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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. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. Differential expression of uterine NO in pregnant and nonpregnant rats with intrauterine bacterial infection.

    PubMed

    Fang, L; Nowicki, B; Yallampalli, C

    2001-05-01

    Previous studies have demonstrated that nitric oxide (NO) is involved in the uterine host defense against bacterial infection. In nonpregnant rats, NO production in the uterus was shown to be lower, and inducible NO synthase (NOS) expression was undetectable. However, studies in pregnant rats show abundant expression of inducible NOS with significant elevation in NO production in the uterus. We have recently reported that intrauterine Escherichia coli infection caused a localized increase in uterine NO production and inducible NOS expression in the nonpregnant rat. In our present study, we examined whether the uterine NO production, NOS expression, and uterine tumor necrosis factor-alpha protein are increased in pregnant rats with intrauterine pathogenic Escherichia coli infection. Unlike the nonpregnant state, the NO production in the infected uterine horn of pregnant rats was not significantly elevated after bacterial inoculation compared with the contralateral uterine horn. The expression of uterine NOS (types II and III) also did not show significant upregulation in the infected horn. This is in contrast to that in nonpregnant animals, in which type II NOS was induced in the uterus on infection. Moreover, intrauterine infection induced an elevated expression of tumor necrosis factor-alpha protein in the infected horn both of nonpregnant and of pregnant rats. These data suggest that the sequential stimulation of NOS expression, especially the inducible isoform, and generation of uterine NO are lacking during pregnancy despite an elevated tumor necrosis factor-alpha after infection. In summary, NO synthesis response may be maximal at pregnancy, and infection may not further induce the NO system. Present studies, together with our previous report that intrauterine infection-induced lethality in pregnancy rats was amplified with the inhibition of NO, suggest that pregnancy is a state predisposed for increased complications associated with intrauterine infection and

  9. 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.

  10. 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.

  11. [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.

  12. [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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  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. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Levonorgestrel Intrauterine System

    MedlinePlus

    ... period begins, or immediately after a first-trimester abortion. If you have given birth, had a miscarriage, or had a second-trimester abortion, your intrauterine system should not be inserted until ...

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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.

  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

    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.

  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. 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

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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)

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  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. 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…

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. [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.

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. Combined affinity labelling and mass spectrometry analysis of differential cell surface protein expression in normal and prostate cancer cells.

    PubMed

    Hastie, Claire; Saxton, Malcolm; Akpan, Akunna; Cramer, Rainer; Masters, John R; Naaby-Hansen, Soren

    2005-09-01

    Differences in the expression of cell surface proteins between a normal prostate epithelial (1542-NP2TX) and a prostate cancer cell line (1542-CP3TX) derived from the same patient were investigated. A combination of affinity chromatographic purification of biotin-tagged surface proteins with mass spectrometry analysis identified 26 integral membrane proteins and 14 peripheral surface proteins. The findings confirm earlier reports of altered expression in prostate cancer for several cell surface proteins, including ALCAM/CD166, the Ephrin type A receptor, EGFR and the prostaglandin F2 receptor regulatory protein. In addition, several novel findings of differential expression were made, including the voltage-dependent anion selective channel proteins Porin 1 and 2, ecto-5'-nucleotidase (CD73) and Scavenger receptor B1. Cell surface protein expression changed both qualitatively and quantitatively when the cells were grown in the presence of either or both interferon INFalpha and INFgamma. Costimulation with type I and II interferons had additive or synergistic effects on the membrane density of several, mainly peripherally attached surface proteins. Concerted upregulation of surface exposed antigens may be of benefit in immuno-adjuvant-based treatment of interferon-responsive prostate cancer. In conclusion, this study demonstrates that differences in the expression of membrane proteins between normal and prostate cancer cells are reproducibly detectable following vectorial labelling with biotin, and that detailed analysis of extracellular-induced surface changes can be achieved by combining surface-specific labelling with high-resolution two-dimensional gel electrophoresis and mass spectrometry.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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).

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. [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.

  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. 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

  19. 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

  20. 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.

  1. 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.

  2. 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...

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. A Synthetic Glycopeptide Vaccine for the Induction of a Monoclonal Antibody that Differentiates between Normal and Tumor Mammary Cells and Enables the Diagnosis of Human Pancreatic Cancer.

    PubMed

    Palitzsch, Björn; Gaidzik, Nikola; Stergiou, Natascha; Stahn, Sonja; Hartmann, Sebastian; Gerlitzki, Bastian; Teusch, Nicole; Flemming, Peer; Schmitt, Edgar; Kunz, Horst

    2016-02-18

    In studies within the realm of cancer immunotherapy, the synthesis of exactly specified tumor-associated glycopeptide antigens is shown to be a key strategy for obtaining a highly selective biological reagent, that is, a monoclonal antibody that completely differentiates between tumor and normal epithelial cells and specifically marks the tumor cells in pancreas tumors. Mucin MUC1, which is overexpressed in many prevalent cancers, was identified as a promising target for this strategy. Tumor-associated MUC1 differs significantly from that expressed by normal cells, in particular by altered glycosylation. Structurally defined tumor-associated MUC1 cannot be isolated from tumor cells. We synthesized MUC1-glycopeptide vaccines and analyzed their structure-activity relationships in immunizations; a monoclonal antibody that specifically distinguishes between human normal and tumor epithelial cells was thus generated.

  9. 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…

  10. 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…

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  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. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. [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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. [Intra-uterine device and nulliparous women].

    PubMed

    Trignol-Viguier, N; Blin, E; Marret, H

    2014-06-01

    Intra-uterine device (IUD) is one of the birth control methods, which is available for nulliparous women, even though misconceptions still remain in medical or popular opinion. Only 1.3 % of nulliparous have a IUD as contraception in France while it is the second methods used by all women, after pill. The best contraception is the one chosen by women; however, the choice for a nulliparous of an IUD may be really difficult, despite the increasing number of women wishing to use it. Long-acting reversible contraceptives utilization, including IUD, is probably one of the issues to decrease the unintended pregnancies. An exhaustive and clear information about IUD is necessary to allow an informed and real choice. This prescription must consider contraindications and medical conditions for safe insertion, especially to avoid infection by screening STD (Chlamydia trachomatis and Nesseria gonorrhoeae) in nulliparous women<25 years old. Insertion must be effected with usual precautions and short or SL IUD preferred. Even if side effects such as expulsion, pelvic pains or dysmenorrhea are more frequent by nulliparous, IUD is a first intention choice for contraception to be consider, that women could obtain easily, including in emergency contraception situation.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. Genetics Home Reference: intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and ...

    MedlinePlus

    ... IMAGe syndrome intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies Enable Javascript to view ... combination of intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies is commonly known by ...

  5. 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

  6. 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.

  7. 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

  8. Normal and Differential SAR Interferometry

    DTIC Science & Technology

    2007-02-01

    Geudtner, B. Schättler, P. Vachon, U. Steinbrecher, J. Holzner, J. Mittermayer , H. Breit, A. Moreira. RADARSAT ScanSAR interferometry. In: Proc.IGARSS’99...IV, Ottawa, Vol. XXXIV, part 4, pp. 470-475 Krieger, G., Wendler, M., Fiedler, H., Mittermayer , J., Moreira, A., 2002. Performance analysis for...bistatic interferometric SAR configurations. In: Proc.IGARSS 2002, Toronto, Canada, vol. 1, pp. 650-652. Krieger, G., Fiedler, H., Mittermayer , J

  9. 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

  10. 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.

  11. [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.

  12. 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.

  13. Relationships between intrauterine infusion of N-acetylcysteine, equine endometrial pathology, neutrophil function, post-breeding therapy, and reproductive performance.

    PubMed

    Gores-Lindholm, Alicia R; LeBlanc, Michelle M; Causey, Robert; Hitchborn, Anna; Fayrer-Hosken, Richard A; Kruger, Marius; Vandenplas, Michel L; Flores, Paty; Ahlschwede, Scott

    2013-08-01

    Persistent endometritis in the mare is associated with hypersecretion of mucus by endometrial epithelium and migration of neutrophils into the uterine lumen. This study examines the relationships between N-acetylcysteine (NAC), a mucolytic agent with anti-inflammatory properties, and endometrial architecture, serum neutrophil function, post-breeding therapy, and reproductive performance of NAC-treated mares in a clinical setting. In study 1, endometrial biopsies from mares receiving intrauterine saline (fertile-control, n = 6) or 3.3% NAC (fertile-treatment, n = 6; barren-treatment, n = 10) were evaluated by histology and image analysis. In study 2, phagocytic activity of serum-derived neutrophils was measured after adding 0.5% or 3% NAC. In study 3, pregnancy rates of repeat breeders (n = 44) receiving an intrauterine infusion of 3.3% NAC 24-36 hours before mating (group 1) was recorded, as was first cycle of the season pregnancy rates of reproductively normal mares (group 2, n = 85), and mares treated for bacterial endometritis the cycle before mating (group 3, n = 25). Intrauterine NAC did not adversely affect endometrial histology. Extracellular mucus thickness and staining intensity were reduced in fertile-treatment mares (P < 0.03). Neutrophil function was inhibited by 3% NAC solution, but not by 0.5% NAC (P < 0.05). In study 3, for groups 1, 2, and 3, respectively, the first-cycle pregnancy rates were 77%, 74%, and 56%, and early embryonic death rates were 15%, 13%, and 7%. In group 2 mares treated with uterine lavage and oxytocin post-mating, the pregnancy rate was 89% (39/44), whereas in mares treated with uterine lavage and 1 g ceftiofur, it was 60% (24/40). Of the oxytocin-treated mares, 18% (8/44) had ≥ 1 cm of intrauterine fluid or marked uterine edema, whereas 80% (32/40) of the antibiotic-treated mares did. In conclusion, intrauterine infusion of a 3.3% solution of NAC was not irritating and inhibited the oxidative burst of neutrophils. Repeat

  14. 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.

  15. Intrauterine growth retardation (IUGR): epidemiology and etiology.

    PubMed

    Romo, Agustín; Carceller, Raquel; Tobajas, Javier

    2009-02-01

    Intrauterine growth retardation (IUGR) is mainly due to a pathologic slow-down in the fetal growth pace, resulting in a fetus that is unable to reach its growth potential. IUGR frequency will vary depending on the discrimination criteria adopted. It is extremely important to use local or national fetal growth graphs in order to avoid some confounding factors. IUGR incidence in newborns would be between 3% and 7% of the total population. In our experience it is 5.13% a figure similar to the one obtained by other authors but with a progressively higher incidence during the last decade. There are multiple maternal factors that can generally be grouped into constitutional and general factors given that they affect age, weight, race, maternal cardiac volume, etc, socioeconomic factors with key incidence in the mother's nutrition level, where a poor maternal nutrition level would be the key factor in this group. We have evaluated multiple factors as possible contributors to the IUGR risk: race, parents' age, mother's height (cm), mother's birth weight and before pregnancy (kg), ponderal gain and blood pressure during pregnancy, and previous SGA newborns. Socioeconomic factors like social class, parents' profession, habitual residence, salary, immigration, and diet were also evaluated. We also included variables such as total daily working time and time mothers spent standing up, daily sleeping time (hrs), stress self-perception test at work and primiparity age. Toxic factors during pregnancy: tobacco (active and passive), alcohol, drugs and coffee consumption. Fetal or utero-placental factors were considered. In our study, the most significant etiologic factors were: Active and passive tobacco consuming, mother's stress level, increase of total months worked during pregnancy, total daily working hours and time mothers spent standing up and finally, the parent's height. Our data support the main objective of reducing the incidence of SGA newborns after IUGR by fighting

  16. 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

  17. Nrf2 regulates gene-environment interactions in an animal model of intrauterine inflammation: Implications for preterm birth and prematurity

    PubMed Central

    Sussan, Thomas E.; Sudini, Kuladeep; Talbot, C. Conover; Wang, Xiaobin; Wills-Karp, Marsha; Burd, Irina; Biswal, Shyam

    2017-01-01

    Preterm birth (PTB) is the leading cause of neonatal mortality, and surviving infants are at increased risk for lifelong disabilities. Intrauterine inflammation is an etiological factor that drives PTB, and oxidative stress is associated with PTB. Nuclear erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that is the key regulator of the response to oxidative and inflammatory stress. Here, we used the established mouse model of intrauterine inflammation-induced PTB to determine whether Nrf2 is a modifier of susceptibility to PTB and prematurity-related morbidity and mortality in the offspring. We determined that Nr2-deficient (Nrf2−/−) mice exhibited a greater sensitivity to intrauterine inflammation, as indicated by decreased time to delivery, reduced birthweight, and 100% mortality. Placentas from preterm Nrf2−/− mice showed elevated levels of markers of inflammation, oxidative stress, and cell death, and transcriptomic analysis identified numerous key signaling pathways that were differentially expressed between wild-type (WT) and Nrf2−/− mice in both preterm and control samples. Thus, Nrf2 could be a critical factor for gene-environment interactions that may determine susceptibility to PTB. Further studies are needed to determine if Nrf2 is a viable therapeutic target in women who are at risk for PTB and associated complications in the affected offspring. PMID:28071748

  18. 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.

  19. 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.

  20. Global diffusion tensor imaging derived metrics differentiate glioblastoma multiforme vs. normal brains by using discriminant analysis: introduction of a novel whole-brain approach

    PubMed Central

    Roldan-Valadez, Ernesto; Rios, Camilo; Cortez-Conradis, David; Favila, Rafael; Moreno-Jimenez, Sergio

    2014-01-01

    Background Histological behavior of glioblastoma multiforme suggests it would benefit more from a global rather than regional evaluation. A global (whole-brain) calculation of diffusion tensor imaging (DTI) derived tensor metrics offers a valid method to detect the integrity of white matter structures without missing infiltrated brain areas not seen in conventional sequences. In this study we calculated a predictive model of brain infiltration in patients with glioblastoma using global tensor metrics. Methods Retrospective, case and control study; 11 global DTI-derived tensor metrics were calculated in 27 patients with glioblastoma multiforme and 34 controls: mean diffusivity, fractional anisotropy, pure isotropic diffusion, pure anisotropic diffusion, the total magnitude of the diffusion tensor, linear tensor, planar tensor, spherical tensor, relative anisotropy, axial diffusivity and radial diffusivity. The multivariate discriminant analysis of these variables (including age) with a diagnostic test evaluation was performed. Results The simultaneous analysis of 732 measures from 12 continuous variables in 61 subjects revealed one discriminant model that significantly differentiated normal brains and brains with glioblastoma: Wilks’ λ = 0.324, χ2 (3) = 38.907, p < .001. The overall predictive accuracy was 92.7%. Conclusions We present a phase II study introducing a novel global approach using DTI-derived biomarkers of brain impairment. The final predictive model selected only three metrics: axial diffusivity, spherical tensor and linear tensor. These metrics might be clinically applied for diagnosis, follow-up, and the study of other neurological diseases. PMID:24991202

  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. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. Intravesical Migration of Intrauterine Contraceptive Devices with Stone Formation

    PubMed Central

    Aggarwal, Simmi; Jindal, Rajinder Paul; Deep, Anupam

    2014-01-01

    Intrauterine contraceptive devices (IUCD) have been associated with the multitude of complications. We present a rare case report of a 30-year-old female in whom the IUCD (Cu-T) migrated into the urinary bladder leading to calculus formation. The migrated IUCD encrusted with stones was successfully retrieved. PMID:25657964

  8. Evaluation of levonorgestrel intrauterine system upon presumed nonintact removal.

    PubMed

    Bukowski, Josh; Rogers, Anna; Cansino, Catherine

    2014-12-01

    A 51 year old woman presented for removal of her expired levonorgestrel intrauterine device (IUD). The IUD arms appeared absent upon IUD removal. Further examination of the device revealed that the arms were concealed inside the hormonal cylinder. Recognizing abnormal presentations of the levonorgestrel IUD upon removal can avoid unnecessary procedures.

  9. Treatment of endometrial hyperplasia with levonorgestrel releasing intrauterine devices.

    PubMed

    Perino, A; Quartararo, P; Catinella, E; Genova, G; Cittadini, E

    1987-01-01

    The effectiveness of a new levo-norgestrel releasing intrauterine device is assessed in fourteen patients with histologically confirmed hyperplastic lesions of the endometrial mucosa. The morphologic response of the hyperplastic endometria to the action of the levo-norgestrel in this study explains the regression of the cases so treated.

  10. Hyperleukocytosis in a premature infant with intrauterine herpes simplex encephalitis.

    PubMed

    Underwood, M A; Wartell, A E; Borghese, R A

    2012-06-01

    Herpes encephalitis is a rare but devastating infection in premature infants. We report a 29 week gestation infant with severe intrauterine cutaneous and central nervous system herpes accompanied by hyperleukocytosis. Leukemoid reactions are not uncommon in this population, but the association of herpes encephalitis and a leukemoid reaction or hyperleukocytosis has not been reported previously.

  11. Early intrauterine embryonic development in Khawia sinensis Hsü, 1935 (Cestoda, Caryophyllidea, Lytocestidae), an invasive tapeworm of carp (Cyprinus carpio): an ultrastructural study.

    PubMed

    Bruňanská, Magdaléna; Mackiewicz, John S; Młocicki, Daniel; Swiderski, Zdzisław; Nebesářová, Jana

    2012-02-01

    Intrauterine embryonic development in the caryophyllidean tapeworm Khawia sinensis has been investigated using transmission electron microscopy and cytochemical staining with periodic acid-thiosemicarbazide-silver proteinate for glycogen. Contrary to previous light microscopy findings that reported the release of non-embryonated eggs of K. sinenesis to the external environment, the present study documents various stages of embryonation (ovoviviparity) within the intrauterine eggs of this cestode. At the initial stage of embryonic development, each fertilised oocyte is accompanied by several vitellocytes that become enclosed within the operculate, electrondense shell. Cleavage divisions result in formation of blastomeres (up to about 24 cells) of various sizes. Mitotic divisions and apparent rosette arrangment of the blastomeres, the latter atypical within the Eucestoda, are observed for the first time in the intrauterine eggs of K. sinenesis. The early embryo enclosed within the electrondense shell is surrounded by a thin membraneous layer which in some enlarged regions shows presence of nuclei. Simultaneously to multiplication and differentiation, some of the blastomeres undergo deterioration. A progressive degeneration of the vitellocytes within eggs provides nutritive reserves, including lipids, for the developing embryo. The possible significance of this atypical timing of the intrauterine embryonic development to (1) the ecology of K. sinensis and that of a recent introduction of another invasive tapeworm, the caryophyllidean Atractolytocestus huronensis Anthony, 1958 to Europe; and (2) the affiliation of caryophyllideans with other lower cestodes, are discussed.

  12. PLASMA PROTEIN Z CONCENTRATIONS IN PREGNANT WOMEN WITH IDIOPATHIC INTRAUTERINE BLEEDING AND IN WOMEN WITH SPONTANEOUS PRETERM LABOR

    PubMed Central

    Kusanovic, Juan Pedro; Espinoza, Jimmy; Romero, Roberto; Hoppensteadt, Debra; Nien, Jyh Kae; Kim, Chong Jai; Erez, Offer; Soto, Eleazar; Fareed, Jawed; Edwin, Sam; Chaiworapongsa, Tinnakorn; Than, Nandor G.; Yoon, Bo Hyun; Gomez, Ricardo; Papp, Zoltan; Hassan, Sonia S.

    2008-01-01

    Objective Preterm parturition has been associated with decidual vascular disorders and excessive thrombin generation. The objective of this study was to examine maternal plasma concentrations of protein Z in normal pregnancies, as well as in those presenting with spontaneous preterm labor (PTL) and intrauterine bleeding during pregnancy. Study design A cross-sectional study was designed to include patients with preterm labor and intact membranes and those with idiopathic intrauterine bleeding during pregnancy. Protein Z plasma concentrations were measured in the following groups: 1) normal pregnant women (n=71); 2) patients at term with (n=67) and without labor (n=88); 3) patients with spontaneous PTL before 34 weeks who were classified into: a) PTL with intra-amniotic infection/inflammation (IAI; n=35), b) PTL without IAI (n=54), and c) patients with PTL who delivered at term (n=49); and 4) patients with idiopathic intrauterine bleeding in the second and third trimester who were divided into: a) subsequent spontaneous PTL and delivery, and b) term delivery. Maternal plasma protein Z concentration was measured by a specific and sensitive immunoassay. Moreover, the amniotic fluid concentration of protein Z was determined in a subset of patients with preterm labor (n=30). Results 1) There was no correlation between maternal plasma protein Z concentration and gestational age in normal pregnant women. 2) The mean maternal plasma concentration of protein Z was significantly lower in women during spontaneous labor at term than in those not in labor [mean: 2.15 μg/mL (95% CI: 2.01-2.29) vs. mean: 2.45 ± 0.52 μg/mL (95% CI: 2.34-2.56), respectively; p=0.001]; 3) Women with PTL without IAI who delivered preterm had a significantly lower mean protein Z concentration than normal pregnant women [mean: 2.12 μg/mL (95% CI: 1.98-2.26) vs. mean: 2.39 μg/mL (95% CI: 2.28-2.5); p=0.008); 4) Of interest, PTL with IAI was not associated with lower plasma concentrations of protein

  13. Increased Rat Placental Fatty Acid, but Decreased Amino Acid and Glucose Transporters Potentially Modify Intrauterine Programming.

    PubMed

    Nüsken, Eva; Gellhaus, Alexandra; Kühnel, Elisabeth; Swoboda, Isabelle; Wohlfarth, Maria; Vohlen, Christina; Schneider, Holm; Dötsch, Jörg; Nüsken, Kai-Dietrich

    2016-07-01

    Regulation of placental nutrient transport significantly affects fetal development and may modify intrauterine growth restriction (IUGR) and fetal programming. We hypothesized that placental nutrient transporters are differentially affected both by utero-placental insufficiency and prenatal surgical stress. Pregnant rats underwent bilateral uterine artery and vein ligation (LIG), sham operation (SOP) or no operation (controls, C) on gestational day E19. Placentas were obtained by caesarean section 4 h (LIG, n=20 placentas; SOP, n=24; C, n=12), 24 h (LIG, n=28; SOP, n=20; C, n=12) and 72 h (LIG, n=20; SOP, n=20; C, n=24) after surgery. Gene and protein expression of placental nutrient transporters for fatty acids (h-FABP, CD36), amino acids (SNAT1, SNAT2) and glucose (GLUT-1, Connexin 26) were examined by qRT-PCR, western blot and immunohistochemistry. Interestingly, the mean protein expression of h-FABP was doubled in placentas of LIG and SOP animals 4, 24 (SOP significant) and 72 h (SOP significant) after surgery. CD36 protein was significantly increased in LIG after 72 h. SNAT1 and SNAT2 protein and gene expressions were significantly reduced in LIG and SOP after 24 h. Further significantly reduced proteins were GLUT-1 in LIG (4 h, 72 h) and SOP (24 h), and Connexin 26 in LIG (72 h). In conclusion, placental nutrient transporters are differentially affected both by reduced blood flow and stress, probably modifying the already disturbed intrauterine milieu and contributing to IUGR and fetal programming. Increased fatty acid transport capacity may affect energy metabolism and could be a compensatory reaction with positive effects on brain development. J. Cell. Biochem. 117: 1594-1603, 2016. © 2015 Wiley Periodicals, Inc.

  14. Differential Lipid Profiles of Normal Human Brain Matter and Gliomas by Positive and Negative Mode Desorption Electrospray Ionization – Mass Spectrometry Imaging

    PubMed Central

    Pirro, Valentina; Hattab, Eyas M.; Cohen-Gadol, Aaron A.; Cooks, R. Graham

    2016-01-01

    Desorption electrospray ionization—mass spectrometry (DESI-MS) imaging was used to analyze unmodified human brain tissue sections from 39 subjects sequentially in the positive and negative ionization modes. Acquisition of both MS polarities allowed more complete analysis of the human brain tumor lipidome as some phospholipids ionize preferentially in the positive and others in the negative ion mode. Normal brain parenchyma, comprised of grey matter and white matter, was differentiated from glioma using positive and negative ion mode DESI-MS lipid profiles with the aid of principal component analysis along with linear discriminant analysis. Principal component–linear discriminant analyses of the positive mode lipid profiles was able to distinguish grey matter, white matter, and glioma with an average sensitivity of 93.2% and specificity of 96.6%, while the negative mode lipid profiles had an average sensitivity of 94.1% and specificity of 97.4%. The positive and negative mode lipid profiles provided complementary information. Principal component–linear discriminant analysis of the combined positive and negative mode lipid profiles, via data fusion, resulted in approximately the same average sensitivity (94.7%) and specificity (97.6%) of the positive and negative modes when used individually. However, they complemented each other by improving the sensitivity and specificity of all classes (grey matter, white matter, and glioma) beyond 90% when used in combination. Further principal component analysis using the fused data resulted in the subgrouping of glioma into two groups associated with grey and white matter, respectively, a separation not apparent in the principal component analysis scores plots of the separate positive and negative mode data. The interrelationship of tumor cell percentage and the lipid profiles is discussed, and how such a measure could be used to measure residual tumor at surgical margins. PMID:27658243

  15. Oxidative stress promotes JNK-dependent amyloidogenic processing of normally expressed human APP by differential modification of alpha-, beta- and gamma-secretase expression.

    PubMed

    Quiroz-Baez, Ricardo; Rojas, Emilio; Arias, Clorinda

    2009-12-01

    The pathogenesis of Alzheimer disease (AD) is complex and is certain to involve diverse etiological factors, but a central role has been strongly suggested for amyloid beta-protein (Abeta), based on genetic, biochemical and neurotoxicological evidence. In contrast with the well-documented effect of genetic mutations in Abeta overproduction, not much is known about the mechanisms involved in sporadic AD (SAD) which account for more than 95% of cases. Extensive data from patients and in vivo animal models indicate that oxidative stress is one of the cardinal factors most frequently associated with this neurodegenerative disease. The aim of the present study was to explore the effect of oxidative stress on the normally expressed wild-type amyloid precursor protein (APP) in human neuroblastoma cells, which represents a more physiological model of neuronal Abeta generation. Since H(2)O(2) is the main source of the highly reactive hydroxyl radical in the brain, and FeCl(2) can stimulate oxidative stress, including the formation of the hydroxyl radical from H(2)O(2), in the present work we studied the effect of these two pro-oxidant molecules on the levels and processing of human APP by alpha-, beta- and gamma-secretase, and the role of the stress-activated kinase c-jun N-terminal kinase (JNK). We provide evidence for a dual modulation of amyloid precursor protein metabolism in differentiated human neuroblastoma cells related with a down-regulation of alpha-secretase and up-regulation of gamma-secretase, and particularly of beta-secretase and also a JNK depending Abeta generation.

  16. The effect of intrauterine inoculation with Ureaplasma diversum on bovine fertility.

    PubMed Central

    Kreplin, C M; Ruhnke, H L; Miller, R B; Doig, P A

    1987-01-01

    To determine the influence of Ureaplasma diversum on bovine fertility 11 uninfected virgin heifers with normal ovarian cyclic activity were randomly allocated to test or control groups. At a synchronized estrus, five test heifers were given an intrauterine broth inoculum containing 1.09 x 10(8) to 1.4 x 10(9) colony forming units of U. diversum and six control animals were infused with sterile ureaplasma broth medium. All animals were artificially inseminated within one hour of infusion. Pregnancy was diagnosed in one of five test heifers and all of six controls by serum progesterone concentrations measured to 25 days postinsemination. The difference in pregnancy rates between the two groups was statistically significant (p = 0.0152). It was concluded that under the conditions of this experiment U. diversum is capable of causing infertility in cattle. PMID:3453263

  17. Intrauterine trophoblast migration: A comparative view of humans and rodents

    PubMed Central

    Silva, Juneo F.; Serakides, Rogéria

    2016-01-01

    ABSTRACT Trophoblast migration and invasion through the decidua and maternal uterine spiral arteries are crucial events in placentation. During this process, invasive trophoblast replace vascular endothelial cells as the uterine arteries are remodeled to form more permissive vessels that facilitate adequate blood flow to the growing fetus. Placentation failures resulting from either extensive or shallow trophoblastic invasion can cause pregnancy complications such as preeclampsia, intrauterine growth restriction, placenta creta, gestational trophoblastic disease and even maternal or fetal death. Consequently, the use of experimental animal models such as rats and mice has led to great progress in recent years with regards to the identification of mechanisms and factors that control trophoblast migration kinetics. This review aims to perform a comparative analysis of placentation and the mechanisms and factors that coordinate intrauterine trophoblast migration in humans, rats and mice under physiological and pathological conditions. PMID:26743330

  18. Intrauterine trophoblast migration: A comparative view of humans and rodents.

    PubMed

    Silva, Juneo F; Serakides, Rogéria

    2016-03-03

    Trophoblast migration and invasion through the decidua and maternal uterine spiral arteries are crucial events in placentation. During this process, invasive trophoblast replace vascular endothelial cells as the uterine arteries are remodeled to form more permissive vessels that facilitate adequate blood flow to the growing fetus. Placentation failures resulting from either extensive or shallow trophoblastic invasion can cause pregnancy complications such as preeclampsia, intrauterine growth restriction, placenta creta, gestational trophoblastic disease and even maternal or fetal death. Consequently, the use of experimental animal models such as rats and mice has led to great progress in recent years with regards to the identification of mechanisms and factors that control trophoblast migration kinetics. This review aims to perform a comparative analysis of placentation and the mechanisms and factors that coordinate intrauterine trophoblast migration in humans, rats and mice under physiological and pathological conditions.

  19. Evaluation of intrauterine adhesion treatment by laser hysteroscopy

    NASA Astrophysics Data System (ADS)

    Mutrynowski, Andrzej; Zabielska, Renata

    1996-03-01

    Hysteroscopy, which is a kind of endoscopy, makes it possible to evaluate macroscopically the cervical canal, uterine cavity, and the uterine opening of the oviducts. Laser hysteroscopy is used for removing septa and intrauterine adhesions, polyps, small submucosus myomas, and for endometrium ablation in abnormal metrorrhagias. The paper aims at the initial evaluation of laser hysteroscopy in removing intrauterine adhesions in the cases of 41 infertile women. Among all infertile patients 16 women (39%) conceived. Among others 1 woman (2.5%) did not want to conceive and 19 had other causes of infertility. Thirteen (93%) out of 14 patients with hypomenorrhea before surgery reported improvement of the menstruation cycle after the treatment. Five patients (12%) had adhesions for the second time. The patients had the second laser hysteroscopy. The control diagnostic hysteroscopy showed no adhesions in those cases.

  20. Intrauterine ozone treatment of retained fetal membrane in Simmental cows.

    PubMed

    Djuricic, D; Vince, S; Ablondi, M; Dobranic, T; Samardzija, M

    2012-10-01

    The aim of research was to determine influence of intrauterine application of two different ozone preparations on reproductive performance in Simmental cows with retained fetal membranes (RFM). The study was performed on 143 Simmental cows aged 2-8 years and divided in three groups. Group A (n=46) consisted of cows treated with foam spray ozone applied into the body of the uterus for 5s using a sterile catheter. Group B (n=50) consisted of cows treated using six ozone pearls intrauterinely at once, as deeply and hygienically possible. Cows were observed and treated during early puerperium, 24-36h after parturition. The third group (n=47) consisted of cows without RFM (control group). To assess the reproductive performance of cows, the interval from calving to first insemination (days not pregnant to first service, DOFS), interval from calving to pregnancy (days not pregnant to pregnancy, DOP), relative pregnancy rate (%), first service conception rate (FSCR, %) and all service conception rate (ASCR, %) were measured. The estimate of hazard ratio for the Groups A and B relative to control group with DOFS were 0.423 (P=0.0006) and 0.434 (P=0.0005), and with DOP were 0.701 (P=0.003) and 0.411 (P=0.0003), respectively, implying that cows in the control group were not pregnant longer until first insemination and pregnancy. Variables that had an influence on DOFS were postpartum fever (PPF) (HR=0.458; P=0.003) and milk yield (HR=0.999; P<0.0001) and an influence on DOP were PPF (HR=0.314; P=0.001) and milk yield (HR=0.999; P<0.0001). Cows with RFM treated with intrauterine Riger spray or Ripromed ovuli O(3) have similar or enhanced reproductive performance results compared to the control group of cows demonstrating the effectiveness of therapy with intrauterine ozone products.

  1. Ovarian pregnancy in association with an intrauterine device.

    PubMed

    de Vries, K; Shapiro, I; Degani, S; Levitan, Z; Mitrani, A; Sharf, M

    1983-02-01

    Within a 1-year period, two cases of primary ovarian pregnancy associated with an intrauterine device (IUD) occurred in our institution. The clinical signs and symptoms were similar to those in any other ectopic pregnancy. Both cases satisfied the criteria of Spiegelberg. The final diagnosis was based on the histopathological findings. A review of the literature is presented summarizing the 53 cases reported until now. The association between IUD, ectopic pregnancy in general, and ovarian pregnancy in particular is discussed.

  2. Factors affecting intrauterine contraceptive device performance. I. Endometrial cavity length.

    PubMed

    Hasson, H M; Berger, G S; Edelman, D A

    1976-12-15

    The relationship of endometrial cavity length to intrauterine contraceptive device (IUD) performance was evaluated in 319 patients wearing three types of devices. The rate of events, defined as pregnancy, expulsion, or medical removal, increased significantly when the length of the IUD was equal to, exceeded, or was shorter by two or more centimeters than the length of the endometrial cavity. Total uterine length was found to be a less accurate prognostic indicator of IUD performance than endometrial cavity length alone.

  3. Intrauterine contraception in nulliparous women: a prospective survey

    PubMed Central

    Kutler, Beth A

    2016-01-01

    Background Intrauterine contraception is a first-line option for young women, yet relatively few prospective studies have been performed in nulliparous women using currently available devices, and many providers are still reluctant to provide this option. Methods Between January 2012 and June 2014, 109 nulliparous women, aged 18–30 years, who had an intrauterine device (IUD) placed at a student health clinic [88 levonorgestrel-intrauterine system (LNG-IUS) users and 21 Cu T 380A (IUD) users] were surveyed at 1, 6, 12 and 18 months after insertion. Results Overall satisfaction was high; at follow-up survey 83% of 100 women (mean use 13.4 months) were ‘happy’ or ‘very happy’ with their IUD, and there were no differences in satisfaction between the two IUD types. Some 75% of participants stated that the insertion procedure went ‘very well’, despite 78% rating insertion pain as moderate to severe, and 46% experiencing vasovagal symptoms. The 12-month continuation rate was 89%, with discontinuations for expulsion (3%), side effects (6%), lack of anticipated benefit (1%) and pregnancy (1%). Users of the Cu T 380A were more likely to have heavy menses (74% vs 2%; p<0.0001) or moderate to severe cramping (68% vs 20%; p=0.0002) compared with LNG-IUS users. There were no uterine perforations or diagnoses of pelvic inflammatory disease. The rate of failed insertions during the study period was 6.2%. Conclusions Despite significant symptoms with insertion, intrauterine contraception is safe, effective and ultimately well tolerated in nulliparous women and should be provided to this population in both university and community health settings. PMID:25854550

  4. Copper-T intrauterine device and levonorgestrel intrauterine system: biological bases of their mechanism of action.

    PubMed

    Ortiz, María Elena; Croxatto, Horacio B

    2007-06-01

    All intrauterine devices (IUDs) that have been tested experimentally or clinically induce a local inflammatory reaction of the endometrium whose cellular and humoral components are expressed in the tissue and the fluid filling the uterine cavity. Depending on the reproductive strategy of the species considered and the anatomical features and physiologic mechanisms that characterize their reproductive system, the secondary consequences of this foreign body reaction can be very localized within the uterus, as in the rabbit, or widespread throughout the entire genital tract as in women or even systemic as in some farm animals. Levonorgestrel released from an IUD causes some systemic effects, but local effects such as glandular atrophy and stromal decidualization, in addition to the foreign body reaction, are dominant. Copper ions released from an IUD enhance the inflammatory response and reach concentrations in the luminal fluids of the genital tract that are toxic for spermatozoa. In the human, the entire genital tract appears affected due to luminal transmission of the noxa that accumulates in the uterine lumen. This affects the function and viability of gametes, decreasing the rate of fertilization and lowering the chances of survival of any embryo that may be formed, before it reaches the uterus. The bulk of the data indicate that if any embryos are formed in the chronic presence of an IUD, it happens at a much lower rate than in non-IUD users. The common belief that the usual mechanism of action of IUDs in women is destruction of embryos in the uterus is not supported by empirical evidence.

  5. Laparoscopic Removal of Migrated Intrauterine Device Embedded in Intestine

    PubMed Central

    Rahnemai-Azar, Amir A.; Apfel, Tehilla; Naghshizadian, Rozhin; Cosgrove, John Morgan

    2014-01-01

    Introduction: The intrauterine device (IUD) is a popular family planning method worldwide. Some of the complications associated with insertion of an IUD are well described in the literature. The frequency of IUD perforation is estimated to be between 0.05 and 13 per 1000 insertions. There are many reports of migrated intrauterine devices, but far fewer reports of IUDs which have penetrated into the small intestine. Case Description: Herein we report a case of perforated intrauterine device embedded in the small intestine. By using a wound protector retraction device, and fashioning the anastomosis extra-corporeally, we were able to more easily perform this laparoscopically. This left the patient with a quicker recovery, and a better cosmetic result. Discussion: IUD perforation into the peritoneal cavity is a known complication, and necessitates close follow-up. Most, if not all, should be removed at the time of diagnosis. In the majority of previously reported cases, removal was done through laparotomy. Even in cases where removal was attempted laparoscopically, many were later converted to laparotomy. Surgeons should be aware of different techniques, including using a wound protector retraction device, in order to facilitate laparoscopic removal. PMID:25419105

  6. Achondrogenesis type II with normally developed extremities: a case report.

    PubMed

    Kocakoc, Ercan; Kiris, Adem

    2002-07-01

    We present a case of achondrogenesis type II with normally developed extremities that was confirmed with postmortem ultrasonographic and radiographic examination. The length of the long bones may vary and the diagnosis of achondrogenesis should not be ruled out with normally developed extremities. Intrauterine sonographic examination of the vertebrae is very important and the absence of vertebral body ossification may be the unique finding of achondrogenesis type II. Axial ultrasonographic images and postmortem plain radiographs are useful to clarify the pathology.

  7. Maternal thyroid dysfunction affects placental profile of inflammatory mediators and the intrauterine trophoblast migration kinetics.

