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Sample records for normal intrauterine differentiation

  1. [Intrauterine tachycardia--differential diagnosis from fetal death].

    PubMed

    Husby, H; Pedersen, K

    1989-01-23

    A case of intrauterine tachycardia is presented. The case was primarily diagnosed as one of foetal death. The correct diagnosis was established by ultrasonic scanning. During the neonatal period, the Wolff-Parkinson-White syndrome was diagnosed. This is a common cause of intrauterine tachycardia.

  2. Intrapartum intrauterine fetal demise with normal umbilical cord blood gas values at birth.

    PubMed

    Benson, Michael D

    2015-01-01

    A case is presented in which a fetus was delivered by cesarean section for failure to progress and a "nonreassuring heart rate tracing" in which the Apgar scores were unexpectedly 0 at 1, 5, and 10 minutes. Resuscitation was unsuccessful after 30 minutes. The venous cord gas was normal and the arterial blood gas was not consistent with intrapartum asphyxia. At the time of surgery, the placenta appeared grossly normal. The autopsy was entirely normal. This case raises questions about our understanding of intrauterine fetal demise and suggests an approach to future research.

  3. DIFFERENTIAL EFFECTS OF INTRAUTERINE GROWTH RESRICTION ON THE REGIONAL NEUROCHEMICAL PROFILE OF THE DEVELOPING RAT BRAIN

    PubMed Central

    Maliszewski-Hall, Anne M.; Alexander, Michelle; Tkáč, Ivan; Öz, Gülin; Rao, Raghavendra

    2016-01-01

    Background Intrauterine growth restricted (IUGR) infants are at increased risk for neurodevelopmental deficits that suggest the hippocampus and cerebral cortex may be particularly vulnerable. Objective Evaluate regional neurochemical profiles in IUGR and normally grown (NG) 7-day old rat pups using in vivo 1H magnetic resonance (MR) spectroscopy at 9.4T. Methods IUGR was induced via bilateral uterine artery ligation at gestational day 19 in pregnant Sprague Dawley dams. MR spectra were obtained from the cerebral cortex, hippocampus and striatum at P7 in IUGR (N=12) and NG (N=13) rats. Results In the cortex, IUGR resulted in lower concentrations of phosphocreatine, glutathione, taurine, total choline, total creatine (P<0.01) and [glutamate]/[glutamine] ratio (P <0.05). Lower taurine concentrations were observed in the hippocampus (P<0.01) and striatum (P <0.05). Conclusion IUGR differentially affects the neurochemical profile of the P7 rat brain regions. Persistent neurochemical changes may lead to cortex-based long-term neurodevelopmental deficits in human IUGR infants. PMID:25972040

  4. Differential Effects of Intrauterine Growth Restriction on the Regional Neurochemical Profile of the Developing Rat Brain.

    PubMed

    Maliszewski-Hall, Anne M; Alexander, Michelle; Tkáč, Ivan; Öz, Gülin; Rao, Raghavendra

    2017-01-01

    Intrauterine growth restricted (IUGR) infants are at increased risk for neurodevelopmental deficits that suggest the hippocampus and cerebral cortex may be particularly vulnerable. Evaluate regional neurochemical profiles in IUGR and normally grown (NG) 7-day old rat pups using in vivo (1)H magnetic resonance (MR) spectroscopy at 9.4 T. IUGR was induced via bilateral uterine artery ligation at gestational day 19 in pregnant Sprague-Dawley dams. MR spectra were obtained from the cerebral cortex, hippocampus and striatum at P7 in IUGR (N = 12) and NG (N = 13) rats. In the cortex, IUGR resulted in lower concentrations of phosphocreatine, glutathione, taurine, total choline, total creatine (P < 0.01) and [glutamate]/[glutamine] ratio (P < 0.05). Lower taurine concentrations were observed in the hippocampus (P < 0.01) and striatum (P < 0.05). IUGR differentially affects the neurochemical profile of the P7 rat brain regions. Persistent neurochemical changes may lead to cortex-based long-term neurodevelopmental deficits in human IUGR infants.

  5. Changes in intrauterine pressure after oxytocin administration in reproductively normal mares and in those with a delay in uterine clearance.

    PubMed

    Cadario, M E; Merritt, A M; Archbald, L F; Thatcher, W W; LeBlanc, M M

    1999-04-01

    Intrauterine pressure was measured in 4 reproductively normal mares and 4 mares with delay in uterine clearance after administration of oxytocin to determine if intrauterine pressure varied between dosage and group. Changes in intrauterine pressure were measured during estrus, when a follicle was > or =35 mm, using a Millar "Mikro-tip" catheter that had 3 discrete pressure sensors/channels. Mares received 4 different treatments of 10, 5, 2.5 or 0 IU (vehicle) of oxytocin. The protocol for each treatment consisted of a 10-min baseline recording, administration of treatment and measurement of changes in intrauterine pressure for 65 min. After administration of the first two treatments, mares were rested for 2 h and the protocol repeated for the remaining 2 treatments. Changes in intrauterine pressure were measured on a physiograph and stored in a computer. The results were analyzed by 4x4 Latin Square Design analysis of variance (ANOVA) using the GLM procedure of the Statistical Analysis System. The ANOVA detected a main effect of treatment (P<0.01) and mare (nested within group; P<0.01) but no effect of channels, group or treatment-by-group interaction. There was a dose-dependent increase in uterine activity in both normal mares and those with delayed uterine clearance. A dose of 10 IU of oxytocin induced a larger number of uterine contractions (5.67+/-0.06) for a longer time (24.09+/-1.18 min) than the 5 IU (4.16+/-0.06 contractions and 16.31+/-1.18; P<0.01 min) or 2.5 IU dose (4.08+/-0.06 contractions and 17.61+/-1.18 min). The first intrauterine wave occurred most often near the tip of the horn in 10 of 12 recordings in normal mares and in 8 of 12 recordings in mares with delayed uterine clearance. It was then propagated from the middle of the horn to the uterine body just cranial to the cervix. There was no pattern of propagation for subsequent intrauterine pressure waves. We conclude that the difference in spontaneous clearance of the uterus between the 2

  6. Fetal cardiac size in normal, intrauterine growth retarded, and diabetic pregnancies.

    PubMed

    Veille, J C; Hanson, R; Sivakoff, M; Hoen, H; Ben-Ami, M

    1993-07-01

    A total of 177 M-mode echocardiography studies were done on three groups of fetuses at different gestational ages: group I, normally grown fetuses; group II, intrauterine growth-retarded fetuses (IUGR); and group III, fetuses of diabetic mothers. Adjusted for gestational age and for fetal weight, the hearts of fetuses with IUGR were found to have an increased minor axis dimension due to free wall hypertrophy. No ventricular dilation was found in this group. Furthermore, IUGR fetuses have a larger heart proportionally to their body weight, raising the possibility of a "sparing effect" in this particular group. The hearts of fetuses of diabetic mothers were also found to have a significantly larger cardiac size than that of a group of normally grown fetuses. The increase was secondary to free wall hypertrophy, interventricular septal hypertrophy, and right ventricular dilation. This study confirms previous reports about fetal diabetic cardiomegaly and documents the contribution of the different cardiac components to this increase in size. The free wall hypertrophy found in these two groups may occur by different processes, which needs to be further investigated.

  7. Relationship of blood rheology to lipoprotein profile during normal pregnancies and those with intrauterine growth retardation.

    PubMed Central

    Muñoz, A; Uberos, J; Molina, A; Valenzuela, A; Cano, D; Ruiz, C; Molina Font, J A

    1995-01-01

    AIMS--The effects on fetal growth of hyperlipidaemia in pregnancy are not well understood at present. In this study the different lipid fractions in normal pregnancies and pregnancies complicated by intrauterine growth retardation (IUGR) were determined and related to changes in plasma and serum viscosity. METHODS--Two groups of pregnant women were studied. Group 1 consisted of 35 healthy pregnant women aged between 21 and 38 years with no previous pathology and a normal pregnancy to term. Group 1 patients were studied at four periods defined at the start of the study: (1) < or = 17 weeks; (2) 18-24 weeks; (3) 25-32 weeks, (4) > or = 33 weeks. Group 2 consisted of 24 pregnant women aged between 16 and 34 years with ultrasound diagnosed IUGR confirmed after birth. Plasma lipids and plasma and serum viscosity were measured. RESULTS--Plasma triglycerides, low density lipoprotein cholesterol, and total cholesterol increased progressively throughout pregnancy, with significantly higher values after week 25. Apolipoprotein A (ApoA) and triglyceride concentrations were significantly lower in the IUGR group than in the normal group. The HDL/ApoA ratio was greater in the IUGR group than in the control group, as was the ApoB/ApoA ratio. There were no differences in the other lipids. Plasma and serum viscosity was higher in the IUGR group than in the normal group. CONCLUSIONS--Haemorheological modifications in the IUGR group are partly secondary to changes in high density lipoprotein metabolism and the competitive inhibition of fibrinolysis by ApoB, which is increased in pregnancies with IUGR. Changes in ApoA, and more specifically in the ApoB/ApoA ratio, could be good markers for the early detection of IUGR. PMID:7665704

  8. The role of transvaginal power Doppler ultrasound in the differential diagnosis of benign intrauterine focal lesions.

    PubMed

    Cogendez, Ebru; Eken, Meryem Kurek; Bakal, Nuray; Gun, Ismet; Kaygusuz, Ecmel Isik; Karateke, Ates

    2015-10-01

    The purpose of this prospective study was to assess the role of power Doppler imaging in the differential diagnosis of benign intrauterine focal lesions such as endometrial polyps and submucous myomas using the characteristics of power Doppler flow mapping. A total of 480 premenopausal patients with abnormal uterine bleeding were evaluated by transvaginal ultrasonography (TVS) searching for intrauterine pathology. Sixty-four patients with a suspicious focal endometrial lesion received saline infusion sonography (SIS) after TVS. Fifty-eight patients with focal endometrial lesions underwent power Doppler ultrasound (PDUS). Three different vascular flow patterns were defined: Single vessel pattern, multiple vessel pattern, and circular flow pattern. Finally, hysteroscopic resection was performed in all cases, and Doppler flow characteristics were then compared with the final histopathological findings. Histopathological results were as follows: endometrial polyp: 40 (69 %), submucous myoma: 18 (31 %). Of the cases with endometrial polyps, 80 % demonstrated a single vessel pattern, 7.5 % a multiple vessel pattern, and 0 % a circular pattern. Vascularization was not observed in 12.5 % of patients with polyps. Of the cases with submucousal myomas, 72.2 % demonstrated a circular flow pattern, 27.8 % a multiple vessel pattern, and none of them showed a single vessel pattern. The sensitivity, specificity, and positive and negative predictive values of the single vessel pattern in diagnosing endometrial polyps were 80, 100, 100, and 69.2 %, respectively; and for the circular pattern in diagnosing submucous myoma, these were 72.2, 100, 100, and 88.9 %, respectively. Power Doppler blood flow mapping is a useful, practical, and noninvasive diagnostic method for the differential diagnosis of benign intrauterine focal lesions. Especially in cases of recurrent abnormal uterine bleeding, recurrent abortion, and infertility, PDUS can be preferred as a first-line diagnostic method.

  9. Normal Forms for Nonautonomous Differential Equations

    NASA Astrophysics Data System (ADS)

    Siegmund, Stefan

    2002-01-01

    We extend Henry Poincarés normal form theory for autonomous differential equations x=f(x) to nonautonomous differential equations x=f(t, x). Poincarés nonresonance condition λj-∑ni=1 ℓiλi≠0 for eigenvalues is generalized to the new nonresonance condition λj∩∑ni=1 ℓiλi=∅ for spectral intervals.

  10. Assessment of Fetal Autonomic Nervous System Activity by Fetal Magnetocardiography: Comparison of Normal Pregnancy and Intrauterine Growth Restriction

    PubMed Central

    Fukushima, Akimune; Nakai, Kenji; Kanasugi, Tomonobu; Terata, Miyuki; Sugiyama, Toru

    2011-01-01

    Objective. To clarify the developmental activity of the autonomic nervous system (ANS) of the normal fetus and intrauterine growth restriction (IUGR) cases using fetal magnetocardiography (FMCG). Subjects and Methods. Normal pregnancy (n = 35) and IUGR (n = 12) cases at 28–39 and 32–37 weeks of gestation, respectively, were included in this study. The R-R interval variability was used to calculate the coefficient of variance (CVRR) and low frequency/high frequency (LF/HF) ratio. Results. The value of CVRR in the normal pregnancy group displayed a slight increasing trend with gestational age. However, no such trend was observed in the IUGR group. In contrast, the LF/HF ratio in both the normal pregnancy group and the IUGR group clearly increased over the gestational period; the normal group showing statistical significance. Conclusion. The development of fetal ANS activity in IUGR cases might differ from that observed in the normal pregnancy group, and this may facilitate early detection of IUGR. PMID:21547087

  11. Ovarian dysgerminoma and synchronic contralateral tubal pregnancy followed by normal intra-uterine gestation: a case report

    PubMed Central

    2012-01-01

    Introduction We report that the coincidence of ovarian tumor and pregnancy poses significant challenges that are more pronounced if the pregnancy is ectopic. Case presentation Here, we report a rare and interesting case of a 24-year-old nulliparous Spanish woman who experienced the coincidental occurrence of left tubal pregnancy and dysgerminoma in the right ovary. The corpus luteum settled in the right ovary. A right adnexectomy and left linear salpingostomy were performed. Remarkably, our patient became pregnant spontaneously after surgery. The pregnancy occurred prior to starting chemotherapy, and the intra-uterine pregnancy was carried to term; later, she also had another normal pregnancy. Our patient has done well without chemotherapy. Conclusions Our report on the challenges of diagnosis and treatment faced in this case can help clinicians better understand and manage these pathologies. We have not found any similar cases in the literature. PMID:23176153

  12. Intrauterine programming

    PubMed Central

    Sedaghat, Katayoun; Zahediasl, Saleh; Ghasemi, Asghar

    2015-01-01

    In mammals, the intrauterine condition has an important role in the development of fetal physiological systems in later life. Suboptimal maternal environment can alter the regulatory pathways that determine the normal development of the fetus in utero, which in post-natal life may render the individual more susceptible to cardiovascular or metabolic adult-life diseases. Changes in the intrauterine availability of nutrients, oxygen and hormones can change the fetal tissue developmental regulatory planning, which occurs genomically and non-genomically and can cause permanent structural and functional changes in the systems, leading to diseases in early years of life and those that particularly become overt in adulthood. In this review we take a brief look at the main elements which program the fetal system development and consequently induce a crucial impact on the cardiovascular, nervous and hormonal systems in adulthood. PMID:25945232

  13. Three-dimensional sonography in the differential diagnosis of interstitial, angular, and intrauterine pregnancies in a septate uterus.

    PubMed

    Tanaka, Yusuke; Mimura, Kazuya; Kanagawa, Takeshi; Kajimoto, Etsuko; Takahashi, Kei; Kakigano, Aiko; Fujita, Satoko; Kinugasa-Taniguchi, Yukiko; Endo, Masayuki; Kimura, Tadashi

    2014-11-01

    Interstitial, angular, and cornual pregnancies and intrauterine pregnancies in an anomalous uterus are separate entities, and the impact of each condition on obstetric outcomes is completely different. However, there is considerable confusion in understanding and managing the natural course of each condition due to a lack of uniform terminology. The single most important factor for differentiating these types of pregnancies is to make an early diagnosis. The differences between interstitial, angular, and cornual pregnancies on 2-dimensional (2D) sonography are subtle. Although magnetic resonance imaging can be used to differentiate these conditions, it is not preferred as the initial assessment tool because of its limited availability and cost-effectiveness. Three-dimensional (3D) sonography has the advantage of providing views of the uterus that cannot be obtained with conventional 2D sonography. We describe 3 cases of interstitial, angular, and intrauterine pregnancies in a septate uterus that were clearly differentiated by 3D sonography. We demonstrate the differences in diagnostic imaging findings and emphasize the importance of 3D sonography in differentiating these entities. © 2014 by the American Institute of Ultrasound in Medicine.

  14. [Color Doppler monitoring the utero-placental-fetal circulation variety of normal pregnancy and intrauterine growth retardation].

    PubMed

    Xu, J; Wen, L; Ma, T

    1998-04-01

    To study the utero-placental-fetal circulation (UPFC) in normal pregnancy and intrauterine growth retardation (IUGR) cases. Color doppler ultrasound was used to detect UPFC in 150 second and third trimester pregnant women, of which 89 cases were normal pregnancy and 58 cases were IUGR. 3 cases were IUGR with chronic renal failure. Hemodynamical value of the umbilical artery (UmA), umbilical vein (UmV) and uterine artery (UtA) were examined directly. The indices included time average velocity (TAV), pulsatility index (PI), resistance index (RI), systolic/diastolic (S/D) ratio, blood flow volume (Q). The maternal serum estriol (E3), human placental lactogen (HPL) and plasma thromboxane B2 (TXB2)/6-keto-PGF1 alpha (6-KP) were measured simultaneously. The result shows that in normal pregnancy group UPFC is abundant gradually with increasing gestational age. In IUGR group 92.53% of cases showed that TAV and Q of UmA, UmV markedly decreased and PI, RI and S/D ratio of UmA elevated at 20 weeks of gestation. There were significant difference between the two groups, maternal serum E3, HPL level in IUGR group were significantly lower than that of the normal pregnancy group, 6-KP level reduced, and TXB2/6-KP ratio significantly increased. Using color doppler ultrasound examining hemodynamical changes of UmA, UmV and UtA could observe UPFC function directly. It is one of the best method to early diagnose and predict the prognosis of IUGR.

  15. Hormonal and nutritional drivers of intrauterine growth.

    PubMed

    Sferruzzi-Perri, Amanda N; Vaughan, Owen R; Forhead, Alison J; Fowden, Abigail L

    2013-05-01

    Size at birth is critical in determining life expectancy with both small and large neonates at risk of shortened life spans. This review examines the hormonal and nutritional drivers of intrauterine growth with emphasis on the role of foetal hormones as nutritional signals in utero. Nutrients drive intrauterine growth by providing substrate for tissue accretion, whereas hormones regulate nutrient distribution between foetal oxidative metabolism and mass accumulation. The main hormonal drivers of intrauterine growth are insulin, insulin-like growth factors and thyroid hormones. Together with leptin and cortisol, these hormones control cellular nutrient uptake and the balance between accretion and differentiation in regulating tissue growth. They also act indirectly via the placenta to alter the materno-foetal supply of nutrients and oxygen. By responding to nutrient and oxygen availability, foetal hormones optimize the survival and growth of the foetus with respect to its genetic potential, particularly during adverse conditions. However, changes in the intrauterine growth of individual tissues may alter their function permanently. In both normal and compromised pregnancies, intrauterine growth is determined by multiple hormonal and nutritional drivers which interact to produce a specific pattern of intrauterine development with potential lifelong consequences for health.

  16. Color Doppler monitoring of changes of utero-placental-fetal circulation in normal pregnancy and intrauterine growth retardation.

    PubMed

    Xu, J; Wen, L; Ma, T; Zhang, Y; Zhang, Q; Gao, S; Zhao, M; Wu, H; Hu, J

    1997-01-01

    The utero-placental-fetal circulation (UPFC) of 150 subjects during second and third trimester was examined by using color Doppler. Of them 89 were normal woman and 58 were patients with intrauterine growth retardation IUGR). Our results showed that UPFC was increased gradually during normal pregnant period. In IUGR patients it was revealed that TAV and Q of UmA, UmV and UtA decreased at 20th week of gestation, especially after 30th week. PI, RI and S/D ratio of UmA were increased, but TAV, Q of UmA and UmV were markly reduced, so was UtA. PI were increased, but the changes of RI, S/D ratio in UtA were not significant. Hemodynamical findings of UmA, UmV and UtA were abnormal in 92.53% of IUGR patients. Only 81.03% present abnormal S/D ratio of UmA (P < 0.01) and the difference was statistically significant. Maternal serum E3, HPL level in IUGR were significantly lower than that of the normal. 6KP level was reduced, TXB2/6KP ratio was significantly increased. TXB2/6KP ratio was markedly related with TAV, Q of UmA, UmV and UtA. Our results suggested that using color doppler ultrasound for examination of hemodynamical changes of UmA, UmV and UtA could revealed UPFC function directly. It is one of the best methods for monitoring IUGR and might be used for early diagnosis of IUGR. The main pathophysiological changes of IUGR were UPFC obstruction and placental disfunction.

  17. Gene expression during normal and malignant differentiation

    SciTech Connect

    Andersson, L.C.; Gahmberg, C.G.; Ekblom, P.

    1985-01-01

    This book contains 18 selections. Some of the titles are: Exploring Carcinogenesis with Retroviral and Cellular Oncogenes; Retroviruses, Oncogenes and Evolution; HTLV and Human Neoplasi; Modes of Activation of cMyc Oncogene in B and T Lymphoid Tumors; The Structure and Function of the Epidermal Growth Factor Receptor: Its Relationship to the Protein Product of the V-ERB-B Oncogene; and Expression of Human Retrovirus Genes in Normal and Neoplastic Epithelial Cells.

  18. [Differential diagnosis of juvenile normal pressure glaucoma].

    PubMed

    Geidel, K; Wiedemann, P; Unterlauft, J D

    2016-12-05

    The case of a 50-year-old female patient with autosomal dominant optic atrophy is described, which was initially misinterpreted and treated as normal pressure glaucoma. Bilateral partial optic atrophy can be diagnosed by chance with mild manifestation of symptoms and can initially be misinterpreted as glaucoma. Taking a detailed medical history and performing a thorough optic nerve head examination can raise the suspicion of hereditary optic atrophy. The reliable detection of autosomal dominant optic atrophy by genetic investigations should be strived for in such cases.

  19. Differential responses to salt supplementation in adult male and female rat adrenal glands following intrauterine growth restriction.

    PubMed

    Bibeau, Karine; Otis, Mélissa; St-Louis, Jean; Gallo-Payet, Nicole; Brochu, Michèle

    2011-04-01

    In low sodium-induced intrauterine growth restricted (IUGR) rat, foetal adrenal steroidogenesis as well as the adult renin-angiotensin-aldosterone system (RAAS) is altered. The aim of the present study was to determine the expression of cytochrome P450 aldosterone synthase (P450aldo) and of angiotensin II receptor subtypes 1 (AT(1)R) and 2 (AT(2)R) in adult adrenal glands and whether this expression could be influenced by IUGR and by high-salt intake in a sex-specific manner. After 6 weeks of 0.9% NaCl supplementation, plasma renin activity, P450aldo expression and serum aldosterone levels were decreased in all groups. In males, IUGR induced an increase in AT(1)R, AT(2)R, and P450aldo levels, without changes in morphological appearance of the zona glomerulosa (ZG). By contrast, in females, IUGR had no effect on the expression of AT(1)R, but increased AT(2)R mRNA while decreasing protein expression of AT(2)R and P450aldo. In males, salt intake in IUGR rats reduced both AT(1)R mRNA and protein, while for AT(2)R, mRNA levels decreased whereas protein expression increased. In females, salt intake reduced ZG size in IUGR but had no affect on AT(1)R or AT(2)R expression in either group. These results indicate that, in response to IUGR and subsequently to salt intake, P450aldo, AT(1)R, and AT(2)R levels are differentially expressed in males and females. However, despite these adrenal changes, adult IUGR rats display adequate physiological and adrenal responses to high-salt intake, via RAAS inhibition, thus suggesting that extra-adrenal factors likely compensate for ZG alterations induced by IUGR.

  20. Differential vulnerability of gray matter and white matter to intrauterine growth restriction in preterm infants at 12 months corrected age.

    PubMed

    Padilla, Nelly; Junqué, Carme; Figueras, Francesc; Sanz-Cortes, Magdalena; Bargalló, Núria; Arranz, Angela; Donaire, Antonio; Figueras, Josep; Gratacos, Eduard

    2014-01-30

    Intrauterine growth restriction (IUGR) is associated with a high risk of abnormal neurodevelopment. Underlying neuroanatomical substrates are partially documented. We hypothesized that at 12 months preterm infants would evidence specific white-matter microstructure alterations and gray-matter differences induced by severe IUGR. Twenty preterm infants with IUGR (26-34 weeks of gestation) were compared with 20 term-born infants and 20 appropriate for gestational age preterm infants of similar gestational age. Preterm groups showed no evidence of brain abnormalities. At 12 months, infants were scanned sleeping naturally. Gray-matter volumes were studied with voxel-based morphometry. White-matter microstructure was examined using tract-based spatial statistics. The relationship between diffusivity indices in white matter, gray matter volumes, and perinatal data was also investigated. Gray-matter decrements attributable to IUGR comprised amygdala, basal ganglia, thalamus and insula bilaterally, left occipital and parietal lobes, and right perirolandic area. Gray-matter volumes positively correlated with birth weight exclusively. Preterm infants had reduced FA in the corpus callosum, and increased FA in the anterior corona radiata. Additionally, IUGR infants had increased FA in the forceps minor, internal and external capsules, uncinate and fronto-occipital white matter tracts. Increased axial diffusivity was observed in several white matter tracts. Fractional anisotropy positively correlated with birth weight and gestational age at birth. These data suggest that IUGR differentially affects gray and white matter development preferentially affecting gray matter. At 12 months IUGR is associated with a specific set of structural gray-matter decrements. White matter follows an unusual developmental pattern, and is apparently affected by IUGR and prematurity combined. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Intrauterine exposure to oestradiol promotes sex-specific differential effects on the prostatic development of neonate gerbils.

    PubMed

    Sanches, Bruno D A; Maldarine, Juliana S; Biancardi, Manoel F; Santos, Fernanda C A; Pinto-Fochi, Maria E; Antoniassi, Julia Q; Góes, Rejane M; Vilamaior, Patrícia S L; Taboga, Sebastião R

    2017-07-25

    The effects of intrauterine exposure to 17β-oestradiol (E2) are well studied for the male prostate and there are accumulating evidences that the exposure to high dosages leads to a hypomorphic development. However, there is a lack of information about the effects of intrauterine exposure to E2 in the prostate of rodent females, and such research becomes relevant in view of the presence of functional prostate in a proportion of women, and the morphophysiological similarities between the prostate of female rodents and the prostate of women. This study uses histochemical, immunohistochemical, immunofluorescence and three-dimensional (3D) reconstruction techniques to evaluate the effects of intrauterine exposure to E2 (500 BW/d) on neonatal prostate development in both male and female gerbils. It was verified that intrauterine exposure to E2 promotes epithelial proliferation and growth of prostatic budding in females, whereas in males the prostatic budding shows hypomorphic growth in the VMP (Ventral Mesenchymal Pad) as well as reduced epithelial proliferation. Together, the data demonstrate that intrauterine exposure to E2 causes different effects on male and female prostates of the gerbil even at the early postnatal development of the gland. © 2017 International Federation for Cell Biology.

  2. [Intrauterine insemination].

    PubMed

    Merviel, Philippe; Cabry, Rosalie; Lourdel, Emmanuelle; Barbier, Frédéric; Scheffler, Florence; Mansouri, Naïma; Devaux, Aviva; Benkhalifa, Moncef; Copin, Henri

    2014-01-01

    The intrauterine insemination with husband's sperm is an assisted reproductive technologie, as proposed in the case of cervical infertility, moderate male infertility, dysovulation, mild or moderate endometriosis or unexplained infertility. In the last three indications the ovarian stimulation is necessary. The couple demographic criteria (age of both partners, lifestyle, duration of infertility) and the results of the infertility evaluation (ovarian reserve, uterus, spermogram-spermocytogram) increase the chances of pregnancy by intrauterine insemination with husband's sperm and reduce the risk of multiple pregnancies. Pregnancy rates observed ranged from 8 to 20% per cycle according to indications.

  3. Fatty acid profile of maternal and fetal erythrocytes and placental expression of fatty acid transport proteins in normal and intrauterine growth restriction pregnancies.

    PubMed

    Assumpção, Renata P; Mucci, Daniela B; Fonseca, Fernanda C P; Marcondes, Henrique; Sardinha, Fátima L C; Citelli, Marta; Tavares do Carmo, Maria G

    2017-10-01

    Long-chain polyunsaturated fatty acids (LC-PUFA), mainly docosahexaenoic (DHA) and arachidonic acids (AA), are critical for adequate fetal growth and development. We investigated mRNA expression of proteins involved in hydrolysis, uptake and/or transport of fatty acids in placenta of fifteen full term normal pregnancies and eleven pregnancies complicated by intrauterine growth restriction (IUGR) with normal umbilical blood flows. The mRNA expression of LPL, FATPs (-1, -2 and -4) and FABPs (-1 and -3) was increased in IUGR placentas, however, tissue profile of LC-PUFA was not different between groups. Erythrocytes from both mothers and fetuses of the IUGR group showed lower concentrations of AA and DHA and inferior DHA/ALA ratio compared to normal pregnancies (P < 0.05). We hypothesize that reduced circulating levels of AA and DHA could up-regulate mRNA expression of placental fatty acids transporters, as a compensatory mechanism, however this failed to sustain normal LC-PUFA supply to the fetus in IUGR. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Transcriptomic profiles differentiate normal rectal epithelium and adenocarcinoma.

    PubMed

    Hogan, J; Dejulius, K; Liu, X; Coffey, J C; Kalady, M F

    2015-05-01

    Adenocarcinoma is a histologic diagnosis based on subjective findings. Transcriptional profiles have been used to differentiate normal tissue from disease and could provide a means of identifying malignancy. The goal of this study was to generate and test transcriptomic profiles that differentiate normal from adenocarcinomatous rectum. Comparisons were made between cDNA microarrays derived from normal epithelium and rectal adenocarcinoma. Results were filtered according to standard deviation to retain only highly dysregulated genes. Genes differentially expressed between cancer and normal tissue on two-groups t test (P < 0.05, Bonferroni P value adjustment) were further analyzed. Genes were rank ordered in terms of descending fold change. For each comparison (tumor versus normal epithelium), those 5 genes with the greatest positive fold change were grouped in a classifier. Five separate tests were applied to evaluate the discriminatory capacity of each classifier. Genetic classifiers derived comparing normal epithelium with malignant rectal epithelium from pooled stages had a mean sensitivity and specificity of 99.6% and 98.2%, respectively. The classifiers derived from comparing normal and stage I cancer had comparable mean sensitivities and specificities (97% and 98%, respectively). Areas under the summary receiver-operator characteristic curves for each classifier were 0.981 and 0.972, respectively. One gene was common to both classifiers. Classifiers were tested in an independent Gene Expression Omnibus-derived dataset. Both classifiers retained their predictive properties. Transcriptomic profiles comprising as few as 5 genes are highly accurate in differentiating normal from adenocarcinomatous rectal epithelium, including early-stage disease.

  5. Laser-induced differential normalized fluorescence method for cancer diagnosis

    DOEpatents

    Vo-Dinh, T.; Panjehpour, M.; Overholt, B.F.

    1996-12-03

    An apparatus and method for cancer diagnosis are disclosed. The diagnostic method includes the steps of irradiating a tissue sample with monochromatic excitation light, producing a laser-induced fluorescence spectrum from emission radiation generated by interaction of the excitation light with the tissue sample, and dividing the intensity at each wavelength of the laser-induced fluorescence spectrum by the integrated area under the laser-induced fluorescence spectrum to produce a normalized spectrum. A mathematical difference between the normalized spectrum and an average value of a reference set of normalized spectra which correspond to normal tissues is calculated, which provides for amplifying small changes in weak signals from malignant tissues for improved analysis. The calculated differential normalized spectrum is correlated to a specific condition of a tissue sample. 5 figs.

  6. Laser-induced differential normalized fluorescence method for cancer diagnosis

    DOEpatents

    Vo-Dinh, Tuan; Panjehpour, Masoud; Overholt, Bergein F.

    1996-01-01

    An apparatus and method for cancer diagnosis are disclosed. The diagnostic method includes the steps of irradiating a tissue sample with monochromatic excitation light, producing a laser-induced fluorescence spectrum from emission radiation generated by interaction of the excitation light with the tissue sample, and dividing the intensity at each wavelength of the laser-induced fluorescence spectrum by the integrated area under the laser-induced fluorescence spectrum to produce a normalized spectrum. A mathematical difference between the normalized spectrum and an average value of a reference set of normalized spectra which correspond to normal tissues is calculated, which provides for amplifying small changes in weak signals from malignant tissues for improved analysis. The calculated differential normalized spectrum is correlated to a specific condition of a tissue sample.

  7. Cerebral ischemia or intrauterine inflammation promotes differentiation of oligodendroglial precursors in preterm ovine fetuses: possible cellular basis for white matter injury.

    PubMed

    Kitanishi, Ryuta; Matsuda, Tadashi; Watanabe, Shinpei; Saito, Masatoshi; Hanita, Takushi; Watanabe, Tatsuya; Kobayashi, Yoshiyasu

    2014-01-01

    White matter injury in premature infants is known to be major cause of long-term neurocognitive disability, but the pathogenic mechanism remains unclear, hampering our ability to develop preventions. Periventricular leukomalacia is a severe form of white matter injury. In the present study, we explored the effects of cerebral ischemia and/or intrauterine inflammation on the development of oligodendroglia in the cerebral white matter using chronically instrumented fetal sheep. Each fetus received one of three insults: hemorrhage, inflammation and their combination. In the hemorrhage group, 40% of the fetoplacental blood volume was acutely withdrawn, and 24 hours after removal, the blood was returned to the fetus. The inflammation group received intravenous granulocyte-colony stimulating factor and intra-amniotic endotoxin and thus suffered from necrotizing funisitis and chorioamnionitis. The inflammatory hemorrhage group underwent acute hemorrhage under the inflammatory state. The sham group received no insults. Importantly, periventricular leukomalacia was not detected in the sham and the inflammation groups. Differentiating oligodendroglia at various developmental stages were identified by immunohistochemical analysis with specific antibodies. No difference in the density of oligodendroglial progenitors was detected among the four groups, whereas oligodendroglial precursors were significantly reduced in the three insult groups, compared to sham control. Moreover, the density of immature oligodendroglia was higher in the inflammation group and the inflammatory hemorrhage group, while the density of mature oligodendroglia was highest in the hemorrhage group. We propose that cerebral ischemia or intrauterine inflammation induces the differentiation of oligodendroglial precursors in preterm fetuses, eventually resulting in their exhaustion.

  8. Differential expression of imprinted genes in normal and IUGR human placentas.

    PubMed

    Diplas, Andreas I; Lambertini, Luca; Lee, Men-Jean; Sperling, Rhoda; Lee, Yin Leng; Wetmur, James; Chen, Jia

    2009-05-16

    Genomic imprinting refers to silencing of one parental allele in the zygotes of gametes depending upon the parent of origin. Loss of imprinting (LOI) is the gain of function from the silent allele that can have a maximum effect of doubling the gene dosage. LOI may play a significant role in the etiology of intrauterine growth restriction (IUGR). Using placental tissue from ten normal and seven IUGR pregnancies, we conducted a systematic survey of the expression of a panel of 74 "putatively" imprinted genes using quantitative RT-PCR. We found that 52/74 ( approximately 70%) of the genes were expressed in human placentas. Nine of the 52 (17%) expressed genes were significantly differentially expressed between normal and IUGR placentas; five were upregulated (PHLDA2, ILK2, NNAT, CCDC86, PEG10) and four downregulated (PLAGL1, DHCR24, ZNF331, CDKAL1). We also assessed LOI profile of 14 imprinted genes in 14 normal and 24 IUGR placentas using a functional and sensitive assay developed in our laboratory. Little LOI was observed in any placentas for five of the genes (PEG10, PHLDA2, MEG3, EPS15, CD44). With the 149 heterozygosities examined, 40 (26.8%) exhibited LOI >3%. Some genes exhibited frequent LOI in placentas regardless of the disease status (IGF2, TP73, MEST, SLC22A18, PEG3), while others exhibited LOI only in IUGR placentas (PLAGL1, DLK1, H19, SNRPN). Importantly, there was no correlation between gene expression and LOI profile. Our study suggests that genomic imprinting may play a role in IUGR pathogenesis, but mechanisms other than LOI may contribute to dysregulation of imprinted genes.

  9. Differentiating Leber Hereditary Optic Neuropathy from Normal-Tension Glaucoma.

    PubMed

    Souto, Fernanda Maria Silveira; de Vasconcellos, José Paulo Cabral; de Melo, Mônica Barbosa; Sartorato, Edi Lúcia; Moura, Frederico Castelo

    2017-04-01

    Glaucoma is a neurodegenerative disorder characterized by thinning of neuroretinal rim, enlarged cup-to-disc ratio (CDR) and visual field damage. Although raised intraocular pressure is main risk factor for development of glaucoma, it can occur with consistently normal measurements in the intraocular pressure as normal tension glaucoma (NTG). Enlargement of CDR is a classical sign of glaucoma, but it can also result from non-glaucomatous optic neuropathies such as Leber hereditary optic neuropathy (LHON). We describe a case of LHON with increased CDR, discuss its differential diagnosis with NTG and highlight the reasons for misdiagnoses between these two entities.

  10. Differential Intracochlear Sound Pressure Measurements in Normal Human Temporal Bones

    NASA Astrophysics Data System (ADS)

    Nakajima, Hideko Heidi; Dong, Wei; Olson, Elizabeth S.; Merchant, Saumil N.; Ravicz, Michael E.; Rosowski, John J.

    2009-02-01

    We present the first simultaneous sound pressure measurements in scala vestibuli and scala tympani of the cochlea in human cadaveric temporal bones. Micro-scale fiberoptic pressure sensors enabled the study of differential sound pressure at the cochlear base. This differential pressure is the input to the cochlear partition, driving cochlear waves and auditory transduction. Results showed that: pressure of scala vestibuli was much greater than scala tympani except at low and high frequencies where scala tympani pressure affects the input to the cochlea; the differential pressure proved to be an excellent measure of normal ossicular transduction of sound (shown to decrease 30-50 dB with ossicular disarticulation, whereas the individual scala pressures were significantly affected by non-ossicular conduction of sound at high frequencies); the middle-ear gain and differential pressure were generally bandpass in frequency dependence; and the middle-ear delay in the human was over twice that of the gerbil. Concurrent stapes velocity measurements allowed determination of the differential impedance across the partition and round-window impedance. The differential impedance was generally resistive, while the round-window impedance was consistent with a compliance in conjunction with distributed inertia and damping. Our techniques can be used to study inner-ear conductive pathologies (e.g., semicircular dehiscence), as well as non-ossicular cochlear stimulation (e.g., round-window stimulation) - situations that cannot be completely quantified by measurements of stapes velocity or scala-vestibuli pressure by themselves.

  11. Foxo1 Is Required for Normal Somatotrope Differentiation.

    PubMed

    Kapali, Jyoti; Kabat, Brock E; Schmidt, Kelly L; Stallings, Caitlin E; Tippy, Mason; Jung, Deborah O; Edwards, Brian S; Nantie, Leah B; Raeztman, Lori T; Navratil, Amy M; Ellsworth, Buffy S

    2016-11-01

    The etiology for half of congenital hypopituitarism cases is unknown. Our long-term goal is to expand the molecular diagnoses for congenital hypopituitarism by identifying genes that contribute to this condition. We have previously shown that the forkhead box transcription factor, FOXO1, is present in approximately half of somatotropes at embryonic day (e) 18.5, suggesting it may have a role in somatotrope differentiation or function. To elucidate the role of FOXO1 in somatotrope differentiation and function, Foxo1 was conditionally deleted from the anterior pituitary (Foxo1(Δpit)). Uncommitted progenitor cells are maintained and able to commit to the somatotrope lineage normally based on the expression patterns of Sox2, a marker of uncommitted pituitary progenitors, and Pou1f1 (also known as Pit1), which marks committed progenitors. Interestingly, Foxo1(Δpit) embryonic mice exhibit delayed somatotrope differentiation as evidenced by an almost complete absence of GH immunoreactivity at e16.5 and reduced expression of Gh at e18.5 and postnatal day (P) 3. Consistent with this conclusion, expression of GHRH receptor, a marker of terminally differentiated somatotropes, is significantly reduced at e18.5 and P3 in the absence of FOXO1. The mechanism of FOXO1 regulation of somatotrope differentiation may involve the basic helix-loop-helix transcription factor, Neurod4, which has been implicated in somatotrope differentiation and is significantly reduced in Foxo1(Δpit) mice. Foxo1(Δpit) mice do not exhibit growth defects, and at P21 their pituitary glands exhibit a normal distribution of somatotropes. These studies demonstrate that FOXO1 is important for initial somatotrope specification embryonically but is dispensable for postnatal somatotrope expansion and growth.

  12. Foxo1 Is Required for Normal Somatotrope Differentiation

    PubMed Central

    Kapali, Jyoti; Kabat, Brock E.; Schmidt, Kelly L.; Stallings, Caitlin E.; Tippy, Mason; Jung, Deborah O.; Edwards, Brian S.; Nantie, Leah B.; Raeztman, Lori T.; Navratil, Amy M.

    2016-01-01

    The etiology for half of congenital hypopituitarism cases is unknown. Our long-term goal is to expand the molecular diagnoses for congenital hypopituitarism by identifying genes that contribute to this condition. We have previously shown that the forkhead box transcription factor, FOXO1, is present in approximately half of somatotropes at embryonic day (e) 18.5, suggesting it may have a role in somatotrope differentiation or function. To elucidate the role of FOXO1 in somatotrope differentiation and function, Foxo1 was conditionally deleted from the anterior pituitary (Foxo1Δpit). Uncommitted progenitor cells are maintained and able to commit to the somatotrope lineage normally based on the expression patterns of Sox2, a marker of uncommitted pituitary progenitors, and Pou1f1 (also known as Pit1), which marks committed progenitors. Interestingly, Foxo1Δpit embryonic mice exhibit delayed somatotrope differentiation as evidenced by an almost complete absence of GH immunoreactivity at e16.5 and reduced expression of Gh at e18.5 and postnatal day (P) 3. Consistent with this conclusion, expression of GHRH receptor, a marker of terminally differentiated somatotropes, is significantly reduced at e18.5 and P3 in the absence of FOXO1. The mechanism of FOXO1 regulation of somatotrope differentiation may involve the basic helix-loop-helix transcription factor, Neurod4, which has been implicated in somatotrope differentiation and is significantly reduced in Foxo1Δpit mice. Foxo1Δpit mice do not exhibit growth defects, and at P21 their pituitary glands exhibit a normal distribution of somatotropes. These studies demonstrate that FOXO1 is important for initial somatotrope specification embryonically but is dispensable for postnatal somatotrope expansion and growth. PMID:27631552

  13. Normalization and microbial differential abundance strategies depend upon data characteristics.

    PubMed

    Weiss, Sophie; Xu, Zhenjiang Zech; Peddada, Shyamal; Amir, Amnon; Bittinger, Kyle; Gonzalez, Antonio; Lozupone, Catherine; Zaneveld, Jesse R; Vázquez-Baeza, Yoshiki; Birmingham, Amanda; Hyde, Embriette R; Knight, Rob

    2017-03-03

    Data from 16S ribosomal RNA (rRNA) amplicon sequencing present challenges to ecological and statistical interpretation. In particular, library sizes often vary over several ranges of magnitude, and the data contains many zeros. Although we are typically interested in comparing relative abundance of taxa in the ecosystem of two or more groups, we can only measure the taxon relative abundance in specimens obtained from the ecosystems. Because the comparison of taxon relative abundance in the specimen is not equivalent to the comparison of taxon relative abundance in the ecosystems, this presents a special challenge. Second, because the relative abundance of taxa in the specimen (as well as in the ecosystem) sum to 1, these are compositional data. Because the compositional data are constrained by the simplex (sum to 1) and are not unconstrained in the Euclidean space, many standard methods of analysis are not applicable. Here, we evaluate how these challenges impact the performance of existing normalization methods and differential abundance analyses. Effects on normalization: Most normalization methods enable successful clustering of samples according to biological origin when the groups differ substantially in their overall microbial composition. Rarefying more clearly clusters samples according to biological origin than other normalization techniques do for ordination metrics based on presence or absence. Alternate normalization measures are potentially vulnerable to artifacts due to library size. Effects on differential abundance testing: We build on a previous work to evaluate seven proposed statistical methods using rarefied as well as raw data. Our simulation studies suggest that the false discovery rates of many differential abundance-testing methods are not increased by rarefying itself, although of course rarefying results in a loss of sensitivity due to elimination of a portion of available data. For groups with large (~10×) differences in the average

  14. Differentiation of normal and disturbed sleep by automatic analysis.

    PubMed

    Hasan, J

    1983-01-01

    The main purpose of the present study was to develop an automatic hybrid system and evaluate its performance in the differentiation of normal and disturbed sleep. The study was carried out in roughly the following steps: At the beginning the quantity of five EEG waveforms, delta, theta, alpha, sigma and beta were examined with respect to sleep stages and their temporal distributions and inter-relationships throughout the nights in young 20-22 year-old, healthy individuals. These data were used as a basis for the choice of parameters for a sleep stage scoring program. Secondly, the sleep stage scoring software was developed using as test material three subject groups: about 10 years older controls, anonymous alcoholics and chronic alcoholics in the withdrawal phase. The last group was examined on two occasions, first in the initial withdrawal and then after two weeks' abstinence between the recordings. The sleep stage scoring program was evaluated in comparison with a visual sleep stage determination and its performance was also tested on the young normals. Attention was paid to three main points: First, how well does an automatic system imitate the visual classification of a human subject, when both the human and the computer classifications are compared side by side at a 20 s epoch level? Second, even if this comparison did not show a satisfactory agreement, could the computer classification still replace the visual sleep stage scoring when the objective is to describe the neurophysiological characteristics of the human whole-night sleep process or differentiate between normal and disturbed sleep. For this purpose it was examined, whether the values for the sleep stage parameters obtained by visual classification corresponded to those obtained by computer scoring and whether the differences found between the groups by manual methods could also be obtained by computer classification. The third goal was to see whether other measures than parameters received by sleep

  15. Ire1 supports normal ER differentiation in developing Drosophila photoreceptors

    PubMed Central

    Xu, Zuyuan; Chikka, Madhusudana Rao; Xia, Hongai; Ready, Donald F.

    2016-01-01

    ABSTRACT The endoplasmic reticulum (ER) serves virtually all aspects of cell physiology and, by pathways that are incompletely understood, is dynamically remodeled to meet changing cell needs. Inositol-requiring enzyme 1 (Ire1), a conserved core protein of the unfolded protein response (UPR), participates in ER remodeling and is particularly required during the differentiation of cells devoted to intense secretory activity, so-called ‘professional’ secretory cells. Here, we characterize the role of Ire1 in ER differentiation in the developing Drosophila compound eye photoreceptors (R cells). As part of normal development, R cells take a turn as professional secretory cells with a massive secretory effort that builds the photosensitive membrane organelle, the rhabdomere. We find rough ER sheets proliferate as rhabdomere biogenesis culminates, and Ire1 is required for normal ER differentiation. Ire1 is active early in R cell development and is required in anticipation of peak biosynthesis. Without Ire1, the amount of rough ER sheets is strongly reduced and the extensive cortical ER network at the rhabdomere base, the subrhabdomere cisterna (SRC), fails. Instead, ER proliferates in persistent and ribosome-poor tubular tangles. A phase of Ire1 activity early in R cell development thus shapes dynamic ER. PMID:26787744

  16. Differential Effect of Intrauterine Hypoxia on Caspase 3 and DNA Fragmentation in Fetal Guinea Pig Hearts and Brains

    PubMed Central

    Evans, LaShauna C.; Liu, Hongshan; Thompson, Loren P.

    2012-01-01

    The aim of this study is to quantify the effect of intrauterine hypoxia (HPX) and the role of nitric oxide (NO) on the apoptotic enzyme, caspase 3, and DNA fragmentation in fetal heart and brain. Hypoxia and NO are important regulators of apoptosis, although this has been little studied in the fetal organs. We investigated the effect of intrauterine HPX on apoptosis and the role of NO in both fetal hearts and brains. Pregnant guinea pigs were exposed to room temperature (N = 14) or 10.5% O2 (N = 12) for 14 days prior to term (term = 65 days) and administered water or l-N6-(1-iminoethyl)-lysine (LNIL), an inducible nitric oxide synthase (iNOS) inhibitor, for 10 days. Fetal hearts and brains were excised from anesthetized near-term fetuses for study. Chronic HPX decreased pro- and active caspase 3, caspase 3 activity, and DNA fragmentation levels in fetal hearts compared with normoxic controls. l-N6-(1-iminoethyl)-lysine prevented the HPX-induced decrease in caspase 3 activity but did not alter DNA fragmentation levels. In contrast, chronic HPX increased both apoptotic indices in fetal brains, which were inhibited by LNIL. Thus, the effect of HPX on apoptosis differs between fetal organs, and NO may play an important role in modulating these effects. PMID:22383778

  17. Intrauterine devices and intrauterine systems.

    PubMed

    2008-01-01

    From a public health viewpoint, the intrauterine device (IUD) is the most widely used contraceptive method in the world. Prevalence rates range among countries from 2 to 80% of contraceptive users. During 5 years of IUD use, pregnancy occurs in less than 2 per 100 insertions. Bleeding and pain are the most common reasons for removal rates of 10% in the first year and up to 50% within 5 years. The contraceptive effects of IUDs may be due to a sterile inflammatory reaction in the endometrial cavity which interferes with sperm function, so that fertilization is less likely to occur. IUDs also interfere with implantation but the extent to which this contributes to their contraceptive action is unknown. In nulliparous women rates of expulsion and removal for bleeding and/or pain are higher than in parous women. Effective use of IUDs for up to 10 years has the same pregnancy rate as tubal interruption. Thus, the IUD may be an alternative to female sterilization, especially in younger women who are more likely to experience regret after sterilization. The levonorgestrel intrauterine system (LNG-IUS) reduces bleeding and dysmenorrhoea, provides superior effectiveness to copper IUDs, and may be a useful treatment for endometriosis or an alternative to hysterectomy for menorrhagia.

  18. Effects of dietary leucine supplementation on the hepatic mitochondrial biogenesis and energy metabolism in normal birth weight and intrauterine growth-retarded weanling piglets

    PubMed Central

    Su, Weipeng; Xu, Wen; Zhang, Hao; Ying, Zhixiong; Zhou, Le; Zhang, Lili

    2017-01-01

    BACKGROUND/OBJECTIVES The study was conducted to evaluate the effects of dietary leucine supplementation on mitochondrial biogenesis and energy metabolism in the liver of normal birth weight (NBW) and intrauterine growth-retarded (IUGR) weanling piglets. MATERIALS/METHODS A total of sixteen pairs of NBW and IUGR piglets from sixteen sows were selected according to their birth weight. At postnatal day 14, all piglets were weaned and fed either a control diet or a leucine-supplemented diet for 21 d. Thereafter, a 2 × 2 factorial experimental design was used. Each treatment consisted of eight replications with one piglet per replication. RESULTS Compared with NBW piglets, IUGR piglets had a decreased (P < 0.05) hepatic adenosine triphosphate (ATP) content. Also, IUGR piglets exhibited reductions (P < 0.05) in the activities of hepatic mitochondrial pyruvate dehydrogenase (PDH), citrate synthase (CS), α-ketoglutarate dehydrogenase (α-KGDH), malate dehydrogenase (MDH), and complexes I and V, along with decreases (P < 0.05) in the concentration of mitochondrial DNA (mtDNA) and the protein expression of hepatic peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). Dietary leucine supplementation increased (P < 0.05) the content of ATP, and the activities of CS, α-KGDH, MDH, and complex V in the liver of piglets. Furthermore, compared to those fed a control diet, piglets given a leucine-supplemented diet exhibited increases (P < 0.05) in the mtDNA content and in the mRNA expressions of sirtuin 1, PGC-1α, nuclear respiratory factor 1, mitochondrial transcription factor A, and ATP synthase, H+ transporting, mitochondrial F1 complex, β polypeptide in liver. CONCLUSIONS Dietary leucine supplementation may exert beneficial effects on mitochondrial biogenesis and energy metabolism in NBW and IUGR weanling piglets. PMID:28386385

  19. Medium-chain TAG improve energy metabolism and mitochondrial biogenesis in the liver of intra-uterine growth-retarded and normal-birth-weight weanling piglets.

    PubMed

    Zhang, Hao; Li, Yue; Hou, Xiang; Zhang, Lili; Wang, Tian

    2016-05-01

    We previously reported that medium-chain TAG (MCT) could alleviate hepatic oxidative damage in weanling piglets with intra-uterine growth retardation (IUGR). There is a relationship between oxidative status and energy metabolism, a process involved in substrate availability and glucose flux. Therefore, the aim of this study was to investigate the effects of IUGR and MCT on hepatic energy metabolism and mitochondrial function in weanling piglets. Twenty-four IUGR piglets and twenty-four normal-birth-weight (NBW) piglets were fed a diet of either soyabean oil (SO) or MCT from 21 d of postnatal age to 49 d of postnatal age. Then, the piglets' biochemical parameters and gene expressions related to energy metabolism and mitochondrial function were determined (n 4). Compared with NBW, IUGR decreased the ATP contents and succinate oxidation rates in the liver of piglets, and reduced hepatic mitochondrial citrate synthase (CS) activity (P<0·05). IUGR piglets exhibited reductions in hepatic mitochondrial DNA (mtDNA) contents and gene expressions related to mitochondrial biogenesis compared with NBW piglets (P<0·05). The MCT diet increased plasma ghrelin concentration and hepatic CS and succinate dehydrogenase activities, but decreased hepatic pyruvate kinase activity compared with the SO diet (P<0·05). The MCT-fed piglets showed improved mtDNA contents and PPARγ coactivator-1α expression in the liver (P<0·05). The MCT diet alleviated decreased mRNA abundance of the hepatic PPARα induced by IUGR (P<0·05). It can therefore be postulated that MCT may have beneficial effects in improving energy metabolism and mitochondrial function in weanling piglets.

  20. Intrauterine contraception.

    PubMed

    Whaley, Natalie S; Burke, Anne E

    2015-11-01

    Intrauterine devices (IUDs) are effective, reversible forms of contraception with high patient satisfaction and continuation. IUDs can be safely used by most women and should be considered the first-line method of contraception for all women. This descriptive review will discuss the clinical issues associated with IUDs - including management of side effects, noncontraceptive uses and insertion and removal. When the burdens of cost are removed, women are more likely to select and IUDs. Health policy changes that increase insurance coverage for contraception will improve access to IUDs. IUDs remain an underutilized form of contraception in USA and efforts to improve availability and access to long-acting reversible contraception methods is needed to optimize their use.

  1. Epithelial cell differentiation in normal and transgenic mouse intestinal isografts

    PubMed Central

    1991-01-01

    Transgenes consisting of segments of the rat liver fatty acid-binding protein (L-FABP) gene's 5' non-transcribed domain linked to the human growth hormone (hGH) gene (minus its regulatory elements) have provided useful tools for analyzing the mechanisms that regulate cellular and spatial differentiation of the continuously renewing gut epithelium. We have removed the jejunum from normal and transgenic fetal mice before or coincident with, cytodifferentiation of its epithelium. These segments were implanted into the subcutaneous tissues of young adult CBY/B6 nude mouse hosts to determine whether the bipolar, migration- dependent differentiation pathways of gut epithelial cells can be established and maintained in the absence of its normal luminal environment. Immunocytochemical analysis of isografts harvested 4-6 wk after implantation revealed that activation of the intact endogenous mouse L-FABP gene (fabpl) in differentiating enterocytes is perfectly recapitulated as these cells are translocated along the crypt-to-villus axis. Similarly, Paneth and goblet cells appear to appropriately differentiate as they migrate to the crypt base and villus tip, respectively. The enteroendocrine cell subpopulations present in intact 4-6-wk-old jejunum are represented in these isografts. Their precise spatial distribution along the crypt-to-villus axis mimics that seen in the intact gut. A number of complex interrelationships between enteroendocrine subpopulations are also recapitulated. In both "intact" and isografted jejunum, nucleotides -596 to +21 of the rat L-FABP gene were sufficient to direct efficient expression of the hGH reporter to enterocytes although precocious expression of the transgene occurred in cells located in the upper crypt, before their translocation to the villus base. Inappropriate expression of hGH occurred in a high percentage (greater than 80%) of secretin, gastrin, cholecystokinin, and gastric inhibitory peptide producing enteroendocrine cells present

  2. Navicular index for differentiation of flatfoot from normal foot.

    PubMed

    Roth, Sandor; Roth, Aron; Jotanovic, Zdravko; Madarevic, Tomislav

    2013-06-01

    The height of navicular bone from the floor is in proportion with the height of longitudinal arch of the foot. The study was conducted to evaluate correlation of navicular bone height with most often used angles, heel valgus and a foot print in order to simplify the procedure for the diagnosis of flatfoot. A total of 218 operated children (436 feet) because of flexible flatfoot were evaluated clinically and radiologically. Meary angle, lateral talonavicular angle, talocalcaneal angle, calcaneal pitch, heel valgus and arch index (Staheli) were evaluated pre-operatively and postoperatively. In 121 (242 feet) chosen children (age eight to 15) with all clinical values and pre-operative angles corresponding flatfoot, all postoperatively measured values were within the normal range. We got the navicular index by dividing length of longitudinal arch with navicular height. Values of navicular index were then compared with pre-operatively and postoperatively measured values. Pearson correlation and ROC test were used for statistical analysis. Values of the navicular index for flatfeet were in the interval from 4.75 to 31.2 (median 8.98), and for normal-arched feet 3.58-22.6 (median 5.48). Pearson correlation of arch index and measured parameters were significant in majority, and degree according to Colton was good. Area under the ROC curve was 0.861 (p = 0.0001). The cut-off value with 86 % sensitivity and 75 % specificity was 6.7407. Navicular index can be used reliably, without measures of the other parameters, to differentiate flatfoot from normal-arched foot. Therefore, the navicular index has an ability to distinguish between the flatfoot and normal-arched foot.

  3. SRY alone can induce normal male sexual differentiation

    SciTech Connect

    Lopez, M.; Torres, L.; Cervantes, A.

    1995-01-30

    Most individuals with the rare 46,XX male {open_quotes}syndrome{close_quotes} arise due to an unequal interchange between Xp and Yp termini during paternal meiosis. The pattern of Y-sequences in these patients varies considerably, but very few cases have been reported showing only SRY. The phenotype in these patients is also variable ranging from severe impairment of the external genitalia through hypospadias and/or cryptorchidism to occasional normal male phenotype. We report a Mexican 46,XX male patient without genital ambiguities in whom DNA analysis showed the presence of SRY and the absence of ZFY. We conclude that in this case SRY alone was enough for complete male sexual differentiation. 25 refs., 1 fig.

  4. FOXO1 differentially regulates both normal and diabetic wound healing

    PubMed Central

    Zhang, Chenying; Ponugoti, Bhaskar; Tian, Chen; Xu, Fanxing; Tarapore, Rohinton; Batres, Angelika; Alsadun, Sarah; Lim, Jason; Dong, Guangyu

    2015-01-01

    Healing is delayed in diabetic wounds. We previously demonstrated that lineage-specific Foxo1 deletion in keratinocytes interfered with normal wound healing and keratinocyte migration. Surprisingly, the same deletion of Foxo1 in diabetic wounds had the opposite effect, significantly improving the healing response. In normal glucose media, forkhead box O1 (FOXO1) enhanced keratinocyte migration through up-regulating TGFβ1. In high glucose, FOXO1 nuclear localization was induced but FOXO1 did not bind to the TGFβ1 promoter or stimulate TGFβ1 transcription. Instead, in high glucose, FOXO1 enhanced expression of serpin peptidase inhibitor, clade B (ovalbumin), member 2 (SERPINB2), and chemokine (C-C motif) ligand 20 (CCL20). The impact of high glucose on keratinocyte migration was rescued by silencing FOXO1, by reducing SERPINB2 or CCL20, or by insulin treatment. In addition, an advanced glycation end product and tumor necrosis factor had a similar regulatory effect on FOXO1 and its downstream targets and inhibited keratinocyte migration in a FOXO1-dependent manner. Thus, FOXO1 expression can positively or negatively modulate keratinocyte migration and wound healing by its differential effect on downstream targets modulated by factors present in diabetic healing. PMID:25918228

  5. Differential effects of intrauterine growth restriction on brain structure and development in preterm infants: a magnetic resonance imaging study.

    PubMed

    Padilla, Nelly; Falcón, Carles; Sanz-Cortés, Magdalena; Figueras, Francesc; Bargallo, Núria; Crispi, Fátima; Eixarch, Elisenda; Arranz, Angela; Botet, Francesc; Gratacós, Eduard

    2011-03-25

    Previous evidence suggests that preterm newborns with intrauterine growth restriction (IUGR) have specific neurostructural and neurodevelopmental anomalies, but it is unknown whether these effects persist in early childhood. We studied a sample of 18 preterm IUGR, 15 preterm AGA - born between 26 and 34 weeks of gestational age (GA) - and 15 healthy born-term infants. Infants were scanned at 12 months corrected age (CA), in a 3T scanner, without sedation. Analyses were made by automated lobar volumetry and voxel-based morphometry (VBM). The neurodevelopmental outcome was assessed in all subjects at 18 months CA with the Bayley Scale for Infant and Toddler Development, third edition. IUGR infants had reduced relative volumes for the insular and temporal lobes. According to VBM, IUGR infants had bilateral reduced gray matter (GM) in the temporal, parietal, frontal, and insular regions compared with the other groups. IUGR infants had increased white matter (WM) in temporal regions compared to the AGA group and in frontal, parietal, occipital, and insular regions compared to the term group. They also showed decreased WM in the cerebellum and a non-significant trend in the hippocampus compared to term infants. IUGR infants had reduced neurodevelopmental scores, which were positively correlated with GM in various regions. These data suggest that the IUGR induces a distinct brain pattern of structural changes that persist at 1 year of life and are associated with specific developmental difficulties. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Differential Receptor for Advanced Glycation End Products Expression in Preeclamptic, Intrauterine Growth Restricted, and Gestational Diabetic Placentas.

    PubMed

    Alexander, Kristen L; Mejia, Camilo A; Jordan, Clinton; Nelson, Michael B; Howell, Brian M; Jones, Cameron M; Reynolds, Paul R; Arroyo, Juan A

    2016-02-01

    Receptor for advanced glycation end products (RAGE) is a receptor implicated in the modulation of inflammation. Inflammation has been associated with pregnancy pathologies including preeclampsia (PE), intrauterine growth restriction (IUGR), and gestational diabetes mellitus (GDM). Our objective was to examine placental RAGE expression in PE, IUGR, and GDM complications. Human placental tissues were obtained for RAGE determination using Q-PCR, immunohistochemistry, and Western blot. Invasive trophoblast cells were cultured and treated with AGES for RAGE activation studies. Compared to control placenta, we observed: (i) decreased RAGE gene expression during GDM, (ii) increased RAGE protein in the PE placenta, and (iii) decreased RAGE protein in the IUGR placenta. In trophoblast cells exposed AGEs, we observed: (i) decreased trophoblast invasion, (ii) increased c-Jun N-terminal kinases (JNK) and Extracellular signal-regulated kinases (ERK), and (iii) increased TNF-α and IL-1β secretion. We conclude that placental RAGE is activated during PE and that RAGE-mediated inflammation in the trophoblast involves increased pro-inflammatory cytokine secretion. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Differentiating cancerous from normal breast tissue by redox imaging

    NASA Astrophysics Data System (ADS)

    Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

    2015-02-01

    Abnormal metabolism can be a hallmark of cancer occurring early before detectable histological changes and may serve as an early detection biomarker. The current gold standard to establish breast cancer (BC) diagnosis is histological examination of biopsy. Previously we have found that pre-cancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. Our technique of quantitatively measuring the mitochondrial redox state has the potential to be implemented as an early detection tool for cancer and may provide prognostic value. We therefore in this present study, investigated the feasibility of quantifying the redox state of tumor samples from 16 BC patients. Tumor tissue aliquots were collected from both normal and cancerous tissue from the affected cancer-bearing breasts of 16 female patients (5 TNBC, 9 ER+, 2 ER+/Her2+) shortly after surgical resection. All specimens were snap-frozen with liquid nitrogen on site and scanned later with the Chance redox scanner, i.e., the 3D cryogenic NADH/oxidized flavoprotein (Fp) fluorescence imager. Our preliminary results showed that both NADH and Fp (including FAD, i.e., flavin adenine dinucleotide) signals in the cancerous tissues roughly tripled to quadrupled those in the normal tissues (p<0.05) and the redox ratio Fp/(NADH+Fp) was about 27% higher in the cancerous tissues than in the normal ones (p<0.05). Our findings suggest that the redox state could differentiate between cancer and non-cancer breast tissues in human patients and this novel redox scanning procedure may assist in tissue diagnosis in freshly procured biopsy samples prior to tissue fixation. We are in the process of evaluating the prognostic value of the redox imaging indices for BC.

  8. Levonorgestrel Intrauterine System

    MedlinePlus

    ... Levonorgestrel intrauterine system is an effective method of birth control but it does not prevent the spread of ... or want to use a different form of birth control.Your levonorgestrel intrauterine system should be inserted within ...

  9. Differential entry of ricin into malignant and normal rat hepatocytes

    SciTech Connect

    Decastel, M.; Haentjens, G.; Aubery, M.; Goussault, Y. )

    1989-02-01

    The authors have compared the mechanisms of ricin binding to and entry into Zajdela hepatoma cells (ZHC) and normal rat hepatocytes (HyC). Lactose but not mannan was found to inhibit ricin binding to and toxicity on ZHC and HyC. This finding suggests that ricin binding, entry, and toxicity are expressed only through the galactose binding sites on ZHC and HyC. Nevertheless, the characteristics of ricin binding and its entry pathway appeared to be different in several respects in ZHC and HyC. Scatchard analysis of equilibrium data determined over a wide range of {sup 125}I-labeled ricin concentrations yielded a curvilinear plot for ZHC, while a straight line was obtained for HyC. These results indicate that only ZHC possess high-affinity receptors for ricin. Analysis of ricin toxicity of ZHC and HyC, in the presence of ammonium chloride or after K{sup +}-depletion in both cell types, suggests that the ricin bound to galactose receptors entered through neutral vesicles in ZHC, and through both neutral and acidic vesicles in HyC. The qualitative and quantitative differences found between the process of receptor-mediated endocytosis of ricin in ZHC and HyC might explain the differential sensitivity of the two cell types toward the toxin.

  10. Intragenic DNA methylation in transcriptional regulation, normal differentiation and cancer.

    PubMed

    Kulis, Marta; Queirós, Ana C; Beekman, Renée; Martín-Subero, José I

    2013-11-01

    Ever since the discovery of DNA methylation at cytosine residues, the role of this so called fifth base has been extensively studied and debated. Until recently, the majority of DNA methylation studies focused on the analysis of CpG islands associated to promoter regions. However, with the upcoming possibilities to study DNA methylation in a genome-wide context, this epigenetic mark can now be studied in an unbiased manner. As a result, recent studies have shown that not only promoters but also intragenic and intergenic regions are widely modulated during physiological processes and disease. In particular, it is becoming increasingly clear that DNA methylation in the gene body is not just a passive witness of gene transcription but it seems to be actively involved in multiple gene regulation processes. In this review we discuss the potential role of intragenic DNA methylation in alternative promoter usage, regulation of short and long non-coding RNAs, alternative RNA processing, as well as enhancer activity. Furthermore, we summarize how the intragenic DNA methylome is modified both during normal cell differentiation and neoplastic transformation.

  11. Progestin intrauterine device and GnRH analogue for uterus-sparing treatment of endometrial precancers and well-differentiated early endometrial carcinoma in young women.

    PubMed

    Minig, L; Franchi, D; Boveri, S; Casadio, C; Bocciolone, L; Sideri, M

    2011-03-01

    To test the efficacy of levonorgestrel-release intrauterine device (LNG-IUD) plus gonadotropin-releasing hormone (GnRH) for treating women aged <40 years with atypical endometrial hyperplasia (AEH) or presumed International Federation of Gynecology and Obstetrics stage IA limited to the endometrium, well differentiated (G1), endometrioid endometrial cancer (EC), who wish to preserve their fertility. A prospective observational study was conducted. Treatment consisted on the insertion of an LNG-IUD for 1 year plus GnRH analogue for 6 months. From January 1996 to June 2009, 20 and 14 patients with AEH and EC, respectively, were studied. Complete response rate was 95% in patients with AEH and 57.1% in women with EC-G1. A progression of the disease was observed in one (5%) and in four patients (28%) with AEH and EC, respectively. Four of 20 patients with AEH and 2 of 14 with EC-G1 experienced recurrences. The average relapse time was 36 months (range: 16-62 months). All of them were alive without evidence of disease at the last follow-up, mean: 29 months (range: 4-102 months). Nine women achieved 11 spontaneous pregnancies. The combined treatment showed effectiveness in a substantial proportion of patients with AEH and EC. Close follow-up during and after treatment is crucial.

  12. [A new intrauterine device].

    PubMed

    Ingemanson, C A

    1971-12-15

    The Lippes Silicone Shell Loop (LSS) was inserted in 310 patients. There were no perforations, 1 intrauterine pregnancy, and 18 removals because of side effects (mostly bleeding or bleeding in conjunction with pain). 267 of the patients later filled out questionnaires abourt their experience with the IUD. The continuation rate was about 90%. 36% of the patients said that they had normal menstrual cycles and 64% that they had increased or lengthened menstrual bleeding. 54% said that their sex lives had improved with IUD use, and 6% said that their sex lives had become worse. 83% were satisfied with IUD use in spite of increased menstrual bleeding. Compared with studies of other IUDs, the LSS has fewer side effects and a higher rate of effectiveness and continuation than other IUDs.

  13. Phenotypic characterization by high-resolution three-dimensional magnetic resonance imaging evidences differential effects of embryo genotype on intrauterine growth retardation in NOS3-deficient mice.

    PubMed

    Pallares, Pilar; Perez-Solana, Maria L; Torres-Rovira, Laura; Gonzalez-Bulnes, Antonio

    2011-05-01

    The Nos3-knockout mouse, deficient for endothelial constitutive nitric oxide synthase (NOS3), is affected by a reduction in the number and weight of the embryos and constitutes a good model for some features of preeclampsia and intrauterine growth retardation (IUGR). Deficiencies in conceptus growth and survival may result from factors inherent in the embryo itself or from deficiencies in uterine function. In the current study, we aimed to determine the effects of embryonic genotype independently of maternal genotype, which can affect uterine environment. Therefore, by using magnetic resonance imaging (MRI), we characterized the phenotypes of NOS3-defective (Nos3(-/-); n = 6), normal wild-type (Nos3(+/+); n = 5), and heterozygous (Nos3(+/-); n = 16) mouse fetuses. All of them were littermates obtained by breeding heterozygous mice (Nos3(+/-)); therefore, the maternal genotype was the same for all the fetuses. At Day 13.5 (i.e., Theiler stage TS 21-22), females were anesthetized and scanned with three-dimensional MRI. Analysis of the different measurements of the embryos and the gestational annexes showed no significant differences between Nos3(+/+) and Nos3(+/-); however, there was a trend toward larger sizes in Nos3(+/+), and values in Nos3(-/-) were significantly smaller than in Nos3(+/+) and Nos3(+/-). The reduction in the crown-rump length of Nos3(-/-) reached 12% when compared to Nos3(+/+) (P < 0.05); the effect was higher for head measurements (16% for occipito-snout length and biparietal diameter, P < 0.05 for both) and trunk diameter (17%, P < 0.05). Overall, the maximum area of fetuses in longitudinal planes decreased 27% (P < 0.05) when comparing Nos3(-/-) to wild-type Nos3(+/+). Finally, Nos3(-/-) showed a reduction of 29% in the maximum thickness of the placenta, which may be related to the appearance of IUGR due to compromised nutritional delivery to the fetus.

  14. Normal and Abnormal Epithelial Differentiation in the Female Reproductive Tract

    PubMed Central

    Kurita, Takeshi

    2011-01-01

    In mammals, the female reproductive tract (FRT) develops from a pair of paramesonephric or Müllerian ducts (MDs), which arise from coelomic epithelial cells of mesodermal origin. During development, the MDs undergo a dynamic morphogenetic transformation from simple tubes consisting of homogeneous epithelium and surrounding mesenchyme into several distinct organs namely the oviduct, uterus, cervix and vagina. Following the formation of anatomically distinctive organs, the uniform MD epithelium (MDE) differentiates into diverse epithelial cell types with unique morphology and functions in each organ. Classic tissue recombination studies, in which the epithelium and mesenchyme isolated from the newborn mouse FRT were recombined, have established that the organ specific epithelial cell fate of MDE is dictated by the underlying mesenchyme. The tissue recombination studies have also demonstrated that there is a narrow developmental window for the epithelial cell fate determination in MD-derived organs. Accordingly, the developmental plasticity of epithelial cells is mostly lost in mature FRT. If the signaling that controls epithelial differentiation is disrupted at the critical developmental stage, the cell fate of MD-derived epithelial tissues will be permanently altered and can result in epithelial lesions in adult life. A disruption of signaling that maintains epithelial cell fate can also cause epithelial lesions in the FRT. In this review, the pathogenesis of cervical/vaginal adenoses and uterine squamous metaplasia is discussed as examples of such incidences. PMID:21612855

  15. Differentiation of normal and cancerous lung tissues by multiphoton imaging

    NASA Astrophysics Data System (ADS)

    Wang, Chun-Chin; Li, Feng-Chieh; Wu, Ruei-Jhih; Hovhannisyan, Vladimir A.; Lin, Wei-Chou; Lin, Sung-Jan; So, Peter T. C.; Dong, Chen-Yuan

    2009-07-01

    We utilize multiphoton microscopy for the label-free diagnosis of noncancerous, lung adenocarcinoma (LAC), and lung squamous cell carcinoma (SCC) tissues from humans. Our results show that the combination of second-harmonic generation (SHG) and multiphoton excited autofluorescence (MAF) signals may be used to acquire morphological and quantitative information in discriminating cancerous from noncancerous lung tissues. Specifically, noncancerous lung tissues are largely fibrotic in structure, while cancerous specimens are composed primarily of tumor masses. Quantitative ratiometric analysis using MAF to SHG index (MAFSI) shows that the average MAFSI for noncancerous and LAC lung tissue pairs are 0.55+/-0.23 and 0.87+/-0.15, respectively. In comparison, the MAFSIs for the noncancerous and SCC tissue pairs are 0.50+/-0.12 and 0.72+/-0.13, respectively. Our study shows that nonlinear optical microscopy can assist in differentiating and diagnosing pulmonary cancer from noncancerous tissues.

  16. Differentiation of normal and cancerous lung tissues by multiphoton imaging

    NASA Astrophysics Data System (ADS)

    Wang, Chun-Chin; Li, Feng-Chieh; Wu, Ruei-Jr; Hovhannisyan, Vladimir A.; Lin, Wei-Chou; Lin, Sung-Jan; So, Peter T. C.; Dong, Chen-Yuan

    2010-02-01

    In this work, we utilized multiphoton microscopy for the label-free diagnosis of non-cancerous, lung adenocarcinoma (LAC), and lung squamous cell carcinoma (SCC) tissues from human. Our results show that the combination of second harmonic generation (SHG) and multiphoton excited autofluorescence (MAF) signals may be used to acquire morphological and quantitative information in discriminating cancerous from non-cancerous lung tissues. Specifically, non-cancerous lung tissues are largely fibrotic in structure while cancerous specimens are composed primarily of tumor masses. Quantitative ratiometric analysis using MAF to SHG index (MAFSI or SAAID) shows that the average MAFSI for noncancerous and LAC lung tissue pairs are 0.55 +/-0.23 and 0.87+/-0.15 respectively. In comparison, the MAFSIs for the noncancerous and SCC tissue pairs are 0.50+/-0.12 and 0.72+/-0.13 respectively. Intrinsic fluorescence ratio (FAD/NADH) of SCC and non-cancerous tissues are 0.40+/-0.05 and 0.53+/-0.05 respectively, the redox ratio of SCC diminishes significantly, indicating that increased cellular metabolic activity. Our study shows that nonlinear optical microscopy can assist in differentiating and diagnosing pulmonary cancer from non-cancerous tissues. With additional development, multiphoton microscopy may be used for the clinical diagnosis of lung cancers.

  17. Glucocorticoid programming of intrauterine development.

    PubMed

    Fowden, A L; Valenzuela, O A; Vaughan, O R; Jellyman, J K; Forhead, A J

    2016-07-01

    Glucocorticoids (GCs) are important environmental and maturational signals during intrauterine development. Toward term, the maturational rise in fetal glucocorticoid receptor concentrations decreases fetal growth and induces differentiation of key tissues essential for neonatal survival. When cortisol levels rise earlier in gestation as a result of suboptimal conditions for fetal growth, the switch from tissue accretion to differentiation is initiated prematurely, which alters the phenotype that develops from the genotype inherited at conception. Although this improves the chances of survival should delivery occur, it also has functional consequences for the offspring long after birth. Glucocorticoids are, therefore, also programming signals that permanently alter tissue structure and function during intrauterine development to optimize offspring fitness. However, if the postnatal environmental conditions differ from those signaled in utero, the phenotypical outcome of early-life glucocorticoid receptor overexposure may become maladaptive and lead to physiological dysfunction in the adult. This review focuses on the role of GCs in developmental programming, primarily in farm species. It examines the factors influencing GC bioavailability in utero and the effects that GCs have on the development of fetal tissues and organ systems, both at term and earlier in gestation. It also discusses the windows of susceptibility to GC overexposure in early life together with the molecular mechanisms and long-term consequences of GC programming with particular emphasis on the cardiovascular, metabolic, and endocrine phenotype of the offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Finite Mixtures for Simultaneously Modelling Differential Effects and Non-Normal Distributions

    PubMed Central

    George, Melissa R.W.; Yang, Na; Jaki, Thomas; Feaster, Daniel J.; Lamont, Andrea E.; Wilson, Dawn K.; Horn, M. Lee Van

    2015-01-01

    Regression mixture models have been increasingly applied in the social and behavioral sciences as a method for identifying differential effects of predictors on outcomes. While the typical specification of this approach is sensitive to violations of distributional assumptions, alternative methods for capturing the number of differential effects have been shown to be robust. Yet, there is still a need to better describe differential effects that exist when using regression mixture models. The current study tests a new approach that uses sets of classes (called differential effects sets) to simultaneously model differential effects and account for non-normal error distributions. Monte Carlo simulations are used to examine the performance of the approach. The number of classes needed to represent departures from normality is shown to be dependent on the degree of skew. The use of differential effects sets reduced bias in parameter estimates. Applied analyses demonstrated the implementation of the approach for describing differential effects of parental health problems on adolescent body mass index using differential effects sets approach. Findings support the usefulness of the approach which overcomes the limitations of previous approaches for handling non-normal errors. PMID:25717214

  19. Finite Mixtures for Simultaneously Modelling Differential Effects and Non-Normal Distributions.

    PubMed

    George, Melissa R W; Yang, Na; Jaki, Thomas; Feaster, Daniel J; Lamont, Andrea E; Wilson, Dawn K; Horn, M Lee Van

    2013-11-01

    Regression mixture models have been increasingly applied in the social and behavioral sciences as a method for identifying differential effects of predictors on outcomes. While the typical specification of this approach is sensitive to violations of distributional assumptions, alternative methods for capturing the number of differential effects have been shown to be robust. Yet, there is still a need to better describe differential effects that exist when using regression mixture models. The current study tests a new approach that uses sets of classes (called differential effects sets) to simultaneously model differential effects and account for non-normal error distributions. Monte Carlo simulations are used to examine the performance of the approach. The number of classes needed to represent departures from normality is shown to be dependent on the degree of skew. The use of differential effects sets reduced bias in parameter estimates. Applied analyses demonstrated the implementation of the approach for describing differential effects of parental health problems on adolescent body mass index using differential effects sets approach. Findings support the usefulness of the approach which overcomes the limitations of previous approaches for handling non-normal errors.

