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Sample records for werner syndrome fibroblasts

  1. Immortalization of Werner syndrome and progeria fibroblasts

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    Saito, H.; Moses, R.E. (Baylor College of Medicine, Houston, TX (USA))

    1991-02-01

    Human fibroblast cells from two different progeroid syndromes, Werner syndrome (WS) and progeria, were established as immortalized cell lines by transfection with plasmid DNA containing the SV40 early region. The lineage of each immortalized cell line was confirmed by VNTR analysis. Each of the immortalized cell lines maintained its original phenotype of slow growth. DNA repair ability of these cells was also studied by measuring sensitivity to killing by uv or the DNA-damaging drugs methyl methansulfonate, bleomycin, and cis-dichlorodiamine platinum. The results showed that both WS and progeria cells have normal sensitivity to these agents.

  2. DNA damage accumulation and TRF2 degradation in atypical Werner syndrome fibroblasts with LMNA mutations.

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    Saha, Bidisha; Zitnik, Galynn; Johnson, Simon; Nguyen, Quyen; Risques, Rosa A; Martin, George M; Oshima, Junko

    2013-01-01

    Segmental progeroid syndromes are groups of disorders with multiple features suggestive of accelerated aging. One subset of adult-onset progeroid syndromes, referred to as atypical Werner syndrome, is caused by mutations in the LMNA gene, which encodes a class of nuclear intermediate filaments, lamin A/C. We previously described rapid telomere attrition and accelerated replicative senescence in cultured fibroblasts overexpressing mutant lamin A. In this study, we investigated the cellular phenotypes associated with accelerated telomere shortening in LMNA mutant primary fibroblasts. In early passage primary fibroblasts with R133L or L140R LMNA mutations, shelterin protein components were already reduced while cells still retained telomere lengths comparable to those of controls. There was a significant inverse correlation between the degree of abnormal nuclear morphology and the level of TRF2, a shelterin subunit, suggesting a potential causal relationship. Stabilization of the telomeres via the introduction of the catalytic subunit of human telomerase, hTERT (human telomerase reverse transcriptase), did not prevent degradation of shelterin components, indicating that reduced TRF2 in LMNA mutants is not mediated by short telomeres. Interestingly, γ-H2AX foci (reflecting double strand DNA damage) in early passage LMNA mutant primary fibroblasts and LMNA mutant hTERT fibroblasts were markedly increased in non-telomeric regions of DNA. Our results raise the possibility that mutant lamin A/C causes global genomic instability with accumulation of non-telomeric DNA damage as an early event, followed by TRF2 degradation and telomere shortening.

  3. DNA Damage Accumulation and TRF2 Degradation in Atypical Werner Syndrome Fibroblasts with LMNA mutations

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    Bidisha eSaha

    2013-07-01

    Full Text Available Segmental progeroid syndromes are groups of disorders with multiple features suggestive of accelerated aging. One subset of adult-onset progeroid syndromes, referred to as atypical Werner syndrome (AWS, is caused by mutations in the LMNA gene, which encodes a class of nuclear intermediate filaments, lamin A/C. We previously described rapid telomere attrition and accelerated replicative senescence in cultured fibroblasts overexpressing mutant lamin A. In this study, we investigated the cellular phenotypes associated with accelerated telomere shortening in LMNA mutant primary fibroblasts. In early passage primary fibroblasts with R133L or L140R LMNA mutations, shelterin protein components were already reduced while cells still retained telomere lengths comparable to those of controls. There was a significant inverse correlation between the degree of abnormal nuclear morphology and the level of TRF2, a shelterin subunit, suggesting a potential causal relationship. Stabilization of the telomeres via the introduction of the catalytic subunit of human telomerase, hTERT, did not prevent degradation of shelterin components, indicating that reduced TRF2 in LMNA mutants is not mediated by short telomeres. Interestingly, -H2AX foci (reflecting double strand DNA damage in early passage LMNA mutant primary fibroblasts and LMNA mutant hTERT fibroblasts were markedly increased in non-telomeric regions of DNA. Our results raise the possibility that mutant lamin A/C causes global genomic instability with accumulation of non-telomeric DNA damage as an early event, followed by TRF2 degradation and telomere shortening.

  4. Contribution of Cdc42 to cholesterol efflux in fibroblasts from Tangier disease and Werner syndrome.

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    Hirano, Ken-ichi; Ikegami, Chiaki; Zhang, Zhongyan

    2008-01-01

    Atherosclerotic cardiovascular disease is a life-threatening disorder. Cholesterol efflux from the cells is the rate-limiting step in regulating the intracellular cholesterol content as well as raft structure in the plasma membrane. The defect of cholesterol efflux leads to the development of atherosclerosis. Tangier disease (TD), a hereditary high-density lipoprotein deficiency, is characterized by the presence of defective cellular cholesterol efflux. Using the cDNA subtraction technique, we found that expression of Cdc42 was decreased markedly in fibroblasts and macrophages from patients with TD. Madin-Darby canine kidney cells expressing the dominant-negative form of Cdc42 had a reduced lipid efflux; inversely, cells expressing the active form had increased efflux. Furthermore, we found that cellular lipid efflux was defective and Cdc42 was reduced in fibroblasts from a premature aging disorder, Werner syndrome. Complementation experiments using an adenovirus carrying wild-type Cdc42 successfully corrected impaired lipid efflux in Werner syndrome cells. We concluded that Cdc42 may play important roles in cellular cholesterol efflux and that dysregulation of this type of RhoGTPase might lead to the development of atherosclerotic cardiovascular disease.

  5. Genetics Home Reference: Werner syndrome

    Science.gov (United States)

    ... growth spurt, resulting in short stature. The characteristic aged appearance of individuals with Werner syndrome typically begins ... of the arteries ( atherosclerosis ), thinning of the bones ( osteoporosis ), and some types of cancer. It is not ...

  6. Early Onset Werner Syndrome

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    Berna İmge Aydoğan

    2015-09-01

    Full Text Available Werner syndrome (WS is a rare autosomal recessive adult-onset progeroid disorder characterized by the early onset of aged-appearance and age-related metabolic disorders. Symptoms of premature aging usually first develop in the second-third decades of life. We report a 27-year-old female who was admitted to our clinic at the age of eighteen with hyperglycemia. She was diagnosed with diabetes and type 4 dyslipidemia at the age of seven. In her family history, her parents were first cousins and she had three healthy brothers. On her first physical examination; she had bird-like face appearance, global hair loss, beaked nose, short stature and she was overweight. She had global hair loss with gray and thin hair. Hoarseness of voice and hyperkeratosis of skin were observed. She had bilateral cataracts and moderate sensorineural hearing loss. On psychiatric examination, borderline mental retardation was detected. She had severe insulin resistance and hypertriglyceridemia despite levothyroxine, gemfibrozil, omega-3 and intensive insulin treatment. Routine lipid apheresis was performed to lower the triglyceride levels reaching 5256 mg/dL. She also had focal segmental glomerulosclerosis, hepatosteatosis, osteoporosis and epilepsy. Disease was accompanied by several congenital deformities, such as Rathke’s cleft cyst, angiomyolipoma and femoral neck hypoplasia. WS is a rare genetic disorder characterized by multiple endocrine manifestations as well as soft tissue changes. We present a case of early disturbances that were diagnosed before typical clinical signs and symptoms. We propose that WS should be kept in mind when type 2 diabetes and hyperlipidemia are diagnosed early in childhood. Turk Jem 2015; 19: 99-104

  7. [Herlyn-Werner-Wunderlich syndrome

    NARCIS (Netherlands)

    Leerdam, L.E.C.M.M. van; Beerendonk, C.C.M.; Klein, W.M.; Sir, O.

    2014-01-01

    BACKGROUND: Many patients are admitted to accident and emergency departments with acute abdominal pain. Herlyn-Werner-Wunderlich syndrome (HWWS) is one of the less well-known causes of this. It is characterised by uterine didelphys with an obstructed hemivagina and ipsilateral renal agenesis or

  8. Investigating the role of c-Jun N-terminal kinases in the proliferation of Werner syndrome fibroblasts using diaminopyridine inhibitors

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    Davis Terence

    2011-12-01

    Full Text Available Abstract Fibroblasts derived from the progeroid Werner syndrome show reduced replicative lifespan and a "stressed" morphology, both alleviated using the MAP kinase inhibitor SB203580. However, interpretation of these data is problematical because although SB203580 has the stress-activated kinases p38 and JNK1/2 as its preferred targets, it does show relatively low overall kinase selectivity. Several lines of data support a role for both p38 and JNK1/2 activation in the control of cellular proliferation and also the pathology of diseases of ageing, including type II diabetes, diseases to which Werner Syndrome individuals are prone, thus making the use of JNK inhibitors attractive as possible therapeutics. We have thus tested the effects of the widely used JNK inhibitor SP600125 on the proliferation and morphology of WS cells. In addition we synthesised and tested two recently described aminopyridine based inhibitors. SP600125 treatment resulted in the cessation of proliferation of WS cells and resulted in a senescent-like cellular phenotype that does not appear to be related to the inhibition of JNK1/2. In contrast, use of the more selective aminopyridine CMPD 6o at concentrations that fully inhibit JNK1/2 had a positive effect on cellular proliferation of immortalised WS cells, but no effect on the replicative lifespan of primary WS fibroblasts. In addition, CMPD 6o corrected the stressed WS cellular morphology. The aminopyridine CMPD 6r, however, had little effect on WS cells. CMDP 6o was also found to be a weak inhibitor of MK2, which may partially explain its effects on WS cells, since MK2 is known to be involved in regulating cellular morphology via HSP27 phosphorylation, and is thought to play a role in cell cycle arrest. These data suggest that total JNK1/2 activity does not play a substantial role in the proliferation control in WS cells.

  9. [Herlyn-Werner syndrome. Case report].

    Science.gov (United States)

    Ivanov, S; Karagjosov, A; Grueva, A

    1990-01-01

    The following study shows a syndrome which is commonly not diagnosed by gynaecologists. It was first described from Herlyn-Werner in 1971. In Bulgaria the same was described by I. Karagjosov in 1983 as a part of Herlyn-Werner-Wunderlich Syndrome.

  10. [Herlyn-Werner-Wunderlich syndrome].

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    van Leerdam, Lotte E C M M; Beerendonk, Catharina C M; Klein, Willemijn M; Sir, Özcan

    2014-01-01

    Many patients are admitted to accident and emergency departments with acute abdominal pain. Herlyn-Werner-Wunderlich syndrome (HWWS) is one of the less well-known causes of this. It is characterised by uterine didelphys with an obstructed hemivagina and ipsilateral renal agenesis or dysplasia. A 16-year-old girl presented to the emergency department with progressive abdominal pain and a previous history of renal and anal abnormalities. Acute appendicitis was suspected because of both tenderness on pressure and rebound tenderness, and a raised C-reactive protein level. Abdominal ultrasonography revealed a cystic structure, probably of ovarian or tubal origin. An emergency laparoscopy was performed as ovarian torsion was suspected. This revealed uterine didelphys with an abnormal right horn. Additional abdominal MRI scan diagnostic revealed abnormalities consistent with HWWS. Congenital urogenital abnormalities should be included in the differential diagnosis of patients with a previous history of renal or anal abnormalities who present with progressive abdominal pain or dysmenorrhoea.

  11. Use of p38 MAPK Inhibitors for the Treatment of Werner Syndrome

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    Mark C. Bagley

    2010-06-01

    Full Text Available Werner syndrome provides a convincing model for aspects of the normal ageing phenotype and may provide a suitable model for therapeutic interventions designed to combat the ageing process. Cultured primary fibroblast cells from Werner syndrome patients provide a powerful model system to study the link between replicative senescence in vitro and in vivo pathophysiology. Genome instability, together with an increased pro-oxidant state, and frequent replication fork stalling, all provide plausible triggers for intracellular stress in Werner syndrome cells, and implicates p38 MAPK signaling in their shortened replicative lifespan. A number of different p38 MAPK inhibitor chemotypes have been prepared rapidly and efficiently using microwave heating techniques for biological study in Werner syndrome cells, including SB203580, VX-745, RO3201195, UR-13756 and BIRB 796, and their selectivity and potency evaluated in this cellular context. Werner syndrome fibroblasts treated with a p38 MAPK inhibitor reveal an unexpected reversal of the accelerated ageing phenotype. Thus the study of p38 inhibition and its effect upon Werner pathophysiology is likely to provide new revelations into the biological mechanisms operating in cellular senescence and human ageing in the future.

  12. WERNER SYNDROME: A NEW CASE REPORT

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    Faida Ajili

    2013-10-01

    Full Text Available “Werner’s syndrome” or premature aging syndrome is a rare autosomal recessive genetic disease. It is responsible of several complications related to age, including atherosclerosis and association with cancer. We report the case of a 36 year-old-patient, admitted to department of Internal Medicine of the military hospital of Tunis for suspicion of systemic sclerosis. The patient had all the major signs of Werner syndrome (bilateral cataract, sclerotic skin, “bird face”, baldness, small size, parental consanguinity and 4 minor signs (type 2 diabetes, hypogonadism, squeaky voice, and flat feet. She has also a brother with the same morphotype died at the age of 32 by a myocardial infarction. The current follow-up time is 9 years..

  13. Pelvic inflammatory disease due to Herlyn-Werner-Wunderlich syndrome

    National Research Council Canada - National Science Library

    Alumbreros-Andújar, Maria Trinidad; Aguilar-Galán, Esther Vanesa; Pérez-Parra, Celia; Céspedes-Casas, Carmen; Ramírez-Gómez, Mercedes; González-López, Ana

    2014-01-01

    Herlyn-Werner-Wunderlich syndrome is a congenital urogenital malformation that is associated with a uterus didelphys and a longitudinal vaginal septum, resulting in a blind hemivagina and ipsilateral renal agenesis...

  14. Perioperative evaluation in Herlyn-Werner-Wunderlich syndrome.

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    Schutt, Amy K; Barrett, Megan R; Trotta, Brian M; Stovall, Dale W

    2012-10-01

    Herlyn-Werner-Wunderlich syndrome is defined by uterine didelphys, obstructed hemivagina, and ipsilateral renal agenesis. We report the presentation, radiographic findings, and outcomes of three patients with Herlyn-Werner-Wunderlich syndrome who underwent surgical management at a tertiary care academic medical center. Two patients were diagnosed by magnetic resonance imaging and one by ultrasonography. All three underwent successful transvaginal septoplasty and drainage of the hematocolpos and hematometra. One required septoplasty revision with temporary vaginal stent placement. Herlyn-Werner-Wunderlich syndrome is a rare condition. The most urgent concern is the obstruction of menstrual effluent. Unlike an isolated transverse vaginal septum, the vaginal septum with Herlyn-Werner-Wunderlich syndrome is parallel to the patent vaginal canal, less pliable, and closer to the cervix. These anatomical differences result in pronounced distortion with significant diagnostic and surgical challenges.

  15. Accelerated epigenetic aging in Werner syndrome.

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    Maierhofer, Anna; Flunkert, Julia; Oshima, Junko; Martin, George M; Haaf, Thomas; Horvath, Steve

    2017-04-01

    Individuals suffering from Werner syndrome (WS) exhibit many clinical signs of accelerated aging. While the underlying constitutional mutation leads to accelerated rates of DNA damage, it is not yet known whether WS is also associated with an increased epigenetic age according to a DNA methylation based biomarker of aging (the "Epigenetic Clock"). Using whole blood methylation data from 18 WS cases and 18 age matched controls, we find that WS is associated with increased extrinsic epigenetic age acceleration (p=0.0072) and intrinsic epigenetic age acceleration (p=0.04), the latter of which is independent of age-related changes in the composition of peripheral blood cells. A multivariate model analysis reveals that WS is associated with an increase in DNA methylation age (on average 6.4 years, p=0.011) even after adjusting for chronological age, gender, and blood cell counts. Further, WS might be associated with a reduction in naïve CD8+ T cells (p=0.025) according to imputed measures of blood cell counts. Overall, this study shows that WS is associated with an increased epigenetic age of blood cells which is independent of changes in blood cell composition. The extent to which this alteration is a cause or effect of WS disease phenotypes remains unknown.

  16. Herlyn-Werner-Wunderlich syndrome--a case report.

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    Nejkovic, L; Stanojevic, D

    2013-01-01

    This is a case report of Herlyn-Werner-Wunderlich syndrome in a 28-year-old patient. She was admitted to hospital for surgical treatment of the pelvic mass accompanied by painful menstruation periods. This syndrome was diagnosed by US and MRI and it was treated by hemi-hysterectomy with vaginectomy. After the surgery, the patient has had regular and painless menstruation.

  17. [Herlyn-Werner and Wunderlich syndromes (author's transl)].

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    Gazárek, F; Kudela, M; Zenisek, L; Nevrla, F

    1979-01-01

    Reported in this paper are four cases of rare, combined, congenital, urogenital abnormalities, that is combination of inhibitory malformation (duplication) of uterus, paracervically localised cystic resistance, and renal aplasia on the same side. With all apparent similarity of the four cases, there were two different syndromes, the Herlyn-Werner syndrome in two cases and the Wunderlich syndrome in the other two. Both syndromes are presented in diagrams and described.

  18. Herlyn-Werner-Wunderlich syndrome with a partially obstructed hemivagina.

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    Moshiri, Mariam; Seyal, Adeel Rahim; Cruite, Irene; Bhargava, Puneet

    2012-01-01

    Uterine didelphys with obstructed hemivagina and ipsilateral renal agenesis is a rare congenital anomaly of the Müllerian duct system referred to as Herlyn-Werner-Wunderlich syndrome. Because of its rare occurrence, a high level of suspicion is often required for diagnosis. Clinically, these patients usually present after menarche with pelvic pain, dysmenorrhea, and a palpable pelvic mass. We present a case of a 31-year-old female patient with infertility. Imaging findings were consistent with Herlyn-Werner-Wunderlich syndrome, with a congenital defect in the longitudinal vaginal septum resulting in partial spontaneous decompression of right-sided hematocolpos.

  19. New Classification of Herlyn-Werner-Wunderlich Syndrome

    OpenAIRE

    Lan Zhu; Na Chen; Jia-Li Tong; Wei Wang; Lei Zhang; Jing-He Lang

    2015-01-01

    Background: Uterus didelphys and blind hemivagina associated with ipsilateral renal agenesis are collectively known as Herlyn-Werner-Wunderlich syndrome (HWWS). In the literature, the syndrome often appears as a single case report or as a small series. In our study, we reviewed the characteristics of all HWWS patients at Peking Union Medical College Hospital (PUMCH) and suggested a new classification for this syndrome because the clinical characteristics differed significantly between the com...

  20. [Pelvic inflammatory disease due to Herlyn-Werner-Wunderlich syndrome].

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    Alumbreros-Andújar, Maria Trinidad; Aguilar-Galán, Esther Vanesa; Pérez-Parra, Celia; Céspedes-Casas, Carmen; Ramírez-Gómez, Mercedes; González-López, Ana

    2014-01-01

    Herlyn-Werner-Wunderlich syndrome is a congenital urogenital malformation that is associated with a uterus didelphys and a longitudinal vaginal septum, resulting in a blind hemivagina and ipsilateral renal agenesis. Clinical presentation is highly variable, delaying diagnosis and leading to important complications. We present the case of a 13-year-old female who was diagnosed with Herlyn-Werner-Wunderlich syndrome following an acute abdomen due to a right tubo-ovarian abscess. She had a vaginal septum giving rise to a right blind hemivagina. It was microperforated, causing intermittent genital bleeding. This hematocolpos was colonized by microorganisms that ascended to the pelvic cavity, causing right tuboovarian abscess. Nuclear magnetic resonance imaging provided theWernermost diagnostic information. We performed a vaginal septum resection, and both hemiuteros communicated with a single vagina, resulting in an asymptomatic patient. Herlyn-Werner-Wunderlich syndrome is a little known entity and can be presented atypically, resulting in diagnostic difficulty and treatment delay. It is important to be aware of this syndrome in order to avoid irreversible complications.

  1. Herlyn-Werner-Wunderlich syndrome: An unusual presentation with pyocolpos.

    Science.gov (United States)

    Jung, Eun Jung; Cho, Moon Hyeong; Kim, Da Hyun; Byun, Jung Mi; Kim, Young Nam; Jeong, Dae Hoon; Sung, Moon Su; Kim, Ki Tae; Lee, Kyung Bok

    2017-07-01

    Herlyn-Werner-Wunderlich syndrome is a rare congenital anomaly of the urogenital tract, which is characterized by the triad of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. It usually presents at puberty with pelvic pain, dysmenorrhea, and a vaginal or pelvic mass. Although rare, it may present with purulent vaginal discharge due to secondary infection of the obstructed hemivagina, making diagnosis difficult. A careful pelvic examination to identify the cervix and vagina is the key to the diagnosis of Müllerian duct anomalies and magnetic resonance imaging can provide additional useful information. The optimal treatment is full excision and marsupialization of the obstructing vaginal septum so that both uteri can drain through the patent vagina. The authors report a case of a 22-year-old female with an unusual presentation of Herlyn-Werner-Wunderlich syndrome complicated by pyocolpos, which was successfully managed by vaginal septum resection and drainage of pus.

  2. Herlyn-Werner-Wunderlich syndrome with a partially obstructed hemivagina

    OpenAIRE

    Moshiri, Mariam; Seyal, Adeel Rahim; Cruite, Irene; Bhargava, Puneet

    2015-01-01

    Uterine didelphys with obstructed hemivagina and ipsilateral renal agenesis is a rare congenital anomaly of the M?llerian duct system referred to as Herlyn-Werner-Wunderlich syndrome. Because of its rare occurrence, a high level of suspicion is often required for diagnosis. Clinically, these patients usually present after menarche with pelvic pain, dysmenorrhea, and a palpable pelvic mass. We present a case of a 31-year-old female patient with infertility. Imaging findings were consistent wit...

  3. Pyometra and Pregnancy with Herlyn-Werner-Wunderlich Syndrome

    OpenAIRE

    Reis, Maria Inês; Vicente, Ana Patrícia; Cominho, Joana; Gomes, Andrea Sousa; Martins, Luísa; Nunes, Filomena

    2016-01-01

    ABSTRACT We describe a Herlyn-Werner-Wunderlich syndrome (HWWS) patient with previous history of infertility who got pregnant without treatment and presented a pyometra in the contralateral uterus throughout the gestational period, despite multiple antibiotic treatments. Due to the uterus' congenital anomaly and the possibility of ascending infection with subsequent abortion, this pregnancy was classified as high-risk. We believe that the partial horizontal septum in the vagina may have contr...

  4. Magnetic resonance imaging diagnosis of Herlyn-Werner-Wunderlich syndrome

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    Taruna Yadav

    2017-01-01

    Full Text Available Herlyn-Werner-Wunderlich syndrome (HWW is a triad of didelphys uterus, obstructed hemivagina, and ipsilateral renal agenesis. It is a combined anomaly of Mullerian and mesonephric ducts. It usually presents in adolescent females after menarche with nonspecific symptoms of pelvic pain, dysmenorrhea, and rarely a palpable pelvic mass. We report here, a case of an 18-year-old female presenting with complaints of lower abdominal pain and dysmenorrhea where magnetic resonance imaging (MRI confirmed the diagnosis of HWW syndrome. MRI is the imaging modality of choice for diagnosis of HWW syndrome and associated complications such as endometriosis.

  5. Gene expression profiling in Werner syndrome closely resembles that of normal aging

    DEFF Research Database (Denmark)

    Kyng, Kasper J; May, Alfred; Kølvraa, Steen

    2003-01-01

    Werner syndrome (WS) is a premature aging disorder, displaying defects in DNA replication, recombination, repair, and transcription. It has been hypothesized that several WS phenotypes are secondary consequences of aberrant gene expression and that a transcription defect may be crucial to the dev......Werner syndrome (WS) is a premature aging disorder, displaying defects in DNA replication, recombination, repair, and transcription. It has been hypothesized that several WS phenotypes are secondary consequences of aberrant gene expression and that a transcription defect may be crucial...... to the development of the syndrome. We used cDNA microarrays to characterize the expression of 6,912 genes and ESTs across a panel of 15 primary human fibroblast cell lines derived from young donors, old donors, and WS patients. Of the analyzed genes, 6.3% displayed significant differences in expression when either...... WS or old donor cells were compared with young donor cells. This result demonstrates that the WS transcription defect is specific to certain genes. Transcription alterations in WS were strikingly similar to those in normal aging: 91% of annotated genes displayed similar expression changes in WS...

  6. Herlyn-Werner-Wunderlich syndrome: a case report.

    Science.gov (United States)

    Piccinini, Pedro Salomao; Doski, John

    2015-04-01

    Herlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital disorder of the Müllerian ducts in which there is uterus didelphys, obstructed hemivagina and unilateral renal agenesis. The most common presentation is an abdominal mass secondary to hematocolpos, pain and dysmenorrhea. However, in some cases, such as the one we present here, menses are normal due to an obstructed hemivagina, and diagnosis can be delayed. We describe evaluation and surgical management of a 13-year-old girl with this condition who was diagnosed by computed tomography (CT) scan and confirmed by pelvic ultrasound and surgical exploration, as well as a review of the literature.

  7. Pyometra and Pregnancy with Herlyn-Werner-Wunderlich Syndrome.

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    Reis, Maria Inês; Vicente, Ana Patrícia; Cominho, Joana; Gomes, Andrea Sousa; Martins, Luísa; Nunes, Filomena

    2016-12-01

    We describe a Herlyn-Werner-Wunderlich syndrome (HWWS) patient with previous history of infertility who got pregnant without treatment and presented a pyometra in the contralateral uterus throughout the gestational period, despite multiple antibiotic treatments. Due to the uterus' congenital anomaly and the possibility of ascending infection with subsequent abortion, this pregnancy was classified as high-risk. We believe that the partial horizontal septum in the vagina may have contributed to the closure of the gravid uterus cervix, thus ensuring that the pregnancy came to term, with an uneventful vaginal delivery. Thieme Publicações Ltda Rio de Janeiro, Brazil.

  8. Endometriosis in association with Herlyn-Werner-Wunderlich syndrome.

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    Tong, Jiali; Zhu, Lan; Chen, Na; Lang, Jinghe

    2014-09-01

    To describe the clinical characteristics of patients with Herlyn-Werner-Wunderlich syndrome (HWWS) and explore the relationship between an obstructive genital abnormality and pelvic endometriosis. Case series. University hospital. A total of 94 women with Herlyn-Werner-Wunderlich syndrome (HWWS). Retrospectively reviewed charts of patients diagnosed with HWWS and follow-up contact. Data for each patient regarding demographics, presenting symptoms, concomitant complications, and anatomic variations were obtained from operation notes and clinical records. The occurrence of pelvic endometriosis was 19.15% (18/94) in patients with HWWS. All ovarian endometrial cysts (100%) occurred ipsilateral to the vaginal septum. Pelvic endometriosis was significantly more frequent in patients with complete hemivaginal obstructions (10/27, 37.0%) than those with incomplete obstructions (8/67, 11.9%). One-fifth of patients with HWWS were susceptible to pelvic endometriosis, and all of the ovarian endometriotic cysts were ipsilateral to the vaginal septum. Pelvic endometriosis in adolescents appeared to be related to the obstructed genital abnormality. Vaginal septum resection should be the first step in treatment and surgery has an important role in the treatment of endometriosis and pelvic adhesion. Copyright © 2014. Published by Elsevier Inc.

  9. Partial lipodystrophy with severe insulin resistance and adult progeria Werner syndrome.

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    Donadille, Bruno; D'Anella, Pascal; Auclair, Martine; Uhrhammer, Nancy; Sorel, Marc; Grigorescu, Romulus; Ouzounian, Sophie; Cambonie, Gilles; Boulot, Pierre; Laforêt, Pascal; Carbonne, Bruno; Christin-Maitre, Sophie; Bignon, Yves-Jean; Vigouroux, Corinne

    2013-07-12

    Laminopathies, due to mutations in LMNA, encoding A type-lamins, can lead to premature ageing and/or lipodystrophic syndromes, showing that these diseases could have close physiopathological relationships. We show here that lipodystrophy and extreme insulin resistance can also reveal the adult progeria Werner syndrome linked to mutations in WRN, encoding a RecQ DNA helicase. We analysed the clinical and biological features of two women, aged 32 and 36, referred for partial lipodystrophic syndrome which led to the molecular diagnosis of Werner syndrome. Cultured skin fibroblasts from one patient were studied. Two normal-weighted women presented with a partial lipodystrophic syndrome with hypertriglyceridemia and liver steatosis. One of them had also diabetes. Both patients showed a peculiar, striking lipodystrophic phenotype with subcutaneous lipoatrophy of the four limbs contrasting with truncal and abdominal fat accumulation. Their oral glucose tolerance tests showed extremely high levels of insulinemia, revealing major insulin resistance. Low serum levels of sex-hormone binding globulin and adiponectin suggested a post-receptor insulin signalling defect. Other clinical features included bilateral cataracts, greying hair and distal skin atrophy. We observed biallelic WRN null mutations in both women (p.Q748X homozygous, and compound heterozygous p.Q1257X/p.M1329fs). Their fertility was decreased, with preserved menstrual cycles and normal follicle-stimulating hormone levels ruling out premature ovarian failure. However undetectable anti-müllerian hormone and inhibin B indicated diminished follicular ovarian reserve. Insulin-resistance linked ovarian hyperandrogenism could also contribute to decreased fertility, and the two patients became pregnant after initiation of insulin-sensitizers (metformin). Both pregnancies were complicated by severe cervical incompetence, leading to the preterm birth of a healthy newborn in one case, but to a second trimester

  10. Review of Two Siblings with Werner's Syndrome: A Case Report

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    Murat Sert

    2009-01-01

    Full Text Available We report the clinical course of two siblings with Werner's syndrome (WS who were diagnosed and followed at our clinics for 12 years. Initial diagnosis of the first sibling (sister was at age 20, the second (brother at 16. At the initial diagnosis, the sister had amenorrhea, muscle atrophy at arms and legs, diabetes mellitus (DM, short stature, bilateral cataracts, genital hypoplasia, osteoporosis, and gray hair. During 12 years follow-up period, high-pitched voice, hepatosteatosis, renal parenchymal disease, and urethral obstruction developed. Regarding the brother, DM, cataracts and genital hypoplasia were observed at the initial diagnosis. During the 12 years follow-up period, gray hair, high-pitched voice, steatohepatosis, and osteoporosis developed.

  11. Clinical characteristics and treatment of Herlyn-Werner-Wunderlich syndrome.

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    Wang, Jinhui; Zhu, Lan; Lang, Jinghe; Liu, Zhufeng; Sun, Dawei; Leng, Jinhua; Fan, Qingbo

    2014-11-01

    To investigate the clinical characteristics and treatment of the Herlyn-Werner-Wunderlich syndrome (HWWS). Sixty-one patients diagnosed with HWWS were retrospectively analyzed. HWWS is categorized into three types in China. Age at presentation of all the cases was after menarche. The most common clinical presentations were dysmenorrhea for type I and vaginal discharge for types II and III. Clinical presentations of types II and III may not occur until reproductive age. HWWS occurred on the right in 39/61. Excision of the obstructed vaginal septum was the treatment utilized in this cohort. After surgery, subsequent pregnancies were ipsilateral in 52.9 %. Clinical presentation in untreated HWWS suggests the anatomic anomaly. Early recognition and treatment can reduce symptoms. Pregnancies occur in both the affected and unaffected uterus.

  12. New classification of Herlyn-Werner-Wunderlich syndrome.

    Science.gov (United States)

    Zhu, Lan; Chen, Na; Tong, Jia-Li; Wang, Wei; Zhang, Lei; Lang, Jing-He

    2015-01-20

    Uterus didelphys and blind hemivagina associated with ipsilateral renal agenesis are collectively known as Herlyn-Werner-Wunderlich syndrome (HWWS). In the literature, the syndrome often appears as a single case report or as a small series. In our study, we reviewed the characteristics of all HWWS patients at Peking Union Medical College Hospital (PUMCH) and suggested a new classification for this syndrome because the clinical characteristics differed significantly between the completely and incompletely obstructed vaginal septum. This new classification allows for earlier diagnosis and treatment. From January 1986 to March 2013, all diagnosed cases of HWWS at PUMCH were reviewed. A retrospective long-term follow-up study of the clinical presentation, surgical prognosis, and pregnancy outcomes was performed. Statistical analyses were performed using SPSS, version 15.0 (IBM, Armonk, NY, USA). Between-group comparisons were performed using the χ2 test, Fisher's exact test, and the t-test. The significance level for all analyses was set at P syndrome be classified by the complete or incomplete obstruction of the hemivagina as follows: Classification 1, a completely obstructed hemivagina and Classification 2, an incompletely obstructed hemivagina. The clinical details associated with these two types are distinctly different. HWWS patients should be differentiated according to these two classifications. The two classifications could be generalized by gynecologists world-wide.

  13. Term pregnancy after minimally invasive surgical treatment of Herlyn-Werner-Wunderlich syndrome

    National Research Council Canada - National Science Library

    Mirković Ljiljana; Ljubić Aleksandar; Janjić Tijana; Milićević Srboljub; Sparić Radmila; Jeremić Katarina; Pantović Sveto; Milenković Vera

    2013-01-01

    Introduction. Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis represents a complex congenital anomaly, also known in the literature as Herlyn-Werner-Wunderlich (HWW) syndrome. Case Outline...

  14. Herlyn-Werner-Wunderlich syndrome: a rare cause of infertility (2009: 2b).

    Science.gov (United States)

    Sarac, Armagan; Demir, Mustafa Kemal

    2009-05-01

    Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis is a rare and specific entity referred to as Herlyn-Werner-Wunderlich syndrome. It usually presents after menarche with remittent pelvic pain and a palpable pelvic mass due to hematocolpos. It rarely presents with primary infertility in early adulthood. In this report, a case of Herlyn-Werner-Wunderlich syndrome with primary infertility in a young woman is described with MR imaging findings.

  15. Stochastic simulations of normal aging and Werner's syndrome.

    KAUST Repository

    Qi, Qi

    2014-04-26

    Human cells typically consist of 23 pairs of chromosomes. Telomeres are repetitive sequences of DNA located at the ends of chromosomes. During cell replication, a number of basepairs are lost from the end of the chromosome and this shortening restricts the number of divisions that a cell can complete before it becomes senescent, or non-replicative. In this paper, we use Monte Carlo simulations to form a stochastic model of telomere shortening to investigate how telomere shortening affects normal aging. Using this model, we study various hypotheses for the way in which shortening occurs by comparing their impact on aging at the chromosome and cell levels. We consider different types of length-dependent loss and replication probabilities to describe these processes. After analyzing a simple model for a population of independent chromosomes, we simulate a population of cells in which each cell has 46 chromosomes and the shortest telomere governs the replicative potential of the cell. We generalize these simulations to Werner\\'s syndrome, a condition in which large sections of DNA are removed during cell division and, amongst other conditions, results in rapid aging. Since the mechanisms governing the loss of additional basepairs are not known, we use our model to simulate a variety of possible forms for the rate at which additional telomeres are lost per replication and several expressions for how the probability of cell division depends on telomere length. As well as the evolution of the mean telomere length, we consider the standard deviation and the shape of the distribution. We compare our results with a variety of data from the literature, covering both experimental data and previous models. We find good agreement for the evolution of telomere length when plotted against population doubling.

  16. Roles of Werner syndrome protein in protection of genome integrity

    DEFF Research Database (Denmark)

    Rossi, Marie L; Ghosh, Avik K; Bohr, Vilhelm A

    2010-01-01

    Werner syndrome protein (WRN) is one of a family of five human RecQ helicases implicated in the maintenance of genome stability. The conserved RecQ family also includes RecQ1, Bloom syndrome protein (BLM), RecQ4, and RecQ5 in humans, as well as Sgs1 in Saccharomyces cerevisiae, Rqh1...... syndrome (WS). WRN is one of the best characterized of the RecQ helicases and is known to have roles in DNA replication and repair, transcription, and telomere maintenance. Studies both in vitro and in vivo indicate that the roles of WRN in a variety of DNA processes are mediated by post......-translational modifications, as well as several important protein-protein interactions. In this work, we will summarize some of the early studies on the cellular roles of WRN and highlight the recent findings that shed some light on the link between the protein with its cellular functions and the disease pathology....

  17. Herlyn-Werner-Wunderlich syndrome: a rare presentation with pyocolpos.

    Science.gov (United States)

    Cox, Deven; Ching, Brian H

    2012-03-01

    Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA), also known as Herlyn-Werner-Wunderlich syndrome, is a rare syndrome with only a few hundred reported cases described since 1922. Only a handful of these cases have been associated with pyocolpos. Mullerian duct anomalies have an incidence of 2-3%. While OHVIRA constitutes 0.16-10% of these Mullerian duct anomalies. Symptoms usually present shortly after menarche when hematocolpos develops during menstruation resulting in dysmenorrhea and a pelvic mass. The pelvic mass is the collection of blood products within the obstructed hemivagina. The first study in the diagnostic work-up is usually ultrasonography, which typically demonstrates a pelvic fluid collection which can simulate other disease processes thus confounding the diagnosis. MRI findings of the pelvis reveal a didelphic uterus. Imaging of the abdomen reveals agenesis of the ipsilateral kidney. MRI is beneficial in characterizing the didelphic uterus and vaginal septum for pre-operative planning. Understanding the imaging findings, in conjunction with the clinical presentation, is critical for early diagnosis in attempting to prevent complications such as endometriosis or adhesions from chronic infections with subsequent infertility.

  18. New Classification of Herlyn-Werner-Wunderlich Syndrome

    Directory of Open Access Journals (Sweden)

    Lan Zhu

    2015-01-01

    Full Text Available Background: Uterus didelphys and blind hemivagina associated with ipsilateral renal agenesis are collectively known as Herlyn-Werner-Wunderlich syndrome (HWWS. In the literature, the syndrome often appears as a single case report or as a small series. In our study, we reviewed the characteristics of all HWWS patients at Peking Union Medical College Hospital (PUMCH and suggested a new classification for this syndrome because the clinical characteristics differed significantly between the completely and incompletely obstructed vaginal septum. This new classification allows for earlier diagnosis and treatment. Methods: From January 1986 to March 2013, all diagnosed cases of HWWS at PUMCH were reviewed. A retrospective long-term follow-up study of the clinical presentation, surgical prognosis, and pregnancy outcomes was performed. Statistical analyses were performed using SPSS, version 15.0 (IBM, Armonk, NY, USA. Between-group comparisons were performed using the χ2 test, Fisher′s exact test, and the t-test. The significance level for all analyses was set at P < 0.05. Results: The clinical data from 79 patients with HWWS were analyzed until March 31, 2013. According to our newly identified characteristics, we recommend that the syndrome be classified by the complete or incomplete obstruction of the hemivagina as follows: Classification 1, a completely obstructed hemivagina and Classification 2, an incompletely obstructed hemivagina. The clinical details associated with these two types are distinctly different. Conclusions: HWWS patients should be differentiated according to these two classifications. The two classifications could be generalized by gynecologists world-wide.

  19. [A report of 2 cases of the Herlyn-Werner-Wunderlich syndrome].

    Science.gov (United States)

    Nalbanski, B; Sirakov, M; Veltova, L; Karag'ozov, I

    1990-01-01

    Two cases are described, illustrating two varieties of comparatively little known, but not rarely encountered syndrome--the syndrome of Herlyn-Werner-Wunderlich. The characteristic and the symptoms of the syndrome are presented and various concepts on therapeutic management are discussed. The question about future fertile capability of the patients is discussed as well.

  20. Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes.

    Science.gov (United States)

    Du, Xiaobing; Shen, Johnny; Kugan, Nishan; Furth, Emma E; Lombard, David B; Cheung, Catherine; Pak, Sally; Luo, Guangbin; Pignolo, Robert J; DePinho, Ronald A; Guarente, Leonard; Johnson, F Brad

    2004-10-01

    The Werner and Bloom syndromes are caused by loss-of-function mutations in WRN and BLM, respectively, which encode the RecQ family DNA helicases WRN and BLM, respectively. Persons with Werner syndrome displays premature aging of the skin, vasculature, reproductive system, and bone, and those with Bloom syndrome display more limited features of aging, including premature menopause; both syndromes involve genome instability and increased cancer. The proteins participate in recombinational repair of stalled replication forks or DNA breaks, but the precise functions of the proteins that prevent rapid aging are unknown. Accumulating evidence points to telomeres as targets of WRN and BLM, but the importance in vivo of the proteins in telomere biology has not been tested. We show that Wrn and Blm mutations each accentuate pathology in later-generation mice lacking the telomerase RNA template Terc, including acceleration of phenotypes characteristic of latest-generation Terc mutants. Furthermore, pathology not observed in Terc mutants but similar to that observed in Werner syndrome and Bloom syndrome, such as bone loss, was observed. The pathology was accompanied by enhanced telomere dysfunction, including end-to-end chromosome fusions and greater loss of telomere repeat DNA compared with Terc mutants. These findings indicate that telomere dysfunction may contribute to the pathogenesis of Werner syndrome and Bloom syndrome.

  1. Laparoscopic Hemi-hysterectomy and Trachelectomy in a Case of Herlyn-Werner-Wunderlich Syndrome.

    Science.gov (United States)

    Al Sawah, Entidhar; Plosker, Shayne M; Mikhail, Emad

    2016-10-26

    Herlyn-Werner-Wunderlich Syndrome (HWWS) is a rare Müllerian anomaly characterized by uterus didelphys coexisting with an obstructed hemivagina and ipsilateral renal agenesis. A 13-year-old female presented one-year after menarche with severe dysmenorrhea and a right-sided pelvic mass. Imaging identified a right uterus with hematometra, hematocolpos, absent right kidney, normal left kidney, ureter, left uterus, and vagina compressed to the left by right hematocolpos. We performed laparoscopic hemi-hysterectomy of the non-communicating hemi-uterus, and laparoscopic trachelectomy. Laparoscopic hemi-hysterectomy and trachelecotmy is a minimally invasive surgical option for patients with Herlyn-Werner-Wunderlich Syndrome.

  2. Telomerase Protects Werner Syndrome Lineage-Specific Stem Cells from Premature Aging

    Directory of Open Access Journals (Sweden)

    Hoi-Hung Cheung

    2014-04-01

    Full Text Available Werner syndrome (WS patients exhibit premature aging predominantly in mesenchyme-derived tissues, but not in neural lineages, a consequence of telomere dysfunction and accelerated senescence. The cause of this lineage-specific aging remains unknown. Here, we document that reprogramming of WS fibroblasts to pluripotency elongated telomere length and prevented telomere dysfunction. To obtain mechanistic insight into the origin of tissue-specific aging, we differentiated iPSCs to mesenchymal stem cells (MSCs and neural stem/progenitor cells (NPCs. We observed recurrence of premature senescence associated with accelerated telomere attrition and defective synthesis of the lagging strand telomeres in MSCs, but not in NPCs. We postulate this “aging” discrepancy is regulated by telomerase. Expression of hTERT or p53 knockdown ameliorated the accelerated aging phenotypein MSC, whereas inhibition of telomerase sensitized NPCs to DNA damage. Our findings unveil a role for telomerase in the protection of accelerated aging in a specific lineage of stem cells.

  3. A rare case of Herlyn-Werner-Wunderlich syndrome-with pregnancy

    OpenAIRE

    Deswal, Vikas; Kumawat, Nauratmal; Purohit, Sunita; Jat, Rajendra

    2016-01-01

    Herlyn-Werner-Wunderlich syndrome also known as uterus didelphys with obstructing hemivaginal septum and ipsilateral renal agenesis (OHVIRA) is a very rare syndrome with only a few case reported. A female patient referred to our hospital with retention of urine revealed uterus didelphys with 8 weeks gestation sac in the left moiety and hematometra and hematocolpous in the right moiety with absent right kidney. Diagnosing this syndrome at an early stage is important to prevent the complication...

  4. Herlyn Werner Wunderlich Syndrome with Hematocolpos: An Unusual Case Report of Full Diagnostic Approach and Treatment

    OpenAIRE

    Rohit Bhoil; Ajay Ahluwalia; Narvir Chauhan

    2016-01-01

    Herlyn-Werner-Wunderlich (HWW) syndrome is an uncommon combined müllerian duct anomalies (MDAs) and mesonephric duct malformation of female urogenital tract characterized by uterus didelphys and obstructed hemi-vagina and ipsilateral renal agenesis (OHVIRA) syndrome. We present a rare and unusual case of this syndrome in a 19 year-old female who suffered from hypomenorrhoea and abdominal pain. She had an obstructed hemi-vagina on right side which led to marked distention of ...

  5. Physical and functional interactions between Werner syndrome helicase and mismatch-repair initiation factors

    DEFF Research Database (Denmark)

    Saydam, Nurten; Kanagaraj, Radhakrishnan; Dietschy, Tobias

    2007-01-01

    Werner syndrome (WS) is a severe recessive disorder characterized by premature aging, cancer predisposition and genomic instability. The gene mutated in WS encodes a bi-functional enzyme called WRN that acts as a RecQ-type DNA helicase and a 3'-5' exonuclease, but its exact role in DNA metabolism...

  6. Adenocarcinoma of the lower female genital tract in patients with Herlyn-Werner-Wunderlich syndrome.

    Science.gov (United States)

    Watanabe, Yoh; Etoh, Tomomaro; Nakai, Hidekatsu

    2012-12-01

    We report 2 patients with Herlyn-Werner-Wunderlich syndrome, 1 with advanced endometrioid adenocarcinoma of the semiobstructed side of the uterine cervix and 1 with primary clear cell carcinoma of the obstructed side of the upper vagina. Copyright © 2012 Mosby, Inc. All rights reserved.

  7. AN UNUSUAL CASE OF HERLYN WERNER WUNDERLICH SYNDROME PRESENTING DURING PREGNANCY: A CASE REPORT

    OpenAIRE

    Priyanka Priyadarshini; Deb Kumar; Chang Hom; Dhaval

    2015-01-01

    INTRODUCTION: Herlyn - Werner - Wunderlich syndrome (HWWS), characterized by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis, is a rare combined Mullerian and mesonephric duct anomaly. It usually presents after menarche with remittent pelvic pain, dysmenorrhoea or palpable pelvic mass due to hematocolpos. Its presentation during adulthood is rare , (1) and in pregnancy is even rarer . (2) It is one of the causes of infert...

  8. Genetics and aging; the Werner syndrome as a segmental progeroid syndrome.

    Science.gov (United States)

    Martin, G M

    1985-01-01

    The maximum lifespan potential is a constitutional feature of speciation and must be subject to polygenic controls acting both in the domain of development and in the domain of the maintenance of macromolecular integrity. The enormous genetic heterogeneity that characterizes our own species, the complexities of numerous nature-nurture interactions, and the quantitative and qualitative variations of the senescent phenotype that are observed suggest that precise patterns of aging in each of us may be unique. Patterns of aging may also differ sharply among species (for example, semelparous vs. multiparous mammals). Some potential common denominators, however, allow one to identify progeroid syndromes in man that could lead to the elucidation of important pathways of gene action. (The suffix "-oid" means "like"; it does not mean identity.) Unimodal progeroid syndromes (eg., familial dementia of the Alzheimer type, an autosomal dominant) can help us understand the pathogenesis of a particular aspect of the senescent phenotype of man. Segmental progeroid syndromes (eg. the Werner syndrome, an autosomal recessive) may be relevant to multiple aspects of the senescent phenotype. Some results of research on the Werner syndrome may be interpreted as support for "peripheral" as opposed to "central" theories of aging; they are consistent with the view that gene action in the domain of development (adolescence, in this instance) can set the stage for patterns of aging in the adult; they point to the importance of mesenchymal cell populations in the pathogenesis of age-related disorders; finally, they underscore the role of chromosomal instability, especially in the pathogenesis of neoplasia.

  9. An Unexpected Cause of Pelvic Pain in a Pubertal Case: Herlyn-Werner-Wunderlich Syndrome

    Directory of Open Access Journals (Sweden)

    Yasemin Kayadibi

    2014-03-01

    Full Text Available Uterovaginal duplication with imperforated hemivagina is a rare type of Mullerian anomaly. If ipsilateral renal agenesis is associated with this complex genital malformation, it is called Herlyn-Werner-Wunderlich syndrome. Clinical presentations of this syndrome include pelvic pain and mass effect due to obstructed hemivagina in pubertal adolescents and adults. Hematocolpos, even after menstruation period, leads to misdiagnosis. Laparotomy is the gold standard for the diagnosis, however, magnetic resonance imaging has an accuracy upto 100% in evaluating uterovajinal anatomy. In this article, we aimed to present ultrasonographic and magnetic resonance imaging findings in a patient with Herlyn-Werner-Wun derlich syndrome who presented with cyclic pelvic pain. (The Me­di­cal Bul­le­tin of Ha­se­ki 2014; 52: 60-3

  10. Hemivaginal septum resection in a patient with a rare variant of Herlyn-Werner-Wunderlich syndrome.

    Science.gov (United States)

    Pereira, Nigel; Anderson, Sharon H; Verrecchio, Elizabeth S; Brown, M Allyson; Glassner, Michael J

    2014-01-01

    Herlyn-Werner-Wunderlich syndrome is characterized by a triad of uterine didelphys, obstructed hemivagina, and ipsilateral renal agenesis. The syndrome should be suspected in any young woman with abdominal pain or cyclic dysmenorrhea, and radiologic evidence of müllerian duct and renal anomalies. Herein is presented the case of a 25-year-old woman with a rare variant of Herlyn-Werner-Wunderlich syndrome, characterized by an anomalous connection between the 2 endocervical canals, who underwent hemivaginal septum resection to relieve progressively worsening dysmenorrhea. The right hemivaginal septum was resected medially from the left cervix and laterally off the right vaginal wall. Hydrodissection between the hemivaginal septum and right cervix facilitated surgical resection. After resection of the hemivaginal septum there was complete resolution of dysmenorrhea and no recurrence of hematometra or hematocolpos. Copyright © 2014 AAGL. Published by Elsevier Inc. All rights reserved.

  11. Imaging Diagnosis of Herlyn-Werner-Wunderlich Syndrome- An Extremely Rare Urogenital Anomaly.

    Science.gov (United States)

    Mehra, Shibani; Chamaria, Komal; Garga, U C; Kataria, Ankur; Ahuja, Ashim

    2015-05-01

    Herlyn-Werner-Wunderlich (HWW) syndrome is a very rare congenital anomaly of the urogenital tract resulting from maldevelopment of both Mullerian and Wolffian ducts. It is characterized by the triad of uterus didelphys, obstructed hemivagina and ipsilateral renal agenesis. It generally presents at puberty shortly following menarche with the symptom of acute pelvic pain. Management of these cases is surgical and consists mainly of vaginoplasty with excision of the vaginal septum in order to release the obstruction and prevent the long term complication of recurrent pyocolpos and infertility. We report here a case of Herlyn-Werner-Wunderlich syndrome in a 13-year-old adolescent girl, emphasizing the role of imaging in the accurate and prompt diagnosis of this rare developmental urogenital anomaly. Only a few hundred such cases have been reported in literature till date.

  12. Term pregnancy after minimally invasive surgical treatment of Herlyn-Werner-Wunderlich syndrome

    OpenAIRE

    Mirković Ljiljana; Ljubić Aleksandar; Janjić Tijana; Milićević Srboljub; Sparić Radmila; Jeremić Katarina; Pantović Sveto; Milenković Vera

    2013-01-01

    Introduction. Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis represents a complex congenital anomaly, also known in the literature as Herlyn-Werner-Wunderlich (HWW) syndrome. Case Outline. A 16­year­old patient presented with secondary amenorrhoea and abdominal pain. Her history revealed anorexia nervosa; she had menarche at the age of 14; her menstrual cycles were regular, with progressive dysmenorrhoea. Nine months after the explorative laparotomy performed...

  13. Herlyn-Werner-Wunderlich Syndrome With Preterm Pregnancy The Presentation Of A Rare Case

    OpenAIRE

    Rusda, Muhammad

    2015-01-01

    Background: Herlyn-Werner-Wunderlich (HWW) syndrome is a very rare congenital anomaly of the urogenital tract involving Mullerian ducts and Wolffian structures, and characterized by the triad of didelphys uterus, obstructed hemivagina and ipsilateral renal agenesis. It generally occurs at puberty and exhibits non-specific and variable symptoms with acute or pelvic pain right before menarche, causing a delay in diagnosis. Moreover, the diagnosis is complicated by the infrequency...

  14. A rare case of Herlyn-Werner-Wunderlich syndrome-with pregnancy

    Directory of Open Access Journals (Sweden)

    Vikas Deswal

    2016-12-01

    Full Text Available Herlyn-Werner-Wunderlich syndrome also known as uterus didelphys with obstructing hemivaginal septum and ipsilateral renal agenesis (OHVIRA is a very rare syndrome with only a few case reported. A female patient referred to our hospital with retention of urine revealed uterus didelphys with 8 weeks gestation sac in the left moiety and hematometra and hematocolpous in the right moiety with absent right kidney. Diagnosing this syndrome at an early stage is important to prevent the complications in these patients.

  15. Urinary Incontinence in Puberty: A Rare Clinical Presentation of the Herlyn-Werner-Wunderlich Syndrome.

    Science.gov (United States)

    Dogan, Askin; Uyar, Ibrahim; Demirtas, Gulsah Selvi; Ekin, Atalay; Gulhan, Ibrahim; Ertas, Ibrahim E; Ozeren, Mehmet

    2016-12-01

    We report on an unusual presentation of Herlyn-Werner-Wunderlich syndrome in two 11-year-old girls within a year of menarche. The setting was a training and research hospital. We present two patients in the pubertal period with cyclic abdominal pain and urinary incontinence who received hysteroscopic septal resection. Menstrual flow was resumed and the complaints of incontinence were eliminated after the hysteroscopic resection of the vaginal septum. Overflow incontinence was completely resolved after septum resection in two patients. The risk of stricture is high in Herlyn-Werner-Wunderlich syndrome if the septum is partially excised to open the obstruction, whereas the risk of stricture is low if a complete or wide excision is performed. In the presence of abdominal pain and urinary incontinence in puberty, Herlyn-Werner-Wunderlich syndrome must be considered in the differential diagnosis, and a detailed evaluation of the urinary system and pelvic anatomy must be performed. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  16. Herlyn-Werner-Wunderlich and Prader-Willi syndromes: more than a coincidence?

    Science.gov (United States)

    Fraga, Beatriz; Gomes, Catarina; Gouveia, Raquel; Oliveira, Graça

    2015-10-21

    A neonate with a prenatal diagnosis of left renal agenesis was born at 33 weeks gestation. A postnatal abdominal ultrasound confirmed the absence of the left kidney and revealed two non-divergent hemiuteri, consistent with the diagnosis of Herlyn-Werner-Wunderlich syndrome. During admission, significant axial hypotonia was noted, warranting additional investigations. Brain ultrasounds and MRI were normal, as were a preliminary metabolic study and comparative genomic hybridisation array. DNA methylation testing confirmed the diagnosis of Prader-Willi syndrome. The baby was discharged after 70 days, breast feeding and with modest hypotonia improvement. 2015 BMJ Publishing Group Ltd.

  17. A rare cause of acute abdominal pain: Herlyn-Werner-Wunderlich syndrome.

    Science.gov (United States)

    Aydin, Ramazan; Ozdemir, Ayse Zehra; Ozturk, Bahadir; Bilgici, Meltem Ceyhan; Tosun, Migraci

    2014-01-01

    Herlyn-Werner-Wunderlich (HWW) syndrome is a rare müllerian duct anomaly with uterus didelphys, unilateral obstructed hemivagina, and ipsilateral renal agenesis. Patients with this syndrome generally present after menarche with pelvic pain and mass and, rarely, primary infertility in later years. Strong suspicion and knowledge of this syndrome are mandatory for an accurate diagnosis. A 14-year-old female patient presented with acute retention of urine and abdominopelvic pain. Her condition was diagnosed with the use ultrasonography and magnetic resonance imaging as a case of HWW syndrome. She was treated with vaginal hemiseptal resection. The HWW syndrome should be considered among the differential diagnoses in girls with renal anomalies presenting with pelvic mass, symptoms of acute abdominal pain, and acute urinary retention.

  18. Werner's syndrome: twenty-four cases with a review of the Japanese medical literature.

    Science.gov (United States)

    Murata, K; Nakashima, H

    1982-05-01

    Twenty-four cases of Werner's syndrome were studied to define the clinical manifestations in comparison with those found in a clinical review of 153 cases in the Japanese medical literature. The conspicuous characteristics of the 24 patients were short stature, stocky trunk with thin limbs, low body weight, bird-like or "masked" face, early graying or loss of hair, high-pitched or hoarse voice, bilateral cataracts, and various scleroderma-like signs. Three signs not stressed previously were hyperreflexia, flat feet, and irregular dental development. The onsets and incidences of these manifestations during the seven-year serial study are described.

  19. Herlyn-Werner-Wunderlich syndrome presenting with infertility: Role of MRI in diagnosis.

    Science.gov (United States)

    Ahmad, Zohra; Goyal, Ankur; Das, Chandan J; Deka, Dipika; Sharma, Raju

    2013-07-01

    Herlyn-Werner-Wunderlich syndrome (HWWS), characterized by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis, is an uncommon combined Mullerian and mesonephric duct anomaly, and its presentation in adulthood is even rarer. We report here a 22-year-old female presenting with primary infertility where magnetic resonance imaging (MRI) suggested the diagnosis of HWWS with endometriosis. In a patient of infertility with endometriosis and unilateral renal agenesis, diagnosis of HWWS should be suspected and MRI is the investigation of choice for such anomalies.

  20. Herlyn-Werner-Wunderlich syndrome presenting with infertility: Role of MRI in diagnosis

    Directory of Open Access Journals (Sweden)

    Zohra Ahmad

    2013-01-01

    Full Text Available Herlyn-Werner-Wunderlich syndrome (HWWS, characterized by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis, is an uncommon combined Mullerian and mesonephric duct anomaly, and its presentation in adulthood is even rarer. We report here a 22-year-old female presenting with primary infertility where magnetic resonance imaging (MRI suggested the diagnosis of HWWS with endometriosis. In a patient of infertility with endometriosis and unilateral renal agenesis, diagnosis of HWWS should be suspected and MRI is the investigation of choice for such anomalies.

  1. Herlyn Werner Wunderlich Syndrome with Hematocolpos: An Unusual Case Report of Full Diagnostic Approach and Treatment

    Directory of Open Access Journals (Sweden)

    Rohit Bhoil

    2016-05-01

    Full Text Available Herlyn-Werner-Wunderlich (HWW syndrome is an uncommon combined müllerian duct anomalies (MDAs and mesonephric duct malformation of female urogenital tract characterized by uterus didelphys and obstructed hemi-vagina and ipsilateral renal agenesis (OHVIRA syndrome. We present a rare and unusual case of this syndrome in a 19 year-old female who suffered from hypomenorrhoea and abdominal pain. She had an obstructed hemi-vagina on right side which led to marked distention of ipsilateral cervix, while proximal hemi-vagina compressed the contralateral side causing its partial obstruction resulting in hypomenorrhoea. Understanding the imaging findings of this rare condition is important for early diagnosis in order to prevent complications which may lead to infertility.

  2. Herlyn Werner Wunderlich Syndrome with Hematocolpos: An Unusual Case Report of Full Diagnostic Approach and Treatment.

    Science.gov (United States)

    Bhoil, Rohit; Ahluwalia, Ajay; Chauhan, Narvir

    2016-01-01

    Herlyn-Werner-Wunderlich (HWW) syndrome is an uncommon combined müllerian duct anomalies (MDAs) and mesonephric duct malformation of female urogenital tract characterized by uterus didelphys and obstructed hemi-vagina and ipsilateral renal agenesis (OHVIRA) syndrome. We present a rare and unusual case of this syndrome in a 19 year-old female who suffered from hypomenorrhoea and abdominal pain. She had an obstructed hemi-vagina on right side which led to marked distention of ipsilateral cervix, while proximal hemi-vagina compressed the contralateral side causing its partial obstruction resulting in hypomenorrhoea. Understanding the imaging findings of this rare condition is important for early diagnosis in order to prevent complications which may lead to infertility.

  3. Herlyn-Werner-Wunderlich syndrome: a very rare urogenital anomaly in a teenage girl.

    Science.gov (United States)

    Karaca, Leyla; Pirimoglu, Berhan; Bayraktutan, Ummugulsum; Ogul, Hayri; Oral, Akgun; Kantarci, Mecit

    2015-03-01

    Herlyn-Werner-Wunderlich (HWW) syndrome is an uncommon variant of Müllerian duct anomalies, consisting of uterine didelphys, obstructed hemivagina, and ipsilateral renal agenesis. It usually presents in a post-pubertal adolescent or adult woman in whom hematometrocolpos produces a pronounced mass effect and pain on the side of the obstructed hemivagina. We report the case of a 13-year-old girl who presented to the emergency radiology department with sudden onset of severe pain at the right lower quadrant of the abdomen; imaging confirmed the diagnosis of HWW syndrome. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: When unilateral renal agenesis and uterus didelphys coexist, the first thing that the physician should remember is to confirm or refute the presence of a blind vagina for diagnosis of HWW syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Case Report: A Rare Cause of Complicated Urinary Tract Infection in a Woman with Herlyn-Werner-Wunderlich Syndrome.

    Science.gov (United States)

    Tsai, Jun-Li; Tsai, Shang-Feng

    2016-11-01

    Urinary tract infection is a common disease in the general population. However, in patients with frequent urinary tract infection, it is important to determine any treatable cause to avoid recurrence. Herlyn-Werner-Wunderlich syndrome or OHVIRA syndrome is a very rare congenital anomaly with uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. The earliest presentation of this syndrome is hematocolpos that develops during menstruation and results in dysmenorrhea and a pelvic mass shortly after menarche. Herein, we report a patient with Herlyn-Werner-Wunderlich syndrome manifested with unusual symptoms, delayed onset and without surgery. The unique point of this patient is the partial obstruction of cervico-vaginal junction. Early diagnosis and timely treatment of OHVIRA syndrome can prevent long-term complications, such as recurrent urinary tract infection and infertility. A high index of suspicion is required, even though OHVIRA syndrome is extremely rare and may have an atypical presentation.

  5. Herlyn-Werner-Wunderlich syndrome: An "early" onset case report and review of Literature.

    Science.gov (United States)

    Angotti, R; Molinaro, F; Bulotta, A L; Bindi, E; Cerchia, E; Sica, M; Messina, M

    2015-01-01

    Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare congenital mullerian anomaly consisting of uterus didelphys, hemivaginal septum, and unilateral renal agenesis [1,2]. Most authors reported cases of Herlyn-Werner-Wunderlich syndrome with prepuberal or postpuberal onset with cyclical abdominal pain and a vaginal mass (3-8). Only six cases are reported in Literature with early onset of this syndrome under 5 years (9-14). Our case is about 3 years old girl, with all the features of this syndrome who came to our attention for lower abdominal mass. The aim of this article is to share our experience and focus the attention on the importance of high level of suspicion of HWWS in neonatal period to early diagnosis and treatment. The possible early presentation of this syndrome should be suspected in all neonates (females) with renal agenesia confirmed postnatally or with prenatal diagnosis. It is common, in fact, an error of evaluation with planning of removal of mass, that can damage patients in term of chance for a successful reproductive outcome. For all these reasons, our team consider HWWS as differential diagnosis in newborn with prenatal ultrasonography of a cystic mass behind the urinary bladder in the absence of a kidney and plan a pelvic ultrasound (with aim to identify an uterus, normal or dydhelfus, and presence or absence of pelvic mass), an examination under anesthesia and cystoscopy and vaginoscopy, if it is necessary. A high level of suspicion, indeed, is the key to early diagnosis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Síndrome de Werner associada a quadro esclerodermiforme: relato de caso e revisão da literatura Werner's syndrome associated with scleroderma-like syndrome: case report and literature revision

    Directory of Open Access Journals (Sweden)

    Cristiane Kayser

    2008-04-01

    Full Text Available A síndrome de Werner é uma doença autossômica recessiva rara associada a envelhecimento precoce, cujo quadro cutâneo deve ser distinguido daquele encontrado na esclerose sistêmica (ES. Descrevemos aqui o caso de uma paciente de 39 anos de idade, portadora de síndrome de Werner, encaminhada ao nosso serviço com hipótese diagnóstica inicial de ES. A paciente apresentava várias manifestações associadas à síndrome de Werner, incluindo cabelos precocemente grisalhos, voz estridente, baixa estatura, alterações cutâneas esclerodermiformes, diabetes melito, catarata, hipogonadismo, hipotireoidismo e hiperlipidemia. Não apresentava fenômeno de Raynaud, manifestações viscerais típicas da ES, alterações capilaroscópicas periungueais ou auto-anticorpos. O diagnóstico de síndrome de Werner, apesar de raro, deve ser lembrado no diagnóstico diferencial de ES, principalmente na presença de manifestações atípicas e na ausência de alterações típicas da ES.Werner's syndrome is a rare autosomal recessive disease associated with premature ageing. Skin alteration must be distinguished from cutaneous manifestation of systemic sclerosis (SSc. We describe a case of a 39 years old patient with Werner's syndrome admitted with an initial diagnostic hypothesis of SSc. The patient had many characteristic features associated with Werner's syndrome including gray hair, hoarseness, short stature, scleroderma-like skin changes, diabetes mellitus, cataracts, hypogonadism, hypothyroidism, and hyperlipidemia. There was no Raynaud's phenomenon, other typical visceral manifestation of SSc, nailfold capillary alterations or autoantibodies. Werner's syndrome diagnosis notwithstanding rare, should be remember in the differential diagnosis of SSc, mainly in the presence of atypical manifestations and in the absence of typical features of SSc.

  7. Herlyn-Werner-Wunderlich syndrome (uterus didelphys, blind hemivagina and ipsilateral renal agenesis) - a case report.

    Science.gov (United States)

    Arıkan, Ilker İnan; Harma, Müge; Harma, Mehmet İbrahim; Bayar, Ulkü; Barut, Aykut

    2010-01-01

    Uterovaginal duplication with obstructed hemivagina and ipsilateral renal agenesis is referred to as the Herlyn-Werner-Wunderlich (HWW) syndrome. A 17 year old woman presented with right pelvic pain and dysmenorrhea, present since menarche at 13 and worsening over the past year. Ultrasound examination revealed a right pelvic mass (5×5 cm), double endometrial echoes, and hematocolpos. A right pelvic mass, agenesis of the right kidney, double uterus, and blind hemivagina with hematocolpos were detected by magnetic resonance imaging and intravenous pyelography. A right tubo-ovarian abscess with dense adhesions and a double uterus were observed on diagnostic laparoscopy. Adhesiolysis was carried out and purulent material irrigated. After a course of antibiotics, a vaginal septum resection was performed and the pyocolpos drained. She remained symptom free after four months of follow-up. Prompt and accurate diagnosis and treatment of this syndrome can significantly improve the lives of sufferers and prevent future complications.