    PubMed

    Silva, Juneo Freitas; Ocarino, Natália Melo; Serakides, Rogéria

    2014-06-01

    The objective of the present study was to evaluate the gene and immunohistochemical expression of inflammatory mediators involved in the immune activity and the intrauterine trophoblast migration of the placentas in hypothyroid and L-thyroxine (L-T4)-treated rats. A total of 144 adult female rats were divided equally into hypothyroid, l-T4-treated, and euthyroid (control) groups. Hypothyroidism was induced by daily administration of propylthiouracil. Rats were killed at 0, 10, 14, 15, 16, 17, 18, and 19 days of gestation. We evaluated the depth of interstitial and endovascular intrauterine trophoblast invasion and the immunohistochemical expression of interferon γ (INFy), migration inhibitory factor (MIF), and inducible nitric oxide synthase (NOS2 (iNOS)). The gene expression of Toll-like receptor 2 (Tlr2) and Tlr4, Infy, Mif, tumor necrosis factor (Tnf (Tnfα)), Il10, Nos2, matrix metalloproteinase 2 (Mmp2) and Mmp9, and placental leptin was also measured in placental disks by real-time RT-PCR. The data were analyzed using an Student-Newman-Keuls (SNK) test. Hypothyroidism reduced the endovascular and interstitial trophoblast migration, and the expression of TLR4, INFy, MIF, interleukin 10 (IL10), NOS2, MMP2 and MMP9, and placental leptin, while increased the expression of TLR2 (P<0.05). T4-treated rats not only increased the expression of IL10 and NOS2 but also reduced the expression of TNF and MIF at 10 days of gestation (P<0.05). However, at 19 days of gestation, expression of INFy and MIF was increased in T4-treated group (P<0.05). Excess of T4 also increased the gene expression of Mmp2 at 10 days of gestation (P<0.05), but reduced the endovascular trophoblast migration at 18 days of gestation (P<0.05). Hypothyroidism and excess of T4 differentially affect the immune profile and the intrauterine trophoblast migration of the placenta, and these effects are dependent on the gestational period.

  8. Cornual pregnancy as a complicaton of the use of a levonorgestrel intrauterine device: a case report

    PubMed Central

    2009-01-01

    Introduction Complications of copper load intrauterine devices, including ectopic pregnancies are well reported. Rates of ectopic pregnancy are 0.6 to 1.1% per year. However, the levonorgestrel intrauterine device has been described as more protective against ectopic pregnancies due to the addition of the hormone levonorgestrel. The hormone released from the intrauterine device causes some systemic effects, but local effects such as glandular atrophy and stromal decidualization, in addition to foreign body reaction, are dominant. Few case reports have described ampullary ectopic pregnancies. However, we report, for the first time, a major complication of levonorgestrel intrauterine device: a cornual pregnancy. Case presentation A 36-year-old Caucasian nulliparous woman presented with complaints of progressive nausea, abdominal pain and irregular vaginal bleeding for 2 months. For 3 years, she had been using a levonorgestrel intrauterine device. A two-dimensional transvaginal sonogram noted a sac situated external to the endometrial cavity in the right cornua of the uterus with an empty uterus. She was successfully treated with chemotherapy. Conclusion Many complications have been described, including ectopic pregnancies, using copper intrauterine devices. The levonorgestrel-releasing intrauterine system is a particularly good choice for adolescents because of associated non-contraceptive benefits such as decreased menstrual bleeding, dysmenorrhea and pain associated with endometriosis [1]. Yet a cornual pregnancy following the use of a levonorgestrel intrauterine device is a complication which, to our knowledge, has not been described before. Physicians prescribing this type of intrauterine device should be aware of this rare event. PMID:19830226

  9. [Fetal pain and intrauterine analgesia/anesthesia--long-term pathologic effects, causes and alleviation of intrauterine pain].

    PubMed

    Deli, Tamás; Szeverényi, Péter

    2010-04-25

    The human fetus can suffer several presumably painful interventions perinatally and even before, during its intrauterine life. In the past years, scientific dispute concerning the existence of fetal pain and the need for its relief has expanded, and a heated social, political, religious, moral and philosophical debate has arisen, focusing mainly on the suffering experienced by the fetus during artificial abortion. In our two connected papers, medical scientific knowledge regarding fetal pain in the literature is reviewed. In the first article published in Orvosi Hetilap volume 150, issue 11, we defined pain and the neuroanatomical structures participating in subjective pain perception, as well as the development of these structures. Then, the objective indicators of intrauterine stress response (such as fetal neuroendocrine, cardiovascular, reflex and behavioral reactions) evoked by noxious stimuli were discussed. The present second article gathers the evidence of long-term pathologic effects caused by early-experienced pain and stress in animal models and humans. Finally, the potentially pain-evoking pre- and perinatal interventions are evaluated, as well as the analgetic/anesthetic methods that can be applied to intrauterine fetuses in everyday obstetrical practice.

  10. The effect of antenatal administration of solcoseryl on hepatic glycogen synthesis in rat fetuses with intrauterine growth retardation.

    PubMed

    Takahashi, H; Cheng, K M; Araki, T

    1993-06-01

    The effect of antenatal solcoseryl administration on hepatic glycogen synthesis and storage was studied in normal developing and intrauterine growth-retarded (IUGR) rat fetuses using biochemical analyses. The maximal effect of solcoseryl occurred 2 hours after administration. The glycogen content of the liver showed a significant increase in normal and IUGR fetuses with antenatal solcoseryl administration compared to their non-solcoseryl counterparts (p < 0.05). The activities of glycogen synthase enzymes, total and active forms, showed significant increases, at p < 0.05 and p < 0.005, respectively, in IUGR fetuses with antenatal solcoseryl administration. Active synthase also increased in normal fetuses with antenatal solcoseryl administration (p < 0.05). There were no significant changes in the activities of glycogen phosphorylase enzyme. These findings suggest that antenatal solcoseryl administration stimulates hepatic glycogen synthesis and storage in IUGR rat fetuses, and thus might favorably influence the development of neonatal hypoglycemia.

  11. Xenon contrast CT-CBF scanning of the brain differentiates normal age-related changes from multi-infarct dementia and senile dementia of Alzheimer type

    SciTech Connect

    Tachibana, H.; Meyer, J.S.; Okayasu, H.; Shaw, T.G.; Kandula, P.; Rogers, R.L.

    1984-07-01

    Local cerebral blood flow (LCBF) and partition coefficients (L lambda) were measured during inhalation of stable xenon gas with serial CT scanning among normal volunteers (N . 15), individuals with multi-infarct dementia (MID, N . 10), and persons with senile dementia of Alzheimer type (SDAT, N . 8). Mean gray matter flow values were reduced in both MID and SDAT. Age-related declines in LCBF values in normals were marked in frontal cortex and basal ganglia. LCBF values were decreased beyond normals in frontal and temporal cortices and thalamus in MID and SDAT, in basal ganglia only in MID. Unlike SDAT and age-matched normals, L lambda values were reduced in fronto-temporal cortex and thalamus in MID. Multifocal nature of lesions in MID was apparent. Coefficients of variation for LCBFs were greater in MID compared with SDAT and/or age-matched normals.

  12. Complications associated with insertion of intrauterine pressure catheters: an unusual case of uterine hypertonicity and uterine perforation resulting in fetal distress after insertion of an intrauterine pressure catheter.

    PubMed

    Rood, Kara M

    2012-01-01

    Insertion of intrauterine pressure catheters is a routine procedure performed in labor and delivery departments, with few associated complications. There are several reports of maternal and neonatal morbidity associated with the use of intrauterine pressure catheters and their rare adverse outcomes. We report an unusual case of uterine hypertonicity resulting in fetal distress, immediately after the placement of an intrauterine pressure catheter. An emergent Cesarean section was performed for fetal distress and revealed a 5 cm vertical rent in the posterior lower uterine segment. The uterine perforation was repaired intraoperatively. Mother and infant did well and were discharged home on postoperative day four.

  13. Low Interferon Relative-Response to Cytomegalovirus Is Associated with Low Likelihood of Intrauterine Transmission of the Virus

    PubMed Central

    Eldar-Yedidia, Yifat; Bar-Meir, Maskit; Hillel, Miriam; Abitbol, Guila; Broide, Eti; Falk, Roni; Assous, Marc; Schlesinger, Yechiel

    2016-01-01

    Background Congenital Cytomegalovirus (CMV) is a very common intrauterine infection which can cause severe mental and hearing impairments. Notably, only 40% of primarily infected women transmit CMV to the fetus. CMV-specific T-cell response has a role in CMV disease but individual immune heterogeneity precludes reliable correlation between measurable T-cells response and intrauterine transmission. Study Aim To establish a correlation between maternal T-cells response and fetal CMV transmission using an individual normalized immune response. Methods We analyzed IFN-γ secretion upon whole blood stimulation from primary CMV-infected pregnant women, with either CMV-peptides or PHA-mitogen. Results We established a new normalization method of individual IFN-γ response to CMV by defining the ratio between specific-CMV response and non-specific mitogen response (defined as IFN-γ relative response, RR), aiming to overcome high person-to-person immune variability. We found a unique subpopulation of women with low IFN-γ RR strongly correlated with absence of transmission. IFN-γ RR lower than 1.8% (threshold determined by ROC analysis) reduces the pre-test probability of transmission from 40% to 8%, revealing an unexpected link between low IFN-γ RR and non-transmission. Conclusion In pregnant women with primary CMV infection, low IFN-γ RR is associated with low risk of transmission. PMID:26881863

  14. Early intrauterine embryonic development of the bothriocephalidean cestode Clestobothrium crassiceps (Rudolphi, 1819), a parasite of the teleost Merluccius merluccius (L., 1758) (Gadiformes: Merlucciidae).

    PubMed

    Swiderski, Zdzisław; Miquel, Jordi; Torres, Jordi; Delgado, Eulàlia

    2013-07-01

    The early intrauterine embryonic development of the bothriocephalidean cestode Clestobothrium crassiceps (Rudolphi, 1819), a parasite of the teleost Merluccius merluccius (L., 1758), was studied by means of light (LM) and transmission electron microscopy (TEM). Contrary to the generic diagnosis given in the CABI Keys to the cestode parasites of vertebrates, the eggs of C. crassiceps, the type of species of Clestobothrium Lühe, 1899, are operculate and embryonated. Our LM and TEM results provide direct evidence that an operculum is present and that the eggs exhibit various stages of intrauterine embryonic development, and in fact represent a good example of early ovoviviparity. The intrauterine eggs of this species are polylecithal and contain numerous vitellocytes, generally ∼30, which are pushed to the periphery and remain close to the eggshell, whereas the dividing zygote and later the early embryo remain in the egg centre. During early intrauterine embryonic development, several cleavage divisions take place, which result in the formation of three types of blastomeres, i.e. macro-, meso- and micromeres. These can be readily differentiated at the TEM level, not only by their size, but also by the ultrastructural characteristics of their nuclei and cytoplasmic organelles. The total number of blastomeres in these early embryos, enclosed within the electron-dense eggshells, can be up to ∼20 cells of various sizes and characteristics. Mitotic divisions of early blastomeres were frequently observed at both LM and TEM levels. Simultaneously with the mitotic cleavage divisions leading to blastomere multiplication and their rapid differentiation, there is also a deterioration of some blastomeres, mainly micromeres. A similar degeneration of vitellocytes begins even earlier. Both processes show a progressive degeneration of both vitellocytes and micromeres, and are good examples of apoptosis, a process that provides nutritive substances, including lipids, for the

  15. Monocarboxylate transporter 8 expression in the human placenta: the effects of severe intrauterine growth restriction.

    PubMed

    Chan, S-Y; Franklyn, J A; Pemberton, H N; Bulmer, J N; Visser, T J; McCabe, C J; Kilby, M D

    2006-06-01

    Thyroid hormones (THs) are essential for normal fetal development, with even mild perturbation in maternal thyroid status in early pregnancy being associated with neurodevelopmental delay in children. Transplacental transfer of maternal THs is critical, with increasing evidence suggesting a role for 3,3',5-tri-iodothyronine (T3) in development and function of the placenta itself, as well as in development of the central nervous and other organ systems. Intrauterine growth restriction (IUGR) is associated with fetal hypothyroxinaemia, a factor that may contribute to neurodevelopmental delay. The recent description of monocarboxylate transporter 8 (MCT8) as a powerful and specific TH membrane transporter, and the association of MCT8 mutations with profound neurodevelopmental delay, led us to explore MCT8 expression in placenta. We describe the expression of MCT8 in normal human placenta throughout gestation, and in normal third-trimester placenta compared with that associated with IUGR using quantitative reverse transcriptase PCR. MCT8 mRNA was detected in placenta from early first trimester, with a significant increase with advancing gestation (P=0.007). In the early third trimester, MCT8 mRNA was increased in IUGR placenta compared with normal samples matched for gestational age (P<0.05), but there was no difference between IUGR and normal placenta in the late third trimester. Western immunoblotting findings in IUGR and normal placentae were in accord with mRNA data. MCT8 immunostaining was demonstrated in villous cytotrophoblast and syncytiotrophoblast as well as extravillous trophoblast cells from the first trimester onwards with increasingly widespread immunoreactivity seen with advancing gestation. In conclusion, expression of MCT8 in placenta from early gestation is compatible with an important role in TH transport during fetal development and a specific role in placental development. Altered expression in placenta associated with IUGR may reflect a

  16. Unusual presentation of translocated intrauterine contraceptive device.

    PubMed

    Beard, R J

    1981-04-11

    A woman who had a copper 7 coil inserted without difficulty, in 1978 decided to have another baby, and in February 1980, she asked for the device to be removed. Her (GP) general practitioner could not find the threads so she was referred to me. She did mention to her GP that she had noticed the threads appearing at her anus after defecation. The GP did a rectal examination and reassured her, suggesting that she had a vivid imagination. I saw her later that month and found no abnormality apart from a retroverted uterus and could not feel the coil with the uterine sound or hook within the uterine cavity. An X-ray of the abdomen showed that the IUD was identifiable in the midline front of the sacrum, and would appear to be in the uterus. In May 1980, she was admitted to hospital for removal of the coil. She told my senior house officer that she had felt the strings rectally: this observation was dismissed and not recorded in the notes. At operation I found a normal pelvis with retroverted uterus but no coil. Laparoscopy revealed no adhesions and no evidence of pelvic infection, but something seemed to be distorting the cavity of the sigmoid colon. It was then that my senior house officer mentioned that it was this patient who had thought she had felt the strings coming out of the rectum. She was asked to return as an outpatient 2 weeks later for sigmoidoscopy, after full bowel preparation. On sigmoidoscopy, the coil threads were readily visible and the copper 7 was found embedded 1/2 under the mucosa of the sigmoid colon at 17 cm. I grasped the free end with biopsy forceps and withdrew the coil, considerable force being needed. I prescribed ampicillin and metronidazole for 4 days and warned her about possible complications. However, the procedure caused no discomfort and there were no complications. Assuming the coil had been inserted into the uterine cavity, it it suprising that it had perforated the uterus and the sigmoid colon without causing pelvic sepsis and

  17. Intrauterine Cannabis Exposure Affects Fetal Growth Trajectories: The Generation R Study

    ERIC Educational Resources Information Center

    El Marroun, Hanan; Tiemeier, Henning; Steegers, Eric A. P.; Jaddoe, Vincent W. V.; Hofman, Albert; Verhulst, Frank C.; van den Brink, Wim; Huizink, Anja C.

    2009-01-01

    Objective: Cannabis is the most commonly consumed illicit drug among pregnant women. Intrauterine exposure to cannabis may result in risks for the developing fetus. The importance of intrauterine growth on subsequent psychological and behavioral child development has been demonstrated. This study examined the relation between maternal cannabis use…

  18. Pyometra Perforation Caused by Actinomyces without Intrauterine Device Involvement

    PubMed Central

    2013-01-01

    An 86-year-old woman with diabetes mellitus and severe decubitus at the sacral and calcaneal regions stemming from poor daily activity was diagnosed with pyometra perforation caused by Actinomyces. No foreign materials, including an IUD, were found inside the uterus. Pyometra is usually caused by Enterobacteriaceae or anaerobes derived from the gastrointestinal tract. The virulence of Actinomyces is rather low, and, in almost all the reported cases of Actinomyces-related pyometra, an intrauterine device (IUD) was involved. Although rare, Actinomyces may be ascribed as a virulent pathogen that causes pyometra in the absence of foreign materials. PMID:23762685

  19. Pyometra Perforation Caused by Actinomyces without Intrauterine Device Involvement.

    PubMed

    Hagiya, Hideharu

    2013-01-01

    An 86-year-old woman with diabetes mellitus and severe decubitus at the sacral and calcaneal regions stemming from poor daily activity was diagnosed with pyometra perforation caused by Actinomyces. No foreign materials, including an IUD, were found inside the uterus. Pyometra is usually caused by Enterobacteriaceae or anaerobes derived from the gastrointestinal tract. The virulence of Actinomyces is rather low, and, in almost all the reported cases of Actinomyces-related pyometra, an intrauterine device (IUD) was involved. Although rare, Actinomyces may be ascribed as a virulent pathogen that causes pyometra in the absence of foreign materials.

  20. Prenatal Programming of Insulin Secretion in Intrauterine Growth Restriction

    PubMed Central

    Gatford, Kathryn L.; Simmons, Rebecca A.

    2014-01-01

    Intrauterine growth restriction (IUGR) impairs insulin secretion in humans and in animal models of IUGR. Several underlying mechanisms have been implicated, including decreased expression of molecular regulators of β-cell mass and function, in some cases shown to be due to epigenetic changes initiated by an adverse fetal environment. Alterations in cell cycle progression contribute to loss of β-cell mass, whereas decreased islet vascularity and mitochondrial dysfunction impair β-cell function in IUGR rodents. Animal models of IUGR sharing similar insulin secretion outcomes as the IUGR human are allowing underlying mechanisms to be identified. This review will focus on models of uteroplacental in sufficiency. PMID:23820120

  1. Use of bipedicular advancement flaps for intrauterine closure of myeloschisis.

    PubMed

    Mangels, K J; Tulipan, N; Bruner, J P; Nickolaus, D

    2000-01-01

    Several groups have begun to explore the feasibility and utility of intrauterine closure of myelomeningocele. A subset of these fetuses have defects which fall into the category of myeloschisis, and therefore have inadequate skin to enable primary closure. After considerable discussion, it was decided to utilize bipedicular flaps to close these lesions. The procedure is described, and representative examples are shown. To date, 13 of 56 fetuses have required this approach for closure in utero. While this technique generally provides adequate coverage of the dural sac, the cosmetic results have been less than optimal.

  2. Laparoscopic removal of an intrauterine device from the sigmoid colon

    PubMed Central

    Şanlıkan, Fatih; Arslan, Oğuz; Avcı, Muhittin Eftal; Göçmen, Ahmet

    2015-01-01

    Uterine wall perforation which is commonly seen through the posterior wall of the uterus is the most serious complication of an intrauterine device (IUD). We present a case of laparoscopic removal of an IUD from the sigmoid colon in a 31-years-old female who was admitted to hospital with a history of pelvic pain and abnormal vaginal bleeding for one month. The dislocated IUD was removed from the sigmoid colon of laparoscopic intervention without any complications. In conclusion, the treatment modality for the removal of a dislocated IUD is possible by laparoscopic surgery in selected patients where the dislocated IUD is accessible. PMID:25878646

  3. Postpartum and postabortal insertion of intrauterine contraceptive devices.

    PubMed

    Martorella, L A; Esposito, J M

    1975-04-01

    One hundred forty-four patients are studied over an 18 month period. Postpartum and postabortal insertions of intrauterine contraceptive devices using the Lippes Loop and the Dalkon Shield are compared. The age, parity, previous methods of contraception, and marital status of the study group indicated a poorly motivated patient population. Although accidental pregnancy rates and expulsion rates are higher, the technique is considered worth-while in the population studied. Future research should be directed toward improved devices in order to decrease side effects and to increase appeal of the technique to those who will benefit most.

  4. Facts and artifacts in the study of intra-uterine mortality: A reconsideration from pregnancy histories.

    PubMed

    Leridon, H

    1976-07-01

    Summary The analysis of intra-uterine mortality is made difficult by the interaction of many factors, some of them being pure artifacts resulting from the way in which the data are collected, or from the under-reporting of induced abortions. This paper deals with some 'real factors' of variation in the risk of spontaneous abortion (mother's age, pregnancy order, number of previous abortions), and with some of these 'artifacts' (inclusion of induced abortion, memory effect, differential continuation rates). Special attention is paid to the effect of heterogeneity of the risk of abortion. After a discussion of problems of observation, data from two different samples are analysed, first in a classic way: variation with age and pregnancy order, comparison between the rates of abortion for current and previous abortion. Next, detailed data on successive pregnancies are used to derive estimates of the distribution of risk between women. It is concluded that this distribution could and should be taken into account, and that its effects are different from those of age. The possibility of differential continuation rates by outcome of pregnancy is discussed briefly, in connection with previous points.

  5. Differential expression of human leukocyte antigen-G (HLA-G) messenger RNAs and proteins in normal human prostate and prostatic adenocarcinoma.

    PubMed

    Langat, Daudi K; Sue Platt, J; Tawfik, Ossama; Fazleabas, Asgerally T; Hunt, Joan S

    2006-08-01

    Human leukocyte antigen-G (HLA-G) is a major histocompatibility complex class Ib gene expressed in normal organs and in some tumors. The glycoproteins encoded by this gene are best known for their immunosuppressive properties. Because isoform-specific expression of HLA-G in male reproductive organs has not been reported, we investigated HLA-G1, -G2, -G5, -G6 mRNAs and proteins in four-to-five samples of normal prostate glands, prostates with benign prostatic hyperplasia and prostate adenocarcinomas using RT-PCR and immunohistochemistry. All tissues contained HLA-G1, -G2, -G5 and -G6 specific mRNAs, but only HLA-G5 protein was detectable. In normal prostate glands, HLA-G5 protein was prominent in the cytoplasm of tubuloglandular epithelia and in glandular secretions. Staining was reduced in samples of benign prostatic hyperplasia but remained localized to the cytoplasm of glandular epithelia and secretions. In prostatic adenocarcinomas, HLA-G5 protein was detectable mainly in the secretions. Thus, HLA-G5 but not HLA-G1, -G2 or -G6 is produced in the normal prostate and is present in prostatic secretions. In addition, normal cellular localization is disturbed in benign and malignant prostatic adenocarcinomas. The results are consistent with this molecule may influencing female immune receptivity to sperm and suggest that such immunosuppression could be disturbed in men with prostatic adenocarcinomas.

  6. New operational technology of intrauterine ventilation the fetus lungs by breathing gas

    NASA Astrophysics Data System (ADS)

    Urakov, A. L.; Nikityuk, D. B.; Urakova, N. A.; Kasankin, A. A.; Chernova, L. V.; Dementiev, V. B.

    2015-11-01

    New operational technology for elimination intrauterine hypoxia and asphyxia of the fetus using endoscopic artificial ventilation lungs by respiratory gas was developed. For intrauterine ventilation of fetal lung it is proposed to enter into the uterus a special breathing mask and wear it on the head of the fetus using the original endoscopic technology. The breathing mask, developed by us is connected with external breathing apparatus with a hose. The device is called "intrauterine aqualung". Intrauterine aqualung includes a ventilator and breathing circuit with a special fold-out breathing mask that is put on inside the uterus on the head of fetus like a mesh hat. Controlled by ultrasound the technology of the introduction of the mask inside of the uterus through the natural opening in the cervix and technology of putting on the respiratory mask on the head of the fetus with its head previa were developed. The technology intrauterine ventilation of the fetus lungs by respiratory gas was developed.

  7. Effects of Aspirin and Intrauterine Balloon on Endometrial Repair and Reproductive Prognosis in Patients with Severe Intrauterine Adhesion: A Prospective Cohort Study

    PubMed Central

    Liu, Lixiang; Luo, Yuanna; Chen, Minghui; Fang, Ruili

    2017-01-01

    This study aimed to investigate the effects of estrogen in combination with aspirin and intrauterine balloon on the uterine endometrial repair and reproductive prognosis in patients after surgery for severe intrauterine adhesion (sIUA). We prospectively recruited 114 patients with sIUA. Intrauterine device (IUD) was placed and oral estrogen was administered after surgery. Patients were divided into control group and aspirin group. In addition, patients in aspirin group were subdivided into nonballoon group and balloon group. Results showed that, after therapy, the increase in endometrial thickness of aspirin groups was superior to control group (P < 0.05). The scores of intrauterine adhesion and menstruation were significantly improved in balloon group as compared to nonballoon group and control group, and significant differences were also observed between nonballoon group and control group (P < 0.05). Of 97 patients, 44.3% became pregnant after surgery, the live birth rate was 27.8%, and the miscarriage rate was 37.2%, but there were no significant differences among three groups (P > 0.05). Thus, aspirin may promote the uterine endometrial growth and repair after surgery for sIUA, and IUD in combination with intrauterine balloon may reduce the recurrence of intrauterine adhesion, but their effect on the reproductive prognosis is required to be further studied. PMID:28251159

  8. The more basic isoform of eEF1A relates to tumour cell phenotype and is modulated by hyper-proliferative/differentiating stimuli in normal lymphocytes and CCRF-CEM T-lymphoblasts.

    PubMed

    Scaggiante, Bruna; Dapas, Barbara; Pozzato, Gabriele; Grassi, Gabriele

    2013-06-01

    The elongation factor 1A proteins (eEF1A1/A2) are known to play a role in tumours. We previously found that a more basic isoform of eEF1A (MBI-eEF1A) is present in the cytoskeletal/nuclear-enriched extracts of CCRF-CEM T-lymphoblasts but not in those of normal lymphocytes. To obtain deeper knowledge about MBI-eEF1A biology, we investigate from which of the eEF1A proteins, eEF1A1 or eEF1A2, MBI-eEF1A originates and the possibility that its appearance can be modulated by the differentiated or proliferative cell status. CCRF-CEM T-lymphoblasts and normal lymphocytes were cultured with or without differentiation/pro-proliferative stimuli (Phorbol 12-Myristate 13-Acetate (PMA) alone or the combination of phytohaemagglutinin (PHA) with PMA, respectively), and the presence of MBI-eEF1A evaluated together with that of the eEF1A1/A2 mRNAs. Our data indicate that the MBI-eEF1A may derive from eEF1A1 as eEF1A2 is not expressed in CCRF-CEM and normal lymphocytes. Moreover, MBI-eEF1A is inducible in normal lymphocytes upon hyper-proliferative stimuli application; in CCRF-CEM, its presence can be abrogated by PMA-induced differentiation. Finally, MBI-eEF1A may have a functional role in hyper-proliferating/tumour cells as its disappearance reduces the growth of CCRF-CEM and that of PHA/PMA-stimulated lymphocytes. The presented data suggest that MBI-eEF1A may be related to oncogenic cell phenotype, rising the possibility to use MBI-eEF1A as target for novel therapeutic strategies.

  9. Regulation of cell growth by Notch signaling and its differential requirement in normal vs. tumor-forming stem cells in Drosophila.

    PubMed

    Song, Yan; Lu, Bingwei

    2011-12-15

    Cancer stem cells (CSCs) are postulated to be a small subset of tumor cells with tumor-initiating ability that shares features with normal tissue-specific stem cells. The origin of CSCs and the mechanisms underlying their genesis are poorly understood, and it is uncertain whether it is possible to obliterate CSCs without inadvertently damaging normal stem cells. Here we show that a functional reduction of eukaryotic translation initiation factor 4E (eIF4E) in Drosophila specifically eliminates CSC-like cells in the brain and ovary without having discernable effects on normal stem cells. Brain CSC-like cells can arise from dedifferentiation of transit-amplifying progenitors upon Notch hyperactivation. eIF4E is up-regulated in these dedifferentiating progenitors, where it forms a feedback regulatory loop with the growth regulator dMyc to promote cell growth, particularly nucleolar growth, and subsequent ectopic neural stem cell (NSC) formation. Cell growth regulation is also a critical component of the mechanism by which Notch signaling regulates the self-renewal of normal NSCs. Our findings highlight the importance of Notch-regulated cell growth in stem cell maintenance and reveal a stronger dependence on eIF4E function and cell growth by CSCs, which might be exploited therapeutically.

  10. Maternal/fetal mortality and fetal growth restriction: Role of nitric oxide and virulence factors in intrauterine infection in rats

    PubMed Central

    Wroblewska-Seniuk, Katarzyna; Nowicki, Stella; Lebouguénec, Chantal; Nowicki, Bogdan; Yallampalli, Chandra

    2011-01-01

    Objective The mechanism of infection-related mortality of pregnant rats and the intrauterine growth restriction (IUGR) are not understood. We assessed if nitric oxide (NO) has differential effects on infection with E. coli Dr/Afa mutants lacking either AfaE or AfaD invasins. Material and Methods Sprague-Dawley rats were intrauterinally infected with the clinical strain of E. coli AfaE+D+ or one of its isogenic mutants in the presence or absence of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Maternal/fetal mortality, feto-placental weight, and the infection rate were evaluated. Results Maternal and/or fetal mortality was associated with the presence of at least one virulence factor (AfaE+D+>AfaE+D−>AfaE-D+) and was increased by L-NAME treatment. The fetal and placental weights were lower than controls and they were further reduced by L-NAME treatment. Conclusions These results demonstrate that NO enhanced AfaE and AfaD mediated virulence and play an important role in Dr/Afa+ E. coli gestational tropism. PMID:21481839

  11. Intrauterine Telemetry to Measure Mouse Contractile Pressure In Vivo

    PubMed Central

    Rada, Cara C.; Pierce, Stephanie L.; Grotegut, Chad A.; England, Sarah K.

    2015-01-01

    A complex integration of molecular and electrical signals is needed to transform a quiescent uterus into a contractile organ at the end of pregnancy. Despite the discovery of key regulators of uterine contractility, this process is still not fully understood. Transgenic mice provide an ideal model in which to study parturition. Previously, the only method to study uterine contractility in the mouse was ex vivo isometric tension recordings, which are suboptimal for several reasons. The uterus must be removed from its physiological environment, a limited time course of investigation is possible, and the mice must be sacrificed. The recent development of radiometric telemetry has allowed for longitudinal, real-time measurements of in vivo intrauterine pressure in mice. Here, the implantation of an intrauterine telemeter to measure pressure changes in the mouse uterus from mid-pregnancy until delivery is described. By comparing differences in pressures between wild type and transgenic mice, the physiological impact of a gene of interest can be elucidated. This technique should expedite the development of therapeutics used to treat myometrial disorders during pregnancy, including preterm labor. PMID:25867820

  12. Long QT Syndrome–Associated Mutations in Intrauterine Fetal Death

    PubMed Central

    Crotti, Lia; Tester, David J.; White, Wendy M.; Bartos, Daniel C.; Insolia, Roberto; Besana, Alessandra; Kunic, Jennifer D.; Will, Melissa L.; Velasco, Ellyn J.; Bair, Jennifer J.; Ghidoni, Alice; Cetin, Irene; Van Dyke, Daniel L.; Wick, Myra J.; Brost, Brian; Delisle, Brian P.; Facchinetti, Fabio; George, Alfred L.; Schwartz, Peter J.; Ackerman, Michael J.

    2013-01-01

    Importance Intrauterine fetal death or stillbirth occurs in approximately 1 out of every 160 pregnancies and accounts for 50% of all perinatal deaths. Postmortem evaluation fails to elucidate an underlying cause in many cases. Long QT syndrome (LQTS) may contribute to this problem. Objective To determine the spectrum and prevalence of mutations in the 3 most common LQTS susceptible genes (KCNQ1, KCNH2, and SCN5A) for a cohort of unexplained cases. Design, Setting, and Patients In this case series, retrospective postmortem genetic testing was conducted on a convenience sample of 91 unexplained intrauterine fetal deaths (mean [SD] estimated gestational age at fetal death, 26.3 [8.7] weeks) that were collected from 2006-2012 by the Mayo Clinic, Rochester, Minnesota, or the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. More than 1300 ostensibly healthy individuals served as controls. In addition, publicly available exome databases were assessed for the general population frequency of identified genetic variants. Main Outcomes and Measures Comprehensive mutational analyses of KCNQ1 (KV7.1, LQTS type 1), KCNH2 (HERG/KV11.1, LQTS type 2), and SCN5A (NaV1.5, LQTS type 3) were performed using denaturing high-performance liquid chromatography and direct DNA sequencing on genomic DNA extracted from decedent tissue. Functional analyses of novel mutations were performed using heterologous expression and patch-clamp recording. Results The 3 putative LQTS susceptibility missense mutations (KCNQ1, p.A283T; KCNQ1, p.R397W; and KCNH2[1b], p.R25W), with a heterozygous frequency of less than 0.05% in more than 10000 publicly available exomes and absent in more than 1000 ethnically similar control patients, were discovered in 3 intrauterine fetal deaths (3.3% [95% CI, 0.68%-9.3%]). Both KV7.1-A283T (16-week male) and KV7.1-R397W (16-week female) mutations were associated with marked KV7.1 loss-of-function consistent with in utero LQTS type 1, whereas the HERG1b-R25W mutation

  13. Intrauterine growth restriction: screening, diagnosis, and management.

    PubMed

    Lausman, Andrea; Kingdom, John; Gagnon, Robert; Basso, Melanie; Bos, Hayley; Crane, Joan; Davies, Gregory; Delisle, Marie-France; Hudon, Lynda; Menticoglou, Savas; Mundle, William; Ouellet, Annie; Pressey, Tracy; Pylypjuk, Christy; Roggensack, Anne; Sanderson, Frank

    2013-08-01

    organismes connexes, dans des collections de directives cliniques, dans des registres d’essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. Valeurs : La qualité des résultats est évaluée au moyen des critères décrits dans le rapport du Groupe d’étude canadien sur les soins de santé préventifs (Tableau). Avantages, désavantages et coûts : La mise en œuvre des recommandations formulées aux présentes devraient accroître la reconnaissance du RCIU par les cliniciens et guider l’intervention, dans les cas où cela s’avère approprié. La mise en œuvre d’un suivi optimal à long terme des nouveau-nés présentant un diagnostic de RCIU pourrait améliorer leur santé à long terme. Déclarations sommaires 1. Dans le cas d’un fœtus in utero, l’hypotrophie fœtale se définit comme suit : un poids fœtal estimé inférieur au 10e percentile au moment de l’échographie. Ce diagnostic n’indique pas nécessairement la présence d’anomalies de croissance pathologiques et pourrait simplement décrire un fœtus se situant dans la partie inférieure de la plage normale. (III) 2. Par « retard de croissance intra-utérin », on entend un fœtus présentant un poids fœtal estimé inférieur au 10e percentile au moment de l’échographie qui, en raison d’un processus pathologique, n’a pas atteint son potentiel de croissance biologiquement déterminé (III). L’estimation clinique du poids fœtal ou de la hauteur utérine compte une sensibilité et une spécificité faibles, et ne devrait pas être utilisée dans le cadre du diagnostic du retard de croissance intra-utérin. La présence de ce dernier devrait être prise en considération aux fins du diagnostic différentiel lorsque l’on constate que le fœtus présente une hypotrophie fœtale. (II-I) 3. Le dépistage efficace du retard de croissance intra-utérin nécessite une datation précise et comprend une analyse des antécédents menstruels de la m

  14. Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

    SciTech Connect

    Bujak, Emil; Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah; Neri, Dario

    2014-09-10

    There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

  15. Differential dietary habits among 570 young underweight Japanese women with and without a desire for thinness: a comparison with normal weight counterparts.

    PubMed

    Mori, Nagisa; Asakura, Keiko; Sasaki, Satoshi

    2016-01-01

    The strong social pressure for thinness in Japanese society has produced a dramatic increase in underweight (body mass index: <18.5 kg/m2) among young women. Being underweight is associated with several negative health outcomes, including nutritional deficiency, osteoporosis, and unfavourable pregnancy outcomes. However, evidence which would help deal with this problem from a public health perspective is scarce. Here, we aimed to identify the dietary characteristics of underweight female university students, particularly those with a desire for thinness. Data on dietary habits and other lifestyle variables, including the desire for thinness, were obtained through a self-administered questionnaire survey conducted at 54 academic institutions in Japan, from which we selected 3634 female students for analysis. The subjects were divided into three groups of normal weight (84.3%), and underweight with (6.4%) or without (9.3%) a desire for thinness. After adjusting for potential confounders, the underweight subjects with a desire for thinness consumed less cereal and rice, whereas those without a desire for thinness consumed more cereal and rice than the normal weight subjects. In addition, those without a desire for thinness consumed less confectionaries, including candies and ice cream, and less fats and oils than the normal weight subjects. These results suggest that dietary habits differ between underweight women with and without a desire for thinness. Although both groups require nutritional education to maintain appropriate body weight, underweight women with a desire for thinness require particular attention to improve recognition of their constitution and dietary habits.

  16. Progesterone levels and days to luteolysis in mares treated with intrauterine fractionated coconut oil.

    PubMed

    Diel de Amorim, Mariana; Nielsen, Kayla; Cruz, Raissa Karolliny Salgueiro; Card, Claire

    2016-07-15

    Intrauterine plant oil infusion, including fractionated coconut oil, has been previously found to be a safe, inexpensive, and reversible method of prolonging the luteal phase in mares when administered on Day 10 of the estrous cycle. Our objective was to understand the uteroovarian response to the administration of fractionated coconut oil infusion in the uterus of diestrous mares. We hypothesized that intrauterine coconut oil administration on Day 10 would prolong luteal life span in a dose-dependent fashion and would result in higher serum progesterone levels than untreated mares at the expected time of luteolysis. Light-horse mares (n = 18) were examined using transrectal palpation and ultrasonography to determine if they had a normal interovulatory interval and were then examined daily in estrus until the day of ovulation (Day 0) and then every other day during an estrous cycle. Jugular blood was drawn on Day 11, Day 13, Day 15, and Day 17, centrifuged, and serum stored until assayed for progesterone (P4; Siemens Coat-a-Count Progesterone RIA, Los Angeles, CA, USA). Mares were randomly assigned to treatment and studied over one to two estrous cycles with a rest cycle after each treatment cycle. Groups were: control (n = 5), fractionated coconut oil 1.0 mL (Miglyol 810; Sasol Oil, Witten, Germany) infused in the uterus with an artificial insemination pipette on Day 10 (Group 1; n = 5) and fractionated coconut oil 0.5 mL infused in the uterus with an embryo transfer gun, on Day 10 (Group 2; n = 5). All statistical analyses were performed using analytical software (Stata SE, version 13.1, College Station, TX, USA) at P < 0.05. Data were first evaluated using the Shapiro-Wilk test for normality. Differences between groups in days to luteolysis (DTL) were examined using analysis of variance and Bonferroni, and the effect of day and treatment on P4 levels were examined using the Kruskal-Wallis and Dunn's all pairwise test. There was a significant

  17. BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas.

    PubMed

    Ibáñez-Costa, Alejandro; López-Sánchez, Laura M; Gahete, Manuel D; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C; Gálvez, María A; de la Riva, Andrés; Venegas-Moreno, Eva; Jiménez-Reina, Luis; Moreno-Carazo, Alberto; Tinahones, Francisco J; Maraver-Selfa, Silvia; Japón, Miguel A; García-Arnés, Juan A; Soto-Moreno, Alfonso; Webb, Susan M; Kineman, Rhonda D; Culler, Michael D; Castaño, Justo P; Luque, Raúl M

    2017-02-09

    Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca(2+) signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3-5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca(2+) concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca(2+) concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca(2+) signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760.