  20. Characterization and differentiation of normal and abnormal semen samples using micro-Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Huang, Zufang; Chen, Xiwen; Chen, Jinhua; Li, Yongzeng; Lei, Jinping; Chen, Rong

    2012-12-01

    Growth in the percentage of male infertility has caused extensive concerns. The fast and reliable method is urgently required for diagnosis of semen samples. In our study, micro-Raman spectroscopy was employed to characterize and differentiate the normal and abnormal semen samples based on the differences of their specific Raman spectra which originated from biochemical components. Our preliminary results demonstrate that micro-Raman spectroscopy combined with multivariate analysis methods has the potential of being used to detect and differentiate semen samples.

  1. Absorbance Differentiation of Burned and Normal Tissue by the Addition of Glycerol

    NASA Astrophysics Data System (ADS)

    Chang, Chuan-I.; de Pedro, Hector; Zarnani, Faranak; Idris, Ahamed; Glosser, R.

    2012-03-01

    Minimizing the removal of healthy/recoverable tissue would significantly increase the chances of the patients' survival. The purpose is to be able to optically differentiate between burned and normal tissue with the addition of glycerol. Under normal conditions (without glycerol), the absorption coefficient is large, which means there is a large amount of absorption in the tissue. Glycerol decreases the absorption coefficient by reducing the cell size as well as providing a more uniform index of refraction in the interstitial environment. A lower overall absorption will reveal absorption peaks specific to the differentiation of the tissue. Results will be presented on the day of the conference.

  2. Dicer1 and miR-219 Are Required for Normal Oligodendrocyte Differentiation and Myelination

    PubMed Central

    Dugas, Jason C.; Cuellar, Trinna L.; Scholze, Anja; Ason, Brandon; Ibrahim, Adiljan; Emery, Ben; Zamanian, Jennifer L.; Foo, Lynette C.; McManus, Michael T.; Barres, Ben A.

    2010-01-01

    To investigate the role of microRNAs in regulating oligodendrocyte (OL) differentiation and myelination, we utilized transgenic mice in which microRNA processing was disrupted in OL precursor cells (OPCs) and OLs by targeted deletion of Dicer1. We found that inhibition of OPC-OL miRNA processing disrupts normal CNS myelination, and that OPCs lacking mature miRNAs fail to differentiate normally in vitro. We identified three miRNAs, miR-219, miR-138, and miR-338, that are induced 10–100x during OL differentiation; the most strongly induced of these, miR-219, is necessary and sufficient to promote OL differentiation, and partially rescues OL differentiation defects caused by total miRNA loss. miR-219 directly represses the expression of PDGFRα, Sox6, FoxJ3, and ZFP238 proteins, all of which normally help to promote OPC proliferation. Together, these findings show that miR-219 plays a critical role in coupling differentiation to proliferation arrest in the OL lineage, enabling the rapid transition from proliferating OPCs to myelinating OLs. PMID:20223197

  3. MicroRNA93 Regulates Proliferation and Differentiation of Normal and Malignant Breast Stem Cells

    PubMed Central

    Liu, Suling; Patel, Shivani H.; Ginestier, Christophe; Ibarra, Ingrid; Martin-Trevino, Rachel; Bai, Shoumin; McDermott, Sean P.; Shang, Li; Ke, Jia; Ou, Sing J.; Heath, Amber; Zhang, Kevin J.; Korkaya, Hasan; Clouthier, Shawn G.; Charafe-Jauffret, Emmanuelle; Birnbaum, Daniel; Hannon, Gregory J.; Wicha, Max S.

    2012-01-01

    MicroRNAs (miRNAs) play important roles in normal cellular differentiation and oncogenesis. microRNA93 (mir-93), a member of the mir106b-25 cluster, located in intron 13 of the MCM7 gene, although frequently overexpressed in human malignancies may also function as a tumor suppressor gene. Using a series of breast cancer cell lines representing different stages of differentiation and mouse xenograft models, we demonstrate that mir-93 modulates the fate of breast cancer stem cells (BCSCs) by regulating their proliferation and differentiation states. In “claudinlow” SUM159 cells, expression of mir-93 induces Mesenchymal-Epithelial Transition (MET) associated with downregulation of TGFβ signaling and downregulates multiple stem cell regulatory genes, including JAK1, STAT3, AKT3, SOX4, EZH1, and HMGA2, resulting in cancer stem cell (CSC) depletion. Enforced expression of mir-93 completely blocks tumor development in mammary fat pads and development of metastases following intracardiac injection in mouse xenografts. The effect of mir-93 on the CSC population is dependent on the cellular differentiation state, with mir-93 expression increasing the CSC population in MCF7 cells that display a more differentiated “luminal” phenotype. mir-93 also regulates the proliferation and differentiation of normal breast stem cells isolated from reduction mammoplasties. These studies demonstrate that miRNAs can regulate the states and fates of normal and malignant mammary stem cells, findings which have important biological and clinical implications. PMID:22685420

  4. Differential gene expression in normal and transformed human mammary epithelial cells in response to oxidative stress

    PubMed Central

    Cortes, Diego F; Sha, Wei; Hower, Valerie; Blekherman, Greg; Laubenbacher, Reinhard; Akman, Steven; Torti, Suzy V; Shulaev, Vladimir

    2011-01-01

    Oxidative stress plays a key role in breast carcinogenesis. To investigate whether normal and malignant breast epithelial cells differ in their responses to oxidative stress, we examined the global gene expression profiles of three cell types, representing cancer progression from a normal to a malignant stage, under oxidative stress. Normal human mammary epithelial cells (HMEC), an immortalized cell line (HMLER-1), and a tumorigenic cell line (HMLER-5), were exposed to increased levels of reactive oxygen species (ROS) by treatment with glucose oxidase. Functional analysis of the metabolic pathways enriched with differentially expressed genes demonstrates that normal and malignant breast epithelial cells diverge substantially in their response to oxidative stress. While normal cells exhibit the up-regulation of antioxidant mechanisms, cancer cells are unresponsive to the ROS insult. However, the gene expression response of normal HMEC cells under oxidative stress is comparable to that of the malignant cells under normal conditions, indicating that altered redox status is persistent in breast cancer cells, which makes them resistant to increased generation of ROS. This study discusses some of the possible adaptation mechanisms of breast cancer cells under persistent oxidative stress that differentiate them from the response to acute oxidative stress in normal mammary epithelial cells. PMID:21397008

  5. Intrauterine surgery in myelomeningocele.

    PubMed

    Bruner, Joseph P

    2007-12-01

    Intrauterine surgery for repair of fetal myelomeningocele has been performed since 1994. Open repair through a hysterotomy has been performed since 1997. Although much has been published about diagnosis, counseling, case selection, pre-, intra-, and postoperative management, delivery and long-term sequelae for both mother and baby, and associated ethical issues, several questions have yet to be openly discussed in a public forum.

  6. Intrauterine infection and prematurity.

    PubMed

    Gonçalves, Luís F; Chaiworapongsa, Tinnakorn; Romero, Roberto

    2002-01-01

    Intrauterine infection is a major cause of premature labor with and without intact membranes. Intrauterine infection is present in approximately 25% of all preterm births and the earlier the gestational age at delivery, the higher the frequency of intra-amniotic infection. Microorganisms may also gain access to the fetus before delivery. A fetal inflammatory response syndrome elicited in response to microbial products is associated with the impending onset of preterm labor and also with multi-systemic organ involvement in the human fetus and a higher rate of perinatal morbidity. The most common microorganisms involved in intrauterine infections are Ureaplasma urealyticum, Fusobacterium species and Mycoplasma hominis. The role of Chlamydia trachomatis and viruses in preterm labor remain to be determined. Use of molecular microbiology techniques to diagnose intrauterine infection may uncover the role of fastidious microorganisms that have not yet been discovered. Antibiotic administration to patients with asymptomatic bacteriuria is associated with a significant reduction in the rate of preterm birth. However, such benefit has not been demonstrated for patients with bacterial vaginosis, or women who carry Streptococcus agalactia, Ureaplasma urealyticum or Trichomonas vaginalis. Antibiotic administration to patients with preterm premature rupture of membranes is associated with prolongation of pregnancy and a reduction in the rate of clinical chorioamnionitis and neonatal sepsis. The benefit has not been demonstrated in patients with preterm labor and intact membranes. Major efforts are required to determine why some women develop an ascending intrauterine infection and others do not and also what interventions may reduce the deleterious effect of systemic fetal inflammation. Copyright 2002 Wiley-Liss, Inc.

  7. Microarray analysis of differentially expressed genes in preeclamptic and normal placental tissues.

    PubMed

    Ma, K; Lian, Y; Zhou, S; Hu, R; Xiong, Y; Ting, P; Xiong, Y; Li, X; Wang, X

    2014-01-01

    To detect the candidate genes for preeclampsia (PE). The gene expression profiles in preeclamptic and normal placental tissues were analyzed using cDNA microarray approach and the altered expression of important genes were further confirmed by real-time RT-PCR (reverse transcription polymerase chain reaction) technique. Total RNA was extracted from placental tissues of three cases with severe PE and from three cases with normal pregnancy. After scanning, differentially expressed genes were detected by software. In two experiments (the fluorescent labels were exchanged), a total of 111 differentially expressed genes were detected. In placental tissue ofpreeclamptic pregnancy, 68 differentially expressed genes were up-regulated, and 44 differentially expressed genes were down-regulated. Of these genes, 16 highly differentially expressed genes were confirmed by real-time fluorescent quantitative RT-PCR, and the result showed that the ratio of gene expression differences was comparable to that detected by cDNA microarray. The results of bioinformatic analysis showed that encoding products of differentially expressed genes were correlated to infiltration of placenta trophoblastic cells, immunomodulatory factors, pregnancy-associated plasma protein, signal transduction pathway, and cell adhesion. Further studies on the biological function and regulating mechanism of these genes will provide new clues for better understanding of etiology and pathogenesis of PE.

  8. Differential Transcriptional Response in Macrophages Infected with Cell Wall Deficient versus Normal Mycobacterium Tuberculosis

    PubMed Central

    Fu, Yu-Rong; Gao, Kun-Shan; Ji, Rui; Yi, Zheng-Jun

    2015-01-01

    Host-pathogen interactions determine the outcome following infection by mycobacterium tuberculosis (Mtb). Under adverse circumstances, normal Mtb can form cell-wall deficient (CWD) variants within macrophages, which have been considered an adaptive strategy for facilitating bacterial survival inside macrophages. However, the molecular mechanism by which infection of macrophages with different phenotypic Mtb elicits distinct responses of macrophages is not fully understood. To explore the molecular events triggered upon Mtb infection of macrophages, differential transcriptional responses of RAW264.7 cells infected with two forms of Mtb, CWD-Mtb and normal Mtb, were studied by microarray analysis. Some of the differentially regulated genes were confirmed by RT-qPCR in both RAW264.7 cells and primary macrophages. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was used to analyze functions of differentially expressed genes. Distinct gene expression patterns were observed between CWD-Mtb and normal Mtb group. Mapt was up-regulated, while NOS2 and IL-11 were down-regulated in CWD-Mtb infected RAW264.7 cells and primary macrophages compared with normal Mtb infected ones. Many deregulated genes were found to be related to macrophages activation, immune response, phagosome maturation, autophagy and lipid metabolism. KEGG analysis showed that the differentially expressed genes were mainly involved in MAPK signaling pathway, nitrogen metabolism, cytokine-cytokine receptor interaction and focal adhesion. Taken together, the present study showed that differential macrophage responses were induced by intracellular CWD-Mtb an normal Mtb infection, which suggested that interactions between macrophages and different phenotypic Mtb are very complex. The results provide evidence for further understanding of pathogenesis of CWD-Mtb and may help in improving strategies to eliminate intracellular CWD-Mtb. PMID:25552926

  9. Ventricular filling patterns of the right and left ventricles in normally grown fetuses: a longitudinal follow-up study from early intrauterine life to age 1 year.

    PubMed

    Veille, J C; Smith, N; Zaccaro, D

    1999-04-01

    Our goal was to determine the effects of advancing age on the Doppler diastolic filling indexes from early gestation to 1 year of life. Seventy-nine fetuses were studied. Initial Doppler studies were started at about the 16th week of gestation and repeated every 4-6 weeks until term, on postnatal day 1 and 2, and at ages 6 weeks, 6 months, and 12 months. A minimum of 5 returning Doppler waveforms were traced and analyzed for (1) peak early flow velocity, (2) late peak atrial flow velocity, (3) total area area under the curve, and (4) the acceleration and deceleration phases. The stiffness of the ventricles was estimated. Slopes of the curves for each of the parameters were analyzed for differences across time periods and between right and left ventricles. (1) Heart rate significantly decreased with advancing age. (2) Left ventricular and right ventricular peak early flow velocity and late peak atrial flow velocity significantly increased during fetal life but not during the 1st year. (3) Atrial predominance was found during fetal life but not during the first year. (4) The deceleration phase of filling significantly increased during the fetal period. (5) Ventricular stiffness progressively decreased during the fetal period. (6) Increased ventricular filling shifted from a right-sided dominance in utero to a left-sided dominance after birth. (1) Fetuses have stiffer fetal ventricles than neonates. (2) The diastolic filling patterns in normally grown fetuses mimic those of the diseased adult heart. We speculate that this maturation process may be affected in fetuses born prematurely or small for gestational age.

  10. Dietary supplementation with β-hydroxy-β-methylbutyrate calcium during the early postnatal period accelerates skeletal muscle fibre growth and maturity in intra-uterine growth-retarded and normal-birth-weight piglets.

    PubMed

    Wan, Haifeng; Zhu, Jiatao; Su, Guoqi; Liu, Yan; Hua, Lun; Hu, Liang; Wu, Caimei; Zhang, Ruinan; Zhou, Pan; Shen, Yong; Lin, Yan; Xu, Shengyu; Fang, Zhengfeng; Che, Lianqiang; Feng, Bin; Wu, De

    2016-04-01

    Intra-uterine growth restriction (IUGR) impairs postnatal growth and skeletal muscle development in neonatal infants. This study evaluated whether dietary β-hydroxy-β-methylbutyrate Ca (HMB-Ca) supplementation during the early postnatal period could improve muscle growth in IUGR neonates using piglets as a model. A total of twelve pairs of IUGR and normal-birth-weight (NBW) male piglets with average initial weights (1·85 (sem 0·36) and 2·51 (sem 0·39) kg, respectively) were randomly allotted to groups that received milk-based diets (CON) or milk-based diets supplemented with 800 mg/kg HMB-Ca (HMB) during days 7-28 after birth. Blood and longissimus dorsi (LD) samples were collected and analysed for plasma amino acid content, fibre morphology and the expression of genes related to muscle development. The results indicate that, regardless of diet, IUGR piglets had a significantly decreased average daily weight gain (ADG) compared with that of NBW piglets (P<0·05). However, IUGR piglets fed HMB-Ca had a net weight and ADG similar to that of NBW piglets fed the CON diet. Irrespective of body weight (BW), HMB-Ca supplementation markedly increased the type II fibre cross-sectional area and the mRNA expression of mammalian target of rapamycin (mTOR), insulin-like growth factor-1 and myosin heavy-chain isoform IIb in the LD of piglets (P<0·05). Moreover, there was a significant interaction between the effects of BW and HMB on mTOR expression in the LD (P<0·05). In conclusion, HMB-Ca supplementation during the early postnatal period could improve skeletal muscle growth and maturity by accelerating fast-twitch glycolytic fibre development in piglets.

  11. Utero-placental vascularisation in normal and preeclamptic and intra-uterine growth restriction pregnancies: third trimester quantification using 3D power Doppler with comparison to placental vascular morphology (EVUPA): a prospective controlled study

    PubMed Central

    Duan, Jie; Chabot-Lecoanet, Anne-Claire; Perdriolle-Galet, Estelle; Christov, Christophe; Hossu, Gabriela; Cherifi, Aboubaker; Morel, Olivier

    2016-01-01

    Introduction Preeclampsia (PE) and intra-uterine growth restriction (IUGR) are two major pregnancy complications related to chronic utero-placental hypoperfusion. Three-dimensional power Doppler (3DPD) angiography has been used for the evaluation of utero-placental vascularisation and three vascular indices have been calculated: the vascularisation index (VI), flow index (FI) and vascularisation-FI (VFI). However, several technical endpoints hinder the clinical use of 3DPD as physical characteristics and machine settings may affect 3DPD indices, and so its clinical significance is not yet clear. Objectives The primary objective is to better understand the clinical significance of 3DPD indices by evaluating the relationship between these indices and placental morphometry. Secondary objectives are (i) to determine the impact of machine settings and physical characteristics on 3DPD indices, and (ii) to evaluate physio-pathological placental vascularisation patterns. Methods and analysis This is a prospective controlled study. We expect to include 112 women: 84 with normal pregnancies and 28 with PE and/or IUGR (based on our former cohort study on 3DPD indices for PE and/or IUGR prediction (unpublished data)). Within 72 h before planned or semi-urgent caesarean section, utero-placental 3DPD images with five different machine settings will be acquired. Placentas will be collected and examined after surgery and stereological indices (volume density, surface density, length density) calculated. The 3DPD indices (VI, FI and VFI) of the placenta and adjacent myometrium will be calculated. Correlation between Doppler and morphological indices will be evaluated by Pearson or Spearman tests. Agreement between 3DPD indices and morphological indices will be assessed by Bland and Altman plots. The impact of Doppler settings and maternal characteristics on 3DPD indices will be evaluated with a multivariate linear regression model. Ethics The study and related consent forms have

  12. Characterization and differentiation of normal and abnormal spermatozoa via micro-Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Huang, Z. F.; Chen, X. W.; Chen, G. N.; Chen, J. H.; Wang, J.; Lin, J. Q.; Zeng, H. S.; Chen, R.

    2013-03-01

    Growth in the percentage of spermatozoa with aberrant sperm head morphologies has been correlated with a rise in male infertility. In our study, micro-Raman spectroscopy using a new substrate was utilized to characterize and differentiate the morphologically normal and abnormal human sperm cells based on their different biochemical components by showing their different specific Raman spectra. A detailed classification based on the PCA-LDA method was performed showing a diagnostic sensitivity of 76% and specificity of 91%, with 80% classification accuracy. Our results suggest that micro-Raman spectroscopy can serve as a reliable and non-invasive tool for detection and differentiation of human spermatozoa.

  13. The intrauterine contraceptive device.

    PubMed Central

    Barwin, B. N.; Tuttle, S.; Jolly, E. E.

    1978-01-01

    This presentation brings into perspective the most recent information on intrauterine contraceptive devices. A comprehensive review of the literature is presented in a manner meaningful to the clinician. The advantages and disadvantages of this method of contraception, the problems that arise and the recommended methods of management are discussed. An updated review of the literature with regard to bleeding, pain, expulsion of the device, infection, uterine perforation and pregnancy is also presented. PMID:620385

  14. Trbp Is Required for Differentiation of Myoblasts and Normal Regeneration of Skeletal Muscle

    PubMed Central

    Ding, Jian; Nie, Mao; Liu, Jianming; Hu, Xiaoyun; Ma, Lixin; Deng, Zhong-Liang; Wang, Da-Zhi

    2016-01-01

    Global inactivation of Trbp, a regulator of miRNA pathways, resulted in developmental defects and postnatal lethality in mice. Recently, we showed that cardiac-specific deletion of Trbp caused heart failure. However, its functional role(s) in skeletal muscle has not been characterized. Using a conditional knockout model, we generated mice lacking Trbp in the skeletal muscle. Unexpectedly, skeletal muscle specific Trbp mutant mice appear to be phenotypically normal under normal physiological conditions. However, these mice exhibited impaired muscle regeneration and increased fibrosis in response to cardiotoxin-induced muscle injury, suggesting that Trbp is required for muscle repair. Using cultured myoblast cells we further showed that inhibition of Trbp repressed myoblast differentiation in vitro. The impaired myogenesis is associated with reduced expression of muscle-specific miRNAs, miR-1a and miR-133a. Together, our study demonstrated that Trbp participates in the regulation of muscle differentiation and regeneration. PMID:27159388

  15. [Differential proteins analysis among human nasal inverted papilloma and nasal polyposis and normal nasal mucosa].

    PubMed

    Meng, Qing-shu; Jin, Sheng; Zhang, Qiu-hang; Zhang, Man

    2010-04-01

    Proteomics-based approach was applied to analyze and compare the difference of proteins among human nasal inverted papilloma (NIP), nasal polyposis and normal nasal mucosa, in order to screen different proteins as marker. The total proteins of NIP, nasal polyposis and normal nasal mucosa were separated by two-dimensional gel electrophoresis (2-DE). Protein image obtained by using the gel of Calibrated GS-800 Densitometer system, and determined different protein spots. Six differential proteins between NIP and nasal polyp tissue were identified, which were galectin-1, Manganese-superoxide dismutase, galectin-7, trichostatin A, prohibitin and transferring. All of them were increased in NIP. Six differential proteins were possibly involved in NIP, which provided a new way for discriminating NIP from nasal polyposis. The data would be good for the establishment of NIP protein 2-DE map.

  16. Sex-differential placentation immunological interactions between male conceptus and gravida during normal pregnancy.

    PubMed

    Vernier, M C

    1975-01-01

    7,773 placentae of newborns were analyzed in order to test a hypothesis of specific immunological concepto-maternal interactions due to maleness and occurring during normal pregnancy. An association between placental weight of newborn male and the sex of conceptuses of previous pregnancies was found which supports the hypothesis. No such an association was found for female newborn. The confirmation of these results could open new avenues in the study of sex-differential survival of the conceptus throughout gestation.

  17. Transcriptome analysis of the normal human mammary cell commitment and differentiation process.

    PubMed

    Raouf, Afshin; Zhao, Yun; To, Karen; Stingl, John; Delaney, Allen; Barbara, Mary; Iscove, Norman; Jones, Steven; McKinney, Steven; Emerman, Joanne; Aparicio, Samuel; Marra, Marco; Eaves, Connie

    2008-07-03

    Mature mammary epithelial cells are generated from undifferentiated precursors through a hierarchical process, but the molecular mechanisms involved, particularly in the human mammary gland, are poorly understood. To address this issue, we isolated highly purified subpopulations of primitive bipotent and committed luminal progenitor cells as well as mature luminal and myoepithelial cells from normal human mammary tissue and compared their transcriptomes obtained using three different methods. Elements unique to each subset of mammary cells were identified, and changes that accompany their differentiation in vivo were shown to be recapitulated in vitro. These include a stage-specific change in NOTCH pathway gene expression during the commitment of bipotent progenitors to the luminal lineage. Functional studies further showed NOTCH3 signaling to be critical for this differentiation event to occur in vitro. Taken together, these findings provide an initial foundation for future delineation of mechanisms that perturb primitive human mammary cell growth and differentiation.

  18. Differentiating gastrointestinal stromal tumors from gastric adenocarcinomas and normal mucosae using confocal Raman microspectroscopy

    NASA Astrophysics Data System (ADS)

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chen, Wenlung

    2016-07-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and gastric adenocarcinomas are a common cancer worldwide. To differentiate GISTs from adenocarcinomas is important because the surgical processes for both are different; the former excises the tumor with negative margins, while the latter requires radical gastrectomy with lymph node dissection. Endoscopy with biopsy is used to distinguish GISTs from adenocarcinomas; however, it may cause tumor bleeding in GISTs. We reported here the confocal Raman microspectroscopy as an effective tool to differentiate GISTs, adenocarcinomas, and normal mucosae. Of 119 patients enrolled in this study, 102 patients underwent gastrectomy (40 GISTs and 62 adenocarcinomas), and 17 patients with benign lesions were obtained as normal mucosae. Raman signals were integrated for 100 s for each spot on the specimen, and 5 to 10 spots, depending on the sample size, were chosen for each specimen. There were significant differences among those tissues as evidenced by different Raman signal responding to phospholipids and protein structures. The spectral data were further processed and analyzed by using principal component analysis. A two-dimensional plot demonstrated that GISTs, adenocarcinomas, and normal gastric mucosae could be effectively differentiated from each other.

  19. Suppression of endogenous lipogenesis induces reversion of the malignant phenotype and normalized differentiation in breast cancer

    PubMed Central

    Schroeder, Barbara; Park, Cheol Hong; Chandra Mohan, KVP; Khurana, Ashwani; Corominas-Faja, Bruna; Cuyàs, Elisabet; Alarcón, Tomás; Kleer, Celina; Menendez, Javier A.; Lupu, Ruth

    2016-01-01

    The correction of specific signaling defects can reverse the oncogenic phenotype of tumor cells by acting in a dominant manner over the cancer genome. Unfortunately, there have been very few successful attempts at identifying the primary cues that could redirect malignant tissues to a normal phenotype. Here we show that suppression of the lipogenic enzyme fatty acid synthase (FASN) leads to stable reversion of the malignant phenotype and normalizes differentiation in a model of breast cancer (BC) progression. FASN knockdown dramatically reduced tumorigenicity of BC cells and restored tissue architecture, which was reminiscent of normal ductal-like structures in the mammary gland. Loss of FASN signaling was sufficient to direct tumors to a reversed phenotype that was near normal when considering the development of polarized growth-arrested acinar-like structure similar to those formed by nonmalignant breast cells in a 3D reconstituted basement membrane in vitro. This process, in vivo, resulted in a low proliferation index, mesenchymal-epithelial transition, and shut-off of the angiogenic switch in FASN-depleted BC cells orthotopically implanted into mammary fat pads. The role of FASN as a negative regulator of correct breast tissue architecture and terminal epithelial cell differentiation was dominant over the malignant phenotype of tumor cells possessing multiple cancer-driving genetic lesions as it remained stable during the course of serial in vivo passage of orthotopic tumor-derived cells. Transient knockdown of FASN suppressed hallmark structural and cytosolic/secretive proteins (vimentin, N-cadherin, fibronectin) in a model of EMT-induced cancer stem cells (CSC). Indirect pharmacological inhibition of FASN promoted a phenotypic switch from basal- to luminal-like tumorsphere architectures with reduced intrasphere heterogeneity. The fact that sole correction of exacerbated lipogenesis can stably reprogram cancer cells back to normal-like tissue architectures

  20. Differentiation of normal and cancer cells induced by sulfhydryl reduction: biochemical and molecular mechanisms.

    PubMed

    Parasassi, T; Brunelli, R; Bracci-Laudiero, L; Greco, G; Gustafsson, A C; Krasnowska, E K; Lundeberg, J; Lundeberg, T; Pittaluga, E; Romano, M C; Serafino, A

    2005-10-01

    We examined the morphological, biochemical and molecular outcome of a nonspecific sulfhydryl reduction in cells, obtained by supplementation of N-acetyl-L-cysteine (NAC) in a 0.1-10 mM concentration range. In human normal primary keratinocytes and in colon and ovary carcinoma cells we obtained evidences for: (i) a dose-dependent inhibition of proliferation without toxicity or apoptosis; (ii) a transition from a proliferative mesenchymal morphology to cell-specific differentiated structures; (iii) a noticeable increase in cell-cell and cell-substratum junctions; (iv) a relocation of the oncogenic beta-catenin at the cell-cell junctions; (v) inhibition of microtubules aggregation; (vi) upregulation of differentiation-related genes including p53, heat shock protein 27 gene, N-myc downstream-regulated gene 1, E-cadherin, and downregulation of cyclooxygenase-2; (vii) inhibition of c-Src tyrosine kinase. In conclusion, a thiol reduction devoid of toxicity as that operated by NAC apparently leads to terminal differentiation of normal and cancer cells through a pleiade of converging mechanisms, many of which are targets of the recently developed differentiation therapy.

  1. Differentially expressed proteins among normal cervix, cervical intraepithelial neoplasia and cervical squamous cell carcinoma.

    PubMed

    Zhao, Q; He, Y; Wang, X-L; Zhang, Y-X; Wu, Y-M

    2015-08-01

    To explore the differentially expressed proteins in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) tissues by differential proteomics technique. Cervical tissues (including normal cervix, CIN and CSCC) were collected in Department of Gynecologic Oncology of Beijing Obstetrics and Gynecology Hospital. Two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) and DeCyder software were used to detect the differentially expressed proteins. Matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) was used to identify the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were performed to validate the expressions of selected proteins among normal cervix, CIN and CSCC. 2-D DIGE images with high resolution and good repeatability were obtained. Forty-six differentially expressed proteins (27 up-regulated and 19 down-regulated) were differentially expressed among the normal cervix, CIN and CSCC. 26 proteins were successfully identified by MALDI-TOF/TOF MS. S100A9 (S100 calcium-binding protein A9) was the most significantly up-regulated protein. Eukaryotic elongation factor 1-alpha-1 (eEF1A1) was the most significantly down-regulated protein. Pyruvate kinase isozymes M2 (PKM2) was both up-regulated and down-regulated. The results of WB showed that with the increase in the severity of cervical lesions, the expression of S100A9 protein was significantly increased among the three groups (P = 0.010). The expression of eEF1A1 was reduced but without significant difference (P = 0.861). The expression of PKM2 was significantly reduced (P = 0.000). IHC showed that protein S100A9 was mainly expressed in the cytoplasm, and its positive expression rate was 20.0 % in normal cervix, 70.0 % in CIN and 100.0 % in CSCC, with a significant difference among them (P = 0.006). eEF1A1 was mainly expressed in the cell plasma, and its

  2. Low-angle normal faults-low differential stress at mid crustal levels

    NASA Technical Reports Server (NTRS)

    Power, W. L.

    1985-01-01

    A simple model for frictional slip on pre-existing faults that considers the local stress state near the fault and the effect of non-hydrostatic fluid pressures predicts that low-angle normal faulting is restricted to areas of the crust characterized by low differential stress and nearly lithostatic fluid pressures. The model considers frictional slip on a cohesionless low-angle normal fault governed by the failure criterion tau = mu sub f (sigma (*) sub n) =mu sub f (sigma sub n - P sub f) where tau and sigma sub n are the shear and normal stresses across the fault plane, mu sub f is the static coefficient of friction, and P sub f is the pore fluid pressure. As a first approximation, the model considers a vertical greatest principal compressive stress, sigma sub 1. It is apparent that if slip on low-angle normal faults is governed by the avove frictional failure criterion, slip on the low-angle normal fault occurs only if the least effective principal stress, sigma (*) sub 3 = sigma sub 3 - P sub f, is tensile, whenever tan superscrip -1(mu sub f d, where d is the dip of the fault. If detachment faulting occurs at any significant depth in the crust, P sub f sigma sub 3 is required. In light of this conclusion I allow P sub f to vary as necessary to allow slip on the low-angle normal fault.

  3. Fluorescence Spectrum and Decay Measurement for Hsil VS Normal Cytology Differentiation in Liquid Pap Smear Supernatant

    NASA Astrophysics Data System (ADS)

    Vaitkuviene, A.; Gegzna, V.; Juodkazis, S.; Jursenas, S.; Miasojedovas, S.; Kurtinaitiene, R.; Rimiene, J.; Vaitkus, J.

    2009-06-01

    Cervical smear material contains endo and exocervical cells, mucus and inflammative, immune cells in cases of pathology. Just not destroyed keratinocytes lay on the glass for microscopy. Liquid cytology supernatant apart other diagnostics could be used for photodiagnostic. The spectroscopic parameters suitable for Normal and HSIL cytology groups supernatant differentiation are demonstrated. The dried liquid PAP supernatant fractions—sediment and liquid were investigated. Excitation and emission matrices (EEM), supernatant fluorescence decay measured under 280 nm diode short pulse excitation and fluorescence spectroscopy by excitation with 355 nm laser light were analyzed. The differences between Normal and HSIL groups were statistically proven in the certain spectral regions. Fluorescence decay peculiarities show spectral regions consisting of few fluorophores. Obtained results on fluorescence differences in Normal and HSIL groups' supernatant shows the potency of photodiagnosis application in cervical screening.

  4. Bone Marrow Cells in Acute Lymphoblastic Leukemia Create a Proinflammatory Microenvironment Influencing Normal Hematopoietic Differentiation Fates

    PubMed Central

    Vilchis-Ordoñez, Armando; Contreras-Quiroz, Adriana; Dorantes-Acosta, Elisa; Reyes-López, Alfonso; Quintela-Nuñez del Prado, Henry Martin; Venegas-Vázquez, Jorge; Mayani, Hector; Ortiz-Navarrete, Vianney; López-Martínez, Briceida; Pelayo, Rosana

    2015-01-01

    B-cell acute lymphoblastic leukemia (B-ALL) is a serious public health problem in the pediatric population worldwide, contributing to 85% of deaths from childhood cancers. Understanding the biology of the disease is crucial for its clinical management and the development of therapeutic strategies. In line with that observed in other malignancies, chronic inflammation may contribute to a tumor microenvironment resulting in the damage of normal processes, concomitant to development and maintenance of neoplastic cells. We report here that hematopoietic cells from bone marrow B-ALL have the ability to produce proinflammatory and growth factors, including TNFα, IL-1β, IL-12, and GM-CSF that stimulate proliferation and differentiation of normal stem and progenitor cells. Our findings suggest an apparently distinct CD13+CD33+ population of leukemic cells contributing to a proinflammatory microenvironment that may be detrimental to long-term normal hematopoiesis within B-ALL bone marrow. PMID:26090405

  5. Human pluripotent stem cells as a model of trophoblast differentiation in both normal development and disease.

    PubMed

    Horii, Mariko; Li, Yingchun; Wakeland, Anna K; Pizzo, Donald P; Nelson, Katharine K; Sabatini, Karen; Laurent, Louise Chang; Liu, Ying; Parast, Mana M

    2016-07-05

    Trophoblast is the primary epithelial cell type in the placenta, a transient organ required for proper fetal growth and development. Different trophoblast subtypes are responsible for gas/nutrient exchange (syncytiotrophoblasts, STBs) and invasion and maternal vascular remodeling (extravillous trophoblasts, EVTs). Studies of early human placental development are severely hampered by the lack of a representative trophoblast stem cell (TSC) model with the capacity for self-renewal and the ability to differentiate into both STBs and EVTs. Primary cytotrophoblasts (CTBs) isolated from early-gestation (6-8 wk) human placentas are bipotential, a phenotype that is lost with increasing gestational age. We have identified a CDX2(+)/p63(+) CTB subpopulation in the early postimplantation human placenta that is significantly reduced later in gestation. We describe a reproducible protocol, using defined medium containing bone morphogenetic protein 4 by which human pluripotent stem cells (hPSCs) can be differentiated into CDX2(+)/p63(+) CTB stem-like cells. These cells can be replated and further differentiated into STB- and EVT-like cells, based on marker expression, hormone secretion, and invasive ability. As in primary CTBs, differentiation of hPSC-derived CTBs in low oxygen leads to reduced human chorionic gonadotropin secretion and STB-associated gene expression, instead promoting differentiation into HLA-G(+) EVTs in an hypoxia-inducible, factor-dependent manner. To validate further the utility of hPSC-derived CTBs, we demonstrated that differentiation of trisomy 21 (T21) hPSCs recapitulates the delayed CTB maturation and blunted STB differentiation seen in T21 placentae. Collectively, our data suggest that hPSCs are a valuable model of human placental development, enabling us to recapitulate processes that result in both normal and diseased pregnancies.

  6. Profiling of differential expression of messenger RNA in normal, benign, and metastatic prostate cell lines.

    PubMed

    Chakrabarti, Ratna; Robles, Liza D; Gibson, Jane; Muroski, Megan

    2002-12-01

    To understand the phenotypic changes associated with prostate cancer development and metastasis, we investigated differential gene expression in primary and established prostate cell lines used as models. We have used a differential display of messenger RNA (DDRT-PCR) technique using 168 primer combinations and total RNA from BPH-1, LNCaP, and PC3 cells to identify filter-based cDNA microarrays containing 18,376 nonredundant clones of genes and expressed sequence tags (EST) using mRNA from PrEC and MDAPCa2a cells to identify genes that are differentially expressed in normal, benign, and cancerous prostate cell lines. Twenty-five cDNA with a significant difference in expression of 76 candidate cDNA, as identified by DDRT-PCR and confirmed by slot-blot analysis, were selected for sequence analysis. Of these, 14 cDNA were further confirmed by Northern blot analysis. Analysis of the cDNA microarray data showed that a variety of genes/EST were up- or down-regulated in the metastatic prostate tumor cells and a majority of these genes encode cytoskeletal proteins and proteins with regulatory function. Expression profile of two EST was confirmed by reverse transcription polymerase chain reaction. We also have identified a number of genes exhibiting differential expression in prostate cancer cells, which were not known earlier to be involved in prostate cancer. This report provides a comparative analysis of differential gene expression between normal prostatic epithelial cells and prostate cancer cells, and a foundation to facilitate in-depth studies on the mechanism of prostate cancer development and metastasis.

  7. Statistical analysis of differential lissajous EMG from normal occlusion and Class III malocclusion.

    PubMed

    Deguchi, T; Garetto, L P; Sato, Y; Potter, R H; Roberts, W E

    1995-01-01

    The method of differential lissajous electromyography (DL-EMG) was applied to investigate the relationship among the integrated EMG activity, timing, and coordination of the bilateral superficial anterior temporal and masseter muscle activities in normal occlusion and Class III malocclusion subjects. In both Class III malocclusion and normal occlusion subjects, the working side muscles showed a higher mean cumulative voltage (MCV) and mean maximum peak voltage (MMPV) compared with the balancing side. In addition, a higher MCV and MMPV of the working side masseter was observed in the normal occlusion group compared with that seen in the Class III group during both right and left side chewing (p < 0.01). Discriminant analysis applied to examine the distribution, the size and the shape of DL-EMG pattern further indicated a statistical difference between subject groups (p < 0.01). Finally, there was a significantly higher percentage of clockwise DL-EMG pattern-generation in the normal group compared with that seen for Class III subjects (p < 0.01). These data indicate that, compared with normal subjects, patients with a Class III malocclusion have a demonstrably abnormal masticatory muscle balance which is well characterized by the DL-EMG method.

  8. Notch signaling is required for normal prostatic epithelial cell proliferation and differentiation.

    PubMed

    Wang, Xi-De; Leow, Ching Ching; Zha, Jiping; Tang, Zhijun; Modrusan, Zora; Radtke, Freddy; Aguet, Michel; de Sauvage, Frederic J; Gao, Wei-Qiang

    2006-02-01

    Notch pathway is crucial for stem/progenitor cell maintenance, growth and differentiation in a variety of tissues. Using a transgenic cell ablation approach, we found in our previous study that cells expressing Notch1 are crucial for prostate early development and re-growth. Here, we further define the role of Notch signaling in regulating prostatic epithelial cell growth and differentiation using biochemical and genetic approaches in ex vivo or in vivo systems. Treatment of developing prostate grown in culture with inhibitors of gamma-secretase/presenilin, which is required for Notch cleavage and activation, caused a robust increase in proliferation of epithelial cells co-expressing cytokeratin 8 and 14, lack of luminal/basal layer segregation and dramatically reduced branching morphogenesis. Using conditional Notch1 gene deletion mouse models, we found that inactivation of Notch1 signaling resulted in profound prostatic alterations, including increased tufting, bridging and enhanced epithelial proliferation. Cells within these lesions co-expressed both luminal and basal cell markers, a feature of prostatic epithelial cells in predifferentiation developmental stages. Microarray analysis revealed that the gene expression in a number of genetic networks was altered following Notch1 gene deletion in prostate. Furthermore, expression of Notch1 and its effector Hey-1 gene in human prostate adenocarcinomas were found significantly down-regulated compared to normal control tissues. Taken together, these data suggest that Notch signaling is critical for normal cell proliferation and differentiation in the prostate, and deregulation of this pathway may facilitate prostatic tumorigenesis.

  9. Unstable normal modes of low T /W dynamical instabilities in differentially rotating stars

    NASA Astrophysics Data System (ADS)

    Saijo, Motoyuki; Yoshida, Shin'ichirou

    2016-10-01

    We investigate the nature of low T /W dynamical instabilities in differentially rotating stars by means of linear perturbation. Here, T and W represent rotational kinetic energy and the gravitational binding energy of the star. This is the first attempt to investigate low T /W dynamical instabilities as a complete set of the eigenvalue problem. Our equilibrium configuration has "constant" specific angular momentum distribution, which potentially contains a singular solution in the perturbed enthalpy at a corotation radius in linear perturbation. We find the unstable normal modes of differentially rotating stars by solving the eigenvalue problem along the equatorial plane of the star, imposing the regularity condition on the center and the vanished enthalpy at the oscillating equatorial surface. We find that the existing pulsation modes become unstable due to the existence of the corotation radius inside the star. The feature of the unstable mode eigenfrequency and its eigenfunction in the linear analysis roughly agrees with that in three-dimensional hydrodynamical simulations in Newtonian gravity. Therefore, our normal mode analysis in the equatorial motion proves valid to find the unstable equilibrium stars efficiently. Moreover, the nature of the eigenfunction that oscillates between corotation and the surface radius for unstable stars requires reinterpretation of the pulsation modes in differentially rotating stars.

  10. MicroRNAs in B-cells: from normal differentiation to treatment of malignancies

    PubMed Central

    Marques, Sara Correia; Laursen, Maria Bach; Bødker, Julie Støve; Kjeldsen, Malene Krag; Falgreen, Steffen; Schmitz, Alexander; Bøgsted, Martin; Johnsen, Hans Erik; Dybkaer, Karen

    2015-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that play important post-transcriptional regulatory roles in a wide range of biological processes. They are fundamental to the normal development of cells, and evidence suggests that the deregulation of specific miRNAs is involved in malignant transformation due to their function as oncogenes or tumor suppressors. We know that miRNAs are involved in the development of normal B-cells and that different B-cell subsets express specific miRNA profiles according to their degree of differentiation. B-cell-derived malignancies contain transcription signatures reminiscent of their cell of origin. Therefore, we believe that normal and malignant B-cells share features of regulatory networks controlling differentiation and the ability to respond to treatment. The involvement of miRNAs in these processes makes them good biomarker candidates. B-cell malignancies are highly prevalent, and the poor overall survival of patients with these malignancies demands an improvement in stratification according to prognosis and therapy response, wherein we believe miRNAs may be of great importance. We have critically reviewed the literature, and here we sum up the findings of miRNA studies in hematological cancers, from the development and progression of the disease to the response to treatment, with a particular emphasis on B-cell malignancies. PMID:25622103

  11. p53-Independent, normal stem cell sparing epigenetic differentiation therapy for myeloid and other malignancies.

    PubMed

    Saunthararajah, Yogen; Triozzi, Pierre; Rini, Brian; Singh, Arun; Radivoyevitch, Tomas; Sekeres, Mikkael; Advani, Anjali; Tiu, Ramon; Reu, Frederic; Kalaycio, Matt; Copelan, Ed; Hsi, Eric; Lichtin, Alan; Bolwell, Brian

    2012-02-01

    Cytotoxic chemotherapy for acute myeloid leukemia (AML) usually produces only temporary remissions, at the cost of significant toxicity and risk for death. One fundamental reason for treatment failure is that it is designed to activate apoptosis genes (eg, TP53) that may be unavailable because of mutation or deletion. Unlike deletion of apoptosis genes, genes that mediate cell cycle exit by differentiation are present in myelodysplastic syndrome (MDS) and AML cells but are epigenetically repressed: MDS/AML cells express high levels of key lineage-specifying transcription factors. Mutations in these transcription factors (eg, CEBPA) or their cofactors (eg., RUNX1) affect transactivation function and produce epigenetic repression of late-differentiation genes that antagonize MYC. Importantly, this aberrant epigenetic repression can be redressed clinically by depleting DNA methyltransferase 1 (DNMT1, a central component of the epigenetic network that mediates transcription repression) using the deoxycytidine analogue decitabine at non-cytotoxic concentrations. The DNMT1 depletion is sufficient to trigger upregulation of late-differentiation genes and irreversible cell cycle exit by p53-independent differentiation mechanisms. Fortuitously, the same treatment maintains or increases self-renewal of normal hematopoietic stem cells, which do not express high levels of lineage-specifying transcription factors. The biological rationale for this approach to therapy appears to apply to cancers other than MDS/AML also. Decitabine or 5-azacytidine dose and schedule can be rationalized to emphasize this mechanism of action, as an alternative or complement to conventional apoptosis-based oncotherapy.

  12. DEK Proto-Oncogene Expression Interferes with the Normal Epithelial Differentiation Program

    PubMed Central

    Wise-Draper, Trisha M.; Morreale, Richard J.; Morris, Teresa A.; Mintz-Cole, Rachael A.; Hoskins, Elizabeth E.; Balsitis, Scott J.; Husseinzadeh, Nader; Witte, David P.; Wikenheiser-Brokamp, Kathryn A.; Lambert, Paul F.; Wells, Susanne I.

    2009-01-01

    Overexpression of the DEK gene is associated with multiple human cancers, but its specific roles as a putative oncogene are not well defined. DEK transcription was previously shown to be induced by the high-risk human papillomavirus (HPV) E7 oncogene via E2F and Rb pathways. Transient DEK overexpression was able to inhibit both senescence and apoptosis in cultured cells. In at least the latter case, this mechanism involved the destabilization of p53 and the decreased expression of p53 target genes. We show here that DEK overexpression disrupts the normal differentiation program in a manner that is independent of either p53 or cell death. DEK expression was distinctly repressed upon the differentiation of cultured primary human keratinocytes, and stable DEK overexpression caused epidermal thickening in an organotypic raft model system. The observed hyperplasia involved a delay in keratinocyte differentiation toward a more undifferentiated state, and expansion of the basal cell compartment was due to increased proliferation, but not apoptosis. These phenotypes were accompanied by elevated p63 expression in the absence of p53 destabilization. In further support of bona fide oncogenic DEK activities, we report here up-regulated DEK protein levels in both human papilloma virus-positive hyperplastic murine skin and a subset of human squamous cell carcinomas. We suggest that DEK up-regulation may contribute to carcinoma development at least in part through increased proliferation and retardation of differentiation. PMID:19036808

  13. Differentiating shunt-responsive normal pressure hydrocephalus from Alzheimer disease and normal aging: pilot study using automated MRI brain tissue segmentation.

    PubMed

    Serulle, Yafell; Rusinek, Henry; Kirov, Ivan I; Milch, Hannah; Fieremans, Els; Baxter, Alexander B; McMenamy, John; Jain, Rajan; Wisoff, Jeffrey; Golomb, James; Gonen, Oded; George, Ajax E

    2014-10-01

    Evidence suggests that normal pressure hydrocephalus (NPH) is underdiagnosed in day to day radiologic practice, and differentiating NPH from cerebral atrophy due to other neurodegenerative diseases and normal aging remains a challenge. To better characterize NPH, we test the hypothesis that a prediction model based on automated MRI brain tissue segmentation can help differentiate shunt-responsive NPH patients from cerebral atrophy due to Alzheimer disease (AD) and normal aging. Brain segmentation into gray and white matter (GM, WM), and intracranial cerebrospinal fluid was derived from pre-shunt T1-weighted MRI of 15 shunt-responsive NPH patients (9 men, 72.6 ± 8.0 years-old), 17 AD patients (10 men, 72.1 ± 11.0 years-old) chosen as a representative of cerebral atrophy in this age group; and 18 matched healthy elderly controls (HC, 7 men, 69.7 ± 7.0 years old). A multinomial prediction model was generated based on brain tissue volume distributions. GM decrease of 33% relative to HC characterized AD (P < 0.005). High preoperative ventricular and near normal GM volumes characterized NPH. A multinomial regression model based on gender, GM and ventricular volume had 96.3% accuracy differentiating NPH from AD and HC. In conclusion, automated MRI brain tissue segmentation differentiates shunt-responsive NPH with high accuracy from atrophy due to AD and normal aging. This method may improve diagnosis of NPH and improve our ability to distinguish normal from pathologic aging.

  14. What is the normal response to structural differentiation within the slump and straight leg raise tests?

    PubMed

    Herrington, Lee; Bendix, Katie; Cornwell, Catherine; Fielden, Nicola; Hankey, Karen

    2008-08-01

    The purpose of the study was to assess the effect of structural differentiation or sensitising manoeuvres on responses of normal subjects to standard neurodynamic tests of straight leg raise (SLR) and slump test. Eighty-eight (39 males and 49 females) asymptomatic subjects were examined (aged 18-39 mean age 21.9+/-4.1 years). Knee flexion angle was measured using a goniometer during the slump test in two conditions cervical flexion and extension. Hip flexion angle was measured using a goniometer during SLR test in two conditions; ankle dorsi-flexion and neutral. The change in knee flexion, following addition of the structural differentiating manoeuvre to the slump test, was a significant increase in knee flexion angle for both males (change in knee angle; 6.6+/-4.7 degrees /18.7+/-17.5%, p<0.01) and females (change in knee angle 5.4+/-5.8 degrees /17.6+/-23.7%, p<0.01), though showed no difference between sides (p>0.05). During the SLR test, a significant reduction in hip flexion occurred following structural differentiation for both groups (change in hip angle; males = 9.5+/-8.3 degrees /21.5+/-18.8%, p<0.01; females = 15.2+/-9.5 degrees /25.9+/-13.9%, p<0.01), though showed no difference between sides (p>0.05). Structural differentiating manoeuvres have a significant effect on test response in terms of range of movement even in normal asymptomatic individuals. These responses should be taken into account during the assessment clinical reasoning process.

  15. Differential roles of ERα and ERβ in normal and neoplastic development in the mouse mammary gland.

    PubMed

    Mehta, Rajendra G; Hawthorne, Michael; Mehta, Rajeshwari R; Torres, Karen E O; Peng, Xinjian; McCormick, David L; Kopelovich, Levy

    2014-01-01

    The present experiments were performed to determine the roles of estrogen receptors α and β (ERα and ERβ) in normal and neoplastic development in the mouse mammary gland. In wild-type mice, in vivo administration of estradiol (E) + progesterone (P) stimulated mammary ductal growth and alveolar differentiation. Mammary glands from mice in which the ERβ gene has been deleted (βERKO mice) demonstrated normal ductal growth and differentiation in response to E + P. By contrast, mammary glands from mice in which the ERα gene has been deleted (αERKO mice) demonstrated only rudimentary ductal structures that did not differentiate in response to E + P. EGF demonstrates estrogen-like activity in the mammary glands of αERKO mice: treatment of αERKO mice with EGF + P (without E) supported normal mammary gland development, induced expression of progesterone receptor (PR), and increased levels of G-protein-coupled receptor (GPR30) protein. Mammary gland development in βERKO mice treated with EGF + P was comparable to that of wild-type mice receiving EGF + P; EGF had no statistically significant effects on the induction of PR or expression of GPR30 in mammary glands harvested from either wild-type mice or βERKO mice. In vitro exposure of mammary glands to 7,12-dimethylbenz[a]anthracene (DMBA) induced preneoplastic mammary alveolar lesions (MAL) in glands from wild-type mice and βERKO mice, but failed to induce MAL in mammary glands from αERKO mice. Microarray analysis of DMBA-treated mammary glands identified 28 functional pathways whose expression was significantly different in αERKO mice versus both βERKO and wild-type mice; key functions that were differentially expressed in αERKO mice included cell division, cell proliferation, and apoptosis. The data demonstrate distinct roles for ERα and ERβ in normal and neoplastic development in the mouse mammary gland, and suggest that EGF can mimic the ERα-mediated effects of E in this organ.

  16. Intrauterine devices and adolescents.

    PubMed

    Gold, Melanie A; Johnson, Lisa M

    2008-10-01

    The purpose of this review is to inform the reader of new information published on intrauterine devices (IUDs) and adolescents. There are few studies on the use of IUDs in adolescents. The article reviews topics related to IUD use such as adolescents' knowledge of and attitudes toward IUDs, mechanism of action of copper-releasing and levonorgestrel-releasing IUDs, benefits of using IUDs with adolescents, safety, side effects, as well as noncontraceptive benefits such as management of menstrual disorders and endometriosis using IUDs. IUDs are a safe and effective long-term contraceptive method with no increase in risk of pelvic inflammatory disease, tubal infertility or ectopic pregnancies. IUDs are underutilized in the United States, especially by adolescents. Because adolescents contribute disproportionately to the epidemic of unintended pregnancy, IUDs should be considered as a first-line contraceptive choice regardless of parity. The levonorgestrel-releasing intrauterine system (LNG IUS) is a particularly good choice for adolescents because of associated noncontraceptive benefits such as decreased menstrual bleeding, dysmenorrhea and pain associated with endometriosis. There is a clear need for further studies in the use of the IUD among adolescents.

  17. A Hypothesis Testing Based Method for Normalization and Differential Expression Analysis of RNA-Seq Data

    PubMed Central

    Zhou, Yan; Wang, Guochang; Zhang, Jun; Li, Han

    2017-01-01

    Next-generation sequencing technologies have made RNA sequencing (RNA-seq) a popular choice for measuring gene expression level. To reduce the noise of gene expression measures and compare them between several conditions or samples, normalization is an essential step to adjust for varying sample sequencing depths and other unwanted technical effects. In this paper, we develop a novel global scaling normalization method by employing the available knowledge of housekeeping genes. We formulate the problem from the hypothesis testing perspective and find an optimal scaling factor that minimizes the deviation between the empirical and the nominal type I error. Applying our approach to various simulation studies and real examples, we demonstrate that it is more accurate and robust than the state-of-the-art alternatives in detecting differentially expression genes. PMID:28072846

  18. Surface modification of microparticles causes differential uptake responses in normal and tumoral human breast epithelial cells

    NASA Astrophysics Data System (ADS)

    Patiño, Tania; Soriano, Jorge; Barrios, Lleonard; Ibáñez, Elena; Nogués, Carme

    2015-06-01

    The use of micro- and nanodevices as multifunctional systems for biomedical applications has experienced an exponential growth during the past decades. Although a large number of studies have focused on the design and fabrication of new micro- and nanosystems capable of developing multiple functions, a deeper understanding of their interaction with cells is required. In the present study, we evaluated the effect of different microparticle surfaces on their interaction with normal and tumoral human breast epithelial cell lines. For this, AlexaFluor488 IgG functionalized polystyrene microparticles (3 μm) were coated with Polyethyleneimine (PEI) at two different molecular weights, 25 and 750 kDa. The effect of microparticle surface properties on cytotoxicity, cellular uptake and endocytic pathways were assessed for both normal and tumoral cell lines. Results showed a differential response between the two cell lines regarding uptake efficiency and mechanisms of endocytosis, highlighting the potential role of microparticle surface tunning for specific cell targeting.

  19. Differentiation between normal and tumor vasculature of animal and human glioma by FTIR imaging.

    PubMed

    Wehbe, Katia; Pineau, Raphael; Eimer, Sandrine; Vital, Anne; Loiseau, Hugues; Déléris, Gérard

    2010-12-01

    Malignant gliomas are very aggressive tumors, highly angiogenic and invading heterogeneously the surrounding brain parenchyma, making their resection very difficult. To overcome the limits of current diagnostic imaging techniques used for gliomas, we proposed using FTIR imaging, with a spatial resolution from 6 to 10 μm, to provide molecular information for their histological examination, based on discrimination between normal and tumor vasculature. Differentiation between normal and tumor blood vessel spectra by hierarchical cluster analysis was performed on tissue sections obtained from xenografted brain tumors of Rag-gamma mice 28 days after intracranial implantation of glioma cells, as well as for human brain tumors obtained in clinics. Classical pathological examination and immunohistochemistry were performed in parallel to the FTIR spectral imaging of brain tissues. First on the animal model, classification of FTIR spectra of blood vessels could be performed using spectral intervals based on fatty acyl (3050-2800 cm(-1)) and carbohydrate (1180-950 cm(-1)) absorptions, with the formation of two clusters corresponding to healthy and tumor parts of the tissue sections. Further data treatments on these two spectral intervals provided interpretable information about the molecular contents involved in the differentiation between normal and tumor blood vessels, the latter presenting a higher level of fatty acyl chain unsaturation and an unexpected loss of absorption from osidic residues. This classification method was further successfully tested on human glioma tissue sections. These findings demonstrate that FTIR imaging could highlight discriminant molecular markers to distinguish between normal and tumor vasculature, and help to delimitate areas of corresponding tissue.

  20. Differential regulation of igf1 and igf1r mRNA levels in the two hepatic lobes following intrauterine growth restriction and its treatment with intra-amniotic insulin-like growth factor-1 in ovine fetuses.

    PubMed

    Darp, Revati A; de Boo, Hendrina A; Phua, Hui Hui; Oliver, Mark H; Derraik, José G B; Harding, Jane E; Bloomfield, Frank H

    2010-01-01

    Intrauterine growth restriction (IUGR) has life-long health implications, yet there is no effective prenatal treatment. Daily intra-amniotic administration of insulin-like growth factor (IGF)-1 to IUGR fetal sheep improves fetal gut maturation but suppresses hepatic igf1 gene expression. Fetal hepatic blood supply is regulated, in part, by shunting of oxygen- and nutrient-rich umbilical venous blood through the ductus venosus, with the left hepatic lobe predominantly supplied by umbilical venous blood and the right hepatic lobe predominantly supplied by the portal circulation. We hypothesised that: (1) once-weekly intra-amniotic IGF-1 treatment of IUGR would be effective in promoting gut maturation; and (2) IUGR and its treatment with intra-amniotic IGF-1 would differentially affect igf1 and igf1r mRNA expression in the two hepatic lobes. IUGR fetuses received 360 µg IGF-1 or saline intra-amniotically once weekly from 110 until 131 days gestation. Treatment of IUGR fetuses with IGF-1 reversed impaired gut growth. In unembolised, untreated control fetuses, igf1 mRNA levels were 19% lower in the right hepatic lobe than in the left; in IUGR fetuses, igf1 and igf1r mRNA levels were sixfold higher in the right lobe. IGF-1 treatment reduced igf1 and igf1r mRNA levels in both lobes compared with IUGR fetuses. Thus, weekly intra-amniotic IGF-1 treatment, a clinically feasible approach, reverses the impaired gut development seen in IUGR. Furthermore, igf1 and igf1r mRNA levels are differentially expressed in the two hepatic lobes and relative expression in the two lobes is altered by both IUGR and intra-amniotic IGF-1 treatment.

  1. Differential expression in normal-adenoma-carcinoma sequence suggests complex molecular carcinogenesis in colon.

    PubMed

    Lee, Seungkoo; Bang, Seunghyun; Song, Kyuyoung; Lee, Inchul

    2006-10-01

    The majority of colon cancers develop from pre-existing adenomas. We analyzed the expression profiles in the sequence of normal colon crypts, adenomas and early-stage carcinomas using microdissected cells from tubular adenomas with foci of malignant transformation. Differentially expressed genes were detected between normal-adenoma and adenoma-carcinoma, and were grouped according to the patterns of expression changes in the sequence. Down-regulated genes in the sequence included PLA2G2A, TSPAN1, PDCD4, FCGBP, AATK, EPLIN, FABP1, AGR2, MTUS1, TSC1, galectin 4 and MT1F. PLA2G2A has been shown to suppress colon tumorigenesis in mice, but the pathobiological role in humans has been controversial. Our data showed continuous down-regulation of PLA2G2A in the sequence supporting an implication in human colon cancer. Tumor suppressor and/ or proapoptotic activities have also been reported in other genes. Up-regulated genes included ribosomal proteins, IER3 and TPR. TGF-beta2 and matrix metalloproteinase 23B were up-regulated in carcinoma but not in adenoma, supporting the pathobiological roles in malignant transformation. Differentially expressed genes partly coincided with those in the adenoma-carcinoma sequence of the stomach, which was published previously, suggesting a partial overlap between the adenoma-carcinoma sequences of the colon and stomach.

  2. Optimized surgical treatment for normal pressure hydrocephalus: comparison between gravitational and differential pressure valves.

    PubMed

    Suchorska, B; Kunz, M; Schniepp, R; Jahn, K; Goetz, C; Tonn, J C; Peraud, A

    2015-04-01

    In idiopathic normal pressure hydrocephalus (NPH) ventriculoperitoneal (VP) shunt insertion is the method of choice to improve cardinal symptoms such as gait disturbance, urge incontinence and/or dementia. With reduced compliance, the brain of the elderly is prone for overdrainage complications. This was especially true with the use of differential pressure valve implantation. The present study compares clinical outcome and complication rates after VP shunt insertion with differential pressure valves in the early years and gravitational valves since 2005. The authors reviewed patients treated at our institution for NPH since 1995. Differential pressure valves were solely used in the initial years, while the treatment regimen changed to gravitational valves in 2005. Clinical improvement/surgical success rates as well as complications were compared between the two groups. Eighty-nine patients were enrolled for the present study. Mean age at the time of surgery was 73.5 ± 6.3 years. Male patients predominated with 73, compared with 16 female patients. Median follow-up time was 28 ± 26 months. Date of last follow-up was 1st October 2013. Forty-nine patients received a gravitational valve, while 40 were treated with differential pressure valves. In the gravitational group a significant improvement was observed after shunt insertion for gait disorder, cognitive impairment and urge incontinence (p < 0.0001, resp. p = 0.004), while a significant change in the differential pressure group was only seen for gait disorder (p = 0.03) but not for cognition or urinary incontinency (p > 0.05). The risk of hygroma as a sign of shunt overdrainage requiring surgical intervention was significantly higher in the differential pressure group (5 versus 0 in the gravitational group). Patients with NPH treated with gravitational valves in the present cohort showed a more profound improvement in their initial symptoms, including gait disorder, cognitive impairment

  3. Intrauterine devices in adolescents.

    PubMed

    Davis, Ann J

    2011-10-01

    The stubborn epidemic of teen pregnancy remains a major public health problem in the United States. This review discusses the use of intrauterine devices (IUDs) in United States teens as a potential strategy to reduce teen pregnancy. Traditionally, the IUD was not thought of as an appropriate teen contraceptive method. Recently, IUDs have become a recommended contraceptive option for adolescent females. This change reflects an understanding of the safety of modern IUDs, the potential for this highly effective method to reduce teen pregnancy, and the promotion of this strategy in teens by national organizations/governmental agencies including the Centers for Disease Control and Prevention, the World Health Organization, and the American College of Obstetricians and Gynecologists. Current data do not support that IUDs affect long-term fertility or increase sexually transmitted diseases in teens. IUDs are now considered by many experts as a first-line contraceptive option for teens in the United States.

  4. Ultrasonography of intrauterine devices.

    PubMed

    Nowitzki, Kristina M; Hoimes, Matthew L; Chen, Byron; Zheng, Larry Z; Kim, Young H

    2015-07-01

    The intrauterine device (IUD) is gaining popularity as a reversible form of contraception. Ultrasonography serves as first-line imaging for the evaluation of IUD position in patients with pelvic pain, abnormal bleeding, or absent retrieval strings. This review highlights the imaging of both properly positioned and malpositioned IUDs. The problems associated with malpositioned IUDs include expulsion, displacement, embedment, and perforation. Management considerations depend on the severity of the malposition and the presence or absence of symptoms. Three-dimensional ultrasonography has proven to be more sensitive in the evaluation of more subtle findings of malposition, particularly side-arm embedment. Familiarity with the ultrasonographic features of properly positioned and malpositioned IUDs is essential.

  5. Ultrasonography of intrauterine devices

    PubMed Central

    Nowitzki, Kristina M.; Hoimes, Matthew L.; Chen, Byron; Zheng, Larry Z.; Kim, Young H.

    2015-01-01

    The intrauterine device (IUD) is gaining popularity as a reversible form of contraception. Ultrasonography serves as first-line imaging for the evaluation of IUD position in patients with pelvic pain, abnormal bleeding, or absent retrieval strings. This review highlights the imaging of both properly positioned and malpositioned IUDs. The problems associated with malpositioned IUDs include expulsion, displacement, embedment, and perforation. Management considerations depend on the severity of the malposition and the presence or absence of symptoms. Three-dimensional ultrasonography has proven to be more sensitive in the evaluation of more subtle findings of malposition, particularly side-arm embedment. Familiarity with the ultrasonographic features of properly positioned and malpositioned IUDs is essential. PMID:25985959

  6. Analysis of differential protein expression in normal and neoplastic human breast epithelial cell lines

    SciTech Connect

    Williams, K.; Chubb, C.; Huberman, E.; Giometti, C.S.

    1997-07-01

    High resolution two dimensional get electrophoresis (2DE) and database analysis was used to establish protein expression patterns for cultured normal human mammary epithelial cells and thirteen breast cancer cell lines. The Human Breast Epithelial Cell database contains the 2DE protein patterns, including relative protein abundances, for each cell line, plus a composite pattern that contains all the common and specifically expressed proteins from all the cell lines. Significant differences in protein expression, both qualitative and quantitative, were observed not only between normal cells and tumor cells, but also among the tumor cell lines. Eight percent of the consistently detected proteins were found in significantly (P < 0.001) variable levels among the cell lines. Using a combination of immunostaining, comigration with purified protein, subcellular fractionation, and amino-terminal protein sequencing, we identified a subset of the differentially expressed proteins. These identified proteins include the cytoskeletal proteins actin, tubulin, vimentin, and cytokeratins. The cell lines can be classified into four distinct groups based on their intermediate filament protein profile. We also identified heat shock proteins; hsp27, hsp60, and hsp70 varied in abundance and in some cases in the relative phosphorylation levels among the cell lines. Finally, we identified IMP dehydrogenase in each of the cell lines, and found the levels of this enzyme in the tumor cell lines elevated 2- to 20-fold relative to the levels in normal cells.

  7. Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas.

    PubMed

    Weigand, Isabel; Ronchi, Cristina L; Rizk-Rabin, Marthe; Dalmazi, Guido Di; Wild, Vanessa; Bathon, Kerstin; Rubin, Beatrice; Calebiro, Davide; Beuschlein, Felix; Bertherat, Jérôme; Fassnacht, Martin; Sbiera, Silviu

    2017-12-01

    Somatic mutations in protein kinase A catalytic α subunit (PRKACA) were found to be causative for 30-40% of cortisol-producing adenomas (CPA) of the adrenal gland, rendering PKA signalling constitutively active. In its resting state, PKA is a stable and inactive heterotetramer, consisting of two catalytic and two regulatory subunits with the latter inhibiting PKA activity. The human genome encodes three different PKA catalytic subunits and four different regulatory subunits that are preferentially expressed in different organs. In normal adrenal glands all regulatory subunits are expressed, while CPA exhibit reduced protein levels of the regulatory subunit IIβ. In this study, we linked for the first time the loss of RIIβ protein levels to the PRKACA mutation status and found the down-regulation of RIIβ to arise post-transcriptionally. We further found the PKA subunit expression pattern of different tumours is also present in the zones of the normal adrenal cortex and demonstrate that the different PKA subunits have a differential expression pattern in each zone of the normal adrenal gland, indicating potential specific roles of these subunits in the regulation of different hormones secretion.

  8. Paneth cell differentiation in the developing intestine of normal and transgenic mice.

    PubMed

    Bry, L; Falk, P; Huttner, K; Ouellette, A; Midtvedt, T; Gordon, J I

    1994-10-25

    Paneth cells represent one of the four major epithelial lineages in the mouse small intestine. It is the only lineage that migrates downward from the stem-cell zone located in the lower portion of the crypt of Lieberkühn to the crypt base. Mature Paneth cells release growth factors, digestive enzymes, and antimicrobial peptides from their apical secretory granules. Some of these factors may affect the crypt stem cell, its transit-cell descendants, differentiating villus-associated epithelial lineages, and/or the gut microflora. We used single and multilabel immunocytochemical methods to study Paneth cell differentiation during and after completion of gut morphogenesis in normal, gnotobiotic, and transgenic mice as well as in intestinal isografts. This lineage emerges coincident with cytodifferentiation of the fetal small intestinal endoderm, formation of crypts from an intervillus epithelium, and establishment of a stem-cell hierarchy. The initial differentiation program involves sequential expression of cryptdins, a phospholipase A2 (enhancing factor), and lysozyme. A dramatic increase in Paneth cell number per crypt occurs during postnatal days 14-28, when crypts proliferate by fission. Accumulation of fucosylated and sialylated glycoconjugates during this period represents the final evolution of the lineage's differentiation program. Establishment of this lineage is not dependent upon instructive interactions from the microflora. Transgenic mice containing nucleotides -6500 to +34 of the Paneth cell-specific mouse cryptdin 2 gene linked to the human growth hormone gene beginning at its nucleotide +3 inappropriately express human growth hormone in a large population of proliferating and nonproliferating cells in the intervillus epithelium up to postnatal day 5. Transgene expression subsequently becomes restricted to the Paneth cell lineage in the developing crypt. Cryptdin 2 nucleotides -6500 to +34 should be a useful marker of crypt morphogenesis and a valuable

  9. Neuronal glycosylation differentials in normal, injured and chondroitinase-treated environments

    SciTech Connect

    Kilcoyne, Michelle; Sharma, Shashank; McDevitt, Niamh; O'Leary, Claire; Joshi, Lokesh; McMahon, Siobhan S.

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer Carbohydrates are important in the CNS and ChABC has been used for spinal cord injury (SCI) treatment. Black-Right-Pointing-Pointer Neuronal glycosylation in injury and after ChABC treatment is unknown. Black-Right-Pointing-Pointer In silico mining verified that glyco-related genes were differentially regulated after SCI. Black-Right-Pointing-Pointer In vitro model system revealed abnormal sialylation in an injured environment. Black-Right-Pointing-Pointer The model indicated a return to normal neuronal glycosylation after ChABC treatment. -- Abstract: Glycosylation is found ubiquitously throughout the central nervous system (CNS). Chondroitin sulphate proteoglycans (CSPGs) are a group of molecules heavily substituted with glycosaminoglycans (GAGs) and are found in the extracellular matrix (ECM) and cell surfaces. Upon CNS injury, a glial scar is formed, which is inhibitory for axon regeneration. Several CSPGs are up-regulated within the glial scar, including NG2, and these CSPGs are key inhibitory molecules of axonal regeneration. Treatment with chondroitinase ABC (ChABC) can neutralise the inhibitory nature of NG2. A gene expression dataset was mined in silico to verify differentially regulated glycosylation-related genes in neurons after spinal cord injury and identify potential targets for further investigation. To establish the glycosylation differential of neurons that grow in a healthy, inhibitory and ChABC-treated environment, we established an indirect co-culture system where PC12 neurons were grown with primary astrocytes, Neu7 astrocytes (which overexpress NG2) and Neu7 astrocytes treated with ChABC. After 1, 4 and 8 days culture, lectin cytochemistry of the neurons was performed using five fluorescently-labelled lectins (ECA MAA, PNA, SNA-I and WFA). Usually {alpha}-(2,6)-linked sialylation scarcely occurs in the CNS but this motif was observed on the neurons in the injured environment only at day 8. Treatment

  10. [A differentiated approach to the treatment of normal-pressure glaucoma].

    PubMed

    Grigor'eva, E G

    2003-01-01

    Seventy patients with normal pressure glaucoma (NPG) were treated on the differential basis with respect to a pathogenetic disease type. The suggested complex therapy of the ischemic variation improves both the microcirculation in the optic nerve disk (OND) by administering different-effect drugs in long courses and the systemic hemodynamics (practitioners of needed skills are involved). The use of local antihypertensive drug to reduce the intraocular pressure to an individual tolerable value is important in the treatment of patients with tension-ischemic glaucoma. The process stabilized in 75.8 +/- 3.9% of patients in the main group and in 47 +/- 8.5% of patients in the control group (p < 0.05) after a follow-up of up to 2.5 years.

  11. Size evolution of ultrafine particles: Differential signatures of normal and episodic events.

    PubMed

    Joshi, Manish; Khan, Arshad; Anand, S; Sapra, B K

    2016-01-01

    The effect of fireworks on the aerosol number characteristics of atmosphere was studied for an urban mega city. Measurements were made at 50 m height to assess the local changes around the festival days. Apart from the increase in total number concentration and characteristic accumulation mode, short-term increase of ultrafine particle concentration was noted. Total number concentration varies an order of magnitude during the measurement period in which peak occurs at a frequency of approximately one per day. On integral scale, it seems not possible to distinguish an episodic (e.g. firework bursting induced aerosol emission) and a normal (ambient atmospheric changes) event. However these events could be differentiated on the basis of size evolution analysis around number concentration peaks. The results are discussed relative to past studies and inferences are drawn towards aerosol signatures of firework bursting. The short-term burst in ultrafine particle concentration can pose an inhalation hazard. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Analyzing ChIP-seq data: preprocessing, normalization, differential identification, and binding pattern characterization.

    PubMed

    Taslim, Cenny; Huang, Kun; Huang, Tim; Lin, Shili

    2012-01-01

    Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is a high-throughput antibody-based method to study genome-wide protein-DNA binding interactions. ChIP-seq technology allows scientist to obtain more accurate data providing genome-wide coverage with less starting material and in shorter time compared to older ChIP-chip experiments. Herein we describe a step-by-step guideline in analyzing ChIP-seq data including data preprocessing, nonlinear normalization to enable comparison between different samples and experiments, statistical-based method to identify differential binding sites using mixture modeling and local false discovery rates (fdrs), and binding pattern characterization. In addition, we provide a sample analysis of ChIP-seq data using the steps provided in the guideline.

  13. Experimental design, preprocessing, normalization and differential expression analysis of small RNA sequencing experiments

    PubMed Central

    2011-01-01

    Prior to the advent of new, deep sequencing methods, small RNA (sRNA) discovery was dependent on Sanger sequencing, which was time-consuming and limited knowledge to only the most abundant sRNA. The innovation of large-scale, next-generation sequencing has exponentially increased knowledge of the biology, diversity and abundance of sRNA populations. In this review, we discuss issues involved in the design of sRNA sequencing experiments, including choosing a sequencing platform, inherent biases that affect sRNA measurements and replication. We outline the steps involved in preprocessing sRNA sequencing data and review both the principles behind and the current options for normalization. Finally, we discuss differential expression analysis in the absence and presence of biological replicates. While our focus is on sRNA sequencing experiments, many of the principles discussed are applicable to the sequencing of other RNA populations. PMID:21356093

  14. A review of cognitive impairment and differential diagnosis in idiopathic normal pressure hydrocephalus

    PubMed Central

    Picascia, Marta; Zangaglia, Roberta; Bernini, Sara; Minafra, Brigida; Sinforiani, Elena; Pacchetti, Claudio

    2015-01-01

    Summary Idiopathic normal pressure hydrocephalus (iNPH) is a complex and still underestimated pathology. In the early stages, the cognitive profile is characterized mainly by impairments of attention, psychomotor speed and memory, suggesting frontal involvement; patients with more advanced iNPH show overall cognitive deterioration. The memory impairment, however, seems to be milder than that seen in Alzheimer’s disease (AD). Clinical and neuroimaging data are crucial for the diagnosis of iNPH, but the presence of different variables, such as comorbidities, and the possible overlapping with other neurodegenerative diseases, AD in particular, make the differential diagnosis difficult. To date studies seeking to identify possible biological markers have provided inconclusive results; moreover reliable indices predictive of a good response to surgery are still lacking. There is a need for further studies with longer follow-ups and for closer interaction among the different professionals involved. PMID:26727700

  15. How the differential load induced by normal fault scarps controls the distribution of monogenic volcanism

    NASA Astrophysics Data System (ADS)

    Maccaferri, F.; Acocella, V.; Rivalta, E.

    2015-09-01

    Understanding shallow magma transfer and the related vent distribution is crucial for volcanic hazard. Here we investigate how the stress induced by topographic scarps linked to normal faults affects the distribution of monogenic volcanoes at divergent plate boundaries. Our numerical models of dyke propagation below a fault scarp show that the dykes tend to propagate toward and erupt on the footwall side. This effect, increasing with the scarp height, is stronger for dykes propagating underneath the hanging wall side and decreases with the distance from the scarp. A comparison to the East African Rift System, Afar and Iceland shows that (1) the inner rift structure, which shapes the topography, controls shallow dyke propagation; (2) differential loading due to mass redistribution affects magma propagation over a broad scale range (100-105 m). Our results find application to any volcanic field with tectonics- or erosion-induced topographic variations and should be considered in any volcanic hazard assessment.

  16. Neuronal glycosylation differentials in normal, injured and chondroitinase-treated environments.

    PubMed

    Kilcoyne, Michelle; Sharma, Shashank; McDevitt, Niamh; O'Leary, Claire; Joshi, Lokesh; McMahon, Siobhán S

    2012-04-13

    Glycosylation is found ubiquitously throughout the central nervous system (CNS). Chondroitin sulphate proteoglycans (CSPGs) are a group of molecules heavily substituted with glycosaminoglycans (GAGs) and are found in the extracellular matrix (ECM) and cell surfaces. Upon CNS injury, a glial scar is formed, which is inhibitory for axon regeneration. Several CSPGs are up-regulated within the glial scar, including NG2, and these CSPGs are key inhibitory molecules of axonal regeneration. Treatment with chondroitinase ABC (ChABC) can neutralise the inhibitory nature of NG2. A gene expression dataset was mined in silico to verify differentially regulated glycosylation-related genes in neurons after spinal cord injury and identify potential targets for further investigation. To establish the glycosylation differential of neurons that grow in a healthy, inhibitory and ChABC-treated environment, we established an indirect co-culture system where PC12 neurons were grown with primary astrocytes, Neu7 astrocytes (which overexpress NG2) and Neu7 astrocytes treated with ChABC. After 1, 4 and 8 days culture, lectin cytochemistry of the neurons was performed using five fluorescently-labelled lectins (ECA MAA, PNA, SNA-I and WFA). Usually α-(2,6)-linked sialylation scarcely occurs in the CNS but this motif was observed on the neurons in the injured environment only at day 8. Treatment with ChABC was successful in returning neuronal glycosylation to normal conditions at all timepoints for MAA, PNA and SNA-I staining, and by day 8 in the case of WFA. This study demonstrated neuronal cell surface glycosylation changes in an inhibitory environment and indicated a return to normal glycosylation after treatment with ChABC, which may be promising for identifying potential therapies for neuronal regeneration strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. MicroRNA-150 Expression Induces Myeloid Differentiation of Human Acute Leukemia Cells and Normal Hematopoietic Progenitors

    PubMed Central

    Morris, Valerie A.; Zhang, Ailin; Yang, Taimei; Stirewalt, Derek L.; Ramamurthy, Ranjani; Meshinchi, Soheil; Oehler, Vivian G.