  8. Clinical characteristics of 70 patients with Herlyn-Werner-Wunderlich syndrome.

    Science.gov (United States)

    Tong, Jiali; Zhu, Lan; Lang, Jinghe

    2013-05-01

    To analyze the clinical characteristics of patients with Herlyn-Werner-Wunderlich (HWW) syndrome. Seventy patients with a confirmed diagnosis of HWW syndrome admitted to the Peking Union Medical College Hospital between January 1995 and December 2010 were retrospectively reviewed, and long-term follow-up data were analyzed. The lateral distribution of hemivaginal obstruction and renal agenesis favored the right side in 42 patients (60.0%). Age at onset of symptoms was significantly different between patients with complete and those with incomplete hemivaginal obstruction (12.86 ± 1.84 vs 20.68 ± 7.43 years; Psyndrome was significantly different between those with complete and those with incomplete hemivaginal obstruction. Full resection of the vaginal septum resulted in good outcomes. Copyright © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  9. [Successful full-term pregnancy in the Herlyn-Werner-Wunderlich syndrome: a case report and review of literature].

    Science.gov (United States)

    Trifonov, I; Uzunova, J

    2014-01-01

    Herlyn-Werner-Wunderlich Syndrome results in a doubling of the internal genitalia accompanied by unilateral gynatresia (with hemi-hematokolpos, hemi-hematometra and/or hemi-hematosalpings) and ipsilateral renal agenesis. The authors considered the case of a successful full-term pregnancy in one uterus after pregnancy failure in the other imposed surgical removal of the same.

  10. The Werner syndrome protein is distinguished from the Bloom syndrome protein by its capacity to tightly bind diverse DNA structures.

    Science.gov (United States)

    Kamath-Loeb, Ashwini; Loeb, Lawrence A; Fry, Michael

    2012-01-01

    Loss of Werner syndrome helicase-exonuclease (WRN) or of its homolog Bloom syndrome helicase (BLM) results in different inherited disorders. Whereas Werner syndrome is characterized by premature onset of aging and age-associated diseases, Bloom syndrome involves developmental abnormalities and increased predisposition to diverse malignancies. To identify biochemical differences between WRN and BLM that might contribute to the dissimilar outcomes of their loss, we compared their abilities to unwind and bind in vitro diverse DNA structures. Full-length recombinant WRN and BLM proteins expressed in and purified from Sf9 insect cells unwound to comparable extents and with similar K(m) values partial DNA duplex, splayed arm DNA and G'2 bimolecular quadruplex DNA. However, WRN resolved bubble DNA ∼25-fold more efficiently than BLM. The two enzymes were mainly distinguished by their contrasting abilities to bind DNA. WRN bound partial duplexes, bubble and splayed arm DNA and G'2 bimolecular and G4 four-molecular quadruplexes with dissociation constants of 0.25 to 25 nM. By contrast, BLM formed substantial complexes with only G4 quadruplex DNA while binding only marginally other DNA structures. We raise the possibility that in addition to its enzymatic activities WRN may act as a scaffold for the assembly on DNA of additional DNA processing proteins.

  11. The Werner syndrome protein is distinguished from the Bloom syndrome protein by its capacity to tightly bind diverse DNA structures.

    Directory of Open Access Journals (Sweden)

    Ashwini Kamath-Loeb

    Full Text Available Loss of Werner syndrome helicase-exonuclease (WRN or of its homolog Bloom syndrome helicase (BLM results in different inherited disorders. Whereas Werner syndrome is characterized by premature onset of aging and age-associated diseases, Bloom syndrome involves developmental abnormalities and increased predisposition to diverse malignancies. To identify biochemical differences between WRN and BLM that might contribute to the dissimilar outcomes of their loss, we compared their abilities to unwind and bind in vitro diverse DNA structures. Full-length recombinant WRN and BLM proteins expressed in and purified from Sf9 insect cells unwound to comparable extents and with similar K(m values partial DNA duplex, splayed arm DNA and G'2 bimolecular quadruplex DNA. However, WRN resolved bubble DNA ∼25-fold more efficiently than BLM. The two enzymes were mainly distinguished by their contrasting abilities to bind DNA. WRN bound partial duplexes, bubble and splayed arm DNA and G'2 bimolecular and G4 four-molecular quadruplexes with dissociation constants of 0.25 to 25 nM. By contrast, BLM formed substantial complexes with only G4 quadruplex DNA while binding only marginally other DNA structures. We raise the possibility that in addition to its enzymatic activities WRN may act as a scaffold for the assembly on DNA of additional DNA processing proteins.

  12. Herlyn-Werner-Wunderlich Syndrome Consisting of Uterine Didelphys, Obstructed Hemivagina and Ipsilateral Renal Agenesis in a Newborn

    OpenAIRE

    Wu, Tsung-Hsin; Wu, Trang-Tiau; Ng, Yan-Yan; Ng, Soo-Cheen; Su, Pen-Hua; Chen, Jia-Yuh; Chen, Suh-Jen

    2012-01-01

    Herlyn-Werner-Wunderlich (HWW) syndrome is a rare variant of Müllerian duct anomalies consisting of uterine didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Patients with HWW syndrome are usually asymptomatic until menarche, when they present with acute lower abdominal pain. Here we report a case of a female newborn with right renal agenesis diagnosed during the pregnancy. The patient presented with a protruding mass over the vaginal introitus that was associated with an obst...

  13. Herlyn-Werner-Wunderlich Syndrome: Sonographic and Magnetic Resonance (MR) Imaging Findings of This Rare Urogenital Anomaly

    OpenAIRE

    Yilmaz, Sukriye; Yildiz, Adalet Elcin; Fitoz, Suat

    2017-01-01

    Summary Background Herlyn-Werner-Wunderlich syndrome is a rare congenital urogenital anomaly characterised by uterus didelphys with blind hemivagina and ipsilateral renal agenesis. Children usually have progressive pelvic pain after menarche, palpable mass due to hemihaemato(metro)colpos or pelvic inflammatory disease. The diagnosis usually requires a suspicion of this rare genitourinary syndrome. Case Reports We present ultrasonography and MR imaging findings of this rare anomaly in two case...

  14. Herlyn Werner Wunderlich syndrome: an unusual presentation of acute vaginal pain.

    Science.gov (United States)

    Beer, William M; Carstairs, Shaun D

    2013-10-01

    Herlyn Werner Wunderlich Syndrome (HWWS) is a congenital abnormality of the Müllerian duct system resulting in uterovaginal duplication, obstructive hemivagina, and ipsilateral renal agenesis. It typically presents shortly after menarche with gradual onset of progressive pelvic pain. We report a case of a 19-year-old female who presented to the Emergency Department with sudden onset of severe vaginal pain that was determined to be due to hematocolpos; imaging confirmed the diagnosis of HWWS. To the best of our knowledge abrupt onset of vaginal pain due to HWWS has not been reported previously. We present this case to increase awareness among emergency physicians of this rare and interesting entity. Published by Elsevier Inc.

  15. Herlyn-Werner-Wunderlich Syndrome Complicated with Pyocolpos: An Unusual Cause of Postabortal Sepsis.

    Science.gov (United States)

    Sharma, Deepti; Janu, M K; Gaikwad, Ramesh; Usha, M G

    2011-01-01

    Obstructive mullerian anomalies give rise to a spectrum of clinical presentations and are uncommon in routine gynecologic practice. The patient usually becomes symptomatic in early reproductive years. Recurrent pelvic pain, dysmenorrhea, enlarging abdominopelvic mass, and abnormal vaginal discharge are the common presenting symptoms. We describe a rare case of a mullerian anomaly getting diagnosed 13 years after attaining menarche during the evaluation of postabortal sepsis. Patient presented 2 weeks following evacuation carried out for missed abortion, with acute abdominal pain, fever and foul smelling discharge per vaginum. The anomaly was identified as uterus didelphys with obstructed left hemivagina and ipsilateral renal agenesis (Herlyn-Werner-Wunderlich syndrome) complicated by pyocolpos. She was successfully managed by single-stage transvaginal septum resection under laparoscopic control.

  16. Herlyn-Werner-Wunderlich syndrome: a rare cause of pelvic pain in adolescent girls.

    Science.gov (United States)

    Aveiro, Ana Cristina; Miranda, Victor; Cabral, António Jorge; Nunes, Sidónia; Paulo, Filomeno; Freitas, Conceição

    2011-07-15

    The Herlyn-Werner-Wunderlich syndrome is a rare congenital anomaly characterised by uterus didelphys with blind hemivagina and ipsilateral renal agenesis. It usually presents after menarche with progressive pelvic pain during menses secondary to haematocolpos. Awareness is necessary in order to diagnose and treat this disorder properly before complications occur. MRI is the preferred modality for the delineation of uterine malformation. When renal anomalies are encountered, a screening should also be made for congenital abnormalities of the reproductive tract and vice versa. The authors report a case of a girl with this condition who had a prenatal diagnose of right renal agenesis and presented at 13 years old with pelvic pain caused by haematocolpos.

  17. An unusual organ involvement in a case of Werner Syndrome: thyroid atrophy

    Directory of Open Access Journals (Sweden)

    Mustafa Altay

    2015-06-01

    Full Text Available Abstract: Werner Syndrome (WS is a premature aging disease that begins in adolescence or early adulthood and results in the appearance of old age by 30-40 years of age. Some endocrinological abnormalities were manifested in this rare disease, such as hypogonadism, diabetes mellitus, hyperlipidemia. In this article, we present a nineteen years-old female patient who had been diagnosed as WS two years ago because of type 2 diabetes mellitus, osteopenia, hyperlipidemia, cataract, gray hair, and skin atrophy. Subclinical hypothyroidism was detected at her laboratory tests. Thyroid ultrasonography (USG showed thyroid atrophy. Fine needle aspiration biopsy of both lobes confirmed this diagnose and excluded some infiltrative diseases such as amyloidosis. It should be kept in mind that thyroid atrophy could be seen in WS and, therefore, detailed thyroid examination including thyroid USG and close follow up should be performed in all patients with WS. [J Contemp Med 2015; 5(2.000: 144-146

  18. [Term pregnancy after minimally invasive surgical treatment of Herlyn-Werner-Wunderlich syndrome].

    Science.gov (United States)

    Mirković, Ljiljana; Ljubić, Aleksandar; Janjić, Tijana; Milićević, Srboljub; Sparić, Radmila; Jeremić, Katarina; Pantović, Sveto; Milenković, Vera

    2013-01-01

    Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis represents a complex congenital anomaly, also known in the literature as Herlyn-Werner-Wunderlich (HWW) syndrome. A 16-year-old patient presented with secondary amenorrhoea and abdominal pain. Her history revealed anorexia nervosa; she had menarche at the age of 14; her menstrual cycles were regular, with progressive dysmenorrhoea. Nine months after the explorative laparotomy performed at the regional healthcare center there was no a definitive diagnosis. Pelvic examination showed a paravaginal pelvic mass located on the right side. Magnetic resonance imaging of the abdomen and pelvis confirmed the diagnosis of HWW syndrome. Transvaginal excision and marsupialisation of the vaginal septum were performed. Regular menstrual cycles were resumed after four years following the treatment of anorexia nervosa. Twelve years after the operation, the patient conceived spontaneously; pregnancy developed in the left non-obstructed uterus. She underwent Cesarean section at the 37th gestational week and gave birth to a healthy female infant. HWW syndrome is an uncommon cause of abdominal pain and progressive menstrual discomfort shortly after menarche. It is therefore essential to maintain a high index of suspicion of the existence of this syndrome in such cases, since prompt and adequate treatment prevents the development of complications and allows for preservation of the reproductive potential of both hemi-uteri.

  19. Metabolic and Phenotypic Differences between Mice Producing a Werner Syndrome Helicase Mutant Protein and Wrn Null Mice

    Science.gov (United States)

    Aumailley, Lucie; Garand, Chantal; Dubois, Marie Julie; Johnson, F. Brad; Marette, André; Lebel, Michel

    2015-01-01

    Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ-family DNA helicase, WRN. Mice lacking part of the helicase domain of the WRN orthologue exhibit many phenotypic features of WS, including metabolic abnormalities and a shorter mean life span. In contrast, mice lacking the entire Wrn protein (i.e. Wrn null mice) do not exhibit a premature aging phenotype. In this study, we used a targeted mass spectrometry-based metabolomic approach to identify serum metabolites that are differentially altered in young Wrn helicase mutant and Wrn null mice. An antibody-based quantification of 43 serum cytokines and markers of cardiovascular disease risk complemented this study. We found that Wrn helicase mutants exhibited elevated and decreased levels, respectively, of the anti-inflammatory cytokine IL-10 and the pro-inflammatory cytokine IL-18. Wrn helicase mutants also exhibited an increase in serum hydroxyproline and plasminogen activator inhibitor-1, markers of extracellular matrix remodeling of the vascular system and inflammation in aging. We also observed an abnormal increase in the ratio of very long chain to short chain lysophosphatidylcholines in the Wrn helicase mutants underlying a peroxisome perturbation in these mice. Remarkably, the Wrn mutant helicase protein was mislocalized to the endoplasmic reticulum and the peroxisomal fractions in liver tissues. Additional analyses with mouse embryonic fibroblasts indicated a severe defect of the autophagy flux in cells derived from Wrn helicase mutants compared to wild type and Wrn null animals. These results indicate that the deleterious effects of the helicase-deficient Wrn protein are mediated by the dysfunction of several cellular organelles. PMID:26447695

  20. Herlyn-Werner-Wunderlich Syndrome with Ureteric Remnant Abscess Managed Laparoscopically: A Case Report.

    Science.gov (United States)

    Meneses, Aurus Dourado; Filho, Walberto Monteiro Neiva Eulálio; Raulino, Débora Maria Ribeiro; Martins, Eduardo Bruno Lobato; Vieira, Sabas Carlos

    2017-03-01

    Herlyn-Werner-Wunderlich (HWW) syndrome is part of a spectrum of Müllerian duct anomalies that occur during embryonic development. The syndrome is characterized by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Only few cases of this disease were reported worldwide. We present a 23-year-old female patient with chronic pelvic pain for years. The patient was diagnosed with HWW syndrome with a history of hematocolpos and vaginoplasty at the age of 12. Five months later, she sought urgent medical care due to intense pain, and a clinical picture suggestive of peritoneal irritation. Clinical condition deteriorated and the patient underwent an exploratory laparotomy, which failed to identify anything to justify the abdominal pain. Uroculture and blood culture were negative. A magnetic resonance imaging showed a tube-shaped formations extending from the right retrovesical region to the mesogastrium corresponding to the persistence of the mesonephric duct, related to ipsilateral renal agenesis. The patient underwent laparoscopic procedure, identifying a right ureteric remnant blind ending, with distal and proximal obliteration, filled with purulent secretion, which was totally resected. This case differs from the other reported cases due to pelvic pain secondary to infection and abscess in ureteric remnant. We did not find any case with similar clinical presentation.

  1. Herlyn-Werner-Wunderlich Syndrome with Ureteric Remnant Abscess Managed Laparoscopically: A Case Report

    Directory of Open Access Journals (Sweden)

    Aurus Dourado Meneses

    2017-03-01

    Full Text Available Herlyn-Werner-Wunderlich (HWW syndrome is part of a spectrum of Müllerian duct anomalies that occur during embryonic development. The syndrome is characterized by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Only few cases of this disease were reported worldwide. We present a 23-year-old female patient with chronic pelvic pain for years. The patient was diagnosed with HWW syndrome with a history of hematocolpos and vaginoplasty at the age of 12. Five months later, she sought urgent medical care due to intense pain, and a clinical picture suggestive of peritoneal irritation. Clinical condition deteriorated and the patient underwent an exploratory laparotomy, which failed to identify anything to justify the abdominal pain. Uroculture and blood culture were negative. A magnetic resonance imaging showed a tube-shaped formations extending from the right retrovesical region to the mesogastrium corresponding to the persistence of the mesonephric duct, related to ipsilateral renal agenesis. The patient underwent laparoscopic procedure, identifying a right ureteric remnant blind ending, with distal and proximal obliteration, filled with purulent secretion, which was totally resected. This case differs from the other reported cases due to pelvic pain secondary to infection and abscess in ureteric remnant. We did not find any case with similar clinical presentation.

  2. Prepubertal presentation of Herlyn-Werner-Wunderlich syndrome: a case report.

    Science.gov (United States)

    Sanghvi, Yogendra; Shastri, Pankaj; Mane, S B; Dhende, Nitin P

    2011-06-01

    Herlyn-Werner-Wunderlich syndrome represents a complex female genital malformation with uterus didelphys, unilateral low vaginal obstruction, and ipsilateral renal agenesis, all 3 being secondary to mesonephric duct-induced müllerian anomalies. Clinically, this usually presents in postpubertal adolescent or adult women where hematometrocolpos produces a more pronounced mass effect and pain on the side of the obstructed hemivagina. It is extremely rare for this to present in infancy and early childhood because imaging may not show the small prepubertal uteri and vaginas clearly. We describe a 4-year-old girl with all of the features of this syndrome. Ipsilateral renal agenesis with a pelvic mass should raise the level of suspicion for this syndrome. Magnetic resonance imaging will confirm the diagnosis, so that early endoscopic resection of the obstructing vaginal septum can be carried out as definitive treatment. Long-term outcome is quite good with expectation of normal fertility. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Strand exchange of telomeric DNA catalyzed by the Werner syndrome protein (WRN) is specifically stimulated by TRF2

    OpenAIRE

    Edwards, Deanna N.; Orren, David K.; Machwe, Amrita

    2014-01-01

    Werner syndrome (WS), caused by loss of function of the RecQ helicase WRN, is a hereditary disease characterized by premature aging and elevated cancer incidence. WRN has DNA binding, exonuclease, ATPase, helicase and strand annealing activities, suggesting possible roles in recombination-related processes. Evidence indicates that WRN deficiency causes telomeric abnormalities that likely underlie early onset of aging phenotypes in WS. Furthermore, TRF2, a protein essential for telomere protec...

  4. Herlyn-Werner-Wunderlich Syndrome: Sonographic and Magnetic Resonance (MR) Imaging Findings of This Rare Urogenital Anomaly.

    Science.gov (United States)

    Yilmaz, Sukriye; Yildiz, Adalet Elcin; Fitoz, Suat

    2017-01-01

    Herlyn-Werner-Wunderlich syndrome is a rare congenital urogenital anomaly characterised by uterus didelphys with blind hemivagina and ipsilateral renal agenesis. Children usually have progressive pelvic pain after menarche, palpable mass due to hemihaemato(metro)colpos or pelvic inflammatory disease. The diagnosis usually requires a suspicion of this rare genitourinary syndrome. We present ultrasonography and MR imaging findings of this rare anomaly in two cases. Early recognition of this rare syndrome can lead to an immediate, proper surgical intervention and is necessary to prevent complications and preserve future fertility. Ultrasound and MR imaging findings can collectively delineate uterine morphology, indicate the absence of ipsilateral kidney and show obstructed hemivagina.

  5. Recent Advances in Understanding Werner Syndrome [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Raghavendra A. Shamanna

    2017-09-01

    Full Text Available Aging, the universal phenomenon, affects human health and is the primary risk factor for major disease pathologies. Progeroid diseases, which mimic aging at an accelerated rate, have provided cues in understanding the hallmarks of aging. Mutations in DNA repair genes as well as in telomerase subunits are known to cause progeroid syndromes. Werner syndrome (WS, which is characterized by accelerated aging, is an autosomal-recessive genetic disorder. Hallmarks that define the aging process include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. WS recapitulates these hallmarks of aging and shows increased incidence and early onset of specific cancers. Genome integrity and stability ensure the normal functioning of the cell and are mainly guarded by the DNA repair machinery and telomeres. WRN, being a RecQ helicase, protects genome stability by regulating DNA repair pathways and telomeres. Recent advances in WS research have elucidated WRN’s role in DNA repair pathway choice regulation, telomere maintenance, resolution of complex DNA structures, epigenetic regulation, and stem cell maintenance.

  6. Scoliosis in Herlyn-Werner-Wunderlich syndrome: a case report and literature review.

    Science.gov (United States)

    Li, Zheng; Yu, Xin; Shen, Jianxiong; Liang, Jinqian

    2014-12-01

    Herlyn-Werner-Wunderlich syndrome (HWWS) is a congenital Müllerian duct anomaly characterized by uterine didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Little is reported about spinal deformity associated with this syndrome. This study presents a case of scoliosis occurring in the setting of HWWS and explores the possible association between the 2 diseases. A previously unreported scoliosis in HWWS is described. The patient is a 12-year-old Chinese female with scoliosis that underwent a posterior correction at thoracic 5-thoracic 12 (T5-T12) levels, using the Moss-SI (Johnson & Johnson, American) spinal system. At 24-month follow-up, the patient was clinically pain free and well balanced. Plain radiographs showed solid spine fusion with no loss of deformity correction. Six months after scoliosis correction surgery, the patient went to our clinics for the treatment of HWWS. She was performed a vaginal septum resection and detected with pyocolpos. Her follow-up was symptom free at the fourth postoperative month. The prevalence of scoliosis among patients with HWWS was 8.57% that is much higher than the incidence of congential scoliosis among general population (1/1000). To the best of our knowledge, this is the first report of HWWS with thoracic scoliosis. During surgery, surgeons and anesthesiologists must pay particular attention to the Müllerian duct anomaly and renal agenesis associated with HWWS. There is a potential association between congenital scoliosis and HWWS.

  7. Herlyn-Werner-Wunderlich syndrome: pre- and post-surgical MRI and US findings.

    Science.gov (United States)

    Dias, João Lopes; Jogo, Renata

    2015-10-01

    Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare congenital anomaly of the female urogenital tract that associates Müllerian duct anomalies with mesonephric duct anomalies. The triad of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis characterizes this syndrome. Patients generally present with non-specific symptoms after menarche. Pelvic pain, dysmenorrhea, and palpable mass due to hematocolpos or hematometra are the most common findings. Pyohematocolpos and pyosalpinx may appear as acute complications, while endometriosis and pelvic adhesions constitute potential long-term complications. When a prenatal diagnosis of unilateral renal agenesis in newborn girls is known, a gynecological imaging study should be performed to exclude uterine and vaginal abnormalities. These patients should be followed up to ensure that a timely surgical correction is performed. The diagnosis of HWWS is difficult due to the lack of specific symptoms or findings upon physical examination. An accurate imaging description of these congenital anomalies is crucial to guide patients toward surgical treatment, relieving acute complications, and preserving the normal fertility. The authors provide a pictorial review of the magnetic resonance imaging and ultrasonography findings of the HWWS with correlation to embryological, clinical, and surgical features.

  8. Chromosomal instability in B-lymphoblasotoid cell lines from Werner and Bloom syndrome patients.

    Science.gov (United States)

    Honma, Masamitsu; Tadokoro, Satoshi; Sakamoto, Hiroko; Tanabe, Hideyuki; Sugimoto, Masanobu; Furuichi, Yasuhiro; Satoh, Takatomo; Sofuni, Toshio; Goto, Makoto; Hayashi, Makoto

    2002-09-26

    Werner's syndrome (WS) and Bloom's syndrome (BS) are rare autosomal genetic diseases that predispose to cancer and are associated with genomic instability. To characterize the genomic instability of WS and BS, we analyzed and compared the cytogenetics of B-lymphoblastoid cell lines (LCLs) from WS and BS patients and healthy donors. Although, similar spontaneous frequencies of micronuclei (MN) and sister chromatid exchanges (SCE) were observed in LCLs from WS patients and healthy donors, they were much higher in BS-LCLs. We also examined the cells' cytotoxic and cytogenetic formation (MN) response to camptothecin (CAM), etoposide (ETO), 4-nitroquinoline 1-oxide (4NQO), and mitomycin C (MMC). Compared to healthy donor LCLs, BS-LCLs but not WS-LCLs tended to be resistant to cytotoxicity and sensitive to MN induction by 4NQO and MMC. Spectrum karyotyping analysis revealed that most WS- and BS-LCLs generated "variegated translocation mosaicism" at high frequencies during cell culture. These findings support the idea that the basis of genomic instability in WS is different from that in BS.

  9. The Herlyn-Werner-Wunderlich Syndrome – A Case Report with Radiological Review

    Science.gov (United States)

    Khaladkar, Sanjay Mhalasakant; Kamal, Vigyat; Kamal, Anubhav; Kondapavuluri, Sushen Kumar

    2016-01-01

    Summary Background HWW syndrome is a very rare congenital anomaly of urogenital tract involving Mullerian ducts and mesonephric ducts. It is characterised by a triad of symptoms - uterus didelphys, obstructed hemivagina and ipsilateral renal agenesis. It can be classified based on a completely or incompletely obstructed hemivagina. It presents soon after menarche or shows delayed presentation depending on the type. It can exhibit acute pelvic pain shortly after menarche and may show non-specific and variable symptoms with resultant delay in diagnosis. The most common presentation is pain and dysmenorrhea, and pain and abdominal mass in the lower abdomen secondary to haematocolpos and/or haematometra. Case Report Presentation of a clinical case of a 13-year-old patient with HWW syndrome presenting with regular menses, dysmenorrhea and painful lump in hypogastric region on the left side of midline. We described the role of imaging modalities in diagnosis of the Herlyn-Werner-Wunderlich syndrome with a review of literature. USG and MRI showed left renal agenesis with compensatory hypertrophy of the right kidney, uterus didelphys with haematometra and haematocervix in the left uterus with evidence of blood in a dilated retort-shaped left fallopian tube and a normal right uterus. The unique feature of our case is haematometra and haematocervix with cervical and vaginal atresia found on the left side (classification 1.2) with associated left renal agenesis. Conclusions HWW syndrome can present early or late, depending on the type. In patients with uterine and vaginal abnormalities, a work-up for associated renal anomalies should be performed. Early intervention is needed to reduce the risk of endometriosis and infertility. PMID:28058067

  10. Term pregnancy after minimally invasive surgical treatment of Herlyn-Werner-Wunderlich syndrome

    Directory of Open Access Journals (Sweden)

    Mirković Ljiljana

    2013-01-01

    Full Text Available Introduction. Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis represents a complex congenital anomaly, also known in the literature as Herlyn-Werner-Wunderlich (HWW syndrome. Case Outline. A 16­year­old patient presented with secondary amenorrhoea and abdominal pain. Her history revealed anorexia nervosa; she had menarche at the age of 14; her menstrual cycles were regular, with progressive dysmenorrhoea. Nine months after the explorative laparotomy performed at the regional healthcare center there was no a definitive diagnosis. Pelvic examination showed a paravaginal pelvic mass located on the right side. Magnetic resonance imaging of the abdomen and pelvis confirmed the diagnosis of HWW syndrome. Transvaginal excision and marsupialisation of the vaginal septum were performed. Regular menstrual cycles were resumed after four years following the treatment of anorexia nervosa. Twelve years after the operation, the patient conceived spontaneously; pregnancy developed in the left non­obstructed uterus. She underwent Cesarean section at the 37th gestational week and gave birth to a healthy female infant. Conclusion. HWW syndrome is an uncommon cause of abdominal pain and progressive menstrual discomfort shortly after menarche. It is therefore essential to maintain a high index of suspicion of the existence of this syndrome in such cases, since prompt and adequate treatment prevents the development of complications and allows for preservation of the reproductive potential of both hemiuteri. [Projekat Ministarstva nauke Republike Srbije: Celularni i molekularni patogenetski mehanizmi poremećaja reprodukcije i genitalnih organa u prevenciji, dijagnostici i terapiji podprojekat, br. 41021: Tretmani antenatalnih hidronefroza

  11. The Herlyn-Werner-Wunderlich Syndrome - A Case Report with Radiological Review.

    Science.gov (United States)

    Khaladkar, Sanjay Mhalasakant; Kamal, Vigyat; Kamal, Anubhav; Kondapavuluri, Sushen Kumar

    2016-01-01

    HWW syndrome is a very rare congenital anomaly of urogenital tract involving Mullerian ducts and mesonephric ducts. It is characterised by a triad of symptoms - uterus didelphys, obstructed hemivagina and ipsilateral renal agenesis. It can be classified based on a completely or incompletely obstructed hemivagina. It presents soon after menarche or shows delayed presentation depending on the type. It can exhibit acute pelvic pain shortly after menarche and may show non-specific and variable symptoms with resultant delay in diagnosis. The most common presentation is pain and dysmenorrhea, and pain and abdominal mass in the lower abdomen secondary to haematocolpos and/or haematometra. Presentation of a clinical case of a 13-year-old patient with HWW syndrome presenting with regular menses, dysmenorrhea and painful lump in hypogastric region on the left side of midline. We described the role of imaging modalities in diagnosis of the Herlyn-Werner-Wunderlich syndrome with a review of literature. USG and MRI showed left renal agenesis with compensatory hypertrophy of the right kidney, uterus didelphys with haematometra and haematocervix in the left uterus with evidence of blood in a dilated retort-shaped left fallopian tube and a normal right uterus. The unique feature of our case is haematometra and haematocervix with cervical and vaginal atresia found on the left side (classification 1.2) with associated left renal agenesis. HWW syndrome can present early or late, depending on the type. In patients with uterine and vaginal abnormalities, a work-up for associated renal anomalies should be performed. Early intervention is needed to reduce the risk of endometriosis and infertility.

  12. Herlyn-Werner-Wunderlich syndrome--timely diagnosis is important to preserve fertility.

    Science.gov (United States)

    Güdücü, Nilgün; Gönenç, Gökçenur; Işçi, Herman; Yiğiter, Alin Başgül; Dünder, Ilkkan

    2012-10-01

    Herlyn-Werner-Wunderlich syndrome is an urogenital malformation with uterus didelphys and obstructed hemivagina with ipsilateral renal agenesis. Most of these patients present after the onset of menstruation. We describe two cases diagnosed too late to prevent the complications. The first patient presented with acute abdomen one year after the onset of menstruation and had salpingectomy due to pyosalpinx. The blind hemivagina was not recognized and she had severe endometriosis. She underwent hysterectomy 8 years later. The second patient presented with foul smelling vaginal discharge when she was 21 years old. She had a simple vaginal septum resection. In the presence of uterine cavities in a regularly menstruating girl with dysmenorrhea, the presence of both kidneys should be checked. When unilateral renal agenesis and uterus didelphys coexist the first thing that we should remember is to confirm or refute the presence of a blind vagina. Copyright © 2012 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  13. Herlyn-Werner-Wunderlich Syndrome Consisting of Uterine Didelphys, Obstructed Hemivagina and Ipsilateral Renal Agenesis in a Newborn

    Directory of Open Access Journals (Sweden)

    Tsung-Hsin Wu

    2012-02-01

    Full Text Available Herlyn-Werner-Wunderlich (HWW syndrome is a rare variant of Müllerian duct anomalies consisting of uterine didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Patients with HWW syndrome are usually asymptomatic until menarche, when they present with acute lower abdominal pain. Here we report a case of a female newborn with right renal agenesis diagnosed during the pregnancy. The patient presented with a protruding mass over the vaginal introitus that was associated with an obstructed hemivagina and uterine didelphys.

  14. Herlyn-Werner-Wunderlich syndrome consisting of uterine didelphys, obstructed hemivagina and ipsilateral renal agenesis in a newborn.

    Science.gov (United States)

    Wu, Tsung-Hsin; Wu, Trang-Tiau; Ng, Yan-Yan; Ng, Soo-Cheen; Su, Pen-Hua; Chen, Jia-Yuh; Chen, Suh-Jen

    2012-02-01

    Herlyn-Werner-Wunderlich (HWW) syndrome is a rare variant of Müllerian duct anomalies consisting of uterine didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Patients with HWW syndrome are usually asymptomatic until menarche, when they present with acute lower abdominal pain. Here we report a case of a female newborn with right renal agenesis diagnosed during the pregnancy. The patient presented with a protruding mass over the vaginal introitus that was associated with an obstructed hemivagina and uterine didelphys. Copyright © 2012. Published by Elsevier B.V.

  15. Spectrum and risk of neoplasia in Werner syndrome: a systematic review.

    Science.gov (United States)

    Lauper, Julia M; Krause, Alison; Vaughan, Thomas L; Monnat, Raymond J

    2013-01-01

    Werner syndrome (WS) is an autosomal recessive genetic instability and progeroid ('premature aging') syndrome which is associated with an elevated risk of cancer. Our study objectives were to characterize the spectrum of neoplasia in WS using a well-documented study population, and to estimate the type-specific risk of neoplasia in WS relative to the general population. We obtained case reports of neoplasms in WS patients through examining previous case series and reviews of WS, as well as through database searching in PubMed, Google Scholar, and J-EAST, a search engine for articles from Japan. We defined the spectrum (types and sites) of neoplasia in WS using all case reports, and were able to determine neoplasm type-specific risk in Japan WS patients by calculating standardized incidence and proportionate incidence ratios (SIR and SPIR, respectively) relative to Osaka Japan prefecture incidence rates. We used a newly assembled study population of 189 WS patients with 248 neoplasms to define the spectrum of neoplasia in WS. The most frequent neoplasms in WS patients, representing 2/3 of all reports, were thyroid neoplasms, malignant melanoma, meningioma, soft tissue sarcomas, leukemia and pre-leukemic conditions of the bone marrow, and primary bone neoplasms. Cancer risk defined by SIRs was significantly elevated in Japan-resident WS patients for the six most frequent neoplasms except leukemia, ranging from 53.5-fold for melanoma of the skin (95% CI: 24.5, 101.6) to 8.9 (95% CI: 4.9, 15.0) for thyroid neoplasms. Cancer risk as defined by SPIR was also significantly elevated for the most common malignancies except leukemia. WS confers a strong predisposition to several specific types of neoplasia. These results serve as a guide for WS clinical care, and for additional analyses to define the mechanistic basis for cancer in WS and the general population.

  16. Spectrum and risk of neoplasia in Werner syndrome: a systematic review.

    Directory of Open Access Journals (Sweden)

    Julia M Lauper

    Full Text Available Werner syndrome (WS is an autosomal recessive genetic instability and progeroid ('premature aging' syndrome which is associated with an elevated risk of cancer.Our study objectives were to characterize the spectrum of neoplasia in WS using a well-documented study population, and to estimate the type-specific risk of neoplasia in WS relative to the general population.We obtained case reports of neoplasms in WS patients through examining previous case series and reviews of WS, as well as through database searching in PubMed, Google Scholar, and J-EAST, a search engine for articles from Japan. We defined the spectrum (types and sites of neoplasia in WS using all case reports, and were able to determine neoplasm type-specific risk in Japan WS patients by calculating standardized incidence and proportionate incidence ratios (SIR and SPIR, respectively relative to Osaka Japan prefecture incidence rates.We used a newly assembled study population of 189 WS patients with 248 neoplasms to define the spectrum of neoplasia in WS. The most frequent neoplasms in WS patients, representing 2/3 of all reports, were thyroid neoplasms, malignant melanoma, meningioma, soft tissue sarcomas, leukemia and pre-leukemic conditions of the bone marrow, and primary bone neoplasms. Cancer risk defined by SIRs was significantly elevated in Japan-resident WS patients for the six most frequent neoplasms except leukemia, ranging from 53.5-fold for melanoma of the skin (95% CI: 24.5, 101.6 to 8.9 (95% CI: 4.9, 15.0 for thyroid neoplasms. Cancer risk as defined by SPIR was also significantly elevated for the most common malignancies except leukemia.WS confers a strong predisposition to several specific types of neoplasia. These results serve as a guide for WS clinical care, and for additional analyses to define the mechanistic basis for cancer in WS and the general population.

  17. Narrowing the position of the Werner syndrome locus by homozygosity analysis - extension of homozygosity analysis

    Energy Technology Data Exchange (ETDEWEB)

    Nakura, Jun; Miki, Tetsuro; Ye, Lin [Osaka Univ. Medical School (Japan)] [and others

    1996-08-15

    Werner syndrome (WS) is an autosomal recessive disorder characterized by the premature occurrence of many age-related features. Previously, the WS gene (WRN) was mapped between D8S131 and D8S87, in an 8.3-cM interval. In this study, regions of homozygosity in 36 WS patients from inbred families were searched for by genotyping for 35 dinucleotide repeat polymorphic markers to narrow down the W-RN critical region. The region most consistently homozygous in these patients was between the D8S1219/D8S1220 cluster and D8S278, within a 4.4-cM interval. For 16 markers mapped in this interval, 24 WS patients (22 Japanese patients and 2 Caucasian patients) in whom consanguinity failed to be proved were also genotyped, under the assumption that some of these patients might still be from consanguineous marriages. The data were analyzed by Fisher`s exact test with a 2 x 2 contingency table for the 22 Japanese patients, excluding the 2 Caucasian patients. The frequencies of homozygosity in the 22 patients at 10 of 16 markers tested were significantly higher than those detected in the general population. Analysis of homozygosity patterns indicated that the region most consistently homozygous was between D8S1445 and D8S278. Thus the WRN locus is most likely between the two markers D8S1445 and D8S278, in a 1.6-cM interval. 49 refs., 4 tabs.

  18. Interaction of Werner and Bloom syndrome genes with p53 in familial breast cancer.

    Science.gov (United States)

    Wirtenberger, Michael; Frank, Bernd; Hemminki, Kari; Klaes, Rüdiger; Schmutzler, Rita K; Wappenschmidt, Barbara; Meindl, Alfons; Kiechle, Marion; Arnold, Norbert; Weber, Bernhard H F; Niederacher, Dieter; Bartram, Claus R; Burwinkel, Barbara

    2006-08-01

    Mutations of the human RecQ helicase genes WRN and BLM lead to rare autosomal recessive disorders, Werner and Bloom syndromes, which are associated with premature ageing and cancer predisposition. We tested the hypothesis whether three polymorphic, non-conservative amino acid exchanges in WRN and BLM act as low-penetrance familial breast cancer risk factors. Moreover, we examined the putative impact of p53 MspI 1798G>A, which is completely linked to p53PIN3, a 16 bp insertion/duplication that has been associated with reduced p53 expression, on familial breast cancer risk. Genotyping analyses, performed on 816 BRCA1/2 mutation-negative German familial breast cancer patients and 1012 German controls, revealed a significant association of the WRN Cys1367Arg polymorphism with familial breast cancer (OR = 1.28, 95% CI 1.06-1.54) and high-risk familial breast cancer (OR = 1.32, 95% CI 1.06-1.65). The analysis of p53 MspI 1798G>A, which is completely linked to p53PIN3, showed a significantly increased familial breast cancer risk for carriers of the 16 bp insertion/duplication, following a recessive mode (OR = 2.15, 95% CI = 1.12-4.11). WRN Cys1367Arg, located in the C-terminus, the binding site of p53, is predicted to be damaging. The joint effect of WRN Cys1367Arg and p53 MspI resulted in an increased breast cancer risk compared to the single polymorphisms (OR = 3.39, 95% CI 1.19-9.71). In conclusion, our study indicates the importance of inherited variants in the WRN and p53 genes for familial breast cancer susceptibility.

  19. Werner syndrome: clinical evaluation of two cases and a novel mutation.

    Science.gov (United States)

    Mansur, A T; Elçioglu, N H; Demirci, G T

    2014-01-01

    Werner syndrome (WS) is a premature aging disorder, inherited in an autosomal recessive pattern and caused by the mutation in the WRN gene. In this report we describe two male patients with negative family history who demonstrate characteristic findings of WS, with different mutations, including one novel mutation. The first case was a 47-year-old man who had been suffering from large, ischemic ulcers on both legs for 7 years. Physical examination revealed a thin and short man with severe wasting of all extremities. He had a high-pitched voice, hoarseness, a characteristic bird-like facies, bilateral cataracts, generalized osteoporosis, hypotrichosis, atrophic and poikilodermic skin, flexion contractures of hands, feet and knees, and soft tissue calcifications. Laboratory investigations revealed anemia, high erythrocyte sedimentation rate, low creatinine clearance, and high liver enzymes. Genetic analysis showed a homozygous novel 1bp-deletion in exon 19 of WRN, 2426/27delG, causing frameshift and protein truncation R809SfsX2, which has not been described before. The second case was a 23-year-old man who was referred for large callosities on both feet, present for 7 years. He complained of weakness, weight loss, wasting of muscles, and early graying of hair. The entire skin was thin, wrinkled and dry. Generalized hypotrichosis, scattered ephelid-like macules, sclerotic fingers, calcinosis cutis on ears, hyperpigmentation on elbows were the other alterations of skin. Skeletal survey revealed osteoporosis. Genetic analysis showed a homozygous known pathogenic splice site mutation c.3460-2A>G, causing skipping of Exon 30 in WRN.

  20. Herlyn-werner-wunderlich syndrome: MRI findings, radiological guide (two cases and literature review, and differential diagnosis

    Directory of Open Access Journals (Sweden)

    Del Vescovo Riccardo

    2012-03-01

    Full Text Available Abstract Background Herlyn-Werner-Wunderlich (HWW syndrome is a very rare congenital anomaly of the urogenital tract involving Müllerian ducts and Wolffian structures, and it is characterized by the triad of didelphys uterus, obstructed hemivagina and ipsilateral renal agenesis. It generally occurs at puberty and exhibits non-specific and variable symptoms with acute or pelvic pain shortly following menarche, causing a delay in the diagnosis. Moreover, the diagnosis is complicated by the infrequency of this syndrome, because Müllerian duct anomalies (MDA are infrequently encountered in a routine clinical setting. Cases presentation two cases of HWW syndrome in adolescents and a differential diagnosis for one case of a different MDA, and the impact of magnetic resonance (MR imaging technology to achieve the correct diagnosis. Conclusions MR imaging is a very suitable diagnostic tool in order to perform the correct diagnosis of HWW syndrome.

  1. Herlyn-Werner-Wunderlich syndrome: MRI findings, radiological guide (two cases and literature review), and differential diagnosis.

    Science.gov (United States)

    Del Vescovo, Riccardo; Battisti, Sofia; Di Paola, Valerio; Piccolo, Claudia L; Cazzato, Roberto L; Sansoni, Ilaria; Grasso, Rosario F; Zobel, Bruno Beomonte

    2012-03-09

    Herlyn-Werner-Wunderlich (HWW) syndrome is a very rare congenital anomaly of the urogenital tract involving Müllerian ducts and Wolffian structures, and it is characterized by the triad of didelphys uterus, obstructed hemivagina and ipsilateral renal agenesis. It generally occurs at puberty and exhibits non-specific and variable symptoms with acute or pelvic pain shortly following menarche, causing a delay in the diagnosis. Moreover, the diagnosis is complicated by the infrequency of this syndrome, because Müllerian duct anomalies (MDA) are infrequently encountered in a routine clinical setting. two cases of HWW syndrome in adolescents and a differential diagnosis for one case of a different MDA, and the impact of magnetic resonance (MR) imaging technology to achieve the correct diagnosis. MR imaging is a very suitable diagnostic tool in order to perform the correct diagnosis of HWW syndrome.

  2. Competition between the DNA unwinding and strand pairing activities of the Werner and Bloom syndrome proteins.

    Science.gov (United States)

    Machwe, Amrita; Lozada, Enerlyn M; Xiao, Liren; Orren, David K

    2006-01-13

    The premature aging and cancer-prone Werner and Bloom syndromes are caused by defects in the RecQ helicase enzymes WRN and BLM, respectively. Recently, both WRN and BLM (as well as several other RecQ members) have been shown to possess a strand annealing activity in addition to the requisite DNA unwinding activity. Since an annealing function would appear to directly oppose the action of a helicase, we have examined in this study the dynamic equilibrium between unwinding and annealing mediated by either WRN or BLM. Our investigation into the competition between annealing and unwinding demonstrates that, under standard reaction conditions, WRN- or BLM-mediated annealing can partially or completely mask unwinding as measured in standard helicase assays. Several strategies were employed to suppress the annealing activity so that the actual strength of WRN- or BLM-dependent unwinding could be more accurately assessed. Interestingly, if a DNA oligomer complementary to one strand of the DNA substrate to be unwound is added during the helicase reaction, both WRN and BLM unwinding is enhanced, presumably by preventing protein-mediated re-annealing. This strategy allowed measurement of WRN-catalyzed unwinding of long (80 base pair) duplex regions and fully complementary, blunt-ended duplexes, both of which were otherwise quite refractory to the helicase activity of WRN. Similarly, the addition of trap strand stimulated the ability of BLM to unwind long and blunt-ended duplexes. The stimulatory effect of the human replication protein A (hRPA, the eukaryotic single-stranded DNA binding protein) on both WRN- and BLM-dependent unwinding was also re-examined in light of its possible role in preventing re-annealing. Our results show that hRPA influences the outcome of WRN and BLM helicase assays by both inhibiting re-annealing and directly promoting unwinding, with the larger contribution from the latter mechanism. These findings indicate that measurements of unwinding by WRN

  3. Competition between the DNA unwinding and strand pairing activities of the Werner and Bloom syndrome proteins

    Directory of Open Access Journals (Sweden)

    Orren David K

    2006-01-01

    Full Text Available Abstract Background The premature aging and cancer-prone Werner and Bloom syndromes are caused by defects in the RecQ helicase enzymes WRN and BLM, respectively. Recently, both WRN and BLM (as well as several other RecQ members have been shown to possess a strand annealing activity in addition to the requisite DNA unwinding activity. Since an annealing function would appear to directly oppose the action of a helicase, we have examined in this study the dynamic equilibrium between unwinding and annealing mediated by either WRN or BLM. Results Our investigation into the competition between annealing and unwinding demonstrates that, under standard reaction conditions, WRN- or BLM-mediated annealing can partially or completely mask unwinding as measured in standard helicase assays. Several strategies were employed to suppress the annealing activity so that the actual strength of WRN- or BLM-dependent unwinding could be more accurately assessed. Interestingly, if a DNA oligomer complementary to one strand of the DNA substrate to be unwound is added during the helicase reaction, both WRN and BLM unwinding is enhanced, presumably by preventing protein-mediated re-annealing. This strategy allowed measurement of WRN-catalyzed unwinding of long (80 base pair duplex regions and fully complementary, blunt-ended duplexes, both of which were otherwise quite refractory to the helicase activity of WRN. Similarly, the addition of trap strand stimulated the ability of BLM to unwind long and blunt-ended duplexes. The stimulatory effect of the human replication protein A (hRPA, the eukaryotic single-stranded DNA binding protein on both WRN- and BLM-dependent unwinding was also re-examined in light of its possible role in preventing re-annealing. Our results show that hRPA influences the outcome of WRN and BLM helicase assays by both inhibiting re-annealing and directly promoting unwinding, with the larger contribution from the latter mechanism. Conclusion These

  4. Interstitial Lung Disease in Werner Syndrome: A Case Report of a 55-Year-Old Male Patient

    Directory of Open Access Journals (Sweden)

    Tiphaine Goletto

    2015-01-01

    Full Text Available Werner syndrome (WS is a progeroid or premature aging syndrome characterized by early onset of age-related pathologies and cancer. The average life expectancy of affected people is 52.8 years and tends to increase. The major causes of death are malignancy and myocardial infarction. Increased telomere attrition and decay are thought to play a causative role in the clinical and pathological manifestations of the disease. Although telomere length, with or without germline mutation, is known to be associated with interstitial lung disease, the latter is not associated with WS. To the best of our knowledge, we report the first case describing a WS patient with fatal ILD. This case suggests that older patients with WS could develop ILD. Clinical outcome of WS patients may thus be improved by counselling them regarding smoking cessation or other exposure and by proposing antifibrotic therapy.

  5. A novel Werner Syndrome mutation: pharmacological treatment by read-through of nonsense mutations and epigenetic therapies.

    Science.gov (United States)

    Agrelo, Ruben; Sutz, Miguel Arocena; Setien, Fernando; Aldunate, Fabian; Esteller, Manel; Da Costa, Valeria; Achenbach, Ricardo

    2015-01-01

    Werner Syndrome (WS) is a rare inherited disease characterized by premature aging and increased propensity for cancer. Mutations in the WRN gene can be of several types, including nonsense mutations, leading to a truncated protein form. WRN is a RecQ family member with both helicase and exonuclease activities, and it participates in several cell metabolic pathways, including DNA replication, DNA repair, and telomere maintenance. Here, we reported a novel homozygous WS mutation (c.3767 C > G) in 2 Argentinian brothers, which resulted in a stop codon and a truncated protein (p.S1256X). We also observed increased WRN promoter methylation in the cells of patients and decreased messenger WRN RNA (WRN mRNA) expression. Finally, we showed that the read-through of nonsense mutation pharmacologic treatment with both aminoglycosides (AGs) and ataluren (PTC-124) in these cells restores full-length protein expression and WRN functionality.

  6. Delayed diagnosis of Herlyn-Werner-Wunderlich syndrome due to microperforation and pyocolpos in obstructed vaginal canal.

    Science.gov (United States)

    Wozniakowska, Ewa; Torres, Anna; Milart, Pawel; Wozniak, Slawomir; Czuczwar, Piotr; Szkodziak, Piotr; Paszkowski, Tomasz

    2014-08-01

    To present a rare anomaly consisting of uterus didelphys, longitudinal vaginal septum, obstructed hemivagina with pyocolpos, fistula to the open vaginal canal, and ipsilateral renal agenesis, referred as Herlyn-Werner-Wunderlich syndrome (HWWS). A 14-year-old girl with recurring purulent vaginal discharge lasting for a few months. Preoperative examination revealed one vaginal canal with one cervical opening on the right side. There was a fistula leading from the obstructed vaginal canal to the left vagina. Intravaginal ultrasound examination demonstrated a longitudinal vaginal septum and a closed pyocolpos on the right side. The longitudinal vaginal septum was excised by way of electrocauterization under direct vision. HWWS should be considered in the differential diagnosis in patients with uterus didelphys and unusual symptoms such as pyocolpos and vaginal discharge. Copyright © 2014 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  7. Herlyn-Werner-Wunderlich syndrome emphasizes ultrasonographic and MR findings: a case report and review of the literatures.

    Science.gov (United States)

    Angthong, Wirana; Visetsripong, Mattana; Amornvithayachan, Ornsiri; Varavithya, Vithya

    2012-12-01

    Herlyn-Werner-Wunderlich (HWW) syndrome is a rare developmental anomaly that is consists of uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis. This rare entity is the spectrum of Mullerian duct anomalies (MDA) accompanied by developmental anomaly of one of Wolffian ducts. The present report demonstrated HWW syndrome and reviewed literatures in term of embryological etiology, clinical manifestation, radiographic findings and surgical management. In this case report is a 11-year-old girl presented with chronic pelvic pain. She had menarche at the age of 10 and her menstrual cycles were regular with moderate dysmenorrhea. Physical examination revealed palpable pelvic mass with tenderness. Transabdominal ultrasonography (US) and Magnetic resonance imaging (MRI) demonstrated uterine didelphys with right-sided hematometrocolpos and absent right kidney. Right hematosalpinx was also detected due to distal tubal occlusion from adhesion. These preoperative images can verify all of the features of this syndrome and correctly anticipated diagnosis was achieved. The patient underwent laparoscopic right tubal drainage with lysis of pelvic adhesion and hysteroscopic resection of vaginal septum. Her symptoms were improved uneventfully. In conclusion, HWW syndrome exhibits unique clinical presentation with characteristic radiographic findings and symptom can be relieved dramatically after receiving appropriate surgical management.

  8. Herlyn-Werner-Wunderlich syndrome: uterus didelphys, blind hemivagina and ipsilateral renal agenesis. Sonographic and MR findings in 11 cases.

    Science.gov (United States)

    Orazi, Cinzia; Lucchetti, M Chiara; Schingo, Paolo M S; Marchetti, Paola; Ferro, Fabio

    2007-07-01

    Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis is a rare entity, sometimes referred to as Herlyn-Werner-Wunderlich syndrome (HWW). It usually presents after menarche with progressive pelvic pain, sometimes with regular menses, and a palpable mass due to hemihaematocolpos. The diagnosis is generally made only if the suspicion of this genitourinary syndrome is raised. To highlight the imaging diagnostic clues in this rare condition. We report on 11 adolescents with this condition. Sonography mostly allowed the correct diagnosis by showing uterovaginal duplication, haematocolpos or haematometrocolpos, and the absence of the ipsilateral kidney. MRI provided more detailed information regarding uterine morphology, the continuity with each vaginal channel (obstructed and nonobstructed), and the bloody nature of the contents. Early and accurate diagnosis of this syndrome is important so that adequate and prompt surgical therapy (excision of the vaginal septum) can provide relief of pain and prevent further complications. It is also advisable to look for an obstructed Müllerian system whenever a multicystic dysplastic kidney or the absence of a kidney is discovered in a fetus, or girl postnatally.

  9. Herlyn-Werner-Wunderlich syndrome: uterus didelphys, blind hemivagina and ipsilateral renal agenesis. Sonographic and MR findings in 11 cases

    Energy Technology Data Exchange (ETDEWEB)

    Orazi, Cinzia; Schingo, Paolo M.S. [I.R.C.C.S. Bambino Gesu Pediatric Hospital, Department of Diagnostic Imaging, Rome (Italy); Lucchetti, M. Chiara; Ferro, Fabio [I.R.C.C.S. Bambino Gesu Pediatric Hospital, Operative Unit of Andrological and Gynecological Surgery, Rome (Italy); Marchetti, Paola [I.R.C.C.S. Bambino Gesu Pediatric Hospital, Department of General Surgery, Rome (Italy)

    2007-07-15

    Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis is a rare entity, sometimes referred to as Herlyn-Werner-Wunderlich syndrome (HWW). It usually presents after menarche with progressive pelvic pain, sometimes with regular menses, and a palpable mass due to hemihaematocolpos. The diagnosis is generally made only if the suspicion of this genitourinary syndrome is raised. To highlight the imaging diagnostic clues in this rare condition. We report on 11 adolescents with this condition. Sonography mostly allowed the correct diagnosis by showing uterovaginal duplication, haematocolpos or haematometrocolpos, and the absence of the ipsilateral kidney. MRI provided more detailed information regarding uterine morphology, the continuity with each vaginal channel (obstructed and nonobstructed), and the bloody nature of the contents. Early and accurate diagnosis of this syndrome is important so that adequate and prompt surgical therapy (excision of the vaginal septum) can provide relief of pain and prevent further complications. It is also advisable to look for an obstructed Muellerian system whenever a multicystic dysplastic kidney or the absence of a kidney is discovered in a fetus, or girl postnatally. (orig.)

  10. [Asymmetric obstructed uterus didelphys/incomplete Herlyn-Werner-Wunderlich syndrome/diagnosed by transvaginal 3D ultrasound--a case report].

    Science.gov (United States)

    Markov, D; Slavchev, B; Markov, P; Apostolova, M

    2009-01-01

    Asymmetric obstructed uterus didelphys (Herlyn-Werner-Wunderlich syndrome-HWWS) is a rare congenital Müllerian anomaly consisting of uterus didelphys, hemivaginal septum and ipsilateral renal agenesis. We present a case of an incomplete HWWS diagnosed by 3D transvaginal ultrasound in a 22 year old patient with absence of the hemivaginal septum. The most contributive diagnostic factors as well as the appropriate therapeutic management in such cases are discussed.

  11. A Herlyn-Werner-Wunderlich syndrome variant with ipsilateral renal absence and a contralateral duplex collecting system in a 26-year-old female.

    Science.gov (United States)

    Zhou, Yong; Fu, Xiujuan; Qian, Honglang; Lin, Kaiqing; Wang, Jinhua; Zhou, Shuyang; Hu, Xian; Jin, Hangmei

    2014-01-01

    Herlyn-Werner-Wunderlich syndrome (HWWS) is a müllerian duct anomaly typically associated with a uterus didelphys with two cervices and two vaginas, one of which is obstructed. A remarkable case of HWWS with contralateral duplex kidneys and duplication of ureters is described, which, to our knowledge, is a rarely reported variant to date. For this congenital anomaly, a strong suspicion and knowledge of HWWS are essential for a precise diagnosis. © 2014 S. Karger AG, Basel.

  12. Uterus didelphys with blind hemivagina and ipsilateral renal agenesis (Herlyn-Werner-Wunderlich syndrome) suspected on the presence of hydrocolpos on prenatal sonography.

    Science.gov (United States)

    Han, Byoung Hee; Park, Sung Bin; Lee, Yu Jin; Lee, Kyung Sang; Lee, Yeon Kyung

    2013-01-01

    We report the case of a female neonate with ipsilateral renal agenesis and uterus didelphys with blind hemivagina, also known as Herlyn-Werner-Wunderlich (HWW) syndrome. Prenatal sonography revealed the absence of the left kidney and a retrovesical cystic lesion suspected as hydrometrocolpos. Postnatal evaluation confirmed that the cystic lesion was a hydrocolpos associated with double uterus and blind hemivagina (HWW syndrome). HWW syndrome can be suspected prenatally if a retrovesical cystic lesion is detected in a female fetus with unilateral absence of kidney. Copyright © 2012 Wiley Periodicals, Inc.

  13. Herlyn-Werner-Wunderlich syndrome: merits of sonographic and magnetic resonance imaging for accurate diagnosis and patient management in 13 cases.

    Science.gov (United States)

    Yavuz, Alpaslan; Bora, Aydın; Kurdoğlu, Mertihan; Goya, Cemil; Kurdoğlu, Zehra; Beyazal, Mehmet; Akdemir, Zülküf

    2015-02-01

    To review the main sonographic and magnetic resonance imaging manifestations of Herlyn-Werner-Wunderlich syndrome, characterized by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis, and to discuss the value of techniques for its diagnosis and treatment. Thirteen patients with Herlyn-Werner-Wunderlich syndrome referred to our department with acute abdomen were identified for the period from 2009-2012. Retrospective chart review. Two tertiary academic centers. None. The evaluation of the clinical features, ultrasonography and magnetic resonance imaging findings, and the treatment protocols. Ultrasonographic evaluation of didelphic or double uterus in 10 and bicornuate-bicollis uterus in 3 patients with hematocolpos or hematometrocolpos associated with agenesis of the ipsilateral kidney revealed the diagnosis. In 10 patients, magnetic resonance imaging provided extra information. In 1 patient, a 25-week pregnancy was additionally detected and follow-up was suggested. Seven patients underwent surgical excision of the septum and drainage of the obstructed vagina. Total hysterectomy and hemicolpectomy were performed in 1 patient with 2 children suffering from severe chronic pelvic pain due to pelvic inflammatory disease. Despite its rarity, accurate diagnosis and morphologic description of Herlyn-Werner-Wunderlich syndrome with radiologic modalities are of importance in relieving the clinical complaints by enabling the suitable surgical treatment to be identified. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  14. The DNA repair endonuclease XPG interacts directly and functionally with the WRN helicase defective in Werner syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Trego, Kelly S.; Chernikova, Sophia B.; Davalos, Albert R.; Perry, J. Jefferson P.; Finger, L. David; Ng, Cliff; Tsai, Miaw-Sheue; Yannone, Steven M.; Tainer, John A.; Campisi, Judith; Cooper, Priscilla K.

    2011-04-20

    XPG is a structure-specific endonuclease required for nucleotide excision repair (NER). XPG incision defects result in the cancer-prone syndrome xeroderma pigmentosum, whereas truncating mutations of XPG cause the severe postnatal progeroid developmental disorder Cockayne syndrome. We show that XPG interacts directly with WRN protein, which is defective in the premature aging disorder Werner syndrome, and that the two proteins undergo similar sub-nuclear redistribution in S-phase and co-localize in nuclear foci. The co-localization was observed in mid- to late-S-phase, when WRN moves from nucleoli to nuclear foci that have been shown to contain protein markers of both stalled replication forks and telomeric proteins. We mapped the interaction between XPG and WRN to the C-terminal domains of each and show that interaction with the C-terminal domain of XPG strongly stimulates WRN helicase activity. WRN also possesses a competing DNA single-strand annealing activity that, combined with unwinding, has been shown to coordinate regression of model replication forks to form Holliday junction/chicken foot intermediate structures. We tested whether XPG stimulated WRN annealing activity and found that XPG itself has intrinsic strand annealing activity that requires the unstructured R- and C-terminal domains, but not the conserved catalytic core or endonuclease activity. Annealing by XPG is cooperative, rather than additive, with WRN annealing. Taken together, our results suggest a novel function for XPG in S-phase that is at least in part carried out coordinately with WRN, and which may contribute to the severity of the phenotypes that occur upon loss of XPG.

  15. Reprogramming suppresses premature senescence phenotypes of Werner syndrome cells and maintains chromosomal stability over long-term culture.

    Directory of Open Access Journals (Sweden)

    Akira Shimamoto

    Full Text Available Werner syndrome (WS is a premature aging disorder characterized by chromosomal instability and cancer predisposition. Mutations in WRN are responsible for the disease and cause telomere dysfunction, resulting in accelerated aging. Recent studies have revealed that cells from WS patients can be successfully reprogrammed into induced pluripotent stem cells (iPSCs. In the present study, we describe the effects of long-term culture on WS iPSCs, which acquired and maintained infinite proliferative potential for self-renewal over 2 years. After long-term cultures, WS iPSCs exhibited stable undifferentiated states and differentiation capacity, and premature upregulation of senescence-associated genes in WS cells was completely suppressed in WS iPSCs despite WRN deficiency. WS iPSCs also showed recapitulation of the phenotypes during differentiation. Furthermore, karyotype analysis indicated that WS iPSCs were stable, and half of the descendant clones had chromosomal profiles that were similar to those of parental cells. These unexpected properties might be achieved by induced expression of endogenous telomerase gene during reprogramming, which trigger telomerase reactivation leading to suppression of both replicative senescence and telomere dysfunction in WS cells. These findings demonstrated that reprogramming suppressed premature senescence phenotypes in WS cells and WS iPSCs could lead to chromosomal stability over the long term. WS iPSCs will provide opportunities to identify affected lineages in WS and to develop a new strategy for the treatment of WS.

  16. Differential expression of Werner and Bloom syndrome genes in the peripheral blood of HIV-1 infected patients.

    Science.gov (United States)

    Bordi, Licia; Gioia, Cristiana; Lalle, Eleonora; Piselli, Pierluca; Poccia, Fabrizio; Capobianchi, Maria R; Amendola, Alessandra

    2007-02-01

    Human immunodeficiency virus (HIV)-induced immunodeficiency and immune-system aging share some analogies. Since Werner (WRN) and Bloom (BLM) helicases are crucial in cell repair and aging, their peripheral blood mononuclear cells (PBMC) mRNA levels were compared in HIV-1 infected patients and in normal donors. The mean levels of WRN mRNA were 3.7-fold higher in PBMCs from HIV-1 infected individuals in comparison to healthy donors, whereas BLM mRNA mean levels were slightly higher, although not significantly. WRN increase was positively correlated to CD4 and CD8 T-cell numbers, and also the percentage of naive T lymphocytes, and was observed also in T-cell subsets. Interestingly, a general trend toward increased WRN mRNA levels in individuals with lower viral load was observed, without association with patient age, time of seroconversion, and on/off antiretroviral therapy regimen. On the whole, this study shows that WRN and BLM are differentially modulated in HIV infection, as WRN--but not BLM--is significantly increased, suggesting that mechanisms different from defect or loss of helicase function, observed in WRN and BLM syndromes, may be at the basis of T-cell aging in HIV infection.

  17. Increased frequency of DNA deletions in pink-eyed unstable mice carrying a mutation in the Werner syndrome gene homologue.

    Science.gov (United States)

    Lebel, Michel

    2002-01-01

    Werner syndrome (WS) is a rare autosomal recessive disorder characterized by genomic instability and the premature onset of a number of age-related diseases, including cancers. Accumulating evidence indicates that the WS gene product is involved in resolving aberrant DNA structures that may arise during the process of DNA replication and/or transcription. To estimate the frequency of DNA deletions directly in the skin of mouse embryos, mice with a deletion of part of the murine WRN helicase domain were created. These mutant mice were then crossed to the pink-eyed unstable animals, which have a 70 kb internal duplication at the pink-eyed dilution (p) gene. This report indicates that the frequency of deletion of the duplicated sequence at the p locus is elevated in mice with a mutation in the WRN allele when compared with wild-type mice. In addition, the inhibitor of topoisomerase I camptothecin also increases the frequency of deletion at the p locus. This frequency is even more elevated in WRN mutant mice treated with camptothecin. In contrast, while the inhibition of poly(ADP-ribose) polymerase (PARP) activity by 3-aminobenzamide increases the frequency of DNA deletion, mutant WRN mice are not significantly more sensitive to the inhibition of PARP activity than wild-type animals.

  18. Strand exchange of telomeric DNA catalyzed by the Werner syndrome protein (WRN) is specifically stimulated by TRF2.

    Science.gov (United States)

    Edwards, Deanna N; Orren, David K; Machwe, Amrita

    2014-07-01

    Werner syndrome (WS), caused by loss of function of the RecQ helicase WRN, is a hereditary disease characterized by premature aging and elevated cancer incidence. WRN has DNA binding, exonuclease, ATPase, helicase and strand annealing activities, suggesting possible roles in recombination-related processes. Evidence indicates that WRN deficiency causes telomeric abnormalities that likely underlie early onset of aging phenotypes in WS. Furthermore, TRF2, a protein essential for telomere protection, interacts with WRN and influences its basic helicase and exonuclease activities. However, these studies provided little insight into WRN's specific function at telomeres. Here, we explored the possibility that WRN and TRF2 cooperate during telomeric recombination processes. Our results indicate that TRF2, through its interactions with both WRN and telomeric DNA, stimulates WRN-mediated strand exchange specifically between telomeric substrates; TRF2's basic domain is particularly important for this stimulation. Although TRF1 binds telomeric DNA with similar affinity, it has minimal effects on WRN-mediated strand exchange of telomeric DNA. Moreover, TRF2 is displaced from telomeric DNA by WRN, independent of its ATPase and helicase activities. Together, these results suggest that TRF2 and WRN act coordinately during telomeric recombination processes, consistent with certain telomeric abnormalities associated with alteration of WRN function. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Telomeric protein TRF2 protects Holliday junctions with telomeric arms from displacement by the Werner syndrome helicase.

    Science.gov (United States)

    Nora, Gerald J; Buncher, Noah A; Opresko, Patricia L

    2010-07-01

    WRN protein loss causes Werner syndrome (WS), which is characterized by premature aging as well as genomic and telomeric instability. WRN prevents telomere loss, but the telomeric protein complex must regulate WRN activities to prevent aberrant telomere processing. Telomere-binding TRF2 protein inhibits telomere t-loop deletion by blocking Holliday junction (HJ) resolvase cleavage activity, but whether TRF2 also modulates HJ displacement at t-loops is unknown. In this study, we used multiplex fluorophore imaging to track the fate of individual strands of HJ substrates. We report the novel finding that TRF2 inhibits WRN helicase strand displacement of HJs with telomeric repeats in duplex arms, but unwinding of HJs with a telomeric center or lacking telomeric sequence is unaffected. These data, together with results using TRF2 fragments and TRF2 HJ binding assays, indicate that both the TRF2 B- and Myb domains are required to inhibit WRN HJ activity. We propose a novel model whereby simultaneous binding of the TRF2 B-domain to the HJ core and the Myb domain to telomeric arms promote and stabilize HJs in a stacked arm conformation that is unfavorable for unwinding. Our biochemical study provides a mechanistic basis for the cellular findings that TRF2 regulates WRN activity at telomeres.