  18. Differential impact of changes in adiposity distribution on insulin resistance and adiponectin variations over 4 years in normal weight young adults.

    PubMed

    Lacerte, G; Langlois, M-F; Doyon, M; Brown, C; Carpentier, A C; Hivert, M-F

    2014-05-01

    The aim of the study was to evaluate the influence of weight gain and changes in adiposity distribution on insulin resistance and circulating adiponectin variations over 4 years in free-living normal weight young adults. In this prospective observational cohort (n=42 women, 18 men), anthropometric measurements and blood samples were collected in the fasting state at baseline and at 4 years. Insulin resistance was estimated using the homeostatic model assessment (HOMA-IR). Circulating adiponectin levels were determined by radioimmunoassay. To investigate increase in adiposity more specifically, subsidiary analyses were performed in a subgroup of individuals (n=31) who gained adiposity over the course of the 4-year follow-up (defined as gain >1% in percent body fat). Regression analyses were performed to adjust for sex, age, parental education, lifestyle, and fitness levels. At baseline, the participants were young adults (age=20.0 years old) in the normal weight range [body mass index (BMI)=22.7 kg/m2 (IQR=21.1-24.4)]. Median change in body fat percentage was +1.4% (IQR=-0.3-3.4; p=0.01) and in waist circumference was +1.2 cm (IQR=-2.6-5.3; p=0.05). In the subgroup of individuals who gained more than 1% body fat, increase in HOMA-IR was associated with an increase in BMI (r=0.44; p=0.01; p<0.01 in fully adjusted model), while decrease in adiponectin levels was associated with an increase in waist circumference (r=-0.38; p=0.03) but this was no longer significant after adjustment for sex and other potential confounders (p=0.14). In a population of young adults, small variations in adiposity within the normal weight range were associated with increase in insulin resistance.

  19. BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas

    PubMed Central

    Ibáñez-Costa, Alejandro; López-Sánchez, Laura M.; Gahete, Manuel D.; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C.; Gálvez, María A.; de la Riva, Andrés; Venegas-Moreno, Eva; Jiménez-Reina, Luis; Moreno-Carazo, Alberto; Tinahones, Francisco J.; Maraver-Selfa, Silvia; Japón, Miguel A.; García-Arnés, Juan A.; Soto-Moreno, Alfonso; Webb, Susan M.; Kineman, Rhonda D.; Culler, Michael D.; Castaño, Justo P.; Luque, Raúl M.

    2017-01-01

    Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca2+ signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3–5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca2+ concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca2+ concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca2+ signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760. PMID:28181484

  20. Nd-YAG laser with a fibertom system in the treatment of intrauterine lesions

    NASA Astrophysics Data System (ADS)

    Wilczak, Maciej; Wozniak, Jakub; Sajdak, Stefan; Dydowicz, Piotr; Opala, Tomasz; Cwojdzinski, Marek; Pisarski, Tadeusz

    1997-10-01

    The results of 31 Nd:YAG hysteroscopic laser surgeries done in the Department of Reproduction, Institute of Gynecology and obstetrics, Karon Marcinkowski School of Medical Sciences, Poznan, Poland were describe. In nine patients the uterine septa and in 22 women the intrauterine adhesion were recognized. Hysteroscopy is a very useful and reliable method in diagnosis and treatment of intrauterine lesions reducing fertility. The laser resection of intrauterine lesions in women with malreproduction is an efficient and safe method. The fertility and parity after laser surgery are highly improved.

  1. Limb hypoplasia resulting from intrauterine infection with herpes simplex virus: a case report.

    PubMed

    Carola, D; Skibo, M; Cannon, S; Cam, K M; Hyde, P; Aghai, Z H

    2014-11-01

    Intrauterine infection with herpes simplex virus, although very rare, has devastating effects on multiple organ systems in the fetus and can lead to in utero fetal demise. Neonates born following intrauterine herpes simplex virus infection commonly manifest with cutaneous lesions, ocular damage and/or brain abnormalities. We describe the case of a dichorionic, diamniotic twin gestation complicated by intrauterine herpes simplex virus infection. This infection led to the fetal demise of twin A and a very uncommon presentation of limb hypoplasia in twin B.

  2. Hyperspectral Raman imaging of human prostatic cells: An attempt to differentiate normal and malignant cell lines by univariate and multivariate data analysis

    NASA Astrophysics Data System (ADS)

    Musto, P.; Calarco, A.; Pannico, M.; La Manna, P.; Margarucci, S.; Tafuri, A.; Peluso, G.

    2017-02-01

    Hyperspectral Raman images of human prostatic cells have been collected and analysed with several approaches to reveal differences among normal and tumor cell lines. The objective of the study was to test the potential of different chemometric methods in providing diagnostic responses. We focused our analysis on the ν(Csbnd H) region (2800-3100 cm- 1) owing to its optimal Signal-to-Noise ratio and because the main differences between the spectra of the two cell lines were observed in this frequency range. Multivariate analysis identified two principal components, which were positively recognized as due to the protein and the lipid fractions, respectively. The tumor cells exhibited a modified distribution of the cytoplasmatic lipid fraction (mainly localized alongside the cell boundary) which may result very useful for a preliminary screening. Principal Component analysis was found to provide high contrast and to be well suited for image-processing purposes. Self-Modelling Curve Resolution made available meaningful spectra and relative-concentration values; it revealed a 97% increase of the lipid fraction in the tumor cell with respect to the control. Finally, a univariate approach confirmed significant and reproducible differences between normal and tumor cells.

  3. Differential effects of transforming growth factor-beta on the synthesis of extracellular matrix proteins by normal fetal rat calvarial bone cell populations

    PubMed Central

    1988-01-01

    To determine the effects of transforming growth factor-beta (TGF-beta) on the different cell types that exist in bone, cell populations (I- IV), progressively enriched in osteoblastic cells relative to fibroblastic cells, were prepared from fetal rat calvaria using timed collagenase digestions. TGF-beta did not induce anchorage-independent growth of these cells, nor was anchorage-dependent growth stimulated in most populations studied, despite a two- to threefold increase in the synthesis of cellular proteins. In all populations the synthesis of secreted proteins increased 2-3.5-fold. In particular, collagen, fibronectin, and plasminogen activator inhibitor synthesis was stimulated. However, different degrees of stimulation of individual proteins were observed both within and between cell populations. A marked preferential stimulation of plasminogen activator inhibitor was observed in each population, together with a slight preferential stimulation of collagen; the effect on collagen expression being directed primarily at type I collagen. In contrast, the synthesis of SPARC (secreted protein acidic rich in cysteine/osteonectin was stimulated approximately two-fold by TGF-beta, but only in fibroblastic populations. Collectively, these results demonstrate that TGF-beta stimulates matrix production by bone cells and, through differential effects on individual matrix components, may also influence the nature of the matrix formed by different bone cell populations. In the presence of TGF-beta, osteoblastic cells lost their polygonal morphology and alkaline phosphatase activity was decreased, reflecting a suppression of osteoblastic features. The differential effects of TGF- beta on bone cell populations are likely to be important in bone remodeling and fracture repair. PMID:3162238

  4. Developmental expression and differentiation-related neuron-specific splicing of metastasis suppressor 1 (Mtss1) in normal and transformed cerebellar cells

    PubMed Central

    Glassmann, Alexander; Molly, Sabine; Surchev, Lachezar; Nazwar, Tommy A; Holst, Martin; Hartmann, Wolfgang; Baader, Stephan L; Oberdick, John; Pietsch, Torsten; Schilling, Karl

    2007-01-01

    Background Mtss1 encodes an actin-binding protein, dysregulated in a variety of tumors, that interacts with sonic hedgehog/Gli signaling in epidermal cells. Given the prime importance of this pathway for cerebellar development and tumorigenesis, we assessed expression of Mtss1 in the developing murine cerebellum and human medulloblastoma specimens. Results During development, Mtss1 is transiently expressed in granule cells, from the time point they cease to proliferate to their synaptic integration. It is also expressed by granule cell precursor-derived medulloblastomas. In the adult CNS, Mtss1 is found exclusively in cerebellar Purkinje cells. Neuronal differentiation is accompanied by a switch in Mtss1 splicing. Whereas immature granule cells express a Mtss1 variant observed also in peripheral tissues and comprising exon 12, this exon is replaced by a CNS-specific exon, 12a, in more mature granule cells and in adult Purkinje cells. Bioinformatic analysis of Mtss1 suggests that differential exon usage may affect interaction with Fyn and Src, two tyrosine kinases previously recognized as critical for cerebellar cell migration and histogenesis. Further, this approach led to the identification of two evolutionary conserved nuclear localization sequences. These overlap with the actin filament binding site of Mtss1, and one also harbors a potential PKA and PKC phosphorylation site. Conclusion Both the pattern of expression and splicing of Mtss1 is developmentally regulated in the murine cerebellum. These findings are discussed with a view on the potential role of Mtss1 for cytoskeletal dynamics in developing and mature cerebellar neurons. PMID:17925019

  5. Normal birth weight piglets with impaired preweaning growth utilize alternative metabolic pathways in the liver

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study was designed to determine if normal weight pigs that grow poorly during the pre-weaning period have altered hepatic metabolism, as reported for intrauterine growth retarded pigs. Eight pairs of average birth weight pigs (1.57 +/- 0.05 kg) were identified that diverged in weight by...

  6. Intrauterine Tobacco Smoke Exposure and Congenital Heart Defects.

    PubMed

    Forest, Sharron; Priest, Sandra

    2016-01-01

    Tobacco use and second-hand smoke exposure during pregnancy are linked to a host of deleterious effects on the pregnancy, fetus, and infant. Health outcomes improve when women quit smoking at any time during the pregnancy. However, the developing heart is vulnerable to noxious stimuli in the early weeks of fetal development, a time when many women are not aware of being pregnant. Congenital heart defects are the most common birth defects. Research shows an association between maternal tobacco exposure, both active and passive, and congenital heart defects. This article presents recent evidence supporting the association between intrauterine cigarette smoke exposure in the periconceptional period and congenital heart defects and discusses clinical implications for practice for perinatal and neonatal nurses.

  7. Fetal Hyperthyroidism: Intrauterine Treatment with Carbimazole in Two Siblings.

    PubMed

    Batra, Chandar Mohan; Gupta, Vidya; Gupta, Nomeeta; Menon, P S N

    2015-10-01

    Hyperthyroidism can manifest very early in fetal life (fetal thyrotoxicosis) or immediately after birth (neonatal thyrotoxicosis). The authors describe outcome of pregnancies in a woman with Graves' disease who received medical management and underwent subtotal thyroidectomy. The first pregnancy resulted in macerated stillbirth at 32 wk. Fetal tachycardia was followed by intrauterine death at 30 wk in the second pregnancy and macerated stillbirth at 26 wk in the third pregnancy. Fetal tachycardia was detected at 17 wk in the fourth pregnancy. Treatment with carbimazole along with thyroxine was followed by a live birth at 35 wk; but the baby developed severe fatal neonatal thyrotoxicosis with crisis on day 9 and died on day 12. Fetal tachycardia was noted in the fifth pregnancy as well and she was treated with carbimazole and thyroxine. She delivered a male baby at 37 wk. He developed neonatal hypothyroidism on day 8 which was controlled with thyroxine.

  8. Intrauterine Exposure to Methylmercury and Neurocognitive Functions: Minamata Disease.

    PubMed

    Yorifuji, Takashi; Kato, Tsuguhiko; Kado, Yoko; Tokinobu, Akiko; Yamakawa, Michiyo; Tsuda, Toshihide; Sanada, Satoshi

    2015-01-01

    A large-scale food poisoning caused by methylmercury was identified in Minamata, Japan, in the 1950s. The severe intrauterine exposure cases are well known, although the possible impact of low-to-moderate methylmercury exposure in utero are rarely investigated. We examined neurocognitive functions among 22 participants in Minamata, mainly using an intelligence quotient test (Wechsler Adults Intelligent Scale III), in 2012/2013. The participants tended to score low on the Index score of processing speed (PS) relative to full-scale IQ, and discrepancies between PS and other scores within each participant were observed. The lower score on PS was due to deficits in digit symbol-coding and symbol search and was associated with methylmercury concentration in umbilical cords. The residents who experienced low-to-moderate methylmercury exposure including prenatal one in Minamata manifested deficits in their cognitive functions, processing speed in particular.

  9. Neurological and neurocognitive functions from intrauterine methylmercury exposure.

    PubMed

    Yorifuji, Takashi; Kado, Yoko; Diez, Midory Higa; Kishikawa, Toshihiro; Sanada, Satoshi

    2016-05-03

    In the 1950s, large-scale food poisoning caused by methylmercury was identified in Minamata, Japan. Although severe intrauterine exposure cases (ie, congenital Minamata disease patients) are well known, possible impacts of methylmercury exposure in utero among residents, which is likely at lower levels than in congenital Minamata disease patients, are rarely explored. In 2014, the authors examined neurological and neurocognitive functions among 18 exposed participants in Minamata, focusing on fine motor, visuospatial construction, and executive functions. More than half of the participants had some fine motor and coordination difficulties. In addition, several participants had lower performance for neurocognitive function tests (the Rey-Osterrieth Complex Figure test and Keio version of the Wisconsin card sorting test). These deficits imply diffuse brain damage. This study suggests possible neurological and neurocognitive impacts of prenatal exposure to methylmercury among exposed residents of Minamata.

  10. Correlation between differential drought tolerability of two contrasting drought-responsive chickpea cultivars and differential expression of a subset of CaNAC genes under normal and dehydration conditions.

    PubMed

    Nguyen, Kien Huu; Ha, Chien Van; Watanabe, Yasuko; Tran, Uyen Thi; Nasr Esfahani, Maryam; Nguyen, Dong Van; Tran, Lam-Son Phan

    2015-01-01

    Drought causes detrimental effect to growth and productivity of many plants, including crops. NAC transcription factors have been reported to play important role in drought tolerance. In this study, we assessed the expression profiles of 19 dehydration-responsive CaNAC genes in roots and leaves of two contrasting drought-responsive chickpea varieties treated with water (control) and dehydration to examine the correlation between the differential expression levels of the CaNAC genes and the differential drought tolerability of these two cultivars. Results of real-time quantitative PCR indicated a positive relationship between the number of dehydration-inducible and -repressible CaNAC genes and drought tolerability. The higher drought-tolerant capacity of ILC482 cultivar vs. Hashem cultivar might be, at least partly, attributed to the higher number of dehydration-inducible and lower number of dehydration-repressible CaNAC genes identified in both root and leaf tissues of ILC482 than in those of Hashem. In addition, our comparative expression analysis of the selected CaNAC genes in roots and leaves of ILC482 and Hashem cultivars revealed different dehydration-responsive expression patterns, indicating that CaNAC gene expression is tissue- and genotype-specific. Furthermore, the analysis suggested that the enhanced drought tolerance of ILC482 vs. Hashem might be associated with five genes, namely CaNAC02, 04, 05, 16, and 24. CaNAC16 could be a potential candidate gene, contributing to the better drought tolerance of ILC482 vs. Hashem as a positive regulator. Conversely, CaNAC02 could be a potential negative regulator, contributing to the differential drought tolerability of these two cultivars. Thus, our results have also provided a solid foundation for selection of promising tissue-specific and/or dehydration-responsive CaNAC candidates for detailed in planta functional analyses, leading to development of transgenic chickpea varieties with improved productivity under

  11. Phenotypic and molecular characterization of intrauterine fetal growth restriction in interspecies sheep pregnancy.

    PubMed

    Chávez-García, A; Vázquez-Martínez, E R; Murcia, C; Rodríguez, A; Cerbón, M; Mejía, O

    2015-10-01

    Interspecies pregnancies between closely related species are usually performed in livestock to obtain improved and enriched offspring. Indeed, different hybrids have been obtained for research purposes since many years ago, and the maternal-fetal interactions have been studied as a possible strategy for species preservation. The aim of this study was to characterize by physiological and molecular approaches the interspecies pregnancy between bighorn sheep () and domestic sheep (). Hybrids were obtained by artificial insemination; the blood pressure and protein urine levels were measured during the last two-thirds of gestation. After parturition, offspring and placentas were weighed and measured and cotyledons were counted and weighed and their surface area determined. Plasma samples were obtained between wk 8 and 21 of gestation to assess progesterone (P4), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) levels and cell-free RNA was isolated during the same period to assess hypoxia-inducible factor-1 α (α) gene expression. Hybrid and normal pregnancies were analyzed using physiological and molecular parameters during the last two-thirds of gestation (wk 8-21). The results show that during the measurement period, ewes with a hybrid pregnancy presented normal blood pressure and no alteration in urinary protein content. However, compared with sheep with a normal pregnancy, those with a hybrid pregnancy had a decrease in fetal and placental growth as well as in the cotyledonary surface area. Furthermore, in the hybrid group, there was placental insufficiency, characterized by a decrease in P4 production, as well as indications of endothelial dysfunction, characterized an increase in plasma levels of VEGF and PlGF as well as in plasma gene expression of α. Overall, the results indicate that hybrids of and presented intrauterine growth restriction, essentially due to altered endothelial function and chronic placental insufficiency

  12. AMPK knockdown in Placental Labyrinthine Progenitor Cells Results in Restriction of Critical Energy Resources and Terminal Differentiation Failure.

    PubMed

    Waker, Christopher A; Albers, Renee E; Pye, Richard L; Doliboa, Savannah R; Wyatt, Christopher N; Brown, Thomas L; Mayes, Debra Ann

    2017-03-23

    Placental abnormalities can cause Pregnancy-Associated Disorders including preeclampsia, intrauterine growth restriction, and placental insufficiency that result in complications for both the mother and fetus. Trophoblast cells within the labyrinthine layer of the placenta facilitate the exchange of nutrients, gases, and waste between mother and fetus; therefore, the development of this cell layer is critical for fetal development. As trophoblast cells differentiate, it is assumed their metabolism changes with their energy requirements. We hypothesize that proper regulation of trophoblast metabolism is a key component of normal placental development; therefore, we examined the role of AMP-activated kinase (AMPK, PRKAA1/2), a sensor of cellular energy status. Our previous studies have shown that AMPK knockdown alters both trophoblast differentiation and nutrient transport. In this study, AMPKα1/2 shRNA was used to investigate the metabolic effects of AMPK knockdown on SM10 placental labyrinthine progenitor cells before and after differentiation. Extracellular flux analysis confirmed that AMPK knockdown was sufficient to reduce trophoblast glycolysis, mitochondrial respiration, and ATP coupling efficiency. A reduction in AMPK in differentiated trophoblasts also resulted in increased mitochondrial volume. These data indicate that a reduction in AMPK disrupts cellular metabolism in both progenitors and differentiated placental trophoblasts. This disruption correlates to abortive trophoblast differentiation that may contribute to the development of Pregnancy-Associated Disorders.

  13. Sex and intrauterine growth restriction modify brain neurotransmitters profile of newborn piglets.

    PubMed

    Vázquez-Gómez, M; Valent, D; García-Contreras, C; Arroyo, L; Óvilo, C; Isabel, B; Bassols, A; González-Bulnes, A

    2016-12-01

    The current study aimed to determine, using a swine model of intrauterine growth restriction (IUGR), whether short- and long-term neurological deficiencies and interactive dysfunctions of Low Birth-Weight (LBW) offspring might be related to altered pattern of neurotransmitters. Hence, we compared the quantities of different neurotransmitters (catecholamines and indoleamines), which were determined by HPLC, at brain structures related to the limbic system (hippocampus and amygdala) in 14 LBW and 10 Normal Body-Weight (NBW) newborn piglets. The results showed, firstly, significant effects of sex on the NBW newborns, with females having higher dopamine (DA) concentrations than males. The IUGR processes affected DA metabolism, with LBW piglets having lower concentrations of noradrenaline at the hippocampus and higher concentrations of the DA metabolites, homovanillic acid (HVA), at both the hippocampus and the amygdala than NBW neonates. The effects of IUGR were modulated by sex; there were no significant differences between LBW and NBW females, but LBW males had higher HVA concentration at the amygdala and higher concentration of 5-hydroxyindoleacetic acid, the serotonin metabolite, at the hippocampus than NBW males. In conclusion, the present study shows that IUGR is mainly related to changes, modulated by sex, in the concentrations of catecholamine neurotransmitters, which are related to adaptation to physical activity and to essential cognitive functions such as learning, memory, reward-motivated behavior and stress.

  14. Metabolic programming of MEST DNA methylation by intrauterine exposure to gestational diabetes mellitus.

    PubMed

    El Hajj, Nady; Pliushch, Galyna; Schneider, Eberhard; Dittrich, Marcus; Müller, Tobias; Korenkov, Michael; Aretz, Melanie; Zechner, Ulrich; Lehnen, Harald; Haaf, Thomas

    2013-04-01

    Epigenetic processes are primary candidates when searching for mechanisms that can stably modulate gene expression and metabolic pathways according to early life conditions. To test the effects of gestational diabetes mellitus (GDM) on the epigenome of the next generation, cord blood and placenta tissue were obtained from 88 newborns of mothers with dietetically treated GDM, 98 with insulin-dependent GDM, and 65 without GDM. Bisulfite pyrosequencing was used to compare the methylation levels of seven imprinted genes involved in prenatal and postnatal growth, four genes involved in energy metabolism, one anti-inflammatory gene, one tumor suppressor gene, one pluripotency gene, and two repetitive DNA families. The maternally imprinted MEST gene, the nonimprinted glucocorticoid receptor NR3C1 gene, and interspersed ALU repeats showed significantly decreased methylation levels (4-7 percentage points for MEST, 1-2 for NR3C1, and one for ALUs) in both GDM groups, compared with controls, in both analyzed tissues. Significantly decreased blood MEST methylation (3 percentage points) also was observed in adults with morbid obesity compared with normal-weight controls. Our results support the idea that intrauterine exposure to GDM has long-lasting effects on the epigenome of the offspring. Specifically, epigenetic malprogramming of MEST may contribute to obesity predisposition throughout life.

  15. [Intrauterine contraception by plastic intrauterine devices (2 personal cases of failure)].

    PubMed

    Notter, A; Moulin, R; Grammont, P

    1968-02-18

    IUDs and tubal sterilization (both defined as types of uterine sterilization suitable for medical indications only) are reviewed, and 2 cases of failure, one with a Lippes loop and one with the Madlener sterilization method are presented. The IUD patient had a Lippes loop inserted in Tunis, then had a normal pregnancy diagnosed 11 months later in France. She delivered a 2780 gm boy prematurely 6 months later. The other patient had a Madlener sterilization performed 11 years before in Germany after 4 caesarean births. She carried the 5th pregnancy to term and received an Irving sterilization. It was concluded that plastic IUDs should be used only where oral contraceptives or tubal sterilization are contraindicated, that the same protocol should be followed as for surgical sterilization, and that the patient and doctor should be alert to the possibility of failure (e.g., expulsion, pregnancy) and the dangers (perforation, occlusion) of the IUD.

  16. The Caenorhabditis elegans GATA factor elt-1 is essential for differentiation and maintenance of hypodermal seam cells and for normal locomotion.

    PubMed

    Smith, Judith A; McGarr, Pamela; Gilleard, John S

    2005-12-15

    The Caenorhabditis elegans GATA transcription factor elt-1 has previously been shown to have a central role in the specification of hypodermal (epidermal) cell fates and acts several cell divisions before the birth of hypodermal cells. Here we report that elt-1 also has essential functions during subsequent development. Reporter gene studies show that elt-1 expression is maintained in lateral seam cells throughout development and elt-1 RNA interference experiments support an essential role for elt-1 in the differentiation of lateral seam cells in the embryo. The maintenance of seam-cell fates in all larval stages including L2d and dauer also requires elt-1. The elt-1 RNAi phenotype shows that seam cells are essential for the structural integrity of adult hermaphrodites in the vulval region and for diametric shrinkage during dauer larval formation. By contrast, severe seam-cell loss in the larval stages has little effect on moulting, indicating that the presence of these cells is not essential for this process. The elt-1 reporter gene is also expressed in neurones of the locomotory circuit. Loss of elt-1 function during postembryonic development results in a hypermotility phenotype whereas overexpression of elt-1 leads to a reciprocal phenotype of reduced motility and paralysis. These results suggest that elt-1 is a key regulator of neuronal function in larvae and adult worms.

  17. Differential expression of metallothioneins (MTs) 1, 2, and 3 in response to zinc treatment in human prostate normal and malignant cells and tissues

    PubMed Central

    Wei, Hua; Desouki, Mohamed Mokhtar; Lin, Shufei; Xiao, Dakai; Franklin, Renty B; Feng, Pei

    2008-01-01

    Background The disturbance of zinc homeostasis featured with a significant decrease of cellular zinc level was well documented to associate with the development and progression of human prostate malignancy. We have previously reported that zinc treatment induces prostate malignant cell apoptosis through mitochondrial pathway. Metallothionein (MT) is a major receptor/donor of zinc in the cells. However, the studies on the expression of MT in association with the prostate pathological and malignant status are very limited, and the zinc regulation of MT isoform expression in prostate cells remains elusive. The goals of this study were to define the expression of endogenous MTs, the isoforms of MT 1, 2, 3 at both messenger ribonucleic acid (mRNA) and protein levels; and to investigate the zinc effect on MT expression in normal prostate, benign prostatic hyperplasia (BPH) and malignant PC-3 cells, and in relevant human tissues. Cellular MT proteins were detected by immunohistochemistry, fluorescence staining and Western blot analysis; reverse transcription polymerase chain reaction (RT-PCR) was used to determine the MT isoform-specific mRNAs. Results Our results demonstrated a significant suppression of endogenous levels of MT1/2 in malignant PC-3 cells (95% reduction compared to the normal prostate cells) and in human adenocarcinoma tissues (73% MT1/2 negative). A moderate reduction of MT1/2 expression was observed in BPH. Zinc treatment remarkably induced MT1/2 expression in PC-3 and BPH cells, which was accordant with the restored cellular zinc level. MT 3, as a growth inhibitory factor, was detected and up-regulated by zinc mainly in BPH cells. Conclusion This study provided evidence of the association of attenuated MT1/2 with prostate tumor progression, and the zinc induction of MT1/2 expression resulting in cellular zinc restoration. The results suggest the potential of MT1/2 as a candidate biomarker for prostate cancer and the utilization of zinc in prostate

  18. Intrauterine Growth Restriction Associated with Hematologic Abnormalities: Probable Manifestations of Placental Mesenchymal Dysplasia

    PubMed Central

    Martinez-Payo, Cristina; Bernabeu, Rocio Alvarez; Villar, Isabel Salas; Goy, Enrique Iglesias

    2015-01-01

    Introduction Placental mesenchymal dysplasia is a rare vascular disease associated with intrauterine growth restriction, fetal demise as well as Beckwith–Wiedemann syndrome. Some neonates present hematologic abnormalities possibly related to consumptive coagulopathy and hemolytic anemia in the placental circulation. Case report We present a case of placental mesenchymal dysplasia in a fetus with intrauterine growth restriction and cerebellar hemorrhagic injury diagnosed in the 20th week of pregnancy. During 26th week, our patient had an intrauterine fetal demise in the context of gestational hypertension. We have detailed the ultrasound findings that made us suspect the presence of hematologic disorders during 20th week. Discussion We believe that the cerebellar hematoma could be the consequence of thrombocytopenia accompanied by anemia. If hemorrhagic damage during fetal life is found, above all associates with an anomalous placental appearance and with intrauterine growth restriction, PMD should be suspected along other etiologies. PMID:26495159

  19. The use of intrauterine contraceptive devices, pelvic inflammatory disease, and Chlamydia trachomatis infection.

    PubMed

    Edelman, D A

    1988-04-01

    With the same epidemiologic approach taken in a recent study that suggested that oral contraceptive use may not protect against chlamydial pelvic inflammatory disease, the risks of chlamydial pelvic inflammatory disease were evaluated for intrauterine contraceptive device users. Compared with women using no method of contraception, intrauterine contraceptive device users were not found to be at any higher risk of cervical chlamydial infection. Whether this places intrauterine contraceptive device users at no increased risk of chlamydial pelvic inflammatory disease cannot be ascertained from the available data. Further research is needed before any conclusions can be made regarding the risks of chlamydial pelvic inflammatory disease to users of intrauterine contraceptive devices, oral contraceptives, and other contraceptive methods.

  20. Placental and fetal findings in intrauterine Candida lusitaniae infection following in vitro fertilization and embryo transfer.

    PubMed

    Huang, Michael; Cham, Elaine M; Eppes, Carey S; Gerber, Susan E; Reed, Kurt D; Ernst, Linda M

    2012-01-01

    Intrauterine infection with non- albicans Candida species is rare but can be catastrophic to the fetus. A subset of intrauterine infections with non- albicans Candida species has occurred in women who have undergone in vitro fertilization and embryo transfer (IVF-ET). We report a case of a 33-year-old healthy woman, pregnant with triplets by in vitro fertilization, who experienced preterm premature rupture of membranes of fetus A at 16 weeks' gestation and subsequently developed oligohydramnios in all 3 fetuses. Following elective pregnancy termination, microscopic examination and molecular analysis demonstrated Candida lusitaniae chorioamnionitis and pneumonia in all 3 fetuses associated with granulomatous inflammation. Our case is only the 2nd report of C. lusitaniae chorioamnionitis and should raise awareness that C. lusitaniae intrauterine infection is associated with IVF-ET. We also show here that C. lusitaniae can cause granulomatous intraplacental inflammation and intrauterine pneumonia.

  1. Differential Proteomic Analysis of Human Placenta-Derived Mesenchymal Stem Cells Cultured on Normal Tissue Culture Surface and Hyaluronan-Coated Surface

    PubMed Central

    Wong, Tzyy Yue; Chen, Ying-Hui; Liu, Szu-Heng; Solis, Mairim Alexandra; Yu, Chen-Hsiang; Chang, Chiung-Hsin; Huang, Lynn L. H.

    2016-01-01

    Our previous results showed that hyaluronan (HA) preserved human placenta-derived mesenchymal stem cells (PDMSC) in a slow cell cycling mode similar to quiescence, the pristine state of stem cells in vivo, and HA was found to prevent murine adipose-derived mesenchymal stem cells from senescence. Here, stable isotope labeling by amino acid in cell culture (SILAC) proteomic profiling was used to evaluate the effects of HA on aging phenomenon in stem cells, comparing (1) old and young passage PDMSC cultured on normal tissue culture surface (TCS); (2) old passage on HA-coated surface (CHA) compared to TCS; (3) old and young passage on CHA. The results indicated that senescence-associated protein transgelin (TAGLN) was upregulated in old TCS. Protein CYR61, reportedly senescence-related, was downregulated in old CHA compared to old TCS. The SIRT1-interacting Nicotinamide phosphoribosyltransferase (NAMPT) increased by 2.23-fold in old CHA compared to old TCS, and is 0.48-fold lower in old TCS compared to young TCS. Results also indicated that components of endoplasmic reticulum associated degradation (ERAD) pathway were upregulated in old CHA compared to old TCS cells, potentially for overcoming stress to maintain cell function and suppress senescence. Our data points to pathways that may be targeted by HA to maintain stem cells youth. PMID:27057169

  2. The 2010 Russian Drought Impact on Satellite Measurements of Solar-Induced Chlorophyll Fluorescence: Insights from Modeling and Comparisons with the Normalized Differential Vegetation Index (NDVI)

    NASA Technical Reports Server (NTRS)

    Yoshida, Y.; Joiner, J.; Tucker, C.; Berry, J.; Lee, J. -E.; Walker, G.; Reichle, R.; Koster, R.; Lyapustin, A.; Wang, Y.

    2015-01-01

    We examine satellite-based measurements of chlorophyll solar-induced fluorescence (SIF) over the region impacted by the Russian drought and heat wave of 2010. Like the popular Normalized Difference Vegetation Index (NDVI) that has been used for decades to measure photosynthetic capacity, SIF measurements are sensitive to the fraction of absorbed photosynthetically-active radiation (fPAR). However, in addition, SIF is sensitive to the fluorescence yield that is related to the photosynthetic yield. Both SIF and NDVI from satellite data show drought-related declines early in the growing season in 2010 as compared to other years between 2007 and 2013 for areas dominated by crops and grasslands. This suggests an early manifestation of the dry conditions on fPAR. We also simulated SIF using a global land surface model driven by observation-based meteorological fields. The model provides a reasonable simulation of the drought and heat impacts on SIF in terms of the timing and spatial extents of anomalies, but there are some differences between modeled and observed SIF. The model may potentially be improved through data assimilation or parameter estimation using satellite observations of SIF (as well as NDVI). The model simulations also offer the opportunity to examine separately the different components of the SIF signal and relationships with Gross Primary Productivity (GPP).

  3. S1P3 confers differential S1P migration by autoreactive and non-autoreactive immature B cells and is required for normal B cell development

    PubMed Central

    Donovan, Erin E.; Pelanda, Roberta; Torres, Raul M.

    2010-01-01

    SUMMARY During B cell development, immature B cell fate is determined by whether the B cell antigen receptor is engaged in the bone marrow. Immature B cells that are non-autoreactive continue maturation and emigrate from the marrow whereas autoreactive immature B cells remain and are tolerized. However, the microenvironment where these events occur and the chemoattractants responsible for immature B cell trafficking within and out of the bone marrow remain largely undefined. Sphingosine 1-phosphate (S1P) is a chemoattractant that directs lymphocyte trafficking and thymocyte egress and in this study we investigated whether S1P contributed to B cell development, egress and positioning within the bone marrow. Our findings show that immature B cells are chemotactic towards S1P but that this response is dependent on antigen receptor specificity: non-autoreactive, but not autoreactive, immature B cells migrate towards S1P and are shown to require S1P3 receptor for this response. Despite this response, S1P3 is shown not to facilitate immature B cell egress but is required for normal B cell development including the positioning of transitional B cells within bone marrow sinusoids. These data indicate that S1P3 signaling directs immature B cells to a bone marrow microenvironment important for both tolerance induction and maturation. PMID:20039302

  4. RP-HPLC method using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate incorporated with normalization technique in principal component analysis to differentiate the bovine, porcine and fish gelatins.

    PubMed

    Azilawati, M I; Hashim, D M; Jamilah, B; Amin, I

    2015-04-01

    The amino acid compositions of bovine, porcine and fish gelatin were determined by amino acid analysis using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate as derivatization reagent. Sixteen amino acids were identified with similar spectral chromatograms. Data pre-treatment via centering and transformation of data by normalization were performed to provide data that are more suitable for analysis and easier to be interpreted. Principal component analysis (PCA) transformed the original data matrix into a number of principal components (PCs). Three principal components (PCs) described 96.5% of the total variance, and 2 PCs (91%) explained the highest variances. The PCA model demonstrated the relationships among amino acids in the correlation loadings plot to the group of gelatins in the scores plot. Fish gelatin was correlated to threonine, serine and methionine on the positive side of PC1; bovine gelatin was correlated to the non-polar side chains amino acids that were proline, hydroxyproline, leucine, isoleucine and valine on the negative side of PC1 and porcine gelatin was correlated to the polar side chains amino acids that were aspartate, glutamic acid, lysine and tyrosine on the negative side of PC2. Verification on the database using 12 samples from commercial products gelatin-based had confirmed the grouping patterns and the variables correlations. Therefore, this quantitative method is very useful as a screening method to determine gelatin from various sources.

  5. Developmental regulation of collagenase-3 mRNA in normal, differentiating osteoblasts through the activator protein-1 and the runt domain binding sites

    NASA Technical Reports Server (NTRS)

    Winchester, S. K.; Selvamurugan, N.; D'Alonzo, R. C.; Partridge, N. C.

    2000-01-01

    Collagenase-3 mRNA is initially detectable when osteoblasts cease proliferation, increasing during differentiation and mineralization. We showed that this developmental expression is due to an increase in collagenase-3 gene transcription. Mutation of either the activator protein-1 or the runt domain binding site decreased collagenase-3 promoter activity, demonstrating that these sites are responsible for collagenase-3 gene transcription. The activator protein-1 and runt domain binding sites bind members of the activator protein-1 and core-binding factor family of transcription factors, respectively. We identified core-binding factor a1 binding to the runt domain binding site and JunD in addition to a Fos-related antigen binding to the activator protein-1 site. Overexpression of both c-Fos and c-Jun in osteoblasts or core-binding factor a1 increased collagenase-3 promoter activity. Furthermore, overexpression of c-Fos, c-Jun, and core-binding factor a1 synergistically increased collagenase-3 promoter activity. Mutation of either the activator protein-1 or the runt domain binding site resulted in the inability of c-Fos and c-Jun or core-binding factor a1 to increase collagenase-3 promoter activity, suggesting that there is cooperative interaction between the sites and the proteins. Overexpression of Fra-2 and JunD repressed core-binding factor a1-induced collagenase-3 promoter activity. Our results suggest that members of the activator protein-1 and core-binding factor families, binding to the activator protein-1 and runt domain binding sites are responsible for the developmental regulation of collagenase-3 gene expression in osteoblasts.

  6. Ultrasound Location of Misplaced Levonorgestrel Releasing Intrauterine System (LNG-IUS) - is it easy?

    PubMed

    Gowri, Vaidyanathan; Mathew, Mariam

    2009-01-01

    The Levonorgestrel intrauterine device (LNG-IUD) is a hormone-containing device licensed for treatment of menorrhagia and contraception. Though complications such as perforation have been reported similar to other non-hormonal intrauterine devices, the diagnosis of such complications is difficult with this device because the LNG-IUD has a different ultrasound appearance compared to copper devices and these case reports are intended to emphasize this point.

  7. Retained intrauterine fetal bone as a rare cause of secondary infertility.

    PubMed

    Lanzarone, Valeria F; Pardey, John M

    2009-12-01

    Retention of intrauterine fetal bone is a rare cause of secondary infertility that should be considered when ultrasound demonstrates strongly shadowing echodensities in the endometrial space. It seems that the bone acts as an intrauterine contraceptive device as long as it is present in the cavity. Hysteroscopy is both diagnostic and therapeutic, with a generally good prognosis for future fertility in the absence of coexisting factors.