    2013-01-01

    In acute myeloid leukemia (AML) and blast crisis (BC) chronic myeloid leukemia (CML) normal differentiation is impaired. Differentiation of immature stem/progenitor cells is critical for normal blood cell function. MicroRNAs (miRNAs or miRs) are small non-coding RNAs that interfere with gene expression by degrading messenger RNAs (mRNAs) or blocking protein translation. Aberrant miRNA expression is a feature of leukemia and miRNAs also play a significant role in normal hematopoiesis and differentiation. We have identified miRNAs differentially expressed in AML and BC CML and identified a new role for miR-150 in myeloid differentiation. Expression of miR-150 is low or absent in BC CML and AML patient samples and cell lines. We have found that expression of miR-150 in AML cell lines, CD34+ progenitor cells from healthy individuals, and primary BC CML and AML patient samples at levels similar to miR-150 expression in normal bone marrow promotes myeloid differentiation of these cells. MYB is a direct target of miR-150, and we have identified that the observed phenotype is partially mediated by MYB. In AML cell lines, differentiation of miR-150 expressing cells occurs independently of retinoic acid receptor α (RARA) signaling. High-throughput gene expression profiling (GEP) studies of the AML cell lines HL60, PL21, and THP-1 suggest that activation of CEPBA, CEBPE, and cytokines associated with myeloid differentiation in miR-150 expressing cells as compared to control cells contributes to myeloid differentiation. These data suggest that miR-150 promotes myeloid differentiation, a previously uncharacterized role for this miRNA, and that absent or low miR-150 expression contributes to blocked myeloid differentiation in acute leukemia cells. PMID:24086639

  18. Responsiveness to testosterone of male gerbils from known intrauterine positions.

    PubMed

    Clark, M M; Bishop, A M; vom Saal, F S; Galef, B G

    1993-06-01

    Following either a) castration or b) both castration and implantation with capsules releasing a constant, physiological dose of testosterone, adult male Mongolian gerbils that had matured in intrauterine positions between two male fetuses still scent marked with greater frequency than did male gerbils that had matured in intrauterine positions between two female fetuses. We also found significant positive correlations between the relative frequency of scent marking exhibited by individual male gerbils when intact, after castration and after both castration and implantation with capsules releasing testosterone. Each of these findings is consistent with the view that differential exposure to testosterone, as a consequence of fetal intrauterine position, has lasting effects on the organization of scent-marking by male gerbils.

  19. Progesterone receptors in normal mammary gland: receptor modulations in relation to differentiation

    PubMed Central

    1980-01-01

    The biological basis for the observed modulation in cytoplasmic progesterone receptors (PgR) of normal mammary gland occurring during mammary development was investigated. Specifically, the relative roles of hormones vs. differentiation on (a) the decrease in PgR concentration during pregnancy and lactation and (b) the loss of mammary responsiveness to estrogen during lactation were examined. PgR were measured using the synthetic progestin, R5020, as the ligand. The hormones estrogen and progesterone were tested in vivo for their effect of PgR concentration. Mammary gland differentiation was assessed morphologically and by measuring enzymatically active alpha- lactalbumin. These studies show that there is a stepwise decrease in PgR that occurs in two stages. The first decrease is completed by day 12 of pregnancy and the second decrease occurs only after parturition. There appears to be a hormonal basis for the first decrease and it appears to be caused by the negative effect of progesterone on estrogen- mediated increase in PgR. In direct contrast, the absence of PgR during lactation and the mammary tissue insensitivity to estrogenic stimulation of PgR were not related to the hormonal milieu of lactation but were directly related to the secretory state of the mammary gland and lactation per se. PMID:7410476

  20. lncRNA requirements for mouse acute myeloid leukemia and normal differentiation.

    PubMed

    Delás, M Joaquina; Sabin, Leah R; Dolzhenko, Egor; Knott, Simon Rv; Munera Maravilla, Ester; Jackson, Benjamin T; Wild, Sophia A; Kovacevic, Tatjana; Stork, Eva Maria; Zhou, Meng; Erard, Nicolas; Lee, Emily; Kelley, David R; Roth, Mareike; Barbosa, Ine S Am; Zuber, Johannes; Rinn, John L; Smith, Andrew D; Hannon, Gregory J

    2017-09-06

    A substantial fraction of the genome is transcribed in a cell type-specific manner, producing long non-coding RNAs (lncRNAs), rather than protein-coding transcripts. Here we systematically characterize transcriptional dynamics during hematopoiesis and in hematological malignancies. Our analysis of annotated and de novo assembled lncRNAs showed many are regulated during differentiation and mis-regulated in disease. We assessed lncRNA function via an in vivo RNAi screen in a model of acute myeloid leukemia. This identified several lncRNAs essential for leukemia maintenance, and found that a number act by promoting leukemia stem cell signatures. Leukemia blasts show a myeloid differentiation phenotype when these lncRNAs were depleted, and our data indicates that this effect is mediated via effects on the c-MYC oncogene. Bone marrow reconstitutions showed that a lncRNA expressed across all progenitors was required for the myeloid lineage, whereas the other leukemia-induced lncRNAs were dispensable in the normal setting.

  1. lncRNA requirements for mouse acute myeloid leukemia and normal differentiation

    PubMed Central

    Knott, Simon RV; Munera Maravilla, Ester; Jackson, Benjamin T; Wild, Sophia A; Kovacevic, Tatjana; Stork, Eva Maria; Zhou, Meng; Erard, Nicolas; Lee, Emily; Kelley, David R; Roth, Mareike; Barbosa, Inês AM; Zuber, Johannes; Rinn, John L

    2017-01-01

    A substantial fraction of the genome is transcribed in a cell-type-specific manner, producing long non-coding RNAs (lncRNAs), rather than protein-coding transcripts. Here, we systematically characterize transcriptional dynamics during hematopoiesis and in hematological malignancies. Our analysis of annotated and de novo assembled lncRNAs showed many are regulated during differentiation and mis-regulated in disease. We assessed lncRNA function via an in vivo RNAi screen in a model of acute myeloid leukemia. This identified several lncRNAs essential for leukemia maintenance, and found that a number act by promoting leukemia stem cell signatures. Leukemia blasts show a myeloid differentiation phenotype when these lncRNAs were depleted, and our data indicates that this effect is mediated via effects on the MYC oncogene. Bone marrow reconstitutions showed that a lncRNA expressed across all progenitors was required for the myeloid lineage, whereas the other leukemia-induced lncRNAs were dispensable in the normal setting. PMID:28875933

  2. Quantitative Analysis of Differential Proteome Expression in Bladder Cancer vs. Normal Bladder Cells Using SILAC Method

    PubMed Central

    Yang, Ganglong; Xu, Zhipeng; Lu, Wei; Li, Xiang; Sun, Chengwen; Guo, Jia; Xue, Peng; Guan, Feng

    2015-01-01

    The best way to increase patient survival rate is to identify patients who are likely to progress to muscle-invasive or metastatic disease upfront and treat them more aggressively. The human cell lines HCV29 (normal bladder epithelia), KK47 (low grade nonmuscle invasive bladder cancer, NMIBC), and YTS1 (metastatic bladder cancer) have been widely used in studies of molecular mechanisms and cell signaling during bladder cancer (BC) progression. However, little attention has been paid to global quantitative proteome analysis of these three cell lines. We labeled HCV29, KK47, and YTS1 cells by the SILAC method using three stable isotopes each of arginine and lysine. Labeled proteins were analyzed by 2D ultrahigh-resolution liquid chromatography LTQ Orbitrap mass spectrometry. Among 3721 unique identified and annotated proteins in KK47 and YTS1 cells, 36 were significantly upregulated and 74 were significantly downregulated with >95% confidence. Differential expression of these proteins was confirmed by western blotting, quantitative RT-PCR, and cell staining with specific antibodies. Gene ontology (GO) term and pathway analysis indicated that the differentially regulated proteins were involved in DNA replication and molecular transport, cell growth and proliferation, cellular movement, immune cell trafficking, and cell death and survival. These proteins and the advanced proteome techniques described here will be useful for further elucidation of molecular mechanisms in BC and other types of cancer. PMID:26230496

  3. Homeodomain-interacting protein kinase 2 plays an important role in normal terminal erythroid differentiation.

    PubMed

    Hattangadi, Shilpa M; Burke, Karly A; Lodish, Harvey F

    2010-06-10

    Gene-targeting experiments report that the homeodomain-interacting protein kinases 1 and 2, Hipk1 and Hipk2, are essential but redundant in hematopoietic development because Hipk1/Hipk2 double-deficient animals exhibit severe defects in hematopoiesis and vasculogenesis, whereas the single knockouts do not. These serine-threonine kinases phosphorylate and consequently modify the functions of several important hematopoietic transcription factors and cofactors. Here we show that Hipk2 knockdown alone plays a significant role in terminal fetal liver erythroid differentiation. Hipk1 and Hipk2 are highly induced during primary mouse fetal liver erythropoiesis. Specific knockdown of Hipk2 inhibits terminal erythroid cell proliferation (explained in part by impaired cell-cycle progression as well as increased apoptosis) and terminal enucleation as well as the accumulation of hemoglobin. Hipk2 knockdown also reduces the transcription of many genes involved in proliferation and apoptosis as well as important, erythroid-specific genes involved in hemoglobin biosynthesis, such as alpha-globin and mitoferrin 1, demonstrating that Hipk2 plays an important role in some but not all aspects of normal terminal erythroid differentiation.

  4. Significance of differential metal loads in normal versus cancerous cadaver tissues - biomed 2010.

    PubMed

    Farah, Ibrahim O; Trimble, Quannesha; Ndebele, Kenneth; Mawson, Anthony

    2010-01-01

    The bodys elemental/ metal loads are known to exert essential influence in maintaining normal and abnormal metabolism leading to eventual pathology of some forms of cancer phenotypes. Accumulation of potentially toxic or nonessential trace metals has been observed but not highly noted as an active factor in toxicogenesis and in the development of many diseases including cancers. The compositional balance and distribution of trace metals in various body tissues are essential key players in homeostasis in life. To this end the etiology of diseases including cancer has been linked with the accumulation of potentially toxic or nonessential trace metals. However, scarce literature / experimental evidence exist as a scientific proof that metal concentrations play important role in the etiology and development of cancer phenotypes. The aim of this study was to investigate the differential relationship of metal concentrations and profiles in cancer and normal tissues from cadavers of humans. The originated hypothesis was that elemental / metal concentrations and profiles seen in post mortem will show significant differences between normal and cancer-derived tissues as well as between various tissue types in humans. This study also establishes critical elemental /metal profiles that may be relevant in providing correlations with the development of three major cancers. Normal human and tumor tissues of cadaverous lung, breast and liver tissues used in this study were obtained from US Biomax Company. Tissue samples were prepared using standardized digestion procedures necessary for use with the Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). This equipment was utilized to determine the concentrations and profiles of 21 elements including Ag, Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Na, Ni, Pb, Sb, Se, Sr, Tl, V, and Zn. Twelve major elements of Al, Ba, Ca, Cr, Cu, Fe, Mg, Na, Pb, Se, Sr, and Zn were found to be significantly different in term of their

  5. Erythropoietin triggers a burst of GATA-1 in normal human erythroid cells differentiating in tissue culture.

    PubMed Central

    Dalyot, N; Fibach, E; Ronchi, A; Rachmilewitz, E A; Ottolenghi, S; Oppenheim, A

    1993-01-01

    GATA-1 is a central transcription-activator of erythroid differentiation. In the present work we have studied the kinetics of its expression and activity during development of normal human erythroid progenitors, grown in primary cultures. In response to the addition of erythropoietin (Epo), the cells undergo proliferation and differentiation in a synchronized fashion. This recently developed experimental system allows biochemical dissection of erythroid differentiation in a physiological meaningful environment. No DNA-binding activity of GATA-1 could be detected before the addition of Epo, although a very low level of mRNA was observed. Following Epo addition there was a sharp parallel rise in both mRNA and DNA-binding activity, consistent with positive autoregulation of the GATA-1 gene. After reaching a peak on day 7-9, both mRNA and protein activity decreased. The binding activity of the ubiquitous factor SP1 showed a biphasic pattern; its second peak usually coincided with the GATA-1 peak, suggesting that SP1 also plays a specific role in erythroid maturation. The highest activity of GATA-1 per erythroid cell was found on day 6-8, immediately preceding the major rise in globin gene mRNA and in the number of hemoglobinized cells. The results imply that a high level of GATA-1 activity is necessary for globin gene expression and erythroid maturation, suggesting that a requirement for a threshold concentration of GATA-1 is part of the mechanism that determines the final steps of erythroid maturation. Images PMID:8371977

  6. Utility of ADC measurement on diffusion-weighted MRI in differentiation of prostate cancer, normal prostate and prostatitis.

    PubMed

    Esen, Meltem; Onur, Mehmet Ruhi; Akpolat, Nusret; Orhan, Irfan; Kocakoc, Ercan

    2013-08-01

    To determine the utility of apparent diffusion coefficient (ADC) values in differentiation of prostate cancer from normal prostate parenchyma and prostatitis we obtained ADC values of 50 patients at b 100, 600 and 1,000 s/mm(2) diffusion gradients. The ADC values of prostate cancer group were significantly lower than normal prostate and prostatitis group at b 600 and 1,000 s/mm(2) gradients. The ADC values at high diffusion gradients may be used in differentiation prostate cancer from normal prostate and prostatitis.

  7. Invariant manifolds of an autonomous ordinary differential equation from its generalized normal forms.

    PubMed

    Palacián, Jesús

    2003-12-01

    A method to approximate some invariant sets of dynamical systems defined through an autonomous m-dimensional ordinary differential equation is presented. Our technique is based on the calculation of formal symmetries and generalized normal forms associated with the system of equations, making use of Lie transformations for smooth vector fields. Once a symmetry is determined up to a certain order, a reduction map allows us to pass from the equation in normal form to a related equation in a certain reduced space, the so-called reduced system of dimension s

  8. Kinematic differentiation of prosodic categories in normal and disordered language development.

    PubMed

    Goffman, Lisa

    2004-10-01

    Prosody is complex and hierarchically organized but is realized as rhythmic movement sequences. Thus, observations of the development of rhythmic aspects of movement can provide insight into links between motor and language processes, specifically whether prosodic distinctions (e.g., feet and prosodic words) are instantiated in rhythmic movement output. This experiment examined 4-7-year-old children's (both normally developing and specifically language impaired) and adults' productions of prosodic sequences that were controlled for phonetic content but differed in morphosyntactic structure (i.e., content vs. function words). Primary analyses included kinematic measures of rhythmic structure (i.e., amplitude and duration of movements in weak vs. strong syllables) across content and function contexts. Findings showed that at the level of articulatory movement, adults produced distinct rhythmic categories across content and function word contexts, whereas children did not. Children with specific language impairment differed from normally developing peers only in their ability to produce well-organized and stable rhythmic movements, not in the differentiation of prosodic categories.

  9. Statistics of differential Lissajous EMG for normal occlusion and Class II malocclusion.

    PubMed

    Deguchi, T; Kumai, T; Garetto, L

    1994-01-01

    Differential Lissajous electromyography (DL-EMG), a method of representing the simultaneous EMG values of two paired muscles as a single, continuous figure, was used in chewing tests with a sample of Japanese women having normal occlusion compared with a like group of Japanese female adolescents, having Class II, Division 1 malocclusion. For the normal sample, the DL-EMG figures described by the coordinated activity of the bilateral temporal and masseter muscles during chewing gum mastication typically appeared as repetitions of loops. Statistical data were gathered on the total EMG voltages, and on the location, rotational direction, and orientations of the DL-EMG loops when graphed onto Cartesian coordinates. These data were compared with those taken from the Class II sample. Significant differences were observed in the latter group for the EMG voltage levels of the balancing-side masseter muscles. The DL-EMG figures of the Class II group also showed irregularities in the shapes, locations, rotational directions, and orientations of the loops, indicative of irregular masticatory patterns. These data suggest that with sufficient control of factors such as age and sex, electromyography and especially DL-EMG techniques can be useful for characterizing masticatory differences between various occlusal groups.

  10. Surface modification of microparticles causes differential uptake responses in normal and tumoral human breast epithelial cells

    PubMed Central

    Patiño, Tania; Soriano, Jorge; Barrios, Lleonard; Ibáñez, Elena; Nogués, Carme

    2015-01-01

    The use of micro- and nanodevices as multifunctional systems for biomedical applications has experienced an exponential growth during the past decades. Although a large number of studies have focused on the design and fabrication of new micro- and nanosystems capable of developing multiple functions, a deeper understanding of their interaction with cells is required. In the present study, we evaluated the effect of different microparticle surfaces on their interaction with normal and tumoral human breast epithelial cell lines. For this, AlexaFluor488 IgG functionalized polystyrene microparticles (3 μm) were coated with Polyethyleneimine (PEI) at two different molecular weights, 25 and 750 kDa. The effect of microparticle surface properties on cytotoxicity, cellular uptake and endocytic pathways were assessed for both normal and tumoral cell lines. Results showed a differential response between the two cell lines regarding uptake efficiency and mechanisms of endocytosis, highlighting the potential role of microparticle surface tunning for specific cell targeting. PMID:26068810

  11. Contraception with intrauterine devices.

    PubMed

    Parr, E L

    1973-05-01

    A review of the history of contraception with intrauterine devices, characteristics of present devices, and directions of current research is presented. The serious need for population control is not yet being met by today's inconvenient, ineffective, or unsafe methods. Intrauterine devices have been best for international family planning programs because they are cheap, easily installed, and provide continuous protection. There are many different models that have been and are being used, with different effectiveness and complication rates. The most commonly used today is the Lippes Loop, with a pregnancy rate of 2.8/100 years of woman use and an expulsion rate of 10.4. Most of these failures occur in the first few months of use, after which these rates are greatly reduced. The removal rate because of bleeding or pain for the Lippes device is 14.0. Other devices commonly used have pregnancy rates ranging 1.3-4.7, expulsion rates of 2.6-25.8, and removal rates of 13.5-22.1. Expulsion is directly related to the size and design of the IUD and the age and parity of t,e recipient. It is important to match the size of the device used to the individual characteristics of the patient. Research is seeking a design that will implant itself in the endometrium to resist expulsion, but not too deeply so that it is covered. Removal for bleeding and pain remains the most frequent complication of the IUD, and it partly depends on the skill of the inserting physician and how well the patient is psychologically prepared for side effects in the first months of use. Pregnancy is the most significant IUD complication. The key to an effective IUD is an understanding of its antifertility mechanism, which has thus far eluded researchers. The IUD prevents implantation of the blastocyst in the uterine wall, which may be due to a foreign-body reaction in the endometrium. IUDs with copper cause a greater reaction than plastic devices and provide hope for a very effective device; particularly

  12. Heme Oxygenase-1 Determines the Differential Response of Breast Cancer and Normal Cells to Piperlongumine

    PubMed Central

    Lee, Ha-Na; Jin, Hyeon-Ok; Park, Jin-Ah; Kim, Jin-Hee; Kim, Ji-Young; Kim, BoRa; Kim, Wonki; Hong, Sung-Eun; Lee, Yun-Han; Chang, Yoon Hwan; Hong, Seok-Il; Hong, Young Jun; Park, In-Chul; Surh, Young-Joon; Lee, Jin Kyung

    2015-01-01

    Piperlongumine, a natural alkaloid isolated from the long pepper, selectively increases reactive oxygen species production and apoptotic cell death in cancer cells but not in normal cells. However, the molecular mechanism underlying piperlongumine-induced selective killing of cancer cells remains unclear. In the present study, we observed that human breast cancer MCF-7 cells are sensitive to piperlongumine-induced apoptosis relative to human MCF-10A breast epithelial cells. Interestingly, this opposing effect of piperlongumine appears to be mediated by heme oxygenase-1 (HO-1). Piperlongumine upregulated HO-1 expression through the activation of nuclear factor-erythroid-2-related factor-2 (Nrf2) signaling in both MCF-7 and MCF-10A cells. However, knockdown of HO-1 expression and pharmacological inhibition of its activity abolished the ability of piperlongumine to induce apoptosis in MCF-7 cells, whereas those promoted apoptosis in MCF-10A cells, indicating that HO-1 has anti-tumor functions in cancer cells but cytoprotective functions in normal cells. Moreover, it was found that piperlongumine-induced Nrf2 activation, HO-1 expression and cancer cell apoptosis are not dependent on the generation of reactive oxygen species. Instead, piperlongumine, which bears electrophilic α,β-unsaturated carbonyl groups, appears to inactivate Kelch-like ECH-associated protein-1 (Keap1) through thiol modification, thereby activating the Nrf2/HO-1 pathway and subsequently upregulating HO-1 expression, which accounts for piperlongumine-induced apoptosis in cancer cells. Taken together, these findings suggest that direct interaction of piperlongumine with Keap1 leads to the upregulation of Nrf2-mediated HO-1 expression, and HO-1 determines the differential response of breast normal cells and cancer cells to piperlongumine. PMID:25813625

  13. Differential expression of the cardiac ryanodine receptor in normal and arrhythmogenic right ventricular cardiomyopathy canine hearts.

    PubMed

    Meurs, Kathryn M; Lacombe, Veronique A; Dryburgh, Keith; Fox, Philip R; Reiser, Peter R; Kittleson, Mark D

    2006-08-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a form of cardiomyopathy characterized by ventricular tachyarrhythmias and a fibrofatty infiltrate that is believed to preferentially affect the right ventricle. Mutations in the cardiac ryanodine receptor (RyR2) gene have been identified in some human families with a unique form of ARVC, ARVC2. Although the RyR2 has significant importance in excitation-contraction coupling across the ventricles, mutations in the gene encoding for it appear to have the greatest impact on the right ventricle in ARVC2. Using a canine model (boxer), the RyR2 protein and message RNA in the right ventricle, left ventricle and interventricular septum from normal dogs and dogs with ARVC were investigated by immunoblotting and real time PCR. The cardiac RyR2 message and protein expression were differentially expressed across the cardiac walls in the normal heart, with the lowest concentration expressed in the right ventricle (P < 0.05). The message and protein expression of the RyR2 were reduced in all chambers in the canine model of ARVC. We propose that the increased susceptibility of the right ventricle to ARVC may be associated with the lower baseline protein concentration of RyR2 in the normal right ventricle compared to the left ventricle and interventricular septum and that all three areas are equally affected in this canine model of ARVC. Using this naturally occurring model of canine ARVC, we may have provided new insights into the pathogenesis of this cardiomyopathy.

  14. Do Mesenchymal Stem Cells Derived From Atypical Lipomatous Tumors Have Greater Differentiation Potency Than Cells From Normal Adipose Tissues?

    PubMed

    Inatani, Hiroyuki; Yamamoto, Norio; Hayashi, Katsuhiro; Kimura, Hiroaki; Takeuchi, Akihiko; Miwa, Shinji; Higuchi, Takashi; Abe, Kensaku; Taniguchi, Yuta; Yamada, Satoshi; Asai, Kiyofumi; Otsuka, Takanobu; Tsuchiya, Hiroyuki

    2017-06-01

    The p53 protein in mesenchymal stem cells (MSCs) regulates differentiation to osteogenic or adipogenic lineage. Because p53 function is depressed in most malignancies, if MSCs in malignancy also have p53 hypofunction, differentiation therapy to osteogenic or adipogenic lineage may be an effective treatment. We therefore wished to begin to explore this idea by evaluating atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) cells, because murine double minute 2 (MDM2) gene amplification, which leads to p53 hypofunction, is found in almost all ALT/WDLs. We compared osteogenic and adipogenic differentiation potency between MSCs isolated and cultured from normal adipose tissues and ALT/WDLs from the same patients. During tumor resections in six patients with ALT/WDL, we analyzed 3 mL of tumor, and for comparison, we harvested a similar amount of normal-appearing subcutaneous adipose tissue from an area remote from the tumor for comparison. Adipogenic differentiation potency was quantitatively assessed using spectrometry after oil red O staining. Osteogenic differentiation potency was semiquantitatively assessed by measuring a specific colored area after alkaline phosphatase (ALP) and alizarin red S staining. ALP is related to preosseous cellular metabolism, and alizarin red is related to calcium deposits in cell culture. There were three observers for each assessment, and each assessment (including induced-differentiation and histologic analysis) was performed in duplicate. We then analyzed the mechanism of the difference of osteogenic differentiation potency using the MDM2-specific inhibitor Nutlin-3 at various concentrations. In terms of adipogenic differentiation potency, contrary to our expectations, more fatty acid droplets were observed in MSCs derived from normal fat than in MSCs derived from ALT/WDL, although we found no significant difference between MSCs derived from ALT/WDL and MSCs derived from normal fat; the mean differentiation potency

  15. Intrauterine contraception: from silver ring to intrauterine contraceptive implant.

    PubMed

    Thiery, M

    2000-06-01

    Gräfenberg introduced his silver ring in 1928 and by his classic paper, published in 1931, provided intrauterine contraception with a scientific basis. For largely non-medical reasons, the Gräfenberg ring vanished from the scene a few years later, and it took almost 30 years before the method was rehabilitated as a result of a change in mental attitude toward birth control, the awareness of world population explosion, and the introduction of improved intrauterine devices (IUDs). The United States became the epicenter of IUD research in the 1960s but, due to adverse publicity and the threat of litigation, the pendulum swung and European investigators took over the job of improving the IUD. Proceeding from Dr Gräfenberg's classic paper, the major steps in the evolution of the intrauterine devices are retraced with focus on the scientists who were innovative in the field.

  16. Keratinocytes display normal proliferation, survival and differentiation in conditional beta4-integrin knockout mice.

    PubMed

    Raymond, Karine; Kreft, Maaike; Janssen, Hans; Calafat, Jero; Sonnenberg, Arnoud

    2005-03-01

    The alpha6beta4 integrin is located at the basal surface of keratinocytes, in hemidesmosomal structures that mediate stable adhesion of epidermal cells to the underlying basement membrane component laminin-5. The absence of alpha6beta4 integrin causes junctional epidermolysis bullosa, a severe blistering disease of the skin leading to perinatal death, confirming its essential role in mediating strong keratinocyte adhesion. Several studies have suggested that alpha6beta4 integrin can also regulate signaling cascades that control cell proliferation, survival and migration through a mechanism independent of its adhesive function. We have generated a conditional knockout mouse strain, in which the gene encoding the beta4 integrin subunit (Itgb4) was inactivated only in small stretches of the skin. These mice were viable and permitted an accurate analysis of the consequences of the loss of beta4 on various biological processes by comparing beta4-positive and -negative parts of the skin in the same animal. Despite the complete loss of hemidesmosomes in regions lacking alpha6beta4 integrin, the distribution of a range of adhesion receptors and basement membrane proteins was unaltered. Moreover, loss of alpha6beta4 did not affect squamous differentiation, proliferation or survival, except for areas in which keratinocytes had detached from the basement membrane. These in vivo observations were confirmed in vitro by using immortalized keratinocytes - derived from beta4-subunit conditional knockout mice - from which the gene encoding beta4 had been deleted by Cre-mediated recombination. Consistent with the established role of alpha6beta4 in adhesion strengthening, its loss from cells was found to increase their motility. Our findings clearly demonstrate that, after birth, epidermal differentiation, proliferation and survival all proceed normally in the absence of alpha6beta4, provided that cell adhesion is not compromised.

  17. In vivo brain glucose measurements: differential normal pulse voltammetry with enzyme-modified carbon fiber microelectrodes.

    PubMed

    Netchiporouk, L I; Shram, N F; Jaffrezic-Renault, N; Martelet, C; Cespuglio, R

    1996-12-15

    The enzyme glucose oxidase was immobilized on the surface of carbon fiber microelectrodes (CFMEs) either by cross-linking in glutaraldehyde vapor or by enzyme entrapment in electropolymerized films of m-phenylenediamine or resorcinol. The cross-linked enzymatic layer was, in the given conditions, covered with an additional membrane of Nafion or cellulose acetate. The prepared glucose sensors were tested using differential normal pulse voltammetry (DNPV, in which the scan comprises successive double pulses ("prepulse and pulse"), the prepulses are of increasing amplitude, and the current measured is the differential of the current existing between each prepulse and pulse). With properly chosen DNPV parameters, the response to glucose presented a peak at a potential of about 1 V versus an Ag/AgC1-reference, owing to the oxidation of enzymatically produced hydrogen peroxide. The calibration curves obtained (peak height/glucose concentration) were linear from 0.3-0.5 up to 1.5-6.5 mM and showed a sensitivity ranging from 1.4 up to 34.5 mA M-1 cm-2, depending on the sensor type. The DNPV response to glucose exhibited an essential insensitivity toward easily oxidizable interfering substances such as ascorbic acid and acetaminophen present at physiological concentrations. Peptides, the interfering species typical of the cerebral medium, were effectively retained by the above additional membranes. Concentration values of glucose in plasma and cerebrospinal fluid, determined in vitro from the DNPV peak height, agreed well with those measured by standard procedures. In the anesthetized rat, extracellular brain concentration of glucose was also monitored during administration of either insulin or glucagon. Under such pharmacological conditions, the changes observed in the peak height were in perfect agreement with the known effects induced by both substances.

  18. Aging and insulin signaling differentially control normal and tumorous germline stem cells.

    PubMed

    Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

    2015-02-01

    Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC-male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging.

  19. Vanadium compounds discriminate hepatoma and normal hepatic cells by differential regulation of reactive oxygen species.

    PubMed

    Wang, Qin; Liu, Tong-Tong; Fu, Ying; Wang, Kui; Yang, Xiao-Gai

    2010-09-01

    Our previous study indicated that vanadium compounds can block cell cycle progression at the G1/S phase in human hepatoma HepG2 cells via a highly activated extracellular signal-regulated protein kinase (ERK) signal. To explore their differential action on normal cells, we investigated the response of an immortalized hepatic cell line, L02 cells. The results demonstrated that a higher concentration of vanadium compounds was needed to inhibit L02 proliferation, which was associated with S and G2/M cell cycle arrest. In addition, in contrast to insignificant reactive oxygen species (ROS) generation in HepG2 cells, all of the vanadium compounds resulted significant increases in both O2.- and H2O2 levels in L02 cells. At the same time, ERK and c-Jun N-terminal kinase (JNK) as well as cell division control protein 2 homolog (Cdc2) were found to be highly phosphorylated, which could be counteracted with the antioxidant N-acetylcysteine (NAC). The current study also demonstrated that both the ERK and the JNK pathways contributed to the cell cycle arrest induced by vanadium compounds in L02 cells. More importantly, it was found that although NAC can ameliorate the cytotoxicity of vanadium compounds in L02 cells, it did not decrease their cytotoxicity in HepG2 cells. It thus shed light on the potential therapeutic applications of vanadium compounds with antioxidants as synergistic agents to reduce their toxicities in human normal cells without affecting their antitumor activities in cancer cells.

  20. Aging and insulin signaling differentially control normal and tumorous germline stem cells

    PubMed Central

    Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

    2015-01-01

    Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC–male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging. PMID:25470527

  1. Differential expression and regional distribution of aquaporins in amnion of normal and gestational diabetic pregnancies.

    PubMed

    Bednar, Amy D; Beardall, Michael K; Brace, Robert A; Cheung, Cecilia Y

    2015-03-01

    The region of the amnion overlying the placenta plays an active role in fluid exchange between amniotic fluid and fetal blood perfusing the surface of the placenta, whereas little transfer occurs across the reflected amnion that contacts the membranous chorion. Because aquaporins (AQPs) facilitate rapid movement of water across cells, we hypothesized that AQP gene expression in placental amnion is higher than in reflected amnion. Furthermore, because gestational diabetes mellitus (GDM) is often associated with polyhydramnios, we hypothesized that amnion AQP gene expression is reduced when amniotic fluid volume is elevated. Human placental and reflected amnion were obtained at cesarean delivery and subjected to relative quantitation of AQP mRNA by real-time RT-qPCR and proteins by western immunoblot. Amnion mRNA levels of five AQPs differed by up to 400-fold (P < 0.001), with AQP1 and AQP3 most abundant, AQP8 least and AQP9 and AQP11 intermediately expressed. Aquaporin proteins showed a similar profile. Aquaporin mRNA abundance was higher (P < 0.001) in placental than reflected amnion, whereas protein levels were lower (P < 0.01). In GDM pregnancies, neither AQP mRNA nor protein levels were different from normal. There was no correlation between AQP mRNA or protein levels with the amniotic fluid index in normal or GDM subjects. We conclude that there is a strong differential expression profile among individual AQPs and between regions of the amnion. These findings suggest differences in contribution of individual AQPs to water transport in the two regions of the amnion. Furthermore, AQP expression in the amnion is not altered in patients with GDM.

  2. Intrauterine devices: an update.

    PubMed

    Hardeman, Julia; Weiss, Barry D

    2014-03-15

    Three intrauterine devices (IUDs) are available in the United States: the copper T 380A and two levonorgestrel-releasing IUDs, one that releases 20 mcg of levonorgestrel per 24 hours, and one that releases 14 mcg per 24 hours. All are safe and effective methods of contraception that work predominantly by prefertilization mechanisms. The copper T 380A IUD may be placed in nonpregnant women at any time in the menstrual cycle. The prescribing information for the 20- and 14-mcg levonorgestrel-releasing IUDs advises that insertion occur during the first seven days of menses. Insertion immediately after vaginal or cesarean delivery may be considered with the copper T 380A and the 20-mcg levonorgestrel-releasing IUDs; however, expulsion rates are higher than with delayed postpartum insertion. The prescribing information for both levonorgestrel-releasing IUDs advises a waiting period of six weeks postpartum or following second-trimester pregnancy loss. Current guidelines indicate that IUDs are acceptable for use in nulliparous women, in adolescents, and in women who are breastfeeding. They may also be used in women who have a history of sexually transmitted infection, although screening is recommended. IUDs should not be inserted for at least three months after resolution of a sexually transmitted infection. Neither antibiotic prophylaxis nor misoprostol use before IUD insertion is beneficial. If pregnancy occurs, the IUD should be removed if feasible. Possible side effects of levonorgestrel-releasing IUDs include headaches, nausea, hair loss, breast tenderness, depression, decreased libido, ovarian cysts, oligomenorrhea, and amenorrhea. The main side effect of the copper T 380A IUD is increased menstrual bleeding, which may continue even with long-term use.

  3. Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain

    PubMed Central

    Montoya, Julio Cesar; Fajardo, Dianora; Peña, Angela; Sánchez, Adalberto; Domínguez, Martha C; Satizábal, José María

    2014-01-01

    Background: The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. Objective: To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. Methods: There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. Results: Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously identified brain structures play a crucial role in the learning process, in different class of memory and in motor skills. Conclusion: The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition. PMID:25767303

  4. Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain.

    PubMed

    Montoya, Julio Cesar; Fajardo, Dianora; Peña, Angela; Sánchez, Adalberto; Domínguez, Martha C; Satizábal, José María; García-Vallejo, Felipe

    2014-01-01

    The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously identified brain structures play a crucial role in the learning process, in different class of memory and in motor skills. The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition.

  5. Differential eye movements in mild traumatic brain injury versus normal controls.

    PubMed

    Cifu, David X; Wares, Joanna R; Hoke, Kathy W; Wetzel, Paul A; Gitchel, George; Carne, William

    2015-01-01

    Objective measures to diagnose and to monitor improvement of symptoms following mild traumatic brain injury (mTBI) are lacking. Computerized eye tracking has been advocated as a rapid, user friendly, and field-ready technique to meet this need. Eye-tracking data collected via a head-mounted, video-based binocular eye tracker was used to examine saccades, fixations, and smooth pursuit movement in military Service Members with postconcussive syndrome (PCS) and asymptomatic control subjects in an effort to determine if eye movement differences could be found and quantified. Sixty Military Service Members with PCS and 26 asymptomatic controls. The diagnosis of mTBI was confirmed by the study physiatrist's history, physical examination, and a review of any medical records. Various features of saccades, fixation and smooth pursuit eye movements were analyzed. Subjects with symptomatic mTBI had statistically larger position errors, smaller saccadic amplitudes, smaller predicted peak velocities, smaller peak accelerations, and longer durations. Subjects with symptomatic mTBI were also less likely to follow a target movement (less primary saccades). In general, symptomatic mTBI tracked the stepwise moving targets less accurately, revealing possible brain dysfunction. A reliable, standardized protocol that appears to differentiate mTBI from normals was developed for use in future research. This investigation represents a step toward objective identification of those with PCS. Future studies focused on increasing the specificity of eye movement differences in those with PCS are needed.

  6. Normal proliferation and differentiation of Hoxc-8 transgenic chondrocytes in vitro

    PubMed Central

    Cormier, Stephania A; Mello, Maria Alice; Kappen, Claudia

    2003-01-01

    Background Hox genes encode transcription factors that are involved in pattern formation in the skeleton, and recent evidence suggests that they also play a role in the regulation of endochondral ossification. To analyze the role of Hoxc-8 in this process in more detail, we applied in vitro culture systems, using high density cultures of primary chondrocytes from neonatal mouse ribs. Results Cultured cells were characterized on the basis of morphology (light microscopy) and production of cartilage-specific extracellular matrix (sulfated proteoglycans and type II Collagen). Hypertrophy was demonstrated by increase in cell size, alkaline phosphatase activity and type X Collagen immunohistochemistry. Proliferation was assessed by BrdU uptake and flow cytometry. Unexpectedly, chondrocytes from Hoxc-8 transgenic mice, which exhibit delayed cartilage maturation in vivo [1], were able to proliferate and differentiate normally in our culture systems. This was the case even though freshly isolated Hoxc-8 transgenic chondrocytes exhibited significant molecular differences as measured by real-time quantitative PCR. Conclusions The results demonstrate that primary rib chondrocytes behave similar to published reports for chondrocytes from other sources, validating in vitro approaches for studies of Hox genes in the regulation of endochondral ossification. Our analysis of cartilage-producing cells from Hoxc-8 transgenic mice provides evidence that the cellular phenotype induced by Hoxc-8 overexpression in vivo is reversible in vitro. PMID:12713673

  7. Differentiation of normal skin and melanoma using high resolution hyperspectral imaging.

    PubMed

    Dicker, David T; Lerner, Jeremy; Van Belle, Pat; Barth, Stephen F; Guerry, Dupont; Herlyn, Meenhard; Elder, David E; El-Deiry, Wafik S

    2006-08-01

    We investigated the use of high resolution hyperspectral imaging microscopy to detect abnormalities in skin tissue using hematoxylin eosin stained preparations of normal and abnormal skin, benign nevi and melanomas. A goal of this study was to provide objective data that could be utilized by any researcher; and form the beginnings of a reference spectral data base. All spectral characterizations were acquired in percent transmission, and absorption, with contiguous wavelength acquisition between 400 and 800 nm; and a spectral resolution of approximately 1 nm. Biopsy sections were characterized with varying sample thickness, staining and magnification in order to determine their impact on spectral characterizations. Spectra were classified using spectral waveform cross correlation analysis, an algorithm that is linearity invariant. Classified spectra were incorporated into spectral libraries; and all spectra acquired from the field of view were correlated with library spectra to a quantified, user determined, confidence threshold (minimum correlation coefficient). The results revealed that all skin conditions in our initial data sets could be objectively differentiated providing that staining and section thickness was controlled. We also demonstrated that it is likely that a reference spectral library database could be created to include bioinformatics and cluster analysis. This would assist multiple laboratories to participate in the input and retrieval of target spectral information.

  8. Portable stimulator design aimed at differentiating facial nerves from normal tissues.

    PubMed

    Kara, S; Kemaloğlu, S; Sener, F; Okandan, M; Erkan, M A

    2004-04-01

    Facial nerves are very prone to risk of being cut away in the facial surgeries. In order to differentiate the normal tissues from the nerves during the surgeries, facial stimulator is very essential. These stimulators are particularly useful in triggering action potentials in the facial muscle tissue. In the case of any damage to these nerves, paralysis is unavoidable. Second use of the stimulator would be to diagnose how severe the facial problems are. Third use, which is a noninvasive application, is the employment of facial stimulator to treat and diagnose facial problems that arose from temperature differences, cuts or strain. The stimulation is achieved through DC voltage pulses that conform to user-specified amplitude, pulse duration and pulse intervals. These variables are set according to the age, sex, and physiological conditions of the patient. Peripheral Interface Controller is used to derive different pulse patterns. The current specifications of our stimulator are a range of 0.1-20 V pulse amplitude, 0.1-2 msec pulse duration, and 0.05-1 sec pulse interval. The main benefits of our stimulator are its graphic display that shows the form of pulse, its compact size, and operation on a battery power supply and adaptability to convert to other stimulation applications.

  9. Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells

    SciTech Connect

    Rettig, W.F.; Garin-Chesa, P.; Beresford, H.R.; Oettgen, H.F.; Melamed, M.R.; Old, L.J.

    1988-05-01

    Normal differentiation and malignant transformation of human cells are characterized by specific changes in surface antigen phenotype. In the present study, the authors have defined six cell-surface antigens of human sarcomas and normal mesenchymal cells, by using mixed hemadsorption assays and immunochemical methods for the analysis of cultured cells and immunohistochemical staining for the analysis of normal tissues and > 200 tumor specimens. Differential patterns of F19, F24, G171, G253, S5, and Thy-1 antigen expression were found to characterize (i) subsets of cultured sarcoma cell lines, (ii) cultured fibroblasts derived from various organs, (iii) normal resting and activated mesenchymal tissues, and (iv) sarcoma and nonmesenchymal tumor tissues. These results provide a basic surface antigenic map for cultured mesenchymal cells and mesenchymal tissues and permit the classification of human sarcomas according to their antigenic phenotypes.

  10. The intrauterine device today.

    PubMed

    Rioux, J E

    1993-10-01

    The intrauterine contraceptive device (IUD) is effective and reversible and has a high continuation rate. It can also be used within 7 days postcoitus. Developed separately by Richter, Grafenberg, and Ota between 1909 and 1934, the IUD gained popularity in the 1960s and 1970s with the introduction of the Margulies Spiral, the Lippes Loop, the Birnberg Bow, and the Dalkon Shield. The last proved dangerous, and the IUD became unpopular. The 4 IUDs which are available in Canada include the TCu-380S (GYNE T Slimline), the TCu-200, the NOVA-T, and the Progestasert. All are T shaped and medicated (copper or progesterone). The 1st and 3rd can be left in situ for 10 years; the 2nd, for 4 years; and the 4th, for 1 year. The NOVA-T has a copper wire with a silver core and is inserted with a unique pull-push technique. The Progestasert, which contains 38 mg of progesterone, releases 65 mcg of the hormone daily. The best candidate for IUD use is parous, but not pregnant, is in a stable monogamous relationship, and has a healthy reproductive tract and no history of ectopic pregnancy, sexually transmitted disease, pelvic inflammatory disease, undiagnosed genital bleeding, endometrial or cervical neoplasia, abnormal endometrial anatomy, compromised immune system, allergy to copper, or Wilson's Disease. The only infection related to the IUD is that associated with insertion. Such an infection is polymicrobial and involves the endogenous, cervicovaginal flora (primarily anaerobes). It is usually asymptomatic and contained by the immune system. 200 mg of Doxycycline can be given orally as a prophylactic 1 hour prior to insertion. A nonprescription, nonsteroidal, anti-inflammatory drug, also taken 1 hour before the procedure, will prevent pain and a vasovagal reaction. Paracervical anesthesia should be used. If the depth of the uterus is less than 6 cm or greater than 10 cm, another form of contraception should be used. Although little research is being done in Canada on new IUDs

  11. Quantitative differentiation of normal and scarred tissues using second-harmonic generation microscopy.

    PubMed

    Yildirim, Murat; Quinn, Kyle P; Kobler, James B; Zeitels, Steven M; Georgakoudi, Irene; Ben-Yakar, Adela

    2016-11-01

    The aim of this study was to differentiate normal and scarred hamster cheek pouch samples by applying a quantitative image analysis technique for determining collagen fiber direction and density in second-harmonic generation microscopy images. This paper presents a collagen tissue analysis of scarred cheek pouches of four adult male Golden Syrian hamsters as an animal model for vocal fold scarring. One cheek pouch was scarred using an electrocautery unit and the other cheek was used as a control for each hamster. A home-built upright microscope and a compact ultrafast fiber laser were used to acquire depth resolved epi-collected second-harmonic generation images of collagen fibers. To quantify the average fiber direction and fiber density in each image, we applied two-dimensional Fourier analysis and intensity thresholding at five different locations for each control and scarred tissue sample, respectively. The resultant depth-resolved average fiber direction variance for scarred hamster cheek pouches (0.61 ± 0.03) was significantly lower (p < 0.05) than control tissue (0.73 ± 0.04), indicating increased fiber alignment within the scar. Depth-resolved average voxel density measurements indicated scarred tissues contained greater (p < 0.005) fiber density (0.72 ± 0.09) compared to controls (0.18 ± 0.03). In the present study, image analysis of both fiber alignment and density from depth-resolved second-harmonic generation images in epi-detection mode enabled the quantification of the increased collagen fiber deposition and alignment typically observed in fibrosis. The epi-detection geometry is the only viable method for in vivo imaging as well as imaging thick turbid tissues. These quantitative endpoints, clearly differentiating between control and scarred hamster cheek pouches, provide an objective means to characterize the extent of vocal fold scarring in vivo in preclinical and clinical research. In particular, this non-invasive method

  12. Differential regulation of renal Klotho and FGFR1 in normal and uremic rats.

    PubMed

    Muñoz-Castañeda, Juan R; Herencia, Carmen; Pendón-Ruiz de Mier, Maria Victoria; Rodriguez-Ortiz, Maria Encarnación; Diaz-Tocados, Juan M; Vergara, Noemi; Martínez-Moreno, Julio M; Salmerón, Maria Dolores; Richards, William G; Felsenfeld, Arnold; Kuro-O, Makoto; Almadén, Yolanda; Rodríguez, Mariano

    2017-09-01

    In renal failure, hyperphosphatemia occurs despite a marked elevation in serum fibroblast growth factor (FGF)-23. Abnormal regulation of the FGFR1-Klotho receptor complex may cause a resistance to the phosphaturic action of FGF23. The purpose of the present study was to investigate the regulation of renal Klotho and FGF receptor (FEFR)-1 in healthy and uremic rats induced by 5/6 nephrectomy. In normal rats, the infusion of rat recombinant FGF23 enhanced phosphaturia and increased renal FGFR1 expression; however, Klotho expression was reduced. Uremic rats on a high-phosphate (HP) diet presented hyperphosphatemia with marked elevation of FGF23 and an increased fractional excretion of phosphate (P) that was associated with a marked reduction of Klotho expression and an increase in FGFR1. After neutralization of FGF23 by anti-FGF23 administration, phosphaturia was still abundant, Klotho expression remained low, and the FGFR1 level was reduced. These results suggest that the expression of renal Klotho is modulated by phosphaturia, whereas the FGFR1 expression is regulated by FGF23. Calcitriol (CTR) administration prevented a decrease in renal Klotho expression. In HEK293 cells HP produced nuclear translocation of β-catenin, together with a reduction in Klotho. Wnt/β-catenin inhibition with Dkk-1 prevented the P-induced down-regulation of Klotho. The addition of CTR to HP medium was able to recover Klotho expression. In summary, high FGF23 levels increase FGFR1, whereas phosphaturia decreases Klotho expression through the activation of Wnt/β-catenin pathway.-Muñoz-Castañeda, J. R., Herencia, C., Pendón-Ruiz de Mier, M. V., Rodriguez-Ortiz, M. E., Diaz-Tocados, J. M., Vergara, N., Martínez-Moreno, J. M., Salmerón, M. D., Richards, W. G., Felsenfeld, A., Kuro-O, M., Almadén, Y., Rodríguez, M. Differential regulation of renal Klotho and FGFR1 in normal and uremic rats. © FASEB.

  13. Power source effects of soft plasma jet and the differential response of skin cancer and normal cells

    NASA Astrophysics Data System (ADS)

    Taylor, Nathaniel; Dobrynin, Danil; Fridman, Alexander; Choi, Eun Ha

    2014-10-01

    The effects of pulsed power direct current energy sources were compared using an indirect discharge plasma jet applied to treat cancerous and normal skin cells. Two power supplies with different voltage and current profiles were compared and optimized through the measurement of physical parameters and evaluated through the treatment of skin cells using an atmospheric pressure nitrogen gas plasma jet. Plasma density and temperature, power output, gas output temperature, and reactive species production were measured. Cell morphology, viability, and ROS generation were investigated using staining. A differential response has been shown between the normal and cancerous cell lines. The cancer cells viability reduced while normal cells did not over the same treatment time.

  14. Differential responses of normal human melanocytes to intra- and extracellular dsRNA.

    PubMed

    Wang, Suiquan; Liu, Dongyin; Jin, Rong; Zhu, Yiping; Xu, Aie

    2015-06-01

    Viral factor has been implicated in the etiopathogenesis of vitiligo. To elucidate the effects of viral double-stranded RNA (dsRNA) on melanocytes and to explore the underlying mechanisms, primary cultured normal human melanocytes were treated with synthetic viral dsRNA analog poly(I:C). The results demonstrated that poly(I:C)-triggered apoptosis when transfected into melanocytes, while extracellular poly(I:C) did not have that effect. Intracellular poly(I:C)-induced melanocyte death was decreased by RIG-I or MDA5 siRNA, but not by TLR3 siRNA. Both intracellular and extracellular poly(I:C) induced the expression of IFNB, TNF, IL6, and IL8. However, extracellular poly(I:C) demonstrated a much weaker induction capacity of cytokine genes than intracellular poly(I:C). Further analysis revealed that phosphorylation of TBK1, IRF3, IRF7, and TAK1 was differentially induced by intra- or extracellular poly(I:C). NFκB inhibitor Bay 11-7082 decreased the induction of all the cytokines by poly(I:C), suggesting the ubiquitous role of NFκB in the process. Poly(I:C) treatment also induced the phosphorylation of p38 and JNK in melanocytes. Both JNK and p38 inhibitors showed suppression on the cytokine induction by intra- or extracellular poly(I:C). However, only the JNK inhibitor decreased the intracellular poly(I:C)-induced melanocyte death. Taken together, this study provides the possible mechanism of viral factor in the pathogenesis of vitiligo.

  15. Regulation of expression of collagenase-3 in normal, differentiating rat osteoblasts

    NASA Technical Reports Server (NTRS)

    Winchester, S. K.; Bloch, S. R.; Fiacco, G. J.; Partridge, N. C.

    1999-01-01

    We investigated the regulation of collagenase-3 expression in normal, differentiating rat osteoblasts. Fetal rat calvarial cell cultures showed an increase in alkaline phosphatase activity reaching maximal levels between 7-14 days post-confluence, then declining with the onset of mineralization. Collagenase-3 mRNA was just detectable after proliferation ceased at day 7, increased up to day 21, and declined at later ages. Postconfluent cells maintained in non-mineralizing medium expressed collagenase-3 but did not show the developmental increase exhibited by cells switched to mineralization medium. Cells maintained in non-mineralizing medium continued to proliferate; cells in mineralization medium ceased proliferation. In addition, collagenase-3 mRNA was not detected in subcultured cells allowed to remineralize. These results suggest that enhanced accumulation of collagenase-3 mRNA is triggered by cessation of proliferation or acquisition of a mineralized extracellular matrix and that other factors may also be required. After initiation of basal expression, parathyroid hormone (PTH) caused a dose-dependent increase in collagenase-3 mRNA. Both the cyclic adenosine monophosphate (cAMP) analogue, 8-bromo-cAMP (8-Br-cAMP), and the protein kinase C (PKC) activator, phorbol myristate acetate, increased collagenase-3 expression, while the calcium ionophore, ionomycin, did not, suggesting that PTH was acting through the protein kinase A (PKA) and PKC pathways. Inhibition of protein synthesis with cycloheximide caused an increase in basal collagenase-3 expression but blocked the effect of PTH, suggesting that an inhibitory factor prevents basal expression while an inductive factor is involved with PTH action. In summary, collagenase-3 is expressed in mineralized osteoblasts and cessation of proliferation and initiation of mineralization are triggers for collagenase-3 expression. PTH also stimulates expression of the enzyme through both PKA and PKC pathways in the

  16. Differential Chromatin Structure Encompassing Replication Origins in Transformed and Normal Cells

    PubMed Central

    Di Paola, Domenic; Rampakakis, Emmanouil; Chan, Man Kid

    2012-01-01

    This study examines the chromatin structure encompassing replication origins in transformed and normal cells. Analysis of the global levels of histone H3 acetylated at K9&14 (open chromatin) and histone H3 trimethylated at K9 (closed chromatin) revealed a higher ratio of open to closed chromatin in the transformed cells. Also, the trithorax and polycomb group proteins, Brg-1 and Bmi-1, respectively, were overexpressed and more abundantly bound to chromatin in the transformed cells. Quantitative comparative analyses of episomal and in situ chromosomal replication origin activity as well as chromatin immunoprecipitation (ChIP) assays, using specific antibodies targeting members of the pre-replication complex (pre-RC) as well as open/closed chromatin markers encompassing both episomal and chromosomal origins, revealed that episomal origins had similar levels of in vivo activity, nascent DNA abundance, pre-RC protein association, and elevated open chromatin structure at the origin in both cell types. In contrast, the chromosomal origins corresponding to 20mer1, 20mer2, and c-myc displayed a 2- to 3-fold higher activity and pre-RC protein abundance as well as higher ratios of open to closed chromatin and of Brg-1 to Bmi-1 in the transformed cells, whereas the origin associated with the housekeeping lamin B2 gene exhibited similar levels of activity, pre-RC protein abundance, and higher ratios of open to closed chromatin and of Brg-1 to Bmi-1 in both cell types. Nucleosomal positioning analysis, using an MNase-Southern blot assay, showed that all the origin regions examined were situated within regions of inconsistently positioned nucleosomes, with the nucleosomes being spaced farther apart from each other prior to the onset of S phase in both cell types. Overall, the results indicate that cellular transformation is associated with differential epigenetic regulation, whereby chromatin structure is more open, rendering replication origins more accessible to initiator

  17. Regulation of expression of collagenase-3 in normal, differentiating rat osteoblasts

    NASA Technical Reports Server (NTRS)

    Winchester, S. K.; Bloch, S. R.; Fiacco, G. J.; Partridge, N. C.

    1999-01-01

    We investigated the regulation of collagenase-3 expression in normal, differentiating rat osteoblasts. Fetal rat calvarial cell cultures showed an increase in alkaline phosphatase activity reaching maximal levels between 7-14 days post-confluence, then declining with the onset of mineralization. Collagenase-3 mRNA was just detectable after proliferation ceased at day 7, increased up to day 21, and declined at later ages. Postconfluent cells maintained in non-mineralizing medium expressed collagenase-3 but did not show the developmental increase exhibited by cells switched to mineralization medium. Cells maintained in non-mineralizing medium continued to proliferate; cells in mineralization medium ceased proliferation. In addition, collagenase-3 mRNA was not detected in subcultured cells allowed to remineralize. These results suggest that enhanced accumulation of collagenase-3 mRNA is triggered by cessation of proliferation or acquisition of a mineralized extracellular matrix and that other factors may also be required. After initiation of basal expression, parathyroid hormone (PTH) caused a dose-dependent increase in collagenase-3 mRNA. Both the cyclic adenosine monophosphate (cAMP) analogue, 8-bromo-cAMP (8-Br-cAMP), and the protein kinase C (PKC) activator, phorbol myristate acetate, increased collagenase-3 expression, while the calcium ionophore, ionomycin, did not, suggesting that PTH was acting through the protein kinase A (PKA) and PKC pathways. Inhibition of protein synthesis with cycloheximide caused an increase in basal collagenase-3 expression but blocked the effect of PTH, suggesting that an inhibitory factor prevents basal expression while an inductive factor is involved with PTH action. In summary, collagenase-3 is expressed in mineralized osteoblasts and cessation of proliferation and initiation of mineralization are triggers for collagenase-3 expression. PTH also stimulates expression of the enzyme through both PKA and PKC pathways in the

  18. Differential Activation of Signaling Pathways by UVA and UVB Radiation in Normal Human Epidermal Keratinocytes†

    PubMed Central

    Syed, Deeba N.; Afaq, Farrukh; Mukhtar, Hasan

    2012-01-01

    Ultraviolet (UV) radiation from the solar spectrum is a major etiological factor for many cutaneous pathologies including cancer. By understanding changes in cell signaling pathways induced by UVA and UVB, novel strategies for prevention and treatment of UV-related pathologies could be developed. However, much of the information in the literature from various laboratories cannot cross talk because of difficulties associated with the use of ill-defined light sources and physiologically irrelevant light dosimetry. Herein, we have assessed the effect of exposure of normal human epidermal keratinocytes (NHEK) to UVA (2 and 4 J cm−2) or UVB (20 and 40 mJ cm−2) radiation. Employing western blot analysis, we found that exposure of NHEK to UVB, but not UVA, phosphorylates JNK1/2 at Th183/Tyr185, STAT3 at Ser727, AKT at Ser473 and increases c-Fos expression, whereas exposure to UVA, but not UVB, phosphorylates AKT at Thr308. UVB as well as UVA exposure leads to increased phosphorylation of (1) ERK1/2 at Th202/Tyr204; (2) p38 at Th180/Tyr204; (3) STAT3 at Tyr705; (4) mTOR at Thr2448; and (v) p70S6k at Thr421/Ser424; enhanced expression of PI3K (p85) and c-jun; and nuclear translocation of NFκB proteins. These findings could be considered as a beginning for understanding the differential effects of UVA and UVB in the human skin and may have implications both with respect to risk assessment from exposure to solar UV radiation, and to target interventions against signaling events mediated by UVA and UVB. PMID:22335604

  19. Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2

    PubMed Central

    Hodson, Daniel J.; Shaffer, Arthur L.; Xiao, Wenming; Wright, George W.; Schmitz, Roland; Phelan, James D.; Yang, Yandan; Webster, Daniel E.; Rui, Lixin; Kohlhammer, Holger; Nakagawa, Masao; Waldmann, Thomas A.; Staudt, Louis M.

    2016-01-01

    The requirement for the B-cell transcription factor OCT2 (octamer-binding protein 2, encoded by Pou2f2) in germinal center B cells has proved controversial. Here, we report that germinal center B cells are formed normally after depletion of OCT2 in a conditional knockout mouse, but their proliferation is reduced and in vivo differentiation to antibody-secreting plasma cells is blocked. This finding led us to examine the role of OCT2 in germinal center-derived lymphomas. shRNA knockdown showed that almost all diffuse large B-cell lymphoma (DLBCL) cell lines are addicted to the expression of OCT2 and its coactivator OCA-B. Genome-wide chromatin immunoprecipitation (ChIP) analysis and gene-expression profiling revealed the broad transcriptional program regulated by OCT2 that includes the expression of STAT3, IL-10, ELL2, XBP1, MYC, TERT, and ADA. Importantly, genetic alteration of OCT2 is not a requirement for cellular addiction in DLBCL. However, we detected amplifications of the POU2F2 locus in DLBCL tumor biopsies and a recurrent mutation of threonine 223 in the DNA-binding domain of OCT2. This neomorphic mutation subtly alters the DNA-binding preference of OCT2, leading to the transactivation of noncanonical target genes including HIF1a and FCRL3. Finally, by introducing mutations designed to disrupt the OCT2–OCA-B interface, we reveal a requirement for this protein–protein interface that ultimately might be exploited therapeutically. Our findings, combined with the predominantly B-cell–restricted expression of OCT2 and the absence of a systemic phenotype in our knockout mice, suggest that an OCT2-targeted therapeutic strategy would be efficacious in both major subtypes of DLBCL while avoiding systemic toxicity. PMID:26993806

  20. Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2.

    PubMed

    Hodson, Daniel J; Shaffer, Arthur L; Xiao, Wenming; Wright, George W; Schmitz, Roland; Phelan, James D; Yang, Yandan; Webster, Daniel E; Rui, Lixin; Kohlhammer, Holger; Nakagawa, Masao; Waldmann, Thomas A; Staudt, Louis M

    2016-04-05

    The requirement for the B-cell transcription factor OCT2 (octamer-binding protein 2, encoded by Pou2f2) in germinal center B cells has proved controversial. Here, we report that germinal center B cells are formed normally after depletion of OCT2 in a conditional knockout mouse, but their proliferation is reduced and in vivo differentiation to antibody-secreting plasma cells is blocked. This finding led us to examine the role of OCT2 in germinal center-derived lymphomas. shRNA knockdown showed that almost all diffuse large B-cell lymphoma (DLBCL) cell lines are addicted to the expression of OCT2 and its coactivator OCA-B. Genome-wide chromatin immunoprecipitation (ChIP) analysis and gene-expression profiling revealed the broad transcriptional program regulated by OCT2 that includes the expression of STAT3, IL-10, ELL2, XBP1, MYC, TERT, and ADA. Importantly, genetic alteration of OCT2 is not a requirement for cellular addiction in DLBCL. However, we detected amplifications of the POU2F2 locus in DLBCL tumor biopsies and a recurrent mutation of threonine 223 in the DNA-binding domain of OCT2. This neomorphic mutation subtly alters the DNA-binding preference of OCT2, leading to the transactivation of noncanonical target genes including HIF1a and FCRL3 Finally, by introducing mutations designed to disrupt the OCT2-OCA-B interface, we reveal a requirement for this protein-protein interface that ultimately might be exploited therapeutically. Our findings, combined with the predominantly B-cell-restricted expression of OCT2 and the absence of a systemic phenotype in our knockout mice, suggest that an OCT2-targeted therapeutic strategy would be efficacious in both major subtypes of DLBCL while avoiding systemic toxicity.

  1. Stage-specific expression of intracisternal A-particle sequences in murine myelomonocytic leukemia cell lines and normal myelomonocytic differentiation.

    PubMed Central

    Takayama, Y; O'Mara, M A; Spilsbury, K; Thwaite, R; Rowe, P B; Symonds, G

    1991-01-01

    The levels of intracisternal A-particle (IAP) mRNA were analyzed in a variety of myelomonocytic leukemia cell lines, peritoneally derived macrophages, and normal hemopoietic progenitors induced to differentiate. In both normal and leukemic cells, the highest level of IAP message was found in cells at an intermediate stage of myelomonocytic differentiation, namely, the promyelomonocyte. These results indicate that IAP sequence transcription is regulated differentially during myelomonocytic cell development and that in general, the expression pattern is preserved in leukemic cell lines in vitro. In addition, Northern (RNA) analysis detected only type I IAP transcripts as the major IAP message and the expressed IAP subtypes varied in certain cell lines. This is the first comprehensive study of IAP expression in the myelomonocytic lineage and provides a useful system to study the biology of IAPs. Images PMID:1848323

  2. Control of growth and squamous differentiation in normal human bronchial epithelial cells by chemical and biological modifiers and transferred genes.

    PubMed Central

    Pfeifer, A M; Lechner, J F; Masui, T; Reddel, R R; Mark, G E; Harris, C C

    1989-01-01

    The majority of human lung cancers arise from bronchial epithelial cells. The normal pseudostratified bronchial epithelium is composed of basal, mucous, and ciliated cells. This multi-differentiated epithelium usually responds to xenobiotics and physical injury by undergoing basal cell hyperplasia, mucous cell hyperplasia, and squamous metaplasia. One step of the multistage process of carcinogenesis is thought to involve aberrations in control of the squamous metaplastic processes. Decreased responsiveness to regulators of terminal squamous differentiation may confer a selective clonal expansion advantage to an initiated cell. We studied the effects of endogenous [e.g., transforming growth factor beta 1 (TGF-beta 1) and serum] and exogenous [e.g., 12-O-tetradecanoyl-13-phorbol-acetate (TPA), tobacco smoke condensate, and aldehydes] modifiers of normal human bronchial epithelial (NHBE) cell in a serum-free culture system. NHBE cells are growth inhibited by all of these compounds and induced to undergo squamous differentiation by TGF-beta 1 or TPA. In contrast, lung carcinoma cell lines are relatively resistant to inducers of terminal squamous differentiation which may provide them with a selective growth advantage. Chemical agents and activated protooncogenes (ras,raf,myc) altered the response to endogenous and exogenous inducers of squamous differentiation and caused extended cellular lifespan, aneuploidy, and/or tumorigenicity. The data suggest a close relationship between dysregulation of terminal differentiation pathways and neoplastic transformation of human bronchial epithelial cells. PMID:2538323

  3. [Pulsoximetric sensor for diagnosis of intrauterine foetus state during parturition].

    PubMed

    Kalakutskiĭ, L I; Manelis, E S; Rodkina, Iu M

    2005-01-01

    Detrimental changes in the degree of blood hemoglobin saturation with oxygen are important evidence of hypoxic states and can be regarded as objective indication to surgical delivery. A new method of fetal pulsoximetry was developed. This method is based on the use of a non-disposable atraumatic pulsoximetric sensor of reflectory type for diagnosis of intrauterine foetus state during parturition. The clinical trial of the system was carried out in 44 women in childbirth and revealed clear differentiation between hypoxic states.

  4. Multimodal non-linear optical imaging for label-free differentiation of lung cancerous lesions from normal and desmoplastic tissues

    PubMed Central

    Xu, Xiaoyun; Cheng, Jie; Thrall, Michael J.; Liu, Zhengfan; Wang, Xi; Wong, Stephen T.C.

    2013-01-01

    Lung carcinoma is the leading cause of cancer-related death in the United States, and non-small cell carcinoma accounts for 85% of all lung cancer cases. One major characteristic of non-small cell carcinoma is the appearance of desmoplasia and deposition of dense extracellular collagen around the tumor. The desmoplastic response provides a radiologic target but may impair sampling during traditional image-guided needle biopsy and is difficult to differentiate from normal tissues using single label free imaging modality; for translational purposes, label-free techniques provide a more promising route to clinics. We thus investigated the potential of using multimodal, label free optical microscopy that incorporates Coherent Anti-Stokes Raman Scattering (CARS), Two-Photon Excited AutoFluorescence (TPEAF), and Second Harmonic Generation (SHG) techniques for differentiating lung cancer from normal and desmoplastic tissues. Lung tissue samples from patients were imaged using CARS, TPEAF, and SHG for comparison and showed that the combination of the three non-linear optics techniques is essential for attaining reliable differentiation. These images also illustrated good pathological correlation with hematoxylin and eosin (H&E) stained sections from the same tissue samples. Automated image analysis algorithms were developed for quantitative segmentation and feature extraction to enable lung tissue differentiation. Our results indicate that coupled with automated morphology analysis, the proposed tri-modal nonlinear optical imaging technique potentially offers a powerful translational strategy to differentiate cancer lesions reliably from surrounding non-tumor and desmoplastic tissues. PMID:24409386

  5. Genes involved in epithelial differentiation and development are differentially expressed in oral and genital lichen planus epithelium compared to normal epithelium.

    PubMed

    Danielsson, Karin; Coates, Philip J; Ebrahimi, Majid; Nylander, Elisabet; Wahlin, Ylva Britt; Nylander, Karin

    2014-09-01

    Lichen planus (LP) is a chronic mucocutaneous disease with unknown cause. Patients with LP often have both oral and genital lesions, but these conditions are often considered as separate diseases and treated accordingly. To find out which genes are differently expressed in mucosal LP compared to normal mucosa and establish whether oral and genital LP are in fact the same disease, whole genome expression analysis was performed on epithelium from 13 patients diagnosed with oral and/or genital LP and normal controls. For confirmation of keratin 4 and corneodesmosin expression, quantitative reverse-transcription PCR and immunohistochemistry were used. Many genes involved in epithelial development and differentiation are differently expressed in epithelium from LP compared to normal epithelium. Several of the differentially expressed genes are common for oral and genital LP and the same biological processes are altered which supports the fact that oral and genital LP are manifestations of the same disease. The change in gene expression indicates that differentiation is altered leading to changes in the epithelial barrier.

  6. Development of a differential pumping system for soft X-ray beamlines for windowless experiments under normal atmospheric conditions.

    PubMed

    Tamenori, Y

    2010-03-01

    A novel design for a differential pumping system has been investigated. This system allows windowless experiments in a soft X-ray beamline under normal atmospheric conditions. The new design consists of an aperture-based four-stage differential pumping system, based on a simple model calculation. A prototype system with a total length of 600 mm was constructed to confirm the validity of the design concept. Relatively short conductance-limiting components allow easy installation and alignment of the system on a synchrotron beamline. The fabricated system was installed on a beamline to test the transmission of soft X-rays through atmospheric helium.

  7. Differential Production of Positive and Negative Discriminative Stimuli by Normal and Retarded Children.

    ERIC Educational Resources Information Center

    Mulvaney, Dallas E.; And Others

    1981-01-01

    Two normal and two mentally retarded children were trained to earn pennies by pressing a key according to a multiple variable-interval extinction schedule of reinforcement. Retarded children differed from normal children by producing more positive than negative discriminative stimuli. (Author/DB)

  8. Frequency analysis of multispectral photoacoustic images for differentiating malignant region from normal region in excised human prostate

    NASA Astrophysics Data System (ADS)

    Sinha, Saugata; Rao, Navalgund A.; Valluru, Keerthi S.; Chinni, Bhargava K.; Dogra, Vikram S.; Helguera, Maria

    2014-03-01

    Frequency domain analysis of the photoacoustic (PA) radio frequency signals can potentially be used as a tool for characterizing microstructure of absorbers in tissue. This study investigates the feasibility of analyzing the spectrum of multiwavelength PA signals generated by excised human prostate tissue samples to differentiate between malignant and normal prostate regions. Photoacoustic imaging at five different wavelengths, corresponding to peak absorption coefficients of deoxyhemoglobin, whole blood, oxyhemoglobin, water and lipid in the near infrared (NIR) (700 nm - 1000 nm) region, was performed on freshly excised prostate specimens taken from patients undergoing prostatectomy for biopsy confirmed prostate cancer. The PA images were co-registered with the histopathology images of the prostate specimens to determine the region of interest (ROI) corresponding to malignant and normal tissue. The calibrated power spectrum of each PA signal from a selected ROI was fit to a linear model to extract the corresponding slope, midband fit and intercept parameters. The mean value of each parameter corresponding to malignant and adjacent normal prostate ROI was calculated for each of the five wavelengths. The results obtained for 9 different human prostate specimens, show that the mean values of midband fit and intercept are significantly different between malignant and normal regions. In addition, the average midband fit and intercept values show a decreasing trend with increasing wavelength. These preliminary results suggest that frequency analysis of multispectral PA signals can be used to differentiate malignant region from the adjacent normal region in human prostate tissue.

  9. Effects of Creatine in Skeletal Muscle Cells and in Myoblasts Differentiating Under Normal or Oxidatively Stressing Conditions.

    PubMed

    Sestili, Piero; Barbieri, Elena; Stocchi, Vilberto

    2016-01-01

    Creatine (Cr) - along with the Cr kinase (CK) system - plays a fundamental role in muscle biochemistry and physiology not limited to its ergogenic role. Indeed, Cr has been shown to exert pleiotropic effects, which promote protein accretion, muscle-specific protein synthesis, growth in cultured myogenic cells and favour the myogenic process either in normal or stressing conditions. This review focuses on the effects of Cr supplementation on cellular and mitochondrial biochemistry and function in the course of skeletal muscle differentiation, either in normal or oxidatively stressing conditions, and on the ensuing nutraceutical/therapeutic perspectives.

  10. Profound Effect of Profiling Platform and Normalization Strategy on Detection of Differentially Expressed MicroRNAs – A Comparative Study

    PubMed Central

    Meyer, Swanhild U.; Kaiser, Sebastian; Wagner, Carola; Thirion, Christian; Pfaffl, Michael W.

    2012-01-01

    Background Adequate normalization minimizes the effects of systematic technical variations and is a prerequisite for getting meaningful biological changes. However, there is inconsistency about miRNA normalization performances and recommendations. Thus, we investigated the impact of seven different normalization methods (reference gene index, global geometric mean, quantile, invariant selection, loess, loessM, and generalized procrustes analysis) on intra- and inter-platform performance of two distinct and commonly used miRNA profiling platforms. Methodology/Principal Findings We included data from miRNA profiling analyses derived from a hybridization-based platform (Agilent Technologies) and an RT-qPCR platform (Applied Biosystems). Furthermore, we validated a subset of miRNAs by individual RT-qPCR assays. Our analyses incorporated data from the effect of differentiation and tumor necrosis factor alpha treatment on primary human skeletal muscle cells and a murine skeletal muscle cell line. Distinct normalization methods differed in their impact on (i) standard deviations, (ii) the area under the receiver operating characteristic (ROC) curve, (iii) the similarity of differential expression. Loess, loessM, and quantile analysis were most effective in minimizing standard deviations on the Agilent and TLDA platform. Moreover, loess, loessM, invariant selection and generalized procrustes analysis increased the area under the ROC curve, a measure for the statistical performance of a test. The Jaccard index revealed that inter-platform concordance of differential expression tended to be increased by loess, loessM, quantile, and GPA normalization of AGL and TLDA data as well as RGI normalization of TLDA data. Conclusions/Significance We recommend the application of loess, or loessM, and GPA normalization for miRNA Agilent arrays and qPCR cards as these normalization approaches showed to (i) effectively reduce standard deviations, (ii) increase sensitivity and accuracy of

  11. Clinical application of intrauterine sonography with high-frequency, real-time miniature transducer in gynecologic disorders. Preliminary report.

    PubMed

    Senoh, D; Yanagihara, T; Hata, T

    1999-01-01

    Our purpose was to determine whether intrauterine sonography with high-frequency, real-time miniature transducer (20 MHz) is useful for the diagnosis of gynecologic disorders. The study consisted of 37 women: 8 normal volunteers, 2 with molar pregnancy, 4 fibromyoma, 4 endometrial polyp, 1 intrauterine adhesion, 1 septate uterus, 5 atypical hyperplasia, 8 endometrial cancer, and 4 with cervical cancer. Comparison of diagnostic efficacy for gynecologic disorders between transvaginal and intrauterine sonography was made. The probe was easily introduced into the endometrial cavity in all patients. No notable complications were encountered. In subjects with a normal uterus, higher resolution for endometrial texture was obtained with intrauterine sonography than with transvaginal scanning. In patients with molar pregnancy, typical vesicular echoes were clearly identified. In patients with fibromyoma, myoma nodules were not clearly visualized because of poor attenuation of ultrasound. In subjects with endometrial polyp, intrauterine adhesion, and septate uterus, intrauterine lesions were clearly identified. In patients with atypical hyperplasia, high echogenicity of the endometrium was characterized. Myometrial invasion of the endometrial cancer was estimated correctly in 6 of 8 patients (75%). Intrauterine sonography could clearly detect early cervical invasion of the cervical cancer in all 4 patients, but transvaginal sonography could not do it. Intrauterine sonography with a high-frequency, real-time miniature transducer might be a useful diagnostic modality in gynecologic disorders, especially in the evaluation of early cervical cancer, endometrial cancer, and possibly in infertility practice.

  12. TEAD transcription factors are required for normal primary myoblast differentiation in vitro and muscle regeneration in vivo.

    PubMed

    Joshi, Shilpy; Davidson, Guillaume; Le Gras, Stéphanie; Watanabe, Shuichi; Braun, Thomas; Mengus, Gabrielle; Davidson, Irwin

    2017-02-01

    The TEAD family of transcription factors (TEAD1-4) bind the MCAT element in the regulatory elements of both growth promoting and myogenic differentiation genes. Defining TEAD transcription factor function in myogenesis has proved elusive due to overlapping expression of family members and their functional redundancy. We show that silencing of either Tead1, Tead2 or Tead4 did not effect primary myoblast (PM) differentiation, but that their simultaneous knockdown strongly impaired differentiation. In contrast, Tead1 or Tead4 silencing impaired C2C12 differentiation showing their different contributions in PMs and C2C12 cells. Chromatin immunoprecipitation identified enhancers associated with myogenic genes bound by combinations of Tead4, Myod1 or Myog. Tead4 regulated distinct gene sets in C2C12 cells and PMs involving both activation of the myogenic program and repression of growth and signaling pathways. ChIP-seq from mature mouse muscle fibres in vivo identified a set of highly transcribed muscle cell-identity genes and sites bound by Tead1 and Tead4. Although inactivation of Tead4 in mature muscle fibres caused no obvious phenotype under normal conditions, notexin-induced muscle regeneration was delayed in Tead4 mutants suggesting an important role in myogenic differentiation in vivo. By combining knockdown in cell models in vitro with Tead4 inactivation in muscle in vivo, we provide the first comprehensive description of the specific and redundant roles of Tead factors in myogenic differentiation.