  20. Telomere-binding Protein TRF2 Binds to and Stimulates the Werner and Bloom Syndrome Helicases

    National Research Council Canada - National Science Library

    Patricia L. Opresko; Cayetano von Kobbe; Jean-Philippe Laine; Jeanine Harrigan; Ian D. Hickson; Vilhelm A. Bohr

    2002-01-01

    .... This interaction is mediated by the RecQ conserved C-terminal region of WRN. In vitro , TRF2 demonstrates high affinity for WRN and for another RecQ family member, the Bloom syndrome protein (BLM...

  1. MANAGEMENT AND OUTCOME OF HERLYN-WERNER-WUNDERLICH SYNDROME: CONSERVATIVE TREATMENT IN PEDIATRIC AGE

    OpenAIRE

    R. Angotti; Bulotta, A. L.; E. Cerchia; E. Brandigi; Mariscoli, F.; Molinaro, F; Messina, M.

    2014-01-01

    Herlyn–Werner–Wunderlich syndrome (HWWS) is a rare congenital mullerian anomaly consisting of uterus didelphys, hemivaginal septum, and unilateral renal agenesis. Reported data in pediatric age are rare. We report our case of HWWS.

  2. The Werner syndrome protein promotes CAG/CTG repeat stability by resolving large (CAG)(n)/(CTG)(n) hairpins.

    Science.gov (United States)

    Chan, Nelson L S; Hou, Caixia; Zhang, Tianyi; Yuan, Fenghua; Machwe, Amrita; Huang, Jian; Orren, David K; Gu, Liya; Li, Guo-Min

    2012-08-31

    Expansion of CAG/CTG repeats causes certain neurological and neurodegenerative disorders, and the formation and subsequent persistence of stable DNA hairpins within these repeats are believed to contribute to CAG/CTG repeat instability. Human cells possess a DNA hairpin repair (HPR) pathway, which removes various (CAG)(n) and (CTG)(n) hairpins in a nick-directed and strand-specific manner. Interestingly, this HPR system processes a (CTG)(n) hairpin on the template DNA strand much less efficiently than a (CAG)(n) hairpin on the same strand (Hou, C., Chan, N. L., Gu, L., and Li, G. M. (2009) Incision-dependent and error-free repair of (CAG)(n)/(CTG)(n) hairpins in human cell extracts. Nat. Struct. Mol. Biol. 16, 869-875), suggesting the involvement of an additional component for (CTG)(n) HPR. To identify this activity, a functional in vitro HPR assay was used to screen partially purified HeLa nuclear fractions for their ability to stimulate (CTG)(n) HPR. We demonstrate here that the stimulating activity is the Werner syndrome protein (WRN). Although WRN contains both a 3'→5' helicase activity and a 3'→5' exonuclease activity, the stimulating activity was found to be the helicase activity, as a WRN helicase mutant failed to enhance (CTG)(n) HPR. Consistently, WRN efficiently unwound large (CTG)(n) hairpins and promoted DNA polymerase δ-catalyzed DNA synthesis using a (CTG)(n) hairpin as a template. We, therefore, conclude that WRN stimulates (CTG)(n) HPR on the template DNA strand by resolving the hairpin so that it can be efficiently used as a template for repair or replicative synthesis.

  3. The Werner Syndrome Protein Promotes CAG/CTG Repeat Stability by Resolving Large (CAG)n/(CTG)n Hairpins*

    Science.gov (United States)

    Chan, Nelson L. S.; Hou, Caixia; Zhang, Tianyi; Yuan, Fenghua; Machwe, Amrita; Huang, Jian; Orren, David K.; Gu, Liya; Li, Guo-Min

    2012-01-01

    Expansion of CAG/CTG repeats causes certain neurological and neurodegenerative disorders, and the formation and subsequent persistence of stable DNA hairpins within these repeats are believed to contribute to CAG/CTG repeat instability. Human cells possess a DNA hairpin repair (HPR) pathway, which removes various (CAG)n and (CTG)n hairpins in a nick-directed and strand-specific manner. Interestingly, this HPR system processes a (CTG)n hairpin on the template DNA strand much less efficiently than a (CAG)n hairpin on the same strand (Hou, C., Chan, N. L., Gu, L., and Li, G. M. (2009) Incision-dependent and error-free repair of (CAG)n/(CTG)n hairpins in human cell extracts. Nat. Struct. Mol. Biol. 16, 869–875), suggesting the involvement of an additional component for (CTG)n HPR. To identify this activity, a functional in vitro HPR assay was used to screen partially purified HeLa nuclear fractions for their ability to stimulate (CTG)n HPR. We demonstrate here that the stimulating activity is the Werner syndrome protein (WRN). Although WRN contains both a 3′→5′ helicase activity and a 3′→5′ exonuclease activity, the stimulating activity was found to be the helicase activity, as a WRN helicase mutant failed to enhance (CTG)n HPR. Consistently, WRN efficiently unwound large (CTG)n hairpins and promoted DNA polymerase δ-catalyzed DNA synthesis using a (CTG)n hairpin as a template. We, therefore, conclude that WRN stimulates (CTG)n HPR on the template DNA strand by resolving the hairpin so that it can be efficiently used as a template for repair or replicative synthesis. PMID:22787159

  4. The Werner and Bloom syndrome proteins help resolve replication blockage by converting (regressed) holliday junctions to functional replication forks.

    Science.gov (United States)

    Machwe, Amrita; Karale, Rajashree; Xu, Xioahua; Liu, Yilun; Orren, David K

    2011-08-16

    Cells cope with blockage of replication fork progression in a manner that allows DNA synthesis to be completed and genomic instability minimized. Models for resolution of blocked replication involve fork regression to form Holliday junction structures. The human RecQ helicases WRN and BLM (deficient in Werner and Bloom syndromes, respectively) are critical for maintaining genomic stability and thought to function in accurate resolution of replication blockage. Consistent with this notion, WRN and BLM localize to sites of blocked replication after certain DNA-damaging treatments and exhibit enhanced activity on replication and recombination intermediates. Here we examine the actions of WRN and BLM on a special Holliday junction substrate reflective of a regressed replication fork. Our results demonstrate that, in reactions requiring ATP hydrolysis, both WRN and BLM convert this Holliday junction substrate primarily to a four-stranded replication fork structure, suggesting they target the Holliday junction to initiate branch migration. In agreement, the Holliday junction binding protein RuvA inhibits the WRN- and BLM-mediated conversion reactions. Importantly, this conversion product is suitable for replication with its leading daughter strand readily extended by DNA polymerases. Furthermore, binding to and conversion of this Holliday junction are optimal at low MgCl(2) concentrations, suggesting that WRN and BLM preferentially act on the square planar (open) conformation of Holliday junctions. Our findings suggest that, subsequent to fork regression events, WRN and/or BLM could re-establish functional replication forks to help overcome fork blockage. Such a function is highly consistent with phenotypes associated with WRN- and BLM-deficient cells.

  5. Management and outcome of patients with combined vaginal septum, bifid uterus, and ipsilateral renal agenesis (Herlyn-Werner-Wunderlich syndrome).

    Science.gov (United States)

    Gholoum, Suad; Puligandla, Pramod S; Hui, Thomas; Su, Wendy; Quiros, Elsa; Laberge, Jean-Martin

    2006-05-01

    Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare müllerian anomaly consisting of uterine didelphy, hemivaginal septum, and ipsilateral renal agenesis. The purpose of this study was to evaluate the natural history and outcome of patients with HWWS. With ethics review board approval, all patients with uterine/vaginal anomalies were reviewed between 1982 and 2004. Patients with cloacal and/or anorectal anomalies were excluded. Presenting symptoms, preoperative investigations, operative management, and long-term follow-up were assessed. Of 80 patients identified with uterine/vaginal anomalies, 12 had HWWS. Median age at presentation was 13 years. Most patients (11/12) in this series presented with either abdominal pain and/or pelvic masses. Two patients had intra-abdominal abscesses. Seven patients were menstruating at presentation with 4 of these patients having dysmenorrhea. Symptom duration ranged from 0.5 to 12 months. Diagnosis was confirmed by ultrasound (n = 11), computed tomographic scan (n = 3), and/or magnetic resonance imaging (n = 2). Operative management included vaginal septectomy and drainage of the hematocolpos/hematometrocolpos. One patient required salpingectomy for pyosalpinx. Follow-up ultrasounds revealed no recurrent collections. Median follow-up was 3 years (2 months to 16 years). Eleven patients were asymptomatic after treatment. One patient complained of irregular menses. This is one of the largest reviews of HWWS in pediatric patients to date. Good long-term outcome occurs after vaginal septectomy. This diagnosis should be suspected in females with a pelvic mass and ipsilateral renal agenesis.

  6. Herlyn-Werner-Wunderlich Syndrome with Unilateral Hemivaginal Obstruction, Ipsilateral Renal Agenesis, and Contralateral Renal Thin GBM Disease: A Case Report with Radiological Follow Up

    Energy Technology Data Exchange (ETDEWEB)

    Park, Noh Hyuck; Park, Hee Jin; Park, Chan Sup [Myongji Hospital, Kwandong University, Koyang (Korea, Republic of); Park, Sung Il [Bucheon Hospital, Soonchunhyang University, Bucheon (Korea, Republic of)

    2010-08-15

    Herlyn-Werner-Wunderlich syndrome is a rare Mullerian ductal anomaly that is characterized by the presence of a hemivaginal septum, a didelphic uterus and ipsilateral renal agenesis. It is generally difficult to diagnose the uterine malformation before menarche owing to its small size. Therefore, a follow-up study is very important for confirming the uterine malformation in girls with renal agenesis. We report a patient with renal agenesis and microscopic hematuria, who showed symptoms before menarche. A follow-up study eventually revealed uterine didelphys with a hemivaginal obstruction. A biopsy proved that the microscopic hematuria was caused by thin glomerular basement membrane disease of the contralateral kidney

  7. Herlyn-Werner-Wunderlich Syndrome: A Rare Cause of Pelvic Pain and High CA 19-9 Levels in an Adolescent Girl.

    Science.gov (United States)

    Unal, Emel; Tanyildiz, Hikmet Gulsah; Sonmezer, Murat; Erkol, Hatice Gul; Fitoz, Suat

    2016-01-01

    Herlyn-Werner-Wunderlich (HWW) syndrome is a rare developmental anomaly that includes uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis. A 13-year-old girl presented with chronic abdominal pain. Magnetic resonance imaging revealed uterus didelphys, hematometrocolpos and renal agenesis on the right side with imperforate hymen. Subsequently the patient was found to have Mullerian duct anomalies. CA 19-9 level was high. At laparoscopy combined with vaginoscopy hematocolpos was drained following which she improved clinically and CA 19-9 level returned to normal.

  8. Herlyn Werner Wunderlich syndrome: A case of obstructed hemivagina with ipsilateral renal agenesis (OHVIRA syndrome and didelphic uterus

    Directory of Open Access Journals (Sweden)

    A.S. El-agwany

    2014-06-01

    Full Text Available We report a rare case of obstructed hemivagina and ipsilateral renal agenesis (OHVIRA syndrome with a didelphic uterus. A 22-year-old female presented with infertility for one year. Imaging studies revealed an absent left kidney, massive hematometrocolpos on the left side with normal other side. She was diagnosed with OHVIRA syndrome. She underwent septostomy of the vaginal septum, drainage of hematometrocolpos and hysterolaparoscopy that showed a bicornuate uterus and hematosalpinx. Given the rarity of the syndrome it is frequently misdiagnosed. Delayed diagnosis can lead to endometriosis.

  9. PTCH1 +/- dermal fibroblasts isolated from healthy skin of Gorlin syndrome patients exhibit features of carcinoma associated fibroblasts.

    Directory of Open Access Journals (Sweden)

    Alexandre Valin

    Full Text Available Gorlin's or nevoid basal cell carcinoma syndrome (NBCCS causes predisposition to basal cell carcinoma (BCC, the commonest cancer in adult human. Mutations in the tumor suppressor gene PTCH1 are responsible for this autosomal dominant syndrome. In NBCCS patients, as in the general population, ultraviolet exposure is a major risk factor for BCC development. However these patients also develop BCCs in sun-protected areas of the skin, suggesting the existence of other mechanisms for BCC predisposition in NBCCS patients. As increasing evidence supports the idea that the stroma influences carcinoma development, we hypothesized that NBCCS fibroblasts could facilitate BCC occurence of the patients. WT (n = 3 and NBCCS fibroblasts bearing either nonsense (n = 3 or missense (n = 3 PTCH1 mutations were cultured in dermal equivalents made of a collagen matrix and their transcriptomes were compared by whole genome microarray analyses. Strikingly, NBCCS fibroblasts over-expressed mRNAs encoding pro-tumoral factors such as Matrix Metalloproteinases 1 and 3 and tenascin C. They also over-expressed mRNA of pro-proliferative diffusible factors such as fibroblast growth factor 7 and the stromal cell-derived factor 1 alpha, known for its expression in carcinoma associated fibroblasts. These data indicate that the PTCH1(+/- genotype of healthy NBCCS fibroblasts results in phenotypic traits highly reminiscent of those of BCC associated fibroblasts, a clue to the yet mysterious proneness to non photo-exposed BCCs in NBCCS patients.

  10. A Marfan syndrome gene expression phenotype in cultured skin fibroblasts

    Directory of Open Access Journals (Sweden)

    Emond Mary

    2007-09-01

    Full Text Available Abstract Background Marfan syndrome (MFS is a heritable connective tissue disorder caused by mutations in the fibrillin-1 gene. This syndrome constitutes a significant identifiable subtype of aortic aneurysmal disease, accounting for over 5% of ascending and thoracic aortic aneurysms. Results We used spotted membrane DNA macroarrays to identify genes whose altered expression levels may contribute to the phenotype of the disease. Our analysis of 4132 genes identified a subset with significant expression differences between skin fibroblast cultures from unaffected controls versus cultures from affected individuals with known fibrillin-1 mutations. Subsequently, 10 genes were chosen for validation by quantitative RT-PCR. Conclusion Differential expression of many of the validated genes was associated with MFS samples when an additional group of unaffected and MFS affected subjects were analyzed (p-value -6 under the null hypothesis that expression levels in cultured fibroblasts are unaffected by MFS status. An unexpected observation was the range of individual gene expression. In unaffected control subjects, expression ranges exceeding 10 fold were seen in many of the genes selected for qRT-PCR validation. The variation in expression in the MFS affected subjects was even greater.

  11. Clonal analysis of stable chromosome rearrangements in Bloom's syndrome fibroblasts.

    Science.gov (United States)

    Hoehn, H; Salk, D

    1984-04-01

    In situ cytogenetic analysis was performed on colonies derived from single cells of cultured skin fibroblast-like strains from two patients with Bloom's syndrome (GM 1492 and GM 2520). Metaphases in all of the colonies displayed structural chromosome rearrangements. Among 212 metaphases from 24 colonies of GM 1492, only 16% were pseudodiploid, and there was a high incidence of de novo rearrangements within individual colonies. There were two "families" of 16 and five colonies, respectively, each containing identical or related aneusomies, and these could be arranged into pedigrees showing clonal evolution. The heterochromatic region of chromosome #1 and the telomeric regions of chromosome arms 2q, 3q, 4p, and 11q were most frequently involved in the rearrangements. In contrast, strain GM 2520 showed less intraclonal variation, was primarily pseudodiploid, and displayed only three clonal types, one of which had extensive subclonal variation (19 of 24 clones). A remarkable finding in GM 2520 was that, in some clones, extra copies of specific chromosome segments were present as translocations. These results caution against the use of strain GM 1492 as a prototype Bloom's syndrome strain for cell biological studies.

  12. Werner Albrecht (1924 - 2014)

    CERN Multimedia

    2014-01-01

    Werner Albrecht, one of the very first mechanical designers recruited by CERN, passed away on 28 March. Born and educated in Zurich, where he spent the first years of his professional life, he joined CERN in June 1955.   Thanks to his experience and personality, he soon became the deputy to Frank Blythe, the head of the Synchrocyclotron (SC) technical office. The office, which included a large mechanical workshop, had been created in the light of the development and construction of the SC - the first of CERN’s accelerators. For around 25 years Werner kept this position at Frank’s side while the services under their responsibility evolved to become the natural facility to provide design and development for a large range of apparatus required by experimental physicists. After Frank’s retirement in 1980, Werner became head of the office, maintaining its typical character as an efficient, informal and friendly service. Omega, UA1, Aleph, Opal and Delphi are example...

  13. A novel ZRS mutation leads to preaxial polydactyly type 2 in a heterozygous form and Werner mesomelic syndrome in a homozygous form.

    Science.gov (United States)

    VanderMeer, Julia E; Lozano, Reymundo; Sun, Miao; Xue, Yuan; Daentl, Donna; Jabs, Ethylin Wang; Wilcox, William R; Ahituv, Nadav

    2014-08-01

    Point mutations in the zone of polarizing activity regulatory sequence (ZRS) are known to cause human limb malformations. Although most mutations cause preaxial polydactyly (PPD), triphalangeal thumb (TPT) or both, a mutation in position 404 of the ZRS causes more severe Werner mesomelic syndrome (WMS) for which malformations include the distal arm or leg bones in addition to the hands and/or feet. Of more than 15 reported families with ZRS mutations, only one homozygous individual has been reported, with no change in phenotype compared with heterozygotes. Here, we describe a novel point mutation in the ZRS, 402C>T (AC007097.4:g.105548C>T), that is transmitted through two Mexican families with one homozygous individual. The homozygous phenotype for this mutation, WMS, is more severe than the numerous heterozygous individuals genotyped from both families who have TPT and PPD. A mouse transgenic enhancer assay shows that this mutation causes an expansion of the enhancer's expression domain in the developing mouse limb, confirming its pathogenicity. Combined, our results identify a novel ZRS mutation in the Mexican population, 402C>T, and suggest that a dosage effect exists for this ZRS mutation. © 2014 WILEY PERIODICALS, INC.

  14. Clinical and radiological findings for early diagnosis of Herlyn-Werner-Wunderlich syndrome in pediatric age: experience of a single center.

    Science.gov (United States)

    Noviello, Carmine; Romano, Mercedes; Nino, Fabiano; Martino, Ascanio; Cobellis, Giovanni

    2018-01-01

    The authors present their experience in the management of pediatric patients with Herlyn-Werner-Wunderlich syndrome (HWWS) considering clinical classification and anatomical characteristics of the malformation. All the data of the patient presented at our Pediatric Surgery Unit from February 2010 to August 2015 were collected. According to the type of malformations, patients were divided in 3 groups: A (completely obstructed hemivagina), B (incompletely obstructed hemivagina), and C (communication between the duplicated cervices). Six patients were treated in the study period. The mean age was 9 years (2 months-15 years). According to the characteristics of the HWWS, we had 5 patients in group A, 1 in group B, and none in group C. One-stage surgical treatment was performed in all cases of complete obstruction, but in one case a second look was necessary for a better resection of the septum. At a mean follow-up of 18 months all patients were symptoms free. Prognosis of this malformation is good in case of early diagnosis and treatment. We suggest that when a renal agenesia is diagnosed, the patient needs an ultrasonographic follow-up of the contralateral kidney but also of the genital tract to find each minimal abnormalities, furthermore, a MRI scanning before the onset of menstruation can be necessary.

  15. Functional deficiency of fibroblasts heterozygous for Bloom syndrome as specific manifestation of the primary defect.

    OpenAIRE

    Bartram, C R; Rüdiger, H W; Schmidt-Preuss, U; Passarge, E

    1981-01-01

    The effect on the rate of sister chromatid exchanges (SCEs) in Bloom syndrome fibroblasts by cocultivation with Fanconi anemia and xeroderma pigmentosum fibroblasts and with Bloom syndrome heterozygotes was studied. Cells of Fanconi anemia and xeroderma origin reduced the rate of SCEs in Bloom cells by about 45%-50%, just as control cells do. In contrast, heterozygous Bloom cells reduced the rate of SCEs by only 16%-28%. In absolute figures, Fanconi cells reduced the mean rate of SCE in Bloom...

  16. Heisenberg, Prof. Werner Karl

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1935 Honorary. Heisenberg, Prof. Werner Karl Nobel Laureate (Physics) - 1932. Date of birth: 5 December 1901. Date of death: 1 February 1976. YouTube; Twitter; Facebook; Blog. Academy News. IAS Logo. Theory Of Evolution. Posted on 23 January 2018. Joint Statement by the ...

  17. Hysteroscopic management of an oblique vaginal septum in a virgin girl with a rare variant of Herlyn-Werner-Wunderlich syndrome.

    Science.gov (United States)

    Xu, Bin; Xue, Min; Xu, Dabao

    2015-01-01

    To demonstrate a technique for hysteroscopic diagnosis and management of a rare variant of Herlyn-Werner-Wunderlich syndrome (HWWS) in a virgin girl. Presentation of a rare variant of HWWS and a step-by-step description of the technique using videos, images, and title slides (educative video) (Canadian Task Force classification III). HWWS is a congenital anomaly of the urogenital tract, typically characterized by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Of HWWS cases, 11.5% are a rare variant of the syndrome, with a septate bicollis uterus and obstructed hemivagina. HWWS is often diagnosed in adolescent girls and virgin patients. Early diagnosis and treatment should be achieved using a convenient, minimally invasive, and effective surgical approach to prevent complications. A 14-year-old virgin girl had aggressive cyclic dysmenorrhea for 7 months. We made a diagnosis of the non-classic HWWS variant: septate uterus with double cervix, obstructed right hemivagina with hematocolpos, and unilateral renal agenesis. Diagnostic hysteroscopy indicated a flat hemivaginal septum, left cervix, and uterine cavity, but no right cervix or other associated channel. Hysteroscopic incision of the bulging oblique vaginal septum was performed medially from the most prominent point of the septum up to the left cervix and then down to the low edge of the oblique septum. An inflated Foley catheter was placed in the right hemivagina for 2 days to prevent adhesion of the incised septum. Surgery was successful, and the intact hymen was preserved. The patient has been symptom-free for 4 months after surgery. Hysteroscopic incision of the oblique vaginal septum is a convenient, minimally invasive, and effective approach for treating HWWS in adolescents with cyclic dysmenorrhea and hematocolpos. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

  18. Wiedemann-Rautenstrauch (neonatal progeroid) syndrome: new case with normal telomere length in skin fibroblasts.

    Science.gov (United States)

    Korniszewski, L; Nowak, R; Oknińska-Hoffmann, E; Skórka, A; Gieruszczak-Białek, D; Sawadro-Rochowska, M

    2001-10-01

    Wiedemann-Rautenstrauch (neonatal progeroid) syndrome is an autosomal recessive condition with characteristic appearance of premature aging present at birth (aged face, natal teeth, and wrinkled skin). Other features of the syndrome are generalized lipoatrophy with specific fat accumulation in the lateral suprabuttock region, hypotrichosis, macrocephaly (pseudohydrocephalus), and mental retardation. We report on a new case that demonstrates all typical features of the syndrome. The girl is now 16 years and 10 months old and has had follow-up from birth. We measured terminal restriction fragment (TRF) length to evaluate whether the patient's premature aging process is accompanied by shortening of telomere length in her cultured fibroblasts. Mean TRF of 13.5 kb found in our patient's fibroblasts is not shortened as compared to that of normal fibroblasts. Our results differ from those observed in Hutchinson-Gilford progeria. Copyright 2001 Wiley-Liss, Inc.

  19. Gamma-ray-enhanced reactivation of irradiated adenovirus in Xeroderma pigmentosum and Cockayne syndrome fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Jeeves, W.P.; Rainbow, A.J.

    1983-06-01

    A ..gamma..-ray-enhanced reactivation (..gamma..RER) of uv-irradiated as well as of ..gamma..-irradiated human adenovirus type 2 (Ad 2) was detected following infection of normal, Xeroderma pigmentosum (XP), and Cockayne syndrome (CS) fibroblasts that had been preirradiated with ..gamma.. rays. Gamma-irradiated or nonirradiated fibroblasts were infected with either nonirradiated or irradiated Ad 2, and 48 hr after infection cells were examined for the presence of viral structural antigens (Vag) using immunofluorescent staining. Results obtained using seven different normal fibroblast strains showed that irradiation of host monolayers with 1 krad immediately prior to infection resulted in a ..gamma..RER factor +-SE of 4.5 +- 1.6 for uv-irradiated virus and 4.3 +- 1.3 for ..gamma..-irradiated virus. CS fibroblasts, as well as excision repair-deficient XP fibroblasts from complementation groups A and D, were all found to be capable of expressing ..gamma..RER of irradiated Ad 2. XP variant cells expressed lower levels of ..gamma..RER compared to most normal strains, suggesting a possible role for cellular postreplication repair in the mechanism responsible for ER in human cells. An excision-deficient XP fibroblast strain belonging to complementation group A, but derived from a patient afflicted with the severe De Sanctis-Cacchione form of XP, although proficient in ..gamma..RER of ..gamma..-irradiated Ad 2, yielded barely detectable levels of ..gamma..RER for uv-irradiated Ad 2.

  20. The expression of pregnancy-specific {beta}1-glycoprotein genes in Meckel-Gruber syndrome fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Shao-Ming; Cham, Wai-Yee [Georgetown Univ. Medical Center, Washington, DC (United States)

    1994-09-01

    Meckel-Gruber syndrome (MS) is an autosomal recessive disorder with multiple congenital malformations. The only available prenatal diagnostic marker for this disorder is the amniotic fluid level of pregnancy-specific {beta}1-glycoprotein (PSG). PSG is a family of proteins which are expressed at high levels during pregnancy. Increasing maternal serum PSG levels correlate with the progression of pregnancy and can be used as indicators for pregnancy outcome and fetal well-being. The amniotic fluid PSG level is about one-tenth of that of the maternal serum level in normal pregnancy, but are elevated in all cases of MS examined so far. On the other hand, the maternal serum PSG level and third trimester placental PSG content are normal in most cases of MS. This study aims at comparing the expression of PSG in fibroblasts derived from a fetus afflicted with MS. Total cellular RNA was extracted from two MS cultured fibroblast lines (M3206 and GM7817) and four age- and sex-matched control fibroblast lines obtained from the Human Genetic Mutant Cell Repository, Camden, NJ. The expression of eight PSG genes namely, PSG1, PSG2, PSG3, PSG4, PSG5, PSG6, PSG9 and PSG11, were examined with reverse transcription-polymerase chain reaction (RT-PCR). All PSG transcripts present in the cell were first amplified using universal primers in a 28-cycle PCR. Specific PSG gene products were then amplified with PSG gene-specific primers. Results showed that there is no significant difference in PSG expression between control and disease fibroblasts. In both cases, the most abundant transcript was the type II transcript of PSG5 followed by the type I transcripts of PSG1 and PG4. PSG9, PSG11 and PSG 3 were expressed at very low levels or not expressed at all in MS as well as in normal control fibroblasts. These results showed that PSG gene expression was not altered in MS fibroblasts.

  1. Decreased host cell reactivation of UV-irradiated adenovirus 5 by fibroblasts from Cockayne's syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Day, R.S. III; Ziolkowski, C.H.J.; DiMattina, M. (National Cancer Inst., Bethesda, MD (USA))

    1981-11-01

    Over a period of 5 years, 29 experiments were performed in which survival curves of UV-irradiated adenovirus were determined using fibroblast strains from 10 normal persons and from 7 persons having Cockayne's syndrome. In all of these, the survival of UV-irradiated adenovirus 5 was less when assayed using monolayers of fibroblasts from Cockayne's syndrome patients than from normal persons. Survival curves using normal fibroblasts were, within error, straight lines on a log survival vs. linear fluence plot. Survival curves obtained using Cockayne's syndrome fibroblasts showed 2 components: an initial sensitive component, reflecting the behavior of approx. 75% of the infected cells, followed by a component having normal sensitivity. In the 28 experiments that were considered reliable, 58 curves were done using Cockayne's fibroblasts, 41 using normal human fibroblasts. Although experimental variation was encountered, there was no individual case in which sensitivity as measured using Cockayne's was equal to (or less than) the sensitivity measured using normal fibroblasts.

  2. Forssmann, Prof. Werner Theodor Otto

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1967 Honorary. Forssmann, Prof. Werner Theodor Otto Nobel Laureate (Medicine) - 1956. Date of birth: 29 August 1904. Date of death: 1 June 1979. YouTube; Twitter; Facebook; Blog. Academy News. IAS Logo. Theory Of Evolution. Posted on 23 January 2018. Joint Statement by ...

  3. Werner Herzog Tallinnas / Aare Ermel

    Index Scriptorium Estoniae

    Ermel, Aare, 1957-2013

    2002-01-01

    Detsembris toimuvat Pimedate Ööde Filmifestivali laiendatakse ka suvele, et sobivates paikades näidata väärtfilme. Alates 6. juunist näidatakse Katariina kirikus kuuel õhtul algusega kell 22 Werner Herzogi (1942) filme. Režissöörist ja näidatavatest filmidest

  4. Werner Helicase Wings DNA Binding

    OpenAIRE

    Hoadley, Kelly A.; Keck, James L.

    2010-01-01

    In this issue of Structure, Kitano et al. describe the structure of the DNA-bound winged-helix domain from the Werner helicase. This structure of a RecQ/DNA complex offers insights into the DNA unwinding mechanisms of RecQ family helicases.

  5. Werner helicase wings DNA binding.

    Science.gov (United States)

    Hoadley, Kelly A; Keck, James L

    2010-02-10

    In this issue of Structure, Kitano et al. describe the structure of the DNA-bound winged-helix domain from the Werner helicase. This structure of a RecQ/DNA complex offers insights into the DNA-unwinding mechanisms of RecQ family helicases. Copyright 2010 Elsevier Inc. All rights reserved.

  6. Preneoplastic phenotype and chromosome changes of cultured human Bloom syndrome fibroblasts (strain GM 1492).

    Science.gov (United States)

    Brothman, A R; Cram, L S; Bartholdi, M F; Kraemer, P M

    1986-02-01

    The Bloom syndrome fibroblast strain, GM 1492, was examined for phenotypic properties generally associated with neoplastic cells. A serial clonogenicity assay indicated that these cells can proliferate in culture, achieving approximately twice the number of population doublings as compared to normal human skin fibroblasts. Strain GM 1492 appeared to be partially transformed in that these cells showed a slight degree of anchorage independence when grown in methylcellulose, and also appeared to have relaxed growth requirements compared to normal fibroblasts. GM 1492 cells are heteroploid, with 20 to 80 chromosomes/cell and a modal chromosome number of 44. Cytogenetic analysis of G-banded metaphase chromosomes indicated that most cells contained at least one copy of each normal human chromosome, and many cells exhibited only aneuploidies with no detectable chromosomal rearrangements. Minute chromosomes were seen in a few of the metaphase cells examined. GM 1492 cells did not form tumors in athymic nude mice. Since many of the characteristics of GM 1492 cells are similar to those seen only in tumor cells, but the strain is nontumorigenic, we suggest that GM 1492 cells are preneoplastic and thus represent an ideal system for the in vitro study of human neoplastic progression.

  7. Redox Imbalance and Morphological Changes in Skin Fibroblasts in Typical Rett Syndrome

    Directory of Open Access Journals (Sweden)

    Cinzia Signorini

    2014-01-01

    Full Text Available Evidence of oxidative stress has been reported in the blood of patients with Rett syndrome (RTT, a neurodevelopmental disorder mainly caused by mutations in the gene encoding the Methyl-CpG-binding protein 2. Little is known regarding the redox status in RTT cellular systems and its relationship with the morphological phenotype. In RTT patients (n = 16 we investigated four different oxidative stress markers, F2-Isoprostanes (F2-IsoPs, F4-Neuroprostanes (F4-NeuroPs, nonprotein bound iron (NPBI, and (4-HNE PAs, and glutathione in one of the most accessible cells, that is, skin fibroblasts, and searched for possible changes in cellular/intracellular structure and qualitative modifications of synthesized collagen. Significantly increased F4-NeuroPs (12-folds, F2-IsoPs (7.5-folds NPBI (2.3-folds, 4-HNE PAs (1.48-folds, and GSSG (1.44-folds were detected, with significantly decreased GSH (−43.6% and GSH/GSSG ratio (−3.05 folds. A marked dilation of the rough endoplasmic reticulum cisternae, associated with several cytoplasmic multilamellar bodies, was detectable in RTT fibroblasts. Colocalization of collagen I and collagen III, as well as the percentage of type I collagen as derived by semiquantitative immunofluorescence staining analyses, appears to be significantly reduced in RTT cells. Our findings indicate the presence of a redox imbalance and previously unrecognized morphological skin fibroblast abnormalities in RTT patients.

  8. Werner Heisenberg - Life and Work

    CERN Multimedia

    2002-01-01

    Werner Heisenberg (centre) with Wolfgang Pauli (left) and Enrico Fermi on Lake Como, September 1927. An exhibition on the life and work of Werner Heisenberg will be on display in the Main Building (Mezzanine) at CERN from 1 - 23 July. The exhibition was produced by the University Archive of Leipzig University (Gerald Wiemers) and the Max-Planck-Institut für Physik in Munich (Helmut Rechenberg) to mark the centenary of Heisenberg's birth in 1901. German theoretical physicist Werner Karl Heisenberg (5 December 1901 - 1 February 1976) was one of the leading scientists of the 20th century. He carried out important work in nuclear and particle physics, but his most significant contribution was to the development of quantum mechanics. He is best known for his uncertainty principle, which restricts the accuracy with which some properties of atoms and particles - such as position and linear momentum - can be determined simultaneously. In 1932 he was awarded the Noble Prize in Physics 'for the creation of q...

  9. Werner Heisenberg - Life and Work

    CERN Document Server

    2002-01-01

    Werner Heisenberg (centre) with Wolfgang Pauli and Enrico Fermi, 1927. An exhibition on the life and work of Werner Heisenberg will be on display in the Main Building (Mezzanine) at CERN from 1 - 30 July*. German theoretical physicist Werner Karl Heisenberg (1901 - 1976) was one of the leading scientists of the 20th century. Nobel Prize in Physics in 1932, his most significant contribution was to the development of quantum mechanics. He is best known for his uncertainty principle, which restricts the accuracy with which some properties of atoms and particles can be determined simultaneously. Heisenberg was a keen supporter of CERN, and was as the first chairman of CERN's Scientific Policy Committee in October 1954. A related celebration will take place in the TH Amphitheatre (4/3-006), on Thursday 18 July at 16:00. After an introduction from the Director-General Luciano Maiani, his daughter, Barbara Blum, his last postgraduate, Helmut Rechenberg and Valentin Telegdi will evoke memories of the life and work ...

  10. An altered redox balance mediates the hypersensitivity of Cockayne syndrome primary fibroblasts to oxidative stress.

    Science.gov (United States)

    Pascucci, Barbara; Lemma, Tiziana; Iorio, Egidio; Giovannini, Sara; Vaz, Bruno; Iavarone, Ivano; Calcagnile, Angelo; Narciso, Laura; Degan, Paolo; Podo, Franca; Roginskya, Vera; Janjic, Bratislav M; Van Houten, Bennett; Stefanini, Miria; Dogliotti, Eugenia; D'Errico, Mariarosaria

    2012-06-01

    Cockayne syndrome (CS) is a rare hereditary multisystem disease characterized by neurological and development impairment, and premature aging. Cockayne syndrome cells are hypersensitive to oxidative stress, but the molecular mechanisms involved remain unresolved. Here we provide the first evidence that primary fibroblasts derived from patients with CS-A and CS-B present an altered redox balance with increased steady-state levels of intracellular reactive oxygen species (ROS) and basal and induced DNA oxidative damage, loss of the mitochondrial membrane potential, and a significant decrease in the rate of basal oxidative phosphorylation. The Na/K-ATPase, a relevant target of oxidative stress, is also affected with reduced transcription in CS fibroblasts and normal protein levels restored upon complementation with wild-type genes. High-resolution magnetic resonance spectroscopy revealed a significantly perturbed metabolic profile in CS-A and CS-B primary fibroblasts compared with normal cells in agreement with increased oxidative stress and alterations in cell bioenergetics. The affected processes include oxidative metabolism, glycolysis, choline phospholipid metabolism, and osmoregulation. The alterations in intracellular ROS content, oxidative DNA damage, and metabolic profile were partially rescued by the addition of an antioxidant in the culture medium suggesting that the continuous oxidative stress that characterizes CS cells plays a causative role in the underlying pathophysiology. The changes of oxidative and energy metabolism offer a clue for the clinical features of patients with CS and provide novel tools valuable for both diagnosis and therapy. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

  11. Effects of DNA damaging agents on cultured fibroblasts derived from patients with Cockayne syndrome.

    Science.gov (United States)

    Wade, M H; Chu, E H

    1979-01-01

    The cytotoxic action of physical and chemical agents on 10 skin fibroblast strains in culture derived from individuals with Cockayne's syndrome was measured in terms of colony-forming ability. As compared to fibroblasts from normal donors, all Cockayne cell strains tested exhibited a significantly increased sensitivity to UV light and a normal sensitivity to X-rays. Cells from two sets of parents of unrelated Cockayne children showed an intermediate level of UV sensitivity. There was no effect of 0.5 mM caffeine on UV survival in normal and two Cockayne strains tested, indicating that postreplicational repair in Cockayne cells as measured by caffeine sensitivity was probably normal. Sensitivity of normal and Cockayne cells to the chemical carcinogens and mutagens 4NQO, N-AcO-AAF, ICR-170 and EMS was also compared. An increased sensitivity of Cockayne cells to 4NQO or N-AcO-AAF, but not the ICR-170 or EMS, was observed. However, unlike the intermediate UV sensitivity, the cell strains from two parents of Cockayne patients showed the same sensitivity to N-AcO-AAF or 4NQO as fibroblasts from normal individuals. Quantiation of damage to the DNA after 20 J . m-2 UV irradiation indicates normal levels of [3H] thymidine incorporation in the Cockayne cells, in contrast to UV-irradiated xeroderma pigmentosum cells (XP 12BE) in which there was a very low level of repari synthesis. Moreover, we have shown previously that excision of UV-induced pyrimidine dimers in 2 of the 10 Cockayne cell strains was normal.

  12. Decreased cell proliferation and higher oxidative stress in fibroblasts from Down Syndrome fetuses. Preliminary study.

    Science.gov (United States)

    Gimeno, Amparo; García-Giménez, José Luis; Audí, Laura; Toran, Nuria; Andaluz, Pilar; Dasí, Francisco; Viña, José; Pallardó, Federico V

    2014-01-01

    Down Syndrome is the most common chromosomal disease and is also known for its decreased incidence of solid tumors and its progeroid phenotype. Cellular and systemic oxidative stress has been considered as one of the Down Syndrome phenotype causes. We correlated, in a preliminary study, the fibroblast proliferation rate and different cell proliferation key regulators, like Rcan1 and the telomere length from Down Syndrome fetuses, with their oxidative stress profile and the Ribonucleic acid and protein expression of the main antioxidant enzymes together with their activity. Increased oxidized glutathione/glutathione ratio and high peroxide production were found in our cell model. These results correlated with a distorted antioxidant shield. The messenger RNA (SOD1) and protein levels of copper/zinc superoxide dismutase were increased together with a decreased mRNA expression and protein levels of glutathione peroxidase (GPx). As a consequence the [Cu/ZnSOD/(catalase+GPx)] activity ratio increases which explains the oxidative stress generated in the cell model. In addition, the expression of thioredoxin 1 and glutaredoxin 1 is decreased. The results obtained show a decreased antioxidant phenotype that correlates with increased levels of Regulator of calcineurin 1 and attrition of telomeres, both related to oxidative stress and cell cycle impairment. Our preliminary results may explain the proneness to a progeroid phenotype. © 2013.

  13. Werner Kienzle (1936 – 2016)

    CERN Multimedia

    2016-01-01

    Werner was born in Wiernsheim, a small town in Baden-Württemberg close to Stuttgart. His childhood was profoundly marked by the war and the death of his father on the German eastern front.   Despite life after the war being difficult for his family, he was very successful in his academic studies and earned a fellowship at the University of Göttingen, where he did his PhD in solid-state physics. Werner joined CERN in 1964 as a post-doc fellow and he remained at the Organization for his entire career in experimental particle physics. Concerned and eager for peace in the tense context of the cold war, he was deeply involved in collaboration with Russian colleagues and participated in experiments in Serpukhov from 1968 to 1972. Back at CERN, his work concentrated on the search for experimental evidence of the presence of quarks in hadrons. He was among the main initiators of the NA3 experiment at the SPS that measured the structure functions of the pions: the results indicated a cro...

  14. Transcriptome-Wide Expression Profiling in Skin Fibroblasts of Patients with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type

    Science.gov (United States)

    Chiarelli, Nicola; Carini, Giulia; Zoppi, Nicoletta; Dordoni, Chiara; Ritelli, Marco; Venturini, Marina; Castori, Marco; Colombi, Marina

    2016-01-01

    Joint hypermobility syndrome/Ehlers–Danlos syndrome hypermobility type (JHS/EDS-HT), is likely the most common systemic heritable connective tissue disorder, and is mostly recognized by generalized joint hypermobility, joint instability complications, minor skin changes and a wide range of satellite features. JHS/EDS-HT is considered an autosomal dominant trait but is still without a defined molecular basis. The absence of (a) causative gene(s) for JHS/EDS-HT is likely attributable to marked genetic heterogeneity and/or interaction of multiple loci. In order to help in deciphering such a complex molecular background, we carried out a comprehensive immunofluorescence analysis and gene expression profiling in cultured skin fibroblasts from five women affected with JHS/EDS-HT. Protein study revealed disarray of several matrix structural components such as fibrillins, tenascins, elastin, collagens, fibronectin, and their integrin receptors. Transcriptome analysis indicated perturbation of different signaling cascades that are required for homeostatic regulation either during development or in adult tissues as well as altered expression of several genes involved in maintenance of extracellular matrix architecture and homeostasis (e.g., SPON2, TGM2, MMP16, GPC4, SULF1), cell-cell adhesion (e.g., CDH2, CHD10, PCDH9, CLDN11, FLG, DSP), immune/inflammatory/pain responses (e.g., CFD, AQP9, COLEC12, KCNQ5, PRLR), and essential for redox balance (e.g., ADH1C, AKR1C2, AKR1C3, MAOB, GSTM5). Our findings provide a picture of the gene expression profile and dysregulated pathways in JHS/EDS-HT skin fibroblasts that correlate well with the systemic phenotype of the patients. PMID:27518164

  15. U. V. enhanced reactivation of U. V. - and. gamma. -irradiated adenovirus in Cockayne syndrome and Xeroderma pigmentosum fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Jeeves, W.P.; Rainbow, A.J. (McMaster Univ., Hamilton, Ontario (Canada). Dept. of Biology; McMaster Univ., Hamilton (Canada). Dept. of Radiology)

    1983-06-01

    U.V.-enhanced reactivation (UVER) of both U.V.-irradiated and ..gamma..-irradiated human adenovirus type 2 (Ad 2) was examined following the infection of a variety of Cockayne Syndrome (CS) and Xeroderma pigmentosum (XP) fibroblast strains which had been pre-irradiated with U.V. light. U.V.-irradiated or non-irradiated fibroblasts were infected with either non-irradiated or irradiated Ad 2, and at 48 hours after infection cells were examined for the presence of viral structural antigens (Vag) using immunofluorescent staining.

  16. Werner State Structure and Entanglement Classification

    Directory of Open Access Journals (Sweden)

    David W. Lyons

    2012-01-01

    Full Text Available We present applications of the representation theory of Lie groups to the analysis of structure and local unitary classification of Werner states, sometimes called the decoherence-free states, which are states of n quantum bits left unchanged by local transformations that are the same on each particle. We introduce a multiqubit generalization of the singlet state and a construction that assembles these qubits into Werner states.

  17. Apocynin Attenuates Cardiac Injury in Type 4 Cardiorenal Syndrome via Suppressing Cardiac Fibroblast Growth Factor-2 With Oxidative Stress Inhibition.

    Science.gov (United States)

    Liu, Yang; Liu, Yu; Liu, Xun; Chen, Jie; Zhang, Kun; Huang, Feifei; Wang, Jing-Feng; Tang, Wanchun; Huang, Hui

    2015-06-24

    Type 4 cardiorenal syndrome (CRS) refers to the cardiac injury induced by chronic kidney disease. We aimed to assess oxidative stress and cardiac injury in patients with type 4 CRS, determine whether the antioxidant apocynin attenuated cardiac injury in rats with type 4 CRS, and explore potential mechanisms. A cross-sectional study was conducted among patients with type 4 CRS (n=17) and controls (n=16). Compared with controls, patients with type 4 CRS showed elevated oxidative stress, which was significantly correlated with cardiac hypertrophy and decreased ejection fraction. In vivo study, male Sprague-Dawley rats underwent 5/6 subtotal nephrectomy and sham surgery, followed with apocynin or vehicle treatment for 8 weeks. Eight weeks after surgery, the 5/6 subtotal nephrectomy rats mimicked type 4 CRS, showing increased serum creatinine, cardiac hypertrophy and fibrosis, and decreased ejection fraction compared with sham-operated animals. Cardiac malondialdehyde, NADPH oxidase activity, fibroblast growth factor-2, and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation increased significantly in the 5/6 subtotal nephrectomy rats. These changes were significantly attenuated by apocynin. In vitro study showed that apocynin reduced angiotensin II-induced NADPH oxidase-dependent oxidative stress, upregulation of fibroblast growth factor-2 and fibrosis biomarkers, and ERK1/2 phosphorylation in cardiac fibroblasts. Importantly, the ERK1/2 inhibitor U0126 reduced the upregulation of fibroblast growth factor-2 and fibrosis biomarkers in angiotensin II-treated fibroblasts. Oxidative stress is a candidate mediator for type 4 CRS. Apocynin attenuated cardiac injury in type 4 CRS rats via inhibiting NADPH oxidase-dependent oxidative stress-activated ERK1/2 pathway and subsequent fibroblast growth factor-2 upregulation. Our study added evidence to the beneficial effect of apocynin in type 4 CRS. © 2015 The Authors. Published on behalf of the American Heart

  18. Werner coordination chemistry and neurodegeneration.

    Science.gov (United States)

    Telpoukhovskaia, Maria A; Orvig, Chris

    2013-02-21

    Neurodegenerative diseases are capturing the world's attention as being the next set of diseases we must tackle collectively. Not only are the patients experiencing gradual cognitive and physical decline in most cases, but these diseases are fatal with no prevention currently available. As these diseases are progressive, providing care and symptom treatment for the ageing population is becoming both a medical and a financial challenge. This review discusses how Werner coordination chemistry plays a role in three diseases - those of Alzheimer's, Parkinson's, and prions. Metal ions are considered to be involved in these diseases in part via their propensity to cause toxic aggregation of proteins. First, the coordination of metal ions, with emphasis on copper(II), to metalloproteins that are hallmarks of these diseases - amyloid β, α-synuclein, and prion, respectively - will be discussed. We will present the current understanding of the metal coordination environments created by the amino acids of these proteins, as well as metal binding affinity. Second, a diverse set of examples of rationally designed metal chelators to outcompete this deleterious binding will be examined based on coordination mode and affinity toward bio-relevant metal ions. Overall, this review will give a general overview of protein and metal chelator coordination environments in neurodegenerative diseases.

  19. Involvement of antipain-sensitive protease activity in the interferon-beta-induced UV-refractoriness of Cockayne syndrome fibroblasts.

    Science.gov (United States)

    Sugita, K; Suzuki, N; Niimi, H

    1996-10-25

    Fibroblast cells obtained from two siblings and a female patient with Cockayne syndrome (CS), when pretreated with human interferon (HuIFN)-beta prior to irradiation with UV light (254 nm wavelength), exhibited transiently induced fibrinolytic protease activity immediately after the irradiation in association with increased refractoriness to UV cell-killing. A protease inhibitor, antipain, inhibited the induction of protease activity in lysates of the CS fibroblasts from these 3 cases after the combination of HuIFN-beta pretreatment and UV irradiation, whereas elastatinal and 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) inhibited the activity less than antipain did. Antipain also suppressed the increase in UV-refractoriness of HuIFN-beta-pretreated CS fibroblasts, as revealed by culturing cells for 24 h in medium containing the inhibitor immediately after UV exposure and thereafter evaluating the ability of colony formation by the cells. Thus, an antipain-sensitive protease may be involved in the UV-refractoriness induced by HuIFN-beta in CS fibroblast strains.

  20. Complementation of transformed fibroblasts from patients with combined xeroderma pigmentosum-Cockayne syndrome.

    Science.gov (United States)

    Ellison, A R; Nouspikel, T; Jaspers, N G; Clarkson, S G; Gruenert, D C

    1998-08-25

    Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are human hereditary disorders characterized at the cellular level by an inability to repair certain types of DNA damage. Usually, XP and CS are clinically and genetically distinct. However, in rare cases, CS patients have been shown to have mutations in genes that were previously linked to the development of XP. The linkage between XP and CS has been difficult to study because few permanent cell lines have been established from XP/CS patients. To generate permanent cell lines, primary fibroblast cultures from two patients, displaying characteristics associated with CS and belonging to XP complementation group G, were transformed with anorigin-of-replication-deficient simian virus 40 (SV40). The new cell lines, summation operatorXPCS1LVo- and summation operatorXPCS1ROo-,were characterized phenotypically and genotypically to verify that properties of the primary cells are preserved after transformation. The cell lines exhibited rapid growth in culture and were shown, by immunostaining, to express the SV40 T antigen. The summation operatorXPCS1LVo- and summation operatorXPCS1ROo- cell lines were hypersensitive to UV light and had an impaired ability to reactivate a UV-irradiated reporter gene. Using polymerase chain reaction (PCR) amplification and restriction enzyme cleavage, the summation operatorXPCS1ROo- cells were shown to retain the homozygous T deletion at XPG position 2972. This mutation also characterizes the parental primary cells and was evident in the XPG RNA. Finally, to characterize the XPG DNA repair deficiency in these cell lines, an episomal expression vector containing wild-type XPG cDNA was used to correct UV-induced damage in a beta-galactosidase reporter gene. Copyright 1998 Academic Press.

  1. Conservative treatment of a Herlyn-Werner-Wunderlich müllerian anomaly variant, noncommunicating hemiuterus with Gartner duct pseudocyst.

    Science.gov (United States)

    Dorais, Jessie; Milroy, Colleen; Hammoud, Ahmad; Chaudhari, Angela; Gurtcheff, Shawn; Peterson, C Matthew

    2011-01-01

    Asymmetric obstructed uterus didelphys (Herlyn-Werner-Wunderlich syndrome) is a rare congenital müllerian anomaly consisting of uterus didelphys, hemivaginal septum, and ipsilateral renal agenesis. Herein is reported a case of incomplete Herlyn-Werner-Wunderlich syndrome diagnosed using 3-dimensional transvaginal ultrasound in a 14-year-old patient with absence of the hemivaginal septum. The most contributive diagnostic factors and appropriate therapeutic management in such cases are discussed. Copyright © 2011 AAGL. Published by Elsevier Inc. All rights reserved.

  2. Relative repair of adenovirus damaged by sunlamp, UV and gamma-irradiation in Cockayne syndrome fibroblasts is different from that in xeroderma pigmentosum fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Rainbow, A.J. (McMaster Univ., Hamilton, ON (Canada))

    1989-08-01

    The DNA repair capacities of three unrelated Cockayne syndrome (CS) fibroblast strains were compared to that of three unrelated xeroderma pigmentosum (XP) strains for three different DNA damaging agents using a sensitive host cell reactivation (HCR) technique. Adenovirus type 2 (Ad 2) was treated with either UV light, gamma-rays or sunlamp-irradiation and subsequently assayed for its ability to form viral structural antigens (Vag) in the CS and XP strains using immunofluorescent straining, D{sub 37} values for the survival of Ad 2 Vag synthesis in the CS and XP strains, expressed as a percentage of those obtained in normal strains, were used as a measure of DNA repair capacity. Percent HCR values in the XP strains XP25RO, XP2BE and XP5BE respectively were lowest for UV (6, 14 and 6%), intermediate for sunlamp-irradiation (18, 32 and 10%) and highest for gamma-irradiation (65, 61 and 60%), whereas for the CS strains CS1BE, CS3BE and CS278CTO respectively, percent HCR values were lowest for UV (26, 30 and 34%), intermediate for gamma-irradiation (61, 64 and 69%) and near normal for sunlamp-irradiation (82, 73 and 89%). These results suggest that the 'spectrum of lesions' which is defectively repaired in CS is not the same as that which is defectively repaired in XP. (author).

  3. Anisotropy in Werner's binocular depth contrast effect

    NARCIS (Netherlands)

    Ee, R. van; Erkelens, Casper J.

    1996-01-01

    We investigated Werner's binocular depth contrast effect. Subjects viewed stereograms consisting of a test pattern and an inducing pattern. The halfimages of the inducing pattern were either horisontally scaled or sheared relative to each other. Subjects judged the (induced) percieved slant of the

  4. Werner Herzogi üksiklased / Kristiina Davidjants

    Index Scriptorium Estoniae

    Davidjants, Kristiina, 1974-

    2002-01-01

    Detsembris toimuvat Pimedate Ööde Filmifestivali laiendatakse ka suvele, et sobivates paikades näidata väärtfilme. Alates 6. juunist näidatakse Katariina kirikus Werner Herzogi (1942) filme. Lähemalt režissöörist

  5. Books by and about Werner Heisenberg

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 9; Issue 8. Books by and about Werner Heisenberg. N Mukunda. Book Review Volume 9 Issue 8 August 2004 pp 83-86. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/009/08/0083-0086. Author Affiliations.

  6. A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Muenke, M.; Gripp, K.W.; McDonald-McGinn, D.M. [Univ. of Pennsylvania, Philadelphia, PA (United States)] [and others

    1997-03-01

    The underlying basis of many forms of syndromic craniosynostosis has been defined on a molecular level. However, many patients with familial or sporadic craniosynostosis do not have the classical findings of those craniosynostosis syndromes. Here we present 61 individuals from 20 unrelated families where coronal synostosis is due to an amino acid substitution (Pro250Arg) that results from a single point mutation in the fibroblast growth factor receptor 3 gene on chromosome 4p. In this instance, a new clinical syndrome is being defined on the basis of the molecular finding. In addition to the skull findings, some patients had abnormalities on radiographs of hands and feet, including thimble-like middle phalanges, coned epiphyses, and carpal and tarsal fusions. Brachydactyly was seen in some cases; none had clinically significant syndactyly or deviation of the great toe. Sensorineural hearing loss was present in some, and developmental delay was seen in a minority. While the radiological findings of hands and feet can be very helpful in diagnosing this syndrome, it is not in all cases clearly distinguishable on a clinical basis from other craniosynostosis syndromes. Therefore, this mutation should be tested for in patients with coronal synostosis. 54 refs., 4 figs., 2 tabs.

  7. Mitochondrial vulnerability and increased susceptibility to nutrient-induced cytotoxicity in fibroblasts from leigh syndrome French canadian patients.

    Directory of Open Access Journals (Sweden)

    Yan Burelle

    Full Text Available Mutations in LRPPRC are responsible for the French Canadian variant of Leigh Syndrome (LSFC, a severe disorder characterized biochemically by a tissue-specific deficiency of cytochrome c oxidase (COX and clinically by the occurrence of severe and deadly acidotic crises. Factors that precipitate these crises remain unclear. To better understand the physiopathology and identify potential treatments, we performed a comprehensive analysis of mitochondrial function in LSFC and control fibroblasts. Furthermore, we have used this cell-based model to screen for conditions that promote premature cell death in LSFC cells and test the protective effect of ten interventions targeting well-defined aspects of mitochondrial function. We show that, despite maintaining normal ATP levels, LSFC fibroblasts present several mitochondrial functional abnormalities under normal baseline conditions, which likely impair their capacity to respond to stress. This includes mitochondrial network fragmentation, impaired oxidative phosphorylation capacity, lower membrane potential, increased sensitivity to Ca2+-induced permeability transition, but no changes in reactive oxygen species production. We also show that LSFC fibroblasts display enhanced susceptibility to cell death when exposed to palmitate, an effect that is potentiated by high lactate, while high glucose or acidosis alone or in combination were neutral. Furthermore, we demonstrate that compounds that are known to promote flux through the electron transport chain independent of phosphorylation (methylene blue, dinitrophenol, or modulate fatty acid (L-carnitine or Krebs cycle metabolism (propionate are protective, while antioxidants (idebenone, N-acetyl cysteine, resveratrol exacerbate palmitate plus lactate-induced cell death. Collectively, beyond highlighting multiple alterations in mitochondrial function and increased susceptibility to nutrient-induced cytotoxicity in LSFC fibroblasts, these results raise

  8. Early onset Cockayne's syndrome: case reports with neuropathological and fibroblast studies.

    OpenAIRE

    Patton, M A; Giannelli, F; Francis, A J; Baraitser, M; Harding, B; Williams, A J

    1989-01-01

    Two patients with early onset Cockayne's syndrome are presented. In each case there was a striking failure of growth and developmental deterioration around six months of age. It has been suggested that early onset Cockayne's syndrome is a syndrome distinct from Cockayne's syndrome, but when the first patient died aged two years 10 months, examination of the brain showed a leucodystrohy with 'tigroid' demyelination similar to that reported in later onset cases of Cockayne's syndrome. Studies o...

  9. Laparoscopic Strassman metroplasty in a postmenarcheal adolescent girl with Herlyn-Werner-Wunderlich müllerian anomaly variant, obstructed noncommunicating didelphic uterus without gartner duct pseudocyst.

    Science.gov (United States)

    Nabeshima, Hiroshi; Nishimoto, Mitsuo; Shiga, Naomi; Utsunomiya, Hiroki; Yaegashi, Nobuo

    2013-01-01

    Asymmetric obstructed uterus didelphys (Herlyn-Werner-Wunderlich syndrome), also known as obstructed hemivagina with ipsilateral renal agenesis syndrome, is a rare congenital müllerian duct anomaly. Herein we present a case report of incomplete Herlyn-Werner-Wunderlich syndrome, with absence of the hemivaginal septum, diagnosed in a 12-year-old girl. Treatment of the severe pain using an analgesic agent was ineffective. Therefore, laparoscopic metroplastic surgery via the modified Strassman procedure was performed. After surgery, the patient no longer reported dysmenorrhea. Copyright © 2013 AAGL. Published by Elsevier Inc. All rights reserved.

  10. Generation of a clonal induced pluripotent stem cell (iPSC line expressing the mutant MECP2 allele from a Rett Syndrome patient fibroblast line

    Directory of Open Access Journals (Sweden)

    Lisa Hunihan

    2017-04-01

    Full Text Available Human fibroblast cells collected from a 3-year old, female Rett Syndrome patient with a 32 bp deletion in the X-linked MECP2 gene were obtained from the Coriell Institute. Fibroblasts were reprogrammed to iPSC cells using a Sendai-virus delivery system expressing human KOSM transcription factors. Cell-line pluripotency was demonstrated by gene expression, immunocytochemistry, in-vitro differentiation trilineage capacity and was of normal karyotype. Interestingly, subsequent clones retained the epigenetic memory of the parent fibroblasts allowing for the segregation of wild-type and mutant expressing clones. This MECP2 mutant expressing clone may serve as a model for investigating MECP2 reactivation in Rett's Syndrome.

  11. Deficiency in the repair of UV and. gamma. -ray damaged DNA in fibroblasts from Cockayne's syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Rainbow, A.J.; Howes, M. (McMaster Univ., Hamilton, Ontario (Canada). Dept. of Biology; McMaster Univ., Hamilton, Ontario (Canada). Dept. of Radiology)

    1982-01-01

    The host-cell reactivation of V antigen production for irradiated adenovirus was examined in fibroblasts from 5 unrelated patients with Cockayne's syndrome (CS) and 2 CS heterozygotes. The fibroblast cultures were infected with either irradiated or non-irradiated adenovirus and subsequently examined for the presence of viral structural antigens using immunofluorescent staining. All CS-homozygous strains showed a reduced host-cell reactivation (HCR) of this viral function for both UV-and ..gamma..-irradiated virus. For UV-irradiation of the virus, D/sub 37/ values expressed as a percentage of that obtained on normal strains, ranged from 14 to 35%. For ..gamma..-irradiation of the virus these values ranged from 61 to 80%. These results indicate some defect in the repair of both UV- and ..gamma..-ray-induced DNA damage for CS. 1 CS-heterozygote strain tested also showed a reduced HCR for UV-irradiated adenovirus intermediate between that of the patient strain and normal, whereas another CS-heterozygote strain showed an apparently normal HCR level.

  12. The mechanism of inhibition of beta-oxidation by aspirin metabolites in skin fibroblasts from Reye's syndrome patients and controls.

    Science.gov (United States)

    Glasgow, J F; Middleton, B; Moore, R; Gray, A; Hill, J

    1999-05-31

    The effects of aspirin metabolites on beta-oxidation were studied in skin fibroblasts from eight typical Reye's syndrome (RS) patients and controls. RS patients' cells did not differ from controls in rates of palmitate oxidation or in the three component activities of the mitochondrial trifunctional enzyme (MTE), indicating no inherited beta-oxidation defect. Aspirin metabolites salicylate, hydroxyhippurate and gentisate, but not aspirin, directly inhibited palmitate oxidation in control and RS cells. RS cells were significantly more sensitive to inhibition than controls at 0.5 to 5 mM salicylate. Inhibition was concentration-dependent and reversible. Inhibition did not occur in fibroblasts lacking activity of the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) activity of MTE. Salicylate was therefore inhibiting beta-oxidation at this step. Hydroxyhippurate and salicylate reversibly inhibited HAD activities in extracts of control and RS cells. Studies with pure short-chain HAD and LCHAD (MTE) showed hydroxyhippurate and salicylate were competitive inhibitors of the former but mixed (not competitive) inhibitors of the latter. Both compounds inhibited the combined, three-step, MTE reaction measured in the physiological direction. We conclude that (1) salicylate and hydroxyhippurate decrease beta-oxidation in intact cells by reversible inhibition of LCHAD activity of the MTE, and (2) beta-oxidation in RS cells is inherently more sensitive to inhibition by low concentrations of salicylate than controls.

  13. Cholesterol metabolism is altered in Rett syndrome: a study on plasma and primary cultured fibroblasts derived from patients.

    Directory of Open Access Journals (Sweden)

    Marco Segatto

    Full Text Available Rett (RTT syndrome is a severe neurological disorder that affects almost exclusively females. Several detectable mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2 are responsible for the onset of the disease. MeCP2 is a key transcription regulator involved in gene silencing via methylation-dependent remodeling of chromatin. Recent data highlight that lipid metabolism is perturbed in brains and livers of MECP2-null male mice. In addition, altered plasma lipid profile in RTT patients has been observed. Thus, the aim of the work is to investigate the protein network involved in cholesterol homeostasis maintenance on freshly isolated fibroblasts and plasma from both RTT and healthy donors. To this end, protein expression of 3-hydroxy-3methyl glutaryl Coenzyme A reductase (HMGR, sterol regulatory element binding proteins (SREBPs, low density lipoprotein receptor (LDLr and scavenger receptor B-1 (SRB-1 was assessed in cultured skin fibroblasts from unaffected individuals and RTT patients. In addition, lipid profile and the abundance of proprotein convertase subtilisin/kexin type 9 (PCSK9 were analyzed on plasma samples. The obtained results demonstrate that the main proteins belonging to cholesterol regulatory network are altered in RTT female patients, providing the proof of principle that cholesterol metabolism may be taken into account as a new target for the treatment of specific features of RTT pathology.

  14. Verifying bound entanglement of dephased Werner states

    Science.gov (United States)

    Thomas, P.; Bohmann, M.; Vogel, W.

    2017-10-01

    The verification of quantum entanglement under the influence of realistic noise and decoherence is crucial for the development of quantum technologies. Unfortunately, a full entanglement characterization is generally not possible with most entanglement criteria such as entanglement witnesses or the partial transposition criterion. In particular, so-called bound entanglement cannot be certified via the partial transposition criterion. Here we present the full entanglement verification of dephased qubit and qutrit Werner states via entanglement quasiprobabilities. Remarkably, we are able to reveal bound entanglement for noisy mixed states in the qutrit case. This example demonstrates the strength of the entanglement quasiprobabilities for verifying the full entanglement of quantum states suffering from noise.

  15. Richard A. Werners forskning i pengeskabelse

    DEFF Research Database (Denmark)

    2016-01-01

    bank, når den låner penge ud? (2) Centralbankens styring af de private bankers pengeudlån er nøglen til Japans økonomiske succes 1945-1985. Den var inspireret af den tyske Reichsbank i mellemkrigstiden, hvis leder, "kreditdiktatoren" Hjalmar Schacht, styrede den tyske kreditpolitik med fast hånd, i...... aktiver som fast ejendom og aktier. (4) Økonomien som videnskab bør rumme en forståelse af penge. Den klassiske pengekvantitetsligning bør opdateres, så den fokuserer på NYE penge, dvs. kredit. Werners kreditkvantitetsteori skelner mellem spekulativ og produktiv kredit og kan bruges til at forstå og...

  16. The cellular phenotype of Roberts syndrome fibroblasts as revealed by ectopic expression of ESCO2.

    Directory of Open Access Journals (Sweden)

    Petra van der Lelij

    Full Text Available Cohesion between sister chromatids is essential for faithful chromosome segregation. In budding yeast, the acetyltransferase Eco1/Ctf7 establishes cohesion during DNA replication in S phase and in response to DNA double strand breaks in G2/M phase. In humans two Eco1 orthologs exist: ESCO1 and ESCO2. Both proteins are required for proper sister chromatid cohesion, but their exact function is unclear at present. Since ESCO2 has been identified as the gene defective in the rare autosomal recessive cohesinopathy Roberts syndrome (RBS, cells from RBS patients can be used to elucidate the role of ESCO2. We investigated for the first time RBS cells in comparison to isogenic controls that stably express V5- or GFP-tagged ESCO2. We show that the sister chromatid cohesion defect in the transfected cell lines is rescued and suggest that ESCO2 is regulated by proteasomal degradation in a cell cycle-dependent manner. In comparison to the corrected cells RBS cells were hypersensitive to the DNA-damaging agents mitomycin C, camptothecin and etoposide, while no particular sensitivity to UV, ionizing radiation, hydroxyurea or aphidicolin was found. The cohesion defect of RBS cells and their hypersensitivity to DNA-damaging agents were not corrected by a patient-derived ESCO2 acetyltransferase mutant (W539G, indicating that the acetyltransferase activity of ESCO2 is essential for its function. In contrast to a previous study on cells from patients with Cornelia de Lange syndrome, another cohesinopathy, RBS cells failed to exhibit excessive chromosome aberrations after irradiation in G2 phase of the cell cycle. Our results point at an S phase-specific role for ESCO2 in the maintenance of genome stability.

  17. Generation of porcine fibroblasts overexpressing 11β-HSD1 with adipose tissue-specific aP2 promoter as a porcine model of metabolic syndrome.