  8. An intrauterine catch-up growth regimen increases food intake and post-natal growth in rats.

    PubMed

    Baik, M; Rajasekar, P; Lee, M S; Kim, J; Kwon, D-H; Kang, W; Nguyen, T H; Vu, T-T T

    2014-12-01

    Nutritional conditions during the intrauterine stage are an important developmental programming factor that can affect the growth and metabolic status during foetal development and permanently alter the phenotypes of newborn offspring and adults. This study was performed to examine the effects of intrauterine catch-up growth (IUCG) on food intake, post-natal body growth and the metabolic status of offspring and growing rats. Control pregnant rats were fed ad libitum during the entire gestation period. For the IUCG regimen, pregnant rats were fed 50% of the food of the controls from pregnancy days 4 through 11 (8 days), followed by ad libitum feeding from pregnancy days 12 through parturition. The birth weight of offspring was not affected by the IUCG regimen. At weaning, offspring from each treatment group were assigned to two groups and given either a normal diet or high-fat diet (HFD) for 12 weeks until 103 days of age. In the normal diet group, the IUCG offspring showed a 9.0% increase (P < 0.05) in total food intake, were 11.2% heavier (p < 0.05) at 103 days of age and had an 11.0% greater (p < 0.05) daily weight gain compared with control offspring. The IUCG regimen did not affect body glucose and lipid metabolism. After exposure to the HFD, the IUCG regimen has not exacerbated metabolic disorders. In conclusion, our findings suggest that the IUCG nutritional regimen during pregnancy can increase the food intake and post-natal body growth of offspring without inducing metabolic disorders such as obesity and insulin resistance. The IUCG nutritional regimen might be used to improve the food intake and post-natal body growth of domestic animals.

  9. Intrauterine growth restricted piglets defined by their head shape ingest insufficient amounts of colostrum.

    PubMed

    Amdi, C; Krogh, U; Flummer, C; Oksbjerg, N; Hansen, C F; Theil, P K

    2013-12-01

    The increasing litter sizes of modern pig breeds have led to a significant number of piglets that are born undersized ("small" piglets) and some have been exposed to different degrees of intrauterine growth restriction (IUGR). The aim of this study was to investigate the physiology and capability to ingest colostrum of these small piglets, suffering from various degrees of IUGR, to see if their IUGR score could be a useful tool for easy identification of piglets in need of intervention in the colostrum period. Piglets were classified at birth based on head morphology. Piglets were classified either "normal," "mildly IUGR" (m-IUGR), or "severe IUGR" (s-IUGR), based on head morphology. Blood samples were collected at birth and at 24 h, and colostrum intake during two 12-h periods and blood metabolites at 0 and 24 h were measured. At 24 h, piglets weighing <900 g at birth and the median piglet in birth order were sacrificed, and organ weights and hepatic glycogen were measured. Overall, there was an influence of the piglets' classification on most characteristics, with normal piglets having a greater colostrum intake between 0 and 12 h (P < 0.001) and between 12 and 24 h (P < 0.05), and higher birth weight, crown rump length, body mass index, and ponderal index (P < 0.001), and a tendency toward a higher vitality score (P < 0.069) than s-IUGR piglets. There was a time × IUGR interaction, with plasma glucose levels being lowered (P < 0.001) and lactate levels elevated (P < 0.001) in s-IUGR piglets at 24 h compared with normal and m-IUGR piglets. Some differences were found in electrolytes; sodium plasma concentrations were greatest for normal piglets (P < 0.05) and highest at 0 h (P < 0.05). At 24 h of age, s-IUGR piglets had a higher heart (P < 0.001) and brain percentage (P < 0.001), and a lower liver percentage (P < 0.001) relative to body weight, compared with normal piglets. In addition, s-IUGR piglets had less hepatic glycogen than m-IUGR piglets and normal

  10. Differential body weight, blood pressure and placental inflammatory responses to normal versus high-fat diet in melanocortin-4 receptor-deficient pregnant rats

    PubMed Central

    Spradley, Frank T.; Palei, Ana C.; Granger, Joey P.

    2016-01-01

    Objectives Although obesity increases the risk for hypertensive disorders of pregnancy, the mechanisms remain unclear. Neural melanocortin-4 receptor (MC4R) deficiency causes hyperphagia and obesity. Effects of MC4R deficiency on body weight, blood pressure (BP) and placental inflammatory responses to high-fat diet (HFD) are unknown. We tested two hypotheses: MC4R deficiency results in higher body weight, BP and placental inflammation under normal-fat diet (NFD) conditions and HFD exaggerates these responses in MC4R-deficient pregnant rats. Methods MC4R+/+ and MC4R+/− rats were maintained on NFD (13% kcal fat) or HFD (40% kcal fat) for ~15 weeks, then measurements made on gestational day 19. Results MC4R+/− pregnant rats had greater body mass and total body fat and visceral adipose tissue weights along with greater circulating total cholesterol (TC) and leptin levels than MC4R+/+ rats regardless of diet. On NFD, circulating adiponectin levels were lower and placental TNFα levels and BP (conscious with carotid catheter) were higher in these heavier rats. Circulating adiponectin levels were lower and placental TNFα levels and BP were higher in MC4R+/+ rats compared with NFD controls. These parameters were not affected by HFD in the already heavier and hypertensive MC4R+/− pregnant rats. Conclusion Obesity in MC4R deficiency and HFD in MC4R+/+ rats result in higher BP and placental inflammation during pregnancy. However, HFD did not exaggerate these responses in already obese MC4R+/− pregnant rats. These data suggest that obesity and HFD are independently related to hypertension and placental inflammation in pregnancy. PMID:27467764

  11. Navigating the site for embryo implantation: biomechanical and molecular regulation of intrauterine embryo distribution.

    PubMed

    Chen, Qi; Zhang, Ying; Elad, David; Jaffa, Ariel J; Cao, Yujing; Ye, Xiaoqin; Duan, Enkui

    2013-10-01

    The distribution of intrauterine embryo implantation site(s) in most mammalian species shows remarkably constant patterns: in monotocous species such as humans, an embryo tends to implant in the uterine fundus; in polytocous species such as rodents, embryos implant evenly along the uterine horns. These long-time evolved patterns bear great biological significance because disruption of these patterns can have adverse effects on pregnancies. However, lack of suitable models and in vivo monitoring techniques has impeded the progress in understanding the mechanisms of intrauterine embryo distribution. These obstacles are being overcome by genetically engineered mouse models and newly developed high-resolution ultrasound. It has been revealed that intrauterine embryo distribution involves multiple events including uterine sensing of an embryo, fine-tuned uterine peristaltic movements, time-controlled uterine fluid reabsorption and uterine luminal closure, as well as embryo orientation. Diverse molecular factors, such as steroid hormone signaling, lipid signaling, adrenergic signaling, developmental genes, ion/water channels, and potentially embryonic signaling are actively involved in intrauterine embryo distribution. This review covers the biomechanical and molecular aspects of intrauterine embryo distribution (embryo spacing at the longitudinal axis and embryo orientation at the vertical axis), as well as its pathophysiological roles in human reproductive medicine. Future progress requires multi-disciplinary research efforts that will integrate in vivo animal models, clinical cases, physiologically relevant in vitro models, and biomechanical/computational modeling. Understanding the mechanisms for intrauterine embryo distribution could potentially lead to development of therapeutics for treating related conditions in reproductive medicine.

  12. Expression of thyroid hormone transporters in the human placenta and changes associated with intrauterine growth restriction.

    PubMed

    Loubière, L S; Vasilopoulou, E; Bulmer, J N; Taylor, P M; Stieger, B; Verrey, F; McCabe, C J; Franklyn, J A; Kilby, M D; Chan, S-Y

    2010-04-01

    Thyroid hormones (TH) are important for the development of the human fetus and placenta from very early gestation. The transplacental passage of TH from mother to fetus and the supply of TH into trophoblasts require the expression of placental TH plasma membrane transporters. We describe the ontogeny of the TH transporters MCT8, MCT10, LAT1, LAT2, OATP1A2 and OATP4A1 in a large series (n = 110) of normal human placentae across gestation and describe their expression changes with intrauterine fetal growth restriction (IUGR n = 22). Quantitative RT-PCR revealed that all the mRNAs encoding TH transporters are expressed in human placenta from 6 weeks gestation and throughout pregnancy. MCT8, MCT10, OATP1A2 and LAT1 mRNA expression increased with gestation. OATP4A1 and CD98 (LATs obligatory associated protein) mRNA expression reached a nadir in mid-gestation before increasing towards term. LAT2 mRNA expression did not alter throughout gestation. Immunohistochemistry localised MCT10 and OATP1A2 to villous cytotrophoblasts and syncytiotrophoblasts, and extravillous trophoblasts while OATP4A1 was preferentially expressed in the villous syncytiotrophoblasts. Whilst MCT8 protein expression was increased, MCT10 mRNA expression was decreased in placentae from IUGR pregnancies delivered in the early 3rd trimester compared to age matched appropriately grown for gestational age controls. No significant change was found in the mRNA expression of the other transporters with IUGR. In conclusion, several TH transporters are present in the human placenta from early 1st trimester with varying patterns of expression throughout gestation. Their coordinated effects may regulate both transplacental TH passage and TH supply to trophoblasts, which are critical for the normal development of the fetus and placenta. Increased MCT8 and decreased MCT10 expression within placentae of pregnancies complicated by IUGR may contribute to aberrant development of the fetoplacental unit.

  13. Nesfatin-130−59 Injected Intracerebroventricularly Differentially Affects Food Intake Microstructure in Rats Under Normal Weight and Diet-Induced Obese Conditions

    PubMed Central

    Prinz, Philip; Teuffel, Pauline; Lembke, Vanessa; Kobelt, Peter; Goebel-Stengel, Miriam; Hofmann, Tobias; Rose, Matthias; Klapp, Burghard F.; Stengel, Andreas

    2015-01-01

    27%, p < 0.05), while meal size was not altered. Taken together, nesfatin-130−59 is the active core of nesfatin-11−82 and acts centrally to reduce food intake in rats. The anorexigenic effect depends on the metabolic condition with increased satiation (reduction in meal size) under normal weight conditions, while in DIO rats satiety (reduction in meal frequency) is induced. PMID:26635512

  14. Differential Superiority of Heavy Charged-Particle Irradiation to X-Rays: Studies on Biological Effectiveness and Side Effect Mechanisms in Multicellular Tumor and Normal Tissue Models.

    PubMed

    Walenta, Stefan; Mueller-Klieser, Wolfgang

    2016-01-01

    This review is focused on the radiobiology of carbon ions compared to X-rays using multicellular models of tumors and normal mucosa. The first part summarizes basic radiobiological effects, as observed in cancer cells. The second, more clinically oriented part of the review, deals with radiation-induced cell migration and mucositis. Multicellular spheroids from V79 hamster cells were irradiated with X-rays or carbon ions under ambient or restricted oxygen supply conditions. Reliable oxygen enhancement ratios could be derived to be 2.9, 2.8, and 1.4 for irradiation with photons, (12)C(+6) in the plateau region, and (12)C(+6) in the Bragg peak, respectively. Similarly, a relative biological effectiveness of 4.3 and 2.1 for ambient pO2 and hypoxia was obtained, respectively. The high effectiveness of carbon ions was reflected by an enhanced accumulation of cells in G2/M and a dose-dependent massive induction of apoptosis. These data clearly show that heavy charged particles are more efficient in sterilizing tumor cells than conventional irradiation even under hypoxic conditions. Clinically relevant doses (3 Gy) of X-rays induced an increase in migratory activity of U87 but not of LN229 or HCT116 tumor cells. Such an increase in cell motility following irradiation in situ could be the source of recurrence. In contrast, carbon ion treatment was associated with a dose-dependent decrease in migration with all cell lines and under all conditions investigated. The radiation-induced loss of cell motility was correlated, in most cases, with corresponding changes in β1 integrin expression. The photon-induced increase in cell migration was paralleled by an elevated phosphorylation status of the epidermal growth factor receptor and AKT-ERK1/2 pathway. Such a hyperphosphorylation did not occur during (12)C(+6) irradiation under all conditions registered. Comparing the gene toxicity of X-rays with that of particles using the γH2AX technique in organotypic cultures of the oral

  15. Differential Superiority of Heavy Charged-Particle Irradiation to X-Rays: Studies on Biological Effectiveness and Side Effect Mechanisms in Multicellular Tumor and Normal Tissue Models

    PubMed Central

    Walenta, Stefan; Mueller-Klieser, Wolfgang

    2016-01-01

    This review is focused on the radiobiology of carbon ions compared to X-rays using multicellular models of tumors and normal mucosa. The first part summarizes basic radiobiological effects, as observed in cancer cells. The second, more clinically oriented part of the review, deals with radiation-induced cell migration and mucositis. Multicellular spheroids from V79 hamster cells were irradiated with X-rays or carbon ions under ambient or restricted oxygen supply conditions. Reliable oxygen enhancement ratios could be derived to be 2.9, 2.8, and 1.4 for irradiation with photons, 12C+6 in the plateau region, and 12C+6 in the Bragg peak, respectively. Similarly, a relative biological effectiveness of 4.3 and 2.1 for ambient pO2 and hypoxia was obtained, respectively. The high effectiveness of carbon ions was reflected by an enhanced accumulation of cells in G2/M and a dose-dependent massive induction of apoptosis. These data clearly show that heavy charged particles are more efficient in sterilizing tumor cells than conventional irradiation even under hypoxic conditions. Clinically relevant doses (3 Gy) of X-rays induced an increase in migratory activity of U87 but not of LN229 or HCT116 tumor cells. Such an increase in cell motility following irradiation in situ could be the source of recurrence. In contrast, carbon ion treatment was associated with a dose-dependent decrease in migration with all cell lines and under all conditions investigated. The radiation-induced loss of cell motility was correlated, in most cases, with corresponding changes in β1 integrin expression. The photon-induced increase in cell migration was paralleled by an elevated phosphorylation status of the epidermal growth factor receptor and AKT-ERK1/2 pathway. Such a hyperphosphorylation did not occur during 12C+6 irradiation under all conditions registered. Comparing the gene toxicity of X-rays with that of particles using the γH2AX technique in organotypic cultures of the oral mucosa, the

  16. Nesfatin-130-59 Injected Intracerebroventricularly Differentially Affects Food Intake Microstructure in Rats Under Normal Weight and Diet-Induced Obese Conditions.

    PubMed

    Prinz, Philip; Teuffel, Pauline; Lembke, Vanessa; Kobelt, Peter; Goebel-Stengel, Miriam; Hofmann, Tobias; Rose, Matthias; Klapp, Burghard F; Stengel, Andreas

    2015-01-01

    not altered. Taken together, nesfatin-130-59 is the active core of nesfatin-11-82 and acts centrally to reduce food intake in rats. The anorexigenic effect depends on the metabolic condition with increased satiation (reduction in meal size) under normal weight conditions, while in DIO rats satiety (reduction in meal frequency) is induced.

  17. New frameless and framed intrauterine devices and systems - an overview.

    PubMed

    Wildemeersch, Dirk

    2007-06-01

    There is a need for new, improved birth control methods which are easier to use, with less side effects and which avoid daily action, such as the pill. Perfect use requires consistent daily use or use at every act of intercourse. Long-acting methods eliminate the need for specific action at the time of coitus, or for daily action. Developing a new contraceptive is a major challenge. It is generally estimated that it takes 10-15 years to develop a new method and bring it to the market, at a cost of 200-300 million US dollars, and the industry is reluctant to take the risk of such long-term investment. However, both risk and investment can be reduced by taking small steps. Slight improvements of existing contraceptives could result in a giant step forward. The development of frameless intrauterine systems (IUS) is an attempt to improve the performance and acceptability of intrauterine contraception. Both the frameless GyneFix IUD and the frameless FibroPlant levonorgestrel (LNG)-IUS possess features which may solve the main problems encountered with conventional IUDs (e.g., expulsion, abnormal or excessive bleeding and pain). The performance of frameless devices, however, is dependent on correct anchoring of the device, which requires technical skill. Becoming a proficient GyneFix(R) or FibroPlant provider is easily acquired if the provider follows the procedural instruction strictly. For the less technically skilled provider, the Femilis LNG-IUS, using the new, simplified insertion technique, could be an excellent contraceptive option. It is usually not necessary to provide pain relief for insertion of an IUD/IUS, particularly in parous women. IUD providers should, however, realize that no woman likes to suffer from the insertion of an IUD. Severe discomfort may create a negative attitude towards the method. If the woman is anxious and fears pain (as most nulliparous women do), probably the most convenient, safe and effective method is to use local (intracervical

  18. [Intrauterine contraception from the viewpoint of an ambulatory gynecologic department].

    PubMed

    Hagen, P

    1981-09-01

    The history, current status, indications and contraindications for intrauterine contraception are described, information on safety and side effects is cited from the literature, and the experience of 1 clinic with IUDs is discussed. In 1976, 200,000 women in the German Democratic Republic used IUDs, or 50/1000 women aged 15-45. Intrauterine contraception had a slower and less steady development than oral contraception. The most widely used 2nd generation IUDs in East Germany were manufactured of plastic in the USSR, while the DANA copper and copper-T are the most widely used 3rd generation devices. The last days of the menstrual period are the best times for insertion, but placement immediately following abortion or birth is also possible. IUDs are indicated in cases where hormonal contraception is contraindicated. Contraindications to IUD use include suspicion of pregnancy, genital infection, atypical cytological finding, serious menstrual disturbances or bleeding of unknown cause, myomatous uterus, genital neoplasia, and deformation of the cervix or uterine cavity. The most significant complications and side effects of IUD use are bleeding disorders, dysmenorrhea, expulsion of the IUD, inflammation of the pelvic organs, undesired pregnancy, extrauterine pregnancy, and perforation of the uterus. Data from a gynecological clinic serving a predominantly rural area on 121 patients who used IUDs for a variety of reasons between June 1975 and August 1980 are presented. Observations covered a total of 4309 cycles and averaged 35.6 cycles per woman. Average age of patients was 31.7 years, no insertions were done in nulliparous patients, and the longest user had an IUD in place for 94 months. 29 patients had DANA superlux, 61 had DANA cor, 10 had DANA copper, and 21 had copper T devices. Complications and side effects were observed in 32 cases, including 19 cases of bleeding problems, of which 6 required removal; 5 of pregnancy, all of which were ended by abortions and

  19. Data Mining of Determinants of Intrauterine Growth Retardation Revisited Using Novel Algorithms Generating Semantic Maps and Prototypical Discriminating Variable Profiles

    PubMed Central

    Buscema, Massimo; Grossi, Enzo; Montanini, Luisa; Street, Maria E.

    2015-01-01

    Objectives Intra-uterine growth retardation is often of unknown origin, and is of great interest as a “Fetal Origin of Adult Disease” has been now well recognized. We built a benchmark based upon a previously analysed data set related to Intrauterine Growth Retardation with 46 subjects described by 14 variables, related with the insulin-like growth factor system and pro-inflammatory cytokines, namely interleukin -6 and tumor necrosis factor -α. Design and Methods We used new algorithms for optimal information sorting based on the combination of two neural network algorithms: Auto-contractive Map and Activation and Competition System. Auto-Contractive Map spatializes the relationships among variables or records by constructing a suitable embedding space where ‘closeness’ among variables or records reflects accurately their associations. The Activation and Competition System algorithm instead works as a dynamic non linear associative memory on the weight matrices of other algorithms, and is able to produce a prototypical variable profile of a given target. Results Classical statistical analysis, proved to be unable to distinguish intrauterine growth retardation from appropriate-for-gestational age (AGA) subjects due to the high non-linearity of underlying functions. Auto-contractive map succeeded in clustering and differentiating completely the conditions under study, while Activation and Competition System allowed to develop the profile of variables which discriminated the two conditions under study better than any other previous form of attempt. In particular, Activation and Competition System showed that ppropriateness for gestational age was explained by IGF-2 relative gene expression, and by IGFBP-2 and TNF-α placental contents. IUGR instead was explained by IGF-I, IGFBP-1, IGFBP-2 and IL-6 gene expression in placenta. Conclusion This further analysis provided further insight into the placental key-players of fetal growth within the insulin-like growth

  20. Peripheral and intrauterine neutrophil function in the cow: the influence of endogenous and exogenous sex steroid hormones.

    PubMed

    Subandrio, A L; Sheldon, I M; Noakes, D E

    2000-05-01

    It has been accepted for many years that the susceptibility of the genital tract to infection is reduced during the follicular phase compared with the luteal phase of the estrous cycle. Since the role of intrauterine neutrophils is paramount in the elimination of bacteria, it can be hypothesized that these differences in resistance to infection could be mediated by differences in uterine-derived neutrophil function. In order to test this hypothesis two groups of cows were used in this study. Group 1 cows (n=5) were studied at estrus, diestrus, after ovariectomy, after exogenous estradiol and after progesterone treatment, at which time they underwent intrauterine infusion with 1% oyster glycogen (OG) and a bacterial-free filtrate (BFF) of Actinomyces genes (BFF), the latter having been recovered from a clinical case of endometritis; neutrophils were harvested by flushing from the lumen 15 to 18 h later. A peripheral blood sample was collected at the time of flushing for the assay of estradiol and progesterone for a WBC and differential count and for the harvesting of neutrophils using a Percoll single-stage discontinuous gradient. After the recovery of the cells they were re-suspended in HBSS. Group 2 (n=4) were infused with BFF during during all reproductive states as Group 1, but with OG only after ovariectomy and after treatment with progesterone and estradiol. Neutrophil chemotaxis was assessed by measuring their migration using a modified Boyden chamber and Zymogen-activated serum as a chemoattractant. Phagocytic activity was measured by determining the number of Candida albicans ingested by each neutrophil after incubation. The percentage of kill was determined using a radiometric assay in which C. albicans was labeled with L-(5-3H) Proline. Peripheral WBC concentration was not influenced by the reproductive state of the cow; however, the mean neutrophil concentration was significantly different between the reproductive states (P<0.001) and between individual

  1. One input-class and two input-class classifications for differentiating olive oil from other edible vegetable oils by use of the normal-phase liquid chromatography fingerprint of the methyl-transesterified fraction.

    PubMed

    Jiménez-Carvelo, Ana M; Pérez-Castaño, Estefanía; González-Casado, Antonio; Cuadros-Rodríguez, Luis

    2017-04-15

    A new method for differentiation of olive oil (independently of the quality category) from other vegetable oils (canola, safflower, corn, peanut, seeds, grapeseed, palm, linseed, sesame and soybean) has been developed. The analytical procedure for chromatographic fingerprinting of the methyl-transesterified fraction of each vegetable oil, using normal-phase liquid chromatography, is described and the chemometric strategies applied and discussed. Some chemometric methods, such as k-nearest neighbours (kNN), partial least squared-discriminant analysis (PLS-DA), support vector machine classification analysis (SVM-C), and soft independent modelling of class analogies (SIMCA), were applied to build classification models. Performance of the classification was evaluated and ranked using several classification quality metrics. The discriminant analysis, based on the use of one input-class, (plus a dummy class) was applied for the first time in this study.

  2. Severe Rh alloimmunization and hemolytic disease of the fetus managed with plasmapheresis, intravenous immunoglobulin and intrauterine transfusion: A case report.

    PubMed

    Houston, Brett L; Govia, Rachelle; Abou-Setta, Ahmed M; Reid, Gregory J; Hadfield, Marie; Menard, Chantalle; Noyd, Jocelyn; Main, Susan; Zarychanski, Ryan

    2015-12-01

    Rh alloimmunization remains a potentially devastating complication of pregnancy, with fetal anemia causing hydrops and intrauterine death. Intrauterine transfusion is the standard treatment, but is particularly dangerous before 20 weeks gestation. When the need for intrauterine transfusion is anticipated early in pregnancy, immune-modulating therapies such as plasmapheresis and IVIG have been used to delay transfusion to a later gestational age. We report a 35-year-old G5P1 Rh(D)-negative woman with severe Rh alloimmunization managed successfully with sequential plasmapheresis, intravenous immune globulin and intrauterine transfusion. The optimal plasmapheresis treatment protocol and incremental benefit of IVIG remains unknown.

  3. Timing of ovulation after gonadotrophin induction and its importance to successful intrauterine insemination in the tiger (Panthera tigris).

    PubMed

    Donoghue, A M; Byers, A P; Johnston, L A; Armstrong, D L; Wildt, D E

    1996-05-01

    The ovarian response to equine chorionic gonadotrophin (eCG) and human chorionic gonadotrophin (hCG), the effect of timing of ovulation relative to hCG injection and the use of laparoscopic intrauterine artificial insemination (AI) were examined in two subspecies of tiger (Panthera tigris). Adult female tigers were subjected to the same eCG/hCG treatment followed by laparoscopy under xylazine/diazapam/ketamine HCl anaesthesia at 39-42 h (Group I, n = 9), 46-49 h (Group II, n = 5) or 51-55 h (Group III, n = 5) after hCG. Six of these females, observed to be postovulatory at the time of laparoscopy (Group II, n = 3; Group III, n = 3), were subjected to intrauterine AI. The number of preovulatory follicles observed on the ovaries of Group I females was twofold greater (P < 0.05) than the number observed on ovaries of females in Group II and III. Fewer (P < 0.05) corpora lutea were observed on ovaries of Group I females (1.3 +/- 0.6) compared with the number of corpora lutea in Group II and III (combined average, 7.8 +/- 0.8 corpora lutea per female). Only one of ten females in Groups II and III failed to ovulate by the time of laparoscopy. Four Group I females never ovulated, based on a laparoscopic re-evaluation 4 weeks later. One female inseminated 46 h after hCG (Group II) became pregnant and delivered a healthy cub after a normal gestation. There were no apparent differences between subspecies in response to the same ovulation induction protocol. Results demonstrate the importance of the relationship between exogenous gonadotrophin treatment and onset of anaesthesia for laparoscopic examination and AI in tigers. Data clearly indicate that anaesthesia/laparoscopy conducted too early (39-42 h after hCG) compromises the number of females and proportion of follicles ovulating. In contrast, ovulation success is high if anaesthesia/laparoscopy is performed after this time, and intrauterine insemination can result in healthy young.

  4. Mislocated extrauterine intrauterine devices: Diagnosis and surgical management

    PubMed Central

    Kaplanoğlu, Mustafa; Bülbül, Mehmet; Yüce, Tuncay; Kaplanoğlu, Dilek; Aban, Meral

    2015-01-01

    Objective Presentation of the diagnostic and surgical treatment methods of our extrauterine intrauterine device (IUD) cases. Material and Methods We retrospectively evaluated the data of 21 extrauterine IUD cases at our clinic between 2008 and 2010. The symptoms, diagnostic methods, and surgical treatments were evaluated. Results A total of 14 copper and seven levonorgestrel (LNG) IUDs were used. IUD had been inserted during lactation in 71.4% of the patients. The reasons for presentation of patients were unintended pregnancy in 19.05%, pelvic pain in 19.05%, and pelvic pain with vaginal bleeding in 23.8%. IUD in two patients were located the retroperitoneal area. IUD string had not been visible during routine follow-up in 38.1% of the patients. Laparoscopy was performed in 14 patients and laparotomy was performed for dense adhesions in seven patients. Conclusion Extrauterine IUDs can present with various clinical symptoms. Ultrasonography and X-Ray are sufficient for the diagnosis. Surgical removal is needed to prevent possible complications, and the preferred surgical technique in appropriate patients is laparoscopy. PMID:26097391

  5. Intrauterine devices and uterine peristalsis: evaluation with MRI.

    PubMed

    Kido, Aki; Togashi, Kaori; Kataoka, Milliam L; Nakai, Asako; Koyama, Takashi; Fujii, Shingo

    2008-01-01

    Intrauterine devices (IUDs) have been viewed as an effective form of contraception. However, the mechanism by which IUDs disturb fertility remains controversial. This study aimed to evaluate the effects of IUDs on uterine contractility using cine MR. Eleven healthy female volunteers of reproductive age bearing IUDs and 12 women not bearing IUDs were evaluated during the periovulatory phase. MR images were obtained with a 1.5-T magnet, acquiring 60 serial images every 3 s via half-Fourier acquisition single-shot turbo spin echo to be displayed on cine mode. Assessments were based on (a) the presence of peristaltic waves, (b) the frequency and direction of peristaltic waves and (c) the extent of peristaltic waves. Static images were evaluated for thickness of the junctional zone (JZ) and myometrium. A fundo-cervical (FC)-directed peristaltic wave was identified in 4 of 11 IUD-bearing subjects and in only 1 of 12 subjects from the control group. FC waves extended through more than half of the thickness of the myometrium. Peristaltic frequency in IUD users (5.0/3 min) was less than that of the control group (6.5/3 min). The JZ and myometrium were significantly thicker in IUD users. FC-directed waves were more often observed in IUD-bearing subjects, which might explain the inhibition of active sperm transport.

  6. Role of the levonorgestrel intrauterine system in effective contraception

    PubMed Central

    Attia, Abdelhamid M; Ibrahim, Magdy M; Abou-Setta, Ahmed M

    2013-01-01

    Norgestrel, a synthetic progestin chemically derived from 19-nortestosterone, is six times more potent than progesterone, with variable binding affinity to various steroid receptors. The levonorgestrel-releasing intrauterine system (LNG IUS) provides a long-acting, highly effective, and reversible form of contraception, with a pearl index of 0.18 per 100 women-years. The locally released hormone leads to endometrial concentrations that are 200–800 times those found after daily oral use and a plasma level that is lower than that with other forms of levonorgestrel-containing contraception. The contraceptive effect of the LNG IUS is achieved mainly through its local suppressive effect on the endometrium, leading to endometrial thinning, glandular atrophy, and stromal decidualization without affecting ovulation. The LNG IUS is generally well tolerated. The main side effects are related to its androgenic activity, which is usually mild and transient, resolving after the first few months. Menstrual abnormalities are also common but well tolerated, and even become desirable (eg, amenorrhea, hypomenorrhea, and oligomenorrhea) with proper counseling of the patient during the choice of the method of contraception. The satisfaction rates after 3 years of insertion are high, reaching between 77% and 94%. The local effect of the LNG IUS on the endometrium and low rates of systemic adverse effects have led to its use in other conditions rather than contraception, as for the treatment of endometrial hyperplasia, benign menorrhagia, endometriosis, adenomyosis, and uterine fibroids. PMID:23990713

  7. Specific serum protein levels in women using intrauterine contraceptive device.

    PubMed

    Wiedermann, D; Kríz, J; Cídl, K

    1980-01-01

    The report is concerned with the levels of 17 specific serum proteins in 46 women using plastic nonmedicated intrauterine contraceptive device (IUCD) Dana-Super. Blood samplings were carried out three times: just before the IUCD introduction, 30 and 54 weeks after the insertion of IUCD. The following proteins except haptoglobin were quantitatively determined by radial immunodiffusion: prealbumin, albumin, orosomucoid, alpha 1-antitrypsin, ceruloplasmin, alpha 2HS-glycoprotein, alpha 2-macroglobulin, hemopexin, C3-component, transferrin, beta 2-glycoprotein I, C-reactive protein and immunoglobulins IgG, IgA, IgM and IgD. Moderately increased values were found for alpha 2HS-glycoprotein and beta 2-glycoprotein I in sera taken 30 weeks after the insertion of IUCD. AT the same time the augmentation of alpha 1-antitrypsin was established. This might be evoked by the raised protease activity in biological fluids of genital region. The raise in consequence of IUCD application of transferrin and the decrease of haptoglobin at the first postinsertion examination and the decrease of hemopexin and albumin at the second may be associated with higher menstrual bleeding followed by iron deficiency. All other proteins as well as the acute phase proteins showed only minor if any differences as compared with the corresponding start values. Similarly, there is no evidence of a systemic immunoglobulin response to IUCD use.

  8. [Placental epigenetic programming in intrauterine growth restriction (IUGR)].

    PubMed

    Casanello, Paola; Castro-Rodríguez, José A; Uauy, Ricardo; Krause, Bernardo J

    2016-01-01

    Intrauterine growth restriction (IUGR) is a perinatal condition affecting foetal growth, with under the 10th percentile of the weight curve expected for gestational age. This condition has been associated with higher cardiovascular and metabolic risk and post-natal obesity. There are also major changes in placental function, and particularly in a key molecule in this regulation, nitric oxide. The synthesis of nitric oxide has numerous control mechanisms and competition with arginase for their common substrate, the amino acid L-arginine. This competition is reflected in various vascular diseases and particularly in the endothelium of the umbilical vessels of babies with IUGR. Along with this, there is regulation at the epigenetic level, where methylation in specific regions of some gene promoters, such as the nitric oxide synthase, regulating their expression. It is currently of great interest to understand the mechanisms by which diseases such as IUGR may be conditioned, particularly by maternal nutritional and metabolic conditions, and epigenetic mechanisms that could eventually be modifiable, and thus a focus of interest for health interventions.

  9. [Maternal serum IgA in intrauterine fetal growth retardation].

    PubMed

    Briese, V; Straube, W

    1983-01-01

    The problem was to prove the significance of IgA estimations in maternal serum samples with regard to the diagnosis and the monitoring of intrauterine fetal growth retardation. IgA was estimated in serum samples from two groups of patients. The first was formed from 62 serum samples of 14 primi- and multiparae delivered from new-borns with a birth weight below the 10th centile. The second was the control group. 82 serum samples from 18 gravidae were available. The IgA estimations were carried out by means of single radial immunodiffusion according to Mancini and co-workers. The IgA values of the two groups were different considering that linear regression model was used; negative correlation between IgA and pregnancy weeks in group with retarded new-borns (y = -151,78 X + 7579,8; r = -0,39) and positive correlation of these parameters in control group (y = 73,59 X -429,38; r = 0,26). It could be that IgA is an additional parameter within placental function tests of the 3rd trimester of pregnancy.

  10. Role of prostaglandins in intrauterine migration of the equine conceptus.

    PubMed

    Stout, T A; Allen, W R

    2001-05-01

    Between at least day 9 and day 16 after ovulation the spherical equine conceptus migrates continuously throughout the uterine lumen, propelled by peristaltic myometrial contractions. This unusually long period of intrauterine movement ensures that the conceptus delivers its anti-luteolytic signal to the entire endometrium to achieve luteostasis. The present experiment tested the hypothesis that prostaglandins stimulate the myometrial contractions that result in the migration of the conceptus. Serial ultrasonographic examinations of the uteri of eight mares performed during 2 h periods between day 10 and day 18 of gestation recorded the pattern of conceptus migration before and after treatment with the cyclo-oxygenase inhibitor flunixin meglumine. Conceptus mobility was high between day 10 and day 14 after ovulation (4.3 +/- 0.8, 4.7 +/- 0.8 and 4.3 +/- 0.9 changes of location per h on day 10, day 12 and day 14, respectively), but was reduced immediately and markedly by an i.v. injection of flunixin meglumine (3.8 +/- 1.5, 1.8 +/- 0.8 and 0.7 +/- 0.2 location changes per h), thereby implicating prostaglandins as the primary stimulus for the myometrial contractions that drive migration of the conceptus.

  11. Prospective risk of intrauterine fetal death in monoamniotic twin pregnancies.

    PubMed

    Morikawa, Mamoru; Yamada, Takashi; Yamada, Takahiro; Sato, Shoji; Minakami, Hisanori

    2012-08-01

    This study was conducted to review the overall short-term outcome of monoamniotic twins in Japan and to determine the prospective risk of fetal death so as to adequately counsel parents with monoamniotic twins. Study subjects were 101 women with monoamniotic twins who were registered with the Japan Society of Obstetrics and Gynecology Successive Pregnancy Birth Registry System and who had given birth at ≥22 weeks of gestation during 2002-2009. The gestational week at delivery (mean±SD) was 31.8±3.7. Fourteen women experienced intrauterine fetal death (IUFD). Short-term outcomes of co-twins born to the 14 women included 8 IUFDs, one early neonatal death within 7 days of life (END), and 5 survivors. Four other women experienced 5 ENDs. Thus, 13.9% (28/202) of infants died perinatally (22 IUFDs and 6 ENDs), 13.9% (14/101) of women experienced IUFD, and 82.2% (83/101) of women experienced neither IUFD nor END. Structural anomalies and twin-to-twin transfusion syndrome explained 17.9% (five infants) and 10.7% (three infants) of the 28 perinatal deaths, respectively. The prospective risk of IUFD was 13.9% (14/101) for women who reached gestational week 22(-0/7), gradually decreasing thereafter but remaining at between 4.5% and 8.0% between gestational week 30(-0/7) and 36(-0/7).

  12. G-CSF Intrauterine for Thin Endometrium, and Pregnancy Outcome

    PubMed Central

    Tehraninejad, Ensieh; Davari Tanha, Fateme; Asadi, Ebrahim; Kamali, Koorosh; Aziminikoo, Elham; Rezayof, Elahe

    2015-01-01

    Objective: To evaluate effects of G-CSF on a cancelled ART cycle due to thin endometrium. Materials and methods: In a nonrandomized clinical trial from January 2011 to January 2013 in two tertiary university based hospitals fifteen patients undergoing embryo transfer and with the history of cycle cancellation due to thin endometrium were studied. Intrauterine infusion of G-CSF was done on the day of oocyte pick-up or 5 days before embryo transfer. The primary outcome to be measured was an endometrium thickened to at least 6 mm and the secondary outcome was clinical pregnancy rate and consequently take-home baby. All previous cycles were considered as control for each patient. Results: The G-CSF was infused at the day of oocyte retrieval or 5 days before embryo transfer. The endometrial thickness reached from 3.593±0.251 mm to 7.120 ± 0.84 mm. The mean age, gravidity, parity, and FSH were 35.13± 9.531 years, 3, 1 and 32.78 ± 31.10 mIU/ml, respectively. The clinical pregnancy rate was 20%, and there was one missed abortion, a mother death at 34 weeks, and a preterm labor at 30 weeks due to PROM. Conclusion: G-CSF may increase endometrial thickness in the small group of patients who had no choice except cycle cancellation or surrogacy. PMID:26622308

  13. Use of drugs and intrauterine devices for birth control.

    PubMed

    Meeker, C I

    1969-05-08

    The current use of oral contraceptives and intrauterine devices for population control is reviewed including the mechanism of their antifertility actions and the use-effectiveness of each method. The use-effectiveness of the IUD has been calculated as 1.5-3.0 pregnancies per 100 woman-years of exposure. The IUD has a high continuation rate (70% after 2 years) and is excellent for poorly motivated population groups. The most serious common side-effect--pelvic infection--can be controlled by more careful screening and modern antibiotic therapy. Other side-effects include irregular bleeding and uterine perforation, but not at significantly high levels. Oral contraceptives have been found to be virtually 100% effective, even in the new lower dose preparations containing around .5 mg progesterone and .05-.15 mg estrogen per tablet. New hormonal contraceptive approaches include pills which progesterone only, high postcoital estrogen administration, and long-acting injectable progestogen (Depo-Provera). All of these methods are highly effective but have some undesirable side-effects and require further study. Careful examination of the recent research reports connecting oral contraceptive use with increased risk of thromboembolism indicate that whatever the danger in oral contraceptive use, the direct physical hazards of pregnancy after contraceptive failure are much higher and more serious. Though a 100% safe contraceptive is a desirable ideal, the safety of current oral contraceptives and IUDs is higher than most other aspects of modern life.

