (EGFR) in ovarian cancer has been well documented. Human NIH:OVCAR-8 ovarian carcinoma cells were transfected with an expression vector containing the anti-sense orientation of truncated human EGFR cDNA. EGFR anti-sense over-expression resulted in decreased EGFR protein and mRNA expression, cell proliferation and tumor formation in nude mice. In accordance with the reduced levels of EGFR in EGFR anti-sense-expressing cells, tyrosine phosphorylation of EGFR was decreased compared to untransfected parental cells treated with EGF. In EGFR anti-sense-transfected cells, expression of erbB-3, but not erbB-2, was increased. In addition, basal and heregulin-beta 1-stimulated tyrosine phosphorylation of erbB-3 was higher in EGFR anti-sense vector-transfected cells. A morphological alteration in EGFR anti-sense gene-expressing cells was correlated with a decrease in the expression of E-cadherin, alpha-catenin and, to a lesser extent, beta-catenin. Changes in the expression of these proteins were associated with a reduction in complex formation among E-cadherin, beta-catenin and alpha-catenin and between beta-catenin and EGFR in EGFR anti-sense-expressing cells compared to sense-transfected control cells. These results demonstrate that EGFR expression in ovarian carcinoma cells regulates expression of cell adhesion proteins that may enhance cell growth and invasiveness. Copyright 2000 Wiley-Liss, Inc.

  16. Conditional expression of constitutively active estrogen receptor α in chondrocytes impairs longitudinal bone growth in mice

    International Nuclear Information System (INIS)

    Ikeda, Kazuhiro; Tsukui, Tohru; Imazawa, Yukiko; Horie-Inoue, Kuniko; Inoue, Satoshi

    2012-01-01

    Highlights: ► Conditional transgenic mice expressing constitutively active estrogen receptor α (caERα) in chondrocytes were developed. ► Expression of caERα in chondrocytes impaired longitudinal bone growth in mice. ► caERα affects chondrocyte proliferation and differentiation. ► This mouse model is useful for understanding the physiological role of ERαin vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caERα ColII , expressing constitutively active mutant estrogen receptor (ER) α in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caERα ColII mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caERα ColII mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caERα ColII mice. These results suggest that ERα is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.

  17. Mechanisms for the proliferation of eosinophilic leukemia cells by FIP1L1-PDGFRα

    International Nuclear Information System (INIS)

    Ishihara, Kenji; Kitamura, Hajime; Hiraizumi, Kenji; Kaneko, Motoko; Takahashi, Aki; Zee, OkPyo; Seyama, Toshio; Hong, JangJa; Ohuchi, Kazuo; Hirasawa, Noriyasu

    2008-01-01

    The constitutively activated tyrosine kinase Fip1-like 1 (FIP1L1)-platelet-derived growth factor receptor α (PDGFRα) causes eosinophilic leukemia EoL-1 cells to proliferate. Recently, we demonstrated that histone deacetylase inhibitors suppressed this proliferation and induced the differentiation of EoL-1 cells into eosinophils in parallel with a decrease in the level of FIP1L1-PDGFRα. In this study, we analyzed the mechanism by which FIP1L1-PDGFRα induces the proliferation and whether the suppression of cell proliferation triggers the differentiation into eosinophils. The FIP1L1-PDGFRα inhibitor imatinib inhibited the proliferation of EoL-1 cells and decreased the level of the oncoprotein c-Myc as well as the phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase (JNK). The proliferation of EoL-1 cells and expression of c-Myc were also inhibited by the MEK inhibitor U0126 and JNK inhibitor SP600125. The expression of the eosinophilic differentiation marker CCR3 was not induced by imatinib. These findings suggest that FIP1L1-PDGFRα induces the proliferation of EoL-1 cells through the induction of c-Myc expression via ERK and JNK signaling pathways, but is not involved in the inhibition of differentiation toward mature eosinophils

  18. Müller Glia, Vision-Guided Ocular Growth, Retinal Stem Cells, and a Little Serendipity

    Science.gov (United States)