    Science.gov (United States)

    Jung, Eui-Man; An, Beum-Soo; Kim, Yu-Kyung; Jeong, Young-Hee; Hwang, Woo-Suk; Jeung, Eui-Bae

    2013-09-01

    Metabolic syndrome arises from a combination of disorders that increase the risk of cardiovascular disease and diabetes. In previous studies, it was observed that overexpression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) induced obesity and the insulin resistance that accompanies metabolic syndrome in rodent adipose tissue. Based on these observations, it was hypothesized that overexpression of 11β-HSD1 may be suitable for the generation of a porcine model of metabolic syndrome. It was evaluated that promoter activities of the porcine adipose fatty acid-binding protein (aP2) gene generates adipose tissue-specific 11β-HSD1 expression. In adipose tissue, the maximum promoter activity (-2,826 to +51 nt) of aP2 was 200-fold higher than that of a promoterless construct. In addition, 11β-HSD1 transcriptional levels were significantly increased following the introduction of the aP2 promoter into 3T3‑L1 adipocytes. These observations indicate that the aP2 promoter may facilitate 11β-HSD1 overexpression in porcine adipose tissue. Transgenic fibroblasts were generated containing 11β-HSD1 cDNA controlled by the aP2 promoter with two screening markers, green fluorescence protein and a neomycin-resistance gene. It was hypothesized that transgenic fibroblasts may be useful for generating a porcine model of metabolic syndrome.

  18. The type localities of Anolis aequatorialis Werner, 1894 (Sauria: Iguania: Dactyloidae) and Pristimantis appendiculatus (Werner, 1894) (Amphibia: Anura: Craugastoridae).

    Science.gov (United States)

    Cisneros-Heredia, Diego F

    2017-01-04

    The eminent Austrian zoologist Franz Werner described several new species of amphibians and reptiles from America, including Anolis aequatorialis Werner, 1894 and Hylodes appendiculatus Werner, 1894. Both species were described based on single specimens, with no more specific type localities than "Ecuador" (Werner 1894a,b). After its description, A. aequatorialis remained unreported until Peters (1967) and Fitch et al. (1976) published information on its distribution and natural history. Anolis aequatorialis is currently known to inhabit low montane and cloud forest on the western slopes of the Andes from extreme southern Colombia to central Ecuador, between 1300 and 2300 m elevation (Ayala-Varela & Velasco 2010; Ayala-Varela et al. 2014; Lynch et al. 2014; D.F. Cisneros-Heredia pers. obs.). Likewise, Hylodes appendiculatus (now Pristimantis appendiculatus) remained only known from its type description until Lynch (1971) and Miyata (1980) provided certain localities and information on its natural history. Pristimantis appendiculatus is currently known to occur in low montane, cloud, and high montane forests on the western slopes of the Andes from extreme southern Colombia to northern Ecuador between 1460 and 2800 m elevation (Lynch 1971; Miyata 1980; Lynch & Burrowes 1990; Lynch & Duellman 1997; Frost 2016). To this date, the type localities of both species remain obscure. The purpose of this paper is to restrict the type localities of Hylodes appendiculatus Werner, 1894 and Anolis aequatorialis Werner, 1894 based on analyses of the travel journals of their original collector.

  19. Intrinsic androgen-dependent gene expression patterns revealed by comparison of genital fibroblasts from normal males and individuals with complete and partial androgen insensitivity syndrome

    Directory of Open Access Journals (Sweden)

    Schweikert Hans-Udo

    2007-10-01

    Full Text Available Abstract Background To better understand the molecular programs of normal and abnormal genital development, clear-cut definition of androgen-dependent gene expression patterns, without the influence of genotype (46, XX vs. 46, XY, is warranted. Previously, we have identified global gene expression profiles in genital-derived fibroblasts that differ between 46, XY males and 46, XY females with complete androgen insensitivity syndrome (CAIS due to inactivating mutations of the androgen receptor (AR. While these differences could be due to cell autonomous changes in gene expression induced by androgen programming, recent work suggests they could also be influenced by the location from which the fibroblasts were harvested (topology. To minimize the influence of topology, we compared gene expression patterns of fibroblasts derived from identical urogenital anlagen: the scrotum in normally virilized 46, XY males and the labia majora from completely feminized 46, XY individuals with CAIS. Results 612 transcripts representing 440 unique genes differed significantly in expression levels between scrotum and CAIS labia majora, suggesting the effects of androgen programming. While some genes coincided with those we had identified previously (TBX3, IGFBP5, EGFR, CSPG2, a significant number did not, implying that topology had influenced gene expression in our previous experiments. Supervised clustering of gene expression data derived from a large set of fibroblast cultures from individuals with partial AIS revealed that the new, topology controlled data set better classified the specimens. Conclusion Inactivating mutations of the AR, in themselves, appear to induce lasting changes in gene expression in cultured fibroblasts, independent of topology and genotype. Genes identified are likely to be relevant candidates to decipher androgen-dependent normal and abnormal genital development.

  20. Spontaneous chromosomal aberrations in Fanconi anaemia, ataxia telangiectasia fibroblast and Bloom's syndrome lymphoblastoid cell lines as detected by conventional cytogenetic analysis and fluorescence in situ hybridisation (FISH) technique.

    Science.gov (United States)

    Sakamoto Hojo, E T; van Diemen, P C; Darroudi, F; Natarajan, A T

    1995-02-01

    Several primary and transformed human cell lines derived from cancer prone patients are employed routinely for biochemical and DNA repair studies. Since transformation leads to some chromosomal instability a cytogenetic analysis of spontaneous chromosome aberrations in fibroblast cell lines derived from patients with Fanconi anaemia (FA), ataxia telangiectasia (AT), and in lymphoblastoid cell lines derived from patients with Bloom's syndrome (BS), was undertaken. Unstable aberrations were analysed in Giemsa stained preparations and the chromosome painting technique was used for evaluating the frequencies of stable aberrations (translocations). In addition, the frequency of sister-chromatid exchanges (SCEs) was determined in differentially stained metaphases. The SV40-transformed fibroblasts from these cell lines have higher frequencies of unstable aberrations than the primary fibroblasts. In the four lymphoblastoid cell lines derived from BS patients higher frequencies of spontaneously occurring chromosomal aberrations in comparison to normal TK6wt cells were also evident. The frequency of spontaneously occurring chromosome translocations was determined with fluorescence in situ hybridisation (FISH) and using DNA libraries specific for chromosomes 1, 2, 3, 4, 7, 8, 11, 14, 19, 20 and X. The translocation levels were found to be elevated for primary FA fibroblasts and lymphoblastoid cells derived from BS patients in comparison with control cell lines, hetero- and homozygote BS cell lines not differing in this respect. The SV40-transformed cell lines showed very high frequencies of translocations independent of their origin and almost every cell contained at least one translocation. In addition, clonal translocations were found in transformed control TK6wt and AT cell lines for chromosomes 20 and 14, respectively. The spontaneous frequencies of SCEs were similar in transformed fibroblasts derived from normal individuals and AT patients, whereas in SV40-transformed FA

  1. [Werner Villinger and National Socialist medical crimes].

    Science.gov (United States)

    Schmuhl, H W

    2002-11-01

    The biography of the psychiatrist and neurologist Werner Villinger reflects the ambivalence of the history of German psychiatry during the first half of the twentieth century. Politically committed to the national conservatives, he was attracted by many elements of National Socialist (Nazi) ideology. Still, he joined the party rather late and reluctantly. Villinger was a eugenist by firm conviction. While he still argued against hasty legal regulation of eugenic sterilisations in the Weimar Republic, he strongly moved for translating the law on preventing hereditarily ill progeny into reality in the institution of von Bodelschwingh in Bethel. Since 1941, Villinger, who had become a professor for psychiatry and neurology in Breslau in the meantime, acted as an expert in the framework of the National Socialist "euthanasia" programme. At the same time, however, he supported the quiet diplomacy of Rev. von Bodelschwingh in his attempt to terminate the mass murder. Villinger was also involved in criminal experiments with human beings. After 1945, he successfully continued his career in the Federal Republic of Germany. He never confronted his past during the Third Reich.

  2. Identification of fragile X syndrome specific molecular markers in human fibroblasts: a useful model to test the efficacy of therapeutic drugs.

    Science.gov (United States)

    Kumari, Daman; Bhattacharya, Aditi; Nadel, Jeffrey; Moulton, Kristen; Zeak, Nicole M; Glicksman, Anne; Dobkin, Carl; Brick, David J; Schwartz, Philip H; Smith, Carolyn B; Klann, Eric; Usdin, Karen

    2014-12-01

    Fragile X syndrome (FXS) is the most frequent cause of inherited intellectual disability and autism. It is caused by the absence of the fragile X mental retardation 1 (FMR1) gene product, fragile X mental retardation protein (FMRP), an RNA-binding protein involved in the regulation of translation of a subset of brain mRNAs. In Fmr1 knockout mice, the absence of FMRP results in elevated protein synthesis in the brain as well as increased signaling of many translational regulators. Whether protein synthesis is also dysregulated in FXS patients is not firmly established. Here, we demonstrate that fibroblasts from FXS patients have significantly elevated rates of basal protein synthesis along with increased levels of phosphorylated mechanistic target of rapamycin (p-mTOR), phosphorylated extracellular signal regulated kinase 1/2, and phosphorylated p70 ribosomal S6 kinase 1 (p-S6K1). The treatment with small molecules that inhibit S6K1 and a known FMRP target, phosphoinositide 3-kinase (PI3K) catalytic subunit p110β, lowered the rates of protein synthesis in both control and patient fibroblasts. Our data thus demonstrate that fibroblasts from FXS patients may be a useful in vitro model to test the efficacy and toxicity of potential therapeutics prior to clinical trials, as well as for drug screening and designing personalized treatment approaches. © 2014 WILEY PERIODICALS, INC.

  3. The Werner gap in the presence of simple coloured noise

    Science.gov (United States)

    Cong Tran, Minh; Laskowski, Wiesław; Paterek, Tomasz

    2014-10-01

    The ‘Werner gap’ is the range of relevant parameters characterizing a quantum state for which it is both entangled and admits a local hidden variable model. Werner showed that the gap becomes maximal for entanglement mixed with white noise if subsystems have infinitely many levels. Here we study pure entangled states mixed with simple coloured noise modelled as a single pure product state. We provide an explicit local hidden variable model for quantum correlations of some states of this family and provide hints that there is probably a model for all quantum predictions. This demonstrates essentially a maximal Werner gap already for just two qubits. Additionally to its fundamental interest, the study has implications for quantum computation and communication. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘50 years of Bell’s theorem’.

  4. Protein kinase A subunit expression is altered in Bloom syndrome fibroblasts and the BLM protein is increased in adrenocortical hyperplasias: inverse findings for BLM and PRKAR1A.

    Science.gov (United States)

    Heyerdahl, S L; Boikos, S; Horvath, A; Giatzakis, C; Bossis, I; Stratakis, C A

    2008-06-01

    Bloom syndrome is a genetic disorder associated with chromosomal instability and a predisposition to tumors that is caused by germline mutations of the BLM gene, a RecQ helicase. Benign adrenocortical tumors display a degree of chromosomal instability that is more significant than benign tumors of other tissues. Cortisol-producing hyperplasias, such as primary pigmented nodular adrenocortical disease (PPNAD), which has been associated with protein kinase A (PKA) abnormalities and/or PRKAR1A mutations, also show genomic instability. Another RecQ helicase, WRN, directly interacts with the PRKAR1B subunit of PKA. In this study, we have investigated the PRKAR1A expression in primary human Bloom syndrome cell lines with known BLM mutations and examined the BLM gene expression in PPNAD and other adrenal tumor tissues. PRKAR1A and other protein kinase A (PKA) subunits were expressed in Bloom syndrome cells and their level of expression differed by subunit and cell type. Overall, fibroblasts exhibited a significant decrease in protein expression of all PKA subunits except for PRKAR1A, a pattern that has been associated with neoplastic transformation in several cell types. The BLM protein was upregulated in PPNAD and other hyperplasias, compared to samples from normal adrenals and normal cortex, as well as samples from cortisol- and aldosterone-producing adenomas (in which BLM was largely absent). These data reveal an inverse relationship between BLM and PRKAR1A: BLM deficiency is associated with a relative excess of PRKAR1A in fibroblasts compared to other PKA subunits; and PRKAR1A deficiency is associated with increased BLM protein in adrenal hyperplasias.

  5. Perceived slant from Werner's illusion affects binocular saccadic eye movements

    NARCIS (Netherlands)

    Both, M.H.|info:eu-repo/dai/nl/304844330; van Ee, R.|info:eu-repo/dai/nl/107286912; Erkelens, C.J.|info:eu-repo/dai/nl/069562296

    2003-01-01

    We examined whether binocular saccadic eye movements are determined solely by disparity-defined slant or whether they are influenced by both disparity-defined and perceived slant. The Werner illusion was used to distinguish a plane’s disparity-defined slant from its perceived slant. Three subjects

  6. Dermal fibroblasts in Hutchinson-Gilford progeria syndrome with the lamin A G608G mutation have dysmorphic nuclei and are hypersensitive to heat stress

    Directory of Open Access Journals (Sweden)

    Worman Howard J

    2005-06-01

    Full Text Available Abstract Background Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670 is a rare sporadic disorder with an incidence of approximately 1 per 8 million live births. The phenotypic appearance consists of short stature, sculptured nose, alopecia, prominent scalp veins, small face, loss of subcutaneous fat, faint mid-facial cyanosis, and dystrophic nails. HGPS is caused by mutations in LMNA, the gene that encodes nuclear lamins A and C. The most common mutation in subjects with HGPS is a de novo single-base pair substitution, G608G (GGC>GGT, within exon 11 of LMNA. This creates an abnormal splice donor site, leading to expression of a truncated protein. Results We studied a new case of a 5 year-old girl with HGPS and found a heterozygous point mutation, G608G, in LMNA. Complementary DNA sequencing of RNA showed that this mutation resulted in the deletion of 50 amino acids in the carboxyl-terminal tail domain of prelamin A. We characterized a primary dermal fibroblast cell line derived from the subject's skin. These cells expressed the mutant protein and exhibited a normal growth rate at early passage in primary culture but showed alterations in nuclear morphology. Expression levels and overall distributions of nuclear lamins and emerin, an integral protein of the inner nuclear membrane, were not dramatically altered. Ultrastructural analysis of the nuclear envelope using electron microscopy showed that chromatin is in close association to the nuclear lamina, even in areas with abnormal nuclear envelope morphology. The fibroblasts were hypersensitive to heat shock, and demonstrated a delayed response to heat stress. Conclusion Dermal fibroblasts from a subject with HGPS expressing a mutant truncated lamin A have dysmorphic nuclei, hypersensitivity to heat shock, and delayed response to heat stress. This suggests that the mutant protein, even when expressed at low levels, causes defective cell stability, which may be responsible for phenotypic

  7. Abnormal responses to the carcinogen 4-nitroquinoline 1-oxide of cultured fibroblasts from patients with dysplastic nevus syndrome and hereditary cutaneous malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Smith, P.J.; Greene, M.H.; Adams, D.; Paterson, M.C.

    1983-01-01

    The dysplastic nevus syndrome (DNS) is a preneoplastic melanocyte abnormality which occurs in families affected by hereditary cutaneous malignant melanoma (HCMM). A putative role of host-environmental interactions in the etiology of hereditary melanoma has been strengthened by the recent finding that fibroblasts derived from HCMM/DNS patients demonstrated enhanced sensitivity to u.v.-irradiation in vitro. An extension of these studies is reported in which we have examined the invitro responses to a model environmental carcinogen, 4-nitroquinoline 1-oxide (4NQO), of six non-tumor skin fibroblast strains from HCMM/DNS patients representing five families. Three of the six HCMM/DNS strains showed enhanced cell killing with sensitivities greater than that of a xeroderma pigmentosum (XP) variant strain but less than those of ataxia telangiectasia and XP Group D cell strains. The inhibition and recovery of de novo DNA synthesis, together with the expression of repair synthesis, following 4NQO exposure appeared to be normal in HCMM/DNS strains, irrespective of their subsequent clonogenic potential. The data point to a metabolic anomaly which may contribute to the carcinogenic risk of the melanoma prone preneoplastic state presented by some DNS patients.

  8. Host cell reactivation of ultraviolet light irradiated adenovirus 5 in fibroblasts from patients with Cockayne syndrome. A study with six Japanese cases

    Energy Technology Data Exchange (ETDEWEB)

    Watatani, Masahiro; Ohtani, Hideaki; Takai, Shin-ichiro; Ikenaga, Mituo (Osaka Univ. (Japan). Faculty of Medicine)

    1984-06-01

    Host cell reactivation of plaque-forming ability of ultraviolet light (UV)-irradiated adenovirus 5 was compared between skin fibroblasts derived from 6 unrelated patients with Cockayne syndrome (CS) and those from normal donors. UV survivals of adenovirus were determined with two different virus stocks, one prepared by infecting to HeLa cells and the other prepared from hamster BHK cells. For both of these virus stocks UV survival curves obtained using CS cells showed two components with an initial sensitive portion followed by a component having almost normal sensitivity. This made a marked contrast to the single-hit inactivation curves obtained with normal cells. Consequently, at low UV dose ranges, CS cells were 2 - 3 times less able to reactivate the UV-inactivated adenovirus than normal cells. These results further support our hypothesis that CS cells may be partially defective in excision repair of damaged DNA.

  9. Herlyn-Werner-Wunderlich syndrome with pregnancy: a rare presentation.

    Science.gov (United States)

    Rana, Ritu; Pasrija, Shika; Puri, Manju

    2008-09-01

    Müllerian duct anomalies are infrequently encountered clinical problems and often present with difficulty in diagnosis. A high level of suspicion is the key to diagnosis, which is usually made soon after menarche. However, this is the first reported case of uterus didelphys with obstructed hemivagina and pyocolpos with ipsilateral renal agenesis in which the diagnosis was delayed until pregnancy.

  10. Werner Herzog - saksa kino atleet ja aadlik / Mart Rummo

    Index Scriptorium Estoniae

    Rummo, Mart

    2002-01-01

    Alates 6. juunist näidatakse Katariina kirikus kuuel õhtul algusega kell 22 Werner Herzogi (1942) filme. Väljavõtteid W. Herzogi poolt 1999. aastal Cannes'i festivali järel antud intervjuust, kus juttu ka režissööri suhetest näitleja Klaus Kinskiga, millest kõneleb ka Tallinnas näidatav "Minu armas vaenlane"

  11. Human 45,X fibroblast transcriptome reveals distinct differentially expressed genes including long noncoding RNAs potentially associated with the pathophysiology of Turner syndrome.

    Directory of Open Access Journals (Sweden)

    Shriram N Rajpathak

    Full Text Available Turner syndrome is a chromosomal abnormality characterized by the absence of whole or part of the X chromosome in females. This X aneuploidy condition is associated with a diverse set of clinical phenotypes such as gonadal dysfunction, short stature, osteoporosis and Type II diabetes mellitus, among others. These phenotypes differ in their severity and penetrance among the affected individuals. Haploinsufficiency for a few X linked genes has been associated with some of these disease phenotypes. RNA sequencing can provide valuable insights to understand molecular mechanism of disease process. In the current study, we have analysed the transcriptome profiles of human untransformed 45,X and 46,XX fibroblast cells and identified differential expression of genes in these two karyotypes. Functional analysis revealed that these differentially expressing genes are associated with bone differentiation, glucose metabolism and gonadal development pathways. We also report differential expression of lincRNAs in X monosomic cells. Our observations provide a basis for evaluation of cellular and molecular mechanism(s in the establishment of Turner syndrome phenotypes.

  12. Fibroblastic rheumatism

    Directory of Open Access Journals (Sweden)

    Jyoti Ranjan Parida

    2017-01-01

    Full Text Available Fibroblastic rheumatism (FR is a rare dermoarthopathy reported from different parts of the world since 1980. Although the exact cause is unknown, few reports implicate infection may be a triggering event. Patients usually present with multiple skin nodules and polyarthropathy with progressive skin contractures. Laboratory parameters including acute phase reactants are usually normal. The confirmatory diagnosis is based on histopathologic study of skin nodules, which demonstrate fibroblastic proliferation, thickened collagen fibers, dermal fibrosis, and decreased number of elastic fibers. Immunoreactivity for b-catenin, smooth muscle actin, and the monoclonal antibody HHF35 show myofibroblastic differentiation. Treatments with oral prednisolone and other disease-modifying drugs such as methotrexate, infliximab, and interferon have been tried with variable success. In general, skin lesions respond more aptly than joint symptoms indicating that skin fibroblast is more amenable to treatment than synovial fibroblasts. Awareness regarding this orphan disease among clinicians and pathologists will help in more reporting of such cases and finding out optimal treatment regimen.

  13. DNA single strand break in fibroblast from Down syndrome patients; Pojedyncze pekniecia DNA fibroblastow od osob z zespolem Downa

    Energy Technology Data Exchange (ETDEWEB)

    Rozga, B. [Lodz Univ. (Poland)

    1992-12-31

    The radiosensitivity of tree trisomic (trisomia +21) strains of human fibroblasts to gamma radiation has been investigated in vitro and the causes of induction and repair of single strand DNA breaks in these cells have been estimated. The single strand breaks in DNA of normal and trisomic cells have been found to be ameliorated with an approximately equal efficiency. Repair has been found to be three times slower in trisomic cells compared to their normal relevant, most likely due to their elevated sensitivity to ionizing radiation and the following mortality of trisomic cells, and/or the potential occurrence of a great number of chromosome aberrations in cells irradiated in vitro. (author). 28 refs, 4 figs, 1 tab.

  14. Transcriptome analysis of skin fibroblasts with dominant negative COL3A1 mutations provides molecular insights into the etiopathology of vascular Ehlers-Danlos syndrome.

    Science.gov (United States)

    Chiarelli, Nicola; Carini, Giulia; Zoppi, Nicoletta; Ritelli, Marco; Colombi, Marina

    2018-01-01

    Vascular Ehlers-Danlos syndrome (vEDS) is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene that encodes type III collagen (COLLIII), which is the major expressed collagen in blood vessels and hollow organs. The majority of disease-causing variants in COL3A1 are glycine substitutions and in-frame splice mutations in the triple helix domain that through a dominant negative effect are associated with the severe clinical spectrum potentially lethal of vEDS, characterized by fragility of soft connective tissues with arterial and organ ruptures. To shed lights into molecular mechanisms underlying vEDS, we performed gene expression profiling in cultured skin fibroblasts from three patients with different structural COL3A1 mutations. Transcriptome analysis revealed significant changes in the expression levels of several genes involved in maintenance of cell redox and endoplasmic reticulum (ER) homeostasis, COLLs folding and extracellular matrix (ECM) organization, formation of the proteasome complex, and cell cycle regulation. Protein analyses showed that aberrant COLLIII expression is associated with the disassembly of many structural ECM constituents, such as fibrillins, EMILINs, and elastin, as well as with the reduction of the proteoglycans perlecan, decorin, and versican, all playing an important role in the vascular system. Furthermore, the altered distribution of the ER marker protein disulfide isomerase PDI and the strong reduction of the COLLs-modifying enzyme FKBP22 are consistent with the disturbance of ER-related homeostasis and COLLs biosynthesis and post-translational modifications, indicated by microarray analysis. Our findings add new insights into the pathophysiology of this severe vascular disorder, since they provide a picture of the gene expression changes in vEDS skin fibroblasts and highlight that dominant negative mutations in COL3A1 also affect post-translational modifications and deposition into the ECM of

  15. Transcriptome analysis of skin fibroblasts with dominant negative COL3A1 mutations provides molecular insights into the etiopathology of vascular Ehlers-Danlos syndrome.

    Directory of Open Access Journals (Sweden)

    Nicola Chiarelli

    Full Text Available Vascular Ehlers-Danlos syndrome (vEDS is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene that encodes type III collagen (COLLIII, which is the major expressed collagen in blood vessels and hollow organs. The majority of disease-causing variants in COL3A1 are glycine substitutions and in-frame splice mutations in the triple helix domain that through a dominant negative effect are associated with the severe clinical spectrum potentially lethal of vEDS, characterized by fragility of soft connective tissues with arterial and organ ruptures. To shed lights into molecular mechanisms underlying vEDS, we performed gene expression profiling in cultured skin fibroblasts from three patients with different structural COL3A1 mutations. Transcriptome analysis revealed significant changes in the expression levels of several genes involved in maintenance of cell redox and endoplasmic reticulum (ER homeostasis, COLLs folding and extracellular matrix (ECM organization, formation of the proteasome complex, and cell cycle regulation. Protein analyses showed that aberrant COLLIII expression is associated with the disassembly of many structural ECM constituents, such as fibrillins, EMILINs, and elastin, as well as with the reduction of the proteoglycans perlecan, decorin, and versican, all playing an important role in the vascular system. Furthermore, the altered distribution of the ER marker protein disulfide isomerase PDI and the strong reduction of the COLLs-modifying enzyme FKBP22 are consistent with the disturbance of ER-related homeostasis and COLLs biosynthesis and post-translational modifications, indicated by microarray analysis. Our findings add new insights into the pathophysiology of this severe vascular disorder, since they provide a picture of the gene expression changes in vEDS skin fibroblasts and highlight that dominant negative mutations in COL3A1 also affect post-translational modifications and deposition

  16. Impaired jun-NH2-terminal kinase activation by ultraviolet irradiation in fibroblasts of patients with Cockayne syndrome complementation group B.

    Science.gov (United States)

    Dhar, V; Adler, V; Lehmann, A; Ronai, Z

    1996-06-01

    c-jun-NH2 kinases (JNK) are among the UV-activated protein kinases that play an important role in cellular stress response via the phosphorylation of c-jun, ATF2, and p53. Activation of JNK by UV irradiation requires cooperation between membrane and nuclear components, including DNA lesions per se. The role of DNA lesions in JNK activation led us to explore the inducibility of these kinases in cells of repair-deficient patients. Analyses of primary fibroblast cell lines from patients with Cockayne Syndrome of complementation group B (CS-B) revealed poor JNK activation after UV irradiation in four of five cases when compared with three repair-proficient, normal human fibroblast cell lines. Impaired ability to activate JNK persisted at various time points and with different doses of UV irradiation and coincided with failure of in vitro damaged DNA to activate these kinases. In contrast to UV irradiation, other forms of stress, such as H2O2 or heat shock were capable of inducing JNK activation in CS-B cells. Interestingly, when UV irradiation was administered after osmotic shock, it led to JNK activation in CS-B cells, indicating that alternate signal transduction pathways that are activated in response to other forms of stress can potentiate JNK activation by UV irradiation. Unlike CS-B cells, those of other repair-deficient cells, including xeroderma pigmentosum of different complementation groups, revealed proper activation of JNK by UV irradiation. Together, our findings point to deficiency of JNK activation by UV irradiation in CS-B cells, a phenomenon which may be associated with impaired CS-B, the mutant repair gene in these patients.

  17. Ex vivo treatment with a novel synthetic aminoglycoside NB54 in primary fibroblasts from Rett syndrome patients suppresses MECP2 nonsense mutations.

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    Manuela Vecsler

    Full Text Available BACKGROUND: Nonsense mutations in the X-linked methyl CpG-binding protein 2 (MECP2 comprise a significant proportion of causative MECP2 mutations in Rett syndrome (RTT. Naturally occurring aminoglycosides, such as gentamicin, have been shown to enable partial suppression of nonsense mutations related to several human genetic disorders, however, their clinical applicability has been compromised by parallel findings of severe toxic effects. Recently developed synthetic NB aminoglycosides have demonstrated significantly improved effects compared to gentamicin evident in substantially higher suppression and reduced acute toxicity in vitro. RESULTS: We performed comparative study of suppression effects of the novel NB54 and gentamicin on three MECP2 nonsense mutations (R294X, R270X and R168X common in RTT, using ex vivo treatment of primary fibroblasts from RTT patients harboring these mutations and testing for the C-terminal containing full-length MeCP2. We observed that NB54 induces dose-dependent suppression of MECP2 nonsense mutations more efficiently than gentamicin, which was evident at concentrations as low as 50 µg/ml. NB54 read-through activity was mutation specific, with maximal full-length MeCP2 recovery in R168X (38%, R270X (27% and R294X (18%. In addition, the recovered MeCP2 was translocated to the cell nucleus and moreover led to parallel increase in one of the most important MeCP2 downstream effectors, the brain derived neurotrophic factor (BDNF. CONCLUSION: Our findings suggest that NB54 may induce restoration of the potentially functional MeCP2 in primary RTT fibroblasts and encourage further studies of NB54 and other rationally designed aminoglycoside derivatives as potential therapeutic agents for nonsense MECP2 mutations in RTT.

  18. Accelerated aging syndromes, are they relevant to normal human aging?

    OpenAIRE

    Dreesen, Oliver; Stewart, Colin L.

    2011-01-01

    Hutchinson-Gilford Progeria (HGPS) and Werner syndromes are diseases that clinically resemble some aspects of accelerated aging. HGPS is caused by mutations in theLMNA gene resulting in post-translational processing defects that trigger Progeria in children. Werner syndrome, arising from mutations in the WRN helicase gene, causes premature aging in young adults. What are the molecular mechanism(s) underlying these disorders and what aspects of the diseases resemble physiological human aging? ...

  19. Mitochondrial reactive oxygen species are scavenged by Cockayne syndrome B protein in human fibroblasts without nuclear DNA damage.

    Science.gov (United States)

    Cleaver, James E; Brennan-Minnella, Angela M; Swanson, Raymond A; Fong, Ka-wing; Chen, Junjie; Chou, Kai-ming; Chen, Yih-wen; Revet, Ingrid; Bezrookove, Vladimir

    2014-09-16

    Cockayne syndrome (CS) is a human DNA repair-deficient disease that involves transcription coupled repair (TCR), in which three gene products, Cockayne syndrome A (CSA), Cockayne syndrome B (CSB), and ultraviolet stimulated scaffold protein A (UVSSA) cooperate in relieving RNA polymerase II arrest at damaged sites to permit repair of the template strand. Mutation of any of these three genes results in cells with increased sensitivity to UV light and defective TCR. Mutations in CSA or CSB are associated with severe neurological disease but mutations in UVSSA are for the most part only associated with increased photosensitivity. This difference raises questions about the relevance of TCR to neurological disease in CS. We find that CSB-mutated cells, but not UVSSA-deficient cells, have increased levels of intramitochondrial reactive oxygen species (ROS), especially when mitochondrial complex I is inhibited by rotenone. Increased ROS would result in oxidative damage to mitochondrial proteins, lipids, and DNA. CSB appears to behave as an electron scavenger in the mitochondria whose absence leads to increased oxidative stress. Mitochondrial ROS, however, did not cause detectable nuclear DNA damage even when base excision repair was blocked by an inhibitor of polyADP ribose polymerase. Neurodegeneration in Cockayne syndrome may therefore be associated with ROS-induced damage in the mitochondria, independent of nuclear TCR. An implication of our present results is that mitochondrial dysfunction involving ROS has a major impact on CS-B pathology, whereas nuclear TCR may have a minimal role.

  20. Fibroblast cholesterol efflux to plasma from metabolic syndrome subjects is not defective despite low high-density lipoprotein cholesterol

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Groen, Albert K.; Dallinga-Thie, Geesje M.; de Vries, Rindert; Sluiter, Wim J.; van Tol, Arie

    Objective: We tested whether in metabolic syndrome (MetS) subjects the ability of plasma to stimulate cellular cholesterol efflux. an early step in the anti-atherogenic reverse cholesterol transport pathway. is maintained despite low high-density lipoprotein (HDL) cholesterol. Design: In 76 subjects

  1. Fibroblast cholesterol efflux to plasma from metabolic syndrome subjects is not defective despite low high-density lipoprotein cholesterol

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Groen, Albert K.; Dallinga-Thie, Geesje M.; de Vries, Rindert; Sluiter, Wim J.; van Tol, Arie

    2008-01-01

    OBJECTIVE: We tested whether in metabolic syndrome (MetS) subjects the ability of plasma to stimulate cellular cholesterol efflux, an early step in the anti-atherogenic reverse cholesterol transport pathway, is maintained despite low high-density lipoprotein (HDL) cholesterol. DESIGN: In 76 subjects

  2. Fibroblast cholesterol efflux to plasma from metabolic syndrome subjects is not defective despite low high-density lipoprotein cholesterol

    NARCIS (Netherlands)

    R.P.F. Dullaart (Robin); A. Groen (Albert); G.M. Dallinga-Thie (Geesje); R. de Vries (Rindert); W. Sluiter (Wim); A. van Tol (Arie)

    2008-01-01

    textabstractObjective: We tested whether in metabolic syndrome (MetS) subjects the ability of plasma to stimulate cellular cholesterol efflux, an early step in the anti-atherogenic reverse cholesterol transport pathway, is maintained despite low high-density lipoprotein (HDL) cholesterol. Design: In

  3. Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes

    NARCIS (Netherlands)

    Pitteloud, Nelly; Meysing, Astrid; Quinton, Richard; Acierno, James S.; Dwyer, Andrew A.; Plummer, Lacey; Fliers, Eric; Boepple, Paul; Hayes, Frances; Seminara, Stephanie; Hughes, Viriginia A.; Ma, Jinghong; Bouloux, Pierre; Mohammadi, Moosa; Crowley, William F.

    2006-01-01

    BACKGROUND: Kallmann's syndrome (KS) is a clinically and genetically heterogeneous disorder consisting of idiopathic hypogonadotropic hypogonadism (IHH) and anosmia. Mutations in KAL1 causing the X-linked form of KS have been identified in 10% of all KS patients and consistently result in a severe

  4. Therapeutic potential of gingival fibroblasts for cutaneous radiation syndrome: comparison to bone marrow-mesenchymal stem cell grafts.

    Science.gov (United States)

    Linard, Christine; Tissedre, Frederique; Busson, Elodie; Holler, Valerie; Leclerc, Thomas; Strup-Perrot, Carine; Couty, Ludovic; L'homme, Bruno; Benderitter, Marc; Lafont, Antoine; Lataillade, Jean Jacques; Coulomb, Bernard

    2015-05-15

    Mesenchymal stem cell (MSC) therapy has recently been investigated as a potential treatment for cutaneous radiation burns. We tested the hypothesis that injection of local gingival fibroblasts (GFs) would promote healing of radiation burn lesions and compared results with those for MSC transplantation. Human clinical- grade GFs or bone marrow-derived MSCs were intradermally injected into mice 21 days after local leg irradiation. Immunostaining and real-time PCR analysis were used to assess the effects of each treatment on extracellular matrix remodeling and inflammation in skin on days 28 and 50 postirradiation. GFs induced the early development of thick, fully regenerated epidermis, skin appendages, and hair follicles, earlier than MSCs did. The acceleration of wound healing by GFs involved rearrangement of the deposited collagen, modification of the Col/MMP/TIMP balance, and modulation of the expression and localization of tenascin-C and of the expression of growth factors (VEGF, EGF, and FGF7). As MSC treatment did, GF injection decreased the irradiation-induced inflammatory response and switched the differentiation of macrophages toward an M2-like phenotype, characterized by CD163(+) macrophage infiltration and strong expression of arginase-1. These findings indicate that GFs are an attractive target for regenerative medicine, for easier to collect, can grow in culture, and promote cutaneous wound healing in irradiation burn lesions.

  5. Roles of poly(ADP-ribose) synthesis in repair and replication in normal human, Cockayne syndrome, and xeroderma pigmentosum fibroblasts after UV irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Y.; Goto, K.; Yamamoto, K.; Ichihashi, M.

    1983-01-01

    Roles of poly(ADP-ribose) in repair and replication were studied in UV-irradiated normal, xeroderma pigmentosum (XP), and Cockayne syndrome (CS) fibroblasts. UV radiation reduced cellular NAD with concurrent synthesis of poly-(ADP-ribose) in a dose-dependent manner in normal and CS cells, but not in XP cells. Enzymatic incision of DNA of UV-irradiated XP cells by T4-endonuclease V activated poly(ADP-ribose) polymerase. Methyl methanesulfonate (MMS) also reduced the cellular NAD in all the above strains. However, inhibitors of poly(ADP-ribose) synthesis did not affect UV-induced unscheduled DNA synthesis (UDS) and UV and MMS survivals. Thus, poly(ADP-ribose) synthesis may have a chromatin-stabilizing effect, but not the key role in excision repair of UV damage, unlike in the repair of dimethyl sulfate alkylation. CS cells were deficient in the NAD pool and in the recovery of post-UV DNA synthesis, which were rescued by an exogenous supply of NAD. Such normalization in CS cells was inhibited by excess nicotinamide as in normal cells, suggesting that replicon reinitiation may require specific poly(ADP-ribosyl)ation in UV-irradiated human cells.

  6. [Werner Leibbrand as psychiatric opponent of National Socialism].

    Science.gov (United States)

    Seidel, R

    2013-09-01

    The psychiatrist and medical historian Werner Leibbrand resigned from the Berlin Medical Association after the seizure of power in protest against the exclusion of Jewish colleagues and lost both the license to practice as well as his professional position in the public health service. After the end of the war the American military authorities appointed him as expert witness for the prosecution in the Nürnberg Doctors Trial. In addition to a biographical review, Leibbrand's resolute although still undisputed attitude as ethical expert in the trials will be roughly outlined.

  7. Sensitivity of excision repair in normal human, xeroderma pigmentosum variant and Cockayne's syndrome fibroblasts to inhibition by cytosine arabinoside

    Energy Technology Data Exchange (ETDEWEB)

    Cleaver, J.E.

    1981-08-01

    Inhibition of the gap-filling, polymerizing step of excision repair by 1-..beta..-D-arabinofuranosylcytosine (ara-C) after irradiation with ultraviolet light in human diploid fibroblasts resulted in the formation of persistent DNA strand breaks in G/sub 1/, G/sub 2/, and plateau phase cells, but not in S phase cells. Addition of hydroxyurea to ara-C resulted in partial inhibition of repair in S phase cells. These observations can be explained either in terms of changing roles in repair for different DNA polymerases throughout the cell cycle or by the presence of a pool of deoxycytidine nucleotides during S phase equivalent to an external source of deoxycytidine at 50 ..mu..M concentration. A similar concentration dependence on ara-C was observed for inhibition of repair in normal human, xeroderma pigmentosum (XP) variant, and Cockayne's syndrome cells. Ara-C produced a similar number of breaks in normal and Cockayne's syndrome cells. Ara-C produced a similar number of breaks in normal and Cockayne's syndrome cells but slightly more in XP variant cells. Exonuclease III and S1 nuclease independently both degraded about 50% of the /sup 3/H-thymidine incorporated into repaired regions in the presence of ara-C. Sequential digestion with both enzymes degraded nearly 90% of the repaired regions. These observations can be explained if excision repair proceeds by displacing the damaged strand so that both the /sup 3/H-labeled patch and the damaged region are still ligated to high molecular weight DNA and compete for the same complementary strand during in vitro incubation with the nucleases. The amount of /sup 3/H-thymidine incorporated in DNA by repair decreased with increasing concentrations of ara-C and hydroxyurea, suggesting that the incomplete patches became shorter under these conditions. Extrapolation of the digestion kinetics with exonuclease III permits an estimate of the normal patch size of about 100 nucleotides, consistent with previous estimates.

  8. Modulation of Telomeres in Alternative Lengthening of Telomeres Type I Like Human Cells by the Expression of Werner Protein and Telomerase

    Directory of Open Access Journals (Sweden)

    Aisha Siddiqa

    2012-01-01

    Full Text Available The alternative lengthening of telomeres (ALT is a recombination-based mechanism of telomere maintenance activated in 5–20% of human cancers. In Saccharomyces cerevisiae, survivors that arise after inactivation of telomerase can be classified as type I or type II ALT. In type I, telomeres have a tandem array structure, with each subunit consisting of a subtelomeric Y′ element and short telomere sequence. Telomeres in type II have only long telomere repeats and require Sgs1, the S. cerevisiae RecQ family helicase. We previously described the first human ALT cell line, AG11395, that has a telomere structure similar to type I ALT yeast cells. This cell line lacks the activity of the Werner syndrome protein, a human RecQ helicase. The telomeres in this cell line consist of tandem repeats containing SV40 DNA, including the origin of replication, and telomere sequence. We investigated the role of the SV40 origin of replication and the effects of Werner protein and telomerase on telomere structure and maintenance in AG11395 cells. We report that the expression of Werner protein facilitates the transition in human cells of ALT type I like telomeres to type II like telomeres in some aspects. These findings have implications for the diagnosis and treatment of cancer.

  9. Postprandial changes in glucose oxidation and insulin sensitivity in metabolic syndrome: Influence of fibroblast growth factor 21 and vitamin D status.

    Science.gov (United States)

    Pathak, Kaveri; Soares, Mario J; Zhao, Yun; James, Anthony P; Sherriff, Jillian L; Newsholme, Philip

    2017-05-01

    Metabolic inflexibility due to insulin resistance has been reported in metabolic syndrome (MetS). Fibroblast growth factor 21 (FGF21) and vitamin D status may improve insulin sensitivity. The aim of this study was to investigate glucose-induced thermogenesis and oxidation in MetS, and to examine whether changes in FGF21 or prevailing vitamin D status modulated defined metabolic parameters. Forty-eight overweight and obese older adults (14 men, 34 women; ages 51 ± 15 y) were studied. Resting metabolic rate (RMR) and respiratory quotient (RQ) were measured before and intermittently for 2 h after an oral glucose tolerance test (OGTT). The total area under the curve (TAUC) was calculated. Insulin sensitivity index (ISI) was determined as 10 4 /(insulin × glucose) for fasting and 2 h venous blood. Fat mass (FM) and fat free mass (FFM) were measured by dual-energy x-ray absorptiometry. Participants were grouped by metabolic syndrome (MetS+ for disease presence; MetS- when no disease was present) and by median 25 hydroxyvitamin D (OHD) concentration as VD_low and VD_high. 25 OHD was also tested as a continuous variable. A parsimonious 2 × 2 analysis of variance included age, FM, FFM and MetS × sex interaction. Adjusted RMR was similar between groups but an interactive effect of MetS and sex was noted. Fasting RQ was significantly different between vitamin groups (VD_low: 0.835 ± 0.008 versus VD_high: 0.810 ± 0.008; P = 0.024) and fasting ISI was significantly greater in MetS- compared with MetS+ (P = 0.037). Postglucose increases in thermogenesis, RQ, and FGF21 were significant, but ISI decreased. Adjusted postprandial TAUC_RQ (VD_low: 1.71 ± 0.01; VD_high: 1.74 ± 0.001; P = 0.041) and ISI_2 h (VD_low: 35.41 ± 0.21; VD_high: 101.90 ± 0.21; P = 0.001) were significantly different. Adjusted FGF21 was similar across all comparisons before and after OGTT. Higher vitamin D status, but not FGF21, was associated with greater postprandial

  10. Quantum Errors and Disturbances: Response to Busch, Lahti and Werner

    Directory of Open Access Journals (Sweden)

    David Marcus Appleby

    2016-05-01

    Full Text Available Busch, Lahti and Werner (BLW have recently criticized the operator approach to the description of quantum errors and disturbances. Their criticisms are justified to the extent that the physical meaning of the operator definitions has not hitherto been adequately explained. We rectify that omission. We then examine BLW’s criticisms in the light of our analysis. We argue that, although the BLW approach favour (based on the Wasserstein two-deviation has its uses, there are important physical situations where an operator approach is preferable. We also discuss the reason why the error-disturbance relation is still giving rise to controversies almost a century after Heisenberg first stated his microscope argument. We argue that the source of the difficulties is the problem of interpretation, which is not so wholly disconnected from experimental practicalities as is sometimes supposed.

  11. The history of Werner Spalteholz's Handatlas der Anatomie des Menschen.

    Science.gov (United States)

    Williams, D J

    1999-12-01

    Werner Spalteholz's Handatlas der Anatomie des Menschen is one of the most elegantly illustrated anatomical atlases of all time. Originally published in Leipzig as three volumes from 1895 to 1903, the atlas is still widely used and remains highly regarded by many. The atlas was remarkably popular during the first half of the 20th century, especially the English version in North America and the UK. Unfortunately, the original illustrations and printing plates for the work disappeared following the Second World War and their fate remains a mystery. And, in spite of the atlas's popularity, little is known to the men who prepared the artwork for Spalteholz. It is commonly believed that Max Brödel contributed illustrations to the atlas, but a close examination of the work does not confirm this. A century after its inception, Spalteholz's atlas remains a classic milestone in the history of anatomical illustration.

  12. Nucleolin inhibits G4 oligonucleotide unwinding by Werner helicase.

    Directory of Open Access Journals (Sweden)

    Fred E Indig

    Full Text Available The Werner protein (WRNp, a member of the RecQ helicase family, is strongly associated with the nucleolus, as is nucleolin (NCL, an important nucleolar constituent protein. Both WRNp and NCL respond to the effects of DNA damaging agents. Therefore, we have investigated if these nuclear proteins interact and if this interaction has a possible functional significance in DNA damage repair.Here we report that WRNp interacts with the RNA-binding protein, NCL, based on immunoprecipitation, immunofluorescent co-localization in live and fixed cells, and direct binding of purified WRNp to nucleolin. We also map the binding region to the C-terminal domains of both proteins. Furthermore, treatment of U2OS cells with 15 µM of the Topoisomerase I inhibitor, camptothecin, causes the dissociation of the nucleolin-Werner complex in the nucleolus, followed by partial re-association in the nucleoplasm. Other DNA damaging agents, such as hydroxyurea, Mitomycin C, and aphidicolin do not have these effects. Nucleolin or its C-terminal fragment affected the helicase, but not the exonuclease activity of WRNp, by inhibiting WRN unwinding of G4 tetraplex DNA structures, as seen in activity assays and electrophoretic mobility shift assays (EMSA.These data suggest that nucleolin may regulate G4 DNA unwinding by WRNp, possibly in response to certain DNA damaging agents. We postulate that the NCL-WRNp complex may contain an inactive form of WRNp, which is released from the nucleolus upon DNA damage. Then, when required, WRNp is released from inhibition and can participate in the DNA repair processes.

  13. [The birth of acknowledgement: Michel Foucault and Werner Leibbrand].

    Science.gov (United States)

    Mildenberger, Florian

    2006-01-01

    In 1964, Werner Leibbrand (1896-1974) was the first German medical historian to present, in Sudhoffs Archiv, a review of the work of Michel Foucault (1926-1984). This paper examines some of the reasons leading to the fact that Leibbrand's own generation refused to acknowledge the importance of Foucault's ideas, while, later on, younger German medical historians, although impressed with Foucault's writings, failed to acknowledge, first, the close relationship between Leibbrand's and Foucault's world views, and, second, Leibbrand's attempts at introducing Foucault to German medical historians. Leibbrand with his Jewish wife had survived the Nazi period partly in hiding. His attempts at clearing post-war German psychiatry and medical historiography of NS-sympathizers isolated him among his colleagues, many of whom had begun their career during the Third Reich. Leibbrand enjoyed the support by the Swiss medical historian and avowed Communist Erwin Ackerknecht (1906-1988), but later turned against him, possibly because Acknerknecht had called Leibbrand's writings "unscientific". Leibbrand was unable to overcome his antagonisms with his contemporaries. At the same time, opposition to Ackerknecht made him appear a respresentative of the past in the eyes of the younger generation. Thus, when Foucault was accepted by the latter, they were not prepared to examine the work of Leibbrand and realize how close some of the ideas developed by Leibbrand and Foucault had been.

  14. Genetically determined chromosome instability syndromes.

    Science.gov (United States)

    Schroeder, T M

    1982-01-01

    Spontaneously increased chromosomal instability is well documented in the three autosomal recessive diseases, Fanconi's anemia (FA), Bloom's syndrome (BS), and ataxia telangiectasia (AT). Other conditions have been reported to be associated with chromosomal breakage. Some are still single observations: in Werner's syndrome only fibroblasts are affected, and systemic sclerosis may not be an inherited disease. Various aspects of FA, BS, and AT are discussed which have emerged since recent reviews have been published. The differential diagnosis in FA has become more important than it was in the past. Proven heterogeneity in FA demands definition of what to name FA and FA variants. The analysis of cancer frequencies and types in FA and AT lacks important clues. This should stimulate all of us to mutual exchange of data and creation of registries not only of patients and follow-ups, but also of characterized cell strains. A synopsis of results from cell and cytogenetic studies demonstrates similarities and differences in detail of the general phenomenon of chromosomal instability which FA, BS, and AT share. Results from biochemical studies at the DNA level together with cytogenetic findings indicate different but still undefined failures in DNA metabolism or DNA repair mechanisms due to the different genes. A new approach to analyzing the impairment of DNA repair in FA is briefly described. DNA related enzymes are produced in the cytoplasm and have to be transported to the nucleus. The subcellular distribution of topoisomerase activity was found to be unusual in three placentas of FA patients. Other DNA enzymes were distributed normally. Thus, a specific mechanism for movement of the enzyme through the nuclear membrane seems to be defective.

  15. Frequency of Werner helicase 1367 polymorphism and age-related morbidity in an elderly Brazilian population

    Directory of Open Access Journals (Sweden)

    M.A.C. Smith

    2005-07-01

    Full Text Available Werner syndrome (WS is a premature aging disease caused by a mutation in the WRN gene. The gene was identified in 1996 and its product acts as a DNA helicase and exonuclease. Some specific WRN polymorphic variants were associated with increased risk for cardiovascular diseases. The identification of genetic polymorphisms as risk factors for complex diseases affecting older people can improve their prevention, diagnosis and prognosis. We investigated WRN codon 1367 polymorphism in 383 residents in a district of the city of São Paulo, who were enrolled in an Elderly Brazilian Longitudinal Study. Their mean age was 79.70 ± 5.32 years, ranging from 67 to 97. This population was composed of 262 females (68.4% and 121 males (31.6% of European (89.2%, Japanese (3.3%, Middle Eastern (1.81%, and mixed and/or other origins (5.7%. There are no studies concerning this polymorphism in Brazilian population. These subjects were evaluated clinically every two years. The major health problems and morbidities affecting this cohort were cardiovascular diseases (21.7%, hypertension (83.7%, diabetes (63.3%, obesity (41.23%, dementia (8.0%, depression (20.0%, and neoplasia (10.8%. Their prevalence is similar to some urban elderly Brazilian samples. DNA was isolated from blood cells, amplified by PCR and digested with PmaCI. Allele frequencies were 0.788 for the cysteine and 0.211 for the arginine. Genotype distributions were within that expected for the Hardy-Weinberg equilibrium. Female gender was associated with hypertension and obesity. Logistic regression analysis did not detect significant association between the polymorphism and morbidity. These findings confirm those from Europeans and differ from Japanese population.

  16. Lyman-Werner escape fractions from the first galaxies

    Science.gov (United States)

    Schauer, Anna T. P.; Agarwal, Bhaskar; Glover, Simon C. O.; Klessen, Ralf S.; Latif, Muhammad A.; Mas-Ribas, Lluís; Rydberg, Claes-Erik; Whalen, Daniel J.; Zackrisson, Erik

    2017-05-01

    Direct collapse black holes forming in pristine, atomically cooling haloes at z ≈ 10-20 may act as the seeds of supermassive black holes (BHs) at high redshifts. In order to create a massive BH seed, the host halo needs to be prevented from forming stars. H2 therefore needs to be irradiated by a large flux of Lyman-Werner (LW) UV photons in order to suppress H2 cooling. A key uncertainty in this scenario is the escape fraction of LW radiation from first galaxies, which is the dominant source of UV photons at this epoch. To better constrain this escape fraction, we have performed radiation-hydrodynamical simulations of the growth of H II regions and their associated photodissociation regions in the first galaxies using the zeus-mp code. We find that the LW escape fraction crucially depends on the propagation of the ionization front (I-front). For an R-type I-front overrunning the halo, the LW escape fraction is always larger than 95 per cent. If the halo recombines later from the outside-in, due to a softened and weakened spectrum, the LW escape fraction in the rest frame of the halo (the near-field) drops to zero. A detailed and careful analysis is required to analyse slowly moving, D-type I-fronts, where the escape fraction depends on the microphysics and can be as small as 3 per cent in the near-field and 61 per cent in the far-field or as large as 100 per cent in both the near-field and the far-field.

  17. Alfred Werner's role in the mid-20th century flourishing of American inorganic chemistry.

    Science.gov (United States)

    Labinger, Jay A

    2014-01-01

    The development of organic and physical chemistry as specialist fields, during the middle and end of the 19th century respectively, left inorganic behind as a decidedly less highly regarded subfield of chemistry. Despite Alfred Werner's groundbreaking studies of coordination chemistry in the early 20th century, that inferior status remained in place - particularly in the US - until the 1950s, when the beginnings of a resurgence that eventually restored its parity with the other subfields can be clearly observed. This paper explores the extent to which Werner's heritage - both direct, in the form of academic descendants, and indirect - contributed to those advances.

  18. On the Work of the German-American Artist Werner Klotz

    DEFF Research Database (Denmark)

    Kacunko, Slavko

    2010-01-01

    as it was interesting then, to observe how in Werner Klotz’s oeuvre, following an artistic logic, they entered into a symbiosis with the closed-circuit video installations but have ultimately left that stage to today’s world-wide Public Art. Especially in his current public installations and projects, Werner Klotz...... succeeds in raising the intense art of self-experience begun in the earlier example, onto a plane of experiencing the world, and in setting up a relationship between intersubjectivity and the as yet little researched phenomenon of interobjectivity....

  19. Generation of Werner-like stationary states of two qubits in a thermal reservoir

    Energy Technology Data Exchange (ETDEWEB)

    Jakobczyk, Lech, E-mail: ljak@ift.uni.wroc.p [Institute of Theoretical Physics, University of Wroclaw, Plac Maxa Borna 9, 50-204 Wroclaw (Poland)

    2010-01-14

    The dynamics of entanglement between two-level atoms immersed in the common photon reservoir at finite temperature is investigated. It is shown that in the regime of strong correlations there are nontrivial asymptotic states which can be interpreted in terms of thermal generalization of Werner states.

  20. Generation of Werner states and preservation of entanglement in a noisy environment

    Energy Technology Data Exchange (ETDEWEB)

    Jakobczyk, Lech [Institute of Theoretical Physics, University of Wroclaw, Pl. M. Borna 9, 50-204 Wroclaw (Poland)]. E-mail: ljak@ift.uni.wroc.pl; Jamroz, Anna [Institute of Theoretical Physics, University of Wroclaw, Pl. M. Borna 9, 50-204 Wroclaw (Poland)

    2005-12-05

    We study the influence of noisy environment on the evolution of two-atomic system in the presence of collective damping. Generation of Werner states as asymptotic stationary states of evolution is described. We also show that for some initial states the amount of entanglement is preserved during the evolution.

  1. A PAIDERASTIA SOB O HISTORICISMO DE WERNER JAEGER. (Dossiê: O Mundo Antigo: Literatura e Historiografia

    Directory of Open Access Journals (Sweden)

    Daniel Barbo

    2015-09-01

    Full Text Available Resumo: Este texto faz uma análise do modo historicista com que o historiador alemão Werner Jaeger, nas décadas de 1930 e 1940, aborda o homoerotismo grego (paiderastia e sua relação com a pedagogia em sua obra Paidéia, a formação do homem grego. Palavras-Chave: Homoerotismo Grego, Historicismo, Werner Jaeger Abstract: This text analyzes the historicist manner with which the German historian Werner Jaeger, in the 1930s and 1940s, addresses the Greek homoeroticism (paiderastia and its relation to pedagogy in his work Paideia, the ideals of the Greek culture. Keywords: Greek Homoerotiscism, Historicism, Werner Jaeger Recebido em: 069/08/2015  – Aceito em 10/09/2015

  2. Peroxisomal very long-chain fatty acid [beta]-oxidation in human skin fibroblasts: activity in Zellweger syndrome and other peroxisomal disorders

    NARCIS (Netherlands)

    Wanders, R.J.A.; Roermund, C.W.T. van; Wijland, M.J.A. van; Heikoop, J.; Schutgens, R.B.H.; Schram, A.W.; Tager, J.M.; Bosch, H. van den; Poll-Thé, B.T.; Saudubray, J.M.; Moser, H.W.; Moser, A.B.

    1987-01-01

    Since very long-chain fatty acids with a chain length of 24 carbons or more are known to accumulate in tissues and body fluids from patients with the cerebro-hepato-renal (Zellweger) syndrome, infantile Refsum disease, neonatal adrenoleukodystrophy and X-linked adrenoleukodystrophy, we studied very

  3. Heinz Werner: His Life, Ideas, and Contributions to Developmental Psychology in the First Half of the 20th Century.

    Science.gov (United States)

    Ostler, Teresa

    2016-01-01

    The author provides an overview of Heinz Werner's life and contributions to the field of developmental psychology during the first half of the 20th century. She focuses on his early work in Vienna and Munich as well as his tenure at the Psychological Institute in Hamburg, up through the time when he became a named Professor in Psychology at Clark University. Recognized as one of the founders of developmental psychology, Heinz Werner worked in the areas of perceptual development, comparative psychology, and symbol formation. Versatile in rigorous experimental methodologies, and in observational and phenomenological methodologies, Werner's approach to development stood in contrast to other approaches of development, both past and current. For Werner, development was a heuristic, a way of looking at processes in a variety of domains, including ontogeny, phylogeny, microgenesis, biology, developmental psychopathology, neuropsychology, and comparative psychology. Werner viewed development as proceeding from a state of relative globality and lack of differentiation to a state of increasing differentiation, articulation, and hierarchical integration, but he also stressed that individuals can function at different developmental levels under different times and conditions. Werner's holistic, organismic, comparative, and contextual approach to development transcended interdisciplinary boundaries, allowing him to study the interrelatedness between thought, language, feeling, perception, and culture.

  4. Using drug treatments to control genome behaviour in normal and Hutchinson-Gilford Progeria Syndrome fibroblasts, with and without hTERT immortalisation

    OpenAIRE

    Bikkul, Mehmet Ural

    2016-01-01

    This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University London Hutchinson-Gilford Progeria Syndrome (HGPS) is an exceedingly rare genetic condition with striking features reminiscent of marked premature ageing. HGPS is commonly caused by a ‘classic’ mutation in the A-type lamin gene, LMNA (G608G). This leads to the expression of an aberrant truncated lamin A protein, progerin. The nuclear lamina is known to anchor chromosomes, stabilising and re...

  5. Fragmentation inside atomic cooling haloes exposed to Lyman-Werner radiation

    Science.gov (United States)

    Regan, John A.; Downes, Turlough P.

    2018-01-01

    Supermassive stars born in pristine environments in the early Universe hold the promise of being the seeds for the supermassive black holes observed as high redshift quasars shortly after the epoch of reionisation. {H_2} suppression is thought to be crucial in order to negate normal Population III star formation and allow high accretion rates to drive the formation of supermassive stars. Only in the cases where vigorous fragmentation is avoided will a monolithic collapse be successful giving rise to a single massive central object. We investigate the number of fragmentation sites formed in collapsing atomic cooling haloes subject to various levels of background Lyman-Werner flux. The background Lyman-Werner flux manipulates the chemical properties of the gas in the collapsing halo by destroying {H_2}. We find that only when the collapsing gas cloud shifts from the molecular to the atomic cooling regime is the degree of fragmentation suppressed. In our particular case we find that this occurs above a critical Lyman-Werner background of J ˜ 10 J21. The important criterion being the transition to the atomic cooling regime rather than the actual value of J, which will vary locally. Once the temperature of the gas exceeds T ≳ 104 K and the gas transitions to atomic line cooling, then vigorous fragmentation is strongly suppressed.

  6. Defective DSB repair correlates with abnormal nuclear morphology and is improved with FTI treatment in Hutchinson-Gilford progeria syndrome fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Constantinescu, Dan [Department of Cell Biology-Physiology, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Pittsburgh Development Center, Magee-Women' s Research Institute, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Csoka, Antonei B. [Division of Geriatrics, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15260 (United States); Navara, Christopher S. [Division of Developmental and Regenerative Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Pittsburgh Development Center, Magee-Women' s Research Institute, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Schatten, Gerald P., E-mail: schattengp@upmc.edu [Division of Developmental and Regenerative Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Department of Cell Biology-Physiology, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Pittsburgh Development Center, Magee-Women' s Research Institute, University of Pittsburgh, Pittsburgh, PA 15260 (United States)

    2010-10-15

    Impaired DSB repair has been implicated as a molecular mechanism contributing to the accelerating aging phenotype in Hutchinson-Gilford progeria syndrome (HGPS), but neither the extent nor the cause of the repair deficiency has been fully elucidated. Here we perform a quantitative analysis of the steady-state number of DSBs and the repair kinetics of ionizing radiation (IR)-induced DSBs in HGPS cells. We report an elevated steady-state number of DSBs and impaired repair of IR-induced DSBs, both of which correlated strongly with abnormal nuclear morphology. We recreated the HGPS cellular phenotype in human coronary artery endothelial cells for the first time by lentiviral transduction of GFP-progerin, which also resulted in impaired repair of IR-induced DSBs, and which correlated with abnormal nuclear morphology. Farnesyl transferase inhibitor (FTI) treatment improved the repair of IR-induced DSBs, but only in HGPS cells whose nuclear morphology was also normalized. Interestingly, FTI treatment did not result in a statistically significant reduction in the higher steady-state number of DSBs. We also report a delay in localization of phospho-NBS1 and MRE11, MRN complex repair factors necessary for homologous recombination (HR) repair, to DSBs in HGPS cells. Our results demonstrate a correlation between nuclear structural abnormalities and the DSB repair defect, suggesting a mechanistic link that may involve delayed repair factor localization to DNA damage. Further, our results show that similar to other HGPS phenotypes, FTI treatment has a beneficial effect on DSB repair.

  7. Relation between replicative senescence of human fibroblasts and life history characteristics

    NARCIS (Netherlands)

    Maier, Andrea B.; Westendorp, Rudi G J

    Replicative ageing of fibroblasts in vitro has often been used as a model for organismal ageing. The general assumption that the ageing process is mirrored by cellular senescence in vitro is based on lower replicative capacity of human fibroblasts from patients with accelerated ageing syndromes,

  8. Werner Forssmann - A Nobel Prize Winner and His Political Attitude before and after 1945.

    Science.gov (United States)

    Packy, Lisa-Maria; Krischel, Matthis; Gross, Dominik

    2016-01-01

    In 1956, the Nobel Prize in Physiology or Medicine was awarded jointly to Werner Forssmann, André Frédéric Cournand and Dickinson W. Richards for their development of cardiac catheterization. Forssmann performed a self-experiment in 1929 by inserting a urethral catheter into his right ventricular cavity via his antecubital vein. Despite his popularity as one of the first German Nobel Laureates after 1945, little is known about Forssmann personally. This contribution aims to close this gap regarding the Nazi period and early post-war Germany. Primary historical sources from Forssmann's private archive were examined, evaluated and interpreted for the first time. Additionally, a comparative analysis based on further archival and secondary sources was performed. Werner Forssmann joined the Nazi Party, the Sturmabteilung (Stormtroopers, SA) and the Nationalsozialistischer Deutscher Ärztebund (Nazi Doctors' Association) in 1932, a year before Hitler's assumption of power. In his autobiography, Forssmann referred to the political situation in passing. However, he expressed his personal thoughts in private letters which he wrote as a medical officer during the war. After World War II, Forssmann underwent denazification and was banned from practicing medicine for 3 years. He did not seem to be averse to Hitler's politics and in some ways expressed his approval. However, correspondence from the 1960s with 2 Jewish colleagues reveals that Forssmann may have changed his attitude toward National Socialism later. Werner Forssmann's political attitudes during the Third Reich and in the post-war era can be characterized as early agreement that gradually changed to a more critical distance to Nazi ideology. In this respect, Forssmann appears to be quite a typical example of a larger proportion of German medical doctors during these eras. © 2016 S. Karger AG, Basel.

  9. Design of the central region in the Gustaf Werner cyclotron at the Uppsala university

    CERN Document Server

    Toprek, D; Lundstrom, B; Wessman, D

    2002-01-01

    This paper describes the design of the central region in the Gustaf Werner cyclotron for h=1, 2 and 3 modes of acceleration. The electric field distribution in the inflector and in the four acceleration gaps has been numerically calculated from an electric potential map produced by the program RELAX3D. The geometry of the central region has been tested with the computations of orbits carried out by means of the computer code CYCLONE. The optical properties of the spiral inflector and the central region were studied by using the programs CASINO and CYCLONE, respectively.

  10. Herlyn-Werner-Wunderlich syndrome: 3D ultrasonographic diagnosis in premenarche

    Directory of Open Access Journals (Sweden)

    Cristina Vilhena

    2014-09-01

    Comments: A high degree of clinical suspicion is important for the diagnoses. 3D ultrasound or MRI are the imaging diagnostic exams of choice, helped by a careful bimanual pelvic examination. An early diagnosis is important to prevent chronic pelvic pain and perhaps severe endometriosis.

  11. Alfred Werner

    Indian Academy of Sciences (India)

    May it be granted to me to justify the confidence which the Swedish Academy of Sciences has placed in me by the award of the Nobel Prize, by making further advances in the field of inorganic constitution research. In concluding allow me to express to you my gratitude for the kind attention you have given to my lecture. ~.

  12. [Werner Catel--a protagonist in Nazi "pediatric euthanasia" and his post-war career].

    Science.gov (United States)

    Petersen, Hans-Christian; Zankel, Sönke

    2003-01-01

    This article deals with the biography of Werner Catel, a German paediatrician and protagonist of the Nazi programme for "euthanasia of children". Based on original research into recently discovered source materials, two aspects of Catel's life are considered. Firstly, Catel's attitude towards "euthanasia" is analysed. This analysis is not limited to the period of National Socialism, but focuses also on the phase before 1933 and especially on the era after 1945. Secondly, the authors explore Catel's academic career. What effects on his career in the later Federal Republic of Germany had his exposed role in the Nazi programme for "euthanasia of children"? In this context it is also examined how the Christian-Albrechts-University of Kiel/Germany, which employed Catel until 1960 in a leading position, judged the work of its former professor after his death.

  13. Un'estrema solitudine la vita e l'opera di Werner Heisenberg

    CERN Document Server

    Cassidy, David C

    1996-01-01

    Il genio di Werner Heisenberg attraversa l'orizzonte della fisica del nostro secolo come una meteora. Testimoniano della fecondità e dell'originalità del suo pensiero non solo il Nobel che gli fu assegnato a soli 32 anni, ma soprattutto i decisivi impulsi da lui dati alla fisica quantistica, alla teoria delle particelle elementari, alla teoria del nucleo. Si deve a Heisenberg quel "principio di indeterminazione" che ha rivoluzionato non solo il corso della fisica ma il modo di concepire la posizione dell'uomo nell'universo. L'interesse del libro, però, vuole andare oltre la fisica, giacché il curriculum del "ragazzo di campagna dei biondi capelli" rispecchia in forma emblematica l'ambiguo rapporto della scienza col potere.