  14. Intrauterine contraceptive device embedded in the omentum – case report

    PubMed Central

    Zolnierczyk, Piotr; Cendrowski, Krzysztof; Sawicki, Wlodzimierz

    2015-01-01

    This report describes the case of a 29-year-old patient, female (nulliparous) who had an intrauterine device (IUD) inserted in 2010 and who has had no gynecological control since then (for 4 years). After this time, the asymptomatic patient had a gynecological appointment, during which a doctor did not find the strings of IUD in the speculum. Ultrasound examination did not reveal the presence of the IUD in the uterine cavity, which led to the suspicion of its presence outside the uterus. The patient was referred to a hospital, where she underwent ultrasound and X-ray examination of the pelvis that confirmed the presence of the IUD outside the uterus. Laparoscopy was performed during which the IUD was localized as being embedded in the omentum. It was removed by performing a resection of a part of the omentum with inflammatory infiltration. The patient was discharged home on the second postoperative day in a good condition. This case confirms the need for gynecological control and ultrasound examination shortly after insertion. An ultrasound or/and X-ray is mandatory in any case of absence of IUD strings previously visible in the vagina, if the patient did not observe its expulsion. PMID:26664227

  15. Adult monozygotic twins discordant for intra-uterine growth have indistinguishable genome-wide DNA methylation profiles

    PubMed Central

    2013-01-01

    Background Low birth weight is associated with an increased adult metabolic disease risk. It is widely discussed that poor intra-uterine conditions could induce long-lasting epigenetic modifications, leading to systemic changes in regulation of metabolic genes. To address this, we acquire genome-wide DNA methylation profiles from saliva DNA in a unique cohort of 17 monozygotic monochorionic female twins very discordant for birth weight. We examine if adverse prenatal growth conditions experienced by the smaller co-twins lead to long-lasting DNA methylation changes. Results Overall, co-twins show very similar genome-wide DNA methylation profiles. Since observed differences are almost exclusively caused by variable cellular composition, an original marker-based adjustment strategy was developed to eliminate such variation at affected CpGs. Among adjusted and unchanged CpGs 3,153 are differentially methylated between the heavy and light co-twins at nominal significance, of which 45 show sensible absolute mean β-value differences. Deep bisulfite sequencing of eight such loci reveals that differences remain in the range of technical variation, arguing against a reproducible biological effect. Analysis of methylation in repetitive elements using methylation-dependent primer extension assays also indicates no significant intra-pair differences. Conclusions Severe intra-uterine growth differences observed within these monozygotic twins are not associated with long-lasting DNA methylation differences in cells composing saliva, detectable with up-to-date technologies. Additionally, our results indicate that uneven cell type composition can lead to spurious results and should be addressed in epigenomic studies. PMID:23706164

  16. Application of complementary luminescent and fluorescent imaging techniques to visualize nuclear and cytoplasmic Ca²⁺ signalling during the in vivo differentiation of slow muscle cells in zebrafish embryos under normal and dystrophic conditions.

    PubMed

    Webb, Sarah E; Cheung, Chris C Y; Chan, Ching Man; Love, Donald R; Miller, Andrew L

    2012-01-01

    1. Evidence is accumulating for a role for Ca²⁺ signalling in the differentiation and development of embryonic skeletal muscle. 2. Imaging of intact, normally developing transgenic zebrafish that express the protein component of the Ca²⁺-sensitive complex aequorin, specifically in skeletal muscle, show that two distinct periods of spontaneous synchronised Ca²⁺ transients occur in the trunk: one at approximately 17.5-19.5 h post-fertilization (h.p.f.; termed signalling period SP1) and the other after approximately 23 h.p.f. (termed SP2). These periods of intense Ca²⁺ signalling activity are separated by a quiet period. 3. Higher-resolution confocal imaging of embryos loaded with the fluorescent Ca²⁺ reporter calcium green-1 dextran shows that the Ca²⁺ signals are generated almost exclusively in the slow muscle cells, the first muscle cells to differentiate, with distinct nuclear and cytoplasmic components. 4. Here, we show that coincidental with the SP1 Ca²⁺ signals, dystrophin becomes localized to the vertical myoseptae of the myotome. Introduction of a dmd morpholino (dmd-MO) resulted in no dystrophin being expressed in the vertical myoseptae, as well as a disruption of myotome morphology and sarcomere organization. In addition, the Ca²⁺ signalling signatures of dmd-MO-injected embryos or homozygous sapje mutant embryos were abnormal such that the frequency, amplitude and timing of the Ca²⁺ signals were altered compared with controls. 5. Our new data suggest that, in addition to a structural role, dystrophin may function in the regulation of [Ca²⁺](i) during the early stages of slow muscle cell differentiation when the Ca²⁺ signals generated in these cells coincide with the first spontaneous contractions of the trunk.

  17. Multivariate normality

    NASA Technical Reports Server (NTRS)

    Crutcher, H. L.; Falls, L. W.

    1976-01-01

    Sets of experimentally determined or routinely observed data provide information about the past, present and, hopefully, future sets of similarly produced data. An infinite set of statistical models exists which may be used to describe the data sets. The normal distribution is one model. If it serves at all, it serves well. If a data set, or a transformation of the set, representative of a larger population can be described by the normal distribution, then valid statistical inferences can be drawn. There are several tests which may be applied to a data set to determine whether the univariate normal model adequately describes the set. The chi-square test based on Pearson's work in the late nineteenth and early twentieth centuries is often used. Like all tests, it has some weaknesses which are discussed in elementary texts. Extension of the chi-square test to the multivariate normal model is provided. Tables and graphs permit easier application of the test in the higher dimensions. Several examples, using recorded data, illustrate the procedures. Tests of maximum absolute differences, mean sum of squares of residuals, runs and changes of sign are included in these tests. Dimensions one through five with selected sample sizes 11 to 101 are used to illustrate the statistical tests developed.

  18. Detection of expressional changes induced by intrauterine growth restriction in the developing rat pancreas

    PubMed Central

    Zhang, Lin; Chen, Wei; Dai, Yuee

    2016-01-01

    Intrauterine growth retardation (IUGR) is a disorder that can result in permanent changes in the physiology and metabolism of the newborn, which increased the risk of disease in adulthood. Evidence supports IUGR as a risk factor for the development of diabetes mellitus, which could reflect changes in pancreas developmental pathways. We sought to characterize the IUGR-induced alterations of the complex pathways of pancreas development in a rat model of IUGR. We analyzed the pancreases of Sprague Dawley rats after inducing IUGR by feeding a maternal low calorie diet from gestational day 1 until term. IUGR altered the pancreatic structure, islet areas, and islet quantities and resulted in abnormal morphological changes during pancreatic development, as determined by HE staining and light microscopy. We identified multiple differentially expressed genes in the pancreas by RT-PCR. The genes of the insulin/FoxO1/Pdx1/MafA signaling pathway were first expressed at embryonic day 14 (E14). The expressions of insulin and MafA increased as the fetus grew while the expressions of FoxO1 and Pdx1 decreased. Compared with the control rats, the expressions of FoxO1, Pdx1, and MafA were lower in the IUGR rats, whereas insulin levels showed no change. Microarray profiling, in combination with quantitative real-time PCR, uncovered a subset of microRNAs that changed in their degree of expression throughout pancreatic development. In conclusion, our data support the hypothesis that IUGR influences the development of the rat pancreas. We also identified new pathways that appear to be programmed by IUGR. PMID:27190278

  19. Analytical study of intrauterine fetal death cases and associated maternal conditions

    PubMed Central

    Sharma, Susmita; Sidhu, Harpreet; Kaur, Sukhbir

    2016-01-01

    Introduction: Intrauterine fetal death is an important indicator of maternal and perinatal health of a given population. This study was undertaken to study the maternal and fetal factors associated with intrauterine fetal death. Materials and Methods: This was a retrospective single center study. The details were entered in a preformed proforma. The details of complaints at admission, obstetrics history, menstrual history, examination findings, per vaginal examination findings, mode of delivery and fetal outcomes, placental examination, condition of cord and investigation reports were recorded. Results: A total of 250 intrauterine fetal deaths were reported amongst 6942 deliveries conducted during the study period. The incidence rate of intrauterine fetal death was 36/1000 live births. Two hundred and twenty-two deliveries were unbooked and unsupervised. The other observations were rural population (58%), low socioeconomic group (71.2%), previous stillbirth (9.2%), gestational hypertension (32.8%), anemia (74.4%), antepartum hemorrhage (18.8%), and congenital malformations (CMFs) (8.8%). Conclusions: The incidence of intrauterine fetal deaths in our population is higher than that reported from developed countries. This is associated with anemia, pregnancy-induced hypertension, illiteracy, low socioeconomic status, and higher incidence of undiagnosed CMFs. PMID:26958515

  20. Intrauterine growth correlation to postnatal growth--influence of risk factors and complications in pregnancy.

    PubMed

    Larsen, T; Greisen, G; Petersen, S

    1997-01-20

    In a population of 616 pregnant women with increased risk of intrauterine growth retardation, we examined the relationship of third trimester fetal growth to maternal and pregnancy risk factors, the infants condition at birth, and postnatal growth. Intrauterine growth velocity was calculated from repeated estimations of fetal weight using ultrasound. Postnatal growth up to 3 months was measured in 313 of the infants. Intrauterine growth velocity was directly correlated to birth weight deviation (R = 0.35, P < 0.0001) and inversely correlated to postnatal growth (R = 0.21, P = 0.0001). Heavy smoking throughout pregnancy was the most pronounced factor associated with loss of fetal growth percentiles (P = 0.006), and it was also associated with postnatal catchup (P = 0.01). Infants who needed neonatal care had significantly lower intrauterine growth velocities compared to the rest of the study group; no correlation was found between intrauterine growth velocity and Apgar scores or umbilical pH. It is concluded that growth retardation in the third trimester can be identified by ultrasound fetometry, and is associated with maladaptation at birth and postnatal catchup. However, the correlations were weak suggesting that deviation at birth reflects, only to a limited degree, acceleration or deceleration of growth in the third trimester.

  1. Sigmoid colocolic fistula caused by intrauterine device migration: a case report

    PubMed Central

    2014-01-01

    Introduction The intrauterine device is a form of contraception with a long duration of action and few systemic side effects. Migration into the abdominal cavity may occur early or years after insertion giving rise to bowel obstruction, perforation, ischemia, mesenteric injury, strictures or fistulae. Colocolic fistula formation is a rare but serious complication of intrauterine device migration, which may lead to difficulties in diagnosis and device retrieval. Case presentation We report the case of a 29-year-old Sri Lankan woman who became pregnant 5 years after intrauterine device insertion. The device could not be located during pregnancy. She was asymptomatic and defaulted follow up during the antenatal period. She had an uncomplicated vaginal delivery. A subsequent laparotomy for device retrieval failed due to technical difficulties. A repeat laparotomy identified a sigmoid colocolic fistula with adhesions to the fallopian tube. The device was removed and colonic defects primarily closed following which the patient made an uneventful recovery. Conclusions All translocated intrauterine devices should be removed regardless of type and location. This case illustrates that they may cause complex bowel lesions leading to serious technical difficulties during retrieval. With the increasing use of minimally invasive approaches for intrauterine device retrieval, a low threshold for open surgery in complicated cases is advocated. PMID:24594141

  2. [Prevention and treatment of intra-uterine synechiae: Review of the literature].

    PubMed

    Warembourg, S; Huberlant, S; Garric, X; Leprince, S; de Tayrac, R; Letouzey, V

    2015-04-01

    Intra-uterine adhesions are a major cause of secondary infertility. The prevalence of adhesions is probably underestimated due to the heterogeneity of the symptoms. An exhaustive literature search using search engines MEDLINE, Pubmed, Cochrane library and Web of Science was performed to make a focus on the origins, consequences and methods of prevention of intra-uterine adhesions. Intra-uterine adhesions are likely to occur after any endo-uterine surgery via dysregulated activation of coagulation chain linked to the inflammatory process. Early and late obstetric complications are also recognized as caused by adhesions. The diagnosis is currently performed by hysteroscopy but it remains an invasive procedure even if it can be done with an ambulatory management. Several research approaches inspired by intra-abdominal surgery for the prevention of pelvic adhesions have been developed. However, no current method of prevention has proven its effectiveness in terms of improving spontaneous fertility. The improvement in surgical practices, the design of new intra-uterine medical devices and new research especially in the field of endometrial stem cells can maybe reduce the rate of adhesions end their complications after intra-uterine surgery.

  3. Clinical and demographic characteristics of women with intrauterine adhesion in abuja, Nigeria.

    PubMed

    Efetie, Efena R; Umezulike, Augustine C; Okafor, Ugochukwu V

    2012-01-01

    Objective. Infertility menstrual abnormalities continue to constitute a significant bulk of gynecological consultation in Africa. Both of these problems are sometimes traced to intrauterine adhesions which are preventable in the majority of cases. Study Design. A retrospective analysis of intrauterine adhesions at the National Hospital Abuja, Nigeria, was carried out, covering the period from 1st September 1999 to 1st September 2004. A total of 72 cases were analyzed. Statical analysis was done using X(2). Results. The incidence of intrauterine adhesions was 1.73% of new patients. Mean age ± SD was 29.97 ± 4.82 years. Patients who were Para 0 to 1 constituted 81.9% of the total. Intrauterine adhesions significantly (P < 0.02) occurred in nulliparae. The majority (68%) were educated only up to secondary level which was significant (P < 0.05). Menstrual abnormalities were present in 90.3%. The commonest predisposing factor identified was a history of dilatation and curettage or uterine evacuation. Conclusion. Intrauterine adhesions are associated with lower educational status and low parity. Increasing educational targets nationally, poverty alleviation, nationwide retraining in manual vacuum aspiration, and wider application of this technique are recommended.

  4. Successful intrauterine insemination of Eld's deer (Cervus eldi thamin) with frozen-thawed spermatozoa.

    PubMed

    Monfort, S L; Asher, G W; Wildt, D E; Wood, T C; Schiewe, M C; Williamson, L R; Bush, M; Rall, W F

    1993-11-01

    This study tested the efficacy of assisted reproduction (synchronization of oestrus and intrauterine artificial insemination (AI)) in contributing to the captive propagation of an endangered species, the Eld's deer (Cervus eldi thamin). Semen was collected from males preselected on the basis of under-represented genotype. Motility of spermatozoa after thawing from ejaculates diluted with BF5F extender (8% glycerol), frozen on dry ice in 0.5 ml straws and stored in liquid nitrogen was 60-70%. Intravaginal progesterone-releasing devices (controlled internal drug release, CIDR-type G) were inserted into 20 adult Eld's deer hinds for 14 days. In all hinds, semen (7.5-10 x 10(6) motile spermatozoa per uterine horn) was deposited by laparoscopy performed 70 h after removal of the CIDR device. Ovarian activity, before and after AI, was monitored by analysing pregnanediol-3 alpha-glucuronide (PdG) concentrations in voided urine collected three to seven times per week. During the period of CIDR device insertion, urinary PdG profiles were equal to, or above, normal luteal phase concentrations in all hinds. Within 48 h of device withdrawal, PdG concentrations returned to baseline values in 17 of the 20 females, and the onset of behavioural oestrus occurred at this time in 12 hinds. On the basis of sustained increases in urinary PdG, 9 of the 20 hinds were diagnosed as pregnant by 90 days after AI, all of which delivered offspring after a mean gestation of 241.1 days (range, 235-245). Seven singletons (two females, five males) were born alive and survived, and one singleton and one set of twins were stillborn (three females).(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Prenatal effects of intra-uterine growth retardation on adult height of conscripts from Hungary.

    PubMed

    Joubert, K; Gyenis, G

    2003-01-01

    Physical development appropriate for age, and the normal rate of development of children, are two well-known indicators of the biological status of populations. Physical development of children is influenced by several factors, and the intrauterine environment may be critical among them. The authors studied the effect of the prenatal environment, as measured by birth length and birth weight, and socio-economic factors, as measured by place of residence and educational level of parents, on the height of 18-year-old conscripts surveyed in 1998. The following results were obtained: 1. The conscripts were classified into one of the following groups: small for gestational age (SGA), appropriate for gestational age (AGA), large for gestational age (LGA) according to their data of birth and their development at birth. Statistically significant differences in birth length and height at 18 years of age were found for the AGA and LGA groups, according to place of residence at birth. In addition, nutrition at birth (and the biological and social inclusion related to this) affects the extent of change in physique between birth and 18 years of age, within each group. The extent of change in height in the SGA group is 122.38 cm, 123.40 cm in the AGA group, and 124.11 cm in the LGA group. With each neonatal developmental group, conscripts from Budapest had the highest values both in body length and height at 18 years of age. 2. The educational level of parents influenced the physical development of their children. Means of birth length, and of body height at the age of 18 years, were greater, the higher the level of education of their parents. The lower the level of education the parents have, the more significant is the difference between birth length and height at the age of 18 years, compared to the sample mean. This is attributed to a health-cultural-information deficit arising from the low level of education of the parents.

  6. Intrauterine devices: an effective alternative to oral hormonal contraception.

    PubMed

    2009-06-01

    (1) Intrauterine devices (IUDs) are placed in the uterine cavity with the objective of providing long-term contraception, mainly by preventing fertilisation. The best-known IUDs contain copper, but there is also an IUD delivering levonorgestrel, a progestin; (2) How effective are these devices, and what are their adverse effects? To answer these questions, we analysed the literature using the standard Prescrire methodology; (3) T-shaped copper IUDs, with a copper surface area of 380 mm2 on 3 arms, and the levonorgestrel-releasing device, have similar contraceptive efficacy as combined oral contraceptives that are used correctly. In contrast, IUDs are more effective than oral contraception used incorrectly; (4) Among IUD users, there are on average about 6 pregnancies per 1000 woman-years. There is less experience with the levonorgestrel IUD which seems to be at least as effective as copper IUDs; (5) The rare intrauterine pregnancies that occur in women using an IUD generally end in miscarriage. About 25% of these pregnancies end in a live birth if the device is left in place, compared to about 90% if the device is removed; (6) Ectopic pregnancies are rarer in IUD users than in women who do not use contraception. However, about one in 20 pregnancies that occur in women using an IUD is ectopic; (7) The IUD is expelled in about 5% to 10% of cases within 5 years, and expulsion recurs in about 30% of these women; (8) Problems such as difficult insertion, pain, bleeding and syncope are reported in less than 1.5% of cases overall; (9) Uterine perforation during insertion is rare, occurring in 0.6 to 16 cases per 1000 insertions, regardless of the type of IUD. The risk of perforation is higher when the IUD is inserted less than 4 to 6 weeks after delivery or elective abortion; (10) During the first 3 months after insertion, the risk of pelvic infection is slightly higher than in the general population, especially in women with pre-existing asymptomatic Chlamydia

  7. Intrauterine devices - upper and lower genital tract infections.

    PubMed

    Meirik, Olav

    2007-06-01

    The clinical diagnosis of a pelvic inflammatory disease (PID) is notoriously difficult. The incidence rate of PIDs among intrauterine device (IUD) users as reported from different studies depends heavily on the definition used and the means available for diagnosing PIDs. It varies by almost 10-fold from 1 per 100 to 1 per 1000 woman-years in different publications. PID risk has been found to be 6-fold higher in the first month after IUD insertion than it is thereafter. It is not known if the overall PID risk in IUD users beyond the first month of IUD insertion is higher than that in nonusers; however, if it is higher, the additional risk is small. The PID risk in IUD users is modified by the number of sexual partners of the IUD user and that of her partner(s), community prevalence of STDs and age of the IUD user. Bacterial vaginosis appears not to be associated with IUD use. Overall, bacterial vaginosis is not associated with PIDs, but specific subgroups of patients with BV that may be difficult to identify clinically are at an increased risk for PIDs. Because of the long duration of use of current copper IUDs, replacement of the IUD is infrequent and insertion-associated PIDs should consequently also be less frequent. IUD use has become safer with respect to PIDs through more effective screening and counseling procedures described in current guidelines for the initiation of IUD use. Current guidance must be followed to preserve the IUD as a safe contraceptive method.

  8. Early intrauterine exposure to tobacco-inhaled products and obesity.

    PubMed

    Toschke, A M; Montgomery, S M; Pfeiffer, U; von Kries, R

    2003-12-01

    An association between maternal smoking during pregnancy and offspring obesity has been reported. This study assessed the impact of maternal smoking during the first trimester. Data on 4,974 German children aged 5-6 years were obtained at school entry health examinations in 2001-2002 in Bavaria. Obesity was defined by body mass index using International Obesity Task Force cutpoints. Prevalence of obesity was 1.9% (95% confidence interval (CI): 1.5, 2.4) in offspring of never smokers, 4.5% (95% CI: 2.9, 6.7) for maternal smoking during the first trimester only, and 5.9% (95% CI: 3.8, 8.7) for maternal smoking throughout pregnancy. Unadjusted odds ratios were higher for maternal smoking throughout pregnancy (odds ratio = 3.23, 95% CI: 2.00, 5.21) compared with the first trimester only (odds ratio = 2.41, 95% CI: 1.49, 3.91). Adjusted odds ratios were similar: 1.70 (95% CI: 1.02, 2.87) for maternal smoking throughout pregnancy and 2.22 (95% CI: 1.33, 3.69) for maternal smoking in the first trimester only. When modeled together, no statistically significant difference in obesity risk was found between maternal smoking in the first trimester compared with throughout pregnancy. The effect of intrauterine tobacco exposure on childhood obesity may depend largely on cigarette smoking during the first trimester, whereas the additional impact of smoking throughout pregnancy might be due to confounding by sociodemographics. Women should be encouraged to quit smoking prior to conception.

  9. Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue.

    PubMed

    Li, Fang; Teng, Hui-Yun; Liu, Jing; Wang, Hua-Wei; Zeng, Li; Zhao, Li-Fang

    2014-09-01

    This study aimed to determine the influence of antenatal taurine supplementation on taurine content in the brains of fetal rats with intrauterine growth restriction (IUGR). Experiments were performed at the Central Laboratory of Bayi Children's Hospital Affiliated to Beijing Military General Hospital in China from January to June 2013. Fifteen pregnant rats were randomly divided into three groups: normal controls, an IUGR group and an IUGR + antenatal taurine supplement group (Taurine group) (n = 5). The IUGR model was induced using a low-protein diet throughout gestation. Rats in the taurine group were fed a diet supplemented with 300 mg/kg/day taurine for 12 days after conception until natural delivery. Two fetal rats were randomly selected in every litter, and taurine levels in the brains of rats were detected using high-performance liquid chromatography-mass spectrometry. Results showed that (1) the mean body weight of the fetal rats in the normal control, IUGR and IUGR + antenatal taurine supplement groups was 6.619 ± 0.4132, 4.509 ± 0.454, and 5.176 ± 0.436 g (F = 429.818, P < 0.01), respectively, and (2) that taurine levels in the brains of the fetal rats in the normal control, IUGR and taurine groups were (2.399 ± 0.134) × 10(5), (1.881 ± 0.166) × 10(5) and (2.170 ± 0.191) × 10(5) μg/g (F = 24.828, P < 0.01), respectively. Overall, our results indicated that taurine levels in IUGR fetal rat brains were lower than in the control animals, and that antenatal taurine supplementation could significantly increase taurine levels in the brains of fetal rats with IUGR.

  10. Barriers to prescribing the Copper T 380A intrauterine device by physicians.

    PubMed Central

    Kooiker, C. H.; Scutchfield, F. D.

    1990-01-01

    From a questionnaire sent to all obstetricians and gynecologists and all family and general practitioners in San Diego County, California, regarding the Copper T 380A intrauterine device, substantial barriers to prescribing it were identified. Of all physicians responding, 40% reported that they were not recommending the Copper T 380A to anyone, the single most common reason given being concern about medical liability. A lack of knowledge about the new device, a lack of intrauterine device insertion skills, and certain medical practice settings were also important barriers to prescribing it. The new intrauterine device is considered in the context of innovation-diffusion theory. Substantial amounts of education and training and improvement in the medical-legal climate are needed before current barriers to prescribing the new device are removed. Images PMID:2219892

  11. Comparison between scissor and laser resections of intrauterine septa in hysteroscopy

    NASA Astrophysics Data System (ADS)

    Wilczak, Maciej; Wozniak, Jakub; Cwojdzinski, Marek; Sajdak, Stefan; Opala, Tomasz; Pisarski, Tadeusz

    1996-03-01

    The comparison between results of scissors- and Nd-YAG laser-resection of intrauterine septa in hysteroscopy was shown. In 12 patients the scissors-resection and in 11 women the laser- resection was done. In the group of patients after laser procedure 10 of them were pregnant and 9 delivered healthy children. One missed abortion was diagnosed in the twenty-first week of gestation. After scissors-resection 7 women became pregnant and 5 of them bore mature children. Two of those seven lost their gestation (spontaneous abortions in the nineteenth and twentieth weeks of pregnancy). In the authors' opinion hysteroscopy is a very useful method of diagnostics and therapy of intrauterine septa. The Nd-YAG laser-resection of intrauterine septa seems to be the method with the lowest number of complications. Fertility and parity highly improves after removal of the septa localized in the uterine cavity.

  12. Using the Normalized Differential Wetness Index to Scale Leaf Area Index, Create Three-Dimensional Classification Maps, and Scale Seasonal Evapotranspiration Depletions in Canopies Along the Middle Rio Grande Riparian CorridorCorridor

    NASA Astrophysics Data System (ADS)

    McDonnell, D. E.; Cleverly, J. R.; Dahm, C. N.; Coonrod, J. A.

    2005-12-01

    This research creates temporally and spatially explicit data layers of vegetation, leaf area index (LAI), three dimensional (3D) vegetation classification maps, and seasonal evapotranspiration (ET) depletions along the middle Rio Grande riparian corridor. The first part of this work produces two dimensional (2D) classification maps of native and non-native canopy vegetation using temporal patterns and the decision tree classifier in ENVI 4.0 (Research Systems Inc. Boulder, Colorado). The second part of this work correlates the normalized differential wetness index (NDWI) with field measurements of plant area index (PAI), stem area index (SAI), and leaf area index (LAI) using the LAI-2000 Plant Canopy Analyzer (PCA) (LICOR Inc., Lincoln, Nebraska). SAI is measured in winter to capture only branches and stems. PAI is measured during the growing season. Field measurements taken within 10 days of image capture dates provide adequate correlations though the closer the dates the better the correlation. LAI represents the surface area of active green leafy vegetation. NDWI correlates with both PAI and estimated LAI in both Tamarisk chinensis and Populus deltoides ssp. Wislizeni sites better than the more traditional normalized differential vegetation index (NDVI). This study also suggests that winter PCA measurements approximate SAI which should be subtracted from PAI in woody vegetation like T. chinensis and Salix exigua stands. The results show that correcting for leaf geometry by multiplying T. chinensis areas with cylindrical cladophylls by pi and the remaining flat leaf vegetation by two yields the best relationship between NDWI and total LAI. The 2Dclassification maps can be placed on top of relief maps of LAI to produce 3D classification maps. The final part of this research scales ET from four 3D eddy covariance towers located in two T. chinensis and two P. deltoides study sites. ET is regressed with LAI, percent daylight (PD), and average hourly incoming net

  13. Doppler ultrasonography in obstetrics: from the diagnosis of fetal anemia to the treatment of intrauterine growth-restricted fetuses.

    PubMed

    Mari, Giancarlo

    2009-06-01

    After the adoption of the use of umbilical artery and middle cerebral artery peak systolic velocity in high-risk pregnancies and in pregnancies that are at risk of having an anemic fetus, the main focus of Doppler ultrasonography in obstetrics today is intrauterine growth-restricted fetuses. What is most needed at this time are (1) training of sonographers and sonologists on how to perform a Doppler study, (2) an international classification of intrauterine growth-restricted fetuses, and (3) a study of the natural history of intrauterine growth-restricted fetuses that might contribute to a better understanding of the intrauterine growth-restriction process and to standard treatment of intrauterine growth-restricted fetuses. Future investigations, which would include randomized studies, could be designed from the results of such studies.

  14. Phase transitions of the system Ag sub 2 HgI sub 4 -Cu sub 2 HgI sub 4 at normal and high pressure studied by differential scanning calorimetry

    SciTech Connect

    Friesel, M.; Baranowski, B.; Lunden, A. )

    1990-02-08

    Differential scanning calorimetry has been applied for studying the system Ag{sub 2}HgI{sub 4}-Cu{sub 2}HgI{sub 4} at both normal and high pressure. It is confirmed that there is a miscibility gap in the ordered phase and that the order-disorder phase transition has a eutectoid point at 307 K and 42.7 mol % Cu{sub 2}HgI{sub 4} at normal pressure, which is about 30 K higher than expected from a calculation for ideal eutectic behavior. The order-disorder transition is of first-order character over the whole composition range, confirming the interpretation by Suchow and ruling out the suggestion by Jaffray that it should be of second-order character in the middle part of the range. The transition enthalpy is equal to 7.3 {plus minus} 0.2 kJ/mol for the eutectoid composition. The phase diagram of the eutectoid composition was determined for pressures up to 0.72 GPa, and the temperature of the order-disorder transition increased from 307 to about 325 K, The correlation was not linear over the whole pressure range, but an average dT/dP slope of 25 K/GPa is in good agreement with the 24 K/GPa calculated by means of van Laar,s formula. The transition enthalpy (kJ/mol) decreased linearly with increasing pressure with d{Delta}H/dp = -4.0 kJ/(mol GPa). A calculation from simple additive rule gives instead d{Delta}H/dp = -1.5 kJ/(mol GPa).

  15. Committee Opinion No. 642: Increasing Access to Contraceptive Implants and Intrauterine Devices to Reduce Unintended Pregnancy.

    PubMed

    2015-10-01

    Unintended pregnancy persists as a major public health problem in the United States. Although lowering unintended pregnancy rates requires multiple approaches, individual obstetrician-gynecologists may contribute by increasing access to contraceptive implants and intrauterine devices. Obstetrician-gynecologists should encourage consideration of implants and intrauterine devices for all appropriate candidates, including nulliparous women and adolescents. Obstetrician-gynecologists should adopt best practices for long-acting reversible contraception insertion. Obstetrician-gynecologists are encouraged to advocate for coverage and appropriate payment and reimbursement for every contraceptive method by all payers in all clinically appropriate circumstances.

  16. Pregnancy rate following post-insemination intrauterine treatment of endometritis in dairy cattle.

    PubMed

    Shams-Esfandabadi, N; Shirazi, A; Ghasemzadeh-Nava, H

    2004-04-01

    Summary Of 1500 examined Holstein cows in milk, there were 315 cows with mucopurulent discharges at the time of insemination (21%). Twenty-four hours after insemination, the infected animals randomly received no treatment (group I, control, n = 93), intrauterine infusion of 1 g oxytetracycline (group II, n = 63) and intrauterine infusion of 5 million IU procain penicillin G sodium (group III, n = 159). First service conception rate following treatment was 48.3, 49.2 and 47.7% in groups I, II and III, respectively. In conclusion, treatment with either antibiotic had no advantage relative to the control on first service conception rate.

  17. Radioimmunoassay of ''free thyroxin'' in dried blood spots on filter paper - preliminary observations on the effective differentiation of subjects with congenital hypothyroidism from those with subnormal thyroxin-binding globulin and normal subjects

    SciTech Connect

    Mizuta, H.; Miyai, K.; Ichihara, K.; Amino, N.; Harada, T.; Nose, O.; Tanizawa, O.

    1982-03-01

    In this sensitive, simple method for measuring ''free thyroxin'' (FT/sub 4/) in eluates of dried blood spots on filter paper by use of a radioimmunoassay kit (Amerlex Free T/sub 4/ RIA), the measurable range of FT/sub 4/ is 1.8 to 57 ng/L (equivalent to the concentration in serum), or 7 to 237 fg/tube. The mean coefficients of variation for within assay-within spots, within assay-between spots, and between assays were 5.3%, 5.0%, and 6.2%, respectively. FT/sub 4/ in blood spotted on filter paper is stable for at least a month when dried and kept at either -20/sup 0/C, 4/sup 0/C, room temperature (about 25/sup 0/C), or 37/sup 0/C. The results for FT/sub 4/ in dried blood spots correlated closely with the free-T/sub 4/ concentration in serum (r = 0.99). The method can be used to differentiate cases of primary and secondary hypothyroidism from normal subjects and those with subnormal thyroxin-binding globulin. This method may be useful in screening for congenital hypothyroidism, because sample-retesting is not necessary.

  18. Metabolomic Research on Newborn Infants With Intrauterine Growth Restriction

    PubMed Central

    Liu, Jing; Chen, Xin-Xin; Li, Xiang-Wen; Fu, Wei; Zhang, Wan-Qiao

    2016-01-01

    Abstract To compare differences in metabolites between newborns with intrauterine growth restriction (IUGR) and those who are appropriate for gestational age (AGA) in order to understand the changes in metabolites of newborns with IUGR and to explore the possible metabolic mechanism of tissue and organ damages in patients with IUGR, with the ultimate goal of providing the basis for clinical intervention. A total of 60 newborns with IUGR and 60 AGA newborns who were hospitalized in the neonatal intensive care unit of our hospital between January 2011 and December 2015 and who underwent metabolic disease screening were enrolled in this study. The differences in 21 amino acids and 55 carnitines in peripheral blood, as well as changes in the ratios of free carnitine and acylcarnitine to total carnitine, were compared. Metabolites, particularly alanine, homocysteine, leucine, methionine, ornithine, serine, tyrosine, isovaleryl carnitine, and eicosenoyl carnitine, differed according to newborns’ birth weight (<3rd percentile, 3rd–5th percentiles, 5th–10th percentiles, and 10th–90th percentiles), with those with lower birth weight showing the greater difference (P < 0.05). Metabolites also differed by gestational age, and the differences observed were mainly as follows: preterm and full-term newborns showed differences in metabolites, mainly in alanine, proline, cerotoyl carnitine, and tetradecanedioyl carnitine (P < 0.05); preterm and full-term AGA newborns showed differences in metabolites, mainly in alanine, glutamine, homocysteine, pipecolic acid, proline, heptanoyl carnitine, and sebacoyl carnitine (P < 0.05); and preterm and full-term newborns with IUGR showed differences in metabolites, mainly in arginine, glutamic acid, homocysteine, histidine, leucine, isoleucine, ornithine, serine, threonine, tryptophan, valine, heptanoyl carnitine, decanoyl carnitine, linoleyl carnitine, methylmalonyl carnitine, glutarylcarnitine, sebacoyl carnitine

  19. Does intrauterine saline infusion by intrauterine insemination (IUI) catheter as endometrial injury during IVF cycles improve pregnancy outcomes among patients with recurrent implantation failure?: An RCT

    PubMed Central

    Salehpour, Saghar; Zamaniyan, Marzieh; Saharkhiz, Nasrin; Zadeh modares, Shahrzad; Hosieni, Sedighe; Seif, Samira; Malih, Narges; Rezapoor, Parinaz; Sohrabi, Mohammad-Reza

    2016-01-01

    Background: Recurrent implantation failure is one of the most issues in IVF cycles. Some researchers found that beneficial effects of endometrial Scratching in women with recurrent implantation failure, while some authors demonstrated contrary results Objective: The present study aimed to investigate the effect of intrauterine. Saline infusion as a form of endometrial injury, during fresh in vitro fertilization-embryo transfer cycle, among patients with recurrent implantation failure. Materials and Methods: In this clinical trial study 63 women undergoing assisted reproductive technology were divided into two groups either local endometrial injury by intrauterine saline infusion during day 3-5 of the ongoing controlled ovarian stimulation cycle, or IVF protocol performed without any other intervention in Taleghani Hospital, Tehran, Iran. The main outcome measure was clinical pregnancy rates. Results: Patients who received intra uterine saline infusion (n=20), had significantly lower clinical pregnancy numbers (1 vs. 9, p<0.05) and implantation rates (4.7% vs. 41.6%, p<0.05), compared to controls (n=39). However, there was no significant difference in miscarriage rates (9.4% vs. 8.7%, p>0.05) and multiple pregnancy numbers (1 vs. 3, p>0.05) between groups. Conclusion: When intrauterine saline infusion as a form of endometrial injury is performed during the ongoing IVF cycles it has negative effect on reproductive outcomes among patients with recurrent implantation failure. PMID:27738660

  20. An evaluation of the simultaneous use of the levonorgestrel-releasing intrauterine device (LNG-IUS, Mirena®) combined with endometrial ablation in the management of menorrhagia.

    PubMed

    Vaughan, D; Byrne, P

    2012-05-01

    The objective of our study was to document the efficacy and possible complications in women who were treated for menorrhagia with the simultaneous use of endometrial ablation and the levonorgestrel-releasing intrauterine device. Women were offered this combined treatment if they complained of menorrhagia and needed contraception. A structured questionnaire was mailed to 150 women who had undergone this combined treatment; 105 (70%) returned a completed questionnaire. The mean duration of follow-up was 25 months (range 6-54 months). Following treatment, 53 women (50.5%) described their periods as being lighter than normal and 49 (46%) had become amenorrhoeic. Overall, 101 (96%) stated that they were satisfied with the treatment. Of the women, 95 (90.5%) said that the treatment had been a 'complete success'; eight (7.6%) 'partly successful' and two women (1.9%) said the treatment had been a 'failure'. One woman subsequently required a hysterectomy. This observational study supports the hypothesis that combined endometrial ablation and insertion of a levonorgestrel-releasing intrauterine device is an effective treatment for menorrhagia and has some advantages when compared with the individual use of these treatments.

  1. Oocyte retrieval versus conversion to intrauterine insemination in patients with poor response to gonadotropin therapy.

    PubMed

    Shahine, Lora K; Lathi, Ruth B; Baker, Valerie L

    2009-10-01

    We compared cycle characteristics and outcomes for planned in vitro fertilization cycles with five or fewer developing follicles that proceeded to retrieval (n = 170) with those that converted to intrauterine insemination (IUI) (n = 50). The risk of no embryo transfer was 24% in cycles that proceeded to retrieval. Live birth rate per cycle started was similar for IUI (6%) compared with retrieval (7%).