  13. TEAD transcription factors are required for normal primary myoblast differentiation in vitro and muscle regeneration in vivo

    PubMed Central

    Joshi, Shilpy; Le Gras, Stéphanie; Watanabe, Shuichi; Braun, Thomas

    2017-01-01

    The TEAD family of transcription factors (TEAD1-4) bind the MCAT element in the regulatory elements of both growth promoting and myogenic differentiation genes. Defining TEAD transcription factor function in myogenesis has proved elusive due to overlapping expression of family members and their functional redundancy. We show that silencing of either Tead1, Tead2 or Tead4 did not effect primary myoblast (PM) differentiation, but that their simultaneous knockdown strongly impaired differentiation. In contrast, Tead1 or Tead4 silencing impaired C2C12 differentiation showing their different contributions in PMs and C2C12 cells. Chromatin immunoprecipitation identified enhancers associated with myogenic genes bound by combinations of Tead4, Myod1 or Myog. Tead4 regulated distinct gene sets in C2C12 cells and PMs involving both activation of the myogenic program and repression of growth and signaling pathways. ChIP-seq from mature mouse muscle fibres in vivo identified a set of highly transcribed muscle cell-identity genes and sites bound by Tead1 and Tead4. Although inactivation of Tead4 in mature muscle fibres caused no obvious phenotype under normal conditions, notexin-induced muscle regeneration was delayed in Tead4 mutants suggesting an important role in myogenic differentiation in vivo. By combining knockdown in cell models in vitro with Tead4 inactivation in muscle in vivo, we provide the first comprehensive description of the specific and redundant roles of Tead factors in myogenic differentiation. PMID:28178271

  14. Immune interferon and leukocyte-conditioned medium induce normal and leukemic myeloid cells to differentiate along the monocytic pathway

    PubMed Central

    1983-01-01

    Conditioned medium from phytohemagglutinin-stimulated human leukocytes contains a factor that can induce promyelocytic cell lines and certain acute myelogenous leukemia cells to differentiate along the monocytic pathway. In this report, we show that immature myeloid cells from normal bone marrow or the peripheral blood of patients with chronic myelogenous leukemia can be induced to differentiate to monocyte-like cells by immune gamma interferon (IFN gamma). We have identified IFN gamma as the predominant differentiation factor contained in the conditioned medium. Purified or recombinant IFN gamma, but not various preparations of IFN alpha or beta, can induce monocytic differentiation in myeloid cells. In cultures containing conditioned medium, the cells fail to continue myeloid maturation, and are induced to express monocyte markers and functions, such as monocyte-specific surface antigens, HLA-DR antigens, Fc receptors for monomeric immunoglobulins, nonspecific esterase, and the ability to mediate antibody-dependent, cell-mediated cytotoxicity. Even myeloid cells as mature as metamyelocytes or band cells can be induced by IFN gamma to undergo monocyte differentiation, but monocyte-specific or HLA-DR antigens are not induced in mature neutrophils. These findings reveal a previously unknown, specific function of human IFN gamma and offer new insights to the regulation of monocyte recruitment and differentiation during a virus infection or immune response. PMID:6417261

  15. Fuel cell system logic for differentiating between rapid and normal shutdown commands

    DOEpatents

    Keskula, Donald H.; Doan, Tien M.; Clingerman, Bruce J.

    2000-01-01

    A method of controlling the operation of a fuel cell system wherein each shutdown command for the system is subjected to decision logic which determines whether the command should be a normal shutdown command or rapid shutdown command. If the logic determines that the shutdown command should be a normal shutdown command, then the system is shutdown in a normal step-by-step process in which the hydrogen stream is consumed within the system. If the logic determines that the shutdown command should be a rapid shutdown command, the hydrogen stream is removed from the system either by dumping to atmosphere or routing to storage.

  16. TSH Receptor Function Is Required for Normal Thyroid Differentiation in Zebrafish

    PubMed Central

    Opitz, Robert; Maquet, Emilie; Zoenen, Maxime; Dadhich, Rajesh

    2011-01-01

    TSH is the primary physiological regulator of thyroid gland function. The effects of TSH on thyroid cells are mediated via activation of its membrane receptor [TSH receptor (TSHR)]. In this study, we examined functional thyroid differentiation in zebrafish and characterized the role of TSHR signaling during thyroid organogenesis. Cloning of a cDNA encoding zebrafish Tshr showed conservation of primary structure and functional properties between zebrafish and mammalian TSHR. In situ hybridization confirmed that the thyroid is the major site of tshr expression during zebrafish development. In addition, we identified tpo, iyd, duox, and duoxa as novel thyroid differentiation markers in zebrafish. Temporal analyses of differentiation marker expression demonstrated the induction of an early thyroid differentiation program along with thyroid budding, followed by a delayed onset of duox and duoxa expression coincident with thyroid hormone synthesis. Furthermore, comparative analyses in mouse and zebrafish revealed for the first time a thyroid-enriched expression of cell death regulators of the B-cell lymphoma 2 family during early thyroid morphogenesis. Knockdown of tshr function by morpholino microinjection into embryos did not affect early thyroid morphogenesis but caused defects in later functional differentiation. The thyroid phenotype observed in tshr morphants at later stages comprised a reduction in number and size of functional follicles, down-regulation of differentiation markers, as well as reduced thyroid transcription factor expression. A comparison of our results with phenotypes observed in mouse models of defective TSHR and cAMP signaling highlights the value of zebrafish as a model to enhance the understanding of functional differentiation in the vertebrate thyroid. PMID:21737742

  17. Intrauterine Environment and PCOS

    PubMed Central

    Dumesic, Daniel A.; Goodarzi, Mark O.; Chazenbalk, Gregorio D.; Abbott, David H.

    2016-01-01

    The maternal-fetal environment plays an important role in developmental programming of adult disease. Metabolic and hormonal dysfunction during human fetal development accompanies gestational diabetes as a common occurrence in polycystic ovary syndrome (PCOS) mothers, while human fetal androgen excess from congenital adrenal hyperplasia or virilizing tumors precedes PCOS-like symptoms after birth. To date, clinical studies of infant blood levels at term have yet to confirm that human fetal androgen excess promotes PCOS development after birth. Earlier in development, however, circulating androgen levels in the second trimester female human fetus can normally rise into the male range. Furthermore, midgestational amniotic testosterone levels are elevated in female fetuses of PCOS compared to normal mothers and might influence fetal development, since experimentally-induced fetal androgen excess in animals produces a PCOS-like phenotype with reproductive and metabolic dysfunction. Such alterations in the maternal-fetal environment likely program adult PCOS by epigenetic modifications of genetic susceptibility of the fetus to PCOS after birth. Understanding this phenomenon requires advanced fetal surveillance technologies and postnatal assessment of midgestational androgen exposure for new clinical strategies to improve reproduction in PCOS women, optimize long-term health of their offspring, and minimize susceptibility to acquiring PCOS in future generations. PMID:24715510

  18. The preferentially expressed antigen in melanoma (PRAME) inhibits myeloid differentiation in normal hematopoietic and leukemic progenitor cells

    PubMed Central

    Guthrie, Katherine A.; Cummings, Carrie L.; Sabo, Kathleen; Wood, Brent L.; Gooley, Ted; Yang, Taimei; Epping, Mirjam T.; Shou, Yaping; Pogosova-Agadjanyan, Era; Ladne, Paula; Stirewalt, Derek L.; Abkowitz, Janis L.; Radich, Jerald P.

    2009-01-01

    The preferentially expressed antigen in melanoma (PRAME) is expressed in several hematologic malignancies, but either is not expressed or is expressed at only low levels in normal hematopoietic cells, making it a target for cancer therapy. PRAME is a tumor-associated antigen and has been described as a corepressor of retinoic acid signaling in solid tumor cells, but its function in hematopoietic cells is unknown. PRAME mRNA expression increased with chronic myeloid leukemia (CML) disease progression and its detection in late chronic-phase CML patients before tyrosine kinase inhibitor therapy was associated with poorer therapeutic responses and ABL tyrosine kinase domain point mutations. In leukemia cell lines, PRAME protein expression inhibited granulocytic differentiation only in cell lines that differentiate along this lineage after all-trans retinoic acid (ATRA) exposure. Forced PRAME expression in normal hematopoietic progenitors, however, inhibited myeloid differentiation both in the presence and absence of ATRA, and this phenotype was reversed when PRAME was silenced in primary CML progenitors. These observations suggest that PRAME inhibits myeloid differentiation in certain myeloid leukemias, and that its function in these cells is lineage and phenotype dependent. Lastly, these observations suggest that PRAME is a target for both prognostic and therapeutic applications. PMID:19625708

  19. Differential Expression of Complement Markers in Normal and AMD Transmitochondrial Cybrids

    PubMed Central

    Nashine, Sonali; Chwa, Marilyn; Kazemian, Mina; Thaker, Kunal; Lu, Stephanie; Nesburn, Anthony; Kuppermann, Baruch D.; Kenney, M. Cristina

    2016-01-01

    Purpose Variations in mitochondrial DNA (mtDNA) and abnormalities in the complement pathways have been implicated in the pathogenesis of age-related macular degeneration (AMD). This study was designed to determine the effects of mtDNA from AMD subjects on the complement pathway. Methods Transmitochondrial cybrids were prepared by fusing platelets from AMD and age-matched Normal subjects with Rho0 (lacking mtDNA) human ARPE-19 cells. Quantitative PCR and Western blotting were performed to examine gene and protein expression profiles, respectively, of complement markers in these cybrids. Bioenergetic profiles of Normal and AMD cybrids were examined using the Seahorse XF24 flux analyzer. Results Significant decreases in the gene and protein expression of complement inhibitors, along with significantly higher levels of complement activators, were found in AMD cybrids compared to Older-Normal cybrids. Seahorse flux data demonstrated that the bioenergetic profiles for Older-Normal and Older-AMD cybrid samples were similar to each other but were lower compared to Young-Normal cybrid samples. Conclusion In summary, since all cybrids had identical nuclei and differed only in mtDNA content, the observed changes in components of complement pathways can be attributed to mtDNA variations in the AMD subjects, suggesting that mitochondrial genome and retrograde signaling play critical roles in this disease. Furthermore, the similar bioenergetic profiles of AMD and Older-Normal cybrids indicate that the signaling between mitochondria and nuclei are probably not via a respiratory pathway. PMID:27486856

  20. Haploid parthenotes express differential response to in vitro exposure of ammonia compared to normally fertilized embryos.

    PubMed

    Nair, Ramya; Mutalik, Srinivas; Dasappa, Jagadeesh Prasad; Kalthur, Guruprasad; Adiga, Satish Kumar

    2017-04-22

    In the present study, we assessed whether absence of paternal genome imparts any differential response in embryos to chemical stress such as ammonia. Parthenogenesis was induced in MII stage oocytes using 10 mM SrCl2 in M16 medium. Parthenotes and normally fertilized embryos at 2 cell stage were exposed to different concentrations of ammonia and cultured till blastocyst. Exposure of ammonia to normally fertilized embryos resulted in significant decrease in the developmental potential (p < 0.0001) and blastocyst quality (p < 0.001). Whereas, in parthenotes, even though lower concentrations of ammonia did not have any effect, at 200 μM concentration the blastocyst rate was two times higher than control. The baseline apoptotic index was higher in parthenotes compared to normally fertilized embryos, which further increased after ammonium exposure (p < 0.001). Unlike in normally fertilized embryos ammonia exposure altered the mitochondrial distribution pattern and lead to increased expression of Oct4, Nanog and Na(+)/K(+) ion exchange channel, while the cytochrome C expression was downregulated. This indicates that haploidy and/or absence of paternal factors in the embryo results in differential tolerance to stress induced by ammonia. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Differential negative air ion effects on learning disabled and normal-achieving children

    NASA Astrophysics Data System (ADS)

    Morton, L. L.; Kershner, J. R.

    1990-03-01

    Forty normal-achieving and 33 learning disabled (LD) children were assigned randomly to either a negative ion or placebo test condition. On a dichotic listening task using consonant-vowel (CV) combinations, both groups showed an ioninduced increase in the normal right ear advantage (REA). However, the mechanisms for this effect were different for each group. The LDs showed the effect at the right ear/left hemisphere (enhancement). The normal achievers showed the effect at the left ear/right hemisphere (inhibition). The results are consistent with an activation-inhibition model of cerebral function and suggest a functional relationship between arousal, interhemispheric activation-inhibition, and learning disabilities. The LDs may have an interhemispheric dysfunction. Both groups showed superior right ear report and the normal achiever showed overall superiority. Normal achievers showed higher consonant intrusion scores, probably due to a greater cognitive capacity. Age was a significant covariate reflecting developmental capacity changes. Negative air ions are seen to be a tool with potential theoretical and remedial applications.

  2. Pmch-deficiency in rats is associated with normal adipocyte differentiation and lower sympathetic adipose drive.

    PubMed

    Mul, Joram D; O'Duibhir, Eoghan; Shrestha, Yogendra B; Koppen, Arjen; Vargoviç, Peter; Toonen, Pim W; Zarebidaki, Eleen; Kvetnansky, Richard; Kalkhoven, Eric; Cuppen, Edwin; Bartness, Timothy J

    2013-01-01

    The orexigenic neuropeptide melanin-concentrating hormone (MCH), a product of Pmch, is an important mediator of energy homeostasis. Pmch-deficient rodents are lean and smaller, characterized by lower food intake, body-, and fat mass. Pmch is expressed in hypothalamic neurons that ultimately are components in the sympathetic nervous system (SNS) drive to white and interscapular brown adipose tissue (WAT, iBAT, respectively). MCH binds to MCH receptor 1 (MCH1R), which is present on adipocytes. Currently it is unknown if Pmch-ablation changes adipocyte differentiation or sympathetic adipose drive. Using Pmch-deficient and wild-type rats on a standard low-fat diet, we analyzed dorsal subcutaneous and perirenal WAT mass and adipocyte morphology (size and number) throughout development, and indices of sympathetic activation in WAT and iBAT during adulthood. Moreover, using an in vitro approach we investigated the ability of MCH to modulate 3T3-L1 adipocyte differentiation. Pmch-deficiency decreased dorsal subcutaneous and perirenal WAT mass by reducing adipocyte size, but not number. In line with this, in vitro 3T3-L1 adipocyte differentiation was unaffected by MCH. Finally, adult Pmch-deficient rats had lower norepinephrine turnover (an index of sympathetic adipose drive) in WAT and iBAT than wild-type rats. Collectively, our data indicate that MCH/MCH1R-pathway does not modify adipocyte differentiation, whereas Pmch-deficiency in laboratory rats lowers adiposity throughout development and sympathetic adipose drive during adulthood.

  3. Distribution of coniferin in differentiating normal and compression woods using MALDI mass spectrometric imaging coupled with osmium tetroxide vapor treatment.

    PubMed

    Yoshinaga, Arata; Kamitakahara, Hiroshi; Takabe, Keiji

    2016-05-01

    Matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) was employed to detect monolignol glucosides in differentiating normal and compression woods of two Japanese softwoods, Chamaecyparis obtusa and Cryptomeria japonica Comparison of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry collision-induced dissociation fragmentation analysis and structural time-of-flight (MALDI-TOF CID-FAST) spectra between coniferin and differentiating xylem also confirmed the presence of coniferin in differentiating xylem. However, as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and MALDI-TOF CID-FAST spectra of sucrose were similar to those of coniferin, it was difficult to distinguish the distribution of coniferin and sucrose using MALDI-MSI and collision-induced dissociation measurement only. To solve this problem, osmium tetroxide vapor was applied to sections of differentiating xylem. This vapor treatment caused peak shifts corresponding to the introduction of two hydroxyl groups to the C=C double bond in coniferin. The treatment did not cause a peak shift for sucrose, and therefore was effective in distinguishing coniferin and sucrose. Thus, it was found that MALDI-MSI combined with osmium tetroxide vapor treatment is a useful method to detect coniferin in differentiating xylem.

  4. Patterns of brain structural connectivity differentiate normal weight from overweight subjects

    PubMed Central

    Gupta, Arpana; Mayer, Emeran A.; Sanmiguel, Claudia P.; Van Horn, John D.; Woodworth, Davis; Ellingson, Benjamin M.; Fling, Connor; Love, Aubrey; Tillisch, Kirsten; Labus, Jennifer S.

    2015-01-01

    Background Alterations in the hedonic component of ingestive behaviors have been implicated as a possible risk factor in the pathophysiology of overweight and obese individuals. Neuroimaging evidence from individuals with increasing body mass index suggests structural, functional, and neurochemical alterations in the extended reward network and associated networks. Aim To apply a multivariate pattern analysis to distinguish normal weight and overweight subjects based on gray and white-matter measurements. Methods Structural images (N = 120, overweight N = 63) and diffusion tensor images (DTI) (N = 60, overweight N = 30) were obtained from healthy control subjects. For the total sample the mean age for the overweight group (females = 32, males = 31) was 28.77 years (SD = 9.76) and for the normal weight group (females = 32, males = 25) was 27.13 years (SD = 9.62). Regional segmentation and parcellation of the brain images was performed using Freesurfer. Deterministic tractography was performed to measure the normalized fiber density between regions. A multivariate pattern analysis approach was used to examine whether brain measures can distinguish overweight from normal weight individuals. Results 1. White-matter classification: The classification algorithm, based on 2 signatures with 17 regional connections, achieved 97% accuracy in discriminating overweight individuals from normal weight individuals. For both brain signatures, greater connectivity as indexed by increased fiber density was observed in overweight compared to normal weight between the reward network regions and regions of the executive control, emotional arousal, and somatosensory networks. In contrast, the opposite pattern (decreased fiber density) was found between ventromedial prefrontal cortex and the anterior insula, and between thalamus and executive control network regions. 2. Gray-matter classification: The classification algorithm, based on 2 signatures with 42

  5. Ultrasonic differentiation of normal versus malignant breast epithelial cells in monolayer cultures

    PubMed Central

    Doyle, Timothy E.; Goodrich, Jeffrey B.; Ambrose, Brady J.; Patel, Hemang; Kwon, Soonjo; Pearson, Lee H.

    2010-01-01

    Normal and malignant mammary epithelial cells were studied using laboratory measurements, wavelet analysis, and numerical simulations of monolayer cell cultures to determine whether microscopic breast cancer can be detected in vitro with high-frequency ultrasound. Pulse-echo waveforms were acquired by immersing a broadband, unfocused 50-MHz transducer in the growth media of cell culture well plates and collecting the first reflection from the well bottoms. The simulations included a multilayer pulse-reflection model and a model of two-dimensional arrays of spherical cells and nuclei. The results show that normal and malignant cells produce time-domain signals and spectral features that are significantly different. PMID:21110531

  6. Comparing the normalization methods for the differential analysis of Illumina high-throughput RNA-Seq data.

    PubMed

    Li, Peipei; Piao, Yongjun; Shon, Ho Sun; Ryu, Keun Ho

    2015-10-28

    , Med, TMM, DESeq, and Q did not noticeably improve gene expression normalization, regardless of read length. Other normalization methods were more efficient when alignment accuracy was low; Sailfish with RPKM gave the best normalization results. When alignment accuracy was high, RC was sufficient for gene expression calculation. And we suggest ignoring poly-A tail during differential gene expression analysis.

  7. Development of Planning Abilities in Normal Aging: Differential Effects of Specific Cognitive Demands

    ERIC Educational Resources Information Center

    Köstering, Lena; Stahl, Christoph; Leonhart, Rainer; Weiller, Cornelius; Kaller, Christoph P.

    2014-01-01

    In line with the frontal hypothesis of aging, the ability to plan ahead undergoes substantial change during normal aging. Although impairments on the Tower of London planning task were reported earlier, associations between age-related declines and specific cognitive demands on planning have not been studied. Here we investigated the impact of…

  8. DIFFERENTIATION BETWEEN NORMAL AND DISORDERED CHILDREN BY A COMPUTER ANALYSIS OF EMOTIONAL AND VERBAL BEHAVIOR.

    ERIC Educational Resources Information Center

    ALEXANDER, THERON; LEAVERTON, PAUL

    IT HAS BEEN SUGGESTED THAT THE EMOTIONAL CHARACTERISTICS OF PEOPLE CAN BE INVESTIGATED BY STUDYING THEIR VERBAL BEHAVIOR. THIS STUDY INVESTIGATED THE USE OF EMOTIONAL WORDS, BOTH POSITIVE AND NEGATIVE, AND THE TOTAL VERBAL OUTPUT OF NORMAL AND DISORDERED CHILDREN TO DETERMINE IF SIGNIFICANT DIFFERENCES IN VERBAL EXPRESSION OCCUR. TWO GROUPS OF…

  9. Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

    2016-03-01

    In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

  10. Differential expression of the urokinase receptor (CD87) in arthritic and normal synovial tissues.

    PubMed Central

    Szekanecz, Z; Haines, G K; Koch, A E

    1997-01-01

    AIM: To determine whether the urokinase plasminogen activator receptor (u-PAR; CD87) exhibits a possible pathogenic role in rheumatoid and osteoarthritis. METHODS: A semiquantitative, indirect immunoperoxidase histochemical analysis was performed on frozen synovial tissue sections. The recently characterised monoclonal antibody 10G7 recognising transfectants bearing u-PAR was used. Synovial tissue was obtained from 10 patients with rheumatoid arthritis, 10 patients with osteoarthritis, and four normal subjects. RESULTS: u-PAR was expressed on 70-90% of synovial tissue lining cells and subsynovial, interstitial macrophages from the arthritis patients, but only on a few myeloid cells from the normal subjects. It was also present on more endothelial cells from the rheumatoid and osteoarthritis patients, than from normal synovial tissue. CONCLUSIONS: Plasminogen activators are important in joint destruction underlying arthritis. The up-regulated expression of u-PAR in diseased versus normal synovial tissue suggests a role for this antigen in the inflammatory and angiogenic mechanisms underlying rheumatoid and osteoarthritis. Images PMID:9215148

  11. Differentiation between dogs with thrombosis and normal dogs using the overall hemostasis potential assay.

    PubMed

    Dengate, Anna L; Morel-Kopp, Marie-Christine; Beatty, Julia A; Barrs, Vanessa; Braddock, Jody A; Churcher, Richard K; Wilson, Bethany J; Ward, Christopher M

    2016-05-01

    To determine whether the overall hemostasis potential (OHP) and calibrated automated thrombogram (CAT) were significantly different between dogs with thrombosis and normal dogs. Ten dogs with clinical evidence of thromboembolic disease had both OHP and CAT performed. Forty healthy control dogs had OHP performed, and 23 of these also had CAT performed. Dogs with thrombosis had significantly higher OHP (P = 0.003), overall coagulation potential (P = 0.0001), and maximum optical density (Max OD, P < 0.0001) than normal dogs, and a significantly longer delay in the start of clot formation (P = 0.01). Max OD was higher than established reference intervals in 80% of the dogs with thrombosis. Using the CAT assay, dogs with thrombosis had a significantly longer lag time than normal dogs (P < 0.001). Plasma fibrinogen concentration correlated positively with overall coagulation potential, OHP, Max OD, and the slope of the OHP curve (P < 0.05), and was increased in 90% of dogs with thrombosis. The OHP assay findings were significantly different between normal dogs and those with thrombosis. CAT did not detect any significant differences between these populations of dogs, other than the lag time of the assay. © Veterinary Emergency and Critical Care Society 2016.

  12. Gene profile identifies zinc transporters differentially expressed in normal human organs and human pancreatic cancer.

    PubMed

    Yang, J; Zhang, Y; Cui, X; Yao, W; Yu, X; Cen, P; Hodges, S E; Fisher, W E; Brunicardi, F C; Chen, C; Yao, Q; Li, M

    2013-03-01

    Deregulated expression of zinc transporters was linked to several cancers. However, the detailed expression profile of all human zinc transporters in normal human organs and in human cancer, especially in pancreatic cancer is not available. The objectives of this study are to investigate the complete expression patterns of 14 ZIP and 10 ZnT transporters in a large number of normal human organs and in human pancreatic cancer tissues and cell lines. We examined the expression patterns of ZIP and ZnT transporters in 22 different human organs and tissues, 11 pairs of clinical human pancreatic cancer specimens and surrounding normal/benign tissues, as well as 10 established human pancreatic cancer cell lines plus normal human pancreatic ductal epithelium (HPDE) cells, using real time RT-PCR and immunohistochemistry. The results indicate that human zinc transporters have tissue specific expression patterns, and may play different roles in different organs or tissues. Almost all the ZIPs except for ZIP4, and most ZnTs were down-regulated in human pancreatic cancer tissues compared to the surrounding benign tissues. The expression patterns of individual ZIPs and ZnTs are similar among different pancreatic cancer lines. Those results and our previous studies suggest that ZIP4 is the only zinc transporter that is significantly up-regulated in human pancreatic cancer and might be the major zinc transporter that plays an important role in pancreatic cancer growth. ZIP4 might serve as a novel molecular target for pancreatic cancer diagnosis and therapy.

  13. Development of Planning Abilities in Normal Aging: Differential Effects of Specific Cognitive Demands

    ERIC Educational Resources Information Center

    Köstering, Lena; Stahl, Christoph; Leonhart, Rainer; Weiller, Cornelius; Kaller, Christoph P.

    2014-01-01

    In line with the frontal hypothesis of aging, the ability to plan ahead undergoes substantial change during normal aging. Although impairments on the Tower of London planning task were reported earlier, associations between age-related declines and specific cognitive demands on planning have not been studied. Here we investigated the impact of…

  14. Pmch-Deficiency in Rats Is Associated with Normal Adipocyte Differentiation and Lower Sympathetic Adipose Drive

    PubMed Central

    Mul, Joram D.; O’Duibhir, Eoghan; Shrestha, Yogendra B.; Koppen, Arjen; Vargoviç, Peter; Toonen, Pim W.; Zarebidaki, Eleen; Kvetnansky, Richard; Kalkhoven, Eric; Cuppen, Edwin; Bartness, Timothy J.

    2013-01-01

    The orexigenic neuropeptide melanin-concentrating hormone (MCH), a product of Pmch, is an important mediator of energy homeostasis. Pmch-deficient rodents are lean and smaller, characterized by lower food intake, body-, and fat mass. Pmch is expressed in hypothalamic neurons that ultimately are components in the sympathetic nervous system (SNS) drive to white and interscapular brown adipose tissue (WAT, iBAT, respectively). MCH binds to MCH receptor 1 (MCH1R), which is present on adipocytes. Currently it is unknown if Pmch-ablation changes adipocyte differentiation or sympathetic adipose drive. Using Pmch-deficient and wild-type rats on a standard low-fat diet, we analyzed dorsal subcutaneous and perirenal WAT mass and adipocyte morphology (size and number) throughout development, and indices of sympathetic activation in WAT and iBAT during adulthood. Moreover, using an in vitro approach we investigated the ability of MCH to modulate 3T3-L1 adipocyte differentiation. Pmch-deficiency decreased dorsal subcutaneous and perirenal WAT mass by reducing adipocyte size, but not number. In line with this, in vitro 3T3-L1 adipocyte differentiation was unaffected by MCH. Finally, adult Pmch-deficient rats had lower norepinephrine turnover (an index of sympathetic adipose drive) in WAT and iBAT than wild-type rats. Collectively, our data indicate that MCH/MCH1R-pathway does not modify adipocyte differentiation, whereas Pmch-deficiency in laboratory rats lowers adiposity throughout development and sympathetic adipose drive during adulthood. PMID:23555928

  15. Differential PAX3 functions in normal skin melanocytes and melanoma cells

    SciTech Connect

    Medic, Sandra; Rizos, Helen; Ziman, Mel

    2011-08-12

    Highlights: {yields} PAX3 retains embryonic roles in adult melanocytes and melanoma cells. {yields} Promotes 'stem' cell-like phenotype via NES and SOX9 in both cells types. {yields} Regulates melanoma and melanocyte migration through MCAM and CSPG4. {yields} PAX3 regulates melanoma but not melanocyte proliferation via TPD52. {yields} Regulates melanoma cell (but not melanocyte) survival via BCL2L1 and PTEN. -- Abstract: The PAX3 transcription factor is the key regulator of melanocyte development during embryogenesis and is also frequently found in melanoma cells. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during development, it is not clear if its function is maintained in adult melanocytes and melanoma cells. To clarify this we have assessed which genes are targeted by PAX3 in these cells. We show here that similar to its roles in development, PAX3 regulates complex differentiation networks in both melanoma cells and melanocytes, in order to maintain cells as 'stem' cell-like (via NES and SOX9). We show also that mediators of migration (MCAM and CSPG4) are common to both cell types but more so in melanoma cells. By contrast, PAX3-mediated regulation of melanoma cell proliferation (through TPD52) and survival (via BCL2L1 and PTEN) differs from that in melanocytes. These results suggest that by controlling cell proliferation, survival and migration as well as maintaining a less differentiated 'stem' cell like phenotype, PAX3 may contribute to melanoma development and progression.

  16. Differential PAX3 functions in normal skin melanocytes and melanoma cells.

    PubMed

    Medic, Sandra; Rizos, Helen; Ziman, Mel

    2011-08-12

    The PAX3 transcription factor is the key regulator of melanocyte development during embryogenesis and is also frequently found in melanoma cells. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during development, it is not clear if its function is maintained in adult melanocytes and melanoma cells. To clarify this we have assessed which genes are targeted by PAX3 in these cells. We show here that similar to its roles in development, PAX3 regulates complex differentiation networks in both melanoma cells and melanocytes, in order to maintain cells as "stem" cell-like (via NES and SOX9). We show also that mediators of migration (MCAM and CSPG4) are common to both cell types but more so in melanoma cells. By contrast, PAX3-mediated regulation of melanoma cell proliferation (through TPD52) and survival (via BCL2L1 and PTEN) differs from that in melanocytes. These results suggest that by controlling cell proliferation, survival and migration as well as maintaining a less differentiated "stem" cell like phenotype, PAX3 may contribute to melanoma development and progression.

  17. Placental Amino Acids Transport in Intrauterine Growth Restriction

    PubMed Central

    Avagliano, Laura; Garò, Chiara; Marconi, Anna Maria

    2012-01-01

    The placenta represents a key organ for fetal growth as it acts as an interface between mother and fetus, regulating the fetal-maternal exchange of nutrients, gases, and waste products. During pregnancy, amino acids represent one of the major nutrients for fetal life, and both maternal and fetal concentrations are significantly different in pregnancies with intrauterine growth restriction when compared to uncomplicated pregnancies. The transport of amino acids across the placenta is a complex process that includes the influx of neutral, anionic, and cationic amino acids across the microvilluos plasma membrane of the syncytiotrophoblast, the passage through the cytoplasm of the trophoblasts, and the transfer outside the trophoblasts across the basal membrane into the fetal circulation. In this paper, we review the transport mechanisms of amino acids across the placenta in normal pregnancies and in pregnancies complicated by intrauterine growth restriction. PMID:22997583

  18. Efficacy of Intrauterine Device in the Treatment of Intrauterine Adhesions

    PubMed Central

    Salma, Umme; Xue, Min; Md Sayed, Ali Sheikh; Xu, Dabao

    2014-01-01

    The primary purpose of this paper is to assess the efficacy of the use of the intrauterine device (IUD) as an adjunctive treatment modality, for intrauterine adhesions (IUAs). All eligible literatures were identified by electronic databases including PubMed, Scopus, and Web of Science. Additional relevant articles were identified from citations in these publications. There were 28 studies included for a systematic review. Of these, 5 studies were eligible for meta-analysis and 23 for qualitative assessment only. Twenty-eight studies related to the use of IUDs as ancillary treatment following adhesiolysis were identified. Of these studies, 25 studies at least one of the following methods were carried out as ancillary treatment: Foley catheter, hyaluronic acid gel, hormonal therapy, or amnion graft in addition to the IUD. There was one study that used IUD therapy as a single ancillary treatment. In 2 studies, no adjunctive therapy was used after adhesiolysis. There was a wide range of reported menstrual and fertility outcomes which were associated with the use of IUD combined with other ancillary treatments. At present, the IUD is beneficial in patients with IUA, regardless of stage of adhesions. However, IUD needs to be combined with other ancillary treatments to obtain maximal outcomes, in particular in patients with moderate to severe IUA. PMID:25254212

  19. Differential expression of cytochrome P450 enzymes in normal and tumor tissues from childhood rhabdomyosarcoma.

    PubMed

    Molina-Ortiz, Dora; Camacho-Carranza, Rafael; González-Zamora, José Francisco; Shalkow-Kalincovstein, Jaime; Cárdenas-Cardós, Rocío; Ností-Palacios, Rosario; Vences-Mejía, Araceli

    2014-01-01

    Intratumoral expression of genes encoding Cytochrome P450 enzymes (CYP) might play a critical role not only in cancer development but also in the metabolism of anticancer drugs. The purpose of this study was to compare the mRNA expression patterns of seven representative CYPs in paired tumor and normal tissue of child patients with rabdomyosarcoma (RMS). Using real time quantitative RT-PCR, the gene expression pattern of CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2W1, CYP3A4, and CYP3A5 were analyzed in tumor and adjacent non-tumor tissues from 13 child RMS patients. Protein concentration of CYPs was determined using Western blot. The expression levels were tested for correlation with the clinical and pathological data of the patients. Our data showed that the expression levels of CYP1A1 and CYP1A2 were negligible. Elevated expression of CYP1B1 mRNA and protein was detected in most RMS tumors and adjacent normal tissues. Most cancerous samples exhibit higher levels of both CYP3A4 and CYP3A5 compared with normal tissue samples. Expression of CYP2E1 mRNA was found to be significantly higher in tumor tissue, however no relation was found with protein levels. CYP2W1 mRNA and/or protein are mainly expressed in tumors. In conclusion, we defined the CYP gene expression profile in tumor and paired normal tissue of child patients with RMS. The overexpression of CYP2W1, CYP3A4 and CYP3A5 in tumor tissues suggests that they may be involved in RMS chemoresistance; furthermore, they may be exploited for the localized activation of anticancer prodrugs.

  20. Differential Expression of Cytochrome P450 Enzymes in Normal and Tumor Tissues from Childhood Rhabdomyosarcoma

    PubMed Central

    Molina-Ortiz, Dora; Camacho-Carranza, Rafael; González-Zamora, José Francisco; Shalkow-Kalincovstein, Jaime; Cárdenas-Cardós, Rocío; Ností-Palacios, Rosario; Vences-Mejía, Araceli

    2014-01-01

    Intratumoral expression of genes encoding Cytochrome P450 enzymes (CYP) might play a critical role not only in cancer development but also in the metabolism of anticancer drugs. The purpose of this study was to compare the mRNA expression patterns of seven representative CYPs in paired tumor and normal tissue of child patients with rabdomyosarcoma (RMS). Using real time quantitative RT-PCR, the gene expression pattern of CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2W1, CYP3A4, and CYP3A5 were analyzed in tumor and adjacent non-tumor tissues from 13 child RMS patients. Protein concentration of CYPs was determined using Western blot. The expression levels were tested for correlation with the clinical and pathological data of the patients. Our data showed that the expression levels of CYP1A1 and CYP1A2 were negligible. Elevated expression of CYP1B1 mRNA and protein was detected in most RMS tumors and adjacent normal tissues. Most cancerous samples exhibit higher levels of both CYP3A4 and CYP3A5 compared with normal tissue samples. Expression of CYP2E1 mRNA was found to be significantly higher in tumor tissue, however no relation was found with protein levels. CYP2W1 mRNA and/or protein are mainly expressed in tumors. In conclusion, we defined the CYP gene expression profile in tumor and paired normal tissue of child patients with RMS. The overexpression of CYP2W1, CYP3A4 and CYP3A5 in tumor tissues suggests that they may be involved in RMS chemoresistance; furthermore, they may be exploited for the localized activation of anticancer prodrugs. PMID:24699256

  1. Cholecystokinin A and B receptors are differentially expressed in normal pancreas and pancreatic adenocarcinoma.

    PubMed Central

    Weinberg, D S; Ruggeri, B; Barber, M T; Biswas, S; Miknyocki, S; Waldman, S A

    1997-01-01

    Cholecystokinin (CCK) plays an important role in pancreatic carcinogenesis. While human CCK-A and -B receptors have been fully characterized, their relative roles in human pancreatic adenocarcinoma remain unclear. Thus, expression of CCK-A and -B receptors in normal human pancreas, pancreatic adenocarcinomas, and other human extrapancreatic tissues and malignancies was examined, using reverse transcription followed by the polymerase chain reaction (RT-PCR). mRNA isolated from 15 normal pancreas specimens, 22 pancreatic adenocarcinomas, and 58 extrapancreatic tissues and tumors was subjected to RT-PCR using primers specific for human CCK-A and -B receptors. Expression of CCK-B receptors was detected in all tissues arising from pancreas and in most extrapancreatic tissues and tumors. In contrast, CCK-A receptors exhibited a more selective pattern of expression in gall bladder, intestine, brain, ovary, spleen, and thymus. Of significance, CCK-A receptors were expressed selectively in all pancreatic adenocarcinomas, but not in any normal pancreas specimens. In situ hybridization, using receptor-specific riboprobes, localized CCK-A receptor expression to ductal cells, the presumed origin of most human pancreatic adenocarcinomas. Southern blot analysis revealed no evidence of CCK-A receptor gene amplification or rearrangement in pancreatic adenocarcinomas. Because of its selective expression, the CCK-A receptor may serve as selective biomarker for pancreatic adenocarcinoma. PMID:9239407

  2. Contraception with intrauterine plastic loops.

    PubMed

    Lippes, J

    1965-12-01

    Intrauterine plastic loops were inserted 2179 times into 1713 patients of the Planned Parenthood Center of Buffalo, New York and from the author's private practice between November 1, 1961 and June 30, 1964 to evaluate the acceptability, effectiveness, reversibility, and side effects of this contraceptive method. Median age of the patients was 26 and their median parity 3. At the Planned Parenthood Center, patients are offered a choice of oral contraception (OC), condoms, diaphragms, jellies, rhythm, and the loop. During 1962, 30% of the new patients chose the loop. In 1963, 48% of new patients chose intrauterine contraception, and this proportion continued through June 1964. It rose to 55% early in 1965. 41 pregnancies occurred giving an overall pregnancy rate of 2.2/100 woman years for all loops. Loop D had a rate of 1.0/100 woman years. The pregnancy rate was calculated according to Potter's life table procedure. These rates compared favorably with a diaphragm failure rate of 4/100 woman years reported in the Indianapolis study or the diaphragm failure rate of 14.4 reported by Westoff and Potter, as well as with the rate of 2.1 for OC reported by Cook, Gamble, and Satterthwaite. 23 patients became pregnant with a loop in situ. There were 20 loop failures where location of the device was undetermined. Before November 30, 1964, 32 patients had discontinued intrauterine contraception because they wanted a child. All but 3 became pregnant. There were no abortions. The devices are not tolerated by all patients. Side effects consisted primarily of expulsions and bleeding, but pain and the possibility of infection were sometimes present. The monthly expulsion rate decreased with continued use. Most expulsions occurred in the 1st 6 months of use, and the largest and heaviest device had the lowest expulsion rate. 90% of the patients exhibited some alteration of their menstrual pattern. Cramps or pain were only a minor reason for terminating intrauterine contraception

  3. Diagnostic potential of near-infrared Raman spectroscopy in the stomach: differentiating dysplasia from normal tissue.

    PubMed

    Teh, S K; Zheng, W; Ho, K Y; Teh, M; Yeoh, K G; Huang, Z

    2008-01-29

    Raman spectroscopy is a molecular vibrational spectroscopic technique that is capable of optically probing the biomolecular changes associated with diseased transformation. The purpose of this study was to explore near-infrared (NIR) Raman spectroscopy for identifying dysplasia from normal gastric mucosa tissue. A rapid-acquisition dispersive-type NIR Raman system was utilised for tissue Raman spectroscopic measurements at 785 nm laser excitation. A total of 76 gastric tissue samples obtained from 44 patients who underwent endoscopy investigation or gastrectomy operation were used in this study. The histopathological examinations showed that 55 tissue specimens were normal and 21 were dysplasia. Both the empirical approach and multivariate statistical techniques, including principal components analysis (PCA), and linear discriminant analysis (LDA), together with the leave-one-sample-out cross-validation method, were employed to develop effective diagnostic algorithms for classification of Raman spectra between normal and dysplastic gastric tissues. High-quality Raman spectra in the range of 800-1800 cm(-1) can be acquired from gastric tissue within 5 s. There are specific spectral differences in Raman spectra between normal and dysplasia tissue, particularly in the spectral ranges of 1200-1500 cm(-1) and 1600-1800 cm(-1), which contained signals related to amide III and amide I of proteins, CH(3)CH(2) twisting of proteins/nucleic acids, and the C=C stretching mode of phospholipids, respectively. The empirical diagnostic algorithm based on the ratio of the Raman peak intensity at 875 cm(-1) to the peak intensity at 1450 cm(-1) gave the diagnostic sensitivity of 85.7% and specificity of 80.0%, whereas the diagnostic algorithms based on PCA-LDA yielded the diagnostic sensitivity of 95.2% and specificity 90.9% for separating dysplasia from normal gastric tissue. Receiver operating characteristic (ROC) curves further confirmed that the most effective diagnostic

  4. Intrauterine closure of myelomeningocele: an update.

    PubMed

    Tulipan, Noel

    2004-02-15

    Preliminary evidence suggests that intrauterine myelomeningocele repair may benefit patients by reducing the both incidence of hydrocephalus and the severity of the Chiari malformation; however, this benefit remains unproved. Furthermore, the procedure entails substantial risks not associated with conventional therapy. A randomized controlled trial of intrauterine and conventional therapies is underway. This study should definitively establish the procedure related risks and benefits. Regardless of the outcome, it is clear that the risks of intrauterine intervention need to be reduced before myelomeningocele, or other congenital malformations, can be effectively treated prior to birth. To that end, studies are being conducted to assess the potential advantages of applying state-of-the-art endoscopic techniques to intrauterine therapy. If benefit can be proven and risks reduced, intrauterine myelomeningocele repair has the potential to become the preferred therapy for patients suffering from this debilitating disease.

  5. Disinhibited Social Engagement in Postinstitutionalized Children: Differentiating Normal from Atypical Behavior

    PubMed Central

    Lawler, Jamie M.; Hostinar, Camelia E.; Mliner, Shanna B.; Gunnar, Megan R.

    2015-01-01

    The most commonly reported socially aberrant behavior in postinstitutionalized (PI) children is disinhibited social engagement (DSE; also known as indiscriminate friendliness). There is no gold standard for measurement of this phenomenon or agreement on how to differentiate it from normative behavior. We adopted a developmental psychopathology approach (Cicchetti, 1984) to study this phenomenon by comparing it to normative social development and by studying its patterns over time in 50 newly adopted PI children (16–36 months at adoption) compared with 41 children adopted early from foster care overseas and 47 nonadopted (NA) controls. Using coded behavioral observations of the child’s interaction with an unfamiliar adult, atypical behaviors were differentiated from normative behaviors. Principal components analysis identified two dimensions of social disinhibition. The nonphysical social dimension (e.g., initiations, proximity) showed wide variation in NA children and is therefore considered a typical form of sociability. Displays of physical contact and intimacy were rare in NA children, suggesting that they represent an atypical pattern of behavior. Both adopted groups demonstrated more physical DSE behavior than NA children. There were no group differences on the nonphysical factor, and it increased over time in all groups. Implications for understanding the etiology of DSE and future directions are discussed. PMID:24621789

  6. Differential localization of TGF-beta-precursor isotypes in normal human skin.

    PubMed

    Wataya-Kaneda, M; Hashimoto, K; Kato, M; Miyazono, K; Yoshikawa, K

    1994-08-01

    Transforming growth factor-beta (TGF-beta) can act as a multi-functional regulator of both cell growth and differentiation. Three isotypes of TGF-beta s namely TGF-beta 1, TGF-beta 2 and TGF-beta 3, have been found in human tissues. Up to now, little is known about the distribution patterns of the TGF-beta isotypes in human skin. Using the TGF-beta-precursor (latency-associated peptides) specific antibodies to confirm the specificity, we studied the immunohistochemical distribution of TGF-beta 1-3 in human skin. TGF-beta 2 was found mainly in the intercellular space of all the layers of the epidermis as well as in the cytoplasm with a weak staining. In contrast, TGF-beta 3 was present in the subepidermal area of the dermis. TGF-beta 1 was observed obviously in neither epidermis nor dermis. These results showed the differential localization of TGF-beta isotypes in human skin, suggesting that the TGF-beta 2 and TGF-beta 3 may regulate the human skin function in an epithelial autocrine or mesenchymal-epithelial interaction manner.

  7. The significant role of autophagy in the granular layer in normal skin differentiation and hair growth.

    PubMed

    Yoshihara, Nagisa; Ueno, Takashi; Takagi, Atsushi; Oliva Trejo, Juan Alejandro; Haruna, Kunitaka; Suga, Yasushi; Komatsu, Masaaki; Tanaka, Keiji; Ikeda, Shigaku

    2015-03-01

    As a major intracellular degradation system, autophagy contributes to the maintenance of skin keratinocyte homeostasis. However, the precise role of autophagy in skin differentiation has not been fully investigated. To clarify whether autophagy plays a role in skin differentiation and maturation, autophagy-related gene 7 (Atg7)-deficient mice were generated. Atg7-deficient mice cannot survive for more than 24 h after birth. Therefore, the skins of Atg7-deficient mice and wild-type mice (as a control) were grafted onto severe combined immunodeficient mice. The resulting morphological and pathological changes were monitored for 28 days. Histopathological examination revealed acanthosis, hyperkeratosis, and abnormal hair growth in the skin grafts from the Atg7-deficient mice. Immune-density analysis of the skin grafts revealed reduced immunostaining of keratinization-related proteins, including loricrin, filaggrin, and involucrin, in the skin grafts from the Atg7-deficient mice. Furthermore, quantitative RT-PCR and Western blot analyses revealed the reduced expression of these three keratinization-related proteins in the skin grafts from the Atg7-deficient mice. Morphometric analysis using electron microscopy further revealed a reduction in the number and diameter of the keratohyalin and trichohyalin granules in these skin grafts. The differences were maintained for at least 1 month after transplantation. These results show that autophagy has a significant role in epidermal keratinization and hair growth until a certain stage of maturation.

  8. Elemental analysis of tissue pellets for the differentiation of epidermal lesion and normal skin by laser-induced breakdown spectroscopy

    PubMed Central

    Moon, Youngmin; Han, Jung Hyun; Shin, Sungho; Kim, Yong-Chul; Jeong, Sungho

    2016-01-01

    By laser induced breakdown spectroscopy (LIBS) analysis of epidermal lesion and dermis tissue pellets of hairless mouse, it is shown that Ca intensity in the epidermal lesion is higher than that in dermis, whereas Na and K intensities have an opposite tendency. It is demonstrated that epidermal lesion and normal dermis can be differentiated with high selectivity either by univariate or multivariate analysis of LIBS spectra with an intensity ratio difference by factor of 8 or classification accuracy over 0.995, respectively. PMID:27231610

  9. Differential Uptake Of Benzoporphyrin Derivative (BPD) By Leukemic Versus Normal Cells

    NASA Astrophysics Data System (ADS)

    David; Julia G.; Levy

    1989-06-01

    Spectrofluorometric and FACS (Fluorescence Activated Cell Sorting) analyses were employed to determine 1) the maximal fluorescence excitation and emission peaks characteristic of BPD, benzoporphyrin derivative, 2) which structural analogue of BPD, BPD-monoacid ring A (BPD-MA), BPD-monoacid ring B (BPD-MB), BPD-diacid ring A (BPD-DA) or BPD-diacid ring B (BPD-DB) fluoresced to the greatest extent in the presence of leukemic cells and 3) to determine whether substantive differences existed in the uptake of BPD by human or murine leukemic versus normal human or murine mononuclear cells. Spectrofluorometric analysis revealed that the maximal fluorescence excitation peak of BPD (BPD-diacid ring A) was situated at 420 nm with a less prominent peak at 356 nm. Fluorescence emission scans, in which 420 nm was used as the excitation wavelength, revealed a single prominent fluorescence peak at 690 nm. FACS analysis revealed that negligible differences in fluorescence existed between leukemic cells incubated with BPD-MA, BPD-MB, BPD-DA, or BPD-DB upon excitation with visible light (488nm). However, subsequent to uv excitation cells incubated with BPD-MA fluoresced to the greatest extent followed by BPD-MB, BPD-DA, and BPD-DB respectively. Pronounced differences in red fluorescence were consistently observed between leukemic cells (HL60, K562, and L1210) and normal human or murine bone marrow cells incubated with BPD-MA. These observed differences in BPD-mediated fluorescence provide the rationale for sorting leukemic from normal cells via FACS and may constitute a novel method for extra-corporeal purging of remission marrow in autologous bone marrow transplantation.

  10. Differential response of normal and malignant urothelial cells to CHK1 and ATM inhibitors.

    PubMed

    Wang, W-T; Catto, J W F; Meuth, M

    2015-05-28

    While DNA damage response pathways are well characterized in cancer cells, much less is known about their status in normal cells. These pathways protect tumour cells from DNA damage and replication stress and consequently present potential therapeutic targets. Here we characterize the response of human telomerase reverse transcriptase (hTERT)-immortalized normal human urothelial (NHU) and bladder cancer cell lines to agents that disrupt the DNA damage response. Effects of replication and DNA damage response inhibitors on cell cycle progression, checkpoint induction and apoptosis were analysed in hTERT-NHU and bladder cancer cell lines. The primary signalling cascade responding to replication stress in malignant cells (ataxia telangiectasia-mutated (ATM) and Rad3-related-checkpoint kinase 1 (ATR-CHK1)) is not activated in hTERT-NHU cells after treatment with a replication inhibitor and these cells do not depend upon CHK1 for protection from apoptosis during replication stress. Instead, ATM signalling is rapidly activated under these conditions. Intriguingly, an ATM inhibitor suppressed S-phase checkpoint activation after exposure to replication inhibitors and stopped entry of cells into S-phase indicating G1 checkpoint activation. Consistent with this, hTERT-NHU cells treated with the ATM inhibitor showed increased levels of cyclin-dependent kinase inhibitor p19(INK4D), reduced levels of cyclin D1 and CDK4, and reduced phosphorylation of the retinoblastoma protein. In contrast, a bladder cancer cell line cotreated with ATM and replication inhibitors progressed more slowly through S phase and showed a marked increase in apoptosis. Taken together, our findings suggest that ATM and CHK1 signalling cascades have different roles in tumour and normal epithelial cells, confirming these as promising therapeutic targets.

  11. Label-free imaging of basement membranes differentiates normal, precancerous, and cancerous colonic tissues by second-harmonic generation microscopy.

    PubMed

    Zhuo, Shuangmu; Yan, Jun; Chen, Gang; Shi, Hong; Zhu, Xiaoqin; Lu, Jianping; Chen, Jianxin; Xie, Shusen

    2012-01-01

    Since changes in the basement membranes are the critical indicators for differentiating normal, precancerous, and cancerous colonic tissues, direct visualization of these warning signs is essential for the early diagnosis and treatment of colonic cancer. Here, we present that second harmonic generation (SHG) microscopy can probe the changes of basement membranes in different colonic cancer stages. Our results also show the capability of using the quantitative analyses of images for quantifying these changes in different cancer stages. These results suggest that SHG microscopy has the potential in label-freely imaging the changes of basement membranes for effectively distinguishing between normal, precancerous, and cancerous colonic tissues. To our knowledge, this is the first demonstration of the dynamics of basement membrane changes in different colonic cancer stages using entirely intrinsic source of contrast.

  12. Differentiation in boron distribution in adult male and female rats' normal brain: a BNCT approach.

    PubMed

    Goodarzi, Samereh; Pazirandeh, Ali; Jameie, Seyed Behnamedin; Khojasteh, Nasrin Baghban

    2012-06-01

    Boron distribution in adult male and female rats' normal brain after boron carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH: 7.4) was studied in this research. Coronal sections of control and trial animal tissue samples were irradiated with thermal neutrons. Using alpha autoradiography, significant differences in boron concentration were seen in forebrain, midbrain and hindbrain sections of male and female animal groups with the highest value, four hours after boron compound injection.

  13. INCREASED LEVELS OF SUPEROXIDE AND HYDROGEN PEROXIDE MEDIATE THE DIFFERENTIAL SUSCEPTIBILITY OF CANCER CELLS VS. NORMAL CELLS TO GLUCOSE DEPRIVATION

    PubMed Central

    Aykin-Burns, Nùkhet; Ahmad, Iman M.; Zhu, Yueming; Oberley, Larry W.; Spitz, Douglas R.

    2009-01-01

    Cancer cells, relative to normal cells, demonstrate increased sensitivity to glucose deprivation-induced cytotoxicity. To determine if oxidative stress mediated by O2•− and hydroperoxides contributed to the differential susceptibility of human epithelial cancer cells to glucose deprivation, oxidation of dihydroethidine (DHE; for O2•−) and 5-(and-6)-carboxy-2', 7'-dichlorodihydrofluorescein diacetate (CDCFH2; for hydroperoxides) were measured in human colon and breast cancer cells (HT29, HCT116, SW480, MB231) and compared to normal human cells (FHC, 33Co, HMEC). Cancer cells showed significant increases in DHE (2–20 fold) and CDCFH2 (1.8–10 fold) oxidation, relative to normal cells that were more pronounced in the presence of the mitochondrial electron transport chain blocker, antimycin A. Furthermore, HCT116 and MB231 cells were more susceptible to glucose deprivation-induced cytotoxicity and oxidative stress, relative to 33Co and HMEC. HT-29 cells were also more susceptible to 2-deoxyglucose-(2DG)-induced cytotoxicity, relative to FHC. Over expression of manganese superoxide dismutase and mitochondrially targeted catalase significantly protected HCT116 and MB231 cells from glucose deprivation-induced cytotoxicity and oxidative stress, as well as protecting HT-29 cells from 2DG-induced cytotoxicity. These results show cancer cells (relative to normal cells) demonstrate increased steady-state levels of reactive oxygen species (ROS, i.e. O2•− and H2O2) that contribute to differential susceptibility to glucose deprivation-induced cytotoxicity and oxidative stress. These studies support the hypotheses that cancer cells increase glucose metabolism to compensate for excess metabolic production of ROS as well as that inhibition of glucose and hydroperoxide metabolism may provide a biochemical target for selectively enhancing cytotoxicity and oxidative stress in human cancer cells. PMID:18937644

  14. Aldehyde dehydrogenase and estrogen receptor define a hierarchy of cellular differentiation in the normal human mammary epithelium

    PubMed Central

    2014-01-01

    Introduction Although estrogen and progesterone play a key role in normal mammary development and in breast cancer, the potential for proliferation and lineage differentiation as well as origin of cells that express the estrogen receptor (ER) in normal breast epithelium are not known. Some evidence suggests that normal human mammary stem/progenitor cells are ER–, but the identity of these cells and the cellular hierarchy of breast epithelium are still subjects of controversy. It is likely that elucidation of these aspects will bring insight into the cellular origin of breast cancer subtypes. Methods We used fluorescence-activated cell sorting of primary human mammary epithelial cells along with in vitro and in vivo functional assays to examine the hierarchic relation between cells with aldehyde dehydrogenase enzymatic activity (ALDH+ cells) and ER+ cells in the normal human breast epithelium. We assessed the proliferation and lineage differentiation potential of these cells in vitro and in vivo. A gene reporter assay was used to separate live ER+ and ER– mammary epithelial cells. With shRNA-mediated knockdown, we investigated the role of ALDH isoforms in the functionality of mammary epithelial progenitor cells. Results We describe a cellular hierarchy in the normal human mammary gland in which ER–/ALDH+ cells with functional properties of stem/progenitor cells generate ER+ progenitor cells, which in turn give rise to cells of luminal lineage. We show that the ALDH1A1 isoform, through its function in the retinoic acid metabolism, affects the proliferation and/or early differentiation of stem/progenitor cells and is important for branching morphogenesis. Conclusions This study presents direct evidence that ER+ cells are generated by ER–/ALDH+ stem/progenitor cells. We also show that ER+ cells are able to generate cell progeny of luminal lineage in vitro and in vivo. Loss of ALDH1A1 function impairs this process, as well as branching morphogenesis and

  15. Differential transferrin expression in placentae from normal and abnormal pregnancies: a pilot study

    PubMed Central

    Kralova, Alena; Svetlikova, Marta; Madar, Jindrich; Ulcova-Gallova, Zdena; Bukovsky, Antonin; Peknicova, Jana

    2008-01-01

    Background The placenta is an important site for iron metabolism in humans. It transfers iron from the mother to the fetus. One of the major iron transport proteins is transferrin, which is a blood plasma protein crucial for iron uptake. Its localization and expression may be one of the markers to distinguish placental dysfunction. Methods In the experimental study we used antibody preparation, mass spectrometric analysis, biochemical and immunocytochemical methods for characterization of transferrin expression on the human choriocarcinoma cell line JAR (JAR cells), placental lysates, and cryostat sections. Newly designed monoclonal antibody TRO-tf-01 to human transferrin was applied on human placentae from normal (n = 3) and abnormal (n = 9) pregnancies. Results Variations of transferrin expression were detected in villous syncytiotrophoblast, which is in direct contact with maternal blood. In placentae from normal pregnancies, the expression of transferrin in the syncytium was significantly lower (p < 0.001) when compared to placentae from abnormal ones (gestational diabetes, pregnancy induced hypertension, drug abuse). Conclusion These observations suggest that in the case of abnormal pregnancies, the fetus may require higher levels of transferrin in order to prevent iron depletion due to the stress from the placental dysfunction. PMID:18597674

  16. Mechanisms for differential effects between natural progesterone and synthetic progestogens on normal breast tissue.

    PubMed

    Söderqvist, Gunnar

    2010-12-01

    Both epidemiological studies and experimental data on normal breast tissue suggest increased cancer risk, proliferation and mammographic breast density (MD) during hormone therapy (HT) containing synthetic progestogens in traditional doses, and the relative risk or RR is approximately 1.5-3 (for women treated vs. untreated with the above therapies), proliferation levels of normal breast epithelial cells of around 10% and increase in MD in up to around 50% of women during treatment. Dose-response relationships have been inferred by correlations between progestogens as levonorgestrel, norethisterone acetate and medroxyprogesterone acetate on the one hand and proliferation and/or MD on the other hand, and of indications of lower relative risk of breast cancer with modern low or ultra-low dose HT. In contrast, natural progesterone endogenously during the menstrual cycle has a weak effect and exogenous estrogen in combination with oral micronized progesterone in HT has shown to yield an indifferent effect on proliferation. Furthermore, in epidemiological studies such as the French E3N cohort, these combinations have not shown any risk increase for breast cancer for at least 5 years of treatment. Experimental data supporting or not supporting the view that the main proliferative mechanism for natural progesterone is through binding to its nascent progesterone receptors is discussed as well as the pros and cons that the non-physiological higher proliferation levels induced by synthetic progestogens is mainly mediated through interaction with potent growth factors and their paracrine and/or cell signaling pathways.

  17. Differential effects of mental stress on plasma homovanillic acid in schizophrenia and normal controls.

    PubMed

    Sumiyoshi, T; Saitoh, O; Yotsutsuji, T; Itoh, H; Kurokawa, K; Kurachi, M

    1999-04-01

    We previously reported that mental stress by Kraepelin's arithmetic test decreases plasma homovanillic acid (pHVA) levels in psychiatrically normal healthy human subjects. The present study was undertaken to determine whether this pattern of changes in pHVA concentrations resulting from mental stress is altered in patients with schizophrenia. Fourteen male patients with schizophrenia including those under ongoing neuroleptic treatment and 14 normal male volunteers participated in the study. Following overnight fast and restricted physical activity, the subjects performed Kraepelin's arithmetic test for 30 minutes. Plasma samples were collected immediately before and after the test for measurement of pHVA levels. A significant diagnosis by Kraepelin's test effect was observed due to a decrease in pHVA levels by the Kraepelin test in control subjects but not in patients with schizophrenia. Changes in pHVA levels during the Kraepelin test positively correlated with pre-test pHVA levels in control subjects, while this correlation was not observed in patients with schizophrenia. These results may be further support for the presence of a dopamine-dependent restitutive system in the brain. The absence of response of pHVA levels to mental stress in patients with schizophrenia may indicate that the dopamine restitutive system in these patients is disrupted or already down-regulated, as previously predicted.

  18. Differentially active origins of DNA replication in tumor versus normal cells.

    PubMed

    Di Paola, Domenic; Price, Gerald B; Zannis-Hadjopoulos, Maria

    2006-05-15

    Previously, a degenerate 36 bp human consensus sequence was identified as a determinant of autonomous replication in eukaryotic cells. Random mutagenesis analyses further identified an internal 20 bp of the 36 bp consensus sequence as sufficient for acting as a core origin element. Here, we have located six versions of the 20 bp consensus sequence (20mer) on human chromosome 19q13 over a region spanning approximately 211 kb and tested them for ectopic and in situ replication activity by transient episomal replication assays and nascent DNA strand abundance analyses, respectively. The six versions of the 20mer alone were capable of supporting autonomous replication of their respective plasmids, unlike random genomic sequence of the same length. Furthermore, comparative analyses of the endogenous replication activity of these 20mers at their respective chromosomal sites, in five tumor/transformed and two normal cell lines, done by in situ chromosomal DNA replication assays, involving preparation of nascent DNA by the lambda exonuclease method and quantification by real-time PCR, showed that these sites coincided with chromosomal origins of DNA replication in all cell lines. Moreover, a 2- to 3-fold higher origin activity in the tumor/transformed cells by comparison to the normal cells was observed, suggesting a higher activation of these origins in tumor/transformed cell lines.

  19. Structured prediction for differentiating between normal rhythms, ventricular tachycardia, and ventricular fibrillation in the ECG.

    PubMed

    Alwan, Yaqub; Cvetkovic, Zoran; Curtis, Michael

    2015-01-01

    Recent studies have been performed on feature selection for diagnostics between non-ventricular rhythms and ventricular arrhythmias, or between non-ventricular fibrillation and ventricular fibrillation. However they did not assess classification directly between non-ventricular rhythms, ventricular tachycardia and ventricular fibrillation, which is important in both a clinical setting and preclinical drug discovery. In this study it is shown that in a direct multiclass setting, the selected features from these studies are not capable at differentiating between ventricular tachycardia and ventricular fibrillation. A high dimensional feature space, Fourier magnitude spectra, is proposed for classification, in combination with the structured prediction method conditional random fields. An improvement in overall accuracy, and sensitivity of every category under investigation is achieved.

  20. Comparison of hematopoietic cancer stem cells with normal stem cells leads to discovery of novel differentially expressed SSRs.

    PubMed

    Hosseinpour, Batool; Bakhtiarizadeh, Mohammad Reza; Mirabbassi, Seyedeh Maryam; Ebrahimie, Esmaeil

    2014-10-15

    addition, a new approach for gene discovery in cancer by target analysis of differentially expressed EST-SSRs between cancer and normal stem cells is presented here. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Sexual differentiation of the copulatory neuromuscular system in green anoles (Anolis carolinensis): normal ontogeny and manipulation of steroid hormones.

    PubMed

    Holmes, Melissa M; Wade, Juli

    2005-09-05

    The copulatory neuromuscular system of green anoles is sexually dimorphic and differentiates during embryonic development, although details of the process were unknown. In Experiment 1, we determined the time course of normal ontogeny. Both male and female embryos possessed bilateral copulatory organs (hemipenes) and associated muscles until incubation day 13; the structures completely regressed in female embryos by incubation day 19 (total incubation 34 days). In Experiment 2, we treated eggs with testosterone, dihydrotestosterone, estradiol, or vehicle on both incubation days 10 and 13 to determine whether these steroid hormones mediate sexual differentiation. These time points fall between gonadal differentiation, which was determined in Experiment 1 to complete before day 10, and regression of the peripheral copulatory system in females. Tissue was collected on the day of hatching. Gonads were classified as testes or ovaries; presence versus absence of hemipenes and muscles, and the number and size of copulatory motoneurons were determined. Copulatory system morphology of vehicle-treated animals matched their gonadal sex. Hemipenes and muscles were absent in estradiol-treated animals, and androgens rescued the hemipenes and muscles in most females. Both testosterone and dihydrotestosterone treatment also caused hypertrophy of the hemipenes, which were everted in animals treated with these steroids. Copulatory motoneurons, assessed on the day of hatching in both experiments, were not dimorphic in size or number. Steroid treatment significantly increased motoneuron size and number overall, but no significant differences were detected in pairwise comparisons. These data demonstrate that differentiation of peripheral copulatory neuromuscular structures occurs during embryonic development and is influenced by gonadal steroids (regression by estradiol and enhancement by androgens), but associated motoneurons do not differentiate until later in life.

  2. Normal Human Lung Epithelial Cells Inhibit Transforming Growth Factor-β Induced Myofibroblast Differentiation via Prostaglandin E2

    PubMed Central

    Epa, Amali P.; Thatcher, Thomas H.; Pollock, Stephen J.; Wahl, Lindsay A.; Lyda, Elizabeth; Kottmann, R. M.; Phipps, Richard P.; Sime, Patricia J.

    2015-01-01

    Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with very few effective treatments. The key effector cells in fibrosis are believed to be fibroblasts, which differentiate to a contractile myofibroblast phenotype with enhanced capacity to proliferate and produce extracellular matrix. The role of the lung epithelium in fibrosis is unclear. While there is evidence that the epithelium is disrupted in IPF, it is not known whether this is a cause or a result of the fibroblast pathology. We hypothesized that healthy epithelial cells are required to maintain normal lung homeostasis and can inhibit the activation and differentiation of lung fibroblasts to the myofibroblast phenotype. To investigate this hypothesis, we employed a novel co-culture model with primary human lung epithelial cells and fibroblasts to investigate whether epithelial cells inhibit myofibroblast differentiation. Measurements and Main Results In the presence of transforming growth factor (TGF)-β, fibroblasts co-cultured with epithelial cells expressed significantly less α-smooth muscle actin and collagen and showed marked reduction in cell migration, collagen gel contraction, and cell proliferation compared to fibroblasts grown without epithelial cells. Epithelial cells from non-matching tissue origins were capable of inhibiting TGF-β induced myofibroblast differentiation in lung, keloid and Graves’ orbital fibroblasts. TGF-β promoted production of prostaglandin (PG) E2 in lung epithelial cells, and a PGE2 neutralizing antibody blocked the protective effect of epithelial cell co-culture. Conclusions We provide the first direct experimental evidence that lung epithelial cells inhibit TGF-β induced myofibroblast differentiation and pro-fibrotic phenotypes in fibroblasts. This effect is not restricted by tissue origin, and is mediated, at least in part, by PGE2. Our data support the hypothesis that the epithelium plays a crucial role in maintaining lung homeostasis

  3. Differentiating fibroadenoma and ductal carcinoma in situ from normal breast tissue by multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Nie, Yuting; Wu, Yan; Lian, Yuane; Fu, Fangmeng; Wang, Chuan; Chen, Jianxin

    2014-09-01

    Fibroadenoma (FA) is the most common benign tumor of the female breast and several studies have reported that women with it have increased risk of breast cancer. While the ductal carcinoma in situ (DCIS) is a very early form of breast cancer. Thus, early detections of FA and DCIS are critical for improving breast tumor outcome and survival. In this paper, we use multiphoton microscopy (MPM) to obtain the high-contrast images of fresh, unfixed, unstained human breast specimens (normal breast tissue, FA and DCIS). Our results show that MPM has the ability to identify the characteristics of FA and DCIS including changes of duct architecture and collagen morphology. These results are consistent with the histological results. With the advancement of MPM, the technique has potential ability to serve as a real-time noninvasive imaging tool for early detection of breast tumor.

  4. Dictyostelium RasD is required for normal phototaxis, but not differentiation

    PubMed Central

    Wilkins, Andrew; Khosla, Meenal; Fraser, Derek J.; Spiegelman, George B.; Fisher, Paul R.; Weeks, Gerald; Insall, Robert H.

    2000-01-01

    RasD, a Dictyostelium homolog of mammalian Ras, is maximally expressed during the multicellular stage of development. Normal Dictyostelium aggregates are phototactic and thermotactic, moving towards sources of light and heat with great sensitivity. We show that disruption of the gene for rasD causes a near-total loss of phototaxis and thermotaxis in mutant aggregates, without obvious effects on undirected movement. Previous experiments had suggested important roles for RasD in development and cell-type determination. Surprisingly, rasD− cells show no obvious changes in these processes. These cells represent a novel class of phototaxis mutant, and indicate a role for a Ras pathway in the connections between stimuli and coordinated cell movement. PMID:10837033

  5. Dictyostelium RasD is required for normal phototaxis, but not differentiation.

    PubMed

    Wilkins, A; Khosla, M; Fraser, D J; Spiegelman, G B; Fisher, P R; Weeks, G; Insall, R H

    2000-06-01

    RasD, a Dictyostelium homolog of mammalian Ras, is maximally expressed during the multicellular stage of development. Normal Dictyostelium aggregates are phototactic and thermotactic, moving towards sources of light and heat with great sensitivity. We show that disruption of the gene for rasD causes a near-total loss of phototaxis and thermotaxis in mutant aggregates, without obvious effects on undirected movement. Previous experiments had suggested important roles for RasD in development and cell-type determination. Surprisingly, rasD(-) cells show no obvious changes in these processes. These cells represent a novel class of phototaxis mutant, and indicate a role for a Ras pathway in the connections between stimuli and coordinated cell movement.

  6. Uninstructed BIAT faking when ego depleted or in normal state: differential effect on brain and behavior.

    PubMed

    Wolff, Wanja; Schindler, Sebastian; Englert, Christoph; Brand, Ralf; Kissler, Johanna

    2016-05-03

    Deception can distort psychological tests on socially sensitive topics. Understanding the cerebral processes that are involved in such faking can be useful in detection and prevention of deception. Previous research shows that faking a brief implicit association test (BIAT) evokes a characteristic ERP response. It is not yet known whether temporarily available self-control resources moderate this response. We randomly assigned 22 participants (15 females, 24.23 ± 2.91 years old) to a counterbalanced repeated-measurements design. Participants first completed a Brief-IAT (BIAT) on doping attitudes as a baseline measure and were then instructed to fake a negative doping attitude both when self-control resources were depleted and non-depleted. Cerebral activity during BIAT performance was assessed using high-density EEG. Compared to the baseline BIAT, event-related potentials showed a first interaction at the parietal P1, while significant post hoc differences were found only at the later occurring late positive potential. Here, significantly decreased amplitudes were recorded for 'normal' faking, but not in the depletion condition. In source space, enhanced activity was found for 'normal' faking in the bilateral temporoparietal junction. Behaviorally, participants were successful in faking the BIAT successfully in both conditions. Results indicate that temporarily available self-control resources do not affect overt faking success on a BIAT. However, differences were found on an electrophysiological level. This indicates that while on a phenotypical level self-control resources play a negligible role in deliberate test faking the underlying cerebral processes are markedly different.

  7. Differential expression of equine muscle biopsy proteins during normal training and intensified training in young standardbred horses using proteomics technology.

    PubMed

    Bouwman, Freek G; van Ginneken, Mireille M E; Noben, Jean-Paul; Royackers, Erik; de Graaf-Roelfsema, Ellen; Wijnberg, Inge D; van der Kolk, Johannes H; Mariman, Edwin C M; van Breda, Eric

    2010-03-01

    The major aim of the present study was to investigate the proteome of standardbred horses at different stages of training and intensified training. We searched for biomarkers using small skeletal muscle biopsies of live animals. 2D gel electrophoresis and mass spectrometry were successfully applied to investigate training-induced differential expression of equine muscle biopsy proteins. Despite the poor resolution of the equine genome and proteome, we were able to identify the proteins of 20 differential spots representing 16 different proteins. Evaluation of those proteins complies with adaptation of the skeletal muscle after normal training involving structural changes towards a higher oxidative capacity, an increased capacity to take up long-chain fatty acids, and to store energy in the form of glycogen. Intensified training leads to additional changed spots. Alpha-1-antitrypsin was found increased after intensified training but not after normal training. This protein may thus be considered as a marker for overtraining in horses and also linked to overtraining in human athletes. Copyright 2009 Elsevier Inc. All rights reserved.

  8. ChIPnorm: A Statistical Method for Normalizing and Identifying Differential Regions in Histone Modification ChIP-seq Libraries

    PubMed Central

    Bucher, Philipp; Moret, Bernard M. E.

    2012-01-01

    The advent of high-throughput technologies such as ChIP-seq has made possible the study of histone modifications. A problem of particular interest is the identification of regions of the genome where different cell types from the same organism exhibit different patterns of histone enrichment. This problem turns out to be surprisingly difficult, even in simple pairwise comparisons, because of the significant level of noise in ChIP-seq data. In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods. We correlate the histone marks with gene expression data and confirm that histone modifications H3K27me3 and H3K4me3 act as respectively a repressor and an activator of genes. Compared to what was previously reported in the literature, we find that a substantially higher fraction of bivalent marks in ES cells for H3K27me3 and H3K4me3 move into a K27-only state. We find that most of the promoter regions in protein-coding genes have differential histone-modification sites. The software for this work can be downloaded from http://lcbb.epfl.ch/software.html. PMID:22870189

  9. Alteration in Expression and Methylation of IGF2/H19 in Placenta and Umbilical Cord Blood Are Associated with Macrosomia Exposed to Intrauterine Hyperglycemia.

    PubMed

    Su, Rina; Wang, Chen; Feng, Hui; Lin, Li; Liu, Xinyue; Wei, Yumei; Yang, Huixia

    2016-01-01

    Macrosomia is one of the most common complications in gestational diabetes mellitus. Insulin-like growth factor 2 and H19 are two of the imprinted candidate genes that are involved in fetal growth and development. Change in methylation at differentially methylated region of the insulin-like growth factor 2 and H19 has been proved to be an early event related to the programming of metabolic profile, including macrosomia and small for gestational age in offspring. Here we hypothesize that alteration in methylation at differentially methylated region of the insulin-like growth factor 2 and H19 is associated with macrosomia induced by intrauterine hyperglycemia. The expression of insulin-like growth factor 2 is significant higher in gestational diabetes mellitus group (GDM group) compared to normal glucose tolerance group (NGT group) both in umbilical cord blood and placenta, while the expression of H19 is significant lower in GDM group in umbilical cord blood. The expression of insulin-like growth factor 2 is significant higher in normal glucose tolerance with macrosomia group (NGT-M) compared to normal glucose tolerance with normal birthweight group (NGT-NBW group) both in placenta and umbilical cord blood. A model with interaction term of gene expression of IGF2 and H19 found that IGF2 and the joint action of IGF2 and H19 in placenta showed significantly relationship with GDM/NGT and GDM-NBW/NGT-NBW. A borderline significant association was seen among IGF2 and H19 in cord blood and GDM-M/NGT-M. The methylation level at different CpG sites of insulin-like growth factor 2 and H19 in umbilical cord blood was also significantly different among groups. Based on the multivariable linear regression analysis, the methylation of the insulin-like growth factor 2 / H19 is closely related to birth weight and intrauterine hyperglycemia. We confirmed the existence of alteration in DNA methylation in umbilical cord blood exposed to intrauterine hyperglycemia and reported a

  10. 21 CFR 884.2700 - Intrauterine pressure monitor and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Intrauterine pressure monitor and accessories. 884... Monitoring Devices § 884.2700 Intrauterine pressure monitor and accessories. (a) Identification. An intrauterine pressure monitor is a device designed to detect and measure intrauterine and amniotic...

  11. An improved parent-centric mutation with normalized neighborhoods for inducing niching behavior in differential evolution.

    PubMed

    Biswas, Subhodip; Kundu, Souvik; Das, Swagatam

    2014-10-01

    In real life, we often need to find multiple optimally sustainable solutions of an optimization problem. Evolutionary multimodal optimization algorithms can be very helpful in such cases. They detect and maintain multiple optimal solutions during the run by incorporating specialized niching operations in their actual framework. Differential evolution (DE) is a powerful evolutionary algorithm (EA) well-known for its ability and efficiency as a single peak global optimizer for continuous spaces. This article suggests a niching scheme integrated with DE for achieving a stable and efficient niching behavior by combining the newly proposed parent-centric mutation operator with synchronous crowding replacement rule. The proposed approach is designed by considering the difficulties associated with the problem dependent niching parameters (like niche radius) and does not make use of such control parameter. The mutation operator helps to maintain the population diversity at an optimum level by using well-defined local neighborhoods. Based on a comparative study involving 13 well-known state-of-the-art niching EAs tested on an extensive collection of benchmarks, we observe a consistent statistical superiority enjoyed by our proposed niching algorithm.

  12. Thyrotropin Stimulates Differentiation Not Proliferation of Normal Human Thyrocytes in Culture

    PubMed Central

    Morgan, Sarah J.; Neumann, Susanne; Marcus-Samuels, Bernice; Gershengorn, Marvin C.

    2016-01-01

    Although TSH has been suggested to be a proliferative agent for thyrocytes, the effect of TSH on human thyroid cells remains controversial. In particular, most of the reported studies relied primarily on changes in DNA synthesis but have not included measurement of the number of cells. We argue that only a direct count of cell number, demonstrating classical exponential expansion, serves as a valid measurement of proliferation. Thus, although some data support TSH as a proliferative agent, most do not provide conclusive evidence. To generate conclusive evidence with regard to a proliferative effect of TSH in human thyrocytes, we performed various experiments using primary cultures of human thyrocytes. In contrast to previous reports, TSH [±insulin-like growth factor 1 (IGF-1)] did not induce proliferation of thyrocytes under a variety of different conditions. However, TSH/IGF-1 cotreatment did upregulate thyroid-specific gene expression including thyroglobulin (TG) and TSHR in a manner consistent with cellular differentiation. Evidence for a proliferative effect of TSH has been used to inform the American Thyroid Association’s guidelines for the management of thyroid cancer patients, which include TSH suppression. While these recommendations are admittedly based on low- to moderate-quality evidence, TSH suppression is still widely used. We present data that question the consensus view that TSH promotes proliferation of human thyrocytes (upon which the American Thyroid Association’s guidelines are based) and suggest that additional studies, including randomized controlled trials, are warranted to address this important clinical question. PMID:28082948

  13. Differential Role of Leptin as an Immunomodulator in Controlling Visceral Leishmaniasis in Normal and Leptin-Deficient Mice.

    PubMed

    Maurya, Radheshyam; Bhattacharya, Parna; Ismail, Nevien; Dagur, Pradeep K; Joshi, Amritanshu B; Razdan, Kundan; McCoy, J Philip; Ascher, Jill; Dey, Ranadhir; Nakhasi, Hira L

    2016-07-06

    Visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania donovani There are no vaccines and available drugs against leishmaniasis are toxic. Immunomodulators that specifically boost the anti-microbial activities of the immune cells could alleviate several of these limitations. Therefore, finding novel immunomodulators for VL therapy is a pressing need. This study is aimed to evaluate the immunomodulatory role of leptin, an adipocyte-derived hormone capable of regulating the immune response, in L. donovani-infected mice. We observed that recombinant leptin treatment reduced splenic parasite burden compared with non-treated infected normal mice. Decrease in parasite burden correlated with an induction of innate immune response in antigen-presenting cells that showed an increase in nitric oxide, enhanced pro-inflammatory cytokine (interferon gamma [IFNγ], interleukin12 [IL]12, and IL1β) response in the splenocytes, indicating host-protecting Th1 response mediated by leptin. Moreover, in infected normal mice, leptin treatment induced IFNγ production from both CD4(+) and CD8(+) T cells, compared with non-treated infected mice. Alternatively, leptin-deficient (Ob/Ob) mice had higher splenic and liver parasite burden compared with the infected normal mice. However, leptin treatment failed to reduce the splenic parasite burden and improve a host-protective cytokine response in these mice. In addition, in contrast to dendritic cells (DCs) from a normal mouse, Ob/Ob mouse-derived DCs showed a defect in the induction of innate immune response on Leishmania infection that could not be reversed by leptin treatment. Therefore, our findings reveal that leptin has a differential immunomodulatory effect in controlling VL in normal and Ob/Ob mice. © The American Society of Tropical Medicine and Hygiene.