  14. Rediscovery of Atelopus subornatus Werner, 1899 (Anura: Bufonidae), with a redescription of the tadpole.

    Science.gov (United States)

    Enciso-Calle, Maria Paula; Viuche-Lozano, Andres; Anganoy-Criollo, Marvin; Bernal, Manuel Hernando

    2017-11-06

    The Neotropical toads of the genus Atelopus are among the most imperiled of all amphibians (La Marca et al. 2005; Gonzalez-Maya et al. 2013; McCaffery et al. 2015). Nowadays, at least 90% of the 93 listed species are threatened and more than 77% are Critically Endangered (McCaffery et al. 2015; IUCN 2016). Colombia has 44 described species of Atelopus (Frost 2017), two of these are categorized as extinct (EX) by the IUCN (2016): A. ignescens and A. longirostris, although they were recently re-discovered in Ecuador (Tapia et al. 2017), 34 as critical endangered (CR), four as endangered (EN), two as vulnerable (VU), one species has data deficient (DD) and another one has not been evaluated. Atelopus subornatus Werner, 1899, is an endemic Colombian harlequin toad described from 2300 to 2800 m.a.s.l in the municipalities of Sibaté (Alto de Sibaté and Agua Bonita) and Fusagasuga (above Fusagasuga and Tierra Negra), in Cundinamarca (Fig. 1A), on the western flank from Cordillera Oriental of Colombia (Werner 1899; Lynch 1986; Lötters 1989, 1992). The last record of this species was in 1993 (Lötters 2005), and it currently is listed as Critically Endangered by the IUCN (2016). Herein, we report the rediscovery of A. subornatus at a new locality from Tolima, Colombia (Fig. 1A), and redescribe its tadpole. The determination of the species was based on comparisons with material deposited in the amphibian collection of the Instituto de Ciencias Naturales, Universidad Nacional de Colombia (ICN-UNAL) for all species of Atelopus reported from the same general area in Cundinamarca and relatively similar to A. subornatus. The specimens are housed in the Herpetological collection of the Tolima University (CZUT-A) and amphibian collection of ICN-UNAL.

  15. Significant gender difference in serum levels of fibroblast growth factor 21 in Danish children and adolescents

    DEFF Research Database (Denmark)

    Bisgaard, Amalie; Sørensen, Kaspar; Johannsen, Trine Holm

    2014-01-01

    INTRODUCTION: Fibroblast Growth Factor 21 (FGF21) is a novel metabolic factor with effect on glucose and lipid metabolism, and shown to be elevated in diseases related to metabolic syndrome. Due to the increasing frequency of metabolic syndrome in the pediatric population, and as FGF21 studies in...

  16. Multikinase activity of fibroblast growth factor receptor (FGFR) inhibitors SU5402, PD173074, AZD1480, AZD4547 and BGJ398 compromises the use of small chemicals targeting FGFR catalytic activity for therapy of short-stature syndromes

    Czech Academy of Sciences Publication Activity Database

    Gudernová, I.; Veselá, Iva; Balek, L.; Buchtová, Marcela; Dosedělová, Hana; Kunová, M.; Pivnička, J.; Jelínková, I.; Roubalová, L.; Kozubík, Alois; Krejčí, P.

    2016-01-01

    Roč. 25, č. 1 (2016), s. 9-23 ISSN 0964-6906 R&D Projects: GA ČR(CZ) GA14-31540S Institutional support: RVO:67985904 ; RVO:68081707 Keywords : fibroblast growth factor receptor * tyrosine kinase domain * ERK MAP kinase Subject RIV: EA - Cell Biology Impact factor: 5.340, year: 2016

  17. Isolation of fibroblasts and epithelial cells in bronchoalveolar lavage (BAL).

    Science.gov (United States)

    Pollock, Kathryn; Albares, Luke; Wendt, Chris; Hubel, Allison

    2013-04-01

    The long-term outcome of lung transplants is poor with 60%-70% of patients developing chronic rejection. Chronic rejection is manifested histologically by obliterative bronchiolitis with bronchiolitis obliterans syndrome (BOS), the clinical surrogate. Recent studies suggest that fibroblasts and epithelial cells present in bronchoalveolar lavage (BAL) may be a clinically relevant biomarker for BOS. The goal of this investigation was to develop a fast, repeatable method to individually isolate these low-frequency cell types. Fibroblasts and epithelial cells were isolated from BAL using attachment methods and the phenotype of the cells confirmed using immunostaining for vimentin (fibroblasts) and epithelial cell adhesion molecule (EpCAM, epithelial cells). Both fibroblasts and epithelial cells were isolated in every sample of BAL processed with the frequency of fibroblasts ranging from 0.03% to 0.48% and epithelial cells ranging from 0.05% to 1.5% of the total sample. Additional studies were performed using cytospins of cells after macrophages were depleted; cells exhibiting characteristics of both fibroblasts and epithelial cells were observed. The frequency of the cells of interest suggests that conventional methods of immunomagnetic isolation will not be effective in isolating these subpopulations. Finally, some of the low-frequency cells isolated via cytospin exhibit characteristics of epithelial to mesenchymal transition (which was not observed in plating incubations), indicating that the epithelial to mesenchymal cell transition fibroblasts may be nonadherent. In future studies, this technique and dataset may be of use to statistically correlate low-frequency cell type abundance to the onset and development of BOS.

  18. [Fibroblast growth factor-2].

    Science.gov (United States)

    Faitová, J

    2004-01-01

    Fibroblast growth factor-2 is a member of a large family of proteins that bind heparin and heparan sulfate and modulate the function of a wide range of cell types. FGF-2 occurs in several isoforms resulting from alternative initiations of traslation: an 18 kDa cytoplasmic isoform and four larger molecular weight nuclear isoforms (22, 22.5, 24 and 34 kDa). It acts mainly through a paracrine/autocrine mechanism involving high affinity transmembrane receptors and heparan sulfate proteoglycan low affinity receptors. It is expressed mostly in tissues of mesoderm and neuroectoderm origin, and plays an important role in mesoderm induction, stimulates the growth and development of the new blood vessels (angiogenesis), normal wound healing and tissue development. FGF-2 positively regulates hematopoiesis by acting on various cellular targets: stromal cells, early and committed hematopoietic progenitors and possibly some mature blood cells. FGF-2 is a potent hematopoietic growth factor that is likely to play an important role in physiological and pathological hematopoiesis.

  19. Endothelial cells, fibroblasts and vasculitis

    OpenAIRE

    Buckley, Christopher D.; Rainger, G.Ed; Nash, Gerard B; Raza, Karim

    2005-01-01

    One of the most important questions in vasculitis research is not why inflammation of blood vessels occurs but why it persists, often in a site-specific manner. In this review we illustrate how stromal cells, such as fibroblasts and pericytes, might play an important role in regulating the site at which vasculitis occurs. Smooth muscle cells and fibroblasts directly influence the behaviour of overlying vascular cells, amplifying the response of the endothelium to proinflammatory agents such a...

  20. Parkinson's disease and the quest for preclinical diagnosis: an interview with Professor Werner Poewe.

    Science.gov (United States)

    Poewe, Werner

    2017-10-01

    Werner Poewe speaks to Laura Dormer, Editorial Director: Professor Werner Poewe is Professor of Neurology and Director of the Department of Neurology at Innsbruck Medical University in Innsbruck, Austria. He held a Residency in Clinical Neurology and Psychiatry at the University of Innsbruck, Austria, from 1977 to 1984. From 1984 to 1985 he teamed up with Gerald Stern and Andrew Lees as a British Council Research Fellow at University College and Middlesex Hospital's Medical School in London to perform clinical studies into levodopa-induced dystonia and pharmacokinetics of levodopa in naive versus L-Dopa treated Parkinson's disease. Following his return to Austria, he held a position as Senior Lecturer in the Department of Neurology at the University of Innsbruck (1986-1989) after which he took over as Professor of Neurology and Acting Director of the Department of Neurology at Virchow Hospital of the Free University of Berlin (1990-1994). Professor Poewe's main research interests in the field of movement disorders are focused on differential and early diagnosis of Parkinson's disease, its natural history and pharmacological treatment. He has been involved in the steering committees of numerous drug trials in different stages of Parkinson's disease for the past 20 years and has authored and coauthored more than 500 original articles and reviews in the field of movement disorders. Professor Poewe served as President of the Austrian Society of Neurology from 2002 to 2004 as well as President of the Austrian Parkinson's Disease Society from 1996 to 2009. He has been awarded honorary membership of the German Society of Neurology as well as the Japanese Society of Neurology. His awards include the Walther-Birkmayer-Prize of the Austrian PD Society, the Dingebauer-Prize of the German Neurological Society as well as the Research Excellence Award of Innsbruck Medical University. Professor Poewe served as President of the International Movement Disorder Society (MDS) from

  1. IGF-I induced genes in stromal fibroblasts predict the clinical outcome of breast and lung cancer patients

    Directory of Open Access Journals (Sweden)

    Herrmann Richard

    2010-01-01

    Full Text Available Abstract Background Insulin-like growth factor-1 (IGF-I signalling is important for cancer initiation and progression. Given the emerging evidence for the role of the stroma in these processes, we aimed to characterize the effects of IGF-I on cancer cells and stromal cells separately. Methods We used an ex vivo culture model and measured gene expression changes after IGF-I stimulation with cDNA microarrays. In vitro data were correlated with in vivo findings by comparing the results with published expression datasets on human cancer biopsies. Results Upon stimulation with IGF-I, breast cancer cells and stromal fibroblasts show some common and other distinct response patterns. Among the up-regulated genes in the stromal fibroblasts we observed a significant enrichment in proliferation associated genes. The expression of the IGF-I induced genes was coherent and it provided a basis for the segregation of the patients into two groups. Patients with tumours with highly expressed IGF-I induced genes had a significantly lower survival rate than patients whose tumours showed lower levels of IGF-I induced gene expression (P = 0.029 - Norway/Stanford and P = 7.96e-09 - NKI dataset. Furthermore, based on an IGF-I induced gene expression signature derived from primary lung fibroblasts, a separation of prognostically different lung cancers was possible (P = 0.007 - Bhattacharjee and P = 0.008 - Garber dataset. Conclusion Expression patterns of genes induced by IGF-I in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients. Furthermore, these IGF-I induced gene signatures derived from stromal fibroblasts might be promising predictors for the response to IGF-I targeted therapies. See the related commentary by Werner and Bruchim: http://www.biomedcentral.com/1741-7015/8/2

  2. Ethnic differences in thermoregulatory responses during resting, passive and active heating: application of Werner's adaptation model.

    Science.gov (United States)

    Lee, Joo-Young; Wakabayashi, Hitoshi; Wijayanto, Titis; Hashiguchi, Nobuko; Saat, Mohamed; Tochihara, Yutaka

    2011-12-01

    For the coherent understanding of heat acclimatization in tropical natives, we compared ethnic differences between tropical and temperate natives during resting, passive and active heating conditions. Experimental protocols included: (1) a resting condition (an air temperature of 28°C with 50% RH), (2) a passive heating condition (28°C with 50% RH; leg immersion in a hot tub at a water temperature of 42°C), and (3) an active heating condition (32°C with 70% RH; a bicycle exercise). Morphologically and physically matched tropical natives (ten Malaysian males, MY) and temperate natives (ten Japanese males, JP) participated in all three trials. The results saw that: tropical natives had a higher resting rectal temperature and lower hand and foot temperatures at rest, smaller rise of rectal temperature and greater temperature rise in bodily extremities, and a lower sensation of thirst during passive and active heating than the matched temperate natives. It is suggested that tropical natives' homeostasis during heating is effectively controlled with the improved stability in internal body temperature and the increased capability of vascular circulation in extremities, with a lower thirst sensation. The enhanced stability of internal body temperature and the extended thermoregulatory capability of vascular circulation in the extremities of tropical natives can be interpreted as an interactive change to accomplish a thermal dynamic equilibrium in hot environments. These heat adaptive traits were explained by Wilder's law of initial value and Werner's process and controller adaptation model.

  3. Treatment of Virgin OHVIRA Syndrome with Haematometrocolpos by Complete Incision of Vaginal Septum without Hymenotomy.

    Science.gov (United States)

    Tug, Niyazi; Sargin, Mehmet Akif; Çelik, Ayhan; Alp, Turgut; Yenidede, Ilter

    2015-11-01

    Mullerian malformations result from defective fusion of the Mullerian ducts during development of the female reproductive system and have an incidence of 2-3%. The American Fertility Society classification of Mullerian anomalies is the most commonly utilized standardized classification. The least common form of these malformations is Herlyn-Werner-Wunderlich syndrome characterized by obstructed hemivagina and ipsilateral renal anomaly (OHVIRA). This syndrome has been described with case reports since 1922. Early diagnosis and surgery that include drainage of fluid and resection of the vaginal septum is necessary for OHVIRA to prevent late complications (i.e. pyocolpos, chronic cryptomenorrhea). Here in we report a case of Herlyn-Werner-Wunderlich syndrome that hymen has been preserved during the operation of non-fenestrated transverse vaginal septum resection with hysteroscopy.

  4. The color of complexes and UV-vis spectroscopy as an analytical tool of Alfred Werner's group at the University of Zurich.

    Science.gov (United States)

    Fox, Thomas; Berke, Heinz

    2014-01-01

    Two PhD theses (Alexander Gordienko, 1912; Johannes Angerstein, 1914) and a dissertation in partial fulfillment of a PhD thesis (H. S. French, Zurich, 1914) are reviewed that deal with hitherto unpublished UV-vis spectroscopy work of coordination compounds in the group of Alfred Werner. The method of measurement of UV-vis spectra at Alfred Werner's time is described in detail. Examples of spectra of complexes are given, which were partly interpreted in terms of structure (cis ↔ trans configuration, counting number of bands for structural relationships, and shift of general spectral features by consecutive replacement of ligands). A more complete interpretation of spectra was hampered at Alfred Werner's time by the lack of a light absorption theory and a correct theory of electron excitation, and the lack of a ligand field theory for coordination compounds. The experimentally difficult data acquisitions and the difficult spectral interpretations might have been reasons why this method did not experience a breakthrough in Alfred Werner's group to play a more prominent role as an important analytical method. Nevertheless the application of UV-vis spectroscopy on coordination compounds was unique and novel, and witnesses Alfred Werner's great aptitude and keenness to always try and go beyond conventional practice.

  5. The 2009 Lindau Nobel Laureate Meeting: Werner Arber, physiology or medicine 1978.

    Science.gov (United States)

    Arber, Werner

    2010-03-10

    Swiss microbial geneticist, Werner Arber shared the 1978 Nobel Prize in Physiology or Medicine with Hamilton Smith and Daniel Nathans for their discovery of restriction endonucleases. Werner Arber was born in Granichen, Switzerland in 1929. Following a public school education, he entered the Swiss Polytechnical School in Zurich in 1949, working toward a diploma in natural sciences. There, his first research experience involved isolating and characterizing an isomer of chlorine. Following graduation in 1953, Arber joined a graduate program at the University of Geneva, taking on an assistanceship in electron microscopy (EM), in which he studied gene transfer in the bacterial virus (bacteriophage) lambda. Eventually encountering limitations with EM as a tool, he began using microbial genetics as a methodology for his studies. The study of microbial genetics had been possible for a relatively short time: DNA had been discovered to carry genetic information only a decade before he d entered the field. After earning his Ph.D. in 1958, Arber continued to develop skills in microbial genetics, working with colleagues in the United States for a short time before returning to Geneva at beginning of 1960. There, he continued working on lambda transduction in E. coli, but found that the virus would not efficiently propagate. Recalling research done seven years earlier by Joe Bertani and Jean Weigle on "host-controlled restriction-modification", he realized there must be a host-controlled modification of the invading DNA, and sought to identify the mechanism. Based on Grete Kallengerger s work that demonstrated degradation of both irradiated and non-irradiated phage lambda following injection in a host, Arber and his graduate student, Daisy Dussoix further investigated the fate of DNA, and found that restriction and modification (later determined to be postreplicative nuclotide methylation) directly affected DNA, but did not cause mutations. They also found that theses were

  6. Scheme for directly measuring the concurrences of Collins-Gisin and Werner classes polarization entangled mixed states

    Science.gov (United States)

    Zeng, Ting; Chu, Wen-Jing; Yang, Qing; Yang, Ming; Song, Wei; Cao, Zhuo-Liang

    2017-10-01

    We present a two-copy-based protocol for directly measuring the concurrence of two-photon polarization entangled mixed states (Collins-Gisin class state and the more complicated bipartite mixed entangled state—Werner class state) without quantum state tomography. The quantum circuit designed for directly measuring concurrence can be realized in an optical system. Our protocol works without the sophisticated controlled-NOT gate, which makes it much simpler than the previous ones. Because all the operations used here are local, the scheme can be used for directly measuring remote mixed entanglement too.

  7. Case report 511: Fibroblastic rheumatism

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, R.J.; Martel, W.; Headington, J.T.; Kaufman, R.A.

    1989-03-01

    We report a ten-year-old child with the newly described entity of fibroblastic rheumatism. This child developed rapid, progressive, symmetrical polyarthritis, similar to the radiographic appearance of juvenile rheumatoid arthritis, except for the rapidity of progression. The polyarthritis was preceded by the development of skin nodules with characteristic histological changes. (orig./GDG).

  8. Micronucleus assay in human fibroblasts: a measure of spontaneous chromosomal instability and mutagen hypersensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Rudd, N.L.; Hoar, D.I.; Greentree, C.L.; Dimnik, L.S.; Hennig, U.S.S.

    1988-01-01

    By comparing fibroblast strains derived from individuals exhibiting chromosome instability and/or mutagen hypersensitivity (Cockayne syndrome, ataxia telangiectasia, and Fanconi anemia) with strains derived from health donors, the fibroblast micronucleus assay has been established as a reproducible measure of the genotypic variation in spontaneous or mitomycin C (MMC)-induced chromosomal instability. The patient strains that were moderately or exquisitely sensitive to MMC could be distinguished readily from the control strains, both in levels of spontaneous micronuclei and in sensitivity to MMC, whereas the mildly sensitive strain (Cockayne syndrome) overlapped with the control range. The reproducibility of the assay was evaluated within and between experiments. In addition to its value as a test system for genotoxins, the fibroblast micronucleus assay may be useful for investigating genetically determined hypersensitivity to mutagens, elevated spontaneous chromosomal breakage, and chromosome segregation errors.

  9. Influence of Dzyaloshinshkii-Moriya interaction on quantum correlations in two-qubit Werner states and MEMS

    Science.gov (United States)

    Sharma, Kapil K.; Pandey, S. N.

    2015-04-01

    In this paper, we study the influence of Dzyaloshinskii-Moriya (DM) interaction on quantum correlations in two-qubit Werner states and maximally entangled mixed states (MEMS). We consider our system as a closed system of a qubit pair and one auxiliary qubit, which interact with any one of the qubit of the pair through DM interaction. We show that DM interaction, taken along any direction ( x or y or z), does not affect two-qubit Werner states. On the other hand, the MEMS are affected by x and z components of DM interaction and remain unaffected by the y component. Further, we find that the state (i.e., probability amplitude) of auxiliary qubit does not affect the quantum correlations in both the states, and only DM interaction strength influences the quantum correlations. So one can avoid the intention to prepare the specific state of auxiliary qubit to manipulate the quantum correlations in both the states. We mention here that avoiding the preparation of state can contribute to cost reduction in quantum information processing. We also observe the phenomenon of entanglement sudden death in the present study.

  10. Characteristics of human infant primary fibroblast cultures from Achilles tendons removed post-mortem

    DEFF Research Database (Denmark)

    Rohde, Marianne Cathrine; Corydon, Thomas Juhl; Hansen, Jakob

    2014-01-01

    Primary cell cultures were investigated as a tool for molecular diagnostics in a forensic setting. Fibroblast cultures had been established from human Achilles tendon resected at autopsies, from cases of sudden infant death syndrome and control infants who died in traumatic events (n=41). After...

  11. Sensitivity of fibroblast growth factor 23 measurements in tumor-induced osteomalacia

    DEFF Research Database (Denmark)

    Imel, Erik A; Peacock, Munro; Pitukcheewanont, Pisit

    2006-01-01

    Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome of hypophosphatemia, decreased renal phosphate reabsorption, normal or low serum 1,25-dihydryxyvitamin-D concentration, myopathy, and osteomalacia. Fibroblast growth factor 23 (FGF23) is a phosphaturic protein overexpressed in tumors...

  12. AGE AND MULTIPLICATION OF FIBROBLASTS.

    Science.gov (United States)

    Carrel, A; Ebeling, A H

    1921-11-30

    Pure cultures of fibroblasts displayed marked differences in their activity in the plasma of young, middle aged, and old chickens. The rate of cell multiplication varied in inverse ratio to the age of the animal from which the plasma was taken. There was a definite relation between the age of the animal and the amount of new tissue produced in its plasma in a given time (Text-figs. 1 to 10). The chart obtained by plotting the rate of cell proliferation in ordinates, and the age of the animal in abscissae, showed that the rate of growth decreased more quickly than the age increased (Text-fig. 12). The decrease in the rate of growth was 50 per cent during the first 3 years of life, while in the following 6 years it was only 30 per cent. When the duration of the life of the cultures in the four plasmas was compared, a curve was obtained which showed about the same characteristics (Text-fig. 11). The duration of life of the fibroblasts in vitro varied in inverse ratio to the age of the animal, and decreased more quickly than the age increased. As the differences in the amount of new tissue produced in the plasma of young, middle aged, and old chickens were large, the growth of a pure culture of fibroblasts could be employed as a reagent for detecting certain changes occurring in the plasma under the influence of age. But the method possesses the necessary accuracy only when it is used as has already been described, and by technicians thoroughly trained in the details of its application. A comparative study of the growth of fibroblasts in media containing no serum, and serum under low and high concentrations, was made in order to ascertain whether the decreasing rate of cell multiplication was due to the loss of an accelerating factor, or to the increase See PDF for Structure of an inhibiting one. In high and low concentrations of the serum of young animals, no difference in the rate of multiplication of fibroblasts was observed. This showed that the serum of an

  13. On the presence of Bufo nasicus Werner in Guiana, with a redescription of the species on the basis of recently collected material

    NARCIS (Netherlands)

    Hoogmoed, M.S.

    1977-01-01

    During research on material recently collected in Guyana and in Venezuelan Guiana, several specimens of the rare toad Bufo nasicus Werner, thus far only known from the holotype without known origin, were discovered. On the basis of this material the species is redescribed and some notes on its

  14. Altered Nuclear Functions in Progeroid Syndromes: a Paradigm for Aging Research

    Directory of Open Access Journals (Sweden)

    Baomin Li

    2009-01-01

    Full Text Available Syndromes of accelerated aging could provide an entry point for identifying and dissecting the cellular pathways that are involved in the development of age-related pathologies in the general population. However, their usefulness for aging research has been controversial, as it has been argued that these diseases do not faithfully reflect the process of natural aging. Here we review recent findings on the molecular basis of two progeroid diseases, Werner syndrome (WS and Hutchinson-Gilford progeria syndrome (HGPS, and highlight functional connections to cellular processes that may contribute to normal aging.

  15. Faulty DNA-polymerase {delta}/{epsilon}-mediated excision-repair in response to gamma-radiation or ultraviolet-light in P53-deficient fibroblast strains from affected members of a cancer-prone family with Li-Fraumeni syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Mirzayans, R.; Enns, L.; Dietrich, K.; Barley, R.D.C.; Paterson, M.C. [Alberta Univ., Edmonton, AB (Canada). Cross Cancer Inst.]|[Alberta Univ., Edmonton, AB (Canada). Dept. of Oncology]|[Alberta Univ., Edmonton, AB (Canada). Dept. of Biological Science

    1996-04-01

    Dermal fibroblast strains cultured from affected members of a cancer-prone family with Li-Fraumeni syndrome (LFS) harbor a point mutation in one allele of the p53 tumor suppressor gene, resulting in loss of normal p53-deficient strains to carry out the long-patch mode of excision repair, mediated by DNA polymerases delta and epsilon, after exposure to Co-60 gamma radiation or far ultraviolet (UV) (chiefly 254 mm) light. Repair was monitored by incubation of the irradiated cultures in the presence of aphidicolin (ape) or 1-beta-D-arabinofuranosylcytosine (araC), each a specific inhibitor of long-patch repair, followed by measurement of drug-induced DNA strand breaks (reflecting non-ligated strand incision events) by alkaline surcrose velocity sedimentation. The LFS strains displayed deficient repair capacity in response to both gamma rays and UV light. The repair anomaly in UV-irradiated LFS cultures was manifested not only in the overall genome, but also in the transcriptionally active, preferentially repaired c-myc gene. Using autoradiography we also assessed unscheduled DNA synthesis (UDS) after UV irradiation and found this conventional measure of repair replication to be deficient in LFS strains. Moreover, both ape and araC decreased the level of UV-induced UDS by similar to 75% in normal cells, but each had only a marginal effect on LFS cells. We further demonstrated that the LFS strains are impaired in the recovery of both RNA and replicative DNA syntheses after UV treatment, two molecular anomalies of the DNA repair deficiency disorders xeroderma pigmentosum and Cockayne`s syndrome. Together these results imply a critical role for wild-type p53 protein in DNA polymerase delta/epsilon-mediated excision repair, both the mechanism operating on the entire genome and that acting on expressed genes. (Author).

  16. Lithium Attenuates TGF-β 1-Induced Fibroblasts to Myofibroblasts Transition in Bronchial Fibroblasts Derived from Asthmatic Patients

    Science.gov (United States)

    Michalik, Marta; Wójcik, Katarzyna Anna; Jakieła, Bogdan; Szpak, Katarzyna; Pierzchalska, Małgorzata; Sanak, Marek; Madeja, Zbigniew; Czyż, Jarosław

    2012-01-01

    Bronchial asthma is a chronic disorder accompanied by phenotypic transitions of bronchial epithelial cells, smooth muscle cells, and fibroblasts. Human bronchial fibroblasts (HBFs) derived from patients with diagnosed asthma display predestination towards TGF-β-induced phenotypic switches. Since the interference between TGF-β and GSK-3β signaling contributes to pathophysiology of chronic lung diseases, we investigated the effect of lithium, a nonspecific GSK-3β inhibitor, on TGF-β 1-induced fibroblast to myofibroblast transition (FMT) in HBF and found that the inhibition of GSK-3β attenuates TGF-β 1-induced FMT in HBF populations derived from asthmatic but not healthy donors. Cytoplasmically sequestrated β-catenin, abundant in TGF-β 1/LiCl-stimulated asthmatic HBFs, most likely interacts with and inhibits the nuclear accumulation and signal transduction of Smad proteins. These data indicate that the specific cellular context determines FMT-related responses of HBFs to factors interfering with the TGF-β signaling pathway. They may also provide a mechanistic explanation for epidemiological data revealing coincidental remission of asthmatic syndromes and their recurrence upon the discontinuation of lithium therapy in certain psychiatric diseases. PMID:22988467

  17. Lithium Attenuates TGF-β1-Induced Fibroblasts to Myofibroblasts Transition in Bronchial Fibroblasts Derived from Asthmatic Patients

    Directory of Open Access Journals (Sweden)

    Marta Michalik

    2012-01-01

    Full Text Available Bronchial asthma is a chronic disorder accompanied by phenotypic transitions of bronchial epithelial cells, smooth muscle cells, and fibroblasts. Human bronchial fibroblasts (HBFs derived from patients with diagnosed asthma display predestination towards TGF-β-induced phenotypic switches. Since the interference between TGF-β and GSK-3β signaling contributes to pathophysiology of chronic lung diseases, we investigated the effect of lithium, a nonspecific GSK-3β inhibitor, on TGF-β1-induced fibroblast to myofibroblast transition (FMT in HBF and found that the inhibition of GSK-3β attenuates TGF-β1-induced FMT in HBF populations derived from asthmatic but not healthy donors. Cytoplasmically sequestrated β-catenin, abundant in TGF-β1/LiCl-stimulated asthmatic HBFs, most likely interacts with and inhibits the nuclear accumulation and signal transduction of Smad proteins. These data indicate that the specific cellular context determines FMT-related responses of HBFs to factors interfering with the TGF-β signaling pathway. They may also provide a mechanistic explanation for epidemiological data revealing coincidental remission of asthmatic syndromes and their recurrence upon the discontinuation of lithium therapy in certain psychiatric diseases.

  18. Lithium Attenuates TGF-β(1)-Induced Fibroblasts to Myofibroblasts Transition in Bronchial Fibroblasts Derived from Asthmatic Patients.

    Science.gov (United States)

    Michalik, Marta; Wójcik, Katarzyna Anna; Jakieła, Bogdan; Szpak, Katarzyna; Pierzchalska, Małgorzata; Sanak, Marek; Madeja, Zbigniew; Czyż, Jarosław

    2012-01-01

    Bronchial asthma is a chronic disorder accompanied by phenotypic transitions of bronchial epithelial cells, smooth muscle cells, and fibroblasts. Human bronchial fibroblasts (HBFs) derived from patients with diagnosed asthma display predestination towards TGF-β-induced phenotypic switches. Since the interference between TGF-β and GSK-3β signaling contributes to pathophysiology of chronic lung diseases, we investigated the effect of lithium, a nonspecific GSK-3β inhibitor, on TGF-β(1)-induced fibroblast to myofibroblast transition (FMT) in HBF and found that the inhibition of GSK-3β attenuates TGF-β(1)-induced FMT in HBF populations derived from asthmatic but not healthy donors. Cytoplasmically sequestrated β-catenin, abundant in TGF-β(1)/LiCl-stimulated asthmatic HBFs, most likely interacts with and inhibits the nuclear accumulation and signal transduction of Smad proteins. These data indicate that the specific cellular context determines FMT-related responses of HBFs to factors interfering with the TGF-β signaling pathway. They may also provide a mechanistic explanation for epidemiological data revealing coincidental remission of asthmatic syndromes and their recurrence upon the discontinuation of lithium therapy in certain psychiatric diseases.

  19. Recombinant interferon regulation of lung fibroblast growth

    Energy Technology Data Exchange (ETDEWEB)

    Elias, J.A.; Freundlich, B.; Rossman, M.D.; Gustilo, K.; Jimenez, S.A.

    1986-03-01

    The authors characterized the effect on human lung fibroblast proliferation of recombinant interferons (gamma (..gamma..), alpha/sub A/ (..cap alpha../sub A/), alpha/sub D/ (..cap alpha../sub D/) and beta (..beta..)). Quiescent and log phase fibroblasts were used. Proliferation was assessed using /sup 3/HTdr uptake and cell counts. ..gamma.. stimulated the /sup 3/HTdr uptake of quiescent cells. Maximal stimulation was seen between 100 and 500 IU/ml. Fibroblasts incubated in 100 IU/ml incorporated 160 +/- 9% as much /sup 3/HTdr as quiescent controls (p < .04). In contrast, ..gamma.. caused a dose dependent inhibition of the /sup 3/HTdr uptake of log phase cells. Fibroblasts incubated in 1000 IU/ml incorporated 41 +/- 9% as much /sup 3/HTdr as log phase controls (p < .02). Unlike ..gamma.., ..cap alpha../sub A/, ..cap alpha../sub D/ and ..beta.. did not stimulate the proliferation of quiescent cells. However, they did inhibit the proliferation of log phase cells. Fibroblasts incubated in 1000 IU/ml of ..cap alpha../sub A/, ..cap alpha../sub D/ and ..beta.. incorporated 64 +/- 10, 81 +/- 4 and 62 +/- 7% as much /sup 3/HTdr as log phase controls (p < .03 for all). ..gamma.., ..cap alpha../sub A/, ..cap alpha../sub D/ and ..beta.. did not stimulate fibroblast prostaglandin E (PGE) production and incubating fibroblasts with indomethacin did not reverse the inhibition of fibroblast proliferation caused by the interferons. Thus, (1) ..gamma.. can stimulate or inhibit fibroblast growth, (2) ..cap alpha../sub A/, ..cap alpha../sub D/ and ..beta.. only inhibit fibroblast growth, (3) the inhibition of fibroblast growth caused by ..gamma.., ..cap alpha../sub A/, ..cap alpha../sub D/ and ..beta.. is largely independent of fibroblast PGE production.

  20. Response of dupuytren fibroblasts to different oxygen environments.

    Science.gov (United States)

    Türker, Tolga; Murphy, Erin; Kaufman, Christina L; Kutz, Joseph E; Meister, Edward A; Hoying, James B

    2013-12-01

    It is thought that local ischemia and oxygen radicals are responsible for fibroblast-to-myofibroblast cell transformation and proliferation. We hypothesized that hypoxia could differentially activate the contractility of fibroblasts from normal human palmar fascia and from fibroblasts-myofibroblasts of Dupuytren cords. Normal palmar fascia from 5 patients with carpal tunnel syndrome and Dupuytren cords from 5 patients were harvested. Cells were cultured from all tissue samples, and collagen lattices were prepared containing these cells. Oxygen treatment subgroups were created and incubated under hypoxic (1% O(2), 5% CO(2), and 94% N(2)), normoxic (21% O(2), 5% CO(2), and 74% N(2)), and hyperoxic (100% oxygen using 2.4 atm pressure twice a day for 7 d) conditions. After 7 days, each subgroup was photographed, and lattices were released from dishes. Postrelease photographs were taken immediately, 5 minutes after release, and after 1 hour. Areas of the lattices at each time point were calculated using MetaMorph software. Actin staining and live/dead cell analysis was performed. Linear repeated measures analysis of variance was used for data analysis given that contraction levels were measured over 3 distinct time points. We found a statistically significant difference between normal samples and Dupuytren samples in mean contraction levels over time. There was no statistically significant difference between tissue groups over the 3 time periods based on the oxygen treatment received. Our results showed a greater degree of contractility in Dupuytren disease cells than normal fibroblasts. However, the contraction in either group was not affected by oxygen level. Future in vivo research is needed to better understand the nature of pathophysiology of Dupuytren disease. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  1. Pfeiffer syndrome

    Directory of Open Access Journals (Sweden)

    Fryns Jean-Pierre

    2006-06-01

    Full Text Available Abstract Pfeiffer syndrome is a rare autosomal dominantly inherited disorder that associates craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly on hands and feet. Hydrocephaly may be found occasionally, along with severe ocular proptosis, ankylosed elbows, abnormal viscera, and slow development. Based on the severity of the phenotype, Pfeiffer syndrome is divided into three clinical subtypes. Type 1 "classic" Pfeiffer syndrome involves individuals with mild manifestations including brachycephaly, midface hypoplasia and finger and toe abnormalities; it is associated with normal intelligence and generally good outcome. Type 2 consists of cloverleaf skull, extreme proptosis, finger and toe abnormalities, elbow ankylosis or synostosis, developmental delay and neurological complications. Type 3 is similar to type 2 but without a cloverleaf skull. Clinical overlap between the three types may occur. Pfeiffer syndrome affects about 1 in 100,000 individuals. The disorder can be caused by mutations in the fibroblast growth factor receptor genes FGFR-1 or FGFR-2. Pfeiffer syndrome can be diagnosed prenatally by sonography showing craniosynostosis, hypertelorism with proptosis, and broad thumb, or molecularly if it concerns a recurrence and the causative mutation was found. Molecular genetic testing is important to confirm the diagnosis. Management includes multiple-staged surgery of craniosynostosis. Midfacial surgery is performed to reduce the exophthalmos and the midfacial hypoplasia.

  2. Alcance y Función de las Teorias Físicas em Hylary Putnam y Werner Heisenberg

    Directory of Open Access Journals (Sweden)

    Christian de Ronde

    2013-08-01

    Full Text Available In this work we attempt to analyze the intra-theoretic characterization provided by Hilary Putnam and Werner Heisenberg between quantum mechanics and other theories. The first defended the idea that physical theories include macro principles that under specific definite historical conditions can be revised on the light of rival principles. Putnam will concentrate in the impact that quantum mechanics has produced in the classical image of knowledge. Heisenberg, on the other hand, develops his analysis from the notion of closed theories, assuming the independence and incommensurability of physical theories. These divergences between the two authors will allow us to analyze how the disagreement in the consideration of the status of physical theories, goes deeper into more profound aspects related to the nature of knowledge and the relation between theory and world

  3. Targeting Werner syndrome protein sensitizes U-2 OS osteosarcoma cells to selenium-induced DNA damage response and necrotic death

    DEFF Research Database (Denmark)

    Cheng, Wen-Hsing; Wu, Ryan T Y; Wu, Min

    2012-01-01

    , but promoted recovery from the MSeA-induced DNA damage. Taken together, WRN protects U-2 OS osteosarcoma cells against MSeA-induced cytotoxicity, suggesting that oxidative DNA repair pathway is a promising target for improving the efficacy of selenium on tumor suppression....... in mouse models of cancer. To test the hypothesis that targeting WRN can potentiate selenium toxicity in cancer cells, isogenic WRN small hairpin RNA (shRNA) and control shRNA U-2 OS osteosarcoma cells were treated with MSeA for 2d, followed by recovery for up to 7d. WRN deficiency sensitized U-2 OS cells...... to MSeA-induced necrotic death. Co-treatment with the ataxia-telangiectasia mutated (ATM) kinase inhibitor KU55933 desensitized the control shRNA cells, but not WRN shRNA cells, to MSeA treatment. WRN did not affect MSeA-induced ATM phosphorylation on Ser-1981 or H2A.X phosphorylation on Ser-139...

  4. Basal Cell Carcinoma in Gorlin's Patients: a Matter of Fibroblasts-Led Protumoral Microenvironment?

    Science.gov (United States)

    Gache, Yannick; Brellier, Florence; Rouanet, Sophie; Al-Qaraghuli, Sahar; Goncalves-Maia, Maria; Burty-Valin, Elodie; Barnay, Stéphanie; Scarzello, Sabine; Ruat, Martial; Sevenet, Nicolas; Avril, Marie-Françoise; Magnaldo, Thierry

    2015-01-01

    Basal cell carcinoma (BCC) is the commonest tumor in human. About 70% sporadic BCCs bear somatic mutations in the PATCHED1 tumor suppressor gene which encodes the receptor for the Sonic Hedgehog morphogen (SHH). PATCHED1 germinal mutations are associated with the dominant Nevoid Basal Cell Carcinoma Syndrome (NBCCS), a major hallmark of which is a high susceptibility to BCCs. Although the vast majority of sporadic BCCs arises exclusively in sun exposed skin areas, 40 to 50% BCCs from NBCCS patients develop in non photo-exposed skin. Since overwhelming evidences indicate that microenvironment may both be modified by- and influence the- epithelial tumor, we hypothesized that NBCCS fibroblasts could contribute to BCCs in NBCCS patients, notably those developing in non photo-exposed skin areas. The functional impact of NBCCS fibroblasts was then assessed in organotypic skin cultures with control keratinocytes. Onset of epidermal differentiation was delayed in the presence of primary NBCCS fibroblasts. Unexpectedly, keratinocyte proliferation was severely reduced and showed high levels of nuclear P53 in both organotypic skin cultures and in fibroblast-led conditioning experiments. However, in spite of increased levels of senescence associated β-galactosidase activity in keratinocytes cultured in the presence of medium conditioned by NBCCS fibroblasts, we failed to observe activation of P16 and P21 and then of bona fide features of senescence. Constitutive extinction of P53 in WT keratinocytes resulted in an invasive phenotype in the presence of NBCCS fibroblasts. Finally, we found that expression of SHH was limited to fibroblasts but was dependent on the presence of keratinocytes. Inhibition of SHH binding resulted in improved epidermal morphogenesis. Altogether, these data suggest that the repertoire of diffusible factors (including SHH) expressed by primary NBCCS fibroblasts generate a stress affecting keratinocytes behavior and epidermal homeostasis. Our findings

  5. Fibroblast spheroids as a model to study sustained fibroblast quiescence and their crosstalk with tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Salmenperä, Pertteli, E-mail: pertteli.salmenpera@helsinki.fi [Department of Virology, Medicum, Faculty of Medicine, University of Helsinki, P.O. Box 21, FIN-00014 (Finland); Karhemo, Piia-Riitta [Research Programs Unit, Translational Cancer Biology, and Institute of Biomedicine, University of Helsinki, P.O. Box 63, FIN-00014 (Finland); Räsänen, Kati [Department of Virology, Medicum, Faculty of Medicine, University of Helsinki, P.O. Box 21, FIN-00014 (Finland); Laakkonen, Pirjo [Research Programs Unit, Translational Cancer Biology, and Institute of Biomedicine, University of Helsinki, P.O. Box 63, FIN-00014 (Finland); Vaheri, Antti [Department of Virology, Medicum, Faculty of Medicine, University of Helsinki, P.O. Box 21, FIN-00014 (Finland)

    2016-07-01

    Stromal fibroblasts have an important role in regulating tumor progression. Normal and quiescent fibroblasts have been shown to restrict and control cancer cell growth, while cancer-associated, i. e. activated fibroblasts have been shown to enhance proliferation and metastasis of cancer cells. In this study we describe generation of quiescent fibroblasts in multicellular spheroids and their effects on squamous cell carcinoma (SCC) growth in soft-agarose and xenograft models. Quiescent phenotype of fibroblasts was determined by global down-regulation of expression of genes related to cell cycle and increased expression of p27. Interestingly, microarray analysis showed that fibroblast quiescence was associated with similar secretory phenotype as seen in senescence and they expressed senescence-associated-β-galactosidase. Quiescent fibroblasts spheroids also restricted the growth of RT3 SCC cells both in soft-agarose and xenograft models unlike proliferating fibroblasts. Restricted tumor growth was associated with marginally increased tumor cell senescence and cellular differentiation, showed with senescence-associated-β-galactosidase and cytokeratin 7 staining. Our results show that the fibroblasts spheroids can be used as a model to study cellular quiescence and their effects on cancer cell progression. - Highlights: • Fibroblasts acquire a sustained quiescence when grown as multicellular spheroids. • This quiescence is associated with drastic change in gene expression. • Fibroblasts spheroids secrete various inflammation-linked cytokines and chemokines. • Fibroblasts spheroids reduced growth of RT3 SCC cells in xenograft model.

  6. From the rarest to the most common: insights from progeroid syndromes into skin cancer and aging.

    Science.gov (United States)

    Capell, Brian C; Tlougan, Brook E; Orlow, Seth J

    2009-10-01

    Despite their rarity, diseases of premature aging, or "progeroid" syndromes, have provided important insights into basic mechanisms that may underlie cancer and normal aging. In this review, we highlight these recent developments in Hutchinson-Gilford progeria syndrome (HGPS), Werner syndrome, Bloom syndrome, Cockayne syndrome, trichothiodystrophy, ataxia-telangiectasia, Rothmund-Thomson syndrome, and xeroderma pigmentosum. Though they are caused by different mutations in various genes and often result in quite disparate phenotypes, deciphering the molecular bases of these conditions has served to highlight their underlying basic similarities. Studies of progeroid syndromes, particularly HGPS, the most dramatic form of premature aging, have contributed to our knowledge of fundamental processes of importance to skin biology, including DNA transcription, replication, and repair, genome instability, cellular senescence, and stem-cell differentiation.

  7. Altered fibroblast proteoglycan production in COPD.

    Science.gov (United States)

    Hallgren, Oskar; Nihlberg, Kristian; Dahlbäck, Magnus; Bjermer, Leif; Eriksson, Leif T; Erjefält, Jonas S; Löfdahl, Claes-Göran; Westergren-Thorsson, Gunilla

    2010-05-11

    Airway remodeling in COPD includes reorganization of the extracellular matrix. Proteoglycans play a crucial role in this process as regulators of the integrity of the extracellular matrix. Altered proteoglycan immunostaining has been demonstrated in COPD lungs and this has been suggested to contribute to the pathogenesis. The major cell type responsible for production and maintenance of ECM constituents, such as proteoglycans, are fibroblasts. Interestingly, it has been proposed that central airways and alveolar lung parenchyma contain distinct fibroblast populations. This study explores the hypothesis that altered depositions of proteoglycans in COPD lungs, and in particular versican and perlecan, is a result of dysregulated fibroblast proteoglycan production. Proliferation, proteoglycan production and the response to TGF-beta1 were examined in vitro in centrally and distally derived fibroblasts isolated from COPD patients (GOLD stage IV) and from control subjects. Phenotypically different fibroblast populations were identified in central airways and in the lung parenchyma. Versican production was higher in distal fibroblasts from COPD patients than from control subjects (p proteoglycan production in distally derived fibroblasts from COPD patients and control subjects. In contrast, centrally derived fibroblasts from COPD patients were less responsive to TGF-beta1 than those from control subjects. The results show that fibroblasts from COPD patients have alterations in proteoglycan production that may contribute to disease development. Distally derived fibroblasts from COPD patients have enhanced production of versican that may have a negative influence on the elastic recoil. In addition, a lower perlecan production in centrally derived fibroblasts from COPD patients may indicate alterations in bronchial basement membrane integrity in severe COPD.

  8. Altered fibroblast proteoglycan production in COPD

    Directory of Open Access Journals (Sweden)

    Erjefält Jonas S

    2010-05-01

    Full Text Available Abstract Background Airway remodeling in COPD includes reorganization of the extracellular matrix. Proteoglycans play a crucial role in this process as regulators of the integrity of the extracellular matrix. Altered proteoglycan immunostaining has been demonstrated in COPD lungs and this has been suggested to contribute to the pathogenesis. The major cell type responsible for production and maintenance of ECM constituents, such as proteoglycans, are fibroblasts. Interestingly, it has been proposed that central airways and alveolar lung parenchyma contain distinct fibroblast populations. This study explores the hypothesis that altered depositions of proteoglycans in COPD lungs, and in particular versican and perlecan, is a result of dysregulated fibroblast proteoglycan production. Methods Proliferation, proteoglycan production and the response to TGF-β1 were examined in vitro in centrally and distally derived fibroblasts isolated from COPD patients (GOLD stage IV and from control subjects. Results Phenotypically different fibroblast populations were identified in central airways and in the lung parenchyma. Versican production was higher in distal fibroblasts from COPD patients than from control subjects (p 1 triggered similar increases in proteoglycan production in distally derived fibroblasts from COPD patients and control subjects. In contrast, centrally derived fibroblasts from COPD patients were less responsive to TGF-β1 than those from control subjects. Conclusions The results show that fibroblasts from COPD patients have alterations in proteoglycan production that may contribute to disease development. Distally derived fibroblasts from COPD patients have enhanced production of versican that may have a negative influence on the elastic recoil. In addition, a lower perlecan production in centrally derived fibroblasts from COPD patients may indicate alterations in bronchial basement membrane integrity in severe COPD.

  9. Endothelial cells, fibroblasts and vasculitis.

    Science.gov (United States)

    Buckley, Christopher D; Rainger, G Ed; Nash, Gerard B; Raza, Karim

    2005-07-01

    One of the most important questions in vasculitis research is not why inflammation of blood vessels occurs but why it persists, often in a site-specific manner. In this review we illustrate how stromal cells, such as fibroblasts and pericytes, might play an important role in regulating the site at which vasculitis occurs. Smooth muscle cells and fibroblasts directly influence the behaviour of overlying vascular cells, amplifying the response of the endothelium to proinflammatory agents such as TNF-alpha and allowing enhanced and inappropriate leucocyte recruitment. An abnormal local vascular stromal environment can therefore influence local endothelial function and drive the persistence of local vascular inflammation. However, such local vascular inflammation can have distant effects on the systemic vascular system, leading to widespread endothelial cell dysfunction. Vascular endothelial dysfunction is common in a range of immune-mediated inflammatory diseases, is seen in multiple vascular beds, and is reversible following the induction of disease remission. The mechanisms that drive such systemic vascular endothelial dysfunction are unclear but factors such as TNF-alpha and CRP may play a role. Persistence of such widespread endothelial dysfunction in systemic vasculitis appears to have long-term consequences, leading to the acceleration of atherosclerosis and premature ischaemic heart disease. It may also underlie the accelerated atherosclerosis seen in other immune-mediated rheumatic diseases, such as rheumatoid arthritis.

  10. OHVIRA syndrome presenting with acute abdomen: a case report and review of the literature.

    Science.gov (United States)

    Gungor Ugurlucan, Funda; Bastu, Ercan; Gulsen, Gokce; Kurek Eken, Meryem; Akhan, Suleyman Engin

    2014-01-01

    Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) or Herlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital urogenital anomaly. A 13-year-old female presented with acute abdominal pain and dysmenorrhea. Ultrasonography and magnetic resonance imaging showed uterus didelphys, hematometrocolpos, obstructed hemivagina, and right renal agenesis. Hemivaginal septal resection and anastomosis between the obstructed hemivagina and the normal vagina was tried, but it was not possible. Unilateral hysterectomy was performed. HWW syndrome may present with acute abdomen and is usually treated with vaginal septum resection and drainage of the hematometrocolpos. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Re-evaluation of in vitro radiosensitivity of human fibroblasts of different genetic origins

    Energy Technology Data Exchange (ETDEWEB)

    Deschavanne, P.J.; Debieu, D.; Malaise, E.P.; Fertil, B.

    1986-08-01

    Statistical analysis of the radiosensitivity of 204 survival curves of non-transformed human fibroblast cell strains of different genetic origins was made using the multi-target one-hit model (characterized by parameters eta and D/sub 0/), the surviving fraction for a 2 Gy dose (S/sub 2/) and the mean inactivation dose (D-bar). D-bar is found to be the parameter for characterization of anomalous radiosensitivity linked to a genetic disorder and discrimination between groups of cell strains of differing radiosensitivity. It allows the description of a range of 'normal' radiosensitivity for control fibroblasts and classification of genetic disorders as a function of their mean radiosensitivity expressed in terms of D-bar. Nine groups of cell strains appear to exhibit radiosensitivity differing significantly from the controls: seven groups are hypersensitive (ataxia-telengiectasia homozygotes and heterozygotes, Cockayne's syndrome, Gardner's syndrome, 5-oxoprolinuria homozygotes and heterozygotes, Fanconi's anaemia) and two groups are more radioresistant (fibroblasts from retinoblastoma patients and individuals with chromosome 13 anomalies). Since the coupled parameter eta and D/sub 0/ failed to discriminate between the radiosensitivity of the different genetic groups, the use of D-bar to make an intercomparison of intrinsic radiosensitivity of non-transformed human fibroblasts is recommended. (U.K.).

  12. Genetics Home Reference: Crouzon syndrome with acanthosis nigricans

    Science.gov (United States)

    ... Neidich JA, Wilcox WR. Subtle radiographic findings of achondroplasia in patients with Crouzon syndrome with acanthosis nigricans ... of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon ...

  13. Epigenetic characterization of the FMR1 promoter in induced pluripotent stem cells from human fibroblasts carrying an unmethylated full mutation

    NARCIS (Netherlands)

    de Esch, Celine E F; Ghazvini, Mehrnaz; Loos, Friedemann; Schelling-Kazaryan, Nune; Widagdo, W; Munshi, Shashini T; van der Wal, Erik; Douben, Hannie; Gunhanlar, Nilhan; Kushner, Steven A; Pijnappel, W W M Pim; de Vrij, Femke M S; Geijsen, Niels; Gribnau, Joost; Willemsen, Rob

    2014-01-01

    Silencing of the FMR1 gene leads to fragile X syndrome, the most common cause of inherited intellectual disability. To study the epigenetic modifications of the FMR1 gene during silencing in time, we used fibroblasts and induced pluripotent stem cells (iPSCs) of an unmethylated full mutation (uFM)

  14. Epigenetic characterization of the FMR1 promoter in induced pluripotent stem cells from human fibroblasts carrying an unmethylated full mutation

    NARCIS (Netherlands)

    C. de Esch (Celine); M. Ghazvini (Mehrnaz); F. Loos (Friedemann); N. Schelling-Kazaryan (Nune); W. Widagdo; S.T. Munshi (Shashini T.); E. van der Wal (Erik); H. Douben (Hannie); N. Gunhanlar (Nilhan); S.A. Kushner (Steven); W.W.M.P. Pijnappel (Pim); F.M.S. Vrij (Femke); N. Geijsen (Niels); J.H. Gribnau (Joost); R. Willemsen (Rob)

    2014-01-01

    textabstractSilencing of the FMR1 gene leads to fragile X syndrome, the most common cause of inherited intellectual disability. To study the epigenetic modifications of the FMR1 gene during silencing in time, we used fibroblasts and induced pluripotent stem cells (iPSCs) of an unmethylated full

  15. Sustained systemic delivery of monoclonal antibodies by genetically modified skin fibroblasts

    DEFF Research Database (Denmark)

    Noël, D; Pelegrin, M; Brockly, F

    2000-01-01

    In vivo production and systemic delivery of therapeutic antibodies by engineered cells might advantageously replace injection of purified antibodies for treating a variety of life-threatening diseases, including cancer, acquired immunodeficiency syndrome, and autoimmune diseases. We report here t....... This supports the notion that skin fibroblasts can potentially be used in antibody-based gene/cell therapy protocols without inducing any adverse immune response in treated individuals....

  16. Fibroblast Growth Factor 23 and Hypophosphatemia: A Case of Hypophosphatemia along the Rickets-Osteomalacia Spectrum

    OpenAIRE

    Georges, George T.; Nájera, O.; Sowers, Kurt; Sowers, James R.

    2016-01-01

    Phosphorus is a key component of bone, and a deficiency results in poor mineralization along with other systemic symptoms of hypophosphatemia. Various causes of hypophosphatemia with renal wasting of phosphorus have been identified. These include the Fanconi syndrome, various genetic mutations of fibroblast growth factor 23 (FGF23) handling and the sodium/phosphate cotransporter, and those due to FGF23 secretion by mesenchymal tumors. Depending on the cause, vitamin D metabolism may also be i...

  17. F. Oliver Brachfeld y Werner Wolff: dos figuras en los inicios de la Sociedad Interamericana de Psicología

    Directory of Open Access Journals (Sweden)

    Ramón León

    2012-01-01

    Full Text Available F. Oliver Brachfeld (1908-1967 y Werner Wolff (1904-1957 fueron dos psicólogos europeos emigrados a América del Sur (Brachfeld y a los Estados Unidos de Norteamérica (Wolff que desempeñaron importantes funciones en los años iniciales de la Sociedad Interamericana de Psicología (SIP. Brachfeld fue su Presidente entre 1953 y 1955, en tanto que Wolff fue uno de los gestores de su creación (al lado de Oswaldo Robles, Guillermo Dávila y Rogelio Díaz-Guerrero, su primer Vicepresidente entre 1951 y 1953 y su Secretario General desde 1953 hasta 1957, el año de su prematura muerte. A pesar de su participación en la SIP y de su activo trabajo científico, expresado en obras como Introducción a la psicología e Introducción a la psicopatología, de Wolff, y, Los sentimientos de inferioridad, de Brachfeld, hoy ambos están casi olvidados. La presente comunicación hace una breve reseña biográfica de uno y otro, y analiza las razones por las cuales en la actualidad se habla muy poco de ambos.

  18. An analytic resolution to the competition between Lyman-Werner radiation and metal winds in direct collapse black hole hosts

    Science.gov (United States)

    Agarwal, Bhaskar; Regan, John; Klessen, Ralf S.; Downes, Turlough P.; Zackrisson, Erik

    2017-10-01

    A near pristine atomic cooling halo close to a star forming galaxy offers a natural pathway for forming massive direct collapse black hole (DCBH) seeds, which could be the progenitors of the z > 6 redshift quasars. The close proximity of the haloes enables a sufficient Lyman-Werner flux to effectively dissociate H2 in the core of the atomic cooling halo. A mild background may also be required to delay star formation in the atomic cooling halo, often attributed to distant background galaxies. In this paper, we investigate the impact of metal pollution from both the background galaxies and the close star forming galaxy under extremely unfavourable conditions such as instantaneous metal mixing. We find that within the time window of DCBH formation, the level of pollution never exceeds the critical threshold (Zcr ˜ 1 × 10-5 Z⊙) and attains a maximum metallicity of Z ˜ 2 × 10- 6 Z⊙. As the system evolves, the metallicity eventually exceeds the critical threshold, long after the DCBH has formed.

  19. Fibroblast Growth Factor 21 Mediates Glycemic Regulation by Hepatic JNK

    Directory of Open Access Journals (Sweden)

    Santiago Vernia

    2016-03-01

    Full Text Available The cJun NH2-terminal kinase (JNK-signaling pathway is implicated in metabolic syndrome, including dysregulated blood glucose concentration and insulin resistance. Fibroblast growth factor 21 (FGF21 is a target of the hepatic JNK-signaling pathway and may contribute to the regulation of glycemia. To test the role of FGF21, we established mice with selective ablation of the Fgf21 gene in hepatocytes. FGF21 deficiency in the liver caused marked loss of FGF21 protein circulating in the blood. Moreover, the protective effects of hepatic JNK deficiency to suppress metabolic syndrome in high-fat diet-fed mice were not observed in mice with hepatocyte-specific FGF21 deficiency, including reduced blood glucose concentration and reduced intolerance to glucose and insulin. Furthermore, we show that JNK contributes to the regulation of hepatic FGF21 expression during fasting/feeding cycles. These data demonstrate that the hepatokine FGF21 is a key mediator of JNK-regulated metabolic syndrome.

  20. Fibroblasts in fibrosis: novel roles and mediators

    Directory of Open Access Journals (Sweden)

    Ryan Thomas Kendall

    2014-05-01

    Full Text Available Fibroblasts are the most common cell type of the connective tissues found throughout the body and the principal source of the extensive extracellular matrix (ECM characteristic of these tissues. They are also the central mediators of the pathological fibrotic accumulation of ECM and the cellular proliferation and differentiation that occurs in response to prolonged tissue injury and chronic inflammation. The transformation of the fibroblast cell lineage involves classical developmental signaling programs and includes a surprisingly diverse range of precursor cell types—most notably, myofibroblasts that are the apex of the fibrotic phenotype. Myofibroblasts display exaggerated ECM production; constitutively secrete and are hypersensitive to chemical signals such as cytokines, chemokines, and growth factors; and are endowed with a contractile apparatus allowing them to manipulate the ECM fibers physically to close open wounds. In addition to ECM production, fibroblasts have multiple concomitant biological roles, such as in wound healing, inflammation, and angiogenesis, which are each interwoven with the process of fibrosis. We now recognize many common fibroblast-related features across various physiological and pathological protracted processes. Indeed, a new appreciation has emerged for the role of noncancerous fibroblast interactions with tumors in cancer progression. Although the predominant current clinical treatments of fibrosis involve nonspecific immunosuppressive and anti-proliferative drugs, a variety of potential therapies under investigation specifically target fibroblast biology.

  1. PDGFRaa Signaling Is Regulated through the Primary Cilium in Fibroblasts

    DEFF Research Database (Denmark)

    Schneider, Linda; Clement, Christian Alexandro; Teilmann, S.C.

    2005-01-01

    Recent findings show that cilia are sensory organelles that display specific receptors and ion channels, which transmit signals from the extracellular environment via the cilium to the cell to control tissue homeostasis and function [ [1] , [2] , [3] , [4] , [5] and [6] ]. Agenesis of primary cilia...... or mislocation of ciliary signal components affects human pathologies, such as polycystic kidney disease [ 7 ] and disorders associated with Bardet-Biedl syndrome [ 8 ]. Primary cilia are essential for hedgehog ligand-induced signaling cascade regulating growth and patterning [ [9] and [10] ]. Here, we show...... is followed by activation of Akt and the Mek1/2-Erk1/2 pathways, with Mek1/2 being phosphorylated within the cilium and at the basal body. Fibroblasts derived from Tg737orpk mutants fail to form normal cilia and to upregulate the level of PDGFRa; PDGF-AA fails to activate PDGFRaa and the Mek1/2-Erk1/2 pathway...

  2. Ca{sup 2+} influx and ATP release mediated by mechanical stretch in human lung fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Murata, Naohiko [Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Ito, Satoru, E-mail: itori@med.nagoya-u.ac.jp [Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Furuya, Kishio [Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Takahara, Norihiro [Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Naruse, Keiji [Department of Cardiovascular Physiology, Okayama University Graduate School of Medicine, Okayama 700-8558 (Japan); Aso, Hiromichi; Kondo, Masashi [Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Sokabe, Masahiro [Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Hasegawa, Yoshinori [Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan)

    2014-10-10

    Highlights: • Uniaxial stretching activates Ca{sup 2+} signaling in human lung fibroblasts. • Stretch-induced intracellular Ca{sup 2+} elevation is mainly via Ca{sup 2+} influx. • Mechanical strain enhances ATP release from fibroblasts. • Stretch-induced Ca{sup 2+} influx is not mediated by released ATP or actin cytoskeleton. - Abstract: One cause of progressive pulmonary fibrosis is dysregulated wound healing after lung inflammation or damage in patients with idiopathic pulmonary fibrosis and severe acute respiratory distress syndrome. The mechanical forces are considered to regulate pulmonary fibrosis via activation of lung fibroblasts. In this study, the effects of mechanical stretch on the intracellular Ca{sup 2+} concentration ([Ca{sup 2+}]{sub i}) and ATP release were investigated in primary human lung fibroblasts. Uniaxial stretch (10–30% in strain) was applied to fibroblasts cultured in a silicone chamber coated with type I collagen using a stretching apparatus. Following stretching and subsequent unloading, [Ca{sup 2+}]{sub i} transiently increased in a strain-dependent manner. Hypotonic stress, which causes plasma membrane stretching, also transiently increased the [Ca{sup 2+}]{sub i}. The stretch-induced [Ca{sup 2+}]{sub i} elevation was attenuated in Ca{sup 2+}-free solution. In contrast, the increase of [Ca{sup 2+}]{sub i} by a 20% stretch was not inhibited by the inhibitor of stretch-activated channels GsMTx-4, Gd{sup 3+}, ruthenium red, or cytochalasin D. Cyclic stretching induced significant ATP releases from fibroblasts. However, the stretch-induced [Ca{sup 2+}]{sub i} elevation was not inhibited by ATP diphosphohydrolase apyrase or a purinergic receptor antagonist suramin. Taken together, mechanical stretch induces Ca{sup 2+} influx independently of conventional stretch-sensitive ion channels, the actin cytoskeleton, and released ATP.

  3. N-cadherin is overexpressed in Crohn's stricture fibroblasts and promotes intestinal fibroblast migration.

    LENUS (Irish Health Repository)

    Burke, John P

    2012-02-01

    BACKGROUND: Intestinal fibroblasts mediate stricture formation in Crohn\\'s disease (CD). Transforming growth factor-beta (TGF-beta) is important in fibroblast activation, while cell attachment and migration is regulated by the adhesion molecule N-cadherin. The aim of this study was to investigate the expression and function of N-cadherin in intestinal fibroblasts in patients with fibrostenosing CD. METHODS: Intestinal fibroblasts were cultured from seromuscular biopsies from patients undergoing resection for terminal ileal fibrostenosing CD (n = 14) or controls patients (n = 8). N-cadherin expression was assessed using Western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Fibroblasts were stimulated with TGF-beta and selective pathway inhibitors Y27632, PD98050, and LY294002 were used to examine the Rho\\/ROCK, ERK-1\\/2, and Akt signaling pathways, respectively. Cell migration was assessed using a scratch wound assay. N-cadherin was selectively overexpressed using a plasmid. RESULTS: Fibroblasts from fibrostenosing CD express increased constitutive N-cadherin mRNA and protein and exhibit enhanced basal cell migration relative to those from directly adjacent normal bowel. Control fibroblasts treated with TGF-beta induced N-cadherin in a dose-dependent manner which was inhibited by Rho\\/ROCK and Akt pathway modulation. Control fibroblasts exhibited enhanced cell migration in response to treatment with TGF-beta or transfection with an N-cadherin plasmid. CONCLUSIONS: Fibroblasts from strictures in CD express increased constitutive N-cadherin and exhibit enhanced basal cell migration. TGF-beta is a potent inducer of N-cadherin in intestinal fibroblasts resulting in enhanced cell migration. The TGF-beta-mediated induction of N-cadherin may potentiate Crohn\\'s stricture formation.

  4. Growth and cell cycle abnormalities of fibroblasts from Tangier disease patients.

    Science.gov (United States)

    Drobnik, W; Liebisch, G; Biederer, C; Tr mbach, B; Rogler, G; Müller, P; Schmitz, G

    1999-01-01

    We have investigated the abnormal proliferation and morphology of fibroblasts from patients with Tangier disease (TD), a high density lipoprotein (HDL) deficiency syndrome that is characterized by impairment of HDL3-mediated lipid efflux and Gi-protein-mediated signaling via phosphatidylinositol-specific phospholipase C (PI-PLC) and phospholipase D (PLD). TD fibroblasts displayed a 30% to 50% reduced in vitro growth rate and a 1.6-fold increased cell surface area. The response to different mitogens was diminished, and asynchronously growing TD fibroblasts showed 4.4+/-0.3% S-phase and 19.1+/-0.5% G2/M-phase cells compared with 9.7+/-0.6% and 7.8+/-0.5%, respectively, in controls. Monensin, but not brefeldin A, induced an S- and G2/M-phase distribution in control cells similar to that found in TD fibroblasts. This effect of monensin was accompanied by an increase of ceramide levels in controls, whereas TD fibroblasts already had a 2.5-fold increased basal ceramide concentration. Incubation of control cells with C2 ceramide and threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) mimicked the effect of monensin on the cell cycle. The inhibition of neither Gi protein function by pertussis toxin nor PLD by butanol resulted in a G2/M-phase arrest. Propranolol, known to increase phosphatidic acid levels, was ineffective in reversing the G2/M-phase arrest in TD fibroblasts. In addition, cDNA sequences and mRNA expression of the participants of PI-PLC or PLD signaling, ie, G-protein subunits alphai1, alphai2, and alphai3; phosphatidylinositol transfer proteins-alpha and -beta; and ADP ribosylation factors 1 and 3 were found to be normal. Thus, growth and cell cycle abnormalities in TD fibroblasts are likely to be related to impaired Golgi function and sphingolipid signaling rather than inoperative G-protein signal transduction. Because PDMP was also found to decrease HDL3-mediated lipid efflux in control but not TD fibroblasts, similar pathways seem to be involved

  5. Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Zhong Xin [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Sun, Cong Cong [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Ting Zhu, Yu; Wang, Ying; Wang, Tao; Chi, Li Sha; Cai, Wan Hui [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zheng, Jia Yong [Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Zhou, Xuan [Ningbo First Hospital, Ningbo, Zhejiang (China); Cong, Wei Tao [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Xiao Kun, E-mail: proflxk@163.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Jin, Li Tai, E-mail: jin_litai@126.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China)

    2017-06-15

    Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

  6. OHVIRA syndrome (obstructed hemivagina and ipsilateral renal anomaly) with uterus didelphys, an unusual presentation.

    Science.gov (United States)

    Mandava, Anitha; Prabhakar, R R; Smitha, S

    2012-04-01

    Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA), or Herlyn-Werner-Wunderlich syndrome, is a rare Mullerian duct anomaly with uterus didelphys, unilateral obstructed hemivagina, and ipsilateral renal agenesis. Patients with this anomaly usually present after menarche with pelvic pain and/or a mass and rarely, in later years, with primary infertility. Strong suspicion and knowledge of this anomaly are essential for a precise diagnosis. A 14-year-old female presented with acute retention of urine and was diagnosed as a case of OHVIRA syndrome with uterus didelphys. Acute retention of urine as the initial clinical presentation has been rarely reported in this syndrome. She was treated with hemivaginal septal resection. OHVIRA syndrome should be considered among the differential diagnoses in young females with renal anomalies presenting with pelvic mass, symptoms of acute abdomen, and acute urinary retention. Copyright © 2012 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  7. Cryopreservation of canine ovarian and testicular fibroblasts.