  2. Intrauterine growth retardation and preterm delivery: prenatal risk factors in an indigent population.

    PubMed

    Wen, S W; Goldenberg, R L; Cutter, G R; Hoffman, H J; Cliver, S P

    1990-01-01

    Prenatally ascertained risk factors for low birth weight were evaluated in a population of 17,000 indigent women for their specific effect on intrauterine growth retardation and on the rate of preterm delivery. In a univariate analysis, intrauterine growth retardation occurred more frequently in women who were black, single, primiparous, less than 17 or greater than 30 years old, short, thin, had a previous preterm delivery, consumed alcohol, took drugs, or gained limited weight. Preterm delivery occurred significantly more frequently in women who were black, single, thin, less than 17 or greater than 30 years old, had less than a twelfth grade education, or gained limited weight. In logistic regression analyses, race, parity, maternal age, a history of preterm delivery, smoking, short stature, low weight, and low weight gain remained significant risk factors of intrauterine growth retardation. Of these factors, smoking, short stature, low weight, and low weight gain showed the greatest correlation. Factors significantly related to preterm delivery included black race, single marital status, younger or older ages, previous preterm delivery, smoking, low weight, and very low or high weight gain. A previous preterm delivery and very low maternal weight had the greatest correlation. Identification of specific risk factors of both intrauterine growth retardation and preterm delivery should aid in the development of strategies to reduce the prevalence of these conditions.

  3. A Real-Time Intrauterine Catheter Technique for Fetal Electrocardiogram Monitoring

    DTIC Science & Technology

    2007-11-02

    Applications and Technology, pp. 348-352, September 1997. [4] T.H. Strong et al., "The intrauterine probe electrode," Am. J. Obstet . Gynecol ., vol. 164, pp. 1233...1234, May 1991. [5] R.H. Paul and E.H. Hon, “Clinical fetal monitoring IV. Experience with a spiral electrode,” Obstet . & Gynecol ., vol. 41, no. 5

  4. Exploring Trends in Intrauterine Device (IUD) Usage among Women in the United States: A Literature Review

    ERIC Educational Resources Information Center

    Nobiling, Brandye; Drolet, Judy C.

    2012-01-01

    Intrauterine devices (IUDs) have not been popular contraceptives in the US for the past 40 years. Recent evidence, however, has shown a slight rebirth in use, from a rate of approximately 2% in 2002 to over 5% in 2008 (Guttmacher Institute, 2010). Empirical evidence is favorable of IUD use in most women, but the still-low usage rate suggests…

  5. What is new in intrauterine devices? Best articles from the past year.

    PubMed

    Hurd, William W

    2013-10-01

    This month, we focus on current research about intrauterine devices. Dr. Hurd discusses four recent publications, and each is concluded with a "bottom line" that is the take-home message. The complete reference for each can be found in on this page, along with direct links to the abstracts.

  6. 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 introducer. 884.5360 Section 884.5360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... IUD's that function by drug activity, which are subject to the new drug provisions of the Federal...

  7. 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 introducer. 884.5360 Section 884.5360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... IUD's that function by drug activity, which are subject to the new drug provisions of the Federal...

  8. Barcoded sequencing reveals diverse intrauterine microbiomes in patients suffering with endometrial polyps

    PubMed Central

    Fang, Rui-Li; Chen, Lin-Xing; Shu, Wen-Sheng; Yao, Shu-Zhong; Wang, Si-Wen; Chen, Yu-Qing

    2016-01-01

    Results of this study showed that the bacterial composition in vagina (V) greatly differed from intrauterine microbiome (I). Microbiomes were present in all intrauterine samples of healthy women (Group H (I)) and patients with endometrial polyps (EP) (including Group EP (I) and Group EP/chronic endometritis (CE) (I)). Indeed, the intrauterine bacteria population in Group EP/CE (I) were more diverse than those in Groups EP (I) and H (I). The result also confirmed the bacterial composition differences between vagina and uterus as well as the intrauterine microbiome alteration in the patients, compared to the healthy. Although bacteria of Proteobacteria, Firmicutes and Actinobacteria, dominated the intrauterine microbiome in all samples, however, proportions of Firmicutes from Group EP/CE (I) and Group EP (I) were much higher than that from Group H (I), in contrast, the proportions of Proteobacteria were far lower than the healthy. At the genus level, compared to Group H (I), it is found that proportions of Lactobacillus, Gardnerella, Bifidobacterium, Streptococcus, and Alteromonas were significantly higher, and that of Pseudomonas were significantly lower in Group EP/CE (I) or Group EP (I). In addition, lower proportions of Enterobacter and Sphingomonas and a higher proportion of Prevotella were also observed in Group EP/CE (I). In conclusion, uterine microbiomes between patients with EP and the healthy are significantly different and all the potentially important variation of uterine microbes may cause EP, but not definitively related to CE. Further experiments should be performed to test these relationships to endometritis occurrence. PMID:27186283

  9. [Intrauterine insemination: state-of-the-art in humans].

    PubMed

    Royère, D

    2004-10-01

    Despite its being used for a long time, intrauterine insemination (i.u.i.) remains debated as to its precise place and efficacy among assisted reproductive technologies. Data issued from the French Health Ministry inquiries are strictly limited to the number of cycles and the pregnancies and births including the multiple ones. Concerning 2000, more than 44,000 cycles were registered with 8% deliveries per cycle and 12% multiple pregnancies. Apart from the cervical female infertility which is considered to have the best prognosis with i.u.i., literature data remain controversial with male and unexplained infertility. Prospective randomized studies are rather scarce, particularly when considering the inclusion of untreated control population. Meta-analyses have been published for ten years, which allowed to better define the place of i.u.i. in patient management. However one may notice that the sperm cut-off parameters for male infertility and the respective contribution of i.u.i. and ovulation treatment do not allow develop some evidence-based guidelines for i.u.i. good practice. Quite all meta-analyses modulated their conclusions by addressing the need for large randomized controlled studies. Such a need seems now quite reinforced since results were until now expressed as pregnancy rate per cycle or pregnancy rate per couple, whereas single live birth rate and drop out rate are claimed to be taken into account nowadays. Moreover the level of controlled hyperstimulation is highly questionable with both hyperstimulation ovary syndrome and multiple pregnancy risks. Patients facing with failed i.u.i. cycles may turn to i.v.f. or i.c.s.i.. Interestingly data coming from the French national register (FIVNAT) did not show major differences between couples turning to i.v.f. (i.c.s.i.) after previously failed i.u.i. cycles or using directly i.v.f. (i.c.s.i.). Moreover the prognostic as evaluated on pregnancy rate per cycle was unchanged between such patients, which does not

  10. [Pathophysiological changes of umbilical vessels in intrauterine growth restriction].

    PubMed

    Jakó, Mária; Surányi, Andrea; Kaiser, László; Domokos, Dóra; Gáspár, Róbert; Bártfai, György

    2014-12-14

    Bevezetés: Évi 100 ezer szülésre számítva hazánkban 4–5 ezer intrauterin növekedésben visszamaradt újszülöttel kell számolnunk, akik jelentős perinatalis morbiditást képviselnek. Célkitűzés: Kórosan kis súlyú újszülöttek köldökzsinórereinek és méhlepényének patológiai és gyógyszerhatástani összehasonlítása kontrollterhességekével. Módszer: A Szegedi Szülészeti és Nőgyógyászati Klinikán vett köldökzsinórmintákat eset- és kontrollcsoportra osztották. A méhlepényeredésnél a köldökzsinórból két darab 10 cm-es mintából egyet 24 órán belül tápoldatban tárolva szervfürdőben dolgoztak fel. A méhlepény és a zsinór további darabjának jellemzőit a Royal College of Pathologists 2011-es protokollja alapján rögzítették. Eredmények: Az érgyűrűk standard alaptónusának beállítását követően oxitocin és dezmopresszin hatására, a várttól eltérően, egyik csoportban sem történt érösszehúzódás. A patomorfológiai és ultrahangvizsgálat adatai az eset- és normál kontrollcsoportban szignifikáns eltérést mutattak. Következtetések: Az eredmények alapján feltételezhető, hogy a köldökerek sem oxitocin-, sem vazopresszinreceptort nem tartalmaznak. A kis születési súly hátterében a placenta elöregedése, a zsinór csökkent kanyarulatossága és a benne lévő kóros áramlás állhat. Orv. Hetil., 2014, 155(50), 1989–1995.

  11. Differential expression of GSK3β and pS9GSK3β in normal human tissues: can pS9GSK3β be an epithelial marker?

    PubMed

    Lee, Hojung; Ro, Jae Y

    2015-01-01

    Glycogen synthase kinase 3β (GSK3β) and phosphorylated GSK3β at Ser9 (pS9GSK3β) are crucial in cellular proliferation and metabolism. GSK3β and pS9GSK3β are deregulated in many diseases including tumors. Data on altered expression of GSK3β and pS9GSK3β are mainly limited to tumor tissues, thus the expression of GSK3β and pS9GSK3β in normal human tissue has been largely unknown. Thus, we examined the immunohistochemical localization of GSK3β and pS9GSK3β in human fetal and adult tissues, and also compared the expression pattern of GSK3β and pS9GSK3β with that of the CK7 and CK20. We found GSK3β expression in neurons of brain, myenteric plexus in gastrointestinal tract, squamous epithelium of skin, and mammary gland. The expression of pS9GSK3β was restricted to the epithelial cells of breast and pancreaticobiliary duct, distal nephron of kidney, gastrointestinal tract, fallopian tube, epididymis, secretory cell of prostatic gland, and umbrella cell of urinary tract. The staining pattern of pS9GSK3β and CK7 was overlapped in most organs except for gastrointestinal tract where CK7 was negative and CK20 was positive. Our results show that the expression of GSK3β may be associated with differentiation of ectodermal derived tissues and pS9GSK3β with that of epithelial cells of endodermal derived tissues in human. In addition, the expression of pS9GSK3β in the selective epithelial cells may indicate its association with secretory or barrier function of specific cells and may serve as another immunohistochemical marker for epithelial cells.

  12. Avoidance of the dimensional incompatibility as the main reason for side effects in intrauterine contraception.

    PubMed

    Kurz, K H

    1981-01-01

    From 1976 until June 1978, 1708 medicated IUDs were inserted in nulliparous (64%), oligoparous (e.g., 1-2 births; 29%), and multiparous women (7%). 53% of the women in this study were nulligravida. The women had been fitted with CuT 200 devices with normal (32 mm) and adapted (15-30 mm) long transversal arms (n = 1550), 7 Cu 200 (n = 60), ML Cu 250 (n = 83) and T progesterone-releasing devices (n = 16). Because most women were nulliparous or oligoparous, with correspondingly small uteri and narrow cavities, prefit measurements of length and width of each individual cavity had to be taken in order to avoid dimensional incompatibility, found to be the main reason for unwanted side effects and high termination rates in intrauterine contraception. The Cavimeter, a new measuring device, was invented to enable the operator to measure cervical length, total length (the difference is the cavity length), fundus transversal, and to determine the shorter optimal fundus transversal corresponding to uterus contractions (e.g., during menstruation). Determination of cavity width appears more important than determination of length when using an IUD with a flexible shaft. Generally, the adapted Cu 200 IUD gives the best results concerning termination rates for medical reasons as well as expulsion rates (0.3%). The shorter the transversal arm of the CuT 200, the higher the acceptance rate. It is interesting to note that adaption of medicated IUDs does not lead to a higher pregnancy rate. The low expulsion rate allows the shortening of the plastic filaments intracervically. Both shortening the plastic filaments and dipping the IUD-holding tube into a 5% Betadine solution before insertion are simple methods to avoid ascending infection. Research efforts should be directed to the formulation of an easy method for outlining the uterine cavity, and to the changes in the design and dimensions and the chemical composition of the device, so as to develop a softly malleable device which can

  13. Glucose replacement to euglycemia causes hypoxia, acidosis, and decreased insulin secretion in fetal sheep with intrauterine growth restriction.

    PubMed

    Rozance, Paul J; Limesand, Sean W; Barry, James S; Brown, Laura D; Hay, William W

    2009-01-01

    Nutritional interventions for intrauterine growth restriction (IUGR) have raised concerns for fetal toxicity, the mechanisms of which are unknown. Most of these attempts did not aim to normalize fetal metabolic conditions. Therefore, we used a model of IUGR to determine whether normalization of fetal hypoglycemia for 2 wks would be tolerated and increase insulin concentrations and pancreatic beta-cell mass. IUGR fetuses received either a direct saline infusion (Sal, the control group) or a 30% dextrose infusion (Glu) to normalize glucose concentrations. Neither insulin concentrations (0.11 +/- 0.01 Glu vs. 0.10 +/- 0.01 ng/mL Sal) nor beta-cell mass (65.2 +/- 10.3 Glu vs. 74.7 +/- 18.4 mg Sal) changed. Glucose stimulated insulin secretion (GSIS) was lower in the Glu group. Glu fetuses became progressively more hypoxic: O2 content 1.4 +/- 0.5 Glu vs. 2.7 +/- 0.4 mM Sal, p < 0.05. Partial pressure of carbon dioxide (Paco2) (53.6 +/- 0.8 Glu vs. 51.6 +/- 0.8 Sal, p < 0.05) and lactate (7.74 +/- 3.82 Glu vs. 2.47 +/- 0.55 mM Sal, p < 0.0001) were greater and pH lower (7.275 +/- 0.071 Glu vs. 7.354 +/- 0.003 Sal, p < 0.01) in the Glu group. We conclude that correction of fetal hypoglycemia is not well tolerated and fails to increase insulin concentrations or beta-cell mass in IUGR fetuses.

  14. Role for the thromboxane A2 receptor β-isoform in the pathogenesis of intrauterine growth restriction

    PubMed Central

    Powell, Katie L.; Stevens, Veronica; Upton, Dannielle H.; McCracken, Sharon A.; Simpson, Ann M.; Cheng, Yan; Tasevski, Vitomir; Morris, Jonathan M.; Ashton, Anthony W.

    2016-01-01

    Intrauterine growth restriction (IUGR) is a pathology of pregnancy that results in failure of the fetus to reach its genetically determined growth potential. In developed nations the most common cause of IUGR is impaired placentation resulting from poor trophoblast function, which reduces blood flow to the fetoplacental unit, promotes hypoxia and enhances production of bioactive lipids (TXA2 and isoprostanes) which act through the thromboxane receptor (TP). TP activation has been implicated as a pathogenic factor in pregnancy complications, including IUGR; however, the role of TP isoforms during pregnancy is poorly defined. We have determined that expression of the human-specific isoform of TP (TPβ) is increased in placentae from IUGR pregnancies, compared to healthy pregnancies. Overexpression of TPα enhanced trophoblast proliferation and syncytialisation. Conversely, TPβ attenuated these functions and inhibited migration. Expression of the TPβ transgene in mice resulted in growth restricted pups and placentae with poor syncytialisation and diminished growth characteristics. Together our data indicate that expression of TPα mediates normal placentation; however, TPβ impairs placentation, and promotes the development of IUGR, and represents an underappreciated pathogenic factor in humans. PMID:27363493

  15. Increased Fetal Plasma Erythropoietin in Monochorionic Twin Pregnancies With Selective Intrauterine Growth Restriction and Abnormal Umbilical Artery Doppler.

    PubMed

    Chang, Yao-Lung; Chao, An-Shine; Peng, Hsiu-Huei; Chang, Shuenn-Dyh; Su, Sheng-Yuan; Chen, Kuan-Ju; Cheng, Po-Jen; Wang, Tzu-Hao

    2016-08-01

    Hypoxia is the primary stimulus for the production of erythropoietin (EPO) in both fetal and adult life. Here, we investigated fetal plasma EPO concentrations in monochorionic (MC) twin pregnancies with selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery (UA) Doppler. We diagnosed sIUGR in presence of (1) birth-weight discordance >20% and (2) either twin with a birth weight <10th percentile. An abnormal UA Doppler was defined as a persistent absent-reverse end diastolic flow (AREDF). The intertwin EPO ratio was calculated as the plasma EPO level of the smaller (or small-for-gestational-age) twin divided by the EPO concentration of the larger (or appropriate-for-gestational-age (AGA)) twin. Thirty-two MC twin pairs were included. Of these, 17 pairs were normal twins (Group 1), seven pairs were twins with sIUGR without UA Doppler abnormalities (Group 2), and eight pairs were twins with sIUGR and UA Doppler abnormalities (Group 3). The highest EPO ratio was identified in Group 3 (p < .001) but no significant differences were observed between Groups 1 and 2. Fetal hemoglobin levels did not differ significantly in the three groups, and fetal EPO concentration did not correlate with gestational age at birth. We conclude that fetal plasma EPO concentrations are selectively increased in MC twin pregnancies with sIUGR and abnormal UA Doppler, possibly as a result of uncompensated hypoxia.

  16. Effects of the levonorgestrel-releasing intrauterine device on the immune microenvironment of the human cervix and endometrium

    PubMed Central

    Shanmugasundaram, Uma; Hilton, Joan F.; Critchfield, J. William; Greenblatt, Ruth M.; Giudice, Linda C.; Averbach, Sarah; Seidman, Dominika; Shacklett, Barbara L.; Smith-McCune, Karen

    2017-01-01

    Problem There is little information regarding the impact of the intrauterine device on immune parameters of the upper female reproductive tract related to risk of HIV acquisition. Method of Study We collected cervical and endometrial samples from women using the hormonal intrauterine device to study its effects on endocervical cytokines/chemokine concentrations, phenotypic markers of T cells, responses of endometrial T cells to activation, and alterations of endometrial cellular infiltrates. Results Hormonal intrauterine device use was associated with: increased concentrations of inflammatory cytokines/chemokines (endocervix); increased coexpression of CXCR4 and CCR5 (endocervix and endometrium); increased coexpression of CD38 and HLADR (endocervix and endometrium); increased intracellular IL-10 production after T-cell stimulation (endometrium); and increased density of T cells, most notably regulatory T cells (endometrium). Conclusion Hormonal intrauterine device use resulted in both inflammatory and immunosuppressive alterations. Further research is needed to determine the significance of these changes for HIV risk. PMID:27401588

  17. Transcervical intrauterine levobupivacaine or lidocaine infusion for pain control during endometrial biopsy

    PubMed Central

    Kosus, Nermin; Kosus, Aydın; Demircioglu, Ruveyda I; Simavli, Serap A; Derbent, Aysel; Keskin, Esra Aktepe; Turhan, Nilgun O

    2014-01-01

    BACKGROUND: Endometrial biopsy is a common procedure for the investigation of many gynecological disorders including abnormal uterine bleeding, postmenopausal bleeding, abnormal cytology and infertility. Most women experience some degree of discomfort and pain during the procedure. Pain may occur during dilation of the cervix for insertion of the catheter and during endometrial biopsy, which further aggravates pain by inducing uterine contraction. OBJECTIVES: To determine pain levels during endometrial biopsy by comparing intrauterine instillation of levobupivacaine or lidocaine with placebo in a randomized, double-blinded trial in pre- and postmenopausal women. METHODS: Ninety patients were allocated to either control or experimental groups before endometrial biopsy. The trial medication was intra-uterine anesthesia, either 5 mL 0.9% saline (control group), or 5 mL 0.5% levobupivacaine or 2% lidocaine (experimental groups). Resident doctors used the same endometrial biopsy technique to minimize the risk of technical variation. All tissue specimens were sent for cytopathological examination. The pathologists, who were blinded to the study solution, analyzed all tissue specimens. The primary outcome measure was pain experienced during the procedure. Pain was assessed using a 10 cm visual analogue pain scale. All observed adverse effects were recorded until the patients were discharged. RESULTS: Pain scores of the intrauterine lidocaine and levobupivacaine groups were found to be significantly lower than the control group. There was no difference between the levobupivacaine and lidocaine groups with regard to pain scores. There was a moderately positive correlation between pain scores and endometrial thickness. No complications were observed due to the procedure. Most of the biopsy results were proliferative and secretory endometrium. Insufficient material causing inconclusive results was observed mostly in the control group. CONCLUSION: Transcervical intrauterine

  18. Uterine Rupture with Cesarean Scar Heterotopic Pregnancy with Survival of the Intrauterine Twin

    PubMed Central

    Behrman, Eric R.; Bembry, James S.; Kovac, Christine M.

    2016-01-01

    Background. Heterotopic pregnancy is a multiple gestation with both intrauterine and ectopic fetuses. A cesarean scar ectopic pregnancy is when the fetus has implanted over the previous hysterotomy site. A known complication of cesarean scar ectopic pregnancy is uterine rupture, which can cause great morbidity and mortality. Case. 28-year-old G5P3105 at 10 weeks with a dichorionic diamniotic gestation was found to have a ruptured uterus with expulsion of a cesarean scar ectopic pregnancy and retention of the intrauterine fetus. After uterine repair, the singleton gestation reached viability was delivered by emergent cesarean section for placental abruption. Conclusion. Safe management of cesarean ectopic pregnancy requires early diagnosis by ultrasonography. With early detection, management can focus on preventing maternal morbidity of uterine rupture and life-threatening hemorrhage. PMID:28116191

  19. Sildenafil citrate therapy for severe early-onset intrauterine growth restriction.

    PubMed

    von Dadelszen, P; Dwinnell, S; Magee, L A; Carleton, B C; Gruslin, A; Lee, B; Lim, K I; Liston, R M; Miller, S P; Rurak, D; Sherlock, R L; Skoll, M A; Wareing, M M; Baker, P N

    2011-04-01

    Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was <25(+0) weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil-naive early-onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early-onset IUGR-complicated pregnancies.

  20. The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices.

    PubMed

    Rivera, R; Yacobson, I; Grimes, D

    1999-11-01

    Modern hormonal contraceptives and intrauterine contraceptive devices have multiple biologic effects. Some of them may be the primary mechanism of contraceptive action, whereas others are secondary. For combined oral contraceptives and progestin-only methods, the main mechanisms are ovulation inhibition and changes in the cervical mucus that inhibit sperm penetration. The hormonal methods, particularly the low-dose progestin-only products and emergency contraceptive pills, have effects on the endometrium that, theoretically, could affect implantation. However, no scientific evidence indicates that prevention of implantation actually results from the use of these methods. Once pregnancy begins, none of these methods has an abortifacient action. The precise mechanism of intrauterine contraceptive devices is unclear. Current evidence indicates they exert their primary effect before fertilization, reducing the opportunity of sperm to fertilize an ovum.

  1. Viable intrauterine pregnancy after spontaneous bilateral tubal ectopics in a multiparous woman: a case report

    PubMed Central

    2013-01-01

    Introduction Bilateral ectopic pregnancies are increasing due to an increase in the incidence of pelvic inflammatory disease and increase in assisted reproductive techniques. Spontaneous conception after bilateral ectopic pregnancies is extremely rare. Case presentation A 33-year-old Indian woman presented with ruptured ectopic pregnancy associated with hemoperitoneum for which she underwent a laparotomy. The diagnosis of bilateral ectopic pregnancies was made during surgery. Salpingectomy was done on one side and the other tube was conserved with salpingostomy. Six months after surgery, she conceived spontaneously and a transvaginal ultrasound examination revealed a 5-weeks live intrauterine pregnancy. Conclusion A meticulous surgical technique conserving one fallopian tube resulted in subsequent viable intrauterine pregnancy. The approach to such a case along with steps to minimize tubal damage is presented. PMID:23786635

  2. Premature delivery due to intrauterine Candida infection that caused neonatal congenital cutaneous candidiasis: a case report.

    PubMed

    Ito, Fumitake; Okubo, Tomoharu; Yasuo, Tadahiro; Mori, Taisuke; Iwasa, Koichi; Iwasaku, Kazuhiro; Kitawaki, Jo

    2013-01-01

    Congenital cutaneous candidiasis is a very rare disease with less than 100 cases published in the medical literature. Neonates having this disease present with systemic skin lesions caused by intrauterine Candida infections. We present a case of threatened premature delivery due to Candida chorioamnionitis, which caused both maternal postpartum endometritis and neonatal congenital cutaneous candidiasis. A 34-year-old woman who was admitted for fetal membrane bulging at 20 weeks of gestation underwent McDonald cervical cerclage. We diagnosed threatened premature delivery due to intrauterine infection; therefore, we terminated the gestation by cesarean section at 24 weeks of gestation. Fungi-like yeast was detected in infantile gastric juice. Histopathological findings of the placenta revealed that Candida albicans mycelium invaded the placenta, chorioamniotic membrane and umbilical cord.

  3. Unusual case of cervical pregnancy after curettage for a presumptive diagnosis of intrauterine blighted ovum.

    PubMed

    Di Serio, C; Caccavale, C; Borriello, M; Rotondi, M; Di Serio, M; Rotondi, M; Tolino, A; Carella, C

    2003-01-01

    A case of cervical pregnancy after curettage for presumptive intrauterine blighted ovum is presented. The woman was successfully treated by vacuum evacuation and curettage. A 29-year-old woman, gravida 2, nulliparous, was admitted to our department at ten weeks and two days of gestation after a diagnosis of cervical pregnancy. She had been treated by curettage five days before for an initial diagnosis of intrauterine blighted ovum. Ultrasound scan examination revealed a gestational sac without foetus in the cervix four days after the first curettage. Vacuum evacuation and curettage of the cervical canal were performed and a Foley catheter was also inserted and left in place for three days. The patient was discharged in good condition on the fourth postoperative day.

  4. Demonstration of gonadotropin during the second half of the cycle in women using intrauterine contraception.

    PubMed

    Beling, C G; Cederqvist, L L; Fuchs, F

    1976-07-15

    A highly sensitive pregnancy test based upon partial purification of urinary gonadotropins by Sephadex gel filtration and concentration of the gonadotropin-containing fraction by lyophilization has been developed. Values over 100 I.U. per liter after Day 22 are considered to indicate conception. They are verified by radioimmunoassay (RIA) of the beta-subunit of human chorionic gonadotropin (HCG) in plasma. Urine samples from users of intrauterine contraception were examined at random. Among samples collected after Day 21, 14 contained more than 100 I.U. per liter. In three of these cases, RIA of the beta-subunit HCG in plasma was employed and verified the results. The results support the hypothesis that intrauterine contraception interferes with implantation and establishment of pregnancy but not with fertilization and blastocyst formation.

  5. Effect of intrauterine PCB (polychlorinated biphenyls) exposure on visual recognition memory

    SciTech Connect

    Jacobson, S.W.; Fein, G.G.; Jacobson, J.L.; Schwartz, P.M.; Dowler, J.K.

    1985-01-01

    Adverse neonatal outcomes have been associated with intrauterine exposure to polychlorinated biphenyls (PCBs). In a follow-up study of exposed and nonexposed infants, 123 infants tested at birth were administered Fagan's test of visual recognition memory at 7 months. Two measures of prenatal PCB exposure, cord serum PCB level and maternal report of contaminated fish consumption, predicted less preference for a novel stimulus. Preference for novelty decreased in a dose-dependent fashion with increasing levels of prenatal PCB exposure. Postnatal exposure from nursing was not related to visual recognition memory. The relation between prenatal exposure and visual recognition was not mediated by the neonatal deficits, suggesting that intrauterine PCB exposure may have a delayed effect on central nervous system functioning.

  6. The IUB (Intrauterine Ball), a Newly Invented IUD: a Brief Report

    PubMed Central

    Baram, Ilan; Trussell, James

    2013-01-01

    Objective To evaluate the initial safety and effectiveness of the Intrauterine Ball, a copper intrauterine device which upon insertion in the uterus takes a three dimensional spherical form. Study Design Fifteen women were followed for one year, with follow-up visits at 1, 3, 6, 9, and 12 months. Results The physician reported that all devices were very easy to insert. One subject discontinued before the 6 month visit (at 119 days post insertion) for a reason not related to the device. There were no perforations, expulsions, mal-positions or complications, or pregnancies. Conclusion No safety or efficacy concerns were raised. Implications Due to its form and deployment process the IUB™ is expected to ease insertion and reduce perforation, malposition and expulsion rates and may also reduce dysmenorrhea and menorrhagia. PMID:24309220

  7. [Fetal pain and intrauterine analgesia/anesthesia: neuroanatomy, ontogenesis and physiology of pain perception].

    PubMed

    Deli, Tamás; Szeverényi, Péter

    2010-03-14

    The human fetus can suffer several presumably painful interventions perinatally and even before, during its intrauterine life. In recent years, a scientific dispute has expanded, concerning the existence of fetal pain and the need for its relief, and a heated social, political, religious, moral and philosophical debate has arisen, focusing mainly on the suffering experienced by the fetus during artificial abortion. We review the medical scientific knowledge regarding fetal pain in the literature. The definition of pain and the neuroanatomical structures participating in subjective pain perception, followed by the development of the latter in the course of ontogeny is presented. The objective indicators of intrauterine stress response (such as fetal neuroendocrine, cardiovascular, reflex and behavioral reactions) evoked by noxious stimuli are discussed.

  8. Intrauterine Adiposity and BMI in 4- to 5-Year-Old Offspring from Diabetic Pregnancies

    PubMed Central

    Hammoud, Nurah M.; de Valk, Harold W.; Biesma, Douwe H.; Visser, Gerhard H.A.

    2016-01-01

    Background Pregnancies complicated by maternal diabetes are associated with disproportionate intrauterine growth that subsequently may lead to pediatric adiposity. Objectives We investigated whether disproportionate intrauterine growth leads to differences in BMI in 4- to 5-year-old offspring from pregnancies complicated by type 1 (ODM1), type 2 (ODM2), or gestational diabetes (OGDM). Methods Ultrasound data of fetal head-to-abdominal circumference (HC/AC) ratio obtained between 32 and 36 weeks of gestational age were related to offspring anthropometrics that were retrieved from infant welfare centers. Results Data from 27 ODM1, 22 ODM2, and 24 OGDM were obtained. Ultrasound measurements for the HC/AC ratio were performed at a mean of 33-34 weeks, with a mean Z-score of the HC/AC ratio of -0.801, -0.879, and 0.017 in ODM1, ODM2, and OGDM. Mean BMI SDS was highest in ODM2 as compared to ODM1 and OGDM. In ODM1 there was a negative correlation between HC/AC ratio and BMI SDS at the ages of 4 and 5 years, but not in ODM2 or OGDM. The birth weight Z-score was positively correlated to BMI SDS in ODM2 and OGDM. Conclusion Disproportionate intrauterine growth, expressed as the HC/AC ratio, was inversely related with BMI SDS in ODM1 at the ages of 4-5 years, but not in ODM2 or OGDM. Weight and maybe obesity in ODM1 offspring are likely to be related to intrauterine adiposity, whereas overweight in ODM2 and OGDM offspring seems more related to other factors such as birth weight centile, maternal obesity, and altered lifestyle factors during childhood. PMID:27788515

  9. Neurodevelopment in children with intrauterine growth restriction: adverse effects and interventions.

    PubMed

    Wang, Yan; Fu, Wei; Liu, Jing

    2016-01-01

    Intrauterine growth restriction (IUGR) is associated with higher rates of fetal, perinatal, and neonatal morbidity and mortality. The consequences of IUGR include short-term metabolic, hematological and thermal disturbances that lead to metabolic syndrome in children and adults. Additionally, IUGR severely affects short- and long-term fetal brain development and brain function (including motor, cognitive and executive function) and neurobehavior, especially neuropsychology. This review details the adverse effects of IUGR on fetal brain development and discusses intervention strategies.

  10. [Incrustation of marker threads of intrauterine devices in the uterine cavity and cervix uteri].

    PubMed

    Patai, K; Berényi, M; Gimes, G

    1986-01-01

    If the indicating thread of intrauterine contraceptive devices is situated inside the uterine cavity, it is incrustated in the same way with calcium carbonate like the device itself. In 20 per cent the intracervical part of the thread is incrustated, too. The danger of an ascending inflammatory disease is increasing with the precipitation of substances, probably, denaturated fibrine or mucine according to the infrared spectral analysis.

  11. Neurodegenerative changes and apoptosis induced by intrauterine and extrauterine exposure of radiofrequency radiation.

    PubMed

    Güler, Göknur; Ozgur, Elcin; Keles, Hikmet; Tomruk, Arin; Vural, Sevil Atalay; Seyhan, Nesrin

    2016-09-01

    Adverse health effects of radiofrequency radiation (RFR) on the ongoing developmental stages of children from conception to childhood are scientifically anticipated subject. This study was performed to identify the effects of global system for mobile communications (GSM) modulated mobile phone like RFR in 1800MHz frequency on oxidative DNA damage and lipid peroxidation beside the apoptotic cell formation, using histopathological and immunohistochemical methods in the brain tissue of 1-month-old male and female New Zealand White rabbits that were exposed to these fields at their mother's womb and after the birth. Oxidative DNA damage and lipid peroxidation levels were investigated by measuring the 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) levels, respectively. Histopathological changes were observed using by hematoxylin and eosin (HE) staining. Apoptotic cells were detected in the examined organs by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. For both male and female infants; 8-OHdG levels increased in the group exposed to RFR in both intrauterine and extrauterine periods compared to the infants that were never exposed to RFR and the ones were exposed when they reached one month of age (p<0.05). MDA results were different for male and female rabbits. There was no difference between all female infant groups (p>0.05), while only intrauterine exposure significantly causes MDA level increase for the male infants. HE staining revealed mild lessions in neuronal necrobiosis in brain tissues of female rabbits that had only intaruterine exposure and male rabbits had only extrauterine exposure. Gliosis were mildly positive in brain tissues of rabbits that are exposed only intrauterine period, also the group exposed both intrauterine and extrauterine periods. However, there was no apoptotic change detected by TUNEL staining in the brain tissues of all groups.

  12. Characterization of corrosion products on a copper-containing intrauterine device during storage at room temperature.

    PubMed

    Bastidas, J M; Simancas, J

    1997-02-01

    This paper studies the characterization of corrosion products formed on corroded and uncorroded copper-containing intrauterine devices stored at room temperature for a period of 30 months. The experimental techniques used were X-ray photo-electron spectroscopy and Auger electron spectroscopy. The compounds found were cuprite (Cu2O) and tenorite (CuO). The latter was the main compound formed on corroded samples, forming thin tarnish films.

  13. Ureteric erosion and obstruction: A rare but dreaded complication of intrauterine contraceptive device

    PubMed Central

    Priyadarshi, Vinod; Sehgal, Nidhi; Sen, Dipanwita

    2017-01-01

    Though intrauterine contraceptive device (IUCD) is a safe and most frequently used long-term contraceptive method, it has some complications. Uterine perforation and intra-abdominal migration have been reported often, but a retroperitoneal migration is exceptional. Here, we are reporting an IUCD which perforated the uterus and migrated to the retroperitoneum; impinging into and obstructing left ureter causing severe hydroureteronephrosis due to the development of the left lower ureteric stricture. PMID:28216944

  14. Committee opinion no. 539: adolescents and long-acting reversible contraception: implants and intrauterine devices.

    PubMed

    2012-10-01

    Long-acting reversible contraception (LARC)—intrauterine devices and the contraceptive implant—are safe and appropriate contraceptive methods for most women and adolescents. The LARC methods are top-tier contraceptives based on effectiveness, with pregnancy rates of less than 1% per year for perfect use and typical use. These contraceptives have the highest rates of satisfaction and continuation of all reversible contraceptives. Adolescents are at high risk of unintended pregnancy and may benefit from increased access to LARC methods.

  15. Contraceptive efficacy of a novel intrauterine device (IUD) in white-tailed deer.

    PubMed

    Malcolm, Karl D; Van Deelen, Timothy R; Drake, David; Kesler, Darrel J; Vercauteren, Kurt C

    2010-02-01

    Overabundant white-tailed deer (Odocoileus virginianus) pose risks to property, health, and safety of human beings. Public concerns about lethal management can impair efforts to address these issues, particularly in urban settings. Several techniques developed for reducing reproductive output of deer have limited utility because they require repeated dosing to achieve permanent effect and face uncertain regulatory approval for use beyond experimentation. From 10 August 2006 through 30 December 2007, we evaluated the contraceptive efficacy of copper-containing intrauterine devices (IUDs) implanted trans-cervically in white-tailed deer at the E.S. George Reserve in Pinckney, Michigan. Intrauterine devices were implanted before (n=9) and shortly after (n=10) the breeding season. Post-breeding season IUD treatment was in conjunction with a 5cm(3) dose of 5mg/ml prostaglandin F(2alpha) (PGF(2alpha)), delivered subcutaneously. Intrauterine devices reduced pregnancy rates when administered prior to breeding (P<0.001) and prevented pregnancy for up to 2 years (the duration of the study). Two of 8 does that received IUDs prior to the breeding season and survived to the end of the study became pregnant (due to loss of the implant) during the second year while all (n=16) does without implants conceived. Cervical changes associated with early pregnancy made trans-cervical implantation after the breeding season challenging, and resulted in improperly placed IUDs in 2 treated does. The apparent expulsion of IUDs by pregnant does that received the combined treatment after breeding suggests IUD treatment should be limited to the pre-breeding season. Intrauterine devices show potential as a tool for small-scale deer population management via non-steroidal reproductive inhibition.

  16. Intraplacental gene therapy with Ad-IGF-1 corrects naturally occurring rabbit model of intrauterine growth restriction.