  14. Differential Role of Leptin as an Immunomodulator in Controlling Visceral Leishmaniasis in Normal and Leptin-Deficient Mice

    PubMed Central

    Maurya, Radheshyam; Bhattacharya, Parna; Ismail, Nevien; Dagur, Pradeep K.; Joshi, Amritanshu B.; Razdan, Kundan; McCoy, J. Philip; Ascher, Jill; Dey, Ranadhir; Nakhasi, Hira L.

    2016-01-01

    Visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania donovani. There are no vaccines and available drugs against leishmaniasis are toxic. Immunomodulators that specifically boost the anti-microbial activities of the immune cells could alleviate several of these limitations. Therefore, finding novel immunomodulators for VL therapy is a pressing need. This study is aimed to evaluate the immunomodulatory role of leptin, an adipocyte-derived hormone capable of regulating the immune response, in L. donovani-infected mice. We observed that recombinant leptin treatment reduced splenic parasite burden compared with non-treated infected normal mice. Decrease in parasite burden correlated with an induction of innate immune response in antigen-presenting cells that showed an increase in nitric oxide, enhanced pro-inflammatory cytokine (interferon gamma [IFNγ], interleukin12 [IL]12, and IL1β) response in the splenocytes, indicating host-protecting Th1 response mediated by leptin. Moreover, in infected normal mice, leptin treatment induced IFNγ production from both CD4+ and CD8+ T cells, compared with non-treated infected mice. Alternatively, leptin-deficient (Ob/Ob) mice had higher splenic and liver parasite burden compared with the infected normal mice. However, leptin treatment failed to reduce the splenic parasite burden and improve a host-protective cytokine response in these mice. In addition, in contrast to dendritic cells (DCs) from a normal mouse, Ob/Ob mouse–derived DCs showed a defect in the induction of innate immune response on Leishmania infection that could not be reversed by leptin treatment. Therefore, our findings reveal that leptin has a differential immunomodulatory effect in controlling VL in normal and Ob/Ob mice. PMID:27114296

  15. Sulforaphane induces differential modulation of mitochondrial biogenesis and dynamics in normal cells and tumor cells.

    PubMed

    Negrette-Guzmán, Mario; Huerta-Yepez, Sara; Vega, Mario I; León-Contreras, Juan Carlos; Hernández-Pando, Rogelio; Medina-Campos, Omar Noel; Rodríguez, Esteban; Tapia, Edilia; Pedraza-Chaverri, José

    2017-02-01

    Antioxidant-based chemotherapy has been intensely debated. Herein, we show that sulforaphane (SFN) induced mitochondrial biogenesis followed by mitochondrial fusion in a kidney cell line commonly used in nephroprotective models. At the same concentration and exposure time, SFN induced cell death in prostate cancer cells accompanied by mitochondrial biogenesis and fragmentation. Stabilization of the nuclear factor E2-related factor-2 (Nrf2) could be associated with these effects in the tumor cell line. An increase in the peroxisome proliferator-activated receptor-γ co-activator-1α (PGC1α) level and a decrease in the hypoxia-inducible factor-1α (HIF1α) level would suggest a possible metabolic shift. The knockdown in the nuclear respiratory factor-1 (NRF1) attenuated the SFN-induced effect on prostate cancer cells demonstrating that mitochondrial biogenesis plays an important role in cell death for this kind of tumor cells. This evidence supports SFN as a potential antineoplastic agent that could inhibit tumor development and could protect normal tissues by modulating common processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Differential Expression of Matrix-Metalloproteinase-1 and -2 Genes in Normal and Fibrotic Human Liver

    PubMed Central

    Milani, Stefano; Herbst, Hermann; Schuppan, Detlef; Grappone, Cecilia; Pellegrini, Giulia; Pinzani, Massimo; Casini, Alessandro; Calabró, Antonio; Ciancio, Giuseppe; Stefanini, Francesco; Ciancio, Andrew K.; Surrenti, Calogero

    1994-01-01

    Altered degradation of extracellular matrix has been implicated in the pathogenesis of hepatic fibrosis. We investigated levels and cellular sites of gene expression of two major collagebn-degrading enzymes, matrix-metalloproteinase (MMP)-l (fibroblast type-interstitial collagenase)and MMP-2 (72-kd gelatinase, type IV collagenase) in five normal and 18 fibrotic human livers as well as in cultured human hepatic fat-storing cells by Northern blot analysis and in situ hybridization. Fatstoring cells expressed both MMP-1 and MMP-2 RNA in vitro. In vivo, MMP-1 was undetectable in mesenchymal and parenchymal cells of all liver specimens, whereas MMP-2 transcripts were expressed in all livers by vimentin-positive, CD68 negative mesenchymal cells. Mesenchymal cells of all fibrotic livers displayed high transcript levels of transforming growth factor-β1, which is known to modulate MMP expression. Along with de novo fibrogenesis and possibly influenced by transforming growth factor-β1, expression of MMP-2 in the absence of MMP-1 expression may be responsible for the quantitative and qualitative changes of extracellular matrix observed in chronic liver disease. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 7 PMID:8129038

  17. Intrauterine Growth Retardation (IUGR) as a Novel Condition of Insulin-Like Growth Factor-1 (IGF-1) Deficiency.

    PubMed

    Martín-Estal, I; de la Garza, R G; Castilla-Cortázar, I

    2016-01-01

    Insulin-like growth factor 1 (IGF-1) is an anabolic hormone with several biological activities, such as proliferation, mitochondrial protection, cell survival, tissue growth and development, anti-inflammatory, antioxidant, antifibrogenic and antiaging. This hormone plays an important role in embryological and postnatal states, being essential for normal foetal and placental growth and differentiation. During gestation, the placenta is one of the major sources of IGF-1, among other hormones. This intrauterine organ expresses IGF-1 receptors and IGF-1 binding proteins (IGFBPs), which control IGF-1 activities. Intrauterine growth restriction (IUGR) is the second most frequent cause of perinatal morbidity and mortality, defined as the inability to achieve the expected weight for gestational age. Different studies have revealed that IUGR infants have placental dysfunction and low circulating levels of insulin, IGF-1, IGF-2 and IGFBPs. Such data suggest that IGF-1 deficiency in gestational state may be one of the major causes of foetal growth retardation. The aim of this review is to study the epidemiology, physiopathology and possible causes of IUGR. Also, it intends to study the possible role of the placenta as an IGF-1 target organ. The purpose is to establish if IUGR could be considered as a novel condition of IGF-1 deficiency and if its treatment with low doses of IGF-1 could be a suitable therapeutic strategy.

  18. Differential responses of tumors and normal brain to the combined treatment of 2-DG and radiation in glioablastoma.

    PubMed

    Prasanna, Venkatesh K; Venkataramana, Neelam K; Dwarakanath, B S; Santhosh, Vani

    2009-09-01

    2-Deoxy-D-glucose (2-DG), an inhibitor of glucose transport and glycolysis, enhances radiation damage selectively in tumor cells by modulating damage response pathways resulting in cell death in vitro and local tumor control. Phase I and II clinical trials in patients with malignant glioma have shown excellent tolerance to a combined treatment of orally administered 2-DG and hypofractionated radiotherapy without any acute toxicity and late radiation damage. Phase III efficacy trials are currently at an advanced stage. Re-exploratory surgery performed in 13 patients due to persistent symptoms of elevated ICP and mass effect at different follow-up periods revealed extensive tumor necrosis with well-preserved normal brain tissue adjoining the tumor included in the treatment volume as revealed by a histological examination. These observations are perhaps the first clinical evidences for differential effects of 2-DG on tumors and normal tissues in conformity with earlier in vitro and in vivo studies in normal and tumor-bearing mice.

  19. Differential effects of vitamin D on normal human prostate epithelial and stromal cells in primary culture.

    PubMed

    Krill, D; Stoner, J; Konety, B R; Becich, M J; Getzenberg, R H

    1999-07-01

    Because epidemiologic evidence has demonstrated that vitamin D may play a role in the etiology of prostate cancer, we tested the inhibitory effect of the biologically active form of vitamin D (1,25-D) on the cell proliferation of human prostate epithelial and stromal cells in a chemically defined situation in the presence and absence of dihydrotestosterone (DHT). We also tested the effect of 1,25-D in castrated rats in the presence and absence of flutamide, an androgen receptor blocker. Prostate stromal and epithelial cells were isolated from freshly collected human prostatectomy specimens, and cell proliferation was measured with the MTT assay. Immunohistochemistry was performed to detect the presence of 1,25-D receptors, androgen receptors, smooth muscle actin, and E-cadherin. For in vivo analysis of 1,25-D, male Sprague-Dawley rats were castrated, then treated with either 1,25-D, 1,25-D with flutamide, or vehicle control. Incubation of primary cultures of prostate epithelial cells with 1,25-D at a concentration of 10(-8) M reduced cell proliferation by 40% of controls. The inhibition of growth by 1,25-D was maintained in the presence of DHT. Conversely, the effect of a similar dose of 1,25-D on stromal cell exposure was increased proliferation. In vivo, 1,25-D increased the prostatic weight of castrated rats that had serum testosterone levels below the detectable limit. The addition of flutamide did not alter this effect. These results confirm that vitamin D may be an effective antiproliferative agent of epithelial cells in prostate cancer therapy and support in vivo studies performed in the normal rat prostate.

  20. ATP-binding cassette sterol transporters are differentially expressed in normal and diseased human gallbladder.

    PubMed

    Yoon, Jai Hoon; Choi, Ho Soon; Jun, Dae Won; Yoo, Kyo-Sang; Lee, Jin; Yang, Sun Young; Kuver, Rahul

    2013-02-01

    Gallbladder epithelial cells (GBEC) are exposed to high cholesterol concentrations in bile, and export cholesterol via an ATP-binding cassette (ABC) transporter-mediated pathway in vitro. These findings suggest that aberrant expression and/or function of ABC sterol transporters may be associated with cholesterol-related gallbladder diseases (CAGD). In this study, we investigated the relative levels of the sterol transporters ABCA1, ABCG5, and ABCG8 in human gallbladders in CAGD, and the relationship between ABCA1 and inflammation. Expression of ABCA1, ABCG5, and ABCG8 was evaluated in 31 gallbladders with CAGD and 6 normal gallbladders by western blotting and immunohistochemistry. RT-PCR was used to measure ABCA1 mRNA expression. To investigate the relationship between ABCA1 and inflammation, wWestern blots were performed on cultured dog GBEC treated with lipopolysaccharide (LPS) using an anti-ABCA1 antibody. Immunohistochemistry showed ABCA1 to be localized predominantly to the basolateral membrane, while ABCG8 formed a diffuse intracellular pattern at the apical pole of human GBEC. ABCA1 and ABCG8 expression was more prominent in GBEC that were surrounded by cholesterol-laden macrophages. ABCA1 and ABCG8 expression was increased in gallbladders with CAGD. Western blots showed increased ABCA1, ABCG5, and ABCG8 expression in CAGD. ABCA1 mRNA levels were increased in all gallbladders with CAGD. LPS treatment of cultured dog GBEC enhanced ABCA1 expression. The sterol transporters ABCA1, ABCG5, and ABCG8 may play a role in the pathogenesis of human CAGD. Inflammation appears to be a key factor that increases ABCA1 expression and activity in the human gallbladder.

  1. IMP-3 is differentially expressed in normal and neoplastic lymphoid tissue.

    PubMed

    King, Rebecca L; Pasha, Theresa; Roullet, Michele R; Zhang, Paul J; Bagg, Adam

    2009-12-01

    IMP-3 is a member of the insulin-like growth factor II mRNA binding protein (IMP) family of proteins that play a role in RNA trafficking and stabilization and cell growth and migration during embryogenesis but which are down-regulated in adult tissue. However, IMP-3 has recently been shown to be overexpressed in several epithelial malignancies, with increased expression correlating with aggressive behavior. To our knowledge, there is no published literature evaluating IMP-3 in lymphoid tissue. Accordingly, we immunohistochemically evaluated IMP-3 expression in normal lymphoid tissue and 141 lymphoid neoplasms. Physiologically, IMP-3 expression was restricted to germinal center B cells. Among lymphoid neoplasms, Hodgkin lymphoma demonstrated the highest percentage of positive cases (26/26, 100%) often with bright staining. Burkitt lymphoma was positive in 10 (83%) of 12 cases with moderate to bright staining. Although follicular lymphoma was also positive in a high percentage of cases (12/15, 80%), the intensity was exclusively weak to moderate. Although 22 (85%) of 26 of diffuse large B-cell lymphomas were positive for IMP-3, there was wide variability in staining intensity, which did not correlate with classification into activated B cell versus germinal center B origin. By contrast, lower proportions (8%-20%) of other non-germinal center B lymphoma subtypes were IMP-3-positive. In conclusion, although IMP-3 expression is seemingly restricted to physiologic germinal center B cells, its expression in lymphomas of germinal center B origin is less robust. However, there does appear to be some association with the latter group of lymphomas, which may prove to have diagnostic or therapeutic relevance as the biologic role of IMP-3 is further elucidated.

  2. Violet Light Down-Regulates the Expression of Specific Differentiation Markers through Rhodopsin in Normal Human Epidermal Keratinocytes

    PubMed Central

    Kim, Hyoung-June; Son, Eui Dong; Jung, Ji-Yong; Choi, Hyun; Lee, Tae Ryong; Shin, Dong Wook

    2013-01-01

    Several recent reports have demonstrated that photoreceptors are expressed in human skin. The rod and cone photoreceptor-like proteins are expressed in human skin and rhodopsin, long wavelength-opsin, and short wavelength-opsin are also present in cultured murine melanocytes. Furthermore, the photopigment rhodopsin is expressed in human melanocytes and is involved in ultraviolet A phototransduction which induces early melanin synthesis. In this study, we investigated whether rhodopsin is expressed and plays any physiological roles in the normal human epidermal keratinocytes (NHEKs). We found that rhodopsin was expressed and localized on the plasma membrane in NHEKs, and only violet light among several wavelengths within the visible range significantly increased the expression of rhodopsin mRNA. We further found that rhodopsin over-expression decreased the mRNA expression levels of keratinocyte differentiation markers, such as keratin-1 and keratin-10, and violet light also decreased the mRNA expression levels of keratinocyte differentiation markers and these decreased expression levels were recovered by a rhodopsin-directed siRNA. Moreover, we further demonstrated that violet light significantly decreased the phosphorylation levels of cAMP responsive element-binding protein (CREB) and that it more effectively decreased the phosphorylation of CREB when rhodopsin was over-expressed. In addition, we observed that pertussis toxin, a Gαi protein inhibitor, restored the rhodopsin-induced decrease in the differentiation markers in NHEKs. Taken together, these results suggest that rhodopsin down-regulates the expression levels of specific keratinocyte differentiation markers via the Gαi signaling pathway in NHEKs. PMID:24069221

  3. Changes in telomerase activity, expression and splicing in response to differentiation of normal and carcinoma colon cells.

    PubMed

    Fajkus, Jirí; Borsky, Marek; Kunická, Zuzana; Kovaríková, Martiná; Dvoráková, Dana; Hofmanová, Jirina; Kozubík, Alois

    2003-01-01

    Telomerase, a ribonucleoprotein complex catalysing synthesis of telomeric DNA, is an essential cellular immortalizing factor whose activation is a critical step in the progression to malignancy. An important agent maintaining the balance between proliferation, differentiation and apoptosis of intestinal epithelial cells in crypts is butyrate, which is formed in the gastrointestinal tract by anaerobic bacterial fermentation. It inhibits cell growth, induces differentiation and triggers apoptosis in neoplastic colonocytes. In this study, the responses of adenocarcinoma (HT-29) and fetal (FHC) human colon cells to 5 mM sodium butyrate (NaBt) have been compared. Despite the similar general response of both cell lines to NaBt, i.e., G0/G1 arrest, decrease of growth rate and increase of differentiation (as indicated by alkaline phosphatase activity), they differ in the level and dynamics of the measured parameters. Telomerase activity and the level of mRNA for its catalytic subunit (hTERT) decline significantly after 48 hours, reaching a complete inhibition after 144 hours. While both cell lines show similar kinetics of hTERT transcriptional silencing, the down-regulation of telomerase activity is faster in FHC cells. Correspondingly, we show that a candidate posttranscriptional regulation step, differential splicing of hTERT mRNA, may be involved in the faster loss of telomerase activity in FHC cells. Differences in hTERT mRNA splicing may represent a useful marker of telomere metabolism in normal and malignant colon cells and that these changes may be connected with different cytokinetic patterns of these cells.

  4. Differential expression of IGF-1 mRNA isoforms in colorectal carcinoma and normal colon tissue.

    PubMed

    Kasprzak, Aldona; Szaflarski, Witold; Szmeja, Jacek; Andrzejewska, Małgorzata; Przybyszewska, Wiesława; Kaczmarek, Elżbieta; Koczorowska, Maria; Kościński, Tomasz; Zabel, Maciej; Drews, Michał

    2013-01-01

    RNA decreased as compared to the normal colon tissues, although however, with conservation of both gene promoter activities and with the continued principal splicing IGF-1 mRNA isoforms.

  5. [Intrauterine contraception in nulliparous women].

    PubMed

    Prilepskaia, V N; Mezhevitinova, E A

    1991-04-01

    Advantages and disadvantages of various methods of contraception in nulliparous women are reviewed with special emphasis in hormonal and intrauterine contraception. The use of hormonal contraceptives in young women can induce changes in the still immature hypothalamo-hypophyseal-ovarian system. One of the most frequent side-effects of hormonal contraceptives in young nulliparous women is amenorrhea. Short-term use of 2 or triphasic contraceptives with low content of estrogens and gestagens can stimulate secretion of hormones by ovaries and lead to development of polycystic ovary or endometrial hyperplasia. Intrauterine devices (IUD) do not have a negative systemic effect on the hypothalamo-hypophyseal-ovarian system. Among the IUD models recommended for the use in nulliparous women are Copper-T, Nova-T, Multiload. Effectiveness of IUD ranges from 91.3% for inert Lippes loop, to 98.3% for copper-containing IUD, and 99.8% for progesterone-containing IUD. Dilatation of narrow cervical canal in nulliparous women prior to insertion of IUD can cause traumatic injury of the cervical canal and subsequent cervix insufficiency. Anatomical characteristics of the uterus in young nulliparous women (greater length of the cervical canal in comparison with the length of the cervix cavity) require careful selection of the IUD size to fit the size of the cervix cavity. Complications associated with the use of an IUD include pelvic inflammation with subsequent tubal infertility. The frequency of ectopic pregnancy ranges from 4.1% after the use of inert IUD, to 3% after the use of copper-containing IUD, and 16% after the use of progesterone-containing IUD. Complications are the most frequent within the first 3-8 months of the use of IUD.

  6. Polyorchidism with presumed contralateral intrauterine testicular torsion

    PubMed Central

    Leodoro, B.M.; Beasley, S.W.; Stringer, M.D.

    2014-01-01

    INTRODUCTION Polyorchidism was first described by Blasius in 16701 during a routine autopsy. We report a child with unilateral polyorchidism and a contralateral absent testis, a combination not reported previously. PRESENTATION OF CASE A 2-year-old boy was referred to the outpatient clinic with an impalpable left testis. At laparoscopy, the left vas deferens and testicular vessels ended blindly proximal to a closed internal ring. No gonadal tissue was identified. On the right side, a single vas deferens and testicular vessels were seen entering the internal ring as normal. The right side of the scrotum was explored and two testes were identified within a single tunica vaginalis. DISCUSSION Polyorchidism is rare with a literature search identifying approximately 230 reported cases. Whilst prenatal testicular torsion is increasing being recognized and treated as a surgical emergency,9 prenatal testicular torsion in association with polyorchidism has not been previously reported. CONCLUSION We describe a unique case of a 2-year-old boy with right-sided polyorchidism and an absent left testis associated with a blind ending vas deferens and testicular vessels, presumed secondary to intrauterine testicular torsion. PMID:25462053

  7. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects

    PubMed Central

    Sharma, Deepak; Shastri, Sweta; Sharma, Pradeep

    2016-01-01

    Intrauterine growth restriction (IUGR), a condition that occurs due to various reasons, is an important cause of fetal and neonatal morbidity and mortality. It has been defined as a rate of fetal growth that is less than normal in light of the growth potential of that specific infant. Usually, IUGR and small for gestational age (SGA) are used interchangeably in literature, even though there exist minute differences between them. SGA has been defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age. These infants have many acute neonatal problems that include perinatal asphyxia, hypothermia, hypoglycemia, and polycythemia. The likely long-term complications that are prone to develop when IUGR infants grow up includes growth retardation, major and subtle neurodevelopmental handicaps, and developmental origin of health and disease. In this review, we have covered various antenatal and postnatal aspects of IUGR. PMID:27441006

  8. [Levonorgestrel intrauterine device associated with ureterpyelocaliceal ectasia].

    PubMed

    Gálvez-Valdovinos, Ramiro; Hernández-López, Rogelio; López-Ambriz, Gustavo; Ramme-Cruzat, Christian

    2015-10-01

    In 2010, Health Canada, the equivalent to the FDA, reported that the risk of uterine perforation caused by levonorgestrel intrauterine device (IUD) is very serious, warning that its use had increased the number of uterine perforation. A 33 years old patient in who was placed three years before a levonorgestrel IUD; She presented evolution of 10 days with pain in hypogastric and both flanks and chronic constipation of two years; in exploration: moderate abdominal distention, IUD strings were not visible in uterine cervix. With translocated IUD diagnosis, a tomography was performed, finding IUD in abdominal cavity and ureter pyelocalyceal bilateral ectasia; preoperative plasma concentration of levonorgestrel 5.1 nmol/L, leukocytosis of 11,000 cells/mm3, and 20-30 erythrocytes in urine exam. Laparoscopic resection of omentum attached to IUD translocated was performed. One month after surgery plasma levonorgestrel in 0.3 nmol/L, normal urinalysis and hematic cytometry and resolution of the urinary tract ectasia. devices translocated with levonorgestrel, must be removed because the inflammatory reaction caused and the perforation of hollow viscera likelihood, with possibility to produce digestive tract and urinary tract ectasia by its pharmacologic action on smooth muscle.

  9. MGSA/GRO transcription is differentially regulated in normal retinal pigment epithelial and melanoma cells.

    PubMed Central

    Shattuck, R L; Wood, L D; Jaffe, G J; Richmond, A

    1994-01-01

    We have characterized constitutive and cytokine-regulated MGSA/GRO alpha, -beta, and -gamma gene expression in normal retinal pigment epithelial (RPE) cells and a malignant melanoma cell line (Hs294T) to discern the mechanism for MGSA/GRO constitutive expression in melanoma. In RPE cells, constitutive MGSA/GRO alpha, -beta, and -gamma mRNAs are not detected by Northern (RNA) blot analysis although nuclear runoff experiments show that all three genes are transcribed. In Hs294T cells, constitutive MGSA/GRO alpha expression is detectable by Northern blot analysis, and the level of basal MGSA/GRO alpha transcription is 8- to 30-fold higher than in RPE cells. In contrast, in Hs294T cells, basal MGSA/GRO beta and -gamma transcription is only twofold higher than in RPE cells and no beta or gamma mRNA is detected by Northern blot. These data suggest that the constitutive MGSA/GRO alpha mRNA in Hs294T cells is due to increased basal MGSA/GRO alpha gene transcription. The cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) significantly increase the mRNA levels for all three MGSA/GRO isoforms in Hs294T and RPE cells, and both transcriptional and posttranscriptional mechanisms are operational. Nuclear runoff assays indicate that in RPE cells, a 1-h IL-1 treatment induces a 10- to 20-fold increase in transcription of MGSA/GRO alpha, -beta and -gamma but only a 2-fold increase in Hs294T cells. Similarly, chloramphenicol acetyltransferase (CAT) reporter gene analysis using the MGSA/GRO alpha, -beta, and -gamma promoter regions demonstrates that IL-1 treatment induces an 8- to 14-fold increase in CAT activity in RPE cells but only a 2-fold increase in Hs294T cells. The effect of deletion or mutation of the MGSA/GRO alpha NF-kappa B element, combined with data from gel mobility shift analyses, indicates that the NF-kappa B p50/p65 heterodimer in RPE cells plays an important role in IL-1- and TNF alpha-enhanced gene transcription. In Hs294T cells, gel shift

  10. Visfatin/Pre-B cell colony-enhancing factor in amniotic fluid in normal pregnancy, spontaneous labor at term, preterm labor and prelabor rupture of membranes: an association with subclinical intrauterine infection in preterm parturition.

    PubMed

    Mazaki-Tovi, Shali; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Mittal, Pooja; Than, Nandor Gabor; Nhan-Chang, Chia-Lang; Hamill, Neil; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Edwin, Samuel S; Nien, Jyh Kae; Gomez, Ricardo; Espinoza, Jimmy; Kendal-Wright, Claire; Hassan, Sonia S; Bryant-Greenwood, Gillian

    2008-01-01

    Visfatin, a novel adipokine originally discovered as a pre-B-cell colony enhancing factor, is expressed by amniotic epithelium, cytotrophoblast, and decidua and is over-expressed when fetal membranes are exposed to mechanical stress and/or pro-inflammatory stimuli. Visfatin expression by fetal membranes is dramatically up-regulated after normal spontaneous labor. The aims of this study were to determine if visfatin is detectable in amniotic fluid (AF) and whether its concentration changes with gestational age, spontaneous labor, preterm prelabor rupture of membranes (preterm PROM) and in the presence of microbial invasion of the amniotic cavity (MIAC). In this cross-sectional study, visfatin concentration in AF was determined in patients in the following groups: 1) mid-trimester (n=75); 2) term not in labor (n=27); 3) term in spontaneous labor (n=51); 4) patients with preterm labor with intact membranes (PTL) without MIAC who delivered at term (n=35); 5) patients with PTL without MIAC who delivered preterm (n=52); 6) patients with PTL with MIAC (n=25); 7) women with preterm PROM without MIAC (n=26); and 8) women with preterm PROM with MIAC (n=26). Non-parametric statistics were used for analysis. 1) The median AF concentration of visfatin was significantly higher in patients at term than in mid-trimester; 2) Among women with PTL who delivered preterm, the median visfatin concentration was significantly higher in patients with MIAC than those without MIAC; 3) Similarly, patients with PTL and MIAC had a higher median AF visfatin concentration than those with PTL who delivered at term; 4) Among women with preterm PROM, the median AF visfatin concentration was significantly higher in patients with MIAC than those without MIAC. 1) Visfatin is a physiologic constituent of AF; 2) The concentration of AF visfatin increases with advancing gestational age; 3) AF visfatin concentration is elevated in patients with MIAC, regardless of the membrane status, suggesting that

  11. Insertion and removal of intrauterine devices.

    PubMed

    Kovacs, G T

    1990-05-01

    Although intrauterine contraceptive devices are becoming less commonly used, all general practitioners need to be able to counsel patients about their use. A practical outline of the recommended regimens is provided in this article.

  12. Visfatin/Pre-B Cell Colony-Enhancing Factor in Amniotic Fluid in Normal Pregnancy, Spontaneous Labor at Term, Preterm Labor and Prelabor Rupture of Membranes: an Association with Subclinical Intrauterine Infection in Preterm Parturition

    PubMed Central

    Mazaki-Tovi, Shali; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Mittal, Pooja; Than, Nandor Gabor; Nhan-Chang, Chia-lang; Hamill, Neil; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Edwin, Samuel S.; Nien, Jyh Kae; Gomez, Ricardo; Espinoza, Jimmy; Kendal-Wright, Claire; Hassan, Sonia S.; Bryant-Greenwood, Gillian

    2008-01-01

    Objective Visfatin, a novel adipokine originally discovered as a pre-B-cell colony enhancing factor, is expressed by amniotic epithelium, cytotrophoblast, and decidua and is over-expressed when fetal membranes are exposed to mechanical stress and/or pro-inflammatory stimuli. Visfatin expression by fetal membranes is dramatically up-regulated after normal spontaneous labor. The aims of this study were to determine if visfatin is detectable in amniotic fluid (AF) and whether its concentration changes with gestational age, spontaneous labor, preterm prelabor rupture of membranes (preterm PROM) and in the presence of microbial invasion of the amniotic cavity (MIAC). Methods In this cross-sectional study, visfatin concentration in AF was determined in patients in the following groups: 1) mid-trimester (n=75); 2) term not in labor (n=27); 3) term in spontaneous labor (n=51); 4) patients with preterm labor with intact membranes (PTL) without MIAC who delivered at term (n=35); 5) patients with PTL without MIAC who delivered preterm (n=52); 6) patients with PTL with MIAC (n=25); 7) women with preterm PROM without MIAC (n=26); and 8) women with preterm PROM with MIAC (n=26). Non-parametric statistics were used for analysis. Results 1) The median AF concentration of visfatin was significantly higher in patients at term than in midtrimester; 2) Among women with PTL who delivered preterm, the median visfatin concentration was significantly higher in patients with MIAC than those without MIAC; 3) Similarly, patients with PTL and MIAC had a higher median AF visfatin concentration than those with PTL who delivered at term; 4) Among women with preterm PROM, the median AF visfatin concentration was significantly higher in patients with MIAC than those without MIAC. Conclusions 1) Visfatin is a physiologic constituent of AF; 2) The concentration of AF visfatin increases with advancing gestational age; 3) AF visfatin concentration is elevated in patients with MIAC, regardless of the

  13. Multiphoton microscopic imaging of histological sections without hematoxylin and eosin staining differentiates carcinoma in situ lesion from normal oesophagus

    NASA Astrophysics Data System (ADS)

    Chen, Jianxin; Xu, Jian; Kang, Deyong; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Jiang, Xingshan

    2013-10-01

    Multiphoton microscopy (MPM) has become a powerful, important tool for tissues imaging at the molecular level. In this paper, this technique was extended to histological investigations, differentiating carcinoma in situ (CIS) lesion from normal oesophagus by imaging histological sections without hematoxylin and eosin (H&E) staining. The results show that the histology procedures of dehydration, paraffin embedding, and de-paraffinizing highlighted two photon excited fluorescence of cytoplasm and nucleolus of epithelial cell and collagen in stroma. MPM has the ability to identify the characteristics of CIS lesion including changes of squamous cells and full epithelium, identification of basement membrane, especially prominent nucleolus. The studies described here show that MPM has the potential for future retrospective studies of tumor staging by employing on histological section specimens without H&E staining.

  14. An effective differential expression analysis of deep-sequencing data based on the Poisson log-normal model.

    PubMed

    Wu, Jun; Zhao, Xiaodong; Lin, Zongli; Shao, Zhifeng

    2015-04-01

    Tremendous amount of deep-sequencing data has unprecedentedly improved our understanding in biomedical science by digital sequence reads. To mine useful information from such data, a proper distribution for modeling all range of the count data and accurate parameter estimation are required. In this paper, we propose a method, called "DEPln," for differential expression analysis based on the Poisson log-normal (PLN) distribution with an accurate parameter estimation strategy, which aims to overcome the inconvenience in the mathematical analysis of the traditional PLN distribution. The performance of our proposed method is validated by both synthetic and real data. Experimental results indicate that our method outperforms the traditional methods in terms of the discrimination ability and results in a good tradeoff between the recall rate and the precision. Thus, our work provides a new approach for gene expression analysis and has strong potential in deep-sequencing based research.

  15. Differential accumulation and organ-specific metabolism of 5-aminolevulinic acid between cancer cells and normal epithelial and stromal cells

    NASA Astrophysics Data System (ADS)

    Krieg, Rene C.; Rauch, Joachim; Seidl, Juergen; Stepp, Herbert G.; Messmann, Helmut; Knuechel, Ruth

    2001-01-01

    To optimize conditions of photodynamic therapy (PDT) with ALA induced protoporphyrin IX (PPIX), topography of accumulation and metabolism of PPIX were analyzed in vitro. Adenocarcinoma cell lines, urothelial carcinoma cell lines, and a normal fibroblast cell line were cultured in plateau phase. ALA-induced PPIX accumulation, porphobilinogendeaminase-, ferrochelatase- activity, intracellular iron content, transferrin receptor expression and PPIX localization were determined using standard techniques. PBG activity as well as PPIX content were found higher in adenocarcinoma cells than in urothelial cells. Urothelial cell lines showed significant alterations in FC values in contrast to similar levels of FC in adenocarcinoma cell lines overall. Well differentiated cells showed higher iron content than lower differentiated cells. Transferrin receptor expression was found independent of PPIX content and intracellular iron content. In HT29, PPIX localizes mostly in the cell membrane, in SW480 and CaCo2 in mitochondria, and in urothelial cells mainly in cytosol. Data presented encourage the systematic and organ- related analysis of PPIX metabolism, since significant differences have been found between urothelial tumor cells and adenocarcinoma cells which may demand different strategies of therapy optimization and combination therapy regimens.

  16. Vascular and degenerative processes differentially affect regional interhemispheric connections in normal aging, mild cognitive impairment, and Alzheimer's disease

    PubMed Central

    Lee, Dong Young; Fletcher, Evan; Martinez, Oliver; Zozulya, Natalia; Kim, Jane; Tran, Jeannie; Buonocore, Michael; Carmichael, Owen; DeCarli, Charles

    2010-01-01

    Background and Purpose Despite the critical importance of the corpus callosum (CC) to the connection between brain hemispheres, little is known about the independent contribution of degenerative and vascular processes to regional changes in the microstructural integrity of the CC. Here, we examine these changes in subjects with mild cognitive impairment (MCI), Alzheimer's disease (AD), and in cognitively normal elderly adults. Methods We used three-dimensional brain MRI with diffusion tensor imaging in 47 AD, 77 MCI, and 107 cognitively normal subjects, and calculated mean fractional anisotropy (FA) values for four CC regions corresponding to four homologous regions of cortical gray matter (GM). To assess vascular and degenerative processes, we also measured cortical GM and white matter hyperintensity (WMH) volume in corresponding regions, along with evaluation of their vascular risk. Results We found that GM volume in anterior and posterior regions was significantly related to FA findings in the corresponding regions of the CC for all three diagnostic groups. Independent of GM volume, frontal WMH volume was also associated with FA values in the corresponding CC regions, but posterior WMH volume was not. Vascular risk was associated with FA of most CC regions, while diagnosis for cognitive state was associated only with FA of the anterior and posterior CC regions. Conclusions We found differential region-specific associations between degenerative and vascular processes and the structural integrity of the CC across the spectrum of cognitive ability. Based on these results, we propose a model to explain regional disruption in the interhemispheric connection. PMID:20595668

  17. Notch system is differentially expressed and activated in pituitary adenomas of distinct histotype, tumor cell lines and normal pituitaries

    PubMed Central

    Perrone, Sofia; Zubeldia-Brenner, Lautaro; Gazza, Elias; Demarchi, Gianina; Baccarini, Leticia; Baricalla, Agustin; Mertens, Freya; Luque, Guillermina; Vankelecom, Hugo; Berner, Silvia

    2017-01-01

    Pituitary adenomas are among the most frequent intracranial neoplasms and treatment depends on tumor subtype and clinical features. Unfortunately, non responder cases occur, then new molecular targets are needed. Notch system component expression and activation data are scarce in pituitary tumorigenesis, we therefore aimed to characterize Notch system in pituitary tumors of different histotype. In human pituitary adenomas we showed NOTCH1-4 receptors, JAGGED1 ligand and HES1 target gene expression with positive correlations between NOTCH1,2,4 and HES1, and NOTCH3 and JAGGED1 denoting Notch system activation in a subset of tumors. Importantly, NOTCH3 positive cells were higher in corticotropinomas and somatotropinomas compared to non functioning adenomas. In accordance, Notch activation was evidenced in AtT20 tumor corticotropes, with higher levels of NOTCH1-3 active domains, Jagged1 and Hes1 compared to normal pituitary. In the prolactinoma cell lines GH3 and MMQ, in vivo GH3 tumors and normal glands, Notch system activation was lower than in corticotropes. In MMQ cells only the NOTCH2 active domain was increased, whereas NOTCH1 active domain was higher in GH3 tumors. High levels of Jagged1 and Dll1 were found solely in GH3 cells, and Hes1, Hey1 and Hey2 were expressed in a model dependent pattern. Prolactinomas harbored by lacDrd2KO mice expressed high levels of NOTCH1 active domain and reduced Hes1. We show a differential expression of Notch system components in tumoral and normal pituitaries and specific Notch system involvement depending on adenoma histotype, with higher activation in corticotropinomas. These data suggest that targeting Notch pathway may benefit non responder pituitary adenomas. PMID:28915655

  18. Automatic Differentiation of Normal and Continuous Adventitious Respiratory Sounds Using Ensemble Empirical Mode Decomposition and Instantaneous Frequency.

    PubMed

    Lozano, Manuel; Fiz, José Antonio; Jané, Raimon

    2016-03-01

    Differentiating normal from adventitious respiratory sounds (RS) is a major challenge in the diagnosis of pulmonary diseases. Particularly, continuous adventitious sounds (CAS) are of clinical interest because they reflect the severity of certain diseases. This study presents a new classifier that automatically distinguishes normal sounds from CAS. It is based on the multiscale analysis of instantaneous frequency (IF) and envelope (IE) calculated after ensemble empirical mode decomposition (EEMD). These techniques have two major advantages over previous techniques: high temporal resolution is achieved by calculating IF-IE and a priori knowledge of signal characteristics is not required for EEMD. The classifier is based on the fact that the IF dispersion of RS signals markedly decreases when CAS appear in respiratory cycles. Therefore, CAS were detected by using a moving window to calculate the dispersion of IF sequences. The study dataset contained 1494 RS segments extracted from 870 inspiratory cycles recorded from 30 patients with asthma. All cycles and their RS segments were previously classified as containing normal sounds or CAS by a highly experienced physician to obtain a gold standard classification. A support vector machine classifier was trained and tested using an iterative procedure in which the dataset was randomly divided into training (65%) and testing (35%) sets inside a loop. The SVM classifier was also tested on 4592 simulated CAS cycles. High total accuracy was obtained with both recorded (94.6% ± 0.3%) and simulated (92.8% ± 3.6%) signals. We conclude that the proposed method is promising for RS analysis and classification.

  19. Retinal vessel density from optical coherence tomography angiography to differentiate early glaucoma, pre-perimetric glaucoma and normal eyes.

    PubMed

    Akil, Handan; Huang, Alex S; Francis, Brian A; Sadda, Sirinivas R; Chopra, Vikas

    2017-01-01

    To evaluate optic nerve vascular density using swept source optical coherence tomography angiography (OCTA) in patients with early primary open angle glaucoma (POAG), pre-perimetric glaucoma and normal eyes. This is a prospective, observational study including 56 eyes in total and divided into 3 groups; 20 eyes with mild POAG, 20 pre-perimetric glaucoma eyes, and 16 age-matched normal eyes as controls. The optic disc region was imaged by a 1050-nm-wavelength swept-source OCT system (DRI OCT Triton, TOPCON). Vessel density was assessed as the ratio of the area occupied by the vessels in 3 distinct regions: 1) within the optic nerve head; 2) in the 3 mm papillary region around the optic disc; and 3) in the peripapillary region, defined as a 700-μm-wide elliptical annulus around the disc. The potential associations between vessel density and structural, functional measures were analyzed. There was a statistically significant difference for the peripapillary vessel density, optic nerve head vessel density, and papillary vessel density among all the groups (p<0.001). Control eyes showed a significant difference for all measured vessel densities compared to glaucomatous eyes (p values from 0.001 to 0.024). There was a statistically significant difference between control and pre-perimetric glaucoma eyes for peripapillary, optic nerve head and papillary vessel density values (p values from 0.001 to 0.007). The optic nerve head vessel density, superior and inferior papillary area vessel density (Pearson r = 0.512, 0.436, 0.523 respectively) were highly correlated with mean overall, superior and inferior RNFL thickness in POAG eyes (p = 0.04, p = 0.02 and p = 0.04 respectively). Multiple linear regression analysis of POAG group showed that optic nerve head vessel density in POAG group was more strongly linked to RNFL thickness than to any other variables. Eyes with mild POAG could be differentiated from pre-perimetric glaucoma eyes, which also could be differentiated from

  20. Retinal vessel density from optical coherence tomography angiography to differentiate early glaucoma, pre-perimetric glaucoma and normal eyes

    PubMed Central

    Akil, Handan; Huang, Alex S.; Francis, Brian A.; Sadda, Sirinivas R.; Chopra, Vikas

    2017-01-01

    Purpose To evaluate optic nerve vascular density using swept source optical coherence tomography angiography (OCTA) in patients with early primary open angle glaucoma (POAG), pre-perimetric glaucoma and normal eyes. Methods This is a prospective, observational study including 56 eyes in total and divided into 3 groups; 20 eyes with mild POAG, 20 pre-perimetric glaucoma eyes, and 16 age-matched normal eyes as controls. The optic disc region was imaged by a 1050-nm-wavelength swept-source OCT system (DRI OCT Triton, TOPCON). Vessel density was assessed as the ratio of the area occupied by the vessels in 3 distinct regions: 1) within the optic nerve head; 2) in the 3 mm papillary region around the optic disc; and 3) in the peripapillary region, defined as a 700-μm-wide elliptical annulus around the disc. The potential associations between vessel density and structural, functional measures were analyzed. Results There was a statistically significant difference for the peripapillary vessel density, optic nerve head vessel density, and papillary vessel density among all the groups (p<0.001). Control eyes showed a significant difference for all measured vessel densities compared to glaucomatous eyes (p values from 0.001 to 0.024). There was a statistically significant difference between control and pre-perimetric glaucoma eyes for peripapillary, optic nerve head and papillary vessel density values (p values from 0.001 to 0.007). The optic nerve head vessel density, superior and inferior papillary area vessel density (Pearson r = 0.512, 0.436, 0.523 respectively) were highly correlated with mean overall, superior and inferior RNFL thickness in POAG eyes (p = 0.04, p = 0.02 and p = 0.04 respectively). Multiple linear regression analysis of POAG group showed that optic nerve head vessel density in POAG group was more strongly linked to RNFL thickness than to any other variables. Conclusions Eyes with mild POAG could be differentiated from pre-perimetric glaucoma eyes, which

  1. A Rare Case of Jejunal Atresia Due to Intrauterine Intussusception

    PubMed Central

    Kinhal, Vidyadhar; Desai, Mahesh; Tilak; Choudhari, Fazal UR Rehman

    2015-01-01

    Intestinal atresia is generally caused by intrauterine vascular obstructions involving mesenteric vessels. Intrauterine intussusceptions (IUI) are one of these disruptive events. Intestinal intussusceptions affects children commonly between 3 months and 3 years of age, but it rarely affects in intrauterine life. The relationship between intrauterine intussusception and intestinal atresia has been demonstrated by few cases in literature, suggesting intrauterine intussusception as a rare cause of intestinal atresia. We report a 7-day-old full term neonate presenting with intrauterine intussusceptions (jejuno-jejunal) resulting in jejunal atresia. PMID:26500958

  2. A Rare Case of Jejunal Atresia Due to Intrauterine Intussusception.

    PubMed

    Joshi, Sanjeev B; Kinhal, Vidyadhar; Desai, Mahesh; Tilak; Choudhari, Fazal Ur Rehman

    2015-09-01

    Intestinal atresia is generally caused by intrauterine vascular obstructions involving mesenteric vessels. Intrauterine intussusceptions (IUI) are one of these disruptive events. Intestinal intussusceptions affects children commonly between 3 months and 3 years of age, but it rarely affects in intrauterine life. The relationship between intrauterine intussusception and intestinal atresia has been demonstrated by few cases in literature, suggesting intrauterine intussusception as a rare cause of intestinal atresia. We report a 7-day-old full term neonate presenting with intrauterine intussusceptions (jejuno-jejunal) resulting in jejunal atresia.

  3. Superfetation after ovulation induction and intrauterine insemination performed during an unknown ectopic pregnancy.

    PubMed

    Lantieri, Teresa; Revelli, Alberto; Gaglioti, Pietro; Menato, Guido; Gennarelli, Gianluca; Delle Piane, Luisa; Massobrio, Marco

    2010-05-01

    This report describes the first case of superfetation after ovarian stimulation with gonadotrophins and intrauterine insemination (IUI) that were performed in the presence of an undiagnosed tubal pregnancy. A 32-year-old woman who underwent repeated attempts of ovarian stimulation and IUI was hospitalized for severe pelvic pain and submitted to laparoscopic salpingectomy because of ruptured salpynx containing a 6-week pregnancy. Transvaginal ultrasound examination showed a simultaneous intrauterine 2-week pregnancy that had been conceived by ovarian stimulation and IUI while the tubal pregnancy was already ongoing and still undiagnosed. The intrauterine pregnancy went on until term and ended with the spontaneous delivery of a healthy baby. This report demonstrates that human superfetation may occur after gonadotrophin treatment and IUI in the presence of an ongoing tubal pregnancy. It is recommended to perform a pregnancy test before starting ovulation induction even when an apparently normal blood discharge appeared.

  4. Cartilage T2 assessment: differentiation of normal hyaline cartilage and reparative tissue after arthroscopic cartilage repair in equine subjects.

    PubMed

    White, Lawrence M; Sussman, Marshall S; Hurtig, Mark; Probyn, Linda; Tomlinson, George; Kandel, Rita

    2006-11-01

    To prospectively assess T2 mapping characteristics of normal articular cartilage and of cartilage at sites of arthroscopic repair, including comparison with histologic results and collagen organization assessed at polarized light microscopy (PLM). Study protocol was compliant with the Canadian Council on Animal Care Guidelines and approved by the institutional animal care committee. Arthroscopic osteochondral autograft transplantation (OAT) and microfracture arthroplasty (MFx) were performed in knees of 10 equine subjects (seven female, three male; age range, 3-5 years). A site of arthroscopically normal cartilage was documented in each joint as a control site. Joints were harvested at 12 (n = 5) and 24 (n = 5) weeks postoperatively and were imaged at 1.5-T magnetic resonance (MR) with a 10-echo sagittal fast spin-echo acquisition. T2 maps of each site (21 OAT harvest, 10 MFx, 12 OAT plug, and 10 control sites) were calculated with linear least-squares curve fitting. Cartilage T2 maps were qualitatively graded as "organized" (normal transition of low-to-high T2 signal from deep to superficial cartilage zones) or "disorganized." Quantitative mean T2 values were calculated for deep, middle, and superficial cartilage at each location. Results were compared with histologic and PLM assessments by using kappa analysis. T2 maps were qualitatively graded as organized at 20 of 53 sites and as disorganized at 33 sites. Perfect agreement was seen between organized T2 and histologic findings of hyaline cartilage and between disorganized T2 and histologic findings of fibrous reparative tissue (kappa = 1.0). Strong agreement was seen between organized T2 and normal PLM findings and between disorganized T2 and abnormal PLM findings (kappa = .92). Quantitative assessment of the deep, middle, and superficial cartilage, respectively, showed mean T2 values of 53.3, 58.6, and 54.9 msec at reparative fibrous tissue sites and 40.7, 53.6, and 61.6 msec at hyaline cartilage sites. A

  5. Intrauterine infections and birth defects.

    PubMed

    Zheng, Xiao-Ying; Zhang, Ting; Wang, Yi-Fei; Xu, Chen; Chen, Gong; Xin, Ruo-Lei; Chen, Jia-Peng; Hu, Xu-Mei; Yang, Qing; Song, Xin-Ming; Pang, Li-Hua; Ji, Ying; Sun, Hong-Mei; Zhang, Lei; Liu, Ju-Fen; Guo, Yan-Ling; Zhang, Yan

    2004-12-01

    Intrauterine infection is an important cause of some birth defects worldwide. The most common pathogens include rubella virus, cytomegaloviurs, ureaplasma urealyticum, toxoplasma, etc. General information about these pathogens in epidemiology, consequence of birth defects, and the possible mechanisms in the progress of birth defects, and the interventions to prevent or treat these pathogens' infections are described. The infections caused by rubella virus, cytomegaloviurs, ureaplasma urealyticum, toxoplasma, etc. are common, yet they are proved to be fatal during the pregnant period, especially during the first trimester. These infections may cause sterility, abortion, stillbirth, low birth weight, and affect multiple organs that may induce loss of hearing and vision, even fetal deformity and the long-term effects. These pathogens' infections may influence the microenvironment of placenta, including levels of enzymes and cytokines, and affect chondriosome that may induce the progress of birth defect. Early diagnosis of infections during pregnancy should be strengthened. There are still many things to be settled, such as the molecular mechanisms of birth defects, the effective vaccines to certain pathogens. Birth defect researches in terms of etiology and the development of applicable and sensitive pathogen detection technology and methods are imperative.

  6. Antiprogestin-releasing intrauterine devices

    PubMed Central

    Nayak, NR; Slayden, OD; Mah, K; Chwalisz, K; Brenner, Robert M

    2007-01-01

    Intrauterine devices (IUDs) that release progestins are highly effective contraceptives, but they induce breakthrough bleeding that some women find unacceptable. Because progesterone (P) antagonists (AP) are known to suppress the endometrium, induce amenorrhea, and inhibit fertility, AP IUDs may provide an effective contraceptive that also controls endometrial bleeding. Here we assessed the effects of empty (blank) vs AP-releasing (ZK 230 211) IUDs on bleeding patterns and endometrial growth in ovariectomized, artificially cycled macaques. The AP IUDs (but not the blank controls) induced extended, frank menstruation when inserted during the late luteal phase, an indication of local AP action. Over time, endometrial glandular and arterial proliferation were inhibited, steroid receptors were elevated, spiral arteries showed degenerative changes, progesterone withdrawal bleeding was prevented and estradiol-dependent proliferation was suppressed by the AP IUDs. In sum, AP IUDs suppressed the effects of P on endometrial progestational development and blocked the effects of estradiol on endometrial proliferation as previously shown for systemic treatment with APs. Therefore, AP IUDs may provide novel contraceptive devices with minimal breakthrough bleeding. PMID:17531599

  7. Progress report on intrauterine devices.

    PubMed

    Tietze, C

    1968-01-01

    This report, the 8th in the series of the Cooperative Statistical Program for the Evaluation of Intrauterine Devices, is based on data from 30 investigators who submitted case records for 27,575 women covering the years 1963-1967. Data are presented for 5 types of IUDs: Lippes loop, Margulies spiral, Birnberg bow, stainless steel ring of Hall and Stone, and double coil. The loop has been studied in 4 sizes, and on the basis of experience, the smaller sizes are generally recommended for nulliparous women only. Tables present acceptor characteristics by age and parity, events and closures by type and size of device, and cumulative rates by type of termination. Major generalizations emerging from the data include: 1) The risk of pregnancy was highest in the 1st year of use as were the risks of expultion and removal for medical reasons. 2) Expulsion rates and pregnancy rates were higher for smaller sizes. 3) Removals for medical reasons were not significantly associated with size except for the spiral. Pregnancy rates by type of device are given.

  8. Intrauterine contraceptive devices: MR imaging.

    PubMed

    Mark, A S; Hricak, H

    1987-02-01

    To assess the safety of magnetic resonance (MR) imaging in women who have an intrauterine contraceptive device (IUD) in place, in vitro and in vivo studies were performed at both 0.35 and 1.5 T. Two commonly used IUDs were tested, one all of plastic, the other with a coil of copper wire on it. Specifically, the study assessed possible motion of the IUD in the magnetic field, potential of the IUD to heat up during two spin-echo imaging sequences commonly used in MR imaging of the pelvis (2,000/30 and 60 [repetition time, msec/echo time, msec], and 500/30), and the appearance on MR images of the IUD devices. A retrospective review of MR images of the pelvis in six women who had an IUD in place was also performed. Results show that an IUD does not move under the influence of the magnetic field, does not heat during spin-echo sequences commonly used for pelvic imaging, and does not produce artifacts in vitro or in vivo. Patients with either type of IUD can be safely imaged with MR, and MR images of the pelvis are not degraded by the presence of an IUD.

  9. Intrauterine infection and preterm labor.

    PubMed

    Agrawal, Varkha; Hirsch, Emmet

    2012-02-01

    Preterm labor is defined as labor that begins before 37 completed weeks of pregnancy. More than 12% of infants born in the USA are preterm. At least 40% of preterm births are associated with intrauterine infection. Toll-like receptors (TLRs) are members of a family of cell-surface proteins responsible for recognition of a diverse spectrum of bacterial, viral and fungal pathogens. TLRs initiate the host innate (i.e. non-adaptive) immune response, inducing a proinflammatory cascade involving cytokines, chemokines, prostaglandins, and other effector molecules that result in the characteristic phenomena of labor, such as uterine contractions and rupture of fetal membranes. These cascades may also be activated by mechanisms that are not primarily infectious but are accompanied by inflammatory responses. Now that the molecular mechanisms linking infection and labor have been, to a large extent, elucidated, the challenge is to identify points of overlap with non-infectious causes of labor and to find intervention strategies that can minimize the negative impact of preterm delivery. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Intrauterine infection and preterm labor

    PubMed Central

    Agrawal, Varkha; Hirsch, Emmet

    2011-01-01

    Summary Preterm labor is defined as labor that begins before 37 completed weeks of pregnancy. More than 12% of infants born in the USA are preterm. At least 40% of preterm births are associated with intrauterine infection. Toll-like receptors (TLRs) are members of a family of cell-surface proteins responsible for recognition of a diverse spectrum of bacterial, viral and fungal pathogens. TLRs initiate the host innate (i.e. non-adaptive) immune response, inducing a proinflammatory cascade involving cytokines, chemokines, prostaglandins, and other effector molecules that result in the characteristic phenomena of labor, such as uterine contractions and rupture of fetal membranes. These cascades may also be activated by mechanisms that are not primarily infectious but are accompanied by inflammatory responses. Now that the molecular mechanisms linking infection and labor have been, to a large extent, elucidated, the challenge is to identify points of overlap with non-infectious causes of labor and to find intervention strategies that can minimize the negative impact of preterm delivery. PMID:21944863

  11. Intra-uterine contraceptive devices.

    PubMed

    Elias, J

    1985-05-01

    Among the advantages of IUDs are the device's high continuation rate, the lack of systemic side effects, and the absence of a need for continual motivation to practice contraception. The effectiveness of plastic IUDs is directly proportional to their surface area, but the degree of excessive bleeding experienced is inversely related to device size. Thus, devices represent a compromise between large size for effectiveness and small size for acceptability. The optimum time to fit an IUD is during the 1st hald of the menstrual cycle. Absolute contraindications to IUD use include the presence of active pelvic inflammatory disease, undiagnosed irregular bleeding, a history of ectopic pregnancy or tubal surgery, and a distorted uteine cavity. Failure rates associated with IUD use range from 2-3% in the 1st year and then decrease. Since the main mechanism of action appears to be production of a sterile inflammatory reaction in the uterine cavity, the IUD prevents intrauterine pregnancy more effectively than ectopic pregnancy. Nonetheless, there is little evidence to suggest that IUD use actually increases the incidence of ectopic pregnancy. Resumption of fertility after IUD removal is not delayed. There is not need to change inert plastic IUDs in women who remain symptom free. The copper devices should be changed every 3-4 years. A search is under way for antifertility agents that can be incorporated into the device to reduce side effects. In general, the IUD is most suitable for older, parous women.

  12. Differentiation of Overweight from Normal Weight Young Adults by Postprandial Heart Rate Variability and Systolic Blood Pressure

    PubMed Central

    Taffe, Lauren; Stancil, Kimani; Bond, Vernon; Pemminati, Sudhakar; Gorantla, Vasavi Rakesh; Kadur, Kishan

    2016-01-01

    Introduction Obesity and cardiovascular disease are inextricably linked and the health community’s response to the current epidemic of adolescent obesity may be improved by the ability to target adolescents at highest risk for developing cardiovascular disease in the future. Overweight manifests early as autonomic dysregulation and current methods do not permit differentiation of overweight adolescents or young adults at highest risk for developing cardiovascular disease. Aim This study was designed to test the hypothesis that scaling exponents motivated by nonlinear fractal analyses of Heart Rate Variability (HRV) differentiate overweight, otherwise healthy adolescent/young adult subjects at risk for developing prehypertension, the primary forerunner of cardiovascular disease. Materials and Methods The subjects were 18-20year old males with Body Mass Index (BMI) 20.1-42.5kg/m2. Electrocardiographic inter-beat (RR) intervals were measured during 3h periods of bed rest after overnight fasting and ingestion of 900Cal high-carbohydrate and high-fat test beverages on separate days. Detrended Fluctuation Analysis (DFA), k-means cluster and ANOVA analyses of scaling coefficients α, α1, and α2, showed dependencies on hourly measurements of systolic blood pressure and on premeasured BMI. Results It was observed that α value increased during the caloric challenge, appears to represent metabolically-induced changes in HRV across the participants. An ancillary analysis was performed to determine the dependency on BMI without BMI as a parameter. Cluster analysis of the high-carbohydrate test beverage treatment and the high-fat treatment produced grouping with very little overlap. ANOVA on both clusters demonstrated significance at p<0.001. We were able to demonstrate increased sympathetic modulation of our study group during ingestion and metabolism of isocaloric high-carbohydrate and high-fat test beverages. Conclusion These findings demonstrate significantly different

  13. Epidermal differentiation complex (locus 1q21) gene expression in head and neck cancer and normal mucosa.

    PubMed

    Tyszkiewicz, Tomasz; Jarzab, Michal; Szymczyk, Cezary; Kowal, Monika; Krajewska, Jolanta; Jaworska, Magdalena; Fraczek, Marcin; Krajewska, Anna; Hadas, Ewa; Swierniak, Michal; Markowski, Jaroslaw; Lange, Dariusz; Poltorak, Stanislaw; Wiench, Malgorzata; Krecicki, Tomasz; Jarzab, Jerzy; Maciejewski, Adam

    2014-01-01

    Epidermal differentiation complex (EDC) comprises a number of genes associated with human skin diseases including psoriasis, atopic dermatitis and hyperkeratosis. These genes have also been linked to numerous cancers, among them skin, gastric, colorectal, lung, ovarian and renal carcinomas. The involvement of EDC components encoding S100 proteins, small proline-rich proteins (SPRRs) and other genes in the tumorigenesis of head and neck squamous cell cancer (HNSCC) has been previously suggested. The aim of the study was to systematically analyze the expression of EDC components on the transcript level in HNSCC. Tissue specimens from 93 patients with HNC of oral cavity and 87 samples from adjacent or distant grossly normal oral mucosawere analyzed. 48 samples (24 tumor and 24 corresponding surrounding tissue) were hybridized to Affymetrix GeneChip Human 1.0 ST Arrays. For validation by quantitative real-time PCR (QPCR) the total RNA from all180 samples collected in the study was analyzed with Real-Time PCR system and fluorescent amplicon specific-probes. Additional set of samples from 14 patients with laryngeal carcinoma previously obtained by HG-U133 Plus 2.0 microarray was also included in the analyses. The expression of analyzed EDC genes was heterogeneous. Two transcripts (S100A1 and S100A4) were significantly down-regulated in oral cancer when compared to normal mucosa (0.69 and 0.36-fold change, respectively), showing an opposite pattern of expression to the remaining S100 genes. Significant up-regulation in tumors was found for S100A11, S100A7, LCE3D, S100A3 and S100A2 genes. The increased expression of S100A7 was subsequently validated by QPCR, confirming significant differences. The remaining EDC genes, including all encoding SPRR molecules, did not show any differences between oral cancer and normal mucosa. The observed differences were also assessed in the independent set of laryngeal cancer samples, confirming the role of S100A3 and LCE3D transcripts in

  14. Differentiation of three biotypes of Malassezia species on human normal skin. correspondence with M. globosa, M. sympodialis and M. restricta.

    PubMed

    Aspiroz, C; Moreno, L A; Rezusta, A; Rubio, C

    1999-01-01

    One hundred and twenty lipid dependent Malassezia spp. isolates were obtained from the clinically normal skin of 38 healthy adult volunteers by swabbing three different body sites (back, chest and scalp). Ninety-six percent of these strains could be grouped into three biotypes on the basis of microscopic, cultural, metabolic and biochemical (catalase, esculin and lipase (C-14)) characteristics. The differential features were simple to determine and easily reproduced. Moreover, the three biotypes were referable to the species M. globosa (biotype 1), M. sympodialis (biotype 2) and M. restricta (biotype 3). Based on their microscopic features, cultural properties and body site locations, we suggest that biotype 1 /M. globosa corresponds to the description of Pityrosporum orbiculare (round yeast cells with a narrow base, very frequently found on the upper trunk), and biotype 3/M. restricta corresponds to the concept of P. ovale (oval yeast cells with a broad budding base, located mainly on the scalp). Pleomorphic biotype 2/M. sympodialis, most frequently found in the back, does not clearly fit into any of the Pityrosporum species.

  15. Differential action on cancer and normal tissue by adrenochrome monoaminoguanidine methanesulfonate and cytochrome C combined with radiotherapy

    SciTech Connect

    Nakatsugawa, S. ); Sugahara, T. )

    1994-06-15

    The possibility that radioprotective effects on potent natural killer (NK) cells by adrenochrome monoaminoguanidine methanesulfonate (AMM) + cytochrome C during radiotherapy (RT) for lung cancer might result in the radiosensitization of human lung cancer cells in vivo is examined. Human lung cancer xenografts in the right hind legs of KSN mice (10 weeks old) were locally irradiated with 20 Gy of X ray. AMM (10 mg/kg/day) and/or cytochrome C (CCC) (5 mg/kg/day) were given intraperitoneally immediately before or after RT, followed by daily administration for 4 days. Natural killer activities of host splenocytes were also tested with the standard [sup 51]Cr releasing assay with YAC-1 cells as target cells. In a clinical study, 65 patients with lung cancer were treated with more than 50 Gy of RT with or without combination with AMM + CCC, OK-432 or AMM + CCC + OK-432. Before and after RT, lymphocyte subsets in the peripheral blood were examined with dichromatic analysis using an Ortho Spectrum IIIFCM system and fluorescent MABs. In this study, the change in the absolute number of each subset was investigated. AMM + cytochrome C augumented NK activity in KSN nude mice, protected potent NK cells in patients with lung cancer against RT and sensitized the human lung cancer xenografts to RT. AMM + cytochrome C may have potential as a differential modulator of radiosensitivity of normal tissues and of tumors. 8 refs., 2 figs., 1 tab.

  16. Use of intrauterine devices in nulliparous women.

    PubMed

    Lohr, Patricia A; Lyus, Richard; Prager, Sarah

    2017-06-01

    Five intrauterine devices (IUDs) are available in the United States: four levonorgestrel-releasing intrauterine systems (two containing 52 mg, one containing 19.5 mg and one containing 13.5 mg) and one copper-bearing device (Copper T 380A). All IUDs have very low typical-use failure rates and high acceptability ratings, yet they are used by a minority of women, with nulliparous women less likely to do so than parous women. The objective of this clinical review is to give evidence-based recommendations for the use of IUDs in nulliparous women. Intrauterine devices are safe and effective for the majority of women including those who are nulliparous, and should be routinely included in the contraception options offered to them. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. The case for intrauterine gene therapy.

    PubMed

    Mattar, Citra N; Waddington, Simon N; Biswas, Arijit; Davidoff, Andrew M; Choolani, Mahesh; Chan, Jerry K Y; Nathwani, Amit C

    2012-10-01

    Single-gene disorders can cause perinatal mortality or severe permanent morbidity. Intrauterine gene therapy seeks to correct the genetic defect in the early stages of pathogenesis through delivery of a vector system expressing the therapeutic transgene to the fetus. Advantages of intrauterine gene therapy include prevention of irreversible organ damage, potentially inducing central tolerance and wider bio-distribution, including the brain after delivery of vector. Already, proof-of-cure has been demonstrated in knockout animal models for several diseases. Long-term outcomes pertaining to efficacy and durability of transgene expression and safety are under investigation in clinically relevant non-human primate models. Bystander effects in the mother from transplacental vector trafficking require further assessment. In this chapter, we discuss the candidate diseases amenable to intrauterine gene therapy, current state-of-the-art evidence, and potential clinical applications.

  18. Forgotten intrauterine device contributing to infertility

    PubMed Central

    Igberase, Gabriel O.

    2011-01-01

    The aim of the study is to show that long standing forgotten intrauterine device contributes to infertility, reporting three cases presented at Central Hospital Warri, Nigeria, a government tertiary health center. Three cases of forgotten intrauterine contraceptive device (IUCD) contributing to infertility were seen. Two were inserted for contraceptive reasons while one was inserted while being managed for uterine synechae. Health care providers should ensure proper documentation of all procedures carried out, adequate counseling which should include taking an informed consent and also ensuring both short and long term follow up of their clients. Also all patients being evaluated for infertility and clients with past history of intrauterine device must have a speculum examination and ultrasound scan carried out. PMID:24765335

  19. Forgotten intrauterine device contributing to infertility.

    PubMed

    Igberase, Gabriel O

    2011-07-01

    The aim of the study is to show that long standing forgotten intrauterine device contributes to infertility, reporting three cases presented at Central Hospital Warri, Nigeria, a government tertiary health center. Three cases of forgotten intrauterine contraceptive device (IUCD) contributing to infertility were seen. Two were inserted for contraceptive reasons while one was inserted while being managed for uterine synechae. Health care providers should ensure proper documentation of all procedures carried out, adequate counseling which should include taking an informed consent and also ensuring both short and long term follow up of their clients. Also all patients being evaluated for infertility and clients with past history of intrauterine device must have a speculum examination and ultrasound scan carried out.

  20. Milestones in intrauterine device development.

    PubMed

    Tatum, H J

    1983-02-01

    Levonorgestrel T, both of which effect a reduction in menstrual blood loss. While major advances have been made in the field of intrauterine contraception, more innovations and improvements can be expected in the future.

  1. Distinct expression patterns of the immunogenic differentiation antigen NY-BR-1 in normal breast, testis and their malignant counterparts.

    PubMed

    Theurillat, Jean-Philippe; Zürrer-Härdi, Ursina; Varga, Zsuzsanna; Barghorn, André; Saller, Elisabeth; Frei, Claudia; Storz, Martina; Behnke, Silvia; Seifert, Burkhardt; Fehr, Mathias; Fink, Daniel; Rageth, Christoph; Linsenmeier, Claudia; Pestalozzi, Bernhard; Chen, Yao-Tseng; Knuth, Alexander; Jäger, Dirk; Moch, Holger

    2008-04-01

    NY-BR-1 is a differentiation antigen and a potential target for cancer immunotherapy. Its mRNA expression is restricted to breast, testis, prostate and breast cancer by RT-PCR. In this study, we correlated NY-BR-1 protein and mRNA expression on tissue microarrays of mammary, prostatic and testicular malignancies using immunohistochemistry and in situ hybridization with probes for exon 4-7 and 30-33. NY-BR-1 mRNA was confined to primary spermatocytes, suggesting a role in spermatogenesis. Exon 4-7 and 30-33 were equally expressed this cell type. However, NY-BR-1 was absent in all germ cell tumours analyzed (n = 475) and present in one of 56 (2%) prostate carcinomas. In breast, NY-BR-1 mRNA expression was detected in 307 of 442 (70%) primary carcinomas, with strong correlation to its protein expression (p < 0.0001). mRNA expression was significantly stronger and more frequently detected by the exon 30-33 probe than by the exon 4-7 probe (70% vs. 35%, p < 0.0001), indicating the presence of alternative splice variants that lack 5-prime sequences. A similar restricted mRNA pattern was also observed in the normal breast epithelium. NY-BR-1 protein and mRNA correlated significantly with estrogen receptor alpha (ER alpha) protein expression (p < 0.0001), with stronger association to NY-BR-1 mRNA than protein (odds ratio 7.7 compared to 4.6). We identified 4 estrogen response elements (ERE)-like sequences nearby the promoter region, suggesting that NY-BR-1 transcription might be controlled by ER alpha. Accordingly, analysis of matching pairs of primary tumors with their recurrences showed a marked decrease of NY-BR-1 expression in recurrences after tamoxifen treatment (p < 0.0001).

  2. Differential CD4+ cell count increase and CD4+ :CD8+ ratio normalization with maraviroc compared with tenofovir

    PubMed Central

    CHAN, Ellen S.; LANDAY, Alan L.; BROWN, Todd T.; RIBAUDO, Heather J.; MIRMONSEF, Paria; OFOTOKUN, Igho; WEITZMANN, M. Neale; MARTINSON, Jeffrey; KLINGMAN, Karin L.; ERON, Joseph J.; FICHTENBAUM, Carl J.; PLANTS, Jill; TAIWO, Babafemi O.

    2016-01-01

    Objective Studies exploring the immunologic effects of maraviroc (MVC) have produced mixed results; hence it remains unclear whether MVC has unique immunologic effects in comparison to other antiretroviral drugs. We sought to determine whether MVC has differential effects compared to tenofovir disoproxil fumarate (TDF) during initial antiretroviral therapy. Design Prospective study in AIDS Clinical Trials Group A5303, a double-blind, placebo-controlled trial (N=262) of MVC versus TDF, each combined with boosted darunavir and emtricitabine Methods A total of 31 cellular and soluble biomarkers were assayed at weeks 0 and 48. Polychromatic flow cytometry was performed on cryopreserved peripheral blood mononuclear cells (PBMC). Soluble markers were assayed in plasma using ELISA kits. Analyses were as-treated. Results Analyses included 230 participants (119 in MVC arm and 111 in TDF arm). Over 48 weeks of treatment, no significant differences were detected in declines in markers of inflammation and activation with MVC versus TDF. A greater CD4+ T-cell count increase (median +234 cells/μl vs. +188 cells/μl, p=0.036), a smaller CD8+ T-cell count decrease (−6 cells/μl vs. −109 cells/μl, p=0.008) and a smaller CD4+:CD8+ ratio increase (0.26 vs. 0.39, p=0.003) occurred with MVC. Among participants with baseline CD4+:CD8+ ratio<1, smaller proportion of MVC group normalized to ratio >1 at week 48 (15% and 36%, p<0.001). Conclusions MVC resulted in less improvement in CD4+:CD8+ ratio driven by greater increase in CD4+ count but smaller decline in CD8+ count. Changes in soluble or cellular biomarkers of inflammation and immune activation were not different between MVC and TDF. PMID:27281061

  3. Effects of prenatal procarbazine administration on intrauterine development in rats.

    PubMed

    Malek, F A; Möritz, K U; Fanghänel, J

    2003-04-01

    The effects of prenatal procarbazine (PCZ) administration on the intrauterine development of rat fetuses were investigated. Gravid rats were treated on day 14 of gestation (GD14) with 25 mg or 50 mg/kg body weight PCZ via stomach tube. Controls received normal saline in the same dosis and manner. On GD20, all fetuses were collected by caesarian section. Live and dead fetuses as well as resorptions were counted. In the live fetuses, the following investigations were conducted: measurement of body weight, occipito-coccygeal-lenght (OCL), tail length (TL), placental weight and diameter, external macroscopic and binocular microscopic examination, and sectional analysis of the animals using the razorblade sectioning technique. Both PCZ doses caused a significant reduction in the number of live fetuses and a significant increase in resorptions. Mean body weight in PCZ groups was antidromic affected. OCL and TL were significantly depressed. Placental weight and diameter as well as number of dead fetuses were comparable to those of controls. External and sectional investigations revealed no PCZ-related deviations. In the light of our findings we conclude that PCZ in the doses used in this experimental study significantly affects the intrauterine development in rats in terms of fetal toxicity but displays no teratological properties.

  4. Possible Involvement of F1F0-ATP synthase and Intracellular ATP in Keratinocyte Differentiation in normal skin and skin lesions

    PubMed Central

    Xiaoyun, Xie; Chaofei, Han; Weiqi, Zeng; Chen, Chen; Lixia, Lu; Queping, Liu; Cong, Peng; Shuang, Zhao; Juan, Su; Xiang, Chen

    2017-01-01

    The F1F0-ATP synthase, an enzyme complex, is mainly located on the mitochondrial inner membrane or sometimes cytomembrane to generate or hydrolyze ATP, play a role in cell proliferation. This study focused on the role of F1F0-ATP synthase in keratinocyte differentiation, and its relationship with intracellular and extracellular ATP (InATP and ExATP). The F1F0-ATP synthase β subunit (ATP5B) expression in various skin tissues and confluence-dependent HaCaT differentiation models was detected. ATP5B expression increased with keratinocyte and HaCaT cell differentiation in normal skin, some epidermis hyper-proliferative diseases, squamous cell carcinoma, and the HaCaT cell differentiation model. The impact of InATP and ExATP content on HaCaT differentiation was reflected by the expression of the differentiation marker involucrin. Inhibition of F1F0-ATP synthase blocked HaCaT cell differentiation, which was associated with a decrease of InATP content, but not with changes of ExATP. Our results revealed that F1F0-ATP synthase expression is associated with the process of keratinocyte differentiation which may possibly be related to InATP synthesis. PMID:28209970

  5. Triplets—one ectopic, two intrauterine

    PubMed Central

    Khan, A. A.

    1973-01-01

    A case of ovarian ectopic conception, complicating a simultaneous twin intra-uterine pregnancy is described, in which the operative diagnosis was confirmed by histological examination. Such cases are extremely rare and comment is made upon this with references. PMID:4786440

  6. Effect of drugs on intrauterine growth.

    PubMed

    Redmond, G P

    1979-03-01

    Although the teratogenic potential of maternally administered drugs is well known, their stimulation of intrauterine growth retardation may be equally deleterious. Possible adverse effects of propranolol, steroids, anticonvulsants, tranquilizers, and maternal smoking and drinking are discussed. Questions of fetal development and maternal management are considered in light of their interference with the mechanism of growth regulation.

  7. Effects of intrauterine challenge with Leptospira interrogans serovar hardjo on fertility in cattle.

    PubMed

    Vahdat, F; Bey, R F; Williamson, N B; Whitmore, H L; Zemjanis, R; Robinson, R A

    1983-11-01

    The purpose of this study was to determine the effects of Leptospira interrogans serovar hardio on fertility in cattle. Twenty seronegative mature dairy cows were assigned to two groups. Group I (challenged cows) was bred by a seronegative bull followed by intrauterine infusion (within 30 minutes) of Leptospira interrogans serovar hardjo. Group II was bred by the same bull followed by intrauterine infusion of 5 ml of sterile culture medium. Blood samples were collected at two-day intervals to monitor serum antibody titers. Daily blood cultures for 10 days and weekly urine cultures for five weeks were performed to monitor the animals for leptospiremia and leptospiuria. Cows were slaughtered 35 days post-breeding, and their reproductive tracts were examined. All animals remained clinically normal following intrauterine challenge. There was no difference in pregnancy rates (Group I, 7/10; Group II, 6/10). All embryos, reproductive tracts, and kidneys appeared normal. A microscopic agglutination test (MA) showed that 4 of 10 challenged cows developed serum antibody titers between 8 and 20 days after challenge. However, on the basis of the hamster passive protection test, all challenged cows had serum antibodies present. All blood and urine cultures were negative through the experimental period, as were the final kidney and uterine cultures. In a second experiment, six seronegative cows were infused with killed microorganisms immediately after insemination. Results of a microscopic agglutination test and a hamster passive protection test indicated that these cows did not develop humoral antibodies against serovar hardjo. These results indicated that intrauterine inoculation of Leptospira interrogans serovar hardjo (hamster-adapted strain) following breeding did not affect pregnancy rates despite an intrauterine challenge which caused the development of humoral antibodies.

  8. Transformation by myc prevents fusion but not biochemical differentiation of C2C12 myoblasts: mechanisms of phenotypic correction in mixed culture with normal cells

    PubMed Central

    1994-01-01

    To study the effects of myc oncogene on muscle differentiation, we infected the murine skeletal muscle cell line C2C12 with retroviral vectors encoding various forms of avian c- or v-myc oncogene. myc expression induced cell transformation but, unlike many other oncogenes, prevented neither biochemical differentiation, nor commitment (irreversible withdrawal from the cell cycle). Yet, myotube formation by fusion of differentiated cells was strongly inhibited. Comparison of uninfected C2C12 myotubes with differentiated myc- expressing C2C12 did not reveal consistent differences in the expression of several muscle regulatory or structural genes. The present results lead us to conclude that transformation by myc is compatible with differentiation in C2C12 cells. myc expression induced cell death under growth restricting conditions. Differentiated cells escaped cell death despite continuing expression of myc, suggesting that the muscle differentiation programme interferes with the mechanism of myc-induced cell death. Cocultivation of v-myc-transformed C2C12 cells with normal fibroblasts or myoblasts restored fusion competence and revealed two distinguishable mechanisms that lead to correction of the fusion defect. PMID:8195295

  9. Evaluation of normalization of cerebro-placental ratio as a potential predictor for adverse outcome in SGA fetuses.

    PubMed

    Monteith, Cathy; Flood, Karen; Mullers, Sieglinde; Unterscheider, Julia; Breathnach, Fionnuala; Daly, Sean; Geary, Michael P; Kennelly, Mairead M; McAuliffe, Fionnuala M; O'Donoghue, Keelin; Hunter, Alison; Morrison, John J; Burke, Gerald; Dicker, Patrick; Tully, Elizabeth C; Malone, Fergal D

    2017-03-01

    Intrauterine growth restriction accounts for a significant proportion of perinatal morbidity and mortality currently encountered in obstetric practice. The primary goal of antenatal care is the early recognition of such conditions to allow treatment and optimization of both maternal and fetal outcomes. Management of pregnancies complicated by intrauterine growth restriction remains one of the greatest challenges in obstetrics. Frequently, however, clinical evidence of underlying uteroplacental dysfunction may only emerge at a late stage in the disease process. With advanced disease the only therapeutic intervention is delivery of the fetus and placenta. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the at-risk fetus in both intrauterine growth restriction and the appropriate-for-gestational-age setting. The cerebroplacental ratio quantifies the redistribution of the cardiac output resulting in a brain-sparing effect. The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect is significantly associated with an adverse perinatal outcome in the intrauterine growth restriction cohort. The aim of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study was to evaluate the optimal management of fetuses with an estimated fetal weight <10th centile. The objective of this secondary analysis was to evaluate if normalizing cerebroplacental ratio predicts adverse perinatal outcome. In all, 1116 consecutive singleton pregnancies with intrauterine growth restriction completed the study protocol over 2 years at 7 centers, undergoing serial sonographic evaluation and multivessel Doppler measurement. Cerebroplacental ratio was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Abnormal cerebroplacental ratio was defined as <1

  10. Micronutrient prenatal supplementation prevents the development of hypertension and vascular endothelial damage induced by intrauterine malnutrition.