    Science.gov (United States)

    Yu, Il-Jeoung; Leibo, S P; Songsasen, Nucharin; Dresser, Betsy L; Kim, In-Shik

    2009-01-01

    To derive a practical procedure to store canine somatic cells, fibroblasts isolated from testicular or ovarian tissues were cryopreserved in 1.2 M ethylene glycol or in 1.2 M dimethylsulfoxide prepared in Dulbecco's Modified Eagle Medium as cryoprotectants, and were frozen either in plastic straws or vials. Thawed cells were cultured for 24 hr at 38.5 degree C in a humidified atmosphere of 5 percent CO2 95 percent air, and then their membrane integrity was assayed with a double fluorescent stain, Fertilight. In addition, frozen-thawed fibroblasts were cultured for 4 days, and then their functional survival was measured after staining small colonies with trypan blue. After freezing and thawing, membrane integrity of testicular fibroblasts was 55-70 percent and functional survival ranged from 20-40 percent. With frozen-thawed ovarian cells, the average membrane integrity was 55-75 percent and the average functional survival was 35-40 percent. When frozen in ethylene glycol, functional survival of ovarian fibroblasts was significantly higher than that of testicular cells (P less than 0.05). These methods should prove useful to preserve cells collected from canids in the wild.

  8. Fibroblast growth factor 23 - et fosfatregulerende hormon

    DEFF Research Database (Denmark)

    Beck-Nielsen, Signe; Pedersen, Susanne Møller; Kassem, Moustapha

    2010-01-01

    Fibroblast growth factor 23 (FGF23) er et nyligt identificeret fosfatonin. FGF23's fysiologiske hovedfunktion er at opretholde normalt serumfosfat og at virke som et D-vitaminmodregulatorisk hormon. Sygdomme, der er koblet til forhøjet serum FGF23, er hypofosfatæmisk rakitis, fibrøs dysplasi og...

  9. UV-induced extracellular factor from human fibroblasts communicates the UV response to nonirradiated cells

    Energy Technology Data Exchange (ETDEWEB)

    Schorpp, M.; Mallick, U.; Rahmsdorf, H.J.; Herrlich, P.

    1984-07-01

    Ultraviolet light enhances the synthesis of at least eight abundant proteins in human fibroblasts within 2 hr. These proteins are identical with those induced by the tumor promoter TPA. The inducing signal is generated by DNA damage, as these proteins are induced by lower doses of UV in fibroblasts from patients with Cockayne's syndrome or Xeroderma pigmentosum. In the supernatant of UV-treated cells, a heat-labile ammonium sulfate precipitable factor of more than 10 kd (EPIF) was detected which, upon transfer to nonirradiated cells, mimicked UV in the UV-induced synthesis of gene products. The response to UV, TPA, or EPIF was inhibited by fluocinolone acetonide, but not by retinoic acid, protease inhibitors, or superoxide dismutase.

  10. Allogeneic fibroblasts in dermal substitutes induce inflammation and scar formation

    NARCIS (Netherlands)

    Lamme, Evert N.; van Leeuwen, Rene T. J.; Mekkes, Jan R.; Middelkoop, Esther

    2002-01-01

    In the present study, we compared the use of autologous versus allogeneic fibroblasts in dermal skin substitutes in a porcine wound model. The allogeneic fibroblast populations were isolated from female and a male pig (allo-1, - 2 and - 3) and the controls, autologous fibroblasts, from female

  11. HETEROGENIC SERUM, AGE, AND MULTIPLICATION OF FIBROBLASTS.

    Science.gov (United States)

    Carrel, A; Ebeling, A H

    1922-01-01

    The presence in a culture medium of heterogenic serum of various concentrations exerts a definite influence on the rate of multiplication of fibroblasts. Dog serum does not inhibit the growth of See PDF for Structure chicken fibroblasts markedly until its concentration reaches 15 per cent. Beyond this figure, each increase of the concentration brings about a rapid decrease in the rate of cell multiplication. When the concentration reaches from 30 to 45 per cent, no growth takes place. The inhibiting action of cat serum begins to manifest itself at a concentration of 25 per cent and prevents cell proliferation completely at a concentration of 55 and 60 per cent. The ratio, See PDF for Equation can be taken as expressing the action of the serum on fibroblast multiplication; that is, as the growth index of the serum. See PDF for Structure The inhibiting influence of heterogenic serum was found to vary in direct ratio to the age of the animal from which it was obtained. The rate of proliferation of chicken fibroblasts was studied comparatively in media containing varied concentrations of serum from young and old animals. For each concentration of serum, the rate of growth in the serum of the old animal was expressed in relation to the rate of growth in the serum of the young animal. When cat serum was used, the curve obtained in plotting this ratio in ordinates and the serum concentration in abscissae showed a rapid increase in the inhibiting action of the old serum as soon as the concentration reached 30 per cent. The same tests were repeated with the serum from young and old dogs. The general results were identical, although See PDF for Structure the quantitative inhibiting action of both sera was greater than that of cat serum. It may be concluded that under the conditions of the experiments: 1. Heterogenicsera inhibit and prevent the growth of chicken fibroblasts when their concentration is made to vary within certain limits. 2. A relation exists between the rate

  12. Fibroblast α11β1 integrin regulates tensional homeostasis in fibroblast/A549 carcinoma heterospheroids.

    Directory of Open Access Journals (Sweden)

    Ning Lu

    Full Text Available We have previously shown that fibroblast expression of α11β1 integrin stimulates A549 carcinoma cell growth in a xenograft tumor model. To understand the molecular mechanisms whereby a collagen receptor on fibroblast can regulate tumor growth we have used a 3D heterospheroid system composed of A549 tumor cells and fibroblasts without (α11+/+ or with a deletion (α11-/- in integrin α11 gene. Our data show that α11-/-/A549 spheroids are larger than α11+/+/A549 spheroids, and that A549 cell number, cell migration and cell invasion in a collagen I gel are decreased in α11-/-/A549 spheroids. Gene expression profiling of differentially expressed genes in fibroblast/A549 spheroids identified CXCL5 as one molecule down-regulated in A549 cells in the absence of α11 on the fibroblasts. Blocking CXCL5 function with the CXCR2 inhibitor SB225002 reduced cell proliferation and cell migration of A549 cells within spheroids, demonstrating that the fibroblast integrin α11β1 in a 3D heterospheroid context affects carcinoma cell growth and invasion by stimulating autocrine secretion of CXCL5. We furthermore suggest that fibroblast α11β1 in fibroblast/A549 spheroids regulates interstitial fluid pressure by compacting the collagen matrix, in turn implying a role for stromal collagen receptors in regulating tensional hemostasis in tumors. In summary, blocking stromal α11β1 integrin function might thus be a stroma-targeted therapeutic strategy to increase the efficacy of chemotherapy.

  13. Herlyn–Werner–Wunderlich syndrome presenting with infertility: Role of MRI in diagnosis

    Science.gov (United States)

    Ahmad, Zohra; Goyal, Ankur; Das, Chandan J; Deka, Dipika; Sharma, Raju

    2013-01-01

    Herlyn-Werner-Wunderlich syndrome (HWWS), characterized by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis, is an uncommon combined Mullerian and mesonephric duct anomaly, and its presentation in adulthood is even rarer. We report here a 22-year-old female presenting with primary infertility where magnetic resonance imaging (MRI) suggested the diagnosis of HWWS with endometriosis. In a patient of infertility with endometriosis and unilateral renal agenesis, diagnosis of HWWS should be suspected and MRI is the investigation of choice for such anomalies. PMID:24347855

  14. [Matthias Asche, Werner Buchholz, Anton Schindling. Die baltischen Lande im Zeitalter der Reformation und Konfessionalisierung : Livland, Estland, Ösel, Ingermanland, Kurland und Lettgallen; Stadt, Land und Konfession 1500-1721. T. 1-3] / Axel von C

    Index Scriptorium Estoniae

    Campenhausen, Axel von

    2015-01-01

    Arvustus: Asche, Matthias, Bucholz, Werner, Achindling, Anton. (Hrsg.) Die baltischen Lande im Zeitalter der Reformation und Konfessionalisierung : Livland, Estland, Ösel, Ingermanland, Kurland und Lettgallen; Stadt, Land und Konfession 1500-1721. T. 1-3. Münster: Aschendorff Verlag 2009, 2010, 2011

  15. [Die baltischen Lande im Zeitalter der Reformation und Konfessionalisierung : Livland, Estland, Ösel, Ingermanland, Kurland und Lettgallen : Stadt, Land und Konfession 1500-1721. Teil 4. Hrsg. von Matthias Asche, Werner Buchholtz und Anton Schindlin

    Index Scriptorium Estoniae

    Maasing, Madis, 1984-

    2013-01-01

    Arvustus: Die baltischen Lande im Zeitalter der Reformation und Konfessionalisierung : Livland, Estland, Ösel, Ingermanland, Kurland und Lettgallen : Stadt, Land und Konfession 1500-1721. Teil 4. (Katholisches Leben und Kirchenreform im Zeitalter der Glaubensspaltung, 72). Hrsg. von Matthias Asche, Werner Buchholtz und Anton Schindling. Verlag Aschendorff. Münster 2012

  16. Serotonin syndrome

    Science.gov (United States)

    Hyperserotonemia; Serotonergic syndrome; Serotonin toxicity; SSRI - serotonin syndrome; MAO - serotonin syndrome ... brain area. For example, you can develop this syndrome if you take migraine medicines called triptans together ...

  17. The effect of tranilast on fibroblast activation protein α (FAP-α expression in normal and keloid fibroblasts in vitro

    Directory of Open Access Journals (Sweden)

    Paweł P. Antończak

    2017-07-01

    Full Text Available Introduction . Tranilast (N-(3’,4’-demethoxycinnamoyl-anthranilic acid is an anti-allergic drug. Its mechanism of action is based on the inhibition of antigen-induced release of chemical mediators from mast cells and basophils. It also reveals antifibroproliferative activities. These properties of tranilast are used in the treatment of hypertrophic scars and keloids. Keloids are characterized by incorrect extracellular matrix components turnover. Fibroblasts derived from keloids reveal overproduction of collagen type I and decreased degradation of extracellular matrix in comparison with normal fibroblasts. Fibroblast activation protein α (FAP-α may play an important role in remodeling of extracellular matrix and the invasive properties of keloids. Objective . In the present study, the effect of tranilast on expression of FAP-α gene and its protein was evaluated in normal human dermal fibroblasts and fibroblasts derived from keloids cultured in vitro . Materials and methods. In the first stage of the study, the influence of tranilast on cell viability was estimated. The second stage of the study included the quantitative evaluation of FAP-α mRNA expression in normal and keloid fibroblasts treated with tranilast. The third stage of the study comprised fibroblast activation protein α expression analysis in the examined cells treated with tranilast. Results and conclusions . The expression of FAP-α gene and fibroblast activation protein α is higher in keloid fibroblasts. Tranilast at concentrations of 3 μM and 30 μM up-regulated mRNA FAP-α expression in normal fibroblasts but did not influence keloid fibroblasts. The drug, at concentrations of 30 μM and 300 μM up-regulated fibroblast activation protein α expression in normal fibroblasts and did not influence keloid fibroblasts. Tranilast antiproliferative effect is not associated with FAP-α expression in keloid fibroblasts.

  18. Cockayne syndrome in two adult siblings.

    Science.gov (United States)

    Miyauchi, H; Horio, T; Akaeda, T; Asada, Y; Chang, H R; Ishizaki, K; Ikenaga, M

    1994-02-01

    Although survival beyond the second decade is unusual in patients who have Cockayne syndrome, we describe two brothers with the syndrome who are 42 and 55 years of age. Their cultured skin fibroblasts showed extreme UV sensitivity but had almost normal UV-induced unscheduled DNA synthesis. The patients were classified as genetic complementation group B after study of the recovery of RNA synthesis after UV irradiation of fused cells. Clinical phototesting revealed a reduced threshold for UVB erythema.

  19. Overexpression of wild-type creatine transporter (SLC6A8) restores creatine uptake in primary SLC6A8-deficient fibroblasts.

    Science.gov (United States)

    Rosenberg, Efraim H; Muñoz, Cristina Martínez; Degrauw, Ton J; Jakobs, Cor nelis; Salomons, Gajja S

    2006-01-01

    In the study reported, we prove that mutations in the SLC6A8 gene are responsible for SLC6A8 deficiency, a cerebral creatine deficiency syndrome (CCDS), since overexpression of the wild-type SLC6A8 open reading frame (ORF) restores the creatine uptake profile in SLC6A8-deficient fibroblasts.

  20. The hypoxia-inducible factor-1? activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia

    OpenAIRE

    Zhang, Qian; Doucet, Michele; Tomlinson, Ryan E; Han, Xiaobin; Quarles, L Darryl; Collins, Michael T; Clemens, Thomas L

    2016-01-01

    Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which ectopic production of fibroblast growth factor 23 (FGF23) by non-malignant mesenchymal tumors causes phosphate wasting and bone fractures. Recent studies have implicated the hypoxia-inducible factor-1? (HIF-1?) in other phosphate wasting disorders caused by elevated FGF23, including X-linked hypophosphatemic rickets and autosomal dominant hypophosphatemia. Here we provide evidence that HIF-1? mediates aberrant FGF23 i...

  1. Acidic Fibroblast Growth Factor Promotes Vascular Repair

    Science.gov (United States)

    Bjornsson, Thorir D.; Dryjski, Maciej; Tluczek, John; Mennie, Robert; Ronan, John; Mellin, Theodore N.; Thomas, Kenneth A.

    1991-10-01

    Intravascular injury to arteries can result in thickening of the intimal smooth muscle layer adjacent to the lumen by migration and proliferation of cells from the underlying medial smooth muscle layer accompanied by deposition of extracellular matrix. This pathological response, which decreases lumen diameter, might, in part, be the result of the access of smooth muscle cells to plasma and platelet-derived growth factors as a consequence of denudation of the overlying confluent monolayer of vascular endothelial cells. Injured rat carotid arteries were treated by i.v. administration of acidic fibroblast growth factor, a heparin-binding protein that is chemotactic and mitogenic for vascular endothelial cells. The growth factor treatment resulted in dose-dependent inhibition of intimal thickening with parallel promotion of endothelial regeneration over the injured area. Therefore, acidic fibroblast growth factor might be efficacious in the prevention of restenosis caused by intimal thickening following angioplasty in humans.

  2. Fibroblasts as architects of cancer pathogenesis.

    Science.gov (United States)

    Marsh, Timothy; Pietras, Kristian; McAllister, Sandra S

    2013-07-01

    Studies of epithelial cancers (i.e., carcinomas) traditionally focused on transformation of the epithelium (i.e., the cancer cells) and how aberrant signaling within the cancer cells modulates the surrounding tissue of origin. In more recent decades, the normal cells, blood vessels, molecules, and extracellular components that surround the tumor cells, collectively known as the "tumor microenvironment" or "stroma", have received increasing attention and are now thought to be key regulators of tumor initiation and progression. Of particular relevance to the work reviewed herein are the fibroblasts, which make up the major cell type within the microenvironment of most carcinomas. Due to their inherent heterogeneity, plasticity, and function, it is perhaps not surprising that fibroblasts are ideal modulators of normal and cancerous epithelium; however, these aspects also present challenges if we are to interrupt their tumor-supportive functions. Here, we review the current body of knowledge and the many questions that still remain about the special entity known as the cancer-associated fibroblast. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease. Copyright © 2012. Published by Elsevier B.V.

  3. Fibroblasts as maestros orchestrating tissue regeneration.

    Science.gov (United States)

    Costa-Almeida, Raquel; Soares, Raquel; Granja, Pedro L

    2017-01-20

    Fibroblasts constitute a dynamic and versatile population of cells of mesenchymal origin, implicated in both regenerative strategies and pathological conditions. Despite being frequently associated to disease development, particularly through the establishment of fibrotic tissue, fibroblasts hold great potential for tissue engineering and regenerative medicine applications. They are responsible for synthesizing and depositing extracellular matrix components, allowing other cells to settle and migrate along a three-dimensional support and thereby generating an organ-specific architecture. Additionally, they produce bioactive molecules that are involved in several physiological processes, including angiogenesis and tissue repair. Although there seems to be much still to unveil about these fascinating cells they have been attracting increasing interest and are now being intensively explored as a cell source to develop bioengineered tissue constructs or to improve stem cell-based technologies. This review intends to highlight the potential of fibroblasts in orchestrating tissue regeneration, as well as to contribute to uncover uncharted prospective applications of these cells. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Alteration of Skin Properties with Autologous Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Rajesh L. Thangapazham

    2014-05-01

    Full Text Available Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound healing and skin repair. Preclinical studies suggest wider applications of dermal fibroblasts ranging from skin based indications to non-skin tissue regeneration in tendon repair. One clinical application for autologous dermal fibroblasts has been approved by the Food and Drug Administration (FDA while others are in preclinical development or various stages of regulatory approval. In this context, we outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous dermal fibroblasts. The microanatomic and phenotypic differences of fibroblasts occupying particular locations within the skin are reviewed, emphasizing the therapeutic relevance of attributes exhibited by subpopulations of fibroblasts. Special focus is provided to fibroblast characteristics that define regional differences in skin, including the thick and hairless skin of the palms and soles as compared to hair-bearing skin. This regional specificity and functional identity of fibroblasts provides another platform for developing regional skin applications such as the induction of hair follicles in bald scalp or alteration of the phenotype of stump skin in amputees to better support their prosthetic devices.

  5. Pericellular Versican Regulates the Fibroblast-Myofibroblast Transition

    Science.gov (United States)

    Hattori, Noriko; Carrino, David A.; Lauer, Mark E.; Vasanji, Amit; Wylie, James D.; Nelson, Courtney M.; Apte, Suneel S.

    2011-01-01

    The cell and its glycosaminoglycan-rich pericellular matrix (PCM) comprise a functional unit. Because modification of PCM influences cell behavior, we investigated molecular mechanisms that regulate PCM volume and composition. In fibroblasts and other cells, aggregates of hyaluronan and versican are found in the PCM. Dermal fibroblasts from Adamts5−/− mice, which lack a versican-degrading protease, ADAMTS5, had reduced versican proteolysis, increased PCM, altered cell shape, enhanced α-smooth muscle actin (SMA) expression and increased contractility within three-dimensional collagen gels. The myofibroblast-like phenotype was associated with activation of TGFβ signaling. We tested the hypothesis that fibroblast-myofibroblast transition in Adamts5−/− cells resulted from versican accumulation in PCM. First, we noted that versican overexpression in human dermal fibroblasts led to increased SMA expression, enhanced contractility, and increased Smad2 phosphorylation. In contrast, dermal fibroblasts from Vcan haploinsufficient (Vcanhdf/+) mice had reduced contractility relative to wild type fibroblasts. Using a genetic approach to directly test if myofibroblast transition in Adamts5−/− cells resulted from increased PCM versican content, we generated Adamts5−/−;Vcanhdf/+ mice and isolated their dermal fibroblasts for comparison with dermal fibroblasts from Adamts5−/− mice. In Adamts5−/− fibroblasts, Vcan haploinsufficiency or exogenous ADAMTS5 restored normal fibroblast contractility. These findings demonstrate that altering PCM versican content through proteolytic activity of ADAMTS5 profoundly influenced the dermal fibroblast phenotype and may regulate a phenotypic continuum between the fibroblast and its alter ego, the myofibroblast. We propose that a physiological function of ADAMTS5 in dermal fibroblasts is to maintain optimal versican content and PCM volume by continually trimming versican in hyaluronan-versican aggregates. PMID:21828051

  6. SOBRE EL LLENGUATGE CINEMATOGRÀFIC DE WERNER SCHROETER A MALINA, A PARTIR DE LA NOVEL·LA D’INGEBORG BACHMANN, AMB GUIÓ D’ELFRIEDE JELINEK

    Directory of Open Access Journals (Sweden)

    M. Loreto Vilar

    2015-12-01

    Full Text Available This paper provides an approach to the cinematic language in the film Malina (1991, directed by Werner Schroeter after Ingeborg Bachmann’s homonymous novel, script by Elfriede Jelinek. Working on the study by Ute Seiderer (1994 and the information provided by film editor Juliane Lorenz, the exposition and analysis of the mise-en-scène focuses on the following items: the temporal sequencing, the insinuatio in the film, the interaction between physical and psychological space, the music and the visual narrative of the end of the woman. Explored are also the motifs of ubiquitous fire, the crack in the wall and the game of mirrors. Together with the representation of the Malina character, they materialize the duality in the psyche of the woman writer in the main role and her struggle for existence.

  7. The Great Detective, by Zach Dundas; Gender and the modern Sherlock Holmes, edited by Nadine Farghaly; and Sherlock Holmes, edited by Alex Werner [book review

    Directory of Open Access Journals (Sweden)

    Julia Knaus

    2017-03-01

    Full Text Available Review of: Zach Dundas. The Great Detective: The amazing rise and immortal life of Sherlock Holmes. Boston: Houghton Mifflin Harcourt, 2015, hardcover, $26 (336p, ISBN 978-0-544-21404-0, e-book $15.95 (2378 KB, ISBN 978-0-544-22020-1, ASIN B00LZ7GP6U. Nadine Farghaly, ed. Gender and the modern Sherlock Holmes: Essays on film and television adaptations since 2009. Jefferson, NC: McFarland, 2015, paperback, $35 (260p, ISBN 978-0-786-49459-0, e-book $9.99 (3353 KB, ISBN 978-1-4766-2281-1, ASIN B019WQQEY8. Alex Werner, ed. Sherlock Holmes: The man who never lived and will never die. London: Ebury Press, 2014, hardcover, £25 (256p, ISBN 978-0-09-195872-5, e-book £12.99, ISBN 978-1-47-350264-2.

  8. Bernard Lerer: Recipient of the 2014 Inaugural Werner Kalow Responsible Innovation Prize in Global Omics and Personalized Medicine (Pacific Rim Association for Clinical Pharmacogenetics)

    Science.gov (United States)

    Aynacıoğlu, Şükrü; Bragazzi, Nicola Luigi; Dandara, Collet; Dove, Edward S.; Ferguson, Lynnette R.; Geraci, Christy Jo; Hafen, Ernst; Kesim, Belgin Eroğlu; Kolker, Eugene; Lee, Edmund J.D.; LLerena, Adrian; Nacak, Muradiye; Shimoda, Kazutaka; Someya, Toshiyuki; Srivastava, Sanjeeva; Tomlinson, Brian; Vayena, Effy; Warnich, Louise; Yaşar, Ümit

    2014-01-01

    Abstract This article announces the recipient of the 2014 inaugural Werner Kalow Responsible Innovation Prize in Global Omics and Personalized Medicine by the Pacific Rim Association for Clinical Pharmacogenetics (PRACP): Bernard Lerer, professor of psychiatry and director of the Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. The Werner Kalow Responsible Innovation Prize is given to an exceptional interdisciplinary scholar who has made highly innovative and enduring contributions to global omics science and personalized medicine, with both vertical and horizontal (transdisciplinary) impacts. The prize is established in memory of a beloved colleague, mentor, and friend, the late Professor Werner Kalow, who cultivated the idea and practice of pharmacogenetics in modern therapeutics commencing in the 1950s. PRACP, the prize's sponsor, is one of the longest standing learned societies in the Asia-Pacific region, and was founded by Kalow and colleagues more than two decades ago in the then-emerging field of pharmacogenetics. In announcing this inaugural prize and its winner, we seek to highlight the works of prize winner, Professor Lerer. Additionally, we contextualize the significance of the prize by recalling the life and works of Professor Kalow and providing a brief socio-technical history of the rise of pharmacogenetics and personalized medicine as a veritable form of 21st century scientific practice. The article also fills a void in previous social science analyses of pharmacogenetics, by bringing to the fore the works of Kalow from 1995 to 2008, when he presciently noted the rise of yet another field of postgenomics inquiry—pharmacoepigenetics—that railed against genetic determinism and underscored the temporal and spatial plasticity of genetic components of drug response, with invention of the repeated drug administration (RDA) method that estimates the dynamic heritabilities of drug response. The prize goes a

  9. True management of Obstructed Hemi-vagina and Ipsilateral Renal Anomaly syndrome.

    Science.gov (United States)

    Yakıştıran, Betül; Şükür, Yavuz Emre; Turgay, Batuhan; Atabekoğlu, Cem

    2016-12-01

    Herlyn-Werner-Wunderlich syndrome is an unusual congenital anomaly of the female genitourinary system, which is described as uterine didelphys with Obstructed Hemi-vagina and Ipsilateral Renal Anomaly (OHIRA), also known as OHVIRA syndrome. Typical symptoms are pelvic pain, tenderness, pelvic mass due to blood collection in the obstructed hemi-vagina and uterus, and dysmenorrhea that usually begins shortly after menarche. Clinical suspicion is very important for diagnosis and correct management avoids both short- and long-term complications. Surgical removal of the vaginal septum is the main treatment method. Herein, we describe the evaluation and surgical management of a patient with OHVIRA syndrome who was diagnosed using magnetic resonance imaging and pelvic ultrasound.

  10. Fibroblast growth factor signaling in mammalian tooth development.

    Science.gov (United States)

    Li, Chun-Ying; Prochazka, Jan; Goodwin, Alice F; Klein, Ophir D

    2014-01-01

    In this review, we discuss the central role of fibroblast growth factor (FGF) signaling in mammalian tooth development. The FGF family consists of 22 members, most of which bind to four different receptor tyrosine kinases, which in turn signal through a cascade of intracellular proteins. This signaling regulates a number of cellular processes, including proliferation, differentiation, cell adhesion and cell mobility. FGF signaling first becomes important in the presumptive dental epithelium at the initiation stage of tooth development, and subsequently, it controls the invagination of the dental epithelium into the underlying mesenchyme. Later, FGFs are critical in tooth shape formation and differentiation of ameloblasts and odontoblasts, as well as in the development and homeostasis of the stem cell niche that fuels the continuously growing mouse incisor. In addition, FGF signaling is critical in human teeth, as mutations in genes encoding FGF ligands or receptors result in several congenital syndromes characterized by alterations in tooth number, morphology or enamel structure. The parallel roles of FGF signaling in mouse and human tooth development demonstrate the conserved importance of FGF signaling in mammalian odontogenesis.

  11. Primary cell culture from human oral tissue: gingival keratinocytes,gingival fibroblasts and periodontal ligament fibroblasts

    Directory of Open Access Journals (Sweden)

    Supreya Wanichpakorn

    2010-08-01

    Full Text Available Primary cell culture of human oral tissue has many applications for oral biology research. There are two techniques in primary culture, which includes the enzymatic and direct explant technique. The objectives of this study were (1 to isolate and investigate the difference in percentage the success in culturing three cell types from human oral tissue: gingival keratinocytes, gingival fibroblasts and periodontal ligament fibroblasts by using the direct explant technique; (2 to compare the effect of sex and age on the success of tissue culturing. Twenty seven tissue samples were obtained from healthy human gingival tissue, 19 female and 8 male patients aged 14-67 years (37.7±17.5. The tissue was cut into 1x1 mm pieces and placed on plastic culture plates containing Dulbecco’s Modified Eagle’s Medium supplemented with 10% fetal calf serum, 100 U/ml penicillin, 100 µg/ml streptomycin and 1% amphotericin B. For the keratinocytes culture, after the epithelial cells started to multiply around the gingival origin and the diameter was 2-5 mm., the fibroblasts were liminated by mechanical removal under inverted microscope to prevent fibroblast overgrowth and the medium was changed to keratinocyte-SFM (Gibco, BRL supplemented with 5 µg/ml gentamycin. The results revealed that gingival fibroblast gave the highest success rate in culture (96.3%, followed by gingival keratinocytes (88.9% and periodontal ligament fibroblasts (81.5%. There was no significant difference in the success rate of cultivation between younger and older individuals, as between sex of the subjects (p>0.05. The risk of failure in culture techniques is mainly caused by microbiological contamination from the tissue samples.

  12. Lipoxin A4 promotes lung epithelial repair whilst inhibiting fibroblast proliferation

    Directory of Open Access Journals (Sweden)

    Shengxing Zheng

    2016-10-01

    Full Text Available Therapy that promotes epithelial repair whilst protecting against fibroproliferation is critical for restoring lung function in acute and chronic respiratory diseases. Primary human alveolar type II cells were used to model the effects of lipoxin A4 in vitro upon wound repair, proliferation, apoptosis and transdifferention. Effects of lipoxin A4 upon primary human lung fibroblast proliferation, collagen production, and myofibroblast differentiation were also assessed. Lipoxin A4 promoted type II cell wound repair and proliferation, blocked the negative effects of soluble Fas ligand/tumour necrosis factor α upon cell proliferation, viability and apoptosis, and augmented the epithelial cell proliferative response to bronchoaveolar lavage fluid (BALF from acute respiratory distress syndrome (ARDS. In contrast, Lipoxin A4 reduced fibroblast proliferation, collagen production and myofibroblast differentiation induced by transforming growth factor β and BALF from ARDS. The effects of Lipoxin A4 were phosphatidylinositol 3′-kinase dependent and mediated via the lipoxin A4 receptor. Lipoxin A4 appears to promote alveolar epithelial repair by stimulating epitheial cell wound repair, proliferation, reducing apoptosis and promoting trans-differentiation of alveolar type II cells into type I cells. Lipoxin A4 reduces fibroblast proliferation, collagen production and myofibroblast differentiation. These data suggest that targeting lipoxin actions may be a therapeutic strategy for treating the resolution phase of ARDS.

  13. Enhanced reactivation of ultraviolet-damaged herpes virus in ultraviolet pretreated skin fibroblasts of cancer prone donors

    Energy Technology Data Exchange (ETDEWEB)

    Coppey, J.; Menezes, S.

    1981-01-01

    An enhanced reactivation of ultraviolet-damaged (u.v. at 254 nm) unclear replicating double-stranded DNA viruses occurs when corresponding host cells are treated with radiation or carcinogens prior to infection. This phenomenon seems to be due to an induced DNA repair activity the nature of which is yet unknown. The u.v.-induced enhanced reactivation (ER) of u.v.-damaged herpes simplex virus (u.v. - HSV) was compared in dividing skin fibroblasts of 30 donors either normal or afflicted by genetic disorders, some of which confer a high risk for sunlight induced skin cancers. Cultures were exposed to a single dose of 1.0-25 J.m-2 from 0-60 h before infection with u.v.-HSV (at about 10-3 survival) and the rate of viral production was determined. ER was maximal for a 36 h time interval in all lines. The u.v. dose eliciting maximal ER was 15 J.m-2 in fibroblasts from normal donors, xeroderma pigmentosum (XP) heterozygotes, Mibelli's porokeratosis, diffused naevomatosis, Down's syndrome, xerodermoids, XP variants and epidermodysplasia verruciformis. However, in the latter 3 cases, ER was almost 10 times more pronounced than in the normal cases. The u.v. dose eliciting maximal ER was 0.1, 0.3 and 2 J.m-2 in excision deficient XP fibroblasts from groups A, D and C, respectively, 2.5 J.m-2 in 11961 fibroblasts and 5 J.m-2 in fibroblast lines from cockayne s syndrome.

  14. [Analysis of chromosome karyotype of oral carcinoma-associated fibroblasts].

    Science.gov (United States)

    Zheng, Xiao-Hui; Liu, Ying; Zhou, Hong-Mei; Chen, Qian-Ming; Li, Bing-Qi

    2005-04-01

    The purpose of this study was to investigate whether the fundamental genetic character of oral carcinoma-associated fibroblasts changes through contrasting and analyzing the oral carcinoma-associated fibroblasts and the normal fibroblasts of oral mucosa. The two kinds of cells were treated with colchicine and microsometic fluid, and then were expanded with cold acetic acid and formalized with methyl alcohol. The cells were observed under the oil microscope after Giemsa staining. The chromosome karyotype of the two kinds of cells was analyzed by Visus 2. 1. There were not obvious differences in the way of chromosome karyotype between the oral carcinoma-associated fibroblasts and the normal fibroblasts of oral mucosa. The basic genetic characteristics of the normal cells are conserved in the oral carcinoma-associated fibroblasts, which means the cells have no malignant changes.

  15. Tumor-secreted LOXL2 activates fibroblasts through FAK signaling

    DEFF Research Database (Denmark)

    Barker, Holly E; Bird, Demelza; Lang, Georgina

    2013-01-01

    models. Here, we discovered that tumor-derived LOXL2 directly activated stromal fibroblasts in the tumor microenvironment. Genetic manipulation or antibody inhibition of LOXL2 in orthotopically grown mammary tumors reduced the expression of α-smooth muscle actin (α-SMA). Using a marker for reticular...... fibroblasts, it was determined that expression of α-SMA was localized to fibroblasts recruited from the host tissue. This marker also revealed that the matrix present in tumors with reduced levels of LOXL2 was more scattered compared with control tumors which exhibited matrices with dense, parallel alignments....... Importantly, in vitro assays revealed that tumor-derived LOXL2 and a recombinant LOXL2 protein induced fibroblast branching on collagen matrices, as well as increased fibroblast-mediated collagen contraction and invasion of fibroblasts through extracellular matrix. Moreover, LOXL2 induced the expression of α-SMA...

  16. Paternal Origin of FGFR2 Mutations in Sporadic Cases of Crouzon Syndrome and Pfeiffer Syndrome

    OpenAIRE

    Glaser, Rivka L.; Jiang, Wen; Boyadjiev, Simeon A.; Tran, Alissa K.; Andrea A. Zachary; Van Maldergem, Lionel; Johnson, David; Walsh, Sinead; Oldridge, Michael; Wall, Steven A.; Wilkie, Andrew O.M.; Jabs, Ethylin Wang

    2000-01-01

    Crouzon syndrome and Pfeiffer syndrome are both autosomal dominant craniosynostotic disorders that can be caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. To determine the parental origin of these FGFR2 mutations, the amplification refractory mutation system (ARMS) was used. ARMS PCR primers were developed to recognize polymorphisms that could distinguish maternal and paternal alleles. A total of 4,374 bases between introns IIIa and 11 of the FGFR2 gene were sequen...

  17. HGF is released from buccal fibroblasts after smokeless tobacco stimulation

    DEFF Research Database (Denmark)

    Dabelsteen, S; Christensen, S; Gron, B

    2005-01-01

    To investigate the effect of smokeless tobacco (ST) on (1) HGF, KGF and GM-CSF expression by buccal fibroblasts and (2) on keratinocyte and fibroblast proliferation. Buccal fibroblasts were stimulated with different concentrations of ST extracts in a double dilution from 0.50% w/v to 0.03% w/v. S....... Keratinocytes and fibroblasts showed no increase in proliferation after stimulation with increased concentrations of ST. The results suggest that HGF and KGF may play an important role as a paracrine growth factor in epithelial hyperplasia in ST lesions....

  18. Hsp90 regulation of fibroblast activation in pulmonary fibrosis

    Science.gov (United States)

    Sontake, Vishwaraj; Wang, Yunguan; Kasam, Rajesh K.; Sinner, Debora; Reddy, Geereddy B.; Naren, Anjaparavanda P.; McCormack, Francis X.; Jegga, Anil G.; Madala, Satish K.

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease associated with fibroblast activation that includes excessive proliferation, tissue invasiveness, myofibroblast transformation, and extracellular matrix (ECM) production. To identify inhibitors that can attenuate fibroblast activation, we queried IPF gene signatures against a library of small-molecule-induced gene-expression profiles and identified Hsp90 inhibitors as potential therapeutic agents that can suppress fibroblast activation in IPF. Although Hsp90 is a molecular chaperone that regulates multiple processes involved in fibroblast activation, it has not been previously proposed as a molecular target in IPF. Here, we found elevated Hsp90 staining in lung biopsies of patients with IPF. Notably, fibroblasts isolated from fibrotic lesions showed heightened Hsp90 ATPase activity compared with normal fibroblasts. 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), a small-molecule inhibitor of Hsp90 ATPase activity, attenuated fibroblast activation and also TGF-β–driven effects on fibroblast to myofibroblast transformation. The loss of the Hsp90AB, but not the Hsp90AA isoform, resulted in reduced fibroblast proliferation, myofibroblast transformation, and ECM production. Finally, in vivo therapy with 17-AAG attenuated progression of established and ongoing fibrosis in a mouse model of pulmonary fibrosis, suggesting that targeting Hsp90 represents an effective strategy for the treatment of fibrotic lung disease. PMID:28239659

  19. Oral fibroblasts produce more HGF and KGF than skin fibroblasts in response to co-culture with keratinocytes

    DEFF Research Database (Denmark)

    Grøn, Birgitte; Stoltze, Kaj; Andersson, Anders

    2002-01-01

    The production of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) in subepithelial fibroblasts from buccal mucosa, periodontal ligament, and skin was determined after co-culture with keratinocytes. The purpose was to detect differences between the fibroblast subpopulations...... that could explain regional variation in epithelial growth and wound healing. Normal human fibroblasts were cultured on polystyrene or maintained in collagen matrix and stimulated with keratinocytes cultured on membranes. The amount of HGF and KGF protein in the culture medium was determined every 24 h for 5...... days by ELISA. When cultured on polystyrene, the constitutive level of KGF and HGF in periodontal fibroblasts was higher than the level in buccal and skin fibroblasts. In the presence of keratinocytes, all three types of fibroblasts in general increased their HGF and KGF production 2-3 times. When...

  20. Gene Signature of Human Oral Mucosa Fibroblasts: Comparison with Dermal Fibroblasts and Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Miyoshi, Keiko; Horiguchi, Taigo; Tanimura, Ayako; Hagita, Hiroko; Noma, Takafumi

    2015-01-01

    Oral mucosa is a useful material for regeneration therapy with the advantages of its accessibility and versatility regardless of age and gender. However, little is known about the molecular characteristics of oral mucosa. Here we report the first comparative profiles of the gene signatures of human oral mucosa fibroblasts (hOFs), human dermal fibroblasts (hDFs), and hOF-derived induced pluripotent stem cells (hOF-iPSCs), linking these with biological roles by functional annotation and pathway analyses. As a common feature of fibroblasts, both hOFs and hDFs expressed glycolipid metabolism-related genes at higher levels compared with hOF-iPSCs. Distinct characteristics of hOFs compared with hDFs included a high expression of glycoprotein genes, involved in signaling, extracellular matrix, membrane, and receptor proteins, besides a low expression of HOX genes, the hDFs-markers. The results of the pathway analyses indicated that tissue-reconstructive, proliferative, and signaling pathways are active, whereas senescence-related genes in p53 pathway are inactive in hOFs. Furthermore, more than half of hOF-specific genes were similarly expressed to those of hOF-iPSC genes and might be controlled by WNT signaling. Our findings demonstrated that hOFs have unique cellular characteristics in specificity and plasticity. These data may provide useful insight into application of oral fibroblasts for direct reprograming.

  1. Differences in motility pattern between human buccal fibroblasts and periodontal and skin fibroblasts

    DEFF Research Database (Denmark)

    Lepekhin, Eugene; Grøn, Birgitte; Berezin, Vladimir

    2002-01-01

    at these sites can be explained by differences in the motile behavior of their respective fibroblast populations. The migratory characteristics were studied in a two-dimensional culture system. The migration of single cells was time-lapse video recorded at intervals of 15 min for a period of 6 h using a computer...

  2. Host cell reactivation by fibroblasts from patients with pigmentary degeneration of the retina

    Energy Technology Data Exchange (ETDEWEB)

    Lytle, C.D. (Food and Drug Administration, Rockville, MD (USA)); Tarone, R.E.; Barrett, S.F.; Robbins, J.H. (National Cancer Inst., Bethesda, MD (USA)); Wirtschafter, J.D. (Minnesota Univ., Minneapolis (USA). Hospitals); Dupuy, J.M. (Quebec Univ., Laval-des-Rapides (Canada). Inst. Armand-Frappier)

    1983-05-01

    Cockayne syndrome (CS) is an autosomal recessive disease characterized by numerous clinical abnormalities including acute sun sensitivity and primary pigmentary degeneration of the retina. Cultured fibroblasts from CS patients are hypersensitive to ultraviolet radiation. Host cell reactivation of irradiated virus was studied in CS and in other diseases with retinal degeneration to evaluate repair. The survival of UV-irradiated Herpes simplex virus type 1 was determined in fibroblast lines from four normal donors, two patients with CS, one with both xeroderma pigmentosum (XP) and CS, and from several other patients with (Usher syndrome, olivopontocerebellar atrophy, retinitis pigmentosa) and without (XP, ataxia telangiectasia) primary pigmentary degeneration of the retina. The viral survival curves in all cell lines showed two components: a very sensitive initial component followed by an exponential, less sensitive component. The exponential component had greater sensitivity than normal in the case of the CS patients, the patient with both XP and CS, and the XP patient. It was proposed that patients with CS have defective repair of DNA which may be the cause of their retinal degeneration.

  3. Metabolic disorders mimicking Reye's syndrome.

    Science.gov (United States)

    Chang, P F; Huang, S F; Hwu, W L; Hou, J W; Ni, Y H; Chang, M H

    2000-04-01

    Several metabolic disorders such as encephalopathy and hepatic dysfunction have been described as Reye's-like syndrome because they present with similar clinical manifestations that mimic Reye's syndrome. We performed a retrospective study to explore the underlying metabolic etiologies of Reye's-like syndrome in patients treated at National Taiwan University Hospital. From January 1991 to June 1998, 19 children with a syndrome fitting the Reye's-like syndrome description were identified for study. Urine organic acid analysis, plasma amino acid analysis, liver pathology, and skin fibroblast enzyme assays were studied during the acute stage of illness. The etiologies of patients' syndromes included urea cycle disorders (n = 7), glycogen storage disease type Ia (4), primary carnitine deficiency (2), hereditary fructose intolerance (1), methylmalonic acidemia (2), and 3-hydroxy-3-methylglutaric acidemia (1). Fatty acid oxidation defects were suspected in the remaining two cases. A significant number of patients who present with Reye's-like syndrome have an underlying inherited metabolic disorder. In patients with Reye's-like syndrome, an accurate diagnosis is essential to ensure normal growth and development and to prevent recurrence of the condition.

  4. Replacement of murine fibroblasts by human fibroblasts irradiated in obtaining feeder layer for the culture of human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Yoshito, Daniele; Sufi, Bianca S.; Santin, Stefany P.; Mathor, Monica B. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Altran, Silvana C.; Isaac, Cesar [Universidade Sao Paulo (USP), Sao Paulo, SP (Brazil). Fac. de Medicina. Lab. de Microcirurgia Plastica; Esteves-Pedro, Natalia M. [Universidade Sao Paulo (USP), Sao Paulo, SP (Brazil). Fac. de Ciencias Farmaceuticas. Lab. de Controle Biologico; Herson, Marisa R. [DonorTissue Bank of Victoria (Australia)

    2011-07-01

    Human autologous epithelia cultivated in vitro, have been used successfully in treating damage to skin integrity. The methodology allowed the cultivation of these epithelia was described by Rheinwald and Green in 1975, this methodology consisted in seeding keratinocytes onto a feeder layer composed of lineage 3T3 murine fibroblasts, the proliferation rate is controlled through the action of ionizing radiation. However, currently there is a growing concern about the possibility of transmitting prions and murine viruses to transplanted patients. Taking into account this concern, in this present work, we replaced the feeder layer originally composed of murine fibroblasts by human fibroblasts. To obtain this new feeder layer was necessary to standardize the enough irradiation dose to inhibit the replication of human fibroblasts and the verification of effectiveness of the development of keratinocytes culture on a feeder layer thus obtained. According to the obtained results we can verify that the human fibroblasts irradiated at various tested doses (60, 70, 100, 200, 250 and 300 Gy) had their mitotic activity inactivated by irradiation, allowing the use of any of these doses to confection of the feeder layer, since these fibroblasts irradiated still showed viable until fourteen days of cultivation. In the test of colony formation efficiency was observed that keratinocytes seeded on irradiated human fibroblasts were able to develop satisfactorily, preserving their clonogenic potential. Therefore it was possible the replacement of murine fibroblasts by human fibroblasts in confection of the feeder layer, in order to eliminate this xenobiotic component of the keratinocytes culture. (author)

  5. Toll-like receptor 9 mediated responses in cardiac fibroblasts.

    Directory of Open Access Journals (Sweden)

    Ingrid Kristine Ohm

    Full Text Available Altered cardiac Toll-like receptor 9 (TLR9 signaling is important in several experimental cardiovascular disorders. These studies have predominantly focused on cardiac myocytes or the heart as a whole. Cardiac fibroblasts have recently been attributed increasing significance in mediating inflammatory signaling. However, putative TLR9-signaling through cardiac fibroblasts remains non-investigated. Thus, our aim was to explore TLR9-signaling in cardiac fibroblasts and investigate the consequence of such receptor activity on classical cardiac fibroblast cellular functions. Cultivated murine cardiac fibroblasts were stimulated with different TLR9 agonists (CpG A, B and C and assayed for the secretion of inflammatory cytokines (tumor necrosis factor α [TNFα], CXCL2 and interferon α/β. Expression of functional cardiac fibroblast TLR9 was proven as stimulation with CpG B and -C caused significant CXCL2 and TNFα-release. These responses were TLR9-specific as complete inhibition of receptor-stimulated responses was achieved by co-treatment with a TLR9-antagonist (ODN 2088 or chloroquine diphosphate. TLR9-stimulated responses were also found more potent in cardiac fibroblasts when compared with classical innate immune cells. Stimulation of cardiac fibroblasts TLR9 was also found to attenuate migration and proliferation, but did not influence myofibroblast differentiation in vitro. Finally, results from in vivo TLR9-stimulation with subsequent fractionation of specific cardiac cell-types (cardiac myocytes, CD45+ cells, CD31+ cells and cardiac fibroblast-enriched cell-fractions corroborated our in vitro data and provided evidence of differentiated cell-specific cardiac responses. Thus, we conclude that cardiac fibroblast may constitute a significant TLR9 responder cell within the myocardium and, further, that such receptor activity may impact important cardiac fibroblast cellular functions.

  6. Direct Conversion of Fibroblasts to Megakaryocyte Progenitors

    Directory of Open Access Journals (Sweden)

    Julian Pulecio

    2016-10-01

    Full Text Available Current sources of platelets for transfusion are insufficient and associated with risk of alloimmunization and blood-borne infection. These limitations could be addressed by the generation of autologous megakaryocytes (MKs derived in vitro from somatic cells with the ability to engraft and differentiate in vivo. Here, we show that overexpression of a defined set of six transcription factors efficiently converts mouse and human fibroblasts into MK-like progenitors. The transdifferentiated cells are CD41+, display polylobulated nuclei, have ploidies higher than 4N, form MK colonies, and give rise to platelets in vitro. Moreover, transplantation of MK-like murine progenitor cells into NSG mice results in successful engraftment and further maturation in vivo. Similar results are obtained using disease-corrected fibroblasts from Fanconi anemia patients. Our results combined demonstrate that functional MK progenitors with clinical potential can be obtained in vitro, circumventing the use of hematopoietic progenitors or pluripotent stem cells.

  7. Cushing syndrome

    Science.gov (United States)

    Hypercortisolism; Cortisol excess; Glucocorticoid excess - Cushing syndrome ... The most common cause of Cushing syndrome is taking too much ... called exogenous Cushing syndrome . Prednisone, dexamethasone, ...

  8. Nuclear targeting of IGF-1 receptor in orbital fibroblasts from Graves' disease: apparent role of ADAM17.

    Directory of Open Access Journals (Sweden)

    Neil Hoa

    Full Text Available Insulin-like growth factor-1 receptor (IGF-1R comprises two subunits, including a ligand binding domain on extra- cellular IGF-1Rα and a tyrosine phosphorylation site located on IGF-1Rβ. IGF-1R is over-expressed by orbital fibroblasts in the autoimmune syndrome, Graves' disease (GD. When activated by IGF-1 or GD-derived IgG (GD-IgG, these fibroblasts produce RANTES and IL-16, while those from healthy donors do not. We now report that IGF-1 and GD-IgG provoke IGF-1R accumulation in the cell nucleus of GD fibroblasts where it co-localizes with chromatin. Nuclear IGF-1R is detected with anti-IGF-1Rα-specific mAb and migrates to approximately 110 kDa, consistent with its identity as an IGF-1R fragment. Nuclear IGF-1R migrating as a 200 kDa protein and consistent with an intact receptor was undetectable when probed with either anti-IGF-1Rα or anti-IGF-1Rβ mAbs. Nuclear redistribution of IGF-1R is absent in control orbital fibroblasts. In GD fibroblasts, it can be abolished by an IGF-1R-blocking mAb, 1H7 and by physiological concentrations of glucocorticoids. When cell-surface IGF-1R is cross-linked with (125I IGF-1, (125I-IGF-1/IGF-1R complexes accumulate in the nuclei of GD fibroblasts. This requires active ADAM17, a membrane associated metalloproteinase, and the phosphorylation of IGF-1R. In contrast, virally encoded IGF-1Rα/GFP fusion protein localizes equivalently in nuclei in both control and GD fibroblasts. This result suggests that generation of IGF-1R fragments may limit the accumulation of nuclear IGF-1R. We thus identify a heretofore-unrecognized behavior of IGF-1R that appears limited to GD-derived fibroblasts. Nuclear IGF-1R may play a role in disease pathogenesis.

  9. Muusikamaailm : Hans Werner Henze sünnipäevaks. "Nibelungide sõrmus" ka Dresdenis. Simon Rattle juhatas Beethovenit. Uued teosed Elliott Carterilt. Echo Klassik 2001 / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    2001-01-01

    Hans Werner Henze 75 sünnipäevapidustustest Saksamaal. R. Wagneri "Nibelungide sõrmus" lavastus Dresdenis. Berliini Filharmoonikute peadirigent Simon Rattle toob Berliini pidunädalate lõppmänguna Berliini Filharmooniasse mahuka Beethoveni tsükli. Detsembris 93 aastaseks saav USA helilooja Elliott Carter kirjutab ikka uusi tellimusteoseid ning tuleb ka ise esiettekandele. Deutsche Phono-Akademie andis Baden-Badenis kätte oma mainekad aasta-auhinnad Echo Klassik

  10. Rac inhibition reverses the phenotype of fibrotic fibroblasts.

    Directory of Open Access Journals (Sweden)

    Shi-wen Xu

    Full Text Available BACKGROUND: Fibrosis, the excessive deposition of scar tissue by fibroblasts, is one of the largest groups of diseases for which there is no therapy. Fibroblasts from lesional areas of scleroderma patients possess elevated abilities to contract matrix and produce alpha-smooth muscle actin (alpha-SMA, type I collagen and CCN2 (connective tissue growth factor, CTGF. The basis for this phenomenon is poorly understood, and is a necessary prerequisite for developing novel, rational anti-fibrotic strategies. METHODS AND FINDINGS: Compared to healthy skin fibroblasts, dermal fibroblasts cultured from lesional areas of scleroderma (SSc patients possess elevated Rac activity. NSC23766, a Rac inhibitor, suppressed the persistent fibrotic phenotype of lesional SSc fibroblasts. NSC23766 caused a decrease in migration on and contraction of matrix, and alpha-SMA, type I collagen and CCN2 mRNA and protein expression. SSc fibroblasts possessed elevated Akt phosphorylation, which was also blocked by NSC23766. Overexpression of rac1 in normal fibroblasts induced matrix contraction and alpha-SMA, type I collagen and CCN2 mRNA and protein expression. Rac1 activity was blocked by PI3kinase/Akt inhibition. Basal fibroblast activity was not affected by NSC23766. CONCLUSION: Rac inhibition may be considered as a novel treatment for the fibrosis observed in SSc.

  11. Analysis of primary cilia in directional cell migration in fibroblasts

    DEFF Research Database (Denmark)

    Christensen, Søren Tvorup; Veland, Iben; Schwab, Albrecht

    2013-01-01

    Early studies of migrating fibroblasts showed that primary cilia orient in front of the nucleus and point toward the leading edge. Recent work has shown that primary cilia coordinate a series of signaling pathways critical to fibroblast cell migration during development and in wound healing. In p...

  12. Fibroblastic rheumatism: Scientific Letter | Kawtar | African Journal of ...

    African Journals Online (AJOL)

    Fibroblastic Rheumatism (FR) is a rare rheumatologic entity of unknown etiology. The pathophysiological mechanism involving fibroblast proliferation is characterized by symmetrical polyarthritis associated with sudden onset of cutaneous nodules, flexion contractures. Bone erosion can occur as the disease progresses and ...

  13. Growth modulation of fibroblasts by chitosan-polyvinyl pyrrolidone ...

    Indian Academy of Sciences (India)

    Wounds in adults and fetuses differ in their healing ability with respect to scar formation. In adults, wounds lacking the epidermis exhibit excess collagen production and scar formation. Fibroblasts synthesize and deposit a collagen rich extracellular matrix. The early migration and proliferation of fibroblasts in the wound area ...

  14. Myogenic conversion of bladder fibroblasts by construction and ...

    African Journals Online (AJOL)

    Gene therapy of detrusor underactivity, by autologous cells transplantation, is limited by the number of primary myogenic. The purpose of this study was to investigate whether Myod1 could induce primary bladder fibroblasts to undergo myogenic conversion. Primary bladder fibroblasts from Sprague-Daley rats were cultured ...

  15. Fibroblasts in myocardial infarction: a role in inflammation and repair

    Science.gov (United States)

    Shinde, Arti V.; Frangogiannis, Nikolaos G.

    2014-01-01

    Fibroblasts do not only serve as matrix-producing reparative cells, but exhibit a wide range of functions in inflammatory and immune responses, angiogenesis and neoplasia. The adult mammalian myocardium contains abundant fibroblasts enmeshed within the interstitial and perivascular extracellular matrix. The current review manuscript discusses the dynamic phenotypic and functional alterations of cardiac fibroblasts following myocardial infarction. Extensive necrosis of cardiomyocytes in the infarcted heart triggers an intense inflammatory reaction. In the early stages of infarct healing, fibroblasts become pro-inflammatory cells, activating the inflammasome and producing cytokines, chemokines and proteases. Pro-inflammatory cytokines (such as Interleukin-1) delay myofibroblast transformation, until the wound is cleared from dead cells and matrix debris. Resolution of the inflammatory infiltrate is associated with fibroblast migration, proliferation, matrix protein synthesis and myofibroblast conversion. Growth factors and matricellular proteins play an important role in myofibroblast activation during the proliferative phase of healing. Formation of a mature cross-linked scar is associated with clearance of fibroblasts, as poorly-understood inhibitory signals restrain the fibrotic response. However, in the non-infarcted remodeling myocardium, local fibroblasts may remain activated in response to volume and pressure overload and may promote interstitial fibrosis. Considering their abundance, their crucial role in cardiac inflammation and repair, and their involvement in myocardial dysfunction and arrhythmogenesis, cardiac fibroblasts may be key therapeutic targets in cardiac remodeling. PMID:24321195

  16. Rho A and the Rho kinase pathway regulate fibroblast contraction: Enhanced contraction in constitutively active Rho A fibroblast cells

    Energy Technology Data Exchange (ETDEWEB)

    Nobe, Koji, E-mail: kojinobe@pharm.showa-u.ac.jp [Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo (Japan); Nobe, Hiromi [Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo (Japan); Department of Physical Therapy, Bunkyo-Gakuin University (Japan); Yoshida, Hiroko [Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo (Japan); Kolodney, Michael S. [Dermatology Division, Department of Medicine, UCLA, Los Angeles, CA (United States); Paul, Richard J. [Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, OH (United States); Honda, Kazuo [Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo (Japan)

    2010-08-20

    Research highlights: {yields} Mechanisms of fibroblast cell contraction in collagen matrix. {yields} Assessed an isometric force development using 3D-reconstituted-fibroblast fiber. {yields} Constitutively active Rho A induced the over-contraction of fibroblast cells. {yields} Rho A and Rho kinase pathway has a central role in fibroblast cell contraction. -- Abstract: Fibroblast cells play a central role in the proliferation phase of wound healing processes, contributing to force development. The intracellular signaling pathways regulating this non-muscle contraction are only partially understood. To study the relations between Rho A and contractile responses, constitutively active Rho A (CA-Rho A) fibroblast cells were reconstituted into fibers and the effects of calf serum (CS) on isometric force were studied. CS-induced force in CA-Rho A fibroblast fibers was twice as large as that in wild type (NIH 3T3) fibroblast fibers. During this response, the translocation of Rho A from the cytosol to the membrane was detected by Rho A activity assays and Western blot analysis. Pre-treatment with a Rho specific inhibitor (C3-exoenzyme) suppressed translocation as well as contraction. These results indicate that Rho A activation is essential for fibroblast contraction. The Rho kinase inhibitor ( (Y27632)) inhibited both NIH 3T3 and CA-Rho A fibroblast fiber contractions. Activation of Rho A is thus directly coupled with Rho kinase activity. We conclude that the translocation of Rho A from the cytosol to the membrane and the Rho kinase pathway can regulate wound healing processes mediated by fibroblast contraction.

  17. Influence of three laser wavelengths on human fibroblasts cell culture.

    Science.gov (United States)

    Crisan, Bogdan; Soritau, Olga; Baciut, Mihaela; Campian, Radu; Crisan, Liana; Baciut, Grigore

    2013-02-01

    Although experimental studies in vitro and vivo have been numerous, the effect of laser wavelength irradiation on human fibroblast cell culture is poorly understood. This emphasizes the need of additional cellular and molecular research into laser influence with low energy and power. The aim of this study was to assess the influence of three different laser wavelengths on the human skin fibroblasts cell culture. We wanted to evaluate if near infrared lasers had any influence in healing of wounds by stimulating mitochondrial activity of fibroblasts. The cells were irradiated using 830-, 980- and 2,940-nm laser wavelengths. The irradiated cells were incubated and their mitochondrial activity was assessed by the MTT assay at 24, 48 and 72 h. Simultaneously, an apoptosis assay was assessed on the irradiated fibroblasts. It can be concluded that laser light of the near-infrared region (830 and 980 nm) influences fibroblasts mitochondrial activity compared to the 2,940-nm wavelength which produces apoptosis.

  18. Hyaluronic acid production by irradiated human synovial fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Yaron, M.; Yaron, I.; Levita, M.; Herzberg, M.

    1977-03-01

    Radioactive particles as well as x irradiation from an external source has been used in the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. In order to clarify effects of ionizing irradiation on synovial cells, radioactive gold (/sup 198/Au) and yttrium (/sup 90/Y) were added to fibroblast cultures derived from human synovial membranes. Other cultures were irradiated by a Picker x-ray machine. Fibroblast growth and hyaluronic acid production were measured. Radioactive gold and yttrium particles induced a significant increase of hyaluronic acid synthesis rate (pg/cell/day) and inhibited fibroblast growth. Fibroblasts continued to overproduce hyaluronic acid and to show growth inhibition 3 weeks after irradiation with radioactive gold. Hydrocortisone inhibited hyaluronic acid overproduction induced by radioactive gold. Overproduction of hyaluronic acid induced by the x-ray machine was inhibited by hydrocortisone, actinomycin-D, and cycloheximide. Fibroblasts derived from normal and rheumatoid patients responded similarly to ionizing irradiation.

  19. Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease

    Science.gov (United States)

    Gourdie, Robert G.; Dimmeler, Stefanie; Kohl, Peter

    2016-01-01

    Our understanding of cardiac fibroblast functions has moved beyond their roles in heart structure and extracellular matrix generation, and now includes contributions to paracrine, mechanical and electrical signalling during ontogenesis and normal cardiac activity. Fibroblasts have central roles in pathogenic remodelling during myocardial ischaemia, hypertension and heart failure. As key contributors to scar formation, they are crucial for tissue repair after interventions including surgery and ablation. Novel experimental approaches targeting cardiac fibroblasts are promising potential therapies for heart disease. Indeed, several existing drugs act, at least partially, through effects on cardiac connective tissue. This Review outlines the origins and roles of fibroblasts in cardiac development, homeostasis and disease; illustrates the involvement of fibroblasts in current and emerging clinical interventions; and identifies future targets for research and development. PMID:27339799

  20. Rothmund-Thomson syndrome

    Directory of Open Access Journals (Sweden)

    Roversi Gaia

    2010-01-01

    (including dyskeratosis congenita, Kindler syndrome and Poikiloderma with Neutropaenia, other rare genodermatoses with prominent telangiectasias (including Bloom syndrome, Werner syndrome and Ataxia-telangiectasia and the allelic disorders, RAPADILINO syndrome and Baller-Gerold syndrome, which also share some clinical features. A few mutations recur in all three RECQL4 diseases. Genetic counselling should be provided for RTS patients and their families, together with a recommendation for cancer surveillance for all patients with RTSII. Patients should be managed by a multidisciplinary team and offered long term follow-up. Treatment includes the use of pulsed dye laser photocoagulation to improve the telangiectatic component of the rash, surgical removal of the cataracts and standard treatment for individuals who develop cancer. Although some clinical signs suggest precocious aging, life expectancy is not impaired in RTS patients if they do not develop cancer. Outcomes in patients with osteosarcoma are similar in RTS and non-RTS patients, with a five-year survival rate of 60-70%. The sensitivity of RTS cells to genotoxic agents exploiting cells with a known RECQL4 status is being elucidated and is aimed at optimizing the chemotherapeutic regimen for osteosarcoma.

  1. Bradykinin-induced asthmatic fibroblast/myofibroblast activities via bradykinin B2 receptor and different MAPK pathways

    NARCIS (Netherlands)

    Sabatini, Federica; Luppi, Fabrizio; Petecchia, Loredana; Stefano, Antonino Di; Longo, Anna M.; Eva, Alessandra; Vanni, Cristina; Hiemstra, Pieter S.; Sterk, Peter J.; Sorbello, Valentina; Fabbri, Leonardo M.; Rossi, Giovanni A.; Ricciardolo, Fabio L. M.

    2013-01-01

    Bradykinin drives normal lung fibroblasts into myofibroblasts, induces fibroblast proliferation and activates mitogen activated protein kinase pathways (MAPK) but its effects on bronchial fibroblasts from asthmatics (HBAFb) have not been yet studied. We studied bradykinin-induced fibroblast

  2. Expression of Werner and Bloom syndrome genes is differentially regulated by in vitro HIV-1 infection of peripheral blood mononuclear cells.

    Science.gov (United States)

    Bordi, L; Amendola, A; Ciccosanti, F; Abbate, I; Camilloni, G; Capobianchi, M R

    2004-11-01

    In HIV infection, continuous immune activation leads to accelerated ageing of the adaptive immune system, similar to that observed in elderly people. We investigated the expression of WRN and BLM (genes involved in disorders characterized by premature ageing, genomic instability and cancer predisposition) in peripheral blood mononuclear cells (PBMC) activated in vitro with phytohaemagglutinin (PHA) and infected with different HIV-1 strains. The steady state levels of mRNA were analysed by reverse transcription-polymerase chain reaction (RT-PCR), and protein expression was assayed using immunocytochemistry and Western blot techniques. In uninfected PBMC, PHA stimulation induced an increase in BLM mRNA and protein expression, while WRN expression remained virtually unchanged. When PBMC were infected in vitro with a lymphotropic HIV-1 strain, the level of BLM mRNA showed a peak at 24 h of infection, followed by a decline to uninfected culture levels. A similar result failed to be seen using an R5-tropic HIV-1 strain. In accordance with mRNA expression, in HIV-infected cultures PBMC were stained more frequently and more intensely by a BLM-specific antibody as compared to uninfected cultures, staining peaking at 24. Conversely, WRN expression was not modulated by HIV-1. The proportion of cells showing BLM up-regulation, established by immunocytochemical staining, was much greater than the proportion of productively infected PBMC, as established by proviral DNA measurement. This result indicates that BLM up-regulation is probably a result of an indirect bystander cell effect. Activation of the BLM gene in infected PBMC suggests that premature ageing could be a further immunopathogenetic mechanism involved in HIV-induced immunodeficiency, and points to a possible new candidate target for innovative therapeutic intervention.

  3. Telomeric D-loops containing 8-oxo-2'-deoxyguanosine are preferred substrates for Werner and Bloom syndrome helicases and are bound by POT1.

    Science.gov (United States)

    Ghosh, Avik; Rossi, Marie L; Aulds, Jason; Croteau, Deborah; Bohr, Vilhelm A

    2009-11-06

    8-Oxo-2'-deoxyguanosine (8-oxodG) is one of the most important oxidative DNA lesions, and G-rich telomeric DNA is especially susceptible to oxidative DNA damage. RecQ helicases WRN and BLM and telomere-binding protein POT1 are thought to play roles in telomere maintenance. This study examines the ability of WRN, BLM, and RecQ5 to unwind and POT1 to bind telomeric D-loops containing 8-oxodG. The results demonstrate that WRN and BLM preferentially unwind telomeric D-loops containing 8-oxodG and that POT1 binds with higher affinity to telomeric D-loops with 8-oxodG but shows no preference for telomeric single-stranded DNA with 8-oxodG. We speculate that telomeric D-loops with 8-oxodG may have a greater tendency to form G-quadruplex DNA structures than telomeric DNA lacking 8-oxodG.

  4. Duane Syndrome

    Science.gov (United States)

    ... Frequently Asked Questions Español Condiciones Chinese Conditions Duane Syndrome En Español Read in Chinese What is Duane Syndrome? Duane syndrome, also called Duane retraction syndrome (DRS), ...

  5. Fanconi syndrome

    Science.gov (United States)

    De Toni-Fanconi syndrome ... Fanconi syndrome can be caused by faulty genes, or it may result later in life due to kidney damage. Sometimes the cause of Fanconi syndrome is unknown. Common causes of Fanconi syndrome in ...

  6. The impact of vascular endothelial growth factor and basic fibroblast growth factor on cardiac fibroblasts grown under altered gravity conditions

    DEFF Research Database (Denmark)

    Ulbrich, Claudia; Leder, Annekatrin; Pietsch, Jessica

    2010-01-01

    Myocardium is very sensitive to gravitational changes. During a spaceflight cardiovascular atrophy paired with rhythm problems and orthostatic intolerance can occur. The aim of this study was to investigate the impact of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor...... (VEGF) on cardiac fibroblasts (CF) grown under altered gravity conditions....

  7. Fibroblastic osteosarcoma in a lion (Panthera leo

    Directory of Open Access Journals (Sweden)

    L. Leonardi

    2014-01-01

    Full Text Available This report describes a case of spontaneous fibroblastic osteosarcoma in the humerus of a lion from a private park in Perugia, Italy. The tumor had an irregular, smooth, brown surface and a generally firm, rubbery consistence with gritty to hard areas interspersed. The mass was poorly vascularized with areas of necrosis at the periphery. The cut surface showed a multilobulated mass that had breached the humeral cortex, with periosteal production of reactive bone. The mass invaded the epiphysis, the synovial membrane, the joint capsule and ligaments. A mild hemorrhagic effusion appeared in the joint space. Clinical signs, gross and histopathologic findings are described in this rare case of a malignant bone tumor.