    PubMed

    Keswani, Sundeep G; Balaji, Swathi; Katz, Anna B; King, Alice; Omar, Khaled; Habli, Mounira; Klanke, Charles; Crombleholme, Timothy M

    2015-03-01

    Intrauterine growth restriction (IUGR) due to placental insufficiency is a leading cause of perinatal complications for which there is no effective prenatal therapy. We have previously demonstrated that intraplacental injection of adenovirus-mediated insulin-like growth factor-1 (Ad-IGF-1) corrects fetal weight in a murine IUGR model induced by mesenteric uterine artery branch ligation. This study investigated the effect of intraplacental Ad-IGF-1 gene therapy in a rabbit model of naturally occurring IUGR (runt) due to placental insufficiency, which is similar to the human IUGR condition with onset in the early third trimester, brain sparing, and a reduction in liver weight. Laparotomy was performed on New Zealand White rabbits on day 21 of 30 days of gestation and litters were divided into five groups: Control (first position)+phosphate-buffered saline (PBS), control+Ad-IGF-1, runt (third position)+PBS, runt+Ad-IGF-1, and runt+Ad-LacZ. The effect of IGF-1 gene therapy on fetal, placental, liver, heart, lung, and musculoskeletal weights of the growth-restricted pups was examined. Protein expression after gene transfer was seen along the maternal-fetal placenta interface (n=12) 48 hr after gene therapy. There was minimal gene transfer detected in the pups or maternal organs. At term, compared with the normally grown first-position control, the runted third-position pups demonstrated significantly lower fetal, placental, liver, lung, and musculoskeletal weights. The fetal, liver, and musculoskeletal weights were restored to normal by intraplacental Ad-IGF-1 gene therapy (p<0.01), with no change in the placental weight. Intraplacental gene therapy is a novel strategy for the treatment of IUGR caused by placental insufficiency that takes advantage of an organ that will be discarded at birth. Development of nonviral IGF-1 gene delivery using placenta-specific promoters can potentially minimize toxicity to the mother and fetus and facilitate clinical translation of

  17. Altered levels of brain neurotransmitter from new born rabbits with intrauterine restriction.

    PubMed

    Hernández-Andrade, E; Cortés-Camberos, A J; Díaz, N F; Flores-Herrera, H; García-López, G; González-Jiménez, M; Santamaría, A; Molina-Hernández, A

    2015-01-01

    Fetal intrauterine growth restriction generates chronic hypoxia due to placental insufficiency. Despite the hemodynamic process of blood flow, redistributions are taking place in key organs such as the fetal brain during intrauterine growth restriction, in order to maintain oxygen and nutrients supply. The risk of short- and long-term neurological effects are still present in hypoxic offspring. Most studies previously reported the effect of hypoxia on the levels of a single neurotransmitter, making it difficult to have a better understanding of the relationship among neurotransmitter levels and the defects reported in products that suffer intrauterine growth restriction, such as motor development, coordination and execution of movement, and the learning-memory process. The aim of this study was to evaluate the levels of gamma-aminobutyric acid, glutamate, dopamine and serotonin in three structures of the brain related to the above-mentioned function such as the cerebral cortex, the striatum, and the hippocampus in the chronic hypoxic newborn rabbit model. Our results showed a significant increase in glutamate and dopamine levels in all studied brain structures and a significant decrease in gamma-aminobutyric acid levels but only in the striatum, suggesting that the imbalance on the levels of several neurotransmitters could be involved in new born brain damage due to perinatal hypoxia.

  18. NDRG1 deficiency attenuates fetal growth and the intrauterine response to hypoxic injury.

    PubMed

    Larkin, Jacob; Chen, Baosheng; Shi, Xiao-Hua; Mishima, Takuya; Kokame, Koichi; Barak, Yaacov; Sadovsky, Yoel

    2014-03-01

    Intrauterine mammalian development depends on the preservation of placental function. The expression of the protein N-myc downstream-regulated gene 1 (NDRG1) is increased in placentas of human pregnancies affected by fetal growth restriction and in hypoxic primary human trophoblasts, where NDRG1 attenuates cell injury. We sought to assess the function of placental NDRG1 in vivo and tested the hypothesis that NDRG1 deficiency in the mouse embryo impairs placental function and consequently intrauterine growth. We found that Ndrg1 knock-out embryos were growth restricted in comparison to wild-type or heterozygous counterparts. Furthermore, hypoxia reduced the survival of female, but not male, knock-out embryos. Ndrg1 deletion caused significant alterations in placental gene expression, with a marked reduction in transcription of several lipoproteins in the placental labyrinth. These transcriptional changes were associated with reduced fetal:maternal serum cholesterol ratio exclusively in hypoxic female embryos. Collectively, our findings indicate that NDRG1 promotes fetal growth and regulates the metabolic response to intrauterine hypoxic injury in a sexually dichotomous manner.

  19. Intrauterine insemination of farmed fallow deer (Dama dama) with frozen-thawed semen via laparoscopy.

    PubMed

    Asher, G W; Kraemer, D C; Magyar, S J; Brunner, M; Moerbe, R; Giaquinto, M

    1990-09-01

    Estrus and ovulation of mature fallow does (n=155) on two North American farms were synchronized by intravaginal silastic devices containing 0.3 g progesterone (CIDR-type G) for 14 d. Each of 151 does received laparoscopic intrauterine inseminations of either 50x10(6) (n=125) or 25x10(6) (n=26) frozen-thawed spermatozoa, 65 to 68 h after CIDR device withdrawal. Four does received intrauterine inseminations per vaginam of 50x10(6) spermatozoa 68 to 69 hours after CIDR device withdrawal. Semen from crossbred Dama dama damaxDama dama mesopotamica sires was collected in New Zealand by electroejaculation. The overall pregnancy rate to artificial insemination, as assessed by rectal ultrasonography at Day 45, was 67.7%. The pregnancy rates for does receiving laparoscopic inseminations were 58.2% (Texas; 50x10(6) spermatozoa; n=79 does); 80.8% (Texas; 25x10(6) spermatozoa; n=26 does) and 76.1% (New York; 50x10(6) spermatozoa; n=46 does). Three of the four does receiving intrauterine inseminations per vaginam became pregnant to the frozen-thawed semen.

  20. Observations on intrauterine oxygen tension measured by fibre-optic microsensors.

    PubMed

    Ottosen, Lars D M; Hindkaer, Johnny; Husth, Merete; Petersen, Dorrit Elschner; Kirk, John; Ingerslev, Hans Jakob

    2006-09-01

    Understanding the biology of reproductive organs is essential for the development of assisted reproductive techniques. There is at present no direct evidence for either the concentration and dynamics of intrauterine oxygen tension at the endometrial surface, nor its importance for the receptiveness of the endometrium. In this study a new method measured mid-cycle (ranging from day 12-18) endometrial surface oxygen tension in 21 patients referred to intrauterine insemination (IUI). Time series was measured online for a period of 5-10 min. The (mean) individual oxygen tension among patients varied from 4 to 27% air saturation. Overall mean oxygen tension among all patients was 11.8% air saturation. Within the same patient, considerable time-related variations were observed. Some patients exhibited rhythmic oscillations with a frequency in the order of 1 min, whereas others did not show any regular patterns. A good description of endometrial surface oxygen concentration and dynamics was thus obtained, but given the relatively small number of participants, an association with pregnancy following insemination could not be established. Further studies using this new method could elucidate the association between individual intrauterine activity, embryo implantation and endometrial surface oxygen tension.

  1. Apparent Rarity of Asymptomatic Herpes Cervicitis in a Woman with Intra-Uterine Contraceptive Device

    PubMed Central

    Okolo, Abu Clement; Manga, Mohammed Mohammed; Anaedobe, Chinenye Gloria; Salami, Ayodeji Akeem; Akang, Effiong Essien Udo

    2013-01-01

    Infection with genital herpes simplex virus (HSV) remains a common viral sexually transmitted disease, often subclinical and a major worldwide problem of women of reproductive age group. Herpes cervicitis is an unusual presentation of Herpes simplex virus infection in females. The finding of herpes cervicitis on routine pap smear of an asymptomatic woman on Intrauterine contraceptive device still further supports the need for increased awareness on the possibility of Herpes simplex virus infection among women, particularly those on Intrauterine contraceptive device. The index case is a 28 years old Nigerian female who was referred to our Special Treatment Clinic on account of an abnormal pap smear cytology which was in keeping with Herpes cervicitis. There was no history of genital ulcer in this patient; however ELISA for HSV 2 IgM was positive in her. We therefore describe a case of herpes cervicitis in an asymptomatic woman on intrauterine contraceptive device. This case highlights to clinicians the need to be aware of the possibility of this association and to carry out relevant investigations so as to identify and treat these patients appropriately. Therefore, there is a need to put in place adequate public health intervention strategy to prevent genital herpes in women of reproductive age group with a view to preventing the possibility of congenital herpes in subsequent pregnancy.

  2. Normal Untreated Jurkat Cells

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. The objective of the research was to define a way to differentiate between effects due to microgravity and those due to possible stress from non-optimal spaceflight conditions. These Jurkat cells, a human acute T-cell leukemia was obtained to evaluate three types of potential experimental stressors: a) Temperature elevation; b) Serum starvation; and c) Centrifugal force. The data from previous spaceflight experiments showed that actin filaments and cell shape are significantly different for the control. These normal cells serve as the baseline for future spaceflight experiments.

  3. AB106. Differential regulation of LncRNA-SARCC suppresses VHL-mutant RCC cell proliferation yet promotes VHL-normal RCC cell proliferation via modulating androgen receptor/HIF-2α/C-MYC axis under hypoxia

    PubMed Central

    Zhai, Wei

    2016-01-01

    Objective It is well established that hypoxia contributes to tumor progression in a HIF-2α-dependent manner in renal cell carcinoma (RCC), yet the role of LncRNAs involved in hypoxia-mediated RCC progression remains unclear. Here we demonstrate that LncRNA-SARCC is differentially regulated by hypoxia in a VHL-dependent manner both in tissue culture and in human RCC clinical samples. LncRNA-SARCC can suppress hypoxic cell cycle progression in the VHL-mutant RCC cells while derepress it in the VHL-restored RCC cells. Mechanism dissection reveals that LncRNA-SARCC can post-transcriptionally regulate androgen receptor (AR) by physically binding and destabilizing AR protein to suppress AR/HIF-2α/C-MYC signals. In return, HIF-2α can transcriptionally regulate the LncRNA-SARCC expression via binding to hypoxia responsive elements (HREs) on the promoter of LncRNA-SARCC. The negative feedback modulation between LncRNA-SARCC/AR complex and HIF-2α signaling may then lead to differentially modulate RCC progression in a VHL-dependent manner. Together, these results may provide us a new therapeutic approach via targeting this newly identified signal from LncRNA-SARCC to AR-mediated HIF-2α/C-MYC signals against RCC progression. Methods Human samples—surgical specimens from human ccRCC tissues were obtained from 16 patients in the Department of Urology, Shanghai Tenth People’s Hospital, Tongji Medical School (Shanghai, China), freshly frozen in liquid nitrogen and stored at −80 °C until use. OCT-embedded blocks were sectioned until cut planes were >70% tumor. Sections were collected for DNA, RNA, and protein extraction. Samples were cataloged, clinical information on cases was obtained through chart review, and patient identifiers were removed before analysis. Informed consent was obtained from patients and the study was approved by the Institutional Review Board of Tongji Medical College. Immunohistochemistry—immunohistochemical staining was performed as previously

  4. Congenital intrahepatic portosystemic shunt diagnosed during intrauterine life

    PubMed Central

    Bellettini, Camila Vieira; Wagner, Rafaela; Balzanelo, Aleocídio Sette; Andretta, André Luis de Souza; de Moura, Arthur Nascimento; Fabris, Catia Carolina; Gubert, Eduardo Maranhão

    2016-01-01

    Abstract Objective: To report a patient with prenatal diagnosis of portosystemic shunt; a rare condition in humans. Case description: 17-Day-old female infant admitted for investigation of suspected diagnosis of portosystemic shunt, presumed in obstetric ultrasound. The hypothesis was confirmed after abdominal angiography and liver Doppler. Other tests such as echocardiography and electroencephalogram were performed to investigate possible co-morbidities or associated complications, and were normal. We chose conservative shunt treatment, as there were no disease-related complications and this was intrahepatic shunt, which could close spontaneously by the age of 2 years. Comments: Portosystemic shunt can lead to various complications such as hepatic encephalopathy, hypergalactosemia, liver tumors, and hepatopulmonary syndrome. Most diagnoses are done after one month of age, after such complications occur. The prenatal diagnosis of this patient provided greater security for the clinical picture management, as well as regular monitoring, which allows the anticipation of possible complications and perform interventional procedures when needed. PMID:27133713

  5. [Bilateral tubal pregnancy with intrauterine device -- a case report].

    PubMed

    Peixoto, R M; Aleixo Neto, A; Guimaraes, O; Portugal, E S

    1988-05-01

    Ectopic pregnancy occurs in Brazil in 1/300 cases. 99% are in the ovarian tubes and are almost always unilateral. The incidence rate for bilateral ectopic pregnancy has been described in literature to be 1/1,580 ectopic pregnancies. The article reports a case history at the maternity hospital of the Federal University in the Minas Gerais region. A 31 year-old leukodermatous patient in December 1980 began using an IUD (Lippes loop), followed by episodes of menorrhagia accompanied by abdominal colics of medium intensity during the following months. After the 3rd cycle menstrual delay occurred with abdominal pains localized mostly in the hypogastrium, but also in the lumbar and anal regions. After the diagnosis of ectopic pregnancy, the IUD was removed, resulting in minor bleeding a few days later. Subsequent ultrasonographic tests exposed a posterior pelvic tumorous mass at the uterus, 5.0x6.5 cm in diameter, and absence of uterine abnormalities, suggesting an ectopic pregnancy on the left. Following a complete physical examination including specular examination of the inner genitals it was decided to perform a diagnostic peritoneoscopy. It revealed an abdominal cavity presenting a large quantity of blood spread diffusely, uterus of normal size, and a cystic mass to the left+-6 cm in diameter apparently with hemorrhagic content. Laparotomy with transversal suprapubic incision was then performed. Final examinations indicated a bilateral tubal pregnancy ruptured on the left. The patient had a normal postoperative period and was discharged from the hospital after 6 days. Diagnosis is generally difficult since the unsuspected opposite tube may be infected and edematized due to bilateral endosalpingitis. For IUD users 2 etiological aspects of tubal pregnancies may be involved: Greater incidence rate of pelvic infection, modified tubal motility altering contractibility and possibly reversal of peristaltic wave. The necessity for examining both tubes when suspecting tubal

  6. [Experience with the copper intrauterine device cu-7 (authors transl)].

    PubMed

    Erb, H

    1976-08-10

    The effectiveness and tolerability of the Copper-7 IUD were studied in a private medical practice by performing insertions for 103 women, 20-48 years of age. Hysteronometric measurements before the study excluded women with a fundus uteri depth less than 5.5 cm, those with severely ante- or retroflected uterus, and those with myoma uteri or double uterus. For women after uteronomy, insertion was performed at least 6 months later. Follow-up rate, with regular check-ups during a total of 1280 cycles, was 100%. The total failure rate, or Pearl Index, was 1% (1 pregnancy). There were 4 (3.9%) expulsions, and 8 (7.8%) removals for medical reasons including 1 for metritis, 2 for bleeding, and 3 for pain and cramps. The continuation rate, after 1 year of use, was 87%. The ensure optimal contraceptive effect, as well as toleration of the CU-7, potential users should be carefully measured for adequate size of the uterine cavity. Consistent follow-up and personal contact with the physician are very important. This reversible contraceptive method is highly recommended for any women with a normal uterus who does not suffer from dysmenorrhea.

  7. FORCED NORMALIZATION: Epilepsy and Psychosis Interaction

    PubMed Central

    Loganathan, Muruga A.; Enja, Manasa

    2015-01-01

    Forced normalization is the emergence of psychoses following the establishment of seizure control in an uncontrolled epilepsy patient. Two illustrative clinical vignettes are provided about people with epilepsy that was newly controlled and followed by emergence of a psychosis; symptoms appeared only after attaining ictal control. For recognition and differential diagnosis purposes, understanding forced normalization is important in clinical practice. PMID:26155377

  8. Normalizing difference in inclusive teaching.

    PubMed

    Baglieri, Susan; Knopf, Janice H

    2004-01-01

    Inclusion practices and special education can be transformed by using a disability studies perspective, which constructs differences as natural, acceptable, and ordinary. Although inclusion is a moral imperative in promoting social justice, some inclusive practices continue to marginalize students with disabilities. A truly inclusive school reflects a democratic philosophy whereby all students are valued, educators normalize difference through differentiated instruction, and the school culture reflects an ethic of caring and community.

  9. Cell proliferation in normal epidermis

    SciTech Connect

    Weinstein, G.D.; McCullough, J.L.; Ross, P.

    1984-06-01

    A detailed examination of cell proliferation kinetics in normal human epidermis is presented. Using tritiated thymidine with autoradiographic techniques, proliferative and differentiated cell kinetics are defined and interrelated. The proliferative compartment of normal epidermis has a cell cycle duration (Tc) of 311 h derived from 3 components: the germinative labeling index (LI), the duration of DNA synthesis (ts), and the growth fraction (GF). The germinative LI is 2.7% +/- 1.2 and ts is 14 h, the latter obtained from a composite fraction of labeled mitoses curve obtained from 11 normal subjects. The GF obtained from the literature and from human skin xenografts to nude mice is estimated to be 60%. Normal-appearing epidermis from patients with psoriasis appears to have a higher proliferation rate. The mean LI is 4.2% +/- 0.9, approximately 50% greater than in normal epidermis. Absolute cell kinetic values for this tissue, however, cannot yet be calculated for lack of other information on ts and GF. A kinetic model for epidermal cell renewal in normal epidermis is described that interrelates the rate of birth/entry, transit, and/or loss of keratinocytes in the 3 epidermal compartments: proliferative, viable differentiated (stratum malpighii), and stratum corneum. Expected kinetic homeostasis in the epidermis is confirmed by the very similar ''turnover'' rates in each of the compartments that are, respectively, 1246, 1417, and 1490 cells/day/mm2 surface area. The mean epidermal turnover time of the entire tissue is 39 days. The Tc of 311 h in normal cells in 8-fold longer than the psoriatic Tc of 36 h and is necessary for understanding the hyperproliferative pathophysiologic process in psoriasis.

  10. Fetal Programming of Body Composition, Obesity, and Metabolic Function: The Role of Intrauterine Stress and Stress Biology

    PubMed Central

    Entringer, Sonja; Buss, Claudia; Swanson, James M.; Cooper, Dan M.; Wing, Deborah A.; Waffarn, Feizal; Wadhwa, Pathik D.

    2012-01-01

    Epidemiological, clinical, physiological, cellular, and molecular evidence suggests that the origins of obesity and metabolic dysfunction can be traced back to intrauterine life and supports an important role for maternal nutrition prior to and during gestation in fetal programming. The elucidation of underlying mechanisms is an area of interest and intense investigation. In this perspectives paper we propose that in addition to maternal nutrition-related processes it may be important to concurrently consider the potential role of intrauterine stress and stress biology. We frame our arguments in the larger context of an evolutionary-developmental perspective that supports roles for both nutrition and stress as key environmental conditions driving natural selection and developmental plasticity. We suggest that intrauterine stress exposure may interact with the nutritional milieu, and that stress biology may represent an underlying mechanism mediating the effects of diverse intrauterine perturbations, including but not limited to maternal nutritional insults (undernutrition and overnutrition), on brain and peripheral targets of programming of body composition, energy balance homeostasis, and metabolic function. We discuss putative maternal-placental-fetal endocrine and immune/inflammatory candidate mechanisms that may underlie the long-term effects of intrauterine stress. We conclude with a commentary of the implications for future research and clinical practice. PMID:22655178

  11. [Tumorous actinomycosis of the pelvis with in situ intrauterine device].

    PubMed

    Bilek, K; Horn, L C; Schinagl, A

    1993-11-01

    The case is described of a 53-year old woman who had given birth three times and had undergone one abortion. After she was treated as an outpatient because of back pain in the lower waist area suppuration occurred from a fistula laterally right to the sacral bone in the area of the buttocks triangle, which persisted even after several outpatient surgical interventions. In addition, she had experienced a weight loss of 24 kg. At admission she had a temperature of 39 degrees Celsius, anemia, and leukocytosis. Sonography indicated slight hepatomegaly, hydroureter, right-sided hydronephrosis, and an right ovarian cyst of 4 cm size. Computer tomography showed a blurry structure that extended from the right kidney pole along the M. iliopsoas caudally up to the small pelvis, pressing against the organs caudally-ventrally, which also broke through dorsally between the lumbar region vertebrae and pelvis in the gluteal region percutaneously. The process was categorized as a frank paranephritis prolapsus abscess. Cessation of urine was determined. Laparotomy was carried out because of the suspicion of an inflammatory adnexal disease with parametritis. The uterus, including both adnexa as well as the conglomeration tumor, were removed. In the uterine cavity a Dana Cor IUD was found that had been inserted 13 years before and forgotten by the patient. At the site of the right adnexum there was a tumor (9 x 6 x 5 cu. cm) as well as a tube changed by inflammation (7 x 1.5 sq. cm). On the right side there was unspecific, suppurative salpingitis and in the ovary an abscess formation on the grounds of actinomycosis. On the left side there was only a suppurative inflammation of the tube without actinomycosis sediment. Immediately a high-dose antibiotic therapy (Penicillin G, 10 million IU) was started, lasting for 1 year. The kidney cessation with the back complaints rapidly disappeared. The cutaneous fistulae healed with scarring, however, a fully normal right-sided kidney function

  12. Early and Late Postnatal Myocardial and Vascular Changes in a Protein Restriction Rat Model of Intrauterine Growth Restriction

    PubMed Central

    Menendez-Castro, Carlos; Fahlbusch, Fabian; Cordasic, Nada; Amann, Kerstin; Münzel, Kathrin; Plank, Christian; Wachtveitl, Rainer; Rascher, Wolfgang; Hilgers, Karl F.; Hartner, Andrea

    2011-01-01

    Intrauterine growth restriction (IUGR) is a risk factor for cardiovascular disease in later life. Early structural and functional changes in the cardiovascular system after IUGR may contribute to its pathogenesis. We tested the hypothesis that IUGR leads to primary myocardial and vascular alterations before the onset of hypertension. A rat IUGR model of maternal protein restriction during gestation was used. Dams were fed low protein (LP; casein 8.4%) or isocaloric normal protein diet (NP; casein 17.2%). The offspring was reduced to six males per litter. Immunohistochemical and real-time PCR analyses were performed in myocardial and vascular tissue of neonates and animals at day 70 of life. In the aortas of newborn IUGR rats expression of connective tissue growth factor (CTGF) was induced 3.2-fold. At day 70 of life, the expression of collagen I was increased 5.6-fold in aortas of IUGR rats. In the hearts of neonate IUGR rats, cell proliferation was more prominent compared to controls. At day 70 the expression of osteopontin was induced 7.2-fold. A 3- to 7-fold increase in the expression of the profibrotic cytokines TGF-β and CTGF as well as of microfibrillar matrix molecules was observed. The myocardial expression and deposition of collagens was more prominent in IUGR animals compared to controls at day 70. In the low-protein diet model, IUGR leads to changes in the expression patterns of profibrotic genes and discrete structural abnormalities of vessels and hearts in adolescence, but, with the exception of CTGF, not as early as at the time of birth. Invasive and non-invasive blood pressure measurements confirmed that IUGR rats were normotensive at the time point investigated and that the changes observed occurred independently of an increased blood pressure. Hence, altered matrix composition of the vascular wall and the myocardium may predispose IUGR animals to cardiovascular disease later in life. PMID:21655297

  13. Different Bleeding Patterns with the Use of Levonorgestrel Intrauterine System: Are They Associated with Changes in Uterine Artery Blood Flow?

    PubMed Central

    Bastianelli, Carlo; Rapiti, Stefania; Bruno Vecchio, Roberta; Benagiano, Giuseppe

    2014-01-01

    Objective. Evaluate if different bleeding patterns associated with the use of the levonorgestrel intrauterine system (LNG-IUS) are associated with different uterine and endometrial vascularization patterns, as evidenced by ultrasound power Doppler analysis. Methodology. A longitudinal study, with each subject acting as its own control was conducted between January 2010 and December 2012. Healthy volunteers with a history of heavy but cyclic and regular menstrual cycles were enrolled in the study. Ultrasonographic examination was performed before and after six months of LNG-IUS placement: uterine volume, endometrial thickness, and subendometrial and myometrial Doppler blood flow patterns have been evaluated. Results. A total of 32 women were enrolled out of 186 initially screened. At six months of follow-up, all subjects showed a reduction in menstrual blood loss; for analysis, they were retrospectively divided into 3 groups: normal cycling women (Group I), amenorrheic women (Group II), and women with prolonged bleedings (Group III). Intergroup analysis documented a statistically significant difference in endometrial thickness among the three groups; in addition, mean pulsatility index (PI) and resistance index (RI) in the spiral arteries were significantly lower in Group I and Group III compared to Group II. This difference persisted also when comparing—within subjects of Group III—mean PI and RI mean values before and after insertion. Conclusions. The LNG-IUS not only altered endometrial thickness, but—in women with prolonged bleedings—also significantly changed uterine artery blood flow. Further studies are needed to confirm these results and enable gynecologists to properly counsel women, improving initial continuation rates. PMID:24868549

  14. Intrauterine contraceptive devices. Complications associated with their use.

    PubMed

    Nagel, T C

    1983-03-01

    Uterine perforation is the most serious complication of IUD insertion; the risk is less than 1/1000 insertions for currently available IUDs. Most perforations occur at the time of insertion and the risk is increased in the 4-8 weeks postpartum. It is important to choose an IUD appropriate to the size of the endometrial cavity and to clean the area with an antiseptic solution. When the string is found to be missing, pregnancy must be excluded, and the endometrial cavity explored. Ultrasonography can often determine if the IUD is in the uterus; most IUDs that perforate the uterus are often found in the pelvis. Alterations in vital signs that occur at the time of insertion have been documented in 35-60% of patients; these generally require no therapy. If there are severe vasovagal reactions, treatment with intravenous atropine sulfate 0.4 mg, may be required. Bleeding is the most common reason for IUD removal, but its cause is not extremely clear. Blood loss is greatest with the large inert devices, less with small copper-containing devices, and least with a progesterone-containing IUD. The addition of supplementary iron to the diet and periodic hemoglobin determinations are recommended for IUD users. The risk of pelvic inflammatory disease (PID) is increased in IUD users, ranging from 1.6-10.5 compared with other forms of contraception. Risk is greatest during the 1st few months after insertion but continues to be higher than normal as long as the IUD is used. Studies have shown that women using hormonal or barrier contraceptives have a decreased incidence of PID. For mild infection, tetracycline 500 mg orally 4 times daily suffices; in more severe cases a regimen consisting of an animoglycoside plus penicillin is adequate. The pregnancy rate in IUD users varies between 1.6-5.3/100 women/year. Pregnancy in an IUD-wearer must be considered ectopic until proven otherwise, although the rate of ectopic pregnancy in this group is extremely low. The IUD's protective effect

  15. Are There Effects of Intrauterine Cocaine Exposure on Delinquency during Early Adolescence? A Preliminary Report

    PubMed Central

    Gerteis, Jessie; Chartrand, Molinda; Martin, Brett; Cabral, Howard J.; Rose-Jacobs, Ruth; Crooks, Denise; Frank, Deborah A.

    2011-01-01

    Objective To ascertain whether level of intrauterine cocaine exposure (IUCE) is associated with early adolescent delinquent behavior, after accounting for prenatal exposures to other psychoactive substances and relevant psychosocial factors. Methods Ninety-three early adolescents (12.5–14.5 years old) participating since birth in a longitudinal study of IUCE reported delinquent acts via an audio computer assisted self interview (ACASI). Level of IUCE and exposure to cigarettes, alcohol, and marijuana were determined by maternal report, maternal and infant urine assays, and infant meconium assays at birth. Participants reported their exposure to violence on the Violence Exposure Scale for Children – Revised (VEX-R) at ages 8.5, 9.5, 11 years and during early adolescence, and the strictness of supervision by their caregivers during early adolescence. Results Of the 93 participants, 24 (26%) reported ≥3 delinquent behaviors during early adolescence. In the final multivariate model (including level of IUCE and cigarette exposure, childhood exposure to violence, and caregiver strictness/supervision) ≥ 3 delinquent behaviors were not significantly associated with level of IUCE but were significantly associated with intrauterine exposure to half a pack or more of cigarettes per day and higher levels of childhood exposure to violence, effects substantially unchanged after control for early adolescent violence exposure. Conclusions In this cohort, prospectively ascertained prenatal exposure to cigarettes and childhood exposure to violence are associated with self-reported delinquent behaviors during early adolescence. Contrary to initial popular predictions, intrauterine cocaine is not a strong predictor of adolescent delinquent behaviors in this cohort. PMID:21558951

  16. Behavioral and Physiological Analyses of Parturition In Pregnant Rats: Insights Derived from Intrauterine Telemetry

    NASA Technical Reports Server (NTRS)

    Villareal, J.; Mallery, E.; Lynch, A.; Mills, N.; Baer, L.; Wade, C.; Ronca, A.; Dalton, Donnie (Technical Monitor)

    2002-01-01

    During labor and birth, fetuses are exposed to considerable physical stimulation associated with labor contractions and expulsion from the womb These forces are important for the neonates' adaptation to tile extrauterine environment. To further our understanding of the relationship between labor and postpartum outcome, we developed a novel method for measuring intrauterine pressure (IUP) in freely-moving, late pregnant and parturient rats that enables us to make precise, reliable measures of the forces experienced by rat fetuses during parturition. A small (1.25 x 4 cm) telemetric blood pressure sensor was fitted within a fluid-filled balloon, similar in size to a full term rat fetus. On Gestational day (G) 19 of the rats' 22/23 day pregnancy, each dam was anesthetized and a balloon/sensor unit surgically implanted within the uterus following removal of two fetuses. Comparisons were made between sensor-implanted dams (IMPL) and a control conditions: 1) LAP-R, laparotomy with two fetuses removed or 2) LAP-NR, laparotomy with no fetuses removed. IUP signals were sampled at 10s intervals from the IMPL dams during labor and birth. Dams in all three conditions were videorecorded enabling us to analyze the effect of the implant on behavioral expressions of parturition. Contraction frequency, duration, pup-to-pup birth intervals and pup-oriented activities of the dams measured from one hour prior to the first pup birth until the birth of the third pup were unaffected by the sensor implant. Intrauterine telemetry of freely-moving dams offers significant advantages over conventional hardwired IUP measurement techniques. These findings establish and validate intrauterine telemetry as a reliable, non-invasive technique for quantifying pressures associated with parturition.

  17. Intrauterine growth and postnatal skeletal development: findings from the Southampton Women's Survey.

    PubMed

    Harvey, Nicholas C; Mahon, Pam A; Kim, Miranda; Cole, Zoe A; Robinson, Sian M; Javaid, Kassim; Inskip, Hazel M; Godfrey, Keith M; Dennison, Elaine M; Cooper, Cyrus

    2012-01-01

    We have previously demonstrated associations between fetal growth in late pregnancy and postnatal bone mass. However, the relationships between the intrauterine and early postnatal skeletal growth trajectory remain unknown. We addressed this in a large population-based mother-offspring cohort study. A total of 628 mother-offspring pairs were recruited from the Southampton Women's Survey. Fetal abdominal circumference was measured at 11, 19 and 34 weeks gestation using high-resolution ultrasound with femur length assessed at 19 and 34 weeks. Bone mineral content was measured postnatally in the offspring using dual-energy X-ray absorptiometry at birth and 4 years; postnatal linear growth was assessed at birth, 6, 12, 24, 36 and 48 months. Late pregnancy abdominal circumference growth (19-34 weeks) was strongly (P < 0.01) related to bone mass at birth, but less robustly associated with bone mass at 4 years. Early pregnancy growth (11-19 weeks) was more strongly related to bone mass at 4 years than at birth. Postnatal relationships between growth and skeletal indices at 4 years were stronger for the first and second postnatal years, than the period aged 2-4 years. The proportion of children changing their place in the distribution of growth velocities progressively reduced with each year of postnatal life. The late intrauterine growth trajectory is a better predictor of skeletal growth and mineralisation at birth, while the early intrauterine growth trajectory is a more powerful determinant of skeletal status at age 4 years. The perturbations in this trajectory which influence childhood bone mass warrant further research.

  18. Small Size at Birth or Abnormal Intrauterine Growth Trajectory: Which Matters More for Child Growth?

    PubMed

    Hutcheon, Jennifer A; Jacobsen, Geir W; Kramer, Michael S; Martinussen, Marit; Platt, Robert W

    2016-06-15

    Small size at birth is linked with lifelong adverse health implications. However, small size is only a proxy for the pathological process of interest, intrauterine growth restriction. We examined the extent to which information on intrauterine growth patterns improved prediction of childhood anthropometry, above and beyond birth weight alone. We obtained fetal weights estimated via serial ultrasound for 478 children in the Scandinavian Successive Small-for-Gestational-Age Births Study (1986-1988). Size at birth was classified using birth weight-for-gestational-age z scores and conditional fetal growth z scores (reflecting growth between 25 weeks' gestation and birth) using internal references. Conditional z scores were also expressed as residuals of birth weight z scores. Growth measures were linked with age-5-years anthropometric characteristics using linear regression. In univariable analyses, conditional fetal growth z scores were positively associated with z scores for child height, body mass index, total skinfold thickness, and head circumference (β = 0.24 (95% confidence interval (CI): 0.18, 0.31), β = 0.16 (95% CI: 0.09, 0.23), β = 0.08 (95% CI: 0.01, 0.16), and β = 0.37 (95% CI: 0.22, 0.52), respectively). However, conditional z scores were highly correlated with birth weight z scores (r = 0.9), and residuals explained minimal additional variation in anthropometric factors (null coefficients; adjusted R(2) increases < 0.01). Information on the intrauterine trajectory through which birth weight was attained provided little additional insight into child growth beyond that obtained from absolute size at birth.

  19. Knowledge and attitudes of Latin American obstetricians and gynecologists regarding intrauterine contraceptives

    PubMed Central

    Bahamondes, Luis; Makuch, Maria Y; Monteiro, Ilza; Marin, Victor; Lynen, Richard

    2015-01-01

    Background Intrauterine contraceptives (IUCs), including the copper intrauterine device and the levonorgestrel-releasing intrauterine system (LNG-IUS), are among the reversible contraceptive methods with high effectiveness. However, use is low in many settings, including some Latin American countries, mainly due to the influences of myths, fears, and negative attitudes, not only of users and potential users, but also of different cadres of health care professionals. The purpose of this study was to assess the knowledge and attitudes of a group of Latin American obstetricians and gynecologists regarding IUCs. Methods A survey was conducted during a scientific meeting organized in Chile in 2014 to present and discuss updated information about contraception. Obstetricians and gynecologists from 12 Latin American countries, who reported that they provide daily contraception services in both the public and private sectors, participated in the meeting. Participants who agreed to take part in the survey responded to a multiple-choice questionnaire on issues regarding knowledge, use, and attitudes about IUCs. Results Of the 210 obstetricians and gynecologists participating in the meeting, the respondents to each question varied from 168 (80.0%) to 205 (97.6%). Almost 50% recognized that the failure rate of combined oral contraceptives, patches, and vaginal rings is 8%–10%. Furthermore, 10% of the participants did not recognize the high contraceptive effectiveness of long-acting reversible contraceptive methods. Additionally, almost 80% of the respondents answered that they did not offer IUCs to nulligravidas and almost 10% did not offer IUCs to adolescents, albeit almost 90% of the respondents reported that nulligravidas are candidates for an LNG-IUS. Conclusion Some deficiencies and contradictions in terms of knowledge and attitudes were identified from the answers of the Latin American obstetricians and gynecologists who participated in the survey. The knowledge and

  20. Long-term neurodevelopmental outcomes after intrauterine and neonatal insults: a systematic review

    PubMed Central

    Mwaniki, Michael K; Atieno, Maurine; Lawn, Joy E; Newton, Charles RJC

    2012-01-01

    Summary Background Neonatal interventions are largely focused on reduction of mortality and progression towards Millennium Development Goal 4 (child survival). However, little is known about the global burden of long-term consequences of intrauterine and neonatal insults. We did a systematic review to estimate risks of long-term neurocognitive and other sequelae after intrauterine and neonatal insults, especially in low-income and middle-income countries. Methods We searched Medline, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, and Embase for studies published between Jan 1, 1966, and June 30, 2011, that reported neurodevelopmental sequelae after preterm or neonatal insult. For unpublished studies and grey literature, we searched Dissertation Abstracts International and the WHO library. We reviewed publications that had data for long-term outcome after defined neonatal insults. We summarised the results with medians and IQRs, and calculated the risk of at least one sequela after insult. Findings Of 28 212 studies identified by our search, 153 studies were suitable for inclusion, documenting 22 161 survivors of intrauterine or neonatal insults. The overall median risk of at least one sequela in any domain was 39·4% (IQR 20·0–54·8), with a risk of at least one severe impairment in any insult domain of 18·5% (7·7–33·3), of at least one moderate impairment of 5·0% (0·0–13·3%), and of at least one mild impairment of 10·0% (1·4–17·9%). The pooled risk estimate of at least one sequela (weighted mean) associated with one or more of the insults studied (excluding HIV) was 37·0% (95% CI 27·0–48·0%) and this risk was not significantly affected by region, duration of the follow-up, study design, or period of data collection. The most common sequelae were learning difficulties, cognition, or developmental delay (n=4032; 59%); cerebral palsy (n=1472; 21%); hearing impairment (n=1340; 20%); and visual impairment (n

  1. [Successful multi-step management of developmental heart defects after intrauterine diagnosis].

    PubMed

    Hartyánszky, I; Kádár, K; Oprea, V; Palik, I; Sápi, E; Prodán, Z; Bodor, G; Mihályi, S

    1997-03-23

    At 28th week of gestation a conotruncal malformation with ventricular septal defect was diagnosed by fetal echocardiography. Postnatal echocardiographic and angiocardiographic examinations confirmed the diagnosis of conotruncal malformation (pulmonary atresia, ventricular septal defect, patent ductus arteriosus, aortopulmonary collateral arteries). The unifocalization (age: 11 months) and total correction with aortic homograft (age: 7 years) were performed. To our knowledge our case is the first whose intrauterine diagnosis of complex congenital heart disease was confirmed after delivery and had successful two-stage surgical management.

  2. [Intrauterine growth of live-born twins in the area of Sibenik, Split and Zadar].

    PubMed

    Mikulandra, F; Tadin, I; Franceschi, A; Sikić, D; Skevin, Z

    1983-01-01

    By a retrospective analysis the authors studied live-born twins by gestation weeks and birth weight and height: there were 1,195 first-born and 1,189 second-born twins, all from three neighbouring Dalmatian towns (Split, Sibenik and Zadar). A common curve was worked out of the intrauterine growth of both the first and the second twins and a separate curve of each of them. The curves have shown that the twins' birth weight was increassing up to the 40th week of pregnancy; in the 41st week the curve already went down. The authors conclude that twin pregnancy should not last more than 40 weeks.

  3. [Coma diabeticum and intrauterine fetal death. Therapeutic considerations on hand of a clinical case (author's transl)].

    PubMed

    Muck, B R

    1975-09-01

    We report about a thirty year old woman in the 34th week of pregnancy, who was hospitalized with ketoacid coma diabeticum. The intrauterine death of the fetus was diagnostisized. Neither the pathological glucose tolerance nor the metabolic disorder had been previously recognized. In the patient history though we find concrete signs of a possible pathological glucose tolerance. We describe our therapy of the coma. In the following we discuss the frequency of carbohydrate metabolism disorders in pregnant women and screening methods for diabets.