    PubMed

    Franco, Maria do Carmo; Ponzio, Beatriz Felice; Gomes, Guiomar Nascimento; Gil, Frida Zaladek; Tostes, Rita; Carvalho, Maria Helena Catelli; Fortes, Zuleica Bruno

    2009-08-12

    The premise that intrauterine malnutrition plays an important role in the development of cardiovascular and renal diseases implies that these disorders can be programmed during fetal life. Here, we analyzed the hypothesis that supplementation with mixed antioxidant vitamins and essential mineral in early life could prevent later elevation of blood pressure and vascular and renal dysfunction associated with intrauterine malnutrition. For this, female Wistar rats were randomly divided into three groups on day 1 of pregnancy: control fed standard chow ad libitum; restricted group fed 50% of the ad libitum intake and a restricted plus micronutrient cocktail group treated daily with a combination of micronutrient (selenium, folate, vitamin C and vitamin E) by oral gavage. In adult offspring, renal function and glomerular number were impaired by intrauterine malnutrition, and the prenatal micronutrient treatment did not prevent it. However, increased blood pressure and reduced endothelium-dependent vasodilation were prevented by the micronutrient prenatal treatment. Intrauterine malnutrition also led to reduced NO production associated with increased superoxide generation, and these parameters were fully normalized by this prenatal treatment. Our current findings indicate that programming alterations during fetal life can be prevented by interventions during the prenatal period, and that disturbance in availability of both antioxidant vitamins and mineral may play a crucial role in determining the occurrence of long-term cardiovascular injury.

  11. Impaired Angiogenic Potential of Human Placental Mesenchymal Stromal Cells in Intrauterine Growth Restriction

    PubMed Central

    Mandò, Chiara; Razini, Paola; Novielli, Chiara; Anelli, Gaia Maria; Belicchi, Marzia; Erratico, Silvia; Banfi, Stefania; Meregalli, Mirella; Tavelli, Alessandro; Baccarin, Marco; Rolfo, Alessandro; Motta, Silvia

    2016-01-01

    Human placental mesenchymal stromal cells (pMSCs) have never been investigated in intrauterine growth restriction (IUGR). We characterized cells isolated from placental membranes and the basal disc of six IUGR and five physiological placentas. Cell viability and proliferation were assessed every 7 days during a 6-week culture. Expression of hematopoietic, stem, endothelial, and mesenchymal markers was evaluated by flow cytometry. We characterized the multipotency of pMSCs and the expression of genes involved in mitochondrial content and function. Cell viability was high in all samples, and proliferation rate was lower in IUGR compared with control cells. All samples presented a starting heterogeneous population, shifting during culture toward homogeneity for mesenchymal markers and occurring earlier in IUGR than in controls. In vitro multipotency of IUGR-derived pMSCs was restricted because their capacity for adipocyte differentiation was increased, whereas their ability to differentiate toward endothelial cell lineage was decreased. Mitochondrial content and function were higher in IUGR pMSCs than controls, possibly indicating a shift from anaerobic to aerobic metabolism, with the loss of the metabolic characteristics that are typical of undifferentiated multipotent cells. Significance This study demonstrates that the loss of endothelial differentiation potential and the increase of adipogenic ability are likely to play a significant role in the vicious cycle of abnormal placental development in intrauterine growth restriction (IUGR). This is the first observation of a potential role for placental mesenchymal stromal cells in intrauterine growth restriction, thus leading to new perspectives for the treatment of IUGR. PMID:26956210

  12. Intrauterine Growth Retardation and Nonalcoholic Fatty Liver Disease in Children

    PubMed Central

    Alisi, Anna; Panera, Nadia; Agostoni, Carlo; Nobili, Valerio

    2011-01-01

    Intrauterine growth retardation (IUGR), the most important cause of perinatal mortality and morbidity, is defined as a foetal growth less than normal for the population, often used as synonym of small for gestational age (SGA). Studies demonstrated the relationships between metabolic syndrome (MS) and birthweight. This study suggested that, in children, adolescents, and adults born SGA, insulin resistance could lead to other metabolic disorders: type 2 diabetes (DM2), dyslipidemia, and nonalcoholic fatty liver disease (NAFLD). NAFLD may evolve to nonalcoholic steatohepatitis (NASH), and it is related to the development of MS. Lifestyle intervention, physical activity, and weight reduction represent the mainstay of NAFLD therapy. In particular, a catch-up growth reduction could decrease the risk to develop MS and NAFLD. In this paper, we outline clinical and experimental evidences of the association between IUGR, metabolic syndrome, insulin resistance, and NAFLD and discuss on a possible management to avoid the risk of MS in adulthood. PMID:22190925

  13. Differential Effects of Lovastatin on Cisplatin Responses in Normal Human Mesothelial Cells versus Cancer Cells: Implication for Therapy

    PubMed Central

    Shi, Yandong; Felley-Bosco, Emanuela; Marti, Thomas M.; Stahel, Rolf A.

    2012-01-01

    The cancer killing efficacy of standard chemotherapeutic agents such as cisplatin (CDDP) is limited by their side effects to normal tissues. Therefore, research efforts optimizing the safety and efficacy of those agents are clinically relevant. We did screen for agents that specifically protect normal human mesothelial cells against CDDP without reducing the cancer cell killing efficacy. Lovastatin was identified from the screen. Lovastatin at a pharmacologically relevant concentration strongly arrested the proliferation of normal cells, whereas cancer cells were less affected. CDDP-induced DNA damage response was not activated and normal cells showed enhanced tolerance to CDDP when normal cells were treated with the combination of CDDP and lovastatin. We demonstrate that interfering with protein geranylgeranylation is involved in the lovastatin-mediated CDDP protective effect in normal cells. In contrast to normal cells, in cancer cells lovastatin did not change the CDDP-induced response, and cancer cells were not protected by lovastatin. Furthermore, lovastatin at the pharmacological relevant concentration per se induced DNA damage, oxidative stress and autophagy in cancer cells but not in normal mesothelial cells. Therefore, our data suggest that lovastatin has a potential to improve the therapeutic index of cisplatin-based therapy. PMID:23028957

  14. Depth-cumulated epithelial redox ratio and stromal collagen quantity as quantitative intrinsic indicators for differentiating normal, inflammatory, and dysplastic epithelial tissues

    NASA Astrophysics Data System (ADS)

    Zhuo, Shuangmu; Zheng, Liqin; Chen, Jianxin; Xie, Shusen; Zhu, Xiaoqin; Jiang, Xingshan

    2010-10-01

    Multiphoton microscopy was used to isolate the intrinsic emission contribution of epithelial cellular origins and stromal collagen in normal, inflammatory, and dysplastic epithelial tissues, and quantify the depth-cumulated epithelial redox ratio and stromal collagen quantity. It was found that both inflammatory and dysplastic epithelial tissues display a large decrease in stromal collagen quantity but have very different epithelial redox ratio. These results suggest that probing differences in epithelial redox ratio in addition to stromal collagen quantity can serve as quantitative intrinsic indicators for differentiating normal, inflammatory, and dysplastic epithelial tissues.

  15. Prognostic Value of Fetal Thymus Size in Intrauterine Growth Restriction.

    PubMed

    Ekin, Atalay; Gezer, Cenk; Taner, Cuneyt Eftal; Solmaz, Ulas; Gezer, Naciye Sinem; Ozeren, Mehmet

    2016-03-01

    Our aim was to evaluate the size of the fetal thymus by sonography in pregnancies with intrauterine growth restriction (IUGR) and to search for a possible relationship between a small fetal thymus and adverse perinatal outcomes. The transverse diameter of the fetal thymus was prospectively measured in 150 healthy and 143 IUGR fetuses between 24 and 40 weeks' gestation. The fetuses with IUGR were further divided according to normal or abnormal Doppler assessment of the umbilical and middle cerebral arteries and ductus venosus. Measurements were compared with reference ranges from controls. To determine which perinatal outcomes were independently associated with a small fetal thymus, a multivariate logistic regression analysis was performed. Thymus size was significantly lower in IUGR fetuses compared to controls (P < .05). Among IUGR fetuses, thymus size was significantly smaller in IUGR fetuses with abnormal Doppler flow compared to normal flow (P < .05). A small thymus in IUGR fetuses was independently associated with early delivery (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.05-1.49; P= .023), respiratory distress syndrome (OR, 1.36; 95% CI, 1.09-1.78; P= .005), early neonatal sepsis (OR, 1.65; 95% CI, 1.11-2.42; P= .001), and a longer stay in the neonatal intensive care unit (OR, 1.33; 95% CI, 1.08-1.71; P = .017). Intrauterine growth restriction is associated with fetal thymic involution, and a small fetal thymus is an early indicator of adverse perinatal outcomes in pregnancies complicated by IUGR. © 2016 by the American Institute of Ultrasound in Medicine.

  16. Immunological sequelae of intrauterine infection.

    PubMed Central

    McMurray, D N; Rey, H

    1981-01-01

    Compared to normal children, pre-natally infected infants had significantly elevated IgM concentrations throughout the first year of life and elevated IgA levels for the first 6 months. In contrast, IgG levels dropped significantly below normal at 3 months post-partum. Infants born without overt disease but with elevated IgM were found to have precocious development of serum IgA when compared to control children. Levels of IgA and IgG in tears were markedly reduced in symptomatic children at 3 months of age. Lymphocyte response in vitro to phytohaemagglutinin and pokeweed mitogen was low in symptomatic infants. These results suggest that intratuerine infection may result in multiple immunological abnormalities. PMID:7198020

  17. The N(6)-methyladenosine (m(6)A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells.

    PubMed

    Vu, Ly P; Pickering, Brian F; Cheng, Yuanming; Zaccara, Sara; Nguyen, Diu; Minuesa, Gerard; Chou, Timothy; Chow, Arthur; Saletore, Yogesh; MacKay, Matthew; Schulman, Jessica; Famulare, Christopher; Patel, Minal; Klimek, Virginia M; Garrett-Bakelman, Francine E; Melnick, Ari; Carroll, Martin; Mason, Christopher E; Jaffrey, Samie R; Kharas, Michael G

    2017-09-18

    N(6)-methyladenosine (m(6)A) is an abundant nucleotide modification in mRNA that is required for the differentiation of mouse embryonic stem cells. However, it remains unknown whether the m(6)A modification controls the differentiation of normal and/or malignant myeloid hematopoietic cells. Here we show that shRNA-mediated depletion of the m(6)A-forming enzyme METTL3 in human hematopoietic stem/progenitor cells (HSPCs) promotes cell differentiation, coupled with reduced cell proliferation. Conversely, overexpression of wild-type METTL3, but not of a catalytically inactive form of METTL3, inhibits cell differentiation and increases cell growth. METTL3 mRNA and protein are expressed more abundantly in acute myeloid leukemia (AML) cells than in healthy HSPCs or other types of tumor cells. Furthermore, METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m(6)A coupled with ribosome profiling reveals that m(6)A promotes the translation of c-MYC, BCL2 and PTEN mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated AKT, which contributes to the differentiation-promoting effects of METTL3 depletion. Overall, these results provide a rationale for the therapeutic targeting of METTL3 in myeloid leukemia.

  18. Intrauterine Growth Restriction and the Fetal Programming of the Hedonic Response to Sweet Taste in Newborn Infants

    PubMed Central

    Ayres, Caroline; Agranonik, Marilyn; Portella, André Krumel; Filion, Françoise; Johnston, Celeste C.; Silveira, Patrícia Pelufo

    2012-01-01

    Intrauterine growth restriction is associated with increased risk for adult metabolic syndrome and cardiovascular disease, which seems to be related to altered food preferences in these individuals later in life. In this study, we sought to understand whether intrauterine growth leads to fetal programming of the hedonic responses to sweet. Sixteen 1-day-old preterm infants received 24% sucrose solution or water and the taste reactivity was filmed and analyzed. Spearman correlation demonstrated a positive correlation between fetal growth and the hedonic response to the sweet solution in the first 15 seconds after the offer (r = 0.864, P = 0.001), without correlation when the solution given is water (r = 0.314, P = 0.455). In fact, the more intense the intrauterine growth restriction, the lower the frequency of the hedonic response observed. IUGR is strongly correlated with the hedonic response to a sweet solution in the first day of life in preterm infants. This is the first evidence in humans to demonstrate that the hedonic response to sweet taste is programmed very early during the fetal life by the degree of intrauterine growth. The altered hedonic response at birth and subsequent differential food preference may contribute to the increased risk of obesity and related disorders in adulthood in intrauterine growth-restricted individuals. PMID:22851979

  19. Intrauterine growth restriction and the fetal programming of the hedonic response to sweet taste in newborn infants.

    PubMed

    Ayres, Caroline; Agranonik, Marilyn; Portella, André Krumel; Filion, Françoise; Johnston, Celeste C; Silveira, Patrícia Pelufo

    2012-01-01

    Intrauterine growth restriction is associated with increased risk for adult metabolic syndrome and cardiovascular disease, which seems to be related to altered food preferences in these individuals later in life. In this study, we sought to understand whether intrauterine growth leads to fetal programming of the hedonic responses to sweet. Sixteen 1-day-old preterm infants received 24% sucrose solution or water and the taste reactivity was filmed and analyzed. Spearman correlation demonstrated a positive correlation between fetal growth and the hedonic response to the sweet solution in the first 15 seconds after the offer (r = 0.864, P = 0.001), without correlation when the solution given is water (r = 0.314, P = 0.455). In fact, the more intense the intrauterine growth restriction, the lower the frequency of the hedonic response observed. IUGR is strongly correlated with the hedonic response to a sweet solution in the first day of life in preterm infants. This is the first evidence in humans to demonstrate that the hedonic response to sweet taste is programmed very early during the fetal life by the degree of intrauterine growth. The altered hedonic response at birth and subsequent differential food preference may contribute to the increased risk of obesity and related disorders in adulthood in intrauterine growth-restricted individuals.

  20. Knockdown of PKD1 in normal human epidermal keratinocytes increases mRNA expression of keratin 10 and involucrin: early markers of keratinocyte differentiation.

    PubMed

    Ivanova, Petya; Atanasova, Ganka; Poumay, Yves; Mitev, Vanyo

    2008-03-01

    Subconfluent normal human keratinocytes exhibit autonomous (autocrine growth factor driven) proliferation and express the specific markers for keratinocyte proliferation K5 (keratin 5) and K14 (keratin 14). Utilizing this model the effects of PKD1 (Protein kinase D1) knockdown on activation of differentiation was studied. siRNA approach was applied to achieve specific knockdown of PKD1 and the mRNA levels of different keratinocyte markers -- K14 and PCNA (markers of basal proliferating keratinocytes), involucrin and K10 (early differentiation markers) were analyzed. Treatment of cultured keratinocytes with siRNA for PKD1 resulted in reduction of mRNA levels of PKD1, altered cell phenotype and promotion of keratinocyte differentiation, demonstrated by increased expression of involucrin and K10 mRNAs. No significant changes in K14 mRNA expression levels were detected, but the expression of PCNA mRNA was markedly diminished. This study was the first to show that mRNA expression of PKD1 in subconfluent normal human keratinocytes is very low, the PKD1 mRNA levels were more than 8-fold lower than the same ones in hTert keratinocytes. These findings suggest antidifferentiative role of PKD1 in normal human keratinocytes, contrary to the prodiferentiative role of PKD1 in human hTert keratinocytes. We came to the conclusion that there are differences between transduction pathways involving PKD1 in primary human keratinocyte cultures and these in immortalized hTert keratinocytes.

  1. Intrauterine contraception: the pendulum swings back.

    PubMed

    MacIsaac, Laura; Espey, Eve

    2007-03-01

    Intrauterine contraception is the most widely used method of reversible fertility regulation in the world. Finally, IUC is undergoing a renaissance in the US and it's role will expand as new devices and systems are developed and as old biases among clinicians and women are erased. Successful fertility regulation is a defining factor of the overall health of a population; the expanded use of IUC can help achieve that public health success.

  2. Using an Intrauterine Device in Immunocompromised Women

    PubMed Central

    Browne, Hyacinth; Manipalviratn, Somjate; Armstrong, Alicia

    2008-01-01

    Intrauterine devices (IUDs) are a viable treatment option for immunocompromised women who need contraception or menses suppression. They may also be an alternative treatment for women who have a contraindication to estrogen use. A review of the literature on IUD use in this population is sparse, but currently available data suggest that immunocompromised women are not at greater risk of developing pelvic infections. PMID:18757667

  3. Pelvic actinomycosis associated with intrauterine devices.

    PubMed

    O'Connor, K F; Bagg, M N; Croley, M R; Schabel, S I

    1989-02-01

    The authors describe two women with pelvic pain, long-term use of an intrauterine device, and a pelvic mass due to Actinomyces israelii. The diagnostic imaging findings were nonspecific but included mass effect and mucosal irregularity of the rectosigmoid colon at barium enema examination and complex masses and inflammatory changes at computed tomography and magnetic resonance imaging. Radiologists should be aware of the imaging findings of this potentially lethal but curable condition.

  4. Intrauterine device found in an ovarian carcinoma.

    PubMed

    Koo, Hye Ryoung; Oh, Young Taik; Kim, Young Tae; Kim, Sang Wun; Kang, Jung-Ho; Kim, Ki Whang

    2008-01-01

    Displacement of an intrauterine device (IUD) through the perforation site is a rare but one of the major complications. Theoretically, an extrauterine IUD can be located anywhere in the abdominopelvic cavity. It may be asymptomatic or may cause serious complications, including infection, fistula, organ perforation, or bowel obstruction. However, there is no report of IUD located within an ovarian carcinoma to our knowledge, and our report is the first case of an IUD found in the center of an ovarian cancer.

  5. [Post-natal growth of the child born with intra-uterine malnutrition].

    PubMed

    Urrusti-Sanz, J; Yoshida-Ando, P; Frenk, S; Velasco-Candano, L; Rosado, A; Miranda-Rodriguez, A; Lilia Aspra, A

    1978-01-01

    Growth and morbidity were studied in a group of children at one and two years of age of which 10 were born with intrauterine malnutrition, 14 were prematures and nine had normal weight. All were evaluated , according to the Gesell test, at two years of age. Malnourished and premature children grew at greater rate than normals, reaching their size at one year of age. However, at the age of two, length of premature children was less than in normals. Gesell's test results were subnormal in 50 percent of the malnourished ones.

  6. Effects of extracellular calcium on the growth-differentiation switch in immortalized keratinocyte HaCaT cells compared with normal human keratinocytes.

    PubMed

    Micallef, Ludovic; Belaubre, Françoise; Pinon, Aline; Jayat-Vignoles, Chantal; Delage, Christiane; Charveron, Marie; Simon, Alain

    2009-02-01

    The keratinocyte growth and differentiation switch, tightly regulated by several mechanisms, is generally associated with decreased proliferation, cell cycle arrest in G0/G1 phase and expression of epidermal differentiation markers, such as keratin 1 (K1), keratin 10 (K10) and involucrin. In vitro, the spontaneously immortalized human keratinocyte cell line HaCaT is often used as a model to study keratinocyte functions. Comparative differentiation studies between HaCaT cells and normal human keratinocytes (NHK) over an extended time-period have rarely been reported. Therefore, we studied their switch from a proliferating to a differentiated state over 13 days. As culture conditions involved changes in cellular responses, cells were cultured in a specific medium for keratinocyte growth and differentiation was induced by increasing extracellular calcium concentration from 0.09 to 1.2 mm. In NHK, addition of calcium-induced morphological changes and concomitant decreased proliferation. For HaCaT cells, calcium addition resulted in morphological changes, but in an unexpected manner, cells were more proliferative than when cultured at low calcium levels. HaCaT cell hyperproliferation correlated with cell cycle analysis, showing an accumulation in S/G2-M phases. Furthermore, RT-PCR and western blot analysis revealed a delay in the expression of the differentiation markers K1, K10 and involucrin in HaCaT cells compared with NHK. In conclusion, even though calcium-induced differentiation was not associated with a decreased cell proliferation, HaCaT cells conserved properties characteristic of differentiation.

  7. Placental Nutrient Transport and Intrauterine Growth Restriction

    PubMed Central

    Gaccioli, Francesca; Lager, Susanne

    2016-01-01

    Intrauterine growth restriction refers to the inability of the fetus to reach its genetically determined potential size. Fetal growth restriction affects approximately 5–15% of all pregnancies in the United States and Europe. In developing countries the occurrence varies widely between 10 and 55%, impacting about 30 million newborns per year. Besides having high perinatal mortality rates these infants are at greater risk for severe adverse outcomes, such as hypoxic ischemic encephalopathy and cerebral palsy. Moreover, reduced fetal growth has lifelong health consequences, including higher risks of developing metabolic and cardiovascular diseases in adulthood. Numerous reports indicate placental insufficiency as one of the underlying causes leading to altered fetal growth and impaired placental capacity of delivering nutrients to the fetus has been shown to contribute to the etiology of intrauterine growth restriction. Indeed, reduced expression and/or activity of placental nutrient transporters have been demonstrated in several conditions associated with an increased risk of delivering a small or growth restricted infant. This review focuses on human pregnancies and summarizes the changes in placental amino acid, fatty acid, and glucose transport reported in conditions associated with intrauterine growth restriction, such as maternal undernutrition, pre-eclampsia, young maternal age, high altitude and infection. PMID:26909042

  8. Intrauterine blood transfusion in immune hydrops fetalis, corrects middle cerebral artery Doppler velocimetry very quickly

    PubMed Central

    Yalinkaya, Ahmet; Evsen, Mehmet Sıddık; Celik, Yusuf; Sak, Muhammet Erdal; Soydinc, Hatice Ender; Taner, Mehmet Zeki

    2012-01-01

    The aim of our study was to evaluate the middle cerebral artery velocimetry before and after intrauterine blood transfusion in immune hydrops fetalis. The current study was conducted in a tertiary research hospital, from February 2009 to January 2011. Nineteen intrauterine blood transfusions performed during the study period. The factors recorded were age of the mothers, gestational weeks, pre-transfusion fetal hematocrit and post-transfusion fetal hematocrit, and also middle cerebral artery peak systolic velocimetry (MCA-PSV) was detected and recorded before and after intrauterine transfusion. A control group of twenty two cases for normal MCA doppler velocimetry was also included to the study. During the study, a total of eleven rhesus isoimmunized pregnancies underwent intrauterine blood transfusions at our perinatal diagnose unit. Before transfusion seventeen severe and two moderate anemias were detected and mean MoM of MCA-PSV was 1.76±0.38 MoM. Post transfusion mean MoM of MCA-PSV in the patient group and control group were 1.08±0.22 MoM and 0.96±0.21 MoM, respectively. The mean MCA-PSV values were higher in RI fetuses than post transfusion and control group. In current study, we found that MCA-PSV is a valuable parameter in detecting fetal anemia requiring intrauterine transfusion and mean MCA-PSV values is higher than 1.5 MoM in fetuses with anemia. And also decrease in MCA-PSV just after transfusion in anemic fetuses showed the quick response of the fetus to correction of anemia. PMID:22364302

  9. Comparison of two- and three-dimensional transvaginal ultrasound in the visualisation of intrauterine devices.

    PubMed

    Kerr, N K; Dunham, R; Wolstenhulme, S; Wilson, J

    2014-08-01

    The aims of the study were to evaluate whether three-dimensional transvaginal ultrasound (3D TV US) is superior to two-dimensional transvaginal ultrasound (2D TV US) at visualising intrauterine devices and determining their position. This prospective study included 52 participants with an intrauterine device fitted, who underwent 2D TV US and 3D TV US. 2D TV US and 3D-reconstructed coronal images were reviewed by two gynaecological radiologists to assess ease of visualisation and position of the intrauterine devices. Statistical analysis was performed using Wilcoxon signed-rank, McNemar and Chi-squared tests. The inter-observer agreement was measured using Cohen's Kappa. Intrauterine device visualisation scores were significantly higher with 2D TV US compared with 3D TV US (Radiologist 1 p = <0.001, Radiologist 2 p = 0.007). A significant number of T-arms appeared to perforate into the adjacent myometrium on the 3D-reconstructed coronal image, but were normal on the 2D images (Radiologist 1 p = <0.001, Radiologist 2 p = 0.008). Radiologist 1 found 19 perforated T-arms on 3D TV US compared with four on 2D TV US. Radiologist 2 found 13 perforated T-arms on 3D TV US compared with five on 2D TV US. Both radiologists agreed on the positions of the intrauterine devices substantially with 3D TV US (Kappa = 0.69) and moderately with 2D TV US (Kappa = 0.55). The 3D TV US did not visualise an intrauterine device better than 2D TV US. The 3D-reconstructed coronal image of the uterus can reliably display cases of T-arm perforation into the adjacent myometrium, which could be missed on 2D TV US images. The 3D TV US should be used in addition to 2D TV US in all cases where an intrauterine device is under evaluation.

  10. [Application of levonorgestrel-releasing intrauterine system in early pregnancy: a case report].

    PubMed

    Gardyszewska, Agnieszka; Czajkowski, Krzysztof

    2012-12-01

    Intrauterine device is a popular cost-effective method of contraception known worldwide. It is extremely effective, with pregnancy rates comparable to tubal ligation (5-year cumulative rate varying from 0.5 to 1.1). LNG-IUS increases in popularity and may be used as the method of choice for adults because it offers non-contraceptive benefits: slight menstrual bleeding, decreased number of incidents of dysmenorrhea, and reduced pain associated with endometriosis. The levonorgestrel-releasing intrauterine system (LNG-IUS) provides a release rate of 20 microg/24 h of levonorgestrel. The hormone released from the intrauterine device causes some systemic changes, however local effects, such as glandular atrophy and stromal decidualization, in addition to foreign body reaction, are dominant. According to the Food and Drug Administration regulations, category X was assigned to LNG. The use of the product is contraindicated in women who are or may become pregnant. We report a case of a 30-year old woman who has already been pregnant before the insertion of a levonorgestrel -releasing intrauterine system (LNG-IUS). The patient was lactating after the previous pregnancy the first menstruation had not appeared yet. The patient planned to have the IUD inserted but she missed her appointed visits twice. The third visit took place 8 weeks postpartum. During that visit, the doctor asked her about the possibility of being pregnant, but the patient denied. The gynecologist inserted the intrauterine device and performed transvaginal ultrasound examination. The location of LNG-IUS was proper and there was no gestation sac in the uterine cavity. After the next six weeks, transvaginal ultrasonography and manual examination showed an intrauterine pregnancy at 8 weeks of gestation. The intrauterine device was not detectable in the uterine cavity by ultrasound, and the IUD strings were not visualized in the vagina. It was impossible to remove the device without causing miscarriage. Other

  11. Comparison of two- and three-dimensional transvaginal ultrasound in the visualisation of intrauterine devices

    PubMed Central

    Dunham, R; Wolstenhulme, S; Wilson, J

    2014-01-01

    The aims of the study were to evaluate whether three-dimensional transvaginal ultrasound (3D TV US) is superior to two-dimensional transvaginal ultrasound (2D TV US) at visualising intrauterine devices and determining their position. This prospective study included 52 participants with an intrauterine device fitted, who underwent 2D TV US and 3D TV US. 2D TV US and 3D-reconstructed coronal images were reviewed by two gynaecological radiologists to assess ease of visualisation and position of the intrauterine devices. Statistical analysis was performed using Wilcoxon signed-rank, McNemar and Chi-squared tests. The inter-observer agreement was measured using Cohen’s Kappa. Intrauterine device visualisation scores were significantly higher with 2D TV US compared with 3D TV US (Radiologist 1 p = <0.001, Radiologist 2 p = 0.007). A significant number of T-arms appeared to perforate into the adjacent myometrium on the 3D-reconstructed coronal image, but were normal on the 2D images (Radiologist 1 p = <0.001, Radiologist 2 p = 0.008). Radiologist 1 found 19 perforated T-arms on 3D TV US compared with four on 2D TV US. Radiologist 2 found 13 perforated T-arms on 3D TV US compared with five on 2D TV US. Both radiologists agreed on the positions of the intrauterine devices substantially with 3D TV US (Kappa = 0.69) and moderately with 2D TV US (Kappa = 0.55). The 3D TV US did not visualise an intrauterine device better than 2D TV US. The 3D-reconstructed coronal image of the uterus can reliably display cases of T-arm perforation into the adjacent myometrium, which could be missed on 2D TV US images. The 3D TV US should be used in addition to 2D TV US in all cases where an intrauterine device is under evaluation. PMID:27433211

  12. Cartilage oligomeric matrix protein (COMP)-mediated cell differentiation to proteolysis mechanism networks from human normal adjacent tissues to lung adenocarcinoma.

    PubMed

    Wang, Lin; Huang, Juxiang; Jiang, Minghu; Diao, Haizhen; Zhou, Huilei; Li, Xiaohe; Chen, Qingchun; Jiang, Zhenfu; Feng, Haitao; Wolfl, Stefan

    2013-01-01

    To understand cartilage oligomeric matrix protein (COMP) mechanism network from human normal adjacent tissues to lung adenocarcinoma. COMP complete different activated (all no positive correlation, Pearson CC < 0.25) and uncomplete (partly no positive correlation except COMP, Pearson CC < 0.25) network were identified in higher lung adenocarcinoma compared with lower human normal adjacent tissues from the corresponding COMP-stimulated (≥0.25) or inhibited (Pearson CC ≤ -0.25) overlapping molecules of Pearson correlation coefficient (CC) and GRNInfer, respectively. COMP complete different activated and inhibited (all no positive correlation, Pearson CC < 0.25) mechanisms networks of higher lung adenocarcinoma and lower human normal adjacent tissues were constructed by integration of Pearson CC, GRNInfer and GO. As visualized by integration of GO, KEGG, GenMAPP, BioCarta and Disease, we deduced COMP complete different activated and inhibited network in higher lung adenocarcinoma and lower human normal adjacent tissues. As visualized by GO, KEGG, GenMAPP, BioCarta and disease database integration, we proposed mainly that the mechanism and function of COMP complete different activated network in higher lung adenocarcinoma was involved in COMP activation with matrix-localized insulin-like factor coupling carboxypeptidase to metallopeptidase-induced proteolysis, whereas the corresponding inhibited network in lower human normal adjacent tissues participated in COMP inhibition with nucleus-localized vasculogenesis, B and T cell differentiation and neural endocrine factors coupling pyrophosphatase-mediated proteolysis. However, COMP complete different inhibited network in higher lung adenocarcinoma included COMP inhibition with nucleus-localized chromatin maintenance, licensing and assembly factors coupling phosphatase-inhibitor to cytokinesis regulators-mediated cell differentiation, whereas the corresponding activated network in lower human normal adjacent tissues

  13. CONDENSED MATTER: ELECTRONIC STRUCTURE, ELECTRICAL, MAGNETIC, AND OPTICAL PROPERTIES: Differential conductance in a normal metal/insulator/metal/d-wave superconductor junction carrying a supercurrent

    NASA Astrophysics Data System (ADS)

    Li, Xiao-Wei

    2009-12-01

    This paper applies the Bogoliubov-de Gennes equation and the Blonder-Tinkham-Klapwijk approach to study the oscillatory behaviour of differential conductance in a normal metal/insulator/metal/d-wave superconductor junction carrying a supercurrent Is. We find that (i) a three-humped structure appears at a nearly critical supercurrent Is and z approx 0.5 for the normal metal/insulator/metal/dx2+y2-wave superconductor junction; (ii) the zero-bias conductance peak splits into two peaks with sufficiently large applied current for the normal metal/insulator/metal/dxy-wave superconductor junction; (iii) the conductance spectrum exhibits oscillating behaviour with the bias voltage and the peaks of the resonances are suppressed by increasing supercurrent Is.

  14. The Differential Outcomes Effect in Normal Human Adults Using a Concurrent-Task Within-Subjects Design and Sensory Outcomes

    ERIC Educational Resources Information Center

    Mok, Leh Woon; Overmier, J. Bruce

    2007-01-01

    The differential outcomes effect is a phenomenon where use of a choice-unique outcome for each type of correct choice in a conditional discrimination task increases rate of learning and overall accuracy, as compared to the traditional use of a single, common outcome for all types of correct choices. This phenomenon was successfully demonstrated…

  15. Use of Spectral/Cepstral Analyses for Differentiating Normal from Hypofunctional Voices in Sustained Vowel and Continuous Speech Contexts

    ERIC Educational Resources Information Center

    Watts, Christopher R.; Awan, Shaheen N.

    2011-01-01

    Purpose: In this study, the authors evaluated the diagnostic value of spectral/cepstral measures to differentiate dysphonic from nondysphonic voices using sustained vowels and continuous speech samples. Methodology: Thirty-two age- and gender-matched individuals (16 participants with dysphonia and 16 controls) were recorded reading a standard…

  16. Use of Spectral/Cepstral Analyses for Differentiating Normal from Hypofunctional Voices in Sustained Vowel and Continuous Speech Contexts

    ERIC Educational Resources Information Center

    Watts, Christopher R.; Awan, Shaheen N.

    2011-01-01

    Purpose: In this study, the authors evaluated the diagnostic value of spectral/cepstral measures to differentiate dysphonic from nondysphonic voices using sustained vowels and continuous speech samples. Methodology: Thirty-two age- and gender-matched individuals (16 participants with dysphonia and 16 controls) were recorded reading a standard…

  17. A suspicious reason for Raynaud's phenomenon: Intrauterine device.

    PubMed

    Diken, Adem I; Yalçınkaya, Adnan; Aksoy, Eray; Yılmaz, Seyhan; Çağlı, Kerim

    2015-06-01

    Primary Raynaud's phenomenon may be insistent in patients under medical therapy, and intrauterine devices may be an unnoticed reason in these patients. Fluctuations in female sex hormone status were reported to be associated with the emergence of primary Raynaud's phenomenon symptoms. The use of intrauterine devices was not reported to be associated with Raynaud's phenomenon previously. Intrauterine device may stimulate vascular hyperactivity regarding hormonal or unknown mechanisms that result in Raynaud's phenomenon. We present a postmenopausal patient who complained of primary Raynaud's phenomenon symptoms and had recovery after the removal of her copper intrauterine device.

  18. The value of REM sleep parameters in differentiating Alzheimer's disease from old-age depression and normal aging.

    PubMed

    Dykierek, P; Stadtmüller, G; Schramm, P; Bahro, M; van Calker, D; Braus, D F; Steigleider, P; Löw, H; Hohagen, F; Gattaz, W F; Berger, M; Riemann, D

    1998-01-01

    Pseudodementia as a common trait in elderly depressives presents a major problem in gerontopsychiatry, especially for the differential diagnosis between Old-Age Depression (OAD) and Dementia of the Alzheimer Type (DAT). The present polysomnographic study examined parameters of sleep continuity, sleep architecture, and REM sleep to differentiate DAT from OAD. The investigation was based on the theoretical framework of the cholinergic-aminergic imbalance model of depression, the cholinergic deficit hypothesis of Alzheimer's disease and the reciprocal interaction model of Non-REM/REM sleep regulation, according to which REM sleep parameters should have high discriminative value to differentiate OAD and DAT. We investigated 35 DAT patients, 39 OAD patients and 42 healthy controls for two consecutive nights in the sleep laboratory. The DAT patients were in relatively early/mild stages of the disease, the severity of depression in the OAD group was moderate to severe. Depressed patients showed characteristic 'depression-like' EEG sleep alterations, i.e. a lower sleep efficiency, a higher amount of nocturnal awakenings and decreased sleep stage 2. Sleep continuity and architecture in DAT was less disturbed. Nearly all REM sleep measures differentiated significantly between the diagnostic groups. OAD patients showed a shortened REM latency, increased REM density and a high rate of Sleep Onset REM periods (SOREM), whereas in DAT REM density was decreased in comparison to control subjects. REM latency in DAT was not prolonged as expected. To assess the discriminative power of REM sleep variables a series of discriminant analyses were conducted. Overall, 86% of patients were correctly classified, using REM density and REM latency measures. Our findings suggest that REM density as an indicator of phasic activity appears to be more sensitive as a biological marker for the differential diagnosis of OAD and DAT than REM latency. The results support the role of central cholinergic

  19. Differential gene expression profiling in aggressive bladder transitional cell carcinoma compared to the adjacent microscopically normal urothelium by microdissection-SMART cDNA PCR-SSH.

    PubMed

    Wang, H T; Ma, F L; Ma, X B; Han, R F; Zhang, Y B; Chang, J W

    2006-01-01

    Identifying novel and known genes that are differentially expressed in aggressive bladder transitional cell carcinoma (BTCC) has important implications in understanding the biology of bladder tumorigenesis and developing new diagnostic and therapeutic agents. In this study we identified the differential gene expression profiles comparing tumor to the adjacent microscopically normal mucosa by manual microdissection on frozen sections. The RNAs extracted from microdissected tissues were amplified by SMART cDNA PCR technology to generate forward subtractive cDNA library by suppressive subtractive hybridization (SSH). We obtained 376 positive clones, one hundred clones of aggressive BTCC subtracted cDNA library were selected at random and inserts were reamplified by PCR. After differential screening by reverse dot blotting, 73 positive clones, that contend inserts putatively upregulated in aggressive BTCC, were further analysed by DNA sequencing, GenBank and EST database searching. Sequencing results showed that 66 clones stand for 23 known genes and 7 clones for three new EST (Genbank number: DN236875, DN236874 and DN236873). In conclusion, microdissection-SMART cDNA PCR-SSH allowed for an efficient way to identify aggressive BTCC-specific differential expressed genes that may potentially be involved in the carcinogenesis and/or progression of aggressive BTCC. These differentially expressed genes may be of potential utility as therapeutic and diagnostic targets for aggressive BTCC.

  20. Genomic biomarkers of prenatal intrauterine inflammation in umbilical cord tissue predict later life neurological outcomes.

    PubMed

    Tilley, Sloane K; Joseph, Robert M; Kuban, Karl C K; Dammann, Olaf U; O'Shea, T Michael; Fry, Rebecca C

    2017-01-01

    Preterm birth is a major risk factor for neurodevelopmental delays and disorders. This study aimed to identify genomic biomarkers of intrauterine inflammation in umbilical cord tissue in preterm neonates that predict cognitive impairment at 10 years of age. Genome-wide messenger RNA (mRNA) levels from umbilical cord tissue were obtained from 43 neonates born before 28 weeks of gestation. Genes that were differentially expressed across four indicators of intrauterine inflammation were identified and their functions examined. Exact logistic regression was used to test whether expression levels in umbilical cord tissue predicted neurocognitive function at 10 years of age. Placental indicators of inflammation were associated with changes in the mRNA expression of 445 genes in umbilical cord tissue. Transcripts with decreased expression showed significant enrichment for biological signaling processes related to neuronal development and growth. The altered expression of six genes was found to predict neurocognitive impairment when children were 10 years old These genes include two that encode for proteins involved in neuronal development. Prenatal intrauterine inflammation is associated with altered gene expression in umbilical cord tissue. A set of six of the differentially expressed genes predict cognitive impairment later in life, suggesting that the fetal environment is associated with significant adverse effects on neurodevelopment that persist into later childhood.

  1. Differential expression of ghrelin and its receptor (GHS-R1a) in various adrenal tumors and normal adrenal gland.

    PubMed

    Ueberberg, B; Unger, N; Sheu, S Y; Walz, M K; Schmid, K W; Saeger, W; Mann, K; Petersenn, S

    2008-03-01

    Ghrelin is a newly characterized, widely distributed peptide thought to be involved in the regulation of appetite. Significant effects on the release of growth hormone (GH) and ACTH have been demonstrated. This study compares the expression of ghrelin and its receptor (GHS-R) in various adrenal tumors and normal adrenal gland. Normal adrenal tissue was obtained after autopsy. Tissue was obtained from 13 pheochromocytomas (PHEOs), 15 cortisol-secreting adenomas (CPAs), 12 aldosterone-secreting adenomas (APAs), and 16 nonfunctional adenomas (NFAs) following laparoscopic surgery. Expression of ghrelin and GHS-R1a was investigated on RNA levels by using real-time reverse transcription polymerase chain reaction (RT-PCR) and on protein levels by using immunohistochemistry. In the seven normal adrenal glands analyzed, ghrelin mRNA levels were 12-fold lower than in stomach. Ghrelin protein expression was confirmed by immunohistochemistry. In all adrenal tumors, relevant levels of ghrelin mRNA were observed, with significantly lower expression in PHEOs and APAs than in normal adrenal gland. Ghrelin protein was detected in 0% of PHEOs, 55% of APAs, 87% of CPAs, and 54% of NFAs. GHS-R1a mRNA expression was detectable in normal adrenal gland, but the receptor protein was absent. In adrenal tumors, detectable levels of receptor mRNA were found in 38% of PHEOs, 13% of CPAs, and 25% of NFAs. GHS-R1a protein was absent in the majority of adrenal tumors. Expression of ghrelin in normal adrenal gland and adrenal tumors may indicate some unknown physiological function. The pathophysiological relevance of ghrelin expression in adrenal tumors remains to be investigated.

  2. Serial analysis of gene expression reveals differential expression between endometriosis and normal endometrium. Possible roles for AXL and SHC1 in the pathogenesis of endometriosis

    PubMed Central

    Honda, Hiroshi; Barrueto, Fermin F; Gogusev, Jean; Im, Dwight D; Morin, Patrice J

    2008-01-01

    Background Endometriosis is a clinical condition that affects up to 10% of the women of reproductive age. Endometriosis is characterized by the presence of endometrial tissues outside the uterine cavity and can lead to chronic pelvic pain, infertility and, in some cases, to ovarian cancer. Methods In order to better understand the pathogenesis of endometriosis, we have used Serial Analysis of Gene Expression (SAGE) to identify genes differentially in this disease by studying three endometriotic tissues and a normal endometrium sample. Promising candidates (AXL, SHC1, ACTN4, PI3KCA, p-AKT, p-mTOR, and p-ERK) were independently validated by immunohistochemistry in additional normal and endometriotic tissues. Results We identified several genes differentially expressed between endometriosis and normal endometrium. IGF2, ACTN4, AXL, and SHC1 were among the most upregulated genes. Comparison of the endometriosis gene expression profiles with the gene expression patterns observed in normal human tissues allowed the identification of endometriosis-specific genes, which included several members of the MMP family (MMP1,2,3,10,11,14). Immunohistochemical analysis of several candidates confirmed the SAGE findings, and suggested the involvement of the PI3K-Akt and MAPK signaling pathways in endometriosis. Conclusion In human endometriosis, the PI3K-Akt and MAPK signaling pathways may be activated via overexpression of AXL and SHC1, respectively. These genes, as well as others identified as differentially expressed in this study, may be useful for the development of novel strategies for the detection and/or therapy of endometriosis. PMID:19055724

  3. Uterine perforation by intrauterine devices: a 16-year review.

    PubMed

    O'Brien, Paul A; Pillai, Sarah

    2017-07-24

    One of the major concerns with the insertion of intrauterine devices is uterine perforation. Though uncommon, it can be debilitating and result in failure of the device. In this article we review uterine perforation with intrauterine contraception (IUC) in a community clinic in the UK over a 16-year period. We prospectively collected data on uterine perforations for the years 2000-2015, reviewed associated factors and calculated the annual rate of perforation, estimating if this lay within the expected range of normal variation using statistical process control (SPC) analysis. We analysed the rates of perforation in relation to the time from delivery and to breastfeeding. We identified 30 uterine perforations in 22 795 IUC insertions over the 16 years of observation, with an annual rate ranging from 0 to 4.3 per 1000 insertions, and a mean annual rate of 1.3 per 1000 insertions (95% CI 0.9 to 1.9), which remain within the SPC limits. Twenty-eight of the perforations were in parous women, 87% of whom were within 18 weeks of delivery, peaking at 13 weeks postpartum. Twenty of these were in breastfeeding women. In 3/28 cases for which we have outcome data the device was adherent to or had perforated either the bladder or bowel. Our perforation rate is consistent with other studies. Most of our perforations were within 18 weeks of childbirth, earlier than in a recent major study. We cannot tell from our data if there is a true peak in perforations 3 months postpartum as that may be a time when a high proportion of insertions are done. © Faculty of Sexual and Reproductive Healthcare of the Royal College of Obstetricians and Gynaecologists (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Differential usage of the transport systems for folic acid and methotrexate in normal human T-lymphocytes and leukemic cells.

    PubMed

    Biswal, Bijesh Kumar; Verma, Rama Shanker

    2009-11-01

    Methotrexate (MTX) has been used as an effective anti-cancer drug for a long time. Conceptually, it is accepted that MTX and folic acid are transported by folate receptors (FRs) in cancerous cells, but the exact mechanism of MTX uptake in human leukemia is unknown. The objective of this study was to investigate different transport systems for FA and MTX, and to delineate their uptake mechanism in MOLT4, K562, Hut78 leukemia cells and normal human T cells. In MOLT4, uptake of MTX was higher than FA, similar to that of K562, Hut78 and normal T cells. In MOLT4 cells, MTX uptake was maximum at pH 7.4 whereas FA uptake was maximum at pH 4.5. Uptake of FA and MTX was significantly inhibited by anions, suggesting anion-dependent transport system. FA uptake was found to be energy dependent whereas MTX uptake was energy independent. RT-PCR and immunofluorescence results demonstrated the presence of reduced folate carrier as well as proton coupled folate transporter and absence of FR in MOLT4 and normal T cells. These data suggest the existence of two separate and independent carrier-mediated transport systems for the uptake of FA and MTX in normal and leukemic human T cells.

  5. Ethanol alters proliferation and differentiation of normal and chromosomally abnormal human embryonic stem cell-derived neurospheres.

    PubMed

    Krishnamoorthy, Malini; Gerwe, Brian A; Scharer, Christopher D; Sahasranaman, Vanita; Eilertson, Carmen D; Nash, Rachel J; Usta, Sümeyra Naz; Kelly, Shasmine; Rose, Matthew; Peraza, Rene; Arumugham, Jagan; Stewart, Bethany; Stice, Steven L; Nash, Rodney J

    2013-06-01

    Ethanol is a powerful substance and, when consumed during pregnancy, has significant psychoactive and developmental effects on the developing fetus. These abnormalities include growth retardation, neurological deficits, and behavioral and cognitive deficiencies, commonly referred to as fetal alcohol spectrum disorder. The effect of ethanol has been reported to affect cellular development on the embryonic level, however, not much is known about mutations contributing to the influence of ethanol. The purpose of our study was to determine if mutation contribute to changes in differentiation patterning, cell-cycle regulatory gene expression, and DNA methylation in human embryonic stem cells after ethanol exposure. We exposed human embryonic stem cells (with and without know DNA mutations) to a low concentration (20 mM) of ethanol and measured neurosphere proliferation and differentiation, glial protein levels, expression of various cell-cycle genes, and DNA methylation. Ethanol altered cell-cycle gene expression between the two cell lines; however, gene methylation was not affected in ether lines.

  6. Nodal lymph flow quantified with afferent vessel input function allows differentiation between normal and cancer-bearing nodes

    PubMed Central

    DSouza, Alisha V.; Elliott, Jonathan T.; Gunn, Jason R.; Barth, Richard J.; Samkoe, Kimberley S.; Tichauer, Kenneth M.; Pogue, Brian W.

    2015-01-01

    Morbidity and complexity involved in lymph node staging via surgical resection and biopsy could ideally be improved using node assay techniques that are non-invasive. While visible blue dyes are often used to locate the sentinel lymph nodes from draining lymphatic vessels near a tumor, they do not provide an in situ metric to evaluate presence of cancer. In this study, the transport kinetics of methylene blue were analyzed to determine the potential for better in situ information about metastatic involvement in the nodes. A rat model with cancer cells in the axillary lymph nodes was used, with methylene blue injection to image the fluorescence kinetics. The lymphatic flow from injection sites to nodes was imaged and the relative kinetics from feeding lymphatic ducts relative to lymph nodes was quantified. Large variability existed in raw fluorescence and transport patterns within each cohort resulting in no systematic difference between average nodal uptake in normal, sham control and cancer-bearing nodes. However, when the signal from the afferent lymph vessel fluorescence was used to normalize the signal of the lymph nodes, the high signal heterogeneity was reduced. Using a model, the lymph flow through the nodes (FLN) was estimated to be 1.49 ± 0.64 ml/g/min in normal nodes, 1.53 ± 0.45 ml/g/min in sham control nodes, and reduced to 0.50 ± 0.24 ml/g/min in cancer-cell injected nodes. This summarizes the significant difference (p = 0.0002) between cancer-free and cancer-bearing nodes in normalized flow. This process of normalized flow imaging could be used as an in situ tool to detect metastatic involvement in nodes. PMID:25909014

  7. Normal spectrum of pulmonary parametric response map to differentiate lung collapsibility: distribution of densitometric classifications in healthy adult volunteers.

    PubMed

    Silva, Mario; Nemec, Stefan F; Dufresne, Valerie; Occhipinti, Mariaelena; Heidinger, Benedikt H; Chamberlain, Ryan; Bankier, Alexander A

    2016-09-01

    Pulmonary parametric response map (PRM) was proposed for quantitative densitometric phenotypization of chronic obstructive pulmonary disease. However, little is known about this technique in healthy subjects. The purpose of this study was to describe the normal spectrum of densitometric classification of pulmonary PRM in a group of healthy adults. 15 healthy volunteers underwent spirometrically monitored chest CT at total lung capacity (TLC) and functional residual capacity (FRC). The paired CT scans were analyzed by PRM for voxel-by-voxel characterization of lung parenchyma according to 4 densitometric classifications: normal lung (TLC ≥ -950 HU, FRC ≥ -856 HU); expiratory low attenuation area (LAA) (TLC ≥ -950 HU, FRC < -856 HU); dual LAA (TLC<-950 HU, FRC < -856 HU); uncharacterized (TLC < -950 HU, FRC ≥ -856 HU). PRM spectrum was 78 % ± 10 % normal lung, 20 % ± 8 % expiratory LAA, and 1 % ± 1 % dual LAA. PRM was similar between genders, there was moderate correlation between dual LAA and spirometrically assessed TLC (R = 0.531; p = 0.042), and between expiratory LAA and VolExp/Insp ratio (R = -0.572; p = 0.026). PRM reflects the predominance of normal lung parenchyma in a group of healthy volunteers. However, PRM also confirms the presence of physiological expiratory LAA seemingly related to air trapping and a minimal amount of dual LAA likely reflecting emphysema. • Co-registration of inspiratory and expiratory computed tomography allows dual-phase densitometry. • Dual-phase co-registered densitometry reflects heterogeneous regional changes in lung function. • Quantification of lung in healthy subjects is needed to set reference values. • Expiratory low attenuation areas <30 % could be considered within normal range.

  8. Nodal lymph flow quantified with afferent vessel input function allows differentiation between normal and cancer-bearing nodes.

    PubMed

    DSouza, Alisha V; Elliott, Jonathan T; Gunn, Jason R; Barth, Richard J; Samkoe, Kimberley S; Tichauer, Kenneth M; Pogue, Brian W

    2015-04-01

    Morbidity and complexity involved in lymph node staging via surgical resection and biopsy could ideally be improved using node assay techniques that are non-invasive. While visible blue dyes are often used to locate the sentinel lymph nodes from draining lymphatic vessels near a tumor, they do not provide an in situ metric to evaluate presence of cancer. In this study, the transport kinetics of methylene blue were analyzed to determine the potential for better in situ information about metastatic involvement in the nodes. A rat model with cancer cells in the axillary lymph nodes was used, with methylene blue injection to image the fluorescence kinetics. The lymphatic flow from injection sites to nodes was imaged and the relative kinetics from feeding lymphatic ducts relative to lymph nodes was quantified. Large variability existed in raw fluorescence and transport patterns within each cohort resulting in no systematic difference between average nodal uptake in normal, sham control and cancer-bearing nodes. However, when the signal from the afferent lymph vessel fluorescence was used to normalize the signal of the lymph nodes, the high signal heterogeneity was reduced. Using a model, the lymph flow through the nodes [Formula: see text] was estimated to be 1.49 ± 0.64 ml/g/min in normal nodes, 1.53 ± 0.45 ml/g/min in sham control nodes, and reduced to 0.50 ± 0.24 ml/g/min in cancer-cell injected nodes. This summarizes the significant difference (p = 0.0002) between cancer-free and cancer-bearing nodes in normalized flow. This process of normalized flow imaging could be used as an in situ tool to detect metastatic involvement in nodes.

  9. AKT1-mediated Lamin A/C degradation is required for nuclear degradation and normal epidermal terminal differentiation.

    PubMed

    Naeem, A S; Zhu, Y; Di, W L; Marmiroli, S; O'Shaughnessy, R F L

    2015-12-01

    Nuclear degradation is a key stage in keratinocyte terminal differentiation and the formation of the cornified envelope that comprises the majority of epidermal barrier function. Parakeratosis, the retention of nuclear material in the cornified layer of the epidermis, is a common histological observation in many skin diseases, notably in atopic dermatitis and psoriasis. Keratinocyte nuclear degradation is not well characterised, and it is unclear whether the retained nuclei contribute to the altered epidermal differentiation seen in eczema and psoriasis. Loss of AKT1 function strongly correlated with parakeratosis both in eczema samples and in organotypic culture models. Although levels of DNAses, including DNase1L2, were unchanged, proteomic analysis revealed an increase in Lamin A/C. AKT phosphorylates Lamin A/C, targeting it for degradation. Consistent with this, Lamin A/C degradation was inhibited and Lamin A/C was observed in the cornified layer of AKT1 knockdown organotypic cultures, surrounding retained nuclear material. Using AKT-phosphorylation-dead Lamin A constructs we show that the retention of nuclear material is sufficient to cause profound changes in epidermal terminal differentiation, specifically a reduction in Loricrin, Keratin 1, Keratin 10, and filaggrin expression. We show that preventing nuclear degradation upregulates BMP2 expression and SMAD1 signalling. Consistent with these data, we observe both parakeratosis and evidence of increased SMAD1 signalling in atopic dermatitis. We therefore present a model that, in the absence of AKT1-mediated Lamin A/C degradation, DNA degradation processes, such as those mediated by DNAse 1L2, are prevented, leading to parakeratosis and changes in epidermal differentiation.

  10. Use of spectral/cepstral analyses for differentiating normal from hypofunctional voices in sustained vowel and continuous speech contexts.

    PubMed

    Watts, Christopher R; Awan, Shaheen N

    2011-12-01

    In this study, the authors evaluated the diagnostic value of spectral/cepstral measures to differentiate dysphonic from nondysphonic voices using sustained vowels and continuous speech samples. Thirty-two age- and gender-matched individuals (16 participants with dysphonia and 16 controls) were recorded reading a standard passage (The Rainbow Passage; Fairbanks, 1960) and sustaining the vowel /α/. Recorded voices were analyzed with custom software that calculated 4 spectral/cepstral measures. Measures of cepstral peak prominence (CPP) and low-high spectral ratio (L/H ratio) were significantly different between groups in both speaking conditions; the standard deviation of the CPP was significantly different between groups in continuous speech only. In differentiating dysphonic individuals with a hypofunctional etiology from nondysphonic individuals, receiver operating characteristic (ROC) analyses demonstrated (a) high sensitivity and high specificity for the CPP in the sustained vowel condition and (b) high sensitivity and moderate specificity for the CPP in the speech condition. In a sample of dysphonic speakers (hypofunctional etiologies) versus typical speakers, spectral/cepstral measures of CPP and L/H ratio were able to differentiate these groups from one another in both vowel prolongation and continuous speech contexts with high sensitivity and specificity. The results of this study support the growing body of literature documenting the significant value of cepstral and other spectral-based acoustic measures to the clinical evaluation and management processes.

  11. Differential gene-expression patterns in genital fibroblasts of normal males and 46,XY females with androgen insensitivity syndrome: evidence for early programming involving the androgen receptor

    PubMed Central

    Holterhus, Paul-Martin; Hiort, Olaf; Demeter, Janos; Brown, Patrick O; Brooks, James D

    2003-01-01

    Background Androgen insensitivity syndrome (AIS) comprises a range of phenotypes from male infertility to complete feminization. Most individuals with AIS carry germline mutations of the androgen receptor (AR) that interfere with or ablate its function. As genital fibroblasts retain expression of the AR in vitro, we used genital skin fibroblasts from normal males and 46,XY females with complete AIS due to known AR mutations to gain insights into the role of the AR in human genital differentiation. Results Using DNA microarrays representing 32,968 different genes, we identified 404 transcripts with significant differences in transcription levels between genital skin fibroblasts cultured from normal and AIS-affected individuals. Gene-cluster analyses uncovered coordinated expression of genes involved in key processes of morphogenesis. On the basis of animal studies and human genetic syndromes, several of these genes are known to have specific roles in genital differentiation. Remarkably, genital fibroblasts from both normal and AIS-affected individuals showed no transcriptional response to dihydrotestosterone treatment despite expression of the AR. Conclusions The results suggest that in addition to differences in the anatomic origin of the cells, androgen signaling during prenatal development contributes to setting long-lasting, androgen-independent transcriptional programs in genital fibroblasts. Our findings have broad implications in understanding the establishment and the stability of sexual dimorphism in human genital development. PMID:12801411

  12. Unequal synthesis and differential degradation of propionyl CoA carboxylase subunits in cells from normal and propionic acidemia patients.

    PubMed Central

    Ohura, T; Kraus, J P; Rosenberg, L E

    1989-01-01

    We have characterized further the molecular basis of human inherited propionyl CoA carboxylase deficiency by measuring steady state levels of the mRNAs coding for the enzyme's two protein subunits (alpha and beta) and by estimating initial synthesis and steady state levels of the protein subunits in skin fibroblasts from controls and affected patients. We studied cell lines from both major complementation groups (pccA and pccBC) corresponding, respectively, to defects in the carboxylase's alpha and beta subunits. Analysis of pccA lines revealed the absence of alpha chain mRNA in three and an abnormally small alpha-mRNA in a fourth. Despite the presence of normal beta-mRNA in each of these pccA lines, there was complete absence of both alpha and beta protein subunits under steady state conditions, even though new synthesis and mitochondrial import of beta precursors was normal. Results in nine pccBC lines revealed normal alpha mRNA in each, while the amounts of beta-mRNA were distinctly reduced in every case. Correspondingly, alpha protein subunits were present in normal amounts at steady-state, but beta subunits were uniformly decreased. In addition, in six of the nine beta deficient cell lines, partially degraded beta-subunits were observed. To help interpret these results, synthesis and stability of carboxylase subunits were studied in intact HeLa cells using a pulse-chase protocol. Whereas alpha chains were stable over the four hour interval studied, beta chains--initially synthesized in large excess over alpha chains--were degraded rapidly reaching equivalence with alpha chains after two hours.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2741949

  13. Identification of Pro-Differentiation p53 Target Genes and Evaluation of Expression in Normal and Malignant Mammary Gland

    DTIC Science & Technology

    2008-04-01

    and Clark A.T. Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinoma . Cancer , 104...benign and malignant oral epithelial lesions. Int J Cancer , 87: 368-372, 2000 23. Pellegrini, G., Dellambra, E., Golisano, O., Martinelli, E., Fantozzi...p53 Target Genes and Evaluation of Expression in Normal and Malignant Mammary Gland PRINCIPAL INVESTIGATOR: Hua Li CONTRACTING

  14. CDK2 differentially controls normal cell senescence and cancer cell proliferation upon exposure to reactive oxygen species

    SciTech Connect

    Hwang, Chae Young; Lee, Seung-Min; Park, Sung Sup; Kwon, Ki-Sun

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer H{sub 2}O{sub 2} differently adjusted senescence and proliferation in normal and cancer cells. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} exposure transiently decreased PCNA levels in normal cells. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} exposure transiently increased CDK2 activity in cancer cells. Black-Right-Pointing-Pointer p21{sup Cip1} is likely dispensable when H{sub 2}O{sub 2} induces senescence in normal cells. Black-Right-Pointing-Pointer Suggestively, CDK2 and PCNA play critical roles in H{sub 2}O{sub 2}-induced cell fate decision. -- Abstract: Reactive oxygen species modulate cell fate in a context-dependent manner. Sublethal doses of H{sub 2}O{sub 2} decreased the level of proliferating cell nuclear antigen (PCNA) in normal cells (including primary human dermal fibroblasts and IMR-90 cells) without affecting cyclin-dependent kinase 2 (CDK2) activity, leading to cell cycle arrest and subsequent senescence. In contrast, exposure of cancer cells (such as HeLa and MCF7 cells) to H{sub 2}O{sub 2} increased CDK2 activity with no accompanying change in the PCNA level, leading to cell proliferation. A CDK2 inhibitor, CVT-313, prevented H{sub 2}O{sub 2}-induced cancer cell proliferation. These results support the notion that the cyclin/CDK2/p21{sup Cip1}/PCNA complex plays an important role as a regulator of cell fate decisions.

  15. Differential nuclear and cytoplasmic expression of PTEN in normal thyroid tissue, and benign and malignant epithelial thyroid tumors.

    PubMed

    Gimm, O; Perren, A; Weng, L P; Marsh, D J; Yeh, J J; Ziebold, U; Gil, E; Hinze, R; Delbridge, L; Lees, J A; Mutter, G L; Robinson, B G; Komminoth, P; Dralle, H; Eng, C

    2000-05-01

    Germline mutations in PTEN (MMAC1/TEP1) are found in patients with Cowden syndrome, a familial cancer syndrome which is characterized by a high risk of breast and thyroid neoplasia. Although somatic intragenic PTEN mutations have rarely been found in benign and malignant sporadic thyroid tumors, loss of heterozygosity (LOH) has been reported in up to one fourth of follicular thyroid adenomas (FAs) and carcinomas. In this study, we examined PTEN expression in 139 sporadic nonmedullary thyroid tumors (55 FA, 27 follicular thyroid carcinomas, 35 papillary thyroid carcinomas, and 22 undifferentiated thyroid carcinomas) using immunohistochemistry and correlated this to the results of LOH studies. Normal follicular thyroid cells showed a strong to moderate nuclear or nuclear membrane signal although the cytoplasmic staining was less strong. In FAs the neoplastic nuclei had less intense PTEN staining, although the cytoplasmic PTEN-staining intensity did not differ significantly from that observed in normal follicular cells. In thyroid carcinomas as a group, nuclear PTEN immunostaining was mostly weak in comparison with normal thyroid follicular cells and FAs. The cytoplasmic staining was more intense than the nuclear staining in 35 to 49% of carcinomas, depending on the histological type. Among 81 informative tumors assessed for LOH, there seemed to be an associative trend between decreased nuclear and cytoplasmic staining and 10q23 LOH (P = 0.003, P = 0.008, respectively). These data support a role for PTEN in the pathogenesis of follicular thyroid tumors.

  16. Selenoprotein Genes Exhibit Differential Expression Patterns Between Hepatoma HepG2 and Normal Hepatocytes LO2 Cell Lines.

    PubMed

    Zhao, Hua; Tang, Jiayong; Xu, Jingyang; Cao, Lei; Jia, Gang; Long, Dingbiao; Liu, Guangmang; Chen, Xiaoling; Wang, Kangning

    2015-10-01

    The purpose of this study was to compare messenger RNA (mRNA) expression of selenoprotein genes between hepatoma HepG2 and normal hepatocytes LO2 cell lines. Liver HepG2 and LO2 cells were cultured in 12-well plates under the same condition until cells grew to complete confluence, and then cells were harvested for total RNA and protein extraction. The qPCRs were performed to compare gene expression of 14 selenoprotein genes and 5 cancer signaling-related genes. Enzyme activities were also assayed. The results showed that human hepatoma HepG2 cells grew faster than normal hepatocytes LO2 cells. Among the genes investigated, 10 selenoprotein genes (Gpx1, Gpx3, Gpx4, Selx, Sepp, Sepw1, Sepn1, Selt, Seli, Selh) and 3 cancer signaling-related genes (Bcl-2A, caspase-3, and P38) were upregulated (P < 0.05), while Selo and Bcl-2B were downregulated (P < 0.05) in hepatoma HepG2 cells compared to LO2 cells. Significant correlations were found between selenoprotein genes and the cancer signaling-related genes Caspase3, P53, Bc1-2A, and Bc1-2B. Our results revealed that selenoprotein genes were aberrantly expressed in hepatoma HepG2 cells compared to normal liver LO2 cells, which indicated that those selenoprotein genes may play important roles in the occurrence and development of liver carcinogenesis.

  17. Lipidomic differentiation between human kidney tumors and surrounding normal tissues using HILIC-HPLC/ESI-MS and multivariate data analysis.

    PubMed

    Cífková, Eva; Holčapek, Michal; Lísa, Miroslav; Vrána, David; Melichar, Bohuslav; Študent, Vladimír

    2015-09-01

    The characterization of differences among polar lipid classes in tumors and surrounding normal tissues of 20 kidney cancer patients is performed by hydrophilic interaction liquid chromatography (HILIC) coupled to electrospray ionization mass spectrometry (ESI-MS). The detailed analysis of identified lipid classes using relative abundances of characteristic ions in negative- and positive-ion modes is used for the determination of more than 120 individual lipid species containing attached fatty acyls of different chain length and double bond number. Lipid species are described using relative abundances, providing a better visualization of lipidomic differences between tumor and normal tissues. The multivariate data analysis methods using unsupervised principal component analysis (PCA) and supervised orthogonal partial least square (OPLS) are used for the characterization of statistically significant differences in identified lipid species. Ten most significant up- and down-regulated lipids in OPLS score plots are also displayed by box plots. A notable increase of relative abundances of lipids containing four and more double bonds is detected in tumor compared to normal tissues.

  18. Mechanisms contributing to differential regulation of PAX3 downstream target genes in normal human epidermal melanocytes versus melanoma cells.

    PubMed

    Bartlett, Danielle; Boyle, Glen M; Ziman, Mel; Medic, Sandra

    2015-01-01

    Melanoma is a highly aggressive and drug resistant form of skin cancer. It arises from melanocytes, the pigment producing cells of the skin. The formation of these melanocytes is driven by the transcription factor PAX3 early during embryonic development. As a result of alternative splicing, the PAX3 gene gives rise to eight different transcripts which encode isoforms that have different structures and activate different downstream target genes involved in pathways of cell proliferation, migration, differentiation and survival. Furthermore, post-translational modifications have also been shown to alter the functions of PAX3. We previously identified PAX3 downstream target genes in melanocytes and melanoma cells. Here we assessed the effects of PAX3 down-regulation on this panel of target genes in primary melanocytes versus melanoma cells. We show that PAX3 differentially regulates various downstream target genes involved in cell proliferation in melanoma cells compared to melanocytes. To determine mechanisms behind this differential downstream target gene regulation, we performed immunoprecipitation to assess post-translational modifications of the PAX3 protein as well as RNAseq to determine PAX3 transcript expression profiles in melanocytes compared to melanoma cells. Although PAX3 was found to be post-translationally modified, there was no qualitative difference in phosphorylation and ubiquitination between melanocytes and melanoma cells, while acetylation of PAX3 was reduced in melanoma cells. Additionally, there were differences in PAX3 transcript expression profiles between melanocytes and melanoma cells. In particular the PAX3E transcript, responsible for reducing melanocyte proliferation and increasing apoptosis, was found to be down-regulated in melanoma cells compared to melanocytes. These results suggest that alternate transcript expression profiles activate different downstream target genes leading to the melanoma phenotype.

  19. [Ectopic Lippes' intrauterine devices. Hysterography].

    PubMed

    Villablanca, E

    1970-01-01

    Statistics on the indicence of ectopia (displacement) of Lippes loop vary significantly by author; from .5/1000 to 6.81/1000 insertions. It is not clear whether ectopia occurs as a result of uterine perforation or of progressive migration. In all reported cases, however, hysterography was used to investigate. 50 patients from a control group of 1064 active Lippes D users chosen from the Family Planning Center of the San Camilo Hospital in San Felipe were studied between 1965-1969. Observations were made using x-ray and hysterography at 10 days, 1 month, 3 months, 6 months, and 1 year or more after insertion. Also studied were some of the characteristics of the loop and techniques for its insertion. In the 50 patients the device was found to be out of place in 6 (an ectopia rate of 5.6/1000 insertions), in a normal position in 30, and in an abnormal one in 14 (the distal part near or across the neck). All the ectopia was observed in patients between 20-34 years who had had 2-5 births. Those with 7-13 births did not seem to be prone to the complication. 8 of the 50 had a retroflexed uterus and 2 of those were displacement cases, suggesting that anomaly of position could be a predisposition for ectopia. Incidence of displacement was not found to vary significantly with doctor. None of the ectopic cases had severe side effects (pain or heavy bleeding) after insertion. In each case displacement was found to have occurred between 1 week and 6 months postinsertion, 2 of them within 2 weeks. It is probably that the later diagnosis of the others was due to the patient not having noticed the disappearance of the threads. It is concluded that ectopia is due to uterine perforation and not to progressive migration. The different positions in which the device was found when it was removed by laparotomy indicated that such perforation was due to the structure of the device and the resistance of the uterine cavity. Through modification of the loop this complication could be

  20. Voltage-gated sodium channels were differentially expressed in human normal prostate, benign prostatic hyperplasia and prostate cancer cells.

    PubMed

    Shan, Bin; Dong, Mei; Tang, He; Wang, Na; Zhang, Jin; Yan, Changqing; Jiao, Xiaocui; Zhang, Hailin; Wang, Chuan

    2014-07-01

    Voltage-gated sodium channels (VGSCs) are expressed not only in excitable cells but also in numerous metastatic cells, particularly in certain types of cancer cells. In some types of cancer, including prostate cancer, the expression of VGSCs is associated with cancer migration, invasion and metastasis in vivo. However, the detailed expression profiles of VGSC α subunits in normal human prostate, in prostatic hyperplasia and prostatic cancer remain controversial. In the present study, quantitative polymerase chain reaction was used to systematically detect all subtypes of VGSC α subunits in normal human prostate, benign prostatic hyperplasia (BPH) and prostate cancer cells. The expression profile of VGSC α subunits was observed to differ between these cell types. Nav1.5 was the major isoform expressed in normal human prostate tissue, while Nav1.5 and Nav1.2 were the predominant isoforms in BPH tissue. However, in PC-3 and LNCaP cells, two typical prostate cancer cell lines, Nav1.6 and Nav1.7 were abundantly expressed. By comparing the relative expression levels of Nav1.5, Nav1.6 and Nav1.7 in these cells, the mRNA levels of Nav1.6 and Nav1.7 were identified to be 6- to 27-fold higher in PC-3 and LNCaP cells than in either normal or BPH samples (P<0.05); however, Nav1.5 mRNA levels were relatively lower compared with those of Nav1.6 or Nav1.7 in all cells analyzed. To confirm whether Nav1.6 and Nav1.7 expression in cancer cells was functional, a patch-clamp technique was used to record whole-cell currents. A tetrodotoxin-sensitive sodium current was successfully recorded in PC-3 cells, but not in LNCaP cells. It was concluded that although all types of VGSC α subunits exhibited low expression levels in normal prostate and BPH cells, both Nav1.6 and Nav1.7 were significantly upregulated in the prostate cancer cell lines, suggesting these subtypes may be potential diagnostic markers and therapeutic targets for certain types of prostate cancer in humans.

  1. Spatial differentiation of the intestinal epithelium: analysis of enteroendocrine cells containing immunoreactive serotonin, secretin, and substance P in normal and transgenic mice.

    PubMed Central

    Roth, K A; Gordon, J I

    1990-01-01

    The mammalian intestinal epithelium undergoes continuous and rapid renewal of its four principal terminally differentiated cell types. These cells arise from multipotent stem cells located at or near the base of the crypts of Lieberkühn. The differentiation process is precisely organized along two spatial dimensions (axes)--from the crypt to the villus tip and from the duodenum to the colon. The enteroendocrine cell population provides a sensitive marker of the intestine's topologic differentiation. At least 15 different regionally distributed subsets have been described based on their principal neuroendocrine products. We have used immunocytochemical methods to characterize the spatial relationships of the serotonin-, secretin-, and substance P-containing enteroendocrine cell subsets in normal adult C57BL/6J x LT/Sv mice as well as in transgenic littermates that contain rat liver fatty acid-binding protein-human growth hormone fusion genes. Our results reveal precise spatial interrelationships between these populations and suggest a differentiation pathway that may involve the sequential expression of substance P, serotonin, and secretin. Images PMID:1696730

  2. Keratin 8/18 regulation of glucose metabolism in normal versus cancerous hepatic cells through differential modulation of hexokinase status and insulin signaling

    SciTech Connect

    Mathew, Jasmin; Loranger, Anne; Gilbert, Stéphane; Faure, Robert; Marceau, Normand

    2013-02-15

    As differentiated cells, hepatocytes primarily metabolize glucose for ATP production through oxidative phosphorylation of glycolytic pyruvate, whereas proliferative hepatocellular carcinoma (HCC) cells undergo a metabolic shift to aerobic glycolysis despite oxygen availability. Keratins, the intermediate filament (IF) proteins of epithelial cells, are expressed as pairs in a lineage/differentiation manner. Hepatocyte and HCC (hepatoma) cell IFs are made solely of keratins 8/18 (K8/K18), thus providing models of choice to address K8/K18 IF functions in normal and cancerous epithelial cells. Here, we demonstrate distinctive increases in glucose uptake, glucose-6-phosphate formation, lactate release, and glycogen formation in K8/K18 IF-lacking hepatocytes and/or hepatoma cells versus their respective IF-containing counterparts. We also show that the K8/K18-dependent glucose uptake/G6P formation is linked to alterations in hexokinase I/II/IV content and localization at mitochondria, with little effect on GLUT1 status. In addition, we find that the insulin-stimulated glycogen formation in normal hepatocytes involves the main PI-3 kinase-dependent signaling pathway and that the K8/K18 IF loss makes them more efficient glycogen producers. In comparison, the higher insulin-dependent glycogen formation in K8/K18 IF-lacking hepatoma cells is associated with a signaling occurring through a mTOR-dependent pathway, along with an augmentation in cell proliferative activity. Together, the results uncover a key K8/K18 regulation of glucose metabolism in normal and cancerous hepatic cells through differential modulations of mitochondrial HK status and insulin-mediated signaling.

  3. [Double bladder lithiasis from an intrauterine device. Report one case].

    PubMed

    Iturralde Codina, Armando; Gozá León, Fernando; Beyríes Tamayo, Walfrido; Iturralde Muñoz, Yinet; Rodríguez Hidalgo, María Elena

    2004-03-01

    To report a new case of an intrauterine device causing bladder lithiasis, because of its rarity as a complication of the intrauterine device contraceptive method. 27-year-old female patient admitted in the urology department of the "Hospital Medico-quirurgico 10 de Octubre" who having an intrauterine device was pregnant, underwent a caesarean section, and a new intrauterine device implant, and a few months later presented with lower urinary tract infectious syndrome, being diagnosed of double bladder lithiasis secondary to intrauterine device migration, for which cystolithotomy was performed. We performed a short review of the bladder foreign bodies reported in the literature, and present this case which is very infrequent because of the finding of 2 stones in the bladder and an intrauterine device inside one of them. The intrauterine device was detected after crushing one of the calculi, 2 cm in size. It seems that first intrauterine device had migrated through the uterine wall into the bladder, creating a calcareous concretion around.

  4. Intrauterine Growth and Infant Temperamental Difficulties: The Generation R Study

    ERIC Educational Resources Information Center

    Roza, Sabine J.; Van Lier, Pol A. C.; Jaddoe, Vincent W. V.; Steegers, Eric A. P.; Moll, Henriette A.; Mackenbach, Johan P.; Hofman, Albert; Verhulst, Frank C.; Tiemeier, Henning

    2008-01-01

    The Generation R Study a population-based prospective cohort study from fetal life to young adulthood is conducted to explore the possibility of an association between infant temperament and intrauterine growth trajectories. Results concluded little indication of any association between infant temperament and intrauterine growth trajectories.

  5. 21 CFR 529.50 - Amikacin sulfate intrauterine solution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Amikacin sulfate intrauterine solution. 529.50 Section 529.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Amikacin sulfate intrauterine solution. (a) Specifications. Each milliliter of sterile aqueous...

  6. Intrauterine Growth and Infant Temperamental Difficulties: The Generation R Study

    ERIC Educational Resources Information Center

    Roza, Sabine J.; Van Lier, Pol A. C.; Jaddoe, Vincent W. V.; Steegers, Eric A. P.; Moll, Henriette A.; Mackenbach, Johan P.; Hofman, Albert; Verhulst, Frank C.; Tiemeier, Henning

    2008-01-01

    The Generation R Study a population-based prospective cohort study from fetal life to young adulthood is conducted to explore the possibility of an association between infant temperament and intrauterine growth trajectories. Results concluded little indication of any association between infant temperament and intrauterine growth trajectories.

  7. Atypical intrauterine parvo b19 infection.

    PubMed

    Drašković, Biljana; Uram-Benka, Anna; Fabri, Izabela; Velisavljev Filipović, Gordana

    2012-08-01

    Human parvovirus B19 is a single-stranded DNA virus. During pregnancy, parvovirus B19 infection can be asymptomatic or cause a variety of signs of fetal damage, fetal anemia, nonimmune hydrops fetalis, spontaneous abortion and can result in fetal death. Recent improvements in diagnosing parvovirus infections and the availability of intrauterine transfusion have reduced the overall rate of fetal loss after maternal exposure. There is an approximately 30% risk of vertical transmission and 1% of hydrops. We report of the first case of vertical parvovirus B19 infection with atypical manifestations in our clinic. The neonate had pleural effusion associated with anaemia.

  8. Emergence of the PI3-kinase pathway as a central modulator of normal and aberrant B cell differentiation.

    PubMed

    Baracho, G V; Miletic, A V; Omori, S A; Cato, M H; Rickert, R C

    2011-04-01

    Phosphoinositide 3-kinase (PI3K) defines a family of lipid kinases that direct a wide range of cellular processes and cell fate decisions. Since its discovery, and that of its enzymatic antagonist PTEN, much of the focus on PI3K has been on its oncogenic potential. In recent years, studies on PI3K signaling in B lymphocytes have established the importance of this pathway in effecting B cell differentiation and associated molecular events such as V(D)J recombination and class switch recombination. Intriguing new findings also indicate that there is specificity in the PI3K pathway in B cells, including preferential expression or usage of particular PI3K isoforms and counter-regulation by the PTEN and SHIP phosphatases. The role of PI3K adaptor proteins (CD19, BCAP, and TC21) has also undergone revision to reflect both shared and unique properties. The emergence of Foxo1 as a critical PI3K regulatory target for B cell differentiation has united membrane proximal regulatory events orchestrated by PI3K/PTEN/SHIP with key transcriptional targets. Insights into the regulation and impact of PI3K signaling have been brought to bear in new treatments for B cell malignancies, and will also be an important topic of consideration for B cell-dependent autoimmune diseases.

  9. Interleukin 22 early affects keratinocyte differentiation, but not proliferation, in a three-dimensional model of normal human skin.