  8. A stromal address code defined by fibroblasts.

    Science.gov (United States)

    Parsonage, Greg; Filer, Andrew D; Haworth, Oliver; Nash, Gerard B; Rainger, G Ed; Salmon, Michael; Buckley, Christopher D

    2005-03-01

    To navigate into and within tissues, leukocytes require guidance cues that enable them to recognize which tissues to enter and which to avoid. Such cues are partly provided at the time of extravasation from blood by an endothelial address code on the luminal surface of the vascular endothelium. Here, we review the evidence that fibroblasts help define an additional stromal address code that directs leukocyte behaviour within tissues. We examine how this stromal code regulates site-specific leukocyte accumulation, differentiation and survival in a variety of physiological stromal niches, and how the aberrant expression of components of this code in the wrong tissue at the wrong time contributes to the persistence of chronic inflammatory diseases.

  9. Beryllium induces premature senescence in human fibroblasts.

    Science.gov (United States)

    Coates, Shannon S A; Lehnert, Bruce E; Sharma, Sunil; Kindell, Susan M; Gary, Ronald K

    2007-07-01

    After cells have completed a sufficient number of cell divisions, they exit the cell cycle and enter replicative senescence. Here, we report that beryllium causes proliferation arrest with premature expression of the principal markers of senescence. After young presenescent human fibroblasts were treated with 3 microM BeSO(4) for 24 h, p21 cyclin-dependent kinase inhibitor mRNA increased by >200%. Longer periods of exposure caused mRNA and protein levels to increase for both p21 and p16(Ink4a), a senescence regulator that prevents pRb-mediated cell cycle progression. BeSO(4) also caused dose-dependent induction of senescence-associated beta-galactosidase activity (SA-beta-gal). Untreated cells had 48 relative fluorescence units (RFU)/microg/h of SA-beta-gal, whereas 3 microM BeSO(4) caused activity to increase to 84 RFU/microg/h. In chromatin immunoprecipitation experiments, BeSO(4) caused p53 protein to associate with its DNA binding site in the promoter region of the p21 gene, indicating that p53 transcriptional activity is responsible for the large increase in p21 mRNA elicited by beryllium. Forced expression of human telomerase reverse transcriptase (hTERT) rendered HFL-1 cells incapable of normal replicative senescence. However, there was no difference in the responsiveness of normal HFL-1 fibroblasts (IC(50) = 1.9 microM) and hTERT-immortalized cells (IC(50) = 1.7 microM) to BeSO(4) in a 9-day proliferation assay. The effects of beryllium resemble those of histone deacetylase-inhibiting drugs, which also cause large increases in p21. However, beryllium produced no changes in histone acetylation, suggesting that Be(2+) acts as a novel and potent pharmacological inducer of premature senescence.

  10. Hamartomatous polyposis syndromes

    DEFF Research Database (Denmark)

    Jelsig, Anne Marie; Qvist, Niels; Brusgaard, Klaus

    2014-01-01

    Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes such as ...

  11. Mitotic defects lead to pervasive aneuploidy and accompany loss of RB1 activity in mouse LmnaDhe dermal fibroblasts.

    Directory of Open Access Journals (Sweden)

    C Herbert Pratt

    2011-03-01

    Full Text Available Lamin A (LMNA is a component of the nuclear lamina and is mutated in several human diseases, including Emery-Dreifuss muscular dystrophy (EDMD; OMIM ID# 181350 and the premature aging syndrome Hutchinson-Gilford progeria syndrome (HGPS; OMIM ID# 176670. Cells from progeria patients exhibit cell cycle defects in both interphase and mitosis. Mouse models with loss of LMNA function have reduced Retinoblastoma protein (RB1 activity, leading to aberrant cell cycle control in interphase, but how mitosis is affected by LMNA is not well understood.We examined the cell cycle and structural phenotypes of cells from mice with the Lmna allele, Disheveled hair and ears (Lmna(Dhe. We found that dermal fibroblasts from heterozygous Lmna(Dhe (Lmna(Dhe/+ mice exhibit many phenotypes of human laminopathy cells. These include severe perturbations to the nuclear shape and lamina, increased DNA damage, and slow growth rates due to mitotic delay. Interestingly, Lmna(Dhe/+ fibroblasts also had reduced levels of hypophosphorylated RB1 and the non-SMC condensin II-subunit D3 (NCAP-D3, a mitosis specific centromere condensin subunit that depends on RB1 activity. Mitotic check point control by mitotic arrest deficient-like 1 (MAD2L1 also was perturbed in Lmna(Dhe/+ cells. Lmna(Dhe/+ fibroblasts were consistently aneuploid and had higher levels of micronuclei and anaphase bridges than normal fibroblasts, consistent with chromosome segregation defects.These data indicate that RB1 may be a key regulator of cellular phenotype in laminopathy-related cells, and suggest that the effects of LMNA on RB1 include both interphase and mitotic cell cycle control.

  12. (+)-Catechin protects dermal fibroblasts against oxidative stress-induced apoptosis

    Science.gov (United States)

    2014-01-01

    Background Oxidative stress has been suggested as a mechanism underlying skin aging, as it triggers apoptosis in various cell types, including fibroblasts, which play important roles in the preservation of healthy, youthful skin. Catechins, which are antioxidants contained in green tea, exert various actions such as anti-inflammatory, anti-bacterial, and anti-cancer actions. In this study, we investigated the effect of (+)-catechin on apoptosis induced by oxidative stress in fibroblasts. Methods Fibroblasts (NIH3T3) under oxidative stress induced by hydrogen peroxide (0.1 mM) were treated with either vehicle or (+)-catechin (0–100 μM). The effect of (+)-catechin on cell viability, apoptosis, phosphorylation of c-Jun terminal kinases (JNK) and p38, and activation of caspase-3 in fibroblasts under oxidative stress were evaluated. Results Hydrogen peroxide induced apoptotic cell death in fibroblasts, accompanied by induction of phosphorylation of JNK and p38 and activation of caspase-3. Pretreatment of the fibroblasts with (+)-catechin inhibited hydrogen peroxide-induced apoptosis and reduced phosphorylation of JNK and p38 and activation of caspase-3. Conclusion (+)-Catechin protects against oxidative stress-induced cell death in fibroblasts, possibly by inhibiting phosphorylation of p38 and JNK. These results suggest that (+)-catechin has potential as a therapeutic agent for the prevention of skin aging. PMID:24712558

  13. Early activation of fibroblasts during PDT treatment in leg ulcers.

    Science.gov (United States)

    Corsi, Alessandro; Lecci, Pier P; Bacci, Stefano; Cappugi, Pietro; Pimpinelli, Nicola

    2016-06-01

    This pilot study was aimed to assess the variations of some microscopical parameters in skin ulcers, caused by chronic venous insufficiency of the lower extremities (chronic leg ulcers), in 15 patients refractory to previous conventional treatments during photodynamic therapy (PDT). Samples of control, wounded and PDT treated skin were taken and analyzed by immunohistochemistry. The cellular infiltrate, as well as the thickness of epidermis, vascularization, mast cell and fibroblast numbers, were increased in chronic wounds as compared to healthy skin. After completion of PDT, fibroblasts appeared further increased in number. Mast cells, closely clustered with fibroblasts, also showed an increase in their numbers, degranulation index and expression of basic fibroblast growth factor. The present findings support a primary role of fibroblasts in the wound healing process upon PDT treatment, given their early and intense reaction to injury. Mast cells seem to play an accessory yet important role, on the basis of their number and degranulation index variations and expression of basic FGF. In addition, the clustering of mast cells with fibroblasts around blood vessels suggest that these cells may stimulate angiogenesis and, in parallel, fibroblasts to secrete extracellular matrix during PDT therapy.

  14. LIF Mediates Proinvasive Activation of Stromal Fibroblasts in Cancer

    Directory of Open Access Journals (Sweden)

    Jean Albrengues

    2014-06-01

    Full Text Available Signaling crosstalk between tumor cells and fibroblasts confers proinvasive properties to the tumor microenvironment. Here, we identify leukemia inhibitory factor (LIF as a tumor promoter that mediates proinvasive activation of stromal fibroblasts independent of alpha-smooth muscle actin (α-SMA expression. We demonstrate that a pulse of transforming growth factor β (TGF-β establishes stable proinvasive fibroblast activation by inducing LIF production in both fibroblasts and tumor cells. In fibroblasts, LIF mediates TGF-β-dependent actomyosin contractility and extracellular matrix remodeling, which results in collective carcinoma cell invasion in vitro and in vivo. Accordingly, carcinomas from multiple origins and melanomas display strong LIF upregulation, which correlates with dense collagen fiber organization, cancer cell collective invasion, and poor clinical outcome. Blockade of JAK activity by Ruxolitinib (JAK inhibitor counteracts fibroblast-dependent carcinoma cell invasion in vitro and in vivo. These findings establish LIF as a proinvasive fibroblast producer independent of α-SMA and may open novel therapeutic perspectives for patients with aggressive primary tumors.

  15. Climateric: fatigue or third stage of the general adaptation syndrome Climaterio: fatiga o tercera etapa del síndrome de adaptación general

    National Research Council Canada - National Science Library

    William Alvarez Gaviria

    2004-01-01

    ...; for him, climacteric is the final response to fatigue or the third stage of the general adaptation syndrome, just as in elderly people there is a loss of the capacity of proliferation of fibroblasts...

  16. Octahedral Werner complexes with substituted ethylenediamine ligands: a stereochemical primer for a historic series of compounds now emerging as a modern family of catalysts.

    Science.gov (United States)

    Ehnbom, Andreas; Ghosh, Subrata K; Lewis, Kyle G; Gladysz, John A

    2016-12-21

    As reported by Alfred Werner in 1911-1912, salts of the formally D3 symmetric [Co(en)3](3+) (en = ethylenediamine) trication were among the first chiral inorganic compounds to be resolved into enantiomers, the absolute configurations of which are denoted Λ (left handed helix) or Δ (right handed helix). After a >100 year dormant period during which few useful reactions of these substitution inert complexes were described, carbon substituted derivatives have recently been found to be potent catalysts for enantioselective organic synthesis. This review systematically outlines the fascinating range of stereoisomers that can arise, such as conformers associated with the five membered chelate rings (λ/δ), alignment modes of the C-C bonds with the C3 symmetry axis (lel/ob), geometric isomers (fac/mer), and configurational diastereomers (R/S) arising from carbon stereocenters. These analyses demonstrate a profound stereochemical diversity that can be applied in catalyst optimization. Efforts are made to bridge the often orthogonal nomenclature systems inorganic and organic chemists employ to describe these phenomena.

  17. Ets2 in tumor fibroblasts promotes angiogenesis in breast cancer.

    Directory of Open Access Journals (Sweden)

    Julie A Wallace

    Full Text Available Tumor fibroblasts are active partners in tumor progression, but the genes and pathways that mediate this collaboration are ill-defined. Previous work demonstrates that Ets2 function in stromal cells significantly contributes to breast tumor progression. Conditional mouse models were used to study the function of Ets2 in both mammary stromal fibroblasts and epithelial cells. Conditional inactivation of Ets2 in stromal fibroblasts in PyMT and ErbB2 driven tumors significantly reduced tumor growth, however deletion of Ets2 in epithelial cells in the PyMT model had no significant effect. Analysis of gene expression in fibroblasts revealed a tumor- and Ets2-dependent gene signature that was enriched in genes important for ECM remodeling, cell migration, and angiogenesis in both PyMT and ErbB2 driven-tumors. Consistent with these results, PyMT and ErbB2 tumors lacking Ets2 in fibroblasts had fewer functional blood vessels, and Ets2 in fibroblasts elicited changes in gene expression in tumor endothelial cells consistent with this phenotype. An in vivo angiogenesis assay revealed the ability of Ets2 in fibroblasts to promote blood vessel formation in the absence of tumor cells. Importantly, the Ets2-dependent gene expression signatures from both mouse models were able to distinguish human breast tumor stroma from normal stroma, and correlated with patient outcomes in two whole tumor breast cancer data sets. The data reveals a key function for Ets2 in tumor fibroblasts in signaling to endothelial cells to promote tumor angiogenesis. The results highlight the collaborative networks that orchestrate communication between stromal cells and tumor cells, and suggest that targeting tumor fibroblasts may be an effective strategy for developing novel anti-angiogenic therapies.

  18. Bacterial lipopolysaccharide promotes profibrotic activation of intestinal fibroblasts.

    LENUS (Irish Health Repository)

    Burke, J P

    2012-02-01

    BACKGROUND: Fibroblasts play a critical role in intestinal wound healing. Lipopolysaccharide (LPS) is a cell wall component of commensal gut bacteria. The effects of LPS on intestinal fibroblast activation were characterized. METHODS: Expression of the LPS receptor, toll-like receptor (TLR) 4, was assessed in cultured primary human intestinal fibroblasts using flow cytometry and confocal microscopy. Fibroblasts were treated with LPS and\\/or transforming growth factor (TGF) beta1. Nuclear factor kappaB (NFkappaB) pathway activation was assessed by inhibitory kappaBalpha (IkappaBalpha) degradation and NFkappaB promoter activity. Fibroblast contractility was measured using a fibroblast-populated collagen lattice. Smad-7, a negative regulator of TGF-beta1 signalling, and connective tissue growth factor (CTGF) expression were assessed using reverse transcriptase-polymerase chain reaction and western blot. The NFkappaB pathway was inhibited by IkappaBalpha transfection. RESULTS: TLR-4 was present on the surface of intestinal fibroblasts. LPS treatment of fibroblasts induced IkappaBalpha degradation, enhanced NFkappaB promoter activity and increased collagen contraction. Pretreatment with LPS (before TGF-beta1) significantly increased CTGF production relative to treatment with TGF-beta1 alone. LPS reduced whereas TGF-beta1 increased smad-7 expression. Transfection with an IkappaBalpha plasmid enhanced basal smad-7 expression. CONCLUSION: Intestinal fibroblasts express TLR-4 and respond to LPS by activating NFkappaB and inducing collagen contraction. LPS acts in concert with TGF-beta1 to induce CTGF. LPS reduces the expression of the TGF-beta1 inhibitor, smad-7.

  19. Cytogenetic demonstration of a corrective factor in Bloom's syndrome.

    Science.gov (United States)

    Rüdiger, H W

    1982-01-01

    Patients with Bloom's syndrome, an autosomal recessively inherited disorder, have a highly increased risk of developing early malignancies of various types. The chromosomes of such patients exhibit an enhanced rate of spontaneous sister chromatid exchange. Cocultivation of patients' fibroblasts (as responder cells) with fibroblasts from healthy donors or from patients with xeroderma pigmentosum or Fanconi's anaemia (as effector cells) produces a dose-dependent reduction in Bloom-specific sister chromatid exchange; however, Bloom heterozygotes exhibit a reduced corrective capacity. The reduction in Bloom-specific sister chromatid exchange is related to the presence of a soluble factor (m.w. 10 000-20 000) which is produced in culture by normal proliferating fibroblasts. This corrective factor might represent a cancer-protective principle that is defective in patients with Bloom's syndrome.

  20. Alzheimer skin fibroblasts show increased susceptibility to free radicals.

    Science.gov (United States)

    Tesco, G; Latorraca, S; Piersanti, P; Piacentini, S; Amaducci, L; Sorbi, S

    1992-11-01

    We have studied the response to toxic oxygen metabolites of fibroblasts derived from skin biopsies of 5 patients with familial (FAD) and 4 with sporadic (AD) Alzheimer's disease compared with those derived from 4 normal controls. Fibroblasts were damaged by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde by 50 munits of xanthine-oxidase (Xo). To quantify cell damage we measured lactate dehydrogenase (LDH) activity in the culture medium and cell viability in fibroblast cultures. We found a significant increase in LDH activity in the FAD vs. controls and also in the AD vs. controls.

  1. Cancer-associated fibroblasts promote proliferation of endometrial cancer cells.

    Directory of Open Access Journals (Sweden)

    Kavita S Subramaniam

    Full Text Available Endometrial cancer is the most commonly diagnosed gynecologic malignancy worldwide; yet the tumor microenvironment, especially the fibroblast cells surrounding the cancer cells, is poorly understood. We established four primary cultures of fibroblasts from human endometrial cancer tissues (cancer-associated fibroblasts, CAFs using antibody-conjugated magnetic bead isolation. These relatively homogenous fibroblast cultures expressed fibroblast markers (CD90, vimentin and alpha-smooth muscle actin and hormonal (estrogen and progesterone receptors. Conditioned media collected from CAFs induced a dose-dependent proliferation of both primary cultures and cell lines of endometrial cancer in vitro (175% when compared to non-treated cells, in contrast to those from normal endometrial fibroblast cell line (51% (P<0.0001. These effects were not observed in fibroblast culture derived from benign endometrial hyperplasia tissues, indicating the specificity of CAFs in affecting endometrial cancer cell proliferation. To determine the mechanism underlying the differential fibroblast effects, we compared the activation of PI3K/Akt and MAPK/Erk pathways in endometrial cancer cells following treatment with normal fibroblasts- and CAFs-conditioned media. Western blot analysis showed that the expression of both phosphorylated forms of Akt and Erk were significantly down-regulated in normal fibroblasts-treated cells, but were up-regulated/maintained in CAFs-treated cells. Treatment with specific inhibitors LY294002 and U0126 reversed the CAFs-mediated cell proliferation (P<0.0001, suggesting for a role of these pathways in modulating endometrial cancer cell proliferation. Rapamycin, which targets a downstream molecule in PI3K pathway (mTOR, also suppressed CAFs-induced cell proliferation by inducing apoptosis. Cytokine profiling analysis revealed that CAFs secrete higher levels of macrophage chemoattractant protein (MCP-1, interleukin (IL-6, IL-8, RANTES and vascular

  2. The radiation response of human dermal fibroblasts

    Science.gov (United States)

    Mitchell, Stephen Andrew

    A clinically reliable predictive assay based on normal-tissue radiosensitivity may lead to improved tumour control through individualised dose prescriptions. In-vitro fibroblast radiosensitivity has been shown, in several studies, to correlate with late radiation morbidity. The aim of this study was to investigate some of the cellular mechanisms underlying the normal-tissue response. In this study, seventeen primary fibroblast strains were established by enzymatic disaggregation of skin biopsies obtained from patients. These comprised seven who experienced acute tissue reactions to radiotherapy, four patients with a normal response and six non-cancer volunteers. An AT cell line was included as a positive control for radiosensitivity. In-vitro radiosensitivity was measured using a clonogenic assay at both high (HDR: 1.6 Gymin-1) and low dose rate (LDR: 0.01 Gymin-1). The radiation parameter HDR SF2 was the most sensitive in discriminating the seven sensitive patients from the remaining ten normal patients (range 0.11-0.19 sensitive patients compared with 0.17-0.34 control patients: pDNA damage. However, a strong correlation was found between clonogenic survival and both residual DNA damage (measured over 10-70 Gy, allowing 4 h repair, correlation coefficient: 0.90, DNA damage, with the sensitive cell lines generally showing a higher level of residual DNA damage. Cell-cycle delays were found in all 18 cell strains in response to 2 Gy irradiation, but were not found to discriminate between sensitive and normal patients. Associated studies found no mutations of the ATM gene in the five radiosensitive patients studied. However, a coding sequence alteration was found in the XRCC1 gene in one of the radiosensitive patients. These findings indicate that a DNA repair defect may be partly responsible for the extreme reactions to radiotherapy observed in a small percentage of patients and that with further modifications, an assay based on measurement of residual DNA damage

  3. Relationship among expression of basic-fibroblast growth factor ...

    African Journals Online (AJOL)

    Relationship among expression of basic-fibroblast growth factor, MTDH/Astrocyte elevated gene-1, adenomatous polyposis coli, matrix metalloproteinase 9,and COX-2 markers with prognostic factors in prostate carcinomas.

  4. Eugenol Toxicity in Human Dental Pulp Fibroblasts of Primary Teeth.

    Science.gov (United States)

    Escobar-García, Maria; Rodríguez-Contreras, Karen; Ruiz-Rodríguez, Socorro; Pierdant-Pérez, Mauricio; Cerda-Cristerna, Bernardino; Pozos-Guillén, Amaury

    2016-01-01

    The aim of the study was to determine the eugenol concentrations at which toxicity occurs in human dental pulp fibroblasts of primary teeth. Samples of primary dental pulp tissue were taken. Tissue samples were seeded by means of explant technique and used in the 4(th)-5th pass. Single Cell Gel Electrophoresis (Comet), phenazine MeThoSulfate (MTS), LIVE/DEAD Cell Viability/Toxicity and trypan blue assays for evaluation of the cytotoxicity of increasing concentrations of eugenol (0.06 to 810 μM) were performed. The results of toxicity tests showed toxic effects on dental pulp fibroblasts, even at very low concentrations of eugenol (0.06 μM). Very low concentrations of eugenol produce high toxicity in human dental pulp fibroblasts. All of the concentrations of eugenol that we evaluated produced high toxicity in human dental pulp fibroblasts of primary teeth.

  5. Improved Fibroblast Functionalities by Microporous Pattern Fabricated by Microelectromechanical Systems

    Science.gov (United States)

    Wei, Hongbo; Zhao, Lingzhou; Chen, Bangdao; Bai, Shizhu; Zhao, Yimin

    2014-01-01

    Fibroblasts, which play an important role in biological seal formation and maintenance, determine the long-term success of percutaneous implants. In this study, well-defined microporous structures with micropore diameters of 10–60 µm were fabricated by microelectromechanical systems and their influence on the fibroblast functionalities was observed. The results show that the microporous structures with micropore diameters of 10–60 µm did not influence the initial adherent fibroblast number; however, those with diameters of 40 and 50 µm improved the spread, actin stress fiber organization, proliferation and fibronectin secretion of the fibroblasts. The microporous structures with micropore diameters of 40–50 µm may be promising for application in the percutaneous part of an implant. PMID:25054322

  6. Further studies on the survival of non-proliferating human diploid fibroblasts irradiated with ultraviolet light

    Energy Technology Data Exchange (ETDEWEB)

    Chan, G.L.; Little, J.B. (Harvard Univ., Boston, MA (USA). School of Public Health)

    1982-04-01

    Labelling index data showed that in AG1518 cells, a diploid human fibroblast strain, there was a lag period of at least 14 hours between subculture from the density-inhibited plateau phase of growth and entry into DNA synthesis. Cells irradiated with 254nm wavelength U.V. light 8 hours after subculture did not exhibit the same degree of resistance as cells irradiated in plateau phase and subcultured immediately. When cells were arrested from proliferation by maintenance in an arginine and glutamine deficient medium for 72 hours, they were nearly as resistant to U.V. light as plateau phase cells although maintenance in this medium for 24 hours after irradiation supported further recovery only after low U.V. doses. One strain of Cockayne syndrome fibroblasts was found to be resistant to U.V. light in plateau phase while another strain was found to have the same survival response whether it was irradiated in the plateau or log phase of growth.

  7. Fibroblast behavior after titanium surfaces exposure.

    Science.gov (United States)

    Danza, Matteo; Zollino, Ilaria; Candotto, Valentina; Cura, Francesca; Carinci, Francesco

    2012-12-01

    The main requirements for a good material are its ability to promote attraction and adhesion of bone precursor cells and their proliferation and differentiation. Different biocompatible materials are currently employed as scaffold. Among these, titanium is considered a gold standard because of its biocompatibility and good corrosion resistance. The aim of this work was to compare two different AoN titanium layers (GR4 and GR5) to investigate which one had a greater osteoconductive power using human fibroblasts (HFb) culture at two different time-points. The expression levels of some adhesion and traction-resistance related genes (COL11A1, COL2A1, COL9A1, DSP, ELN, HAS1, and TFRC) were analyzed using real time reverse transcription-polymerase chain reaction. After 7 days of treatment with TiA 4GR, the only two up-regulated genes were COL2A1 and DSP. After 15 days of treatment, none of genes over expressed. Our preliminary results suggest that neither AoN 4GR nor AoN 5GR are able to promote the production of protein involved in cell-cell and cell-matrix adhesion and in stress-resistance, required for a good outcome in dental implantology.

  8. The Fibroblast Growth Factor signaling pathway

    Science.gov (United States)

    Ornitz, David M; Itoh, Nobuyuki

    2015-01-01

    The signaling component of the mammalian Fibroblast Growth Factor (FGF) family is comprised of eighteen secreted proteins that interact with four signaling tyrosine kinase FGF receptors (FGFRs). Interaction of FGF ligands with their signaling receptors is regulated by protein or proteoglycan cofactors and by extracellular binding proteins. Activated FGFRs phosphorylate specific tyrosine residues that mediate interaction with cytosolic adaptor proteins and the RAS-MAPK, PI3K-AKT, PLCγ, and STAT intracellular signaling pathways. Four structurally related intracellular non-signaling FGFs interact with and regulate the family of voltage gated sodium channels. Members of the FGF family function in the earliest stages of embryonic development and during organogenesis to maintain progenitor cells and mediate their growth, differentiation, survival, and patterning. FGFs also have roles in adult tissues where they mediate metabolic functions, tissue repair, and regeneration, often by reactivating developmental signaling pathways. Consistent with the presence of FGFs in almost all tissues and organs, aberrant activity of the pathway is associated with developmental defects that disrupt organogenesis, impair the response to injury, and result in metabolic disorders, and cancer. © 2015 Wiley Periodicals, Inc. PMID:25772309

  9. Rosmarinic acid potentiates carnosic acid induced apoptosis in lung fibroblasts

    OpenAIRE

    Bahri, Sana; Mies, Fr?d?rique; Ben Ali, Ridha; Mlika, Mona; Jameleddine, Saloua; Mc Entee, Kathleen; Shlyonsky, Vadim

    2017-01-01

    Pulmonary fibrosis is characterized by over-population and excessive activation of fibroblasts and myofibroblasts disrupting normal lung structure and functioning. Rosemary extract rich in carnosic acid (CA) and rosmarinic acid (RA) was reported to cure bleomycin-(BLM)-induced pulmonary fibrosis. We demonstrate that CA decreased human lung fibroblast (HLF) viability with IC50 value of 17.13?1.06 ?M, while RA had no cytotoxic effect. In the presence of 50 ?M of RA, dose-response for CA shifted...

  10. Abscisic acid ameliorates the systemic sclerosis fibroblast phenotype in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Bruzzone, Santina, E-mail: santina.bruzzone@unige.it [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Advanced Biotechnology Center, Largo Rosanna Benzi 10, 16132 Genova (Italy); Battaglia, Florinda [Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Mannino, Elena [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Parodi, Alessia [Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Fruscione, Floriana [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Advanced Biotechnology Center, Largo Rosanna Benzi 10, 16132 Genova (Italy); Basile, Giovanna [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Salis, Annalisa; Sturla, Laura [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Negrini, Simone; Kalli, Francesca; Stringara, Silvia [Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Filaci, Gilberto [Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Department of Internal Medicine, Viale Benedetto XV 6, 16132 Genova (Italy); and others

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer ABA is an endogenous hormone in humans, regulating different cell responses. Black-Right-Pointing-Pointer ABA reverts some of the functions altered in SSc fibroblasts to a normal phenotype. Black-Right-Pointing-Pointer UV-B irradiation increases ABA content in SSc cultures. Black-Right-Pointing-Pointer SSc fibroblasts could benefit from exposure to ABA and/or to UV-B. -- Abstract: The phytohormone abscisic acid (ABA) has been recently identified as an endogenous hormone in humans, regulating different cell functions, including inflammatory processes, insulin release and glucose uptake. Systemic sclerosis (SSc) is a chronic inflammatory disease resulting in fibrosis of skin and internal organs. In this study, we investigated the effect of exogenous ABA on fibroblasts obtained from healthy subjects and from SSc patients. Migration of control fibroblasts induced by ABA was comparable to that induced by transforming growth factor-{beta} (TGF-{beta}). Conversely, migration toward ABA, but not toward TGF-{beta}, was impaired in SSc fibroblasts. In addition, ABA increased cell proliferation in fibroblasts from SSc patients, but not from healthy subjects. Most importantly, presence of ABA significantly decreased collagen deposition by SSc fibroblasts, at the same time increasing matrix metalloproteinase-1 activity and decreasing the expression level of tissue inhibitor of metalloproteinase (TIMP-1). Thus, exogenously added ABA appeared to revert some of the functions altered in SSc fibroblasts to a normal phenotype. Interestingly, ABA levels in plasma from SSc patients were found to be significantly lower than in healthy subjects. UV-B irradiation induced an almost 3-fold increase in ABA content in SSc cultures. Altogether, these results suggest that the fibrotic skin lesions in SSc patients could benefit from exposure to high(er) ABA levels.

  11. Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0512 TITLE: Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer PRINCIPAL INVESTIGATOR: Andrew...SUBTITLE 5a. CONTRACT NUMBER Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0512 5c. PROGRAM...blocked by the addition of Pim inhibitors. These results suggest that the Pim protein kinase can regulate stromal cell biology to modulate epithelial

  12. Regulating Cancer Associated Fibroblast Biology in Prostate Cancer

    Science.gov (United States)

    2016-10-01

    SUPPLEMENTARY NOTES 14. ABSTRACT There is an urgent need to develop both new approaches to the treatment of prostate cancer. Analysis of human prostate...AWARD NUMBER: W81XWH-15-1-0512 TITLE: Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer PRINCIPAL INVESTIGATOR: Andrew...CONTRACT NUMBER Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0512 5c. PROGRAM ELEMENT NUMBER 6

  13. Small molecules enable highly efficient neuronal conversion of human fibroblasts.

    Science.gov (United States)

    Ladewig, Julia; Mertens, Jerome; Kesavan, Jaideep; Doerr, Jonas; Poppe, Daniel; Glaue, Finnja; Herms, Stefan; Wernet, Peter; Kögler, Gesine; Müller, Franz-Josef; Koch, Philipp; Brüstle, Oliver

    2012-06-01

    Forced expression of proneural transcription factors has been shown to direct neuronal conversion of fibroblasts. Because neurons are postmitotic, conversion efficiencies are an important parameter for this process. We present a minimalist approach combining two-factor neuronal programming with small molecule-based inhibition of glycogen synthase kinase-3β and SMAD signaling, which converts postnatal human fibroblasts into functional neuron-like cells with yields up to >200% and neuronal purities up to >80%.

  14. SPATIAL ORGANIZATION OF FIBROBLAST NUCLEAR CHROMOCENTERS: COMPONENT TREE ANALYSIS

    OpenAIRE

    Snapp, Robert R.; Goveia, Elyse; Peet, Lindsay; Bouffard, Nicole A; Badger, Gary J.; Langevin, Helene M

    2013-01-01

    The nuclei of mouse connective tissue fibroblasts contain chromocenters which are well-defined zones of heterochromatin that can be used as positional landmarks to examine nuclear remodeling in response to a mechanical perturbation. This study used component tree analysis, an image segmentation algorithm that detects high intensity voxels that are topologically connected, to quantify the spatial organization of chromocenters in fibroblasts within whole mouse connective tissue fixed and staine...

  15. FIBROBLAST CYTOSKELETAL REMODELING INDUCED BY TISSUE STRETCH INVOLVES ATP SIGNALING

    OpenAIRE

    Langevin, HM; Fujita, T.; Bouffard, NA; Takano, T; Koptiuch, C; Badger, GJ; Nedergaard, M

    2013-01-01

    Fibroblasts in whole areolar connective tissue respond to static stretching of the tissue by expanding and remodeling their cytoskeleton within minutes both ex vivo and in vivo. This study tested the hypothesis that the mechanism of fibroblast expansion in response to tissue stretch involves extracellular ATP signaling. In response to tissue stretch ex vivo, ATP levels in the bath solution increased significantly, and this increase was sustained for 20 minutes, returning to baseline at 60 min...

  16. Autophagy is required for IL-2-mediated fibroblast growth

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Rui [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219 (United States); Tang, Daolin, E-mail: tangd2@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219 (United States); Lotze, Michael T., E-mail: lotzemt@upcm.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219 (United States); Zeh III, Herbert J., E-mail: zehh@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219 (United States)

    2013-02-15

    Autophagy is an evolutionarily conserved pathway responsible for delivery of cytoplasmic material into the lysosomal degradation pathway to enable vesicular exocytosis. Interleukin (IL)-2 is produced by T-cells and its activity is important for immunoregulation. Fibroblasts are an immune competent cell type, playing a critical role in wound healing, chronic inflammation, and tumor development. Although autophagy plays an important role in each of these processes, whether it regulates IL-2 activity in fibroblasts is unknown. Here, we show that autophagy is required for IL-2-induced cell growth in fibroblasts. IL-2 significantly induced autophagy in mouse embryonic fibroblasts (MEFs) and primary lung fibroblasts. Autophagy inhibitors (e.g., 3-methylamphetamine and bafilomycin A1) or knockdown of ATG5 and beclin 1 blocked clinical grade IL-2-induced autophagy. Moreover, IL-2 induced HMGB1 cytoplasmic translocation in MEFs and promoted interaction between HMGB1 and beclin1, which is required for autophagy induction. Pharmacological and genetic inhibition of autophagy inhibited IL-2-induced cell proliferation and enhanced IL-2-induced apoptosis. These findings suggest that autophagy is an important pro-survival regulator for IL-2-induced cell growth in fibroblasts.

  17. Fascial components of the myofascial pain syndrome.

    Science.gov (United States)

    Stecco, Antonio; Gesi, Marco; Stecco, Carla; Stern, Robert

    2013-08-01

    Myofascial pain syndrome (MPS) is described as the muscle, sensory, motor, and autonomic nervous system symptoms caused by stimulation of myofascial trigger points (MTP). The participation of fascia in this syndrome has often been neglected. Several manual and physical approaches have been proposed to improve myofascial function after traumatic injuries, but the processes that induce pathological modifications of myofascial tissue after trauma remain unclear. Alterations in collagen fiber composition, in fibroblasts or in extracellular matrix composition have been postulated. We summarize here recent developments in the biology of fascia, and in particular, its associated hyaluronan (HA)-rich matrix that address the issue of MPS.

  18. Oncogenes induce the cancer-associated fibroblast phenotype: metabolic symbiosis and "fibroblast addiction" are new therapeutic targets for drug discovery.

    Science.gov (United States)

    Lisanti, Michael P; Martinez-Outschoorn, Ubaldo E; Sotgia, Federica

    2013-09-01

    Metabolic coupling, between mitochondria in cancer cells and catabolism in stromal fibroblasts, promotes tumor growth, recurrence, metastasis, and predicts anticancer drug resistance. Catabolic fibroblasts donate the necessary fuels (such as L-lactate, ketones, glutamine, other amino acids, and fatty acids) to anabolic cancer cells, to metabolize via their TCA cycle and oxidative phosphorylation (OXPHOS). This provides a simple mechanism by which metabolic energy and biomass are transferred from the host microenvironment to cancer cells. Recently, we showed that catabolic metabolism and "glycolytic reprogramming" in the tumor microenvironment are orchestrated by oncogene activation and inflammation, which originates in epithelial cancer cells. Oncogenes drive the onset of the cancer-associated fibroblast phenotype in adjacent normal fibroblasts via paracrine oxidative stress. This oncogene-induced transition to malignancy is "mirrored" by a loss of caveolin-1 (Cav-1) and an increase in MCT4 in adjacent stromal fibroblasts, functionally reflecting catabolic metabolism in the tumor microenvironment. Virtually identical findings were obtained using BRCA1-deficient breast and ovarian cancer cells. Thus, oncogene activation (RAS, NFkB, TGF-β) and/or tumor suppressor loss (BRCA1) have similar functional effects on adjacent stromal fibroblasts, initiating "metabolic symbiosis" and the cancer-associated fibroblast phenotype. New therapeutic strategies that metabolically uncouple oxidative cancer cells from their glycolytic stroma or modulate oxidative stress could be used to target this lethal subtype of cancers. Targeting "fibroblast addiction" in primary and metastatic tumor cells may expose a critical Achilles' heel, leading to disease regression in both sporadic and familial cancers.

  19. Preparation of extracellular matrices produced by cultured and primary fibroblasts

    Science.gov (United States)

    Franco-Barraza, Janusz; Beacham, Dorothy A.; Amatangelo, Michael D.; Cukierman, Edna

    2016-01-01

    Fibroblasts secrete and organize extracellular matrix (ECM), which provides structural support for their adhesion, migration, and tissue organization, besides regulating cellular functions such as growth and survival. Cell-to-matrix interactions are vital for vertebrate development. Disorders in these processes have been associated with fibrosis, developmental malformations, cancer, and other diseases. This unit describes a method for preparing a three-dimensional matrix derived from fibroblastic cells; the matrix is three-dimensional, cell and debris free, and attached to a two-dimensional culture surface. Cell adhesion and spreading are normal on these matrices. This matrix can also be compressed into a two-dimensional matrix and solubilized to study the matrix biochemically. Culturing fibroblasts on traditional two-dimensional (2-D) substrates induces an artificial polarity between lower and upper surfaces of these normally nonpolar cells. Not surprisingly, fibroblast morphology and migration differ once suspended in three-dimensional (3-D) collagen gels (Friedl and Brocker, 2000). However, the molecular composition of collagen gels does not mimic the natural fibroblast (i.e., mesenchymal) microenvironment. Fibroblasts secrete and organize ECM, which provides structural support for their adhesion, migration, and tissue organization, in addition to regulating cellular functions such as growth and survival (Buck and Horwitz, 1987; Hay, 1991; Hynes, 1999; Geiger et al., 2001). Cell-to-matrix interactions are vital for vertebrate development. Disorders in these processes have been associated with fibrosis, developmental malformations, cancer (i.e., desmoplastic tumor microenvironment), and other diseases (Rybinski et al., 2014). This unit describes methods for generating tissue culture surfaces coated with a fibroblast-derived 3-D ECM produced and deposited by both established and primary fibroblasts. The matrices closely resemble in vivo mesenchymal matrices and

  20. Williams syndrome

    Science.gov (United States)

    A support group can be helpful for emotional support and for giving and receiving practical advice. The following organization provides additional information about Williams Syndrome: Williams Syndrome Association -- www.williams-syndrome.org

  1. WIEDEMANN SYNDROME

    African Journals Online (AJOL)

    hi-tech

    BILATERAL BENIGN HAEMORRHAGIC ADRENAL CYSTS IN BECKWITH - WIEDEMANN. SYNDROME: CASE REPORT. P. ANOOP and M. A. ANJAY. SUMMARY. Beckwith-Wiedemann syndrome is the most common overgrowth malformation syndrome. The classical features include macrosomia, macroglossia, ...

  2. Marfan Syndrome

    Science.gov (United States)

    Marfan syndrome is a disorder that affects connective tissue. Connective tissues are proteins that support skin, bones, blood vessels, ... A problem with the fibrillin gene causes Marfan syndrome. Marfan syndrome can be mild to severe, and ...

  3. Brown Syndrome

    Science.gov (United States)

    ... extraction) have also been linked to acquired Brown syndrome. Inflammation of the tendon-trochlea complex (from adult and juvenile rheumatoid arthritis, systemic lupus erythematosus and sinusitis) can be ... syndrome hereditary? Hereditary cases of Brown syndrome are rare. ...

  4. Asperger Syndrome

    Science.gov (United States)

    ... Page You are here Home » Disorders » All Disorders Asperger Syndrome Information Page Asperger Syndrome Information Page What research is being done? ... Definition Treatment Prognosis Clinical Trials Organizations Publications Definition Asperger syndrome (AS) is a developmental disorder. It is ...

  5. The influence of genistein on free radicals in normal dermal fibroblasts and keloid fibroblasts examined by EPR spectroscopy.

    Science.gov (United States)

    Jurzak, Magdalena; Ramos, Paweł; Pilawa, Barbara

    2017-01-01

    Normal and keloid fibroblasts were examined using X-band (9.3 GHz) electron paramagnetic resonance spectroscopy. The effect of genistein on the concentration of free radicals in both normal dermal and keloid fibroblasts after ultraviolet irradiation was investigated. The highest concentration of free radicals was seen in keloid fibroblasts, with normal fibroblasts containing a lower concentration. The concentration of free radicals in both normal and keloid fibroblasts was altered in a concentration-dependent manner by the presence of genistein. The change in intra-cellular free radical concentration after the ultraviolet irradiation of both normal and keloid fibroblasts is also discussed. The antioxidant properties of genistein, using its 1,1-Diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging activity as a model, were tested, and the effect of ultraviolet irradiation on its interaction with free radicals was examined. The electron paramagnetic resonance spectra of DPPH showed quenching by genistein. The interaction of genistein with DPPH free radicals in the absence of ultraviolet irradiation was shown to be slow, but this interaction was much faster under ultraviolet irradiation. Ultraviolet irradiation enhanced the free radical-scavenging activity of genistein.

  6. ROVIBRATIONALLY RESOLVED DIRECT PHOTODISSOCIATION THROUGH THE LYMAN AND WERNER TRANSITIONS OF H{sub 2} FOR FUV/X-RAY-IRRADIATED ENVIRONMENTS

    Energy Technology Data Exchange (ETDEWEB)

    Gay, C. D.; Porter, R. L.; Stancil, P. C. [Department of Physics and Astronomy and Center for Simulational Physics, University of Georgia, Athens, GA 30602-2451 (United States); Abel, N. P. [Math, Computers, Geology, and Physics Department, University of Cincinnati, Clermont Campus, Batavia, OH 45103 (United States); Ferland, G. J. [Department of Physics and Astronomy, University of Kentucky, Lexington, KY (United States); Shaw, G. [Centre for Excellence in Basic Sciences, UM-DAE, Vidhyanagari Campus, Mumbai-400098 (India); Van Hoof, P. A. M. [Royal Observatory of Belgium, Ringlaan 3, 1180 Brussels (Belgium); Williams, R. J. R., E-mail: cgay1383@gmail.com, E-mail: ryanlporter@gmail.com, E-mail: stancil@physast.uga.edu, E-mail: npabel2@gmail.com, E-mail: gary@pa.uky.edu, E-mail: gargishaw@gmail.com, E-mail: p.vanhoof@oma.be, E-mail: robin.williams@awe.co.uk [AWE plc, Aldermaston, Reading RG7 4PR (United Kingdom)

    2012-02-10

    Using ab initio potential curves and dipole transition moments, cross-section calculations were performed for the direct continuum photodissociation of H{sub 2} through the B{sup 1}{Sigma}{sup +}{sub u} <- X{sup 1}{Sigma}{sup +}{sub g} (Lyman) and C{sup 1}{Pi}{sub u} <- X{sup 1}{Sigma}{sup +}{sub g} (Werner) transitions. Partial cross-sections were obtained for wavelengths from 100 A to the dissociation threshold between the upper electronic state and each of the 301 bound rovibrational levels v''J'' within the ground electronic state. The resulting cross-sections are incorporated into three representative classes of interstellar gas models: diffuse clouds, photon-dominated regions, and X-ray-dominated regions (XDRs). The models, which used the CLOUDY plasma/molecular spectra simulation code, demonstrate that direct photodissociation is comparable to fluorescent dissociation (or spontaneous radiative dissociation, the Solomon process) as an H{sub 2} destruction mechanism in intense far-ultraviolet or X-ray-irradiated gas. In particular, changes in H{sub 2} rotational column densities are found to be as large as 20% in the XDR model with the inclusion of direct photodissociation. The photodestruction rate from some high-lying rovibrational levels can be enhanced by pumping from H Ly{beta} due to a wavelength coincidence with cross-section resonances resulting from quasi-bound levels of the upper electronic states. Given the relatively large size of the photodissociation data set, a strategy is described to create truncated, but reliable, cross-section data consistent with the wavelength resolving power of typical observations.

  7. Cobalt(III) Werner Complexes with 1,2-Diphenylethylenediamine Ligands: Readily Available, Inexpensive, and Modular Chiral Hydrogen Bond Donor Catalysts for Enantioselective Organic Synthesis.

    Science.gov (United States)

    Lewis, Kyle G; Ghosh, Subrata K; Bhuvanesh, Nattamai; Gladysz, John A

    2015-03-25

    In the quest for new catalysts that can deliver single enantiomer pharmaceuticals and agricultural chemicals, chemists have extensively mined the "chiral pool", with little in the way of inexpensive, readily available building blocks now remaining. It is found that Werner complexes based upon the D3 symmetric chiral trication [Co(en)3](3+) (en = 1,2-ethylenediamine), which features an earth abundant metal and cheap ligand type, and was among the first inorganic compounds resolved into enantiomers 103 years ago, catalyze a valuable carbon-carbon bond forming reaction, the Michael addition of malonate esters to nitroalkenes, in high enantioselectivities and without requiring inert atmosphere conditions. The title catalysts, [Co((S,S)-dpen)3](3+) ((S,S)-3 (3+)) 3X(-), employ a commercially available chiral ligand, (S,S)-1,2-diphenylethylenediamine. The rates and ee values are functions of the configuration of the cobalt center (Λ/Δ) and the counteranions, which must be lipophilic to solubilize the trication in nonaqueous media. The highest enantioselectivities are obtained with Λ and 2Cl(-)BArf (-), 2BF4 (-)BArf (-), or 3BF4 (-) salts (BArf (-) = B(3,5-C6H3(CF3)2)4 (-)). The substrates are not activated by metal coordination, but rather by second coordination sphere hydrogen bonding involving the ligating NH2 groups. Crystal structures and NMR data indicate enthalpically stronger interactions with the NH moieties related by the C3 symmetry axis, as opposed to those related by the C2 symmetry axes; rate trends and other observations suggest this to be the catalytically active site. Both Λ- and Δ-(S,S)-3 (3+) 2Cl(-)BArf (-) are effective catalysts for additions of β-ketoesters to RO2CN=NCO2R species (99-86% yields, 81-76% ee), which provide carbon-nitrogen bonds and valuable precursors to α-amino acids.

  8. [Werner Leibbrand, Annemarie Wettley and controversies on "euthanasia" the background of medico-historical and ethical debates in the Post World War II era].

    Science.gov (United States)

    Wiesinger, Christine; Frewer, Andreas

    2014-01-01

    Psychiatrists and medical historians Werner Leibbrand (1896 - 1974) and Annemarie Wettley (1913 - 1996) are amongst the most striking figures in the field of history of medicine. Leibbrand was appointed director of the "Heil- und Pflegeanstalt" in Erlangen shortly after the war. Fuelled by his own experiences of suppression and persecution during the Nazi era he promised to unearth the crimes and atrocities which had happened under watch of the Nazi regime. He was joined by Annemarie Wettley, who worked as a physician at the hospital and had developed an increasing interest in the history of medicine. In 1946 they published "Um die Menschenrechte der Geisteskranken" ("Human Rights of the Mentally Ill") about the "euthanasia" campaign of the Nazi regime. Although a number of substantial works followed, Leibbrand and Wettley failed to inform in more depth on crimes and atrocities, for instance killings of patients and forced malnutrition. Doubts and charges against Wettley regarding her role in dietary programmes at the Erlangen hospital and against Leibbrand regarding special expert's reports--both had a short-term arrest warrant--might have contributed to stagnation in their efforts. In 1953 Leibbrand accepted the offer of a chair at the University in Munich, Wettley followed and habilitated in history of medicine; in the year 1962 they married. Contacts and exchange amongst medico-historical experts shed light on developments during the post-war era; still, a critical and fundamental review of the crimes within the medical system of the Nazi regime did not take place during this time.

  9. Fibroblast growth factor signaling in metabolic regulation

    Directory of Open Access Journals (Sweden)

    Vera eNies

    2016-01-01

    Full Text Available The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases, and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed.In this review we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease, and to provide starting points for the development of FGF-based therapies against metabolic conditions.

  10. POLYDACTYLY IN P FEIFFER SYNDROME II - OMIM #10160 0 A RARE ASSOCIATION

    Directory of Open Access Journals (Sweden)

    Deepa

    2015-03-01

    Full Text Available Pfeiffer syndrome (PS is a rare autosomal dominantly inherited disorder occurring in approximately 1:100,000 live births. Mutations of the fibroblast growth factor receptor 1(FGFR1 or FGFR2 gene can cause Pfeiffer syndrome. Craniosynostosis, brachycephaly, mid - facial hypoplasia, broad deviated thumbs and great toes c haracterize the syndrome. Pfeiffer syndrome depending on severity of the phenotype is of three types. The types 2 and 3 occur as sporadic cases and have poor prognosis. We report a case of Pfeiffer Syndrome type 2 having polydactyly, which to the best of o ur knowledge is first case of such an association

  11. Binding, uptake, and release of nicotine by human gingival fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Hanes, P.J.; Schuster, G.S.; Lubas, S. (Medical College of Georgia, Augusta (USA))

    1991-02-01

    Previous studies of the effects of nicotine on fibroblasts have reported an altered morphology and attachment of fibroblasts to substrates and disturbances in protein synthesis and secretion. This altered functional and attachment response may be associated with changes in the cell membrane resulting from binding of the nicotine, or to disturbances in cell metabolism as a result of high intracellular levels of nicotine. The purpose of the present study, therefore, was to (1) determine whether gingival fibroblasts bound nicotine and if any binding observed was specific or non-specific in nature; (2) determine whether gingival fibroblasts internalized nicotine, and if so, at what rate; (3) determine whether gingival fibroblasts also released nicotine back into the extracellular environment; and (4) if gingival fibroblasts release nicotine intact or as a metabolite. Cultures of gingival fibroblasts were prepared from gingival connective tissue biopsies. Binding was evaluated at 4{degree}C using a mixture of {sup 3}H-nicotine and unlabeled nicotine. Specific binding was calculated as the difference between {sup 3}H-nicotine bound in the presence and absence of unlabeled nicotine. The cells bound 1.44 (+/- 0.42) pmols/10(6) cells in the presence of unlabeled nicotine and 1.66 (+/- 0.55) pmols/10(6) cells in the absence of unlabeled nicotine. The difference was not significant. Uptake of nicotine was measured at 37{degree}C after treating cells with {sup 3}H-nicotine for time periods up to 4 hours. Uptake in pmols/10(6) cells was 4.90 (+/- 0.34) at 15 minutes, 8.30 (+/- 0.75) at 30 minutes, 12.28 (+/- 2.62) at 1 hour and 26.31 (+/- 1.15) at 4 hours.

  12. Functional screen of paracrine signals in breast carcinoma fibroblasts.

    Directory of Open Access Journals (Sweden)

    Gui Su

    Full Text Available Stromal fibroblasts actively participate in normal mammary gland homeostasis and in breast carcinoma growth and progression by secreting paracrine factors; however, little is known about the identity of paracrine mediators in individual patients. The purpose of this study was to characterize paracrine signaling pathways between breast carcinoma cells and breast carcinoma-associated fibroblasts (CAF or normal mammary fibroblasts (NF, respectively. CAF and NF were isolated from breast carcinoma tissue samples and adjacent normal mammary gland tissue of 28 patients. The fibroblasts were grown in 3D collagen gel co-culture with T47D human breast carcinoma cells and T47D cell growth was measured. CAF stimulated T47D cell growth to a significantly greater degree than NF. We detected a considerable inter-individual heterogeneity of paracrine interactions but identified FGF2, HB-EGF, heparanase-1 and SDF1 as factors that were consistently responsible for the activity of carcinoma-associated fibroblasts. CAF from low-grade but not high-grade carcinomas required insulin-like growth factor 1 and transforming growth factor beta 1 to stimulate carcinoma growth. Paradoxically, blocking of membrane-type 1 matrix metalloprotease stimulated T47D cell growth in co-culture with NF. The results were largely mirrored by treating the fibroblasts with siRNA oligonucleotides prior to co-culture, implicating the fibroblasts as principal production site for the secreted mediators. In summary, we identify a paracrine signaling network with inter-individual commonalities and differences. These findings have significant implications for the design of stroma-targeted therapies.

  13. Werner Heisenberg. The language of the atoms. Life and work - a scientific biography - the ''joyous science'' (youth until Nobel price); Werner Heisenberg. Die Sprache der Atome. Leben und Wirken - Eine wissenschaftliche Biographie - Die ''froehliche Wissenschaft'' (Jugend bis Nobelpreis)

    Energy Technology Data Exchange (ETDEWEB)

    Rechenberg, Helmut [MPI fuer Physik, Muenchen (Germany). Werner-Heisenberg-Institut

    2010-07-01

    With his discovery that measuring values of complementary fundamental quantities in the microscopic world cannot by arbitrarily precisely determined cutted Werner Heisenberg the Gordian knot for the finishing of quantum theory developed by Planck, Einstein, and others and opened by this a new ''golden era'' in the physics of the 20th century. On the base of the documents from his life and work, i. e. deeds, letters and reports of contemporaries, as well as the published and unpublished essays, books, and articles of Heisenberg - also the later on found, publications or manuscripts mainly coming from the inheritance - resulted this systematic biography of Heisenberg. The author, the last doctoral candidate of Heisenberg relied furthermore on factual and personal knowledges, mainly own remembrances on his doctoral father and his teachers, colleagues, and students. Because of the interest of an authentical biography of the theoretical physicist Heisenberg the presentation of the mathematical approaches and the corresponding derivations could not completely be abandoned. This biography appeals by this both to a scientifically cultivated as a wider in science interested audience and covers the first phase of Heisenberg's life until his Nobel price 1933. [German] Mit seiner Entdeckung, dass sich Messwerte komplementaerer Groessen in der mikroskopischen Welt nicht beliebig genau bestimmen lassen, durchschnitt Werner Heisenberg den Gordischen Knoten zur Vollendung der von Planck, Einstein und anderen entwickelten Quantentheorie und eroeffnete damit ein neues ''goldenes Zeitalter'' in der Physik des 20. Jahrhunderts. Auf der Grundlage der Dokumente aus seinem Leben und Wirken, d.h. der Urkunden, Briefe und Berichte von Zeitzeugen sowie der publizierten und unpublizierten Abhandlungen, Buecher und Artikel Heisenbergs - auch der spaeter aufgefundenen, ueberwiegend aus dem Nachlass Heisenbergs stammenden Veroeffentlichungen oder

  14. DOWN SYNDROME WITH MOYAMOYA SYNDROME

    National Research Council Canada - National Science Library

    Mohan Makwana; R. K. Vishnoi; Jai Prakash Soni; Kapil Jetha; Suresh Kumar Verma; Pradeep Singh Rathore; Monika Choudhary

    2017-01-01

    ...,” in which the arterial changes are seen among patients with various syndromes or other disease processes- Down syndrome, sickle cell anaemia, neurofibromatosis type-1, congenital heart disease...

  15. Site-Specific Keloid Fibroblasts Alter the Behaviour of Normal Skin and Normal Scar Fibroblasts through Paracrine Signalling

    Science.gov (United States)

    Bayat, Ardeshir

    2013-01-01

    Keloid disease (KD) is an abnormal cutaneous fibroproliferative disorder of unknown aetiopathogenesis. Keloid fibroblasts (KF) are implicated as mediators of elevated extracellular matrix deposition. Aberrant secretory behaviour by KF relative to normal skin fibroblasts (NF) may influence the disease state. To date, no previous reports exist on the ability of site-specific KF to induce fibrotic-like phenotypic changes in NF or normal scar fibroblasts (NS) by paracrine mechanisms. Therefore, the aim of this study was to investigate the influence of conditioned media from site-specific KF on the cellular and molecular behaviour of both NF and NS enabled by paracrine mechanisms. Conditioned media was collected from cultured primary fibroblasts during a proliferative log phase of growth including: NF, NS, peri-lesional keloid fibroblasts (PKF) and intra-lesional keloid fibroblasts (IKF). Conditioned media was used to grow NF, NS, PKF and IKF cells over 240 hrs. Cellular behavior was monitored through real time cell analysis (RTCA), proliferation rates and migration in a scratch wound assay. Fibrosis-associated marker expression was determined at both protein and gene level. PKF conditioned media treatment of both NF and NS elicited enhanced cell proliferation, spreading and viability as measured in real time over 240 hrs versus control conditioned media. Following PKF and IKF media treatments up to 240 hrs, both NF and NS showed significantly elevated proliferation rates (pmedia from growing marginal PKF elicited the strongest effects. In conclusion, primary NF and NS cells treated with PKF or IKF conditioned media exhibit enhanced expression of fibrosis-associated molecular markers and increased cellular activity as a result of keloid fibroblast-derived paracrine factors. PMID:24348987

  16. Orthodontic adhesives induce human gingival fibroblast toxicity and inflammation.

    Science.gov (United States)

    Huang, Tsui-Hsien; Liao, Pao-Hsin; Li, Han Yu; Ding, Shinn Jyh; Yen, Min; Kao, Chia-Tze

    2008-05-01

    To test the null hypothesis that the resin base and the resin hybrid glass ionomer base adhesives do not cause inflammation after contacting primary human gingival fibroblasts in vitro. The resin base and resin hybrid glass ionomer base adhesives were used to treat human gingival fibroblasts to evaluate the survival rate using MTT colorimetric assay to detect the level of cyclooxygenase-2 (COX-2) mRNA by reverse transcription polymerase chain reaction (RT-PCR) technique and COX-2 protein expression using Western blot analysis. The results were analyzed using one-way analysis of variance (ANOVA). Tests of differences of the treatments were analyzed using the Tukey test and a value of P adhesive and the liquid of glass ionomer adhesive showed decreasing survival rates after 24 hours of treatment (P adhesives induced COX-2 protein expression in human gingival fibroblasts. The exposure of quiescent human gingival fibroblasts to adhesives resulted in the induction of COX-2 mRNA expression. The investigations of the time-dependent COX-2 mRNA expression in adhesive-treated human gingival fibroblasts revealed different patterns. The hypothesis is rejected. For orthodontic patients with gingival inflammation, except for those with oral hygiene problems, the activation of COX-2 expression by orthodontic adhesive may be one of the potential mechanisms.

  17. Cultured Human Fibroblast Biostimulation Using a 940 nm Diode Laser.

    Science.gov (United States)

    Illescas-Montes, Rebeca; Melguizo-Rodríguez, Lucía; Manzano-Moreno, Francisco Javier; García-Martínez, Olga; Ruiz, Concepción; Ramos-Torrecillas, Javier

    2017-07-13

    Fibroblasts are the main cells involved in regeneration during wound healing. The objective was to determine the effect of 940 nm diode laser on cultured human fibroblasts using different irradiation regimens. The CCD-1064Sk human epithelial fibroblast cell line was treated with a 940 nm diode laser at different energy doses (power: 0.2-1 W and energy density: 1-7 J/cm²) using different transmission modes (continuous or pulsed). The effect on cell growth at 24 and 72 h post-treatment was examined by measuring the proliferative capacity, the impact on the cell cycle, and the effect on cell differentiation. fibroblast proliferative capacity was increased at 24 and 72 h post-treatment as a function of the energy dose. The greatest increase was observed with a power of 0.2 or 0.5 W and energy density between 1 and 4 J/cm²; no difference was observed between continuous and pulsed modes. There were no significant differences in cell cycle between treated groups and controls. α-actin expression was increased by treatment, indicating enhanced cell differentiation. The 940 nm diode laser has biostimulating effects on fibroblasts, stimulating proliferative capacity and cell differentiation without altering the cell cycle. Further researches are necessary to explore its potential clinical usefulness in wound healing.

  18. Androgen receptor characteristics in skin fibroblasts from hirsute women.

    Science.gov (United States)

    Eil, C; Cutler, G B; Loriaux, D L

    1985-01-01

    Hormonal measurements in some women with hirsutism often reveal little or no elevation in androgen levels to explain the disorder. Thus, it has been postulated that increased sensitivity of the hair follicle to androgen may contribute to the development of hirsutism in such patients. We, therefore, sought androgen receptor abnormalities in skin fibroblasts cultured from 10 hirsute women (ages 17-43) and normal or mildly elevated plasma testosterone levels (28-82 ng/dl). Androgen receptor content (Ro) and binding affinity (Kd) in cultured pubic skin fibroblasts were measured using a dispersed, whole cell assay. Ten such cell lines from these women were compared with 19 pubic skin cell lines from 9 normal volunteers (6 males and 3 females) and from 10 other subjects (males with gynecomastia or hypospadias). There was no statistically significant difference in the mean androgen receptor content (11,600 +/- 2700 (SE) sites/cell fibroblasts vs 7900 +/- 700 sites/cell or binding affinity (2.0 +/- 0.3 (SE) X 10(-9) M vs 1.5 +/- 0.2 X 10(-9) M, respectively) between the patients' fibroblasts and those of the controls. We conclude that hirsutism cannot be explained by abnormalities in fibroblast androgen receptor number or affinity. These observations do not exclude the possibility that other mechanisms might lead to increased peripheral androgen sensitivity in such patients.

  19. Dysregulated proinflammatory and fibrogenic phenotype of fibroblasts in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    François Huaux

    Full Text Available Morbi-mortality in cystic fibrosis (CF is mainly related to chronic lung infection and inflammation, uncontrolled tissue rearrangements and fibrosis, and yet the underlying mechanisms remain largely unknown. We evaluated inflammatory and fibrosis responses to bleomycin in F508del homozygous and wild-type mice, and phenotype of fibroblasts explanted from mouse lungs and skin. The effect of vardenafil, a cGMP-specific phosphodiesterase type 5 inhibitor, was tested in vivo and in culture. Responses of proinflammatory and fibrotic markers to bleomycin were enhanced in lungs and skin of CF mice and were prevented by treatment with vardenafil. Purified lung and skin fibroblasts from CF mice proliferated and differentiated into myofibroblasts more prominently and displayed higher sensitivity to growth factors than those recovered from wild-type littermates. Under inflammatory stimulation, mRNA and protein expression of proinflammatory mediators were higher in CF than in wild-type fibroblasts, in which CFTR expression reached similar levels to those observed in other non-epithelial cells, such as macrophages. Increased proinflammatory responses in CF fibroblasts were reduced by half with submicromolar concentrations of vardenafil. Proinflammatory and fibrogenic functions of fibroblasts are upregulated in CF and are reduced by vardenafil. This study provides compelling new support for targeting cGMP signaling pathway in CF pharmacotherapy.

  20. Cultured Human Fibroblast Biostimulation Using a 940 nm Diode Laser

    Directory of Open Access Journals (Sweden)

    Rebeca Illescas-Montes

    2017-07-01

    Full Text Available Background: Fibroblasts are the main cells involved in regeneration during wound healing. The objective was to determine the effect of 940 nm diode laser on cultured human fibroblasts using different irradiation regimens. Methods: The CCD-1064Sk human epithelial fibroblast cell line was treated with a 940 nm diode laser at different energy doses (power: 0.2–1 W and energy density: 1–7 J/cm2 using different transmission modes (continuous or pulsed. The effect on cell growth at 24 and 72 h post-treatment was examined by measuring the proliferative capacity, the impact on the cell cycle, and the effect on cell differentiation. Results: fibroblast proliferative capacity was increased at 24 and 72 h post-treatment as a function of the energy dose. The greatest increase was observed with a power of 0.2 or 0.5 W and energy density between 1 and 4 J/cm2; no difference was observed between continuous and pulsed modes. There were no significant differences in cell cycle between treated groups and controls. α-actin expression was increased by treatment, indicating enhanced cell differentiation. Conclusion: The 940 nm diode laser has biostimulating effects on fibroblasts, stimulating proliferative capacity and cell differentiation without altering the cell cycle. Further researches are necessary to explore its potential clinical usefulness in wound healing.

  1. Anatomic demarcation by positional variation in fibroblast gene expression programs.

    Directory of Open Access Journals (Sweden)

    John L Rinn

    2006-07-01

    Full Text Available Fibroblasts are ubiquitous mesenchymal cells with many vital functions during development, tissue repair, and disease. Fibroblasts from different anatomic sites have distinct and characteristic gene expression patterns, but the principles that govern their molecular specialization are poorly understood. Spatial organization of cellular differentiation may be achieved by unique specification of each cell type; alternatively, organization may arise by cells interpreting their position along a coordinate system. Here we test these models by analyzing the genome-wide gene expression profiles of primary fibroblast populations from 43 unique anatomical sites spanning the human body. Large-scale differences in the gene expression programs were related to three anatomic divisions: anterior-posterior (rostral-caudal, proximal-distal, and dermal versus nondermal. A set of 337 genes that varied according to these positional divisions was able to group all 47 samples by their anatomic sites of origin. Genes involved in pattern formation, cell-cell signaling, and matrix remodeling were enriched among this minimal set of positional identifier genes. Many important features of the embryonic pattern of HOX gene expression were retained in fibroblasts and were confirmed both in vitro and in vivo. Together, these findings suggest that site-specific variations in fibroblast gene expression programs are not idiosyncratic but rather are systematically related to their positional identities relative to major anatomic axes.

  2. Sporadic Alzheimer disease fibroblasts display an oxidative stress phenotype.

    Science.gov (United States)

    Ramamoorthy, Mahesh; Sykora, Peter; Scheibye-Knudsen, Morten; Dunn, Christopher; Kasmer, Cindy; Zhang, Yongqing; Becker, Kevin G; Croteau, Deborah L; Bohr, Vilhelm A

    2012-09-15

    Alzheimer disease (AD) is a major health problem in the United States, affecting one in eight Americans over the age of 65. The number of elderly suffering from AD is expected to continue to increase over the next decade, as the average age of the U.S. population increases. The risk factors for and etiology of AD are not well understood; however, recent studies suggest that exposure to oxidative stress may be a contributing factor. Here, microarray gene expression signatures were compared in AD-patient-derived fibroblasts and normal fibroblasts exposed to hydrogen peroxide or menadione (to simulate conditions of oxidative stress). Using the 23K Illumina cDNA microarray to screen expression of >14,000 human genes, we identified a total of 1017 genes that are chronically up- or downregulated in AD fibroblasts, 215 of which were also differentially expressed in normal human fibroblasts within 12h after exposure to hydrogen peroxide or menadione. Pathway analysis of these 215 genes and their associated pathways revealed cellular functions that may be critically dysregulated by oxidative stress and play a critical role in the etiology and/or pathology of AD. We then examined the AD fibroblasts for the presence of oxidative DNA damage and found increased accumulation of 8-oxo-guanine. These results indicate the possible role of oxidative stress in the gene expression profile seen in AD. Published by Elsevier Inc.

  3. Modeled Microgravity Affects Fibroblast Functions Related to Wound Healing

    Science.gov (United States)

    Cialdai, Francesca; Vignali, Leonardo; Morbidelli, Lucia; Colciago, Alessandra; Celotti, Fabio; Santi, Alice; Caselli, Anna; Cirri, Paolo; Monici, Monica

    2017-02-01

    Wound healing is crucial for the survival of an organism. Therefore, in the perspective of space exploration missions, it is important to understand if and how microgravity conditions affect the behavior of the cell populations involved in wound healing and the evolution of the process. Since fibroblasts are the major players in tissue repair, this study was focused on the behavior of fibroblasts in microgravity conditions, modeled by a RCCS. Cell cytoskeleton was studied by immunofluorescence microscopy, the ability to migrate was assessed by microchemotaxis and scratch assay, and the expression of markers of fibroblast activation, angiogenesis, and inflammation was assessed by western blot. Results revealed that after cell exposure to modeled microgravity conditions, a thorough rearrangement of microtubules occurred and α-SMA bundles were replaced by a tight network of faulty and disorganized filaments. Exposure to modeled microgravity induced a decrease in α-SMA and E-CAD expressions. Also, the expression of the pro-angiogenic protein VEGF decreased, while that of the inflammatory signal COX-2 increased. Fibroblast ability to adhere, migrate, and respond to chemoattractants (PRP), closely related to cytoskeleton integrity and membrane junctions, was significantly impaired. Nevertheless, PRP was able to partially restore fibroblast migration.