  4. Persistence of oxytetracycline residues in milk after the intrauterine treatment of lactating cows for endometritis.

    PubMed

    Tan, X; Huang, Y-J; Jiang, Y-W; Hu, S-H

    2007-10-27

    Milk samples were collected at one day intervals after the last dose from 31 cows that had received an intrauterine infusion of oxytetracycline once daily between one and five times. The tetrazolium chloride assay was used to determine whether there were significant residues of the antibiotic in the samples. A single treatment resulted in residues for between one and eight days, and the period tended to be longer in the cows that had received more than one dose. Of the 31 cows, six remained tetracycline-positive for more than five days after their last dose of the drug.

  5. Medical treatment of a grossly enlarged adenomyotic uterus with the levonorgestrel-releasing intrauterine system.

    PubMed

    Fong, Y F; Singh, K

    1999-09-01

    Adenomyosis is an important cause of menorrhagia. Besides hysterectomy, the treatment options for adenomyosis have been limited. Presented here is the successful treatment of adenomyosis in a woman presenting with menorrhagia, dysmenorrhea, and an enlarging uterus, for whom conservative therapy initiated with mefenamic acid was unsatisfactory. The patient had insertion of the levonorgestrel-releasing intrauterine system (LNG-IUS). A marked decrease in uterine size occurred within 12 months of insertion accompanied by resolution of the menorrhagia and dysmenorrhea. Thus, the LNG-IUS is a viable option and represents a real advance in the treatment of adenomyosis.

  6. Effect of the levonorgestrel-releasing intrauterine system on uterine myomas in a renal transplant patient.

    PubMed

    Fong, Y F; Singh, K

    1999-07-01

    The levonorgestrel-releasing intrauterine system (LNG-IUS) has been used in the treatment of both idiopathic menorrhagia and adenomyosis. An electronic search of the on-line medical literature revealed no reports of its use for menorrhagia secondary to uterine myomas. Presented here is the successful treatment of uterine myomas with menorrhagia in a woman with a renal transplant. There was a significant reduction in menorrhagia, dysmenorrhea, and uterine and myoma size with the use of the LNG-IUS. We believe that this system provides an alternative to conventional hysterectomy and gonadotrophin-releasing hormonal analog medical treatment for uterine myomas, with a possibly inhibitory effect on myoma growth.

  7. Barriers to Intrauterine Device Uptake in a Rural Setting in Ghana

    PubMed Central

    ROBINSON, NURIYA; MOSHABELA, MOSA; OWUSU-ANSAH, LYDIA; KAPUNGU, CHISINA; GELLER, STACIE

    2015-01-01

    Long-acting reversible contraception is an underutilized method in low-resource areas. Our study aims to: (a) assess knowledge and attitudes around contraception; (b) identify barriers to intrauterine device (IUD) uptake; and (c) develop interventions to address this gap in contraceptive care. We conducted focus group discussions with pregnant, postpartum, and reproductive-aged women, males, and health care workers in rural Ghana. Lack of IUD-specific knowledge, provider discomfort with insertion, and incomplete contraceptive counseling contribute to lack of IUD use. Participant- and provider-related barriers contribute to poor uptake of IUDs within the community. Targeted interventions are necessary to improve IUD use. PMID:25153448

  8. [Reasons for removal of intrauterine devices among women in general practice].

    PubMed

    Kolding, Line; Majeed, Huda Galib

    2013-03-25

    Prolonged bleeding or spotting and pain are the most common reasons for women to request early removal of intrauterine device (IUD). We wanted to investigate which parameters influenced the removal of IUDs among women in general practice and to see if there was a difference between copper-releasing IUDs and levonorgestrel-releasing IUDs. In general the women were satisfied with both types of IUDs. More women with copper-releasing IUDs had an early removal because of complaints than women with levonorgestrel-releasing IUDs.

  9. The combined GnRH-agonist and intrauterine levonorgestrel-releasing system treatment of complicated atypical hyperplasia and endometrial cancer: a pilot study.

    PubMed

    Pashov, Alexandr I; Tskhay, Vitaly B; Ionouchene, Svetlana V

    2012-07-01

    In this article, we present the results of organ-preserving treatment applied in 24 patients of reproductive age with atypical endometrial hyperplasia or early-stage endometrial cancer. All of them would like to preserve their reproductive potential. Thirteen women with atypical endometrial hyperplasia were treated with the combination of six intramuscular injections of 3.75 mg gonadotropin-releasing hormone agonist (GnRHa)--leuproreline acetate depot every 4 weeks. After the third injection of 3.75 mg of leuproreline acetate, the levonorgestrel intrauterine hormonal system containing 52 mg levonorgestrel (Mirena®, Bayer, Germany) was inserted for at least 6 months. In 11 women with stage IA well-differentiated endometrial adenocarcinoma, hormonal therapy included nine intramuscular injections of 3.75 mg of GnRHa every 4 weeks. After the third injection of 3.75 mg of GnRHa, we also inserted a GnRH-IUS (Mirena®) for at least 12 months. This type of therapy was effective for all these patients and may be offered to be used as an alternative to surgery in women with atypical endometrial hyperplasia or early stage 1A well-differentiated endometrial cancer in women of reproductive age. Three women with endometrial cancer became pregnant and two of them delivered at term and one has an ongoing pregnancy.

  10. Tissue concentration of intrauterine and intravenously administered amoxicillin in the isolated hemoperfused bovine uterus model and in healthy cows.

    PubMed

    Braun, Michael; Zerbe, Holm; Kietzmann, Manfred

    2009-01-01

    The tissue distribution of amoxicillin in the bovine uterus in dependence of the administration route was examined using the in vitro model of the isolated hemoperfused bovine uterus. Four hours after intrauterine instillation or onset of perfusion with amoxicillin ("systemic" treatment), respectively, samples of the uterine tissue were taken from different locations of the organ. The tissue concentration of amoxicillin in the single layers of the uterine wall was determined via high performance liquid chromatography (HPLC) analysis. To compare the results with data achieved in vivo, healthy cows were treated post partum intrauterinely or systemically, respectively, and the concentration of amoxicillin was determined in endometrial biopsies. In vitro intrauterine instillation resulted in significantly higher levels of amoxicillin in the inner layers of the uterine wall compared to systemic treatment, whereas the drug is distributed more homogenously through all layers in the systemically treated organs. In the in vivo experiments the tissue concentration of amoxicillin is significantly lower after intrauterine instillation compared to the in vitro data. In contrast, the endometrial concentrations in the uteri perfused with amoxicillin in vitro are comparable to those measured in endometrium of systemically treated cows. The MIC for gram positive and negative bacteria was exceeded in the uterine wall of all organs in vitro and in vivo after intrauterine treatment. In systemic treated cows the MIC for gram negative bacteria was exceeded in two of three cases, but never in the hemoperfused uteri. The data indicate that combined systemic and intrauterine treatment results in the best distribution of sufficient antibiotic concentrations in the uterine tissue. The isolated hemoperfused bovine uterus is shown to be suitable as an in vitro model for pharmacokinetic examinations, especially with regard to detailed information on the tissue distribution of drugs.

  11. Targeting of CD25 and glucocorticoid-induced TNF receptor family-related gene-expressing T cells differentially modulates asthma risk in offspring of asthmatic and normal mother mice.

    PubMed

    Hubeau, Cedric; Apostolou, Irina; Kobzik, Lester

    2007-02-01

    Immunological mechanisms leading to increased asthma susceptibility in early life remain obscure. In this study, we examined the effects of neonatal Ab treatments targeting T cell populations on the development of an asthma syndrome. We used a model of increased asthma susceptibility where offspring of asthmatic BALB/c mother mice are more prone (than normal pups) to develop the disease. Neonatal pretreatment of naive pups with mAb directed against the IL-2Ralpha chain (CD25), the costimulatory molecule glucocorticoid-induced TNFR family related gene, and the inhibitory molecule CTLA-4 elicited contrasting effects in offspring depending on the mother's asthma status. Specifically, neonatal CD25(high) T cell depletion stimulated asthma susceptibility in normal offspring whereas it ameliorated the condition of pups born of asthmatic mothers. Conversely, glucocorticoid-induced TNFR family related gene ligation as a primary signal reduced the spleen cellularity and largely abrogated asthma susceptibility in asthma-prone offspring, without inducing disease in normal pups. Striking changes in Th1/Th2 cytokine levels, especially IL-4, followed mAb pretreatment and were consistent with the impact on asthma susceptibility. These results point to major differences in neonatal T cell population and responsiveness related to maternal asthma history. Interventions that temporarily remove and/or inactivate specific T cell subsets may therefore prove useful to attenuate early life asthma susceptibility and prevent the development of Th2-driven allergic airway disease.

  12. Intrauterine Exposure to Paracetamol and Aniline Impairs Female Reproductive Development by Reducing Follicle Reserves and Fertility.

    PubMed

    Holm, Jacob Bak; Mazaud-Guittot, Severine; Danneskiold-Samsøe, Niels Banhos; Chalmey, Clementine; Jensen, Benjamin; Nørregård, Mette Marie; Hansen, Cecilie Hurup; Styrishave, Bjarne; Svingen, Terje; Vinggaard, Anne Marie; Koch, Holger Martin; Bowles, Josephine; Koopman, Peter; Jégou, Bernard; Kristiansen, Karsten; Kristensen, David Møbjerg

    2016-03-01

    Studies report that fetal exposure to paracetamol/acetaminophen by maternal consumption can interfere with male reproductive development. Moreover, recent biomonitoring data report widespread presence of paracetamol in German and Danish populations, suggesting exposure via secondary (nonpharmaceutical) sources, such as metabolic conversion from the ubiquitous industrial compound aniline. In this study, we investigated the extent to which paracetamol and aniline can interfere with female reproductive development. Intrauterine exposure to paracetamol by gavage of pregnant dams resulted in shortening of the anogenital distance in adult offspring, suggesting that fetal hormone signaling had been disturbed. Female offspring of paracetamol-exposed mothers had ovaries with diminished follicle reserve and reduced fertility. Fetal gonads of exposed animals had also reduced gonocyte numbers, suggesting that the reduced follicle count in adults could be due to early disruption of germ cell development. However, ex vivo cultures of ovaries from 12.5 days post coitum fetuses showed no decrease in proliferation or expression following exposure to paracetamol. This suggests that the effect of paracetamol occurs prior to this developmental stage. Accordingly, using embryonic stem cells as a proxy for primordial germ cells we show that paracetamol is an inhibitor of cellular proliferation, but without cytotoxic effects. Collectively, our data show that intrauterine exposure to paracetamol at levels commonly observed in pregnant women, as well as its precursor aniline, may block primordial germ cell proliferation, ultimately leading to reduced follicle reserves and compromised reproductive capacity later in life.

  13. The risk of childhood cancer from intrauterine and preconceptional exposure to ionizing radiation

    SciTech Connect

    Wakeford, R.

    1995-11-01

    The findings of studies investigating whether exposures to ionizing radiation before birth, either pre- or post-conception, increase the risk of childhood cancer have provoked much scientific controversy. An epidemiological association between the abdominal exposure or pregnant women to diagnostic X-rays and childhood cancer was first reported in the 1950s, while an association between the recorded dose of radiation received occupationally by fathers before the conception of their offspring and childhood leukemia was reported only recently in 1990. The scientific interpretation of these particular statistical associations is by no means straightforward, but the latest analyses of intrauterine irradiation and childhood cancer indicate that a causal inference is likely. Scientific committees have adopted risk coefficients for the intrauterine exposure of somatic tissues, which for childhood leukemia are comparable to those accepted for exposure in infancy, although questions remain about the level of risk of childhood solid tumors imparted by exposure to radiation in utero and shortly after birth. In contrast, the association has been found to be restricted to children born in one village, it does not extend to cancers other than leukemia, and it is markedly inconsistent with the established body of knowledge on radiation-induced hereditary disease. A causal interpretation of this association has effectively been abandoned by scientific authorities. 84 refs., 1 tab.

  14. Effects of intrauterine substance and postnatal violence exposure on aggression in children.

    PubMed

    Barthelemy, Olivier J; Richardson, Mark A; Rose-Jacobs, Ruth; Forman, Leah S; Cabral, Howard J; Frank, Deborah A

    2016-01-01

    During the cocaine epidemic of the 1980s and early 1990s, many expressed fears that children with intrauterine cocaine exposure (IUCE) would grow up to be unusually violent. The present study examines the relationship of caregiver reports of school-age children's aggressive behavior with IUCE and postnatal exposure to violence. Respondents were 140 low-income, primarily African American children, ages 8-11, and each child's current primary caregiver from a longitudinal study evaluating potential long term sequelae of IUCE. Multiple regression analyses were used to investigate the independent and interactive effects of level of IUCE (None (n = 69), Lighter (n = 47), Heavier (n =  24)) and exposure to violence (Violence Exposure Scale for Children-Revised) on aggressive behavior (Child Behavior Checklist), while also controlling for other intrauterine substance exposures and additional contextual factors. Children's self-reported exposure to violence was significantly positively associated with caregivers' reports of aggressive behavior (β = 2.17, P = .05), as was concurrent caregiver's psychiatric distress (β = .15, P = .003). However, neither IUCE nor its interaction with exposure to violence showed a significant association with aggressive behavior. Findings suggest the importance of postnatal social environment rather than IUCE in predicting aggressive behavior in childhood.

  15. The risk of childhood cancer from intrauterine and preconceptional exposure to ionizing radiation.

    PubMed Central

    Wakeford, R

    1995-01-01

    The findings of studies investigating whether exposures to ionizing radiation before birth, either pre- or post-conception, increase the risk of childhood cancer have provoked much scientific controversy. An epidemiological association between the abdominal exposure of pregnant women to diagnostic X-rays and childhood cancer was first reported in the 1950s, while an association between the recorded dose of radiation received occupationally by fathers before the conception of their offspring and childhood leukemia was reported only recently in 1990. The scientific interpretation of these particular statistical associations is by no means straightforward, but the latest analyses of intrauterine irradiation and childhood cancer indicate that a causal inference is likely. Scientific committees have adopted risk coefficients for the intrauterine exposure of somatic tissues, which for childhood leukemia are comparable to those accepted for exposure in infancy, although questions remain about the level of risk of childhood solid tumors imparted by exposure to radiation in utero and shortly after birth. In contrast, the association between paternal preconceptional radiation dose and childhood leukemia has not been confirmed by studies using objectively determined doses. The original association has been found to be restricted to children born in one village, it does not extend to cancers other than leukemia, and it is markedly inconsistent with the established body of knowledge on radiation-induced hereditary disease. A causal interpretation of this association has effectively been abandoned by scientific authorities. Images p1018-a PMID:8605850

  16. Endocrine-Immune Interactions in Pregnant Non-Human Primates With Intrauterine Infection

    PubMed Central

    Novy, Miles J.

    1997-01-01

    Preterm birth remains the most common cause of perinatal mortality. Although the causes of preterm labor are multifactorial and vary according to gestational age, preterm labor and term labor share common cellular and molecular mechanisms, including stimulation of the fetal hypothalamic-pituitary-adrenal (HPA) axis and endocrine/immune system interactions. We have developed a non-human primate experimental model for intrauterine infection and preterm labor using chronically instrumented rhesus monkeys (Macaca mulatta) with timed gestations. We have documented the temporal and quantitative relationships among intrauterine infection, the synthesis and release of proinflammatory cytokines, prostaglandins, and fetal-placental steroid biosynthesis in this model. Infection-induced preterm parturition is characterized by significant elevations in amniotic fluid proinflammatory cytokines and by increases in fetal adrenal steroid biosynthesis, but not by corresponding increases in placental estrogen biosynthesis characteristic of spontaneous parturition. This suggests that activation of the fetal HPA axis by the stress of infection is accompanied by placental dysfunction and also that infection-induced preterm parturition is not dependent upon the increased estrogen biosynthesis observed in spontaneous parturition. These different endocrine and immune responses have important diagnostic and therapeutic implications in the management of preterm labor. PMID:18476167

  17. Association between air pollution and intrauterine mortality in São Paulo, Brazil.

    PubMed Central

    Pereira, L A; Loomis, D; Conceição, G M; Braga, A L; Arcas, R M; Kishi, H S; Singer, J M; Böhm, G M; Saldiva, P H

    1998-01-01

    The associations among daily counts of intrauterine mortality and pollutant concentrations (NO2, SO2, CO, O3, and particulate matter (3/4)10 microm) were investigated for the period ranging from January 1991 to December 1992 in the city of São Paulo, Brazil. We used Poisson regression techniques, adjusted for season and weather. The association between intrauterine mortality and air pollution was strong for NO2 (coefficient = 0.0013/ microg/m3; p<0.01) but lesser for SO2 (coefficient = 0.0005/ microg/m3; p<0.10) and CO (coefficient = 0.0223/ppm; p<0.10). A significant association was observed when an index that combined these three pollutants was considered in the models instead of considering each pollutant individually (p<0.01). These associations exhibited a short time lag, not over 5 days. In addition, some evidence of fetal exposure to air pollution was obtained by disclosing a significant association between the levels of carboxyhemoglobin of blood sampled from the umbilical cord and ambient CO levels in children delivered by nonsmoking pregnant women in the period from May to July 1995. Our results suggest that air pollution in São Paulo may promote adverse health effects on fetuses. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:9618348

  18. Long-acting reversible contraceptives: intrauterine devices and the contraceptive implant.

    PubMed

    Espey, Eve; Ogburn, Tony

    2011-03-01

    The provision of effective contraception is fundamental to the practice of women's health care. The most effective methods of reversible contraception are the so-called long-acting reversible contraceptives, intrauterine devices and implants. These methods have multiple advantages over other reversible methods. Most importantly, once in place, they do not require maintenance and their duration of action is long, ranging from 3 to 10 years. Despite the advantages of long-acting reversible contraceptive methods, they are infrequently used in the United States. Short-acting methods, specifically oral contraceptives and condoms, are by far the most commonly used reversible methods. A shift from the use of short-acting methods to long-acting reversible contraceptive methods could help reduce the high rate of unintended pregnancy in the United States. In this review of long-acting reversible contraceptive methods, we discuss the intrauterine devices and the contraceptive implant available in the United States, and we describe candidates for each method, noncontraceptive benefits, and management of complications.

  19. Intraplacental Gene Therapy with Ad-IGF-1 Corrects Naturally Occurring Rabbit Model of Intrauterine Growth Restriction

    PubMed Central

    Keswani, Sundeep G.; Balaji, Swathi; Katz, Anna B.; King, Alice; Omar, Khaled; Habli, Mounira; Klanke, Charles

    2015-01-01

    Abstract Intrauterine growth restriction (IUGR) due to placental insufficiency is a leading cause of perinatal complications for which there is no effective prenatal therapy. We have previously demonstrated that intraplacental injection of adenovirus-mediated insulin-like growth factor-1 (Ad-IGF-1) corrects fetal weight in a murine IUGR model induced by mesenteric uterine artery branch ligation. This study investigated the effect of intraplacental Ad-IGF-1 gene therapy in a rabbit model of naturally occurring IUGR (runt) due to placental insufficiency, which is similar to the human IUGR condition with onset in the early third trimester, brain sparing, and a reduction in liver weight. Laparotomy was performed on New Zealand White rabbits on day 21 of 30 days of gestation and litters were divided into five groups: Control (first position)+phosphate-buffered saline (PBS), control+Ad-IGF-1, runt (third position)+PBS, runt+Ad-IGF-1, and runt+Ad-LacZ. The effect of IGF-1 gene therapy on fetal, placental, liver, heart, lung, and musculoskeletal weights of the growth-restricted pups was examined. Protein expression after gene transfer was seen along the maternal–fetal placenta interface (n=12) 48 hr after gene therapy. There was minimal gene transfer detected in the pups or maternal organs. At term, compared with the normally grown first-position control, the runted third-position pups demonstrated significantly lower fetal, placental, liver, lung, and musculoskeletal weights. The fetal, liver, and musculoskeletal weights were restored to normal by intraplacental Ad-IGF-1 gene therapy (p<0.01), with no change in the placental weight. Intraplacental gene therapy is a novel strategy for the treatment of IUGR caused by placental insufficiency that takes advantage of an organ that will be discarded at birth. Development of nonviral IGF-1 gene delivery using placenta-specific promoters can potentially minimize toxicity to the mother and fetus and facilitate clinical

  20. Differential regulation of LncRNA-SARCC suppresses VHL-mutant RCC cell proliferation yet promotes VHL-normal RCC cell proliferation via modulating androgen receptor/HIF-2α/C-MYC axis under hypoxia.

    PubMed

    Zhai, W; Sun, Y; Jiang, M; Wang, M; Gasiewicz, T A; Zheng, J; Chang, C

    2016-09-15

    It is well established that hypoxia contributes to tumor progression in a hypoxia inducible factor-2α (HIF-2α)-dependent manner in renal cell carcinoma (RCC), yet the role of long noncoding RNAs (LncRNAs) involved in hypoxia-mediated RCC progression remains unclear. Here we demonstrate that LncRNA-SARCC (Suppressing Androgen Receptor in Renal Cell Carcinoma) is differentially regulated by hypoxia in a von Hippel-Lindau (VHL)-dependent manner both in RCC cell culture and clinical specimens. LncRNA-SARCC can suppress hypoxic cell cycle progression in the VHL-mutant RCC cells while derepress it in the VHL-restored RCC cells. Mechanism dissection reveals that LncRNA-SARCC can post-transcriptionally regulate androgen receptor (AR) by physically binding and destablizing AR protein to suppress AR/HIF-2α/C-MYC signals. In return, HIF-2α can transcriptionally regulate the LncRNA-SARCC expression via binding to hypoxia-responsive elements on the promoter of LncRNA-SARCC. The negative feedback modulation between LncRNA-SARCC/AR complex and HIF-2α signaling may then lead to differentially modulated RCC progression in a VHL-dependent manner. Together, these results may provide us a new therapeutic approach via targeting this newly identified signal from LncRNA-SARCC to AR-mediated HIF-2α/C-MYC signals against RCC progression.

  1. Adipocytes as immune cells: differential expression of TWEAK, BAFF, and APRIL and their receptors (Fn14, BAFF-R, TACI, and BCMA) at different stages of normal and pathological adipose tissue development.

    PubMed

    Alexaki, Vassilia-Ismini; Notas, George; Pelekanou, Vassiliki; Kampa, Marilena; Valkanou, Maria; Theodoropoulos, Panayiotis; Stathopoulos, Efstathios N; Tsapis, Andreas; Castanas, Elias

    2009-11-01

    Adipose tissue represents a rich source of multipotent stem cells. Mesenchymal cells, isolated from this source, can differentiate to other cell types in vitro and therefore can be used for a number of regenerative therapies. Our view of adipose tissue has recently changed, establishing adipocytes as new members of the immune system, as they produce a number of proinflammatory cytokines (such as IL-6 and TNFalpha and chemokines, in addition to adipokines (leptin, adiponectin, resistin) and molecules associated with the innate immune system. In this paper, we report the differential expression of TNF-superfamily members B cell activating factor of the TNF Family (BAFF), a proliferation inducing ligand (APRIL), and TNF-like weak inducer of apoptosis (TWEAK) in immature-appearing and mature adipocytes and in benign and malignant adipose tissue-derived tumors. These ligands act through their cognitive receptors, BAFF receptor, transmembrane activator and calcium signal-modulating cyclophilic ligand (TACI), B cell maturation Ag (BCMA), and fibroblast growth factor-inducible 14 (Fn14), which are also expressed in these cells. We further report the existence of functional BCMA, TACI, and Fn14 receptors and their ligands BAFF, APRIL, and TWEAK on adipose tissue-derived mesenchymal cells, their interaction modifying the rate of adipogenesis. Our data integrate BAFF, APRIL, and TWEAK and their receptors BCMA, TACI, and Fn14 as novel potential mediators of adipogenesis, in addition to their specific role in immunity, and define immature and mature adipocytes as source of immune mediators.

  2. Differential mRNA expression of the human DNA methyltransferases (DNMTs) 1, 3a and 3b during the G0/G1 to S phase transition in normal and tumor cells

    PubMed Central

    Robertson, Keith D.; Keyomarsi, Khandan; Gonzales, Felicidad A.; Velicescu, Mihaela; Jones, Peter A.

    2000-01-01

    DNA methylation is essential for mammalian development, X-chromosome inactivation, and imprinting yet aberrant methylation patterns are one of the most common features of transformed cells. One of the proposed causes for these defects in the methylation machinery is overexpression of one or more of the three known catalytically active DNA methyltransferases (DNMTs) 1, 3a and 3b, yet there are clearly examples in which overexpression is minimal or non-existent but global methylation anomalies persist. An alternative mechanism which could give rise to global methylation errors is the improper expression of one or more of the DNMTs during the cell cycle. To begin to study the latter possibility we examined the expression of the mRNAs for DNMT1, 3a and 3b during the cell cycle of normal and transformed cells. We found that DNMT1 and 3b levels were significantly downregulated in G0/G1 while DNMT3a mRNA levels were less sensitive to cell cycle alterations and were maintained at a slightly higher level in tumor lines compared to normal cell strains. Enzymatic activity assays revealed a similar decrease in the overall methylation capacity of the cells during G0/G1 arrest and again revealed that a tumor cell line maintained a higher methylation capacity during arrest than a normal cell strain. These results reveal a new level of control exerted over the cellular DNA methylation machinery, the loss of which provides an alternative mechanism for the genesis of the aberrant methylation patterns observed in tumor cells. PMID:10773079

  3. Ciprofloxacin as a potential radio-sensitizer to tumor cells and a radio-protectant for normal cells: differential effects on γ-H2AX formation, p53 phosphorylation, Bcl-2 production, and cell death

    PubMed Central

    Kiang, Juliann G.; Garrison, Bradley R.; Smith, Joan T.; Fukumoto, Risaku

    2014-01-01

    Ionizing radiation increases cell mortality in a dose-dependent manner. Increases in DNA double strand breaks, γ-H2AX, p53 phophorylation, and protein levels of p53 and Bax also occur. We investigated the ability of ciprofloxacin (CIP), a widely prescribed antibiotic, to inhibit DNA damage induced by ionizing radiation. Human tumor TK6, NH32 (p53−/− of TK6) cells, and human normal peripheral blood mononuclear cells (PBMCs) were exposed to 2–8 Gy 60Co-γ-photon radiation. γ-H2AX (an indicator of DNA strand breaks), phosphorylated p53 (responsible for cell-cycle arrest), Bcl-2, apoptotic proteins, and cell death were measured. Ionizing irradiation increased γ-H2AX amounts in TK6 cells (p53+/+) within 1 hr in a radiation dose-dependent manner. CIP pretreatment and post-treatment effectively inhibited the increase in γ-H2AX. CIP pretreatment reduced Bcl-2 production but promoted p53 phosphorylation, caspase-3 activation and cell death. In NH32 cells, CIP failed to significantly inhibit the radiation-induced γ-H2AX increase, suggesting that CIP inhibition involves in p53-dependent mechanisms. In normal healthy human PBMCs, CIP failed to block the radiation-induced γ-H2AX increase but effectively increased Bcl-2 production but blocked the phospho-p53 increase and subsequent cell death. CIP increased Gadd45α, and enhanced p21 protein 24 hr postirradiation. Results suggest that CIP exerts its effect in TK6 cells by promoting p53 phosphorylation and inhibiting Bcl-2 production and in PBMCs by inhibiting p53 phosphorylation and increasing Bcl-2 production. Our data are the first to support the view that CIP may be effective to protect normal tissue cells from radiation injury, while enhancing cancer cell death in radiation therapy. PMID:24802382

  4. Problematic Substance Use in Urban Adolescents: Role of Intrauterine Exposures to Cocaine and Marijuana and Post-Natal Environment

    PubMed Central

    Frank, Deborah A.; Kuranz, Seth; Appugliese, Danielle; Cabral, Howard; Chen, Clara; Crooks, Denise; Heeren, Timothy; Liebschutz, Jane; Richardson, Mark; Rose-Jacobs, Ruth

    2014-01-01

    Background Linkages between intrauterine exposures to cocaine and marijuana and adolescents’ problematic substance use have not been fully delineated. Methods Prospective longitudinal study with assessors unaware of intrauterine exposure history followed 157 urban participants from birth until late adolescence. Level of intrauterine exposures was identified by mother's report and infant’s meconium. Problematic substance use, identified by the Voice Diagnostic Interview Schedule for Children (V-DISC) or the Audio Computer Assisted Self-Interview (ACASI) and urine assay, was a composite encompassing DSM-IV indication of tolerance, abuse, and dependence on alcohol, marijuana, and tobacco and any use of cocaine, glue, or opiates. Results Twenty percent (32/157) of the sample experienced problematic substance use by age 18 years, of whom the majority (22/157) acknowledged abuse, tolerance or dependence on marijuana with or without other substances. Structural equation models examining direct and indirect pathways linking a Cox survival model for early substance initiation to a logistic regression models found effects of post-natal factors including childhood exposure to violence and household substance use, early youth substance initiation, and ongoing youth violence exposure contributing to adolescent problematic substance use. Conclusion We did not identify direct relationships between intrauterine cocaine or marijuana exposure and problematic substance use, but did find potentially modifiable post-natal risk factors also noted to be associated with problematic substance use in the general population including earlier substance initiation, exposure to violence and to household substance use. PMID:24999059

  5. Transgenerational Glucose Intolerance of Tumor Necrosis Factor with Epigenetic Alteration in Rat Perirenal Adipose Tissue Induced by Intrauterine Hyperglycemia

    PubMed Central

    Su, Rina; Yan, Jie; Yang, Huixia

    2016-01-01

    Changes in DNA methylation may play a role in the genetic mechanism underlying glucose intolerance in the offspring of mothers with diabetes. Here, we established a rat model of moderate intrauterine hyperglycemia induced by streptozotocin to detect glucose and lipid metabolism of first-generation (F1) and second-generation (F2) offspring. Moderate intrauterine hyperglycemia induced high body weight in F1 and F2 offspring of diabetic mothers. F1 offspring had impaired glucose tolerance and abnormal insulin level. Additionally, F1 and F2 offspring that were exposed to intrauterine hyperglycemia had impaired insulin secretion from the islets. The tumor necrosis factor (Tnf) gene was upregulated in perirenal adipose tissue from F1 offspring and relatively increased in F2 offspring. Both F1 and F2 offspring showed similar hypomethylation level at the −1952 site of Tnf. We confirmed that DNA methylation occurs in offspring exposed to intrauterine hyperglycemia and that the DNA methylation is intergenerational and inherited. PMID:26881249

  6. Hormonal Profiles of Late Gestation Ewes Following Intra-Uterine Inoculation With and Without Lux-Modified Escherichia Coli

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objectives of these investigations were to develop an ovine model for Escherichia coli (E. coli)-induced preterm delivery, and monitor ewe hormonal response. EXP 1: Ewes (105 ± 13 d of gestation) were allotted to the following intra-uterine inoculations: Saline-(CON; n=5); 1×106 CFU/ml (Low Tre...

  7. Ex Vivo Bioluminescence Imaging of Late Gestation Ewes Following Intra-uterine Inoculation With Lux-modified Escherichia coli

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our objectives were to develop an ovine model for Escherichia coli-induced preterm delivery, and monitor E. coli (lux modified for photonic detection) invasion of the fetal environment—ewes (124 ± 18 d of gestation) received intrauterine inoculations using E. coli-lux as follows: control (n = 5), 1....

  8. Reproductive efficiency of cows with endometritis after treatment with intrauterine infusions or prostaglandin injections, or no treatment.

    PubMed

    Knutti, B; Küpfer, U; Busato, A

    2000-12-01

    Data from 3276 cows with 6598 lactations in 85 herds participating in a herd health monitoring programme were selected for an observational study. Cases of endometritis were diagnosed based on a clinical examination after 21 days postpartum. The cases were grouped by the severity of endometritis (mild, severe) and by the treatment performed (intrauterine infusion, prostaglandin injection, no treatment). The conception rates and the calving-to-conception intervals of these groups were compared statistically. Conception rate was lower in cows with severe endometritis compared to cows with mild endometritis while it did not differ between treatment groups. In cows with mild endometritis a significantly longer calving-to-conception interval was observed if intrauterine infusions were performed compared to the other two treatment options. The occurrence of other fertility problems during the same service period had a significant effect on conception rate and calving-to-conception intervals. In cows with severe endometritis intrauterine or prostaglandin treatments appeared to be beneficial, whereas intrauterine infusions in cows with slight endometritis had a negative effect on reproductive efficiency.

  9. Readiness and Adjustments to School for Children with Intrauterine Growth Restriction (IUGR): An Extreme Test Case Paradigm

    ERIC Educational Resources Information Center

    Geva, Ronny; Yosipof, Rina; Eshel, Rina; Leitner, Yael; Valevski, Aviva Fattal; Harel, Shaul

    2009-01-01

    This long-term, prospective study evaluated repeatedly school readiness and adjustment at kindergarten and first grade of children with extreme intrauterine growth restriction (IUGR; n = 20) in relation to controls (n = 19). Methods included individual testing of cognitive competence, self-perception, motivation, loneliness and academic…

  10. In vitro study of the possible role of the intrauterine contraceptive device tail in ascending infection of the genital tract.

    PubMed

    Purrier, B G; Sparks, R A; Watt, P J; Elstein, M

    1979-05-01

    Potentially pathogenic bacteria colonized the mucus coating the tails of both monofilamentous and multifilamentous intrauterine contraceptive devices (IUCD) in 72 (55 per cent) out of 132 in vitro tests. This suggests that the IUCD tail may be responsible for the passage of vaginal bacteria into the uterus.

  11. Mouse model of intrauterine inflammation: sex-specific differences in long-term neurologic and immune sequelae.

    PubMed

    Dada, Tahani; Rosenzweig, Jason M; Al Shammary, Mofeedah; Firdaus, Wance; Al Rebh, Shorouq; Borbiev, Talaibek; Tekes, Aylin; Zhang, Jiangyang; Alqahtani, Eman; Mori, Susumu; Pletnikov, Mikhail V; Johnston, Michael V; Burd, Irina

    2014-05-01

    Preterm infants, especially those that are exposed to prenatal intrauterine infection or inflammation, are at a major risk for adverse neurological outcomes, including cognitive, motor and behavioral disabilities. We have previously shown in a mouse model that there is an acute fetal brain insult associated with intrauterine inflammation. The objectives of this study were: (1) to elucidate long-term (into adolescence and adulthood) neurological outcomes by assessing neurobehavioral development, MRI, immunohistochemistry and flow cytometry of cells of immune origin and (2) to determine whether there are any sex-specific differences in brain development associated with intrauterine inflammation. Our results have shown that prenatal exposure appeared to lead to changes in MRI and behavior patterns throughout the neonatal period and during adulthood. Furthermore, we observed chronic brain inflammation in the offspring, with persistence of microglial activation and increased numbers of macrophages in the brain, ultimately resulting in neuronal loss. Moreover, our study highlights the sex-specific differences in long-term sequelae. This study, while extending the growing literature of adverse neurologic outcomes following exposure to inflammation during early development, presents novel findings in the context of intrauterine inflammation.

  12. Use of the levonorgestrel 52-mg intrauterine system in adolescent and young adult solid organ transplant recipients: a case series.

    PubMed

    Huguelet, P S; Sheehan, C; Spitzer, R F; Scott, S

    2017-04-01

    This case series reports on the safety and efficacy of the levonorgestrel 52-mg intrauterine system in adolescent and young adult solid organ transplant recipients. All patients used the device for contraception, with no documented cases of disseminated pelvic infection or unplanned pregnancy.

  13. Adolescent initiation of licit and illicit substance use: Impact of intrauterine exposures and post-natal exposure to violence.

    PubMed

    Frank, Deborah A; Rose-Jacobs, Ruth; Crooks, Denise; Cabral, Howard J; Gerteis, Jessie; Hacker, Karen A; Martin, Brett; Weinstein, Zohar B; Heeren, Timothy

    2011-01-01

    Whether intrauterine exposures to alcohol, tobacco, marijuana, or cocaine predispose offspring to substance use in adolescence has not been established. We followed a sample of 149 primarily African American/African Caribbean, urban adolescents, recruited at term birth, until age 16 to investigate intrauterine cocaine exposure (IUCE). We found that in Kaplan-Meier analyses higher levels of IUCE were associated with a greater likelihood of initiation of any substance (licit or illicit), as well as marijuana and alcohol specifically. Adolescent initiation of other illicit drugs and cigarettes were analyzed only in the "any" summary variable since they were used too infrequently to analyze as individual outcomes. In Cox proportional hazard models controlling for intrauterine exposure to alcohol, tobacco, and marijuana and demographic and post-natal covariates, those who experienced heavier IUCE had a greater likelihood of initiation of any substance, and those with lighter intrauterine marijuana exposure had a greater likelihood of initiation of any substance as well as of marijuana specifically. Time-dependent higher levels of exposure to violence between ages of 8 and 16 were also robustly associated with initiation of any licit or illicit substance, and of marijuana, and alcohol particularly.

  14. EPHA7 and EPHA10 Physically Interact and Differentially Co-localize in Normal Breast and Breast Carcinoma Cell Lines, and the Co-localization Pattern Is Altered in EPHB6-expressing MDA-MB-231 Cells

    PubMed Central

    JOHNSON, CANDACE; SEGOVIA, BRIANA; KANDPAL, RAJ P

    2016-01-01

    Erythropoietin-producing hepatocellular carcinoma cell (EPH) receptors comprise the most abundant receptor tyrosine kinase family characterized to date in mammals including humans. These proteins are involved in axon guidance, tissue organization, vascular development and the intricate process of various diseases including cancer. These diverse functions of EPH receptors are attributed, in part, to their abilities for heterodimerization. While the interacting partners of kinase-deficient EPHB6 receptor have been characterized, the interaction of the kinase-dead EPHA10 with any other receptor has not been identified. By using co-immunoprecipitation, we demonstrated physical interaction between kinase-deficient EPHA10 with kinase-sufficient EPHA7 receptor. Immunocytochemical analyses have revealed that these two receptors co-localize on the cell surface, and soluble portions of the receptors exist as a complex in the cytoplasm as well as the nuclei. While EPHA7 and EPHA10 co-localize similarly on the membrane in MCF10A and MCF7 cells, they were differentially co-localized in MDA-MB-231 cells stably transfected with empty pcDNA vector (MDA-MB-231-PC) or an expression construct of EPHB6 (MDA-MB-231-B6). The full-length isoforms of these receptors were co-localized on the cell surface, and the soluble forms were present as a complex in the cytoplasm as well as the nucleus in MDA-MB-231-PC cells. MDA-MB-231-B6 cells, on the other hand, were distinguished by the absence of any signal in the nuclei. Our results represent the first demonstration of physical interaction between EPHA10 and EPHA7 and their cellular co-localization. Furthermore, these observations also suggest gene-regulatory functions of the complex of the soluble forms of these receptors in breast carcinoma cells of differential invasiveness. PMID:27566654

  15. Constructing Involutive Tableaux with Guillemin Normal