    PubMed

    Donetti, Elena; Cornaghi, Laura; Arnaboldi, Francesca; Landoni, Federica; Romagnoli, Paolo; Mastroianni, Nicolino; Pescitelli, Leonardo; Baruffaldi Preis, Franz W; Prignano, Francesca

    2016-07-15

    Interleukin (IL)-22 is a pro-inflammatory cytokine driving the progression of the psoriatic lesion with other cytokines, as Tumor Necrosis Factor (TNF)-alpha and IL-17. Our study was aimed at evaluating the early effect of IL-22 alone or in combination with TNF-alpha and IL-17 by immunofluorescence on i) keratinocyte (KC) proliferation, ii) terminal differentiation biomarkers as keratin (K) 10 and 17 expression, iii) intercellular junctions. Transmission electron microscopy (TEM) analysis was performed. A model of human skin culture reproducing a psoriatic microenvironment was used. Plastic surgery explants were obtained from healthy young women (n=7) after informed consent. Fragments were divided before adding IL-22 or a combination of the three cytokines, and harvested 24 (T24), 48 (T48), and 72 (T72)h later. From T24, in IL-22 samples we detected a progressive decrease in K10 immunostaining in the spinous layer paralleled by K17 induction. By TEM, after IL-22 incubation, keratin aggregates were evident in the perinuclear area. Occludin immunostaining was not homogeneously distributed. Conversely, KC proliferation was not inhibited by IL-22 alone, but only by the combination of cytokines. Our results suggest that IL-22 affects keratinocyte terminal differentiation, whereas, in order to induce a proliferation impairment, a more complex psoriatic-like microenvironment is needed. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Sp1 Upregulates cAMP Response Element-Binding Protein Expression During Retinoic Acid-Induced Mucous Differentiation of Normal Human Bronchial Epithelial Cells

    PubMed Central

    Hong, Jeong Soo; Kim, Seung-Wook; Koo, Ja Seok

    2010-01-01

    Cyclic 3′,5′-adenosine monophosphate (cAMP) response-element (CRE) binding protein (CREB) is an important transcription factor that is differentially regulated in cells of various types. We recently reported that RA rapidly activates CREB without using retinoic acid (RA) receptors RAR and RXR in normal human tracheobronchial epithelial (NHTBE) cells. However, little is known about RA’s role in the physiologic regulation of CREB expression in the early mucous differentiation of NHTBE cells. Here, we report that RA upregulated CREB gene expression and that using 5′-serial deletion promoter analysis and mutagenesis analyses, two Sp1-binding sites located at nucleotides −217 and −150, which flank the transcription initiation site, were essential for RA induction of CREB gene transcription. Furthermore, we found that CREs located at nucleotides −119 and −98 contributed to basal promoter activity. Interestingly, RA also upregulated Sp1 in a time- and dose-dependent manner. Knockdown of endogenous Sp1 using small interfering RNA (siRNA) decreased RA-induced CREB gene expression. However, the converse was not true: knockdown of CREB using CREB siRNA did not affect RA-induced Sp1 gene expression. We conclude that RA upregulates CREB gene expression during the early stage of NHTBE cell differentiation and that RA-inducible Sp1 plays a major role in upregulating human CREB gene expression. This result implies that cooperation of these two transcription factors play a crucial role in mediating early events of normal mucous cell differentiation of bronchial epithelial cells. PMID:17937658

  11. Differential expression of utrophin-A and -B promoters in the central nervous system (CNS) of normal and dystrophic mdx mice.

    PubMed

    Baby, Santhosh M; Bogdanovich, Sasha; Willmann, Gabriel; Basu, Utpal; Lozynska, Olga; Khurana, Tejvir S

    2010-03-01

    Utrophin (Utrn) is the autosomal homolog of dystrophin, the Duchene Muscular Dystrophy (DMD) locus product and of therapeutic interest, as its overexpression can compensate dystrophin's absence. Utrn is transcribed by Utrn-A and -B promoters with mRNAs differing at their 5' ends. However, previous central nervous system (CNS) studies used C-terminal antibodies recognizing both isoforms. As this distinction may impact upregulation strategies, we generated Utrn-A and -B promoter-specific antibodies, Taqman Polymerase chain reaction (PCR)-based absolute copy number assays, and luciferase-reporter constructs to study CNS of normal and dystrophic mdx mice. Differential expression of Utrn-A and -B was noted in microdissected and capillary-enriched fractions. At the protein level, Utrn-B was predominantly expressed in vasculature and ependymal lining, whereas Utrn-A was expressed in neurons, astrocytes, choroid plexus and pia mater. mRNA quantification demonstrated matching patterns of differential expression; however, transcription-translation mismatch was noted for Utrn-B in caudal brain regions. Utrn-A and Utrn-B proteins were significantly upregulated in olfactory bulb and cerebellum of mdx brain. Differential promoter activity, mRNA and protein expressions were studied in cultured C2C12, bEnd3, neurons and astrocytes. Promoter activity ranking for Utrn-A and -B was neurons > astrocytes > C2C12 > bEnd3 and bEnd3 > astrocytes > neurons > C2C12, respectively. Our results identify promoter usage patterns for therapeutic targeting and define promoter-specific differential distribution of Utrn isoforms in normal and dystrophic CNS.

  12. Inhibitor of DNA Binding 4 (ID4) Is Highly Expressed in Human Melanoma Tissues and May Function to Restrict Normal Differentiation of Melanoma Cells

    PubMed Central

    Peretz, Yuval; Wu, Hong; Patel, Shayan; Bellacosa, Alfonso; Katz, Richard A.

    2015-01-01

    Melanoma tissues and cell lines are heterogeneous, and include cells with invasive, proliferative, stem cell-like, and differentiated properties. Such heterogeneity likely contributes to the aggressiveness of the disease and resistance to therapy. One model suggests that heterogeneity arises from rare cancer stem cells (CSCs) that produce distinct cancer cell lineages. Another model suggests that heterogeneity arises through reversible cellular plasticity, or phenotype-switching. Recent work indicates that phenotype-switching may include the ability of cancer cells to dedifferentiate to a stem cell-like state. We set out to investigate the phenotype-switching capabilities of melanoma cells, and used unbiased methods to identify genes that may control such switching. We developed a system to reversibly synchronize melanoma cells between 2D-monolayer and 3D-stem cell-like growth states. Melanoma cells maintained in the stem cell-like state showed a striking upregulation of a gene set related to development and neural stem cell biology, which included SRY-box 2 (SOX2) and Inhibitor of DNA Binding 4 (ID4). A gene set related to cancer cell motility and invasiveness was concomitantly downregulated. Intense and pervasive ID4 protein expression was detected in human melanoma tissue samples, suggesting disease relevance for this protein. SiRNA knockdown of ID4 inhibited switching from monolayer to 3D-stem cell-like growth, and instead promoted switching to a highly differentiated, neuronal-like morphology. We suggest that ID4 is upregulated in melanoma as part of a stem cell-like program that facilitates further adaptive plasticity. ID4 may contribute to disease by preventing stem cell-like melanoma cells from progressing to a normal differentiated state. This interpretation is guided by the known role of ID4 as a differentiation inhibitor during normal development. The melanoma stem cell-like state may be protected by factors such as ID4, thereby potentially identifying a

  13. A differential role for CXCR4 in the regulation of normal versus malignant breast stem cell activity

    PubMed Central

    Ablett, Matthew P.; O'Brien, Ciara S.; Sims, Andrew H.; Farnie, Gillian; Clarke, Robert B.

    2014-01-01

    C-X-C chemokine receptor type 4 (CXCR4) is known to regulate lung, pancreatic and prostate cancer stem cells. In breast cancer, CXCR4 signalling has been reported to be a mediator of metastasis, and is linked to poor prognosis. However its role in normal and malignant breast stem cell function has not been investigated. Anoikis resistant (AR) cells were collected from immortalised (MCF10A, 226L) and malignant (MCF7, T47D, SKBR3) breast cell lines and assessed for stem cell enrichment versus unsorted cells. AR cells had significantly higher mammosphere forming efficiency (MFE) than unsorted cells. The AR normal cells demonstrated increased formation of 3D structures in Matrigel compared to unsorted cells. In vivo, SKBR3 and T47D AR cells had 7- and 130-fold enrichments for tumour formation respectively, compared with unsorted cells. AR cells contained significantly elevated CXCR4 transcript and protein levels compared to unsorted cells. Importantly, CXCR4 mRNA was higher in stem cell-enriched CD44+ /CD24− - patient-derived breast cancer cells compared to non-enriched cells. CXCR4 stimulation by its ligand SDF-1 reduced MFE of the normal breast cells lines but increased the MFE in T47D and patient-derived breast cancer cells. CXCR4 inhibition by AMD3100 increased stem cell activity but reduced the self-renewal capacity of the malignant breast cell line T47D. CXCR4 + FACS sorted MCF7 cells demonstrated a significantly increased MFE compared with CXCR4- cells. This significant increase in MFE was further demonstrated in CXCR4 over-expressing MCF7 cells which also had an increase in self-renewal compared to parental cells. A greater reduction in self-renewal following CXCR4 inhibition in the CXCR4 over-expressing cells compared with parental cells was also observed. Our data establish for the first time that CXCR4 signalling has contrasting effects on normal and malignant breast stem cell activity. Here, we demonstrate that CXCR4 signalling specifically regulates

  14. Mild intrauterine hypoperfusion reproduces neurodevelopmental disorders observed in prematurity

    PubMed Central

    Ohshima, Makiko; Coq, Jacques-Olivier; Otani, Kentaro; Hattori, Yorito; Ogawa, Yuko; Sato, Yoshiaki; Harada-Shiba, Mariko; Ihara, Masafumi; Tsuji, Masahiro

    2016-01-01

    Severe intrauterine ischemia is detrimental to the developing brain. The impact of mild intrauterine hypoperfusion on neurological development, however, is still unclear. We induced mild intrauterine hypoperfusion in rats on embryonic day 17 via arterial stenosis with metal microcoils wrapped around the uterine and ovarian arteries. All pups were born with significantly decreased birth weights. Decreased gray and white matter areas were observed without obvious tissue damage. Pups presented delayed newborn reflexes, muscle weakness, and altered spontaneous activity. The levels of proteins indicative of inflammation and stress in the vasculature, i.e., RANTES, vWF, VEGF, and adiponectin, were upregulated in the placenta. The levels of mRNA for proteins associated with axon and astrocyte development were downregulated in fetal brains. The present study demonstrates that even mild intrauterine hypoperfusion can alter neurological development, which mimics the clinical signs and symptoms of children with neurodevelopmental disorders born prematurely or with intrauterine growth restriction. PMID:27996031

  15. An Effective Technique for Enhancing an Intrauterine Catheter Fetal Electrocardiogram

    NASA Astrophysics Data System (ADS)

    Horner, Steven L.; Holls, William M.

    2003-12-01

    Physician can obtain fetal heart rate, electrophysiological information, and uterine contraction activity for determining fetal status from an intrauterine catheters electrocardiogram with the maternal electrocardiogram canceled. In addition, the intrauterine catheter would allow physicians to acquire fetal status with one non-invasive to the fetus biosensor as compared to invasive to the fetus scalp electrode and intrauterine pressure catheter used currently. A real-time maternal electrocardiogram cancellation technique of the intrauterine catheters electrocardiogram will be discussed along with an analysis for the methods effectiveness with synthesized and clinical data. The positive results from an original detailed subjective and objective analysis of synthesized and clinical data clearly indicate that the maternal electrocardiogram cancellation method was found to be effective. The resulting intrauterine catheters electrocardiogram from effectively canceling the maternal electrocardiogram could be used for determining fetal heart rate, fetal electrocardiogram electrophysiological information, and uterine contraction activity.

  16. Differential sensitivity of a mouse myeloid leukemia cell line and normal mouse bone marrow cells to X-ray-induced chromosome aberrations

    SciTech Connect

    Aardema, M.J.; Au, W.W.; Hand, R.E. Jr.; Preston, R.J.

    1985-11-01

    Cell line ML-1 was established from a myelogenous leukemia of an RFM mouse. The ML-1 cells and in vitro normal mouse bone marrow cells were analyzed to determine if there was a differential sensitivity to X-ray-induced chromosome aberrations in G1 cells and/or differences in postirradiation cell cycle progression. Cells identified as being in G1 at the time of irradiation by their staining pattern after replication in 5-bromodeoxyuridine were analyzed for all types of chromosomal aberrations following X-ray doses of 0.5, 1.0, 1.5, and 2.0 Gy. ML-1 cells showed a greater sensitivity to the induction of both chromosome-type aberrations and chromatid-type aberrations compared to normal mouse bone marrow cells, which only contained chromosome-type aberrations. The presence of chromatid-type aberrations in the ML-1 cells and not normal bone marrow cells suggested a differential progression through the cell cycle for the two cell types after irradiation. Mitotic index and flow cytometric analyses were performed and showed that both cell types have a delay in progression from G2 into mitosis, but only the normal mouse bone marrow cells have a delay in progression from G1 into S, as well as delayed progression through the S phase following X-irradiation. These results indicate that the ML-1 leukemia cells have an increased radiosensitivity. These same characteristics have been observed in ataxia telangiectasia cells and may well represent a general feature of cells with increased radiosensitivity.

  17. Differentiation of ICOS+ and ICOS- recent thymic emigrant regulatory T cells (RTE T regs) during normal pregnancy, pre-eclampsia and HELLP syndrome.

    PubMed

    Wagner, M I; Jöst, M; Spratte, J; Schaier, M; Mahnke, K; Meuer, S; Zeier, M; Steinborn, A

    2016-01-01

    Two different subsets of naturally occurring regulatory T cells (nTregs), defined by their expression of the inducible co-stimulatory (ICOS) molecule, are produced by the human thymus. To examine the differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(+) recent thymic emigrant (RTE) T regs during normal pregnancy and in the presence of pre-eclampsia or haemolysis elevated liver enzymes low platelet (HELLP)-syndrome, we used six-colour flow cytometric analysis to determine the changes in the composition of the ICOS(+) and ICOS(-) T reg pools with CD45RA(+) CD31(+) RTE T regs, CD45RA(+) CD31(-) mature naive (MN) T regs, CD45RA(-) CD31(+) and CD45RA(-) CD31(-) memory Tregs. With the beginning of pregnancy until term, we observed a strong differentiation of both ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE, but not CD45RA(+) CD31(-) MN T regs, into CD45RA(-) CD31(-) memory T regs. At the end of pregnancy, the onset of spontaneous term labour was associated with a significant breakdown of ICOS(+) CD45RA(-) CD31(-) memory T regs. However, in the presence of pre-eclampsia, there was a significantly increased differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE T regs into CD45RA(-) CD31(+) memory T regs, wherein the lacking differentiation into CD45RA(-) CD31(-) memory T regs was partially replaced by the increased differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(-) MN Tregs into CD45RA(-) CD31(-) memory T regs. In patients with HELLP syndrome, this alternatively increased differentiation of CD45RA(-) CD31(-) MN T regs seemed to be exaggerated, and presumably restored the suppressive activity of magnetically isolated ICOS(+) and ICOS(-) T regs, which were shown to be significantly less suppressive in pre-eclampsia patients, but not in HELLP syndrome patients. Hence, our findings propose that the regular differentiation of both ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE T regs ensures a healthy pregnancy course, while their disturbed differentiation is

  18. Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion

    PubMed Central

    Sokolova, Maria; Turunen, Mikko; Mortusewicz, Oliver; Björklund, Mikael; Taipale, Minna; Helleday, Thomas; Taipale, Jussi

    2017-01-01

    ABSTRACT To identify cell cycle regulators that enable cancer cells to replicate DNA and divide in an unrestricted manner, we performed a parallel genome-wide RNAi screen in normal and cancer cell lines. In addition to many shared regulators, we found that tumor and normal cells are differentially sensitive to loss of the histone genes transcriptional regulator CASP8AP2. In cancer cells, loss of CASP8AP2 leads to a failure to synthesize sufficient amount of histones in the S-phase of the cell cycle, resulting in slowing of individual replication forks. Despite this, DNA replication fails to arrest, and tumor cells progress in an elongated S-phase that lasts several days, finally resulting in death of most of the affected cells. In contrast, depletion of CASP8AP2 in normal cells triggers a response that arrests viable cells in S-phase. The arrest is dependent on p53, and preceded by accumulation of markers of DNA damage, indicating that nucleosome depletion is sensed in normal cells via a DNA-damage -like response that is defective in tumor cells. PMID:27929715

  19. Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion.

    PubMed

    Sokolova, Maria; Turunen, Mikko; Mortusewicz, Oliver; Kivioja, Teemu; Herr, Patrick; Vähärautio, Anna; Björklund, Mikael; Taipale, Minna; Helleday, Thomas; Taipale, Jussi

    2017-01-17

    To identify cell cycle regulators that enable cancer cells to replicate DNA and divide in an unrestricted manner, we performed a parallel genome-wide RNAi screen in normal and cancer cell lines. In addition to many shared regulators, we found that tumor and normal cells are differentially sensitive to loss of the histone genes transcriptional regulator CASP8AP2. In cancer cells, loss of CASP8AP2 leads to a failure to synthesize sufficient amount of histones in the S-phase of the cell cycle, resulting in slowing of individual replication forks. Despite this, DNA replication fails to arrest, and tumor cells progress in an elongated S-phase that lasts several days, finally resulting in death of most of the affected cells. In contrast, depletion of CASP8AP2 in normal cells triggers a response that arrests viable cells in S-phase. The arrest is dependent on p53, and preceded by accumulation of markers of DNA damage, indicating that nucleosome depletion is sensed in normal cells via a DNA-damage -like response that is defective in tumor cells.

  20. Differential expression of protease-activated receptors-1 and -2 in stromal fibroblasts of normal, benign, and malignant human tissues.

    PubMed

    D'Andrea, M R; Derian, C K; Santulli, R J; Andrade-Gordon, P

    2001-06-01

    The serine proteases thrombin and trypsin are among many factors that malignant cells secrete into the extracellular space to mediate metastatic processes such as cellular invasion, extracellular matrix degradation, angiogenesis, and tissue remodeling. The degree of protease secretion from malignant cells has been correlated to their metastatic potential. Protease activated receptors (PAR)-1 and -2, which are activated by thrombin and trypsin respectively, have not been extensively characterized in human tumors in situ. We investigated the presence of PAR-1 and PAR-2 in human normal, benign and malignant tissues using immunohistochemistry and in situ hybridization. Our results demonstrate PAR-1 and PAR-2 expression in the tumor cells, mast cells, macrophages, endothelial cells, and vascular smooth muscle cells of the metastatic tumor microenvironment. Most notably, an up-regulation of PAR-1 and PAR-2 observed in proliferating, smooth muscle actin (SMA)-positive stromal fibroblasts surrounding the carcinoma cells was not observed in normal or benign conditions. Furthermore, in vitro studies using proliferating, SMA-positive, human dermal fibroblasts, and scrape-wounded human dermal fibroblasts demonstrated the presence of PAR-1 and PAR-2 not detected in quiescent, SMA-negative cultures. PAR-1 and PAR-2 in the cells forming the tumor microenvironment suggest that these receptors mediate the signaling of secreted thrombin and trypsin in the processes of cellular metastasis.

  1. Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice.

    PubMed

    Favaudon, Vincent; Caplier, Laura; Monceau, Virginie; Pouzoulet, Frédéric; Sayarath, Mano; Fouillade, Charles; Poupon, Marie-France; Brito, Isabel; Hupé, Philippe; Bourhis, Jean; Hall, Janet; Fontaine, Jean-Jacques; Vozenin, Marie-Catherine

    2014-07-16

    In vitro studies suggested that sub-millisecond pulses of radiation elicit less genomic instability than continuous, protracted irradiation at the same total dose. To determine the potential of ultrahigh dose-rate irradiation in radiotherapy, we investigated lung fibrogenesis in C57BL/6J mice exposed either to short pulses (≤ 500 ms) of radiation delivered at ultrahigh dose rate (≥ 40 Gy/s, FLASH) or to conventional dose-rate irradiation (≤ 0.03 Gy/s, CONV) in single doses. The growth of human HBCx-12A and HEp-2 tumor xenografts in nude mice and syngeneic TC-1 Luc(+) orthotopic lung tumors in C57BL/6J mice was monitored under similar radiation conditions. CONV (15 Gy) triggered lung fibrosis associated with activation of the TGF-β (transforming growth factor-β) cascade, whereas no complications developed after doses of FLASH below 20 Gy for more than 36 weeks after irradiation. FLASH irradiation also spared normal smooth muscle and epithelial cells from acute radiation-induced apoptosis, which could be reinduced by administration of systemic TNF-α (tumor necrosis factor-α) before irradiation. In contrast, FLASH was as efficient as CONV in the repression of tumor growth. Together, these results suggest that FLASH radiotherapy might allow complete eradication of lung tumors and reduce the occurrence and severity of early and late complications affecting normal tissue.

  2. Differentiation of isomeric N-glycan structures by normal-phase liquid chromatography-MALDI-TOF/TOF tandem mass spectrometry.

    PubMed

    Maslen, Sarah; Sadowski, Pawel; Adam, Alex; Lilley, Kathryn; Stephens, Elaine

    2006-12-15

    The detailed characterization of protein N-glycosylation is very demanding given the many different glycoforms and structural isomers that can exist on glycoproteins. Here we report a fast and sensitive method for the extensive structure elucidation of reducing-end labeled N-glycan mixtures using a combination of capillary normal-phase HPLC coupled off-line to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and TOF/TOF-MS/MS. Using this method, isobaric N-glycans released from honey bee phospholipase A2 and Arabidopsis thaliana glycoproteins were separated by normal-phase chromatography and subsequently identified by key fragment ions in the MALDI-TOF/TOF tandem mass spectra. In addition, linkage and branching information were provided by abundant cross-ring and "elimination" fragment ions in the MALDI-CID spectra that gave extensive structural information. Furthermore, the fragmentation characteristics of N-glycans reductively aminated with 2-aminobenzoic acid and 2-aminobenzamide were compared. The identification of N-glycans containing 3-linked core fucose was facilitated by distinctive ions present only in the MALDI-CID spectra of 2-aminobenzoic acid-labeled oligosaccharides. To our knowledge, this is the first MS/MS-based technique that allows confident identification of N-glycans containing 3-linked core fucose, which is a major allergenic determinant on insect and plant glycoproteins.

  3. Differential effects of approach bias and eating style on unhealthy food consumption in overweight and normal weight women.

    PubMed

    Kakoschke, Naomi; Kemps, Eva; Tiggemann, Marika

    2017-05-22

    The current study aimed to examine the effects of approach bias for unhealthy food and trait eating style on consumption of unhealthy food in overweight and normal weight individuals. Participants were 245 undergraduate women aged 17 - 26 years. They completed an Approach-Avoidance Task, the Dutch Eating Behaviour Questionnaire (to assess restrained, emotional, and external eating), and a taste test to measure consumption of unhealthy food. An external eating style predicted increased consumption of unhealthy food. Among overweight participants, external and emotional eating style individually moderated the relationship between approach bias for unhealthy food and subsequent consumption. Specifically, approach bias was positively related to consumption in high external and emotional eaters, but negatively related to consumption in low emotional eaters. These interactions were not observed among normal weight participants. Practically, the results suggest that overweight individuals who are external or emotional eaters may benefit from interventions that aim to modify approach bias towards unhealthy food cues to reduce problematic eating behaviour.

  4. The canonical NF-κB pathway differentially protects normal and human tumor cells from ROS-induced DNA damage

    PubMed Central

    Sfikas, Alexandros; Batsi, Christina; Tselikou, Evangelia; Vartholomatos, George; Monokrousos, Nikolaos; Pappas, Periklis; Christoforidis, Savvas; Tzavaras, Theodoros; Kanavaros, Panagiotis; Gorgoulis, Vassilis G.; Marcu, Kenneth B.; Kolettas, Evangelos

    2012-01-01

    DNA damage responses (DDR) invoke senescence or apoptosis depending on stimulus intensity and the degree of activation of the p53-p21Cip1/Waf1 axis; but the functional impact of NF-κB signaling on these different outcomes in normal vs. human cancer cells remains poorly understood. We investigated the NF-κB-dependent effects and mechanism underlying reactive oxygen species (ROS)-mediated DDR outcomes of normal human lung fibroblasts (HDFs) and A549 human lung cancer epithelial cells. To activate DDR, ROS accumulation was induced by different doses of H2O2. The effect of ROS induction caused the G2-M phase cell cycle arrest of both human cell types. However, ROS-mediated DDR eventually culminated in different end points with HDFs undergoing premature senescence and A549 cancer cells succumbing to apoptosis. NF-κB p65/RelA nuclear translocation and Ser536 phosphorylation were induced in response to H2O2-mediated ROS accumulation. Importantly, blocking the activities of canonical NF-κB subunits with an IκBα super-repressor or suppressing canonical NF-κB signaling by IKKβ knock-down accelerated HDF premature senescence by up-regulating the p53-p21Cip1/Waf1 axis; but inhibiting the canonical NF-κB pathway exacerbated H2O2-induced A549 cell apoptosis. HDF premature ageing occurred in conjunction with γ-H2AX chromatin deposition, senescence-associated heterochromatic foci and beta-galactosidase staining. P53 knock-down abrogated H2O2-induced premature senescence of vector control- and IκBαSR-expressing HDFs functionally linking canonical NF-κB-dependent control of p53 levels to ROS-induced HDF senescence. We conclude that IKKβ-driven canonical NF-κB signaling has different functional roles for the outcome of ROS responses in the contexts of normal vs. human tumor cells by respectively protecting them against DDR-dependent premature senescence and apoptosis. PMID:22750558

  5. Cerebrospinal fluid and blood flow in mild cognitive impairment and Alzheimer's disease: a differential diagnosis from idiopathic normal pressure hydrocephalus

    PubMed Central

    2011-01-01

    Background Phase-contrast magnetic resonance imaging (PC-MRI) enables quantification of cerebrospinal fluid (CSF) flow and total cerebral blood (tCBF) flow and may be of value for the etiological diagnosis of neurodegenerative diseases. This investigation aimed to study CSF flow and intracerebral vascular flow in patients with Alzheimer's disease (AD) and patients with amnesic mild cognitive impairment (a-MCI) and to compare the results with patients with idiopathic normal pressure hydrocephalus (NPH) and with healthy elderly volunteers (HEV). Methods Ten a-MCI and 9 mild AD patients were identified in a comprehensive neurological and neuropsychological assessment. They underwent brain MRI; PC-MRI pulse sequence was performed with the following parameters: two views per segment; flip angle: 25° for vascular flow and 20° for CSF flow; field-of-view (FOV): 14 × 14 mm²; matrix: 256 × 128; slice thickness: 5 mm; with one excitation for exams on the 3 T machine, and 2 excitations for the 1.5 T machine exams. Velocity (encoding) sensitization was set to 80 cm/s for the vessels at the cervical level, 10 or 20 cm/s for the aqueduct and 5 cm/s for the cervical subarachnoid space (SAS). Dynamic flow images were analyzed with in-house processing software. The patients' results were compared with those obtained for HEVs (n = 12), and for NPH patients (n = 13), using multivariate analysis. Results Arterial tCBF and the calculated pulsatility index were significantly greater in a-MCI patients than in HEVs. In contrast, vascular parameters were lower in NPH patients. Cervical CSF flow analysis yielded similar values for all four populations. Aqueductal CSF stroke volumes (in μl per cardiac cycle) were similar in HEVs (34 ± 17) and AD patients (39 ± 18). In contrast, the aqueductal CSF was hyperdynamic in a-MCI patients (73 ± 33) and even more so in NPH patients (167 ± 89). Conclusion Our preliminary data show that a-MCI patients present with high systolic arterial peak

  6. Differentiating the two main histologic categories of fibroadenoma tissue from normal breast tissue by using multiphoton microscopy.

    PubMed

    Nie, Y T; Wu, Y; Fu, F M; Lian, Y E; Zhuo, S M; Wang, C; Chen, J X

    2015-04-01

    Multiphoton microscopy has become a novel biological imaging technique that allows cellular and subcellular microstructure imaging based on two-photon excited fluorescence and second harmonic generation. In this work, we used multiphoton microscopy to obtain the high-contrast images of human normal breast tissue and two main histologic types of fibroadenoma (intracanalicular, pericanalicular). Moreover, quantitative image analysis was performed to characterize the changes of collagen morphology (collagen content, collagen orientation). The results show that multiphoton microscopy combined with quantitative method has the ability to identify the characteristics of fibroadenoma including changes of the duct architecture and collagen morphology in stroma. With the advancement of multiphoton microscopy, we believe that the technique has great potential to be a real-time histopathological diagnostic tool for intraoperative detection of fibroadenoma in the future.

  7. NOTE: Arterio-venous flow between monochorionic twins determined during intra-uterine transfusion

    NASA Astrophysics Data System (ADS)

    van Gemert, Martin J. C.; van den Wijngaard, Jeroen P. H. M.; Lopriore, Enrico; Pasman, Suzanne A.; Vandenbussche, Frank P. H. A.

    2008-04-01

    Twin-twin transfusion syndrome (TTTS) is a severe complication of monozygotic (identical) twin fetuses sharing one single (monochorionic) placenta. TTTS is caused by a net inter-twin transfusion of blood through placental anastomoses, from one twin (the donor) to the other (the recipient), which link the two feto-placental circulations. Currently, the only reliable method to measure the net inter-twin transfusion clinically is when incomplete laser therapy of TTTS occurs and one of the twins becomes anemic and requires an intra-uterine transfusion of adult red blood cells. Then, differences between adult hemoglobin concentrations measured during the transfusion and at birth relate not only to the net inter-twin transfusion but also to the finite lifetime of the adult red blood cells. We have analyzed this situation, derived the differential equations of adult hemoglobin in the donor and recipient twins, given the solutions and given expressions relating the net inter-twin flow with clinically measured parameters. We have included single and multiple intra-uterine transfusions. In conclusion, because incomplete laser therapy occurs frequently, and some cases require an intra-uterine transfusion, this method may allow collecting a wealth of net inter-twin flow data from clinicians involved in laser therapy of TTTS. To aid to the widespread use of this method, we have presented the equations as clearly as possible in tables for easy use by others.

  8. Respiratory Syncytial Virus Inhibits Ciliagenesis in Differentiated Normal Human Bronchial Epithelial Cells: Effectiveness of N-Acetylcysteine

    PubMed Central

    Mata, Manuel; Sarrion, Irene; Armengot, Miguel; Carda, Carmen; Martinez, Isidoro; Melero, Jose A.; Cortijo, Julio

    2012-01-01

    Persistent respiratory syncytial virus (RSV) infections have been associated with the exacerbation of chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). This virus infects the respiratory epithelium, leading to chronic inflammation, and induces the release of mucins and the loss of cilia activity, two factors that determine mucus clearance and the increase in sputum volume. These alterations involve reactive oxygen species-dependent mechanisms. The antioxidant N-acetylcysteine (NAC) has proven useful in the management of COPD, reducing symptoms, exacerbations, and accelerated lung function decline. NAC inhibits RSV infection and mucin release in human A549 cells. The main objective of this study was to analyze the effects of NAC in modulating ciliary activity, ciliagenesis, and metaplasia in primary normal human bronchial epithelial cell (NHBEC) cultures infected with RSV. Our results indicated that RSV induced ultrastructural abnormalities in axonemal basal bodies and decreased the expression of β-tubulin as well as two genes involved in ciliagenesis, FOXJ1 and DNAI2. These alterations led to a decrease in ciliary activity. Furthermore, RSV induced metaplastic changes to the epithelium and increased the number of goblet cells and the expression of MUC5AC and GOB5. NAC restored the normal functions of the epithelium, inhibiting ICAM1 expression, subsequent RSV infection through mechanisms involving nuclear receptor factor 2, and the expression of heme oxygenase 1, which correlated with the restoration of the antioxidant capacity, the intracellular H2O2 levels and glutathione content of NHBECs. The results presented in this study support the therapeutic use of NAC for the management of chronic respiratory diseases, including COPD. PMID:23118923

  9. Differential growth factor regulation of N-cadherin expression and motility in normal and malignant oral epithelium.

    PubMed

    Diamond, Michelle E; Sun, Limin; Ottaviano, Adam J; Joseph, Mathew J; Munshi, Hidayatullah G

    2008-07-01

    Aberrant expression of N-cadherin is associated with tumor progression in squamous cell carcinomas (SCCs). Consequently, we examined the regulation of N-cadherin by TGFbeta1, an important mediator of keratinocyte and SCC function. N-cadherin expression was increased in oral SCC (OSCC) cell lines, regulating motility and correlating with TGFbeta1 production. Moreover, in normal keratinocytes TGFbeta1 increased expression of N-cadherin to regulate motility. TGFbeta1-mediated N-cadherin expression in the oral keratinocytes was blocked using siRNA targeting Smads. Unexpectedly, we found that EGF blocked TGFbeta1-mediated N-cadherin expression in oral keratinocytes and not in OSCC cells. Mechanistically, EGF enhanced Smad phosphorylation in the linker region, and attenuated TGFbeta1-mediated phosphorylation of Smad at the C-terminus, localization of Smad to the nucleus as well as Smad-driven promoter activity exclusively in oral keratinocytes but not in OSCC cells. The effect of EGF on TGFbeta1-mediated Smad-driven promoter activity and N-cadherin expression was reversed when activation of ERK1/2 was blocked. Although EGF and TGFbeta1 independently promoted migration of both oral keratinocytes and OSCC cells, EGF decreased TGFbeta1-mediated migration of oral keratinocytes but enhanced migration of OSCC cells. Together, these data support a model wherein EGF signaling has an important negative regulatory role on TGFbeta1-mediated N-cadherin expression and motility in normal oral keratinocytes, and in which loss of this regulatory mechanism accompanies malignant transformation of the oral epithelium.

  10. Respiratory syncytial virus inhibits ciliagenesis in differentiated normal human bronchial epithelial cells: effectiveness of N-acetylcysteine.

    PubMed

    Mata, Manuel; Sarrion, Irene; Armengot, Miguel; Carda, Carmen; Martinez, Isidoro; Melero, Jose A; Cortijo, Julio

    2012-01-01

    Persistent respiratory syncytial virus (RSV) infections have been associated with the exacerbation of chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). This virus infects the respiratory epithelium, leading to chronic inflammation, and induces the release of mucins and the loss of cilia activity, two factors that determine mucus clearance and the increase in sputum volume. These alterations involve reactive oxygen species-dependent mechanisms. The antioxidant N-acetylcysteine (NAC) has proven useful in the management of COPD, reducing symptoms, exacerbations, and accelerated lung function decline. NAC inhibits RSV infection and mucin release in human A549 cells. The main objective of this study was to analyze the effects of NAC in modulating ciliary activity, ciliagenesis, and metaplasia in primary normal human bronchial epithelial cell (NHBEC) cultures infected with RSV. Our results indicated that RSV induced ultrastructural abnormalities in axonemal basal bodies and decreased the expression of β-tubulin as well as two genes involved in ciliagenesis, FOXJ1 and DNAI2. These alterations led to a decrease in ciliary activity. Furthermore, RSV induced metaplastic changes to the epithelium and increased the number of goblet cells and the expression of MUC5AC and GOB5. NAC restored the normal functions of the epithelium, inhibiting ICAM1 expression, subsequent RSV infection through mechanisms involving nuclear receptor factor 2, and the expression of heme oxygenase 1, which correlated with the restoration of the antioxidant capacity, the intracellular H(2)O(2) levels and glutathione content of NHBECs. The results presented in this study support the therapeutic use of NAC for the management of chronic respiratory diseases, including COPD.

  11. Evidence for differential regulation of the adipokine visfatin in the maternal and fetal compartments in normal spontaneous labor at term

    PubMed Central

    Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Kim, Sun Kwon; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Dong, Zhong; Pacora, Percy; Yeo, Lami; Hassan, Sonia S.

    2012-01-01

    Objective Visfatin, a novel adipokine with metabolic and immunoregulatory properties, has been implicated in the regulation of fetal growth, as well as in preterm labor. A gap in knowledge is whether spontaneous labor at term is associated with changes in the maternal and fetal concentrations of visfatin. The aim of this study was to determine if the presence of labor at term is associated with alterations in maternal and neonatal plasma visfatin concentrations. Study design This cross-sectional study included 50 normal pregnant women at term and their appropriate-for-gestational age (AGA) neonates in the following groups: 1) 25 mother-neonate pairs delivered by elective cesarean section without spontaneous labor, and 2) 25 mother-neonate pairs who delivered vaginally following spontaneous labor. Maternal plasma and cord blood visfatin concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results 1) The median visfatin concentration was higher in umbilical cord plasma of neonates born following a spontaneous labor at term than that of those who were born by an elective cesarean section (p=0.02); 2) in contrast, the median maternal plasma visfatin concentration did not differ significantly between patients with and without labor (p=0.44); and 3) there was a significant correlation between umbilical cord plasma concentration of visfatin and both maternal visfatin concentration (r= 0.54, p=0.005) and gestational age at delivery (r= 0.58; p=0.002) only in the absence of labor. Conclusion Term labor is associated with increased fetal, but not maternal, circulating visfatin concentrations. Previous reports indicate that preterm labor leading to preterm delivery is characterized by an increase in maternal plasma concentrations of visfatin. The observations reported herein support the view that there are fundamental differences in the endocrine and metabolic adaptations in normal labor at term and preterm labor. PMID:20146661

  12. Trinucleotide-repeat expanded and normal DMPK transcripts contain unusually long poly(A) tails despite differential nuclear residence.

    PubMed

    Gudde, Anke E E G; van Kessel, Ingeborg D G; André, Laurène M; Wieringa, Bé; Wansink, Derick G

    2017-06-01

    In yeast and higher eukaryotes nuclear retention of transcripts may serve in control over RNA decay, nucleocytoplasmic transport and premature cytoplasmic appearance of mRNAs. Hyperadenylation of RNA is known to be associated with nuclear retention, but the cause-consequence relationship between hyperadenylation and regulation of RNA nuclear export is still unclear. We compared polyadenylation status between normal and expanded DMPK transcripts in muscle cells and tissues derived from unaffected individuals and patients with myotonic dystrophy type 1 (DM1). DM1 is an autosomal dominant disorder caused by (CTG)n repeat expansion in the DMPK gene. DM1 etiology is characterized by an almost complete block of nuclear export of DMPK transcripts carrying a long (CUG)n repeat, including aberrant sequestration of RNA-binding proteins. We show here by use of cell fractionation, RNA size separation and analysis of poly(A) tail length that a considerable fraction of transcripts from the normal DMPK allele is also retained in the nucleus (~30%). They carry poly(A) tails with an unusually broad length distribution, ranging between a few dozen to >500 adenosine residues. Remarkably, expanded DMPK (CUG)n transcripts from the mutant allele, almost exclusively nuclear, carry equally long poly(A) tails. Our findings thus suggest that nuclear retention may be a common feature of regulation of DMPK RNA expression. The typical forced nuclear residence of expanded DMPK transcripts affects this regulation in tissues of DM1 patients, but not through hyperadenylation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  13. NIMROD: a program for inference via a normal approximation of the posterior in models with random effects based on ordinary differential equations.

    PubMed

    Prague, Mélanie; Commenges, Daniel; Guedj, Jérémie; Drylewicz, Julia; Thiébaut, Rodolphe

    2013-08-01

    Models based on ordinary differential equations (ODE) are widespread tools for describing dynamical systems. In biomedical sciences, data from each subject can be sparse making difficult to precisely estimate individual parameters by standard non-linear regression but information can often be gained from between-subjects variability. This makes natural the use of mixed-effects models to estimate population parameters. Although the maximum likelihood approach is a valuable option, identifiability issues favour Bayesian approaches which can incorporate prior knowledge in a flexible way. However, the combination of difficulties coming from the ODE system and from the presence of random effects raises a major numerical challenge. Computations can be simplified by making a normal approximation of the posterior to find the maximum of the posterior distribution (MAP). Here we present the NIMROD program (normal approximation inference in models with random effects based on ordinary differential equations) devoted to the MAP estimation in ODE models. We describe the specific implemented features such as convergence criteria and an approximation of the leave-one-out cross-validation to assess the model quality of fit. In pharmacokinetics models, first, we evaluate the properties of this algorithm and compare it with FOCE and MCMC algorithms in simulations. Then, we illustrate NIMROD use on Amprenavir pharmacokinetics data from the PUZZLE clinical trial in HIV infected patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. The diagnostic accuracy of an incidental memory modification of the Boston Naming Test (memo-BNT) in differentiating between normal aging and mild Alzheimer's disease.

    PubMed

    Karrasch, Mira; Myllyniemi, Anna; Latvasalo, Linda; Söderholm, Carina; Ellfolk, Ulla; Laine, Matti

    2010-11-01

    Early Alzheimer's disease (AD) is associated with deficits in episodic memory. Semantic memory and naming have also been found to be affected, although to a lesser degree than episodic memory. Most episodic memory tests used in clinical settings assess intentional memory. The aim of the present paper was to present an incidental memory modification of the Boston Naming Test (memo-BNT) and to study the diagnostic accuracy of the BNT and the memo-BNT in differentiating between healthy old controls and AD patients. There were three groups in the study: 22 young controls (mean age 21.7), 23 normally aged old controls (mean age 70.6), and 23 patients with mild AD (mean age 74.0). There were no differences in the memo-BNT test scores between the old and young control participants. There were, however, significant differences between the AD patients and both control groups in several of the memo-BNT measures. Incidental free recall was the best measure in discriminating between the healthy aged controls and the AD patients (AUC = .939) and it had a better diagnostic accuracy than naming (AUC = 880). The results indicate that the memo-BNT could be used in clinical settings especially to differentiate between normal aging and mild AD.

  15. Differential Item Functioning of the Boston Naming Test in Cognitively Normal African American and Caucasian Older Adults

    PubMed Central

    Pedraza, Otto; Graff-Radford, Neill R.; Smith, Glenn E.; Ivnik, Robert J.; Willis, Floyd B.; Petersen, Ronald C.; Lucas, John A.

    2010-01-01

    Scores on the Boston Naming Test (BNT) are frequently lower for African American when compared to Caucasian adults. Although demographically-based norms can mitigate the impact of this discrepancy on the likelihood of erroneous diagnostic impressions, a growing consensus suggests that group norms do not sufficiently address or advance our understanding of the underlying psychometric and sociocultural factors that lead to between-group score discrepancies. Using item response theory and methods to detect differential item functioning (DIF), the current investigation moves beyond comparisons of the summed total score to examine whether the conditional probability of responding correctly to individual BNT items differs between African American and Caucasian adults. Participants included 670 adults age 52 and older who took part in Mayo's Older Americans and Older African Americans Normative Studies. Under a 2-parameter logistic IRT framework and after correction for the false discovery rate, 12 items where shown to demonstrate DIF. Six of these 12 items (“dominoes,” “escalator,” “muzzle,” “latch,” “tripod,” and “palette”) were also identified in additional analyses using hierarchical logistic regression models and represent the strongest evidence for race/ethnicity-based DIF. These findings afford a finer characterization of the psychometric properties of the BNT and expand our understanding of between-group performance. PMID:19570311

  16. Long non-coding RNAs differentially expressed between normal versus primary breast tumor tissues disclose converse changes to breast cancer-related protein-coding genes.

    PubMed

    Reiche, Kristin; Kasack, Katharina; Schreiber, Stephan; Lüders, Torben; Due, Eldri U; Naume, Bjørn; Riis, Margit; Kristensen, Vessela N; Horn, Friedemann; Børresen-Dale, Anne-Lise; Hackermüller, Jörg; Baumbusch, Lars O

    2014-01-01

    Breast cancer, the second leading cause of cancer death in women, is a highly heterogeneous disease, characterized by distinct genomic and transcriptomic profiles. Transcriptome analyses prevalently assessed protein-coding genes; however, the majority of the mammalian genome is expressed in numerous non-coding transcripts. Emerging evidence supports that many of these non-coding RNAs are specifically expressed during development, tumorigenesis, and metastasis. The focus of this study was to investigate the expression features and molecular characteristics of long non-coding RNAs (lncRNAs) in breast cancer. We investigated 26 breast tumor and 5 normal tissue samples utilizing a custom expression microarray enclosing probes for mRNAs as well as novel and previously identified lncRNAs. We identified more than 19,000 unique regions significantly differentially expressed between normal versus breast tumor tissue, half of these regions were non-coding without any evidence for functional open reading frames or sequence similarity to known proteins. The identified non-coding regions were primarily located in introns (53%) or in the intergenic space (33%), frequently orientated in antisense-direction of protein-coding genes (14%), and commonly distributed at promoter-, transcription factor binding-, or enhancer-sites. Analyzing the most diverse mRNA breast cancer subtypes Basal-like versus Luminal A and B resulted in 3,025 significantly differentially expressed unique loci, including 682 (23%) for non-coding transcripts. A notable number of differentially expressed protein-coding genes displayed non-synonymous expression changes compared to their nearest differentially expressed lncRNA, including an antisense lncRNA strongly anticorrelated to the mRNA coding for histone deacetylase 3 (HDAC3), which was investigated in more detail. Previously identified chromatin-associated lncRNAs (CARs) were predominantly downregulated in breast tumor samples, including CARs located in the

  17. Long Non-Coding RNAs Differentially Expressed between Normal versus Primary Breast Tumor Tissues Disclose Converse Changes to Breast Cancer-Related Protein-Coding Genes

    PubMed Central

    Reiche, Kristin; Kasack, Katharina; Schreiber, Stephan; Lüders, Torben; Due, Eldri U.; Naume, Bjørn; Riis, Margit; Kristensen, Vessela N.; Horn, Friedemann; Børresen-Dale, Anne-Lise; Hackermüller, Jörg; Baumbusch, Lars O.

    2014-01-01

    Breast cancer, the second leading cause of cancer death in women, is a highly heterogeneous disease, characterized by distinct genomic and transcriptomic profiles. Transcriptome analyses prevalently assessed protein-coding genes; however, the majority of the mammalian genome is expressed in numerous non-coding transcripts. Emerging evidence supports that many of these non-coding RNAs are specifically expressed during development, tumorigenesis, and metastasis. The focus of this study was to investigate the expression features and molecular characteristics of long non-coding RNAs (lncRNAs) in breast cancer. We investigated 26 breast tumor and 5 normal tissue samples utilizing a custom expression microarray enclosing probes for mRNAs as well as novel and previously identified lncRNAs. We identified more than 19,000 unique regions significantly differentially expressed between normal versus breast tumor tissue, half of these regions were non-coding without any evidence for functional open reading frames or sequence similarity to known proteins. The identified non-coding regions were primarily located in introns (53%) or in the intergenic space (33%), frequently orientated in antisense-direction of protein-coding genes (14%), and commonly distributed at promoter-, transcription factor binding-, or enhancer-sites. Analyzing the most diverse mRNA breast cancer subtypes Basal-like versus Luminal A and B resulted in 3,025 significantly differentially expressed unique loci, including 682 (23%) for non-coding transcripts. A notable number of differentially expressed protein-coding genes displayed non-synonymous expression changes compared to their nearest differentially expressed lncRNA, including an antisense lncRNA strongly anticorrelated to the mRNA coding for histone deacetylase 3 (HDAC3), which was investigated in more detail. Previously identified chromatin-associated lncRNAs (CARs) were predominantly downregulated in breast tumor samples, including CARs located in the

  18. Differential Accumulation of Proteinase Inhibitor I in Normal and Crown Gall Tissue of Tobacco, Tomato, and Potato 1

    PubMed Central

    Wong, Peter P.; Kuo, Tsungmin; Ryan, Clarence A.; Kado, Clarence I.

    1976-01-01

    A proteinase inhibitor (inhibitor I) is induced in crown gall tumors of tobacco (Nicotiana tabacum) initiated through infection with the tumorinducing bacterium, Agrobacterium tumefaciens, strains B6 or CG-14. Uninfected tissues do not contain immunologically detectable quantities of inhibitor I. Inhibitor I synthesis in tobacco crown gall tumors paralleled tumor growth at the average rate of about 4.5 μg of inhibitor I per 200 mg of fresh tissue per day. Infection of variegated tobacco mutant Dp-I with A. tumefaciens strain CG-14 produced tumors with 25% more inhibitor than tumors induced with strain B6. Unlike tobacco, tumors induced by either bacterial strain on potato (Solanum tuberosum) and on tomato (Lycopersicum esculentum) did not accumulate inhibitor I. Consequently, inhibitor I accumulation is modulated by the type of plant host used in spite of familial relatedness (Solanaceae) and the strain of A. tumefaciens used for infection. Immunological and electrophoretic properties of inhibitor I from tobacco crown gall tumor, callus, etiolated, and variegated tissues were compared. Agar immunodiffusion assays showed no apparent differences among precipitin reaction lines between inhibitor I of tumor, callus, variegated, and etiolated tissues. The immunoelectrophoretic mobilities of inhibitor I of tumor, variegated, and etiolated tissues were the same, but differed from that of either normal or crown gall callus tissues. These results suggest that different isoinhibitors of inhibitor I could account for the observed differences in electrophoretic mobilities, or that modification of the inhibitor has occurred sometime during, or after, its synthesis. Images PMID:16659453

  19. Normalization genes for quantitative RT-PCR in differentiated Caco-2 cells used for food exposure studies.

    PubMed

    Vreeburg, Robert A M; Bastiaan-Net, Shanna; Mes, Jurriaan J

    2011-02-01

    Exposure of food products to small-intestinal-like Caco-2 cells, combined with a gene expression based response analysis can be a valuable tool to classify potential bioactive effects of food homogenates. In order to study changes in gene expression upon food exposure, a robust set of stably expressed genes is required for normalization. Here we present a set of reference genes suitable for RT-qPCR that has been validated for exposure studies with the intestinal-like Caco-2 cell line. This study identified ribosomal phosphoprotein P0 (RPLP0) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as best reference genes. The set can be extended with β-2-microglobulin (B2M), splicing factor 3A, subunit 1 (SF3A1), and mitochondrial ribosomal protein L19 (MRPL19). Food homogenates did provoke responses in the Caco-2 cells, as was demonstrated by changed expression of NAD(P)H Quinone dehydrogenase 1 (NQO1), Claudin 4 (CLDN4), Nitric Oxide Synthase 2 (NOS2), and ATP-binding cassette, subfamily B, member 1 (ABCB1) in the same experiment. Results indicate that: i) natural food homogenates can exert effects in Caco-2 cells, and ii) stability in expression of the reference genes is not due to a lack of response of the Caco-2 cells.

  20. Stem cells and the role of ETS transcription factors in the differentiation hierarchy of normal and malignant prostate epithelium.

    PubMed

    Archer, Leanne K; Frame, Fiona M; Maitland, Norman J

    2017-02-01

    Prostate cancer is the most common cancer of men in the UK and accounts for a quarter of all new cases. Although treatment of localised cancer can be successful, there is no cure for patients presenting with invasive prostate cancer and there are less treatment options. They are generally treated with androgen-ablation therapies but eventually the tumours become hormone resistant and patients develop castration-resistant prostate cancer (CRPC) for which there are no further successful or curative treatments. This highlights the need for new treatment strategies. In order to prevent prostate cancer recurrence and treatment resistance, all the cell populations in a heterogeneous prostate tumour must be targeted, including the rare cancer stem cell (CSC) population. The ETS transcription factor family members are now recognised as a common feature in multiple cancers including prostate cancer; with aberrant expression, loss of tumour suppressor function, inactivating mutations and the formation of fusion genes observed. Most notably, the TMPRSS2-ERG gene fusion is present in approximately 50% of prostate cancers and in prostate CSCs. However, the role of other ETS transcription factors in prostate cancer is less well understood. This review will describe the prostate epithelial cell hierarchy and discuss the evidence behind prostate CSCs and their inherent resistance to conventional cancer therapies. The known and proposed roles of the ETS family of transcription factors in prostate epithelial cell differentiation and regulation of the CSC phenotype will be discussed, as well as how they might be targeted for therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Flow cytometric analysis of normal B cell differentiation: a frame of reference for the detection of minimal residual disease in precursor-B-ALL.

    PubMed

    Lúcio, P; Parreira, A; van den Beemd, M W; van Lochem, E G; van Wering, E R; Baars, E; Porwit-MacDonald, A; Bjorklund, E; Gaipa, G; Biondi, A; Orfao, A; Janossy, G; van Dongen, J J; San Miguel, J F

    1999-03-01

    During the last two decades, major progress has been made in the technology of flow cytometry and in the availability of a large series of monoclonal antibodies against surface membrane and intracellular antigens. Flow cytometric immunophenotyping has become a diagnostic tool for the analysis of normal and malignant leukocytes and it has proven to be a reliable approach for the investigation of minimal residual disease (MRD) in leukemia patients during and after treatment. In order to standardize the flow cytometric detection of MRD in acute leukemia, a BIOMED-1 Concerted Action was initiated with the participation of six laboratories in five different European countries. This European co-operative study included the immunophenotypic characterization and enumeration of different precursor and mature B cell subpopulations in normal bone marrow (BM). The phenotypic profiles in normal B cell differentiation may form a frame of reference for the identification of aberrant phenotypes of precursor-B cell acute lymphoblastic leukemias (precursor-B-ALL) and may therefore be helpful in MRD detection. Thirty-eight normal BM samples were analyzed with five different pre-selected monoclonal antibody combinations: CD10/CD20/CD19, CD34/CD38/CD19, CD34/CD22/CD19, CD19/CD34/CD45 and TdT/CD10/CD19. Two CD19- immature subpopulations which coexpressed B cell-associated antigens were identified: CD34+/CD22+/CD19- and TdT+/CD10+/CD19-, which represented 0.11 +/- 0.09% and 0.04 +/- 0.05% of the total BM nucleated cells, respectively. These immunophenotypes may correspond to the earliest stages of B cell differentiation. In addition to these minor subpopulations, three major CD19+ B cell subpopulations were identified, representing three consecutive maturation stages; CD19dim/CD34+/TdT+/CD10bright/CD22dim/CD45dim /CD38bright/CD20- (subpopulation 1), CD19+/CD34-/TdT-/CD10+/CD22dim/CD45+/CD38bright/ CD20dim (subpopulation 2) and CD19+/CD34-/TdT-/CD10-/CD22bright/CD45bright/ CD38dim/CD20

  2. Differentiating pediatric epileptic brain tissue from normal brain tissue by using time-dependent diffuse reflectance spectroscopy in vivo: comprehensive data analysis method in the time domain

    NASA Astrophysics Data System (ADS)

    Oh, Sanghoon; Fernald, Bradley; Bhatia, Sanjiv; Ragheb, John; Sandberg, David; Johnson, Mahlon; Lin, Wei-Chiang

    2009-05-01

    This research investigated the feasibility of using time-dependent diffuse reflectance spectroscopy to differentiate pediatric epileptic brain tissue from normal brain tissue. The optical spectroscopic technique monitored the dynamic optical properties of the cerebral cortex that are associated with its physiological, morphological, and compositional characteristics. Due to the transient irregular epileptic discharge activity within the epileptic brain tissue it was hypothesized that the lesion would express abnormal dynamic optical behavior that would alter normal dynamic behavior. Thirteen pediatric epilepsy patients and seven pediatric brain tumor patients (normal controls) were recruited for this clinical study. Dynamic optical properties were obtained from the cortical surface intraoperatively using a timedependent diffuse reflectance spectroscopy system. This system consisted of a fiber-optic probe, a tungsten-halogen light source, and a spectrophotometer. It acquired diffuse reflectance spectra with a spectral range of 204 nm to 932 nm at a rate of 33 spectra per second for approximately 12 seconds. Biopsy samples were taken from electrophysiologically abnormal cortex and evaluated by a neuropathologist, which served as a gold standard for lesion classification. For data analysis, spectral intensity changes of diffuse reflectance in the time domain at two different wavelengths from each investigated site were compared. Negative correlation segment, defined by the periods where the intensity changes at the two wavelengths were opposite in their slope polarity, were extracted. The total duration of negative correlation, referred to as the "negative correlation time index", was calculated by integrating the negative correlation segments. The negative correlation time indices from all investigated sites were sub-grouped according to the corresponding histological classifications. The difference between the mean indices of two subgroups was evaluated by standard

  3. Intrauterine lidocaine for pain control during laminaria insertion: a randomized controlled trial.

    PubMed

    Mercier, Rebecca J; Liberty, Abigail

    2014-12-01

    To determine if intrauterine administration of 5 cc of 2% lidocaine in addition to paracervical block reduces pain during laminaria insertion, when compared with paracervical block and saline placebo. This was a randomized, double blind placebo-controlled trial. Women presenting for abortion by dilation and evacuation (D&E) at 14-24 weeks gestational age were randomized to receive an intrauterine instillation of either 5 mL of 2% lidocaine or 5 mL of normal saline, in addition to standard paracervical block with 20 cc of 0.25% bupivacaine. Our primary outcome was self-reported pain scores on a 100mm Visual Analogue Scale (VAS) immediately following laminaria insertion. Secondary outcome was self-reported VAS pain score indicating the maximum level of pain experienced during the 24-48-h interval between laminaria insertion and D&E procedure. Seventy-two women were enrolled, and data for 67 women were analyzed, only two of whom were more than 21 weeks on gestation. The range of pain scores at both time points was large (1-90 mm at laminaria insertion; 0-100mm in laminaria-D&E interval). Mean pain scores were not different between treatment groups at laminaria insertion, (33 vs. 32, p=.8) or in the laminaria - D&E interval (43 vs. 44, p=.9). Intrauterine administration of 5 cc of 2% lidocaine in addition to paracervical block did not reduce pain with laminaria insertion when compared to paracervical block with saline placebo. Intrauterine lidocaine combined with paracervical block does not improve pain control at laminaria insertion when compared with paracervical block and saline placebo. Wide variation in pain scores and persistent pain after laminaria insertion suggests patient would benefit from more effective methods of pain control at laminaria insertion and during the post-laminaria interval. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Intrauterine Pressure (IUP) Telemetry in Pregnant and Parturient Rats: Potential Applications for Spacecraft and Centrifugation Studies

    NASA Technical Reports Server (NTRS)

    Ronca, A. E.; Baer, L. A.; Wade, C. E.

    2003-01-01

    Rats exposed to spaceflight or centrifugation from mid-to late pregnancy undergo either more or fewer labor contractions at birth, respectively, as compared to those in normal Earth gravity (1-g). In this paper, we report the development and validation of a new telemetric method for quantifying intrauterine pressure (IUP) in freely-moving, late pregnant and parturient rats. We plan to utilize this technique for studies of labor in altered gravity, specifically, to ascertain forces of uterine during birth, which we believe may be changed in micro- and hypergravity. The technique we describe yields precise, reliable measures of the forces experienced by rat fetuses during parturition. A small, surgically-implantable telemetric pressure sensor was fitted within a fluid-filled balloon. The total volume of the sensor-balloon assembly matched that of a full term rat fetus. Real-time videorecordings of sensor-implanted rat dams and non- implanted control dams enabled us to characterize effects of the intrauterine implant on behavioral aspects of parturition. Contraction frequency, duration, pup-to-pup birth intervals and pup-oriented activities of the dams measured during the peri-birth period were unaffected by the sensor implant. These findings establish intrauterine telemetry as a reliable, non-invasive technique for quantifying intrauterine pressures associated with parturition on Earth and in altered gravity environments. This new technology, readily amenable to spaceflight and centrifugation platforms, will enable us to answer key questions regarding the role of altered labor frequency labor in the adaptation of newborn mammals to hypo- and hypergravity.

  5. Intrauterine Pressure (IUP) Telemetry in Pregnant and Parturient Rats: Potential Applications for Spacecraft and Centrifugation Studies

    NASA Technical Reports Server (NTRS)

    Ronca, A. E.; Baer, L. A.; Wade, C. E.

    2003-01-01

    Rats exposed to spaceflight or centrifugation from mid-to late pregnancy undergo either more or fewer labor contractions at birth, respectively, as compared to those in normal Earth gravity (1-g). In this paper, we report the development and validation of a new telemetric method for quantifying intrauterine pressure (IUP) in freely-moving, late pregnant and parturient rats. We plan to utilize this technique for studies of labor in altered gravity, specifically, to ascertain forces of uterine during birth, which we believe may be changed in micro- and hypergravity. The technique we describe yields precise, reliable measures of the forces experienced by rat fetuses during parturition. A small, surgically-implantable telemetric pressure sensor was fitted within a fluid-filled balloon. The total volume of the sensor-balloon assembly matched that of a full term rat fetus. Real-time videorecordings of sensor-implanted rat dams and non- implanted control dams enabled us to characterize effects of the intrauterine implant on behavioral aspects of parturition. Contraction frequency, duration, pup-to-pup birth intervals and pup-oriented activities of the dams measured during the peri-birth period were unaffected by the sensor implant. These findings establish intrauterine telemetry as a reliable, non-invasive technique for quantifying intrauterine pressures associated with parturition on Earth and in altered gravity environments. This new technology, readily amenable to spaceflight and centrifugation platforms, will enable us to answer key questions regarding the role of altered labor frequency labor in the adaptation of newborn mammals to hypo- and hypergravity.

  6. Complications and Continuation of Intrauterine Device Use Among Commercially Insured Teenagers

    PubMed Central

    Berenson, Abbey B.; Tan, Alai; Hirth, Jacqueline M.; Wilkinson, Gregg S.

    2014-01-01

    Objective Many U.S. providers remain reluctant to prescribe intrauterine devices (IUDs) to teenagers due to concerns about serious complications. This study examined whether 15–19 year-old IUD users were more likely to experience complications, failure, or early discontinuation than adult users aged 20–24 and 25–44 years and whether there were differences in between users of levonorgestrel-releasing intrauterine systems and copper IUDs. Methods A retrospective cohort study was conducted using health insurance claims obtained from a private insurance company of 90,489 women who had an IUD inserted between 2002 and 2009. Logistic regression models were used to estimate the odds of experiencing complications, method failure, or early discontinuation within 12 months of insertion by age group and type of IUD inserted. Results Serious complications, including ectopic pregnancy and pelvic inflammatory disease, occurred in less than 1% of patients regardless of age or IUD type. Women aged 15–19 years were more likely than those aged 25–44 years to have a claim for dysmenorrhea OR=1.4, CI=1.1, 1.6), amenorrhea (OR=1.3, CI=1.1, 1.5), or normal pregnancy (OR=1.4, CI=1.1, 1.8). Overall, early discontinuation did not differ between teenagers and women aged 25–44 years (13% vs. 11%, p>.05). However, use of the levonorgestrel-releasing intrauterine system was associated with fewer complications and less early discontinuation than the copper IUD in all age groups. Conclusions The IUD is as appropriate for teenagers to use as it is for older women, with serious complications occurring infrequently in all groups. The levonorgestrel-releasing intrauterine system may be a better choice than copper IUD due to lower odds of complications, discontinuation, and failure. PMID:23635730

  7. Transcriptome analysis reveals a dynamic and differential transcriptional response to sulforaphane in normal and prostate cancer cells and suggests a role for Sp1 in chemoprevention.

    PubMed

    Beaver, Laura M; Buchanan, Alex; Sokolowski, Elizabeth I; Riscoe, Allison N; Wong, Carmen P; Chang, Jeff H; Löhr, Christiane V; Williams, David E; Dashwood, Roderick H; Ho, Emily

    2014-10-01

    Epidemiological studies provide evidence that consumption of cruciferous vegetables, like broccoli, can reduce the risk of cancer development. Sulforaphane (SFN) is a phytochemical derived from cruciferous vegetables that induces anti-proliferative and pro-apoptotic responses in prostate cancer cells, but not in normal prostate cells. The mechanisms responsible for this cancer-specific cytotoxicity remain unclear. We utilized RNA sequencing and determined the transcriptomes of normal prostate epithelial cells, androgen-dependent prostate cancer cells, and androgen-independent prostate cancer cells treated with SFN. SFN treatment dynamically altered gene expression and resulted in distinct transcriptome profiles depending on prostate cell line. SFN also down-regulated the expression of genes that were up-regulated in prostate cancer cells. Network analysis of genes altered by SFN treatment revealed that the transcription factor Specificity protein 1 (Sp1) was present in an average of 90.5% of networks. Sp1 protein was significantly decreased by SFN treatment in prostate cancer cells and Sp1 may be an important mediator of SFN-induced changes in expression. Overall, the data show that SFN alters gene expression differentially in normal and cancer cells with key targets in chemopreventive processes, making it a promising dietary anti-cancer agent. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Lipid metabolism during bacterial growth, sporulation, and germination: differential synthesis of individual branched- and normal-chain fatty acids during spore germination and outgrowth of Bacillus thuringiensis.

    PubMed

    Nickerson, K W; Bulla, L A; Mounts, T L

    1975-12-01

    The biosynthesis of individual branched- and normal-chain fatty acids during Bacillus thuringiensis spore germination and outgrowth was studied by comparing pulsed and continuous labeling of these fatty acids with [U-14C]acetate. The relative specific activity of each fatty acid varies with time as the cell progresses through outgrowth. However, fatty acid synthesis does occur in two distinct phases. Upon germination, acetate is incorporated only into the iso-isomers i-C13, i-C14, and i-C16; no normal or anteiso synthesis occurs. Subsequent to T30, the full complement of branched- and normal-chain homologues is formed and there is a dramatic enhancement in the overall rate of fatty acid synthesis. Significantly, this rate increase coincides with a marked shift from the synthesis of short-chain to long-chain fatty acids. These findings illustrate a dichotomy in synthesis that may result from initial fatty acid formation by preexisting spore fatty acid biosynthetic enzymes in the absence of de novo protein synthesis. Elucidation of the timing and kinetics of individual fatty acid formation provides a biochemical profile of activities directly related to membrane differentiation and cellular development.

  9. Acute aerobic exercise differentially alters acylated ghrelin and perceived fullness in normal-weight and obese individuals.

    PubMed

    Heden, Timothy D; Liu, Ying; Park, Youngmin; Dellsperger, Kevin C; Kanaley, Jill A

    2013-09-01

    Adiposity alters acylated ghrelin concentrations, but it is unknown whether adiposity alters the effect of exercise and feeding on acylated ghrelin responses. Therefore, the purpose of this study was to determine whether adiposity [normal-weight (NW) vs. obese (Ob)] influences the effect of exercise and feeding on acylated ghrelin, hunger, and fullness. Fourteen NW and 14 Ob individuals completed two trials in a randomized counterbalanced fashion, including a prior exercise trial (EX) and a no exercise trial (NoEX). During the EX trial, the participants performed 1 h of treadmill walking (55-60% peak O2 uptake) during the evening, 12 h before a 4-h standardized mixed meal test. Frequent blood samples were taken and analyzed for acylated ghrelin, and a visual analog scale was used to assess perceived hunger and fullness. In NW individuals, EX, compared with NoEX, reduced fasting acylated ghrelin concentrations by 18% (P = 0.03), and, in response to feeding, the change in acylated ghrelin (P = 0.02) was attenuated by 39%, but perceived hunger and fullness were unaltered. In Ob individuals, despite no changes in fasting or postprandial acylated ghrelin concentrations with EX, postprandial fullness was attenuated by 46% compared with NoEX (P = 0.05). In summary, exercise performed the night before a meal suppresses acylated ghrelin concentrations in NW individuals without altering perceived hunger or fullness. In Ob individuals, despite no changes in acylated ghrelin concentrations, EX reduced the fullness response to the test meal. Acylated ghrelin and perceived fullness responses are differently altered by acute aerobic exercise in NW and Ob individuals.

  10. Alcohol-Induced miR-27a Regulates Differentiation and M2 Macrophage Polarization of Normal Human Monocytes

    PubMed Central

    Saha, Banishree; Bruneau, Johanna C.; Kodys, Karen; Szabo, Gyongyi

    2015-01-01

    Alcohol abuse is a leading cause of liver disease characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Immunomodulatory effects of alcohol on monocytes and macrophages contribute to alcoholic liver disease. Alcohol use, an independent risk factor for progression of hepatitis C virus (HCV) infection–mediated liver disease, impairs host defense and alters cytokine production and monocyte/macrophage activation. We hypothesized that alcohol and HCV have synergistic effects on the phenotype and function of monocytes. Our data show that acute alcohol binge drinking in healthy volunteers results in increased frequency of CD16+ and CD68+ and M2-type (CD206+, dendritic cell [DC]-SIGN+–expressing and IL-10–secreting) circulating CD14+ monocytes. Expression of HCV-induced CD68 and M2 markers (CD206 and DC-SIGN) in normal monocytes was further enhanced in the presence of alcohol. The levels of microRNA (miR)-27a was significantly upregulated in monocytes cultured in the presence of alcohol or alcohol and HCV as compared with HCV alone. The functional role of miR-27a in macrophage polarization was demonstrated by transfecting monocytes with an miR-27a inhibitor that resulted in reduced alcohol- and HCV- mediated monocyte activation (CD14 and CD68 expression), polarization (CD206 and DC-SIGN expression), and IL-10 secretion. Over-expression of miR-27a in monocytes enhanced IL-10 secretion via activation of the ERK signaling pathway. We found that miR-27a promoted ERK phosphorylation by downregulating the expression of ERK inhibitor sprouty2 in monocytes. Thus, we identified that sprouty2 is a target of miR-27a in human monocytes. In summary, our study demonstrates the regulatory role of miR-27a in alcohol-induced monocyte activation and polarization. PMID:25716995

  11. Intrauterine fetal death and risk of shoulder dystocia at delivery.

    PubMed

    Larsen, Sandra; Dobbin, Joanna; McCallion, Oliver; Eskild, Anne

    2016-12-01

    Vaginal delivery is recommended after intrauterine fetal death. However, little is known about the risk of shoulder dystocia in these deliveries. We studied whether intrauterine fetal death increases the risk of shoulder dystocia at delivery. In this population-based register study using the Medical Birth Registry of Norway, we included all singleton pregnancies with vaginal delivery of offspring in cephalic presentation in Norway during the period 1967-2012 (n = 2 266 118). Risk of shoulder dystocia was estimated as absolute risk (%) and odds ratio with 95% confidence interval. Adjustment was made for offspring birthweight (in grams). We performed sub-analyses within categories of birthweight (<4000 and ≥4000 g) and in pregnancies with maternal diabetes. Shoulder dystocia occurred in 1.1% of pregnancies with intrauterine fetal death and in 0.8% of pregnancies without intrauterine fetal death (p < 0.0001) (crude odds ratio 1.5, 95% confidence interval 1.2-4.9). After adjustment for birthweight, the odds ratio was 5.9 (95% confidence interval 4.7-7.4). In pregnancies with birthweight ≥4000 g, shoulder dystocia occurred in 14.6% of pregnancies with intrauterine fetal death and in 2.8% of pregnancies without intrauterine fetal death (p < 0.001) (crude odds ratio 5.9, 95% confidence interval 4.5-7.9). In pregnancies with birthweight ≥4000 g and concurrent maternal diabetes, shoulder dystocia occurred in 57.1% of pregnancies with intrauterine fetal death and 9.6% of pregnancies without intrauterine fetal death (p < 0.001) (crude odds ratio 12.6, 95% confidence interval 5.9-26.9). Intrauterine fetal death increased the risk of shoulder dystocia at delivery, and the absolute risk of shoulder dystocia was particularly high if offspring birthweight was high and the mother had diabetes. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  12. Impaired Angiogenic Potential of Human Placental Mesenchymal Stromal Cells in Intrauterine Growth Restriction.

    PubMed

    Mandò, Chiara; Razini, Paola; Novielli, Chiara; Anelli, Gaia Maria; Belicchi, Marzia; Erratico, Silvia; Banfi, Stefania; Meregalli, Mirella; Tavelli, Alessandro; Baccarin, Marco; Rolfo, Alessandro; Motta, Silvia; Torrente, Yvan; Cetin, Irene

    2016-04-01

    Human placental mesenchymal stromal cells (pMSCs) have never been investigated in intrauterine growth restriction (IUGR). We characterized cells isolated from placental membranes and the basal disc of six IUGR and five physiological placentas. Cell viability and proliferation were assessed every 7 days during a 6-week culture. Expression of hematopoietic, stem, endothelial, and mesenchymal markers was evaluated by flow cytometry. We characterized the multipotency of pMSCs and the expression of genes involved in mitochondrial content and function. Cell viability was high in all samples, and proliferation rate was lower in IUGR compared with control cells. All samples presented a starting heterogeneous population, shifting during culture toward homogeneity for mesenchymal markers and occurring earlier in IUGR than in controls. In vitro multipotency of IUGR-derived pMSCs was restricted because their capacity for adipocyte differentiation was increased, whereas their ability to differentiate toward endothelial cell lineage was decreased. Mitochondrial content and function were higher in IUGR pMSCs than controls, possibly indicating a shift from anaerobic to aerobic metabolism, with the loss of the metabolic characteristics that are typical of undifferentiated multipotent cells. This study demonstrates that the loss of endothelial differentiation potential and the increase of adipogenic ability are likely to play a significant role in the vicious cycle of abnormal placental development in intrauterine growth restriction (IUGR). This is the first observation of a potential role for placental mesenchymal stromal cells in intrauterine growth restriction, thus leading to new perspectives for the treatment of IUGR. ©AlphaMed Press.

  13. Comparison of copper intrauterine device with levonorgestrel-bearing intrauterine system for post-abortion contraception.

    PubMed

    Bilgehan, Fatma; Dilbaz, Berna; Karadag, Burak; Deveci, Canan Dura

    2015-09-01

    The aim of this study was to compare the safety, bleeding pattern, effects, side-effects, complications and 6-month continuity rates of levonorgestrel-bearing intrauterine system (LNG-IUS) with conventional copper intrauterine device (Cu-IUD) inserted immediately after voluntary termination of pregnancy up to 10 weeks of gestation. One hundred women who underwent voluntary pregnancy termination and preferred IUD insertion as a contraceptive method after counseling were enrolled. The patients were randomly allocated to Cu-IUD or LNG-IUS and followed up at 10 days, and at 1, 3 and 6 months. The expulsion rates, continuation rates, side-effects, and bleeding patterns were compared. Fifty women in the Cu-IUD group and 44 women in the LNG-IUS group were followed up. The continuity and expulsion rate for Cu-IUD and LNG-IUS at the end of 6 months was 74%, 12%, and 75%, 11.3%, respectively. In LNG-IUS users, the incidence of amenorrhea and the number of spotting days were higher and hemoglobin increased throughout the follow-up period. The side-effects related to both methods were not different from interval insertions. Immediate post-abortion intrauterine contraception with Cu-IUD or LNG-IUS is a safe, reliable method. The incidence of side-effects is similar, and there is only a slightly higher rate of expulsion but an acceptable rate of method continuation. © 2015 Japan Society of Obstetrics and Gynecology.

  14. Correlation between urothelial differentiation and sensory proteins P2X3, P2X5, TRPV1, and TRPV4 in normal urothelium and papillary carcinoma of human bladder.

    PubMed

    Sterle, Igor; Zupančič, Daša; Romih, Rok

    2014-01-01

    Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5) and transient receptor potential vanilloid channels (TRPV1, and TRPV4). Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns.

  15. Sonographic appearances of Chinese intrauterine devices.

    PubMed

    Cheung, Vincent Y T

    2010-07-01

    The purpose of this presentation is to familiarize physicians about the different types of intrauterine devices (IUDs) used in China. The characteristic features and the sonographic appearances of the different types of IUDs commonly used in China are described. The stainless steel ring is the most commonly used IUD in China. However, various different types of copper-bearing IUDs are gaining popularity. Most Chinese IUDs do not have an attached thread and are more difficult to remove than the IUDs commonly used in North America. Also, most Chinese IUDs have a distinct sonographic appearance; therefore, sonography can play an important role when assessing a woman who has a retained Chinese IUD or has a complication associated with the IUD. Knowledge about the different types of Chinese IUDs will enable physicians to provide optimal care to their patients.

  16. Intrauterine Programming of Diabetes and Adiposity.

    PubMed

    Tomar, Ashutosh Singh; Tallapragada, Divya Sri Priyanka; Nongmaithem, Suraj Singh; Shrestha, Smeeta; Yajnik, Chittaranjan S; Chandak, Giriraj Ratan

    2015-12-01

    The prevalence of diabetes and adiposity has increased at an alarming rate and together they contribute to the rise in morbidity and mortality worldwide. Genetic studies till date have succeeded in explaining only a proportion of heritability, while a major component remains unexplained. Early life determinants of future risk of these diseases are likely contributors to the missing heritability and thus have a significant potential in disease prevention. Epidemiological and animal studies show the importance of intrauterine and early postnatal environment in programming of the fetus to adverse metabolic outcomes and support the notion of Developmental Origins of Health and Disease (DOHaD). Emerging evidence highlights the role of epigenetic mechanisms in mediating effects of environmental exposures, which in certain instances may exhibit intergenerational transmission even in the absence of exposure. In this article, we will discuss the complexity of diabetes and increased adiposity and mechanisms of programming of these adverse metabolic conditions.

  17. Differential immunotoxic effects of ethanol on murine EL-4 lymphoma and normal lymphocytes is mediated through increased ROS production and activation of p38MAPK.

    PubMed

    Premachandran, Sudha; Khan, Nazir M; Thakur, Vikas S; Shukla, Jyoti; Poduval, T B

    2012-08-01

    Ethanol has been used to achieve thymic depletion in myasthenia gravis patients. Ethanol (95%) has also been used widely in the therapy of many tumors including hepatocellular carcinoma. In light of these findings, we delineated the differential immunotoxic behavior and mechanism of lower concentration of ethanol towards murine EL-4 lymphoma and its normal counterpart lymphocytes. EL-4 lymphoma and normal lymphocytes were cultured with ethanol (0%-5%) for 6 h and cytotoxicity was measured by various methods. EL-4 cells treated with ethanol showed concentration-dependent loss of viability at 2%-5% ethanol concentration and exhibit proliferative arrest at preG1 stage. Acridine-orange and ethidium-bromide staining indicated that ethanol induced death in EL-4 cells, by induction of both apoptosis and necrosis which was further supported by findings of DNA-fragmentation and trypan blue dye exclusion test. However, treatment of lymphocytes with similar concentration of ethanol did not show any death-associated parameters. Furthermore, ethanol induced significantly higher ROS generation in EL-4 cells as compared to lymphocytes and caused PARP cleavage and activation of apoptotic proteins like p53 and Bax, in EL-4 cells and not in normal lymphocytes. In addition, ethanol exposure to EL-4 cells led to phosphorylation of p38MAPK, and upregulation of death receptor Fas (CD95). Taken together, these results suggest that ethanol upto a concentration of 5% caused no significant immunotoxicity towards normal lymphocytes and induced cell death in EL-4 cells via phosphorylation of p38MAPK and regulation of p53 leading to further activation of both extrinsic (Fas) and intrinsic (Bax) apoptotic markers.

  18. Differential expression of galectins in normal, benign and malignant prostate epithelial cells: silencing of galectin-3 expression in prostate cancer by its promoter methylation.