    2011-01-01

    Hypothesis-driven science is expected to result in a continuum of studies and findings along a discrete path. By comparison, serendipity can lead to new directions that branch into different paths. Herein, I describe a diverse series of findings that were motivated by hypotheses, but driven by serendipity. I summarize how investigations into vision-guided ocular growth in the chick eye led to the identification of glucagonergic amacrine cells as key regulators of ocular elongation. Studies designed to assess the impact of the ablation of different types of neurons on vision-guided ocular growth led to the finding of numerous proliferating cells within damaged retinas. These proliferating cells were Müller glia–derived retinal progenitors with a capacity to produce new neurons. Studies designed to investigate Müller glia–derived progenitors led to the identification of a domain of neural stem cells that form a circumferential marginal zone (CMZ) that lines the periphery of the retina. Accelerated ocular growth, caused by visual deprivation, stimulated the proliferation of CMZ progenitors. We formulated a hypothesis that growth-regulating glucagonergic cells may regulate both overall eye size (scleral growth) and the growth of the retina (proliferation of CMZ cells). Subsequent studies identified unusual types of glucagonergic neurons with terminals that ramify within the CMZ; these cells use visual cues to control equatorial ocular growth and the proliferation of CMZ cells. Finally, while studying the signaling pathways that stimulate CMZ and Müller glia–derived progenitors, serendipity led to the discovery of a novel type of glial cell that is scattered across the inner retinal layers. PMID:21960640

  19. Morphology and physiology of the epiphyseal growth plate.

    Directory of Open Access Journals (Sweden)

    Robert Klepacz

    2009-05-01

    Full Text Available The epiphyseal growth plate develops from the cartilaginous-orientated mesenchymal cells that express SOX family genes. This multilayer structure is formed by the proliferation and hypertrophy of cells that synthesize the extracellular matrix composed of collagen (mainly type II, IX, X, XI and proteoglycans (aggrecan, decorin, annexin II, V and VI. The resting zone is responsible for protein synthesis and maintaining a germinal structure. In the proliferative zone, cells rapidly duplicate. The subsequent morphological changes take place in the transformation zone, divided into the upper and lower hypertrophic layers. In the degenerative zone, the mineralization process becomes intensive due to increased release of alkaline phosphate, calcium and matrix vesicles by terminally differentiated chondrocytes and some other factors e.g., metaphyseal ingrowth vessels. At this level, as well as in the primary and secondary spongiosa zones, chondrocytes undergo apoptosis and are physiologically eliminated. Unlike adult cartilage, in fetal and early formed growth plates, unusual forms such as authophagal bodies, paralysis and dark chondrocytes were also observed. Their ultrastructure differs greatly from apoptotic and normal cartilage cells. Chondrocyte proliferation and differentiation are regulated by various endocrine, paracrine, and autocrine agents such as growth, thyroid and sex hormones, beta-catenin, bone morphogenetic proteins, insulin-like growth factor, iodothyronine deiodinase, leptin, nitric oxide, transforming growth factor beta and vitamin D metabolites. However, the most significant factor is parathyroid hormone-related protein (PTHrP which is synthesized in the perichondrium by terminally differentiated chondrocytes. Secondary to activation of PTH/PTHrP receptors, PTHrP stimulates cell proliferation by G protein activation and delays their transformation into prehypertrophic and hypertrophic chondrocytes. When proliferation is completed

  20. Homeobox A7 stimulates breast cancer cell proliferation by up-regulating estrogen receptor-alpha

    International Nuclear Information System (INIS)

    Zhang, Yu; Cheng, Jung-Chien; Huang, He-Feng; Leung, Peter C.K.

    2013-01-01

    Highlights: •HOXA7 regulates MCF7 cell proliferation. •HOXA7 up-regulates ERα expression. •HOXA7 mediates estrogen-induced MCF7 cell proliferation. -- Abstract: Breast cancer is the most common hormone-dependent malignancy in women. Homeobox (HOX) transcription factors regulate many cellular functions, including cell migration, proliferation and differentiation. The aberrant expression of HOX genes has been reported to be associated with human reproductive cancers. Estradiol (E2) and its nuclear receptors, estrogen receptor (ER)-alpha and ER-beta, are known to play critical roles in the regulation of breast cancer cell growth. However, an understanding of the potential relationship between HOXA7 and ER in breast cancer cells is limited. In this study, our results demonstrate that knockdown of HOXA7 in MCF7 cells significantly decreased cell proliferation and ERα expression. In addition, HOXA7 knockdown attenuated E2-induced cell proliferation as well as progesterone receptor (PR) expression. The stimulatory effects of E2 on cell proliferation and PR expression were abolished by co-treatment with ICI 182780, a selective ERα antagonist. In contrast, overexpression of HOXA7 significantly stimulated cell proliferation and ERα expression. Moreover, E2-induced cell proliferation, as well as PR expression, was enhanced by the overexpression of HOXA7. Neither knockdown nor overexpression of HOXA7 affected the ER-beta levels. Our results demonstrate a novel mechanistic role for HOXA7 in modulating breast cancer cell proliferation via regulation of ERα expression. This finding contributes to our understanding of the role HOXA7 plays in regulating the proliferation of ER-positive cancer cells