  4. Fibroblast cytoskeletal remodeling induced by tissue stretch involves ATP signaling.

    Science.gov (United States)

    Langevin, Helene M; Fujita, Takumi; Bouffard, Nicole A; Takano, Takahiro; Koptiuch, Cathryn; Badger, Gary J; Nedergaard, Maiken

    2013-09-01

    Fibroblasts in whole areolar connective tissue respond to static stretching of the tissue by expanding and remodeling their cytoskeleton within minutes both ex vivo and in vivo. This study tested the hypothesis that the mechanism of fibroblast expansion in response to tissue stretch involves extracellular ATP signaling. In response to tissue stretch ex vivo, ATP levels in the bath solution increased significantly, and this increase was sustained for 20 min, returning to baseline at 60 min. No increase in ATP was observed in tissue incubated without stretch or tissue stretched in the presence of the Rho kinase inhibitor Y27632. The increase in fibroblast cross sectional area in response to tissue stretch was blocked by both suramin (a purinergic receptor blocker) and apyrase (an enzyme that selectively degrades extracellular ATP). Furthermore, connexin channel blockers (octanol and carbenoxolone), but not VRAC (fluoxetine) or pannexin (probenecid) channel blockers, inhibited fibroblast expansion. Together, these results support a mechanism in which extracellular ATP signaling via connexin hemichannels mediate the active change in fibroblast shape that occurs in response to a static increase in tissue length. Copyright © 2013 Wiley Periodicals, Inc.

  5. Interaction of human gingival fibroblasts with PVA/gelatine sponges.

    Science.gov (United States)

    Moscato, Stefania; Mattii, Letizia; D'Alessandro, Delfo; Cascone, Maria Grazia; Lazzeri, Luigi; Serino, Lorenzo Pio; Dolfi, Amelio; Bernardini, Nunzia

    2008-07-01

    Tissue engineering scaffolds should be able to reproduce optimal microenvironments in order to support cell attachment, three-dimensional growth, migration and, regarding fibroblasts, must also promote extracellular matrix production. Various bioactive molecules are employed in the preparation of spongy scaffolds to obtain biomimetic matrices by either surface-coating or introducing them into the bulk composition of the biomaterial. The biomimetic properties of a spongy matrix composed of PVA combined with the natural component gelatine were evaluated by culturing human gingival fibroblasts on the scaffold. Cell adhesion, morphology and distribution within the scaffold were assessed by histology and electron microscopy; viability and metabolic activity as well as extracellular matrix production were analyzed by MTT assay, cytochemistry and immunocytochemistry. Fibroblasts interacted positively with PVA/gelatine. They adhered to the PVA/gelatine matrix in which they had good spreading activity and active metabolism; fibroblasts were also able to produce extracellular matrix molecules (type I collagen, fibronectin and laminin) compared to bi-dimensionally grown cells. The in situ creation of a biological matrix by human fibroblasts together with the ability to produce growth factor TGF-beta1 and the intracellular signal transduction molecule RhoA, suggests that this kind of PVA/gelatine sponge may represent a suitable support for in vitro extracellular matrix production and connective tissue regeneration.

  6. Cockayne syndrome: a cellular sensitivity to ultraviolet light.

    Science.gov (United States)

    Schmickel, R D; Chu, E H; Trosko, J E; Chang, C C

    1977-08-01

    Two unrelated children, a boy 2 1/2 years old and a girl 4 years old, were affected with the cachectic dwarfism of Cockayne syndrome. Fibroblast cultures derived from these patients exhibited increased sensitivity to ultraviolet (UV) light, but not to x-irradiation, as measured by colony-forming ability. In both Cockayne fibroblast cultures, the rate of removal of thymidine dimer from the irradiated cellular DNA was normal. This demonstration of a cellular defect in Cockayne cells suggests that there may be an enzymatic defect in the repair of UV light-induced damage.

  7. Keratinocyte growth factor mRNA expression in periodontal ligament fibroblasts

    DEFF Research Database (Denmark)

    Dabelsteen, S; Wandall, H H; Grøn, B

    1997-01-01

    Keratinocyte growth factor (KGF) is a fibroblast growth factor which mediates epithelial growth and differentiation. KGF is expressed in subepithelial fibroblasts, but generally not in fibroblasts of deep connective tissue, such as fascia and ligaments. Here we demonstrate that KGF mRNA is expres......Keratinocyte growth factor (KGF) is a fibroblast growth factor which mediates epithelial growth and differentiation. KGF is expressed in subepithelial fibroblasts, but generally not in fibroblasts of deep connective tissue, such as fascia and ligaments. Here we demonstrate that KGF m...

  8. Kindler syndrome

    Directory of Open Access Journals (Sweden)

    Kaviarasan P

    2005-01-01

    Full Text Available Kindler syndrome is a rare autosomal recessive disorder associated with skin fragility. It is characterized by blistering in infancy, photosensitivity and progressive poikiloderma. The syndrome involves the skin and mucous membrane with radiological changes. The genetic defect has been identified on the short arm of chromosome 20. This report describes an 18-year-old patient with classical features like blistering and photosensitivity in childhood and the subsequent development of poikiloderma. The differential diagnosis of Kindler syndrome includes diseases like Bloom syndrome, Cockayne syndrome, dyskeratosis congenita, epidermolysis bullosa, Rothmund-Thomson syndrome and xeroderma pigmentosum. Our patient had classical cutaneous features of Kindler syndrome with phimosis as a complication.

  9. Model of human aging: Recent findings on Werner’s and Hutchinson-Gilford progeria syndromes

    Directory of Open Access Journals (Sweden)

    Shian-ling Ding

    2008-09-01

    Full Text Available Shian-ling Ding1, Chen-Yang Shen2,3,41Department of Nursing, Kang-Ning Junior College of Medical Care and Management, Taipei, Taiwan; 2Institute of Biomedical Sciences, and 3Life Science Library, Academia Sinica, Taipei, Taiwan; 4Graduate Institute of Environmental Science, China Medical University, Taichong, TaiwanAbstract: The molecular mechanisms involved in human aging are complicated. Two progeria syndromes, Werner’s syndrome (WS and Hutchinson-Gilford progeria syndrome (HGPS, characterized by clinical features mimicking physiological aging at an early age, provide insights into the mechanisms of natural aging. Based on recent findings on WS and HGPS, we suggest a model of human aging. Human aging can be triggered by two main mechanisms, telomere shortening and DNA damage. In telomere-dependent aging, telomere shortening and dysfunction may lead to DNA damage responses which induce cellular senescence. In DNA damage-initiated aging, DNA damage accumulates, along with DNA repair deficiencies, resulting in genomic instability and accelerated cellular senescence. In addition, aging due to both mechanisms (DNA damage and telomere shortening is strongly dependent on p53 status. These two mechanisms can also act cooperatively to increase the overall level of genomic instability, triggering the onset of human aging phenotypes.Keywords: human aging, Hutchinson-Gilford Progeria syndrome, Werner syndrome

  10. Fibroblasts from phenotypically normal palmar fascia exhibit molecular profiles highly similar to fibroblasts from active disease in Dupuytren's Contracture

    Directory of Open Access Journals (Sweden)

    Satish Latha

    2012-05-01

    Full Text Available Abstract Background Dupuytren's contracture (DC is a fibroproliferative disorder characterized by the progressive development of a scar-like collagen-rich cord that affects the palmar fascia of the hand and leads to digital flexion contractures. DC is most commonly treated by surgical resection of the diseased tissue, but has a high reported recurrence rate ranging from 27% to 80%. We sought to determine if the transcriptomic profiles of fibroblasts derived from DC-affected palmar fascia, adjacent phenotypically normal palmar fascia, and non-DC palmar fascial tissues might provide mechanistic clues to understanding the puzzle of disease predisposition and recurrence in DC. Methods To achieve this, total RNA was obtained from fibroblasts derived from primary DC-affected palmar fascia, patient-matched unaffected palmar fascia, and palmar fascia from non-DC patients undergoing carpal tunnel release (6 patients in each group. These cells were grown on a type-1 collagen substrate (to better mimic their in vivo environments. Microarray analyses were subsequently performed using Illumina BeadChip arrays to compare the transcriptomic profiles of these three cell populations. Data were analyzed using Significance Analysis of Microarrays (SAM v3.02, hierarchical clustering, concordance mapping and Venn diagram. Results We found that the transcriptomic profiles of DC-disease fibroblasts and fibroblasts from unaffected fascia of DC patients exhibited a much greater overlap than fibroblasts derived from the palmar fascia of patients undergoing carpal tunnel release. Quantitative real time RT-PCR confirmed the differential expression of select genes validating the microarray data analyses. These data are consistent with the hypothesis that predisposition and recurrence in DC may stem, at least in part, from intrinsic similarities in the basal gene expression of diseased and phenotypically unaffected palmar fascia fibroblasts. These data also demonstrate that

  11. Fibroblasts from phenotypically normal palmar fascia exhibit molecular profiles highly similar to fibroblasts from active disease in Dupuytren's Contracture

    Science.gov (United States)

    2012-01-01

    Background Dupuytren's contracture (DC) is a fibroproliferative disorder characterized by the progressive development of a scar-like collagen-rich cord that affects the palmar fascia of the hand and leads to digital flexion contractures. DC is most commonly treated by surgical resection of the diseased tissue, but has a high reported recurrence rate ranging from 27% to 80%. We sought to determine if the transcriptomic profiles of fibroblasts derived from DC-affected palmar fascia, adjacent phenotypically normal palmar fascia, and non-DC palmar fascial tissues might provide mechanistic clues to understanding the puzzle of disease predisposition and recurrence in DC. Methods To achieve this, total RNA was obtained from fibroblasts derived from primary DC-affected palmar fascia, patient-matched unaffected palmar fascia, and palmar fascia from non-DC patients undergoing carpal tunnel release (6 patients in each group). These cells were grown on a type-1 collagen substrate (to better mimic their in vivo environments). Microarray analyses were subsequently performed using Illumina BeadChip arrays to compare the transcriptomic profiles of these three cell populations. Data were analyzed using Significance Analysis of Microarrays (SAM v3.02), hierarchical clustering, concordance mapping and Venn diagram. Results We found that the transcriptomic profiles of DC-disease fibroblasts and fibroblasts from unaffected fascia of DC patients exhibited a much greater overlap than fibroblasts derived from the palmar fascia of patients undergoing carpal tunnel release. Quantitative real time RT-PCR confirmed the differential expression of select genes validating the microarray data analyses. These data are consistent with the hypothesis that predisposition and recurrence in DC may stem, at least in part, from intrinsic similarities in the basal gene expression of diseased and phenotypically unaffected palmar fascia fibroblasts. These data also demonstrate that a collagen

  12. Secretome Analysis of Human Primary Fibroblasts Undergoing Senescence

    DEFF Research Database (Denmark)

    Rogowska-Wrzesinska, Adelina; Micutkova, Lucia; Diener, Thomas

    Introduction Cultures of diploid human fibroblasts can replicate only a finite number of times; rapid proliferation is followed by decline in replicative frequency and finally cells become senescent and are incapable of further proliferation. Senescencent cells display altered growth, morphology......-degrading. In this study we use proteomic tools to characterise the secretome of young and senescent fibroblasts.   Methods Three independent preparations of primary human foreskin fibroblasts were grown to senescence. Young, rapidly proliferating cells at passage 11 and cells from passage 28 displaying senescent...... spectrometry; peptide count was used to estimate protein abundance.   Results 2DGE based analysis of secretion profiles of young and senescent cells derived from the same cell lineage revealed a number of protein spots differentially expressed. We have observed an increased secretion of matrix...

  13. Chemical Conversion of Human Fibroblasts into Functional Schwann Cells

    Directory of Open Access Journals (Sweden)

    Eva C. Thoma

    2014-10-01

    Full Text Available Direct transdifferentiation of somatic cells is a promising approach to obtain patient-specific cells for numerous applications. However, conversion across germ-layer borders often requires ectopic gene expression with unpredictable side effects. Here, we present a gene-free approach that allows efficient conversion of human fibroblasts via a transient progenitor stage into Schwann cells, the major glial cell type of peripheral nerves. Using a multikinase inhibitor, we transdifferentiated fibroblasts into transient neural precursors that were subsequently further differentiated into Schwann cells. The resulting induced Schwann cells (iSCs expressed numerous Schwann cell-specific proteins and displayed neurosupportive and myelination capacity in vitro. Thus, we established a strategy to obtain mature Schwann cells from human postnatal fibroblasts under chemically defined conditions without the introduction of ectopic genes.

  14. Systems-level modeling of cancer-fibroblast interaction.

    Directory of Open Access Journals (Sweden)

    Raymond C Wadlow

    2009-09-01

    Full Text Available Cancer cells interact with surrounding stromal fibroblasts during tumorigenesis, but the complex molecular rules that govern these interactions remain poorly understood thus hindering the development of therapeutic strategies to target cancer stroma. We have taken a mathematical approach to begin defining these rules by performing the first large-scale quantitative analysis of fibroblast effects on cancer cell proliferation across more than four hundred heterotypic cell line pairings. Systems-level modeling of this complex dataset using singular value decomposition revealed that normal tissue fibroblasts variably express at least two functionally distinct activities, one which reflects transcriptional programs associated with activated mesenchymal cells, that act either coordinately or at cross-purposes to modulate cancer cell proliferation. These findings suggest that quantitative approaches may prove useful for identifying organizational principles that govern complex heterotypic cell-cell interactions in cancer and other contexts.

  15. A case of the higher-level classification of praying mantises (Mantodea) obscuring the synonymy of Majangella Giglio-Tos, 1915 (Liturgusidae, Liturgusinae) and Ephippiomantis Werner, 1922 (Hymenopodidae, Acromantinae).

    Science.gov (United States)

    Svenson, Gavin J; Vollmer, William

    2014-05-21

    The praying mantis genus Majangella Giglio-Tos, 1915 is taxonomically treated with a re-description of the genus and the two included species, M. moultoni Giglio-Tos, 1915 and M. carli Giglio-Tos, 1915. The genus Ephippiomantis Werner, 1922 is newly determined to be the junior synonym of Majangella Giglio-Tos, 1915 based on morphology. The species for which the genus name Ephippiomantis was erected, E. ophirensis Werner, 1922, is re-described and now included within Majangella. This synonymy was determined herein as the direct result of erroneous higher-level placement of Majangella within the Majanginae by Giglio-Tos and was not recognized even after the genus was moved to within Liturgusidae. Action is now taken to move Majangella from within Liturgusidae to within the Hymenopodidae subfamily of Acromantinae, which is supported by morphological and molecular data. A key to the three species is provided along with habitus images, images of the head, pronotum, and foreleg, and illustrations of the male genitalia. Species distributions are presented and locality coordinates are provided in print as well as being available for download as a KML file viewable in Google Earth.

  16. Pleromatización, fisionomización y metaforicidad: una articulación teórica de los procesos de construcción de sentido de Valsiner, Werner y McNeill

    Directory of Open Access Journals (Sweden)

    Pablo Fossa

    Full Text Available Resumen El presente trabajo tiene por objetivo desarrollar una articulación teórica sobre los diferentes procesos de construcción de sentido en la experiencia humana propuestos por Valsiner, Werner y McNeill. Con este fin, se desarrollan los mecanismos de construcción de significados propuestos por Valsiner -pleromatización y esquematización-, la fisionomización en la percepción del mundo desarrollada por Werner, y el concepto de metaforicidad como representación gestual de una construcción mental desarrollada por McNeill. Como conclusión se establece una relación entre pleromatización, fisionomización y metaforicidad como fenómenos que se integran en la percepción y construcción de la experiencia humana dando cuenta de una experiencia holística, total y organísmica. Por otro lado, se establece una relación directa entre esquematismo, dimensión geométrica-técnica e iconicidad, como otra dimensión - objetivable, particularista y cognitiva- de la construcción de sentido en la experiencia humana.

  17. Expression of the endocannabinoid system in fibroblasts and myofascial tissues.

    Science.gov (United States)

    McPartland, John M

    2008-04-01

    The endocannabinoid (eCB) system, like the better-known endorphin system, consists of cell membrane receptors, endogenous ligands and ligand-metabolizing enzymes. Two cannabinoid receptors are known: CB(1) is principally located in the nervous system, whereas CB(2) is primarily associated with the immune system. Two eCB ligands, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are mimicked by cannabis plant compounds. The first purpose of this paper was to review the eCB system in detail, highlighting aspects of interest to bodyworkers, especially eCB modulation of pain and inflammation. Evidence suggests the eCB system may help resolve myofascial trigger points and relieve symptoms of fibromyalgia. However, expression of the eCB system in myofascial tissues has not been established. The second purpose of this paper was to investigate the eCB system in fibroblasts and other fascia-related cells. The investigation used a bioinformatics approach, obtaining microarray data via the GEO database (www.ncbi.nlm.nih.gov/geo/). GEO data mining revealed that fibroblasts, myofibroblasts, chondrocytes and synoviocytes expressed CB(1), CB(2) and eCB ligand-metabolizing enzymes. Fibroblast CB(1) levels nearly equalled levels expressed by adipocytes. CB(1) levels upregulated after exposure to inflammatory cytokines and equiaxial stretching of fibroblasts. The eCB system affects fibroblast remodeling through lipid rafts associated with focal adhesions and dampens cartilage destruction by decreasing fibroblast-secreted metalloproteinase enzymes. In conclusion, the eCB system helps shape biodynamic embryological development, diminishes nociception and pain, reduces inflammation in myofascial tissues and plays a role in fascial reorganization. Practitioners wield several tools that upregulate eCB activity, including myofascial manipulation, diet and lifestyle modifications, and pharmaceutical approaches.

  18. Chloride transport in human fibroblasts is activated by hypotonic shock

    Energy Technology Data Exchange (ETDEWEB)

    Rugolo, M.; Mastocola, T.; Flamigni, A.; Lenaz, G. (Universita' di Bologna (Italy))

    1989-05-15

    Incubation of human skin fibroblasts in hypotonic media induced the activation of {sup 36}Cl- efflux which was roughly proportional to the decrease in the osmolality of the media. The efflux of {sup 36}Cl- was insensitive to DIDS plus furosemide and inhibited by addition of a Cl- channel blocker such as 5-nitro-2-(3-phenyl propylamino) benzoic acid (NPPB). We propose that a conductive pathway for Cl- transport, almost silent in isotonic conditions, is activated by exposing human fibroblasts to hypotonic shock, this conclusion being supported by evidence that also {sup 36}Cl- influx was enhanced by hypotonic medium.

  19. Application of Allogeneic Fibroblast Cells in Cellular Therapy of Recessive Dystrophic Epidermolysis Bullosa

    Directory of Open Access Journals (Sweden)

    Zare

    2015-09-01

    Full Text Available Context Connective tissue cells include fibroblasts, chondrocytes, adipocyte, and osteocytes. These cells are specialized for the secretion of collagenous extracellular matrix and are responsible for the architectural framework of the human body. Evidence Acquisition Connective tissue cells play a central role in supporting as well as repairing tissues and organs. Fibroblast cell therapy could be used for the treatment of burn wounds, scars, diabetic foot ulcers, acne scars and skin aging. This review focused on biology of fibroblasts and their role in cell therapy of recessive dystrophic epidermolysis bullosa (RDEB. Results Fibroblasts are known to play a pivotal role in skin structure and integrity, and dermal fibroblasts are believed to promote skin regeneration and rejuvenation via collagen production. Conclusions Fibroblasts can be used in transplantations to ameliorate an immune system response, in order to reduce antigen production. Human fibroblasts suppress ongoing mixed lymphocyte reactions (MLRs between lymphocyte cells from two individuals, and supernatant materials from fibroblast cultures suppress MLRs.

  20. Gingival fibroblast responsiveness is differentially affected by Porphyromonas gingivalis: implications for the pathogenesis of periodontitis

    NARCIS (Netherlands)

    Scheres, N.; Crielaard, W.

    2013-01-01

    In periodontitis, tissue damage results mainly from aberrant host responses to oral microorganisms. Fibroblasts can play an important role in this. Gingival fibroblasts do not develop tolerance against the lipopolysaccharide of Porphyromonas gingivalis, a keystone pathogen in periodontitis, which

  1. Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy

    National Research Council Canada - National Science Library

    Bang, Claudia; Batkai, Sandor; Dangwal, Seema; Gupta, Shashi Kumar; Foinquinos, Ariana; Holzmann, Angelika; Just, Annette; Remke, Janet; Zimmer, Karina; Zeug, Andre; Ponimaskin, Evgeni; Schmiedl, Andreas; Yin, Xiaoke; Mayr, Manuel; Halder, Rashi; Fischer, Andre; Engelhardt, Stefan; Wei, Yuanyuan; Schober, Andreas; Fiedler, Jan; Thum, Thomas

    2014-01-01

    ...; however, miRNAs have emerged recently as paracrine signaling mediators. Thus, we investigated a potential paracrine miRNA crosstalk between cardiac fibroblasts and cardiomyocytes and found that cardiac fibroblasts secrete miRNA-enriched exosomes...

  2. Phytanic acid alpha-oxidation in peroxisomal disorders: studies in cultured human fibroblasts

    NARCIS (Netherlands)

    Verhoeven, N. M.; Schor, D. S.; Roe, C. R.; Wanders, R. J.; Jakobs, C.

    1997-01-01

    We studied the alpha-oxidation of phytanic acid in human fibroblasts of controls and patients affected with classical Refsum disease, rhizomelic chondrodysplasia punctata, generalized peroxisomal disorders and peroxisomal bifunctional protein deficiency. Cultured fibroblasts were incubated with

  3. Water-filtered near-infrared influences collagen synthesis of keloid-fibroblasts in contrast to normal foreskin fibroblasts.

    Science.gov (United States)

    Zöller, Nadja; König, Anke; Butting, Manuel; Kaufmann, Roland; Bernd, August; Valesky, Eva; Kippenberger, Stefan

    2016-10-01

    Hypertrophic scar development is associated to impaired wound healing, imbalanced fibroblast proliferation and extracellular matrix synthesis. Stigmatization, physical restrictions and high recurrence rates are only some aspects that illustrate the severe influence impaired wound healing can have on patients' life. The treatment of hypertrophic scars especially keloids is still a challenge. In recent years water-filtered near-infrared irradiation (wIRA) composed of near-infrared (NIR) and a thermal component is applied for an increasing penal of clinical purposes. It is described to beneficially influence e.g. wound healing. But discrimination between the thermal and the NIR dependent components of these effects has not been conclusively elucidated. Aim of our study was therefore to investigate the influence of the light fraction on the thermal impact of wIRA irradiation in dermal cells. We concentrated our analysis on morphological properties and collagen synthesis. Foreskin fibroblasts and the keloid fibroblast cell line KF111 were exposed to temperatures between 37°C and 46°C with or without additional irradiation with 360J/cm(2) NIR. Our results show that viability was not influenced by irradiation. Independent of the analysed fibroblast species temperature dependent occurrence of spheric cells could be observed. These morphological changes were clearly counteracted by additional light exposure. Convective heat reduced collagen type I synthesis in both cell species depending on the applied temperature. Co-treatment with NIR significantly reversed this effect in keloid fibroblast cultures treated at 46°C whereas no difference could be observed in the foreskin fibroblasts. The observed influence on collagen type I synthesis was associated to a temperature dependent TGF-β1 secretion reduction. Co-stimulation of keloid cultures with NIR at 46°C completely abolished the temperature dependent TGF-β1 secretion reduction. In foreskin fibroblast cultures co

  4. Switch in FGFR3 and -4 expression profile during human renal development may account for transient hypercalcemia in patients with Sotos syndrome due to 5q35 microdeletions

    NARCIS (Netherlands)

    Mutsaers, Henricus A M; Levtchenko, Elena N; Martinerie, Laetitia; Pertijs, Jeanne C L M; Allegaert, Karel; Devriendt, Koenraad; Masereeuw, Roos; Monnens, Leo A H; Lombès, Marc

    CONTEXT: Sotos syndrome is a rare genetic disorder with a distinct phenotypic spectrum including overgrowth and learning difficulties. Here we describe a new case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth factor receptor 4 (FGFR4) gene, presenting with infantile

  5. Switch in FGFR3 and -4 expression profile during human renal development may account for transient hypercalcemia in patients with Sotos syndrome due to 5q35 microdeletions

    NARCIS (Netherlands)

    Mutsaers, H.A.M.; Levtchenko, E.N.; Martinerie, L.; Pertijs, J.C.L.M.; Allegaert, K.; Devriendt, K.; Masereeuw, R.; Monnens, L.A.; Lombes, M.

    2014-01-01

    CONTEXT: Sotos syndrome is a rare genetic disorder with a distinct phenotypic spectrum including overgrowth and learning difficulties. Here we describe a new case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth factor receptor 4 (FGFR4) gene, presenting with infantile

  6. Protective Effect of Modified Human Acidic Fibroblast Growth Factor ...

    African Journals Online (AJOL)

    Purpose: To investigate whether modified acidic fibroblast growth factor (MaFGF) can protect NRK52E cell against apoptotic death induced by actinomycin D (Act D) and the effect of MaFGF on PI3K/Akt signaling pathway. Methods: NRK52E cell apoptotic death was measured by several methods including cell morphologic ...

  7. Transient expression of acidic fibroblast growth factor in pea ( Pisum ...

    African Journals Online (AJOL)

    Nowadays, there are many therapeutic proteins produced in different host plants in transient easy to perform, short production cycle, efficient and inexpensive. In this study, the modified pea early browning virus (PEBV) vector containing GFP and acidic fibroblast growth factor (aFGF) was introduced into pea plants by leave ...

  8. Fibroblast growth factor 23 and dietary factors in renal disease

    NARCIS (Netherlands)

    da Cunha Baia, Leandro

    2015-01-01

    Omega-3 poly-unsaturated fatty acids and mineral metabolism: novel therapy for cardiovascular disease in renal patients? Deregulations in mineral metabolism, particularly related to phosphate and its regulating hormone fibroblast growth factor 23 (FGF23), are common in patients with chronic kidney

  9. Airway smooth muscle and fibroblasts in the pathogenesis of asthma

    NARCIS (Netherlands)

    Johnson, Peter R A; Burgess, Janette K

    2004-01-01

    Asthma is a disease characterized by marked structural changes within the airway wall. These changes include deposition of extracellular matrix proteins and an increase in the numbers of airway smooth muscle cells and subepithelial fibroblasts. Both these cell types possess properties that would

  10. Cancer-Associated Fibroblasts: Perspectives in Cancer Therapy

    NARCIS (Netherlands)

    Prakash, Jai

    2016-01-01

    The interplay between cancer cells and stromal cells is increasingly recognized as a main driver of tumor progression and metastasis. This Forum article highlights the role of cancer-associated stromal fibroblasts (CAFs) in tumorigenesis and discusses the potential for developing specific stromal

  11. Optimum microcurrent stimulation intensity for galvanotaxis in human fibroblasts.

    Science.gov (United States)

    Sugimoto, M; Maeshige, N; Honda, H; Yoshikawa, Y; Uemura, M; Yamamoto, M; Terashi, H

    2012-01-01

    In this study, we develop methods to measure galvanotaxis of fibroblasts and determined the optimum conditions of electrical stimulation. An inverted 35mm dish containing cell suspensions (3×105 primary human skin fibroblasts, DMEM, and 10% FBS) was placed on the centre of a 100mm dish. The 35mm dish was removed 24 hours later, and culture medium was added to the 100mm dish. Fibroblasts were randomised (double-blind) into three groups, where electrical stimulation was given at varying intensities: 0UA (control), 50UA, and 100UA. Electrical stimulation (frequency=0.3Hz) was conducted, for a duration of 4 hours, with platinum electrodes in a CO2 incubator. We took pictures immediately before and 20 hours after stimulation. We calculated the migration ratio to the negative pole by dividing the area of attached fibroblasts after stimulation with that before stimulation. The migration ratio to the negative pole was significantly higher in the 100UA group than in the control group (pmicrocurrent efficacy for pressure ulcer healing. Electrical stimulation based on our in vitro experiment might be important for the development of physical therapy for pressure ulcers.

  12. Fibroblast growth factor 23: a potential cause of cardiovascular ...

    African Journals Online (AJOL)

    Fibroblast growth factor 23 (FGF-23) has been identified as one of the risk factors for the development of cardiovascular diseases (CVDs) in chronic kidney disease (CKD) patients. Although FGF-23 is necessary for the maintenance of phosphate balance, it has been implicated in the pathogenesis of left ventricular ...

  13. Pulsed short-wave diathermy effects on human fibroblast proliferation.

    Science.gov (United States)

    Hill, Jonathan; Lewis, Martyn; Mills, Pauline; Kielty, Cay

    2002-06-01

    To investigate the influence of pulsed short-wave diathermy (PSWD) on fibroblast and chondrocyte cell proliferation rates and to establish the influences of different dosages applied. Four single-blind trials. Laboratory, in vitro study. Human adult dermal fibroblast and chondrocyte cells were plated at known concentrations and incubated for 5 days. Exposure to PSWD, twice daily, on days 2, 3, and 4. After crystal violet staining (day 5), optical density (cell number) was determined spectrophotometrically. PSWD, given at mean power of 48W for 10 minutes, increased fibroblast proliferation compared with control groups (P<.001). There was a relationship between cell proliferation and the amount of energy given (P<0.001). The optimal mean power for proliferation was estimated to be 13.8W. While keeping mean power constant at 6W, altering pulse duration and pulse repetition rate dosage parameters did not have a significant effect on proliferation (P=.519). Chondrocyte proliferation also increased with PSWD exposure of 6W at 10 minutes duration (P=.015). In addition, treatment time was significantly associated with chondrocyte proliferation (P<.001). PSWD is associated with increased rates of fibroblast and chondrocyte proliferation in vitro, which is dose dependent. These results contribute to an understanding of the physiologic mechanisms underlying the therapeutic effects of PSWD. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

  14. The Living Scar – Cardiac Fibroblasts and the Injured Heart

    Science.gov (United States)

    Rog-Zielinska, Eva A; Norris, Russell A; Kohl, Peter; Markwald, Roger

    2015-01-01

    Cardiac scars, often perceived as “dead” tissue, are very much alive, with heterocellular activity ensuring the maintenance of structural and mechanical integrity following heart injury. To form a scar, non-myocytes such as fibroblasts, proliferate and are recruited from intra- and extra-cardiac sources. Fibroblasts perform important autocrine and paracrine signalling functions. They also establish mechanical and, as is increasingly evident, electrical junctions with other cells. While fibroblasts were previously thought to act simply as electrical insulators, they may be electrically connected among themselves and, under certain circumstances, to other cells, including cardiomyocytes. A better understanding of these interactions will help target scar structure and function and facilitate the development of novel therapies aimed at modifying scar properties for patient benefit. This review explores available insight and recent concepts on fibroblast integration in the heart, and highlights potential avenues for harnessing their roles to optimise scar function following heart injury such as infarction, and therapeutic interventions such as ablation. PMID:26776094

  15. Fibroblast Growth Factor-2 Alters the Nature of Extinction

    Science.gov (United States)

    Graham, Bronwyn M.; Richardson, Rick

    2011-01-01

    These experiments examined the effects of the NMDA-receptor (NMDAr) antagonist MK801 on reacquisition and re-extinction of a conditioned fear that had been previously extinguished before injection of fibroblast growth factor-2 (FGF2) or vehicle. Recent findings have shown that relearning and re-extinction, unlike initial learning and extinction,…

  16. Photodynamic inactivation of fibroblasts by a cationic porphyrin

    NARCIS (Netherlands)

    Lambrechts, Saskia A. G.; Schwartz, Kevin R.; Aalders, Maurice C. G.; Dankert, Jacob B.

    2005-01-01

    An important determinant of the clinical applicability and value of antimicrobial photodynamic inactivation (PDI) is the cytotoxicity of the treatment to human cells. We evaluated the in vitro cytotoxicity of PDI to human dermal fibroblasts using 5-phenyl-10,15,20-tris(N-methyl-4-pyridyl)porphyrin

  17. Constitutive Reprogramming of Fibroblast Mitochondrial Metabolism in Pulmonary Hypertension

    Czech Academy of Sciences Publication Activity Database

    Plecitá-Hlavatá, Lydie; Tauber, Jan; Li, M.; Zhang, H.; Flockton, A. R.; Pullamsetti, S. S.; Chelladurai, P.; D'Alessandro, A.; El Kasmi, K. C.; Ježek, Petr; Stenmark, K. R.

    2016-01-01

    Roč. 55, č. 1 (2016), s. 47-57 ISSN 1044-1549 R&D Projects: GA MŠk(CZ) LH11055; GA MŠk(CZ) LH15071 Institutional support: RVO:67985823 Keywords : mitochondria * complex I * oxidative metabolism * pulmonary hypertension * adventitial fibroblasts Subject RIV: ED - Physiology Impact factor: 4.100, year: 2016

  18. Spatial organization of fibroblast nuclear chromocenters: component tree analysis.

    Science.gov (United States)

    Snapp, Robert R; Goveia, Elyse; Peet, Lindsay; Bouffard, Nicole A; Badger, Gary J; Langevin, Helene M

    2013-09-01

    The nuclei of mouse connective tissue fibroblasts contain chromocenters which are well-defined zones of heterochromatin that can be used as positional landmarks to examine nuclear remodeling in response to a mechanical perturbation. This study used component tree analysis, an image segmentation algorithm that detects high intensity voxels that are topologically connected, to quantify the spatial organization of chromocenters in fibroblasts within whole mouse connective tissue fixed and stained with 4',6-diamidino-2-phenylindole (DAPI). The component tree analysis method was applied to confocal microscopy images of whole mouse areolar connective tissue incubated for 30 min ex vivo with or without static stretch. In stretched tissue, the mean distance between chromocenters within fibroblast nuclei was significantly greater (vs. non-stretched, P stretch and no stretch. Average chromocenter distance was positively correlated with nuclear cross-sectional area (r = 0.78, P Static stretching of mouse areolar connective tissue for 30 min resulted in substantially increased separation of nuclear chromocenters in connective tissue fibroblasts. This interior remodeling of the nucleus induced by tissue stretch may impact transcriptionally active euchromatin within the inter-chromocenter space. © 2013 Anatomical Society.

  19. fibroblast growth factor, MTDH/Astrocyte elevated gene-1

    African Journals Online (AJOL)

    2012-12-05

    Dec 5, 2012 ... Background: The etiopathogenesis of prostate cancer (PC) is still not clear, but hormonal, genetic, and environmental factors are thought to play a role in the tumor pathogenesis. ... many genetic and epigenetic alterations have been detected in human PC.[1]. Basic fibroblast growth factor (bFGF), also ...

  20. Involvement of the mitochondrial compartment in human NCL fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Pezzini, Francesco; Gismondi, Floriana [Department of Neurological, Psychological, Morphological and Motor Sciences, Divisions of Neurology (Child Neurology) and Neuropathology, University of Verona Medical School, Verona (Italy); Tessa, Alessandra [IRCCS Fondazione Stella Maris-Molecular Medicine Unit, Pisa (Italy); Tonin, Paola [Department of Neurological, Psychological, Morphological and Motor Sciences, Divisions of Neurology (Child Neurology) and Neuropathology, University of Verona Medical School, Verona (Italy); Carrozzo, Rosalba [IRCCS Bambino Gesu Hospital-Molecular Medicine Unit, Roma (Italy); Mole, Sara E. [MRC Laboratory for Molecular Cell Biology, Molecular Medicines Unit, UCL Institute of Child Health and Department of Genetics, Evolution and Environment, University College London (United Kingdom); Santorelli, Filippo M. [IRCCS Fondazione Stella Maris-Molecular Medicine Unit, Pisa (Italy); Simonati, Alessandro, E-mail: alessandro.simonati@univr.it [Department of Neurological, Psychological, Morphological and Motor Sciences, Divisions of Neurology (Child Neurology) and Neuropathology, University of Verona Medical School, Verona (Italy)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer Mitochondrial reticulum fragmentation occurs in human CLN1 and CLN6 fibroblasts. Black-Right-Pointing-Pointer Likewise mitochondrial shift-to periphery and decreased mitochondrial density are seen. Black-Right-Pointing-Pointer Enhanced caspase-mediated apoptosis occurs following STS treatment in CLN1 fibroblasts. -- Abstract: Neuronal ceroid lipofuscinosis (NCL) are a group of progressive neurodegenerative disorders of childhood, characterized by the endo-lysosomal storage of autofluorescent material. Impaired mitochondrial function is often associated with neurodegeneration, possibly related to the apoptotic cascade. In this study we investigated the possible effects of lysosomal accumulation on the mitochondrial compartment in the fibroblasts of two NCL forms, CLN1 and CLN6. Fragmented mitochondrial reticulum was observed in all cells by using the intravital fluorescent marker Mitotracker, mainly in the perinuclear region. This was also associated with intense signal from the lysosomal markers Lysotracker and LAMP2. Likewise, mitochondria appeared to be reduced in number and shifted to the cell periphery by electron microscopy; moreover the mitochondrial markers VDCA and COX IV were reduced following quantitative Western blot analysis. Whilst there was no evidence of increased cell death under basal condition, we observed a significant increase in apoptotic nuclei following Staurosporine treatment in CLN1 cells only. In conclusion, the mitochondrial compartment is affected in NCL fibroblasts invitro, and CLN1 cells seem to be more vulnerable to the negative effects of stressed mitochondrial membrane than CLN6 cells.

  1. Fibroblastic osteosarcoma in a lion ( Panthera leo ) | Leonardi ...

    African Journals Online (AJOL)

    This report describes a case of spontaneous fibroblastic osteosarcoma in the humerus of a lion from a private park in Perugia, Italy. The tumor had an irregular, smooth, brown surface and a generally firm, rubbery consistence with gritty to hard areas interspersed. The mass was poorly vascularized with areas of necrosis at ...

  2. Adhesion, growth, and matrix production by fibroblasts on laminin substrates

    DEFF Research Database (Denmark)

    Couchman, J R; Höök, M; Rees, D A

    1983-01-01

    Human embryonic skin fibroblasts have been shown to attach and spread on laminin substrates in the absence of protein synthesis and presence of fibronectin-depleted serum and anti-fibronectin antibodies. Rates of attachment and the type of spreading are virtually identical on fibronectin and lami...

  3. Cellular electrophysiological principles that modulate secretion from synovial fibroblasts.

    Science.gov (United States)

    Clark, R B; Schmidt, T A; Sachse, F B; Boyle, D; Firestein, G S; Giles, W R

    2017-02-01

    Rheumatoid arthritis (RA) is a progressive disease that affects both pediatric and adult populations. The cellular basis for RA has been investigated extensively using animal models, human tissues and isolated cells in culture. However, many aspects of its aetiology and molecular mechanisms remain unknown. Some of the electrophysiological principles that regulate secretion of essential lubricants (hyaluronan and lubricin) and cytokines from synovial fibroblasts have been identified. Data sets describing the main types of ion channels that are expressed in human synovial fibroblast preparations have begun to provide important new insights into the interplay among: (i) ion fluxes, (ii) Ca2+ release from the endoplasmic reticulum, (iii) intercellular coupling, and (iv) both transient and longer duration changes in synovial fibroblast membrane potential. A combination of this information, knowledge of similar patterns of responses in cells that regulate the immune system, and the availability of adult human synovial fibroblasts are likely to provide new pathophysiological insights. © 2016 University of Calgary. The Journal of Physiology © 2016 The Physiological Society.

  4. High level expression of human basic fibroblast growth factor in ...

    African Journals Online (AJOL)

    USER

    2010-04-19

    Apr 19, 2010 ... High-level expression of recombinant human basic fibroblast growth factor in Escherichia coli presents research opportunities such as analysis ... The general agreement from the published data on heterologous gene ..... for protein expression (Casimiro et al., 1997; Gold et al.,. 1981; Hamdan et al., 2002; ...

  5. Basic FGF and PDGF-BB synergistically stimulate hyaluronan and IL-6 production by orbital fibroblasts

    NARCIS (Netherlands)

    S. Virakul (Sita); J.W. Heutz (Judith W.); V.A.S.H. Dalm (Virgil); R.P. Peeters (Robin); A.D.A. Paridaens (Dion); W.A. van den Bosch (Willem); N. Hirankarn (Nattiya); P.M. van Hagen (Martin); W.A. Dik (Willem)

    2016-01-01

    textabstractOrbital fibroblast activation is a central pathologic feature of Graves' Ophthalmopathy (GO). Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have been proposed to contribute to GO, but their effects on orbital fibroblasts are largely unknown.We found

  6. File list: DNS.Oth.05.AllAg.Fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Oth.05.AllAg.Fibroblasts hg19 DNase-seq Others Fibroblasts SRX100966,SRX480646,...SRX480648,SRX135564,SRX089279,SRX480647,SRX089280,SRX480645,SRX100965 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Oth.05.AllAg.Fibroblasts.bed ...

  7. File list: ALL.Oth.05.AllAg.Fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Oth.05.AllAg.Fibroblasts hg19 All antigens Others Fibroblasts SRX396266,SRX4814...X651506,SRX480793,SRX480792,SRX396262 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Oth.05.AllAg.Fibroblasts.bed ...

  8. File list: Unc.Oth.50.AllAg.Tail_fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.50.AllAg.Tail_fibroblast mm9 Unclassified Others Tail fibroblast SRX306689,...SRX306688,SRX306687,SRX306686,SRX306691,SRX306690 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.50.AllAg.Tail_fibroblast.bed ...

  9. File list: His.Oth.20.AllAg.Fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.20.AllAg.Fibroblast mm9 Histone Others Fibroblast SRX024353,SRX024354,SRX02...4352 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.20.AllAg.Fibroblast.bed ...

  10. File list: ALL.Oth.20.AllAg.Fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Oth.20.AllAg.Fibroblast mm9 All antigens Others Fibroblast SRX191057,SRX024353,...SRX024354,SRX024355,SRX024352 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Oth.20.AllAg.Fibroblast.bed ...

  11. File list: ALL.Oth.50.AllAg.Fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Oth.50.AllAg.Fibroblasts hg19 All antigens Others Fibroblasts SRX338979,SRX4814...X396257,SRX396265,SRX396258,SRX396256 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Oth.50.AllAg.Fibroblasts.bed ...

  12. File list: Unc.Oth.10.AllAg.Tail_fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.10.AllAg.Tail_fibroblast mm9 Unclassified Others Tail fibroblast SRX306689,...SRX306688,SRX306691,SRX306690,SRX306687,SRX306686 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.10.AllAg.Tail_fibroblast.bed ...

  13. Effect of β3-adrenoceptor on cardiac fibrosis in rat cardiac fibroblast ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of β3-adrenoceptors (β3-AR) up-regulation on fibrosis in cardiac fibroblast cells in rats and its potential mechanism. Methods: Cardiac fibroblast cells (CFB) were isolated and identified from rats' hearts. The β3-ARupregulated cardiac fibroblast cells were constructed by lentiviral transfection ...

  14. Enhanced ROCK1 dependent contractility in fibroblast from chronic obstructive pulmonary disease patients.

    Science.gov (United States)

    Hallgren, Oskar; Rolandsson, Sara; Andersson-Sjöland, Annika; Nihlberg, Kristian; Wieslander, Elisabet; Kvist-Reimer, Martina; Dahlbäck, Magnus; Eriksson, Leif; Bjermer, Leif; Erjefält, Jonas S; Löfdahl, Claes-Göran; Westergren-Thorsson, Gunilla

    2012-08-22

    During wound healing processes fibroblasts account for wound closure by adopting a contractile phenotype. One disease manifestation of COPD is emphysema which is characterized by destruction of alveolar walls and our hypothesis is that fibroblasts in the COPD lungs differentiate into a more contractile phenotype as a response to the deteriorating environment. Bronchial (central) and parenchymal (distal) fibroblasts were isolated from lung explants from COPD patients (n = 9) (GOLD stage IV) and from biopsies from control subjects and from donor lungs (n = 12). Tissue-derived fibroblasts were assessed for expression of proteins involved in fibroblast contraction by western blotting whereas contraction capacity was measured in three-dimensional collagen gels. The basal expression of rho-associated coiled-coil protein kinase 1 (ROCK1) was increased in both centrally and distally derived fibroblasts from COPD patients compared to fibroblasts from control subjects (p < 0.001) and (p < 0.01), respectively. Distally derived fibroblasts from COPD patients had increased contractile capacity compared to control fibroblasts (p < 0.01). The contraction was dependent on ROCK1 activity as the ROCK inhibitor Y27632 dose-dependently blocked contraction in fibroblasts from COPD patients. ROCK1-positive fibroblasts were also identified by immunohistochemistry in the alveolar parenchyma in lung tissue sections from COPD patients. Distally derived fibroblasts from COPD patients have an enhanced contractile phenotype that is dependent on ROCK1 activity. This feature may be of importance for the elastic dynamics of small airways and the parenchyma in late stages of COPD.

  15. File list: His.Oth.05.AllAg.Tail_fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.05.AllAg.Tail_fibroblast mm9 Histone Others Tail fibroblast SRX335673,SRX33...5668,SRX335667,SRX335674,SRX335665 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.05.AllAg.Tail_fibroblast.bed ...

  16. File list: Pol.Oth.20.AllAg.Tail_fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.20.AllAg.Tail_fibroblast mm9 RNA polymerase Others Tail fibroblast SRX33566...6 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Oth.20.AllAg.Tail_fibroblast.bed ...

  17. File list: ALL.Oth.05.AllAg.Tail_fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Oth.05.AllAg.Tail_fibroblast mm9 All antigens Others Tail fibroblast SRX306690,...5 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Oth.05.AllAg.Tail_fibroblast.bed ...

  18. File list: His.Oth.05.AllAg.Fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.05.AllAg.Fibroblast mm9 Histone Others Fibroblast SRX024353,SRX024354,SRX02...4352 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.05.AllAg.Fibroblast.bed ...

  19. File list: Pol.Oth.50.AllAg.Tail_fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.50.AllAg.Tail_fibroblast mm9 RNA polymerase Others Tail fibroblast SRX33566...6 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Oth.50.AllAg.Tail_fibroblast.bed ...

  20. File list: Oth.Oth.10.AllAg.Fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Oth.10.AllAg.Fibroblasts hg19 TFs and others Others Fibroblasts SRX396266,SRX39...396255,SRX396268,SRX396252,SRX396257,SRX396260,SRX396256,SRX396253,SRX396265 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Oth.10.AllAg.Fibroblasts.bed ...

  1. File list: DNS.Oth.20.AllAg.Fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Oth.20.AllAg.Fibroblasts hg19 DNase-seq Others Fibroblasts SRX135564,SRX089279,...SRX480648,SRX100966,SRX480645,SRX480646,SRX089280,SRX100965,SRX480647 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Oth.20.AllAg.Fibroblasts.bed ...

  2. File list: ALL.Oth.10.AllAg.Fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Oth.10.AllAg.Fibroblast mm9 All antigens Others Fibroblast SRX024353,SRX191057,...SRX024355,SRX024354,SRX024352 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Oth.10.AllAg.Fibroblast.bed ...

  3. File list: His.Oth.05.AllAg.Fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.05.AllAg.Fibroblasts hg19 Histone Others Fibroblasts SRX651503,SRX651504,SR...X651505,SRX651506,SRX480793,SRX480792 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Oth.05.AllAg.Fibroblasts.bed ...

  4. File list: Oth.Oth.50.AllAg.Fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Oth.50.AllAg.Fibroblasts hg19 TFs and others Others Fibroblasts SRX338979,SRX48...396255,SRX481483,SRX396260,SRX396266,SRX396257,SRX396265,SRX396258,SRX396256 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Oth.50.AllAg.Fibroblasts.bed ...

  5. File list: His.Oth.10.AllAg.Fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.10.AllAg.Fibroblasts hg19 Histone Others Fibroblasts SRX651503,SRX651504,SR...X651505,SRX651506,SRX480793,SRX480792 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Oth.10.AllAg.Fibroblasts.bed ...

  6. File list: Unc.Oth.05.AllAg.Tail_fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.05.AllAg.Tail_fibroblast mm9 Unclassified Others Tail fibroblast SRX306690,...SRX306689,SRX306688,SRX306691,SRX306687,SRX306686 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.05.AllAg.Tail_fibroblast.bed ...

  7. File list: DNS.Oth.10.AllAg.Fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Oth.10.AllAg.Fibroblasts hg19 DNase-seq Others Fibroblasts SRX100966,SRX135564,...SRX480646,SRX480648,SRX089279,SRX480647,SRX480645,SRX089280,SRX100965 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Oth.10.AllAg.Fibroblasts.bed ...

  8. File list: His.Oth.10.AllAg.Fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.10.AllAg.Fibroblast mm9 Histone Others Fibroblast SRX024353,SRX024354,SRX02...4352 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.10.AllAg.Fibroblast.bed ...

  9. File list: Oth.Oth.05.AllAg.Fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Oth.05.AllAg.Fibroblasts hg19 TFs and others Others Fibroblasts SRX396266,SRX48...396251,SRX396255,SRX396257,SRX396268,SRX396260,SRX396253,SRX396256,SRX396265 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Oth.05.AllAg.Fibroblasts.bed ...

  10. File list: ALL.Oth.10.AllAg.Tail_fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Oth.10.AllAg.Tail_fibroblast mm9 All antigens Others Tail fibroblast SRX335673,...5 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Oth.10.AllAg.Tail_fibroblast.bed ...

  11. File list: His.Oth.10.AllAg.Tail_fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.10.AllAg.Tail_fibroblast mm9 Histone Others Tail fibroblast SRX335673,SRX33...5668,SRX335667,SRX335674,SRX335665 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.10.AllAg.Tail_fibroblast.bed ...

  12. Progeroid syndrome patients with ZMPSTE24 deficiency could benefit when treated with rapamycin and dimethylsulfoxide

    Science.gov (United States)

    Akinci, Baris; Sankella, Shireesha; Gilpin, Christopher; Ozono, Keiichi; Garg, Abhimanyu; Agarwal, Anil K.

    2017-01-01

    Patients with progeroid syndromes such as mandibuloacral dysplasia, type B (MADB) and restrictive dermopathy (RD) harbor mutations in zinc metalloproteinase (ZMPSTE24), an enzyme essential for posttranslational proteolysis of prelamin A to form mature lamin A. Dermal fibroblasts from these patients show increased nuclear dysmorphology and reduced proliferation; however, the efficacy of various pharmacological agents in reversing these cellular phenotypes remains unknown. In this study, fibroblasts from MADB patients exhibited marked nuclear abnormalities and reduced proliferation that improved upon treatment with rapamycin and dimethylsulfoxide but not with other agents, including farnesyl transferase inhibitors. Surprisingly, fibroblasts from an RD patient with a homozygous null mutation in ZMPSTE24, resulting in exclusive accumulation of prelamin A with no lamin A on immunoblotting of cellular lysate, exhibited few nuclear abnormalities and near-normal cellular proliferation. An unbiased proteomic analysis of the cellular lysate from RD fibroblasts revealed a lack of processing of vimentin, a cytoskeletal protein. Interestingly, the assembly of the vimentin microfibrils in MADB fibroblasts improved with rapamycin and dimethylsulfoxide. We conclude that rapamycin and dimethylsulfoxide are beneficial for improving nuclear morphology and cell proliferation of MADB fibroblasts. Data from a single RD patient's fibroblasts also suggest that prelamin A accumulation by itself might not be detrimental and requires additional alterations at the cellular level to manifest the phenotype. PMID:28050601

  13. Effects of microelectrical current on migration of nasal fibroblasts.

    Science.gov (United States)

    Choi, Hyuk; Cho, Jung-Sun; Park, Il Ho; Yoon, Hu Geun; Lee, Heung-Man

    2011-01-01

    Migration of fibroblasts is critical in wound healing. The question of how wounded electric fields guide migration of nasal fibroblasts remains to be elucidated. This study was designed to determine morphology, directedness, and migration rate of nasal fibroblasts during microcurrent application, which is simulated by an endogenous electric field at the vicinity of the wound. Nasal fibroblasts were exposed to a microelectric field at 50, 100, and 250 mV/mm for 3 hours at 37°C. In this experiment, the field polarity was reversed for an additional 3 hours. During in vitro testing, the cells were incubated in a newly developed miniature, microcurrent generating chamber system, with 5% CO(2), at 37°C; the media was circulated by a pump system. A wound was created by scratching a cell-free area (∼150 μm wide) into a confluent monolayer. The average migration speed was calculated as the distance traveled by the cell divided by time. A microelectric field of 100 mV/mm or more induced significant cell migration in the direction of the cathode. Trajectory speeds at 50, 100, and 250 mV/mm were 9.8 ± 0.3, 11.8 ± 0.3, and 13.5 ± 0.9 μm/mm, respectively. A significant difference was observed between migratory rate of controls and that of 50 mV/mm (p < 0.05). Microelectric fields appear to have a crucial role in control of nasal fibroblast activity in the process of wound healing.

  14. Reprogramming of fibroblast nuclei after transfer into bovine oocytes.

    Science.gov (United States)

    De Sousa, P A; Winger, Q; Hill, J R; Jones, K; Watson, A J; Westhusin, M E

    1999-01-01

    Recent landmark achievements in animal cloning have demonstrated that the events of cell differentiation can, in principle, be reversed. This reversal necessarily requires large-scale genetic reprogramming, of which little is known. In the present study we characterized the extent to which blastocyst stage-specific mRNA expression would be conserved in bovine embryos produced by nuclear transfer (NT) using fetal fibroblasts as nuclei donors (FF NT). The mRNA pool of FF NT embryos was compared with that of NT embryos reconstructed from embryonic blastomeres (Emb NT), with embryos produced under in vivo or in vitro conditions, and finally with fibroblast cells. Embryo/cell-specific mRNA pools were contrasted using differential display methodology. Random oligonucleotide primer pair combinations were used to subfractionate mRNA populations and represent individual mRNAs as copy DNA (cDNA) bands ranging in size from 100 to 800 base pairs. Regardless of whether bovine blastocysts developed in vivo or in vitro, or were derived after nuclear transplantation with embryonic blastomeres or fetal fibroblasts, their mRNA profile was highly conserved and distinct from that of fetal fibroblast cells. There was approximately 95% conservation in cDNA banding patterns between FF NT, Emb NT, and in vivo derived blastocysts, when compared with in vitro derived blastocysts. In contrast, the cDNA banding in fibroblasts was only 67% conserved with in vitro derived blastocysts (p types to serve as nuclear donors for embryo reconstruction and provide information that can be used to improve the efficiency of cloning animals by nuclear transplantation.

  15. Dumping Syndrome

    Science.gov (United States)

    ... Intestinal Pseudo-obstruction Irritable Bowel Syndrome (IBS) Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Irritable Bowel Syndrome (IBS) in Children Lactose Intolerance Ménétrier’s Disease Microscopic Colitis Ostomy Surgery of the ...

  16. Piriformis syndrome

    Science.gov (United States)

    Pseudosciatica; Wallet sciatica; Hip socket neuropathy; Pelvic outlet syndrome; Low back pain - piriformis ... Sciatica is the main symptom of piriformis syndrome. Other symptoms include: Tenderness or a dull ache in ...

  17. Alagille Syndrome

    Science.gov (United States)

    ... Liver Tumors Biliary Atresia Cirrhosis of the Liver Galactosemia Gilbert’s Syndrome Diseases of the Liver Glycogen Storage ... Liver Tumors Biliary Atresia Cirrhosis of the Liver Galactosemia Gilbert’s Syndrome Diseases of the Liver Glycogen Storage ...

  18. Reye Syndrome

    Science.gov (United States)

    ... Liver Tumors Biliary Atresia Cirrhosis of the Liver Galactosemia Gilbert’s Syndrome Diseases of the Liver Glycogen Storage ... Liver Tumors Biliary Atresia Cirrhosis of the Liver Galactosemia Gilbert’s Syndrome Diseases of the Liver Glycogen Storage ...

  19. Zellweger Syndrome

    Science.gov (United States)

    ... Zellweger syndrome (ZS, the most severe form), neonatal adrenoleukodystrophy (NALD), and Infantile Refsum disease (IRD, the least ... Zellweger syndrome (ZS, the most severe form), neonatal adrenoleukodystrophy (NALD), and Infantile Refsum disease (IRD, the least ...

  20. Proteus syndrome

    Directory of Open Access Journals (Sweden)

    Criton S

    1995-01-01

    Full Text Available Proteus syndrome is a hamartomatous disorder characterised by focal overgrowths that can involve any structure of the body. An eleven-year-old girl with Proteus syndrome has been described with clitoromegaly.

  1. Overlap syndromes

    NARCIS (Netherlands)

    Beuers, Ulrich; Rust, Christian

    2005-01-01

    In hepatology, the term overlap syndrome describes variant forms of the major hepatobiliary autoimmune diseases, autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). Patients with overlap syndromes present with both hepatitic and cholestatic

  2. Metabolic Syndrome

    Science.gov (United States)

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These ... doctors agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  3. Reye Syndrome

    Science.gov (United States)

    Reye syndrome is a rare illness that can affect the blood, liver, and brain of someone who has recently ... a viral illness, seek medical attention immediately. Reye syndrome can lead to a coma and brain death, ...

  4. Usher Syndrome

    Science.gov (United States)

    Usher syndrome is an inherited disease that causes serious hearing loss and retinitis pigmentosa, an eye disorder that causes ... and vision. There are three types of Usher syndrome: People with type I are deaf from birth ...

  5. Turner Syndrome

    Science.gov (United States)

    Turner syndrome is a genetic disorder that affects a girl's development. The cause is a missing or incomplete X ... work properly. Other physical features typical of Turner syndrome are Short, "webbed" neck with folds of skin ...

  6. Felty syndrome

    Science.gov (United States)

    Seropositive rheumatoid arthritis (RA); Felty's syndrome ... The cause of Felty syndrome is unknown. It is more common in people who have had rheumatoid arthritis (RA) for a long time. People with ...

  7. Rett Syndrome

    Science.gov (United States)

    Rett syndrome is a rare genetic disease that causes developmental and nervous system problems, mostly in girls. It's related to autism spectrum disorder. Babies with Rett syndrome seem to grow and develop normally at first. ...

  8. Alport Syndrome

    Science.gov (United States)

    ... body. Many people with Alport syndrome also have hearing problems and abnormalities with their eyes. Other signs and ... and inherited type of Alport syndrome. For example, hearing and vision problems tend to be more common in males than ...

  9. Moebius Syndrome

    Science.gov (United States)

    ... eye sensitivity; motor delays; high or cleft palate; hearing problems and speech difficulties. Children with Moebius syndrome are ... eye sensitivity; motor delays; high or cleft palate; hearing problems and speech difficulties. Children with Moebius syndrome are ...

  10. A novel role of EMMPRIN/CD147 in transformation of quiescent fibroblasts to cancer-associated fibroblasts by breast cancer cells

    Science.gov (United States)

    Xu, Jing; Lu, Yang; Qiu, Songbo; Chen, Zhi-Nan; Fan, Zhen

    2013-01-01

    We tested the novel hypothesis that EMMPRIN/CD147, a transmembrane glycoprotein overexpressed in breast cancer cells, has a previously unknown role in transforming fibroblasts to cancer-associated fibroblasts, and that cancer-associated fibroblasts in turn induce epithelial-to-mesenchymal transition of breast cancer cells. Co-culture of fibroblasts with breast cancer cells or treatment of fibroblasts with breast cancer cell conditioned culture medium or recombinant EMMPRIN/CD147 induced expression of α-SMA in the fibroblasts in an EMMPRIN/CD147-dependent manner and promoted epithelial-to-mesenchymal transition of breast cancer cells and enhanced cell migration potential. These findings support a novel role of EMMPRIN/CD147 in regulating the interaction between cancer and stroma. PMID:23474495

  11. Heart and Down Syndrome

    Science.gov (United States)

    ... 4602 [email protected] Down Syndrome What Is Down Syndrome? Down Syndrome Facts Myths & Truths Preferred Language Guide Q& ... Helpline » Follow us Down Syndrome What Is Down Syndrome? Down Syndrome Facts Myths & Truths Preferred Language Guide Q& ...

  12. Down Syndrome: Education

    Science.gov (United States)

    ... 4602 [email protected] Down Syndrome What Is Down Syndrome? Down Syndrome Facts Myths & Truths Preferred Language Guide Q& ... Helpline » Follow us Down Syndrome What Is Down Syndrome? Down Syndrome Facts Myths & Truths Preferred Language Guide Q& ...

  13. Dental Issues & Down Syndrome

    Science.gov (United States)

    ... 4602 [email protected] Down Syndrome What Is Down Syndrome? Down Syndrome Facts Myths & Truths Preferred Language Guide Q& ... Helpline » Follow us Down Syndrome What Is Down Syndrome? Down Syndrome Facts Myths & Truths Preferred Language Guide Q& ...

  14. Down Syndrome: Education

    Science.gov (United States)

    ... Our Team Financial Information NDSS History About Down Syndrome Down Syndrome Preferred Language Guide Down Syndrome Facts Down ... Our Team Financial Information NDSS History About Down Syndrome Down Syndrome Down Syndrome Facts Preferred Language Guide Publications ...

  15. Facts About Usher Syndrome

    Science.gov (United States)

    ... Usher Syndrome > Facts About Usher Syndrome Facts About Usher Syndrome This information was developed by the National Eye ... is the best person to answer specific questions. Usher Syndrome Defined What is Usher syndrome? Usher syndrome is ...

  16. International Rett Syndrome Foundation

    Science.gov (United States)

    ... Newsletters & Reports About Rett Syndrome What is Rett Syndrome? Rett Syndrome Diagnosis Boys with MECP2 Clinics FAQs Glossary ... Newsletters & Reports About Rett Syndrome What is Rett Syndrome? Rett Syndrome Diagnosis Boys with MECP2 Clinics FAQs Glossary ...

  17. [Capgras syndrome].

    Science.gov (United States)

    Alcoverro Fortuny, O; Sierra Acín, A C

    2001-01-01

    The authors report a case of Capgras' syndrome in a 16-years-old child, who had been hospitalized for psychotic disorder. A review of the literature is performed. Most authors state that Capgras' syndrome would represent a symptom of underlying medical o functional disorders, although the term syndrome is used. The main etiopathogenic hypothesis of this syndrome are put forward (psychodynamic, disconnection, neuropsychological and medical).

  18. Caspase 3 activity in isolated fetal rat lung fibroblasts and rat periodontal ligament fibroblasts: cigarette smoke-induced alterations

    Directory of Open Access Journals (Sweden)

    James Elliot Scott

    2016-03-01

    Full Text Available Background Cigarette smoking is the leading cause of preventable death in the world. It has been implicated in the pathogenesis of pulmonary, oral and systemic diseases. Smoking during pregnancy is clearly a risk factor for the developing fetus and may be a major cause of infant mortality. Moreover, the oral cavity is the first site of exposure to cigarette smoke and may be a possible source for the spread of toxins to other organs of the body. Fibroblasts in general are morphologically heterogeneous connective tissue cells with diverse functions. Apoptosis or programmed cell death is a crucial process during embryogenesis and for the maintenance of homeostasis throughout life. Deregulation of apoptosis has been implicated in abnormal lung development in the fetus and disease progression in adults. Caspases, are proteases which belong to the family of cysteine aspartic acid proteases and are the key components for the downstream amplification of intra-cellular apoptotic signals. Of the 14 caspases known, caspase-3 is the key executioner of apoptosis. Fetal rat lung fibroblasts but not PDL viability is reduced by exposure to CSE. In addition Caspase 3 activity is elevated after CSE exposure in fetal lung fibroblasts but not in PDLs. Expression of caspase 3 is induced in CSE exposed lung fibroblasts but not in PDLs. Caspase 3 was localized to the cytoplasm in both cell types.

  19. ERCC4 variants identified in a cohort of patients with segmental progeroid syndromes.

    Science.gov (United States)

    Mori, Takayasu; Yousefzadeh, Matthew J; Faridounnia, Maryam; Chong, Jessica X; Hisama, Fuki M; Hudgins, Louanne; Mercado, Gabriela; Wade, Erin A; Barghouthy, Amira S; Lee, Lin; Martin, George M; Nickerson, Deborah A; Bamshad, Michael J; Niedernhofer, Laura J; Oshima, Junko

    2018-02-01

    Pathogenic variants in genes, which encode DNA repair and damage response proteins, result in a number of genomic instability syndromes with features of accelerated aging. ERCC4 (XPF) encodes a protein that forms a complex with ERCC1 and is required for the 5' incision during nucleotide excision repair. ERCC4 is also FANCQ, illustrating a critical role in interstrand crosslink repair. Pathogenic variants in this gene cause xeroderma pigmentosum, XFE progeroid syndrome, Cockayne syndrome (CS), and Fanconi anemia. We performed massive parallel sequencing for 42 unsolved cases submitted to the International Registry of Werner Syndrome. Two cases, each carrying two novel heterozygous ERCC4 variants, were identified. The first case was a compound heterozygote for: c.2395C > T (p.Arg799Trp) and c.388+1164_792+795del (p.Gly130Aspfs*18). Further molecular and cellular studies indicated that the ERCC4 variants in this patient are responsible for a phenotype consistent with a variant of CS. The second case was heterozygous for two variants in cis: c.[1488A > T; c.2579C > A] (p.[Gln496His; Ala860Asp]). While the second case also had several phenotypic features of accelerated aging, we were unable to provide biological evidence supporting the pathogenic roles of the associated ERCC4 variants. Precise genetic causes and disease mechanism of the second case remains to be determined. © 2017 Wiley Periodicals, Inc.

  20. [Müllerian anomalies. Obstructed hemivagina and ipsilateral renal anomaly syndrome (OHVIRA)].

    Science.gov (United States)

    Afrashtehfar, Cyrus Dean Mario; Piña-García, Adrián; Afrashtehfar, Kelvin Ian

    2014-01-01

    Müllerian duct anomalies are a group of uncommon and underdiagnosed entities, which cause specific symptoms in adolescent females and may be associated with infertility as well as adverse pregnancy outcomes. These malformations occur as a result of an arrest or abnormal development of the Müllerian ducts in different stages of the female reproductive tract during gestation. Obstructed hemivagina and ipsilateral renal anomaly syndrome (OHVIRA), formerly known as the Herlyn-Werner-Wunderlich syndrome, is a rare entity characterized by the presence of a uterus didelphys with an obstructed hemivagina cause by a vaginal septum and the association of a renal anomaly (most commonly renal agenesis) ipsilateral to the obstruction. This syndrome may remain undiagnosed during childhood and usually becomes symptomatic after menarche, causing obstructive symptoms. Occasionally it may be identified after the evaluation of a patient with infertility or recurrent pregnancy loss. The clinical diagnosis is very challenging and requires imaging studies in which ultrasound and MRI play an essential role in the diagnosis, classification and treatment plan. Opportune diagnosis and treatment achieve complete improvement of symptoms, adequate reproductive prognosis and avoid major complications such as endometriosis, pelvic adhesions and infertility. The purpose of this review is to demonstrate the pathophysiology, clinical manifestations, diagnostic methods and treatment of the obstructed hemivagina and ipsilateral renal anomaly syndrome.