    PubMed

    Ahmed, Hafiz; Banerjee, Partha P; Vasta, Gerardo R

    2007-06-22

    Galectins (gal), a family of soluble beta-galactoside-binding proteins present at the cell surface, are involved in cancer progression and metastasis. Here we investigated the expression of several galectins in normal (PrEC), benign (BPH-1), and malignant (LNCaP) prostate epithelial cells and found that all galectins, except gal1 are differentially expressed. The gal3, 7, and 9 are highly expressed in PrEC, but not in LNCaP cells. Out of seven isoforms of gal8, the proto isoform gal8e and our newly discovered proto isoform gal8g were upregulated in LNCaP cells compared to PrEC, whereas the two tandem-repeat isoforms gal8a and gal8b were equally expressed in these cells. To determine if the silencing of gal3 in LNCaP cells was due to promoter methylation, LNCaP cells were treated with azacytidine. Azacytidine treatment induced the expression of gal3 in LNCaP cells, indicating that the gal3 gene was silenced by methylation of its promoter. To examine further, we evaluated cytosine methylation in gal3 promoter in LNCaP, normal prostate and placenta DNA and observed that it is highly methylated in LNCaP but not in normal cells and azacytidine completely abolished this methylation in LNCaP cells. Similar to prostate cancer cells, gal3 promoter was highly methylated in human prostate cancer tissue but not in normal tissue. To our knowledge, this is the first report indicating that gal3 expression is regulated by promoter methylation in LNCaP cells and prostate tumors. The methylation of gal3 promoter may constitute a powerful tool for early diagnosis of prostate cancer.

  19. Genome-Wide Profiling Identified a Set of miRNAs that Are Differentially Expressed in Glioblastoma Stem Cells and Normal Neural Stem Cells

    PubMed Central

    Lang, Ming-Fei; Murai, Kiyohito; Wu, Xiwei; Wang, Jinhui; Gao, Hanlin; Brown, Christine E.; Liu, Xiaoxuan; Zhou, Jiehua; Peng, Ling; Rossi, John J.; Shi, Yanhong

    2012-01-01

    A major challenge in cancer research field is to define molecular features that distinguish cancer stem cells from normal stem cells. In this study, we compared microRNA (miRNA) expression profiles in human glioblastoma stem cells and normal neural stem cells using combined microarray and deep sequencing analyses. These studies allowed us to identify a set of 10 miRNAs that are considerably up-regulated or down-regulated in glioblastoma stem cells. Among them, 5 miRNAs were further confirmed to have altered expression in three independent lines of glioblastoma stem cells by real-time RT-PCR analysis. Moreover, two of the miRNAs with increased expression in glioblastoma stem cells also exhibited elevated expression in glioblastoma patient tissues examined, while two miRNAs with decreased expression in glioblastoma stem cells displayed reduced expression in tumor tissues. Furthermore, we identified two oncogenes, NRAS and PIM3, as downstream targets of miR-124, one of the down-regulated miRNAs; and a tumor suppressor, CSMD1, as a downstream target of miR-10a and miR-10b, two of the up-regulated miRNAs. In summary, this study led to the identification of a set of miRNAs that are differentially expressed in glioblastoma stem cells and normal neural stem cells. Characterizing the role of these miRNAs in glioblastoma stem cells may lead to the development of miRNA-based therapies that specifically target tumor stem cells, but spare normal stem cells. PMID:22558405

  20. Differentiating normal and basal cell carcinoma human skin tissues in vitro using dispersive Raman spectroscopy: a comparison between principal components analysis and simplified biochemical models.

    PubMed

    Bodanese, Benito; Silveira, Landulfo; Albertini, Regiane; Zângaro, Renato Amaro; Pacheco, Marcos Tadeu Tavares

    2010-08-01

    Raman spectroscopy has been used to detect spectral differences between normal and basocellular cell carcinoma (BCC) skin tissues that are related to biochemical alterations between tissues. Raman spectroscopy is an analytic tool that could detect biochemical alterations in tissues, and its use would lead to real-time and less-invasive cancer diagnosis. Raman spectra from human tissue fragments (normal and BCC) were obtained in a dispersive, near-infrared Raman spectrometer (laser parameters: 830 nm, 80 mW) with a CCD detector. Spectral changes between normal and BCC were analyzed with a principal components analysis (PCA) algorithm and a simplified biochemical model based on the relative amount of collagen and cell fat extracted from tissue Raman spectra. Main spectral differences between these samples were in the region of 800 to 1,000 per centimeter and 1,200 to 1,300 per centimeter, corresponding to vibrational bands from lipids and proteins (C-C bonds and amide III, respectively). The diagnostic algorithm based on PCA and Mahalanobis distance applied to the scores of principal components vectors PC1 and PC2 could identify tissue with sensitivity and specificity of 89% and 93%, respectively, for the training group and 96% and 92% for the prospective group. The simplified biochemical model for collagen amount had sensitivity and specificity of 95% and 83% for the training group and 87% and 92% for the prospective group. Raman spectroscopy could differentiate between normal and BCC tissues in both the PCA and biochemical models, showing higher sensitivity and specificity for the PCA model, although the simplified biochemical model is easier to implement.

  1. Intrauterine radiation exposures and mental retardation

    SciTech Connect

    Miller, R.W.

    1988-08-01

    Small head size and mental retardation have been known as effects of intrauterine exposure to ionizing radiation since the 1920s. In the 1950s, studies of Japanese atomic-bomb survivors revealed that at 4-17 wk of gestation, the greater the dose, the smaller the brain (and head size), and that beginning at 0.5 Gy (50 rad) in Hiroshima, mental retardation increased in frequency with increasing dose. No other excess of birth defects was observed. Otake and Schull (1984) pointed out that the period of susceptibility to mental retardation coincided with that for proliferation and migration of neuronal elements from near the cerebral ventricles to the cortex. Mental retardation could be the result of interference with this process. Their analysis indicated that exposures at 8-15 wk to 0.01-0.02 Gy (1-2 rad) doubled the frequency of severe mental retardation. This estimate was based on small numbers of mentally retarded atomic-bomb survivors. Although nuclear accidents have occurred recently, new cases will hopefully be too rare to provide further information about the risk of mental retardation. It may be possible, however, to learn about lesser impairment. New psychometric tests may be helpful in detecting subtle deficits in intelligence or neurodevelopmental function. One such test is PEERAMID, which is being used in schools to identify learning disabilities due, for example, to deficits in attention, short- or long-term memory, or in sequencing information. This and other tests could be applied in evaluating survivors of intrauterine exposure to various doses of ionizing radiation. The results could change our understanding of the safety of low-dose exposures.

  2. [Prognostic factors of pregnancy in intrauterine insemination].

    PubMed

    Barros Delgadillo, Juan Carlos; Rojas Ruiz, Juan Carlos; Molina Munguía, Ana Cecilia; Villalobos Acosta, Sergio; Sánchez Solís, Víctor; Barroso Villa, Gerardo; Gaviño Gaviño, Fernando

    2006-12-01

    The artificial insemination is the introduction of spermatozoa in the feminine genital tract without carrying out sexual contact and with the purpose of obtaining the pregnancy. The insemination intrauterine has improved its rate of success thanks to the technological advances and the best knowledge of human reproductive physiology. To evaluate the prognostic factors for the pregnancy success and calculate the cumulative rate per cycle in IUI (intrauterine insemination). This study was descriptive, retrospective, analytic, and longitudinal. The cycles of IUI were analyzed from January 1st 2003 to December 31st 2005. Couples 24-41 years old with primary and secondary infertility were included. The following variables were studied: age of participant, type of infertility, length of infertility, aetiology, postcapacitation sperm density and motility, number of follicles, endometrial thickness, and the cycle number in which the IUI was performed. Patients carried out a protocol of ovarian stimulation and follicular follow up. The results were analyzed with 11.0 SPSS, continuous variables were analyzed and reported as means +/- SD with univariate logistic regression to determine statistic significance. Categoric variables were reported in frequencies and percentages. ROC curves were calculated to determine optimal cutting points. 668 cycles were analyzed in 391 couples. The pregnancy rate per cycle and couple was of 13.0 and 21.7% respectively. Means +/- SD patient age was 33.5 +/- 3.4 years old. The three variables with p < 0.05 were: the infertility duration, sperm motility and the cycle number in which IUI was performed. No statistical significance was found in the remaining variables. The greatest success in IUI will be achieved with infertility of 4 years or less, with sperm motility of 77.6% and in the first two cycles of treatment.

  3. B cell origin of non-T cell acute lymphoblastic leukemia. A model for discrete stages of neoplastic and normal pre-B cell differentiation.

    PubMed Central

    Nadler, L M; Korsmeyer, S J; Anderson, K C; Boyd, A W; Slaughenhoupt, B; Park, E; Jensen, J; Coral, F; Mayer, R J; Sallan, S E

    1984-01-01

    The expression of B cell associated and restricted antigens on tumor cells isolated from 138 patients with non-T cell acute lymphoblastic leukemia (non-T cell ALL) was investigated by flow cytometric analysis by means of a panel of monoclonal antibodies. Tumor cells from these patients could be assigned to one of four subgroups: human leukocyte antigen-DR-related Ia-like antigens (Ia) alone (4%, stage I); IaB4 (14%, stage II); IaB4CALLA (33%, stage III); and IaB4CALLAB1 (49%, stage IV). The expression of B cell-restricted antigens (B4 and B1) and rearrangements of Ig heavy chain genes provided strong evidence for the B cell lineage of stages II, III, and IV tumors. The lineage of the Ia alone group is still unknown. The B4 antigen was expressed on approximately 95% of all non-T cell ALLs tested, and given its absence on T cell and myeloid tumors, it appears to be an exceptional marker to define cells of B lineage. The demonstration that Ia alone, IaB4, IaB4CALLA, and IaB4CALLAB1 positive cells can be readily identified by dual fluorescence analysis in normal fetal and adult bone marrow provided critical support for the view that these leukemic pre-B cell phenotypes were representative of the stages of normal pre-B cell differentiation. It was interesting that the IaB4+ cell was more frequently identified in fetal bone marrow than in adult marrow, whereas the predominant cell found in adult marrow expressed the IaB4CALLAB1 phenotype. These data suggest that the leukemogenic event may be random, since the predominant pre-B cell leukemic phenotype appears to correspond to the normal pre-B cell phenotype present in these hematopoietic organs. Our observations provide an additional distinction between adult and childhood ALL, since these studies show that most non-T cell ALLs seen in children less than 2 yr old are of stage II phenotype, whereas the majority of non-T ALLs in adults are of stage IV phenotype. Finally, it should be noted that the present study suggests

  4. Safety of intrauterine contraceptive devices during MR imaging.

    PubMed

    Hess, T; Stepanow, B; Knopp, M V

    1996-01-01

    Three intrauterine contraceptive devices (IUD) were examined in an experimental in vitro setup to test their MR compatibility: Multiload CU375. Nova T (containing copper and silver), and Gyne T. The devices were fixed in a polyacrylamide gel and exposed to the magnetic field and the radiofrequency (RF) of standard MR sequences (spin-echo, turbo-spin-echo, turboFLASH, and magnetization transfer prepared FLASH). The RF power of a turbo-spin-echo sequence was increased by a factor of 5. Temperatures of the IUDs and the gel were measured during the MR examination. No deflection of the IUDs exposed to the magnetic field of 1.5 Tesla was detected. Under normal imaging conditions no temperature increase could be observed. Using an increased RF power, a maximal temperature rise of 0.4 degree C per examination was seen. No differences between the gel and the IUDs were observed, indicating that there is no specific heating of the tested IUDs.

  5. Levonorgestrel Intrauterine Device Use in Overweight and Obese Women

    PubMed Central

    Soon, Reni A; Harris, Sara C; Salcedo, Jennifer; Kaneshiro, Bliss E

    2015-01-01

    The levonorgestrel intrauterine device (LNG-IUD) is a safe, effective, long-acting, reversible contraceptive that reduces unintended pregnancy and decreases heavy menstrual bleeding. Many procedures such as IUD insertion are more challenging in overweight and obese women. The objective of this study was to describe LNG-IUD insertion, continuation, and complications in overweight and obese women in an ethnically diverse population in Hawai‘i. A retrospective cohort study of women who had a LNG-IUD inserted at the University of Hawai‘i, Department of Obstetrics and Gynecology Resident and Faculty practice sites between January 2009 and December 2010 was performed. A total of 149 women were followed. The most commonly reported races were Asian (32%), Native Hawaiian (26%), and non-Hawaiian Pacific Islander (20%). The mean BMI of the study population was 28.4 (standard deviation 7.2) with 37% classified as normal weight, 30% as overweight, and 33% as obese. Overall, 76% of women continued the LNG-IUD 12 months after insertion. No statistically significant difference emerged in 12-month IUD continuation between the BMI groups. Difficult (5%) and failed (3%) IUD insertions were rare for all BMI groups. IUD complications occurred in 9% of women and included expulsion and self-removal. In this diverse population, the majority of women continued to use the LNG-IUD one year after insertion with low rates of difficult insertions and complications. PMID:26568900

  6. Flow cytometric differentiation of abnormal and normal plasma cells in the bone marrow in patients with multiple myeloma and its precursor diseases.

    PubMed

    Tembhare, Prashant R; Yuan, Constance M; Venzon, David; Braylan, Raul; Korde, Neha; Manasanch, Elisabet; Zuchlinsky, Diamond; Calvo, Katherine; Kurlander, Roger; Bhutani, Manisha; Tageja, Nishant; Maric, Irina; Mulquin, Marcia; Roschewski, Mark; Kwok, Mary; Liewehr, David; Landgren, Ola; Stetler-Stevenson, Maryalice

    2014-03-01

    Flow cytometric (FC) enumeration of abnormal plasma cells (APCs) for diagnosis and prognostication of plasma cell dyscrasias (PCD) is challenging. We studied antigen expression in normal plasma cells (NPC) (N = 34) and APC in a series of unselected PCD (N = 59). NPC subpopulations often demonstrated CD19(-), CD20(+), CD45(-) or dim and CD56(+), an immunophenotype observed in PCD. However abnormal CD81 was only observed in APCs (APC detection sensitivity 95%; specificity 100%). We evaluated differences in antigen expression patterns among MGUS (N = 14), SMM (N = 35) and MM (N = 10), finding the combination of CD45 and CD56 helpful in differentiating MGUS from SMM and MM (p = 0.0002). Published by Elsevier Ltd.

  7. Epigenetic deregulation across chromosome 2q14.2 differentiates normal from prostate cancer and provides a regional panel of novel DNA methylation cancer biomarkers.

    PubMed

    Devaney, James; Stirzaker, Clare; Qu, Wenjia; Song, Jenny Z; Statham, Aaron L; Patterson, Kate I; Horvath, Lisa G; Tabor, Bruce; Coolen, Marcel W; Hulf, Toby; Kench, James G; Henshall, Susan M; Pe Benito, Ruth; Haynes, Anne-Maree; Mayor, Regina; Peinado, Miguel A; Sutherland, Robert L; Clark, Susan J

    2011-01-01

    Previously, we showed that gene suppression commonly occurs across chromosome 2q14.2 in colorectal cancer, through a process of long-range epigenetic silencing (LRES), involving a combination of DNA methylation and repressive histone modifications. We now investigate whether LRES also occurs in prostate cancer across this 4-Mb region and whether differential DNA methylation of 2q14.2 genes could provide a regional panel of prostate cancer biomarkers. We used highly sensitive DNA methylation headloop PCR assays that can detect 10 to 25 pg of methylated DNA with a specificity of at least 1:1,000, and chromatin immunoprecipitation assays to investigate regional epigenetic remodeling across 2q14.2 in prostate cancer, in a cohort of 195 primary prostate tumors and 90 matched normal controls. Prostate cancer cells exhibit concordant deacetylation and methylation of histone H3 Lysine 9 (H3K9Ac and H3K9me2, respectively), and localized DNA hypermethylation of EN1, SCTR, and INHBB and corresponding loss of H3K27me3. EN1 and SCTR were frequently methylated (65% and 53%, respectively), whereas INHBB was less frequently methylated. Consistent with LRES in colorectal cancer, we found regional epigenetic remodeling across 2q14.2 in prostate cancer. Concordant methylation of EN1 and SCTR was able to differentiate cancer from normal (P < 0.0001) and improved the diagnostic specificity of GSTP1 methylation for prostate cancer detection by 26%. For the first time we show that DNA methylation of EN1 and SCTR promoters provide potential novel biomarkers for prostate cancer detection and in combination with GSTP1 methylation can add increased specificity and sensitivity to improve diagnostic potential. ©2011 AACR.

  8. Intrauterine intussusception: a rare cause of intestinal atresia.

    PubMed

    Pueyo, Carlos; Maldonado, Joaquín; Royo, Yolanda; Skrabski, Robert; Di Crosta, Ida; Raventós, Antoni

    2009-10-01

    Intrauterine intussusception is an uncommon cause of intestinal atresia. We report a case of ileal atresia owing to antenatal intussusception revealed as an intraluminal polypoid lesion after surgical intervention.

  9. Differential expression of extracellular-signal-regulated kinase 5 (ERK5) in normal and degenerated human nucleus pulposus tissues and cells

    SciTech Connect

    Liang, Weiguo; Fang, Dejian; Ye, Dongping; Zou, Longqiang; Shen, Yan; Dai, Libing; Xu, Jiake

    2014-07-11

    Highlights: • ERK5 involved in NP cells. • ERK5 involved in NP tissue. • It was important modulator. - Abstract: Extracellular-signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family and regulates a wide variety of cellular processes such as proliferation, differentiation, necrosis, apoptosis and degeneration. However, the expression of ERK5 and its role in degenerated human nucleus pulposus (NP) is hitherto unknown. In this study, we observed the differential expression of ERK5 in normal and degenerated human nucleus pulposus tissues by using immunohistochemical staining and Western blot. Treatment of NP cells with Pro-inflammatory cytokine, TNF-α decreased ERK5 gene expression as well as NP marker gene expression; including the type II collagen and aggrecan. Suppression of ERK5 gene expression in NP cells by ERK5 siRNA resulted in decreased gene expression of type II collagen and aggrecan. Furthermore, inhibition of ERK5 activation by BIX02188 (5 μM) decreased the gene expression of type II collagen and aggrecan in NP cells. Our results document the expression of ERK5 in degenerated nucleus pulposus tissues, and suggest a potential involvement of ERK5 in human degenerated nucleus pulposus.

  10. The Bayer: Activities of Daily Living Scale (B-ADL) in the differentiation between mild to moderate dementia and normal aging.

    PubMed

    Folquitto, Jefferson C; Bustamante, Sonia E Z; Barros, Sérgio B; Azevedo, Dionisio; Lopes, Marcos A; Hototian, Sergio R; Jacob Filho, Wilson; Litvoc, Júlio; Bottino, Cássio M C

    2007-12-01

    To investigate the applicability of the Bayer - Activities of Daily Living scale and its efficiency in differentiating individuals with mild to moderate dementia from normal elderly controls. We selected 33 patients with diagnosis of mild to severe dementia, according to ICD-10 criteria, and 59 controls. All the subjects were evaluated with the Mini-Mental State Examination and the Clinical Dementia Rating Scale and the Bayer - Activities of Daily Living scale was applied to informants. The internal consistency of the Bayer - Activities of Daily Living was high (Cronbach's alpha = 0.981). Mean Mini-Mental State Examination and Bayer - Activities of Daily Living scores of demented patients and controls were significantly different (p < 0.001). Mean Mini-Mental State Examination and Bayer - Activities of Daily Living scores were significantly different between Clinical Dementia Rating Scale 0 (controls; n = 59) versus Clinical Dementia Rating Scale 1 (mild dementia; n = 15), Clinical Dementia Rating Scale 0 versus Clinical Dementia Rating Scale 2 (moderate dementia; n = 13), and for Clinical Dementia Rating Scale 1 versus Clinical Dementia Rating Scale 2 (p < 0.003). The Bayer - Activities of Daily Living scale and Mini-Mental State Examination differentiated elderly controls from patients with mild or moderate dementia, and patients with mild dementia from those with moderate dementia. The results suggest that the Bayer - Activities of Daily Living scale applied to an informant can help in the diagnosis and follow-up of Brazilian patients with mild to moderate dementia.

  11. Global simulation of tropospheric water vapor measurements through the Normalized Differential Spectral Attenuation (NDSA) approach: setup, scintillation model and performance evaluation

    NASA Astrophysics Data System (ADS)

    Facheris, L.; Cuccoli, F.; Martini, E.; Kirchengast, G.; Schweitzer, S.

    2009-09-01

    NDSA (Normalized Differential Spectral Absorption) was recently proposed as a differential attenuation measurement method to estimate the total content of water vapor (IWV, Integrated Water Vapor) along a tropospheric propagation path between two Low Earth Orbit (LEO) satellites during a relative set/rise (occultation) event. The NDSA approach is based on the simultaneous estimate of the total attenuations at two relatively close frequencies and of a "spectral sensitivity parameter" that can be directly converted into IWV through empirical relationships that can be previously derived based on statistical regressions between spectral sensitivity and IWV simulated through real radiosonde data and a propagation model. In this paper we present the error performance in the IWV profile retrievals in the troposphere (up to 14 km) on the basis of an entire day of occultation events in a ECMWF-model simulated atmosphere. For the first time, we present results of simulations of NDSA measurements made in the millimeter band (in addition to the Ku/K bands analysed in previous works), specifically at 179 and 182 GHz.

  12. The use of differential staining of sister chromatid to estimate the in vitro effect of human alpha interferon on cell division in normal and tumour cells.

    PubMed

    Georgian, L; Moraru, I; Ghyka, G; Savi, I; Călugăru, A

    1986-01-01

    Concentration of 10, 100 and 1000 I.U./ml of human leukocyte alpha interferon (IFN) were added into peripheral human blood (PBL) cultures and in KB cell cultures in the presence of 5-bromdeoxyuridine (BrdU) at 10 micrograms/ml. After 72 hours the differential staining of sister chromatid (harlequin) technique was applied in order to differentiate among the metaphases of successive cell generations occurring in the presence of IFN. The frequency of the first (M1), second (M2) and third (M3) metaphases was recorded and the replication index (RI) as well as the average generation time (AGT) was calculated for untreated controls and for each of the IFN concentrations used, both in the blood cultures and in the KB cells. In the PBL cultures a clear dose-related inhibitory effect of IFN on cell division was observed, the RI values being lessened whereas the AGT concomitantly increased by increasing the IFN concentrations. An increase in M1 metaphase frequency was observed concomitantly with a diminished number of M3 cells. In KB cells the division kinetics was not influenced by IFN as indicated by similar RI and AGT values observed in controls and in IFN treated cells. However, the frequencies of both M1 and M3 cells were slightly diminished concomitantly with a discrete augmentation of M2 cell number. The differential staining of sister chromatid thus proved a highly useful technique to investigate the different sensitivity of the normal and malignant cells to the growth inhibitory effect induced by alpha IFN in vitro.

  13. Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development.

    PubMed Central

    Hansen, L. A.; Alexander, N.; Hogan, M. E.; Sundberg, J. P.; Dlugosz, A.; Threadgill, D. W.; Magnuson, T.; Yuspa, S. H.

    1997-01-01

    Mice harboring a targeted disruption of the epidermal growth factor receptor (EGFR) allele exhibit a severely disorganized hair follicle phenotype, fuzzy coat, and systemic disease resulting in death before 3 weeks. This skin phenotype was reproduced in whole skin grafts and in grafts of EGFR null hair follicle buds onto nude mice, providing a model to evaluate the natural evolution of skin lacking the EGFR. Hair follicles in grafts of null skin did not progress from anagen to telogen and scanning electron micrografts revealed wavy, flattened hair fibers with cuticular abnormalities. Many of the EGFR null hair follicles in the grafted skin were consumed by an inflammatory reaction resulting in complete hair loss in 67% of the grafts by 10 weeks. Localization of follicular differentiation markers including keratin 6, transglutaminase, and the hair keratins mHa2 and hacl-1 revealed a pattern of premature differentiation within the null hair follicles. In intact EGFR null mice, proliferation in the interfollicular epidermis, but not hair follicles, was greatly decreased in the absence of EGFR. In contrast, grafting of EGFR null skin resulted in a hyperplastic response in the epidermis that did not resolve even after 10 weeks, although the wound-induced hyperplasia in EGFR wild-type grafts had resolved within 3 to 4 weeks. Thus, epithelial expression of the EGFR has complex functions in the skin. It is important in delaying follicular differentiation, may serve to protect the hair follicle from immunological reactions, and modifies both normal and wound-induced epidermal proliferation but seems dispensable for follicular proliferation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:9176390

  14. Novel concepts about normal sexual differentiation of reproductive neuroendocrine function and the developmental origins of female reproductive dysfunction: the sheep model.

    PubMed

    Foster, D L; Jackson, L M; Padmanabhan, V

    2007-01-01

    The neuroendocrine regulation of GnRH secretion plays a central role in timing gamete release in both sexes. This regulation is more complex in the female because the discontinuous release of ova is more complex than the continuous release of spermatozoa. This review provides an evolving understanding of the sex differences in reproductive neuroendocrine controls and how these differences arise. The rules for sexual differentiation of steroid feedback control of GnRH secretion conceptually parallel the well-established principles that underlie the sexual differentiation of the internal and external genitalia. In the context of the neuroendocrine regulation of the ovarian cycle, and using the sheep as a model, four steroid feedback controls for GnRH secretion are inherent (default). They require no ovarian developmental input to function appropriately during adulthood. Two steroid feedback controls regulate the preovulatory surge mode of GnRH secretion, and two regulate the pulsatile mode. If the individual is a male, three steroid feedback controls of GnRH secretion become unnecessary or irrelevant, and these are abolished or become functionally inoperative through programmed reductions in hypothalamic sensitivity. This central programming occurs through exposure of presynaptic GnRH neurons in the developing male brain to the androgenic and estrogenic actions of testicular steroids. In precocial species such as ruminants, this programming begins well before birth. Understanding how GnRH secretion normally becomes sexually differentiated is of practical importance to determining how inappropriate hormonal environments during development can variously malprogram the neuroendocrine system to produce a variety of reproductive dysfunctions relating to patterning of gonadotropin secretion.

  15. Multimodality imaging of intrauterine devices with an emphasis on the emerging role of 3-dimensional ultrasound.

    PubMed

    Reiner, Jeffrey S; Brindle, Kathleen A; Khati, Nadia Juliet

    2012-12-01

    The intrauterine contraceptive device (IUD) is one of the most widely used reversible contraception methods throughout the world. With advancing technology, it has rapidly gained acceptance through its increased effectiveness and practicality compared with more invasive means such as laparoscopic tubal ligation. This pictorial essay will present the IUDs most commonly used today. It will illustrate both normal and abnormal positions of IUDs across all cross-sectional imaging modalities including 2-dimensional ultrasound, computed tomography, and magnetic resonance imaging, with a focus on the emerging role of 3-dimensional ultrasound as the modality of choice.

  16. [Combined intra-uterine and ectopic pregnancy following the treatment with clomiphen (author's transl)].

    PubMed

    Janata, J

    1978-06-01

    Report on a case of combined pregnancy in a 25 year old patient who was treated with Clomiphen for anovulatory cycles. The left tubal pregnancy was removed at 12 weeks gestation. The intra-uterine pregnancy resulted in a term delivery of a 3 kg. 670 g. normal infant. Combined pregnancies rarely occur without treatment with ovulation inducing agents by superfecundation and superfetation. Ovulation inducing agents increase the theoretical possibility of combined pregnancy. Obstetricians should be alert to the possibility of combined pregnancy following induction of ovulation.

  17. Early Adolescent Executive Functioning, Intrauterine Exposures and Own Drug Use

    PubMed Central

    Rose-Jacobs, Ruth; Soenksen, Shayna; Appugliese, Danielle P.; Cabral, Howard J.; Richardson, Mark A.; Beeghly, Marjorie; Heeren, Timothy C.; Frank, Deborah A.

    2011-01-01

    Individual differences in adolescents' executive functioning are often attributed either to intrauterine substance exposure or to adolescents' own substance use, but both predictors typically have not been evaluated simultaneously in the same study. This prospective study evaluated whether intrauterine drug exposures, the adolescents' own substance use, and/or their potential interactions are related to poorer executive functioning after controlling for important contextual variables. Analyses were based on data collected on a sample of 137 predominantly African-American/ African Caribbean adolescents from low-income urban backgrounds who were followed since their term birth. Intrauterine substance exposures (cocaine, marijuana, alcohol, cigarettes) and adolescents' substance use were documented using a combination of biological assays and maternal and adolescent self-report. At 12-14 years of age, examiners masked to intrauterine exposures and current substance use assessed the adolescents using the Delis-Kaplan Executive Function System (D-KEFS), an age-referenced instrument evaluating multiple dimensions of executive functioning (EF). Results of covariate-controlled analyses in this study suggest that when intrauterine substance exposures and young adolescents' substance use variables were in the same analysis models, subtle differences in specific EF outcomes were identifiable in this non-referred sample. While further study with larger samples is indicated, these findings suggest that 1) research on adolescent substance use and intrauterine exposure research should evaluate both predictors simultaneously; 2) subtle neurocognitive effects associated with specific intrauterine drug exposures can be identified during early adolescence; and 3) intrauterine substance exposure effects may differ from those associated with adolescents' own drug use. PMID:21371553

  18. Early adolescent executive functioning, intrauterine exposures and own drug use.

    PubMed

    Rose-Jacobs, Ruth; Soenksen, Shayna; Appugliese, Danielle P; Cabral, Howard J; Richardson, Mark A; Beeghly, Marjorie; Heeren, Timothy C; Frank, Deborah A

    2011-01-01

    Individual differences in adolescents' executive functioning are often attributed either to intrauterine substance exposure or to adolescents' own substance use, but both predictors typically have not been evaluated simultaneously in the same study. This prospective study evaluated whether intrauterine drug exposures, the adolescents' own substance use, and/or their potential interactions are related to poorer executive functioning after controlling for important contextual variables. Analyses were based on data collected on a sample of 137 predominantly African-American/African Caribbean adolescents from low-income urban backgrounds who were followed since their term birth. Intrauterine substance exposures (cocaine, marijuana, alcohol, and cigarettes) and adolescents' substance use were documented using a combination of biological assays and maternal and adolescent self-report. At 12-14 years of age, examiners masked to intrauterine exposures and current substance use assessed the adolescents using the Delis-Kaplan Executive Function System (D-KEFS), an age-referenced instrument evaluating multiple dimensions of executive functioning (EF). Results of covariate-controlled analyses in this study suggest that when intrauterine substance exposures and young adolescents' substance use variables were in the same analysis models, subtle differences in specific EF outcomes were identifiable in this non-referred sample. While further study with larger samples is indicated, these findings suggest that 1) research on adolescent substance use and intrauterine exposure research should evaluate both predictors simultaneously, 2) subtle neurocognitive effects associated with specific intrauterine drug exposures can be identified during early adolescence, and 3) intrauterine substance exposure effects may differ from those associated with adolescents' own drug use.

  19. Complications associated with intrauterine glass marbles in five mares.

    PubMed

    de Amorim, Mariana Diel; Chenier, Tracey; Nairn, Dawne; Green, Jodyne; Manning, Stephen; Card, Claire

    2016-11-15

    CASE DESCRIPTION 5 mares were evaluated because of reproductive complications following long-term (> 1 year) use of intrauterine glass marbles for estrus suppression. CLINICAL FINDINGS 3 mares had 1 intrauterine glass marble, and 2 mares had 2 intrauterine glass marbles. On examination, 2 mares had signs of chronic endometritis, and 3 had signs of pyometra. Marbles or glass shards adhered to the endometrium were identified by means of hysteroscopy in 3 of 5 mares. Five of 7 marbles had surface imperfections or were broken. TREATMENT AND OUTCOME All patients were treated with uterine lavage and intrauterine and systemic administration of antimicrobials chosen on the basis of results of bacterial culture and susceptibility testing. Two of 5 mares were treated with intrauterine Tris-EDTA. One mare underwent 3 unsuccessful embryo transfer procedures and was subsequently lost to follow-up. One mare was euthanized because of severe vaginal and cervical adhesions and chronic vaginal discharge. Three mares had no apparent signs of reproductive disease at the time of follow-up but were not rebred. CLINICAL RELEVANCE Results of the present small case series suggested that use of intrauterine glass marbles should be discouraged because of the potential for severe reproductive consequences.

  20. The effect of differentiated curriculum enhancements on the achievement of at-risk and normally achieving students in 5th grade science

    NASA Astrophysics Data System (ADS)

    Simpkins, Pamela Mccrea

    2007-12-01

    At-risk students show consistent patterns of under achievement and social maladjustment in school which leads to their demise in high school (McMillian & Reed, 1994). Similarly, special education students are at increased risk of not completing high school and do not perform as well on national achievement tests than their nondisabled peers (Land & Legters, 2002). It is possible that students at-risk for academic failure will not meet graduation requirements unless interventions are put in place to alleviate this problem. It has been documented that science textbooks contain difficult vocabulary and high reading levels that are challenging for struggling students. Using approaches such as activities oriented instruction, which supports the cooperative learning/peer tutoring model is one approach that has been successful with normally achieving and special education students. This research examined the effect of differentiated curriculum enhancements with peer tutoring on the achievement of at-risk and normally achieving students in science. A crossover design was implemented in three fifth grade inclusive classes, consisting of typically achieving students, students at-risk, and students with learning disabilities. The participants included 16 at-risk students, three special education students and 44 normally achieving students. The science review activities were implemented during two consecutive science units. One unit covered Earth and Space science. The other unit covered Light and Sound. Each curriculum enhancement had identification and production level activities. The identification level provided prompts; the production level did not provide prompts. Pretest and posttest were administered. Overall findings of the study revealed a significant interaction between experimental condition and treatment order, suggesting an advantage for students using differentiated curriculum enhancements. Main effects analysis suggested that students performed better on one

  1. Continuation of copper and levonorgestrel intrauterine devices: a retrospective cohort study.

    PubMed

    Phillips, Sharon J; Hofler, Lisa G; Modest, Anna M; Harvey, Lara F B; Wu, Lily H; Hacker, Michele R

    2017-07-01

    Studies conflict on whether the duration of use of the copper intrauterine device is longer than that of the levonorgestrel intrauterine device, and whether women who continue using intrauterine devices differ from those who discontinue. We sought to assess continuation rates and performance of levonorgestrel intrauterine devices compared with copper intrauterine devices over a 5-year period. We performed a retrospective cohort study of 1164 individuals who underwent intrauterine device placement at an urban academic medical center. The analysis focused on a comparison of continuation rates between those using levonorgestrel intrauterine device and copper intrauterine device, factors associated with discontinuation, and intrauterine device performance. We assessed the differences in continuation at discrete time points, pregnancy, and expulsion rates using χ(2) tests and calculated hazard ratios using a multivariable Cox model. Of 1164 women who underwent contraceptive intrauterine device insertion, 956 had follow-up data available. At 2 years, 64.9% of levonorgestrel intrauterine device users continued their device, compared with 57.7% of copper intrauterine device users (P = .11). At 4 years, continuation rates were 45.1% for levonorgestrel intrauterine device and 32.6% for copper intrauterine device (P < .01), and at 5 years continuation rates were 28.1% for levonorgestrel intrauterine device and 23.8% for copper intrauterine device (P = .33). Black race, primiparity, and age were positively associated with discontinuation; education was not. The hazard ratio for discontinuation of levonorgestrel intrauterine device compared with copper intrauterine device >4 years was 0.71 (95% confidence interval, 0.55-0.93) and >5 years was 0.82 (95% confidence interval, 0.64-1.05) after adjusting for race, age, parity, and education. Copper intrauterine device users were more likely to experience expulsion (10.2% copper intrauterine device vs 4.9% levonorgestrel

  2. Normal and Differential SAR Interferometry

    DTIC Science & Technology

    2007-02-01

    This Interferogramme is defined as the product of the complex SAR values of the second image with the complex conjugate of the reference image...which is covered by vegetation in the yellow Square. The phase information can be used for Digital Elevation Model (DEM) production , provided the...and X-Band There are a number of causes for de-correlation in Interferometry, and it is possible to write the coherence as a product of factors

  3. Normal and Differential SAR Interferometry

    DTIC Science & Technology

    2005-02-01

    Geudtner, B. Schättler, P. Vachon, U. Steinbrecher, J. Holzner, J. Mittermayer , H. Breit, A. Moreira. RADARSAT ScanSAR interferometry. In: Proceedings of...part 4, pp. 470-475 Krieger, G., Wendler, M., Fiedler, H., Mittermayer , J., Moreira, A., 2002. Performance analysis for bistatic interferometric...SAR configurations. In: Proceedings of IGARSS 2002, Toronto, Canada, vol. 1, pp. 650-652. Krieger, G., Fiedler, H., Mittermayer , J., Papathanassiou, K

  4. Placental Glucose transporter 3 (GLUT3) is Up-regulated in Human Pregnancies Complicated by Late-onset Intrauterine Growth Restriction

    PubMed Central

    Janzen, Carla; Lei, Margarida Y.Y.; Cho, John; Sullivan, Peggy; Shin, Bo-Chul; Devaskar, Sherin U.

    2013-01-01

    Introduction Transport of glucose from maternal blood across the placental trophoblastic tissue barrier is critical to sustain fetal growth. The mechanism by which GLUTs are regulated in trophoblasts in response to ischemic hypoxia encountered with intra-uterine fetal growth restriction (IUGR) has not been suitably investigated. Objective To investigate placental expression of GLUT1, GLUT3 and GLUT4 and possible mechanisms of GLUT regulation in idiopathic IUGR. Methods We analyzed clinical, biochemical and histological data from placentas collected from women affected by idiopathic full-term IUGR (n=10) and gestational age-matched healthy controls (n=10). Results We found increased GLUT3 protein expression in the trophoblast (cytotrophoblast greater than syncytiotrophoblast) on the maternal aspect of the placenta in IUGR compared to normal placenta, but no differences in GLUT1 or GLUT4 were found. No differential methylation of the GLUT3 promoter between normal and IUGR placentas was observed. Increased GLUT3 expression was associated with an increased nuclear concentration of HIF-1α, suggesting hypoxia may play a role in the up-regulation of GLUT3. Discussion Further studies are needed to elucidate whether increased GLUT3 expression in IUGR is a marker for defective villous maturation or an adaptive response of the trophoblast in response to chronic hypoxia. Conclusions Patients with IUGR have increased trophoblast expression of GLUT3, as found under the low-oxygen conditions of the first trimester. PMID:24011442

  5. Effect of treatment of intrauterine pathologies with office hysteroscopy in patients with recurrent IVF failure.

    PubMed

    Demirol, Aygul; Gurgan, Timur

    2004-05-01

    The study was conducted to evaluate if the diagnosis and treatment of intrauterine lesions with office hysteroscopy is of value in improving the pregnancy outcome in patients with recurrent in-vitro fertilization and embryo transfer failure. Four hundred and twenty-one patients who had undergone two or more failed IVF-embryo transfer cycles were prospectively randomized into two groups. Group I (n = 211) did not have office hysteroscopic evaluation, Group II (n = 210) had office hysteroscopy. The patients who had normal hysteroscopic findings were included in Group IIa (n = 154) and patients who had abnormal hysteroscopic findings were included in Group IIb (n = 56). Intrauterine lesions diagnosed were operated during the office procedure. Fifty-six (26%) patients in Group II had intrauterine pathologies and the treatment was performed at the same time. No difference existed in the mean number of oocyte retrieved, fertilization rate, number of embryos transferred or first trimester abortion rates among the patients in groups. Clinical pregnancy rates in Group I, Group IIa and Group IIb were 21.6%, 32.5% and 30.4% respectively. There was a significant difference in the clinical pregnancy rates between patients in Group I and Group IIa (21.6% and 32.5%, P = 0.044, respectively) and Group I and Group IIb (21.6% and 30.4%, P = 0.044, respectively). There was no significant difference in the clinical pregnancy rate of patients in Groups IIa and IIb. Patients with normal hysterosalpingography but recurrent IVF-embryo transfer failure should be evaluated prior to commencing IVF-embryo transfer cycle to improve the clinical pregnancy rate.

  6. Intrauterine Growth Restriction: Hungry for an Answer

    PubMed Central

    Chu, Alison

    2016-01-01

    Intrauterine growth restriction (IUGR) has been defined in several ways, but in general describes a condition in which the fetus exhibits poor growth in utero. This complication of pregnancy poses a significant public health burden as well as increased morbidity and mortality for the offspring. In human IUGR, alteration in fetal glucose and insulin homeostasis occurs in an effort to conserve energy and survive at the expense of fetal growth in an environment of inadequate nutrient provision. Several animal models of IUGR have been utilized to study the effects of IUGR on fetal glucose handling, as well as the postnatal reprogramming of energy metabolite handling, which may be unmasked in adulthood as a maladaptive propensity for cardiometabolic disease. This developmental programming may be mediated in part by epigenetic modification of essential regulators of glucose homeostasis. Several pharmacological therapies and nonpharmacological lifestyle modifications have shown early promise in mitigating the risk for or severity of adult metabolic phenotypes but still require further study of unanticipated and/or untoward side effects. PMID:26889018

  7. A clinical evaluation of intrauterine contraceptive devices.

    PubMed

    Mukherjee, S N; Mukherjee, S

    1968-04-01

    A report on a small clinical trial with a plastic intrauterine contraceptive device (Lippes loop) among South Indian women is presented. A total of 450 women were fitted with the IUDs and were observed from July 1966 to June 1967, with a total exposure of 1411 woman-months. Women aged 20-30 years comprised 73.3% of the cases. Two-thirds of the cases belonged to the 3-6 parity group. The complication rate was 21.1%. The commonest side effect was vaginal bleeding in 13.3% of the cases. The spontaneous expulsion rate was 5.5%, and the removal rate was 5.3%. The commonest reason for removal was vaginal bleeding. The pregnancy rate was 2.55 per 100 woman-years of exposure. A total of 52 women (11.5%) were found unsuitable for the device. Most of the insertions were performed within the first week of the menstrual period. It was concluded that the acceptance of the method was satisfactory.

  8. Umbilical cord stricture and intrauterine fetal death.

    PubMed

    Sun, Y; Arbuckle, S; Hocking, G; Billson, V

    1995-01-01

    Umbilical cord stricture is an uncommon but distinctive condition associated with intrauterine fetal death. Although cases have been reported periodically since the last century, there has been considerable speculation as to whether the condition is real or a postmortem artifact. In the present study, 25 cases reported since 1925 are reviewed and 8 new cases are described. Clinically, a decrease in fetal movements is usually the only symptom during the second or third trimester of pregnancy and fetal death occurs soon after. The women's age, health, and previous history have shown no link with this condition, but a higher incidence is noted in twin pregnancies. Morphologically, most infants are macerated and an extremely narrow segment of umbilical cord is usually seen at the fetal end and rarely at the placental end or in multiple sites along the cord. Absence of Wharton's jelly, stenosis, or obliteration of cord vessels at the narrow segment and intravascular cord thrombosis are the major pathological features. The findings of this study support the view that the condition can cause fetal death and alerts both pathologists and clinicians to the important features identifying this cause of perinatal wastage.

  9. Comprehensive processing of high throughput small RNA sequencing data including quality checking, normalization and differential expression analysis using the UEA sRNA Workbench.

    PubMed

    Beckers, Matthew L; Mohorianu, Irina; Stocks, Matthew B; Applegate, Christopher; Dalmay, Tamas; Moulton, Vincent

    2017-03-13

    Recently High Throughput Sequencing (HTS) has revealed compelling details about the small RNA (sRNA) population in eukaryotes. These 20-25 nt non-coding RNAs can influence gene expression by acting as guides for the sequence-specific regulatory mechanism known as RNA silencing. The increase in sequencing depth and number of samples per project enables a better understanding of the role sRNAs play by facilitating the study of expression patterns. However, the intricacy of the biological hypotheses coupled with a lack of appropriate tools often leads to inadequate mining of the available data and thus, an incomplete description of the biological mechanisms involved. To enable a comprehensive study of differential expression in sRNA datasets we present a new interactive pipeline that guides researchers through the various stages of data pre-processing and analysis. This includes various tools, some of which we specifically developed for sRNA analysis, for quality checking and normalization of sRNA samples as well as tools for the detection of differentially expressed sRNAs and identification of the resulting expression patterns. The pipeline is available within the UEA sRNA Workbench, a user-friendly software package for the processing of sRNA datasets. We demonstrate the use of the pipeline on a H. sapiens dataset; additional examples on a B. terrestris dataset and on an A. thaliana dataset are described in the supplementary information. A comparison with existing approaches is also included, which exemplifies some of the issues that need to be addressed for sRNA analysis, and how the new pipeline may be used to do this.

  10. MO-F-CAMPUS-I-04: Characterization of Fan Beam Coded Aperture Coherent Scatter Spectral Imaging Methods for Differentiation of Normal and Neoplastic Breast Structures

    SciTech Connect

    Morris, R; Albanese, K; Lakshmanan, M; Greenberg, J; Kapadia, A

    2015-06-15

    Purpose: This study intends to characterize the spectral and spatial resolution limits of various fan beam geometries for differentiation of normal and neoplastic breast structures via coded aperture coherent scatter spectral imaging techniques. In previous studies, pencil beam raster scanning methods using coherent scatter computed tomography and selected volume tomography have yielded excellent results for tumor discrimination. However, these methods don’t readily conform to clinical constraints; primarily prolonged scan times and excessive dose to the patient. Here, we refine a fan beam coded aperture coherent scatter imaging system to characterize the tradeoffs between dose, scan time and image quality for breast tumor discrimination. Methods: An X-ray tube (125kVp, 400mAs) illuminated the sample with collimated fan beams of varying widths (3mm to 25mm). Scatter data was collected via two linear-array energy-sensitive detectors oriented parallel and perpendicular to the beam plane. An iterative reconstruction algorithm yields images of the sample’s spatial distribution and respective spectral data for each location. To model in-vivo tumor analysis, surgically resected breast tumor samples were used in conjunction with lard, which has a form factor comparable to adipose (fat). Results: Quantitative analysis with current setup geometry indicated optimal performance for beams up to 10mm wide, with wider beams producing poorer spatial resolution. Scan time for a fixed volume was reduced by a factor of 6 when scanned with a 10mm fan beam compared to a 1.5mm pencil beam. Conclusion: The study demonstrates the utility of fan beam coherent scatter spectral imaging for differentiation of normal and neoplastic breast tissues has successfully reduced dose and scan times whilst sufficiently preserving spectral and spatial resolution. Future work to alter the coded aperture and detector geometries could potentially allow the use of even wider fans, thereby making coded

  11. Effects of intrauterine contraception on the vaginal microbiota.

    PubMed

    Bassis, Christine M; Allsworth, Jenifer E; Wahl, Heather N; Sack, Daniel E; Young, Vincent B; Bell, Jason D

    2017-09-01

    There have been conflicting reports of altered vaginal microbiota and infection susceptibility associated with contraception use. The objectives of this study were to determine if intrauterine contraception altered the vaginal microbiota and to compare the effects of a copper intrauterine device (Cu-IUD) and a levonorgestrel intrauterine system (LNG-IUS) on the vaginal microbiota. DNA was isolated from the vaginal swab samples of 76 women using Cu-IUD (n=36) or LNG-IUS (n=40) collected prior to insertion of intrauterine contraception (baseline) and at 6 months. A third swab from approximately 12 months following insertion was available for 69 (Cu-IUD, n=33; LNG-IUS, n=36) of these women. The V4 region of the bacterial 16S rRNA-encoding gene was amplified from the vaginal swab DNA and sequenced. The 16S rRNA gene sequences were processed and analyzed using the software package mothur to compare the structure and dynamics of the vaginal bacterial communities. The vaginal microbiota from individuals in this study clustered into 3 major vaginal bacterial community types: one dominated by Lactobacillus iners, one dominated by Lactobacillus crispatus and one community type that was not dominated by a single Lactobacillus species. Changes in the vaginal bacterial community composition were not associated with the use of Cu-IUD or LNG-IUS. Additionally, we did not observe a clear difference in vaginal microbiota stability with Cu-IUD versus LNG-IUS use. Although the vaginal microbiota can be highly dynamic, alterations in the community associated with the use of intrauterine contraception (Cu-IUD or LNG-IUS) were not detected over 12 months. We found no evidence that intrauterine contraception (Cu-IUD or LNG-IUS) altered the vaginal microbiota composition. Therefore, the use of intrauterine contraception is unlikely to shift the composition of the vaginal microbiota such that infection susceptibility is altered. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Differential Mechanisms Associated with Vascular Disrupting Action of Electrochemotherapy: Intravital Microscopy on the Level of Single Normal and Tumor Blood Vessels

    PubMed Central

    Markelc, Bostjan; Sersa, Gregor; Cemazar, Maja

    2013-01-01

    Electropermeabilization/electroporation (EP) provides a tool for the introduction of molecules into cells and tissues. In electrochemotherapy (ECT), cytotoxic drugs are introduced into cells in tumors, and nucleic acids are introduced into cells in gene electrotransfer. The normal and tumor tissue blood flow modifying effects of EP and the vascular disrupting effect of ECT in tumors have already been determined. However, differential effects between normal vs. tumor vessels, to ensure safety in the clinical application of ECT, have not been determined yet. Therefore, the aim of our study was to determine the effects of EP and ECT with bleomycin on the HT-29 human colon carcinoma tumor model and its surrounding blood vessels. The response of blood vessels to EP and ECT was monitored in real time, directly at the single blood vessel level, by in vivo optical imaging in a dorsal window chamber in SCID mice with 70 kDa fluorescently labeled dextrans. The response of tumor blood vessels to EP and ECT started to differ within the first hour. Both therapies induced a vascular lock, decreased functional vascular density (FVD) and increased the diameter of functional blood vessels within the tumor. The effects were more pronounced for ECT, which destroyed the tumor blood vessels within 24 h. Although the vasculature surrounding the tumor was affected by EP and ECT, it remained functional. The study confirms the current model of tumor blood flow modifying effects of EP and provides conclusive evidence that ECT is a vascular disrupting therapy with a specific effect on the tumor blood vessels. PMID:23555705

  13. Differential mechanisms associated with vascular disrupting action of electrochemotherapy: intravital microscopy on the level of single normal and tumor blood vessels.

    PubMed

    Markelc, Bostjan; Sersa, Gregor; Cemazar, Maja

    2013-01-01

    Electropermeabilization/electroporation (EP) provides a tool for the introduction of molecules into cells and tissues. In electrochemotherapy (ECT), cytotoxic drugs are introduced into cells in tumors, and nucleic acids are introduced into cells in gene electrotransfer. The normal and tumor tissue blood flow modifying effects of EP and the vascular disrupting effect of ECT in tumors have already been determined. However, differential effects between normal vs. tumor vessels, to ensure safety in the clinical application of ECT, have not been determined yet. Therefore, the aim of our study was to determine the effects of EP and ECT with bleomycin on the HT-29 human colon carcinoma tumor model and its surrounding blood vessels. The response of blood vessels to EP and ECT was monitored in real time, directly at the single blood vessel level, by in vivo optical imaging in a dorsal window chamber in SCID mice with 70 kDa fluorescently labeled dextrans. The response of tumor blood vessels to EP and ECT started to differ within the first hour. Both therapies induced a vascular lock, decreased functional vascular density (FVD) and increased the diameter of functional blood vessels within the tumor. The effects were more pronounced for ECT, which destroyed the tumor blood vessels within 24 h. Although the vasculature surrounding the tumor was affected by EP and ECT, it remained functional. The study confirms the current model of tumor blood flow modifying effects of EP and provides conclusive evidence that ECT is a vascular disrupting therapy with a specific effect on the tumor blood vessels.

  14. Laminin alpha 5, a major transcript of normal and malignant rat liver epithelial cells, is differentially expressed in developing and adult liver.

    PubMed

    Seebacher, T; Medina, J L; Bade, E G

    1997-11-25

    The laminin family of extracellular matrix glycoproteins plays a major role in cell migration and differentiation and in tumor cell invasion. As previously shown, the laminin deposited by normal and malignant rat liver epithelial cells in their extracellular matrix (ECM) and into their ECM migration tracks does not contain a typical (EHS-like) alpha 1 heavy chain. By RT-PCR screening we have now identified two alpha chains among a total of five additional laminin chains produced by these cells. Three of the newly identified chains were not previously known for the rat. Their sequences have been deposited in the EMBL nucleotide sequence data bank. The alpha 5 chain now identified is expressed at comparably high levels by both the normal and the malignant liver epithelial cells. The chain is also expressed in fetal liver together with the alpha 2 and beta 2 chains, but it is only vestigially expressed in the mature organ as shown by RT-PCR. These results suggest for alpha 5 a role in development and production of the chain by only a small subset of cells in adult liver. At the level of detection used, no changes were observed in regenerating liver after partial hepatectomy. In addition to the alpha 5 chain, the cultured cells express the beta 1 and beta 2 light chains, indicating the expression of more than one laminin isoform by the same cell line. The expression of the alpha 5 chain and of the other new non-EHS isoform chains was also analyzed in various tissues. The malignant liver epithelial cells, but not their nontumorigenic parental cells, also express, in addition to the alpha 5 chain the alpha 2 chain, which is expressed at high level by the NBT II bladder carcinoma cell line, suggesting a relationship with malignancy.

  15. Differentiation of the mRNA transcripts originating from the alpha 1- and alpha 2-globin loci in normals and alpha-thalassemics.

    PubMed

    Liebhaber, S A; Kan, Y W

    1981-08-01

    The alpha-globin polypeptide is encoded by two adjacent genes, alpha 1 and alpha 2. In the normal diploid state (alpha alpha/alpha alpha) all four alpha-globin genes are expressed. Loss or dysfunction of one or more of these genes leads to deficient alpha-globin production and results in alpha-thalassemia. We present a technique to differentially assess the steady-state levels of the alpha 1- and alpha-2-globin messenger RNA (mRNA) transcripts and thus delineate the relative level of expression of the two alpha-globin loci in a variety of alpha-thalassemia states. Only alpha 1 mRNA was produced in the alpha-thalassemia-2 haplotype (-alpha) (one of the two alpha-globin genes deleted from chromosome 16). This confirms previous gene mapping data which demonstrate deletion of the alpha 2 gene. The triple alpha-globin gene haplotype (alpha alpha alpha) is the reciprocal of the alpha-thalassemia-2 haplotype and thus contains an extra alpha 2-globin gene. RNA from this haplotype contained a greater than normal level of alpha 2-relative to alpha 1-globin mRNA. This data implies that the extra alpha 2 gene in the triple alpha-globin haplotype is functional. We detected a relative instability of the alpha 2-globin mRNA encoding the alpha-globin structural mutant Constant Spring. This instability may contribute to the low level of expression of the alpha-Constant Spring protein. In a Chinese patient with nondeletion hemoglobin-H disease (- -/alpha alpha T) (both alpha-globin genes are present but not fully functional) a normal ratio was maintained between the levels of alpha 1- and alpha 2-globin mRNA, implying that mRNA production from both alpha-globin genes is suppressed in a balanced manner. These observations extended previous findings concerning the structural rearrangements in the deletion types of alpha-thalassemia and the pathophysiology of two nondeletion variants.

  16. Stem Cell Differentiation Stage Factors from Zebrafish Embryo: A Novel Strategy to Modulate the Fate of Normal and Pathological Human (Stem) Cells

    PubMed Central

    Biava, Pier M.; Canaider, Silvia; Facchin, Federica; Bianconi, Eva; Ljungberg, Liza; Rotilio, Domenico; Burigana, Fabio; Ventura, Carlo

    2015-01-01

    In spite of the growing body of evidence on the biology of the Zebrafish embryo and stem cells, including the use of Stem Cell Differentiation Stage Factors (SCDSFs) taken from Zebrafish embryo to impact cancer cell dynamics, comparatively little is known about the possibility to use these factors to modulate the homeostasis of normal human stem cells or to modulate the behavior of cells involved in different pathological conditions. In the present review we recall in a synthetic way the most important researches about the use of SCDSFs in reprogramming cancer cells and in modulating the high speed of multiplication of keratinocytes which is characteristic of some pathological diseases like psoriasis. Moreover we add here the results about the capability of SCDSFs in modulating the homeostasis of human adipose-derived stem cells (hASCs) isolated from a fat tissue obtained with a novel-non enzymatic method and device. In addition we report the data not yet published about a first protein analysis of the SCDSFs and about their role in a pathological condition like neurodegeneration. PMID:26201607

  17. COMMUNICATION: Folate and S-adenosylmethionine modulate synaptic activity in cultured cortical neurons: acute differential impact on normal and apolipoprotein-deficient mice

    NASA Astrophysics Data System (ADS)

    Serra, Michael; Chan, Amy; Dubey, Maya; Gilman, Vladimir; Shea, Thomas B.

    2008-12-01

    Folate deficiency is accompanied by a decline in the cognitive neurotransmitter acetylcholine and a decline in cognitive performance in mice lacking apolipoprotein E (ApoE-/- mice), a low-density lipoprotein that regulates aspects of lipid metabolism. One direct consequence of folate deficiency is a decline in S-adenosylmethionine (SAM). Since dietary SAM supplementation maintains acetylcholine levels and cognitive performance in the absence of folate, we examined herein the impact of folate and SAM on neuronal synaptic activity. Embryonic cortical neurons from mice expressing or lacking ApoE (ApoE+/+ or -/-, respectively) were cultured for 1 month on multi-electrode arrays, and signaling was recorded. ApoE+/+ cultures displayed significantly more frequent spontaneous signals than ApoE-/- cultures. Supplementation with 166 µm SAM (not normally present in culture medium) increased signal frequency and decreased signal amplitude in ApoE+/+ cultures. SAM also increased the frequency of tightly clustered signal bursts. Folate deprivation reversibly reduced signal frequency in ApoE+/+ cultures; SAM supplementation maintained signal frequency despite folate deprivation. These findings support the importance of dietary supplementation with folate and SAM on neuronal health. Supplementation with 166 µm SAM did not alter signaling in ApoE-/- cultures, which may be a reflection of the reduced SAM levels in ApoE-/- mice. The differential impact of SAM on ApoE+/+ and -/- neurons underscores the combined impact of nutritional and genetic deficiencies on neuronal homeostasis.

  18. Stem Cell Differentiation Stage Factors from Zebrafish Embryo: A Novel Strategy to Modulate the Fate of Normal and Pathological Human (Stem) Cells.

    PubMed

    Biava, Pier M; Canaider, Silvia; Facchin, Federica; Bianconi, Eva; Ljungberg, Liza; Rotilio, Domenico; Burigana, Fabio; Ventura, Carlo

    2015-01-01

    In spite of the growing body of evidence on the biology of the Zebrafish embryo and stem cells, including the use of Stem Cell Differentiation Stage Factors (SCDSFs) taken from Zebrafish embryo to impact cancer cell dynamics, comparatively little is known about the possibility to use these factors to modulate the homeostasis of normal human stem cells or to modulate the behavior of cells involved in different pathological conditions. In the present review we recall in a synthetic way the most important researches about the use of SCDSFs in reprogramming cancer cells and in modulating the high speed of multiplication of keratinocytes which is characteristic of some pathological diseases like psoriasis. Moreover we add here the results about the capability of SCDSFs in modulating the homeostasis of human adiposederived stem cells (hASCs) isolated from a fat tissue obtained with a novel-non enzymatic method and device. In addition we report the data not yet published about a first protein analysis of the SCDSFs and about their role in a pathological condition like neurodegeneration.

  19. Characterization of six small HSP genes from Chironomus riparius (Diptera, Chironomidae): Differential expression under conditions of normal growth and heat-induced stress.

    PubMed

    Martín-Folgar, Raquel; de la Fuente, Mercedes; Morcillo, Gloria; Martínez-Guitarte, José-Luis

    2015-10-01

    Small heat shock proteins (sHSPs) comprise the most numerous, structurally diverse, and functionally uncharacterized family of heat shock proteins. Several Hsp genes (Hsp 90, 70, 40, and 27) from the insect Chironomus riparius are widely used in aquatic toxicology as biomarkers for environmental toxins. Here, we conducted a comparative study and characterized secondary structure of the six newly identified sHsp genes Hsp17, Hsp21, Hsp22, Hsp23, Hsp24, and Hsp34. A characteristic α-crystallin domain is predicted in all the new proteins. Phylogenetic analysis suggests a strong relation to other sHSPs from insects and interesting evidence regarding evolutionary origin and duplication events. Comparative analysis of transcription profiles for Hsp27, Hsp70, and the six newly identified genes revealed that Hsp17, Hsp21, and Hsp22 are constitutively expressed under normal conditions, while under two different heat shock conditions these genes are either not activated or are even repressed (Hsp22). In contrast, Hsp23, Hsp24, and Hsp34 are significantly activated along with Hsp27 and Hsp70 during heat stress. These results strongly suggest functional differentiation within the small HSP subfamily and provide new data to help understand the coping mechanisms induced by stressful environmental stimuli.

  20. Characterization and differential expression of a newly identified phosphorylated isoform of the human 20S proteasome beta7 subunit in tumor vs. normal cell lines.

    PubMed

    Eang, Rothmony; Girbal-Neuhauser, Elisabeth; Xu, Bo; Gairin, Jean Edouard

    2009-04-01

    The search of new pharmacological targets with original mechanism of action within the ubiquitin-proteasome pathway is still a goal to be reached in oncopharmacology. Modification by phosphorylation/dephosphorylation has been found to be involved in cancer and to regulate functional activity of proteasome. Until now, phosphorylated forms of alpha subunits of the 20S human proteasome have been mostly reported. Here, we have rationally designed a polyclonal antibody specifically directed against a phosphorylated peptide sequence bearing the beta7 subunit Ser249 residue of the human 20S proteasome. This anti-beta7 phosphoSer249 antibody appeared to be a probe of choice to detect the presence of a phosphorylated isoform of the beta7 subunit of the human 20S proteasome using mono or two-dimensional gel electrophoresis. PhosphoSer249 was sensitive to acid phosphatase treatment of native 20S proteasome. Dephosphorylation affected the peptidylglutamyl-peptide hydrolyzing activity whereas the chymotrypsin-like and trypsin-like activities remained unchanged. A comparative analysis between human normal and tumor cells showed a differential expression of the phosphoSer249 beta7 isoform with a significantly lower detection in the proteasome isolated from tumor cells, suggesting its possible use as a biomarker.

  1. Measurements of normalized differential cross sections for tt¯ production in pp collisions at (s)=7  TeV using the ATLAS detector

    DOE PAGES

    Aad, G.; Abajyan, T.; Abbott, B.; ...

    2014-10-13

    We present measurements of normalized differential cross sections for top-quark pair production as a function of the top-quark transverse momentum, and of the mass, transverse momentum, and rapidity of the t¯t system, in proton–proton collisions at a center-of-mass energy of √ s=7 TeV. The data set corresponds to an integrated luminosity of 4.6 fb₋1, recorded in 2011 with the ATLAS detector at the CERN Large Hadron Collider. Events are selected in the lepton + jets channel, requiring exactly one lepton and at least four jets with at least one of the jets tagged as originating from a b-quark. The measuredmore » spectra are corrected for detector efficiency and resolution effects and are compared to several Monte Carlo simulations and theory calculations. The results are in fair agreement with the predictions in a wide kinematic range. Nevertheless, data distributions are softer than predicted for higher values of the mass of the t¯t system and of the top-quark transverse momentum. Lastly, the measurements can also discriminate among different sets of parton distribution functions.« less

  2. SpliceNet: recovering splicing isoform-specific differential gene networks from RNA-Seq data of normal and diseased samples.

    PubMed

    Yalamanchili, Hari Krishna; Li, Zhaoyuan; Wang, Panwen; Wong, Maria P; Yao, Jianfeng; Wang, Junwen

    2014-09-01

    Conventionally, overall gene expressions from microarrays are used to infer gene networks, but it is challenging to account splicing isoforms. High-throughput RNA Sequencing has made splice variant profiling practical. However, its true merit in quantifying splicing isoforms and isoform-specific exon expressions is not well explored in inferring gene networks. This study demonstrates SpliceNet, a method to infer isoform-specific co-expression networks from exon-level RNA-Seq data, using large dimensional trace. It goes beyond differentially expressed genes and infers splicing isoform network changes between normal and diseased samples. It eases the sample size bottleneck; evaluations on simulated data and lung cancer-specific ERBB2 and MAPK signaling pathways, with varying number of samples, evince the merit in handling high exon to sample size ratio datasets. Inferred network rewiring of well established Bcl-x and EGFR centered networks from lung adenocarcinoma expression data is in good agreement with literature. Gene level evaluations demonstrate a substantial performance of SpliceNet over canonical correlation analysis, a method that is currently applied to exon level RNA-Seq data. SpliceNet can also be applied to exon array data. SpliceNet is distributed as an R package available at http://www.jjwanglab.org/SpliceNet.

  3. Lost intrauterine devices during pregnancy: maternal and fetal outcome after ultrasound-guided extraction. An analysis of 82 cases.

    PubMed

    Schiesser, M; Lapaire, O; Tercanli, S; Holzgreve, W

    2004-05-01

    It is generally agreed that intrauterine devices (IUDs) with visible strings in pregnancy should be removed because of the increased risk of miscarriage, septic complications and premature delivery. The precise management of pregnancies in association with so-called 'lost IUDs', and especially the technique of their removal, has remained controversial. We present our experience of the management of intrauterine pregnancies with a lost IUD. Ultrasound-guided extraction of a lost IUD was performed in 82 intrauterine pregnancies. The subsequent outcome of the pregnancies is described. There were no intra- or post-procedure maternal complications. Although the miscarriage rate in the first 3 weeks after the procedure was higher than that in normal pregnancy, the complication rate approached that of normal pregnancy as the pregnancies progressed. The total miscarriage rate of 22% was comparable to that following extraction of IUDs with visible filaments. The rate of live births was 77.0%. Delivery before 37 weeks occurred in 13.5% of cases. Ultrasound-guided extraction is a minimally invasive and inexpensive procedure that is associated with few postoperative complications. It has a high success rate and is associated with a moderate miscarriage rate and no maternal complications. Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd.

  4. Management of Intrauterine Contraception in Early Pregnancy.

    PubMed

    Ramesh, Shanthi S; Charm, Samantha; Kalinowski, Alison; Liberty, Abigail L; Stuart, Gretchen S

    2017-08-01

    Women with rare intrauterine contraception (IUC) failures are advised to have their IUC removed because of the risk of poor obstetric outcomes with a retained IUC. Specifics regarding IUC removal in early pregnancy including techniques for removal, rates of success, and immediate pregnancy outcomes following removal are not well described, however. The objective of this study was to identify women with an IUC in early pregnancy examined at a tertiary care center with the primary objective of describing IUC removal attempts, IUC removal successes, and pregnancy outcomes at 20 weeks following IUC removal. Case series of women with concurrent IUC and early pregnancy who presented to a tertiary care ultrasound center by 12 weeks' gestation. A total of 3116 women had an early pregnancy ultrasound during the study period. Nineteen (19/3116, 0.61%) women underwent ultrasounds that identified a pregnancy before 12 weeks and an IUC in the uterus. A copper IUC was identified in 11 women (11/19, 58%) on their first ultrasound, and a levonogestrel IUC was identified in 5 women (5/19, 26%). Seventeen (17/19, 88%) women attempted to remove their IUC; 11 of 69 (69%) were successfully removed on the first attempt. Fourteen (14/19; 74%) women with an IUC examined by 12 weeks' gestation had an ongoing pregnancy at 20 weeks compared with 1782 (1782/2678, 67%; P = 0.209) women without an IUC. Pregnancy with IUC is rare. Among the 19 women who were found to have an in situ IUC and early pregnancy, most had a successful IUC removal and had an ongoing pregnancy at 20 weeks' gestation. In our case series, IUC removal in the first trimester was a straightforward procedure and likely successful.

  5. Patterns of Candida biofilm on intrauterine devices.

    PubMed

    Zahran, Kamal M; Agban, Michael N; Ahmed, Shaaban H; Hassan, Ehsan A; Sabet, Marwa A

    2015-04-01

    Biofilms are colonies of microbial cells encased in a self-produced organic polymeric matrix and represent a common mode of microbial growth. Microbes growing as biofilm are highly resistant to commonly used antimicrobial drugs. We aimed to screen and characterize biofilm formation by different isolates of Candida on removed intrauterine devices (IUDs), to perform experimental biofilm formation with isolated strains, and to examine biofilm by the crystal violet and XTT reduction assays and scanning electron microscopy (SEM). A total of 56 IUDs were examined for biofilm formation using Sabouraud's dextrose chloramphenicol agar. Suspected colonies were identified by different methods. Antifungal susceptibility testing with fluconazole (FLU) and amphotericin B for the isolated strains and in vitro experimental biofilm formation was carried out. The biofilm was quantified by crystal violet, XTT reduction assay and SEM. Among the 56 IUDs investigated, 26 were Candida positive (46.4 %). Candida albicans was recovered from 15 isolates. The biofilm MIC of FLU was increased 64 to 1000 times compared to the MIC for planktonic cells. The XTT method results were dependent on the Candida species; biofilm formation was highest in Candida krusei and Candida glabrata strains, followed by C. albicans and Candida tropicalis. SEM of Candida biofilm revealed a heterogeneous thick biofilm with a mixture of micro-organisms. The main conclusion from this study was non-albicans Candida represents more than a half of the Candida biofilm. Better understanding of Candida biofilms may lead to the development of novel therapeutic approaches for the treatment of fungal infections, especially resistant ones among IUD users. © 2015 The Authors.

  6. Hysteroscopic sterilization of patient with intrauterine device Mirena®

    PubMed Central

    Depes, Daniella De Batista; Pereira, Ana Maria Gomes; Yatabe, Salete; Lopes, Reginaldo Guedes Coelho

    2013-01-01

    ABSTRACT Tubal sterilization is the definitive procedure most often used worldwide to control fecundity. Laparoscopic ligature is safe, but invasive and with possible surgical and anesthetic risks. The hysteroscopic approach enables tubal occlusion at outpatient's setting without the need of incisions or anesthesia. A microdevice (Essure®) is inserted directly into the tubes and its polyethelene fibers cause obstruction of tubes in about three months. During this period, it is recommended that patients continue the use of a temporary birth control method. Several women use the levonorgestrel-releasing intrauterine system, which is called in the market as Mirena®. This report evaluated the possibility of inserting Essure® without remove the intrauterine device; patient tolerance to the procedure was also assessed. The tubal device was successfully placed in the patient without the need to remove Mirena®. After three months the intrauterine device was removed with no intercurrent events. PMID:23579753

  7. A Lower-Cost Option for Intrauterine Contraception.

    PubMed

    Angelini, Kim

    2016-01-01

    In March 2015, the U.S. Food and Drug Administration approved Liletta (Actavis, Dublin, Ireland), a new intrauterine device for contraception. The Centers for Disease Control and Prevention recommend use of long-acting reversible contraception (LARC) as first-line pregnancy prevention. LARC efficacy rates are similar to those of sterilization, with the possibility for quick return of fertility upon removal of the device. Despite benefits and recommendations for this form of contraception, access and high cost remain barriers to use. Liletta is the first lower-cost option for intrauterine contraception. Available to qualified clinics and health centers at a reduced rate, this device may increase availability and decrease the overall cost to women who desire intrauterine contraception.

  8. Duplex Doppler ultrasonographic evaluation of the fetal renal artery in normal and abnormal fetuses.

    PubMed

    Veille, J C; Kanaan, C

    1989-12-01

    Using duplex Doppler ultrasonography in asymmetrically grown fetuses with decreased amniotic fluid, we found the renal artery waveform pattern was different from that in the normally grown fetus. Such an abnormal waveform may reflect an increase in vascular resistance within the renal bed in oligohydramnios and intrauterine growth retardation. This would suggest that local mechanisms are operational and may influence renal blood flow in the human fetus with intrauterine growth retardation.

  9. 21 CFR 884.5360 - Contraceptive intrauterine device (IUD) and introducer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Contraceptive intrauterine device (IUD) and... Gynecological Therapeutic Devices § 884.5360 Contraceptive intrauterine device (IUD) and introducer. (a) Identification. A contraceptive intrauterine device (IUD) is a device used to prevent pregnancy. The device is...

  10. 21 CFR 884.5360 - Contraceptive intrauterine device (IUD) and introducer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Contraceptive intrauterine device (IUD) and... Gynecological Therapeutic Devices § 884.5360 Contraceptive intrauterine device (IUD) and introducer. (a) Identification. A contraceptive intrauterine device (IUD) is a device used to prevent pregnancy. The device is...

  11. 21 CFR 884.5360 - Contraceptive intrauterine device (IUD) and introducer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Contraceptive intrauterine device (IUD) and... Gynecological Therapeutic Devices § 884.5360 Contraceptive intrauterine device (IUD) and introducer. (a) Identification. A contraceptive intrauterine device (IUD) is a device used to prevent pregnancy. The device is...

  12. 21 CFR 884.5360 - Contraceptive intrauterine device (IUD) and introducer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Contraceptive intrauterine device (IUD) and... Gynecological Therapeutic Devices § 884.5360 Contraceptive intrauterine device (IUD) and introducer. (a) Identification. A contraceptive intrauterine device (IUD) is a device used to prevent pregnancy. The device is...

  13. 21 CFR 884.5360 - Contraceptive intrauterine device (IUD) and introducer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Contraceptive intrauterine device (IUD) and... Gynecological Therapeutic Devices § 884.5360 Contraceptive intrauterine device (IUD) and introducer. (a) Identification. A contraceptive intrauterine device (IUD) is a device used to prevent pregnancy. The device is...

  14. Effects of intrauterine growth retardation and postnatal high-fat diet on hepatic inflammatory response in pigs.

    PubMed

    Liu, Jingbo; He, Jian; Yang, Yuekui; Yu, Jie; Mao, Xiangbing; Yu, Bing; Chen, Daiwen

    2014-01-01

    The objective of this study was to investigate the glucose and insulin response of pigs with intrauterine growth retardation (IUGR) to a high-fat (HF) feeding regimen and to observe the underlying toll-like receptor-4 (TLR4) signalling pathway. Weaned piglets with IUGR or normal birthweight (NBW) (n = 20 each) received during the whole fattening period control diets (0% lard) or HF diets (HF, 10% lard). At about 110 kg body weight, pigs were euthanised to collect hepatic samples. Compared with NBW pigs, IUGR pigs had lower daily gain and feed intake. Growth rate of pigs was increased by HF feeding. Pigs fed HF diets had lower peak concentrations of glucose and insulin, which decreased more slowly than in pigs that received the control diets. The mRNA expression abundances of peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), TLR4, myeloid differentiation factor 88 (MyD88), tumour necrosis factor-α (TNF-α), interleukin 6 (IL-6) and IL-1 receptor antagonist (IL-1Rn) were significantly affected by HF feeding, and IL-6 and IL-1Rn mRNA expressions were up-regulated in IUGR pigs compared with NBW pigs. Western blot analysis indicated that HF feeding elevated the protein expressions of TLR4 signalling pathway, as TLR4, MyD88, IκB kinase β and nuclear factor-κB, and insulin signalling-related proteins, as phosphorylated insulin receptor substrate-1 and phosphorylated protein kinase B. In summary, hepatic TLR4 signalling pathway and inflammatory response induced by HF feeding played an important role in the aggravated development of insulin resistance in pigs.

  15. Intrauterine tamponade balloon use in the treatment of uterine inversion.

    PubMed

    Haeri, Sina; Rais, Sheliza; Monks, Brian

    2015-01-06

    Uterine inversion is a rare but life-threatening obstetrical emergency that occurs when the fundus of the uterus prolapses through the cervix, hence turning the uterus inside out. In this case report, we present our experience using an intrauterine tamponade balloon for management of uterine inversion, and a review of the literature. The utility of an intrauterine tamponade balloon in cases of uterine inversion, especially when maternal medical conditions preclude the use of uterotonics, or reinversion is observed should be kept in mind.

  16. Clinical Experience with the Dalkon Shield Intrauterine Device

    PubMed Central

    Jones, R. W.; Parker, A.; Elstein, Max

    1973-01-01

    Preliminary acceptability and reliability tests of the Dalkon Shield were done in 377 women over 17 months, amounting to 3,028 months of use. There was a 98% follow-up. The pregnancy rate of 4·7 and expulsion rate of 6·3 do not meet the claims described in initial trials by the developers of the device. Nevertheless, the Dalkon Shield seems to be an advance in intrauterine contraception since it has the advantages of a lower expulsion rate than the “first generation” inert intrauterine devices. Imagesp144-a PMID:4720765

  17. Retained foetal bones: an intrauterine cause of chronic pelvic pain.

    PubMed

    Kalu, Emmanuel; Richardson, Robert

    2009-02-01

    Intrauterine retention of foetal bones is an uncommon but recognised complication of late termination of pregnancy. Secondary subfertility, abnormal uterine bleeding and vaginal discharge are the usual presenting complaints. We report a case of prolonged retention of foetal bones for 14 years in a woman who presented with chronic pelvic pain. Hysteroscopic examination was diagnostic and therapeutic. Retained foetal bones are an uncommon intrauterine cause of chronic pelvic pain that should be considered particularly when a woman with a history of late termination presents with pelvic pain. Hysteroscopic evacuation is curative.

  18. [Intrauterine programming of reproductive function--a valid concept?].

    PubMed

    Schleussner, Ekkehard

    2009-01-01

    Early intrauterine fetal (mis)programming determines not only cardiovascular and metabolic regulation in later life, but also reproductive function. Intrauterine growth restriction may be associated with precocious maturation of gonadal function and an earlier onset of puberty and menarche. Especially prenatal androgen excess has negative effects on the development of the ovaries and female genital phenotype itself as well as on the neuroendocrine feedback regulation of the hypothalamic-pituitary-gonadal axis followed by a polycystic ovary syndrome with hyperandrogenism and anovulation in later life. These associations, which can be clearly demonstrated in animal experiments, need further confirmation by epidemiological and clinical trials in humans.

  19. Intra-uterine fetal demise caused by amniotic band syndrome after standard amniocentesis.

    PubMed

    Strauss, A; Hasbargen, U; Paek, B; Bauerfeind, I; Hepp, H

    2000-01-01

    The amniotic band syndrome represents a prime example of exogenous disruption of an otherwise normal fetal development. It may be a sequel of invasive diagnostic procedures such as amniocentesis or fetal blood sampling. A 38-year-old gravida II, para II delivered a morphologically normal male stillborn at term. The pregnancy history had been unremarkable but for an early 2nd-trimester amniocentesis. Cause of the intra-uterine fetal demise was noted to be an amniotic band constricting the umbilical cord. An amniotic band is a rare but potentially fatal condition which may be induced by, e.g., invasive prenatal procedures. Such bands are not usually diagnosed prenatally; however, selected patients with augmented risk may profit f